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Of the eleven species of shrews described in Iran, the Etruscan shrew (Suncus etruscus), the smallest known extant mammal by mass, is recorded in northern and southern provinces. During rodent control programs, a female S. etruscus was trapped and found naturally infected with a trematode which was morphologically identified as Brachylaima sp. This finding represents the first report of trematodiasis in this host species.

The Etruscan shrew (Suncus etruscus) is one of the smallest mammals on earth and is used in many fields of research, including physiology, behavioral science and neuroscience. However, establishing and maintaining a breeding colony of this species in the laboratory can be challenging, as it requires specific husbandry conditions that greatly differ from those of more common laboratory species such as mice or rats. Over the past 15 y, we have successfully established a long-term thriving colony of 150 to 200 animals originating from 36 founders. The colony shows longer life expectancy and larger litter sizes than wild conspecifics. Breeding occurs year-round, independent of seasons, and a breeding pair can regularly produce 2 to 6 offspring with an average life expectancy of more than 3 y. The shrews are housed in glass or plastic enclosures on a specific soil-sand-mixture bedding and are provided with hideouts and nesting material consisting of moss, wood, or bark. Due to their high basal metabolic rate, the shrews require food intake greater than their body weight per day, can hunt arthropods as large as themselves, and cannot survive more than a few hours without food. Live feed such as crickets or mealworms is crucial and must be provided daily or, at the very least, every 2 d. Although our husbandry practices have constantly been adapted and refined, shrew husbandry remains challenging, and great care is necessary to meet the specific needs of this species. Here, we describe the establishment of a long-term stable colony of Etruscan shrews in a research animal facility and the specific husbandry requirements for animal wellbeing.

Background Ixodid ticks are important vectors for zoonotic pathogens, with Ixodes ricinus being the most important in Europe. Rodents are hosts of immature life stages of I. ricinus ticks and are considered main reservoirs for tick-borne pathogens, e.g. Borrelia burgdorferi. The aim of this study was to analyse the prevalence as well as genospecies and sequence type (ST) diversity of Borrelia burgdorferi sensu lato in ticks and small mammals from central Germany and to elaborate on the influence of environmental and/or individual host and vector factors on Borrelia prevalence. Methods After species identification, 1167 small mammal skin samples and 1094 ticks from vegetation were screened by B. burgdorferi sensu lato real-time polymerase chain reaction, and positive samples were characterized by multilocus sequence typing. Generalized linear (mixed) models were used to estimate how seasonality, small mammal species/tick life stage and habitat affect individual infection status. Results In total, 10 small mammal species and three tick species, Ixodes ricinus, Ixodes inopinatus (both considered members of the I. ricinus complex) and Dermacentor reticulatus, were investigated. Borrelia DNA was detected in eight host species, i.e. the striped field mouse (Apodemus agrarius), the yellow-necked field mouse (Apodemus flavicollis), the wood mouse (Apodemus sylvaticus), the water vole (Arvicola amphibius), the bank vole (Clethrionomys glareolus), the field vole (Microtus agrestis), the common vole (Microtus arvalis), and the common shrew (Sorex araneus). Two species were Borrelia negative, the greater white-toothed shrew (Crocidura russula) and the pygmy shrew (Sorex minutus). The average prevalence was 6.2%, with two genospecies detected, Borrelia afzelii and Borrelia garinii, and at least three STs that had not been previously reported in small mammals. Borrelia prevalence in small mammals did not differ between seasons. Six genospecies of Borrelia—Borrelia afzelii, Borrelia valaisiana, Borrelia garinii, Borrelia lusitaniae, Borrelia spielmanii, and Borrelia burgdorferi sensu stricto—and 25 STs of Borrelia, of which 12 have not been previously described at all and five have not been previously reported in Germany, were detected in 13% of I. ricinus complex ticks. Prevalence was highest in adult females (25.3%) and lowest in nymphs (11.4%). Prevalence was significantly higher in ticks from grassland (16.8%) compared to forests (11.4%). Conclusions The high level of small mammal diversity in this region of Germany seems to be reflected in a wide variety of genospecies and STs of B. burgdorferi. Graphical abstract

Objectives: Lymphocytic choriomeningitis virus (LCMV), a human pathogenic arenavirus, is distributed worldwide. However, no human cases have been reported in Africa. This study aimed to investigate the current situation and potential risks of LCMV infection in Gabon, Central Africa. Methods: A total of 492 human samples were screened to detect LCMV genome RNA and anti-LCMV IgG antibodies using reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay (ELISA), respectively. ELISA-positive samples were further examined using a neutralization assay. Viral RNAs and antibodies were also analyzed in 326 animal samples, including rodents, shrews, and bushmeat. Results: While no LCMV RNA was detected in human samples, the overall seroprevalence was 21.5% and was significantly higher in male and adult populations. The neutralization assay identified seven samples with neutralizing activity. LCMV RNA was detected in one species of rodent (Lophuromys sikapusi) and a porcupine, and anti-LCMV IgG antibodies were detected in four rodents and three shrews. Conclusions: This study determined for the first time the seroprevalence of LCMV in Gabon, and revealed that local rodents, shrews, and porcupines in areas surrounding semi-urban cities posed an infection risk. Hence, LCMV infection should be considered a significant public health concern in Africa., International Journal of Infectious Diseases, 105, pp. 452-459; 2021

Gastric contractions show two specific patterns in many species, migrating motor contractions (MMC) and postprandial contractions (PPCs), that occur in the fasted and fed states, respectively. In this study, we examined the role of somatostatin (SST) in gastric motility both in vivo and in vitro using the Asian house shrew (Suncus murinus). We performed in vivo recordings of gastric motility and in vitro organ bath experiments using S. murinus, which was recently established as a small laboratory animal for use in tests of gastrointestinal motility. SST (1.65 µg kg−1 min−1) was intravenously administered during phase II of MMC and PPCs. Next, the effect of SST on motilin-induced gastric contractions at phase I of MMC was measured. Cyclosomatostatin (CSST), an SST receptor antagonist, was administered at the peak of phase III of MMC. In addition, the effect of SST (10−11–10−9 M) on motilin-induced gastric contractions was evaluated using an organ bath experiment in vitro. In conscious, free-moving S. murinus, the administration of SST decreased the occurrence of the spontaneous phase II of MMC and PPCs. Pretreatment with SST and octreotide suppressed the induction of motilin-induced gastric contractions both in vivo and in vitro. Administration of CSST before the peak of spontaneous phase III contractions had no effect on gastric contractions. Endogenous SST is not involved in the regulation of gastric MMC and PPCs, but exogenous SST suppresses spontaneous gastric contractions. Thus, SST would be good for treating abnormal gastrointestinal motility disorders.

Significance To survive, animals need to adapt to changes of their ecosystem by changing their behaviors or even morphing the organs responsible for generating these behaviors. Small mammals have a high metabolic rate, and to balance energy deficits during winter they can decrease their brain and body size, a phenomenon termed Dehnel’s effect. We find specific seasonal changes in the brain of the smallest terrestrial mammal, the Etruscan shrew. Their cortex shrinks in the winter, with layer-width and neuron number reduction in the energetically expensive somatosensory cortical layer 4. Imaging of neural activity revealed reduced suppressive responses to whisker touch during winter, indicating that such cortical adaptation may have synergistic functional and behavioral effects in addition to direct metabolic benefits., Seasonal cycles govern life on earth, from setting the time for the mating season to influencing migrations and governing physiological conditions like hibernation. The effect of such changing conditions on behavior is well-appreciated, but their impact on the brain remains virtually unknown. We investigate long-term seasonal changes in the mammalian brain, known as Dehnel’s effect, where animals exhibit plasticity in body and brain sizes to counter metabolic demands in winter. We find large seasonal variation in cellular architecture and neuronal activity in the smallest terrestrial mammal, the Etruscan shrew, Suncus etruscus. Their brain, and specifically their neocortex, shrinks in winter. Shrews are tactile hunters, and information from whiskers first reaches the somatosensory cortex layer 4, which exhibits a reduced width (−28%) in winter. Layer 4 width (+29%) and neuron number (+42%) increase the following summer. Activity patterns in the somatosensory cortex show a prominent reduction of touch-suppressed neurons in layer 4 (−55%), the most metabolically active layer. Loss of inhibitory gating occurs with a reduction in parvalbumin-positive interneurons, one of the most active neuronal subtypes and the main regulators of inhibition in layer 4. Thus, a reduction in neurons in layer 4 and particularly parvalbumin-positive interneurons may incur direct metabolic benefits. However, changes in cortical balance can also affect the threshold for detecting sensory stimuli and impact prey choice, as observed in wild shrews. Thus, seasonal neural adaptation can offer synergistic metabolic and behavioral benefits to the organism and offer insights on how neural systems show adaptive plasticity in response to ecological demands.

When acutely administered intraperitoneally, the non-psychoactive cannabinoid cannabidiol (CBD), its acidic precursor cannabidiolic acid (CBDA) and a stable methyl ester of CBDA (HU-580) reduce lithium chloride (LiCl)–induced conditioned gaping in male rats (a selective preclinical model of acute nausea) via activation of the serotonin 1A (5-HT1A) receptor. To utilise these compounds to manage nausea in the clinic, we must determine if their effectiveness is maintained when injected subcutaneously (s.c) and when repeatedly administered. First, we compared the effectiveness of each of these compounds to reduce conditioned gaping following repeated (7-day) and acute (1-day) pretreatments and whether these anti-nausea effects were mediated by the 5-HT1A receptor. Next, we assessed whether the effectiveness of these compounds can be maintained when administered prior to each of 4 conditioning trials (once per week). We also evaluated the ability of repeated CBD (7 days) to reduce LiCl-induced vomiting in Suncus murinus. Finally, we examined whether acute CBD was equally effective in male and female rats. Both acute and repeated (7 day) s.c. administrations of CBD (5 mg/kg), CBDA (1 μg/kg) and HU-580 (1 μg/kg) similarly reduced LiCl-induced conditioned gaping, and these effects were blocked by 5HT1A receptor antagonism. When administered over 4 weekly conditioning trials, the anti-nausea effectiveness of each of these compounds was also maintained. Repeated CBD (5 mg/kg, s.c.) maintained its anti-emetic efficacy in S. murinus. Acute CBD (5 and 20 mg/kg, s.c.) administration reduced LiCl-induced conditioned gaping similarly in male and female rats. When administered repeatedly (7 days), CBD, CBDA and HU-580 did not lose efficacy in reducing nausea and continued to act via agonism of the 5-HT1A receptor. When administered across 4 weekly conditioning trials, they maintained their effectiveness in reducing LiCl-induced nausea. Repeated CBD also reduced vomiting in shrews. Finally, CBD’s anti-nausea effects were similar in male and female rats. This suggests that these cannabinoids may be useful anti-nausea and anti-emetic treatments for chronic conditions, without the development of tolerance.

Ancient biomolecule analyses are proving increasingly useful in the study of evolutionary patterns, including extinct organisms. Proteomic sequencing techniques complement genomic approaches, having the potential to examine lineages further back in time than achievable using ancient DNA, given the less stringent preservation requirements. In this study, we demonstrate the ability to use collagen sequence analyses via proteomics to assist species delimitation as a foundation for informing evolutionary patterns. We uncover biogeographic information of an enigmatic and recently extinct lineage of Nesophontes across their range on the Caribbean islands. First, evolutionary relationships reconstructed from collagen sequences reaffirm the affinity of Nesophontes and Solenodon as sister taxa within Solenodonota. This relationship helps lay the foundation for testing geographical isolation hypotheses across islands within the Greater Antilles, including movement from Cuba toward Hispaniola. Second, our results are consistent with Cuba having just two species of Nesophontes (N. micrus and N. major) that exhibit intrapopulation morphological variation. Finally, analysis of the recently described species from the Cayman Islands (N. hemicingulus) indicates that it is a closer relative to N. major rather than N. micrus as previously speculated. This proteomic sequencing improves our understanding of the origin, evolution, and distribution of this extinct mammal lineage, particularly with respect to the approximate timing of speciation. Such knowledge is vital for this biodiversity hotspot, where the magnitude of recent extinctions may obscure true estimates of species richness in the past.

The molecular genetic mechanisms underlying postoperative nausea and vomiting (PONV) in the brain have not been fully elucidated. This study aimed to determine the changes in whole transcriptome in the nucleus of the solitary tract (NTS) in an animal model of PONV, to screen a drug candidate and to elucidate the molecular genetic mechanisms of PONV development.Twenty-one female musk shrews were assigned into three groups: the Surgery group (shrew PONV model, n = 9), the Sham group (n = 6), and the Naïve group (n = 6). In behavioral studies, the main outcome was the number of emetic episodes. In genetic experiments, changes in the transcriptome in the NTS were measured. In a separate study, 12 shrews were used to verify the candidate mechanism underlying PONV.A median of six emetic episodes occurred in both the Sham and Surgery groups. Whole-transcriptome analysis indicated the inhibition of the GABAOur findings suggest that the GABA

Multiple representatives of eulipotyphlan mammals such as shrews have oral venom systems. Venom facilitates shrews to hunt and/or hoard preys. However, little is known about their venom composition, and especially the mechanism to hoard prey in comatose states for meeting their extremely high metabolic rates. A toxin (BQTX) was identified from venomous submaxillary glands of the shrew Blarinella quadraticauda. BQTX is specifically distributed and highly concentrated (~ 1% total protein) in the organs. BQTX shares structural and functional similarities to toxins from snakes, wasps and snails, suggesting an evolutional relevancy of venoms from mammalians and non-mammalians. By potentiating thrombin and factor-XIIa and inhibiting plasmin, BQTX induces acute hypertension, blood coagulation and hypokinesia. It also shows strong analgesic function by inhibiting elastase. Notably, the toxin keeps high plasma stability with a 16-h half-life in-vivo, which likely extends intoxication to paralyze or immobilize prey hoarded fresh for later consumption and maximize foraging profit.

Background: This study aimed to determine the presence and species of the rats and shrews that can potentially cause leptospirosis in West Jakarta, Indonesia, and the species of ectoparasites found in them. Methods: The research was a descriptive study employing a cross-sectional approach. The study population was all species of rats and shrews in the region and the sample collection technique used was purposive sampling. The traps were installed in the homes of respondents who had suffered from leptospirosis and their closest neighbors, with a total of 521 traps. Leptospirosis data based on secondary data was obtained from West Jakarta Health Office (2016-August 2019). The technique for catching rats involved using humane live traps, while the identification of the rats and ectoparasites was done in the laboratory. Results: It was found that more rats were caught in Cengkareng Timur sub-district, Cengkareng District, with a percentage of 14.8%, while the least in Duri Kepa, Kapuk, Kedaung Kali Angke and Kedoya Utara with a percentage of 3.7%. The rats were mostly found in East Cengkareng Sub-District, with the most common type being Rattus rattus (74.1 %) and the least Suncus murinus (11.1%); more male rats were caught (66.7%) than female (33.3%). The type of ectoparasite found in the rats was fleas. Xenopsylla cheopis was the most common type, at 83.3% and more fleas were male, at 66.7%. The most common rat species was Rattus rattus. The ectoparasite most commonly found in them was the female flea Xenopsylla cheopis. Conclusions: Rattus rattus and Xenopsylla cheopis were found in an East Cengkareng sub-district. Surveys, monitoring, and control of rats and ectoparasites are essential for the preparedness and development of an early warning system of possible diseases that they can cause.

Cercarial emission of schistosomes is a determinant in the transmission to the definitive host and constitutes a good marker to identify which definitive host is responsible for transmission, mainly in introgressive hybridization situations. Our goal was to test the hypothesis that micro-mammals play a role inSchistosoma haematobium,S.bovis, and/orS.haematobiumxS.bovistransmission. Small mammal sampling was conducted in seven semi-lacustrine villages of southern Benin. Among the 62 animals trapped, 50 individuals were investigated forSchistosomaadults and eggs: 37Rattus rattus, 3Rattus norvegicus, 9Mastomys natalensis, and 1Crocidura olivieri.Schistosomaadults were found in fourR. rattusand twoM. natalensis, with a local prevalence reaching 80% and 50%, respectively.Two cercarial chronotypes were found fromBulinus globosusexperimentally infected with miracidia extracted from naturally infectedM. natalensis: a late diurnal and nocturnal chronotype, and an early diurnal, late diurnal, and nocturnal chronotype. The cytochrome C oxidase subunit I mtDNA gene of the collected schistosomes (adults, miracidia, and cercariae) belonged to theS.bovisclade. Eleven internal transcribed spacer rDNA profiles were found; four belonged toS.bovisand seven toS.haematobiumxS.bovis. These molecular results together with the observed multi-peak chronotypes addM. natalensisas a new host implicated inS.haematobiumxS.bovistransmission. We discuss the origin of the new chronotypes which have become more complex with the appearance of several peaks in a 24-h day. We also discuss how the new populations of offspring may optimize intra-host ecological niche, host spectrum, and transmission time period.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with a high morbidity and mortality. Some of the mechanisms of fibrosis development have been described using rodent models; however, the relevance of findings in these animal models is difficult to assess. New innovative models are needed that closely mimic IPF disease pathology.MethodsTo overcome this unmet need of investigating IPF with a relevant model, we utilized tree shrews, which are genetically, anatomically, and metabolically similar to primates and humans. Using human antibodies and primers, we investigated the role of macrophage phenotypic switching in normal and IPF subjects and bleomycin-injured tree shrews.ResultsBronchoalveolar lavage (BAL) cells from tree shrews expressed human markers, and there was recruitment of monocyte-derived macrophages (MDMs) to the lung in IPF subjects and bleomycin-injured tree shrews. MDMs were polarized to a profibrotic phenotype in IPF and in bleomycin-injured tree shrews. Resident alveolar macrophages (RAMs) expressed proinflammatory markers regardless of bleomycin exposure. Tree shrews developed bleomycin-induced pulmonary fibrosis with architectural distortion in parenchyma and widespread collagen deposition.ConclusionThe profibrotic polarization of macrophages has been demonstrated to be present in IPF subjects and in fibrotic mice. Although the lung macrophages have long been considered to be homogeneous, recent evidence indicates that these cells are heterogeneous during multiple chronic lung diseases. Here, we show new data that indicate a critical and essential role for macrophage-fibroblast crosstalk promoting fibroblast differentiation and collagen production. in the development and progression of fibrosis. The current data strongly suggest development of therapeutics that attenuate of the profibrotic activation of MDMs may mitigate macrophage-fibroblast interaction. These observations demonstrate that tree shrews are an ideal animal model to investigate the pathogenesis of IPF as they are genetically, anatomically, and metabolically closer to humans than the more commonly used rodent models.

International audience; Large brains in prey may select for adoption of anti-predator behavior that facilitates escape. Prey species with relatively large brains have been shown to be less likely to fall prey to predators. This results in the prediction that individuals that have been captured by predators on average should have smaller brains than sympatric conspecifics. We exploited the fact that Eurasian pygmy owls Glaucidium passerinum hoard small mammals and birds in cavities and nest-boxes for over-winter survival, allowing for comparison of the phenotype of prey with that of live conspecifics. In Northern Europe, main prey of pygmy owls are voles of the genera Myodes and Microtus, while forest birds and shrews are the most important alternative prey. Large fluctuations (amplitude 100-200-fold) in vole populations induce rapid numerical responses of pygmy owls to main prey populations, which in turn results in varying predation pressure on small birds. We found, weighed and measured 153 birds in foodstores of pygmy owls and mist-netted, weighed and measured 333 live birds of 12 species in central-western Finland during two autumns with low (2017) and high (2018) pygmy owl predation risk. In two autumns, individuals with large brains were captured later compared to individuals with small brains, consistent with the hypothesis that such individuals survived for longer. Avian prey of pygmy owls had smaller heads than live birds in autumn 2018 when predation risk by pygmy owls was high. This difference in head size was not significant in 2017 when predation risk by pygmy owls was reduced. Finally, avian survivors were in better body condition than avian prey individuals. These findings are consistent with the hypothesis that pygmy owls differentially prey on birds in poor condition with small brains. These findings are consistent with the hypothesis that predation risk imposed by pygmy owls on small birds in boreal forests varies depending on the abundance of the main prey (voles).

In this study, the physiological values of volumes of plasma, cells, total blood and the F blood factors were identified in 24 adult tree shrews (Tupaia belangeri; 12 male and 12 female; average BW of 123.9±19.19 g). The two-compartment model method of Evans Blue dye was used to obtain the plasma volume and the venous hematocrit was measured by microhematocrit method. To establish the relationship between body weight (BW) and blood volume of tree shrews, We performed linear fitting for these two datasets. Results were analyzed according to gender and weight (120g). Statistical significance was assessed using the unpaired student t test and one-way ANOVA. The average volumes per 100g body weight of plasma, red blood cell (RBC) and total blood were 5.42±0.543, 3.24±0.445, and 8.66±0.680ml respectively. The mean body hematocrit, cardiac hematocrit, jugular vein hematocrit, femoral vein hematocrit, and tail vein hematocrit was 37.43±4.096, 39.72±3.219, 43.04±4.717, 40.84±3.041, and 38.71±3.442% respectively. The F cardiac was 0.94±0.072, F jugular vein 0.88±0.118, F femoral vein 0.92±0.111, and the F tail vein 0.97±0.117. Blood volume (ml) was 85.89103×BW (kg). This is the first study to provide the parameters of plasma volume, cell volume, total blood volume and F factor and a baseline for future research on blood physiology of tree shrews.

Animals that use venom to feed on a wide diversity of prey may evolve a complex mixture of toxins to target a variety of physiological processes and prey-defense mechanisms. Blarina brevicauda, the northern short-tailed shrew, is one of few venomous mammals, and is also known to eat evolutionarily divergent prey. Despite their complex diet, earlier proteomic and transcriptomic studies of this shrew’s venom have only identified two venom proteins. Here, we investigated with comprehensive molecular approaches whether B. brevicauda venom is more complex than previously understood. We generated de novo assemblies of a B. brevicauda genome and submaxillary-gland transcriptome, as well as sequenced the salivary proteome. Our findings show that B. brevicauda’s venom composition is simple relative to their broad diet and is likely limited to seven proteins from six gene families. Additionally, we explored expression levels and rate of evolution of these venom genes and the origins of key duplications that led to toxin neofunctionalization. We also found three proteins that may be involved in endogenous self-defense. The possible synergism of the toxins suggests that vertebrate prey may be the main target of the venom. Further functional assays for all venom proteins on both vertebrate and invertebrate prey would provide further insight into the ecological relevance of venom in this species.

Mammary gland cancer is the most common cancer occurring in women globally. Incidences of this cancer in Japan are on the increase. Annually, more than 70,000 new cases are recorded in Japan and about 1.7 million in the world. Many cases are still difficult to cure completely, and animal models are required for the characterization of the biology, therapeutic strategy, and preventive measures for spontaneous mammary tumor. The mouse model used currently has some limitations owing to structural differences between mouse and human mammary glands. Tupaia belangeri (tree shrew), which belongs to the Tupaiidae family, shows relatively high genetic homology and structural similarity to human mammary glands. Here, we characterized the spontaneous mammary tumors in 61 female tree shrews of different ages. The incidence rate was 24.6% (15/61), and the rate of simultaneous or metachronous multiplex tumors was 60% (9/15). From the incidence pattern, some cases seemed to be of familial mammary gland tumor, as the offspring of female tree shrews No. 3 and 9 and male tree shrew No. 11 showed a high incidence rate, of 73.3% (11/15). Average incidence age for tumor development was 2 years and 3 months, and the earliest was 10 months. Histochemical analysis indicated that spontaneous mammary gland tumors in the tree shrew show the features of intraductal papillary adenomas (22 cases), except 2 tubulopapillary carcinoma cases (No. 75 and 131). All the cases were positive for the progesterone receptor, whereas 91.3% were positive for the estrogen receptor, and 4.3% were HER-2 positive. We have also confirmed the expression of nectin-4 in some mammary tumor cells. Additionally, we subjected tree shrews to cytodiagnosis or X-ray CT. Thus, the findings of this study highlight the potential of the tree shrew as a valuable new animal model for mammary gland tumor study.

Published studies have shown that the transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX), has pro and antiemetic effects. RTX can suppress vomiting evoked by a variety of nonselective emetogens such as copper sulfate and cisplatin in several vomit-competent species. In the least shrew, we have already demonstrated that combinations of ultra-low doses of RTX and low doses of the cannabinoid CB1/2 receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) produce additive antiemetic effects against cisplatin-evoked vomiting. In the current study, we investigated the broad-spectrum antiemetic potential of very low nonemetic doses of RTX against a diverse group of specific emetogens including selective and nonselective agonists of serotonergic 5-hydroxytrptamine (5-HT3) receptor (5-HT and 2-Me-5-HT), dopaminergic D2 receptor (apomorphine and quinpirole), cholinergic M1 receptor (pilocarpine and McN-A-343), as well as the selective substance P neurokinin NK1 receptor agonist GR73632, the selective L-Type calcium channel agonist FPL64176, and the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin. When administered subcutaneously, ultra-low (0.01 µg/kg) to low (5.0 µg/kg) doses of RTX suppressed vomiting induced by the aforementioned emetogens in a dose-dependent fashion with 50% inhibitory dose values ranging from 0.01 to 1.26 µg/kg. This study is the first to demonstrate that low nanomolar nonemetic doses of RTX have the capacity to completely abolish vomiting caused by diverse receptor specific emetogens in the least shrew model of emesis.

Proteus spp. are commensal gastrointestinal bacteria in many hosts, but information regarding the mutual relationships between these bacteria and their hosts is limited. The tree shrew is an alternative laboratory animal widely used for human disease research. However, little is known about the relationship between Proteus spp. and tree shrews. In this study, the complete genome sequencing method was used to analyse the characteristics of Proteus spp. isolated from tree shrews, and comparative genomic analysis was performed to reveal their relationships. The results showed that 36 Proteus spp. bacteria were isolated, including 34 Proteus mirabilis strains and two Proteus vulgaris strains. The effective rate of sequencing was 93.53%±2.73%, with an average GC content of 39.94%±0.25%. Briefly, 3682.89±90.37, 2771.36±36.01 and 2832.06±42.49 genes were annotated in the NCBI non-redundant nucleotide database (NR), SwissProt database and KEGG database, respectively. The high proportions of macrolide-, vancomycin-, bacitracin-, and tetracycline-resistance profiles of the strains were annotated in the Antibiotic Resistance Genes Database (ARDB). Flagella, lipooligosaccharides, type 1 fimbriae and P fimbriae were the most abundantly annotated virulence factors in the Virulence Factor Database (VFDB). SNP variants indicated high proportions of base transitions (Ts), homozygous mutations (Hom) and non-synonymous mutations (Non-Syn) in Proteus spp. (P

Ambient temperature has a substantial influence on the thermoregulation costs of small mammals due to their high surface-to-volume ratio. Shrews are among the smallest of mammals and have adopted different behavioral and physiological strategies to deal with cold temperatures. In this study, we assessed the use of an external heat source in the thermoregulatory strategy of two Crocidurinae species, Crocidura russula and C. suaveolens, and one Soricinae species, Sorex araneus. Crocidura russula inhabits western Europe and is better adapted to a Mediterranean climate; C. suaveolens inhabits central Europe; and S. araneus inhabits northern Europe and is better adapted to a Palearctic climate. We predicted that C. russula (most southern species) would spend larger amounts of time using an external heat source because it is the most cold-sensitive species, while S. araneus (most northern species) would spend less time using an external heat source or not respond to it. Shrews were experimentally tested in captivity inside a terrarium where they had access to a heat rock, which could be turned off (cold) or on (heated), depending on treatment. Our results confirmed our initial prediction: C. russula was the species that spent significantly more time on the heated rock, followed by C. suaveolens. Only a quarter of S. araneus individuals spent large amounts of time on the heat rock, which suggests this thermoregulation strategy is not generally adopted by this species, but may be rather associated with some individual personalities. We also analyzed the influence of the heat rock on rewarming from heterothermy, but heterothermy was not different between rock treatments. Overall, our results show that shrew species use external heat sources for thermoregulation according to their sensitivity to cold.

Maupasina weissi (Seurat, 1913), is redescribed from the eastern rock sengi, Elephantulus myurus Thomas & Schwann, from Limpopo Province and compared with material collected from Free State and North West Provinces, South Africa, as well as the description of the type-material from South Tunisia. Distinguishing features of the species include a corona radiata of 12 pointed leaflike elements, a complex bipartite buccal capsule with 3 large bicuspid denticular lobes and 4 smaller club-shaped lobes and 11 (occasionally 10) pairs of cloacal papillae in the male. The complex taxonomic history of the genus Maupasina Seurat, 1917 is discussed. The probable misidentification of Macroscelides proboscideus Shaw, the short eared sengi, from North West Province, South Africa, as a host of M. weissi is explained, indicating that M. weissi occurs only in species of the genus Elephantulus Thomas & Schwann. The widely separated geographical regions, stretching the length of the African continent, in which M. weissi has been found are indicative of a conservative species with a broad geographical distribution. Tenebrionid beetles, up to 50% of stomach contents of E. myurus in Limpopo Province may act as intermediate hosts in the life-cycle of M. weissi.

Of the 18 sub-Saharan elephant-shrew species, only eastern rock elephant-shrews reproduce seasonally throughout their distribution, a process seemingly independent of photoperiod. The present study characterizes gonadal status and location/intensity of gonadotrophin-releasing hormone-1 (GnRH-1) and kisspeptin immunoreactivities in this polyovulating species in the breeding and nonbreeding seasons. GnRH-1-immunoreactive (ir) cell bodies are predominantly in the medial septum, diagonal band, and medial preoptic area; processes are generally sparse except in the external median eminence. Kisspeptin-ir cell bodies are detected only within the arcuate nucleus; the density of processes is generally low, except in the septohypothalamic nucleus, ventromedial bed nucleus of the stria terminalis, arcuate nucleus, and internal and external median eminence. Kisspeptin-ir processes are negligible at locations containing GnRH-1-ir cell bodies. The external median eminence is the only site with conspicuously overlapping distributions of the respective immunoreactivities and, accordingly, a putative site for kisspeptin's regulation of GnRH-1 release in this species. In the nonbreeding season in males, there is an increase in the rostral population of GnRH-1-ir cell bodies and density of GnRH-1-ir processes in the median eminence. In both sexes, the breeding season is associated with increased kisspeptin-ir process density in the rostral periventricular area of the third ventricle and arcuate nucleus; at the latter site, this is positively correlated with gonadal mass. Cross-species comparisons lead us to hypothesize differential mechanisms within these peptidergic systems: that increased GnRH-1 immunoreactivity during the nonbreeding season reflects increased accumulation with reduced release; that increased kisspeptin immunoreactivity during the breeding season reflects increased synthesis with increased release.

The seasonal changes in brain size of some shrews represent the most drastic reversible transformation in the mammalian central nervous system known to date. Brain mass decreases 10–26% from summer to winter and regrows 9–16% in spring, but the underlying structural changes at the cellular level are not yet understood. Here, we describe the volumetric differences in brain structures between seasons and sexes of the common shrew (Sorex araneus) in detail, confirming that changes in different brain regions vary in the magnitude of change. Notably, shrews show a decrease in hypothalamus, thalamus, and hippocampal volume and later regrowth in spring, whereas neocortex and striatum volumes decrease in winter and do not recover in size. For some regions, males and females showed different patterns of seasonal change from each other. We also analyzed the underlying changes in neuron morphology. We observed a general decrease in soma size and total dendrite volume in the caudoputamen and anterior cingulate cortex. This neuronal retraction may partially explain the overall tissue shrinkage in winter. While not sufficient to explain the entire seasonal process, it represents a first step toward understanding the mechanisms beneath this remarkable phenomenon. Electronic supplementary material The online version of this article (10.1007/s00429-018-1666-5) contains supplementary material, which is available to authorized users.

5-HT receptors are implicated in many gastrointestinal disorders. However, the precise role of 5-HT in mediating GI responses in Suncus murnius is still unclear. Therefore in this study, the effects of 5-HT and its agonists were investigated in Suncus. The involvement of 5-HT2C receptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT1A and 5-HT2 to modify GI motility was investigated in vitro and in vivo. WAY100635 (a 5-HT1A antagonist) inhibited the contraction response to 5-HT in the proximal segments without affecting the maximum response; whilst enhancing the contraction to 5-HT (>30.0 nM) in the distal intestine. The selective 5-HT2A and 5-HT2B receptor antagonists MDL-100907 and RS-127445 attenuated 5-HT-induced contractions ( 3.0 nM) in the proximal and central but not the distal regions. 8-OH-DPAT-induced relaxation was resistant to the antagonism by 5-HT1A/7 antagonists. DOI in the presence of 5-HT1A/2A/2B/2C antagonists induced greater contraction responses ( > 1.0 µM) in most tissues, whilst RS-127445, or SB-242084, reduced the responses to DOI ( 1.0 µM) in some tissues. SB-242084 also suppressed emesis-induced by motion and intragastric CuSO4. In conclusion, within different regions of intestine, 5-HT2 receptors are differently involved in contraction and emetic responses and that 8-OH-DPAT induces relaxation via non-5-HT1A/7 receptors. Suncus could provide a model to investigate these diverse actions of 5-HT.

Keskin, Adem/0000-0002-1681-8363; selcuk, ahmet yesari/0000-0002-2785-2823 WOS: 000417864800017 PubMed: 29110169 Ticks are obligate ectoparasites of a vast range of terrestrial vertebrates which may play an important role in the transmission of many zoonotic pathogens to humans and animals. In the current study, we performed an investigation on ticks infesting some small mammals captured from Samsun and Tokat provinces, Northern Turkey. One hundred forty-five mammalian samples belonging to four species, namely Cricetulus migratorius (n = 1), Apodemus flavicollis (n = 17), Crocidura suaveolens (n = 102) and Sorex volnuchini (n = 25), were examined for the presence of tick infestations. A total of 273 (74 larvae, 194 nymphs, 5 females) hard ticks were collected from 88 mammalian samples. Ticks were identified as Ixodes laguri (1 nymph), I. redikorzevi (22 larvae, 186 nymphs, 5 females), I. ricinus (52 larvae, 4 nymphs) and Rhipicephalus turanicus (3 nymphs). Here, we also provided new tick mammalian host associations for Turkey. In addition, I. laguri and I. redikorzevi ticks were recorded for the first time in Samsun province of Turkey.

Introduction: Recently, hantaviruses have been discovered in insectivores in Europe, Asia, Africa, and North America. Imjin virus (MJNV) was first isolated from the lung tissues of Ussuri white-toothed shrew (Crocidura lasiura) from South Korea in 2009. We aim to detect the species and prevalence of insectivore- and rodent-borne hantaviruses in shrews and rodents. Materials and Methods: Shrews and rodents were captured in Jiaonan County of Shandong Province, China, in 2014. RT-PCR was used to amplify viral RNA of Hantavirus species, including insectivore-borne Imjin virus (MJNV), rodent-borne Hantaan virus (HTNV), and Seoul virus (SEOV) from shrews and rodents. Results and Discussion: We found that MJNV infected 10.7% (19/178) of Crocidura shrews, but it infected none of rodents (0/475); we also found that 2 of 178 (1.1%) Crocidura shrews were PCR positive to SEOV. This study indicated that the major animal hosts of Imjin virus are shrews, and rodent-borne SEOV can infect shrews.

Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. J. Comp. Neurol. 525:1586-1598, 2017. © 2016 Wiley Periodicals, Inc.

The incidence of postoperative nausea and vomiting (PONV) can be as high as 80% in patients with risk factors (e.g., females, history of motion sickness). PONV delays postoperative recovery and costs several hundred million dollars annually. Cell-based assays show that halogenated ethers (e.g., isoflurane) activate 5-HT3 receptors, which are found on gastrointestinal vagal afferents and in the hindbrain - key pathways for producing nausea and vomiting. This project evaluated the role of the vagus and activation of the hindbrain in isoflurane-induced emesis in musk shrews – a small animal model with a vomiting reflex, which is lacking in rats and mice. Sham-operated and abdominal vagotomized shrews were exposed to 1 to 3% isoflurane to determine effects on emesis; vagotomy was confirmed by lack of vagal transport of the neuronal tracer Fluoro-Gold. In an additional study, shrews were exposed to isoflurane and hindbrain c-Fos was measured at 90 min after exposure using immunohistochemistry. There were no statistically significant effects of vagotomy on isoflurane-induced emesis compared to sham-operated controls. Isoflurane exposure produced a significant increase in c-Fos-positive cells in the nucleus of the solitary tract and vestibular nuclei but not in the area postrema or dorsal motor nucleus. These results indicate that the abdominal vagus plays no role in isoflurane-induced emesis and suggest that isoflurane activates emesis by action on the hindbrain, as shown by c-Fos labeling. Ultimately, knowledge of the mechanisms of inhalational anesthesia-induced PONV could lead to more targeted therapies to control PONV.

Diseases caused by Rickettsiales bacteria are a global public health problem. To better understand the diversity and origins of Rickettsiales infection in humans and animals, we sampled 134 febrile patients, 173 rodents and 43 shrews, as well as 358 ticks, from two cities in Jiangsu and Jiangxi provinces, China. Our data revealed a relatively high prevalence of scrub typhus cases in both localities. In addition, both serological tests and genetic analysis identified three patients infected with Anaplasma bovis, Rickettsia monacensis, and Orientia tsutsugamushi bacteria. Molecular epidemiological investigation revealed the co-circulation of multiple species of Rickettsiales bacteria in small mammals and ticks in both provinces, potentially including novel bacterial species. In sum, these data demonstrate the ongoing importance of Rickettsiales infection in China and highlight the need for the regular surveillance of local arthropods, mammals and humans.

The Asian house shrew, Suncus murinus, is an insectivore (Eulipotyphla, Mammalia) and an important laboratory animal for life-science studies. The gastrointestinal tract of Suncus is simple: the length of the entire intestine is very short relative to body size, the large intestine is quite short, and there are no fermentative chambers such as the forestomach or cecum. These features imply that Suncus has a different nutritional physiology from those of humans and mice, but little is known about whether Suncus utilizes microbial fermentation in the large (LI) or small (SI) intestine. In addition, domestication may affect the gastrointestinal microbial diversity of Suncus. Therefore, we compared the gastrointestinal microbial diversity of Suncus between laboratory and wild Suncus and between the SI and LI (i.e., four groups: Lab-LI, Lab-SI, Wild-LI, and Wild-SI) using bacterial 16S rRNA gene library sequencing analyses with a sub-cloning method. We obtained 759 cloned sequences (176, 174, 195, and 214 from the Lab-LI, Lab-SI, Wild-LI, and Wild-SI samples, respectively), which revealed that the gastrointestinal microbiota of Suncus is rich in Firmicutes (mostly lactic acid bacteria), with few Bacteroidetes. We observed different bacterial communities according to intestinal region in laboratory Suncus, but not in wild Suncus. Furthermore, the gastrointestinal microbial diversity estimates were lower in laboratory Suncus than in wild Suncus. These results imply that Suncus uses lactic acid fermentation in the gut, and that the domestication process altered the gastrointestinal bacterial diversity.

Δ(9)-THC suppresses cisplatin-induced vomiting through activation of cannabinoid CB(1) receptors. Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT(3)- and neurokinin NK(1)-receptors to induce vomiting. Δ(9)-THC can inhibit vomiting caused either by the serotonin precursor 5-HTP, or the 5-HT(3) receptor selective agonist, 2-methyserotonin. In the current study, we explored whether Δ(9)-THC and related CB(1)/CB(2) receptor agonists (WIN55,212-2 and CP55,940) inhibit vomiting evoked by SP (50 mg/kg, i.p.) or the NK(1) receptor selective agonist GR73632 (5 mg/kg, i.p.). Behavioral methods were employed to determine the antiemetic efficacy of cannabinoids in least shrews. Our results showed that administration of varying doses of Δ(9)-THC (i.p. or s.c.), WIN55,212-2 (i.p.), or CP55,940 (i.p.) caused significant suppression of SP-evoked vomiting in a dose-dependent manner. When tested against GR73632, Δ(9)-THC also dose-dependently reduced the evoked emesis. The antiemetic effect of Δ(9)-THC against SP-induced vomiting was prevented by low non-emetic doses of the CB(1) receptor inverse-agonist/antagonist SR141716A (< 10 mg/kg). We also found that the NK(1) receptor antagonist netupitant can significantly suppress vomiting caused by a large emetic dose of SR141716A (20 mg/kg). In sum, Δ(9)-THC and related cannabinoids suppress vomiting evoked by the nonselective (SP) and selective (GR73632) neurokinin NK(1) receptor agonists via stimulation of cannabinoid CB(1) receptors.

Rationale Acute naloxone-precipitated morphine withdrawal (MWD) produces a conditioned place aversion (CPA) in rats even after one or two exposures to high-dose (20 mg/kg, sc) morphine followed 24-h later by naloxone (1 mg/kg, sc). However, the somatic withdrawal reactions produced by acute naloxone-precipitated MWD in rats have not been investigated. A recently discovered fatty acid amide, N-oleoylglycine (OlGly), which has been suggested to act as a fatty acid amide hydrolase (FAAH) inhibitor and as a peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, was previously shown to interfere with a naloxone-precipitated MWD-induced CPA in rats. Objectives The aims of these studies were to examine the somatic withdrawal responses produced by acute naloxone-precipitated MWD and determine whether OlGly can also interfere with these responses. Results Here, we report that following two exposures to morphine (20 mg/kg, sc) each followed by naloxone (1 mg/kg, sc) 24 h later, rats display nausea-like somatic reactions of lying flattened on belly, abdominal contractions and diarrhea, and display increased mouthing movements and loss of body weight. OlGly (5 mg/kg, ip) interfered with naloxone-precipitated MWD-induced abdominal contractions, lying on belly, diarrhea and mouthing movements in male Sprague-Dawley rats, by both a cannabinoid 1 (CB1) and a PPAR alpha mechanism of action. Since these withdrawal reactions are symptomatic of nausea, we evaluated the potential of OlGly to interfere with lithium chloride (LiCl)-induced and MWD-induced conditioned gaping in rats, a selective measure of nausea; the suppression of MWD-induced gaping reactions by OlGly was both CB1 and PPAR alpha mediated. Conclusion These results suggest that the aversive effects of acute naloxone-precipitated MWD reflect nausea, which is suppressed by OlGly.

Rotaviruses are an important cause of severe diarrheal illness in children globally. We characterized rotaviruses sampled in humans, insectivores (shrews) and rodents from urban and rural regions of Zhejiang province, China. Phylogenetic analyses revealed seven genotypic constellations of human rotaviruses with six different combinations of G and P genotypes – G3P[8] (50.06%), G9P[8] (36.16%), G1P[8] (8.92%), G2P[4] (4.63%), G3P[3] (0.12%), and G3P[9] (0.12%). In rodents and shrews sampled from the same locality we identified a novel genotype constellation (G32-P[46]-I24-R18-C17-M17-A28-N17-T19-E24-H19), a novel P genotype (P[45]), and two different AU-1-like rotaviruses associated with a G3P[3] genotype combination. Of particular note was a novel rotavirus from a human patient that was closely related to viruses sampled from rodents in the same region, indicative of a local species jump. In sum, these data are suggestive of the cross-species transmission of rodent rotaviruses into humans and for reassortment among human and animal rotaviruses., Highlights • Rotaviruses are an important cause of severe diarrheal illness. • Although rotaviruses are associated with a diverse range of animals, relatively little attention has been directed toward rotaviruses in rodents. • However, as rodents often live in close proximity to humans and domestic animals, rodents may play an important role in the cross-species transmission of rotaviruses among animals and perhaps directly or indirectly to humans. • Our data suggest the direct spill-over of rodent rotaviruses in human populations, as well as the reassortment between human and zoonotic rotaviruses.

Background Serotonin (5-hydroxytryptamine, 5-HT) is a regulatory factor in motility of the gastrointestinal tract including the esophagus. Although we proposed that vagal cholinergic and mast cell-derived non-cholinergic components including serotonin coordinately shorten the esophagus, the precise mechanism of serotonin-induced contractions in the suncus esophagus is still unclear. Therefore, the aims of this study were to determine characteristics of contractile responses induced by serotonin and to identify 5-HT receptor subtypes responsible for regulating motility in the suncus esophagus. Methods An isolated segment of the suncus esophagus was placed in an organ bath, and longitudinal or circular mechanical responses were recorded using a force transducer. Key Results Serotonin evoked contractile responses of the suncus esophagus in the longitudinal direction but not in the circular direction. Tetrodotoxin did not affect the serotonin-induced contractions. Pretreatment with a non-selective 5-HT receptor antagonist or double application of 5-HT1 and 5-HT2 receptor antagonists blocked the serotonin-induced contractions. 5-HT1 and 5-HT2 receptor agonists, but not a 5-HT3 receptor agonist, evoked contractile responses in the suncus esophagus. Conclusion & Inferences The findings suggest that serotonin induces contractile responses of the longitudinal smooth muscle in the muscularis mucosae of the suncus esophagus that are mediated via 5-HT1 and 5-HT2 receptors on muscle cells. The serotonin-induced contractions might contribute to esophageal peristalsis and emetic response.

The migrating motor complex (MMC) is responsible for emptying the stomach during the interdigestive period, in preparation for the next meal. It is known that gastric phase III of MMC starts from the proximal stomach and propagates the contraction downwards. We hypothesized that a certain region of the stomach must be more responsive to motilin than others, and that motilin-induced strong gastric contractions propagate from that site. Stomachs of the Suncus or Asian house shrew, a small insectivorous mammal, were dissected and the fundus, proximal corpus, distal corpus, and antrum were examined to study the effect of motilin using an organ bath experiment. Motilin-induced contractions differed in different parts of the stomach. Only the proximal corpus induced gastric contraction even at motilin 10(-10) M, and strong contraction was induced by motilin 10(-9) M in all parts of the stomach. The GPR38 mRNA expression was also higher in the proximal corpus than in the other sections, and the lowest expression was observed in the antrum. GPR38 mRNA expression varied with low expression in the mucosal layer and high expression in the muscle layer. Additionally, motilin-induced contractions in each dissected part of the stomach were inhibited by tetrodotoxin and atropine pretreatment. These results suggest that motilin reactivity is not consistent throughout the stomach, and an area of the proximal corpus including the cardia is the most sensitive to motilin.

Cytoplasmic calcium (Ca(2+)) mobilization has been proposed to be an important factor in the induction of emesis. The selective sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin, is known to deplete intracellular Ca(2+) stores, which consequently evokes extracellular Ca(2+) entry through cell membrane-associated channels, accompanied by a prominent rise in cytosolic Ca(2+). A pro-drug form of thapsigargin is currently under clinical trial as a targeted cancer chemotherapeutic. We envisioned that the intracellular effects of thapsigargin could cause emesis and planned to investigate its mechanisms of emetic action. Indeed, thapsigargin did induce vomiting in the least shrew in a dose-dependent and bell-shaped manner, with maximal efficacy (100%) at 0.5 mg/kg (i.p.). Thapsigargin (0.5 mg/kg) also caused increases in c-Fos immunoreactivity in the brainstem emetic nuclei including the area postrema (AP), nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNX), as well as enhancement of substance P (SP) immunoreactivity in DMNX. In addition, thapsigargin (0.5 mg/kg, i.p.) led to vomit-associated and time-dependent increases in phosphorylation of Ca(2+)/calmodulin kinase IIα (CaMKIIα) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) in the brainstem. We then explored the suppressive potential of diverse chemicals against thapsigargin-evoked emesis including antagonists of: i) neurokinin-1 receptors (netupitant), ii) the type 3 serotonin receptors (palonosetron), iii) store-operated Ca(2+) entry (YM-58483), iv) L-type Ca(2+) channels (nifedipine), and v) SER Ca(2+)-release channels inositol trisphosphate (IP3Rs) (2-APB)-, and ryanodine (RyRs) (dantrolene)-receptors. In addition, the antiemetic potential of inhibitors of CaMKII (KN93) and ERK1/2 (PD98059) were investigated. All tested antagonists/blockers attenuated emetic parameters to varying degrees except palonosetron, however a combination of non-effective doses of netupitant and palonosetron exhibited additive antiemetic efficacy. A low-dose combination of nifedipine and 2-APB plus dantrolene mixture completely abolished thapsigargin-evoked vomiting, CaMKII-ERK1/2 activation and SP elevation. In addition, pretreatment with KN93 or PD98059 suppressed thapsigargin-induced increases in SP and ERK1/2 activation. Intracerebroventricular injection of netupitant suppressed vomiting caused by thapsigargin which suggests that the principal site of evoked emesis is the brainstem. In sum, this is the first study to demonstrate that thapsigargin causes vomiting via the activation of the Ca(2+)-CaMKII-ERK1/2 cascade, which is associated with an increase in the brainstem tissue content of SP, and the evoked emesis occurs through SP-induced activation of neurokinin-1 receptors.

The Asian musk shrew (shrew) is a new reservoir of a rat hepatitis E virus (HEV) that has been classified into genotype HEV-C1 in the species Orthohepevirus C. However, there is no information regarding classification of the new rat HEV based on the entire genome sequences, and it remains unclear whether rat HEV transmits from shrews to humans. We herein inoculated nude rats (Long-Evans rnu/rnu) with a serum sample from a shrew trapped in China, which was positive for rat HEV RNA, to isolate and characterize the rat HEV distributed in shrews. A rat HEV strain, S1129, was recovered from feces of the infected nude rat, indicating that rat HEV was capable of replicating in rats. S1129 adapted and grew well in PLC/PRF/5 cells, and the recovered virus (S1129c1) infected Wistar rats. The entire genomes of S1129 and S1129c1 contain four open reading frames and share 78.3&ndash, 81.8% of the nucleotide sequence identities with known rat HEV isolates, demonstrating that rat HEVs are genetically diverse. We proposed that genotype HEV-C1 be further classified into subtypes HEV-C1a to HEV-C1d and that the S1129 strain circulating in the shrew belonged to the new subtype HEV-C1d. Further studies should focus on whether the S1129 strain infects humans.

Wild rodents are an important source of the tick-borne pathogens Coxiella burnetii and Francisella tularensis. The aim of our study was to assess the prevalence of antibodies and possible coexistence of these pathogens in wild small mammals from three localities in the Czech Republic. A total of 614 wild small mammals (324 Apodemus flavicollis, 145 Myodes glareolus, 50 Sorex araneus, 48 A. sylvaticus, 40 A. agrarius, six Microtus arvalis and one Talpa europaea) were trapped between 2012 and 2015. Their sera or heart extracts were examined by modified indirect enzyme-linked immunosorbent assay, with the detection of antibodies against C. burnetii and F. tularensis in 12 % and 7 % of animals, respectively; coinfection was identified in 4.4 % of animals. The prevalence of C. burnetii and F. tularensis antibodies statistically differed according to animal species and sex (p

Chronic pulmonary inflammation (CPI) gives rise to serious lung injuries in rheumatoid arthritis (RA) patients. However, the molecular mechanism underlying the pathogenesis of RA-associated CPI remains little understood. Here we established a novel tree shrew-based collagen-induced arthritis (TsCIA) model to study RA-associated CPI. Our results showed that typical CPI but not fibrosis developed pathologically in the TsCIA model. Furthermore, abnormal up-regulation of pulmonary chemokine CXCL10 was directly associated with lung damage. Specific blockage of CXCR3 (a CXCL10 receptor) significantly decreased the severity of CPI by decreasing the recruitment of inflammatory cells. Therefore, CXCL10 is proposed as a key player responsible for the development of TsCIA-associated CPI. Our findings also suggest that CXCR3 could be developed as a potential diagnosis biomarker for RA-associated CPI.

Low coherence laser interferometry has revolutionised quantitative biomedical imaging of optically transparent structures at cellular resolutions. We report the first optical recording of neuronal excitation at cellular resolution in the inner retina by quantifying optically recorded stimulus-evoked responses from the retinal ganglion cell layer and comparing them with an electrophysiological standard. We imaged anaesthetised paralysed tree shrews, gated image acquisition, and used numerical filters to eliminate noise arising from retinal movements during respiratory and cardiac cycles. We observed increases in contrast variability in the retinal ganglion cell layer and nerve fibre layer with flash stimuli and gratings. Regions of interest were subdivided into three-dimensional patches (up to 5–15 μm in diameter) based on response similarity. We hypothesise that these patches correspond to individual cells, or segments of blood vessels within the inner retina. We observed a close correlation between the patch optical responses and mean electrical activity of the visual neurons in afferent pathway. While our data suggest that optical imaging of retinal activity is possible with high resolution OCT, the technical challenges are not trivial.

Motilin was discovered in the 1970s as the most important hormone for stimulating strong gastric contractions; however, the mechanisms by which motilin causes gastric contraction are not clearly understood. Here, we determined the coordinated action of motilin and ghrelin on gastric motility during fasted and postprandial contractions by using house musk shrew (Suncus murinus; order: Insectivora, suncus named as the laboratory strain). Motilin-induced gastric contractions at phases I and II of the migrating motor complex were inhibited by pretreatment with (d-Lys3)-GHRP-6 (6 mg/kg/h), a ghrelin receptor antagonist. Administration of the motilin receptor antagonist MA-2029 (0.1 mg/kg) and/or (d-Lys3)-GHRP-6 (0.6 mg/kg) at the peak of phase III abolished the spontaneous gastric phase III contractions in vivo. Motilin did not stimulate gastric contractions in the postprandial state. However, in the presence of a low dose of ghrelin, motilin evoked phase III–like gastric contractions even in the postprandial state, and postprandial gastric emptying was accelerated. In addition, pretreatment with (d-Lys3)-GHRP-6 blocked the motilin-induced gastric contraction in vitro and in vivo, and a γ-aminobutyric acid (GABA) antagonist reversed this block in gastric contraction. These results indicate that blockade of the GABAergic pathway by ghrelin is essential for motilin-induced gastric contraction.

The ability of adult and subadult piebald shrews ( Diplomesodon pulchellum ) to produce 160 Hz seismic waves is potentially reflected in their vocal ontogeny and ear morphology. In this study, the ontogeny of call variables and body traits was examined in 11 litters of piebald shrews, in two-day intervals from birth to 22 days (subadult), and ear structure was investigated in two specimens using micro-computed tomography (micro-CT). Across ages, the call fundamental frequency (f0) was stable in squeaks and clicks and increased steadily in screeches, representing an unusual, non-descending ontogenetic pathway of f0. The rate of the deep sinusoidal modulation (pulse rate) of screeches increased from 75 Hz at 3–4 days to 138 Hz at 21–22 days, probably relating to ontogenetic changes in contraction rates of the same muscles which are responsible for generating seismic vibrations. The ear reconstructions revealed that the morphologies of the middle and inner ears of the piebald shrew are very similar to those of the common shrew ( Sorex araneus ) and the lesser white-toothed shrew ( Crocidura suaveolens ), which are not known to produce seismic signals. These results suggest that piebald shrews use a mechanism other than hearing for perceiving seismic vibrations.

To better understand the anti-emetic profile of the 5-HT3 (palonosetron)- and the tachykinin NK1 (netupitant) -receptor antagonists, either alone or in combination, we evaluated the effects of palonosetron and/or netupitant pretreatment on cisplatin-evoked vomiting and changes in the phosphorylation of brainstem kinases such as the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), protein kinase C alpha/beta (PKCα/β), and protein kinase A (PKA) in the least shrew. Our results demonstrate that cisplatin (10mg/kg, i.p.) causes emesis in the least shrew over 40h with respective peak early- and delayed-phases occurring at 1 - 2 and 32 - 34h post-injection. During the early phase (0 - 16h post cisplatin), palonosetron (0.1mg/kg, s.c.) significantly protected shrews from vomiting with a near complete suppression of vomit frequency. Palonosetron also significantly protected shrews from vomiting during the delayed phase (27 - 40h post cisplatin), but the reduction in mean vomit frequency failed to achieve significance. On the other hand, netupitant (5mg/kg, i.p.) totally abolished vomiting during the delayed phase, and tended to suppress the mean vomit frequency during the acute phase. The combined treatment protected shrews almost completely from vomiting during both phases. Brainstem pERK1/2 levels were significantly elevated at all time-points except at 40h post-cisplatin administration. PKA phosphorylation tended to be elevated throughout the delayed phase, but a significant increase only occurred at 33h. Brainstem pPKCα/β levels were enhanced during acute-phase with a significant elevation at 2h. Palonosetron, netupitant or their combination had no effect on elevated pERK1/2 levels during acute phase, but the combination reversed ERK1/2 phosphorylation at 33h post-cisplatin treatment. In addition, only the combined regimen prevented the cisplatin-induced PKCα/β phosphorylation observed at the acute phase. On the other hand, palonosetron and netupitant, either alone or in combination, were effective in reducing the induced elevated pPKA levels during the delayed phase. These effects on cisplatin-related emetic signals downstream of 5-HT3- and NK1-receptors help us to better understand the intracellular basis of cisplatin-induced vomiting.

Based on a re-examination of type-specimens of Filaria hyalina von Linstow, 1890 from Sorex araneus L. (Mammalia: Soricidae) and morphological studies (light and scanning electron microscopy) of specimens collected from the same host species in Bulgaria and previously identified as Stammerinema rhopalocephalum (Sołtys, 1952), both these forms are considered to be conspecific. Accordingly, F. hyalina is transferred to the genus Stammerinema Osche, 1955 as Stammerinema hyalinum n. comb. and the species originally described as Synhimantus rhopalocephalus Sołtys, 1952 is considered its junior synonym.

In the non-equatorial zones of the Earth, species concentrate their reproductive effort in the more favorable season. A consequence of seasonal breeding is seasonal testis regression, which implies the depletion of the germinative epithelium, permeation of the blood-testis barrier, and reduced androgenic function. This process has been studied in a number of vertebrates, but the mechanisms controlling it are not yet well understood. Apoptosis was assumed for years to be an important effector of seasonal germ cell depletion in all vertebrates, including mammals, but an alternative mechanism has recently been reported in the Iberian mole as well as in the large hairy armadillo. It is based on the desquamation of meiotic and post-meiotic germ cells as a consequence of altered Sertoli-germ cell adhesion molecule expression and distribution. Desquamated cells are either discarded alive through the epididymis, as in the mole, or subsequently die by apoptosis, as in the armadillo. Also, recent findings on the reproductive cycle of the greater white-toothed shrew at the meridional limits of its distribution area have revealed that the mechanisms controlling seasonal breeding are in fact far more plastic and versatile than initially suspected. Perhaps these higher adaptive capacities place mammals in a better position to face the ongoing climate change.

Background Wild mammals serve as reservoirs for a variety of microbes and play an important role in the enzootic cycles of these microbes. Some of them are vector-borne bacteria in the genera Anaplasma, Ehrlichia and Rickettsia of the order Rickettsiales, which can cause febrile illnesses in human beings as well as animals. Anaplasma spp., Ehrlichia spp. and many spotted fever group (SFG) Rickettsia spp. are transmitted to mammalian hosts by tick vectors during blood meals. As a powerful sequencing method, the next generation sequencing can reveal the complexity of bacterial communities in humans and animals. Compared with limited studies on blood microbiota, however, much fewer studies have been carried out on spleen microbiota, which is very scarce in wild mammals. Chongming Island is the third biggest island in China. It was unclear whether there were any vector-borne bacteria in Chongming Island. In the present study, we explored the bacterial microbiota in the spleens of wild mice and shrews from the rural areas of Chongming Island and investigated the prevalence of vector-borne bacteria. Methodology/Principal findings Genomic DNAs were extracted from the spleen samples of 35 mice and shrews. The 16S rDNA V3-V4 regions of the DNA extracts were amplified by PCR and subjected to the 16S rDNA-targeted metagenomic sequencing on an Illumina MiSeq platform. All the 35 spleen samples obtained data with sufficient coverage (99.7–99.9%) for analysis. More than 1,300,000 sequences were obtained after quality control and classified into a total of 1,967 operational taxonomic units (OTUs) clustered at 97% similarity. The two most abundant bacterial phyla were Firmicutes and Proteobacteria according to the analysis of rarefied sequences. Among the bacterial communities detected in this study, Anaplasma, Rickettsia and Coxiella were adjacently clustered by hierarchical analysis. Significant differences in many bacterial features between Anaplasma-positive and Anaplasma-negative samples were identified by LEfSe analysis and Wilcoxon rank-sum test, suggesting that the Anaplasma-infection of small wild mammals was associated with a specific pattern of spleen microbiota. Conclusions/Significance Our study has comprehensively characterized the complex bacterial profiles in the spleens of wild mice and shrews from Chongming Island, Shanghai city. This work has revealed distinct spleen bacterial communities associated with tick-borne bacteria in wild animals. The detection of tick-borne bacteria highlights the risk of contracting pathogens with public health importance upon tick-exposure in the studied areas., Author summary In this study, the 16S rDNA-targeted metagenomic sequencing was used to determine the bacterial community and diversity in the spleens of small wild mammals from China. The 16S rDNAs were amplified from the spleen genomic DNAs of 35 small wild mice and shrews and sequenced by Illumina MiSeq technology. More than 1,300,000 sequences were obtained after quality control and classified into a total of 1,967 operational taxonomic units (OTUs) clustered at 97% similarity. The two most abundant bacterial phyla were Firmicutes and Proteobacteria according to the analysis of rarefied sequences. Within the bacterial communities detected in this study, vector-borne bacteria, Anaplasma, Rickettsia and Coxiella, were adjacently clustered by hierarchical analysis. Significant differences in many bacterial features between Anaplasma-positive and Anaplasma-negative samples were observed, suggesting that the infection of small wild mammals with Anaplasma is associated with a distinct pattern of spleen microbiota. This study has revealed the complex bacterial profiles in the spleens of wild mice and shrews. The detection of vector-borne bacteria highlights the role of wild mice and shrews as animal reservoirs with potential public health importance in the studied areas.

In a rare phenomenon, shrews and a few other species cope with seasonal environments by reducing and regrowing brain size, potentially at the cost of changes in cognitive abilities. Here, we confirm an extensive seasonal shrinkage (21.4%) and regrowth (17.0%) of brain mass in winter and spring, respectively, in the common shrew (

This work describes the whole-mount immunohistochemistry staining method in detail, using neurofilament protein antibody to label the innervation of the biliary tract in Suncus murinus (S. murinus ). First, the specimen was dissected from S. murinus and fixed in 4% paraformaldehyde (PFA). Second, an enzymatic treatment and potential endogenous peroxidase inactivation were performed. The specimen was then exposed to the primary antibody, anti-neurofilament protein antibody, for 3-6 days. It was then incubated with the secondary antibody conjugated with horseradish peroxidase. The color reaction was revealed by reacting the specimen with a 3,3'-diaminobenzidine (DAB) substrate. This method can be applied to analyze the innervation of all visceral organs. Furthermore, this protocol can also be adapted to test other neuronal antibodies, but optimization of the antibodies should be done first. This method was originally introduced by Kuratani and Tanaka123.