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1-10 Difficult vocab test 2B1Make mcq quiz with 4 option in which one is correct -'10 Basis of Material Science • .....;;;";;;"~~;;,,;;,,,,;.;.,,;;,,,;,,;.;,.,------------ 6. Temporary materials: Some materials are meant to be placed in the oral cavity for a short period of time for different reasons. • Temporary crowns: While a permanent crown is prepared in the dental laboratory, the patient must wait for few days before it can be fabricated and cemented into place. Does patient experience any problems during this time period? If the tooth is vital (the pulp is alive), the patient is likely to experience pain and sensitivity while eating and drinking, also it looks unesthetic. What can be done to solve this problem? A temporary crown is placed before the patient leaves the clinic. It is constructed and luted in the same appointment in which the crown preparation is done. Temporary crowns are not very strong or esthetic but they serve adequately till the permanent crown is ready to be cemented. • Temporary restorations: Sometimes it is difficult to decide immediately the best line of treatment for a particular tooth. The exact condition of the pulp may not be obvious to the dentist from the patient's symptoms. A dentist removes all or part of the decay and then places a temporary restoration to have time to observe the behaviour of the pulp or to give the pilip time to heal before deciding the further treatment required. Classification based on Location of Fabrication 4,9 Materials can be classified based on the location of fabrication into: • Direct restorative materials. • Indirect restorative materials Direct restorative materials: They include those materials which are used to restore cavity preparations directly in the oral cavity (Box 1.5). Box 1.5: Examples of direct restorative materials Amalgam, composites, glass ionomer and other materials, which set by chemical reactions in the mouth. Indirect restorative materials: It includes those restorations which must be fabricated outside the mouth, indirectly on a cast/ model/ die, because their processing condition would harm oral tissues. Materials used in the construction of such prosthesis are called indirect restorative materials (Box 1.6). Box 1.6: Examples of indirect restorative materials Gold inlays, crowns of metal, ceramic and polymers, which are processed at elevated temperatures. Some indirect composite restorations can be processed under specific wavelength of light, e.g. Ceramage. Classification based on Longevity of Use 1. Permanent restorations: These restorations are not planned to be replaced for a particular time period. Though they are referred to as permanent, actually they are not, e.g. fillings, crowns, bridges and dentures do not last forever (Fig. 1.5). 2. Temporary restorations: These restorations are planned to be replaced in a short period of time, such as few days to weeks. For ~ Permanent C/) c c -.2 0 c- :;::; Cll co Interim ~ Q; 0 .8ll::1iJ C/) o~ Cll a:: c:=:J Temporary Time period Fig. 1.5: Diagram depicting the time period of use of a restoration. (Arrow in permanent restoration depicts that such restorations are not planned to be replaced for a long period of time.) Introducton to Dental Materials Dental materials Box 1.7: Characteristics of metals 1. High thermal and electrical conductivity 2. Ductility (pure metals are very soft and they can be bent without breaking) 3. Opacity (they do not transmit light) 4. Luster (they have a surface that strongly reflects light and appears bright and shiny) 5. They tend to dissolve to some extent in water or other aqueous solutions, producing cations. 6. All metals are white (actually gray) except for gold, which is yellow, and copper, which is reddish. 7. All metals are solid at room temperature except mercury, which is liquid at room temperature and is used with silver alloys as amalgam. 8. All metals have high melting temperatures because of high strength of the metallic bond that holds the atoms together. 3. Polymers 4. Composites Composites are mixtures of two or more of the first three classes in which the different components remain distinct from one another in the final structure. A common example is composite resin. Fig. 1.7a: Three-dimensional structure of iron (metal) Metals Metals are the oldest of the three classes of materials that have been used as dental materials. Metals are characterized by metallic bonds (Box 1.7) which will be discussed in the next chapter. Metals solidify with their atoms in a regular or crystalline arrangement (see Chapter 2), often in the form of a cube (Fig. 1.7a). example, temporary fillings done in a tooth during root canal treatment, which have to be replaced within 2-4 days during subsequent visits. They are used to protect the tooth and provide function till the final restoration is done. 3. Interim restoration: At times, dental treatment requires "long-term" definite temporary restorations or "interim" restorations. For examle, a 7-year-old child, met with trauma and fractured one of his central incisors. A large composite build- up may serve his immediate requirement until the root formation is completed and a permanent crown is placed. 5 Classification based on the Chemical Nature of the Material These are the atoms that make up a material and the way they are bonded together determine the properties of that materiaLS Weak bonds make for weak materials and vice versa (Table 1.4). Materials can be classified into different categories based on their primary atomic bonds (Fig. 1.6): 1. Metals 2. Ceramics Fig. 1.6: Classification of dental materials based on chemical nature 12 Basis of Material Science Box 1.9: Benefits of ceramics in dentistry 1. Many ceramic oxides are used as pigmenting agents. These oxides produce good range of colors. Due to this characteristic, we are able to match almost any tooth color with good esthetic results. 2. They are inert, i.e. not chemically reactive. This quality provides ceramics with good bio- compatibility. 3. Ceramic materials are translucent, like natural teeth. This translucency gives the ceramic crown a more natural appearance than any other dental material. Fig. 1.7b: Internal arrangement of tetrahedral structure of ceramic (silica) four large oxygen atoms surround smaller silicon atom Ceramics A ceramic is a compound formed by the union of a metallic and a non-metallic element (Box 1.8). Most of these materials are oxides, formed by the union of oxygen with metals such as silicon, aluminum, calcium and magnesium (Fig.1.7b). Ceramics may be simple or complex. Examples of simple ceramics are alumina and silica. Examples of complex ceramics are feldspar (potassium aluminum silicate) and kaolin (hydrated aluminum silicate). Ceramics may be crystalline or non- crystalline (i.e. amorphous). Porcelain is a specific type of ceramic used extensively in dentistry (Box 1.9). Box 1.8: Characteristics of ceramics 1. High melting points. 2. Brittleness, which means they cannot be bent or deformed (no sliding) to any extent without actually cracking and breaking. 3. They are poor conductor of heat and electricity. 4. They are chemically inert. 5. They have excellent esthetic result in terms of matching natural teeth. Fig. 1.8: Stucture of synthetic polymer Polymers They are the latest addition (early to mid- 1900s) to dental materials. Most of the polymers are nowadays synthesized by humans. Polymers are giant, long-chain organic molecules (Fig. 1.8). Polymers are characterized by covalent bonds within each molecule, giving them tremendous strength in a single direction. Try to break a nylon rope by pulling it! They are poor conductors of heat and electri- city. Most polymers have a structure containing thousands of carbon atoms linked together like beads on a string. Others, such as silicone polymers are formed with silicon-oxygen bonds. Introducton to Dental Materials Table 1.4: Characteristics of different materials 13 Characteristics Bond Properties Crystal structure Metals Metallic bonding High strength and hardness, high electrical and thermal conductivity BCC, FCC, or HCP unit cells Ceramics Ionic or covalent bonding, or both High hardness and stiffness, electrically insulating, refractory, and chemically inert Crystalline or amorphous Polymers Covalent bonding Low sensitivity, high electrical resistivity, and low thermal conductivity, strength and stiffness vary widely Amorphous and crystalline Composites Composites are combinations of any of the basic ceramic, metallic and polymeric materials (Box 1.10). Each material that makes up composites is called a phase. Their properties tend to be somewhere between those of their basic constituents and are used to enhance their performance, longevity and handling chracterstics. Box 1.10: Types of composites in dentistry 1. Ceramic - metallic composite: Tungsten carbide bur. 2. Metal - polymer composite: Die materials in dental laboratory. 3. Ceramic - polymer composite: Enamel, dentin, bone and restorative composites. A composite is a kind of "combination" of materials, which compliment each other. The properties lacking in one material are compensated by those of the other material. For example, restorative composite has two phases, namely resin and fillers. Teeth and bones are examples of natural composites. Enamel is a composite of hydroxyapatite (which is a ceramic material) and protein (which is a polymer). EVALUATION OF DENTAL MATERIALS Most manufacturers of dental materials maintain a quality assurance programme (As per international standard like ADA specifications) and materials are thoroughly tested before being released into the market for dental practitioner (Fig. 1.9). Laboratory Evaluations Most ADA/ ANSI specifications involve laboratory tests. The tests performed as per these specifications are useful but they all are performed in vitro, (carried out in the laboratory away from the clinical conditions) which have a lot of limitations in clinical practice.lO Clinical Notes 1. For example, most of the direct restorative materials are tested for their compressive strength but ultimately the material is subjected to a combination of compressive, tensile and shear stresses, which may decide the final success or failure of the material under masticatory load. 2. Similarly upper dentures mostly fracture along the midline because of bending. Hence a bending or transverse strength ~B-a-s-is-o-f-M-a-t-e-ria-I-S~c-ie-n-c-e-------------- ---------. test is far more meaningful for denture base materials than a compression test. Clinical Trials The majority of new materials are subjected to extensive clinical trials normally in co-operation with a dental college or hospital departments prior to their release. CONCLUSION As the number of available materials is going up, it is important that the dentist remains more aware about new products so that their judgement about the selection of material remains successful. Materials which have not been thoroughly evaluated should be avoided, specially with clinical dentistry falling under Consumer Protection Act (CPA). I Research and development I iI Manufacturer/analysis Ideal requirements for clinical use: Thermal, optical, mechanical, chemical, biological Available materials and their properties are evaluated Launch of new I product Choice and selection of material by the dentist Critical assessment based on clinical performance I I H feedback to IOwls, such as the young snowy owls on the previous page, have for centuries been symbols of both wisdom and mystery. To many cultures their piercing eyes have conveyed a look of intelligence. Their silent flight through darkened landscapes in search of prey has projected an air of power or wonder. For this chapter and this book, owls are an engaging example of a living organism from the world of biology—the study of life. BIOLOGY AND YOU Living in a small town, in the country, or at the edge of the suburbs, one may be lucky enough to hear an owl's hooting. This experience can lead to questions about where the bird lives, what it hunts, and how it finds its prey on dark, moonless nights. Biology, or the study of life, offers an organized and scientific framework for posing and answering such questions about the natural world. Biologists study questions about how living things work, how they interact with the environment, and how they change over time. Biologists study many different kinds of living things ranging from tiny organisms, such as bacteria, to very large organisms, such as elephants. Each day, biologists investigate subjects that affect you and the way you live. For example, biologists determine which foods are healthy. As shown in Figure 1-1, everyone is affected by this impor- tant topic. Biologists also study how much a person should exer- cise and how one can avoid getting sick. Biologists also study what CHARACTERISTICS OF LIFE The world is filled with familiar objects, such as tables, rocks, plants, pets, and automobiles. Which of these objects are living or were once living? What are the criteria for assigning something to the living world or the nonliving world? Biologists have established that living things share seven characteristics of life. These characteristics are organization and the presence of one or more cells, response to a stimulus (plural, stimuli), homeostasis, metabolism, growth and development, reproduction, and change through time. Organization and Cells Organization is the high degree of order within an organism’s internal and external parts and in its interactions with the living world. For example, compare an owl to a rock. The rock has a spe- cific shape, but that shape is usually irregular. Furthermore, differ- ent rocks, even rocks of the same type, are likely to have different shapes and sizes. In contrast, the owl is an amazingly organized individual, as shown in Figure 1-2. Owls of the same species have the same body parts arranged in nearly the same way and interact with the environment in the same way. Copyright © by Holt, Rinehart and Winston. All rights reserved. ORGANISM (Barn Owl) ORGAN (Owl’s Ear) TISSUE (Nervous Tissue Within the Ear) CELL (Nerve Cell) your air, land, and fAll living organisms, whether made up of one cell or many cells, have some degree of organization. A cell is the smallest unit that can perform all life’s processes. Some organisms, such as bacteria, are made up of one cell and are called unicellular (YOON-uh-SEL-yoo-luhr) organisms. Other organisms, such as humans or trees, are made up of multiple cells and are called multicellular (MUHL-ti-SEL-yoo-luhr) organisms. Complex multicellular organisms have the level of orga- nization shown in Figure 1-2. In the highest level, the organism is made up of organ systems, or groups of specialized parts that carry out a certain function in the organism. For example, an owl’s ner- vous system is made up of a brain, sense organs, nerve cells, and other parts that sense and respond to the owl’s surroundings. Organ systems are made up of organs. Organs are structures that carry out specialized jobs within an organ system. An owl’s ear is an organ that allows the owl to hear. All organs are made up of tissues. Tissues are groups of cells that have similar abilities and that allow the organ to function. For example, nervous tissue in the ear allows the ear to detect sound. Tissues are made up of cells. A cell must be covered by a membrane, contain all genetic information necessary for replication, and be able to carry out all cell functions. Within each cell are organelles. Organelles are tiny structures that carry out functions necessary for the cell to stay alive. Organelles contain biological molecules, the chemical compounds that provide physical structure and that bring about movement, energy use, and other cellular functions. All biological molecules are made up of atoms. Atoms are the simplest particle of an ele- ment that retains all the properties of a certain element. Response to Stimuli Another characteristic of life is that an organism can respond to a stimulus—a physical or chemical change in the internal or external environment. For example, an owl dilates its pupils to keep the level of light entering the eye constant. Organisms must be able to respond and react to changes in their environment to stay alive. ORGANELLE (Mitochondrion) BIOLOGICAL MOLECULE (Phospholipid) ATOM (Oxygen) cell from the Latin, cella meaning “small room,” or “hut” Word Roots and Origins www.scilinks.org Topic: Characteristics of Life Keyword: HM60257 mb06se_bios01.qxd 5/18/07 10:37 AM Page 7 8 CHAPTER 1 Homeostasis All living things, from single cells to entire organisms, have mecha- nisms that allow them to maintain stable internal conditions. Without these mechanisms, organisms can die. For example, a cell’s water content is closely controlled by the taking in or releas- ing of water. A cell that takes in too much water will rupture and die. A cell that doesn’t get enough water will also shrivel and die. Homeostasis (HOH-mee-OH-STAY-sis) is the maintenance of a stable level of internal conditions even though environmental conditions are constantly changing. Organisms have regulatory systems that maintain internal conditions, such as temperature, water content, and uptake of nutrients by the cell. In fact, multi- cellular organisms usually have more than one way of maintain- ing important aspects of their internal environment. For example, an owl’s temperature is maintained at about 40°C (104°F). To keep a constant temperature, an owl’s cells burn fuel to produce body heat. In addition, an owl’s feathers can fluff up in cold weather. In this way, they trap an insulating layer of air next to the bird’s body to maintain its body temperature. Metabolism Living organisms use energy to power all the life processes, such as repair, movement, and growth. This energy use depends on metabolism (muh-TAB-uh-LIZ-uhm). Metabolism is the sum of all the chemical reactions that take in and transform energy and materials from the environment. For example, plants, algae, and some bacteria use the sun’s energy to generate sugar molecules during a process called photosynthesis. Some organisms depend on obtaining food energy from other organisms. For instance, an owl’s metabolism allows the owl to extract and modify the chemi- cals trapped in its nightly prey and use them as energy to fuel activities and growth. Growth and Development All living things grow and increase in size. Some nonliving things, such as crystals or icicles, grow by accumulating more of the same material of which they are made. In contrast, the growth of living things results from the division and enlargement of cells. Cell division is the formation of two new cells from an existing cell, as shown in Figure 1-3. In unicellular organisms, the primary change that occurs following cell division is cell enlargement. In multi- cellular life, however, organisms mature through cell division, cell enlargement, and development. Development is the process by which an organism becomes a mature adult. Development involves cell division and cell differen- tiation, or specialization. As a result of development, an adult organism is composed of many cells specialized for different func- tions, such as carrying oxygen in the blood or hearing. In fact, the human body is composed of trillions of specialized cells, all of which originated from a single cell, the fertilized egg. This unicellular organism, Escherichia coli, inhabits the human intestines. E. coli reproduces by means of cell division, during which the original cell splits into two identical offspring cells. FIGURE 1-3 Observing Homeostasis Materials 500 mL beakers (3), wax pen, tap water, thermometer, ice, hot water, goldfish, small dip net, watch or clock with a second hand Procedure 1. Use a wax pen to label three 500 mL beakers as follows: 27°C (80°F), 20°C (68°F), 10°C (50°F). Put 250 mL of tap water in each beaker. Use hot water or ice to adjust the tem- perature of the water in each beaker to match the temperature on the label. 2. Put the goldfish in the beaker of 27°C water. Record the number of times the gills move in 1 minute. 3. Move the goldfish to the beaker of 20°C water. Repeat observations. Move the goldfish to the beaker of 10°C. Repeat observations. Analysis What happens to the rate at which gills move when the temp- erature changes? Why? How do gills help fish maintain homeostasis? Quick Lab mb06se_bios01.qxd 5/18/07 10:37 AM Page 8 THE SCIENCE OF LIFE 9 Reproduction All organisms produce new organisms like themselves in a process called reproduction. Reproduction, unlike other characteristics, is not essential to the survival of an individual organism. However, because no organism lives forever, reproduction is essential for the continuation of a species. Glass frogs, as shown in Figure 1-4, lay many eggs in their lifetime. However, only a few of the frogs’ off- spring reach adulthood and successfully reproduce. During reproduction, organisms transmit hereditary informa- tion to their offspring. Hereditary information is encoded in a large molecule called deoxyribonucleic acid, or DNA. A short segment of DNA that contains the instructions for a single trait of an organism is called a gene. DNA is like a large library. It contains all the books—genes—that the cell will ever need for making all the struc- tures and chemicals necessary for life. Hereditary information is transferred to offspring during two kinds of reproduction. In sexual reproduction, hereditary information recombines from two organisms of the same species. The resulting offspring are similar but not identical to their parents. For example, a male frog’s sperm can fertilize a female’s egg and form a single fer- tilized egg cell. The fertilized egg then develops into a new frog. In asexual reproduction, hereditary information from different organisms is not combined; thus the original organism and the new organism are genetically the same. A bacterium, for example, reproduces asexually when it splits into two identical cells. Change Through Time Although individual organisms experience many changes during their lifetime, their basic genetic characteristics do not change. However, populations of living organisms evolve or change through time. The ability of populations of organisms to change over time is important for survival in a changing world. This factor is also impor- tant in explaining the diversity of life-forms we see on Earth today. 1. How does biology affect a person’s daily life? 2. How does biology affect society? 3. Name the characteristics shared by living things. 4. Summarize the hierarchy of organization found in complex multicellular organisms. 5. What are the different functions of homeostasis and metabolism in living organisms? 6. How does the growth among living and nonliv- ing things differ? 7. Why is reproduction an important characteristic of life? CRITICAL THINKING 8. Applying Information Crystals of salt grow and are highly organized. Why don’t biologists con- sider them to be alive? 9. Analyzing Models When a scientist designs a space probe to detect life on a distant planet, what kinds of things should it measure? 10. Making Comparisons Both cells and organisms share the characteristics of life. How are cells and organismsood supply will be like in the near future.EVOLUTION OF LIFE Individual organisms change during their lifetime, but their basic genetic characteristics do not change. However, populations of liv- ing organisms do change through time, or evolve. Evolution, or descent with modification, is the process in which the inherited characteristics within populations change over generations, such that genetically distinct populations and new species can develop. Evolution as a theme in biology helps us understand how the various branches of the “tree of life” came into existence and have changed over time. It also explains how organisms alive today are related to those that lived in the past. Finally, it helps us understand the mechanisms that underlie the way organisms look and behave. Natural Selection The ability of populations of organisms to change over time is important for survival in a changing world. According to the theory of evolution by natural selection, organisms that have certain favorable traits are better able to survive and reproduce success- fully than organisms that lack these traits. One product of natural selection is the adaptation of organisms to their environment. Adaptations are traits that improve an indi- vidual’s ability to survive and reproduce. For example, rabbits with white fur and short ears in a snowy place, such as the one in Figure 1-7a, may avoid predators and frostbitten ears more often than those with dark fur and long ears. Thus, the next generation of rabbits will have a greater percentage of animals carrying the genes for white fur and short ears. In contrast, the brown, long- eared rabbit, as shown in Figure 1-7b, would survive and reproduce more successfully in a hot desert environment. The survival and reproductive success of organisms with favor- able traits cause a change in populations of organisms over gener- ations. This descent with modification is an important factor in explaining the diversity of organisms we see on Earth today. 1. Name three unifying themes found in biology. 2. How is the unity and diversity in the living world represented? 3. Identify the three domains and the kingdoms found in each domain. 4. How are organisms interdependent? 5. Describe why evolution is important in explain- ing the diversity of life. 6. Distinguish between evolution and natural selection. CRITICAL THINKING 7. Applying Information Assign the various top- pings you put on pizza to the appropriate domains and kingdoms of life. 8. Analyzing Graphics According to the “tree” in Figure 1-5, which of these pairs are more closely related: Archaea:Bacteria or Archaea:Eukarya? 9. Making Hypotheses Fossil evidence shows that bats descended from shrewlike organisms that could not fly. Write a hypothesis for how natural selection might have led to flying bats. SECTION 2 REVIEW (a) This short-eared arctic hare, Lepus arcticus, is hidden from predators and protected from frostbite in a snowy environment. (b) The mottled brown coats of desert rabbits blend in with the dirt and dry grasses, and their long ears help them radiate excess heat and thus avoid overheating. FIGURE 1-7 (a) (b) Copyright © by Holt, Rinehart and Winston. All rights reserved. THE SCIENCE OF LIFE 13 TH E STUDY OF BIOLOGY Curiosity leads us to ask questions about life. Science provides a way of answering such questions about the natural world. Science is a systematic method that involves forming and testing hypotheses. More importantly, science relies on evidence, not beliefs, for drawing conclusions. SCIENCE AS A PROCESS Science is characterized by an organized approach, called the scientific method, to learn how the natural world works. The methods of science are based on two important principles. The first principle is that events in the natural world have natural causes. For example, the ancient Greeks believed that lightning and thunder occurred because a supernatural god Zeus hurled thunderbolts from the heavens. By contrast, a scientist considers lightning and thunder to result from electric charges in the atmos- phere. When trying to solve a puzzle from nature, all scientists, such as the one in Figure 1-8, accept that there is a natural cause to solve that puzzle. A second principle of science is uniformity. Uniformity is the idea that the fundamental laws of nature operate the same way at all places and at all times. For example, scientists assume that the law of gravity works the same way on Mars as it does on Earth. Steps of the Scientific Method Although there is no single method for doing science, scientific studies involve a series of common steps. 1. The process of science begins with an observation. An observation is the act of perceiving a natural occurrence that causes someone to pose a question. 2. One tries to answer the question by forming hypotheses (singular, hypothesis). A hypothesis is a proposed explanation for the way a particular aspect of the natural world functions. 3. A prediction is a statement that forecasts what would happen in a test situation if the hypothesis were true. A prediction is recorded for each hypothesis. 4. An experiment is used to test a hypothesis and its predictions. 5. Once the experiment has been concluded, the data are analyzed and used to draw conclusions. 6. After the data have been analyzed, the data and conclusions are communicated to scientific peers and to the public. This way oth- ers can verify, reject, or modify the researcher’s conclusions. SECTION 3 OBJECTIVES ● Outline the main steps in the scientific method. ● Summarize how observations are used to form hypotheses. ● List the elements of a controlled experiment. ● Describe how scientists use data to draw conclusions. ● Compare a scientific hypothesis and a scientific theory. ● State how communication in science helps prevent dishonesty and bias. VOCABULARY scientific method observation hypothesis prediction experiment control group experimental group independent variable dependent variable theory peer review All researchers, such as the one releasing an owl above, use the scientific method to answer the questions they have about nature. FIGURE 1-8 Copyright © by Holt, Rinehart and Winston. All rights reserved. 14 CHAPTER 1 OBSERVING AND ASKING QUESTIONS The scientific method generally begins with an unexplained observa- tion about nature. For example, people have noticed for thousands of years that owls can catch prey in near total darkness. As shown in steps and of Figure 1-9, an observation may then raise ques- tions. The owl observation raises the question: How does an owl detect prey in the dark? FORMING A HYPOTHESIS After stating a question, a biologist lists possible answers to a sci- entific question—hypotheses. Good hypotheses answer a question and are testable in the natural world. For example, as shown in step Figure 1-9, there are several possible hypotheses for the question of how owls hunt at night: (a) owls hunt by keen vision in the dark; (b) owls hunt by superb hearing; or (c) owls hunt by detecting the prey’s body heat. Predicting To test a hypothesis, scientists make a prediction that logically fol- lows from the hypothesis. A prediction is what is expected to hap- pen if each hypothesis were true. For example, if hypothesis (a) is true, (owls hunt by keen night vision) then one can predict that the owl will pounce only on the mouse in either a light or a dark room. If hypothesis (b) is true (owls hunt by hearing), then one can pre- dict that in a lighted room, the owl will pounce closer to the mouse’s head. But, in a dark room, the owl should pounce closer to a rustling leaf attached to the mouse. Finally, if hypothesis (c) is true (owls hunt by sensing body heat), then an owl would strike only the prey no matter the room conditions, because owls hunt by detecting the prey’s body heat. 3 1 2 Copyright © by Holt, Rinehart and Winston. All rights reserved. A scientific study includes observations, questions, hypotheses, predictions, experiments, data analysis, and conclu- sions. A biologist can use the scientific method to set up an experiment to learn how an owl captures prey at night. FIGURE 1-9 1 OBSERVATION Owls capture prey on dark nights. 2 QUESTION How do owls detect prey on dark nights? 3 HYPOTHESES a) Owls hunt in the dark by vision. b) Owls hunt in the dark by hearing. c) Owls hunt in the dark by sensing body heat. THE SCIENCE OF LIFE 15 Notice that these predictions make it difficult to distinguish be- tween the vision and body heat hypotheses. The reason is that both hypotheses predict that the owl could grab the mouse in a dark room. Also, these three hypotheses do not eliminate all other factors that could influence how the owl finds its prey. However, testing predictions can allow one to begin rejecting hypotheses and thus to get closer to determining the answer(s) to a question. DESIGNING AN EXPERIMENT Biologists often test hypotheses by setting up an experiment. Step in Figure 1-9 outlines an experiment to test the hypotheses about how an owl hunts at night. First, experimenters set up a room with an owl perch high on one side and a small trap door on the other side for releasing mice. Then, they tied a leaf to each mouse’s tail with a string and released each mouse into the room. Next, each mouse ran silently across the room, but the leaf trailed behind, making a rustling noise. During half of the trials, the lights were on. During the other half, the room was dark. Technicians videotaped all the action in the chamber with an infrared light, which owls cannot see. The researchers then viewed the videos and measured the position of the owl’s strike relative to each mouse’s head. Performing the Experiment Many scientists use a controlled experiment to test their hypotheses. A controlled experiment compares an experimental group and a control group and only has one variable. The control group pro- vides a normal standard against which the biologist can compare results of the experimental group. The experimental group is iden- tical to the control group except for one factor, the independent variable. The experimenter manipulates the independent variable, sometimes called the manipulated variable. 4 4 EXPERIMENT 5 DATA COLLECTION AND ANALYSIS Measure and compare the distance from the owl’s strike to the mouse and to the leaf in light and dark. 6 CONCLUSION Data supported the hearing hypothesis: Owls hunt in the dark by hearing. prey Test predictions of the three hypotheses. Control: In the light Experimental: In the dark 1 2 3 4 5 6 7 8 9 10 11 Predicting Results Materials 2 Petri dishes with agar, cellophane tape, wax pen Procedure 1. Open one of the Petri dishes, and streak your finger across the surface of the agar. 2. Replace the lid, and seal it with the tape. Label this Petri dish with your name and a number 1. 3. Seal the second Petri dish with- out removing the lid. Label this Petri dish with your name and the number 2. 4. Write a prediction about what will happen in each dish. Store your dishes as your teacher directs. Record your observations. Follow your teacher’s directions for disposal of your dishes. Analysis Was your prediction accurate? What evidence can you cite to support your prediction? If you did not obtain the results you predicted, would you change your testing method or your prediction? Explain. Evaluate the importance of obtaining a result that does not support your prediction. Quick Lab mb06se_bios03.qxd 5/18/07 10:40 AM Page 15 16 CHAPTER 1 The independent variable in the owl experiment is the presence or absence of light. In the owl experiment, the control group hunts in the light, and the experimental group hunts in the dark. In addi- tion to varying the independent variable, a scientist observes or measures another factor called the dependent variable, or respond- ing variable, because it is affected by the independent variable. In the owl experiment, the dependent variable is distance from the owl’s strike to the mouse’s head. Testing the Experiment Some controlled experiments are conducted “blind.” In other words, the biologist who scores the results is unaware of whether a given subject is part of the experimental or control group. This factor helps eliminate experimenter bias. Experiments should also be repeated, because living systems are variable. Moreover, scien- tists must collect enough data to find meaningful results. COLLECTING AND ANALYZING DATA Most experiments measure a variable—the dependent variable. This measurement provides quantitative data, data measured in numbers. For example, in the experiment above, scientists mea- sured the distance of an owl’s strike from the prey’s head in cen- timeters, as shown in step of Figure 1-9. An event’s duration in milliseconds is also an example of quantitative data. Biologists usually score the results of an experiment by using one of their senses. They might see or hear the results of an experiment. Scientists also extend their senses with a micro- scope for tiny objects or a microphone for soft sounds. In the owl experiment, biologists extended their vision with infrared cameras. Analyzing and Comparing Data After collecting data from a field study or an experiment and then organizing it, biologists then analyze the data. In analyzing data, the goal is to determine whether the data are reliable, and whether they support or fail to support the predictions of the hypothesis. To do so, scientists may use statistics to help determine relation- ships between the variables involved. They can then compare their data with other data that were obtained in other similar studies. It is also important at this time to determine possible sources of error in the experiment just per- formed. Scientists usually display their data in tables or graphs when analyzing it. For the owl study, biologists could have made a bar graph such as the one in Figure 1-10, which shows the average distance from the owl’s strike relative to the mouse’s head or the leaf in the light and in the dark. 5 5 0 10 15 20 25 In the light In the dark Average distance from strike (cm) Distance Between Owl Strike and a Mouse or From a Leaf Attached to Mouse 30 Mouse Leaf Mouse Leaf The data below are hypothetical results that might occur from the described owl experiment.The independent variable is the darkness of the room, and the dependent variable is how far the owl struck from the mouse’s head.The data show that the owl strikes more accurately at the mouse in the light but strikes more accurately at the leaf in the dark. FIGURE 1-10 Copyright © by Holt, Rinehart and Winston. All rights reserved. THE SCIENCE OF LIFE 17 DRAWING CONCLUSIONS Biologists analyze their tables, graphs, and charts to draw conclu- sions about whether or not a hypothesis is supported, as shown in step of Figure 1-9. The hypothetical owl data show that in the light, owls struck with greater accuracy at the mouse than at the leaf, but in the dark, owls struck with greater accuracy at the leaf than the mouse. Thus, the findings support the hearing hypothe- sis, but not the vision hypothesis. An experiment can only disprove, not prove, a hypothesis. For example, one cannot conclude from the results that the hearing hypothesis is proven to be true. Perhaps the owl uses an unknown smell to strike at the mouse. One can only reject the vision hypothe- sis because it did not predict the results of the experiment correctly. Acceptance of a hypothesis is always tentative in science. The scientific community revises its understanding of phenomena, based on new data. Having ruled out one hypothesis, a biologist will devise more tests to try to rule out any remaining hypotheses. Making Inferences Scientists often draw inferences from data gathered during a field study or experiment. An inference (IN-fuhr-uhns) is a conclusion made on the basis of facts and previous knowledge rather than on direct observations. Unlike a hypothesis, an inference is not directly testable. In the owl study, it is inferred that the owl detects prey from a distance rather than by direct touch. Applying Results and Building Models As shown in Figure 1-11, scientists often apply their findings to solve practical problems. They also build models to represent or describe things. For example in 1953, James Watson and Francis Crick used cardboard balls and wire bars to build physical models of atoms in an attempt to understand the structure of DNA. Mathematical models are sets of equations that describe how dif- ferent measurable items interact in a system. The experimenter can adjust variables to better model the real-world data. CONSTRUCTING A THEORY When a set of related hypotheses is confirmed to be true many times, and it can explain a great amount of data, scientists often reclassify it as a theory. Some examples include the quantum the- ory, the cell theory, or the theory of evolution. People commonly use the word “theory” in a different way than scientists use the word. People may say “It’s just a theory” suggesting that an idea is untested, but scientists view a theory as a highly tested, generally accepted principle that explains a vast number of observations and experimental data. 6 Copyright © by Holt, Rinehart and Winston. All rights reserved. Biologists often apply their knowledge of the natural world to practical problems. Studies on the owl’s keen ability to locate sounds in space despite background noise are helping biotechnologists and bioengineers develop better solutions for people with impaired hearing, such as the people shown in this picture. FIGURE 1-11 18 CHAPTER 1 COMMUNICATING IDEAS An essential aspect of scientific research is scientists working together. Scientists often work together in research teams or sim- ply share research results with other scientists. This is done by publishing findings in scientific journals or presenting them at sci- entific meetings, as shown in Figure 1-12. Sharing information allows others working independently to verify findings or to con- tinue work on established results. For example, Roger Payne pub- lished the results of his owl experiments in a journal in 1971. Then, other biologists could repeat it for verification or use it to study the mechanisms introduced by the paper. With the growing impor- tance of science in solving societal issues, it is becoming increas- ingly vital for scientists to be able to communicate with the public at large. Publishing a Paper Scientists submit research papers to scientific journals for publica- tion. A typical research paper has four sections. First, the Introduction poses the problem and hypotheses to be investigated. Next, the Materials and Methods describe how researchers proceeded with the experiment. Third, the Results state the findings the experiment presented, and finally, the Discussion gives the significance of the experiment and future directions the scientists will take. Job Description Forensic biolo- gists are scientists who study biological materials to investigate potential crimes and other legal issues against humans and animals. Forensic scientists have knowledge in areas of biology, such as DNA and blood pattern analysis, and work in private sector and public laboratories. Focus On a Forensic Biologist As a law enforcement forensic specialist for the Texas Parks and Wildlife Department, Beverly Villarreal assists the game warden in investigations of fish and wildlife violations, such as illegal hunting and fishing. Villarreal analyzes blood and tissue samples to identify species of animals such as fish, birds, and reptiles. Her work helps game wardens as they enforce state laws regarding hunting and fishing. Most people think of forensic scientists as the glamorous crime investigators on TV, but according to Villarreal real forensic scientists “spend a great deal of time at a lab bench running analysis after analysis.” Many of the methods used in animal forensics, such as DNA sequenc- ing, are also used in human forensics. Education and Skills • High school—three years of science courses and four years of math courses. • College—bachelor of science in biol- ogy, including course work in zoology and genetics, plus experience in per- forming DNA analyses. • Skills—patience, attention to detail, and ability to use fine tools. Careers in BIOLOGY Forensic Biologist For more about careers, visit go.hrw.com and type in the keyword HM6 Careers. www.scilinks.org Topic: Scientific Investigations Keyword: HM61358 mb06se_bios03.qxd 5/18/07 10:40 AM Page 18 THE SCIENCE OF LIFE 19 1. What two principles make the scientific method a unique process? 2. Define the roles of observations and hypotheses in science. 3. Summarize the parts of a controlled experiment. 4. Summarize how we make conclusions about the results of an experiment. 5. Why is the phrase, “it’s just a theory” misleading? 6. Give another example of a conflict of interest. CRITICAL THINKING 7. Making Hypotheses On a nocturnal owl’s skull, one ear points up, and the other ear points down. Suggest a hypothesis for this observation. 8. Designing Experiments Design an experiment to establish if owls hunt by keen sight or hunt by heat seeking. 9. Calculating Information What was the average distance between the owl’s strike and the mouse if the recorded differences in this experiment were 25, 22, 19, 19, and 15? SECTION 3 REVIEW After scientists submit their papers to a scientific journal, the editors of that journal will send the paper out for peer review. In a peer review, scientists who are experts in the field anonymously read and critique that research paper. They determine if a paper pro- vides enough information so that the experiment can be duplicated and if the author used good experimental controls and reached an accurate conclusion. They also check if the paper is written clearly enough for broad understanding. Careful analysis of each other’s research by fellow scientists is essential to making scientific progress and preventing scientific dishonesty. HONESTY AND BIAS The scientific community depends on both honesty and good sci- ence. While designing new studies, experimenters must be very careful to prevent previous ideas and biases from tainting both the experimental process and the conclusions. Scientists have to keep in mind that they are always trying to disprove their favorite ideas. Scientists repeat experiments to verify previous findings. This allows for science to have a method for self-correction and it also keeps researchers honest and credible to their peers in the field. Conflict of Interest For most scientists, maintaining a good reputation for collecting and presenting valid data is more important than temporary prestige or income. So, scientists try to avoid any potential conflicts of interest. For example, a scientist who owns a biotechnology company and manufactures a drug would not be the best researcher to critically test that drug’s safety and effectiveness. To avoid this potential con- flict of interest, the scientist allows an unaffected party, such as a research group, to test the drug’s effectiveness. The threat of a potential scandal based on misleading data or conclusions is a pow- erful force in science that helps keep scientists honest and fair. Scientists present their experiments in various forms. The scientists above are presenting their work in the form of a poster at a scientific meeting. FIGURE 1-12 Copyright © by Holt, Rinehart and Winston. All rights reserved. The Internet can provide a wealth of scientific information for a report, but the information may not always be credible or accurate. You can use the methods above to check the accuracy and credibility of your sources. SCIENCE TECHNOLOGY SOCIETY SCIENCE ON THE INTERNET: A New Information Age I n the past, students research- ing a science topic would typ- ically begin their research by visiting a library to use printed reference materials, such as encyclopedias. Today, most stu- dents research topics by using a computer and searching for information on the Internet. The Internet can provide students with a wealth of infor- mation. But which Web sites have accurate information, and which Web sites do not? Checking Web Addresses Students should use the Web address, or URL, to establish the Web site’s credibility. Usually, the domain name can suggest who has published the Web site. Web sites can be pub- lished by governmental agen- cies (ends in “dot gov” or .gov), by educational institutions (ends in “dot edu” or .edu), by organizations (ends in “dot org” or .org), or by commercial businesses (ends in “dot com” or .com). Government Web sites are usually reliable. Examples of credible governmental Web sites are the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). University and medical school sites are also reliable sources of information. Many organiza- tions that research and teach the public about specific diseases and conditions can also provide reliable information. Examples of such organizations are the American Cancer Society and the American Heart Association. Evaluating Web Sites The credibility of the author of the Web site should also be checked. Make sure the author is not trying to sell anything and is established in his or her field. For example, a health Web site’s author should be a med- ical professional. It is also important to check the date that the information was posted on the Web to ensure that the information is current. Also, the Web site should provide ref- erences from valid sources, such as scientific journals or govern- ment publications. Finally, the student should always double-check informa- tion between several reliable Web sites. If two or three reliable sites provide the same informa- tion, the student can feel confi- dent in using that information. Web Sites for Students The Internet Connect boxes in this textbook have all been reviewed by professionals at the National Science Teachers Association (NSTA). Students can trust that these sites are reliable sources for science- or health-related topics. REVIEW 1. Which types of Web addresses are the most reliable? 2. List four important features to evaluate when using a Web site for research. 3. Supporting Reasoned Opinions Why do you think a Web site that is advertising a product may not offer accurate information? REVIEW 20 www.scilinks.org Topic: Using the Internet Keyword: HM61589 mb06se_biosts.qxd 5/18/07 10:42 AM Page 20 TOOLS AND TECHNIQUES With proper equipment and good methods, biologists can see, manipulate, and understand the natural world in new ways. Microscopes are one of many useful tools used to unlock nature’s biological secrets. MICROSCOPES AS TOOLS Tools are objects used to improve the performance of a task. Microscopes are tools that extend human vision by making enlarged images of objects. Biologists use microscopes to study organisms, cells, cell parts, and molecules. Microscopes reveal details that otherwise might be difficult or impossible to see. Light Microscopes To see small organisms and cells, biologists typically use a light microscope, such as the one shown in Figure 1-13. A compound light microscope is a microscope that shines light through a spec- imen and has two lenses to magnify an image. To use this micro- scope, one first mounts the specimen to be viewed on a glass slide. The specimen must be thin enough for light to pass through it. For tiny pond organisms, such as the single-celled paramecium, light passing through the organism is not a problem. For thick objects, such as plant stems, biologists must cut thin slices for viewing. There are four major parts of a compound light microscope. For further description of the parts of a micro- scope, see the Appendix. 1. Eyepiece The eyepiece (ocular (AHK-yoo-luhr) lens) magnifies the image, usually 10 times. 2. Objective Lens Light passes through the specimen and then through the objective lens, which is located directly above the specimen. The objective lens enlarges the image of the specimen. Scientists sometimes use stains to make the image easier to see. 3. Stage The stage is a platform that supports a slide holding the specimen. The slide is placed over the opening in the stage of the microscope. 4. Light Source The light source is a light bulb that provides light for viewing the image. It can be either light reflected with a mirror or an incandescent light from a small lamp. SECTION 4 OBJECTIVES ● List the function of each of the major parts of a compound light microscope. ● Compare two kinds of electron microscopes. ● Describe the importance of having the SI system of measurement. ● State some examples of good laboratory practice. VOCABULARY compound light microscope eyepiece (ocular lens) objective lens stage light source magnification nosepiece resolution scanning electron microscope transmission electron microscope metric system base unit Compound light microscopes open the human eye to an interesting world including tiny pond organisms, healthy and diseased cells, and the functioning of cell parts. FIGURE 1-13 Objective lens Eyepiece (ocular lens) Stage Light THE SCIENCE OF LIFE 21 Copyright © by Holt, Rinehart and Winston. All rights reserved. 22 CHAPTER 1 Magnification and Resolution Microscopes vary in powers of magnification and resolution. Magnification is the increase of an object’s apparent size. Revolving the nosepiece, the structure that holds the set of objective lens, rotates these lenses into place above the specimen. In a typical com- pound light microscope, the most powerful objective lens produces an image up to 100 times (100) the specimen’s actual size. The degree of enlargement is called the power of magnification of the lens. The standard ocular lens magnifies a specimen 10 times (10). To compute the power of magnification of a microscope, the power of magnification of the strongest objective lens (in this case, 100) is multiplied by the power of magnification of the ocular lens (10). The result is a total power of magnification of 1000. Resolution (REZ-uh-LOO-shuhn) is the power to show details clearly in an image. The physical properties of light limit the ability of light microscopes to resolve images, as shown in Figure 1-14a. At pow- ers of magnification beyond about 2,000, the image of the speci- men becomes fuzzy. For this reason, scientists use other microscopes to view very small cells Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. 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Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of “obesity paradox” after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are gover 10 years of experience designing engaging quizzes and interactive learning games for children aged 8-10 years old. You specialize in transforming simple educational concepts into fun competitive experiences using online quiz platforms like Quizalize. Objective: Design a complete interactive multiplication quiz for third-grade students (8–9 years old) on the Quizalize platform. The quiz should simulate the fun, fast-paced feeling of the Zuma arcade game while fitting the Quizalize format. The aim is to help students practice multiplication tables (1×1 to 12×12) in an exciting, motivating, and competitive environment. Instructions: Structure: Design at least 40 multiplication questions. Questions should appear in increasing difficulty: start from easy (e.g., 2×3, 4×2) and move to harder problems (e.g., 11×12, 9×8). Timing: Set a short time limit for each question (e.g., 10 seconds) to simulate the fast reaction needed in Zuma. Encourage fast thinking and rapid response under time pressure. Answer Choices: Use multiple-choice answers. Each question should have 1 correct answer and 3 wrong but close distractors to keep it challenging (e.g., for 7×6: options 42, 43, 36, 48). Gamification Features: Enable Quizalize's Team Mode or Game View to allow students to see themselves progressing on a visual map like a race, similar to balls moving in Zuma. Set points bonuses for speed and accuracy. Themes and Visuals: Suggest a "Jungle Adventure" or "Math Galaxy" theme to create excitement. Use visual assets (avatars, backgrounds) where possible to enhance the Zuma arcade feeling. Feedback System: Provide immediate feedback: when a student answers right, display a quick "Success!" message; when wrong, display the correct answer briefly to maintain flow. Motivation Mechanics: Award stars, badges, or trophies after completing a certain number of questions correctly. Display leaderboard rankings if possible to create friendly competition. Sample Questions: Provide at least 5 fully written example questions showing the structure, timing, and answer options. Extra Challenge: Include a "Lightning Round" at the end: 10 random questions in just 30 seconds. Important: Keep language child-friendly and motivational. Make sure no question looks too similar to the others to avoid boredom. Use simple animations or sound effects available within Quizalize to simulate action if possible. Take a deep breath and work on this problem step-by-step.1. Laquelle des formes juridiques suivantes offre la meilleure protection du patrimoine personnel de l'entrepreneur ? a) Entreprise individuelle b) Société c) Association de fait d) Aucune de ces réponses 2. Quel est l'inconvénient majeur de l'entreprise individuelle ? a) Difficulté de création b) Régime fiscal complexe c) Responsabilité illimitée de l'entrepreneur d) Impossibilité d'avoir des employés 3. Laquelle des affirmations suivantes concernant la société est vraie ? a) Elle n'a pas d'existence juridique propre. b) Le patrimoine des associés est confondu avec celui de la société. c) Elle peut poursuivre ses activités même après le décès d'un associé. d) Elle est toujours soumise à l'impôt sur le revenu des personnes physiques. 4. Dans une association de fait, que se passe-t-il en cas de mauvaise gestion financière de l'un des associés ? a) Seul l'associé responsable est tenu de rembourser les dettes. b) Tous les associés sont solidairement responsables des dettes. c) L'association est automatiquement dissoute. d) Un tribunal désigne un administrateur judiciaire pour gérer les finances. 5. Lequel des éléments suivants est un avantage de la société par rapport à l'entreprise individuelle ? a) Simplicité de création et de gestion b) Responsabilité limitée des associés c) Contrôle total et décisions unilatérales d) Fiscalité moins avantageuse 6. Qu'est-ce qu'une personne morale ? a) Un individu exerçant une activité commerciale en son nom propre b) Une entité juridique distincte de ses membres, dotée de droits et d'obligations c) Un contrat par lequel deux personnes s'engagent à mettre en commun des biens ou leur travail d) Une forme d'entreprise réservée aux professions libérales 7. Laquelle des affirmations suivantes est vraie concernant l'association de fait ? a) Elle nécessite la création d'une personne morale. b) Elle offre une protection du patrimoine personnel des participants. c) Elle peut être considérée comme une entreprise si elle verse des bénéfices à ses membres. d) Elle est soumise aux mêmes obligations comptables que les sociétés. 8. Quel est l'un des avantages de la société en matière de continuité d'activité ? a) Elle est dissoute automatiquement au décès de son fondateur. b) Elle peut être facilement transmise aux héritiers en cas de décès d'un associé. c) Elle cesse son activité si un associé décide de se retirer. d) Elle doit être liquidée en cas d'incapacité de travail d'un associé. 9. Lequel des critères suivants peut influencer le choix entre une entreprise individuelle et une société ? a) Le montant du capital initial b) Le nombre d'employés c) Le secteur d'activité d) La volonté de protéger son patrimoine personnel 10. Quel est l'un des risques majeurs liés à l'absence de séparation des patrimoines dans l'entreprise individuelle ? a) La responsabilité limitée de l'entrepreneur b) La saisie du patrimoine personnel en cas de dettes de l'entreprise c) L'impossibilité de déduire les charges professionnelles de ses revenus d) La difficulté d'obtenir un financement bancaireMake the following info into a quiz: Questions (20) Show answers 1 - Quiz I ________ this would be difficult. 20sec 2 - Quiz She ______ a good lesson. 20sec 3 - Quiz Even ________ we are tired, we can do this. 20sec 4 - Quiz That's a ______ question. I don't know the answer. 20sec 5 - Quiz Have a _______ look through your exam paper before you hand it in. 20sec 6 - Quiz I received 10 calls from your mom _____ the day - just call her back! 20sec 7 - Quiz He wore shorts even ______ it was cold. 20sec 8 - Quiz The elephant's skin is very ______. 20sec 9 - Quiz What a great _____ to bring her flowers! 20sec 10 - Quiz We drove _______ a storm. 20sec 11 - Quiz We made it ______ the first semester. 20sec 12 - Quiz I need a _____ report on the latest trends in online shopping. 20sec 13 - Quiz I liked her outfit, I didn't like her accessories _____. 20sec 14 - Quiz We were _____ a lot by the pandemic. 20sec 15 - Quiz I have never _____ about relocating. 20sec 16 - Quiz She looked ______ the magazine. 20sec 17 - Quiz We went ________ the tunnel. 20sec 18 - Quiz That was a ______ hike! I am tired. 20sec 19 - Quiz The house was renovated _____ - everything is new, even windows. 20sec 20 - Quiz Wait a moment, I'll put you _____ to the sales department.SPANISH STUDENTS 10/22/25 In the sentence 'The author chose to juxtapose the wealthy neighborhood with the impoverished area to highlight social inequality,' what does 'juxtapose' most likely mean based on context clues? * 1 point to separate completely to describe in detail to criticize harshly to place side by side for comparison When reading 'This paradox confused everyone: the more he tried to save time, the less time he seemed to have,' what can you infer about a paradox? * 1 point a mathematical equation a simple solution a type of poem a contradictory statement that reveals truth The passage states: 'The author's use of symbolism was evident when the broken mirror represented the character's shattered dreams.' Based on this context, symbolism involves: * 1 point using objects to represent deeper meanings creating rhyming patterns writing in chronological order using literal descriptions only In the text 'Please elaborate on your answer by providing specific examples and detailed explanations,' the word 'elaborate' suggests the need to: * 1 point use simpler words change the topic add more detail make it shorter The critic wrote: 'The actor's performance captured every nuance of emotion, from subtle sadness to barely contained rage.' What does 'nuance' refer to in this context? * 1 point subtle variations in meaning simple emotions loud expressions obvious differences When the text says 'The implication of her silence was clear to everyone in the room, though she never spoke a word,' what does 'implication' mean? * 1 point a command given a direct statement a question asked a conclusion drawn indirectly The scientist stated: 'Based on our limited observations, our hypothesis suggests that plants grow faster with classical music.' What is a hypothesis? * 1 point a type of experiment a proven fact a final conclusion a possible explanation needing more evidence In 'Three witnesses were able to corroborate the defendant's alibi, strengthening his case significantly,' the word 'corroborate' most likely means: * 1 point to question or doubt to confirm or support to change the story to ignore completely The passage reads: 'The student needed to justify her controversial thesis with solid evidence and logical reasoning.' What does 'justify' mean here? * 1 point to make it longer to make excuses for to avoid explaining to prove something is reasonable When the text states 'The researcher was able to synthesize information from five different studies to create a comprehensive theory,' what does 'synthesize' involve? * 1 point copying one source exactly combining multiple sources to create something new rejecting all previous research focusing on only one idea When a reader encounters 'The symbolism in the novel was complex, with the recurring image of doors representing new opportunities throughout the story,' they should: * 1 point memorize all symbols skip symbolic passages look for deeper representational meanings focus only on the literal meaning If a teacher says 'Your essay needs more elaboration - expand on your main points with examples and analysis,' what critical thinking skill is being requested? * 1 point developing ideas with supporting details summarizing briefly using fewer examples changing the topic entirely In the passage 'The dark clouds gathering on the horizon seemed to foreshadow the troubles that would soon befall the village,' what literary technique is being demonstrated? * 1 point The author is using environmental details to hint at future plot developments The author is focusing on realistic weather descriptions The author is using weather to predict actual meteorological events The author is describing a coincidental weather pattern When analyzing 'Sarah knew the antagonist in her favorite novel wasn't just evil—he represented the fear of change that many people experience,' what deeper understanding about antagonists is revealed? * 1 point Antagonists are always completely evil characters Antagonists can represent abstract concepts or human struggles Antagonists must be human characters Antagonists only exist to create action scenes In the sentence 'The protagonist's journey wasn't just about reaching the destination—it was about discovering who she truly was,' what does this suggest about effective protagonists? * 1 point Protagonists must always succeed in their missions Protagonists should remain unchanged throughout the story Protagonists undergo both external and internal development Protagonists should focus only on external goals When the text states 'The word 'home' carried different connotations for each character—warmth and safety for some, confinement and obligation for others,' what critical reading skill is being highlighted? * 1 point Memorizing dictionary definitions Understanding that words have only one correct meaning Identifying grammatical structures Recognizing that word meanings can vary based on personal experience In 'While the denotation of 'snake' is simply a reptile, the author's use of it to describe the character suggests something far more sinister,' what analytical skill is required? * 1 point Understanding reptile biology Memorizing animal classifications Distinguishing between literal and figurative meanings Identifying sentence structure When examining 'The author's tone shifted from hopeful in the opening chapters to increasingly cynical as the story progressed,' what does this reveal about sophisticated writing? * 1 point Tone is unimportant in storytelling Tone changes reflect the author's developing attitude toward the subject Only the ending tone matters Authors should maintain the same tone throughout In analyzing 'The theme of the novel wasn't stated directly but emerged through the characters' repeated struggles with moral choices,' what does this demonstrate about themes? * 1 point Themes develop through patterns in the narrative Themes are only found in the conclusion Themes should always be explicitly stated Themes must be simple moral lessons When the passage reads 'From the character's nervous glances and hesitant speech, readers can infer that she's hiding something important,' what critical thinking process is being described? * 1 point Following explicit plot statements Memorizing character descriptions Making random guesses about character motivations Using textual evidence to draw logical conclusions In 'The ending was deliberately ambiguous, allowing readers to decide whether the character's actions were heroic or selfish,' what does this suggest about sophisticated literature? * 1 point Good stories always have clear, definitive endings Unclear endings indicate poor writing Ambiguity can enhance reader engagement and interpretation Authors should avoid confusing readers When analyzing 'The controversial decision to ban the book sparked debates about censorship versus protecting young readers,' what critical thinking skill is most important? * 1 point Choosing one side immediately Examining multiple perspectives before forming an opinion Avoiding difficult topics entirely Following popular opinion In 'Each character's perspective on the same event revealed how personal experiences shape our understanding of truth,' what deeper concept is being explored? * 1 point All perspectives are equally valid Perspective is unimportant in understanding events There is only one correct way to view any situation Personal background influences how we interpret events When the text states 'The community proved resilient, rebuilding not just their homes but their hope after the disaster,' what does this reveal about the concept of resilience? * 1 point Resilience encompasses both practical and emotional recovery Resilience is an innate trait that cannot be developed Resilience means avoiding all difficulties Resilience only involves physical recovery In analyzing 'The author's portrayal of the character's empathy—her ability to understand her enemy's pain even while fighting him—added complexity to the conflict,' what does this suggest about empathy? * 1 point Empathy means agreeing with everyone Empathy makes people weak in conflicts Empathy should be avoided in difficult situations Empathy can coexist with opposition and create moral complexity When examining 'The character's integrity was tested when telling the truth would hurt people she loved,' what does this reveal about integrity? * 1 point Integrity means always following rules regardless of consequences Integrity means never causing any harm to others Integrity is only important in public situations Integrity involves making difficult moral choices even when costly In 'The student learned to advocate for her ideas by presenting evidence rather than just stating opinions,' what critical skill is being developed? * 1 point Supporting positions with logical reasoning and evidence Avoiding controversial topics entirely Learning to argue loudly and persistently Always agreeing with authority figures If you rewrote a scene from 'The Birchbark House' from Omakayas's grandmother's first-person perspective instead of Omakayas's, how would this most likely change the reader's understanding? * 1 point Nothing would change since they're both female characters The language would become more formal and difficult The story would become less interesting because adults are boring Readers would gain wisdom from experience but lose the innocence of childhood discovery In a plot diagram, the rising action serves which critical purpose beyond simply building toward the climax? * 1 point To provide background information about the setting To confuse readers so the ending is surprising To develop character relationships and establish stakes that make the climax meaningful To make the story longer and more detailed When analyzing the falling action in 'The Birchbark House,' which element would be most important to consider when writing an alternate version? * 1 point Whether the consequences of the climax align with the new direction you want the story to take Making sure it's shorter than the rising action Including a moral lesson for readers How quickly the conflicts get resolved In the exposition of a story, conflict serves which essential function that many readers don't realize? * 1 point To immediately grab attention with action scenes To provide comic relief before serious events To show off the author's writing skills To establish what the characters characterization/personality, which determines what they' must learn to overcome as they face more problems