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Integrative Physiology (Fall 2016) Lecture / recitation course: 11:067:300:01;4cr; index:09914; T1W1 lectures (9:15-10:35AM), F3 recitation (12:35-1:55PM); This course meets in Bartlett 123. Dr. JP Advis; (848) 932-9240; e-mail: advis@aesop.rutgers.edu Facebook site: Dr. Advis class help Office Hours: in Bartlett r102 (MT 11AM - 2PM and on F 11AM - 12PM), or by appointment. Course website: http://rci.rutgers.edu/~advis/ MEETINGS & DATES TOPICS TEXTBOOK CHAPTERS 01 Tue, Sept 06 Lecture: The Basis of Animal Function and Homeostasis (prerequisites) 1-5 02 Wed 07 Lecture: Membranes, Homeostasis & Signal Transduction (prerequisite) 1-6 03 Fri 09 Recitation: Homeostasis, Signal Transduction and Recitations #01 - #02 1-6 04 Tue 13 Lecture: Endocrine Communication (principles of hormonal systems) 7 05 Wed 14 Lecture: Neural Communication (mechanisms and sensory systems) 8-11 06 Fri 16 Recitation: Neuroendocrine communication and Recitation #03 7-11 07 Tue 20 Lecture: Muscle contraction and the Control of body movement 12-13 08 Wed 21 REVIEW #1 - Material from lectures #1 through lecture #7 1-13 09 Fri 23 EXAM #1-20% of final grade (lectures #1 through #8) 1-13 10 Tue 27 Lecture: Cardiovascular (CV) Design and the Heart as a Pump 14-16 11 Wed 28 Lecture: Blood Pressure and CV function (in health and disease) 17 12 Fri 30 Recitation: Heart, Blood Pressure and Recitation # 04 14-17 13 Tue, Oct 04 Lecture: CV integration and Basics of Respiratory System Mechanics 17-18 14 Wed 05 Lecture: Gas Transport and Control of Respiration / The renal system 18-19 15 Fri 07 Recitation: CV Integration, the Respiratory System and Recitation # 05 14-18 16 Tue 11 Lecture: The Kidney, Clearance and the Countercurrent Mechanism 19 17 Wed 12 Lecture: Clearance and the Regulation of Water and Inorganic Ions 19-20 18 Fri 14 Recitation: The basic functions of the Renal System and Recitation #06 19-20 19 Tue 18 Lecture: Gastrointestinal (GI) motility, secretion, digestion and absorption 21 20 Wed 19 REVIEW #2 - Material from lecture #10 through lecture #18 1-20Fri 21 Fri 21 EXAM #2-20% of final grade (lectures #1 through #18 + #20) 1-20 22 Tue 25 Lecture: Regulation of Organic Metabolism, Growth and Energy Balance 21-23 23 Wed 26 Lecture: Neuroendocrine Control of Food Intake and Energy Balance 23-25 24 Fri 28 Recitation and Lab #7 on Metabolism, Food intake and Energy Balance 21-25 25 Tue, Nov 01 Lecture: From Sex Differentiation to Adult Reproduction in males / females 26 26 Wed 02 Lecture: Neuroendocrine Control of Reproduction & Reproduction Cycles 26 27 Fri 04 Recitation and Lab #8 on basic physiology of the Reproductive System 26 28 Tue 08 Lecture: Role of Biological Clocks in Animal Health and Production 1-26 29 Wed 09 REVIEW #3- Material from lecture #19 + lectures #22 through #27 1-26 30 Fri 11 EXAM #3-20% final grade (lectures #1 through #27 + #29) 1-26 1

MEETINGS & DATES TOPICS TEXTBOOK CHAPTERS 31 Tue 15 Lecture: Stress, Immunity and the Physiology of Health and Production 21-23 32 Wed 16 Lecture: Physiology of Health and Production: Growth and Muscles 23-25 33 Fri 18 Recitation and Lab #9 on Stress and Physiology of Health and Production 21-25 34 Tue 22 Lecture: Physiology of Health and Production: Exercise and Racing 26 (Friday meting due to Thanksgiving recess, lecture instead of recitation) 35 Fri 25 NO CLASSES THANKSGIVING RECESS (from Thu Nov 24 to Sun Nov 27) 36 Tue 29 Lecture: Physiology of Health and Production: Ovulation and Lactation 26 37 Wed 30 Recitation: Stress and Physiology of Health & Production 1-26 38 Fri, Dec 02 Discussion of lectures #01-09 / Recitations #01-03, and / test #1 1-26 39 Tue 06 Discussion of lectures #10-30 / Recitations #04-06, and / test #2 1-26 40 Wed 07 Discussion of lecture #31-36 / Recitations #07-10, and / test #3 1-26 41 Fri 09 REVIEW #4 - Material from lecture #28 + lectures #31 through #37 1-26 Deadline for submitting edited final answers of recitation questions 42 Tue 13 EXAM #4-20% final grade (meetings #01 through #41) 1-26 EXAM #5 20% of final grade (mean final answers recitation questions) Textbook: Human Physiology, 7ed, by Dee Ungleb Silverthorn, Pearson, Benjamin Cummins Publishers (2016). The 6 th ed. Of this book (2013) is also acceptable for this course. All students are required to have access to this text. This book is available at the Rutgers Fennen Mall College Bookstore. Exams and grades: There are no make-up exams. Student s problems with exam dates must be discussed with the instructor BEFORE the exam. If a student fails to do so, and does not show up to take the exam at the appointed time a grade of F might be assigned for the missing test. Students with a medical excuse will receive an essay test to replace their missing test. The letter and % grade equivalence, for a final 75% class average corrected grade, are: A=91-100%; B+=86-90%; B=81-85%;C +=76-80%; C=71-75%; D=61-70%; F=0-60%. The individual (weekly) recitation questions are as follows: Question #01: Introduction to this lecture / recitation course (pre-requisite material) Please remember that your answers for questions #1 and #6 do not follow the structural answer defined above but they have their own formats. The question for this week is as follows: An active learning process is the best approach to study, physiology. This first recitation uses the first two lectures to outline and practice an active learning process technique. In your report for recitation #01 provide a list of 5 questions that in your opinion, summarize the prerequisite lecture material (first two lectures), as well as that provided in the assigned chapters of the course textbook (first five chapters). Answer each of these five questions using no more than 10 sentences per question. Then start editing your answer for each question, if it is possible, into a single sentence. Keep in mind that it is quite difficult to summarize information into a single sentence, since it requires that you comprehend the material you are studying. Thus, accept that if you are not able to write an answer initially using less than 10 sentences and then editing this answer into a single sentence, you have not yet fully understand the topic and keep trying, or ask help from your instructor. It is important you attempt to master this technique (or a similar one) ASAP. Please remember that the best answers for each of your 5 questions for this report are at the most 2 sentences long, Question #02: Membrane and Homeostasis / related events The question for this week is as follows: Select a homeostatic event and/or physiological system in which you can show the importance of structure/ function relationship, organization levels, and feedback control. Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question you select both the structure and the function on which your answer will be based. Hint: think on the circle. Question #03: Endocrine and Neural Physiological Communication The question for this week is as follows: Select a neuroendocrine event in which you can show the importance of structure/function relationship, organization levels, and feedback control. Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question you select both the structure and the function on which your answer will be based. Important hint for your answer: what does a neuroendocrine event means??. Hint: think on the circle. Question #04: Heart and Blood Pressure - related functions The question for this week is as follows: Select four charac teristics of cardio cytes not present in skeletal muscle cells, in which you can show the importance of structure / function relationship, levels of organization, and feedback control. Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question both the structure and the function of the four characteristics on which your answer will be based, were presented in the heart lecture. Please remember that your answer should be structured as follows: Characteristic #1 (answers a,b,c,d),; characteristic #2 (answers a,b,c,d); characteristic #3 (answers a,b,c,d); and characteristic #4 (answers a,b,c,d). Hint: think on the circle for each one of these four characteristics. Question #05: CV Integration and the Respiratory System The question for this week is as follows: Select a position on the question how good an athlete is the horse. Do you think the respiratory limitations of this specie (e.g. pulmonary hypertension, exercise induced pulmonary hemorrhage or EIPH) are expression of physiological compensation for a fit athlete, or are they manifestation of a system being run down to the ground in a very stressed athlete? Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question both the structure and the function you are asked to select must be related to the EIPH syndrome. Hint: think on the circle. 2

Question #06: Basic functions of Renal, CV and Respiratory Systems The question for this week is as follows: Name the physiological responses and/or the relationships among buffers, respiratory, circulatory and renal systems involved in the homeostatic control following a metabolic acidosis. It is an absolute requirement that you answer this question based on the outline below. Precede each section of your an swer with its head ing, and make sure you answer ALL aspects outlined in each sec tion. Hint: for this question you really have to think on the circle. The following are the section headings and their requirements: a) the example: which are the physiological responses and/or relationships among buffers, respiratory, circulatory and renal systems on which your answer will be based. Which was the origin of the metabolic acidosis in your example. Be as specific as you can in delimiting the boundaries of your ex ample and the level(s) of organization your example will involve. b) the buffer involvement: how does the buffer system attempt to control the homeostatic variable (blood ph). Which, how and where is the signal to the buffer system recognized as input (receptors, afferent loop, and integration center), and how did the output of the integration center reached their tar gets (efferent loop, targets). The response this signal elic its is an acute (fast) or chronic (slow) compen satory mechanism. c) the respiratory involvement: how does the respiratory system attempt to control the homeostatic variable (blood ph). Which, how and where is the signal to the respiratory system recognized as input (receptors, afferent loop, and integration center), and how did the output of the integration center reached their targets (efferent loop, targets). The response this signal elicits is an acute (fast) or chronic (slow) compen satory mechanism. d) the circulatory involvement: how does the circulatory system attempt to control the homeostatic variable (blood ph). Which, how and where is the signal to the cardiovascular system recognized as input (receptors, afferent loop, and integration center), and how did the output of the integration center reached the targets (efferent loop, targets). The response this signal elicits is an acute (fast) or chronic (slow) compensatory mechanism. e) the renal involvement: how does the renal system attempt to control the homeostatic variable (blood ph). Which, how and where is the signal to the renal system recognized as input (receptors, afferent loop, and integration center), and how did the output of the integration center reached the targets (efferent loop, targets). The response this signal elicits is an acute (fast) or chronic (slow) compensatory mechanism. f) the integration pathways: how (the sensor, afferent, integrator, efferent, effector and feedback signals) and in which order (buffers, respiratory, cardiovascular, kidney) were the physiological systems involved, and re cruited to participate in the homeostatic response to a metabolic acidosis. The most important component of this answer is: Why do you think such a sequential order in this homeostatic response was achieved? Please notice that this subquestion does NOT ask you to tell me what is the order, but it asks why that order occurred. Question #07: Physiology of Metabolism, Food intake AND Energy Balance The question for this week is as follows: The neuroendocrine control of food intake AND thyroid function involves neurotransmitters / neuropeptides as inputs and outputs to an integrator located in the PVN (paraventricular nucleus of the hypothalamus, a main integrator center). From a conceptual view of cell connectivity and function, describe a possible circuitry consisting of neuronal and endocrine signals to and from the PVN integrator, operating during a typical Thanksgiving day, an hypermetabolic AND thermogenic condition. Your answer must follow the outline shown in the introduction (subquestions a, b, c, d, see above). Please notice that in this question the structure is defined as the PVN integrator in relation to food intake AND thyroid involvement. You should define a function associated to the PVN in relation to this hypermetabolic condition (hint: TRH cell bodies are located in the PVN). Hint: think on the circle. This question is an attempt to make you navigate through two circles. The answer will be achieved if you are able to transform these two circle into one. It s a good exercise and summary. Question #08: Basic physiology of the Reproductive System The question for this week is as follows: From a conceptual view of nerve cell connectivity and function describe a mechanism that would allow for a hypothalamic network of GnRH (or two GnRH sub-networks e.g. tonic vs. phasic) to synchronize both its tonic (or basal pulsatile gonadotropin release) and its phasic (or preovulatory surge like release of gonadotropin) operation, as it is observed during the estrous or menstrual reproductive cycles. Consider how the pulsatile output of such hypothalamic network might affect gonadotropin release during puberty, reproductive adulthood and menopause (aging). Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question the structure is defined as the GnRH neuronal network (or two GnRH sub-networks e.g. tonic vs. phasic) and you should define a specific function common to puberty, reproductive adulthood and menopause (aging). Hint: think on the circle. Question #09: Case Studies on Stress, Growth and Meat Production The question for this week is as follows: Select an homeostatic event and/or physiological system or question in which you can show the importance of structure/function relationship, levels of organization, and feedback control related to the use of Ractopamine, a beta-agonist, as a growth promoter in both animals and humans. Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question you should define both a structure and a function associated to the use of Ractopamine as a growth promoter (remember which was the main punch-line of the growth and production lecture). Hint: think on the circle. Question #10: Case Studies on Stress, Milk and Egg Production The question for this week is as follows: Select a homeostatic event and/or physiological system or question in which you can show the importance of structure / function relationship, levels of organization, and feedback control related to the toxicity induced by fescue in dairy cows. Your answer must follow the outline shown in the introduction (sub-questions a, b, c, d, see above). Please notice that in this question you should define both a structure and a function associated with the thermogenic effect of fescue toxicity in dairy cows (remember which was the main punch-line of the stress and production lectures). Hint: think on the circle. 3

The four sub-questions to be used in answering most recitation questions (except for questions #1 and #6, read these questions for their answer format) are: a) Name the structure and the function on which your overall answer will be based? Be as specific as you can in delimiting the boundaries of your example (the most important part of your answer, since the following b, c, & d sub-questions are based on your answer to this first sub-question, a). Please notice that only 1 item is required (in your answer it should be labeled as a ). This answer should look like: a.-my structure (S) is. and its function (F) is. In same cases a second sentence might be needed. b) Why do you think that your structure and your function are related? Support your contention based on 3 lines of evidence based on the chemistry, physics, anatomy, or physiology involved in your example. Please notice that 3 items are required (answers should be labeled as b1, b2, and b3 ). One of this answers might look like: b1.- If I do this experiment and measure this variable using this technique, this result will suggest that my S/F is correct. Please notice that MY question does not ask you to tell me what happens since this can be copy from any source, but it asked how do you know that your S/F relationship is true. c) Which are the levels of organization involved in your example (c1)? Cite events occurring at its main level of organization (c2) and indicate how they relate to the whole body level (c3). Please notice that 3 items are required (thus, answers should be labeled as c1, c2, and c3 ). These answers should look as follows: c1.- molecular or any level of organization involved in your a answer (S/F); c2.- the first event is; the next even is; the middle event is; the next event is; the last event is. Five events distributed equidistant from each other is a good summary for the story line of the your S/F named in your a answer. Finally, c3.- at a whole individual level my S/F described in a plays this role. d) Which are the main feedback mechanisms involved in your example (cite at least two) (d1)? Expand on one of them (d2) and name 2 absolute requirement for that feedback to work (d3). Please notice that 3 items are required (answers should be labeled as d1, d2, and d3 ). These answers should look as follows: d1.- an increase in this negative feedback ligand must decrease this variable under control. This is how you NAME a negative feedback. For d1 you need to name two negative feedbacks; d2.- the first event is; the next even is; the middle event is; the next event is; the last event is. Five events distributed equidistant from each other is a good summary for the most important negative feedback story line involved as a control of the your S/F named in your a answer, that you named in d1; d3.- this two components are absolutely necessary for the negative feedback described in d2 to be operational. Other undergraduate courses taught by JP Advis DVM, PhD: 011: 067: 300 Integrative Physiology (Fall term, 4 credits) 011: 067: 327 Animal Reproduction (Spring term, 3 credits) 011: 146: 356 System Physiology (Summer term, 3 credits) 011: 067: 410 Neuroendocrinology (Spring term, 3 credits) 011: 067: 450 Endocrinology (Fall and Summer terms, 4 credits) 011: 067: 490 Pathophysiology (Spring term, 3 credits) 011: 067: 493 Research in Animal Sciences (credits by arrangement) You can not teach anybody anything. You can only create the conditions for them to learn (E. Redish). 4

A STUDENT E-MAIL TO THE CURRENT STUDENTS IN PHYSIOLOGY AND ENDOCRINOLOGY COURSES 1. The way you study/learn: The first major piece of advice I give you is to really listen to Professor Advis & the advice that he gives. He designed this class, so obviously he knows the keys to succeeding in it. One of the things he tells you to do is to write down all the information you have on a certain topic, and then edit it down to one core sentence. This worked so well for me, and I realized it was because it makes you truly understand the material, rather than memorize it. This is because as you are editing down different facts about a certain topic, you are making associations in your head. And once an association is made, you don't need to memorize it. Also, making simple lists or charts of related hormones grouped together under one larger concept will make your life so much easier when studying. Once again: associations. 2. The way you take an exam: The exams are probably different from any other exam you've taken by another professor. The best way to describe them is as a marathon. They are 100 questions long, and most of the questions require you to pick the answer choice that is wrong, rather than right. This requires you to know more information than you usually would, which is why memorizing won't work. Memorizing mass amounts of information is probably the worst thing you can do, because you will find yourself utterly confused and flustered during the exam. You need to pace yourself and be well rested and well prepared for these exams because they are exhausting. They require much more mental work than just picking out an answer choice that has familiar key words related to the topic like in some other science exam. These exams truly test your understanding- all he does sometimes is change one word in the sentence, making it completely wrong. The answer choices are full thoughts, threads of logic, rather than a few words long. And he's right when he says that when they're wrong, they're really wrong. 3. The way you understand/think: When he asks you a question in class, most of the time, it's part of a string of questions. Every time you answer, he'll ask why? until you get down to some really basic concept. This is another way of asking so what? This was probably the biggest way he changed the way I process information that I learn in class, because after a while, it becomes intrinsic, and you start to ask yourself so what? about what you are studying, and get to a much deeper understanding. This made me realize that in most of my classes, I didn't truly understand the information I was learning at a very deep and basic level, but rather superficially, just enough to get the question right. Also, don't take for granted the concepts that he simplifies or repeats over and over again. Those concepts will come up on all of the exams. His little jokes like if you scream I don't listen to you would come back to me on the exam, and although they seem very simple, they would actually help me. I am so glad I took this class. The only regret I have is that this was the last and not the first upper level science class I took with him. Introduction 01 The goal of these two lectures is to review pre-requisite material for this course and to provide students with an overview of the material to be covered in the course The sections for this lecture are: Physiology, homeostasis, integrators and signal transduction (slides related Review: energy and cells to each of these Review: structure of a cell topics are Review: chemical reactions labeled with the Review: from genes to proteins topic heading) Introduction to the Recitation section of this course 5

Course Outline (approximately) Topic # Topic lecture, recitation and laboratory Silverthorn Week 1 to week 4 Topic #1 Introduction (pre-requisite material) 1-5 lectures, recitations, labs, Membranes (pre-requisite material) 1-5 review, exam1 Topic #2 Homeostasis and Signal Transduction 6 Endocrine Communication and the Endocrine System 7 Neural Communication and the Sensory System 8-11 Topic #3 Muscle, Muscle Contaction and their Regulation 12-13 Week 5 to week 8 Topic #4 Topic #5 Basic Physiology of the Cardiovascular System Basic Physiology of the Respiratory System 14-17 18 lectures, recitations, labs, review, exam2 Topic #6 Basic Physiology of the Renal System 19-20 Week 9 to week 12 Topic #7 Basic Physiology of the Gastrointestinal System Regulation of Organic Metab, Growth, Energy Balance 21 21-23 lectures, recitations, labs, review, exam3 Neuroendo Regulation of Food Intake & Energy Balance 23-25 Topic #8 From Sexual Differentiation to Adult Reproduction 26 Neuroendocrine Control of Reproductive Cyclicity 26 Topic #9 Biological Clocks in Animal Health and Production 1-26 Week 13 to week 14 Topic #10 Stress & Basic Physiology of Animal Health / Production Physiology of Animal Growth and Muscle Production 1-26 1-26 lectures, recitations, labs, review, exam4 Physiology of Animal Exercise, Training and Racing 1-26 Physiology of Animal Ovulation, Lactation & Production 1 26 Physiology Course (from cell to system and a suggestion for your first recitation topic) 6

Physiology Course Organ Systems of the Body (for recitations you should think on how are these functions achieved) Physiology (what is life?) Life is a series of chemical reactions occurring in compartmentalized environments. The main purpose of life is to keep itself alive Physiology, the study of how life works, is based on simultaneous occurrence of these 3 concepts: levels of organization structure / function relationship homeostatic regulation 7

Physiology (main concepts) levels of organization structure - function homeostatic regulation life as seen from conceptual ideas of everyday structures to control systems Physiology (main concepts) Life is a series of chemical reactions occurring in compartmentalized environments. The main purpose of life is to keep itself alive. life as seen from black boxes diagrams of biological elements to control systems 8

9/1/16 Physiology (main concepts) Life is a series of chemical reactions occurring in compartmentalized environments. The main purpose of life is to keep itself alive. life as seen from the plasma membrane and subcellular structures to control systems Physiology (main concepts) Life is a series of chemical reactions occurring in compartmentalized environments. The main purpose of life is to keep itself alive. life is maintained predominantly through negative feedback mechanisms 9

Physiology (main concepts) Homeostasis-related diagrams from your textbook life is maintained predominantly through negative feedback mechanisms Physiology (main concepts) Homeostasis, or constancy of the internal environment, is needed for chemical reactions underlying life to occur. It is maintained, predominantly, through negative feedback mechanisms. Why??? life is maintained predominantly through negative feedback mechanisms 10

Physiology (integrator concept) Homeostasis, or constancy of the internal environment, is needed for chemical reactions underlying life to occur. It is maintained, predominantly, through negative feedback mechanisms. but, how does this works in physiology?? life is maintained predominantly through negative feedback mechanisms Physiology (integrator concept) (the plasma membrane as a possible electrochemical integrator) how do you imagine the function of an integrator in a physiological system 11

Physiology (integrator concept) (signal transduction as possible biochemical integrators) remember that enzymes, transporters and channels are proteins and therefore water-soluble Physiology (homeostasis concept) Set Point Homeostatic Control Systems preview of things to come, from feed-back to. Remember that in lectures I usually refer to this concept as a circle or as a reflex arc 12

Physiology (set point concept) Set Point preview of things to come, from feed-back to feed-forward life is maintained predominantly through negative feedback mechanisms Physiology (set point concept) -Fb Set point preview of things to come, from feed-back to feed-forward life is maintained predominantly through negative feedback mechanisms 13

Physiology prerequisites Summary of main concepts energy sources chemical reactions mechanistic viewpoint from cell to organism organization levels structure / function homeostatic regulation negative feedback Energy energy chemical bond Intermediary metabolism ATP, a high energy molecule CHEMICAL BONDS Covalent bonds equal sharing e pair Ionic single, bonds double, triple unequal sharing Hydrogen bonds weak but many between / within e.g. water, dipole 14

Energy Bonding Forces between Atoms and Molecules Energy energy is the capacity to do work work, supra-cellular and sub-cellular structures ultimately, work is linked to enzymes and / or to channels 15

Structure size range of cells basic cell structure e.g. mitochondria as cellular power-houses e.g. lysosomes as cellular terminators e.g. endoplasmic reticulum as cellular highways e.g. nucleus as a cellular integrator or town hall Structure Examples of cellular structures and of their associated roles why membranes??? 16

chemical reactions in a water environment biological membranes models??? Structure Structure another view of a biological membrane model 17

Structure Characteristics of Enzymes another view of a biological membrane model why enzymes??? enzymes decrease activational energy of chemical reactions Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation 18

Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation The most important figure of the course Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation 19

Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation Life as enzymatic-driven chemical reactions Chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation Characteristics of Glycolysis 20

Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation 21

Chemical reactions Characteristics of the Krebs Cycle Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation Chemical reactions Characteristics of Oxidative Phosphorylation Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation 22

Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation diagram from another textbook Chemical reactions Life as enzymatic-driven chemical reactions reactions have a Vmax and a Km intermediary metabolism Krebs cycle, oxidative phosphorylation and ATP formation but, How are these reactions controlled? 23

Chemical reactions Negative feedback, as regulator of chemical reactions end - product inhibition e.g. supra-cellular level e.g. sub-cellular level Biological systems are regulated predominantly through negative feedback mechanisms From genes to proteins a blueprint on how to make proteins is your only inheritance unless your family has money. remember that enzymes, transporters and channels are proteins and therefore water-soluble 24

From genes to proteins mrna are templates, to make proteins (e.g. enzymes & channels) remember that enzymes, transporters and channels are proteins and therefore water-soluble From genes to proteins mrna are templates, From DNA to Protein Synthesis to make proteins (e.g. enzymes & channels) remember that enzymes, transporters and channels are proteins and therefore water-soluble 25

From genes to proteins proteins acquire a 3D structure in water and molecular bonding achieve their lowest energy state remember that enzymes, transporters and channels are proteins and therefore water-soluble Physiology Homeostasis, or constancy of the internal environment, is needed for chemical reactions underlying life to occur. It is maintained, predominantly, through negative feedback mechanisms. how do you imagine the function of an integrator in a physiological system 26

Physiology (signal transduction as possible biochemical integrators) remember that enzymes, transporters and channels are proteins and therefore water-soluble Introduction 01 The goal of this lecture was to review pre-requisite material for this course and to provide students with an overview of the material to be covered in the course The sections for this lecture were: Physiology, homeostasis, integrators and signal transduction (slides related Review: energy and cells to each of these Review: structure of a cell topics are Review: chemical reactions labeled with the Review: from genes to proteins topic heading) Introduction to the Recitation section of this course 27

Physiology Recitation a Active Learning is the best way of both studying and understanding Physiology b S E c c) Write physiological concepts in a simple sentence as you go along. Recognize that if you can not do this, you do not understand the concept. Use the summary notes at the end of each chapter. Rank the information. Students listen more to other students (see students comments in website) Professor Advis: (Physiology and ) Endocrinology (were) was definitely one of the most fulfilling and challenging courses I have taken in my undergraduate years. There is so much information to understand and so many complications that can arise from the slightest of changes in the endocrine system that, I must admit, after seeing my first exam grade I never thought I'd be able to retain it all in order to do satisfactory in this class. There were 3 things I did after my first exam that really made (physiology) endocrinology class a lot easier and I'd like to share them hopefully with the next year class in order to make their lives a little less complicated. 1) WRITE SENTENCES - this was probably the single most important factor in retaining all the knowledge you need to know in this class. However overwhelming it seems, I found that (just as you said) if you can summarize all the information you have and keep editing down until you have one sentence to describe the whole bag of information, not only did I remember almost everything that I edited down (because it takes a lot of effort to do so), but I had the main idea down and that's really what you test us on. I was really surprised by my results when i approached the test in this manner because although the questions on your exams seem very specific they aren't AT ALL. They all just test the VERY basics. 2) GO TO REVIEW TESTS - By doing this FROM THE VERY BEGGINING OF THE COURSE*, not only did I hammer into my head all the information that would show up on the next exams (this class is VERY cumulative) but I also learned your thought process when you made the exams and that's very important to do well in this class because I never had a class that asked questions the way this class did. 3) GO TO CLASE - By doing this you understand the otherwise complicated Powerpoint slides that are given out and help reinforce the material from the book. Also LISTEN to professor Advis's small, seemingly useless jokes, they are all said for a reason. By listening to these jokes (i.e. the bearded lady) you will have a one sentence trigger phrase that will help you remember complicated information. Anyway, good luck to your next class and thanks for everything. Girish Harinath You can not teach, anybody, anything. You can only create conditions for them to learn. 28

Physiology Recitation The average grade of your recitation answers is your exam #5. It has the same weight as each of your other exams (20%), and is an essay with ten questions (one per week) whose answers you edit before submitting them for grading. If you can not write an idea into a single sentence, you probably have not yet understood the material. First recitation question Probably a single most important tip for the course is to prepare SENTENCES with what you consider are the main punch lines for each lecture. You should RANK them in what you consider is a list from most to less important ideas given in each lecture. You should EDIT them, as for example, checking if more than one sentence might be combined into a better sentence. Finally, make sure that your sentences cover the whole of the topic presented in each lecture. Use this list to discuss material with fellow students and with your instructor. Please be aware that in order to write a single, concise and informative sentence you need to UNDERSTAND, rather than memorize, a piece of information. To test yourself on how good you are doing, check if your sentence used your own words or if you are just borrowing part of a sentence you read in your textbook. Consider that if you can not write an idea into a single sentence, you probably have not yet understood the material. When you are editing your notes, either from lectures or from your textbook, it is important to have a PLAN that tells you where are you going with your editing. A good suggestion for this plan is to develop a set of QUESTIONS that you think each lecture was attempting to answer. List all possible questions, then edit and rank the questions, and finally answer them by merging your lecture notes and the notes you might have summarized from your textbook. The PARAGRAPHS in the following slides are an example of notes you might have taken from a lecture or from a textbook. Use this notes as an exercise to define a set of questions, to answer them, to turn them into sentences, to edit them, and finally to rank them. 29

First recitation question Information in the text from the following three slides. This information is related to your first lecture and they might be some student s notes. Select a set of questions you think might be relevant to the information provided in the text from the following three slides. Rank them in order of importance. This questions will serve you as guides when editing the information. Write short paragraph (less than 10 sentences), as answers to the questions you have just ranked, and start editing the answers. Turn these paragraphs into single sentences. Rank these single sentences in order of importance. First recitation question 1 Integrative system approach: vertical vs horizontal integration or matriushkas vs homeostasis. Both the course and your textbook promote understanding of the basic principles and physiology concepts rather than memorization of details, without missing depth were it is needed. 2 Operationally life is: a bunch of chemical reaction (metabolism) occurring in compartmentalized environments. These reactions maintain integrity (steady state) in the face of disturbances (homeostasis). Life can reproduce itself and its only purpose is to keep itself alive. Physiology is the study of how life works. 3 Physiological processes arise through evolution: a mechanistic explanation of life deals with how does life work (the main physiological approach). The evolutionary explanation of life asks how did life evolve to be this way and puts an emphasis in the fact that specific biological features result from gene variation and natural selection. 4 Cells are progressively organized into tissues, organs, systems and finally the whole body (levels of organization or matriushka idea). The structure of these cellular arrangements is intimately related to their specific functions (structure / function relationship or the car with square wheels). Finally, the function of these cells and cellular structures is controlled by homeostatic mechanisms that are based on negative feedbacks (homeostatic control or the refrigerator story). 30

First recitation question 5 Scaling is the effects of size on the anatomy and physiology of animals and it is largely based on surface area to volume ratio. Since volume is related to the cube of an object radius, while surface area is related to the square of its radius, their ratio is implicated in a variety of physiological functions (e.g. waste removal, heat production, skeletal mechanics). Remember that larger animals have smaller surface to volume ratio. 6 Maintenance of a steady state in the face of disturbances is homeostasis. Body cells are in contact with a private internal environment instead than with the external environment which surrounds the organism (ECF). Homeostasis is essential for cell function and each cell, as part of an organized system, contributes to it. Negative feedback is the main homeostatic regulatory mechanism, as proposed by Claude Bernard (1813-1878) and Walter Cannon (1871-1945). Thus, it is important to remember that homeostasis is basic for the survival of each cell, and each cell, through its specialized activities, contributes as part of the body system to maintain the internal environment shared by all cells. Thus, homeostasis should be view not as a fixed state but as a dynamic steady state in which changes that do occur are minimized by compensatory physiological responses. 7 In contrast to homeostasis in mammals, there are also other multi-cellular organisms that have a larger variability in their internal fluids. Thus, from this viewpoint, animals have been described as conformers and regulators. The internal state of the former group matches that of their external environment (eg. marine snail) while the latter group defends a relatively constant state (eg. mammals). A third group exist, avoiders, which may not be capable of internal regulation, but nevertheless minimize internal variations by avoiding environmental disturbances (eg. monarch butterflies). First recitation question 8 Negative feedback is the main regulatory mechanism for homeostasis. Feedback effectors can be antagonistic and can include behaviors as well as internal organs. Inadequacies in negative feedbacks systems (eg. delayed response) can be improved by anticipation (eg.glp-1) and acclimatization or adaptation (eg. upregulation and down regulation). 9 Some internal processes are not always homeostatic but may be changed by reset and positive feedback systems. Fever and puberty onset are examples of the former while parturition and the ascending phase of action potential are examples of the latter. Finally, it is well known that disruption of homeostatic regulation can lead to illness and death, as depicted by the pathophysiology of congestive heart disease. 10 Homeostasis (and other regulation) is hierarchically distributed, as shown by the existence of intrinsic and extrinsic controls of the different organs and systems. Furthermore, organ systems can also be grouped according to their whole-body contributions. For example, (1) nervous and endocrine are whole-body control systems; (2) skeletal and muscular are support and movement systems; (3) cardiovascular, immune, excretory, digestive and integumentary are maintenance systems; and (4) reproductive system, which is not essential for the survival of the individual, is a system important for perpetuation of the species. Finally, it is important to keep in mind that the function of the whole is greater than the sum of its parts. 31

Introduction 01 The goal of this lecture is to review pre-requisite material for this course and to provide students with an overview of the material to be covered in the course The sections for this lecture were: Physiology, homeostasis, integrators and signal transduction (slides related Review: energy and cells to each of these Review: structure of a cell topics are Review: chemical reactions labeled with the Review: from genes to proteins topic heading) Introduction to the Recitation section of this course 32