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• For the first time 100% accuracy for epileptic seizure detection using electroencephalogram signals is demonstrated. • Both balanced and unbalanced datasets are studied. • Wavelet extraction from the original EEG signal enhances the feature extraction and selection steps. • Automatic segmentation with algorithmic intelligence is used. • As opposed to Genetic algorithms fast GA is used to achieve fast analysis. The precise electroencephalogram (EEG) signal classification with the highest possible accuracy is a key goal in the brain-computer interface (BCI). Considering the complexity and nonstationary nature of the EEG signals, there is an urgent need for effective feature extraction and data mining techniques. Here, we introduce a novel pipeline based on Bat and genetic algorithms for feature construction and dimension reduction of EEG signals. After wavelet extraction and segmentation, the Bat algorithm identifies the most relevant features. We use these features and a genetic algorithm combined with a neural network method to automatically classify the segments of the epilepsy EEG signals. We also use available classification methods based on k-Nearest Neighbors or naïve Bayes for comparison purposes. The code distinguishes individual signals within various combinations of data obtained from healthy volunteers with open or closed eyes and patients suffering from epilepsy disorders during seizure-free periods or seizure activities. Compared to the previously introduced methods, our proposed framework demonstrates a superior balance of high accuracy and short runtime. The minimum achieved accuracies for balanced and unbalanced classes are 100% and 75.9%, respectively. This approach has the potential for direct applications in clinics, enabling accurate and rapid analysis of the epilepsy EEG signals obtained from patients. [ABSTRACT FROM AUTHOR]

Bats have garnered increased attention in the field of life sciences for their typical biological characteristics of carrying a variety of zoonotic viruses without disease, long lifespans, low tumorigenesis rates, and high metabolism. When it was found that bats can carry the rabies virus, over 60 years of research revealed that bats host over 4100 distinct viruses, including Ebola virus and SARS-CoV. This paper primarily reviews the profiles of zoonotic viruses carried by bats across various regions globally. The review aims to provide a foundation and reference for future research on monitoring zoonotic viruses in diverse global regions and bat species, exploring the coevolutionary relationship between bats and viruses, understanding the tolerance mechanisms of bat B cells, prevention, and treatment of zoonotic diseases caused by bats. The search used 'bat', 'bats', 'rabies virus', 'Dengue virus', 'West Nile virus', 'Zika virus', 'St. Louis encephalitis virus', 'Japanese encephalitis virus', 'Hantavirus', 'Novel hantavirus', 'Rift Valley fever virus', 'Crimean Congo hemorrhagic fever virus', 'Paramyxovirus', 'Nipah virus', 'Hendra virus', 'Menangle virus', 'Tioman virus', 'Marburg Virus', 'Bombali virus', 'Ebola virus', 'Influenza A virus', 'coronavirus', 'Hepatitis B virus', and 'Hepatitis E virus' as text in PubMed. A total of 147 references were obtained. Surveys on severe zoonotic virus carriage have been limited to only 83 bat species belonging to nine families, which are distributed all over the world. We also briefly describe the antibody responses and B-cell molecules in bats. Several viruses have been found in different species of bats. This suggests that bats may be important hosts for future viral infectious diseases. Particularly in recent years, the close correlation between human infection pandemics caused by coronaviruses and bats highlights the pressing need to comprehend the species, tolerance, and coevolutionary mechanisms of zoonotic viruses carried by different bat species. [ABSTRACT FROM AUTHOR]

Cross-species transmission of viruses from wildlife animal reservoirs, such as bats, poses a threat to human and domestic animal health. Previous studies have shown that domestic animals have important roles as intermediate hosts, enabling the transmission of genetically diverse coronaviruses from natural hosts to humans. Here, we report the identification and characterization of a novel canine coronavirus (VuCCoV), which caused an epidemic of acute diarrhea in Vulpes (foxes) in Shenyang, China. The epidemic started on November 8, 2019, and caused more than 39,600 deaths by January 1, 2022. Full-length viral genomic sequences were obtained from 15 foxes with diarrhea at the early stage of this outbreak. The VuCCoV genome shared more than 90% nucleotide identity with canine coronavirus (CCoV) for three of the four structural genes, with the S gene showing a larger amount of divergence. In addition, 67% (10/15) of the VuCCoV genomes contained an open reading frame (ORF3) gene, which was previously only detected in CCoV-I genomes. Notably, VuCCoV had only two to three amino acid differences at the partial RNA-dependent RNA polymerase (RdRp) level to bat CoV, suggesting a close genetic relationship. Therefore, these novel VuCCoV genomes represent a previously unsampled lineage of CCoVs. We also show that the VuCCoV spike protein binds to canine and fox aminopeptidase N (APN), which may allow this protein to serve as an entry receptor. In addition, cell lines were identified that are sensitive to VuCCoV using a pseudovirus system. These data highlight the importance of identifying the diversity and distribution of coronaviruses in domestic animals, which could mitigate future outbreaks that could threaten livestock, public health, and economic growth. [ABSTRACT FROM AUTHOR]

• Extractive industry workers are more likely to be exposed to sarbecoviruses. • People who are in contact with bats are more likely to be exposed to sarbecoviruses. • Evidence for zoonotic origin of SARS-CoV-2. • Zoonotic spillover of coronaviruses in rural communities exposed to bats. • Multiplex surrogate virus neutralization assay to differentiate sarbecoviruses. Sarbecoviruses are a subgenus of Coronaviridae that mostly infect bats with known potential to infect humans (SARS-CoV and SARS-CoV-2). Populations in Southeast Asia, where these viruses are most likely to emerge, have been undersurveyed to date. We surveyed communities engaged in extractive industries and bat guano harvesting from rural areas in Myanmar. Participants were screened for exposure to sarbecoviruses, and their interactions with wildlife were evaluated to determine the factors associated with exposure to sarbecoviruses. Of 693 people screened between July 2017 and February 2020, 12.1% were seropositive for sarbecoviruses. Individuals were significantly more likely to have been exposed to sarbecoviruses if their main livelihood involved working in extractive industries (logging, hunting, or harvesting of forest products; odds ratio [OR] = 2.71, P = 0.019) or had been hunting/slaughtering bats (OR = 6.09, P = 0.020). Exposure to a range of bat and pangolin sarbecoviruses was identified. Exposure to diverse sarbecoviruses among high-risk human communities provides epidemiologic and immunologic evidence that zoonotic spillover is occurring. These findings inform risk mitigation efforts needed to decrease disease transmission at the bat-human interface, as well as future surveillance efforts warranted to monitor isolated populations for viruses with pandemic potential. [ABSTRACT FROM AUTHOR]

Scientists in China announced on 25th of November with great concern that there is a new Covid-like virus out of the five viruses of concern discovered among bats across Yunnan province. It was reported that this Covid-like virus BtSY2 has high potential of infecting humans as it comprises a receptor binding domain which is a vital part of the spike protein used to lay hold of human cells and subsequently utilize human ACE2 receptor for cell entry similar to the SARS-CoV-2. In a bid to address this global threat in affected countries , it is expedient for authorized health professionals, policy makers and the world to keep an eye on this Covid-like virus capable of spreading from bats to humans because most pandemic outbreaks in recent decades have arisen in such a manner. Strict actions should be implemented in impeding transmission to humans which is paramount to battling viral diseases as learnt from history that viral outbreaks are very impossible to eradicate after global outbreak. Health officials and the World Health Organization should invest urgently in more research to further study this new Covid-like virus with an approach to prepare for a possible viral outbreak, and develop treatment options and possible vaccines to outsmart the danger posed to human health. [ABSTRACT FROM AUTHOR]

Among their many unique biological features, bats are increasingly recognized as a key reservoir of many emerging viruses that cause massive morbidity and mortality in humans. Bats are capable of harboring many of these deadly viruses without any apparent signs of pathology, in a mechanism known as viral disease tolerance. However, the immunological mechanisms behind viral tolerance remain poorly understood. As a non-model organism species, there are very limited research resources and tools available to study bat immunology. In the cave nectar bat Eonycteris spelaea , we have a panel of monoclonal antibodies (mAbs) against major immune markers. An immunophenotyping survey of major immune compartments and barrier sites using these mAbs reveals differences in the immunological landscape of bats. [Display omitted] • Development of a panel of monoclonal antibodies specific to E. spelaea • Flow cytometric phenotyping of multiple tissues to compare bats and mice • Bats have fewer B cells and a skewing of monocytes toward the non-classical lineage • CD4 and CD21 mAbs demonstrate cross-reactivity to two other bat species Bats are reservoir hosts of many viruses, harboring these viruses using unique mechanisms of viral tolerance. However, immunological study has been impaired by a lack of suitable tools. Chen et al. address this limitation by the usage of a panel of bat-specific monoclonal antibodies for flow cytometry. [ABSTRACT FROM AUTHOR]

• Icv infusion of prokineticin 2 (1.5 nMol) did not alter food and water consumption in rats, but infusion of prokineticin 2 (4.5 nMol) decreased food consumption. • Icv prokineticin 2 (4.5 nMol) infusion reduced the body weight of rats. • Icv prokineticin 2 (4.5 nMol) infusion induced the hypothalamus-pituitary-thyroid (HPT) axis. • Icv prokineticin 2 (4.5 nMol) infusion increased the expression level of PGC-1α and UCP1 genes in white and brown adipose tissue. The hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue. A total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n =10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1α and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR. Icv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p <0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p <0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1α UCP1 in the WAT and BAT (p <0.05). Icv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis. [ABSTRACT FROM AUTHOR]

Les phénomènes d'hypersensibilité aux vaccins à ARNm dirigés contre le SARS-CoV-2 sont très rares. Ils peuvent être liés à un mécanisme IgE-dépendant impliquant les PEG contenus dans les vaccins sous forme de liposomes. Une activation directe de la voie classique du complément (CARPA) a été également fortement suspectée. En complément des tests cutanés, des biomarqueurs ont été proposés, en particulier la recherche d'anticorps anti-PEG, le dosage des anaphylatoxines C5a et C3a ou du complexe soluble C5b-9. Les anticorps anti-PEG sont dosables par quelques méthodes non standardisées mais leur présence dans ces réactions n'a pas été confirmée. Il en est de même pour les protéines du complément. L'histamine et la tryptase ont rarement pu être dosées au moment de la réaction et leur augmentation est inconstante selon les études. Une tryptase basale un peu élevée chez certains patients suggère qu'une hyper-alpha-tryptasémie pourrait être impliquée. Le test d'activation des basophiles s'est imposé comme un examen pouvant être utile mais les résultats sont encore difficiles à interpréter en raison de la variabilité des allergènes utilisés : PEG, PEG sous forme de liposomes ou vaccin lui-même. L'absence de positivité des tests cutanés alors que les basophiles sont capables de s'activer en présence du même allergène ex vivo chez certains patients est en faveur, dans ce cas, d'un phénomène non IgE-dépendant. En conclusion, dans l'exploration des réactions immédiates aux vaccins à ARNm contre le SARS-CoV-2, l'importance de la place de marqueurs biologiques nécessite des études complémentaires afin de mieux identifier les acteurs et les mécanismes impliqués. Hypersensitivity to mRNA vaccines directed against SARS-CoV-2 are rare. They may be related to an IgE-dependent mechanism involving PEG contained in vaccines in the form of liposomes. Direct activation of the classical complement pathway (CARPA) has also been strongly suspected. In addition to skin tests, biomarkers have been proposed: anti-PEG antibodies, determination of anaphylatoxins C5a and C3a, or soluble complex C5b-9. Anti-PEG antibodies can be measured by non-standardized in house methods; their presence in post-vaccination reactions against SARS-CoV2 has not been confirmed by all the studies as well as for complement proteins. Mast cell mediators (histamine and tryptase) could rarely be assayed at the time of reaction and their increase is inconstant depending on studies. A slightly elevated baseline tryptase level in some patients suggests that hyper-alphatryptasemia might be involved. A basophil activation test (BAT) can be performed but the results are still preliminary depending on the allergens used: PEG, PEG in the form of liposomes or vaccine itself. The lack of positivity of skin tests in some patients even though basophils are able to be activated in the presence of the same allergen confirms the hypothesis in this case of a possible non-IgE-dependent phenomenon. In conclusion, concerning the exploration of immediate reactions to mRNA vaccines directed against SARS-CoV-2, the place of biological markers requires additional studies in order to better identify the actors and mechanisms involved. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is a debilitating mast cell–driven disease characterized by recurrent wheals and/or angioedema. Substantial progress has been made in dissecting the 2 main autoimmune mechanisms that drive the pathogenesis of CSU. Type I autoimmune (autoallergic) CSU is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type IIb autoimmune CSU is mediated by autoantibodies that activate mast cells, for example, via IgE and FcεRI, and is present in less than 10% of patients with CSU when strict criteria are used, that is, triple positivity of autologous serum skin test, immunoassays for IgG autoantibodies, and basophil activation tests. A subpopulation of patients with CSU has both types. Type IIb autoimmune CSU is characterized by higher disease severity, concomitant autoimmune diseases, low levels of total IgE, elevated levels of IgG-anti–thyroid peroxidase, basopenia, eosinopenia, poor response to antihistamines and to omalizumab, and a good response to cyclosporine. Novel targeted therapies for CSU are under development such as ligelizumab, an anti-IgE, fenebrutinib and remibrutinib, Bruton's tyrosine kinase inhibitors, and dupilumab, an anti–IL-4Rα. Further studies should investigate the overlap between autoallergic and type IIb autoimmune CSU, optimize the diagnosis of both autoimmune endotypes using easy-to-perform, noninvasive, and inexpensive markers, and assess differences in response to therapy. [ABSTRACT FROM AUTHOR]

Haemosporidians infect a wide diversity of bat genera and species, yet little is known about their transmission cycles or epidemiology. Though several recent studies have focused on the genus Hepatocystis , an Old World parasite primarily infecting bats, monkeys, and squirrels, this group is still understudied with little known about its transmission and molecular ecology. These parasites lack an asexual erythrocytic stage, making them unique from the Plasmodium vertebrate life cycle. In this study, we detected a prevalence of 31% of Hepatocystis in short-nosed fruit bats (Cynopterus brachyotis) in Singapore. Phylogenetic reconstruction with a partial cytochrome b sequence revealed a monophyletic group of Hepatocystis from C. brachyotis in Malaysia, Singapore, and Thailand. There was no relationship with infection and bat age, sex, location, body condition or monsoon season. The absence of this parasite in the five other bat species sampled in Singapore indicates this Hepatocystis species may be host restricted. [Display omitted] • A bat haemosporidian (Hepatocystis) was detected in short nose fruit bats (Cynopterus brachyotis) in Singapore. • Infection was not associated with bat age, sex, sample location, body condition or monsoon season. • Infection was detected in only one bat species, indicating this Hepatocystis species may be host specific. [ABSTRACT FROM AUTHOR]

Transcription factor MAFB regulates various homeostatic functions of macrophages. This study explores the role of MAFB in brown adipose tissue (BAT) thermogenesis using macrophage-specific Mafb -deficient (Mafb f/f ::LysM-Cre) mice. We find that Mafb deficiency in macrophages reduces thermogenesis, energy expenditure, and sympathetic neuron (SN) density in BAT under cold conditions. This phenotype features a proinflammatory environment that is characterized by macrophage/granulocyte accumulation, increases in interleukin-6 (IL-6) production, and IL-6 trans -signaling, which lead to decreases in nerve growth factor (NGF) expression and reduction in SN density in BAT. We confirm MAFB regulation of IL-6 expression using luciferase readout driven by IL-6 promoter in RAW-264.7 macrophage cell lines. Immunohistochemistry shows clustered organization of NGF-producing cells in BAT, which are primarily TRPV1+ vascular smooth muscle cells, as additionally shown using single-cell RNA sequencing and RT-qPCR of the stromal vascular fraction. Treating Mafb f/f ::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure. [Display omitted] • Macrophage MAFB deficiency impairs cold-induced BAT thermogenesis • MAFB loss reduces BAT sympathetic neuron density in the cold • MAFB represses macrophage IL-6 expression via promoter binding • MAFB deficiency in macrophages induces inflammatory environment in BAT Yadav et al. elucidates the role of the transcription factor MAFB in regulating brown adipose tissue (BAT) thermogenesis. They demonstrate that MAFB deficiency in macrophages decreases the neuronal density and thermogenesis of BAT in response to cold, due to an inflammatory state caused by an increase in IL-6, with accumulation of macrophages and granulocytes. [ABSTRACT FROM AUTHOR]

Pathology records of bats submitted to the University of Georgia from managed care settings were reviewed to identify naturally occurring diseases. Fifty-nine cases were evaluated during an 11-year period (2008–2019), including representatives from four families: Pteropodidae (Yinpterochiroptera), Phyllostomidae, Vespertilionidae and Molossidae (Yangochiroptera). Pathology reports were reviewed to determine the primary pathological process resulting in death or the decision to euthanize. Cases were categorized as non-infectious (34/59; 58%), infectious/inflammatory (17/59; 29%) or undetermined due to advanced autolysis (8/59; 14%). Musculoskeletal diseases and reproductive losses were the most frequent pathological processes. Among the infectious processes identified, bacterial infections of the reproductive and haemolymphatic systems were most frequently observed. The first two reports of neoplasia in small flying foxes (Pteropus hypomelanus) are described. Bats under managed care present with a wide range of histopathological lesions. In this cohort, non-infectious disease processes were common. [ABSTRACT FROM AUTHOR]

The carnivorous pitcher plants of the genus Nepenthes usually attract, capture and digest arthropod prey to obtain mineral nutrients. But few members of the genus have evolved specialized nutrient sequestration strategies to acquire nitrogen from the faeces and urine of mutualistic mammals, which they attract. Because the plants obtain significant amounts of nitrogen in a more available form, we hypothesized that they have relaxed the production of digestive enzymes. If so, species that digest mammal faeces should show fewer digestive enzymes than closely related species that rely on arthropods. We tested this hypothesis by comparing digestive enzymes in 1) Nepenthes hemsleyana , whose pitchers serve as roosts for the mutualistic woolly bat Kerivoula hardwickii , which also defecate inside the pitchers, and 2) the close relative Nepenthes rafflesiana , a typical arthropod capturing species. To investigate the dynamics of aspartic proteases (nepenthesin I and II) and type III and IV chitinases in both species, we conducted qPCR, western blotting, mass spectrometry, and enzyme activity measurements. We found that mRNA in pitcher tissue and enzyme abundance in the digestive fluid is upregulated in both species in response to faeces and insect feeding. Contrary to our initial hypothesis, the final nepenthesin proteolytic activity in the digestive fluid is higher in response to faeces addition than to insect prey irrespective of Nepenthes species. This indicates that faeces can mimic arthropod prey triggering the production of digestive enzymes and N. hemsleyana retained capacity for production of them. • Carnivorous pitcher plant Nepenthes hemsleyana in contrast to N. rafflesiana is adapted to obtain nutrients from bat faeces. • Feeding on bat faeces as well as arthropod prey increased production of digestive enzymes in both species. • There is no relaxation of digestive physiology in N. hemsleyana plants in response to coprophagous lifestyle. [ABSTRACT FROM AUTHOR]

Leishmaniasis involves the participation of several species of both wild and domestic mammal hosts and sandfly vectors, which demonstrates the eco-epidemiological complexity observed in this disease. Bats are among the most abundant types of mammals and the scarcity of research on Leishmania infection in these animals gives evidence of the importance of new studies that aim to clarify this relationship. This study aimed to detect the Leishmania spp. in bats. 146 bats, representing 16 different species belonging to the Molossidae, Vespertilionidae, and Phyllostomidae families, were received and processed for collection of tissues. Skin samples were collected from 100% of the bats, and liver samples were collected from 87% (n = 127). After evaluating the quality of the DNA extracted by means of PCR directed to the IRBP gene, the samples considered suitable for the Leishmania detection test were submitted for PCR directed to Leishmania kDNA, and to confirm positivity, were tested to the SSUrRNA gene-directed Nested-PCR. The Leishmania presence in the species Molossus pretiosus, Nyctinomops macrotis , and Lasiurus cinereus are the first reports this encounter in these species of bats in Brazil. Furthermore, new species of bats as possible hosts for L. infantum are reported, such as Molossus pretiosus, Myotis nigricans, Nyctinomops laticaudatus, Nyctinomops macrotis , and, for L. braziliensis , Lasiurus cinereus and Cynomops planirostris. These findings in bats in an area endemic for leishmaniasis indicate that these animals may be involved in sustaining the disease cycle in this location. Image 1 • Leishmaniasis is an endemic zoonosis that is expanding in Brazil and is considered an important public health problem. • The role of bats in the epidemiology of leishmaniais is still unclear. • The ability of bats to disperse and their longevity could facilitate the maintenance and dispersal of Leishmania. • We detected presence of L. infantum and L. braziliensis DNA in bats in the Brazilian Midwest. • Infected bats in areas endemic for leishmaniasis may indicate participation in the maintenance of parasites in these places. [ABSTRACT FROM AUTHOR]

At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV. [ABSTRACT FROM AUTHOR]

• Frequency and binaurality representation in the AC of the big brown bat, Eptesicus fuscus , is studied. • The number of impulses and latency of AC neurons varied with sound level and inter-aural level differences (ILD). • AC neurons are columnarly organized in best frequency, minimum threshold, binaurality and ILD curves. • Different frequency and binaurality representation in the AC of three bat species is compared and discussed. This study examines binaural response properties and sensitivity to interaural level difference of single neurons in the primary auditory cortex (AC) of the big brown bat, Eptesicus fuscus under earphone stimulation conditions. Contralateral sound stimulation always evoked response from all 306 AC neurons recorded but ipsilateral sound stimulation either excited, inhibited or did not affect their responses. High best frequency (BF) neurons typically had high minimum threshold (MT) and low BF neurons had low MT. However, both BF and MT did not correlate with their recording depth. The BF of these AC neurons progressively changed from high to low along the anteromedial-posterolateral axis of the AC. Their number of impulses and response latency varied with sound level and inter-aural level differences (ILD). Their number of impulses typically increased either monotonically or non-monotonically to a maximum and the latency shortened to a minimum at a specific sound level. Among 205 AC neurons studied at varied ILD, 178 (87%) and 127 (62%) neurons discharged maximally and responded with the shortest response latency at a specific ILD, respectively. Neurons sequentially isolated within an orthogonal electrode puncture shared similar BF, MT, binaurality and ILD curves. However, the response latency of these AC neurons progressively shortened with recording depth. Species-specific difference among this bat, the mustached bat and the pallid bat is discussed in terms of frequency and binaurality representation in the AC. [ABSTRACT FROM AUTHOR]

Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome. We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared their metabolic phenotypes. We also carried out ex vivo assays with primary and immortalized mouse brown adipocytes to establish the autonomy of the effect of loss of iRhom2 on thermogenesis and respiration. Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improved insulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beige adipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced thermogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak. Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasis during metabolic disease. • Deletion of iRhom2 protects mice from metabolic syndrome. • In obesity, iRhom2 deletion increases energy expenditure, thermogenesis and white adipose tissue beiging. • iRhom2 deletion enhances thermogenesis in naïve brown adipocytes. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 19 (FGF19) is a postprandial hormone which plays diverse roles in the regulation of bile acid, glucose, and lipid metabolism. Administration of FGF19 to obese/diabetic mice lowers body weight, improves insulin sensitivity, and enhances glycemic control. The primary target organ of FGF19 is the liver, where it regulates bile acid homeostasis in response to nutrient absorption. In contrast, the broader pharmacologic actions of FGF19 are proposed to be driven, in part, by the recruitment of the thermogenic protein uncoupling protein 1 (UCP1) in white and brown adipose tissue. However, the precise contribution of UCP1-dependent thermogenesis to the therapeutic actions of FGF19 has not been critically evaluated. Using WT and germline UCP1 knockout mice, the primary objective of the current investigation was to determine the in vivo pharmacology of FGF19, focusing on its thermogenic and anti-obesity activity. We report that FGF19 induced mRNA expression of UCP1 in adipose tissue and show that this effect is required for FGF19 to increase caloric expenditure. However, we demonstrate that neither UCP1 induction nor an elevation in caloric expenditure are necessary for FGF19 to induce weight loss in obese mice. In contrast, the anti-obesity action of FGF19 appeared to be associated with its known physiological role. In mice treated with FGF19, there was a significant reduction in the mRNA expression of genes associated with hepatic bile acid synthesis enzymes, lowered levels of hepatic bile acid species, and a significant increase in fecal energy content, all indicative of reduced lipid absorption in animals treated with FGF19. Taken together, we report that the anti-obesity effect of FGF19 occurs in the absence of UCP1. Our data suggest that the primary way in which exogenous FGF19 lowers body weight in mice may be through the inhibition of bile acid synthesis and subsequently a reduction of dietary lipid absorption. • FGF19 increases UCP1 transcription in adipose tissue and is associated with significant weight loss. • The increase in metabolic rate observed with FGF19 is dependent upon the presence of UCP1. • In the absence of UCP1, the anti-obesity effect of FGF19 are associated with a greater reduction in energy absorption. [ABSTRACT FROM AUTHOR]

Bats serve as natural hosts for various infectious agents that can affect both humans and animals, and they are geographically widespread. In recent years, the prevalence of bat-associated pathogens has surged on a global scale, consequently generating significant interest in bats and their ectoparasites. In this study, we specifically selected the Miniopterus fuliginosus as the host and conducted bat captures in Nanjian Yi Autonomous County, Dali Bai Autonomous Prefecture, and the other in Mouding Township, Chuxiong Yi Autonomous Prefecture, located in Yunnan Province, China. Ectoparasites were meticulously collected from the bat body surface, alongside blood samples for subsequent analyses. Following collection, the ectoparasites were methodically identified and subjected to comprehensive ecological analysis. Additionally, DNA was extracted from both the bat blood and bat flies, with conventional PCR techniques utilized for molecular screening of four pathogens: Anaplasma sp., Babesia sp., Hepatozoon sp., and Bartonella sp. The capture efforts yielded a total of 37 M. fuliginosus , from which 388 ectoparasites were recovered, including 197 gamasid mites (C r = 50.77%, P M = 94.59%, M A = 5.32, M I = 5.63) and 191 bat flies (C r = 49.23%, P M = 75.68%, M A = 5.16, M I = 6.82). Notably, Steatonyssus nyctali (Y = 0.28, m*/m = 2.44) and Nycteribia allotopa (Y = 0.23, m*/m = 1.54) predominated among different individuals of M. fuliginosus , exhibiting an aggregated distribution pattern. The infection rates of Bartonella sp. were identified to be 18.92% (7/37) among bats and 37.17% (71/191) among bat flies, based on the testing of 37 bats and 191 bat flies. Phylogenetic analysis demonstrated that the Bartonella sequences exhibited similarity to those found in bats and bat flies within China and South Korea. This study not only contributes to our comprehension of ectoparasite infection in M. fuliginosus but also establishes a foundation for potential exploration of their role as vectors. [Display omitted] • Ecological analysis of ectoparasites on bats collected from Yunnan, China. • Investigating the presence of four pathogens carried by bats and their ectoparasites. • Providing reference for the vector potential of ectoparasites on bats. [ABSTRACT FROM AUTHOR]

Energy-dissipating brown adipocytes have significant potential for improving systemic metabolism. Vanin-1, a membrane-bound pantetheinase, is involved in various biological processes in mice. However, its role in BAT mitochondrial function is still unclear. In this study, we aimed to elucidate the impact of Vanin-1 on BAT function and contribution during overnutrition-induced obesity. Vanin-1 expression was analyzed in different adipose depots in mice. The cellular localization of Vanin-1 was analyzed by confocal microscopy and western blots. Mice lacking Vanin-1 (Vanin-1−/−) were continuously fed either a chow diet or a high-fat diet (HFD) to establish an obesity model. RNA-seq analysis was performed to identify the molecular changes associated with Vanin-1 deficiency during obesity. BAT-specific Vanin-1 overexpression mice were established to determine the effects of Vanin-1 in vivo. Cysteamine treatment was used to examine the effect of enzymatic reaction products of Vanin-1 on BAT mitochondria function in Vanin-1−/− mice. The results indicate that the expression of Vanin-1 is reduced in BAT from both diet-induced and leptin-deficient obese mice. Study on the subcellular location of Vanin-1 shows that it has a mitochondrial localization. Vanin-1 deficiency results in increased adiposity, BAT dysfunction, aberrant mitochondrial structure, and promotes HFD induced-BAT whitening. This is attributed to the impairment of the electron transport chain (ETC) in mitochondria due to Vanin-1 deficiency, resulting in reduced mitochondrial respiration. Overexpression of Vanin-1 significantly enhances energy expenditure and thermogenesis in BAT, renders mice resistant to diet-induced obesity. Furthermore, treatment with cysteamine rescue the mitochondrial dysfunction in Vanin-1−/− mice. Collectively, these findings suggest that Vanin-1 plays a crucial role in promoting mitochondrial respiration to counteract diet-induced obesity, making it a potential therapeutic target for obesity. [Display omitted] • Vanin-1 is downregulated in BAT of obese mice. • Vanin-1 deficiency leads to the decrease and dysfunction of mitochondrial in BAT of mice. • BAT-specific Vanin-1 overexpression protects mice against diet-induced metabolic dysfunction. • Vanin-1 regulates mitochondrial homeostasis in brown adipocytes in a cysteamine-dependent manner. [ABSTRACT FROM AUTHOR]

• Twenty studies were revised. Brazil accounted for most studies (60 %). • 48 bat species were recorded that hosted seven Leishmania species. • Desmodus rotundus and Glossophaga soricina showed greater interaction with Leishmania species. • Leishmania infantum interaction with bat species showed the highest frequency. • Leishmania spp has been detected in spleen, liver, skin, and blood samples of bats. A wide variety of mammals, including domestic and wild species, have been considered potential hosts and reservoirs for Leishmania. Bats have longevity, dispersal capacity, and adaptability to synotropic environments, characteristics that may favor their role in maintaining the life cycle of parasites. Therefore, the objective of this study was to carry out a worldwide systematic review of the occurrence of Leishmania species in bats, as well as to identify associations between eating habits and the type of sample collected with the occurrence of the infection. Data were obtained from a bibliographic search for studies that used molecular methods to identify parasites, employing the keywords "bats" AND " Leishmania " and their synonyms. We found 68 original studies, of which 20 were included in this review. Most studies were conducted in Brazil (60 %) and only 10 % were conducted in Old World countries. In all, 48 bat species were recorded that hosted seven Leishmania species, resulting in 62 different host-parasite interactions, and the Leishmania infantum interaction with bat species presented higher frequency. There was no significant difference between Leishmania species richness, infection percentage, and type of sample analyzed, but in general, it is observed that the use of different biological samples seems to expand the possibility of parasite detection. The patterns observed here indicate that bats can become infected with a wide variety of Leishmania species and likely play an important role in maintaining the parasite's life cycle. Thus, we suggest that studies aimed at understanding the transmission cycle of leishmaniasis include the investigation of bats as potential hosts or reservoirs of Leishmania. [ABSTRACT FROM AUTHOR]

Bat trypanosomes consist of more than 30 trypanosome species from over 70 species of bats. Recent studies suggest that bats play a role in disseminating trypanosomes from African continent to the terrestrial mammals both in the Afrotropic-Palearctic Ecozones and Nearctic Ecozone. However, the diversity, distribution, and evolution of bat trypanosomes are still unclear. To better understand their evolution, more genetic data of bat trypanosomes from a variety of locations are required. During a survey of Borrelia spp. of bats inhabiting a cave in Zambia, we observed flagellate parasites from 5 of 43 hemocultures. Sequence and phylogenetic analyses of the glycosomal glyceraldehyde 3-phosphate dehydrogenase gene (gGAPDH ; 572 bp) and the 18S ribosomal RNA gene (18S rRNA gene; 1,079–1,091 bp) revealed that all were Trypanosoma spp. belonged to the Trypanosoma cruzi clade. Three and two of them exhibited the similarity with T. conorhini and T. dionisii , respectively. The present study provides the first genetic data on Trypanosoma spp. of bats inhabiting Zambia. Image 1 • Two putative species of trypanosomes were detected from bats. • First molecular characterization of bat trypanosome in Zambia. • First record of trypanosome in Hipposideros vittatus. [ABSTRACT FROM AUTHOR]

Highlights • Trypanosoma dionisii infecting bats from China. • Eptesicus serotinus and Myotis pequinius were detected positive for Trypanosoma dionisii. • First report of Trypanosoma dionisii in Myotis pequinius. Abstract Although bats were considered as a major host of trypanosomatid flagellates, information of trypanosomes in bats is unknown in China. We collected bats in 2015 from Shandong Province of China and used PCR to amplify the Trypanosoma glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) gene and 18S rRNA gene from the bat blood samples and heart tissues. The results showed that 10.3% (13/126) of bats (Eptesicus serotinus and Myotis pequinius) were positive for trypanosomatid DNA and DNA sequencing showed that all PCR amplified Trypanosoma DNA belonged to T. dionisii. We concluded that T. dionisii had a infection rate in bats from China. For the first time, Trypanosoma infections were detected in bats from China, providing valuable information on the prevalence of these parasites in Asia. This is also the first report of Trypanosoma dionisii in Myotis pequinius , suggesting that Trypanosoma dionisii has a broad host species. [ABSTRACT FROM AUTHOR]

Highlights • Reducing hedgerow trimming frequency benefits macro-moths and shrub/tree-feeders (all moths species combined). • Abundance of four nationally-declining moth species was higher on hedgerows left untrimmed for at least three years. • Increasing woodland amount and connectivity may enhance moth abundance and diversity. • Arable fields adjacent to hedgerows may have a negative impact on hedgerow-dependent moths. • Moth conservation in farmland requires a multi-scale management approach. Abstract Hedgerows provide valuable habitats and corridors for many species in farmland, yet a lack of appropriate management may threaten their benefits to biodiversity. Although agri-environment scheme (AES) prescriptions on hedgerow management have the potential to reverse the detrimental effect of over-trimming on wildlife, their effectiveness has rarely been addressed. The aims of the study were to (i) assess moth responses to trimming regimes; and (ii) investigate the influence of the surrounding landscape on moth assemblages. We specifically tested the effectiveness of the trimming regime recommended by the targeted AES that was implemented on farms near greater horseshoe bat (Rhinolophus ferrumequinum) colonies since it represented the most sympathetic hedgerow management option among English AES options. We sampled adult micro- and macro-moths along 64 hedgerows located within 20 English farms using light traps, and classified moths into two guilds reflecting their larval food preferences, namely grass/herb- and shrub/tree-feeders. Our results suggest that reducing trimming has a positive impact on macro-moth species richness as well as on shrub/tree-feeder abundance and species richness. It also benefited four moth species that are significantly declining in Britain. Furthermore, while the proportion of woodland at a large spatial scale (3.0 km radius around the sampling sites) was positively associated with the abundance of macro-moths and grass/herb-feeders, woodland connectivity had a positive effect on the species richness of grass/herb- and shrub/tree-feeders at large and medium (1.5 km radius) scales, respectively. Both the abundance and species richness of macro-moths and the abundance of shrub/tree-feeders were negatively affected by the presence of arable fields adjacent to hedgerows. Overall, these findings reveal the wider biodiversity benefits of targeted AESs focusing on habitat improvement for R. ferrumequinum , and the importance of woodland in the wider landscape. We therefore strongly recommend implementing a multi-scale management approach (i.e. from field to landscape) through the use of adequate AES prescriptions to conserve moths in agricultural landscapes. [ABSTRACT FROM AUTHOR]

Abstract Objective Sympathetic nervous system and immune cell interactions play key roles in the regulation of metabolism. For example, recent convergent studies have shown that macrophages regulate obesity through brown adipose tissue (BAT) activation and beiging of white adipose tissue (WAT) via effects upon local catecholamine availability. However, these studies have raised issues about the underlying mechanisms involved including questions regarding the production of catecholamines by macrophages, the role of macrophage polarization state and the underlying intracellular signaling pathways in macrophages that might mediate these effects. Methods To address such issues we generated mice lacking Irs2 , which mediates the effects of insulin and interleukin 4, specifically in LyzM expressing cells (Irs2 LyzM −/− mice). Results These animals displayed obesity resistance and preservation of glucose homeostasis on high fat diet feeding due to increased energy expenditure via enhanced BAT activity and WAT beiging. Macrophages per se did not produce catecholamines but Irs2 LyzM −/− mice displayed increased sympathetic nerve density and catecholamine availability in adipose tissue. Irs2 -deficient macrophages displayed an anti-inflammatory transcriptional profile and alterations in genes involved in scavenging catecholamines and supporting increased sympathetic innervation. Conclusions Our studies identify a critical macrophage signaling pathway involved in the regulation of adipose tissue sympathetic nerve function that, in turn, mediates key neuroimmune effects upon systemic metabolism. The insights gained may open therapeutic opportunities for the treatment of obesity. Highlights • Irs2 deletion in macrophages improves metabolic health and BAT activity in mice. • Irs2 -deficient BMDM are protected from M1 polarisation by LPS. • BAT norepinephrine levels and TH density mirror increases in BAT activity. • Cross-talk between macrophages and BAT sympathetic neurons underpin these findings. • Macrophage Irs2 modulates energy homeostasis. [ABSTRACT FROM AUTHOR]

Abstract Objectives Brown adipose tissue (BAT) dissipates nutritional energy as heat through uncoupling protein 1 (UCP1). The discovery of functional BAT in healthy adult humans has promoted the search for pharmacological interventions to recruit and activate brown fat as a treatment of obesity and diabetes type II. These efforts require in vivo models to compare the efficacy of novel compounds in a relevant physiological context. Methods We generated a knock-in mouse line expressing firefly luciferase and near-infrared red florescent protein (iRFP713) driven by the regulatory elements of the endogenous Ucp1 gene. Results Our detailed characterization revealed that firefly luciferase activity faithfully reports endogenous Ucp1 gene expression in response to physiological and pharmacological stimuli. The iRFP713 fluorescence signal was detected in the interscapular BAT region of cold-exposed reporter mice in an allele-dosage dependent manner. Using this reporter mouse model, we detected a higher browning capacity in female peri-ovarian white adipose tissue compared to male epididymal WAT, which we further corroborated by molecular and morphological features. In situ imaging detected a strong luciferase activity signal in a previously unappreciated adipose tissue depot adjunct to the femoral muscle, now adopted as femoral brown adipose tissue. In addition, screening cultured adipocytes by bioluminescence imaging identified the selective Salt-Inducible Kinase inhibitor, HG-9-91-01, to increase Ucp1 gene expression and mitochondrial respiration in brown and brite adipocytes. Conclusions In our mouse model, firefly luciferase activity serves as a bona fide reporter for dynamic regulation of Ucp1. In addition, by means of iRFP713 we are able to monitor Ucp1 expression in a non-invasive fashion. Highlights • A new reporter mouse model enables bona fide monitoring of endogenous Ucp1 gene expression. • The new generation near-infrared fluorescent protein iRFP713 enables noninvasive imaging of brown fat. • Reporter mice show sex-specific differences in browning propensity of gonadal WAT. • We discovered a novel brown adipose tissue depot, now adopted as femoral brown fat. • Our reporter cell assays revealed the pan -Salt-Inducible Kinase as an inhibitor of Ucp1 gene expression. [ABSTRACT FROM AUTHOR]

Abstract Physical exercise leads to beneficial effects in numerous tissues and organ systems and offers protection against obesity and type 2 diabetes. Recent studies have investigated the role of exercise on brown adipose tissue (BAT) and white adipose tissue (WAT), and have indicated marked adaptations to each tissue with exercise. Studies investigating the effects of exercise on BAT have produced conflicting results, with some showing an increase in the thermogenic activity of BAT and some demonstrating a decrease in the thermogenic activity of BAT. Human studies have observed a down-regulation of BAT activity (measured by a reduction in glucose uptake) in response to exercise. In WAT, exercise decreases adipocyte size, alters gene expression, and increases mitochondrial activity. Transplantation of exercise-trained subcutaneous WAT (scWAT) improves whole-body metabolic health. In rodents, exercise also results in a beiging of scWAT. Thus, exercise-induced changes to adipose tissue may be part of the mechanism by which exercise improves metabolic health. [ABSTRACT FROM AUTHOR]

Abstract Brown adipose tissue (BAT) is a crucial regulator of energy expenditure. Emerging evidence suggests that n-3 PUFA potentiate brown adipogenesis in vitro. Since the pregnancy and lactation is a critical time for brown fat formation, we hypothesized that maternal supplementation of n-3 PUFA promotes BAT development in offspring. Female C57BL/6 mice were fed a diet containing n-3 PUFA (3%) derived from fish oil (FO), or an isocaloric diet devoid of n-3 PUFA (Cont) during pregnancy and lactation. Maternal n-3 PUFA intake was delivered to the BAT of neonates significantly reducing the n-6/n-3 ratio. The maternal n-3 PUFA exposure was linked with upregulated brown-specific gene and protein profiles and the functional cluster of brown-specific miRNAs. In addition, maternal n-3 PUFA induced histone modifications in the BAT evidenced by 1) increased epigenetic signature of brown adipogenesis, i.e., H3K27Ac and H3K9me2, 2) modified chromatin-remodeling enzymes, and 3) enriched the H3K27Ac in the promoter region of Ucp1. The offspring received maternal n-3 PUFA nutrition exhibited a significant increase in whole-body energy expenditure and better maintenance of core body temperature against acute cold treatment. Collectively, our results suggest that maternal n-3 PUFA supplementation potentiates fetal BAT development via the synergistic action of miRNA production and histone modifications, which may confer long-lasting metabolic benefits to offspring. Highlights • Maternal n-3 PUFA intake potentiates the transcriptional program of the fetal BAT. • Maternal n-3 PUFA intake promotes the brown-specific miRNA biogenesis. • Maternal n-3 PUFA intake alters site-specific histone PTM marks in the fetal BAT (i.e., H3K27Ac and H3K9me2). • Maternal n-3 PUFA intake increases energy expenditure in offspring. • Maternal n-3 PUFA intake may result in long-lasting metabolic benefits in offspring. [ABSTRACT FROM AUTHOR]

Abstract Development of therapeutic agents directed towards increasing brown adipose tissue (BAT) energy expenditure to combat obesity and its comorbidities is currently an area of intense research. Both preclinical and clinical studies have suggested a potentially significant role for BAT in regulating whole body energy expenditure as well as glucose and lipid metabolism. Lipids, particularly long chain fatty acids (LCFAs), are recognized as integral substrates in mediating the primary heat-producing functions of BAT, and to date thought to be principally sourced from stored intracellular lipid droplets. While this prior understanding is not disputed, recent evidence has demonstrated the importance of lipids derived from the circulation, including those from dietary sources and from tissue lipolysis, especially white adipose tissue lipolysis. Moreover, recent studies have shed further light on a potential role for BAT as an autocrine, paracrine and endocrine organ, with lipids as key signaling molecules. Advances in metabolomics have enabled high-resolution exploration of biomolecules that may be associated with various physiological processes and potentially pathological states. Such approaches have led to several novel lipid species recently being associated with BAT function and dysfunction. Further exploration of the circulating lipidome will likely reveal additional novel BAT biomarkers that can inform development of BAT-directed therapies. This review will address current progress and new strategies to identify and characterize BAT-associated lipids which may represent both novel activators and/or activity biomarkers with both research and clinical utility. [ABSTRACT FROM AUTHOR]

Long-term mark-recapture studies are essential for bat conservation. Over the last decades, millions of bats across Europe and America have been marked with forearm rings for this purpose. Although it is considered a cost-effective method compared to Passive Integrated Transponders (PIT) tags, direct injuries from using forearm rings have been reported since their very first use. Yet, their impact on bats' welfare has not been systematically evaluated and remains a highly controversial issue among the scientific community and policymakers. Here we assess the impact of forearm rings and PIT tags on the health of different bat species. We reviewed 12 years of the existing recapture data of free-ranging bats from NE Spain and evaluated the impact of both marking tools in a captive colony of Carollia perspicillata , by assessing the development of skin lesions and levels of cortisol metabolites in guano (CG) after marking. We report that 55.1 % (435/790) of the recaptured free-ranging bats with forearm rings presented skin lesions. All banded C. perspicillata (n = 22, 100 %) developed skin lesions, whereas none of the PIT-tagged (n = 21) presented lesions. Levels of CG were significantly higher after marking with forearm rings only for one group. Banded C. perspicillata exhibited discomfort-associated behaviours due to forearm rings. Under the "precautionary principle", we recommend the ban of forearm rings for all bat species until species-specific studies under controlled conditions are performed and approved by a legally constituted ethics committee. Consideration of other long-term marking tools is mandatory to align with global bat conservation strategies. • Bat banding activities are performed worldwide on a large scale. • Band injuries are continually reported but it remains a controversial topic. • Banding activities assumptions introduce important biases in bat population studies. • A 12-year review and captive study highlight the impact of bands on bats' health. • Aligning with global conservation strategies, bat banding should be banned. [ABSTRACT FROM AUTHOR]

Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues. [Display omitted] • Cold induces a change in serum metabolites that are essential to NAD+ metabolism • Circulatory NAM, tryptophan, and kynurenine are linked to BAT activation during cold • NAD+ biosynthesis pathways are upregulated in BAT compared with WAT • BAT NAD+ biosynthesis is related to whole-body metabolic health U-Din et al. show that cold-stimulated BAT metabolism is linked to circulatory serum metabolites crucial for NAD+ biosynthesis. In BAT, the pathways of NAD+ biosynthesis, upregulated in comparison to WAT, are linked to thermogenic mechanisms and with whole-body metabolic health. [ABSTRACT FROM AUTHOR]

Local allergic rhinitis (LAR) is a condition involving a localized nasal allergic response in absence of systemic atopy. Most studies on LAR have been performed in adults. We aimed to describe clinical characteristics of LAR pediatric patients, its clinical evolution over a 7-year follow-up period and to study the role of basophil activation test (BAT), for its diagnosis. Forty-four children with non-allergic rhinitis (NAR) were included (24 males, 20 females, aged under 15 years). Nasal allergen provocation test (NAPT) and BAT were performed with Dermatophagoides pteronyssinus and Phleum pratense. Seven patients (16%) were diagnosed of LAR. Six reacted to D pteronyssinus and one to P pratense. All LAR and 86% of NAR patients presented perennial symptoms. Fifty-seven percent of NAR and LAR patients referred persistent symptoms. Around half of NAR and LAR patients reported mild-moderate clinical manifestations. Three LAR patients associated conjunctival symptoms, proportionally more than NAR patients (19%, 7 out of 37). NAR patients presented bronchial asthma (n = 10) more frequently than LAR children (n = 1). More than half of LAR and NAR patients presented family history of atopy. BAT was negative in all LAR patients. On follow-up, 3 LAR patients and 10 of the 25 NAR patients who agreed to be retested, presented systemic sensitization. Dust mites were the most frequent allergen involved. LAR should be ruled out in children with NAR. Almost half of children with LAR develop systemic sensitization over time. BAT shows low sensitivity for the diagnosis of LAR in children. • Local allergic rhinitis should be considered in children diagnosed as non-allergic. • BAT seems to be less sensitive for the diagnosis of LAR in children than in adults. • Almost half of LAR children and one fourth of NAR children will eventually develop AR. [ABSTRACT FROM AUTHOR]

Mitochondrial antiviral signaling protein (MAVS) is an essential articulatory protein in immune responses against most RNA viruses. Whether bats, the natural hosts of numerous zoonotic RNA viruses, utilize conserved signaling pathways involving MAVS-mediated interferon (IFN) responses remains elusive. In this study, we performed the cloning and functional analysis of bat MAVS (BatMAVS). Amino acid sequence analysis revealed that BatMAVS was poorly conserved among species and evolutionarily closer to other mammals. Overexpression of BatMAVS significantly inhibited the replication of green fluorescent protein (GFP)-tagged VSV (VSV-GFP) and GFP-tagged Newcastle disease virus (NDV) (NDV-GFP) by activating the type I IFN pathway, and its expression at the transcriptional level was upregulated at the late stage of VSV-GFP infection. We further demonstrated that the CARD_2 and TM domains occupy a large proportion in the ability of BatMAVS to activate IFN-β. These results suggest that BatMAVS acts as an important regulatory molecule in IFN-induction and anti-RNA viruses in bats. • The full length of BatMAVS is identified and its basic characteristics is investigated. • BatMAVS can inhibit the replication of RNA viruses by activating the type I IFN pathway. • The expression of BatMAVS can be upregulated in the late stage of VSV-GFP infection. • The deletion of the CARD_2 or TM domains severely hinders BatMAVS from being functional. [ABSTRACT FROM AUTHOR]

Abstract Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans. Conversely, its level was induced during the differentiation course of human white pre-adipocytes derived from visceral fat. miR-199a-3p expression was relatively abundant in interscapular BAT (iBAT) and differentially regulated in the activated and aging BAT in mice. Additionally, miR-199a-3p expression level in human brown adipocytes was observed decreased upon thermogenic activation and increased by aging-related stimuli. Using primary pre-adipocytes, miR-199a-3p over-expression was capable of attenuating lipid accumulation and adipogenic gene expression as well as impairing brown adipocytes’ metabolic characteristics as revealed by decreased mitochondrial DNA content and respiration. Suppression of miR-199a-3p by a locked nucleic acid (LNA) modified-anti-miR led to increased differentiation and thermogenesis in human brown adipocytes. By combining target prediction and examination, we identified mechanistic target of rapamycin kinase (mTOR) as a direct target of miR-199a-3p that affected brown adipogenesis and thermogenesis. Our results point to a novel role for miR-199a-3p and its downstream effector mTOR in human brown adipocyte differentiation and maintenance of thermogenic characteristics, which can be manipulated as therapeutic targets against obesity and its related metabolic disorders. Highlights • miR-199a-3p expression was decreased during brown adipocyte differentiation in mice and human. • miR-199a-3p expression was differentially regulated in the activated and aging BAT in mice or brown adipocytes in vitro. • miR-199a-3p negatively regulated lipid accumulation and thermogenic program in human brown adipocytes. • miR-199a-3p directly targeted human 3′UTR of mTOR mRNA, which affected brown adipogenesis and thermogenic capacity. [ABSTRACT FROM AUTHOR]

Highlights • Fusion devices including ITER will generate tritiated waste. • An interim storage period up to 50 years is the reference solution for tritiated radwaste management. • Alternative strategies or additional processing options have to be sought for highly tritiated waste requiring an interim storage period longer than 50 years. • Defining the BAT for reduction of tritium inventory is relevant to identify ahead of time the studies to be launched and the actions to ensure a route. Abstract Fusion facilities will use tritium as a part of fuel. As a consequence, most of waste is expected to be contaminated with tritium and specific waste management strategies need to be developed taking into account physical and chemical properties of tritium. In France, the reference strategy for waste exceeding acceptance limits for disposal due to its tritium inventory is an interim storage period up to 50 years, corresponding approximately to detritiation factor of 16 due to radioactive decay. This article is mainly focused on the most tritiated categories of waste that would require an interim storage period longer than 50 years. Alternative strategies or additional processing options have been sought for these categories and the article defines methodology of identification of the Best Available Technique (BAT) for reduction of tritium inventory in the waste. Furthermore, the methodology is demonstrated on the case of purely tritiated metallic waste made from stainless steel. The methodology has been divided into three main steps: 1) Identification of the most relevant detritiation techniques; 2) Comparative analysis; and 3) Economical assessment. In order to simplify the first step, a software tool has been developed by CEA and its main features are described in this article. The results given by this tool are then analysed in the second step, which takes into account several non-economic criteria. Results of the comparative analysis show that detritiation of purely tritiated metallic waste made from stainless steel appears to be very attractive, allowing a significant reduction of interim storage duration before disposal in a surface repository. The last step, briefly described in this article, is ongoing and will economically assess the results from the previous steps. [ABSTRACT FROM AUTHOR]

Transformation of white adipose tissue (WAT) to a brown adipose tissue-like (BAT-like) phenotype has emerged as an attractive approach against obesity e.g. using g ß3 adrenergic receptor agonists. These could however, produce side-effects following systemic exposure. The present study explored the possibility of local use of CL-316,243 - a selective ß3 agonist - to circumvent this problem. Rats treated s.c. for 2 weeks (0.3 and 1 mg/kg) showed decreased inguinal fat pad (IFP) weight/volume, increased UCP-1 staining and expressed BAT-like features in H&E stained micrographs. Interscapular BAT increased in weight/volume. In contrast, local treatment into the IFP was not efficacious in terms of weight/volume, despite slight increases in UCP-1 staining and changes in histological features. After local treatment, the exposure of the IFP was lower than after systemic treatment. In turn higher local doses (0.5 and 5 mg/ml) were then tested which produced a strong trend for decreased volume of the IFP, a significant increase in UCP-1 staining, and also a decrease in adipocytes size but increased number. However, after this treatment the systemic exposure was in the same range as following systemic treatment. In conclusion, we saw no evidence for the possibility of converting inguinal WAT to a BAT-phenotype solely through local activation of ß3 receptors. This is in concert with our in vitro experiments which detected direct effects of PPARγ agonists at the gene/protein expression and functional level, but were unable to detect any effect of CL-316,243. [ABSTRACT FROM AUTHOR]

Abstract A divergent strain of Rickettsia japonica was isolated from a Dew's Australian bat argasid tick, Argas (Carios) dewae , collected in southern Victoria, Australia and a full-genome analysis along with sequencing of 5 core gene fragments was undertaken. This isolate was designated Rickettsia japonica str. argasii (ATCC VR-1665, CSUR R179). [ABSTRACT FROM AUTHOR]

Summary Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4. [ABSTRACT FROM AUTHOR]

A large number of animal models are currently used in appetite and obesity research. Because the worldwide incidence of obesity continues to climb, it is imperative that animal models sharing characteristics of human obesity and its co-morbidities be used appropriately in the quest for novel preventions or treatments. There is probably no animal model, at least in rodents, that recapitulates all aspects of “common” human obesity and its comorbidities, but rodent models allow insight into specific mechanisms of disease or its consequences. Frequently used obesity models can be partitioned into different categories, the major ones being a) based on mutations or manipulations of one or a few individual genes or b) those in genetically intact animals exposed to obesogenic environments such as, e.g., being maintained on high-fat diets or being raised in small litters. Characteristics of these models include distinct phenotypes of obesity, hyperphagia or changes in energy metabolism, and frequent comorbidities of obesity, like hyperglycemia, insulin resistance or diabetes-like syndromes. This review which is based on a presentation given during the Annual Meeting of the Society for the Study of Ingestive Behavior in July 2017 points out some observations and characteristics of rodent models in obesity and diabetes research. The choice of rodent models discussed here is subjective and based on the author's own experience or on fruitful discussions with colleagues about the pros and cons of specific models. Hence, this review, by no means, is meant to give a complete picture of rodent models used in this type of research, but the review tries to bring up some issues which, in the author's mind, may also be relevant for models not discussed here. For example, by discussing specific mouse and rat models, similarities and differences between mice and rats will be discussed that need to be considered to interpret experimental findings cautiously and in the context of the respective animal model. Knowing which animal model to use means, knowing its limitations. [ABSTRACT FROM AUTHOR]

Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum , comprising T. cruzi and bat-restricted trypanosomes, and Tra[Tve-Tco] formed by T. rangeli , Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis -like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, Tra[Tve-Tco] species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum . In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted Tra[Tve-Tco] and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli ) being pathogenic to humans. [ABSTRACT FROM AUTHOR]

The family Circoviridae comprises a large group of small circular single-stranded DNA viruses with several members causing severe pig and poultry diseases. In recent years the number of new viruses within the family has had an explosive increase showing a high level of genetic diversity and a broad host range. In this report we describe two more circoviruses identified from bats in Yunnan and Heilongjiang provinces in China. Full genome sequencing has revealed that these bat associated circoviruses (bat ACV) should be classified as new species within the genus Circovirus based on the demarcation criteria of the International Committee on the Taxonomy of Viruses (ICTV). The most striking result is the novel finding of a 21–28 nt polythymidine (poly-T) tract in the 3′ terminal intergenic region of bat ACV isolates from Heilongjiang province. To understand its role in viral replication, a wild type bat ACV and a mutated version with the entire poly-T deleted were rescued through construction of infectious clones. Replication comparison in vitro showed that the poly-T is not essential for viral replication. Identification of additional bat ACV isolates and study of their biological characteristics will be the main task in future to understand the potential roles of bats in transmission of circoviruses to terrestrial mammals and humans. [ABSTRACT FROM AUTHOR]

Urban species and habitats provide important ecosystem services such as summertime cooling, recreation, and pollination at a variety of scales. Many studies have assessed how biodiversity responds to urbanization, but little work has been done to try and create recommendations that can be easily applied to urban planning, design and management practice. Urban planning often operates at broad spatial scales, typically using relatively simplistic targets for land-cover mix to influence biodiversity and ecosystem service provision. Would more complicated, but still easily created, prescriptions for urban vegetation be beneficial? Here we assess the importance of vegetation measures (percentage vegetation cover, tree canopy cover and variation in canopy height) across four taxonomic groups (bats, bees, hoverflies and birds) at multiple spatial scales (100, 250, 500, 1000 m) within a major urban area (Birmingham, the United Kingdom). We found that small-scale (100–250-m radius) measures of vegetation were important predictors for hoverflies and bees, and that bats were sensitive to vegetation at a medium spatial-scale (250–500 m). In contrast, birds responded to vegetation characteristics at both small (100 m) and large (1000 m) scales. Vegetation cover, tree cover and variation in canopy height were expected to decrease with built surface cover; however, only vegetation cover showed this expected trend. The results indicate the importance of relatively small patches of vegetationfor supporting urban biodiversity, and show that relatively simple measures of vegetation characteristics can be useful predictors of species richness (or activity density, in the case of bats). They also highlight the danger of relying upon percentage built surface cover as an indicator of urban biodiversity potential. [ABSTRACT FROM AUTHOR]

Bats carry a great diversity of zoonotic viruses with a high-impact on human health and livestock. Since the emergence of new coronaviruses and paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can maintain some of these viruses. Improving our understanding on the role of bats in the epidemiology of the pathogens they harbour is necessary to prevent cross-species spill over along the wild/domestic/human gradient. In this study, we screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in two caves frequently visited by local people to collect manure and/or to hunt bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of Alpha and Betacoronavirus together with the partial polymerase gene of Paramyxovirus . Identified coronaviruses were related to pathogenic human strains and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our results highlighted the importance of monitoring virus circulation in wildlife, especially bats, in the context of intense human-wildlife interfaces in order to strengthen prevention measures among local populations and to implement sentinel surveillance in sites with high zoonotic diseases transmission potential. [ABSTRACT FROM AUTHOR]

The Industrial Emission Directive (IED) has strengthened the requirement to apply Best Available Techniques (BATs) first introduced by the IPPC Directive. The so-called “Sevilla Process”, which is the formal European process to define and revise BATs, is based upon an exchange of information among different stakeholders and relies on data analysis and expert judgements. If the process to collect and to share information between stakeholders at sectoral and installation levels is well defined, the determination of BATs and BAT-Associated Environmental Levels has evolved along with the revision of the BAT REFerence documents (BREFs). Nevertheless, no formal tool to support the analysis exists. The objective of this article is to present a 5-steps methodology aimed to classify installations according to two multicriteria approaches, either a representative angle or a performant approach, and then to identify reference installations, which would help to propose reference values and possible BATs. The methodology is supported by statistical tools (Principal Component analysis, hierarchical clustering) and algorithmic approach (MissForest). The application to French dairy sectors has validated the methodology and mathematical tools used. Two reference classes has been identified for the representative approach and 19 installations selected. For the performant installations, seven (7) installations has been selected. BATAELs for COD flow are proposed considering these classifications and an effort rate comprised between 23 and 96% has been revealed. [ABSTRACT FROM AUTHOR]

The Rhabdoviridae is among the most diverse families of RNA viruses and currently classified into 18 genera with some rhabdoviruses lethal to humans and other animals. Herein, we describe genetic characterization of three novel rhabdoviruses from bats in China. Of these, two viruses (Jinghong bat virus and Benxi bat virus) found in Rhinolophus bats showed a phylogenetic relationship with vesiculoviruses, and sequence analyses indicate that they represent two new species within the genus Vesiculovirus . The remaining Yangjiang bat virus found in Hipposideros larvatus bats were only distantly related to currently known rhabdoviruses. [ABSTRACT FROM AUTHOR]

• The invasive pest Spodoptera frugiperda poses a great threat to global food security. • Bats are natural pest samplers and feed on a variety of agricultural pests. • FAW was monitored in bat fecal samples one month earlier than traditional methods. • The date when bats first prey on FAW coincides with the FAW moth migration time. • Bats are sentinels for invasive pests with enough temporal and spatial resolution. Loss of crop yield due to non-native invasive pests is a global phenomenon with profound population, biodiversity, ecosystem, and economic impacts. The polyphagous and migratory fall armyworm (FAW) Spodoptera frugiperda (Lepidoptera, Noctuidae) has become a major invasive pest around the globe in the past decade, posing a great threat to global food security. Early warning and timely detection of this pest and its associated agricultural risks are essential for preventing, intervening, controlling, and mitigating invasion threats, which could reduce crop losses and economic damage. However, one key challenge is how to effectively and accurately monitor pest invasion as soon as possible prior to their establishment. Here, we aimed to determine the effectiveness of four different methods for identifying the presence of FAW, namely DNA metabarcoding, field survey, light trap, and sex pheromone trap. We collected fecal samples of six bat species in the FAW colonization area, including Rhinolophus pearsonii , Rhinolophus rex , Ia io , Myotis altarium , Myotis pilosus , and Myotis chinensis. We then utilized bat fecal samples to monitor FAW through DNA metabarcoding during its early establishment stages and compared this approach to three traditional surveillance methods. The results revealed interspecific differences in the occurrence frequency of FAW in different bat species. Furthermore, bat fecal DNA metabarcoding successfully monitored the occurrence of this pest nearly one month in advance compared with traditional approaches, which coincides with the adult migration time of larval counterparts found in the field based on effective accumulated temperature calculations. Our results showed that DNA metabarcoding dietary analysis of generalist insectivorous bats can be an effective, noninvasive, and economically viable tool for invasion pests monitoring to inform management decisions. [ABSTRACT FROM AUTHOR]

Polyomaviruses (PyVs) are known to infect a diverse range of vertebrate host species. We report the discovery of PyVs in vesper bats (family Vespertilionidae) from sampling in Central Europe. Seven partial VP1 sequences from different PyVs were detected in samples originating from six distinct vesper bat species. Using a methodology based on conserved segments within the major capsid virus protein 1 (VP1) among known PyVs, the complete genomes of two different novel bat PyVs were determined. The genetic distances of the large T antigen coding sequences from these PyVs compared to previously-described bat PyVs exceeded 15% meriting classification as representatives of two novel PyV species: Alphapolyomavirus epserotinus and Alphapolyomavirus myodaubentonii. Phylogenetic analysis revealed that both belong to the genus Alphapolyomavirus and clustered together with high confidence in clades including other bat alphapolyomaviruses reported from China, South America and Africa. In silico protein modeling of the VP1 subunits and capsid pentamers, and electrostatic surface potential comparison of the pentamers showed significant differences between the reference template (murine polyomavirus) and the novel bat PyVs. An electrostatic potential difference pattern between the two bat VP1 pentamers was also revealed. Disaccharide molecular docking studies showed that the reference template and both bat PyVs possess the typical shallow sialic acid-binding site located between two VP1 subunits, with relevant oligosaccharide-binding affinities. The characterisation of these novel bat PyVs and the reported properties of their capsid proteins will potentially contribute in the elucidation of the conditions creating the host-pathogen restrictions associated with these viruses. • Complete genome sequences of two novel vesper bat polyomaviruses were determined. • Proposed species: Alphapolyomavirus epserotinus, Alphapolyomavirus myodaubentonii. • Phylogenetic analysis shows a close relationship with bat PyVs from China. • The VP1 proteins show significant differences in electrostatic surface potential. • Shallow sialic acid binding sites were determined on the surface of VP1 proteins. [ABSTRACT FROM AUTHOR]

Mice with global deletion of the transient receptor potential channel melastatin family member 8 (TRPM8) are obese, and treatment of diet-induced obese (DIO) mice with TRPM8 agonists decrease body weight. Whether TRPM8 signaling regulates energy metabolism via central or peripheral effects is unknow. Here we assessed the metabolic phenotype of mice with either Nestin Cre-mediated neuronal loss of TRPM8, or with deletion of TRPM8 in Advillin Cre positive sensory neurons of the peripheral nervous system (PNS). Nestin Cre- and Advillin Cre- Trpm8 knock-out (KO) mice were metabolically phenotyped under chronic exposure to either chow or high-fat diet (HFD), followed by assessment of energy and glucose metabolism. At room temperature, chow-fed neuronal Trpm8 KO are obese and show decreased energy expenditure when acutely treated with the TRPM8 selective agonist icilin. But body weight of neuronal Trpm8 KO mice is indistinguishable from wildtype controls at thermoneutrality, or when mice are chronically exposed to HFD-feeding. In contrast to previous studies, we show that the TRPM8 agonist icilin has no direct effect on brown adipocytes, but that icilin stimulates energy expenditure, at least in part, via neuronal TRPM8 signaling. We further show that lack of TRPM8 in sensory neurons of the PNS does not lead to a metabolically relevant phenotype. Our data indicate that obesity in TRPM8-deficient mice is centrally mediated and likely originates from alterations in energy expenditure and/or thermal conductance, but does not depend on TRPM8 signaling in brown adipocytes or sensory neurons of the PVN. • Chow-fed mice with neuronal loss of Trpm8 (Nes Trpm8 KO) are obese and have decreased icilin-induced energy expenditure. • Obesity in chow-fed Nes Trpm8 KO mice vanishes at thermoneutrality or when mice are chronically fed with a high-fat diet. • TRPM8 agonist icilin has no direct and cell autonomous effects on cultured brown adipocytes, but increases energy expenditure via CNS mechanisms. • Obesity in chow-fed Nes-Trpm8 Ko mice does not result from lack of Trpm8 signaling in sensory neurons. [ABSTRACT FROM AUTHOR]