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COVID-19, an infectious disease caused by SARS-CoV-2, was declared a pandemic by the WHO in 2020. Psychiatric symptoms including sleep disturbance, memory impairment, and depression are associated with SARS-CoV-2 infection. These symptoms are causes long-term mental and physical distress in recovering patients; however, the underlying mechanism is unclear. In this study, we determined the effects of SARS-CoV-2 infection on brain tissue using k18hACE2 mice. Using brain tissue from 18hACE2 mice infected with SARS-CoV-2 through intranasal administration, SARS-CoV-2 spike protein and RNA were analyzed by immunohistochemical staining and in-situ hybridization. Immunohistochemical analysis revealed that Tryptophan hydroxylase 2 (TPH2)-positive cells and SARS-CoV-2 spike protein were co-localized in the ventral tegmental area of SARS-CoV-2-infected mice. We observed decreased TPH2 expression and increased accumulation of phosphorylated tau protein and Phospho-Histone H2A.X (γH2AX) expression in the ventral tegmental region. In addition, activation of glycogen synthase kinase 3β (GSK3β) was induced by SARS-CoV-2 infection. Overall, our results suggest that SARS-CoV-2 infection of TPH2-positive cells in the ventral tegmental area induces neuronal cell death through increased accumulation of phosphorylated tau. Attenuation of the GSK3β pathway and decreased serotonin synthesis through suppression of TPH2 expression may contribute to the development of neurological symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Imai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A macrourid, Coryphaenoides yaquinae sp. inc., was observed to be attracted to bait and exhibiting normal foraging behaviour during a period of 80 min within view of a baited video camera on the sea floor at 7259 m - the deepest ever observation of a fish species with a swim bladder. The buoyancy provided by an oxygen-filled swim bladder at 74.4 MPa pressure was estimated to be 0.164 N, at a theoretical energy cost of 20 kJ, 200 times less than the cost of equivalent lipid buoyancy. During normal metabolism, 192 days would be required to fill the swimbladder. At these depths, oxygen is very incompressible, so changes in volume during ascent or descent are small. However, swimbladder function is crucially dependent on a very low rate of diffusion of oxygen across the swimbladder wall. The oxygen in the swimbladder could theoretically sustain aerobic metabolism for over 1 year but is unlikely to be used as a reserve., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are reported to prevent cardiovascular events by a mechanism possibly including diuresis and sodium excretion. In this respect, diuresis-induced compensatory upregulation of the renin-angiotensin-aldosterone (RAA) system should be clarified and we performed a randomized controlled trial using dapagliflozin, an SGLT2I. Hypertensive diabetic patients taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were randomly assigned to a dapagliflozin group (DAPA) or a control group (CTRL) with the difference in the changes in plasma renin activity (PRA) after 24 weeks of the treatment as the primary outcome. PRA, plasma aldosterone concentration (PAC), age, sex, BMI, blood pressure, pulse rate, eGFRcys, and HbA1c were not different between the groups at baseline. After 24 weeks, the changes in the PRA from the baseline of the DAPA (n = 44) and CTRL (n = 39) groups were 6.30 ± 15.55 and 1.42 ± 11.43 ng/mL/h, respectively (p = 0.11) although the power of detection was too small. However, post hoc nonparametric analyses revealed that there was a definite increase in the PRA and PAC in the DAPA group (p < 0.0001 and p = 0.00025, respectively) but not in the CTRL group. The PRA in the DAPA group after 24 weeks treatment was significantly elevated compared to the CTRL group (p = 0.013) but not for the PAC. Accordingly, it would be suggested that dapagliflozin may not induce a profound increase, if any, in PAC after 24 weeks of treatment in hypertensive type 2 diabetic patients under RAA suppression.

Here we investigated the diversity of bacterial communities from deep-sea surface sediments under influence of asphalt seeps at the Sao Paulo Plateau using next-generation sequencing method. Sampling was performed at North São Paulo Plateau using the human occupied vehicle Shinkai 6500 and her support vessel Yokosuka. The microbial diversity was studied at two surficial sediment layers (0-1 and 1-4 cm) of five samples collected in cores in water depths ranging from 2456 to 2728 m. Bacterial communities were studied through sequencing of 16S rRNA gene on the Ion Torrent platform and clustered in operational taxonomic units. We observed high diversity of bacterial sediment communities as previously described by other studies. When we considered community composition, the most abundant classes were Alphaproteobacteria (27.7%), Acidimicrobiia (20%), Gammaproteobacteria (11.3%) and Deltaproteobacteria (6.6%). Most abundant OTUs at family level were from two uncultured bacteria from Actinomarinales (5.95%) and Kiloniellaceae (3.17%). The unexpected high abundance of Alphaproteobacteria and Acidimicrobiia in our deep-sea microbial communities may be related to the presence of asphalt seep at North São Paulo Plateau, since these bacterial classes contain bacteria that possess the capability of metabolizing hydrocarbon compounds.

The planktonic foraminifera genus Globigerinoides provides a prime example of a species-rich genus in which genetic and morphological divergence are uncorrelated. To shed light on the evolutionary processes that lead to the present-day diversity of Globigerinoides, we investigated the genetic, ecological and morphological divergence of its constituent species. We assembled a global collection of single-cell barcode sequences and show that the genus consists of eight distinct genetic types organized in five extant morphospecies. Based on morphological evidence, we reassign the species Globoturborotalita tenella to Globigerinoides and amend Globigerinoides ruber by formally proposing two new subspecies, G. ruber albus n.subsp. and G. ruber ruber in order to express their subspecies level distinction and to replace the informal G. ruber "white" and G. ruber "pink", respectively. The genetic types within G. ruber and Globigerinoides elongatus show a combination of endemism and coexistence, with little evidence for ecological differentiation. CT-scanning and ontogeny analysis reveal that the diagnostic differences in adult morphologies could be explained by alterations of the ontogenetic trajectories towards final (reproductive) size. This indicates that heterochrony may have caused the observed decoupling between genetic and morphological diversification within the genus. We find little evidence for environmental forcing of either the genetic or the morphological diversification, which allude to biotic interactions such as symbiosis, as the driver of speciation in Globigerinoides., Competing Interests: The authors have declared that no competing interests exist.

The present study addresses the microbiome of the first whale fall (YOKO 16) that has been described in the deep sea in the southern Atlantic Ocean (São Paulo Plateau; 4204 m depth), in terms of its metabolic uniqueness. Sets of ten thousand protein sequences from YOKO 16 and 29 public domain metagenomes (SRA and GenBank databases) that represent various marine, terrestrial and gut-associated microbial communities were analyzed. The determination of protein functionality, based on the KAAS server, indicated that the YOKO 16 microbiome has industrially-relevant proteins, such as proteases and lipases, that have low similarity (~50%) with previously-described enzymes. The amino acid usage in the YOKO 16 protein sequences (based on blastp and Clustal analysis) revealed a pattern of preference similar to that of extremophiles, with an increased usage of polar, charged and acidic amino acids and a decreased usage of nonpolar residues. We concluded that the targeted microbiome is of potential biotechnological use, which justifies the allocation of resources for the discovery of enzymes in deep-sea whale fall communities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An unfamiliar gastropod was collected from a deep-sea whale carcass at the base of the São Paulo Ridge in the Southwest Atlantic by the manned research submersible Shinkai 6500, and is here described as a new species of the abyssochrysoidean genus Rubyspira, R. brasiliensis sp. nov., following morphological and molecular phylogenetic examinations. There are only two other known species in the genus, which occur together in the Monterey Submarine Canyon off California. The present new species was shown by the molecular analysis to be closer to one of the Californian species than the other. It was found aggregated on and around a whale carcass at a depth of 4204 m, which represents the deepest record of whale- fall ecosystems ever discovered.

Hadal environments sustain diverse microorganisms. A few studies have investigated hadal microbial communities consisting of free-living or particle-associated bacteria and archaea. However, animal-associated microbial communities in hadal environments remain largely unexplored, and comparative analyses of animal gut microbiota between two isolated hadal environments have never been done so far. In the present study, 228 Gb of gut metagenomes of the giant amphipod Hirondellea gigas from two hadal trenches, the Mariana Trench and Japan Trench, were sequenced and analyzed. Taxonomic analysis identified 49 microbial genera commonly shared by the gut microbiota of the two H. gigas populations. However, the results of statistical analysis, in congruency with the alpha and beta diversity analyses, revealed significant differences in gut microbial composition across the two trenches. Abundance variation of Psychromonas , Propionibacterium , and Pseudoalteromonas species was observed. Microbial cooccurrence was demonstrated for microbes that were overrepresented in the Mariana trench. Comparison of functional potential showed that the percentage of carbohydrate metabolic genes among the total microbial genes was significantly higher in the guts of H. gigas specimens from the Mariana Trench. Integrating carbon input information and geological characters of the two hadal trenches, we propose that the differences in the community structure might be due to several selective factors, such as environmental variations and microbial interactions. IMPORTANCE The taxonomic composition and functional potential of animal gut microbiota in deep-sea environments remain largely unknown. Here, by performing comparative metagenomics, we suggest that the gut microbial compositions of two Hirondellea gigas populations from the Mariana Trench and the Japan Trench have undergone significant divergence. Through analyses of functional potentials and microbe-microbe correlations, our findings shed light on the contributions of animal gut microbiota to host adaptation to hadal environments., (Copyright © 2018 American Society for Microbiology.)

Background: The hadal zone encompasses the deepest parts of the world's ocean trenches from depths of ∼6,000-11,000 m. The communities observed at these depths are dominated by scavenging amphipods that rapidly intercept and consume carrion as it falls to the deepest parts of the trenches. New samples collected in the Tonga Trench provide an opportunity to compare the amphipod assemblages and the population structure of a dominant species, Hirondellea dubia Dahl, 1959, between trenches and with earlier data presented for the Tonga Trench, and other trenches in the South Pacific., Methods: Over 3,600 individual scavenging amphipods across 10 species were collected in seven baited traps at two sites; in the Horizon Deep site, the deepest part of the Tonga Trench (10,800 m) and a site directly up-slope at the trench edge (6,250 m). The composition of the bait-attending amphipods is described and a morphometric analysis of H. dubia examines the bathymetric distribution of the different life stages encountered., Results: The amphipod assemblage was more diverse than previously reported, seven species were recorded for the first time from the Tonga Trench. The species diversity was highest at the shallower depth, with H. dubia the only species captured at the deepest site. At the same time, the abundance of amphipods collected at 10,800 m was around sevenfold higher than at the shallower site. H. dubia showed clear ontogenetic vertical structuring, with juveniles dominant at the shallow site and adults dominant at the deep site. The amphipods of the deeper site were always larger at comparable life stage., Discussion: The numbers of species encountered in the Tonga Trench is less than reported from the New Hebrides and Kermadec trenches, and six species encountered are shared across trenches. These findings support the previous suggestion that the fauna of the New Hebrides, Tonga and Kermadec Trenches may represent a single biogeographic province. The ontogenetic shift in H. dubia between the two Tonga Trench sites supports the hypothesis of interspecific competition at the shallower bathymetric range of the species, and the presence of competitive physiological advantages that allow the adults at the trench axis to exploit the more labile organic material that reaches the bottom of the trench., Competing Interests: Kareen E. Schnabel and Rachael A. Peart are employed by National Institute of Water & Atmospheric Research Ltd., Ken G. Ryan is employed by the Victoria University of Wellington (VUW), Ashley A. Rowden is employed by both the above. Hiroshi Kitazato is employed by the Japan Agency for Marine-Earth Science and Technology (JAMSTEC). James P.A. Wilson was a student at the VUW and is currently employed at the New Zealand Ministry for Business, Innovation & Employment. The authors declare that they have no competing interests.

Introduction: It is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i., Methods: Sixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics., Results: HbA1c was significantly lower at week 24 (- 1.0 ± 0.9% in the IGlar group and - 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (- 2.9 ± 3.2% vs. - 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. - 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups., Conclusion: For poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial., Trial Registration: Trial Registry (UMIN-CTR) as UMIN000012224.

Hirondellea species are common inhabitants in the hadal region deeper than 7,000 m. We found that Hirondellea gigas thrived in the Challenger Deep possessed polysaccharide hydrolases as digestive enzymes. To obtain various enzymes of other H. gigas, we captured amphipods from the Japan Trench, and Izu-Ogasawara (Bonin) Trench. A phylogenetic analysis based on the cytochrome oxidase I gene showed close relationships among amphipods, despite the geographic distance between the localities. However, several differences in enzymatic properties were observed in these H. gigas specimens. We also carried out RNA sequencing of H. gigas from the Izu-Ogasawara Trench. The cellulase gene of H. gigas was highly homologous to cellobiohydrolase of Glucosyl Hydrolase family 7 (GH7). On the other hand, enzymatic properties of H. gigas's cellulase were different from those of typical GH7 cellobiohydrolase. Thus, these results indicate that hadal-zone amphipod can be good candidates as the new enzyme resource.

Diverse biological communities mediate the transformation, transport, and storage of elements fundamental to life on Earth, including carbon, nitrogen, and oxygen. However, global biogeochemical model outcomes can vary by orders of magnitude, compromising capacity to project realistic ecosystem responses to planetary changes, including ocean productivity and climate. Here, we compare global carbon turnover rates estimated using models grounded in biological versus geochemical theory and argue that the turnover estimates based on each perspective yield divergent outcomes. Importantly, empirical studies that include sedimentary biological activity vary less than those that ignore it. Improving the relevance of model projections and reducing uncertainty associated with the anticipated consequences of global change requires reconciliation of these perspectives, enabling better societal decisions on mitigation and adaptation., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO 2 levels. We furthermore show that a V-type H + ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO 2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO 2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production., Competing Interests: The authors declare no competing financial interests.

Whale carcasses create remarkable habitats in the deep-sea by producing concentrated sources of organic matter for a food-deprived biota as well as places of evolutionary novelty and biodiversity. Although many of the faunal patterns on whale falls have already been described, the biogeography of these communities is still poorly known especially from basins other than the NE Pacific Ocean. The present work describes the community composition of the deepest natural whale carcass described to date found at 4204 m depth on Southwest Atlantic Ocean with manned submersible Shinkai 6500. This is the first record of a natural whale fall in the deep Atlantic Ocean. The skeleton belonged to an Antarctic Minke whale composed of only nine caudal vertebrae, whose degradation state suggests it was on the bottom for 5-10 years. The fauna consisted mainly of galatheid crabs, a new species of the snail Rubyspira and polychaete worms, including a new Osedax species. Most of the 41 species found in the carcass are new to science, with several genera shared with NE Pacific whale falls and vent and seep ecosystems. This similarity suggests the whale-fall fauna is widespread and has dispersed in a stepping stone fashion, deeply influencing its evolutionary history.

The benthic foraminifer Virgulinella fragilis Grindell and Collen 1976 has multiple putative symbioses with both bacterial and kleptoplast endobionts, possibly aiding its survival in environments from dysoxia (5-45 μmol-O2 /L) to microxia (0-5 μmol-O2 /L) and in the dark. To clarify the origin and function of V. fragilis endobionts, we used genetic analyses and transmission electron microscope observations. Virgulinella fragilis retained δ-proteobacteria concentrated at its cell periphery just beneath the cell membranes. Unlike another foraminifer Stainforthia spp., which retains many bacterial species, V. fragilis has a less variable bacterial community. This suggests that V. fragilis maintains a specific intracellular bacterial flora. Unlike the endobiotic bacteria, V. fragilis klepto-plasts originated from various diatom species and are found in the interior cytoplasm. We found evidence of both retention and digestion of kleptoplasts, and of fragmentation of the kleptoplastid outer membrane that likely facilitates transport of kleptoplastid products to the host. Accumulations of mitochondria were observed encircling endobiotic bacteria. It is likely that the bacteria use host organic material for carbon oxidation. The mitochondria may use oxygen available around the δ-proteobacteria and synthesize adenosine triphosphate, perhaps for sulfide oxidation., (© 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.)