Mucilage extracted from Chilean papaya seeds is enriched with homogalacturonan domains.

Chilean papaya, also known as mountain papaya (Vasconcellea pubescens), is a fruit valued for its nutritional value and pleasant fragrance. The oblong fruit, featuring five ridges and a seed-filled mucilage cavity, is typically consumed cooked due to its high protease content. The mucilage and the seeds are usually discarded as byproducts. This study analyzed the biochemical composition of mountain papaya seed mucilage using methods such as HPAEC and immunolabeling. Results revealed that papaya seeds yield nearly 20% of their weight in mucilage polysaccharides, which can be separated into soluble and adherent layers. The mucilage exhibited a high proportion of acidic sugars, indicating that homogalacturonan (HG) is the predominant domain. It also contained other domains like rhamnogalacturonan-I (RG-I) and hemicelluloses, predominantly xyloglucan. The HG-rich mucilage, currently considered waste, emerges as a promising source of polysaccharides, indicating its multifaceted utility in various industrial applications.

Platelets favor the outgrowth of established metastases.

Despite abundant evidence demonstrating that platelets foster metastasis, anti-platelet agents have low therapeutic potential due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subject syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases via immune suppression. Genetic depletion and pharmacological targeting of the glycoprotein VI (GPVI) platelet-specific receptor in humanized mouse models efficiently reduce the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study demonstrates therapeutic efficacy when targeting animals bearing growing metastases. It further identifies GPVI as a molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.

30-sit-to-stand power is a better tool than isometric knee extensor strength to detect motor impairment in people with haemophilic arthropathy.

INTRODUCTION: Regular assessment of motor impairments is crucial in people with haemophilic arthropathy (PwHA). This study aimed to determine if there are differences in 30-seconds sit-to-stand (30-STS) power and maximal voluntary isometric contraction (MVIC) of the knee extensors between PwHA and healthy control group (CG). The secondary aims were to investigate the correlation between 30-STS power and MVIC of knee extensors with clinical characteristics and to assess their effectiveness in identifying motor impairment in PwHA. METHODS: A cross-sectional study was conducted by collecting data from PwHA (n = 17) and a sedentary CG (n = 15). MVIC (torque) and 30-STS power were normalised to body mass. Correlation analysis and simple linear regression adjusted for age were used to assess the association between tests and clinical variables. Using z-scores derived from the mean and standard deviation of the CG, we compared the MVIC and the 30-STS power in PwHA. RESULTS: PwHA showed lower MVIC and 30-STS power compared to CG (p < .001; large effect size d > .8). Lower 30-STS power was associated with greater joint impairment and greater fear of movement, whereas MVIC showed no association with clinical variables. 30-STS power showed a lower z-score compared to MVIC (p < .001). In addition, 30-STS power detected 47% of PwHA with motor impairment compared to 0% for MVIC (p = .002). CONCLUSIONS: Our results suggest that 30-STS power may be more effective than knee extensors MVIC in detecting motor impairment in PwHA. Consequently, lower limb skeletal muscle power, rather than maximum knee extensor strength, appears to be more affected in PwHA.

LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review.

The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes of morbidity and mortality worldwide. According to current knowledge, the heart-brain axis is more than a theoretical concept, with many common pathophysiological mechanisms involved in the onset and evolution of both coronary and cerebral ischemia. Moreover, the focus is on the prevention and early intervention of risk factors in searching for targeted and personalized medical treatment. In this context, this narrative review aims to offer, in a didactic and practice-oriented manner, an up-to-date overview of the role played by lipid-derived biomarkers (from low-density lipoprotein cholesterol to oxylipin and apolipoproteins) in chronic coronary syndrome and ischemic stroke. Firstly, the authors highlight, via relevant epidemiological data, the significant burden of chronic coronary syndrome and ischemic stroke in the general population, thus explaining the need for updated information on this topic. Subsequently, the most important lipid-derived biomarkers and their multiple roles in the pathogenesis of these two disorders are listed. Currently available and experimental targeted therapies based on these lipid-derived biomarkers are presented in the final part of this paper, representing this manuscript's original and novel input.

Development of SCAR Markers for Genetic Authentication of Metarhizium acridum.

In this study, molecular typing using Randomly Amplified Polymorphic DNA (RAPD-PCR) was conducted on 16 original isolates of Metarhizium acridum obtained from locusts (Schistocerca piceifrons ssp. piceifrons.) in Mexico (MX). The analysis included reference strains of the genus Metarhizium sourced from various geographical regions. The isolates were identified by phenotypic (macro and micromorphology) and genotypic methods (RAPD-PCR and Amplified Fragment Length Polymorphisms (AFLP), through a multidimensional analysis of principal coordinates (PCoA) and a minimum spanning network (MST). Subsequently, Sequences-Characterized Amplified Region (SCAR) markers were developed for the molecular detection of M. acridum, these markers were chosen from polymorphic patterns obtained with 14 primers via RAPD-PCR. Phenotypic and genotypic characterization identified the MX isolates as M. acridum. Of all the polymorphic patterns obtained, only OPA04 and OPA05 were chosen, which presented species-specific bands for M. acridum, and further utilized to create SCAR markers through cloning and sequencing of the specific bands. The specificity of these two markers was confirmed via Southern hybridization. The SCAR markers (Ma-160OPA-05 and Ma-151OPA-04) exhibit remarkable sensitivity, detecting down to less than 0.1 ng, as well as high specificity, as evidenced by their inability to cross-amplify or generate amplification with DNAs from other strains of Metarhizium (as Metarhizium anisopliae) or different genera of entomopathogenic fungi (Cordyceps fumosorosea and Akanthomyces lecanii). These SCAR markers yield readily detectable results, showcasing high reproducibility. They serve as a valuable tool, especially in field applications.

Evaluation of a new CT/NG/TV/MG Real-Time PCR Kit (Vircell) versus the Allplex STI Essential Assay (Seegene) for the diagnosis of sexually transmitted infections.

Sexually transmitted infections (STI) are a public health problem. Real-time PCR assays are the most sensitive test for screening and diagnosis of these infections. The aim of this study was to evaluate a new CT/NG/TV/MG Real-Time PCR (RT-PCR) kit (Vircell) for the detection of Chamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis for the diagnosis of sexual transmitted infections using the Allplex STI Essential Assay (Seegene) as the reference's method. A total of 497 samples from different anatomical sites (endocervical, urethral, rectal, pharyngeal and urine) were analysed from October 2022 to February 2023. A total of 108 (21.73 %) and 106 (21.33 %) positive samples were found for any of the assays used. The most commonly detected pathogen was N. gonorrhoeae (52 samples; 10.46 %), and the least commonly detected was T. vaginalis (three samples; 0.60 %). The anatomical site with the highest prevalence of micro-organisms was a non-urogenital site, the pharynx (26 positive samples; 5.23 %). Using the Allplex STI Essential Assay (Seegene) as the reference method, the diagnosis performance showed that the average specificity of CT/NG/TV/MG RT-PCR Kit (Vircell) was 99.84 % and the sensitivity was 99.53 %. The overall concordance was k=0.98 (CI95 %; 0.96-1). In conclusion, the CT/NG/TV/MG RT-PCR Kit (Vircell) assay shows a good sensitivity and specificity and constitutes a promising and additional alternative to routine procedures for distinct types of clinical specimen in diagnosis STI.

Effect of Ambrosia arborescens Mill. ethanolic extract on breast cancer induced in rats.

Background and Aims: Ambrosia arborescens Mill. (A. arborescens) is an aromatic plant used in traditional medicine as an anti-inflammatory, anti-tussive, anti-rheumatic, and anti-diarrheal agent. This study aimed to evaluate the effect of A. arborescens Mill. on a Rattus norvegicus var. albinus-induced breast cancer model. Materials and Methods: We collected A. arborescens from the province of Julcán, La Libertad Region, Per, and prepared an ethanolic extract using pulverized leaves macerated in 96° ethanol for 72 h with magnetic stirring. In the evaluation of anticancer activity, four experimental groups with 10 female rats each were formed: Group I (Control-7,12-dimethylbenz[a]anthracene [DMBA]), which received DMBA (single dose) and physiological saline solution for 4 months, and Groups II, III, and IV, which received DMBA (single dose) and 200, 400, and 600 mg/kg/day of the ethanolic extract of A. arborescens, respectively, for 4 months. Results: The DMBA control group presented histological characteristics of ductal carcinoma in situ with necrotic and inflammatory areas, whereas the A. arborescens extract group showed a decrease in tumor volume and recovery of the ductal duct. Conclusion: Ethanol extract of A. arborescens leaves decreases tumor development in rats with induced breast cancer, and this effect is dose-dependent.

Inflammatory blood cells and ratios at remission for psychosis relapse prediction: A three-year follow-up of a cohort of first episodes of schizophrenia.

BACKGROUND: The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored. METHODS: In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint. The participants were recruited from the multicenter 2EPS Project. Data on inflammatory blood cells and ratios were collected at baseline and at the time of relapse or after three years of follow-up. RESULTS: Monocyte counts (OR = 1.91; 95 % CI = 1.07-3.18; p = 0.009) and basophil counts (OR = 1.09; 95 % CI = 1.01-1.12; p = 0.005) at baseline were associated with an increased risk of relapse, while the platelet-lymphocyte ratio (OR = 0.98; 95 % CI = 0.97-0.99; p = 0.019) was identified as a protective factor. However, after adjusting for cannabis and tobacco use during the follow-up, only monocyte counts (OR = 1.73; 95 % CI = 1.03-2.29; p = 0.027) and basophil counts (OR = 1.08; 95 % CI = 1.01-1.14; p = 0.008) remained statistically significant. ROC curve analysis indicated that the optimal cut-off values for discriminating relapsers were 0.52 × 10^9/L (AUC: 0.66) for monocytes and 0.025 × 10^9/L (AUC: 0.75) for basophils. When considering baseline inflammatory levels, no significant differences were observed in the inflammatory biomarkers at the endpoint between relapsers and non-relapsers. CONCLUSION: This study provides evidence that higher monocyte and basophil counts measured at remission after a FES are associated with an increased risk of relapse during a three-year follow-up period.

Remarkable Phenotypic Virulence Factors of Microsporum canis and Their Associated Genes: A Systematic Review.

Microsporum canis is a widely distributed dermatophyte, which is among the main etiological agents of dermatophytosis in humans and domestic animals. This fungus invades, colonizes and nourishes itself on the keratinized tissues of the host through various virulence factors. This review will bring together the known information about the mechanisms, enzymes and their associated genes relevant to the pathogenesis processes of the fungus and will provide an overview of those virulence factors that should be better studied to establish effective methods of prevention and control of the disease. Public databases using the MeSH terms "Microsporum canis", "virulence factors" and each individual virulence factor were reviewed to enlist a series of articles, from where only original works in English and Spanish that included relevant information on the subject were selected. Out of the 147 articles obtained in the review, 46 were selected that reported virulence factors for M. canis in a period between 1988 and 2023. The rest of the articles were discarded because they did not contain information on the topic (67), some were written in different languages (3), and others were repeated in two or more databases (24) or were not original articles (7). The main virulence factors in M. canis are keratinases, fungilisins and subtilisins. However, less commonly reported are biofilms or dipeptidylpeptidases, among others, which have been little researched because they vary in expression or activity between strains and are not considered essential for the infection and survival of the fungus. Although it is known that they are truly involved in resistance, infection and metabolism, we recognize that their study could strengthen the knowledge of the pathogenesis of M. canis with the aim of achieving effective treatments, as well as the prevention and control of infection.

Psychometric properties of the Spanish version of the Health of Nation Outcome Scales for schizophrenia patients.

Accessible Summary What is known on the subject? Functioning is one of the most affected areas in schizophrenia. Social, occupational and personal domains are affected, and these deficits are responsible for a major part of the disability associated with the disorder. There are several instruments to measure functioning, but the HoNOS provides a wide assessment of impairment in 12 areas of functioning. What does the paper add to existing knowledge? The Spanish version of the HoNOS shows good properties in terms of reliability and validity for use in schizophrenia patients. Although some authors divide the scale according to proposed underlying dimensions, in schizophrenia this division may not be appropriate. What are the implications for practice? A reliable and easy-to-use measure of impairment in different areas of functioning is useful for optimizing the treatment and rehabilitation of patients with schizophrenia. ABSTRACT: INTRODUCTION: The HoNOS scale was designed for the assessment of psychosocial impairment in various domains. While it is widely used in psychiatric settings, it has not been validated in Spanish for use in patients with schizophrenia. AIM: To examine the psychometric properties of the Spanish version of the HoNOS scale in a sample of schizophrenia patients. METHOD: A total of 194 individuals aged 18 to 65 with schizophrenia spectrum diagnoses were evaluated using the HoNOS. Illness severity and level of functioning were also assessed. RESULTS: The HoNOS showed moderate internal consistency, good inter-observer reliability and good test-retest reliability. Factor analysis revealed an internal structure consisting of four factors, with item distribution differing from the theoretical dimensions proposed for the original scale. DISCUSSION: The Spanish version of the HoNOS scale is a reliable and valid instrument for assessing psychosocial impairment in individuals diagnosed with schizophrenia spectrum disorders. However, further research is needed to determine its internal structure more accurately. IMPLICATIONS FOR PRACTICE: The HoNOS scale provides researchers and clinicians with a valid measure of impairment in twelve different domains, which can facilitate and guide the treatment of schizophrenia patients.

Influence of Education, Cognition, and Physical Disability on Quality of Life of Romanian Patients with Multiple Sclerosis-A Cohort Study.

Background and Objectives: objective measures of disability and neurological impairmentare used to search for disease activity and monitor disease evolution in multiple sclerosis (MS). These are sometimes in disagreement with subjective quality-of-life measures. We aimed to establish the relations between the Multiple Sclerosis Quality of Life instrument (MSQOL-54) and objective measures of neurological impairment. Materials and Methods: 107 patients with MS were evaluated with the Single Digit Modalities Test (SDMT) for cognition, Nine Holes Peg Test (9HPT) for upper limb function, 25 Feet Walk Test (25FWT) for gait, and EDSS for global disability in a cohort study. Age and education level were recorded as sociodemographic factors. Results: the median EDSS was 3.5 (IQR 2.5); average SDMT score was 30.38 ± 13.54; and 9HPT speed was significantly higher for the dominant upper limb (0.3 ± 0.1 pegs/s versus 0.28 ± 0.11 pegs/s) (p = 0.016). The mental health composite score of the MSQOL-54 correlated with the SDMT, education level, and EDSS. Education level correlated with cognition and quality of life. The physical health composite score of the MSQOL-54 correlated with motor-function parameters and with SDMT. The motor-function parameters correlated well among themselves. A linear regression model found an important influence of SDMT and education level on the mental health composite score of the MSQOL-54. Although the linear regression model predicting the physical health composite score from physical disability parameters was statistically sound, none of the determinants had a significant individual influence. Conclusions: the subscores of the MSQOL-54 correlated well with the objective parameters. The strongest correlations were those with the cognitive function. Correlations with physical disability were less powerful, probably reflecting their indirect and more limited influence on quality of life compared to cognition and perception of disability.

Halobacterium hubeiense sp. nov., a haloarchaeal species isolated from a bore core drilled in Hubei Province, PR China.

Eight colonies of live microbes were isolated from an extensively surface-sterilized halite sample which had been retrieved from a depth of 2000 m from a salt mine in the Qianjiang Depression, Hubei Province, PR China. The eight colonies, obtained after 4 weeks of incubation, were named JI20-1T-JI20-8 and JI20-1T was selected as the type strain. The strains have been previously described, including a genomic analysis based on the complete genome for strain JI20-1T and draft genomes for the other strains. In that study, the name Halobacterium hubeiense was suggested, based on the location of the drilling site. Previous phylogenomic analysis showed that strain JI20-1T is most closely related to the Permian isolate Halobacterium noricense from Alpine rock salt. The orthologous average nucleotide identity (orthoANI) and digital DNA-DNA hybridization (dDDH) percentages between the eight strains are 100-99.6 % and 99.8-96.4 %, respectively. The orthoANI and dDDH values of these strains with respect to the type strains of species of the genus Halobacterium are 89.9-78.2 % and 37.3-21.6 %, respectively, supporting their placement in a novel extremely halophilic archaeal species. The phylogenomic tree based on the comparison of sequences of 632 core-orthologous proteins confirmed the novel species status for these haloarchaea. The polar lipid profile includes phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate, and sulfated galactosyl mannosyl galactosyl glucosyl diether, a profile compatible with that of Halobacterium noricense. Based on genomic, phenotypic, and chemotaxonomic characterization, we propose strain JI20-1T (=DSM 114402T = HAMBI 3616T) as the type strain of a novel species in the genus Halobacterium, with the name Halobacterium hubeiense sp. nov.

CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data.

Recent reports have suggested that the susceptibility of cells to SARS-CoV-2 infection can be influenced by various proteins that potentially act as receptors for the virus. To investigate this further, we conducted simulations of viral dynamics using different cellular systems (Vero E6, HeLa, HEK293, and CaLu3) in the presence and absence of drugs (anthelmintic, ARBs, anticoagulant, serine protease inhibitor, antimalarials, and NSAID) that have been shown to impact cellular recognition by the spike protein based on experimental data. Our simulations revealed that the susceptibility of the simulated cell systems to SARS-CoV-2 infection was similar across all tested systems. Notably, CaLu3 cells exhibited the highest susceptibility to SARS-CoV-2 infection, potentially due to the presence of receptors other than ACE2, which may account for a significant portion of the observed susceptibility. Throughout the study, all tested compounds showed thermodynamically favorable and stable binding to the spike protein. Among the tested compounds, the anticoagulant nafamostat demonstrated the most favorable characteristics in terms of thermodynamics, kinetics, theoretical antiviral activity, and potential safety (toxicity) in relation to SARS-CoV-2 spike protein-mediated infections in the tested cell lines. This study provides mathematical and bioinformatic models that can aid in the identification of optimal cell lines for compound evaluation and detection, particularly in studies focused on repurposed drugs and their mechanisms of action. It is important to note that these observations should be experimentally validated, and this research is expected to inspire future quantitative experiments.

A data-driven typology of emotion regulation profiles.

Typologies serve to organize knowledge and advance theory for many scientific disciplines, including more recently in the social and behavioral sciences. To date, however, no typology exists to categorize an individual's use of emotion regulation strategies. This is surprising given that emotion regulation skills are used daily and that deficits in this area are robustly linked with mental health symptoms. Here, we attempted to identify and validate a working typology of emotion regulation across six samples (collectively comprised of 1,492 participants from multiple populations) by using a combination of computational techniques, psychometric models, and growth curve modeling. We uncovered evidence for three types of regulators: a type that infrequently uses emotion regulation strategies (Lo), a type that uses them frequently but indiscriminately (Hi), and a third type that selectively uses some (cognitive reappraisal and situation selection), but not other (expressive suppression), emotion regulation strategies frequently (Mix). Results showed that membership in the Hi and Mix types is associated with better mental health, with the Mix type being the most adaptive of the three. These differences were stable over time and across different samples. These results carry important implications for both our basic understanding of emotion regulation behavior and for informing future interventions aimed at improving mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cortical volume abnormalities in schizophrenia: Correlations with symptoms and cognitive impairment.

BACKGROUND: Schizophrenic symptoms are known to segregate into reality distortion, negative and disorganization syndromes, but the correlates of these syndromes with regional brain structural change are not well established. Cognitive impairment is a further clinical feature of schizophrenia, whose brain structural correlates are the subject of conflicting findings. METHODS: 165 patients with schizophrenia were rated for symptoms using the PANSS, and cognitive impairment was indexed by estimated premorbid-current IQ discrepancy. Cortical volume was measured using surface-based morphometry in the patients and in 50 healthy controls. Correlations between clinical and cognitive measures and cortical volume were examined using whole-brain FreeSurfer tools. RESULTS: No clusters of volume reduction were seen associated with reality distortion or disorganization. Negative symptom scores showed a significant inverse correlation with volume in a small cluster in the left medial orbitofrontal gyrus. Larger estimated premorbid-current IQ discrepancies were associated with clusters of reduced cortical volume in the left precentral gyrus and the left temporal lobe. The cluster of association with negative symptoms disappeared when estimated premorbid-current IQ discrepancy was controlled for. CONCLUSIONS: This study does not provide support for an association between brain structural abnormality and reality distortion or disorganization syndromes in schizophrenia. The cluster of volume reduction found in the left medial orbitofrontal cortex correlated with negative symptoms may have reflected the association between this class of symptoms and cognitive impairment. The study adds to existing findings of an association between cognitive impairment and brain structural changes in the disorder.

Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity.

Introduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in ß-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.

Quantifying water-use efficiency in plant canopies with varying leaf angle and density distribution.

BACKGROUND AND AIMS: Variation in architectural traits related to the spatial and angular distribution of leaf area can have considerable impacts on canopy-scale fluxes contributing to water-use efficiency (WUE). These architectural traits are frequent targets for crop improvement and for improving the understanding and predictions of net ecosystem carbon and water fluxes. METHODS: A three-dimensional, leaf-resolving model along with a range of virtually generated hypothetical canopies were used to quantify interactions between canopy structure and WUE by examining its response to variation of leaf inclination independent of leaf azimuth, canopy heterogeneity, vegetation density and physiological parameters. KEY RESULTS: Overall, increasing leaf area index (LAI), increasing the daily-averaged fraction of leaf area projected in the sun direction (Gavg) via the leaf inclination or azimuth distribution and increasing homogeneity had a similar effect on canopy-scale daily fluxes contributing to WUE. Increasing any of these parameters tended to increase daily light interception, increase daily net photosynthesis at low LAI and decrease it at high LAI, increase daily transpiration and decrease WUE. Isolated spherical crowns could decrease photosynthesis by ~60 % but increase daily WUE ≤130 % relative to a homogeneous canopy with equivalent leaf area density. There was no observed optimum in daily canopy WUE as LAI, leaf angle distribution or heterogeneity was varied. However, when the canopy was dense, a more vertical leaf angle distribution could increase both photosynthesis and WUE simultaneously. CONCLUSIONS: Variation in leaf angle and density distributions can have a substantial impact on canopy-level carbon and water fluxes, with potential trade-offs between the two. These traits might therefore be viable target traits for increasing or maintaining crop productivity while using less water, and for improvement of simplified models. Increasing canopy density or decreasing canopy heterogeneity increases the impact of leaf angle on WUE and its dependent processes.

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.