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Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues. [ABSTRACT FROM AUTHOR]

The anterior-posterior patterning of the vertebrate limb bud requires closely coordinated signaling interactions, including Sonic Hedgehog (Shh)-mediated counteraction of the Gli3 transcription factor in the distal and posterior mesenchyme of the limb bud. Suppressor of Fused (Sufu), an intracellular negative regulator of Shh signaling via Gli2 and Gli3, is implicated in early development of the mouse limb bud. However, how Sufu is involved in the genetic regulation of limb bud patterning still remains elusive. In this study, we show that the conditional deletion of Sufu in the mesenchyme of the early limb bud results in polydactyly with loss of digit identity and supernumerary bones in the wrist and the ankle. These pattern alterations are associated with anterior expansion of HoxD genes located at the 5’ end of the cluster. By focusing on gene expression analysis of Shh/Gremlin1/Fgf signaling critical for the establishment and maintenance of anterior-posterior patterning, we show that early response to loss of Sufu involves anterior prolongation of Fgf4 and Fgf8 expression in the apical ectodermal ridge at E10.5. We also reveal the anterior activation of Shh-dependent posterior markers Ptc1, Gli1 and Gremlin in limb buds lacking Sufu. Furthermore, we find that loss of Sufu leads to attenuated levels of repressor Gli2 and repressor Gli3 in the early limb bud. Moreover, expression of Hand2 is activated in the entire limb bud at the early outgrowth stage in the mutant lacking Sufu. Thus, we provide evidence that Sufu is involved in the genetic network that restricts the posterior expression of Gli2/3/Hand2 and Gremlin/Fgf in limb bud patterning. [ABSTRACT FROM AUTHOR]

Endothermy in birds and mammals is associated with high body temperatures, and high rates of metabolism that are aerobically supported by elevated rates of cardiovascular O2 transport. The purpose of this meta-analysis was to examine cardiovascular data from ectothermic and endothermic vertebrates, at rest and during exercise, with the goal of identifying key variables that may have contributed to the role of the cardiovascular system in supporting high rates of O2 transport associated with endothermy. Vascular conductance, cardiac power and stroke work were summarized and calculated from a variety of studies at rest and during exercise for five classes of vertebrates where data were available. Conductance and cardiac power were linearly related to cardiac output from rest to exercise and also interspecifically. Exercise cardiac power and stroke work were greater in the endothermic species, owing to increased flow resulting from increased heart rate and increased pressure. Increased relative ventricle mass (RVM) was related to increased stroke volume in both groups. However, the increased RVM of endotherms was related to the increased pressure, as stroke work per gram of ventricle during exercise was equivalent between the groups. Cardiac power was linearly related to aerobic metabolic power, with 158 mW aerobic power output achieved per mW of cardiac power input. This analysis indicates that the greatly increased heart rate and cardiac stroke work leading to increased blood flow rate and blood pressure was necessary to support the metabolic requirements of endothermy. [ABSTRACT FROM AUTHOR]

Extraretinal photoreceptors located within the medio-basal hypothalamus regulate the photoperiodic control of seasonal reproduction in birds. An action spectrum for this response describes an opsin photopigment with a λ max of ∼492 nm. Beyond this however, the specific identity of the photopigment remains unresolved. Several candidates have emerged including rod-opsin; melanopsin (OPN4); neuropsin (OPN5); and vertebrate ancient (VA) opsin. These contenders are evaluated against key criteria used routinely in photobiology to link orphan photopigments to specific biological responses. To date, only VA opsin can easily satisfy all criteria and we propose that this photopigment represents the prime candidate for encoding daylength and driving seasonal breeding in birds. We also show that VA opsin is co-expressed with both gonadotropin-releasing hormone (GnRH) and arginine-vasotocin (AVT) neurons. These new data suggest that GnRH and AVT neurosecretory pathways are endogenously photosensitive and that our current understanding of how these systems are regulated will require substantial revision. [ABSTRACT FROM AUTHOR]

Jawless vertebrates utilize a form of adaptive immunity that is functionally based on molecular effectors that are completely different from those of vertebrates. This observation raises an intriguing question: why did vertebrates, representing only 5% of all animals, twice evolve a system as complex as adaptive immunity? Theories aimed at identifying a selective pressure that would ‘drive’ the development of an adaptive immune system (AIS) fail to explain why invertebrates would not similarly develop an AIS. We argue that an AIS can only be implemented in a certain physiological context, i.e., that an AIS represents an unevolvable trait for invertebrates. The immune system is functionally integrated with other systems; therefore a preexisting physiological innovation unique to vertebrates may have acted as the prerequisite infrastructure that allowed the development of an AIS. We propose that future efforts should be directed toward identifying the evolutionary release that allowed the development of an adaptive immune system in vertebrates. In particular, the advent of specialized adipocytes might have expanded the metabolic scope of vertebrates, allowing the opportunistic incorporation of an AIS. However, physiological innovations, unique to (or more developed in) vertebrates, support the implementation of an AIS. Thus, understanding the interaction between systems (e.g. neural–immune–adipose connection) may illuminate our understanding regarding the perplexing immunological dimorphism within the animal kingdom. [ABSTRACT FROM AUTHOR]

Summary Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here, we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de-novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2–3 months. As a proof of principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high-throughput manner and for investigating candidates arising from human genome-wide studies. Video Abstract [ABSTRACT FROM AUTHOR]

The Merkel cell–neurite complex is a unique vertebrate touch receptor comprising two distinct cell types in the skin. Its presence in touch-sensitive skin areas was recognized more than a century ago, but the functions of each cell type in sensory transduction have been unclear. Three recent studies demonstrate that Merkel cells are mechanosensitive cells that function in touch transduction via Piezo2. One study concludes that Merkel cells, rather than sensory neurons, are principal sites of mechanotransduction, whereas two other studies report that both Merkel cells and neurons encode mechanical inputs. Together, these studies settle a long-standing debate on whether or not Merkel cells are mechanosensory cells, and enable future investigations of how these skin cells communicate with neurons. [ABSTRACT FROM AUTHOR]

The optic tectum is a visual center of nonmammalian vertebrates derived from the mesencephalon. In this review, function of Engrailed (En) in tectum development is reviewed. En plays crucial roles at three steps of tectum development. First, Engrailed is expressed in the mesencephalon and the metencephalon and essential for the regionalization of the mesencephalon. En is expressed in a gradient of caudal-to-rostral in the tectum primordial, and regulates the rostrocaudal polarity of the tectum. In the advanced stage of tectum development, En is expressed in a lamina-specific manner and it is suggested that En regulates cell migration in the tectal laminar formation. [ABSTRACT FROM AUTHOR]

Hedgehog is a morphogen, which is widely involved in the regulation of cell proliferation, differentiation and tissue patterning during development in both vertebrate and invertebrate, such as in coordination of eye, brain, gonad, gut and tracheal development. In invertebrate, Cubitus interruptus ( Ci) modification process is the last identified step before transcriptional activation in the Hh signaling pathway. Ci can form a truncated repressor ( CiR/ Ci75) or act as an activator ( CiA/ Ci155) based on Hh gradient to regulate the expressions of target genes. The activity of Ci is mediated by different mechanisms, including processing, trafficking and degradation. While in vertebrate, Glioblastomas ( Glis), homologs of Ci, play similar but more complex roles in the regulation of mammals Hh pathway. Hh signaling is responsible for a wide variety of processes during embryonic development and adult tissue homeostasis. Malfunction of Hh signaling could cause various diseases including birth defects and cancers. Enormous efforts were made in the past decades to explore the Hh pathway regulation and the results have provided us important insights into disease diagnosis and therapeutic treatment. In this review, we focus on a small branch of Hh pathway regulation based on studies in the Drosophila system, mainly about Ci degradation, aiming to explain how Ci is modified by different ubiquitin ligases due to the strong or moderate Hh signals and then been subjected to complete or partial degradation by proteasomes. Overall, we intend to offer an overview on how Ci responds to and relays Hh signals in a precise manner to control target genes expressions and ensures proper Hh signal transduction. [ABSTRACT FROM AUTHOR]

Neural crest cells ( NC) are a group of multipotent stem cells uniquely present in vertebrates. They are destined to form various organs according to their anterior-posterior (A-P) levels of origin in the neural tube ( NT). They develop into a wide spectrum of cell lineages under the influence of signaling cascades, neural plate border genes and NC specifier genes. Although this complex gene regulatory network ( GRN) specifies the fate of NC and the combinatory action of Hox genes executed at the time of NC induction governs the patterning of NC for the formation of specific structures along the A-P axis, not much information on how GRN and Hox genes directly interact and orchestrate is available. This review summarizes recent findings on the multiple roles of Hoxb5 on the survival and cell lineage differentiation of vagal and trunk NC cells during early development, by direct transcriptional regulation of NC specifier genes ( Sox9 and Foxd3) of the GRN. We will also review findings on the transcriptional regulation of Ret by Hoxb5 in the population of the vagal NC that are committed to the enteric neuron and glia lineages. Functional redundancy between Hox proteins (Hoxa5 and Hoxc5) from the same paralogue group as Hoxb5, and the cooperative effects of Hox cofactors, collaborators and transcription factors in the Hoxb5 transcriptional regulation of target genes will also be discussed. [ABSTRACT FROM AUTHOR]

As the most basal chordate, the cephalochordate amphioxus has unique features that make it a valuable model for understanding the phylogeny of immunity. Vertebrate adaptive immunity (VAI) mediated by lymphocytes bearing variable receptors has been well-studied in mammals but not observed in invertebrates. However, the identification of lymphocyte-like cells in the gill along with genes related with lymphoid proliferation and differentiation indicates the presence of some basic components of VAI in amphioxus. Without VAI, amphioxus utilizes about 10% of its gene repertoires, and an ongoing domain reshuffling mechanism among these genes, for innate immunity, suggesting extraordinary innate complexity and diversity not observed in other species. Innate diversity may not be comparable to the somatic diversity of the VAI, but there is no doubt of the success of this immune system, since amphioxus has existed for over 500 million years. Studies of amphioxus immunity may provide information on the reduction of innate immune complexity and the conflict between microbiota and host shaped the evolution of adaptive immune systems (AIS) during chordate evolution. [ABSTRACT FROM AUTHOR]

Contents The prevalence of endocrine-disrupting chemicals ( EDCs) in the aquatic environment has been associated with the wide detection of alterations in the development and physiology of vertebrates. Zebrafish, as a model species, has been extensively used in toxicological research. In this review, we focus on recent published evidence of the harmful effects of EDCs on reproductive function in zebrafish, including skewed sex ratio, immature gonads, diminished sexual behaviour, decreased sperm count, reduced spawning and fertilization. These impairments mostly result from disruption to sex-steroid hormones induced by endocrine disruptors. We also discuss other effects of exposure to EDCs. In EDC exposure research, despite incomplete assessments of altered gonad histopathology and sexual behaviour, these present potential effective biomarkers or pathways for evaluating the reproductive function in zebrafish on EDC exposure. To date, the pernicious effects of some EDCs on the reproductive performance in laboratory zebrafish are well understood; however, similar alterations remain for further determination in wild-type fish and more kinds of EDCs. More studies should be performed under established scientific regulatory criteria to investigate the impact of EDCs on reproduction in zebrafish. Moreover, further research is required to explain the definite mechanism of sexual differentiation, which helps in understanding the shift of sexual phenotype with EDC exposure. [ABSTRACT FROM AUTHOR]

The interest in experimental studies on avian malaria caused by Plasmodium species has increased recently due to the need of direct information about host–parasite interactions. Numerous important issues (host susceptibility, development of infection, the resistance and tolerance to avian malaria) can be answered using experimental infections. However, specificity of genetically different lineages of malaria parasites and their isolates is largely unknown. This study reviews recent experimental studies and offers additional data about susceptibility of birds to several widespread cytochrome b (cyt b ) lineages of Plasmodium species belonging to four subgenera. We exposed two domesticated avian hosts (canaries Serinus canaria and ducklings Anas platyrhynchos ) and also 16 species of common wild European birds to malaria infections by intramuscular injection of infected blood and then tested them by microscopic examination and PCR-based methods. Our study confirms former field and experimental observations about low specificity and wide host-range of Plasmodium relictum (lineages SGS1 and GRW11) and P. circumflexum (lineage TURDUS1) belonging to the subgenera Haemamoeba and Giovannolaia, respectively. However, the specificity of different lineages and isolates of the same parasite lineage differed between species of exposed hosts. Several tested Novyella lineages were species specific, with a few cases of successful development in experimentally exposed birds. The majority of reported cases of mortality and high parasitaemia were observed during parasite co-infections. Canaries were susceptible mainly for the species of Haemamoeba and Giovannolaia , but were refractory to the majority of Novyella isolates. Ducklings were susceptible to three malaria infections (SGS1, TURDUS1 and COLL4), but parasitaemia was light (<0.01%) and transient in all exposed birds. This study provides novel information about susceptibility of avian hosts to a wide array of malaria parasite lineages, outlining directions for future experimental research on various aspects of biology and epidemiology of avian malaria. [ABSTRACT FROM AUTHOR]

Cilia are highly conserved for their structure and also for their sensory functions. They serve as antennae for extracellular information. Whether the cilia are motile or not, they respond to environmental mechanical and chemical stimuli and send signals to the cell body. The information from extracellular stimuli is commonly converted to electrical signals through the repertoire of ion-conducting channels in the ciliary membrane, which results in changes in concentrations of ions, especially calcium ions, in the cilia. These changes, in turn, affect motility and the ability of the signaling pathways in the cilia and cell body to carry on the signal transduction. We review here the activities of ion channels in cilia in animals from protists to vertebrates. [ABSTRACT FROM PUBLISHER]

The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2 and LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including receptor tyrosine and serine/threonine kinases. LRIGs have been found to both negatively (LRIG1 and LRIG3) and positively (Sma-10 and LRIG3) regulate growth factor receptor expression and signaling, although the precise molecular mechanisms by which LRIGs function are not yet understood. The most is known about LRIG1, which was recently demonstrated to be a tumor suppressor. Indeed, in vivo experiments reinforce the essential link between LRIG1 and repression of its targets for tissue homeostasis. LRIG1 has also been identified as a stem cell marker and regulator of stem cell quiescence in a variety of tissues, discussed within. Comparably, less is known about LRIG2 and LRIG3, although studies to date suggest that their functions are largely distinct from that of LRIG1 and that they likely do not serve as growth/tumor suppressors. Finally, the translational applications of expressing soluble forms of LRIG1 in LRIG1-deficient tumors are being explored and hold tremendous promise. [ABSTRACT FROM AUTHOR]

Unsaturated fatty acids (UFAs), such as omega-3 and omega-6 poly- and omega-9 monounsaturated fatty acids are important nutrients and major components of neuronal cell membranes. They play a major role in modulating brain functions and physiology and may therefore diminish behavioral and physiological stress reactions in corroboration with decreased cortisol concentrations. Functionally, cortisol itself can modulate several behaviors and also the fatty acid metabolism in the long term. But only little is known about the behavioral and physiological influences of dietary UFAs in a social group, where individuals are regularly exposed to stressful situations. Therefore, the aim of this study was to determine the effects of dietary UFAs on saliva cortisol concentrations and behavioral responses in socially confronted guinea pigs. Three groups of animals were additionally supplemented with 500 mg chia seeds (high in omega-3), walnuts (high in omega-6), or peanuts (high in omega-9) per kg bodyweight each day and compared to a control group. During social confrontation saliva cortisol concentrations significantly increased in all groups, which was accompanied by a loss in bodyweight. However, cortisol levels remained lower in the chia and walnut groups compared to controls. Additionally, the walnut group displayed significantly increased locomotion, while no differences between groups were detected in socio-positive, sexual, or aggressive behaviors. Total plasma omega-3, omega-6, and omega-9 fatty acids were significantly increased in the corresponding groups, due to the dietary supplementations. However, a significant decrease in plasma omega-3 and an increase in plasma n-6 fatty acids were detected in the chia group when comparing the measurements before and after social confrontation. We conclude that both omega-3 and omega-6 polyunsaturated fatty acids can diminish behavioral and physiological stress responses to the social environment, enabling individuals to cope with social stressors, but at the expense of plasma derived omega-3 fatty acids. [ABSTRACT FROM AUTHOR]

Bats and birds must balance time and energy budgets during migration. Migrating bats face similar physiological challenges to birds, but nocturnality creates special challenges for bats, such as a conflict between travelling and refueling, which many birds avoid by feeding in daylight and flying at night. As endothermic animals, bats and birds alike must expend substantial amounts of energy to maintain high body temperatures. For migratory birds refueling at stopovers, remaining euthermic during inactive periods reduces the net refuelling rate, thereby prolonging stopover duration and delaying subsequent movement. We hypothesized that bats could mitigate similar ambient-temperature dependent costs by using a torpor-assisted migration strategy. We studied silver-haired bats Lasionycteris noctivagans during autumn migration using a combination of respirometry and temperature-sensitive radiotelemetry to estimate energy costs incurred under ambient temperature conditions, and the energy that bats saved by using torpor during daytime roosting periods. All bats, regardless of sex, age, or body condition used torpor at stopover and saved up to 91% of the energy they would have expended to remain euthermic. Furthermore, bats modulated use of torpor depending on ambient temperature. By adjusting the time spent torpid, bats achieved a rate of energy expenditure independent of the ambient temperature encountered at stopover. By lowering body temperature during inactive periods, fuel stores are spared, reducing the need for refuelling. Optimal migration models consider trade-offs between time and energy. Heterothermy provides a physiological strategy that allows bats to conserve energy without paying a time penalty as they migrate. Although uncommon, some avian lineages are known to use heterothermy, and current theoretical models of migration may not be appropriate for these groups. We propose that thermoregulatory strategies should be an important consideration of future migration studies of both bats and birds. [ABSTRACT FROM AUTHOR]

White-nose Syndrome (WNS) is the primary cause of over-winter mortality for little brown (Myotis lucifugus), northern (Myotis septentrionalis), and tricolored (Perimyotis subflavus) bats, and is due to cutaneous infection with the fungus Pseudogymnoascus (Geomyces) destructans (Pd). Cutaneous infection with P. destructans disrupts torpor patterns, which is thought to lead to a premature depletion of body fat reserve. Field studies were conducted at 3 WNS-affected hibernation sites to determine if big brown bats (Eptesicus fuscus) are resistant to Pd. Radio telemetry studies were conducted during 2 winters to determine the torpor patterns of 23 free-ranging E. fuscus hibernating at a site where Pd occurs. The body fat contents of free-ranging E. fuscus and M. lucifugus during hibernation at 2 different WNS-affected sites were also determined. The numbers of bats hibernating at the same site was determined during both: a) 4–7 years prior to the arrival of Pd, and, b) 2–3 years after it first appeared at this site. The torpor bouts of big brown bats hibernating at a WNS-affected site were not significantly different in length from those previously reported for this species. The mean body fat content of E. fuscus in February was nearly twice that of M. lucifugus hibernating at the same WNS-affected sites during this month. The number of M. lucifugus hibernating at one site decreased by 99.6% after P. destructans first appeared, whereas the number of E. fuscus hibernating there actually increased by 43% during the same period. None of the E. fuscus collected during this study had any visible fungal growth or lesions on their skin, whereas virtually all the M. lucifugus collected had visible fungal growth on their wings, muzzle, and ears. These findings indicate that big brown bats are resistant to WNS. [ABSTRACT FROM AUTHOR]

RFamides (RFa) are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here, we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play. [ABSTRACT FROM AUTHOR]

The sarcoplasmic reticulum (SR) is crucial for contraction and relaxation of the mammalian cardiomyocyte, but its role in other vertebrate classes is equivocal. Recent evidence suggests differences in SR function across species may have an underlying structural basis. Here, we discuss how SR recruitment relates to the structural organization of the cardiomyocyte to provide new insight into the evolution of cardiac design and function in vertebrates. [ABSTRACT FROM AUTHOR]

Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine. [ABSTRACT FROM AUTHOR]

Ground squirrel, a hibernating mammalian species, is more resistant to ischemic brain stress than rat. Gaining insight into the adaptive mechanisms of ground squirrels may help us design treatment strategies to reduce brain damage in patients suffering ischemic stroke. To understand the anti-stress mechanisms in ground squirrel neurons, we studied glutamate toxicity in primary cultured neurons of the Daurian ground squirrel (Spermophilus dauricus). At the neuronal level, for the first time, we found that ground squirrel was more resistant to glutamate excitotoxicity than rat. Mechanistically, ground squirrel neurons displayed a similar calcium influx to the rat neurons in response to glutamate or N-methyl-D-aspartate (NMDA) perfusion. However, the rate of calcium removal in ground squirrel neurons was markedly faster than in rat neurons. This allows ground squirrel neurons to maintain lower level of intracellular calcium concentration ([Ca2+]i) upon glutamate insult. Moreover, we found that Na+/Ca2+ exchanger (NCX) activity was higher in ground squirrel neurons than in rat neurons. We also proved that overexpression of ground squirrel NCX2, rather than NCX1 or NCX3, in rat neurons promoted neuron survival against glutamate toxicity. Taken together, our results indicate that ground squirrel neurons are better at maintaining calcium homeostasis than rat neurons and this is likely achieved through the activity of ground squirrel NCX2. Our findings not only reveal an adaptive mechanism of mammalian hibernators at the cellular level, but also suggest that NCX2 of ground squirrel may have therapeutic value for suppressing brain ischemic damage. [ABSTRACT FROM AUTHOR]

Many captive animals are fed diets that are drastically different in mechanical properties than their wild diet. Most captive pantherines are fed a nutritionally supplemented diet consisting almost entirely of ground meat. While many zoos supplement this diet with bones, the fact remains that large captive felids are fed diets that require substantially less masticatory effort than those of their wild counterparts. The osteological effects of this dietary difference have not been fully evaluated. To this end, we compared linear measurements and 3D geometric morphometric landmarks of captive and wild lions and tigers. Using Principal Component (PC) analysis of the linear measurements, not only were the sexes and species statistically distinct, but so too was the population clearly divisible in terms of captivity status. The 3D analysis supported these findings: although the most influential variable in the sample (PC1, 21.5% of the variation) separates the two species, the second most influential contributor (PC2) to the overall skull shape is driven not by the sex differences in these highly dimorphic species, but rather by their captivity status. In fact, captivity status drives nearly twice as much of the 3D variation as sexual dimorphism (14.8% vs. 8.0% for PC2 vs. PC3). Thus the shape is influenced nearly twice as much by whether the animal was captive or wild than by whether it was male or female. If a causal relationship can be demonstrated between dietary mechanical properties and morphology, people who oversee the diets of captive carnivores should consider modifying these diets to account for not only nutritional but also the mechanical properties of a carcass-based diet as well. In addition to the husbandry implications, our analyses show the ways in which captive specimens are different than their wild counterparts – findings that have implications for morphologists when considering anatomical samples. [ABSTRACT FROM AUTHOR]

Only little is known about whether single volatile compounds are as efficient in eliciting behavioral responses in animals as the whole complex mixture of a behaviorally relevant odor. Recent studies analysing the composition of volatiles in mammalian blood, an important prey-associated odor stimulus for predators, found the odorant trans-4,5-epoxy-(E)-2-decenal to evoke a typical “metallic, blood-like” odor quality in humans. We therefore assessed the behavior of captive Asian wild dogs (Cuon alpinus), African wild dogs (Lycaon pictus), South American bush dogs (Speothos venaticus), and Siberian tigers (Panthera tigris altaica) when presented with wooden logs that were impregnated either with mammalian blood or with the blood odor component trans-4,5-epoxy-(E)-2-decenal, and compared it to their behavior towards a fruity odor (iso-pentyl acetate) and a near-odorless solvent (diethyl phthalate) as control. We found that all four species displayed significantly more interactions with the odorized wooden logs such as sniffing, licking, biting, pawing, and toying, when they were impregnated with the two prey-associated odors compared to the two non-prey-associated odors. Most importantly, no significant differences were found in the number of interactions with the wooden logs impregnated with mammalian blood and the blood odor component in any of the four species. Only one of the four species, the South American bush dogs, displayed a significant decrease in the number of interactions with the odorized logs across the five sessions performed per odor stimulus. Taken together, the results demonstrate that a single blood odor component can be as efficient in eliciting behavioral responses in large carnivores as the odor of real blood, suggesting that trans-4,5-epoxy-(E)-2-decenal may be perceived by predators as a “character impact compound” of mammalian blood odor. Further, the results suggest that odorized wooden logs are a suitable manner of environmental enrichment for captive carnivores. [ABSTRACT FROM AUTHOR]

An estimated 5.7 million or more bats died in North America between 2006 and 2012 due to infection with the fungus Pseudogymnoascus destructans (Pd) that causes white-nose syndrome (WNS) during hibernation. The behavioral and physiological changes associated with hibernation leave bats vulnerable to WNS, but the persistence of bats within the contaminated regions of North America suggests that survival might vary predictably among individuals or in relation to environmental conditions. To investigate variables influencing WNS mortality, we conducted a captive study of 147 little brown myotis (Myotis lucifugus) inoculated with 0, 500, 5 000, 50 000, or 500 000 Pd conidia and hibernated for five months at either 4 or 10°C. We found that female bats were significantly more likely to survive hibernation, as were bats hibernated at 4°C, and bats with greater body condition at the start of hibernation. Although all bats inoculated with Pd exhibited shorter torpor bouts compared to controls, a characteristic of WNS, only bats inoculated with 500 conidia had significantly lower survival odds compared to controls. These data show that host and environmental characteristics are significant predictors of WNS mortality, and that exposure to up to 500 conidia is sufficient to cause a fatal infection. These results also illustrate a need to quantify dynamics of Pd exposure in free-ranging bats, as dynamics of WNS produced in captive studies inoculating bats with several hundred thousand conidia may differ from those in the wild. [ABSTRACT FROM AUTHOR]

Snout shape is a prominent aspect of herbivore feeding ecology, interacting with both forage selectivity and intake rate. Previous investigations have suggested ruminant feeding styles can be discriminated via snout shape, with grazing and browsing species characterised by ‘blunt’ and ‘pointed’ snouts respectively, often with specification of an ‘intermediate’ sub-grouping to represent ambiguous feeding styles and/or morphologies. Snout shape morphology is analysed here using a geometric morphometric approach to compare the two-dimensional profiles of the premaxilla in ventral aspect for a large sample of modern ruminant species, for which feeding modes are known from secondary criteria. Results suggest that, when browsing and grazing ruminants are classified ecologically based on a range of feeding style indicators, they cannot be discriminated unambiguously on the basis of snout profile shape alone. Profile shapes in our sample form a continuum with substantial overlap between groupings and a diverse range of morphologies. Nevertheless, we obtained an 83.8 percent ratio of correct post hoc feeding style categorisations based on the proximity of projected profile shapes to group centroids in the discriminant space. Accordingly, this procedure for identifying species whose feeding strategy is ‘unknown’ can be used with a reasonable degree of confidence, especially if backed-up by additional information. Based on these results we also refine the definitions of snout shape varieties, taking advantage of the descriptive power that geometric morphometrics offers to characterize the morphological disparities observed. The shape variance exhibited by both browsing and grazing ruminants corresponds strongly to body mass, providing further evidence for an interaction between snout shape, feeding style, and body size evolution. Finally, by exploring the role of phylogenetic similarity in snout shape, we find a slight increase in successful categorisation when repeating the analysis with phylogenetic control on the geometric profiles. [ABSTRACT FROM AUTHOR]

Vasopressin–oxytocin (VP–OT) nonapeptides modulate numerous social and stress-related behaviors, yet these peptides are made in multiple nuclei and brain regions (e.g., >20 in some mammals), and VP–OT cells in these areas often exhibit overlapping axonal projections. Furthermore, the magnocellular cell groups release peptide volumetrically from dendrites and soma, which gives rise to paracrine modulation in distal brain areas. Nonapeptide receptors also tend to be promiscuous. Hence, behavioral effects that are mediated by any given receptor type (e.g., the OT receptor) in a target brain region cannot be conclusively attributed to either VP or OT, nor to a specific cell group. We here review what is actually known about the social behavior functions of nonapeptide cell groups, with a focus on aggression, affiliation, bonding, social stress, and parental behavior, and discuss recent studies that demonstrate a diversity of sex-specific contributions of VP–OT cell groups to gregariousness and pair bonding. [ABSTRACT FROM AUTHOR]

The field of eco-immunology seeks to address the causes and consequences of natural variation in immune responses. Recently, the development of more immunological resources for nonmodel systems along with the growing availability of genomic data has made it feasible to explore more complex immunological differences in nonmodel systems., Cytokines are small molecular weight proteins that are the major signalling molecules of the immune system. Studies in mice and humans have demonstrated the importance of tightly regulated cytokine signalling, and thus, cytokines may play a major, unexplored role in explaining natural variation in immune responses., In this review, we highlight cytokines that are likely to be important for eco-immunology studies and what is currently known about their presence or absence in the major vertebrate groups. We also explore what types of questions an eco-immunologist might ask involving cytokines and discuss potential ways to measure cytokines in nonmodel systems., Inclusion of cytokines in eco-immunology will advance the field as it will help us to better understand mechanisms behind both natural variation in immune responses and how different taxa respond to immune challenges. [ABSTRACT FROM AUTHOR]

5-Lipoxygenase (ALOX5) plays a key role in the biosynthesis of pro-inflammatory leukotrienes whereas 15-lipoxygenases (ALOX15) have been implicated in the formation of pro-resolving eicosanoids (lipoxins, resolvins). Recently, it has been suggested that a phosphorylation mimicking mutant (Ser663Asp) of a stabilized variant of human ALOX5 exhibits dominant arachidonic acid 15-lipoxygenase activity (> 95%). To test whether similar alterations in the reaction specificity can also be observed for ALOX5 orthologs of other species we expressed wildtype and phosphorylation mimicking mutants (Ser271Asp, Ser523Asp, Ser663Asp, Ser663Glu) of human, mouse and zebrafish ALOX5 in pro- and eukaryotic overexpression systems and characterized their reaction specificities. We found that neither of the phosphorylation mimicking mutants produced significant amounts of 15-hydroperoxyeicosatetraenoic acid and the 5-lipoxygenation/15-lipoxygenation ratio for all wildtype and mutant enzyme species was lower than 100:2. Taken together, this data suggest that phosphorylation of native ALOX5 orthologs of different vertebrates may not induce major alterations in the reaction specificity and thus may not inverse their biological activity. [ABSTRACT FROM AUTHOR]

The ability to change colour rapidly is widespread among ectotherms and has various functions including camouflage, communication and thermoregulation. The process of colour change can occur as an aperiodic event or be rhythmic, induced by cyclic environmental factors or regulated by internal oscillators. Despite the importance of colour change in reptile ecology, few studies have investigated the occurrence of a circadian rhythm in lizard pigmentation. Additionally, although colour change also entails changes in near-infrared reflectance, which may affect thermoregulation, little research has examined this part of the spectrum. We tested whether the bearded dragon lizard, Pogona vitticeps, displays an endogenous circadian rhythm in pigmentation changes that could be entrained by light/dark (LD) cycles and how light affected the relative change in reflectance in both ultraviolet-visible and near-infrared spectra. We subjected 11 lizards to four photoperiodic regimens: LD 12∶12; LD 6∶18; LD 18∶6 and DD; and measured their dorsal skin reflectance at 3-hour intervals for 72 hours after a habituation period. A proportion of lizards displayed a significant rhythm under constant darkness, with maximum reflectance occurring in the subjective night. This endogenous rhythm synchronised to the different artificial LD cycles, with maximum reflectance occurring during dark phases, but did not vary in amplitude. In addition, the total ultraviolet-visible reflectance in relation to the total near-infrared reflectance was significantly higher during dark phases than during light phases. We conclude that P. vitticeps exhibits a circadian pigmentation rhythm of constant amplitude, regulated by internal oscillators and that can be entrained by light/dark cycles. [ABSTRACT FROM AUTHOR]

As global temperatures increase throughout the coming decades, species ranges will shift. New combinations of abiotic conditions will make predicting these range shifts difficult. Biophysical mechanistic niche modeling places bounds on an animal’s niche through analyzing the animal’s physical interactions with the environment. Biophysical mechanistic niche modeling is flexible enough to accommodate these new combinations of abiotic conditions. However, this approach is difficult to implement for aquatic species because of complex interactions among thrust, metabolic rate and heat transfer. We use contemporary computational fluid dynamic techniques to overcome these difficulties. We model the complex 3D motion of a swimming neonate and juvenile leatherback sea turtle to find power and heat transfer rates during the stroke. We combine the results from these simulations and a numerical model to accurately predict the core temperature of a swimming leatherback. These results are the first steps in developing a highly accurate mechanistic niche model, which can assists paleontologist in understanding biogeographic shifts as well as aid contemporary species managers about potential range shifts over the coming decades. [ABSTRACT FROM AUTHOR]

Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R2 = 0.9548, R2 = 0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of −0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of −0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors. [ABSTRACT FROM AUTHOR]