Variations In Physiological Functions Research Articles

Metalloproteins and metalloproteomics in health and disease.

Metalloproteins represents more than one third of human proteome, with huge variation in physiological functions and pathological implications, depending on the metal/metals involved and tissue context. Their functions range from catalysis, bioenergetics, redox, to DNA repair, cell proliferation, signaling, transport of vital elements, and immunity. The human metalloproteomic studies revealed that many families of metalloproteins along with individual metalloproteins are dysregulated under several clinical conditions. Also, several sorts of interaction between redox- active or redox- inert metalloproteins are observed in health and disease. Metalloproteins profiling shows distinct alterations in neurodegenerative diseases, cancer, inflammation, infection, diabetes mellitus, among other diseases. This makes metalloproteins -either individually or as families- a promising target for several therapeutic approaches. Inhibitors and activators of metalloenzymes, metal chelators, along with artificial metalloproteins could be versatile in diagnosis and treatment of several diseases, in addition to other biomedical and industrial applications.

Astrocytes of the eye and optic nerve: heterogeneous populations with unique functions mediate axonal resilience and vulnerability to glaucoma.

The role of glia, particularly astrocytes, in mediating the central nervous system's response to injury and neurodegenerative disease is an increasingly well studied topic. These cells perform myriad support functions under physiological conditions but undergo behavioral changes - collectively referred to as 'reactivity' - in response to the disruption of neuronal homeostasis from insults, including glaucoma. However, much remains unknown about how reactivity alters disease progression - both beneficially and detrimentally - and whether these changes can be therapeutically modulated to improve outcomes. Historically, the heterogeneity of astrocyte behavior has been insufficiently addressed under both physiological and pathological conditions, resulting in a fragmented and often contradictory understanding of their contributions to health and disease. Thanks to increased focus in recent years, we now know this heterogeneity encompasses both intrinsic variation in physiological function and insult-specific changes that vary between pathologies. Although previous studies demonstrate astrocytic alterations in glaucoma, both in human disease and animal models, generally these findings do not conclusively link astrocytes to causative roles in neuroprotection or degeneration, rather than a subsequent response. Efforts to bolster our understanding by drawing on knowledge of brain astrocytes has been constrained by the primacy in the literature of findings from peri-synaptic 'gray matter' astrocytes, whereas much early degeneration in glaucoma occurs in axonal regions populated by fibrous 'white matter' astrocytes. However, by focusing on findings from astrocytes of the anterior visual pathway - those of the retina, unmyelinated optic nerve head, and myelinated optic nerve regions - we aim to highlight aspects of their behavior that may contribute to axonal vulnerability and glaucoma progression, including roles in mitochondrial turnover and energy provisioning. Furthermore, we posit that astrocytes of the retina, optic nerve head and myelinated optic nerve, although sharing developmental origins and linked by a network of gap junctions, may be best understood as distinct populations residing in markedly different niches with accompanying functional specializations. A closer investigation of their behavioral repertoires may elucidate not only their role in glaucoma, but also mechanisms to induce protective behaviors that can impede the progressive axonal damage and retinal ganglion cell death that drive vision loss in this devastating condition.

Variation in physiological function within and between menstrual cycles: uncovering the contributing factors.

Variation in physiological function within and between menstrual cycles: uncovering the contributing factors.

Interspecific differences and ecological correlations of energy metabolism traits in freshwater fishes

Abstract Metabolic energy fuels all biological processes, and thus, energy metabolism is vitally important for organisms. It has been suggested that interspecific variation in physiological functions is associated with the energetic metabolism of organisms, which varies considerably due to selection, adaptation and evolution. Thus, the present study aimed to clarify the relationship between the interspecific diversification of maintenance energy expenditure and two forms of anaerobic capacity (in terms of exercise and hypoxia tolerance) in freshwater fishes. Moreover, in the context of environmental adaptation, we hypothesized that selection for increased locomotor performance in species with a fast‐flow lifestyle favours a high aerobic and anaerobic capacity and, consequently, a high maintenance metabolism, whereas selection for strong hypoxia tolerance in species with a slow‐flow lifestyle favours a reduced maintenance metabolism and a reduced aerobic capacity. We examined these topics among 30 species of freshwater fish with different lifestyles based on the flow regimes of their habitats (fast, intermediate and slow flow). The resting metabolic rate of each species was measured, and then, the fish were subjected to two treatments: (a) exercise to exhaustion, after which we measured the maximum metabolic rate, excess post‐exercise oxygen consumption and metabolic recovery rate; and (b) hypoxia to the point of loss of equilibrium (LOE), after which we measured the metabolic response to recovery from hypoxia, including the peak metabolic rate (PMRh) and the excess post‐hypoxia oxygen consumption (EPOCh). We found that the resting metabolic rate was positively correlated with both the aerobic and anaerobic capacity of the fishes and that species from fast‐flow habitats have higher aerobic and anaerobic capacity with concomitantly increased resting metabolism. However, neither EPOCh nor LOE was correlated with resting metabolic rate. In summary, we suggest that selection for increased aerobic and anaerobic capacity to facilitate the demands of exercise has occurred in fast‐flow species, that selection for hypoxia tolerance may have favoured a reduction in this capacity in intermediate and slow‐flow species, and that specialized adaptations (such as flexibility in gill morphology and altered metabolic pathways) play important roles in hypoxia tolerance in some species. A free Plain Language Summary can be found within the Supporting Information of this article.

Circadian Rhythms of Physiological Functions of the Pregnant Woman and the Fetus and the Biological Solemnity Thereof

The basic rhythms of nature that left their imprint on the existence of all living organism on the Earth, arose under the influence of the Earth’s rotation relative to the Sun, the Moon and other planets and stars of the Universe. This periodicity gave rise to the rhythm that has become essential for their life. Life is a continual chemical process of building up and breaking down of organic substances, which results from the substance exchange between an organism and the environment. This makes it impossible for a living organism to exist without the external environment. Since 1978-1979 we have been carrying out a task-oriented research with the aim to approximate the moment when we are able to answer all these questions. Daily fluctuations of cardiac and motor activity of the fetus have been studied (uninterrupted daily recording of fetal ECG); polysomnography of nocturnal sleep was recorded; daily fluctuations of endocrine system activity in the pregnant were studied. A correlation was made between the functional state of maternal sleep-wakefulness biological rhythm, biological clock of the human fetus and the “light-darkness” cycle of a 24-hour solar day. In the process of the study we have developed an original method of day-to-day analysis of maternal and fetal ECGs. It has been established that a healthy fetus has distinct, diurnal variations of physiological functions. The fetal biorhythms coordinate with the status of the maternal organism being, however, in an opposite phase. The curve of the dynamics of fetal physiological system functioning shows a biphasic nature (one-phase in adults). “Active” and “quiet” (sleep-like) periods have been singled out in the human fetus. No reaction is observed in “quiet” periods. However, the “zero”-type fetal reaction recorded by us within the period from 2 p.m. to 9 p.m. does not indicate unsatisfactory condition of the fetus but rather is suggestive of a definite reduction of functional levels of the fetal physiological systems, which is necessary for vital activity. Although conventionally recognized as an indicator of poor state of the fetus, this type only calls for precise attention when recorded in fetal “active” hours. The present study has been the first in the world’s medicine and biorhythmology to detect and establish the daily rhythms of cardiac and motor activity in the human fetus.

Species-Specific Comparison of the Cardiac Sodium/Potassium Pump Based on a Minimal Biophysical Model

The Na+/K+ ATPase (NKA) plays a critical role in maintaining the concentration gradients, across the plasma membrane, of potassium (which determines the cell's membrane potential) and sodium, the driving force behind crucial ion-exchange processes, including calcium extraction via the sodium/calcium exchanger. This function has been extensively studied, experimentally and by computational simulations, within the context of the excitation/contraction coupling in cardiac myocytes. An important source of complexity in these strongly couple systems is the significant species-dependent variability of physiological conditions under which NKA operates, particularly the intracellular sodium concentration [Na+]i. For example, [Na+]i ∼ 11 mM in rat ventricular myocytes, and ∼ 5 mM in guinea pig. An important question is whether (1) NKA is maintained across species and operates in different species-specific regimes; or (2) NKA shows significant species-dependent variations and hence participates directly in defining physiological conditions. Most existing models neglect this fundamental question by assuming a generic NKA formulation derived from disparate experimental sources. To address this problem, we propose a biophysical framework for characterizing NKA function, specifically designed for species-specific parameterization, and produce separate models for rat and guinea pig NKA, each parameterized from fully consistent data sets. We find that the apparent binding affinity for sodium in the rat is lower by a factor of approximately three, whereas the overall pump current magnitude is roughly doubled, relative to guinea pig. These trends mirror those for the [Na+]i differences, suggesting that NKA kinetics compensates or has adapted to its physiological conditions. Such comparisons allow an analysis of the relative influence of cellular components, ionic conditions, and the action potential on ion transport in cardiac contraction, and ultimately enable the quantification of variations in physiological function of NKA across biological contexts.

Study of cardiovascular reactivity to mental stress in different phases of menstrual cycle.

It is a well known fact that normally female sex hormone levels fluctuate during the menstrual cycle. The presence of receptors for these hormones on both heart and blood vessels may also hint at variations in physiological functions during menstrual cycle. So this study was an attempt to determine whether the follicular and luteal phases of menstrual cycle are characterized by variations in cardiovascular parameters in the resting state and also examine changes in cardiovascular reactivity to mental stress challenge during both the phases of menstrual cycle. Thirty healthy females in the age group of 18-25 years with regular menstrual cycles fulfilling the inclusion criteria were examined for cardiovascular parameters (heart rate and blood pressures) at rest and their reactivity to mental stress during the follicular and luteal phase and were compared by using paired t-test. A p-value of <0.05 was considered as statistically significant. The women included in the study produced the well known reactivity to mental stress, in terms of blood pressure and heart rate increases, but the two phases of menstrual cycle were indistinguishable in so far as reactivity patterns were considered. The resting values of these cardiovascular parameters were also alike during the two phases. We were unable to unearth any differences in resting and reactivity values of cardiovascular parameters during the course of a normal menstrual cycle. This shows that stress reactivity variations during different phases of menstrual cycle may not be due to variations in hormonal levels per se, but due to collusion of hormonal variations and unknown genetic influences.

Ruled by the Clock

### Circadian Rhythms Govern Cardiac Repolarization and Arrhythmogenesis Jeyaraj et al Nature . 2012;483:96–99. The ability of organisms to respond to time allows for anticipation of cyclic changes in the environment that provide a survival advantage. The time variance of environmental influences on an organism may occur over years, months, or days. Biological clocks are ubiquitous and hierarchical in mammals and provide cell autonomous, transcriptionally mediated mechanism(s) to regulate function over several time scales.1 The master clock in mammals is in the suprachiasmatic nucleus (SCN) of the hypothalamus, which is regulated by external cues (zeitgebers), prominently light. Circadian rhythmicity is maintained by endogenous 24-hour cycle clocks that can be regulated by external signals to produce diurnal behaviors. Circadian clocks are characteristic of most mammalian tissues and are coupled to produce complex diurnal behaviors.2 The main molecular components of mammalian biological clocks include a series of transcription factors that regulate the expression of clock-controlled genes (CCG) in a negative feedback fashion. CLOCK and BMAL1 heterodimerize and bind to an E-box motif, activating transcription of the period (PER1, 2, 3) and cryptochrome (CRY1, 2) proteins. As period proteins accumulate, they complex with cryptochromes and translocate to the nucleus, suppressing CLOCK/BMAL1 mediated transcription. Casein kinase 1e (CK1e) phosphorylates period proteins targeting them for proteasomal degredation, derepressing CLOCK/BMAL1-mediated transcription. These core components of the clock are regulated by a number of other CCGs including arginine vasopressin and other transcription factors such as D-element–binding proteins, hepatic leukemia factor, and thyrotrophic embryonic factor. The central clock in the SCN regulates autonomic nervous system function, levels of humoral factors, and peripheral clocks to produce circadian variation in physiological function.1 Peripheral clocks exist in virtually every tissue in the body and are believed to have similar molecular mechanisms. Cardiovascular physiology and the clinical presentation of heart and vascular disease …

Expression of cardiac myosin light chain 2 during embryonic heart development in medaka fish, Oryzias latipes, and phylogenetic relationship with other myosin light chains

Cardiac myosin light chain 2 (MLC-2) plays a key role in heart development, contraction, and embryo and adult heart maintenance. In some animals, defects in the function of cardiac MLC-2 cause hypertrophic cardiomyopathy. To illuminate the functions of cardiac MLC-2 in embryonic heart formation and contraction, and into the evolution of MLC-2, we characterized the expression and requirement for medaka cardiac MLC-2 gene in the developing heart. Medaka cardiac MLC-2 cDNA (mcmlc2) was isolated and its gene expression pattern was determined. The mcmlc2 was found to be expressed in the bilateral cardiac mesoderm, the formed heart tube, and in both the differentiated ventricle and atrium. Knockdown of mcmlc2 function caused severe cardiac disorders, including edema in the atrium and sinus venosus. Using phylogenetic analysis, we found that physiological variations in the MLC-2 molecules evolved due to amino acid changes in the Ca(2+) binding domain during molecular evolution. Our findings concerning the function and expression of mcmlc2 are nearly identical with those of other MLC-2 genes, and our phylogenetic analysis suggests that during evolution, the variations in physiological function within the MLC-2 gene family have arisen from a change in the amino acids in the Ca(2+) binding domain in the MLC-2 molecule.

Mechanisms of Behavioral Toxicology: An Integrated Approach

Behavior provides the link between an animal's internal physiology and external environment; specific variations in physiological function can yield specific, definable and predictable behaviors. Disruptions in the physico-chemical nature of environmental cues or the internal biological responses have the potential to induce changes in behavior, changes which may subtly alter a population's ability to survive. Numerous scientists, using a wide range of invertebrates and vertebrates, including humans, have developed a significant body of knowledge on behavioral alterations due to sublethal environmental contaminant exposure. These behaviors include reflexive motions and neurobehavioral assessments, social interactions, activity and feeding patterns, and learning. However, this work has often been accomplished without investigating the physiological mechanisms that produce the observed changes. This situation has occurred not for lack of interest among behavioral toxicologists to investigate the physiological underpinnings of the observed alterations, but rather due to lack of resources and outlets for collaboration. At the other end of the biological spectrum, physiologists, biochemists and molecular biologists have presented a wealth of important data on the effects of toxicants on terrestrial and aquatic organisms, but from an entirely different perspective. These data provide insight into the relationships between toxicants and metabolic processes, detoxification mechanisms, and neurophysiological and endocrine system disrupters. Each process may, through a series of intermediate pathways, affect animal behavior. Unfortunately, this information has

Circadian variation of physiological functions related to physical work capacity.

The circadian variation of selected physiological functions related to physical work capacity was studied in four trained young male subjects. The twofold objective was to describe, in parametric terms, the variation of these functions and estimate the times and values of their maximum and minimum responses. Statistically significant periodic regression effects were found for the following functions: oral temperature; systolic blood pressure; heart rate at rest, during work (245 and 270 W) and after a 5-min recovery; ratings of perceived exertion; strength of hand grip; and neuromuscular coordination measured with a seesaw board balance test. The Fourier curve (sine curve) accounted for 63 % of the variation in oral temperature and from 13 to 38 % of the variation in the other significant harmonic intensities. In phase with the rhythm of oral temperature, but with larger amplitude, were systolic blood pressure, heart rate at rest and heart rate during work; roughly in phase were strength of hand grip and neuromuscular coordination. Ratings of perceived exertion and heart rate after a 5-min recovery showed a rhythm which was out of phase with the oral temperature. The number of disturbances in neuromuscular coordination was greatest at 2400 and smallest at 1200, the difference being as large as 44 %. The results suggest that the measured capacities of muscle strength and neuromuscular coordination are the lowest, that physical work is perceived as the heaviest, and recovery after work is the slowest at night. These findings appear to support the notion that performance capacity is reduced during the night.

On reproducibility of circadian rhythms in man (author's transl)

On the basis of our own experimental data and those from the literature, the reproducibility of day-night variations in physiological functions--their 'circadian pattern'--is examined in five sections. They concern the problem of intra- and interindividual variability, demonstrated by the rhythm of deep body temperature, the dependence of the pattern on experimental conditions, and as further examples circadian rhythms in the endocrine system, in blood constituents, in blood pressure and in psychomotor performance. The survey is considered to contribute to the question of how important the circadian temporal structure may be in the search for reference values and hence in diagnosis.

Health as the physician views it, and the use of space technology to achieve and maintain it.

At the outset it should be manifestly obvious to all that there are many definitions of health, and certainly discussion of these is one of the primary concerns of our gathering. Health is defined in the dictionary as ‘a normal condition of body or mind; that is, with all of the parts functioning normally’. Such a definition immediately raises questions in my mind for we are faced with a second definition which may be even more difficult — that of what is normal? In my daily medical activities in support of manned space flight, I deal with ‘normal’ individuals who are being exposed to a rather hostile environment. Normal in this sense could be defined as ‘free from disease’, for many of the individuals the average physician deals with in his daily practice are certainly persons who have some variation of normal in mind or body and are therefore seeking assistance and are willing to pay the charge incurred. One of the unseen benefits of the space program is the continuing effort to define more precisely what we mean by ‘normal’ as regards functioning of body and mind. The range is great and in our program, which depends upon measuring sometimes minute variations in physiological function, we have resorted to using the individual as his own ‘normal’ or control and thus measuring his variations from that ‘normal’ baseline.

Seasonal Variations in Physiological Functions during Adolescence

Seasonal Variations in Physiological Functions during Adolescence