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We recently described the discovery, genome, clinical features, genotypes and evolution of a novel and global human respiratory virus named human coronavirus HKU1 (HCoV-HKU1) which is not yet culturable. We expressed a C-terminal FLAG-tagged CoV-HKU1 spike (S) protein by the Semliki Forest Virus (SFV) system and investigated its maturation profile. Pulse chase labeling revealed that S-FLAG was expressed as high-mannose N-glycans of monomers and trimers. It was predominantly cleaved into subdomains S1 and S2 during maturation. S1 was secreted into the medium. Immunofluorescence analysis visualized S along the secretory pathway from endoplasmic reticulum to plasma membrane. Cleavage of S and release of HCoV-HKU1 S pseudotyped virus were inhibited by furin or furin-like enzyme inhibitors. The cell-based expressed full-length S-FLAG could be recognized by the convalescent serum obtained from a patient with HCoV-HKU1 pneumonia. The data suggest that the native form of HCoV-HKU1 spike expressed in our system can be used in developing serological diagnostic assay and in understanding the role of S in the viral life cycle.

Using two-sensor electrochemical recordings in freely moving rats, we examined the relationship between physiological and drug-induced oxygen fluctuations in the brain and periphery. Animals chronically implanted with oxygen sensors in the nucleus accumbens (NAc) and subcutaneous (SC) space were subjected to several mildly arousing stimuli (sound, tail-pinch and social interaction) and intravenous injections of cocaine and heroin. Arousing stimuli induced rapid increases in NAc oxygen levels followed by and correlated with oxygen decreases in the SC space. Therefore, cerebral vasodilation that increases cerebral blood flow and oxygen entry into brain tissue results from both direct neuronal activation and peripheral vasoconstriction, which redistributes arterial blood from periphery to the brain. The latter factor could also explain a similar pattern of oxygen responses found in the substantia nigra reticulata, suggesting hyperoxia as a global phenomenon with minor structural differences during early time intervals following the stimulus onset. While arousing stimuli and cocaine induced similar oxygen responses in the brain and SC space, heroin induced a biphasic down-up brain oxygen fluctuation associated with a monophasic oxygen decrease in the SC space. Oxygen decreases occurred more rapidly and stronger in the SC space, reflecting a drop in blood oxygen levels due to respiratory depression.

Aminoacyl-tRNA synthetases (ARSs) are an important class of enzymes with an evolutionarily conserved mechanism for protein synthesis. In higher eukaryotic systems, eight ARSs and three ARS-interacting multi-functional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC), which seems to contribute to cellular homeostasis. Of these, AIMPs are generally considered as non-enzyme factors, playing a scaffolding role during MSC assembly. Although the functions of AIMPs are not fully understood, increasing evidence indicates that these scaffold proteins usually exert tumor-suppressive activities. In addition, endothelial monocyte-activating polypeptide II (EMAP II), as a cleavage product of AIMP1, and AIMP2-DX2, as a splice variant of AIMP2 lacking exon 2, also have a pivotal role in regulating tumorigenesis. In this review, we summarize the biological functions of AIMP1, EMAP II, AIMP2, AIMP2-DX2, and AIMP3. Also, we systematically introduce their emerging roles in cancer, aiming to provide new ideas for the treatment of cancer.

Funder: The Kennel Club Charitable Trust, The conformation of the German shepherd dog (GSD) varies considerably within the breed. These differences may result in large variation in the movement and limb loading and undesirable consequences to their musculoskeletal health. This study aimed to investigate the relationship between conformation and biomechanical measures in 60 GSDs. Full body kinematic and kinetic measures were computed from 3D motion capture and pressure data. The dogs were divided into groups based on their back slope and curvature. Correlation analysis and statistical differences between groups showed that GSDs with a greater back slope have a greater contact area in their forelimbs and place them closer together when standing (n = 60). During trot, the dogs with sloped back showed a greater vertical force in the forelimbs and a greater mid-thoracic flexion (n = 60). Unilateral differences were found in the stifle flexion, hock flexion and hock adduction, suggesting greater movement asymmetry with an increase in the back slope (n = 30). In conclusion, several biomechanical parameters are affected by the GSD’s slope of the back and not by its curvature. Further studies are required to determine whether the variation in movement, posture and conformation within the breed relates to an increased susceptibility to musculoskeletal disorders.

Despite a huge range in lung size between species, there is little measured difference in the ability of the lung to provide a well-matched air flow (ventilation) to blood flow (perfusion) at the gas exchange tissue. Here, we consider the remarkable similarities in ventilation/perfusion matching between species through a biophysical lens and consider evidence that matching in large animals is dominated by gravity but in small animals by structure.

Homeostasis is a founding principle of integrative physiology. In current systems biology, however, homeostasis seems almost invisible. Is homeostasis a key goal driving body processes, or is it an emergent mechanistic fact? In this perspective piece, I propose that the integrative physiological and systems biological viewpoints about homeostasis reflect different epistemologies, different philosophies of knowledge. Integrative physiology is concept driven. It attempts to explain biological phenomena by continuous formation of theories that experimentation or observation can test. In integrative physiology, “function” refers to goals or purposes. Systems biology is data driven. It explains biological phenomena in terms of “omics”–i.e., genomics, gene expression, epigenomics, proteomics, and metabolomics–it depicts the data in computer models of complex cascades or networks, and it makes predictions from the models. In systems biology, “function” refers more to mechanisms than to goals. The integrative physiologist emphasizes homeostasis of internal variables such as Pco2 and blood pressure. The systems biologist views these emphases as teleological and unparsimonious in that the “regulated variable” (e.g., arterial Pco2 and blood pressure) and the “regulator” (e.g., the “carbistat” and “barostat”) are unobservable constructs. The integrative physiologist views systems biological explanations as not really explanations but descriptions that cannot account for phenomena we humans believe exist, although they cannot be observed directly, such as feelings and, ultimately, the conscious mind. This essay reviews the history of the two epistemologies, emphasizing autonomic neuroscience. I predict rapprochement of integrative physiology with systems biology. The resolution will avoid teleological purposiveness, transcend pure mechanism, and incorporate adaptiveness in evolution, i.e., “Darwinian medicine.”

The present research reports the results of a long-term study (70 days) of the dynamics of Staphylococcus aureus artificially inoculated in a Tenebrio molitor rearing chain for human consumption. To this end, a rearing substrate consisting of organic wheat middlings was spiked with S. aureus to obtain three initial contamination levels, namely 1 (low level), 5 (medium level) and 7 (high level) Log colony forming unit per gram. Microbial viable counting coupled with metataxonomic analysis were performed to evaluate: i) the persistence and growth of S. aureus in the rearing substrate; ii) the colonization and growth of S. aureus in the insect larvae; iii) the occurrence and load of S. aureus in the frass (excrement from larvae mixed with substrate residues); iv) the presence of S. aureus enterotoxins in the rearing substrate, frass, and larvae. The results of the present study highlighted that wheat middlings contaminated with S. aureus do not represent a suitable environment for the multiplication of the pathogen, irrespective of the initial contamination level. Of note, frass originated from the larvae reared on contaminated wheat middlings might potentially represent a source of S. aureus, with cell loads depending on the initial contamination level. A complex resident microbiota was revealed by metataxonomic analysis. Interestingly, co-occurrence/co-exclusions analysis did not reveal associations between the target microorganism and the microbiota of wheat middlings, larvae, or frass. Considering safety aspects of larvae, the results overall collected suggested that, under the applied conditions, T. molitor represents an inhospitable or even hostile environment for S. aureus, with this latter showing counts below the detection limit in the larvae at the end of the 70-day rearing trial, irrespective of the initial contamination level. The results also suggested that a combination of bactericidal factors, including unfavorable environmental conditions (such as low a

A theoretical basis for Ecosystem-based Fisheries Management (EBFM) was derived for pelagic fish by applying marine ecology theory of analytical relationships of predator-prey biological production transfers between trophic levels to FAO guidelines for an ecosystem approach to fisheries. The aim is to describe a simple method for data-limited fisheries to estimate ecosystem-based FMSY and how EBFM modellers could mimic the way natural fish communities function for maintaining ecological processes of biological production, biomass and ecosystem stability. Ecosystem stability (ES) FMSY were estimated by proportion of biological production allocated to predators, giving ESFMSY of 0.23 for small pelagic and 0.27 for pelagic finfish, prioritising ecosystem over economics. To maintain both stability and biomass (SB) a full pelagic EBFM SBFMSY of about 0.08 was obtained for both small pelagic and pelagic finfish, having mostly ecosystem considerations. As the FMSY are single-species averages of catchable species targeted in a specific trophic level, multispecies fishing mortalities were proportioned by the biological production of each species in the trophic level. This way catches for each species are consistent with the average ecosystem FMSY for a trophic level. The theoretical estimates gave similar results to other fisheries for sustainable fish catches that maintain the fishery ecosystem processes. They were also tested using six tropical Ecopath Models and showed the effects of imposing commercial fishing mortalities on predominantly EBFM conditions. The ecosystem stability ESFMSY is suggested to be investigated for sustainable fish catches and the full EBFM SBFMSY for protected areas or recovery of heavily depleted stocks.

Synchronized mass coral spawning typically occurs several days after a full moon once a year. It is expected that spawning day is determined by corals sensing environmental change regulated by the lunar cycle (i.e., tide or moonlight); however, the exact regulatory mechanism remains unknown. Here, we demonstrate how moonlight influences the spawning process of coral, Dipsastraea speciosa. When corals in the field were shaded 1 and 3 d before the full moon or 1 d after the full moon, spawning always occurred 5 d after shading commenced. These results suggest moonlight suppresses spawning: a hypothesis supported by laboratory experiments in which we monitored the effects of experimental moonlight (night-light) on spawning day. Different night-light treatments in the laboratory showed that the presence of a dark period between day-light and night-light conditions eliminates the suppressive effect of night-light on spawning. In nature, moonrise gets progressively later during the course of the lunar cycle, shifting to after sunset following the day of the full moon. Our results indicate that this period of darkness between sunset and moonrise triggers synchronized mass spawning of D. speciosa in nature.

Adaptations to control heat transfer through the integument are a key component of temperature regulation in animals. However, there remain significant gaps in our understanding of how different optical and morphological properties of the integument affect heating rates. To address these gaps, we examined the effect of reflectivity in both ultraviolet–visible and near-infrared wavelengths, surface rugosity (roughness), effective area (area subjected to illumination) and cuticle thickness on radiative heat gain in jewel beetles (Buprestidae). We measured heating rate using a solar simulator to mimic natural sunlight, a thermal chamber to control the effects of conduction and convection, and optical filters to isolate different wavelengths. We found that effective area and reflectivity predicted heating rate. The thermal effect of reflectivity was driven by variation in near-infrared rather than ultraviolet–visible reflectivity. By contrast, cuticle thickness and surface rugosity had no detectable effect. Our results provide empirical evidence that near-infrared reflectivity has an important effect on radiative heat gain. Modulating reflectance of near-infrared wavelengths of light may be a more widespread adaptation to control heat gain than previously appreciated.

Regeneration of uterine tissue is an important physiological process that allows for maintenance of fertility after menstruation or pregnancy. Stem cells, especially bone marrow–derived progenitors, play a crucial role in this regeneration. Here, we describe the conversion of DsRed-labeled bone marrow–derived stem cells (BMDSCs) into specific uterine cell types with both differentiated and stem cell properties in a murine model. Irradiated recipient mice underwent bone marrow transplant with DsRed-expressing BMDSCs and were analyzed for engraftment and differentiation of BMDSCs in the uterus after 2, 6, and 16 weeks. Microarray and qRT-PCR analysis of bone marrow–derived cells obtained from the uterus identified upregulation of markers indicating a contribution to the population of stromal, epithelial, endothelial, and muscle cells, followed by a late expansion of epithelial cells. Other engrafted BMDSCs in the uterus were characterized by the continued expression of specific stem cell markers such as Sca1, CD44, CD146, and CD133, indicating the some BMDSCs remain as progenitor cells. BMDSCs established in recipient mice by the 16th week were sorted by flow cytometry using DsRed and progenitor cell surface markers. In vitro cell culture studies showed that single sorted cells had clonogenic properties. These results suggest that engrafted BMDSCs in the uterus had both a stem cell component and were able to differentiate into several differentiated cell types. The pool of progenitor cells likely continues to supply differentiated uterine cells in the process of uterine repair and remodeling.

Mitochondrial reactive oxygen species (mROS) are routinely produced at several sites within the organelle. The balance in their formation and elimination is maintained by a complex and robust antioxidant system. mROS may act as second messengers and regulate a number of physiological processes, such as insulin signaling, cell differentiation and proliferation, wound healing, etc. Nevertheless, when a sudden or sustained increase in ROS formation is not efficiently neutralized by the endogenous antioxidant defense system, the detrimental impact of high mROS levels on cell function and viability eventually results in disease development. In this review, we will focus on the dual role of mROS in pathophysiology, emphasizing the physiological role exerted by a regulated mROS production/elimination, and discussing the detrimental effects evoked by an imbalance in mitochondrial redox state. Furthermore, we will touch upon the interplay between mROS and Ca2+ homeostasis.

7 pages; International audience; Once infected, hosts can rely on two strategies to cope with parasites: fight them (resist the infection) or minimize the damage they induce (tolerate the infection). While there is evidence that aging reduces resistance, how tolerance varies as hosts become old has been barely studied. Here, we used a rodent malaria parasite (Plasmodium yoelii) to investigate whether 2- and 12-month old house mice differ in their capacity to resist and tolerate the infection. We found that 12-month old mice harbored higher parasitemia, showing that age reduces resistance to malaria. Infection-induced deterioration of host health was assessed using red blood cell and body mass loss. Using both traits, the rate of decline in host health, as parasitemia increased, was more pronounced in 12- than in 2-month old mice, showing that age is also associated with impaired tolerance to malaria. Overall, resistance and tolerance positively covaried; however, this was only due to the age effect, since, within age classes, the two traits were not correlated. These results show that senescing individuals might be both more susceptible to infectious diseases and less able to cope with the damage that infection induces.

Objective: To investigate the effect of Shenfu (SF) injection on donor heart preservation. Methods: Twelve pigs were randomly divided into SF group (n=6) and control group (n=6). After eight hours of perfusion, the differences in hemoglobin, the expression of Bcl-2 and BAX, and changes in the myocardial ultrastructure were compared to illustrate the effects of SF injection in heart preservation. Results: The differences in free hemoglobin between the SF group and the control group were statistically significant (P=0.001), and there was significant interaction of groups with times (P=0.019), but the perfusion time may not be associated with the hemoglobin concentration (P=0.616). According to Western blotting analysis, the expression of Bcl-2 was higher in the SF group than in the control group, while the expression of BAX was not different between the two groups. As to ultrastructural changes, both groups exhibited mitochondrial swelling and myofilament lysis, but the degree of damage in the SF group was smaller. Conclusion: Our study suggests that the application of SF injection for heart preservation may protect against cardiomyocytes and erythrocytes apoptosis, and Bcl-2 protein may play a role in these physiological processes.

Erik Őrfi,1,2 Tamás Mészáros,1,2 Mark Hennies,3 Tamás Fülöp,1,2 László Dézsi,1,2 Alexander Nardocci,1 László Rosivall,1,2 Péter Hamar,4,5 Barry W Neun,6 Marina A Dobrovolskaia,6 János Szebeni,1,2,7,* Gábor Szénási1,8,* 1Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; 2SeroScience LCC., Cambridge, MA, USA; 3TECOdevelopment GmbH, Rheinbach, Germany; 4Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary; 5Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; 6Nanotechnology Characterization Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA; 7Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary; 8Institute of Pathophysiology, Semmelweis University, Budapest, Hungary *These authors contributed equally to this work Purpose: Undesirable complement (C) activation by nanomedicines can entail an adverse immune reaction known as C activation-related pseudoallergy (CARPA) in sensitive patients. The syndrome includes cardiopulmonary, hemodynamic, and a variety of other physiological changes that have been well described in man, pigs, dogs, and rats. However, the information on CARPA is scarce and ambiguous in mice, a species widely used in preclinical studies. The present study aimed to fill this gap by exploring signs of CARPA in mice following i.v. administration of AmBisome and Abelcet, which are nano-formulations of Amphotericin B with high risk to cause CARPA. Materials and methods: Anesthetized NMRI mice were intravenously injected with liposomal amphotericin B (Abelcet and AmBisome; 30–300 mg phospholipid/kg), drug-free high cholesterol multilamellar vesicles (HC-MLV), and positive controls, cobra venom factor (CVF) and zymosan, followed by the measurement of blood pressure (BP), heart rate, white blood cell, and platelet counts and plasma thromboxane B2 (TXB2) levels. C activation was assessed by C3a ELISA, a C3 consumption assay (PAN-C3) and a modified sheep red blood cell hemolytic assay. Results: All test agents, except HC-MLV, caused transient hypertension, thrombocytopenia, and elevation of plasma TXB2, which were paralleled by significant rises of plasma C3a in CVF and zymosan-treated animals, wherein the initial hypertension turned into hypotension and shock. Abelcet and AmBisome caused minor, delayed rise of C3a that was not associated with hypertension. The C3a receptor inhibitor SB-290157 attenuated the hypertension caused by Abelcet and decreased the BP thereafter. Conclusion: The parallelism between C3a anaphylatoxin production and severity of physiological changes caused by the different agents is consistent with CARPA underlying these changes. Although the reactive dose of liposomal phospholipids was substantially higher than that in other species (pigs, dogs), the mouse seems suitable for studying the mechanism of hypersensitivity reactions to liposomal formulations of amphotericin B, a frequent side effect of these drugs. Keywords: hypersensitivity, infusion reactions, zymosan, cobra venom factor, TXB2, cholesterol, anaphylatoxins, platelets

During primate swallowing, tongue base retraction (TBR) drives the food bolus across the oropharynx towards the esophagus and flips the epiglottis over the laryngeal inlet, protecting against penetration and aspiration of food into the airway. Despite the importance of TBR for swallowing performance, the mechanics of TBR are poorly understood. Using biplanar videoradiography (XROMM) of four macaque monkeys, we tested the extrinsic muscle shortening hypothesis, which posits that shortening of the hyoglossus and styloglossus muscles pulls the tongue base posteriorly, and the muscular hydrostat or intrinsic tongue muscle hypothesis, which suggests that, because the tongue is composed of incompressible fluid, intrinsic muscle shortening increases tongue length and displaces the tongue base posteriorly. Our data falsify these hypotheses. Instead we suggest a novel hydraulic mechanism of TBR: shortening and rotation of suprahyoid muscles compresses the tongue between the hard palate, hyoid and mouth floor, squeezing the midline tongue base and food bolus back into the oropharynx. Our hydraulic mechanism is consistent with available data on human tongue swallowing kinematics. Rehabilitation for poor tongue base retraction might benefit from including suprahyoid muscle exercises during treatment.

Control of morbidity associated with schistosomiasis via chemotherapy largely relies on the drug praziquantel. Repeated therapy with praziquantel has created concerns about the possible selection of resistant worms and necessitated the search for novel drugs to treat schistosomiasis. Here, a murine model was infected with Schistosoma mansoni and treated with oral 1,2,6,7-tetraoxaspiro [7.11] nonadecane (N-89), which caused a significant reduction in fecundity and egg burden and reduced morbidity when administered at 5-weeks post-infection. The analysis showed that the mode of action occurred through the ingestion of activated N-89 by the worms, and that there was no direct external effect on the S. mansoni worms. Ultrastructural analysis of the treated worms showed disruptions in the gut lumen and the presence of large volumes of material, suggestive of undigested blood meals or red blood cells. In addition, there were reduced vitelline cells in female worms and damage to sub-tegmental musculature in male worms. Eggs recovered from the treated mice showed both damage to the eggs and the production of immature eggs. Expression of mRNA responsible for gut and digestive function and egg production was also significantly affected by N-89 treatment, whereas control genes for musculature showed no significant changes. Thus, N-89 drastically affected the total digestive function and egg production of S. mansoni worms. Physiological processes requiring heme uptake such as egg production and eggshell formation were subsequently affected, suggesting that the compound could be a possible therapeutic drug candidate for schistosomiasis control.

Background Air ions are molecules of air that have become ionized—that is, they have either lost or gained an electrical charge. Past speculation has suggested that exposure to positive air ions may be harmful to one’s health, while exposure to negative air ions may be associated with beneficial health effects. Air ions arise from natural sources as well as direct-current transmission lines and commercial ionizers. Several recent clinical studies have suggested therapeutic effects of air ions on various types of depression at exposure levels 10- to 1000-fold higher than most previous human studies. The aim of this study was to assess the evidence from studies of laboratory animals for beneficial or adverse effects of air ions on health. Methods Sixty-two studies (1935–2015) in nine topics areas were evaluated for quality and potential systematic bias by ARRIVE guidelines. Standardized mean differences or proportional differences between exposed and control groups were computed for 44 studies to quantitatively assess the strength of the evidence for exposure-related effects. Results Many of the studies were conducted before 1990 and exhibited various reporting and methodological deficiencies, including small sample size, failure to control for the influence of potential confounding variables, lack of randomized assignment to treatment groups and blinded analyses, and statistical errors relating to treating group-exposed animals as individuals. The highest quality studies consistently reported no effects of exposure on any of the endpoints examined. There were no evident dose–response relationships within or across studies. Conclusions Experimental studies of laboratory animals exposed to positive and negative air ions for minutes to years over a five-log unit range of intensities did not suggest any consistent or reliable effects on measures of behavior, learning and memory, neurotransmitters, tracheal function, respiratory infection, cardiovascular function, reproduction and growth, carcinogenesis, or other health endpoints. These data do not provide evidence of adverse or beneficial effects of air ion exposure on health, and did not suggest any biological mechanism of interaction, except perhaps for mechanosensory stimulation of body surfaces by static electric fields at high air ion concentrations. Electronic supplementary material The online version of this article (10.1186/s12938-018-0499-z) contains supplementary material, which is available to authorized users.

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

Parturition is a challenging physiological process with perfect timing dictated by the events leading to the end of pregnancy in the female, and by the maturation of the fetus(es). The process of parturition remains an intricate interaction of hormones in a fine-tuned timing that remains to be better elucidated in the dog. In the dog pregnancy is maintained by the progesterone production by the corpora lutea, in which some hormones play a luteotrophic action. At term of pregnancy, the pre-parturient luteolytic cascade is the most apparent event, characterized by a rapid decline in plasma progesterone concentrations and useful in predicting the onset of spontaneous parturition. In contrast, cortisol plasma concentrations measurement showed high variability and suggested to be related to the stress condition instead of the onset of parturition. Both prostaglandin F2α and E2 concur in the process of parturition in the dog. The measurement of oxytocin plasma concentrations, also very variable, is implicated in uterine contractions. The measurement of plasma oxytocin concentrations showed to be useful to distinguish between normal and disturbed parturition, allowing the prompt recognition of dystocia and the immediate obstetrical intervention. In contrast to other species, no significant roles of estrogens for the initiating of parturition were demonstrated. Relaxin, the main pregnancy hormonal marker in the dog, beside an endocrine action, is also supposed to play a paracrine/autocrine role at the utero-placental unit and to support the maintenance of high plasma progesterone concentrations through a luteotrophic action, concurring to the main action of prolactin. Although important information has been provided, some aspects in the understanding the hormonal interactions and action timing implications in the process of parturition in the dog remains to be better investigated and represent intriguing topic for basic knowledge and applied research.

Ring 1 and YY1 binding protein (RYBP) was first identified in 1999, and its structure includes a conserved Npl4 Zinc finger motif at the N‐terminus, a central region that is characteristically enriched with arginine and lysine residues and a C‐terminal region enriched with serine and threonine amino acids. Over nearly 20 years, multiple studies have found that RYBP functions as an organ developmental adaptor. There is also evidence that RYBP regulates the expression of different genes involved in various aspects of biological processes, via a mechanism that is dependent on interactions with components of PcG complexes and/or through binding to different transcriptional factors. In addition, RYBP interacts directly or indirectly with apoptosis‐associated proteins to mediate anti‐apoptotic or pro‐apoptotic activity in both the cytoplasm and nucleus of various cell types. Furthermore, RYBP has also been shown to act as tumour suppressor gene in different solid tumours, but as an oncogene in lymphoma and melanoma. In this review, we summarize our current understanding of the functions of this multifaceted RYBP in physiological and pathological conditions, including embryonic development, apoptosis and cancer, as well as its role as a component of polycomb repressive complex 1.

The growth hormone (GH)/insulin-like growth factor (IGF) axis plays fundamental roles during development, maturation, and aging. Members of this axis, composed of various ligands, receptors, and binding proteins, are regulated in a tissue-and time-specific manner that requires precise control that is not completely understood. Some of the most recent advances in understanding the implications of this axis in human growth are derived from the identifications of new mutations in the gene encoding the pregnancy-associated plasma protein PAPP-A2 protease that liberates IGFs from their carrier proteins in a selective manner to allow binding to the IGF receptor 1. The identification of three nonrelated families with mutations in the PAPP-A2 gene has shed light on how this protease affects human physiology. This review summarizes our understanding of the implications of PAPP-A2 in growth physiology, obtained from studies in genetically modified animal models and the PAPP-A2 deficient patients known to date., This research was funded by the Spanish Ministry of Science and Innovation with the help of European FEDER funding (FIS PI19/00166 and PI19/00343), Ministerio de Economía y Competitividad (BFU 2017-82565-C2-1-R) and the Network Center for Biomedical Research on Obesity and Nutrition (CIBEROBN) Instituto Carlos III. S.G.-C. was supported by CIBEROBN

The skin is the largest sensory organ of the human body. The skin not only prevents loss of water and other components of the body, but also is involved in regulation of body temperature and serves as an essential barrier, protecting mammals from both routine and extreme environments. Given the importance of the skin in temperature regulation, it is surprising that adaptive alterations in skin functions and morphology only vaguely have been associated with systemic physiological responses. Despite that impaired lipid metabolism in the skin often impairs the epidermal permeability barrier and insulation properties of the skin, its role in regulating systemic physiology and metabolism is yet to be recognized. Lipid metabolism and acyl-chain trafficking must be strictly coordinated to ensure synthesis of structural lipids required for the epidermal barrier and of lipids that are secreted and coat the skin and the fur. Perturbation of ceramide biosynthesis and turnover impairs the epidermal permeability barrier and results in systemic physiologic effects. Cold exposure of the skin is sensed by cold-sensitive thermoreceptors located in the skin, which initiates receptor-mediated neural signaling that ultimately activates thermogenesis in muscle and in brown adipose tissue and increases browning of white adipose tissue. An impaired epidermal permeability barrier has systemic effects on physiology and metabolism including increased calorie intake, energy expenditure, activation of thermogenic mechanisms, increased glucose tolerance, and resistance to diet-induced obesity.

SYNOPSIS A major focus of current ecological research is to understand how global change makes species vulnerable to extirpation. To date, mechanistic ecophysiological analyses of global change vulnerability have focused primarily on the direct effects of changing abiotic conditions on whole-organism physiological traits, such as metabolic rate, locomotor performance, cardiac function, and critical thermal limits. However, species do not live in isolation within their physical environments, and direct effects of climate change are likely to be compounded by indirect effects that result from altered interactions with other species, such as competitors and predators. The Society for Integrative and Comparative Biology 2017 Symposium "Indirect Effects of Global Change: From Physiological and Behavioral Mechanisms to Ecological Consequences" was designed to synthesize multiple approaches to investigating the indirect effects of global change by bringing together researchers that study the indirect effects of global change from multiple perspectives across habitat, type of anthropogenic change, and level of biological organization. Our goal in bringing together researchers from different backgrounds was to foster cross-disciplinary insights into the mechanistic bases and higher-order ecological consequences of indirect effects of global change, and to promote collaboration among fields.

Modeling has enabled fundamental advances in our understanding of the mechanisms of health and disease for centuries, since at least the time of William Harvey almost 500 years ago. Recent technological advances in molecular methods, computation, and imaging generate optimism that mathematical modeling will enable the biomedical research community to accelerate its efforts in unraveling the molecular, cellular, tissue-, and organ-level processes that maintain health, predispose to disease, and determine response to treatment. In this review, we discuss some of the roles of mathematical modeling in the study of human physiology and pathophysiology and some challenges and opportunities in general and in two specific areas: in vivo modeling of pulmonary function and in vitro modeling of blood cell populations.

Since the discovery of the three isoforms of the Na+/Ca2+ exchanger, NCX1, NCX2 and NCX3 in 1990s, many studies have been devoted to identifying their specific roles in different tissues under several physiological or pathophysiological conditions. In particular, several seminal experimental works laid the foundation for better understanding gene and protein structures, tissue distribution, and regulatory functions of each antiporter isoform. On the other hand, despite the efforts in the development of specific compounds selectively targeting NCX1, NCX2 or NCX3 to test their physiological or pathophysiological roles, several drawbacks hampered the achievement of these goals. In fact, at present no isoform-specific compounds have been yet identified. Moreover, these compounds, despite their potency, possess some nonspecific actions against other ion antiporters, ion channels, and channel receptors. As a result, it is difficult to discriminate direct effects of inhibition/activation of NCX isoforms from the inhibitory or stimulatory effects exerted on other antiporters, channels, receptors, or enzymes. To overcome these difficulties, some research groups used transgenic, knock-out and knock-in mice for NCX isoforms as the most straightforward and fruitful strategy to characterize the biological role exerted by each antiporter isoform. The present review will survey the techniques used to study the roles of NCXs and the current knowledge obtained from these genetic modified mice focusing on the advantages obtained with these strategies in understanding the contribution exerted by each isoform.

p53, first described four decades ago, is now established as a master regulator of cellular stress response, the “guardian of the genome”. p53 contributes to biological robustness by behaving in a cellular-context dependent manner, influenced by several factors (e.g., cell type, active signalling pathways, the type, extent and intensity of cellular damage, cell cycle stage, nutrient availability, immune function). The p53 isoforms regulate gene transcription and protein expression in response to the stimuli so that the cell response is precisely tuned to the cell signals and cell context. Twelve isoforms of p53 have been described in humans. In this review, we explore the interactions between p53 isoforms and other proteins contributing to their established cellular functions, which can be both tumour-suppressive and oncogenic in nature. Evidence of p53 isoform in human cancers is largely based on RT-qPCR expression studies, usually investigating a particular type of isoform. Beyond p53 isoform functions in cancer, it is implicated in neurodegeneration, embryological development, progeroid phenotype, inflammatory pathology, infections and tissue regeneration, which are described in this review.

The attachment efficiency of biofouling organisms on solid surfaces depends on a variety of factors, including fouler species, nutrition abundance, flow rate, surface morphology and the stiffness of the solid to which attachment is to be made. So far, extensive research has been carried out to investigate the effects of these factors on the attachment of various fouling species. However, the results obtained are species-dependent and scattered. There is no universal rule that can be applied to predict the attachment efficiency of different species. To solve this problem, the authors carried out meta-analysis of the effects of ten selected factors on attachment efficiency, resulting in a universal correlation between the attachment density and the selected factors, which was validated by attachment tests of tubeworms on PDMS surfaces. The results provide a practical approach to predicting the attachment efficiency of fouling organisms and should be of great value in the design of anti-biofouling materials.

Exposure to methylmercury (MeHg) can result in detrimental health effects in wildlife. With advances in ecological indicators and analytical techniques for measurement of MeHg in a variety of tissues, numerous processes have been identified that can influence MeHg concentrations in wildlife. This review presents a synthesis of theoretical principals and applied information for measuring MeHg exposure and interpreting MeHg concentrations in wildlife. Mercury concentrations in wildlife are the net result of ecological processes influencing dietary exposure combined with physiological processes that regulate assimilation, transformation, and elimination. Therefore, consideration of both physiological and ecological processes should be integrated when formulating biomonitoring strategies. Ecological indicators, particularly stable isotopes of carbon, nitrogen, and sulfur, compound-specific stable isotopes, and fatty acids, can be effective tools to evaluate dietary MeHg exposure. Animal species differ in their physiological capacity for MeHg elimination, and animal tissues can be inert or physiologically active, act as sites of storage, transformation, or excretion of MeHg, and vary in the timing of MeHg exposure they represent. Biological influences such as age, sex, maternal transfer, and growth or fasting are also relevant for interpretation of tissue MeHg concentrations. Wildlife tissues that represent current or near-term bioaccumulation and in which MeHg is the predominant mercury species (such as blood and eggs) are most effective for biomonitoring ecosystems and understanding landscape drivers of MeHg exposure. Further research is suggested to critically evaluate the use of keratinized external tissues to measure MeHg bioaccumulation, particularly for less-well studied wildlife such as reptiles and terrestrial mammals. Suggested methods are provided to effectively use wildlife for quantifying patterns and drivers of MeHg bioaccumulation over time and space, as well as for assessing the potential risk and toxicological effects of MeHg on wildlife.

The microbialization of coral reefs predicts that microbial oxygen consumption will cause reef deoxygenation. Here we tested this hypothesis by analyzing reef microbial and primary producer oxygen metabolisms. Metagenomic data and in vitro incubations of bacteria with primary producer exudates showed that fleshy algae stimulate incomplete carbon oxidation metabolisms in heterotrophic bacteria. These metabolisms lead to increased cell sizes and abundances, resulting in bacteria consuming 10 times more oxygen than in coral incubations. Experiments probing the dissolved and gaseous oxygen with primary producers and bacteria together indicated the loss of oxygen through ebullition caused by heterogenous nucleation on algae surfaces. A model incorporating experimental production and loss rates predicted that microbes and ebullition can cause the loss of up to 67% of gross benthic oxygen production. This study indicates that microbial respiration and ebullition are increasingly relevant to reef deoxygenation as reefs become dominated by fleshy algae., eLife digest Rising water temperatures, pollution and other factors are increasingly threatening corals and the entire reef ecosystems they build. The potential for corals to resist and recover from the stress these factors cause ultimately depends on their ability to compete against fast-growing fleshy algae that can rapidly take over the reefs. Living on the fleshy algae, the coral and in the surrounding water are communities of bacteria and other microbes that help maintain the health of the coral reef. Both corals and algae modify the chemical and physical environment of the reef to alter the composition of the microbial communities for their own benefit. Algae, for instance, release large amounts of sugars and other molecules of organic carbon into the water. These carbon molecules are then taken up by the bacteria, along with oxygen, to produce chemical energy via a process called respiration. This could cause the levels of oxygen in the water to decrease, potentially damaging the corals and creating more open space for the algae. Previous studies have revealed how communities of microbes on coral reefs use organic carbon, but it remains unclear how they affect the levels of oxygen in the reefs. To address this question, Silveira et al. used an approach called metagenomics to analyze the bacteria in samples of water from 87 reefs across the Pacific and the Caribbean, and also performed experiments with reef bacteria grown in the laboratory. The experiments showed that bacteria growing in the presence of fleshy algae became larger and more abundant than bacteria growing near corals, resulting in the water containing lower levels of oxygen. Furthermore, the fleshy algae produced bubbles of oxygen that were released from the water. Silveira et al. developed a mathematical model that predicted that these bubbles, combined with the respiration of bacteria that live near algae, caused the loss of 67% of the oxygen in the water surrounding the reef. These findings represent a fundamental step towards understanding how changes in the levels of oxygen in water affect the ability of coral reefs to resist and recover from stress.

Pyridalyl is one of the recently discovered insecticides which has shown toxicity against several insect pests with slight- or non-lethal effects against natural enemies. Cytotoxicity and prevention of protein synthesis have been reported as pyridalyl mode of action. In the current study, adults of Bacterocera oleae, as a major pest of olive, were fed on protein hydrolysate diet containing LC50 concentration of pyridalyl to determine the possible mode of action through gene expression and amino acid profile. Results showed that treated flies had significantly higher gene expressions of cytochrome P450, insulin receptor-like, antioxidant enzymes (catalase, peroxidase, superoxide dismutase) and the enzymes involved in cell death; caspase1, caspase3, caspase8 and caspase9 compared to control. Moreover, determination of amino acid profile in the whole body of both control and pyridalyl-treated B. oleae revealed the significant higher amounts of glutamic acid, glutamine, histidine, threonine, citrulin, arginine, taurine, alanine, tyrosine, α-amino butric acid, methionine and isoleucine in the treated adults while the control flies had the higher amounts of serine, glycine and tryptophane. No significant differences were found in the amounts of asparagine and phenylalanine between control and treatments. These results are in accordance with earlier findings on mode of action of pyridalyl through activation of cytochrome P450 system and alterations in protein synthesis machinery although here other mechanisms were also reported including activation of insulin receptor and antioxidant enzymes. Moreover, it is the first report on cytotoxicity through apoptosis with engagement of caspases.

Research aimed at more fully emulating human biology in vitro has rapidly progressed in recent years with advancements in 3D tissue engineering and microphysiological systems. The initial target of such systems has been directed towards drug and chemical safety assessment, with the goal of improving sensitivity and predictive capabilities. Here we discuss recent developments of in vitro organ culture systems, and their future applications in modeling human disease.

International audience; Complex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However, epigenetic studies have demonstrated violations to this rule that are necessary for mammalian physiology; the most notable parental allele expression phenomenon is genomic imprinting. With the identification of endogenous imprinted genes, genomic imprinting became well-established as an epigenetic mechanism in which the expression pattern of a parental allele influences phenotypic expression. The expanding study of genomic imprinting is revealing a significant impact on brain functions and associated diseases. Here, we review key milestones in the field of imprinting and discuss mechanisms and systems in which imprinted genes exert a significant role.

Biosensors are composed of (bio)receptors, transducers, and detection systems and are able to convert the biological stimulus into a measurable signal. This systematic review evaluates the current state of the art of innovation and research in this field, identifying the biosensors that in vitro monitor the musculoskeletal system cellular processes. Two databases found 20 in vitro studies, from January 1, 2008 to December 31, 2017, dealing with musculoskeletal system cells. The biosensors were divided into two groups based on the transduction mechanism: optical or electrochemical. The first group evaluated osteoblasts or mesenchymal stem cell (MSC) biocompatibility, viability, differentiation, alkaline phosphatase, enzyme, and protein detection. The second group detected cell impedance, ATP release, and superoxide concentration in tenocytes, osteoblasts, MSCs, and myoblasts. This review highlighted that the in vitro scenario is still at an early phase and limited for what concerns both the type of bioanalyte and for the type of system detector used.

The influence of physical oceanographic processes on the dispersal of larvae is critical for understanding the ecology of species and for anticipating settlement into fisheries to aid long-term sustainable harvest. This study examines the mechanisms by which ocean currents shape larval dispersal and supply to the continental shelf-break, and the extent to which circulation determines settlement patterns using Sagmariasus verreauxi (Eastern Rock Lobster, ERL) as a model species. Despite the large range of factors that can impact larval dispersal, we show that within a Western Boundary Current system, mesoscale circulation explains broad spatio-temporal patterns of observed settlement including inter-annual and decadal variability along 500 km of coastline. To discern links between ocean circulation and settlement, we correlate a unique 21- year dataset of observed lobster settlement (i.e., early juvenilepueruli abundance), with simulated larval settlement. Simulations use outputs of an eddy-resolving, data-assimilated, hydrodynamic model, incorporating ERL spawning strategy and larval duration. The latitude where the East Australian Current (EAC) deflects east and separates from the continent determines the limit between regions of low and high ERL settlement. We found that years with a persistent EAC flow have low settlement while years when mesoscale eddies prevail have high settlement; in fact, mesoscale eddies facilitate the transport of larvae to the continental shelf-break from offshore. Proxies for settlement based on circulation features observed with satellites could therefore be useful in predicting broadscale patterns of settlement orders of magnitudes to guide harvest limits.

Dbl (B-cell lymphoma)-related guanine nucleotide exchange factors (GEFs), the largest family of GEFs, are directly responsible for the activation of Rho family GTPases and essential for a number of cellular events such as proliferation, differentiation and movement. The members of the Ephexin (Eph-interacting exchange protein) family, a subgroup of Dbl GEFs, initially were named for their interaction with Eph receptors and sequence homology with Ephexin1. Although the first Ephexin was identified about two decades ago, their functions in physiological and pathological contexts and regulatory mechanisms remained elusive until recently. Ephexins are now considered as GEFs that can activate Rho GTPases such as RhoA, Rac, Cdc42, and RhoG. Moreover, Ephexins have been shown to have pivotal roles in neural development, tumorigenesis, and efferocytosis. In this review, we discuss the known and proposed functions of Ephexins in physiological and pathological contexts, as well as their regulatory mechanisms.

Physiologically based toxicokinetic (PBTK) modeling enables researchers to predict internal tissue concentrations for various species exposed to exogenous compounds through different routes at varying concentrations without having to run in vivo experiments for each scenario. Parameters for the models may be gathered from in vivo or in vitro measurements, cross-species or cross-chemical extrapolations, literature reviews, or other models. The PBTK models, described using ordinary differential equations (ODEs), are then simulated using these parameters for a given compound/exposure/species scenario. Although they are potentially useful for regulatory toxicology, the complexity of ODE programming and simulation remains a barrier for many would-be researchers. Petri nets, a graphical modeling framework, offers a more intuitive approach to PBTK modeling. To demonstrate their utility and ease of use, we present a model of waterborne fluoranthene exposure to rainbow trout (Oncorhynchus mykiss) written and simulated in Snoopy, a graphical Petri net development and simulation software package. We converted an existing ODE PBTK model and evaluated the Petri net model against the ODE model results. The simulated tissue concentrations of the Petri net model closely mirrored the simulated concentrations of the ODE model. To convert the ODE model to a Petri net model, we introduced a new parameter, blood volume (V BLOOD ). Sensitivity analysis found V BLOOD to be very robust when varied over an order of magnitude. The resulting Petri net PBTK model has a number of advantages over ODE models, while maintaining equivalent predictive functionality. Environ Toxicol Chem 2019;00:1-10. © 2019 SETAC.

International audience; The extracellular matrix is comprised of 1100 core-matrisome and matrisome-associated proteins and of glycosaminoglycans. This structural scaffold contributes to the organization and mechanical properties of tissues and modulates cell behavior. The extracellular matrix is dynamic and undergoes constant remodeling, which leads to diseases if uncontrolled. Bioactive fragments, called matricryptins, are released from the extracellular proteins by limited proteolysis and have biological activities on their own. They regulate numerous physiological and pathological processes such as angiogenesis, cancer, diabetes, wound healing, fibrosis and infectious diseases and either improve or worsen the course of diseases depending on the matricryptins and on the molecular and biological contexts. Several protease families release matricryptins from core-matrisome and matrisome-associated proteins both in vitro and in vivo. The major proteases, which decrypt the extracellular matrix, are zinc metalloproteinases of the metzincin superfamily (matrixins, adamalysins and astacins), cysteine proteinases and serine proteases. Some matricryptins act as enzyme inhibitors, further connecting protease and matricryptin fates and providing intricate regulation of major physiopathological processes such as angiogenesis and tumorigenesis. They strengthen the role of the extracellular matrix as a key player in tissue failure and core-matrisome and matrisome-associated proteins as important therapeutic targets.

Summary This study aimed to systematically investigate the effects of different anaesthetics on postoperative physiological reactions compared with placebo. The literature search was conducted using three databases: PubMed, EMBASE, and the Cochrane Library. Studies published from January 1990 to January 2015 were screened. The language was restricted to English. Heterogeneity was analyzed by the Q test and I2 statistic. A fixed-effect model was used for homogenous data and a random-effects model for heterogeneous data. The odds ratio (OR) and 95% confidence interval (CI) were calculated to monitor the incidences of overall adverse events, arterial blood pressure, and cardiac abnormalities. Sensitivity analysis was performed to estimate the strength of the meta-analysis, and publication bias was analyzed using Egger's test. A total of 24 articles were included in this meta-analysis. There were 1,810 and 1,806 cases in the anaesthetic group and the placebo group, respectively. The incidence of overall adverse events was significantly lower in the anaesthetic group compared with the placebo group (OR = 0.57; 95% CI, 0.38–0.84). No publication bias was observed, and no inverse estimates were calculated using sensitivity analysis. There was no significant difference for the incidence of arterial blood pressure (OR = 4.62; 95% CI, 0.90–23.70) and cardiac abnormalities (OR = 1.18; 95% CI, 0.53–2.63) between the two groups. Although the incidence of overall adverse events was decreased in the anaesthetic group, it is impossible to determine whether the use of anaesthetics during surgical operation has a protective effect on postoperative physiological reactions.

Research on the optical properties of animal integuments, including fur, feather, skin and cuticle, has focussed almost exclusively on animal-visible wavelengths within the narrow range of 300–700 nm. By contrast, the near-infrared (NIR) portion of direct sunlight, spanning 700–2600 nm, has been largely ignored despite its potentially important thermal consequences. We quantified variation in visible and NIR reflectance and transmission for white body contour feathers of 50 bird species, and examined how well they are predicted by feather macro- and micro-structural morphology. Both visible and NIR reflectance of the feathers varied substantially across species. Larger, thicker, and sparser feathers that are characteristic of larger species, and feathers with rounder barbs and more closely spaced barbules, had high average reflectance, particularly within avian-visible wavelengths (300–700 nm). Feathers with rounder barbs and more closely situated barbules also had high average reflectance, particularly for NIR wavelengths. Barb roundness and barbule density were the only predictors of NIR reflectance after accounting for variation in visible reflectance and body size. Our results highlight the potential for adaptive variation in NIR reflectance mediated by feather structure, which may inform the design of functional materials to control light and heat.

Source at https://doi.org/10.7554/eLife.41044.001. Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROSgenerating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice. Myocardial Nox4 levels increase during acute exercise and trigger activation of the transcription factor Nrf2, with the induction of multiple endogenous antioxidants. Cardiomyocyte-specific Nox4- deficient (csNox4KO) mice display a loss of exercise-induced Nrf2 activation, cardiac oxidative stress and reduced exercise performance. Cardiomyocyte-specific Nrf2-deficient (csNrf2KO) mice exhibit similar compromised exercise capacity, with mitochondrial and cardiac dysfunction. Supplementation with an Nrf2 activator or a mitochondria-targeted antioxidant effectively restores cardiac performance and exercise capacity in csNox4KO and csNrf2KO mice respectively. The Nox4/Nrf2 axis therefore drives a hormetic response that is required for optimal cardiac mitochondrial and contractile function during physiological exercise.

A prospective completely randomized experimental study was conducted using 48 animals to evaluate the physiometabolic effects of Agave salmiana fructans as a dietary supplement in healthy Wistar rats. Five fructans concentrations from 5 to 20% (w/w) and one control were used in the rats' diet and were divided into six groups (n=8 rats/group). The treatments were carried out for 35days, during which glucose, cholesterol, triglycerides, body-weight gain, food intake, fecal excretion, organ weights, renal and hepatic functions and a histological analysis of the cecum were evaluated. Glucose, cholesterol, triglycerides, renal and hepatic functions were not significantly affected by any treatment. Body-weight gain and food intake were lower in the rat groups fed fructans than in the control group. Increased fecal excretion (p0.05) was observed only in animals fed 12.5 and 20% fructans. Mice supplemented with fructans exhibited increased weight and length (p0.05) in the cecum and colon. A histological analysis of the cecum showed cellular proliferation with a dose of 12.5% and membrane lysis at doses of 15 and 20%. In conclusion, the inclusion of 12.5% of Agave salmiana fructans in the animals' diets exerts beneficial physiometabolic effects after the seventh treatment day.

Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional pathology. Using machine learning, we discover a spatiotemporal dynamic network that predicts the emergence of major depressive disorder (MDD)-related behavioral dysfunction in mice subjected to chronic social defeat stress. Activity patterns in this network originate in prefrontal cortex and ventral striatum, relay through amygdala and ventral tegmental area, and converge in ventral hippocampus. This network is increased by acute threat, and it is also enhanced in three independent models of MDD vulnerability. Finally, we demonstrate that this vulnerability network is biologically distinct from the networks that encode dysfunction after stress. Thus, these findings reveal a convergent mechanism through which MDD vulnerability is mediated in the brain.

In response to a territory intrusion, neighboring males of the African cichlid fish Astatotilapia burtoni engage in aggressive joint territory defense in a manner that depends on their social role. Here, we examine the possible function of several neuroendocrine and neuromodulator pathways previously implicated in the regulation of complex social behavior. We find that the neuromolecular regulation of aggression during joint territory defense is very much dependent on an individual's role in this context. In neighbors but not in residents, aggression is correlated to gene expression in the medial part of the dorsal telencephalon (area Dm), the putative homolog to the mammalian basolateral amygdala. This correlation is strikingly high for expression of the serotonin receptor 5-HT2c, suggesting the serotonin system is important in regulating context-dependent behavior. Furthermore, by examining candidate gene expression co-variance patterns in area Dm and in the lateral part of the dorsal telencephalon (area Dl), the putative homolog to the mammalian hippocampus, we identify two main patterns: gene expression is co-regulated within, but not across, brain regions, and co-regulation is synergistic rather than antagonistic. Our results highlight the critical effect of social context on both behavior and its neuromolecular basis.

Mathematical models are invaluable tools for understanding the relationships between components of a complex system. In the biological context, mathematical models help us understand the complex web of interrelations between various components (DNA, proteins, enzymes, signaling molecules etc.) in a biological system, gain better understanding of the system as a whole, and in turn predict its behavior in an altered state (e.g. disease). Mathematical modeling has enhanced our understanding of multiple complex biological processes like enzyme kinetics, metabolic networks, signal transduction pathways, gene regulatory networks, and electrophysiology. With recent advances in high throughput data generation methods, computational techniques and mathematical modeling have become even more central to the study of biological systems. In this review, we provide a brief history and highlight some of the important applications of modeling in biological systems with an emphasis on the study of excitable cells. We conclude with a discussion about opportunities and challenges for mathematical modeling going forward. In a larger sense, the review is designed to help answer a simple but important question that theoreticians frequently face from interested but skeptical colleagues on the experimental side: “What is the value of a model?”

We report the effects of protein from different duck products on the intestinal flora and physiology of rats. After 30 days of feeding, rats fed water–boiled salted duck protein had the lowest gut microbial diversity and richness. Allobaculum, Lactobacillus, Coprococcus and Eubacterium increased in rats fed wine-cured duck protein, while rats fed water–boiled salted and wine-cured duck protein showed increased serum urea (UREA) concentrations and serum cholesterol (CHOL) to HDL-cholesterol (HDL C) ratios, but decreased retroperitoneal white adipose tissue (rWAT) and perirenal white adipose tissue (pWAT) to body weight ratios. The changes in gut bacteria were mainly associated with the fat-mass index (weight of rWAT or pWAT to body weight ratio), accompanied by the opposite correlation with UREA content. Significance It showed that protein from different duck products impacted the intestinal flora and caused physiological changes in rats. Different sources of processed protein vary in their digestibility and digestive kinetics, all of which can affect the intestinal microbiota and physiology. We report the effects is an effort to map the complex interactions of “host physiology-nutrition-microbiota” in order to provide some insights into that food processing can be improved to promote beneficial gut microbes and enhance human health.

The world is rapidly changing, and is exhibiting increased variability in environmental conditions. One of the grand challenges of current biology is to understand how, and predict which species will be able to cope with uncertain environments. The goal of this symposium was to explore how integrating physiological mechanisms with behavior and evolutionary ecology can help us understand how organisms cope with uncertainty. Here, we briefly review core principles that emerged in the symposium and topics covered by the presenters. Ecological studies can benefit from considering physiological mechanisms as these mechanisms may indicate constraints and trade-offs. In addition, considering the entire phenotype in an integrated way (the phenome) may reveal how different traits may trade-off or affect each other. Finally, considering the range of phenotypic plasticity is critical in exploring how organisms may cope with uncertainty via plasticity and/or adaptive evolution.