Gonadotropin-inhibitory hormone and its receptors in teleosts: Physiological roles and mechanisms of actions.

Gonadotropin-inhibitory hormone (GnIH) was the first reported hypothalamic neuropeptide inhibiting reproduction in vertebrates. Since its discovery in the quail brain, its orthologs have been identified in a variety of vertebrate species and even protochordates. Depending on the species, the GnIH precursor polypeptides comprise two, three or four mature peptides of the RFamide family. It has been well documented that GnIH inhibits reproduction at the brain-pituitary-gonadal levels and participates in metabolism, stress response, and social behaviors in birds and mammals. However, most studies in fish have mainly been focused on the physiological roles of GnIH in the control of reproduction and results obtained are in some cases conflicting, leaving aside its potential roles in the regulation of other functions. In this manuscript we summarize the information available in fish with respect to the structural diversity of GnIH peptides and functional roles of GnIH in reproduction and other physiological processes. We also highlight the molecular mechanisms of GnIH actions on target cells and possible interactions with other neuroendocrine factors.

Anatomical organization of forebrain circuits in the primate.

The primate forebrain is a complex structure. Thousands of connections have been identified between cortical areas, and between cortical and sub-cortical areas. Previous work, however, has suggested that a number of principles can be used to reduce this complexity. Here, we integrate four principles that have been put forth previously, including a nested model of neocortical connectivity, gradients of connectivity between frontal cortical areas and the striatum and thalamus, shared patterns of sub-cortical connectivity between connected posterior and frontal cortical areas, and topographic organization of cortical-striatal-pallidal-thalamocortical circuits. We integrate these principles into a single model that accounts for a substantial amount of connectivity in the forebrain. We then suggest that studies in evolution and development can account for these four principles, by assuming that the ancestral vertebrate pallium was dominated by medial, hippocampal and ventral-lateral, pyriform areas, and at most a small dorsal pallium. The small dorsal pallium expanded massively in the lineage leading to primates. During this expansion, topological, adjacency relationships were maintained between pallial and sub-pallial areas. This maintained topology led to the connectivity gradients seen between cortex, striatum, pallidum, and thalamus.

The oldest gnathostome teeth.

Mandibular teeth and dentitions are features of jawed vertebrates that were first acquired by the Palaeozoic ancestors1-3 of living chondrichthyans and osteichthyans. The fossil record currently points to the latter part of the Silurian period4-7 (around 425 million years ago) as a minimum date for the appearance of gnathostome teeth and to the evolution of growth and replacement mechanisms of mandibular dentitions in the subsequent Devonian period2,8-10. Here we provide, to our knowledge, the earliest direct evidence for jawed vertebrates by describing Qianodus duplicis, a new genus and species of an early Silurian gnathostome based on isolated tooth whorls from Guizhou province, China. The whorls possess non-shedding teeth arranged in a pair of rows that demonstrate a number of features found in modern gnathostome groups. These include lingual addition of teeth in offset rows and maintenance of this patterning throughout whorl development. Our data extend the record of toothed gnathostomes by 14 million years from the late Silurian into the early Silurian (around 439 million years ago) and are important for documenting the initial diversification of vertebrates. Our analyses add to mounting fossil evidence that supports an earlier emergence of jawed vertebrates as part of the Great Ordovician Biodiversification Event (approximately 485-445 million years ago).

Effects of the social environment on vertebrate fitness and health in nature: Moving beyond the stress axis.

Social interactions are a ubiquitous feature of the lives of vertebrate species. These may be cooperative or competitive, and shape the dynamics of social systems, with profound effects on individual behavior, physiology, fitness, and health. On one hand, a wealth of studies on humans, laboratory animal models, and captive species have focused on understanding the relationships between social interactions and individual health within the context of disease and pathology. On the other, ecological studies are attempting an understanding of how social interactions shape individual phenotypes in the wild, and the consequences this entails in terms of adaptation. Whereas numerous studies in wild vertebrates have focused on the relationships between social environments and the stress axis, much remains to be done in understanding how socially-related activation of the stress axis coordinates other key physiological functions related to health. Here, we review the state of our current knowledge on the effects that social interactions may have on other markers of vertebrate fitness and health. Building upon complementary findings from the biomedical and ecological fields, we identify 6 key physiological functions (cellular metabolism, oxidative stress, cellular senescence, immunity, brain function, and the regulation of biological rhythms) which are intimately related to the stress axis, and likely directly affected by social interactions. Our goal is a holistic understanding of how social environments affect vertebrate fitness and health in the wild. Whereas both social interactions and social environments are recognized as important sources of phenotypic variation, their consequences on vertebrate fitness, and the adaptive nature of social-stress-induced phenotypes, remain unclear. Social flexibility, or the ability of an animal to change its social behavior with resulting changes in social systems in response to fluctuating environments, has emerged as a critical underlying factor that may buffer the beneficial and detrimental effects of social environments on vertebrate fitness and health.

Struggle for phosphorus and the Devonian overturn.

Organisms with external phosphatic shells diversified and became abundant at the beginning of the Early Paleozoic but gradually declined and were rare by its end. The decreasing availability of phosphorus in oceans is thought to be responsible for this evolutionary trend. Responses of organisms to changes in the phosphorus cycle can be traced to the late Neoproterozoic, and likely had a significant role in the Cambrian explosion, the Great Ordovician Biodiversification Event (GOBE), and the Devonian nekton revolution. Effective use of phosphorus by vertebrates during the Devonian nekton revolution caused the phosphorus pool to shift from benthic external shells to the skeletons of pelagic vertebrates, and moved the marine faunas toward the dominance patterns and ecological structure of the Modern Evolutionary Fauna.

Solanum pubescens Wild Fruits Essential Oil - A Golden Casket for its Antimicrobial and Anti-inflammatory Mediated Wound Healing Efficacy in Vertebrate Model Mus musculus.

BACKGROUND: Solanum pubescens Willd, growing wild in the hills of Rayadurg jurisdiction of Southwestern Andhra Pradesh, has gained significant attention among researchers for its diverse folkloric applications, existence of novel phytochemicals and leaf extracts which hold great medicinal promises. To date, the S. pubescens fruit's essential oil (SPO) has never been investigated. METHODS: The current research has been focused to evaluate the chemical composition of S. pubescens fruit essential oil through Gas Chromatography-Mass Spectrometry (GC-MS), followed by the investigation of antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities in appropriate models to uncover its biological potentials. Extraction of (Solanopuboil/SPO) from the fresh unripe fruits of Solanum pubescens was carried out in Buchner funnel and Whatman no.10 filter paper and concentrated at 40°C using a rotary evaporator. The metabolic profiling of SPO was analysed by GC-MS technique. The MIC, MBC, activity index, and total antimicrobial activity of SPO were evaluated using standard procedures. Anti-inflammatory activity of SPO was screened using Carrageenan induced paw oedema and Cotton pellet-induced granuloma. Tail immersion test, Acetic acid writhing response and Formalin paw lick test was performed in rats in order to examine the analgesic activity of SPO. Wound healing activity of SPO was investigated by performing the incision wound model, Excision wound model and Dead space wound model in rats. RESULTS: The SPO displayed a constant degree of antimicrobial activity against B. cereus, B. subtilis, E. coli, A. niger, A. fumigatus and C. albicans with significant anti-inflammatory and analgesic activities. Also, a prominent wound healing potential of it was observed in excision, incision and dead space wound models with considerable elevation in granulation tissue hydroxyproline, hexuronic acid and hexosamine content in association with remarkable regulation of anti-inflammatory and antioxidant markers i.e., Lipid peroxidase (LPO), Nitric Oxide (NO), Superoxide dismutase (SOD), Glutathione (GSH), Catalase (CAT), Glutathione Peroxidase (GPx). CONCLUSION: These findings strongly validate the therapeutic potential of S. pubescens fruit essential oil in antimicrobial and anti-inflammatory mediated wound healing and suggests its promising application as valuable and novel indigenous leads in the food and pharmaceutical industries. To the best of our knowledge, this is the first-ever investigatory report on the systematic phytochemical and therapeutic examination of S. pubescens fruit essential oil.

Is There a Prechordal Region and an Acroterminal Domain in Amphioxus?

This essay re-examines the singular case of the supposedly unique rostrally elongated notochord described classically in amphioxus. We start from our previous observations in hpf 21 larvae [Albuixech-Crespo et al.: PLoS Biol. 2017;15(4):e2001573] indicating that the brain vesicle has rostrally a rather standard hypothalamic molecular configuration. This correlates with the notochord across a possible rostromedian acroterminal hypothalamic domain. The notochord shows some molecular differences that specifically characterize its pre-acroterminal extension beyond its normal rostral end under the mamillary region. We explored an alternative interpretation that the putative extension of this notochord actually represents a variant form of the prechordal plate in amphioxus, some of whose cells would adopt the notochordal typology, but would lack notochordal patterning properties, and might have some (but not all) prechordal ones instead. We survey in detail the classic and recent literature on gastrulation, prechordal plate, and notochord formation in amphioxus, compare the observed patterns with those of some other vertebrates of interest, and re-examine the literature on differential gene expression patterns in this rostralmost area of the head. We noted that previous literature failed to identify the amphioxus prechordal primordia at appropriate stages. Under this interpretation, a consistent picture can be drawn for cephalochordates, tunicates, and vertebrates. Moreover, there is little evidence for an intrinsic capacity of the early notochord to grow rostralwards (it normally elongates caudalwards). Altogether, we conclude that the hypothesis of a prechordal nature of the elongated amphioxus notochord is consistent with the evidence presented.

Gonadotropin-inhibitory hormone as a regulator of social interactions in vertebrates.

The social environment changes circulating hormone levels and expression of social behavior in animals. Social information is perceived by sensory systems, leading to cellular and molecular changes through neural processes. Peripheral reproductive hormone levels are regulated by activity in the hypothalamic-pituitary-gonadal (HPG) axis. Until the end of the last century, the neurochemical systems that convey social information to the HPG axis were not well understood. Gonadotropin-inhibitory hormone (GnIH) was the first hypothalamic neuropeptide shown to inhibit gonadotropin release, in 2000. GnIH is now regarded as a negative upstream regulator of the HPG axis, and it is becoming increasingly evident that it responds to social cues. In addition to controlling reproductive physiology, GnIH seems to modulate the reproductive behavior of animals. Here, we review studies investigating how GnIH neurons respond to social information and describe the mechanisms through which GnIH regulates social behavior.

A review of the toxicology of oil in vertebrates: what we have learned following the Deepwater Horizon oil spill.

In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.

First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions.

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human-environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26,000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe.

Low bee visitation rates explain pollinator shifts to vertebrates in tropical mountains.

Evolutionary shifts from bee to vertebrate pollination are common in tropical mountains. Reduction in bee pollination efficiency under adverse montane weather conditions was proposed to drive these shifts. Although pollinator shifts are central to the evolution and diversification of angiosperms, we lack experimental evidence of the ecological processes underlying such shifts. Here, we combine phylogenetic and distributional data for 138 species of the Neotropical plant tribe Merianieae (Melastomataceae) with pollinator observations of 11 and field pollination experiments of six species to test whether the mountain environment may indeed drive such shifts. We demonstrate that shifts from bee to vertebrate pollination coincided with occurrence at high elevations. We show that vertebrates were highly efficient pollinators even under the harsh environmental conditions of tropical mountains, whereas bee pollination efficiency was lowered significantly through reductions in flower visitation rates. Furthermore, we show that pollinator shifts in Merianieae coincided with the final phases of the Andean uplift and were contingent on adaptive floral trait changes to alternative rewards and mechanisms facilitating pollen dispersal. Our results provide evidence that abiotic environmental conditions (i.e. mountain climate) may indeed reduce the efficiency of a plant clade's ancestral pollinator group and correlate with shifts to more efficient new pollinators.

A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics.

Over one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to the anthelmintics currently used to treat nematode infection, prompting the need to develop new anthelmintics. Towards this end, we identified a set of kinases that may be targeted in a nematode-selective manner. We first screened 2040 inhibitors of vertebrate kinases for those that impair the model nematode Caenorhabditis elegans. By determining whether the terminal phenotype induced by each kinase inhibitor matched that of the predicted target mutant in C. elegans, we identified 17 druggable nematode kinase targets. Of these, we found that nematode EGFR, MEK1, and PLK1 kinases have diverged from vertebrates within their drug-binding pocket. For each of these targets, we identified small molecule scaffolds that may be further modified to develop nematode-selective inhibitors. Nematode EGFR, MEK1, and PLK1 therefore represent key targets for the development of new anthelmintic medicines.

Relative demographic susceptibility does not explain the extinction chronology of Sahul's megafauna.

The causes of Sahul's megafauna extinctions remain uncertain, although several interacting factors were likely responsible. To examine the relative support for hypotheses regarding plausible ecological mechanisms underlying these extinctions, we constructed the first stochastic, age-structured models for 13 extinct megafauna species from five functional/taxonomic groups, as well as 8 extant species within these groups for comparison. Perturbing specific demographic rates individually, we tested which species were more demographically susceptible to extinction, and then compared these relative sensitivities to the fossil-derived extinction chronology. Our models show that the macropodiformes were the least demographically susceptible to extinction, followed by carnivores, monotremes, vombatiform herbivores, and large birds. Five of the eight extant species were as or more susceptible than the extinct species. There was no clear relationship between extinction susceptibility and the extinction chronology for any perturbation scenario, while body mass and generation length explained much of the variation in relative risk. Our results reveal that the actual mechanisms leading to the observed extinction chronology were unlikely related to variation in demographic susceptibility per se, but were possibly driven instead by finer-scale variation in climate change and/or human prey choice and relative hunting success.

Ethno-medicinal uses of vertebrates in the Chitwan-Annapurna Landscape, central Nepal.

Traditional knowledge on the use of animal products to maintain human health is important since time immemorial. Although a few studies reported food and medicinal values of different animals, a comprehensive ethno-medicinal study of vertebrates in Nepal is still lacking. Thus, present study is aimed at documenting the ethno-medicinal knowledge related to vertebrate fauna among different ethnic communities in the Chitwan-Annapurna Landscape, central Nepal. Data was collected by using semi-structured questionnaires and analyzed by using Use Value (UV), Informant Consensus Factor (ICF) and Fidelity level (FL). Results showed a total of 58 (53 wild and 5 domestic) species of vertebrate animals. They were used to treat 62 types human ailments. Four animals were also used for veterinary diseases and agriculture benefits. The most widely used species was Felis chaus (UV = 0.25) with 3 use-reports by 10 informants. Cardiovascular and dental problems had the highest ICF value (0.974) with cardiovascular problems having 351 use-reports for 10 animal species and dental problems having 77 use-reports for 3 animal species. The least ICF was found in ophthalmological problems (ICF = 0.833, use reports = 7 for 2 species). We concluded that the different animals were an important part of traditional medicine for the local people living in the Chitwan-Annapurna Landscape. However, the majority of animals and most likely to be threatened due to their uses. The present documented ethnozoological knowledge can be used in conservation and management of vertebrates so that they could be protected for future generations.

Tissue Micro-channels Formed by Collagen Fibers and their Internal Components: Cellular Evidence of Proposed Meridian Conduits in Vertebrate Skin.

In order to clarify fine structures of the hypothetical meridian conduits of Chinese traditional medicine (CTM) in the skin, the present study used light and transmission electron microscopy to examine fasciae in different vertebrate species. Collagen fiber bundles and layers were arranged in a crisscross pattern, which developed into a special tissue micro-channel (TMC) network, in a manner that was analogs to the proposed skin meridian conduits. It was further revealed that tissue fluid in lateral TMC branches drained into wide longitudinal channels, which were distinctly different from lymphatic capillary. Mast cells, macrophages, and extracellular vesicles such as ectosomes and exosomes were distributed around telocytes (TCs) and their long processes (Telopodes, Tps) within the TMC. Cell junctions between TCs developed, which could enable the communication between contiguous but distant Tps. On the other hand, winding free Tps without cell junctions were also uncovered inside the TMC. Tissue fluid, cell junctions of TCs, mast cells, macrophages, and extracellular vesicles within the TMC corresponded to the circulating "" ("Qi-Xue", i.e., information, message, and energy) of meridian conduits at the cytological level. These results could provide morphological evidence for the hypothesis that "meridians are the conduit for Qi-Xue circulation" in CTM.

Effects of timed food availability on reproduction and metabolism in zebra finches: Molecular insights into homeostatic adaptation to food-restriction in diurnal vertebrates.

Food availability affects metabolism and reproduction in higher vertebrates including birds. This study tested the idea of adaptive homeostasis to time-restricted feeding (TRF) in diurnal zebra finches by using multiple (behavioral, physiological and molecular) assays. Adult birds were subjected for 1 week or 3 weeks to food restriction for 4 h in the evening (hour 8-12) of the 12 h light-on period, with controls on ad lib feeding. Birds on TRF showed enhanced exploratory behavior and plasma triglycerides levels, but did not show differences from ad lib birds in the overall food intake, body mass, and plasma corticosterone and thyroxine levels. As compared to ad lib feeding, testis size and circulation testosterone were reduced after first but not after third week of TRF. The concomitant change in the mRNA expression of metabolic and reproductive genes was also found after week 1 of TRF. Particularly, TRF birds showed increased expression of genes coding for gonadotropin releasing hormone (GnRH) in hypothalamus, and for receptors of androgen (AR) and estrogen (ER-alpha) in both hypothalamus and testes. However, genes coding for the deiodinases (Dio2, Dio3) and gonadotropin inhibiting hormone (GnIH) showed no difference between feeding conditions in both hypothalamus and testes. Further, increased Sirt1, Fgf10 and Ppar-alpha, and decreased Egr1 expression in the liver suggested TRF-effects on the overall metabolism. Importantly, TRF-effects on gene expressions by week 1 seemed alleviated to a considerable extent by week 3. These results on TRF-induced reproductive and metabolic effects suggest homeostatic adaptation to food-restriction in diurnal vertebrates.

Telocytes in Different Organs of Vertebrates: Potential Essence Cells of the Meridian in Chinese Traditional Medicine.

Telocytes (TCs) are very long, non-neuronal, somatic cells whose function is widely believed to be involved in providing connections between different cells within the body. The cellular characteristics of TCs in various organs have been studied by immunohistochemistry, double immunofluorescence and electron microscopy in different vertebrate species, and here we investigate the proposed properties of these cells in the context of the "meridian" in Chinese Traditional Medicine (CTM). The results show that TCs and their long extensions, telopodes (Tps) develop a complicated network by homo- and heterocellular junctions in the connective tissue throughout the body, which can connect the skin with distant organs. In concept, this is the analogue of ancient meridian maps connecting skin acupoints with the viscera. Various active cells and extracellular vesicles including exosomes move along Tps, which, along with developed mitochondria within the podoms of Tps, may account for the structural evidence for "Qi" (vital energy and signal communication) in CTM. Morphological associations of TCs with the nerve, vascular, endocrine, and immune systems are also compatible with previously proposed meridian theories in CTM. Close relationships exist between TCs and collagen fiber bundles and some structures in skin fascia provide the microanatomical support for acupuncture treatment based on the meridian principle. The dynamicity in the distribution and structure of TCs reflects the plasticity of the meridian at the cellular level. As the same attribute, both the meridian and the TC have been associated with various diseases. Here, we summarize structural analogues between the TC and the meridian, suggesting that TCs have the cytological characteristics of the CTM meridian. We, therefore, hypothesize that TCs are the "essence cells" of the CTM meridian, which can connect and integrate different cells and structures in the connective tissue.

First continuous pre-Jaramillo to Jaramillo terrestrial vertebrate succession from Europe.

In this paper, the early Pleistocene small vertebrate sequence of Quibas-Sima (Quibas karstic complex, Murcia, SE Spain) is presented. The available magnetostratigraphic information together with the small vertebrate association, allow to reliably constrain the age of the different units. The basal unit of the section has recorded a reversed polarity assigned to the pre-Jaramillo Matuyama (C1r.2r, i.e., between 1.2 and 1.07 Ma). The intermediate units have recorded a normal polarity correlated directly with the Jaramillo subchron (C1r.1n, between 1.07 and 0.99 Ma), while the upper units record the post-Jaramillo reverse polarity (C1r.1r, i.e., between 0.99 and 0.78). Jaramillo subchron is especially significant regarding the earliest hominin dispersal in Western Europe. However, vertebrate faunas unambiguously correlatable with Jaramillo subchron are extremely rare in Europe. Thereby, the study of the Quibas-Sima sequence allows to characterize the vertebrate association synchronous to this paleomagnetic episode in southern Iberian Peninsula, and contributes to increase knowledge of the biotic and climatic events that took place in southern Europe at the beginning of the Early-Middle Pleistocene transition, prior to the Matuyama-Brunhes boundary. A continuous small vertebrate succession has been reported, including representatives of the families Bufonidae, Pelodytidae, Testudinidae, Gekkonidae, Blanidae, Lacertidae, Colubridae, Viperidae, Soricidae, Erinaceidae, Rhinolophidae, Vespertilionidae, Muridae, Gliridae, Sciuridae, Leporidae and Ochotonidae The ecological affinities of the faunal association suggest a progressive reduction in forest cover in the onset of the Jaramillo subchron.

Functional Pituitary Networks in Vertebrates.

The pituitary is a master endocrine gland that developed early in vertebrate evolution and therefore exists in all modern vertebrate classes. The last decade has transformed our view of this key organ. Traditionally, the pituitary has been viewed as a randomly organized collection of cells that respond to hypothalamic stimuli by secreting their content. However, recent studies have established that pituitary cells are organized in tightly wired large-scale networks that communicate with each other in both homo and heterotypic manners, allowing the gland to quickly adapt to changing physiological demands. These networks functionally decode and integrate the hypothalamic and systemic stimuli and serve to optimize the pituitary output into the generation of physiologically meaningful hormone pulses. The development of 3D imaging methods and transgenic models have allowed us to expand the research of functional pituitary networks into several vertebrate classes. Here we review the establishment of pituitary cell networks throughout vertebrate evolution and highlight the main perspectives and future directions needed to decipher the way by which pituitary networks serve to generate hormone pulses in vertebrates.