Angelo Mosso and muscular fatigue: 116 years after the first Congress of Physiologists: IUPS commemoration

At the first International Congress of Physiologists in Basel, Switzerland, the Italian physiologist Angelo Mosso (1846-1910) discussed his findings on muscular fatigue while demonstrating the functioning of an ergograph (work recorder). One hundred sixteen years later, Mosso's career, scientific accomplishments, and legacy in the study of muscular fatigue were commemorated at the 2005 International Congress of Physiological Sciences. After receiving his degree in Medicine and Surgery from Turin, Italy, in 1870, Mosso was able to study and interact with renowned physiologists as Wilhelm Ludwig, Du Bois-Reymond, Hugo Kronecker, and Etienne Marey. By 1879, he was Professor of Physiology at the University in Turin, where he conducted research pertaining to blood circulation, respiration, physical education, high-altitude physiology, and muscular fatigue. Using tracings from the ergograph (concentric contractions of the flexor muscles of the middle finger that were volitionally or electrically stimulated), he was able to characterize muscle fatigue and to associate its occurrence with central or peripheral influences. He demonstrated that exercise would increase muscular strength and endurance while prolonging the occurrence of fatigue, which he postulated was a chemical process that involved the production of toxic substances such as carbonic acid. The phenomenon of contracture was described, and his collective studies led to the formulation of laws pertaining to exhaustion and to the 1891 publication of La Fatica (Fatigue). Besides La Fatica, Mosso will be remembered as a scientist with a love for physiology, a concern for the social welfare of his countrymen, and as one who sought to integrate physiological, philosophical, and psychological concepts in his experimental studies.     

I. P. Pavlov and the development of neuroscience

Ivan Petrovitch Pavlov significantly changed and developed our knowledge of the brain functions and of the behaviour by his fundamental experimental and theoretical work on the physiology and pathophysiology of the higher nervous activity. He was one of the scientists who prepared the development of neuroscience in our century. During the Pavlovian Conference, 1950 in Moscow Stalin and the Communist Party tried to dogmatize his and his pupil's fundamental theories. But his pupils continued to develop Pavlovian ideas in open discussions with representatives of other schools in a very creative way, opening the doors for a system approach to understand the integrative functional systems of brain and behavior. Pavlov emphasized the high plasticity of the central nervous system. He investigated the complex functional systems within the brain and between the organism and its environment, and the designed models for pathology of the higher nervous activity. During his last years, Pavlov freed himself from the strong deterministic view and characterized the organism and its environment as a self-organizing system.     

The physiologist Johann Autenrieth (1772–1835) at Tübingen University: early reports on biological rhythms and their use for medical lectures

Johann, Heinrich, Ferdinand von Autenrieth [1772–1835], was a teacher of anatomy, physiology and pharmacology at the University of Tübingen, Germany. He was the author of a famous textbook on Physiology and one of the earliest pharmacologists [Öffentlicher Lehrer der Arzneykunst]. In his textbooks, he presented a lot of information that and how biological rhythms influenced physiological functions in the human body, the book was used for his medical lectures for students. He can be regarded as on of the earliest chronophysiologists. Most important, he assumed a chemical stimulation responsible for generating the periodicities in the human body.     

Cerebral Paragonimiasis Presenting with Dementia

We report a case of an 80-year-old Korean man with chronic cerebral paragonimiasis who presented with progressive memory impairment. He suffered from pulmonary paragonimiasis 60 years ago and has been experiencing epilepsy since the age of 45. He began experiencing memory and cognitive deterioration 3 years ago. He visited the neuropsychiatric department of our hospital to check his symptoms and health from a year ago. Contrast-enhanced brain magnetic resonance imaging study revealed calcifications and cystic lesions encompassing the right temporo-occipital region. Encephalomalatic changes were also observed in the right occipital and temporal areas. The anti-Paragonimus specific IgG antibodies in his serum showed a strong positive response. The neuropsychological test results showed a Global Deterioration Scale of 4 and a Clinical Dementia Rating Scale of 1. The chronic cerebral paragonimiasis lesions in the patient’s right temporo-occipital region might induce the dementic change.     

Taurine in the developing cat: Uptake and release in different brain areas

Taurine is an important modulator of neuronal activity in the immature brain. In kittens, taurine deficiency causes serious dysfunction in the cerebellar and cerebral visual cortex. The processes of taurine transport in vitro were now studied for the first time in different brain areas in developing and adult cats. The uptake of taurine consisted initially of two saturable components, high- and low-affinity, in synaptosomal preparations from the developing cerebral cortex and cerebellum, but the high-affinity uptake component completely disappeared during maturation. The release of both endogenous and preloaded labeled taurine from brain slices measured in a superfusion system was severalfold stimulated with a slow onset by depolarizing K⁺ (50 mM) concentrations. K⁺ stimulation released markedly more taurine from the cerebral cortex, cerebellum and brain stem in kittens than in adult cats. The responses were largest in the cerebellum. Both uptake and release of taurine are thus highly efficient in the brain of kittens and may be of significance in view of the vulnerability of cats to taurine deficiency.     

Regulation of brain water during acute hyperosmolality in ovine fetuses, lambs, and adults.

In adult rats, when plasma osmolality increases, water flows across the blood-brain barrier down its concentration gradient from brain to plasma, and brain volume deceases. The brain responds to this stress by gaining osmotically active solutes, which limit water loss. This phenomenon is termed brain volume (water) regulation. We tested the hypothesis that brain volume regulation is more effective in young lambs and adult sheep than in fetuses, premature lambs, and newborn lambs. Brain water responses to acute hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60 and 90% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, young lambs at 20-30 days of age, and adult sheep. After exposure of the sheep to increases in systemic osmolality with mannitol plus NaCl, brain water content and electrolytes were quantified. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. There were significant differences from an ideal osmometer in the cerebral cortex of fetuses at 90% of gestation, cerebral cortex, and cerebellum of newborn lambs, and cerebral cortex, cerebellum, and medulla of young lambs and adult sheep; however, there were no differences in the brain regions of fetuses at 60% of gestation and premature lambs, cerebellum and medulla of fetuses at 90% of gestation, and medulla of newborn lambs. We conclude that 1) brain water loss is maximal and brain volume regulation impaired in most brain regions of fetuses at 60 and 90% of gestation and premature lambs; 2) brain volume regulation develops first in the cerebral cortex of the fetuses at 90% of gestation and in the cerebral cortex and cerebellum of newborn lambs, and then it develops in the medulla of the lambs at 20-30 days of age; 3) brain water loss is limited and volume regulation present in the brain regions of young lambs and adult sheep; and 4) the ability of the brain to exhibit volume regulation develops in a region- and age-related fashion.     

Reflections on Cellular Physiology as a Catalytic Framework for Medicine

These are the reflections of a retired physician who was introduced to cellular physiology in 1947 at the University of Pennsylvania. I majored in Zoology. I took the required major courses, which were interesting but not exciting. I was a premedical student at the time. Fortunately I was introduced to cellular physiology in 1947. The teacher was Professor Louis Heilbrunn, an amazing man dedicated to teaching and the love of his students. He had a number of graduate students at the time. The undergraduates were well integrated with these advanced students. We used his textbook of physiology and we were all proud of being his students. He gave us a new way of thinking about biology. It was exciting and we were treated as mature students. J. Cell. Physiol. 9999: 2596–2597, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.     

Sergei Winogradsky: a founder of modern microbiology and the first microbial ecologist

Sergei Winogradsky, was born in Russia in 1856 and was to become a founder of modern microbiology. After his Master's degree work on the nutrition and growth physiology of the yeast Mycoderma vini at the University of St. Petersburg, he joined the laboratory of Anton DeBary in Strassburg. There he carried out his studies on the sulfur-oxidizing bacterium Beggiatoa which resulted in his formulation of the theory of chemolithotrophy. He then joined the Swiss Polytechnic Institute in Zurich where he did his monumental work on bacterial nitrification. He isolated the first pure cultures of the nitrifying bacteria and confirmed that they carried out the separate steps of the conversion of ammonia to nitrite and of nitrite to nitrate. This led directly to the concept of the cycles of sulfur and nitrogen in Nature. He returned to Russia and there was the first to isolate a free-living dinitrogen-fixing bacterium. In the flush of success, he retired from science and spent 15?years on his familial estate in the Ukraine. The Russian revolution forced him to flee Russia. He joined the Pasteur Institute in Paris where he spent his remaining 24?years initiating and developing the field of microbial ecology. He died in 1953.     

Regulation of Five Tubulin Isotypes by Thyroid Hormone During Brain Development

Nucleic acid probes derived from the 3' noncoding region of five tubulin cDNAs were used to study the effects of thyroid hormone deficiency on the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2)- and three beta (beta 2, beta 4, and beta 5)-tubulin isotypes in the developing cerebral hemispheres and cerebellum. The content of alpha 1, which markedly declines during development in both brain regions, is maintained at high levels in the hypothyroid cerebellum, whereas it is decreased in the cerebral hemispheres. The alpha 2 level also declines during development and is decreased in both regions by thyroid hormone deficiency, but only during the two first postnatal weeks. Thyroid hormone deficiency slightly increases at all stages the beta 2 level in the cerebellum, whereas a decrease is observed at early stages in the cerebral hemispheres. The beta 5 level seems to be independent of thyroid hormone in the cerebral hemispheres, whereas it decreases at early stages in the hypothyroid cerebellum. Finally, the expression of the brain-specific beta 4 isotype is markedly depressed by thyroid hormone deficiency, particularly in the cerebellum. These data suggest that the genes encoding the tubulin isotypes are, directly or not, differently regulated by thyroid hormone during brain development. This might contribute to abnormal neurite outgrowth seen in the hypothyroid brain and therefore to impairment in brain functions produced by thyroid hormone deficiency.     

I. P. Pavlov's teacher of physiology I. F. Tsion (1842-1912)]

In 1866, at the C. Ludwig's laboratory, E. F. Cyon discovered n. depressor, and after C. Bernard's presentation he was awarded with the Montion Prize of the Paris Academy of Sciences. In 1867, together with his brother M. Cyon, he discovered nn. accelerantes of heart, which increase the heart rate when being stimulated. From 1868 to 1874 he was a privatdocent an professor of physiology at Saint-Petersburg University, where under his guidance I.P. Pavlov mastered the brilliant technique of vivisection experiment and accomplished his first works on the physiology of circulation and digestion. From 1872 to 1874 E. F. Cyon was physiology professor at Saint-Petersburg Medical-Surgical Academy. He published "Course of Physiology" in 2 volumes, the official speech "Heart and Brain" and others, proposed an original theory of inhibition, improved the reflex theory. He published 197 works, including 151 in German and French. I. P. Pavlov paid a worthy tribute to his teacher and continued the main direction of his investigations.     

Anencephaly: structural characterization of gangliosides in defined brain regions

Gangliosides from histopathologically-defined human cerebrum-resembling remnant and cerebellum from 37 and 30 gestational week-old anencephaluses were identified using mass spectrometry and high performance thin layer chromatography combined with immunochemical analysis in comparison to respective normal newborn/fetal and adult brain regions. A novel strategy of nano-electrospray ionization quadrupole time-of-flight tandem MS has been developed for identification of ganglioside components in complex mixtures. By morphoanatomical and histological investigation the anencephalic cerebral remnant was found to be aberrant, while the anencephalic cerebellum was defined as normal. Total ganglioside concentrations in the anencephalic cerebral remnant and the cerebellum were 34% and 13% lower in relation to the age-matched controls. In the cerebral remnant, GD3, GM2 and GT1b were elevated, while GD1a was decreased in the anencephalic cerebral remnant, but enriched in anencephalic cerebellum. GQ1b was reduced in both anencephalic regions. Gg4Cer, GM1b and GD1alpha, members of the alpha-series biosynthetic pathway, and neolacto-series gangliosides were found to be present in anencephalic, as well as in normal, fetal and adult brain tissues, indicating the occurrence of these biosynthetic pathways in human brain. In both cerebral and cerebellar anencephalic tissues, GM1b, GD1alpha, nLM1 and nLD1 were expressed at a higher rate in relation to normal tissue. It can be demonstrated that the anencephalic cerebral remnant, as a primitive brain structure, represents a naturally-occurring model to study the ganglioside involvement in induction of aberrant brain development.     

Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices

Background

Emerging evidence suggests that DNA methylation plays an expansive role in the central nervous system (CNS). Large-scale whole genome DNA methylation profiling of the normal human brain offers tremendous potential in understanding the role of DNA methylation in brain development and function.

Methodology/Significant Findings

Using methylation-sensitive SNP chip analysis (MSNP), we performed whole genome DNA methylation profiling of the prefrontal, occipital, and temporal regions of cerebral cortex, as well as cerebellum. These data provide an unbiased representation of CpG sites comprising 377,509 CpG dinucleotides within both the genic and intergenic euchromatic region of the genome. Our large-scale genome DNA methylation profiling reveals that the prefrontal, occipital, and temporal regions of the cerebral cortex compared to cerebellum have markedly different DNA methylation signatures, with the cerebral cortex being hypermethylated and cerebellum being hypomethylated. Such differences were observed in distinct genomic regions, including genes involved in CNS function. The MSNP data were validated for a subset of these genes, by performing bisulfite cloning and sequencing and confirming that prefrontal, occipital, and temporal cortices are significantly more methylated as compared to the cerebellum.

Conclusions

These findings are consistent with known developmental differences in nucleosome repeat lengths in cerebral and cerebellar cortices, with cerebrum exhibiting shorter repeat lengths than cerebellum. Our observed differences in DNA methylation profiles in these regions underscores the potential role of DNA methylation in chromatin structure and organization in CNS, reflecting functional specialization within cortical regions.     

RATE OF ACCUMULATION OF ACETYLCHOLINE IN DISCRETE REGIONS OF THE RAT BRAIN AFTER DICHLORVOS TREATMENT

Abstract– The time course for accumulation of acetylcholine was measured in rat brain regions after treatment with 15 mg/kg, i.v., dichlorvos. With this dose of dichlorvos 84-96% of the brain cholinester-ase is inhibited within 1 min. After killing and concomitant enzyme inactivation through microwave irradiation, the acetylcholine levels were measured by pyrolysis-gas chromatography. In the brain regions studied, the striatum had the highest rate of accumulation of acetylcholine and the cerebellum had the lowest. The calculated turnover time in minutes for the regions of the brain were cerebral cortex 0.9; hippocampus 1; striatum 1.4; cerebellum 1.7; medulla-pons 2.2; midbrain 4.5; thalamus 5.6.     

Development of brain networks for orienting to novelty

Among the many contributions of I.P. Pavlov to the study of the higher nervous system was his exploration of the physical basis of attention. Pavlov's analysis of the orienting reflex (OR), together with the contributions of Y.N. Sokolov, demonstrated that attention could be studies by the objective methods of neurophysiology. Cognitive neuroscience has continued these effort by using neuroimaging to explore the anatomy and physiology of attention in the working human brain. It is now possible to show that the appearance of a novel visual event invokes multiple attentional networks that work in concert to orient to and process a novel object within a very brief exposure. In this paper, we describe cognitive studies of orienting to novelty in adults, examine the networks of neural areas involved in processing novel objects, and review the development in early life of these attentional networks. Orienting to novelty provides an excellent vehicle for examining how biology and experience shape the mechanisms of self-regulation and cognitive control.     

The Brain Collections of the Museum of Anthropology and Ethnography, University of Turin: Re-Evaluation and Scientific Investigation

The study of brain collections has played an important role in research on the Natural History of Man. Current knowledge on cerebral morphological evolution and development of the psyche, from non-human primates to Man, is the result of analyses of endocranial casts and brains collected in the nineteenth century from the various primate species dissected. This paper presents the brain collections of non-human and human primates housed in the Museum of Anthropology and Ethnography of the University of Turin put together in the early 1900s by A. Marro, father of Prof. Giovanni Marro, the founder of the Museum. These collections, which have required constant interventions aimed at their preservation and scientific re-evaluation, have undoubted historical interest and are essential to define Man, both biologically and culturally.     

Advances in the Understanding and Treatment of Head Injury

The author describes his personal involvement in head injury prevention and management over the past 40 years. He reviews the evolution of knowledge concerning the role of increased intracranial pressure, and considers the importance of cerebral vasoparalysis in the production of signs and symptoms following head injury, and the development of methods of recording intracranial pressure continuously, over hours and days.The development of an experimental compression model has led to a fuller understanding of edema of the brain and has provided a means of studying, by light and electron microscopy, the histological changes that result from edema. More recently, analyses of biochemical changes and disturbed membrane function have opened up a new avenue of potential treatment. Moreover, it is now clear that cerebral vascular dilatation and abrupt pressure increase can be produced in the monkey, in over 50% of cases, by lesions in the dorsomedial nucleus of the hypothalamus. Similar lesions may occur in the human and this suggests other therapeutic approaches. There is, then, a genuine hope of a breakthrough in the management of head injuries.     

Localization of a brain sulfotransferase, SULT4A1, in the human and rat brain: an immunohistochemical study.

Cytosolic sulfotransferases are believed to play a role in the neuromodulation of certain neurotransmitters and drugs. To date, four cytosolic sulfotransferases have been shown to be expressed in human brain. Recently, a novel human brain sulfotransferase has been identified and characterized, although its role and localization in the brain are unknown. Here we present the first immunohistochemical (IHC) localization of SULT4A1 in human brain using an affinity-purified polyclonal antibody raised against recombinant human SULT4A1. These results are supported and supplemented by the IHC localization of SULT4A1 in rat brain. In both human and rat brains, strong reactivity was found in several brain regions, including cerebral cortex, cerebellum, pituitary, and brainstem. Specific signal was entirely absent on sections for which preimmune serum from the corresponding animal, processed in the same way as the postimmune serum, was used in the primary screen. The findings from this study may assist in determining the physiological role of this SULT isoform.     

Léon Athanase Gosselin (1815–1887) et ses recherches sur les maladies du testicule

Leon Athanase Gosselin was one of the greatest French surgeons of the 19th century. He successfully directed many university surgical departments and excelled in orthopaedics, anatomy, physiology and urology. Thanks to his advanced research into testicular, scrotal and spermatic cord diseases and their effects on fertilisation and virility, Gosselin is rightly considered to have been a great andrologist before this branch of medical science had been recognised.