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Climate change has physiological consequences on organisms, ecosystems and human societies, surpassing the pace of organismal adaptation. Hibernating mammals are particularly vulnerable as winter survival is determined by short-term physiological changes triggered by temperature. In these animals, winter temperatures cannot surpass a certain threshold, above which hibernators arouse from torpor, increasing several fold their energy needs when food is unavailable. Here, we parameterized a numerical model predicting energy consumption in heterothermic species and modelled winter survival at different climate change scenarios. As a model species, we used the arboreal marsupial monito del monte (genus Dromiciops), which is recognized as one of the few South American hibernators. We modelled four climate change scenarios (from optimistic to pessimistic) based on IPCC projections, predicting that northern and coastal populations (Dromiciops bozinovici) will decline because the minimum number of cold days needed to survive the winter will not be attained. These populations are also the most affected by habitat fragmentation and changes in land use. Conversely, Andean and other highland populations, in cooler environments, are predicted to persist and thrive. Given the widespread presence of hibernating mammals around the world, models based on simple physiological parameters, such as this one, are becoming essential for predicting species responses to warming in the short term. [ABSTRACT FROM AUTHOR]

The study of the immune function in marine mammals is essential to understand their physiology and can help to improve their welfare in the aquariums. Dedicating efforts to studying marine mammal physiology, pathophysiology, and implementing new diagnostic and therapeutic tools promote progress towards preventive medicine in aquariums by facilitating early detection and treatment of diseases. However, biological and clinical research on marine mammals is currently very limited due to difficult access to these species and their biological samples. With this objective, our group has adapted to marine mammals a commercially available assay routinely used to evaluate the phagocytic capacity of monocytes and granulocytes in human whole blood samples. We adapted IngoflowEx kit to bottlenose dolphins (Tursiops truncatus), beluga whales (Delphinapterus leucas), walruses (Odobenus rosmarus), Patagonian sea lions (Otaria flavescens), and harbor (Phoca vitulina). In this paper, we report the modifications carried out on the original protocol for their correct functioning in marine mammals. We obtained physiological values of phagocytic capacity in each species after repeated sampling for 4 years in various individuals of each species. Specific results revealed that the % phagocytic cells that ingested E.coli in bottlenose dolphins were 59.6 ± 1.27, in walruses 62.6 ± 2.17, in sea lions 57.5 ± 4.3, and in beluga whales 61.7 ± 1.4. In the case of the % phagocytic cells producing respiratory burst in bottlenose dolphins were 34.2 ± 3.6, in walruses 36.3 ± 4.3, in sea lions 40.8 ± 10.2, and in beluga whales 26.3 ± 3.7. These preliminary results can be used as a reference to detect alterations in phagocytic capacity either by immunosuppression or by exacerbation of the response in infectious inflammatory processes. Clinical applicability of the assay was verified in two clinical cases in which Ingoflow was useful to detect immune alterations in two diseased individuals, before and after the onset of clinical signs. [ABSTRACT FROM AUTHOR]

Microplastics are considered an emerging environmental pollutant due to their ubiquitous presence in the environment. However, the potential impact of microplastics on human health warrants further research. Recent studies have reported neurobehavioral and neurotoxic effects in marine and rodent models; however, their impact on the underlying cellular physiology in mammals remains unclear. Herein, we exposed neural stem cells and neural stem cell-derived astrocytes, oligodendrocytes, and neurons to various sizes and concentrations of polystyrene nano- and microplastics. We investigated their cellular uptake, impact on cytotoxicity, and alteration of gene expression through transcriptome profiling. The cell type most affected by decreased viability were astrocytes after 7 days of repeated exposure. Transcriptional analysis showed that 1274 genes were differentially expressed in astrocytes exposed to 500 nm microplastics, but only 531 genes were altered in astrocytes exposed to 50 nm nanoplastics. Both canonical pathway and Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated pathways were involved in neuroinflammation, innate and adaptive immunity, cell migration, proliferation, extracellular matrix remodeling, and cytoskeleton structures. The downregulated pathways were involved in lipid metabolism, specifically fatty acid oxidation and cholesterol metabolism. Our results show that neural stem cell-derived astrocytes repeatedly exposed to nano- and microplastics for 7 days undergo changes that are hallmarks of astrogliosis. [ABSTRACT FROM AUTHOR]

The dive response, or the 'master switch of life', is probably the most studied physiological trait in marine mammals and is thought to conserve the available O2 for the heart and brain. Although generally thought to be an autonomic reflex, several studies indicate that the cardiovascular changes during diving are anticipatory and can be conditioned. The respiratory adaptations, where the aquatic breathing pattern resembles intermittent breathing in land mammals, with expiratory flow exceeding 160 litres s−1 has been measured in cetaceans, and where exposure to extreme pressures results in alveolar collapse (atelectasis) and recruitment upon ascent. Cardiorespiratory coupling, where breathing results in changes in heart rate, has been proposed to improve gas exchange. Cardiorespiratory coupling has also been reported in marine mammals, and in the bottlenose dolphin, where it alters both heart rate and stroke volume. When accounting for this respiratory dependence on cardiac function, several studies have reported an absence of a diving‐related bradycardia except during dives that exceed the duration that is fuelled by aerobic metabolism. This review summarizes what is known about the respiratory physiology in marine mammals, with a special focus on cetaceans. The cardiorespiratory coupling is reviewed, and the selective gas exchange hypothesis is summarized, which provides a testable mechanism for how breath‐hold diving vertebrates may actively prevent uptake of N2 during routine dives, and how stress results in failure of this mechanism, which results in diving‐related gas emboli. What is the topic of this review?Current knowledge of the respiratory physiology in small cetaceans and its influence on cardiac function.What advances does it highlight?The selective gas exchange hypothesis is presented, which is a framework for how marine mammals manage gases during diving and is based upon the current understanding of cardiorespiratory coupling in breath‐hold diving vertebrates. [ABSTRACT FROM AUTHOR]

The majority of a mammal's physiology and behavior are time-dependent due to an innate "circadian" clock. Consequently, it is not unexpected that numerous facets of In pharmacology and medicine, the discovery of the biological clock has challenged some long-held beliefs and theories. The only way to cure diseases brought on by disruptions or dysregulation of the biological clock is to reset it. Numerous natural and lifestyle factors cause the clock to become deregulate. This review sheds light on the several chronotherapeutic medicines that have been identified and tested recently. The 24-hour clocks are also used to drive oscillations in toxicology and pharmacology.Circadian pharmacokinetics are based on daily fluctuations in the quantity of proteins required for medication absorption or metabolism; circadian pharmacodynamics are based on daily fluctuations in the physiological systems that these drugs target. The majority of bodily cells have these clocks, although they are arranged hierarchically. It's interesting to note that while some elements of physiology and behavior are directly regulated by a "slave" oscillator located in different brain areas or bodily tissues, others are regulated by a "master clock" located in the suprachiasmatic nuclei of the hypothalamus. [ABSTRACT FROM AUTHOR]

Autophagy is a widespread biological process that controls cellular growth, survival, development, and death. Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity. Most of the fundamental physiological processes in mammals, such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism, are governed by circadian rhythms. Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions. Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock. The potential regulatory connection between the two has been a popular subject of clinical and fundamental research. Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future. The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm, as well as the pathological importance of the disrupted regulatory association between these two phenomena. [ABSTRACT FROM AUTHOR]

Stranded animals offer valuable information on marine mammal physiology and pathology; however, the decomposition state of the carcasses and lack of a rigorous cold chain for sample preservation can sometimes discourage diagnostic analyses based on nucleic acid detection. The present paper aims at evaluating the reliability of FTA® card tissue imprints as an alternative matrix to frozen tissues for virological analyses based on biomolecular methods. Given the contribution of Cetacean morbillivirus (CeMV) to strandings and the increase of herpesvirus detection in cetaceans, these two pathogens were selected as representative of RNA and DNA viruses. Dolphin morbillivirus (DMV) and herpesvirus presence was investigated in parallel on tissue imprints on FTA® cards and frozen tissues collected during necropsy of dolphins stranded in Italy. Samples were analysed by nested RT-PCR for DMV and nested-PCR for herpesvirus. Only one animal was positive for herpesvirus, hampering further considerations on this virus. DMV was detected in all animals, both in FTA® card imprints and tissue samples, with differences possibly related to the decomposition condition category of the carcasses. Tissue sampling on FTA® cards seems a promising alternative to frozen tissues for biomolecular analyses, especially when ensuring adequate storage and shipment conditions for frozen tissues is difficult. [ABSTRACT FROM AUTHOR]

Sodium (Na) plays a critical role in the functioning of terrestrial ecosystems. In Na‐poor regions, plant consumers may experience Na deficiency and adapt by seeking supplementary Na resources. This can markedly impact animal behavior, space‐use, and co‐existence, with concomitant impacts on ecosystems. Many studies have noted that Na‐seeking behaviors, such as soil consumption from mineral licks, are predominately observed for larger‐bodied herbivores. However, the mechanisms that drive interspecific variation in Na deficiency and mineral lick use remain poorly understood. Here, we examine whether allometric scaling of Na requirements can explain variation in mineral lick use by herbivorous and omnivorous mammals. We 1) collated data from published literature to derive an allometric scaling of Na requirements in mammals, 2) compared predicted Na requirements to estimated Na intake of mammal communities in three globally distant sites: the Peruvian Amazon, Kalahari Desert, and Malaysian Borneo and 3) examined the relationship between predicted Na deficiency and mineral lick use utilizing camera‐trap and mammal abundance data at each site. We found that minimum daily Na maintenance requirements in mammals scaled allometrically at a higher factor (BM0.91 (CI: 0.80–1.0)) than that of food and water Na intake (BM0.71–0.79), indicating that larger species may be more susceptible to Na limitation. This aligned with a positive association between mineral lick use and body mass (BM), as well as Na deficiency, by species at all sites, and increased artificial salt and mineral lick consumption by larger‐bodied mammals in the Kalahari. Our results suggest that larger herbivores may be more sensitive to anthropogenic impacts to Na availability, which may alter their functional roles in ecosystems, particularly in Na‐poor regions. Further research is needed to explore the consequences of changing Na availability on animals and ecosystems, as well as advance our understanding of Na physiology in mammals. [ABSTRACT FROM AUTHOR]

Introduction: Asprosin is an adipokine released from white adipose tissue during fasting and acts through the olfactory receptor. It is known that adipokines play roles in reproductive physiology in mammals. However, there are very few studies conducted on role of asprosin in reproductive functions. There are no studies on its relationship with sexual motivation. It was shown in the literature that administration of asprosin to male mice improves olfaction. It is also known that there is a strong correlation between smell and sexual desire. In view of this, it was hypothesized that chronic administration of asprosin would improve olfactory performance and increase sexual incentive motivation in female rats for male partners. Methods: This hypothesis was tested by applying the hidden cookie test, sexual incentive test, active research test, and sexual behavior test. The changes in serum hormone levels in female rats that chronically received asprosin were also measured and compared. Results: Chronic asprosin exposure increased olfactory performance, male preference ratio, male investigation preference ratio, activity index, and anogenital investigation behavior. Also, serum oxytocin and estradiol levels increased following chronic administration of asprosin in female rats. Conclusion: These data suggest that chronic administration of asprosin can result in increased sexual incentive motivation for opposite sex in female rats over increased olfactory performance and changes in reproductive hormones. [ABSTRACT FROM AUTHOR]

Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of deer mice (Peromyscus maniculatus), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between gestational parent and fetus. We then use compartment-specific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify candidate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia. [ABSTRACT FROM AUTHOR]

Avian anesthesia is a controversial area of study due to the differences between birds and mammals morpho physiology. This makes necessary to develop reliable protocols for birds in captivity, which contributes to their welfare under human care. Bird anesthesiology today represents a veterinary clinical activity that demands special care for patients requiring surgical procedures. This study describes the parameters of SpO2, cardiac activity, heart and respiratory rate during anesthesia with isoflurane for Melopsittacus undulatus. 12 males and 7 females were monitored during the anesthetic stages. Anesthetic induction lasted 1:30 ± 0:31 min in males and 2:19 ± 0:16 min in females, with an average maintenance time of 7:00 ± 1:39 min. No significant differences were found in anesthetic times between females and males (p>0.05). There was a statistically significant variation (p<0.05) of SpO2 in the recovery period, females had higher oxygen saturation (71±4%) compared to males (89±2%). In the assessment of cardiac function during anesthesia, no significant differences were detected between males and females (p>0.05). It is concluded as a safe anesthetic protocol for clinical procedures of short duration for small birds such as M. undulates. [ABSTRACT FROM AUTHOR]

Hibernation is a natural model of extreme physiology in a mammal. Throughout winter, small hibernators repeatedly undergo rapid, dramatic swings in body temperature, perfusion, and oxygen delivery. To gain insight into the molecular mechanisms that support homeostasis despite the numerous challenges posed by this dynamic physiology, we collected 13-lined ground squirrel adrenal glands from at least five individuals representing six key timepoints across the year using body temperature telemetry. Differentially expressed genes were identified using RNA-seq, revealing both strong seasonal and torpor-arousal cycle effects on gene expression. Two novel findings emerge from this study. First, transcripts encoding multiple genes involved in steroidogenesis decreased seasonally. Taken together with morphometric analyses, the data are consistent with preservation of mineralocorticoids but suppression of glucocorticoid and androgen output throughout winter hibernation. Second, a temporally orchestrated, serial gene expression program unfolds across the brief arousal periods. This program initiates during early rewarming with the transient activation of a set of immediate early response (IER) genes, comprised of both transcription factors and the RNA degradation proteins that assure their rapid turnover. This pulse in turn activates a cellular stress response program to restore proteostasis comprised of protein turnover, synthesis, and folding machinery. These and other data support a general model for gene expression across the torpor-arousal cycle that is facilitated in synchrony with whole body temperature shifts; induction of the immediate early response upon rewarming activates a proteostasis program followed by a restored tissue-specific gene expression profile enabling renewal, repair, and survival of the torpid state. [ABSTRACT FROM AUTHOR]

Long-term recording of a person's activity (actimetry or actigraphy) using devices typically worn on the wrist is increasingly applied in sleep/wake, chronobiological, and clinical research to estimate parameters of sleep and sleep-wake cycles. With the recognition of the importance of light in influencing these parameters and with the development of technological capabilities, light sensors have been introduced into devices to correlate physiological and environmental changes. Over the past two decades, many such new devices have appeared from different manufacturers. One of the aims of this review is to help researchers and clinicians choose the data logger that best fits their research goals. Seventeen currently available light-and-motion recorders entered the analysis. They were reviewed for appearance, dimensions, weight, mounting, battery, sensors, features, communication interface, and software. We found that all devices differed from each other in several features. In particular, six devices are equipped with a light sensor that can measure blue light. It is noteworthy that blue light most profoundly influences the physiology and behavior of mammals. As the wearables market is growing rapidly, this review helps guide future developments and needs to be updated every few years. [ABSTRACT FROM AUTHOR]

Prospective epidemiological studies in industrial societies indicate that 7 h of sleep per night in people aged 18 years or older is optimum, with higher and lower amounts of sleep predicting a shorter lifespan. Humans living a hunter-gatherer lifestyle (eg, tribal groups) sleep for 6-8 h per night, with the longest sleep durations in winter. The prevalence of insomnia in hunter-gatherer populations is low (around 2%) compared with the prevalence of insomnia in industrial societies (around 10-30%). Sleep deprivation studies, which are done to gain insights into sleep function, are often confounded by the effects of stress. Consideration of the duration of spontaneous daily sleep across species of mammals, which ranges from 2 h to 20 h, can provide important insights into sleep function without the stress of deprivation. Sleep duration is not related to brain size or cognitive ability. Rather, sleep duration across species is associated with their ecological niche and feeding requirements, indicating a role for wake-sleep balance in food acquisition and energy conservation. Brain temperature drops from waking levels during non-rapid eye movement (non-REM) sleep and rises during REM sleep. Average daily REM sleep time of homeotherm orders is negatively correlated with average body and brain temperature, with the largest amount of REM sleep in egg laying (monotreme) mammals, moderate amounts in pouched (marsupial) mammals, lower amounts in placental mammals, and the lowest amounts in birds. REM sleep might, therefore, have a key role in the regulation of temperature and metabolism of the brain during sleep and in the facilitation of alert awakening. [ABSTRACT FROM AUTHOR]

Sam worked with and cared for many dolphins in his career, but no memory of Sam would be complete without mentioning the most important dolphin in Sam's life - Tuffy. Sam's book, I Dolphin Doctor i , is a testament to the special relationship between Sam and Tuffy (Ridgway, 1987). GRAPH Sam Ridgway, also known as the "Dolphin Doctor", was a giant in the field of marine mammalogy with impacts that spread from marine mammal veterinary medicine, to dive physiology, and bioacoustics. [Extracted from the article]

The ability to maintain a high core body temperature is a defining characteristic of all mammals, yet their diverse habitats present disparate thermal challenges that have led to specialized adaptations. Marine mammals inhabit a highly conductive environment. Their thermoregulatory capabilities far exceed our own despite having limited avenues of heat transfer. Additionally, marine mammals must balance their thermoregulatory demands with those associated with diving (i.e. oxygen conservation), both of which rely on cardiovascular adjustments. This review presents the progress and novel efforts in investigating marine mammal thermoregulation, with a particular focus on the role of peripheral perfusion. Early studies in marine mammal thermal physiology were primarily performed in the laboratory and provided foundational knowledge through in vivo experiments and ex vivo measurements. However, the ecological relevance of these findings remains unknown because comparable efforts on free-ranging animals have been limited. We demonstrate the utility of biologgers for studying their thermal adaptations in the context in which they evolved. Our preliminary results from freely diving northern elephant seals (Mirounga angustirostris) reveal blubber's dynamic nature and the complex interaction between thermoregulation and the dive response due to the dual role of peripheral perfusion. Further exploring the potential use of biologgers for measuring physiological variables relevant to thermal physiology in other marine mammal species will enhance our understanding of the relative importance of morphology, physiology, and behavior for thermoregulation and overall homeostasis. [ABSTRACT FROM AUTHOR]

Male and female stump-tailed macaques (Macaca arctoides) form close relationships akin to human friendships. Oxytocin and vasopressin modulate these and other social relationships and reproductive behavior and physiology in various mammal species. Besides the behavioral effects of oxytocin, this hormone plays an essential role in the ejaculatory process, favoring sperm transport upward the female reproductive tract. Therefore, we investigated the influence of friendships on postcopulatory serum levels of oxytocin and vasopressin in the stump-tailed macaque (Macaca arctoides). In addition, we searched for a correlation between this kind of social relationship and sperm transport in the vagina during the periovulatory and luteal phases. Six female and six male adult macaques having different friendship indices served as experimental animals. Allocated in 57 mating pairs combinations, these animals were allowed to copulate once in the luteal and periovulatory phases. Blood samples were collected from each animal finishing copulation to measure oxytocin and vasopressin. Afterward, we profoundly sedated the females and collected three semen samples from the vagina every 10 min to perform spermatobioscopies. Males' post-copulation oxytocin values increased along with the friendship index, while vasopressin behaves oppositely. Sperm concentration and immotile and motile sperm decreased from one sample to another as male-female closeness increased. Finally, in the periovulatory phase, only in the first vaginal sample, sperm velocities significantly increased with friendship indices. Our results showed that in stump-tailed macaques, heterosexual friendships promote higher postcopulatory oxytocin concentrations and better physiological conditions to males, which probably enhance reproductive success. • Males' post-copulatory oxytocin increase in relation to the strength of the male-female friendship. • Semen characteristics are better when copulation occur between friends. • Heterosexual friendships appear to enhance semen migration from the vagina to the uterus. • Vasopressin does not play a significant role in male stump-tailed macaques post-copulation behavior or ejaculate quality. [ABSTRACT FROM AUTHOR]

In the 1940s, Scholander and Irving revealed fundamental physiological responses to forced diving of marine mammals and birds, setting the stage for the study of diving physiology. Since then, diving physiology research hasmoved from the laboratory to the field. Modern biologging, with the development of microprocessor technology, recorder memory capacity and battery life, has advanced and expanded investigations of the diving physiology of marine mammals and birds. This review describes a brief history of the start of field diving physiology investigations, including the invention of the time depth recorder, and then tracks the use of biologging studies in four key diving physiology topics: heart rate, blood flow, body temperature and oxygen store management. Investigations of diving heart rates in cetaceans and O2 store management in diving emperor penguins are highlighted to emphasize the value of diving physiology biologging research. The review concludes with current challenges, remaining diving physiology questions and what technologies are needed to advance the field. [ABSTRACT FROM AUTHOR]

The genus status of Urocricetus was defined recently based on morphological and molecular data. Even though the amount of evidence for a separate phylogenetic position of this genus among Cricetinae continues to increase, there is still no consensus on its relationship to other groups. Here we give the first comprehensive description of the U. kamensis karyotype (2n = 30, NFa = 50) including results of comparative cytogenetic analysis and detailed examination of its phylogenetic position by means of numerous molecular markers. The molecular data strongly indicated that Urocricetus is a distant sister group to Phodopus. Comparative cytogenetic data showed significant reorganization of the U. kamensis karyotype compared to karyotypes of all other hamsters investigated earlier. The totality of findings undoubtedly means that Urocricetus belongs to a separate divergent lineage of Cricetinae. [ABSTRACT FROM AUTHOR]

Diet shifts can alter tissue fatty acid composition in birds, which is subsequently related to metabolic patterns. Eicosanoids, short-lived fatty acid-derived hormones, have been proposed to mediate these relationships but neither baseline concentrations nor the responses to diet and exercise have been measured in songbirds. We quantified a stable derivative of the vasodilatory eicosanoid prostacyclin in the plasma of male European Starlings (Sturnus vulgaris , N = 25) fed semisynthetic diets with either high (PUFA) or low (MUFA) amounts of n6 fatty acid precursors to prostacyclin. Plasma samples were taken from each bird before, immediately after, and two days following a 15-day flight-training regimen that a subset of birds (N = 17) underwent. We found elevated prostacyclin levels in flight-trained birds fed the PUFA diet compared to those fed the MUFA diet and a positive relationship between prostacyclin and body condition, indexed by fat score. Prostacyclin concentrations also significantly decreased at the final time point. These results are consistent with the proposed influences of precursor availability (i.e., dietary fatty acids) and regulatory feedback associated with exercise (i.e., fuel supply and inflammation), and suggest that prostacyclin may be an important mediator of dietary influence on songbird physiology. [Display omitted] • Eicosanoid hormones mediate dietary influence physiology in mammals and poultry. • We measured the eicosanoid prostacyclin, a vasodilator, in songbirds. • Plasma prostacyclin levels were linked to both dietary fatty acids and activity. • Eicosanoid levels in songbirds were likely constrained by precursor availability. • Endurance exercise likely modulates the scope of eicosanoid signaling pathways. [ABSTRACT FROM AUTHOR]

Jaw morphology is closely linked to both diet and biomechanical performance, and jaws are one of the most common Mesozoic mammal fossil elements. Knowledge of the dietary and functional diversity of early mammals informs on the ecological structure of palaeocommunities throughout the longest era of mammalian evolution: the Mesozoic. Here, we analyse how jaw shape and mechanical advantage of the masseter (MAM) and temporalis (MAT) muscles relate to diet in 70 extant and 45 extinct mammals spanning the Late Triassic-Late Cretaceous. In extant mammals, jaw shape discriminates well between dietary groups: insectivores have long jaws, carnivores intermediate to short jaws, and herbivores have short jaws. Insectivores have low MAM and MAT, carnivores have low MAM and high MAT, and herbivores have high MAM and MAT. These traits are also informative of diet among Mesozoic mammals (based on previous independent determinations of diet) and set the basis for future ecomorphological studies. Nuria Melisa Morales-García et al. analyze jaw shape and mechanical advantage of 70 small modern mammals and 45 Mesozoic mammals and find that these metrics can be used to distinguish dietary groups for most extant mammals, and to infer diet in Mesozoic taxa. [ABSTRACT FROM AUTHOR]

Species that live in degraded habitats often show signs of physiological stress. Glucocorticoid hormones (e.g., corticosterone and cortisol) are often assessed as a proxy of the extent of physiological stress an animal has experienced. Our goal was to quantify glucocorticoids in free-ranging small mammals in fragments of Interior Atlantic Forest. We extracted glucocorticoids from fur samples of 106 small mammals (rodent genera Akodon and Oligoryzomys, and marsupial genera Gracilinanus and Marmosa) from six forest fragments (2–1200 ha) in the Reserva Natural Tapytá, Caazapá Department, Paraguay. To our knowledge, this is the first publication of corticosterone and cortisol levels for three of the four sampled genera (Akodon, Oligoryzomys, and Marmosa) in this forest system. We discovered three notable results. First, as predicted, glucocorticoid levels were higher in individuals living withing small forest fragments. Second, animals captured live using restraint trapping methods (Sherman traps) had higher glucocorticoid levels than those animals captured using kill traps (Victor traps), suggesting that hair glucocorticoid measures can reflect acute stress levels in addition to long-term glucocorticoid incorporation. These acute levels are likely due to urinary steroids diffusing into the hair shaft. This finding raises a concern about the use of certain trapping techniques in association with fur hormone analysis. Finally, as expected, we also detected genus-specific differences in glucocorticoid levels, as well as cortisol/corticosterone ratios. [ABSTRACT FROM AUTHOR]

Monotremes are a group of egg-laying mammals, possessing a mosaic of ancestral and derived anatomical features. Despite much interest in monotremes from phylogenetic, morphological, and ecological perspectives, they have been the subject of relatively few biomechanical studies. In this study, we examined shoulder and proximal forelimb muscle anatomy and architecture in the short-beaked echidna, Tachyglossus aculeatus, through contrast-enhanced computed tomography and gross dissection. Muscle architecture is a major determinant of muscle function and can indicate specialized muscle roles, such as the capacity for generating large forces (through large physiological cross-sectional area, PCSA) or working ranges (through long fascicle lengths). We hypothesized that some muscles would exhibit architectural specializations convergent with other fossorial and/or sprawling animals, and that other muscles would reflect the echidna's unusual anatomy and locomotor style. Instead, we found the shoulder and proximal forelimb muscles in echidna to have little variation in their architecture. The muscles generally had long fascicles and small-to-intermediate PCSAs, consistent with force production over a wide working range. Further, muscles did not show overt differences in architecture that, in therian mammals, have been linked to increased forelimb mobility and the transition from sprawling to parasagittal posture. Our measures of architectural disparity placed the echidna closer to the tegu lizard than other sprawling fossorial mammals (e.g., mole). The low architectural diversity found in the echidna's shoulder and proximal forelimb muscles is interpreted as a lack of functional specialization into distinct roles. We hope our study will contribute to greater understanding of monotreme anatomy and biomechanical function, and to the reconstruction of musculoskeletal evolution in mammals. [ABSTRACT FROM AUTHOR]

There are marked differences between the physiology of birds and mammals. These reflect the evolutionary distance between the two classes with the last common ancestor estimated as existing 318 million years ago. There are analogous organ systems in birds and mammals. However, marked differences exist. For instance, in the avian gastro-intestinal tract, there is a crop at the lower end of the esophagus. This functions both to store feed and for microbial action. The avian immune system lacks lymph nodes and has a distinct organ producing B-lymphocytes, namely the bursa Fabricius. The important of spleen has been largely dismissed until recently. However, its importance in both innate and specific immunity is increasingly recognized. There is a major difference between birds and mammals is the female reproductive system as birds produce large yolk filled eggs. The precursors of the yolk are synthesized by the liver. Another difference is that there is a single ovary and oviduct in birds. [ABSTRACT FROM AUTHOR]

Background: High rumen-degradable starch (RDS) diets decrease milk fat. The increase of LPS in plasma associated with increased RDS impairs liver function, immune response and lipid metabolism, which depress the precursors for milk fat.Objective: This study investigated the mechanism of depression of milk fat precursors in the liver and small intestine of dairy goats fed different RDS diets.Method: Eighteen Guanzhong lactating goats (second lactation, 45.8 ± 1.54 kg) and 6 ruminally cannulated dairy goats (aged 2-3 y, 54.0 ± 2.40 kg) were fed 3 different diets with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) for 36 and 21 d, respectively, in experiments 1 and 2. The liver metabolites and jejunal microbiota in experiment 1 and LPS concentrations in rumen fluid and plasma in experiment 2 were measured. One-way ANOVA was used to analyze the biochemical parameters and mRNA or protein expression. The MIXED procedure was used to analyze LPS concentrations.Results: In experiment 1, the HRDS diet showed increased activity of alkaline phosphatase (27.4 to 41.4 U/L) in plasma (P < 0.05) compared with LRDS treatment. The HRDS diet significantly increased the hepatic concentrations of l-carnitine (129%), l-palmitoylcarnitine (306%), taurochenodeoxycholate (856%), and taurodeoxycholic acid (588%) in liver (variable importance in the projection > 1, P < 0.10) compared with the LRDS treatment. Goats fed the HRDS diet had 33.6% greater liver protein expression of carnitine palmitoyltransferase-1 (P < 0.05), and greater relative abundance of Firmicutes and Ruminococcus 2 in the jejunal content (linear discriminant analysis > 2.0, P < 0.05) than did goats fed LRDS diet. In experiment 2, goats fed the HRDS diet had greater LPS concentrations in rumen fluid (7.57 to 13.6 kEU/mL) and plasma (0.037 to 0.179 EU/mL) (P < 0.05) than did goats fed LRDS diet.Conclusions: Feeding the HRDS diet promoted hepatic lipid β-oxidation and disrupted phospholipid and bile acids metabolisms in liver, thereby reducing the supply of lipogenic precursors to the mammary gland in dairy goats. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end products (RAGE) plays a key role in mammal physiology and in the etiology and progression of inflammatory and oxidative stress-based diseases. In adults, RAGE expression is normally high only in the lung where the protein concentrates in the basal membrane of alveolar Type I epithelial cells. In diseases, RAGE levels increase in the affected tissues and sustain chronic inflammation. RAGE exists as a membrane glycoprotein with an ectodomain, a transmembrane helix, and a short carboxyl-terminal tail, or as a soluble ectodomain that acts as a decoy receptor (sRAGE). VC1 domain is responsible for binding to the majority of RAGE ligands including advanced glycation end products (AGEs), S100 proteins, and HMGB1. To ascertain whether other ligands exist, we analyzed by MS the material pulled down by VC1 from human plasma. Twenty of 295 identified proteins were selected and associated to coagulation and complement processes and to extracellular matrix. Four of them contained a g-carboxyl glutamic acid (Gla) domain, a calcium-binding module, and prothrombin (PT) was the most abundant. Using MicroScale thermophoresis, we quantified the interaction of PT with VC1 and sRAGE in the absence or presence of calcium that acted as a competitor. PT devoid of the Gla domain (PT des-Gla) did not bind to sRAGE, providing further evidence that the Gla domain is critical for the interaction. Finally, the presence of VC1 delayed plasma clotting in a dose-dependent manner. We propose that RAGE is involved in modulating blood coagulation presumably in conditions of lung injury. [ABSTRACT FROM AUTHOR]

Introduction: The impala is a widely distributed African ungulate. Detailed studies of the placenta and ovaries in impala undertaken in the 1970s did not address the endocrine functions of the placenta.Methods: The uteri of 25 pregnant impala estimated to be between 49 and 113 days of the 190 day gestation were examined grossly, histologically and immunohistochemically.Results: A single corpus luteum was present in either maternal ovary but the conceptus was always situated in the right uterine horn. The fetal membranes extended to the tips of both uterine horns. The amnion was in intimate contact with, but not fused to, the allantochorion. Placentation was typically ruminant with fetal macrocotyledons attached to the rows of maternal caruncles. The fetal villi were highly branched, especially in the centre of each placentome where the attenuated maternal epithelium lining the placental crypts was absent in some places. Both the corpus luteum and the uninucleate trophoblast cells of the interplacentomal allantochorion stained strongly for 3-β hydroxysteroid dehydrogenase, and progestagen concentrations in allantoic and amniotic fluids increased significantly as gestation progressed, with a tendency to do likewise in maternal serum. Binucleate trophoblast cells stained positively for bovine placental lactogen, but neither the placenta nor the maternal corpus luteum showed evidence of oestrogen synthesis.Discussion: Despite exhibiting the same basic type of placentation, both the gross and histological structure of the impala placenta, along with its immunohistochemical properties, demonstrates that great variation exists across ruminant placentas. [ABSTRACT FROM AUTHOR]

As 2020 is "The Year of the Rat" in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became preeminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages. Herein, we compare and contrast the mouse and rat in the context of several biological domains relevant to their use as appropriate models of aging: phylogeny/domestication, longevity interventions, pathology/physiology, and behavior/cognition. It is not the goal of this review to give a complete characterization of the differences between mice and rats, but to provide important examples of why using rats as well as mice is important to advance our understanding of the biology of aging. [ABSTRACT FROM AUTHOR]

Many factors, including the inner status of the individuals and external environment, can influence the parasite infections and stress physiology in mammals. Here, we explored the influence of the sex, age, reproductive season and seasonal food availability on the parasitism and stress physiology in wild giant pandas (Ailuropoda melanoleuca) through nutrient and steroid hormone analysis and parasitic infection measurement. Diet composition had significant influences on the faecal cortisol levels and parasite load of wild giant pandas. The seasonal dynamic of the cortisol levels and parasite load in faeces co-vary with the seasonal nutrient intake levels of the pandas, which concurrently arrived the peaks at the wood bamboo shoot-eating period in May (parasite infection intensity, 41.47 ± 12.11 eggs/g of wet faeces; cortisol levels, 619.34 ± 70.55 ng/g dry faeces) that the nutrition intake by wild pandas was the highest (protein/fibre, 69.23 ± 9.93). Meanwhile, age class is also as an important factor to affect the parasite load and stress physiology of wild giant pandas. Cubs and sub-adults suffered more helminth burden and stress physiology than adults and old individuals. This is the first study to evaluate the inner and external factors influence on parasitism and stress physiology in wild giant pandas. The findings facilitate a better understanding of how environmental factors might influence the physiology, behaviour and health of pandas and other species and have implications for the conservation and management of the endangered species. [ABSTRACT FROM AUTHOR]

Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers. [ABSTRACT FROM AUTHOR]

Various endocrine factors that regulate energy homeostasis are also implicated in the reproductive physiology of mammals. However, the hormonal link between metabolism and reproduction in fish is poorly understood. Ghrelin is a multifunctional hormone with both metabolic and reproductive roles in vertebrates. Post-translational acylation by ghrelin-O-acyltransferase (GOAT) is critical for its biological actions. The expression of ghrelin, ghrelin or growth hormone secretagogue receptor (GHSR), and GOAT (which forms the ghrelinergic system) in fish under metabolic stress remains unclear. In this research, we used RT-qPCR and Western blot analysis to determine the expression of the ghrelinergic system in goldfish (during the reproductively active phase) hypothalamus and gonads under 7 and 28 days of fasting. We found a significant increase in preproghrelin mRNA expresson in the ovary, and GOAT mRNA expression in the testis of goldfish deprived of food for 7 days. In fish deprived of food for 28 days, preproghrelin, GHSR and GOAT mRNA expression was significantly increased in the hypothalamus of male goldfish. Such differences were not observed in the hypothalamus of female fish, and in the testis of 28 days fasted fish. Meanwhile, preproghrelin, GHSR, and GOAT expression (both mRNA and protein) was significantly increased in the ovary of female fish fasted for 28 days. Ghrelin has been shown to suppress oocyte maturation in fish. The upregulation of a system that has ovarian inbititory roles suggests a role for ghrelin in maintaining reduced reproductive capability during metabolically challenging periods. Unlabelled Image • Ghrelinergic system is modulated by food deprivation. • Changes in ghrelin in ovary support its suppressive role on oocytes. • Food deprivation induced changes in ghrelin in the brain and ovary are dissimilar. [ABSTRACT FROM AUTHOR]

The evidence that diel patterns of physiology and behaviour in mammals are governed by circadian ‘clocks’ is based almost entirely on studies of nocturnal rodents. The emergent circadian paradigm, however, neglects the roles of energy metabolism and alimentary function (feeding and digestion) as determinants of activity pattern. The temporal control of activity varies widely across taxa, and ungulates, microtine rodents, and insectivores provide examples in which circadian timekeeping is vestigial. The nocturnal rodent/human paradigm of circadian organisation is unhelpful when considering the broader manifestation of activity patterns in mammals. [ABSTRACT FROM AUTHOR]

Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4. A cross-sectional case-control study included 288 individuals (61% women, 34[±11] years old, diabetes duration of 22[±9] years, mean [±SD]) sorted according to DR stages: absence of DR (ADR), non-proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed. The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38–13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11–0.80, p = 0.017) in female T1D individuals. The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication. • Proliferative diabetic retinopathy is not fully explained by glucose control. • Genetics also plays an important role in diabetic retinopathy susceptibility. • Redox imbalance is associated with diabetic microvascular complications. • Glutathione (GSH) is one of the major antioxidants in the body. • Variants in genes from GSH system modulate proliferative diabetic retinopathy risk. [ABSTRACT FROM AUTHOR]

Gala Lake National Park (GLNP) consists of terrestrial and aquatic ecosystems covering 6.087 hectares of area in Enez and İpsala district boundaries of Edirne province. Extensive field studies were performed on mammals within the boundaries of GLNP for 26 days from 29 July to 07 November 2016. A total of 44 mammalian species from 16 families within 6 orders were determined in the studied area and an up-to-date inventory of mammals was prepared. Myocastor coypus (coypu) were detected as an invasive species in the region. [ABSTRACT FROM AUTHOR]

Acetamiprid (ACP) belonging to the neonicotinoid family used against wide array of pests in agriculture and domestic purposes. In this study, we evaluated the attenuating effects of ethanolic extract of Mangifera indica leaves (EEMI) in averting reproductive toxicity caused by ACP in male guinea pigs. Thirty male guinea pigs were randomly assigned to five treatment groups (n = 6). Group 1 (T0) received distilled water orally; group 2 (T0-) was given 80 mg kg-1 of ACP and groups 3, 4 and 5 were treated, respectively, with EEMI at doses of 50, 100 and 200 mg kg-1 plus ACP. After 90 days, the reaction time, sexual organ weights, sperm count, motility and anomalies, spermatozoa with entire plasma membrane, testicular histology, serum testosterone concentration, testicular malondialdehyde (MDA) level, reduced glutathione (GSH) concentration, testicular superoxide dismutase (SOD) and catalase (CAT) activities were assessed. Co-administration of EEMI significantly reduced the reaction time, sperm anomalies and testicular MDA, SOD and CAT levels compared to the T0- group. Co-treatment of EEMI significantly alleviated sperm count and motility, percentage of spermatozoa with the normal plasma membrane, serum testosterone concentration, accessory sex gland weights, and testicular GSH concentrations. The ACP treatment induced cell membrane degradation in the testis and this effect was prevented with the addition of EEMI. In conclusion, ACP negatively affected the animal reproductive function and induced oxidative stress. The addition of EEMI alleviated the toxic effects of ACP on the reproductive function of male guinea pigs. [ABSTRACT FROM AUTHOR]

Pubertal onset is thought to be timed by an increase in pulsatile gonadotropin-releasing hormone (GnRH)/gonadotropin secretion in mammals. The underlying mechanism of pubertal onset in mammals is still an open question. Evidence accumulated in the last 15 years suggests that kisspeptin/neurokinin B/dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus play a key role in pubertal onset by triggering pulsatile GnRH/gonadotropin secretin in mammals. Specifically, KNDy neurons are now considered a part of GnRH pulse generator, in which neurokinin B facilitates and dynorphin A inhibits, the synchronized discharge of KNDy neurons in autocrine and/or paracrine manners. Kisspeptin serves as a potent secretagogue of GnRH secretion and thus its release is fundamental to pubertal increase in GnRH/gonadotropin secretion in mammals. Proposed mechanisms inhibiting Kiss1 (kisspeptin gene) expression during childhood to juvenile varies from species to species: we envisage that negative feedback action of estrogen plays a key role in the inhibition of Kiss1 expression in KNDy neurons in rodents and sheep, whereas estrogen-independent inhibition of kisspeptin secretion by γ-amino butyric acid or neuropeptide Y are suggested to be responsible for the pre-pubertal suppression of GnRH/gonadotropin secretion in primates. Taken together, the timing of pubertal onset is postulated to be controlled by upstream regulators for kisspeptin biosynthesis and secretion in mammals. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Different diesel exhaust particles (DEP) induce diverse biological responses. • Particles with the highest content of PAHs (DEP EuroIV) are more effective. • DEP EuroIV induces cytotoxicity, oxidative stress, inflammation and endothelial activation. Abstract Diesel exhaust particles (DEP) are responsible for both respiratory and cardiovascular effects. However many questions are still unravelled and the mechanisms behind the health effects induced by the exposure to ultrafine particles (UFP) need further investigations. Furthermore, different emission sources can lead to diverse biological responses. In this perspective, here we have compared the effects of three DEPs, two standard reference materials (SRM 1650b and 2975) and one DEP directly sampled from a EuroIV vehicle without Diesel Particulate Filter (DPF). For the biological investigations, different in vitro lung models involving both epithelial and vascular endothelial cells, were used. Cell viability, oxidative stress, inflammation, DNA damage and endothelial activation markers were investigated at sub-cytotoxic DEP doses. The data obtained have shown that only DEP EuroIV, which had the major content of polycyclic aromatic hydrocarbons (PAHs) and metals, was able to induce oxidative stress, inflammation and consequent endothelial activation, as demonstrated by the expression of adhesion molecules (ICAM-1 and VCAM-1) and the release of inflammatory markers (IL-8) from endothelial cells. Standard reference materials were not effective under our experimental conditions. These data suggest that oxidative stress, endothelial activation and systemic inflammatory cytokines release are crucial events after DEP exposure and that the source of DEP emission, responsible of the particle chemical fingerprint, may have a key role in the resulting adverse biological outcomes. [ABSTRACT FROM AUTHOR]

The Chinese forest musk deer (Moschus berezovskii) is an economically important species distributed throughout southwest China and northern Vietnam. Occurrence and development of disease are aggravated by inbreeding and genetic diversity declines in captive musk deer populations. Deep transcriptomics investigation may provide a promising way to improve genetic health of captive and wild FMD population. MicroRNAs (miRNAs), which regulate gene expression by targeting and suppressing of mRNAs, play an important role in physiology and organism development control. In this study, RNA-seq technology was adopted to characterize the miRNA transcriptome signature among six tissues (heart, liver, spleen, lung, kidney, and muscle) in Chinese forest musk deer at two years of age. Deep sequencing generated a total of 103,261,451 (~87.87%) good quality small RNA reads; of them 6,622,520 were unique across all six tissues. A total of 2890 miRNAs were identified, among them 1129 were found to be expressed in all tissues. Moreover, coexpression of 20 miRNAs (>2000RPM) in all six tissues and top five highly expressed miRNAs in each tissue implied the crucial and particular function of them in FMD physiological processes. Our findings of forest musk deer miRNAs supplement the database of transcriptome information for this species and conduce to our understanding of forest musk deer biology. [ABSTRACT FROM AUTHOR]

Abstract Oxidative stress is an important cause of neurodegenerative diseases. Antioxidant is an potential important method to treat such diseases. The aim of this study is to discover new and effective antioxidants and their mechanism. The neuroprotective effect of six curcumin pyrozole compounds were first evaluated on sodium nitroprusside (SNP) - induced PC12 cell injury by testing cell viability and LDH release. The results showed that four compounds (C1-C4) have more significant protective effects compared to curcumin and edaravone. Furthermore, compounds C1-C4 can attenuate the intracellular ROS, and compound C3 is the most effective one which can preservate the mitochondria function by inhibiting the mitochondrial membrane potential loss and enhance nuclear translocation of Nrf2 in PC12 cell. These results indicated that C3 may be a potential candidate drug for treating neurodegenerative diseases. Highlights • Curcumin pyrazole derivatives C1-C4 can alleviate oxidative stress-induced PC12 neuronal damage. • C1-C4 can effectively reduce intracellular ROS, and C3 is the most effective. • The protective effect of C3 is related to the protection of mitochondrial function. • The protective effect of C3 is related to activation of Nrf2 signaling pathway. • C3 may be a potential candidate compound for neuroprotectants in the future. [ABSTRACT FROM AUTHOR]

Abstract α-Synuclein plays a central role in synucleinopathies pathogenesis such as Parkinson's disease (PD). Phosphorylation is the most common and important protein modification linked to α-synuclein pathologies. There is mounting evidence suggested iron and α-synuclein are closely related in PD. We previously reported iron up-regulated α-synuclein mRNA levels and induced α-synuclein aggregation. In the present study, we aimed to investigate whether and how phosphorylation was involved in iron-induced α-synuclein regulations. The results showed that iron could induce pS129 α-synuclein (phosphorylation at Ser129) and α-synuclein upregulation in the substantia nigra of iron-overloaded rats and iron-treated SH-SY5Y cells, accompanied by the elevated levels of polo-like kinase 2 (PLK2) and casein kinase 2 (CK2). Over-expression of CK2 or PLK2 induced pS129 α-synuclein up-regulation and inhibitors of CK2 or PLK2 could suppress iron-induced α-synuclein phosphorylation. Antioxidant NAC could fully block iron-induced upregulation of CK2, PLK2 and pS129 α-synuclein levels, indicating oxidative stress plays a critical role in iron-induced α-synuclein phosphorylation. However, iron-induced α-synuclein up-regulation could only be partially blocked by CK2/PLK2 inhibitor or NAC. These findings demonstrate that iron-induced oxidative stress is largely responsible for α-synuclein phosphorylation and upregulation via CK2 and PLK2, and α-synuclein upregulation is not fully phosphorylation-dependent. Highlights • Iron induced α-synuclein phosphorylation and upregulation in vivo and in vitro. • CK2 and PLK2 were involved in iron-induced α-synuclein phosphorylation. • Oxidative stress is responsible for iron-induced kinases up-regulation and α-synuclein phosphorylation. • Iron-induced α-synuclein up-regulation is not fully phosphorylation-dependent. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has a high mortality rate due to the absence of early symptoms and subsequent late diagnosis; additionally, pancreatic cancer has a high resistance to radio‐ and chemotherapy. Multiple inflammatory pathways are involved in the pathophysiology of pancreatic cancer. Melatonin an indoleamine produced in the pineal gland mediated and receptor‐independent action is the pancreas and other where has both receptors. Melatonin is a potent antioxidant and tissue protector against inflammation and oxidative stress. In vivo and in vitro studies have shown that melatonin supplementation is an appropriate therapeutic approach for pancreatic cancer. Melatonin may be an effective apoptosis inducer in cancer cells through regulation of a large number of molecular pathways including oxidative stress, heat shock proteins, and vascular endothelial growth factor. Limited clinical studies, however, have evaluated the role of melatonin in pancreatic cancer. This review summarizes what is known regarding the effects of melatonin on pancreatic cancer and the mechanisms involved. [ABSTRACT FROM AUTHOR]

Benzo[ghi]perylene (B[ghi]P) is a polycyclic aromatic hydrocarbon widely found in haze. Long‐term exposure to humans or animals can cause serious damage to the respiratory system. Melatonin is an endogenous natural hormone synthesized and released by the pineal gland. In this study, we investigated the effects of melatonin on in vitro cultured B[ghi]P‐exposed mouse oocytes and the protective roles of melatonin. Our data indicate that B[ghi]P exposure leads to meiotic maturation arrest and reduced ability of sperm binding and parthenogenetic activation. Also, B[ghi]P exposure disrupts actin filament dynamics, spindle assembly, and kinetochore–microtubule attachment stability, which results in oocyte aneuploidy. Simultaneously, B[ghi]P exposure disturbs the distribution of mitochondria, increases the level of oxidative stress, and induces apoptosis of oocytes. Whereas all of these toxic effects of B[ghi]P can be restored after melatonin supplement. In conclusion, our findings validate that melatonin has a certain protective effect on preventing the reduced oocyte quality caused by B[ghi]P exposure during meiotic maturation in mouse oocytes. The benzo[ghi]perylene can reduce the quality of oocytes by disrupting cytoskeletal integrality, chromosome euploidy, and mitochondrial functions, whereas melatonin has a certain protective effect on preventing the reduced oocyte quality during meiotic maturation. [ABSTRACT FROM AUTHOR]

Abstract Light has pervasive effects on the physiology and behavior of mammals. Several human studies have shown that light modulates cognitive functions; however, the mechanisms responsible for the effects of light remain unclear. Our previous work using diurnal male Nile grass rats (Arvicanthis niloticus) revealed that reduced illuminance during the day leads to impairments in hippocampal-dependent spatial learning/memory, reduced CA1 dendritic spine density, and attenuated hippocampal brain-derived neurotrophic factor (BDNF) expression in males. The present study examined the impact of ambient light intensity on hippocampal functions in female grass rats and explored sex differences in behavioral and hippocampal responses. Female grass rats were housed in either a 12:12-hr bright light–dark (brLD, 1000 lx) or dim light–dark (dimLD, 50 lx) cycle for four weeks. The dimLD group showed impaired spatial memory in the Morris water maze task and reduced CA1 apical dendritic spine density, similar to prior observations in males. However, the behavioral deficits seen in females were more severe than those seen in males, with dimLD females showing no evidence of long-term retention over the 24-hour periods between training sessions. In contrast to the attenuated hippocampal BDNF expression found in dimLD males, there was no significant difference in the expression of BDNF and of its receptor TrkB between females in brLD and dimLD. The results suggest that, as seen in male grass rats, reduced illuminance during the day impairs hippocampal-dependent spatial memory and hippocampal plasticity in female diurnal grass rats, but the underlying signaling pathways responsible for the effects of light restriction may differ between the sexes. Highlights • Dim light housing during the day leads to impaired spatial learning and memory in female diurnal grass rats. • Female grass rats housed in dim light had reduced CA1 dendritic spine density. • Dim light housing had no significant effect on hippocampal BDNF expression and TrkB phosphorylation in female grass rats. [ABSTRACT FROM AUTHOR]

Abstract Perfluoroalkyl acids (PFAAs) are widely used in industrial and commercial products and possess endocrine disrupting properties. Perfluorononanoic acid (PFNA), one of PFAAs, has been mainly reported to produce testicular toxicity in adult animals. The objective of the present study was to examine the effect of acute exposure of PFNA to prepubertal male Parkes (P) mice on spermatogenesis and testicular steroidogenesis, and to study the possible mechanism(s) of its action. PFNA (2 and 5 mg/kg) was orally administered to male P mice for 14 days from postnatal day 25–38. Histologically, testis in PFNA-treated mice showed non-uniform diverse degenerative changes in the seminiferous tubules; both normal and affected tubules were seen in the same testicular sections. The treatment caused a reduction in intra-testicular and serum testosterone levels accompanied by a decrease in testicular expression of SF1, StAR, CYP11A1, and 3β- and17β-HSD. Further, the activity of antioxidant enzymes and expression of Nrf2 and HO-1 in the testis were markedly decreased, while the level of lipid peroxidation and expression of IKKβ, NF-κB and caspase-3 were significantly increased in testis of PFNA-treated mice. There was also a decrease in PCNA expression and in PCNA-index and an increase in TUNEL-positive germ cells in testes of PFNA-treated mice. In conclusion, the results suggest that PFNA exposure to prepubertal male mice altered antioxidant enzymes activity and Nrf2-HO-1 signaling, leading to oxidative stress and a decrease in testosterone biosynthesis in the testis; these changes, in turn, caused increased apoptosis and decreased proliferation of germ cells, thereby suppression of spermatogenesis. Highlights • Prepubertal exposure to PFNA impaired spermatogenesis and testosterone biosynthesis. • Treatment decreased antioxidant enzymes activities in testis. • Treatment also modulated expressions of Nrf2, HO-1, IKKβ and NF-κB in testis. • Treatment increased level of lipid peroxidation in testis. • PFNA decreased germ cell proliferation and increased apoptosis in testis. [ABSTRACT FROM AUTHOR]

Abstract Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and molecular mechanism remain under-explored. In this study, we employed human breast cancer cell as a model to investigate the concentration-dependent toxicity and underlying mechanisms of tetrabromo bisphenol A (TBBPA) and tetrachloro bisphenol A (TCBPA). An integrated method involving molecular toxicology and mass spectrometry (MS)-based global metabolomics was applied to evaluate the toxicity of TCBPA and TBBPA on cell viability, reactive oxygen species (ROS), and metabolic alterations. The results demonstrated that low micromolar levels (0–10 μM) of TCBPA/TBBPA exposure induced cell proliferation and activated the energy metabolism of both glycolysis and amino acid. On the other hand, high micromolar levels (10–50 μM) of TCBPA/TBBPA exposure perturbed the balance between ROS and antioxidative defense process by promoting the ROS generation via the down-regulation of glutathione biosynthesis and up-regulation of nucleotide metabolism. This study, for the first time, provides evidence and mechanism for better understanding the cytotoxicity of TCBPA and TBBPA by regulating the specific metabolic pathways. Graphical abstract fx1 Highlights • X-BPA induced toxicity by a concentration-dependent manner in breast cancer cell. • Low micromolar levels of X-BPA induced proliferation and activated glycolysis and amino acid. • High micromolar levels of X-BPA promoted oxidative stress by perturbing glutathione and nucleotide. • Metabolomics play a significant role in exploring the toxicity mechanism of X-BPA. [ABSTRACT FROM AUTHOR]

Objectives: Chronic stress exposure can disrupt the balance of organisms, result in learning and memory impairments and induce oxidative stress. However, there is a lack of safe and effective long-term therapeutic agents for stress-related injuries. Fresh ginseng (FG), an unprocessed raw root of ginseng, has antioxidant and neuroprotective activities and has been used as functional health food in Asian countries for many years. The aim of this study was to verify the protective effects of FG on chronic restraint stress (CRS)-induced learning and memory impairments as well as oxidative stress damage in mice. Methods: Animals were subjected to object location recognition test (OLRT) and novel object recognition test (NORT) to evaluate discriminative ability and spatial learning and memory, and Morris water maze test (MWMT) was used to evaluate the acquisition and retention of spatial memory. In addition, oxidative stress parameters were assessed by measuring the malondialdehyde (MDA) and total antioxidant reactivity levels in serum. Results: Experimental results demonstrated that CRS-induced mice exhibited significantly decreased discrimination index (DI) in OLRT and NORT, longer escape latency and swimming distance, and decreased crossing numbers in MWMT. FG (2 and 6 g/kg) treatment markedly enhanced the discriminative ability by elevating DI in OLRT and NORT, improved the acquisition and retention of spatial memory by decreasing escape latency and swimming distance in the acquisition phase, and increased the crossing numbers in the probe phase of MWMT. Administration of FG (2 and 6 g/kg) significantly reduced the elevated MDA level caused by CRS. Discussion: Our results suggest that FG treatment could improve CRS-induced learning and memory impairments and oxidative stress damage. FG is an intriguing therapeutic agent and functional health food in stress-related dementia. [ABSTRACT FROM AUTHOR]

Background: Red yeast rice supplements are broadly accepted as treatment for dyslipidaemia in subjects without high cardiovascular (CV) risk. Their effect on lipid profile is well known, but few data are available on their effect on endothelial function. Objectives: To study the effect of a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones and antioxidants on lipid profile, endothelial function and oxidative stress. Methods: Fifty-two subjects with low-moderate CV risk and dyslipidaemia (according to European guidelines) were enrolled and treated for 8 weeks with the NC. Blood samples were collected at baseline and at the end of treatment to assess changes in lipid profile, endothelial function and oxidative stress. The primary endpoint was the reduction of low density lipoprotein (LDL) cholesterol. Endothelial function was assessed through measurement of rate of apoptosis and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) treated with subject's serum. High-sensitivity C-reactive protein, 4-hydroxynonenal (HNE) and oxidized LDL (oxLDL) were markers of oxidative stress. Results: Fifty subjects completed the study. The treatment caused a significant decrease in LDL (−15.6%, p < 0.001), oxLDL (−21.5%, p < 0.001), total cholesterol (TC), triglycerides, and ApoB. Apoptosis rate of HUVECs significantly decreased (−15.9%, p < 0.001). No changes were noted for NO levels and 4-HNE protein adducts. The reduction of the apoptosis rate was correlated to the reduction of oxLDL. Conclusion: An 8-week treatment based on a novel NC containing low manocolin K dose, polymethoxyflavones and antioxidants improved lipid profile in subjects with dyslipidaemia and low-moderate CV risk. Secondarily, we observed an improvement in surrogate markers of endothelial function that may result from the reduction of oxLDL (Registered at www.clinicaltrials.gov, NCT03216811). [ABSTRACT FROM AUTHOR]

G protein–coupled receptors (GPCRs) play an important role in physiology and disease and represent the most productive drug targets. Orphan GPCRs, with their endogenous ligands unknown, were considered a source of drug targets and consequently attract great interest to identify their endogenous cognate ligands for deorphanization. However, a contrary view to the ubiquitous existence of endogenous ligands for every GPCR is that there might be a significant overlooked fraction of orphan GPCRs that function constitutively in a ligand-independent manner only. Here, we investigated the evolution of the bombesin receptor–ligand family in vertebrates in which one member—bombesin receptor subtype-3 (BRS3)—is a potential orphan GPCR. With analysis of 17 vertebrate BRS3 structures and 10 vertebrate BRS3 functional data, our results demonstrated that nonplacental vertebrate BRS3 still connects to the original ligands—neuromedin B (NMB) and gastrin-releasing peptide (GRP)—because of adaptive evolution, with significantly changed protein structure, especially in three altered key residues (Q127R, P205S, and R294H) originally involved in ligand binding/activation, whereas the placental mammalian BRS3 lost the binding affinity to NMB/GRP and constitutively activates Gs/Gq/G12 signaling in a ligand-independent manner. Moreover, the N terminus of placental mammalian BRS3 underwent positive selection, exhibiting significant structural differences compared to nonplacental vertebrate BRS3, and this domain plays an important role in constitutive activity of placental mammalian BRS3. In conclusion, constitutively active BRS3 is a genuinely orphan GPCR in placental mammals, including human. To our knowledge, this study identified the first example that might represent a new group of genuinely orphan GPCRs that will never be deorphanized by the discovery of a natural ligand and provided new perspectives in addition to the current ligand-driven GPCR deorphanization. [ABSTRACT FROM AUTHOR]