Physiology Flies with Time.

The 2017 Nobel Prize in Medicine or Physiology has been awarded to Jeffrey Hall, Michael Rosbash, and Michael Young for elucidating molecular mechanisms of the circadian clock. From studies beginning in fruit flies, we now know that circadian regulation pervades most biological processes and has strong ties to human health and disease.

Barbara McClintock's Final Years as Nobelist and Mentor: A Memoir.

September 2, 2017, marks the 25th year after the passing of Dr. Barbara McClintock, geneticist and recipient of the 1983 Nobel Prize in Physiology or Medicine for her discovery of transposable elements in maize. This memoir focuses on the last years of her life-after the prize-and includes personal recollections of how she mentored young scientists and inspired the age of genetics, epigenetics, and genomics.

TOR, the Gateway to Cellular Metabolism, Cell Growth, and Disease.

Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target.

Autophagy Captures the Nobel Prize.

This year's Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi for the discovery of the molecular principles governing autophagy, an intracellular degradation pathway routed via lysosomes or vacuoles. It is a story of a simple yet insightful yeast genetic screen that revealed the inner circuitry of one of the most powerful quality-control pathways in cells.

A New Golden Age of Natural Products Drug Discovery.

The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell, Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning.

A place and a grid in the sun.

The 2014 Nobel Prize in Physiology or Medicine, awarded to John O'Keefe, May-Britt Moser, and Edvard I. Moser, recognizes the first deep-brain insights into a cognitive function. Their insights established a new view for how the brain represents spatial location.

A prize for membrane magic.

The 2013 Nobel Prize in Physiology or Medicine has been awarded to James Rothman, Randy Schekman, and Thomas Südhof "for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells". I present a personal view of the membrane trafficking field, highlighting the contributions of these three Nobel laureates in a historical context.

Cellular alchemy and the golden age of reprogramming.

The 2012 Nobel Prize in Medicine or Physiology recognizes the architects of two of the great paradigm-shifting discoveries of the last half-century of biology. In experiments performed nearly 50 years apart, Gurdon and Yamanaka made feasible the reawakening of pluripotency inherent in all cells and challenged forever our notions of cellular identity.

Bridging innate and adaptive immunity.

The Nobel Prize in Physiology or Medicine for 2011 to Jules Hoffmann, Bruce Beutler, and the late Ralph Steinman recognizes accomplishments in understanding and unifying the two strands of immunology, the evolutionarily ancient innate immune response and modern adaptive immunity.

Lasker lauds leptin.

This year, the Albert Lasker Basic Medical Research Award will be shared by Douglas Coleman and Jeffrey Friedman for their discovery of leptin, a hormone that regulates appetite and body weight. By uncovering a critical physiologic system, their discovery markedly accelerated our capacity to apply molecular and genetic techniques to understand obesity.

The ends have arrived.

The 2009 Nobel Prize in Physiology or Medicine has been awarded to Elizabeth Blackburn, Carol Greider, and Jack Szostak for their contributions to our understanding of how the ends of eukaryotic chromosomes, telomeres, are replicated by a specialized reverse transcriptase, telomerase. I present a personal view of the telomere field, putting the contributions of these three Nobel laureates into historical context.

A century of exercise physiology: key concepts in neural control of the circulation.

Early in the twentieth century, Walter B. Cannon (1871-1945) introduced his overarching hypothesis of "homeostasis" (Cannon 1932)-the ability to sustain physiological values within a narrow range necessary for life during periods of stress. Physical exercise represents a stress in which motor, respiratory and cardiovascular systems must be integrated across a range of metabolic stress to match oxygen delivery to oxygen need at the cellular level, together with appropriate thermoregulatory control, blood pressure adjustments and energy provision. Of these, blood pressure regulation is a complex but controlled variable, being the function of cardiac output and vascular resistance (or conductance). Key in understanding blood pressure control during exercise is the coordinating role of the autonomic nervous system. A long history outlines the development of these concepts and how they are integrated within the exercise context. This review focuses on the renaissance observations and thinking generated in the first three decades of the twentieth century that opened the doorway to new concepts of inquiry in cardiovascular regulation during exercise. The concepts addressed here include the following: (1) exercise and blood pressure, (2) central command, (3) neurovascular transduction with emphasis on the sympathetic nerve activity and the vascular end organ response, and (4) tonic neurovascular integration.

[About the first publication of I.M. Sechenov. (To the 195th anniversary of his birth)]. / O pervoi publikatsii I.M. Sechenova. (K 195-letiyu so dnya rozhdeniya).

Ivan Mikhailovich Sechenov is a Russian physiologist, a natural scientist, and the creator of the Russian physiological school. The classic work «Reflexes of the Brain¼, published in 1863, became revolutionary in its own way for medicine and society, since the reflex nature of conscious and unconscious activity was proved. Along with numerous well-known scientific works, there is an early student publication in the Moscow Medical Journal published by A. I. Polunin. It describes the medical history of a patient with a tumor who was unsuccessfully treated for a long time in accordance with the humoral theory of pathology. This publication makes it possible to understand why I. M. Sechenov became disillusioned with practical medicine, but found his vocation in the study of physiology. The article is devoted to the 195th anniversary of the birth of I. M. Sechenov.

[Beginning of the teaching of Physiology in Chile]. / Inicio de la enseñanza de la Fisiología en Chile.

This work intends to present the beginning and early development of physiological studies in Chile. Physiology, as a scientific discipline, began to be taught from the moment the School of Medicine was founded in 1833, closely associated with anatomy and hygiene. The three disciplines were taught by the same professor. His first professor was the outstanding Chilean anatomist Pedro Morán, who was continued by the outstanding professors Dr. Julio Francisco Lafargue and Dr. Vicente Padín del Valle. In a second period (1868-1901), the teaching of physiology was severely weakened, as it was taught by various clinicians who did not know this discipline in depth. After this initial period (1833-1900), which we could call the theoretical stage, the so-called experimental physiology was born, which, through classes with experimental demonstrations and then practical work, tried to bring the student closer to the reality of the physiological phenomenon.

[Johannes Müller (1801-1858) and his school: pioneer and giant of German physiology]. / Johannes Müller (1801­1858) und seine Schule ­ Wegbereiter und Gigant der deutschen Physiologie.

Johannes Müller was indisputably the most versatile and brilliant physiologist in the mid-nineteenth century. Müller was born in Koblenz in 1801 as the eldest of five children. He received an excellent education in mathematics and the ancient languages and was thus able to read with ease the writings of Aristotle in the original.He served a year with the Pioneers after graduating from high school in 1818. In 1819 he enrolled at the University of Bonn. In 1821, while still a student, he was awarded the scientific university prize for his work on foetal respiration. Müller received his doctorate at the university of Bonn in 1822. He moved to Berlin, where he continued to attend lectures by the anatomist Karl Asmund Rudolphi.He obtained his habilitation in physiology and comparative anatomy in 1824. After his years in Bonn, he accepted a chair at the University of Berlin in 1833 as Rudolphi's successor. His famous "Handbuch der Physiologie" (1833-1840) was published in Berlin. Müller's main areas of interest were physiology, human anatomy, comparative anatomy and anatomical pathology.Müller has numerous publications in addition to his famous book on physiology. He and his distinguished students (Emil du Bois-Reymond, Ernst Haeckel, Hermann von Helmholtz, Friedrich Gustav Jakob Henle, Carl Ludwig, Theodor Schwann and Rudolf Virchow amongst others) made the Berlin Physiological Institute world famous. The natural-philosophical approach to medicine that was still dominant at the beginning of the 19th century was increasingly replaced by a scientifically oriented methodology by Müller.

Claude Bernard and life in the laboratory.

Much has been written on Claude Bernard as a relentless promoter of the experimental method in physiology. Although the paper will touch Bernard's experimental intuitions and his experimental practice as well, its focus is slightly different. It will address the laboratory, that is, the space in which experimentation in the life sciences takes place, and it will analyze the scattered remarks that Bernard made on the topic both in his books and in his posthumously published writings. The paper is divided into four parts. The introduction briefly sketches the coming into being of the physiological laboratory in the first half of the nineteenth century. The second section will give an overview of Claude Bernard's own itinerary in physiology and his personal laboratory experience. The third part of the paper will have a look at the image of the laboratory that Claude depicted in his Introduction to Experimental Medicine. In the subsequent section and by contrast, the image of the laboratory will come into focus as it can be reconstructed from Bernard's notebook that he kept between 1850 and 1860, the Cahier rouge. Finally, the fifth part of the paper will spotlight Claude Bernard's comparison of the sciences and the arts and their respective practices. A brief concluding statement tries to summarize Bernard's epistemological position toward experimentally practiced science.

Kathryn Howell (1939-2020) "The Secretory Pathway was Imprinted in her Heart".

On April 10, 2020, a treasured cell biologist and ardent champion of the Golgi complex passed away. This has caused deep sadness, and we seek to commemorate her remarkable scientific contributions, her warm and generous personality, and her endearing sense of humor.

Kresimir Krnjevic (1927-2021) and GABAergic inhibition: a lifetime dedication.

After over seven decades of neuroscience research, it is now well established that γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. In this paper dedicated to Kresimir Krnjevic (1927-2021), a pioneer and leader in neuroscience, we briefly highlight the fundamental contributions he made in identifying GABA as an inhibitory neurotransmitter in the brain and our personal interactions with him. Of note, between 1972 and 1978 Dr. Krnjevic was a highly reputed Chief Editor of the Canadian Journal of Physiology and Pharmacology.

The magnitude of the Bohr effect profoundly influences the shape and position of the blood oxygen equilibrium curve.

For the past century, the importance of the Bohr effect for blood oxygen delivery has been deemed secondary to the influence of the uptake of carbon dioxide when the blood is deoxygenated (the Haldane effect). This is, however, not the case. The simultaneous oxygen and proton binding to hemoglobin can be modelled by a two-ligand, two-state formulation, while the resulting changes in acid-base status of the surrounding solution can be assessed according to Stewart's model for strong ion difference. This approach shows that an abolishment of the Bohr effect (by either equalizing pKa values of the Bohr groups of T and R states, or by removing the Bohr groups in the calculations) dramatically increases oxygen affinity, and that the Bohr effect plays a crucial role in determining the overall position and shape of the oxygen equilibrium curve. Thus, the magnitude of the Bohr effect (the Bohr factor) and oxygen affinity are directly related, and any change in hemoglobin structure that affects the Bohr factor will inevitably influence hemoglobin oxygen affinity. The modelling approach also emphasizes that pH, PCO2 and PO2 in capillaries are dependent variables, determined by arterial blood gases, the Bohr effect, the respiratory quotient (RQ) of tissue metabolism and the buffer capacity of blood. Thus, the full extent of the Bohr effect cannot be appreciated by comparing oxygen equilibrium curves made at constant PCO2 or pH, but only by comparing curves at constant proton saturation of the Bohr groups. This is because, it is the protons bound to the Bohr groups that directly influence hemoglobin­oxygen binding.