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RNA interference (RNAi) mediated by the small interfering RNA (siRNA) pathway is a major antiviral mechanism in insects. This pathway is triggered when double-stranded RNA (dsRNA) produced during virus replication is recognized by Dicer-2, leading to the formation of virus-derived siRNA duplexes. These siRNAs are loaded onto the programmable nuclease Argonaute-2 (AGO2), with one strand serving as a guide to target and cleave fully complementary sequences of viral RNAs. While siRNAs are generated from viral dsRNA, the specific viral RNA species targeted for silencing during RNA virus replication remains unclear. In this study, we characterized the primary viral RNA targets of the Drosophila siRNA pathway during infections caused by negative and positive RNA viruses, namely Vesicular stomatitis virus (VSV) and Sindbis virus (SINV). Our findings reveal that polyadenylated transcripts of VSV and SINV are the major targets of silencing by the siRNA pathway during infection, likely when they are poised for translation. Consistent with earlier findings, we show that AGO2 is associated with ribosomes in control and virus infected cells. Therefore, we propose that the inhibition of the replication of RNA viruses in Drosophila results from the silencing of incoming viral transcripts, facilitated by the association of AGO2 with ribosomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Silva 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.)

Knowledge about seafloor depth, or bathymetry, is crucial for various marine activities, including scientific research, offshore industry, safety of navigation, and ocean exploration. Mapping the central Arctic Ocean is challenging due to the presence of perennial sea ice, which limits data collection to icebreakers, submarines, and drifting ice stations. The International Bathymetric Chart of the Arctic Ocean (IBCAO) was initiated in 1997 with the goal of updating the Arctic Ocean bathymetric portrayal. The project team has since released four versions, each improving resolution and accuracy. Here, we present IBCAO Version 5.0, which offers a resolution four times as high as Version 4.0, with 100 × 100 m grid cells compared to 200 × 200 m. Over 25% of the Arctic Ocean is now mapped with individual depth soundings, based on a criterion that considers water depth. Version 5.0 also represents significant advancements in data compilation and computing techniques. Despite these improvements, challenges such as sea-ice cover and political dynamics still hinder comprehensive mapping., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The MICA gene encodes a glycoprotein upregulated upon cellular stress, particularly in oxidative stress, intracellular infections, and tumorigenesis. This stress-signaling molecule interacts with the activating receptor NKG2D from Natural Killer (NK) and some T lymphocytes, stimulating their cytotoxic activity. MICA is encoded within the human Major Histocompatibility Complex next to the HLA-B locus and is highly polymorphic. MICA might be absent from chromosome 6 due to a large deletion of approximately 100 Kb between HLA-B and MICB. Therefore, some individuals may not produce any isoform of MICA. The distribution of this phenotype may vary among different populations. We evaluated the distribution of the MICA*del and other MICA null alleles in different biogeographic regions and the Linkage Disequilibrium (LD) pattern between this allele and HLA-B. We detected at least two different patterns of deletion, one with full deletion of MICA and surrounding sequences and one partial MICA deletion. The presence of different patterns of deletion suggests independent deletion events. We confirm that the previously described MICA*del allele is mainly associated with B*48 and MICB*009N in Asia and America, but other haplotypes also occur. While most samples with complete or partial MICA deletion are heterozygous and present one functional copy of both MICA and MICB genes, we detected two samples with no functional MICA and one with no functional MIC genes. Therefore, other mechanisms might be in place to compensate for the absence of MIC molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18-≤32 years; n = 70) or disease duration (0.13-≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores., Results: Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18-≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13-≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400., Conclusions: In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400., (© 2024. The Author(s).)

Objective: The present study aimed to evaluate the association between muscle mass variation, estimated by different equations, during hospitalization with the energy and protein intake and clinical and nutrition outcomes of patients using nutrition support., Methods: A prospective observational study with patients older than 18 years in use of enteral and/or parenteral nutrition therapy and monitored by the Nutritional Therapy Committee between December 14, 2021, and December 14, 2022. Data were collected from the electronic records and were applied in 11 equations to estimate the four different portions of muscle mass of patients receiving nutrition support at the beginning and the end of hospitalization., Results: A total of 261 patients were evaluated, with a median age of 61.0 (49.0-69.75) years, and 106 were women (40.6%). According to the nutrition diagnosis, several participants had severe malnutrition (39.5%). The most muscle mass estimation equations indicated a reduction of muscle mass during hospitalization. All patients presented negative energy and protein balances during hospitalization, but greater protein intake increased the lean soft tissue. Also, the greater the number of infections, metabolic complications, and scheduled diet interruption, the greater was the chance of losing muscle mass., Conclusion: There can be an association between the variation in muscle mass and energy and protein intake during hospitalization of patients using nutrition support. In addition, variation in muscle mass was associated with complications from nutrition support. The results emphasize the importance of anthropometric measurements to estimate muscle mass when other methods are not available., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects., Results: Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference., Conclusions: Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors., (© 2024. The Author(s).)

Context: Reduced muscle mass is linked to poor outcomes in both inpatients and outpatients, highlighting the importance of muscle mass assessment in clinical practice. However, laboratory methods to assess muscle mass are not yet feasible for routine use in clinical practice because of limited availability and high costs., Objective: This work aims to review the literature on muscle mass prediction by anthropometric equations in adults or older people., Data Sources: The following databases were searched for observational studies published until June 2022: MEDLINE, Embase, Scopus, SPORTDiscus, and Web of Science., Data Extraction: Of 6437 articles initially identified, 63 met the inclusion criteria for this review. Four independent reviewers, working in pairs, selected and extracted data from those articles., Data Analysis: Two studies reported new equations for prediction of skeletal muscle mass: 10 equations for free-fat mass and lean soft tissue, 22 for appendicular lean mass, 7 for upper-body muscle mass, and 7 for lower-body muscle mass. Twenty-one studies validated previously proposed equations. This systematic review shows there are numerous equations in the literature for muscle mass prediction, and most are validated for healthy adults. However, many equations were not always accurate and validated in all groups, especially people with obesity, undernourished people, and older people. Moreover, in some studies, it was unclear if fat-free mass or lean soft tissue had been assessed because of an imprecise description of muscle mass terminology., Conclusion: This systematic review identified several feasible, practical, and low-cost equations for muscle mass prediction, some of which have excellent accuracy in healthy adults, older people, women, and athletes. Malnourished individuals and people with obesity were understudied in the literature, as were older people, for whom there are only equations for appendicular lean mass., Systematic Review Registration: PROSPERO registration number CRD42021257200., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T. cruzi. Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major, for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T. cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L. major IPCS. However, disruption of the T. cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T. cruzi IPCS null mutants are unable to establish an infection in vivo, even in immune deficient mice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dos Santos 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.)

Background: Electronic cigarette (e-cigarette) vapour is gaining popularity as an alternative to tobacco smoking and can induce acute lung injury. However, the specific role of nicotine in e-cigarette vapour and its long-term effects on the airways, lung parenchyma and vasculature remain unclear., Results: In vitro exposure to nicotine-containing e-cigarette vapour extract (ECVE) or to nicotine-free e-cigarette vapour extract (NF ECVE) induced changes in gene expression of epithelial cells and pulmonary arterial smooth muscle cells (PASMCs), but ECVE in particular caused functional alterations ( e.g. a decrease in human and mouse PASMC proliferation by 29.3±5.3% and 44.3±8.4%, respectively). Additionally, acute inhalation of nicotine-containing e-cigarette vapour (ECV) but not nicotine-free e-cigarette vapour (NF ECV) increased pulmonary endothelial permeability in isolated lungs. Long-term in vivo exposure of mice to ECV for 8 months significantly increased the number of inflammatory cells, in particular lymphocytes, compared to control and NF ECV in the bronchoalveolar fluid (BALF) (ECV: 853.4±150.8 cells·mL -1 ; control: 37.0±21.1 cells·mL -1 ; NF ECV: 198.6±94.9 cells·mL -1 ) and in lung tissue (ECV: 25.7±3.3 cells·mm -3 ; control: 4.8±1.1 cells·mm -3 ; NF ECV: 14.1±2.2 cells·mm -3 ). BALF cytokines were predominantly increased by ECV. Moreover, ECV caused significant changes in lung structure and function ( e.g. increase in airspace by 17.5±1.4% compared to control), similar to mild tobacco smoke-induced alterations, which also could be detected in the NF ECV group, albeit to a lesser degree. In contrast, the pulmonary vasculature was not significantly affected by ECV or NF ECV., Conclusions: NF ECV components induce cell type-specific effects and mild pulmonary alterations, while inclusion of nicotine induces significant endothelial damage, inflammation and parenchymal alterations., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan ( 18 F-APN-1607) revealed low-to-moderate uptake in the substantia nigra, globus pallidus, thalamus and posterior cortical areas, including temporal, parietal and occipital cortices. Neuropathological evaluation revealed widespread neuronal and glial tau pathology in cortical and subcortical structures, including tufted astrocytes in the motor cortex, striatum and midbrain tegmentum. The subthalamic nucleus had mild-to-moderate neuronal loss with globose neurofibrillary tangles, consistent with PSP. On the other hand, there were also astrocytic plaques, a pathological hallmark of CBD, in the neocortex and striatum. To further characterize the mixed pathology, we applied two machine learning-based diagnostic pipelines. These models suggested diagnoses of PSP and CBD depending on the brain region - PSP in the motor cortex and superior frontal gyrus and CBD in caudate nucleus. Western blots of insoluble tau from motor cortex showed a banding pattern consistent with mixed features of PSP and CBD, whereas tau from the superior frontal gyrus showed a pattern consistent with CBD. Real-time quaking-induced conversion (RT-QuIC) using brain homogenates from the motor cortex and superior frontal gyrus showed ThT maxima consistent with PSP, while reaction kinetics were consistent with CBD. There were no pathogenic variants in MAPT with whole genome sequencing. We conclude that this patient had an unclassified tauopathy and features of both PSP and CBD. The different pathologies in specific brain regions suggests caution in diagnosis of tauopathies with limited sampling., (© 2023. The Author(s).)

Background: During the COVID-19 pandemic in 2020, concerns were raised about the potential impact of pandemic-related social distancing measures on existing health disparities among sexual and gender minority (SGM) young adults, including HIV transmission risk and intimate partner violence (IPV). Another concern was the potential for increased methamphetamine use during the pandemic, which is a known risk factor for HIV transmission and IPV., Methods: The present analysis examines the impact of COVID-19 social distancing (social distancing and quarantining) and methamphetamine use on HIV risk and IPV in a combined dataset from 3 cohort studies of SGM young adults (two in Los Angeles and one in Chicago) from May 2020 to April 2021 (n = 1142). Bivariate analyses and multivariable logistic regressions were estimated., Results: The median age was 26. All participants were assigned male at birth and most participants were men (93.8%). The largest racial groups were Hispanic/Latinx (44.6%) and Black (29.0%). In adjusted models methamphetamine use was consistently associated with having a new sex partner, higher numbers of sex partners, and experience of IPV, during the pandemic. Reporting no social distancing and reporting one social distancing behavior, were associated with experience of IPV relative to reporting 2 social distancing behaviors. Social distancing was not associated with sexual risk behavior or Pre-exposure Prophylaxis use., Conclusions: SGM young adults live at the intersection of multiple vulnerabilities during the COVID-19 pandemic. Addiction services, HIV prevention services, and violence support services should be prepared to support young adult SGM needs, particularly those who use methamphetamine., (Copyright © 2022 Elsevier B.V. All rights reserved.)