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A male infant presented with swelling of the left leg and fever. Over the next 2 days, the area developed fasciitis extending to the left thigh, abdomen, and lower chest. Meanwhile, the parents found a giant brown spider within the infant’s cot belonging to the genusLoxosceles, otherwise called the brown recluse spider. The dermo-myonecrosis progressed to deeper tissues involving the lung parenchyma requiring invasive ventilation. CT of the thorax showed multiple pneumatoceles, and lung biopsy showed alveolar necrosis. The infant was treated with intravenous antibiotics and corticosteroids. We drained the pneumothoraces by thoracostomy and insertion of intercostal drainage tubes. The infant required respiratory support initially by conventional ventilation, which was escalated to high-frequency oscillatory ventilation. He had refractory hypoxaemia and died. This is the first fatal case of acute spider envenomation described in India. Spider envenomation must be considered in patients with sudden onset, rapidly progressive necrotising fasciitis unresponsive to antibiotic therapy.

Across vertebrate species, gonadal hormones coordinate physiology with behavior to facilitate social interactions essential for reproduction and survival. In adulthood, these hormones activate neural circuits that regulate behaviors presenting differently in females and males, such as parenting and territorial aggression. Yet long before sex-typical behaviors emerge at puberty, transient hormone production during sensitive periods of neurodevelopment establish the circuits upon which adult hormones act. How transitory waves of early-life hormone signaling exert lasting effects on the brain remains a central question. Here we discuss how perinatal estradiol signaling organizes cellular and molecular sex differences in the rodent brain. We review classic anatomic studies revealing sex differences in cell number, volume, and neuronal projections, and consider how single-cell sequencing methods enable distinction between sex-biased cell-type abundance and gene expression. Finally, we highlight the recent discovery of a gene regulatory program activated by estrogen receptor α (ERα) following the perinatal hormone surge. A subset of this program displays sustained sex-biased gene expression and chromatin accessibility throughout the postnatal sensitive period, demonstrating a bona fide epigenetic mechanism. We propose that ERα-expressing neurons throughout the social behavior network use similar gene regulatory programs to coordinate brain sexual differentiation.

Mast cells are critical innate immune effectors located throughout the body that are crucial for host defense mechanisms via orchestrating immune responses to a variety of host and environmental stimuli necessary for survival. The role of mast cells in brain development and behavior, meningeal function, and stress-related disorders has also been increasingly recognized. While critical for survival and development, excessive mast cell activation has been linked with an increasing number of inflammatory, stress-associated, and neuroimmune disorders including allergy/anaphylaxis, autoimmune diseases, migraine headache, and chronic pain disorders. Further, a strong sex bias exists for mast cell-associated diseases with females often at increased risk. Here we review sex differences in human mast cell-associated diseases and animal models, and the underlying biological mechanisms driving these sex differences, which include adult gonadal sex hormones as well the emerging organizational role of perinatal gonadal hormones on mast cell activity and development.

Rabies is a fatal aggressive disease of the nervous system which predominantly causes motor and autonomic dysfunction. Limbic system involvement has been reported rarely, with limited data on its prevalence. The diagnosis becomes challenging when a patient presents with limbic system involvement in the absence of a clear history of an animal bite. We herein illustrate a case of a young man who presented with recurrent episodes of inappropriate ejaculation. He eventually developed hydrophobia and aerophobia, leading to a diagnosis of rabies. This case emphasises the importance of considering the possibility of rabies encephalitis when a patient presents with symptoms of limbic system involvement since early diagnosis helps in instituting appropriate public health measures and reducing exposure to infection. Furthermore, high-quality intensive care with supportive management is the mainstay of therapy in such patients until we have novel and effective antiviral drugs for rabies treatment.

The apparent virilization of the female spotted hyena raises questions about sex differences in behavior and morphology. We review these sex differences to find a mosaic of dimorphic traits, some of which conform to mammalian norms. These include space-use, dispersal behavior, sexual behavior, and parental behavior. By contrast, sex differences are reversed from mammalian norms in the hyena's aggressive behavior, social dominance, and territory defense. Androgen exposure early in development appears to enhance aggressiveness in female hyenas. Weapons, hunting behavior, and neonatal body mass do not differ between males and females, but females are slightly larger than males as adults. Sex differences in the hyena's nervous system are relatively subtle. Overall, it appears that the "masculinized" behavioral traits in female spotted hyenas are those, such as aggression, that are essential to ensuring consistent access to food; food critically limits female reproductive success in this species because female spotted hyenas have the highest energetic investment per litter of any mammalian carnivore. Evidently, natural selection has acted to modify traits related to food access, but has left intact those traits that are unrelated to acquiring food, such that they conform to patterns of sexual dimorphism in other mammals.

A stablehand in his 20s presented with increasing dyspnoea on exertion and chest pain months after being kicked directly in the chest by a horse. Further investigations revealed severe isolated, primary tricuspid regurgitation due to partial avulsion of the anterior leaflet. Open surgical repair was successfully performed from which he recovered uneventfully with resolution of his symptoms and minimal residual tricuspid regurgitation. Although uncommon, blunt force trauma to the chest is becoming increasingly recognised as a rare cause of tricuspid regurgitation. Symptoms may be insidious, and a high index of suspicion is required to avoid missing the diagnosis.

A 49-year-old man was admitted with altered mental status, high-grade fevers, tachycardia and leucocytosis. Cerebrospinal fluid (CSF) was purulent with a markedly elevated nucleated cell count with neutrophilic predominance, elevated protein and low glucose. CSF gram stain was negative. Patient received vancomycin, cefepime, ampicillin and acyclovir for presumed meningitis. He was intubated for protection of airway and underwent bronchoscopy. Microscopic examination of the bronchoalveolar lavage noted Strongyloides filariform larvae. Ivermectin was prescribed. Other laboratory tests showed a positive HIV test associated with a low CD4 count. Stool ova and parasite also revealed Strongyloides and repeat lumbar puncture identified larvae in the CSF. Albendazole was added for adjunctive therapy. However, the patient suffered a large intraparenchymal haemorrhage extending into the ventricles and he expired 36 days after admission.

Females have long been underrepresented in preclinical research and clinical drug trials. Directives by the U.S. National Institutes of Health have increased female participation in research protocols, although analysis of outcomes by sex remains infrequent. The long-held view that traits of female rats and mice are more variable than those of males is discredited, supporting equal representation of both sexes in most studies. Drug pharmacokinetic analysis reveals that, among subjects administered a standard drug dose, women are exposed to higher blood drug concentrations and longer drug elimination times. This contributes to increased adverse drug reactions in women and suggests that women are routinely overmedicated and should be administered lower drug doses than men. The past decade has seen progress in female inclusion, but key subsequent steps such as sex-based analysis and sex-specific drug dosing remain to be implemented.

Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.

BACKGROUND: SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.METHODS: Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood-brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68 + Iba1 + cells; morphological analysis).RESULTS: Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood-brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1 + CD68 + cells, increased soma size and shortened processes, was partly reduced by amlodipine.CONCLUSION: Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation.

We report the unusual case of a 5-year-old migrant boy from a rural area of Morocco with an almost-giant lung hydatid cyst that was an incidental finding on a chest X-ray performed during routine visa procedures.Echinococcus granulosusserology test was initially negative with subsequent positive seroconversion. Albendazole was started at 4 weeks before surgery and maintained for 4 months, with a favourable outcome. Cystic echinococcosis (CE) is considered aneglected tropical diseaseand affects more than one million people worldwide, mostly from a lower socioeconomic background. Preventive measures have been limited in underdeveloped regions. Children with CE are especially vulnerable, due not only to the high pathogenic potential of the disease but also to their frequent involvement in challenging socioeconomic situations, including migration. The incidence of CE is increasing in Europe because of high immigration flows from endemic countries. Nevertheless, CE is not covered by current migrant screening protocols.

Cooperation in food acquisition is a hallmark of the human species. Given that costs and benefits of cooperation vary among production regimes and work activities, the transition from hunting-and-gathering to agriculture is likely to have reshaped the structure of cooperative subsistence networks. Hunter–gatherers often forage in groups and are generally more interdependent and experience higher short-term food acquisition risk than horticulturalists, suggesting that cooperative labour should be more widespread and frequent for hunter–gatherers. Here we compare female cooperative labour networks of Batek hunter–gatherers of Peninsular Malaysia and Tsimane forager–horticulturalists of Bolivia. We find that Batek foraging results in high daily variation in labour partnerships, facilitating frequent cooperation in diffuse networks comprised of kin and non-kin. By contrast, Tsimane horticulture involves more restricted giving and receiving of labour, confined mostly to spouses and primary or distant kin. Tsimane women also interact with few individuals in the context of hunting/fishing activities and forage mainly with spouses and primary kin. These differences give rise to camp- or village-level networks that are more modular (have more substructure when partitioned) among Tsimane horticulturalists. Our findings suggest that subsistence activities shape the formation and extent of female social networks, particularly with respect to connections with other women and non-kin. We discuss the implications of restricted female labour networks in the context of gender relations, power dynamics and the adoption of farming in humans. This article is part of the theme issue ‘Cooperation among women: evolutionary and cross-cultural perspectives’.

The American Barn Owl (Tyto furcata) lives in urban, periurban and wild environments and feeds mainly on small rodents, meaning it has great importance in the biological control of pests. The aim of this work was to describe the reproductive, parental and eating habits of a pair of American barn owls naturally living outside a residence in the urban area of the municipality of Campos dos Goytacazes, Rio de Janeiro state, Brazil. A wood box was installed on an outside wall of the home, monitored by a video camera. A spreadsheet was created to keep track of the observations recorded. The female laid four eggs, and after an incubation period of 30-32 days all the eggs hatched, but only two chicks survived after cannibalism among the chicks. Initially, the male provided the food to the chicks and the female remained in the nest caring for the brood. After approximately a month, the female also began to leave the nest and return with prey, which was offered to the chicks, with the male also continuing this behavior. The chicks left the nest in September, 2017. The data obtained show the existence of cooperation and division of tasks between male and female owls during the reproductive period. Resumo A coruja-das-torres americana (Tyto furcata) vive em ambientes urbanos e se alimenta principalmente de pequenos roedores, sendo de grande importância no controle biológico de pragas. O objetivo deste trabalho foi descrever os hábitos alimentares, parentais e reprodutivos de um casal de corujas-das-torres americanas, naturalmente vivendo fora de uma residência na zona urbana do município de Campos dos Goytacazes, estado do Rio de Janeiro, Brasil. Uma caixa de madeira foi instalada em uma parede externa da casa, monitorada por uma câmera de vídeo. Uma planilha foi criada para manter o controle das observações registradas. A fêmea pôs quatro ovos, e após período de incubação de 30-32 dias todos os ovos eclodiram, mas apenas dois filhotes sobreviveram após o canibalismo entre os filhotes. Inicialmente, o macho fornecia a comida aos filhotes e a fêmea permanecia no ninho cuidando da ninhada. Depois de cerca de um mês, a fêmea também começou a sair do ninho e voltar com a presa, que era oferecida aos filhotes, com o macho também continuando com esse comportamento. Os filhotes deixaram o ninho em setembro de 2017. Os dados obtidos mostram a existência de cooperação e divisão de tarefas entre corujas machos e fêmeas durante o período reprodutivo.

Biological samples obtained from a small temporary pond of northern Colombia yielded the first record Coronatella undata Sousa, Elmoor-Loureiro and Santos, 2015 and of the male of C. monacantha (Sars, 1901) for Colombia. In this study, the morphology of female of Coronatella undata and female and male of C. monacantha was described and compared to other species within the genus. C. undata was originally described from Brazil and, among the species of the Coronatella monacantha complex, seems to be closely related to C. acuticostata (Sars, 1903). C. undata shows some similarities with C. monacantha, but it can be identified by important diagnostic characters such as: 1) posterior-ventral corner of valve with two denticles, 2) seta on exopodite of trunk limb II rudimentary, 3) filter comb of trunk limb II with six setae, 4) ODL seta of trunk limb I shorter than longest seta of IDL. C. monacantha is the most reported species in the Neotropical region and the male most resemble C. paulinae Sousa, Elmoor-Loureiro & Santos, 2015 in relation to (i), length/wide of postabdomen ratio (ii) basal spine almost straight and (iii)) long basal spine reaching the mid-length of basal spine. However, they can be separated by (i) number of lateral seta on the antennule, (ii) postanal angle, (iii) position of gonopore (iv) presence of a denticle on posterior-ventral corner of valve Resumo Amostras biológicas obtidas de uma pequena lagoa temporária do norte da Colômbia proporcionaram o primeiro registro de Coronatella undata Sousa, Elmoor-Loureiro e Santos, 2015 e do macho de Coronatella monacantha (Sars, 1901) na Colômbia. Neste estudo, foi descrita a morfologia de fêmeas de C. undata e de fêmeas e machos de C. monacantha, comparando-a com outras espécies do gênero. Coronatella undata foi descrita originalmente no Brasil e, entre as espécies do complexo C. monacantha, parece estar intimamente relacionada com Coronatella acuticostata (Sars, 1903). Coronatella undata apresenta algumas semelhanças com C. monacantha, mas pode ser identificada por seus principais caracteres, tais como: 1) ângulo posterior ventral da valva com dois dentículos; 2) cerda rudimentar no exopodito do ramo do tronco II; 3) filtro da gnatobase do apêndice torácico II com seis cerdas; 4) cerda ODL do membro do tronco I mais curta que a cerda mais longa do IDL. Coronatella monacantha é a espécie mais relatada na região neotropical, e o macho se assemelha mais a Coronatella paulinae Sousa, Elmoor-Loureiro & Santos em relação à/ao: (i) razão comprimento / largura do pós-abdômen, (ii) espinho basal quase reto e (iii) espinho basal longo com a metade do comprimento do espinho basal. No entanto, eles podem ser separados pelo/pela: (i) número de cerdas laterais na antênula, (ii) ângulo postanal, (iii) posição do gonóporo e (iv) presença de dentículo no canto ventral posterior da valva.

One of the most common palm pests is the red palm weevil, Rhynchophorus ferrugineus Olivier. Five artificial diets were evaluated to rear RPW, and to facilitate its behavioral and biological studies. The developmental of R. ferruginus was studied on the tested artificial diets based on primarily composed of sugarcane stem pieces (1st diet; control), sweet pumpkin (2nd diet), ground sugarcane + sweet pumpkin (3rd diet), sweet potato (4th diet) and ground sugarcane + sweet potato (5th diet) under rearing room (28 ± 1 °C and 75 ± 5 RH%) at Faculty of Agriculture in Benha district. The biological aspects, pre-oviposition, oviposition, larval & pupal durations, the longevity of male and female adults and the generation period of R. ferrugineus have all been estimated. Moreover, the impact of these artificial diets on the quantities of total proteins, carbohydrates and lipids were determined in the full-grown larvae. Obtained results showed that the insect manifested the shortest larval and pupal periods and the longest longevity for males and females when rearing of R. ferruginus took place on an artificial diet based on sweet potato as a successful and economical for mass rearing of the red palm weevil under laboratory conditions. Larvae fed on diet 4 (sweet potato) was exhibited the shortest duration (114.80 days), while 1st diet (Sugarcane stem pieces) was recorded the longest period (125.00 ± days). Similarly for pupation and both male and female longevity, the shortest periods resulted from larvae feeding on 4th diet (14.65, 49.40 and 48.0 days, respectively). Contrariwise, the longest pupal period was reported with 5th diet (15.70 days). The highest of eggs hatchability % (96.53%) resulted from the rearing nof R. ferruginus larvae on the 4th diet. Chemical analyses of the full-grown larva were indicated that the highest contents of total carbohydrates (45.57 µg/g), lipids (28.46 µg/g) and proteins (20.01µg/g) were obtained in case of larvae reared on 1st and 4th diets, respectively. Consequently, the development of R. ferruginus stages was slightly lower on both 1st and 4th artificial diets. So that, both of them were a successful and economic artificial diet for RPW development under laboratory conditions. Therefore, this study added valuable alternative ingredients to prepare more practical and economical feeding substrate for weevil rearing to help for proposal of its management and conservation in palm plantations. Resumo Uma das pragas mais comuns das palmeiras é o gorgulho vermelho da palmeira, Rhynchophorus ferrugineus Olivier. Cinco dietas artificiais foram avaliadas para criar RPW e facilitar seus estudos comportamentais e biológicos. O desenvolvimento de R. ferruginus foi estudado nas dietas artificiais testadas baseadas principalmente em pedaços de caule de cana-de-açúcar (1ª dieta; controle), abóbora-doce (2ª dieta), cana-de-açúcar + abóbora-doce (3ª dieta), batata-doce (4ª dieta) e cana-de-açúcar moída + batata-doce (5ª dieta) em sala de criação (28 ± 1 °C e 75 ± 5 UR%) na Faculdade de Agricultura do distrito de Benha. Os aspectos biológicos, pré-oviposição, oviposição, durações de larvas e pupas, a longevidade de machos e fêmeas adultos e o período de geração de R. ferrugineus foram todos estimados. Além disso, o impacto dessas dietas artificiais nas quantidades de proteínas totais, carboidratos e lipídios foi determinado nas larvas adultas. Os resultados obtidos mostraram que o inseto manifestou os menores períodos larval e pupal e a maior longevidade para machos e fêmeas quando a criação de R. ferruginus ocorreu em uma dieta artificial à base de batata-doce como uma forma bem-sucedida e econômica para a criação massal do gorgulho vermelho da palmeira em condições de laboratório. Larvas alimentadas com a dieta 4 (batata-doce) foram as que apresentaram a menor duração (114,80 dias), enquanto a 1ª dieta (pedaços de caule de cana-de-açúcar) foi a que apresentou o maior período (125,00 ± dias). Da mesma forma para a pupação e longevidade de machos e fêmeas, os períodos mais curtos resultaram da alimentação das larvas na 4ª dieta (14,65, 49,40 e 48,0 dias, respectivamente). Ao contrário, o período pupal mais longo foi relatado com a 5ª dieta (15,70 dias). A maior porcentagem de eclodibilidade dos ovos (96,53%) resultou da criação de larvas de R. ferruginus na 4ª dieta. As análises químicas das larvas adultas indicaram que os maiores teores de carboidratos totais (45,57 µg/g), lipídios (28,46 µg/g) e proteínas (20,01µg/g) foram obtidos no caso de larvas criadas na 1ª e 4ª dietas, respectivamente. Consequentemente, o desenvolvimento dos estádios de R. ferruginus foi ligeiramente menor tanto na 1ª quanto na 4ª dieta artificial. Assim, ambas foram dietas artificiais bem-sucedida e econômica para o desenvolvimento de RPW em condições de laboratório. Portanto, este estudo adicionou ingredientes alternativos valiosos para preparar substrato alimentar mais prático e econômico para a criação do gorgulho para auxiliar na proposta de seu manejo e conservação em plantações de palmeiras.

Cystic hydatid disease or cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval cyst stage of the tapeworm Echinococcus granulosus. Concomitant presence of CE and hepatocellular carcinoma (HCC) is a rare clinical scenario. A 70-year-old male patient presented with acute abdominal pain to the surgical outpatient department. On evaluation, a cystic lesion with solid components and free fluid in the abdomen was observed, which led to multiple differentials in the working diagnosis. A CT showed the mass to have a delayed enhancement. Surgical exploration revealed a partially ruptured hydatid cyst with daughter cysts in the abdominal cavity and a solid-component mass lesion. We proceeded with a right partial hepatectomy. Pathological evaluation revealed a pale mass lesion with a large collapsed cyst. HCC with unusual dense fibrillar fibrosis and cystic interface with normal parenchyma was observed. This case connects the multimodal assessment of radiology, surgery and pathology.

Changes in vascular structure contribute to vascular events and loss of brain health. We examined the inherent structural plasticity of cerebral arterioles during and after a period of hypertension. Arteriolar wall thickness, diameter, wall-to-lumen ratio, and biological stiffness changed rapidly during hypertension and recovered with blood pressure. In contrast, inward remodeling developed slowly and did not recover. This lack of recovery of arteriolar diameter has implications for the long-term impact of hypertension on vascular determinants of brain health.

We investigated the impact of tumor burden on muscle wasting in metastatic (m) and xenograft (x) models of colorectal cancer (CRC). Male Nod SCID γ and CD2F1 mice were injected subcutaneously or intrasplenically with HCT116 or C26 tumor cells, respectively. CRC tumors resulted in significant muscle wasting regardless of tumor type or model, although muscle loss was exacerbated in mHCT116 hosts. The mHCT116 model decreased ribosomal (r)RNA content and rDNA transcription, whereas the mC26 model showed no loss of rRNA and the upregulation of rDNA transcription. The xHCT116 model reduced mTOR, RPS6, and 4E-BP1 phosphorylation, whereas the mHCT116 model had a similar effect on RPS6 and 4E-BP1 without altering mTOR phosphorylation. The C26 models caused a reduction in 4E-BP1 phosphorylation independent of mTOR. Muscle interleukin (IL)-6 mRNA was elevated in all models except xHCT116, and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) mRNA was induced only in the mC26 model. IL-1β mRNA increased in all groups with greater expression in metastatic relative to the xenograft model regardless of tumor types. Our findings indicate that HCT116 tumor burden results in more drastic muscle wasting and anabolic deficits, whereas C26 tumor burden causes similar muscle wasting but exhibits a divergent proinflammatory phenotype. These results highlight potentially important divergence in the pathogenesis of muscle wasting among preclinical models of CRC and demonstrate that tumor burden plays a role in determining anabolic deficits and the expression of proinflammatory effectors of muscle wasting in a tumor-type-dependent manner.

Hypoxia is the reduction of alveolar partial pressure of oxygen ([Formula: see text]). Military members and people who practice recreational activities from moderate to high altitudes are at risk for hypoxic exposure. Hypoxemia’s signs and symptoms vary from asymptomatic to severe responses, such as excessive hypoxic ventilatory responses and residual neurobehavioral impairment. Therefore, it is essential to identify hypoxia-induced biomarkers to indicate people with exposure to hypoxia. Advances have been made in understanding physiological responses to hypoxia, including elevations in circulating levels of endothelin 1 (ET-1) and microRNA 21 (miR-21) and reduction in circulating levels of hydrogen sulfide (H2S). Although the levels of these factors change upon exposure to hypoxia, it is unclear if these changes are sustained on return to normoxia. We hypothesize that hypoxia-induced ET-1 and miR-21 remain elevated, whereas hypoxia-reduction in H2S sustains after returning to normoxic conditions. To test this hypothesis, we exposed male rats to 6 h of 12% O2 and measured circulating levels of ET-1 and miR-21, pre, during, and posthypoxia. We found that ET-1 plasma levels increased in response to hypoxia but returned to normal levels within 30 min after the restoration of normoxia. miR-21 plasma levels and transdermal H2S emissions decreased in response to hypoxia, remaining decreased on return to normoxia, thus following the biomarker criteria. Therefore, this study supports a unique role for plasma miR21 and transdermal H2S as hypoxia biomarkers that could be used to identify individuals after exposure to hypoxia.

To date, there has been a lag between the rise in E-cigarette use and an understanding of the long-term health effects. Inhalation of E-cigarette aerosol delivers high doses of nicotine, raises systemic cytokine levels, and compromises cardiopulmonary function. The consequences for muscle function have not been thoroughly investigated. The present study tests the hypothesis that exposure to nicotine-containing aerosol impairs locomotor muscle function, limits exercise tolerance, and interferes with muscle repair in male mice. Nicotine-containing aerosol reduced the maximal force produced by the extensor digitorum longus (EDL) by 30%–40% and, the speed achieved in treadmill running by 8%. Nicotine aerosol exposure also decreased adrenal and increased plasma epinephrine and norepinephrine levels, and these changes in catecholamines manifested as increased muscle and liver glycogen stores. In nicotine aerosol exposed mice, muscle regenerating from overuse injury only recovered force to 80% of noninjured levels. However, the structure of neuromuscular junctions (NMJs) was not affected by e-cigarette aerosols. Interestingly, the vehicle used to dissolve nicotine in these vaping devices, polyethylene glycol (PG) and vegetable glycerin (VG), decreased running speed by 11% and prevented full recovery from a lengthening contraction protocol (LCP) injury. In both types of aerosol exposures, cardiac left ventricular systolic function was preserved, but left ventricular myocardial relaxation was altered. These data suggest that E-cigarette use may have a negative impact on muscle force and regeneration due to compromised glucose metabolism and contractile function in male mice.

Microcystin-leucine-arginine (MC-LR) is positively linked with multiple cancers in humans. However, the association between MC-LR and the risk and prognosis of prostate cancer has not been conducted in epidemiological studies. No reported studies have linked MC-LR exposure to the poor prognosis of prostate cancer by conducting experimental studies. The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers. MC-LR levels in both prostate cancer tissues and serum were significantly higher than controls. The adjusted odds ratio (OR) for prostate cancer risk by serum MC-LR was 1.75 (95%CI: 1.21-2.52) in the whole subjects, and a positive correlation between MC-LR and advanced tumor stage was observed. Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival. Human, animal, and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α (ERα) and promotes epithelial-mesenchymal transition (EMT) in prostate cancer. Moreover, MC-LR-induced decreased E-cadherin levels, increased vimentin levels, and increased migratory and invasive capacities of prostate cancer cells were markedly suppressed upon ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα, promoting migration and invasion of prostate cancer cells. Our findings highlight the role of MC-LR in prostate cancer, providing new perspectives to understand MC-LR-induced prostatic toxicity.

Fibroblast growth factor 21 (FGF21) plays a key role in hepatic lipid metabolism and long-acting FGF21 analogs have emerged aspromising drug candidates for the treatment of nonalcoholic steatohepatitis (NASH). It remains to characterize this drug class intranslational animal models that recapitulate the etiology and hallmarks of human disease. To this end, we evaluated the longactingFGF21 analog PF-05231023 in the GAN (Gubra Amylin NASH) diet-induced obese (DIO) and biopsy-confirmed mousemodel of NASH. Male C57BL/6J mice were fed the GAN diet high in fat, fructose, and cholesterol for 34 wk before the start ofthe study. GAN DIO-NASH mice with biopsy-confirmed NAFLD Activity Score (NAS 5) and fibrosis (stage F1) were biweeklyadministered with PF-05231023 (10 mg/kg sc) or vehicle (sc) for 12 wk. Vehicle-dosed chow-fed C57BL/6J mice served ashealthy controls. Pre-to-post liver biopsy histopathological scoring was performed for within-subject evaluation of NAFLD ActivityScore (NAS) and fibrosis stage. Terminal endpoints included quantitative liver histology and transcriptome signatures as well asblood and liver biochemistry. PF-05231023 significantly reduced body weight, hepatomegaly, plasma transaminases, andplasma/liver lipids in GAN DIO-NASH mice. Notably, PF-05231023 reduced both NAS (2-point improvement) and fibrosis stage(1-point improvement). Improvements in NASH and fibrosis severity were supported by reduced quantitative histological markersof steatosis, inflammation, and fibrogenesis as well as improvements in disease-associated liver transcriptome signatures. In conclusion,PF-05231023 reduces NASH and fibrosis severity in a translational biopsy-confirmed mouse model of NASH, supportingdevelopment of FGF21 analogs for the treatment of NASH.NEW & NOTEWORTHY It is unclear if long-acting FGF21 analogs have antifibrotic efficacy in NASH. We therefore profiled theclinically relevant FGF21 analog PF-05231023 in a translational diet-induced obese and biopsy-confirmed mouse model ofNASH. We found PF-05231023 to exert hepatoprotective effects as indicated by notable improvements in plasma markers andhistological hallmarks of NASH, including improved fibrosis stage. Collectively, the present study supports the continued explorationof long-acting FGF21 analogs for the treatment of NASH and other fibrotic diseases. Fibroblast growth factor 21 (FGF21) plays a key role in hepatic lipid metabolism and long-acting FGF21 analogs have emerged as promising drug candidates for the treatment of nonalcoholic steatohepatitis (NASH). It remains to characterize this drug class in translational animal models that recapitulate the etiology and hallmarks of human disease. To this end, we evaluated the long-acting FGF21 analog PF-05231023 in the GAN (Gubra Amylin NASH) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH. Male C57BL/6J mice were fed the GAN diet high in fat, fructose, and cholesterol for 34 wk before the start of the study. GAN DIO-NASH mice with biopsy-confirmed NAFLD Activity Score (NAS ≥5) and fibrosis (stage ≥F1) were biweekly administered with PF-05231023 (10 mg/kg sc) or vehicle (sc) for 12 wk. Vehicle-dosed chow-fed C57BL/6J mice served as healthy controls. Pre-to-post liver biopsy histopathological scoring was performed for within-subject evaluation of NAFLD Activity Score (NAS) and fibrosis stage. Terminal endpoints included quantitative liver histology and transcriptome signatures as well as blood and liver biochemistry. PF-05231023 significantly reduced body weight, hepatomegaly, plasma transaminases, and plasma/liver lipids in GAN DIO-NASH mice. Notably, PF-05231023 reduced both NAS (≥2-point improvement) and fibrosis stage (1-point improvement). Improvements in NASH and fibrosis severity were supported by reduced quantitative histological markers of steatosis, inflammation, and fibrogenesis as well as improvements in disease-associated liver transcriptome signatures. In conclusion, PF-05231023 reduces NASH and fibrosis severity in a translational biopsy-confirmed mouse model of NASH, supporting development of FGF21 analogs for the treatment of NASH.NEW & NOTEWORTHY It is unclear if long-acting FGF21 analogs have antifibrotic efficacy in NASH. We therefore profiled the clinically relevant FGF21 analog PF-05231023 in a translational diet-induced obese and biopsy-confirmed mouse model of NASH. We found PF-05231023 to exert hepatoprotective effects as indicated by notable improvements in plasma markers and histological hallmarks of NASH, including improved fibrosis stage. Collectively, the present study supports the continued exploration of long-acting FGF21 analogs for the treatment of NASH and other fibrotic diseases.

Benzo[a]pyrene (BaP), a ubiquitous pollutant, raises environmental health concerns due to induction of bone toxicity in the unexposed offspring. Exposure of F0 ancestor medaka (Oryzias latipes) to 1 µg/L BaP for 21 days causes reduced vertebral bone thickness in the unexposed F3 male offspring. To reveal the inherited modifications, osteoblast (OB) abundance and molecular signaling pathways of transgenerational BaP-induced bone thinning were assessed. Histomorphometric analysis showed a reduction in OB abundance. Analyses of the miRNA and mRNA transcriptomes revealed the dysregulation of Wnt signaling (frzb/ola-miR-1-3p, sfrp5/ola-miR-96-5p/miR-455-5p) and bone morphogenetic protein (Bmp) signaling (bmp3/ola-miR-96-5p/miR-181b-5p/miR-199a-5p/miR-205-5p/miR-455-5p). Both pathways are major indicators of impaired bone formation, while the altered Rank signaling in osteoclasts (c-fos/miR-205-5p) suggests a potentially augmented bone resorption. Interestingly, a typical BaP-responsive pathway, the Nrf2-mediated oxidative stress response (gst/ola-miR-181b-5p/miR-199a-5p/miR-205), was also affected. Moreover, mRNA levels of epigenetic modification enzymes (e.g., hdac6, hdac7, kdm5b) were found dysregulated. The findings indicated that epigenetic factors (e.g., miRNAs, histone modifications) may directly regulate the expression of genes associated with transgenerational BaP bone toxicity and warrants further studies. The identified candidate genes and miRNAs may serve as potential biomarkers for BaP-induced bone disease and as indicators of historic exposures in wild fish for conservation purposes.

IntroductionWhile phosphodiesterase type 5 inhibitors (PDE5is) and others are used to treat Erectile dysfunction (ED), many patients are either unresponsive or resistant to it. Stem cell therapy (SCT) is a promising alternative approach. Numerous preclinical trials have demonstrated improved erectile function in animal models using SCT, although the number of clinical trials investigating SCT for men with ED is limited. Nonetheless, findings from human clinical trials suggest that SCT may be a useful treatment option.Areas coveredBiomedical literature, including PubMed, ClinicalTrials.gov, and European Union Clinical Trials Registry, were analyzed to summarize and synthesize information on stem cell therapy for ED in this narrative review. The achievements in preclinical and clinical evaluations are presented and critically analyzed.Expert opinionSCT has demonstrated some benefits in improving erectile function, while further studies are urgently needed. Such studies would provide valuable insights into the optimal use of stem cell therapy and its potential as a therapeutic option for ED. Taking advantage of different mechanisms of action involved in various regenerative therapies, combination therapies such as SCT and low-energy shock waves or platelet-rich plasma may provide a more effective therapy and warrant further research.

Rationale The endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued. Objective and methods We examined if repeated THC exposure (5 mg/kg/day for 14 days) during adolescence or adulthood led to long-term changes in rats’ capacity to flexibly encode and use action-outcome associations for goal-directed decision making. Effects on hedonic feeding and progressive ratio responding were also assessed. Results THC exposure had no effect on rats’ ability to flexibly select actions following reward devaluation. However, instrumental contingency degradation learning, which involves avoiding an action that is unnecessary for reward delivery, was augmented in rats with a history of adult but not adolescent THC exposure. THC-exposed rats also displayed more vigorous instrumental behavior in this study, suggesting a motivational enhancement. A separate experiment found that while THC exposure had no effect on hedonic feeding behavior, it increased rats’ willingness to work for food on a progressive ratio schedule, an effect that was more pronounced when THC was administered to adults. Adolescent and adult THC exposure had opposing effects on the CB1 receptor dependence of progressive ratio performance, decreasing and increasing sensitivity to rimonabant-induced behavioral suppression, respectively. Conclusions Our findings reveal that exposure to a translationally relevant THC exposure regimen induces long-lasting, age-dependent alterations in cognitive and motivational processes that regulate the pursuit of rewards.

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are the pontine reticular nucleus (PnC) and pedunculopontine tegmentum (PPTg), respectively. Multi-unit responses from the PnC and PPTg in vivo of the same rats revealed sex-specific effects of loss of CASPR2 expression on PnC activity, but no effects on PPTg activity. Female Cntnap2

Microtubules are cytoskeletal elements that play key roles throughout the different steps of sperm development. As an integral part of the sperm flagellum, the molecular machine that generates sperm motility, microtubules are also essential for the progressive swimming of sperm to the oocyte, which is a prerequisite for fertilisation. Given the central role of microtubules in all steps of spermatogenesis, their functions need to be tightly controlled. Recent work has showcased tubulin posttranslational modifications as key players in sperm development and function, with aberrations often leading to male infertility with a broad spectrum of sperm defects. Posttranslational modifications are part of the tubulin code, a mechanism that can control microtubule functions by modulating the properties of their molecular building blocks, the tubulin proteins. Here we review the current knowledge on the implications of the tubulin code in sperm development and functions and its importance for male fertility.

Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development.

Birds are highly visually oriented and use plumage coloration as an important signalling trait in social communication. Hence, males and females may have different patterns of plumage coloration, a phenomenon known as sexual dichromatism. Because males tend to have more complex plumages, sexual dichromatism is usually attributed to female choice. However, plumage coloration is partly condition-dependent; therefore, other selective pressures affecting individuals' success may also drive the evolution of this trait. Here, we used tanagers as model organisms to study the relationships between dichromatism and plumage coloration complexity in tanagers with parasitism by haemosporidians, investment in reproduction and life-history traits. We screened blood samples from 2849 individual birds belonging to 52 tanager species to detect haemosporidian parasites. We used publicly available data for plumage coloration, bird phylogeny and life-history traits to run phylogenetic generalized least-square models of plumage dichromatism and complexity in male and female tanagers. We found that plumage dichromatism was more pronounced in bird species with a higher prevalence of haemosporidian parasites. Lastly, high plumage coloration complexity in female tanagers was associated with a longer incubation period. Our results indicate an association between haemosporidian parasites and plumage coloration suggesting that parasites impact mechanisms of sexual selection, increasing differences between the sexes, and social (non-sexual) selection, driving females to develop more complex coloration.

Evolutionary theory predicts a late-life decline in the force of natural selection, possibly leading to late-life deregulations of the immune system. A potential outcome of such deregulations is the inability to produce specific immunity against target pathogens. We tested this possibility by infecting multiple

The evolution of costly signalling traits has largely focused on male ornaments. However, our understanding of ornament evolution is necessarily incomplete without investigating the causes and consequences of variation in female ornamentation. Here, we study the

A 4-week-old boy presented to the hospital with symptoms of diarrhoea and vomiting initially thought to be due to cow’s milk allergy. He was discharged with extensively hydrolysed formula. The patient represented with worsening of symptoms with metabolic acidosis and was screened and treated for sepsis. However, his condition deteriorated further and he developed methaemoglobinaemia. He was transferred to the high dependency unit and was given two doses of methylene blue. Further investigations were carried out, including rapid trio exome sequencing, which identified a homozygous pathogenic Peptidase D (PEPD) variant (c.978G>A, p.(Trp326*)). This was consistent with a diagnosis of prolidase deficiency.

Mating with another species is often maladaptive because it generally results in no or low-fitness offspring. When hybridization is sufficiently costly, individuals should avoid mating with heterospecifics even if it reduces their ability to mate with high-quality conspecifics that resemble heterospecifics. Here, we used spadefoot toads, Spea multiplicata, to evaluate whether females alter their preferences for conspecific male sexual signals (call rate) depending on heterospecific presence. When presented with conspecific signals against a background including both conspecific and heterospecific signals, females preferred male traits that were most dissimilar to heterospecifics—even though these signals are potentially associated with lower-quality mates. However, when these same females were presented with a background that included only conspecific signals, some females switched their preferences, choosing conspecific signals that were exaggerated and indicative of high-quality conspecific mates. Because only some females switched their preferences between these two chorus treatments, there was no population-level preference for exaggerated conspecific male signals in the absence of heterospecifics. These results show that hybridization risk can alter patterns of mate choice and, consequently, sexual selection on male signals. Moreover, they emphasize that the strength and expression of reproductive barriers between species (such as mate choice) can be context-dependent.

We present a case of a 51-year-old immunosuppressed man with underlying chronic lymphoproliferative leukaemia (CLL), who presented to us in emergency with breathlessness, hydrophobia, anxiety and restlessness. He had a history of category 3 dog bite 2 months ago and had received a full course of rabies immunoglobulin and antirabies vaccine (ARV) as per the national schedule. As there were frank clinical reports of rabies, the patient was managed according to Milwaukee regimen. The patients died within a week of the appearance of symptoms. The brain autopsy revealed Negri bodies conforming the mortality due to rabies.Immunosuppressed patients, like our patient who had CLL have low antibody formation after rabies prophylaxis. Antibody titres in immunosuppressed patients need to be measured after the 2–4 weeks of the last injection of ARV to decide whether a booster of ARV needs to be administered or not.

The greater male variability (GMV) hypothesis proposes that traits are more variable among males than females, and is supported by numerous empirical studies. Interestingly, GMV is also observed for human brain size and internal brain structure, a pattern which may have implications for sex-biased neurological and psychiatric conditions. A better understanding of neuroanatomical variability in non-human primates may illuminate whether certain species are appropriate models for these conditions. Here, we tested for sex differences in the variability of endocranial volume (ECV, a proxy for brain size) in a sample of 542 rhesus macaques ( Macaca mulatta ) from a large pedigreed free-ranging population. We also examined the components of phenotypic variance (additive genetic and residual variance) to tease apart the potential drivers of sex differences in variability. Our results suggest that males exhibit more variable ECVs, and that this pattern reflects either balancing/disruptive selection on male behaviour (associated with alternative male mating strategies) or sex chromosome effects (associated with mosaic patterns of X chromosome gene expression in females), rather than extended neurodevelopment among males. This represents evidence of GMV for brain size in a non-human primate species and highlights the potential of rhesus macaques as a model for sex-biased brain-based disorders.

Maternal obesity is exceedingly common and strongly linked to offspring obesity and metabolic disease. Hypothalamic function is critical to obesity development. Hypothalamic mechanisms causing obesity following exposure to maternal obesity have not been elucidated. Therefore, we studied a cohort of C57BL/6J dams, treated with a control or high-fat-high-sugar diet, and their adult offspring to explore potential hypothalamic mechanisms to explain the link between maternal and offspring obesity. Dams treated with obesogenic diet were heavier with mild insulin resistance, which is reflective of the most common metabolic disease in pregnancy. Adult offspring exposed to maternal obesogenic diet had no change in body weight but significant increase in fat mass, decreased glucose tolerance, decreased insulin sensitivity, elevated plasma leptin, and elevated plasma thyroid-stimulating hormone. In addition, offspring exposed to maternal obesity had decreased energy intake and activity without change in basal metabolic rate. Hypothalamic neurochemical profile and transcriptome demonstrated decreased neuronal activity and inhibition of oxidative phosphorylation. Collectively, these results indicate that maternal obesity without diabetes is associated with adiposity and decreased hypothalamic energy production in offspring. We hypothesize that altered hypothalamic function significantly contributes to obesity development. Future studies focused on neuroprotective strategies aimed to improve hypothalamic function may decrease obesity development.

Blood pressure (BP) is influenced by genetic variation and sodium intake with sex-specific differences; however, studies to identify renal molecular mechanisms underlying the influence of sodium intake on BP in nonhuman primates (NHP) have focused on males. To address the gap in our understanding of molecular mechanisms regulating BP in female primates, we studied sodium-naïve female baboons ( n = 7) fed a high-sodium (HS) diet for 6 wk. We hypothesized that in female baboons variation in renal transcriptional networks correlates with variation in BP response to a high-sodium diet. BP was continuously measured for 64-h periods throughout the study by implantable telemetry devices. Sodium intake, blood samples for clinical chemistries, and ultrasound-guided kidney biopsies were collected before and after the HS diet for RNA-Seq and bioinformatic analyses. We found that on the LS diet but not the HS diet, sodium intake and serum 17 β-estradiol concentration correlated with BP. Furthermore, kidney transcriptomes differed by diet-unbiased weighted gene coexpression network analysis revealed modules of genes correlated with BP on the HS diet but not the LS diet. Our results showed variation in BP on the HS diet correlated with variation in novel kidney gene networks regulated by ESR1 and MYC; i.e., these regulators have not been associated with BP regulation in male humans or rodents. Validation of the mechanisms underlying regulation of BP-associated gene networks in female NHP will inform better therapies toward greater precision medicine for women.

We show that hypertension is evident in female 5-HT-deficient TPH2−/− rats when sex hormones are controlled, an effect most evident upon the transition to REM sleep. In addition, our data strongly suggest that increased sympathetic vascular tone contributes to the hypertension present in this 5-HT-deficient model of neurogenic hypertension.

The complexity of neuropathic pain and its associated comorbidities, including dysautonomia, make it difficult to treat. Overlap of anatomical regions and pharmacology of sympathosensory systems in the central nervous system (CNS) provide targets for novel treatment strategies. The dorsal periaqueductal gray (dPAG) is an integral component of both the descending pain modulation system and the acute stress response and is critically involved in both analgesia and the regulation of sympathetic activity. Local manipulation of the endocannabinoid signaling system holds great promise to provide analgesia without excessive adverse effects and also influence autonomic output. Inhibition of fatty acid amide hydrolase (FAAH) increases brain concentrations of the endocannabinoid N-arachidonoylethanolamine (AEA) and reduces pain-related behaviors in neuropathic pain models. Neuropathic hyperalgesia and reduced sympathetic tone are associated with increased FAAH activity in the dPAG, which suggests the hypothesis that inhibition of FAAH in the dPAG will normalize pain sensation and autonomic function in neuropathic pain. To test this hypothesis, the effects of systemic or intra-dPAG FAAH inhibition on hyperalgesia and dysautonomia developed after spared nerve injury (SNI) were assessed in male and female rats. Administration of the FAAH inhibitor PF-3845 into the dPAG reduces hyperalgesia behavior and the decrease in sympathetic tone induced by SNI. Prior administration of the CB1 receptor antagonist AM281, attenuated the antihyperalgesic and sympathetic effects of FAAH inhibition. No sex differences were identified. These data support an integrative role for AEA/CB1 receptor signaling in the dPAG contributing to the regulation of both hyperalgesia behavior and altered sympathetic tone in neuropathic pain.

Dilutional hyponatremia associated with liver cirrhosis is due to inappropriate release of arginine vasopressin (AVP). Elevated plasma AVP causes water retention resulting in a decrease in plasma osmolality. Cirrhosis, in this study caused by ligation of the common bile duct (BDL), leads to a decrease in central vascular blood volume and hypotension, stimuli for nonosmotic AVP release. The A1/A2 neurons stimulate the release of AVP from the supraoptic nucleus (SON) in response to nonosmotic stimuli. We hypothesize that the A1/A2 noradrenergic neurons support chronic release of AVP in cirrhosis leading to dilutional hyponatremia. Adult, male rats were anesthetized with 2–3% isoflurane (mixed with 95% O2/5% CO2) and injected in the SON with anti-dopamine β-hydroxylase (DBH) saporin (DSAP) or vehicle followed by either BDL or sham surgery. Plasma copeptin, osmolality, and hematocrit were measured. Brains were processed for ΔFosB, dopamine β-hydroxylase (DBH), and AVP immunohistochemistry. DSAP injection: 1) significantly reduced the number of DBH immunoreactive A1/A2 neurons (A1, P < 0.0001; A2, P = 0.0014), 2) significantly reduced the number of A1/A2 neurons immunoreactive to both DBH and ΔFosB positive neurons (A1, P = 0.0015; A2, P < 0.0001), 3) reduced the number of SON neurons immunoreactive to both AVP and ΔFosB ( P < 0.0001), 4) prevented the increase in plasma copeptin observed in vehicle-injected BDL rats ( P = 0.0011), and 5) normalized plasma osmolality and hematocrit (plasma osmolality, P = 0.0475; hematocrit, P = 0.0051) as compared with vehicle injection. Our data suggest that A1/A2 neurons contribute to increased plasma copeptin and hypoosmolality in male BDL rats.

Background: Circadian rhythms play an essential role in physiological function. The molecular clock that underlies circadian physiological function consists of a core group of transcription factors, including the protein PER1 (Period1). Studies in mice show that PER1 plays a role in the regulation of blood pressure and renal sodium handling; however, the results are dependent on the strain being studied. Using male Dahl salt-sensitive (SS) rats with global knockout of PER1 (SS Per1−/− ), we aim to test the hypothesis that PER1 plays a key role in the regulation of salt-sensitive blood pressure. Methods: The model was generated using CRISPR/Cas9 and was characterized using radiotelemetry and measures of renal function and circadian rhythm. Results: SS Per1−/− rats had similar mean arterial pressure when fed a normal 0.4% NaCl diet but developed augmented hypertension after three weeks on a high-salt (4% NaCl) diet. Despite being maintained on a normal 12:12 light:dark cycle, SS Per1−/− rats exhibited desynchrony mean arterial pressure rhythms on a high-salt diet, as evidenced by increased variability in the time of peak mean arterial pressure. SS Per1−/− rats excrete less sodium after three weeks on the high-salt diet. Furthermore, SS Per1−/− rats exhibited decreased creatinine clearance, a measurement of renal function, as well as increased signs of kidney tissue damage. SS Per1−/− rats also exhibited higher plasma aldosterone levels. Conclusions: Altogether, our findings demonstrate that loss of PER1 in Dahl SS rats causes an array of deleterious effects, including exacerbation of the development of salt-sensitive hypertension and renal damage.

Recent empirical investigations have characterized the synchronized flashing behaviours of male

Butterflies have variable sets of spectral photoreceptors that underlie colour vision. The photoreceptor organization may be optimized for the detection of body coloration. Fritillaries (Argynnini) are nymphalid butterflies exhibiting varying degrees of sexual dimorphism in wing coloration. In two sister species, the females have orange ( Argynnis paphia ) and dark wings ( Argynnis sagana ), respectively, while the males of both species have orange wings with large patches of pheromone-producing androconia. In spite of the differences in female coloration, the eyes of both species exhibit an identical sexual dimorphism. The female eyeshine is uniform yellow, while the males have a complex retinal mosaic with yellow and red-reflecting ommatidia. We found the basic set of ultraviolet-, blue- and green-peaking photoreceptors in both sexes. Males additionally have three more photoreceptor classes, peaking in green, yellow and red, respectively. The latter is the basal R9, indirectly measured through hyperpolarizations in the green-peaking R1-2. In many nymphalid tribes, including the closely related Heliconiini, the retinal mosaic is complex in both sexes. We hypothesize that the simple mosaic of female Argynnini is a secondary reduction, possibly driven by the use of olfaction for intraspecific recognition, whereas vision remains the primary sense for the task in the males. This article is part of the theme issue ‘Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods’.

As an emerging two-dimensional nanomaterial with promising prospects, mono- or few-layer black phosphorus (BP) is potentially toxic to humans. We investigated the effects of two types of BPs on adult male mice through intratracheal instillation. Using the flow cytometry method, the generation, migration, and recruitment of immune cells in different organs have been characterized on days 1, 7, 14, and 21 post-exposure. Compared with small BP (S-BP, lateral size at ∼188 nm), large BP (L-BP, lateral size at ∼326 nm) induced a stronger stress lymphopoiesis and B cell infiltration into the alveolar sac. More importantly, L-BP dramatically increased peripheral neutrophil (NE) counts up to 1.9-fold on day 21 post-exposure. Decreased expression of the CXCR4 on NEs, an important regulator of NE retention in the bone marrow, explained the increased NE release into the circulation induced by L-BP. Therefore, BP triggers systemic inflammation via the disruption of both the generation and migration of inflammatory immune cells.

Introduction: Phytocannabinoids have emerged as a potential alternative treatment option for individuals experiencing persistent pain. However, evidence-based research regarding their clinical utility in both males and females remains incomplete. In addition, it is unknown whether combining readily available cannabinoids with opioids has a synergistic or subadditive effect on pain modulation. To begin to fill this knowledge gap, we investigated the antinociceptive effects of the phytocannabinoid, CBD, either alone or in combination with opioids in male and female C57BL/6J mice. Results: Using the formalin test, our results show that CBD (10 mg/kg, i.p.) treatment evoked antinociception in phase I, but not in phase II, of the formalin test in male mice. However, in female mice, CBD showed no significant antinociceptive effect. In addition, a direct sex comparison showed that CBD evoked a significant increase in nociceptive behaviors in female versus male mice during phase I of the formalin test. Furthermore, we show that CBD (10 mg/kg, i.p.) in combination with low-dose morphine (1 mg/kg, i.p.) was ineffective at eliciting a synergistic antinociceptive response in both male and female mice. Lastly, consistent with previous literature, we showed that females treated with a relatively higher dose of morphine (10 mg/kg, i.p.) displayed a significant increase in the variability of nociceptive behaviors compared to morphine-treated male mice. Conclusion: Overall, our results suggest that CBD treatment may have beneficial antinociceptive effects during the acute phase of persistent pain, but these effects are more beneficial to males than females. We provide further pre-clinical support that treatments geared toward reducing nociceptive behaviors differentially affect males and females.

The sensory bias hypothesis proposes that female preferences for male sexual signalling traits evolved in contexts other than mating. Individuals of both sexes may experience similar selection pressures in these contexts; thus males may have similar biases to females for variation in signal traits. We tested this prediction in the grey treefrog

Nicotinamide adenine dinucleotide (NAD

Vascular contributions to cognitive impairment/dementia (VCID) are a leading cause of dementia, a known neurodegenerative disorder characterized by progressive cognitive decline. Although diabetes increases the risks of stroke and the development of cerebrovascular disease, the cellular and vascular mechanisms that lead to VCID in diabetes are yet to be determined. A growing body of research has identified that cerebrovascular cells within the neurovascular complex display an array of cellular responses that impact their survival and reparative properties, which plays a significant role in VCID development. Specifically, endothelial cells and pericytes are the primary cell types that have gained much attention in dementia-related studies due to their molecular and phenotypic heterogeneity. In this review, we will discuss the various morphological subclasses of endothelial cells and pericytes as well as their relative distribution throughout the cerebrovasculature. Furthermore, the use of diabetic and stroke animal models in preclinical studies has provided more insight into the impact of sex differences on cerebral vascularization in progressive VCID. Understanding how cellular responses and sex differences contribute to endothelial cell and pericyte survival and function will set the stage for the development of potential preventive therapies for dementia-related disorders in diabetes.

A 9-mo-old, male domestic shorthair cat was presented for castration because of mounting behavior observed by the owner. On physical examination, the cat was bilaterally cryptorchid, but had penile spines. Abdominal exploration through a midline laparotomy revealed 2 pairs of masses. All 4 masses had gross features of testes, and ranged from 7 × 5 × 5 mm to 12 × 6 × 7 mm, with associated epididymal tissue. Histologically, each mass contained seminiferous tubules consistent with testicular tissue, and epididymal tubules, confirming a diagnosis of polyorchidism; deferent ducts were not found. There was no evidence of neoplastic, infectious, or inflammatory disease. Mounting behavior ceased 4 wk post-surgery. Histologic confirmation of more than 2 testes is needed to establish a diagnosis of polyorchidism, a rare congenital anomaly that has been reported infrequently in the veterinary literature; reports have been of animals with triorchidism, with the exception of 1 cat with 4 intraabdominal testes. Our report emphasizes that, although rare, polyorchidism should be considered in cryptorchid cats, or whenever penile spines are present in a previously castrated cat. Our case also highlights the value of checking for penile spines in a bilaterally cryptorchid cat if abdominal ultrasound is not an option to aid in surgical planning.