bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between flight muscle dimorphism and wing morphometry in Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae, Triatominae)
Authors: Nattero Julieta , Piccinali Romina V. , Fiad Federico G. , Cano Florencia , Carbajal-de-la-Fuente Ana Laura
Published: June 2023

Triatoma infestans, the primary vector of Chagas disease in southern South America, is reported as a dimorphic species for flight muscle development and presents a marked phenotypic plasticity in traits related to flight. In triatomines, studying the relationship between flight muscle development and wing variation is important, since it involves flight capacity and dispersion. Therefore, we examined the association between flight muscle dimorphism and morphological wing variation in T. infestans individuals. We hypothesized that if the underdeveloped flight muscle were associated with a decrease in wing developmental stability, canalization and morphological aspect of wings, and with a loss of wing modularity, then wing variation would be associated with flight muscle dimorphism. Wing size and shape were characterized using geometric morphometrics. Patterns of canalization, developmental instability, and modularity were inferred from fluctuating asymmetry analysis of wing shape. Morphological aspects of wings were estimated using maximum wing length and wing area. The results showed that there are differences in wing shape but not in wing size among groups. Canalization and developmental stability were positively associated in individuals with muscle development and negatively associated in individuals with underdeveloped flight muscles. The covariance structure of variation among individuals was different between groups but not for fluctuating asymmetry, both for females and males. Modularity hypothesis related to the wing subdivision into two parts, a stiff part and a membranous one, showed significant association for the variation among individuals and fluctuating asymmetry variation in females with flight muscles. Wing aspect showed that females with flight muscles exhibited more elongated and thinner wings than those without flight muscles. The results obtained in this study reveal an association between flight muscle development and forewing variation in T. infestans. Females with flight muscles have certain differential characteristics in their wings that would be related to an enhanced flight performance.
Candidate gene association study suggests potential role of dopamine beta-hydroxylase in pain heterogeneity in sickle cell disease
Authors: Sadhu Nilanjana , He Ying , Yao Yingwei , Wilkie Diana J. , Molokie Robert E. , Wang Zaijie Jim
Published: June 2023

Introduction: Pain is a lifelong companion of individuals with sickle cell disease (SCD) and has a severe impact on their quality of life. Both acute crisis pain and chronic non-crisis pain exhibit high variability between individuals, making it difficult to effectively manage sickle cell-related pain. We investigated the role of dopamine beta-hydroxylase (DBH) gene polymorphisms on pain variability in SCD. DBH is a key enzyme in the catecholamine biosynthesis pathway that catalyzes the conversion of dopamine to norepinephrine, both of which are known mediators of pain and pain-related behaviors.

Methods: Acute crisis pain-related utilization and non-crisis chronic pain scores of 131 African Americans with SCD were obtained.

Results and discussion: Association analyses revealed that the T allele of upstream variant rs1611115 and downstream variant rs129882 correlated with higher severity of chronic pain in an additive model. On the other hand, the A allele of missense variant rs5324 associated with lower risk of both acute crisis pain and chronic pain. Similarly, the C allele of intronic variant rs2797849 was associated with lower incidence of acute crisis pain in the additive model. In addition, tissue-specific eQTL revealed that the T allele of rs1611115 correlated with decreased expression of DBH in the frontal cortex and anterior cingulate cortex (GTEx), and decreased expression of DBH-AS1 in blood (eQTLGen). Bioinformatic approaches predicted that rs1611115 may be altering a transcription factor binding site, thereby, contributing to its potential effect. Taken together, findings from this study suggest that potential functional polymorphisms of DBH may modulate pain perception in SCD.
IP3R-dependent mitochondrial dysfunction mediates C5b-9-induced ferroptosis in trichloroethylene-caused immune kidney injury
Authors: Liu Zhibing , Ma Jinru , Zuo Xulei , Zhang Xuesong , Xie Haibo , Wang Feng , Wu Changhao , Zhang Jiaxiang , Zhu Qixing
Published: June 2023

Patients with occupational medicamentose-like dermatitis due to trichloroethylene often suffer from immune kidney injury. Our previous study reveals that C5b-9-dependent cytosolic Ca2+ overload-induced ferroptosis is involved in trichloroethylene sensitized kidney injury. However, how C5b-9 causes cytosolic Ca2+ rise and the specific mechanism whereby overloaded Ca2+ induces ferroptosis remain unknown. The purpose of our study was to explore the role of IP3R-dependent mitochondrial dysfunction in C5b-9 mediated ferroptosis in trichloroethylene sensitized kidney. Our results showed that IP3R was activated, and mitochondrial membrane potential was decreased in the renal epithelial cells of trichloroethylene-sensitized mice, and these changes were antagonized by CD59, a C5b-9 inhibitory protein. Moreover, this phenomenon was reproduced in a C5b-9-attacked HK-2 cell model. Further investigation showed that RNA interference with IP3R not only alleviated C5b-9-induced cytosolic Ca2+ overload and mitochondrial membrane potential loss but also attenuated C5b-9-induced ferroptosis in HK-2 cells. Mechanistically, IP3R-dependent cytosolic Ca2+ overload activated the mitochondrial permeability transition pore, resulting in the loss of mitochondrial membrane potential and ferroptosis of HK-2 cells. Finally, cyclosporin A, a mitochondrial permeability transition pore inhibitor, not only ameliorated IP3R-dependent mitochondrial dysfunction but also blocked C5b-9-induced ferroptosis. Taken together, these results suggest that IP3R-dependent mitochondrial dysfunction plays an important role in trichloroethylene sensitized renal tubular ferroptosis.
The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
Authors: Wang Fangyan , Qian Fanyu , Zhang Qihao , Zhao Jian , Cen Jianke , Zhang Jiamin , Zhou Jinhui , Luo Ming , Jia Chang , Rong Xing , Chu Maoping
Published: June 2023

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host’s inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.
Single-cell RNA sequencing highlights the role of PVR/PVRL2 in the immunosuppressive tumour microenvironment in hepatocellular carcinoma
Authors: Li Ang , Ji Bai , Yang Yongsheng , Ye Bicheng , Zhu Qinmei , Hu Xintong , Liu Yong , Zhou Peiwen , Liu Juanjuan , Gao Ranran , Zhou Qi , Kang Boxi , Jiang Yanfang
Published: June 2023

Introduction

The conflict between cancer cells and the host immune system shapes the immune tumour microenvironment (TME) in hepatocellular carcinoma (HCC). A deep understanding of the heterogeneity and intercellular communication network in the TME of HCC will provide promising strategies to orchestrate the immune system to target and eradicate cancers.

Methods

Here, we performed single-cell RNA sequencing (scRNA-seq) and computational analysis of 35786 unselected single cells from 3 human HCC tumour and 3 matched adjacent samples to elucidate the heterogeneity and intercellular communication network of the TME. The specific lysis of HCC cell lines was examined in vitro using cytotoxicity assays. Granzyme B concentration in supernatants of cytotoxicity assays was measured by ELISA.

Results

We found that VCAN+ tumour-associated macrophages (TAMs) might undergo M2-like polarization and differentiate in the tumour region. Regulatory dendritic cells (DCs) exhibited immune regulatory and tolerogenic phenotypes in the TME. Furthermore, we observed intensive potential intercellular crosstalk among C1QC+ TAMs, regulatory DCs, regulator T (Treg) cells, and exhausted CD8+ T cells that fostered an immunosuppressive niche in the HCC TME. Moreover, we identified that the TIGIT-PVR/PVRL2 axis provides a prominent coinhibitory signal in the immunosuppressive TME. In vitro, antibody blockade of PVR or PVRL2 on HCC cell lines or TIGIT blockade on immune cells increased immune cell-mediated lysis of tumour cell. This enhanced immune response is paralleled by the increased secretion of Granzyme B by immune cells.

Discussion

Collectively, our study revealed the functional state, clinical significance, and intercellular communication of immunosuppressive cells in HCC at single-cell resolution. Moreover, PVR/PVRL2, interact with TIGIT act as prominent coinhibitory signals and might represent a promising, efficacious immunotherapy strategy in HCC.
Chaperone function in antigen presentation by MHC class I molecules—tapasin in the PLC and TAPBPR beyond
Authors: Margulies David H. , Jiang Jiansheng , Ahmad Javeed , Boyd Lisa F. , Natarajan Kannan
Published: June 2023

Peptide loading of MHC-I molecules plays a critical role in the T cell response to infections and tumors as well as to interactions with inhibitory receptors on natural killer (NK) cells. To facilitate and optimize peptide acquisition, vertebrates have evolved specialized chaperones to stabilize MHC-I molecules during their biosynthesis and to catalyze peptide exchange favoring high affinity or optimal peptides to permit transport to the cell surface where stable peptide/MHC-I (pMHC-I) complexes are displayed and are available for interaction with T cell receptors and any of a host of inhibitory and activating receptors. Although components of the endoplasmic reticulum (ER) resident peptide loading complex (PLC) were identified some 30 years ago, the detailed biophysical parameters that govern peptide selection, binding, and surface display have recently been understood better with advances in structural methods including X-ray crystallography, cryogenic electron microscopy (cryo-EM), and computational modeling. These approaches have provided refined mechanistic illustration of the molecular events involved in the folding of the MHC-I heavy chain, its coordinate glycosylation, assembly with its light chain, β2-microglobulin (β2m), its association with the PLC, and its binding of peptides. Our current view of this important cellular process as it relates to antigen presentation to CD8+ T cells is based on many different approaches: biochemical, genetic, structural, computational, cell biological, and immunological. In this review, taking advantage of recent X-ray and cryo-EM structural evidence and molecular dynamics simulations, examined in the context of past experiments, we attempt a dispassionate evaluation of the details of peptide loading in the MHC-I pathway. By critical evaluation of several decades of investigation, we outline aspects of the peptide loading process that are well-understood and indicate those that demand further detailed investigation. Further studies should contribute not only to basic understanding, but also to applications for immunization and therapy of tumors and infections.
Trained immunity as a potential target for therapeutic immunomodulation in Duchenne muscular dystrophy
Authors: Petrof Basil J. , Podolsky Tom , Bhattarai Salyan , Tan Jiahui , Ding Jun
Published: June 2023

Dysregulated inflammation involving innate immune cells, particularly of the monocyte/macrophage lineage, is a key contributor to the pathogenesis of Duchenne muscular dystrophy (DMD). Trained immunity is an evolutionarily ancient protective mechanism against infection, in which epigenetic and metabolic alterations confer non-specific hyperresponsiveness of innate immune cells to various stimuli. Recent work in an animal model of DMD (mdx mice) has shown that macrophages exhibit cardinal features of trained immunity, including the presence of innate immune system “memory”. The latter is reflected by epigenetic changes and durable transmissibility of the trained phenotype to healthy non-dystrophic mice by bone marrow transplantation. Mechanistically, it is suggested that a Toll-like receptor (TLR) 4-regulated, memory-like capacity of innate immunity is induced at the level of the bone marrow by factors released from the damaged muscles, leading to exaggerated upregulation of both pro- and anti-inflammatory genes. Here we propose a conceptual framework for the involvement of trained immunity in DMD pathogenesis and its potential to serve as a new therapeutic target.
Gut microbiota and Sjögren’s syndrome: a two-sample Mendelian randomization study
Authors: Cao Yu , Lu Hao , Xu Wangzi , Zhong Ming
Published: June 2023

Background

The link between the gut microbiota (GM) and Sjögren’s Syndrome (SS) is well-established and apparent. Whether GM is causally associated with SS is uncertain.

Methods

The MiBioGen consortium’s biggest available genome-wide association study (GWAS) meta-analysis (n=13,266) was used as the basis for a two-sample Mendelian randomization study (TSMR). The causal relationship between GM and SS was investigated using the inverse variance weighted, MR-Egger, weighted median, weighted model, MR-PRESSO, and simple model methods. In order to measure the heterogeneity of instrumental variables (IVs), Cochran’s Q statistics were utilized.

Results

The results showed that genus Fusicatenibacter (odds ratio (OR) = 1.418, 95% confidence interval (CI), 1.072–1.874, P = 0.0143) and genus Ruminiclostridium9 (OR = 1.677, 95% CI, 1.050–2.678, P = 0.0306) were positively correlated with the risk of SS and family Porphyromonadaceae (OR = 0.651, 95% CI, 0.427–0.994, P = 0.0466), genus Subdoligranulum (OR = 0.685, 95% CI, 0.497–0.945, P = 0.0211), genus Butyricicoccus (OR = 0.674, 95% CI, 0.470–0.967, P = 0.0319) and genus Lachnospiraceae (OR = 0.750, 95% CI, 0.585–0.961, P = 0.0229) were negatively correlated with SS risk using the inverse variance weighted (IVW) technique. Furthermore, four GM related genes: ARAP3, NMUR1, TEC and SIRPD were significant causally with SS after FDR correction (FDR<0.05).

Conclusions

This study provides evidence for either positive or negative causal effects of GM composition and its related genes on SS risk. We want to provide novel approaches for continued GM and SS-related research and therapy by elucidating the genetic relationship between GM and SS.
Involvement of extracellular vesicles in the progression, diagnosis, treatment, and prevention of whole-body ionizing radiation-induced immune dysfunction
Authors: Seim Roland F. , Herring Laura E. , Mordant Angie L. , Willis Micah L. , Wallet Shannon M. , Coleman Leon G. , Maile Robert
Published: June 2023

Acute radiation syndrome (ARS) develops after exposure to high doses of ionizing radiation and features immune suppression and organ failure. Currently, there are no diagnostics to identify the occurrence or severity of exposure and there are limited treatments and preventative strategies to mitigate ARS. Extracellular vesicles (EVs) are mediators of intercellular communication that contribute to immune dysfunction across many diseases. We investigated if EV cargo can identify whole body irradiation (WBIR) exposure and if EVs promote ARS immune dysfunction. We hypothesized that beneficial EVs derived from mesenchymal stem cells (MSC-EVs) would blunt ARS immune dysfunction and might serve as prophylactic radioprotectants. Mice received WBIR (2 or 9 Gy) with assessment of EVs at 3 and 7 days after exposure. LC-MS/MS proteomic analysis of WBIR-EVs found dose-related changes as well as candidate proteins that were increased with both doses and timepoints (34 total) such as Thromboxane-A Synthase and lymphocyte cytosolic protein 2. Suprabasin and Sarcalumenin were increased only after 9 Gy suggesting these proteins may indicate high dose/lethal exposure. Analysis of EV miRNAs identified miR-376 and miR-136, which were increased up to 200- and 60-fold respectively by both doses of WBIR and select miRNAs such as miR-1839 and miR-664 were increased only with 9 Gy. WBIR-EVs (9 Gy) were biologically active and blunted immune responses to LPS in RAW264.7 macrophages, inhibiting canonical signaling pathways associated with wound healing and phagosome formation. When given 3 days after exposure, MSC-EVs slightly modified immune gene expression changes in the spleens of mice in response to WBIR and in a combined radiation plus burn injury exposure (RCI). MSC-EVs normalized the expression of certain key immune genes such as NFκBia and Cxcr4 (WBIR), Map4k1, Ccr9 and Cxcl12 (RCI) and lowered plasma TNFα cytokine levels after RCI. When given prophylactically (24 and 3 hours before exposure), MSC-EVs prolonged survival to the 9 Gy lethal exposure. Thus, EVs are important participants in ARS. EV cargo might be used to diagnose WBIR exposure, and MSC-EVs might serve as radioprotectants to blunt the impact of toxic radiation exposure.
Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
Authors: Zhang Chiyu , Huang Gaomin , Yang Jiale , Jiang Yi , Huang Ruizhen , Ye Zhenfeng , Huang Yawei , Hu Honglin , Xi Xiaoqing
Published: June 2023

Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT’s predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.
Biomarkers in the era of targeted therapy in giant cell arteritis and polymyalgia rheumatica: is it possible to replace acute-phase reactants?
Authors: Carvajal Alegria Guillermo , Nicolas Mathilde , van Sleen Yannick
Published: June 2023

Research into giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) has become more important in the last few decades. Physicians are facing several challenges in managing the diagnosis, treatment, and relapses of GCA and PMR patients. The search for biomarkers could provide elements to guide a physician’s decision. In this review, we aim to summarize the scientific publications about biomarkers in GCA and PMR in the past decade. The first point raised by this review is the number of clinical situations in which biomarkers could be useful: differential diagnosis of either GCA or PMR, diagnosis of underlying vasculitis in PMR, prediction of relapse or complications, disease activity monitoring, choice, and modification of treatments. The second point raised by this review is the large number of biomarkers studied, from common markers like C-reactive protein, erythrocyte sedimentation rate, or elements of blood count to inflammatory cytokines, growth factors, or immune cell subpopulations. Finally, this review underlines the heterogeneity between the studies and proposes points to consider in studies evaluating biomarkers in general and particularly in the case of GCA and PMR.
Ants are more than just curious bystanders to some flowers—they act as significant pollinators
Authors: Das Susmita , Das Amlan
Published: June 2023

Ant–plant associations are ubiquitous and highly diverse in almost all terrestrial environments, resulting in complex ecological networks. Although ant–plant mutualism is prevalent, ant-mediated pollination is uncommon, and only a few investigations have demonstrated their role in pollination. Thus, the topic of ant-mediated pollination requires revision to assess its significance in pollination biology. Ants are frequent floral visitors, but their impact on plant reproductive fitness is rarely acknowledged; nonetheless, numerous flower-visiting ants have been investigated for their involvement in promoting floral development and hybrid vigor in crops. In this study, we present a summary of the scientific literature published over the last four decades on ants’ involvement in pollination, the diversity of pollinating ants to various host plants, the ant–plant pollinating networks, and seasonal patterns of ant-mediated pollination. Ants generally forage for flowers in quest of nectar and other sustenance, and in doing so they pollinate the flowers that they encounter. This review identified the pollination networks between ants and plants at the species and family levels. Pollination is often affected by a number of aspects, including the flower’s sex, its ovary position, the inflorescence it bears, and the time of year. The available literature demonstrates that ants visit the inflorescences of the same species only to promote cross-pollination, a process known as “geitonogamy”; however, we conclude that ants may visit different inflorescences of different plants in the field. If ant pollination is the norm, there is less selection pressure to acquire self-compatibility; nonetheless, ants' cross-pollination may have caused ants to co-evolve with the pollinating flowers. This indicates that ants are more than just curious bystanders to some flowers; they act as significant pollinators.
The influence of cold filaments on the evolution of dipole structures
Authors: Yang Qi , Wang Guihua , Xu Chi , Gao Guoping , Sun Ruili
Published: June 2023

Mesoscale eddy dipoles are oceanographic structures that can transport ocean water parcels horizontally and vertically in ways that differ from individual mesoscale eddies. The most conspicuous additional feature that presents in dipoles is the cold filament (CF) that can be spontaneously generated between a dipole’s anticyclonic eddy (AE) and cyclonic eddy (CE). A case study in this paper shows that the interaction between the CF and the CE component of the dipole is associated with the structural evolution of the dipole. This interaction is verified in synthesis and normalization studies of the CF dipoles. The CF-dipole interaction entrains CF water into the center of the dipole’ CE and leads to a cold and high chlorophyll center in the upper layer of the CE. The formation of this cold center changes the dipole’s structure by eliminating the phase difference between the thermal and dynamic centers of the dipole. The entrainment also provides a new mechanism for the development of high chlorophyll levels in the CE. In the analysis of the HYCOM (Hybrid Coordinate Ocean Model) simulation of a synthetic CF dipole, the AE has a three-zone structure while the CE only has two. The convergence of the CE’s outermost zone results in a biased interaction.
Fighting Post-COVID and ME/CFS – development of curative therapies
Authors: Scheibenbogen Carmen , Bellmann-Strobl Judith Theresia , Heindrich Cornelia , Wittke Kirsten , Stein Elisa , Franke Christiana , Prüss Harald , Preßler Hannah , Machule Marie-Luise , Audebert Heinrich , Finke Carsten , Zimmermann Hanna Gwendolyn , Sawitzki Birgit , Meisel Christian , Toelle Markus , Krueger Anne , Aschenbrenner Anna C. , Schultze Joachim L. , Beyer Marc D. , Ralser Markus , Mülleder Michael , Sander Leif Erik , Konietschke Frank , Paul Friedemann , Stojanov Silvia , Bruckert Lisa , Hedderich Dennis M. , Knolle Franziska , Riemekasten Gabriela , Vehreschild Maria J. G. T. , Cornely Oliver A. , Behrends Uta , Burock Susen
Published: June 2023

The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms. However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS. There is an overlap of symptoms and pathomechanisms of PCS with postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). No curative therapies are available for ME/CFS or PCS. The mechanisms identified so far provide targets for therapeutic interventions. To accelerate the development of therapies, we propose evaluating drugs targeting different mechanisms in clinical trial networks using harmonized diagnostic and outcome criteria and subgrouping patients based on a thorough clinical profiling including a comprehensive diagnostic and biomarker phenotyping.
Antithrombotic therapy in antiphospholipid syndrome with arterial thrombosis: a systematic review and network meta-analysis
Authors: Attachaipanich Tanawat , Aungsusiripong Aimpat , Piriyakhuntorn Pokpong , Hantrakool Sasinee , Rattarittamrong Ekarat , Rattanathammethee Thanawat , Tantiworawit Adisak , Norasetthada Lalita , Chai-Adisaksopha Chatree
Published: June 2023

Introduction

The optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to evaluate the comparative efficacy and safety of various antithrombotic strategies in APS with arterial thrombosis.

Methods

A comprehensive literature search was conducted using OVID MEDLINE, EMBASE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until 30 September 2022, with no language restrictions. The inclusion criteria for eligible studies were as follows: inclusion of APS patients with arterial thrombosis, treatment with either antiplatelet agents, warfarin, direct oral anticoagulants (DOACs), or a combination of these therapies, and reporting of recurrent thrombotic events.

Results

We conducted a frequentist random-effects network meta-analysis (NMA) involving 13 studies with a total of 719 participants, comprising six randomized and seven non-randomized studies. In comparison to single antiplatelet therapy (SAPT), the combined use of antiplatelet and warfarin demonstrated a significant reduction in the risk of recurrent overall thrombosis, with a risk ratio (RR) of 0.41 (95% CI 0.20 to 0.85). Dual antiplatelet therapy (DAPT) showed a lower risk of recurrent arterial thrombosis compared to SAPT although the difference did not reach statistical significance, with an RR of 0.29 (95% CI 0.08 to 1.07). DOAC was associated with a significant increase in the risk of recurrent arterial thrombosis, with an RR of 4.06 (95% CI 1.33 to 12.40) when compared to SAPT. There was no significant difference in major bleeding among various antithrombotic strategies.

Discussion

Based on this NMA, the combination of warfarin and antiplatelet therapy appears to be an effective approach in preventing recurrent overall thrombosis in APS patients with a history of arterial thrombosis. While DAPT may also show promise in preventing recurrent arterial thrombosis, further studies are needed to confirm its efficacy. Conversely, the use of DOACs was found to significantly increase the risk of recurrent arterial thrombosis.
A systematic review of mental health interventions to reduce self-stigma in medical students and doctors
Authors: Bannatyne Amy Jean , Jones Cindy , Craig Belinda M. , Jones Dominique , Forrest Kirsty
Published: June 2023

Background

A growing body of literature has revealed that many medical students and doctors do not seek professional help for their mental health due to fear of stigma (both public- and self-stigma) and questioning of their clinical competency. The aim of this systematic review was to identify and evaluate direct and indirect interventions that address mental health stigma in medical students and/or doctors. We focused explicitly on studies that measured the impact on self-stigma outcomes.

Method

A systematic search of the following electronic databases was undertaken from inception to 13 July 2022: PubMed, Embase, PsycINFO, and CINAHL, together with manual searching of reference lists. Screening of titles, abstracts, and full texts of eligible studies, plus quality appraisal using the Mixed Methods Appraisal Tool, were independently conducted by multiple reviewers with disagreements resolved via discussion.

Results

From 4,018 citations, five publications met the inclusion criteria. None of the studies explicitly aimed to reduce self-stigmatisation, with the majority focusing on medical students. Most of the identified interventions focused on reducing professional stigma (i.e., stigma toward patients with mental illness) and measurement of self-stigma was incidentally collected via a subscale of the general stigma measure selected. Three studies found significant reductions in self-stigma following the delivered intervention. These studies were of moderate quality, had medical student samples, employed combined education and contact interventions, and used the same outcome measure.

Discussion

Intentional development and evaluation of interventions specifically designed to decrease self-stigma among doctors and medical students are needed, with further research required on the optimal components, format, length, and delivery of such interventions. Researchers delivering public/professional stigma reduction interventions should strongly consider measuring the impact of such interventions on self-stigma outcomes, using fit-for-purpose, psychometrically sound instruments.
Microbial mats as model to decipher climate change effect on microbial communities through a mesocosm study
Authors: Mazière C. , Duran R. , Dupuy C. , Cravo-Laureau C.
Published: June 2023

Marine environments are expected to be one of the most affected ecosystems by climate change, notably with increasing ocean temperature and ocean acidification. In marine environments, microbial communities provide important ecosystem services ensuring biogeochemical cycles. They are threatened by the modification of environmental parameters induced by climate change that, in turn, affect their activities. Microbial mats, ensuring important ecosystem services in coastal areas, are well-organized communities of diverse microorganisms representing accurate microbial models. It is hypothesized that their microbial diversity and metabolic versatility will reveal various adaptation strategies in response to climate change. Thus, understanding how climate change affects microbial mats will provide valuable information on microbial behaviour and functioning in changed environment. Experimental ecology, based on mesocosm approaches, provides the opportunity to control physical-chemical parameters, as close as possible to those observed in the environment. The exposure of microbial mats to physical-chemical conditions mimicking the climate change predictions will help to decipher the modification of the microbial community structure and function in response to it. Here, we present how to expose microbial mats, following a mesocosm approach, to study the impact of climate change on microbial community.
Trichoderma koningiopsis (Hypocreaceae) has the smallest mitogenome of the genus Trichoderma
Authors: Castrillo María Lorena , Bich Gustavo Ángel , Amerio Natalia Soledad , Barengo Marcela Paola , Zapata Pedro Darío , Saparrat Mario Carlos Nazareno , Villalba Laura Lidia
Published: June 2023

Introduction

Fungal mitogenomes exhibit remarkable variation in conformation, size, gene content, arrangement and expression, including their intergenic spacers and introns.

Methods

The complete mitochondrial genome sequence of the mycoparasitic fungus Trichoderma koningiopsis was determined using the Illumina next-generation sequencing technology. We used data from our recent Illumina NGS-based project of T. koningiopsis genome sequencing to study its mitochondrial genome. The mitogenome was assembled, annotated, and compared with other fungal mitogenomes.

Results

T. koningiopsis strain POS7 mitogenome is a circular molecule of 27,560 bp long with a GC content of 27.80%. It harbors the whole complement of the 14 conserved mitochondrial protein-coding genes (PCG) such as atp6, atp8, atp9, cox1, cox2, cox3, cob, nad1, nad2, nad3, nad4, nad4L, nad5, and nad6, also found in the same gene order to other Hypocreales. The mitogenome also contains 26 transfer RNA genes (tRNAs), 5 of them with more than one copy. Other genes also present in the assembled mitochondrial genome are a small rRNA subunit and a large rRNA subunit containing ribosomal protein S3 gene. Despite the small genome size, two introns were detected in the T. koningiopsis POS7 mitogenome, one of them in cox3 gene and the other in rnl gene, accounting 7.34% of this mitogenome with a total size of 2,024 bp. A phylogenetic analysis was done using the 14 PCGs genes of T. koningiopsis strain POS7 mitogenome to compare them with those from other fungi of the Subphyla Pezizomycotina and Saccharomycotina. T. koningiopsis strain POS7 was clustered together with other representatives of Trichoderma lineage, within the Hypocreales group, which is also supported by previous phylogenetic studies based on nuclear markers.

Discussion

The mitochondrial genome of T. koningiopsis POS7 will allow further investigations into the taxonomy, phylogenetics, conservation genetics, and evolutionary biology of this important genus as well as other closely related species.
Diversity of CRISPR-Cas type II-A systems in Streptococcus anginosus
Authors: Bauer Richard , Haider Dorina , Grempels Aline , Roscher Rebecca , Mauerer Stefanie , Spellerberg Barbara
Published: June 2023

Streptococcus anginosusis a commensal Streptococcal species that is often associated with invasive bacterial infections. However, little is known about its molecular genetic background. Many Streptococcal species, includingS. anginosus, harbor clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. A CRISPR-Cas type II-A system as well as a type II-C system have been reported for this species. To characterize the CRISPR-Cas type II systems ofS. anginosusin more detail, we conducted a phylogenetic analysis of Cas9 sequences from CRISPR-Cas type II systems with a special focus on streptococci andS. anginosus. In addition, a phylogenetic analysis ofS. anginosusstrains based on housekeeping genes included in MLST analysis, was performed. All analyzed Cas9 sequences ofS. anginosusclustered with the Cas9 sequences of CRISPR type II-A systems, including the Cas9 sequences ofS. anginosusstrains reported to harbor a type II-C system. The Cas9 genes of the CRISPR-Cas type II-C systems of other bacterial species separated into a different cluster. Moreover, analyzing the CRISPR loci found inS. anginosus, two distinctcsn2genes could be detected, a short form showing high similarity to the canonical form of thecsn2gene present inS. pyogenes. The second CRISPR type II locus ofS. anginosuscontained a longer variant ofcsn2with close similarities to acsn2gene that has previously been described inStreptococcus thermophilus.Since CRISPR-Cas type II-C systems do not contain acsn2gene, theS. anginosusstrains reported to have a CRISPR-Cas type II-C system appear to carry a variation of CRISPR-Cas type II-A harboring a long variant ofcsn2.
Comparison of the gut virus communities between patients with Crohn’s disease and healthy individuals
Authors: Ding Yuzhu , Wan Mengtian , Li Zheng , Ma Xiao , Zhang Wen , Xu Min
Published: June 2023

Introduction

The escalating incidence of Crohn’s disease (CD), a debilitating ailment that ravages individuals and their families, has become a formidable issue over recent decades.

Method

In this study, fecal samples from patients with CD and healthy individuals were investigated by means of viral metagenomics.

Results

The fecal virome was analyzed and some suspected disease-causing viruses were described. A polyomavirus named HuPyV with 5,120 base pairs (bp) was found in the disease group. In a preliminary analysis employing large T region-specific primers, it was found that HuPyV was present in 3.2% (1/31) of healthy samples and 43.2% (16/37) of disease samples. Additionally, two other viruses from the anellovirus and CRESS-DNA virus families were found in fecal samples from CD patients. The complete genome sequences of these two viruses were described respectively, and the phylogenetic trees have been built using the anticipated amino acid sequences of the viral proteins.

Discussion

Further research is required to elucidate the relationship between these viruses and the onset and development of Crohn’s disease.
Effects of respiratory virus vaccination and bovine respiratory disease on the respiratory microbiome of feedlot cattle
Authors: McAtee Taylor B. , Pinnell Lee J. , Powledge Sherri A. , Wolfe Cory A. , Morley Paul S. , Richeson John T.
Published: June 2023

Introduction

The objectives of this study were to evaluate the impacts of two modified-live virus (MLV) vaccination protocols and respiratory disease (BRD) occurrence on the microbial community composition of the nasopharynx in feedlot cattle.

Methods

The treatment groups included in this randomized controlled trial included: 1) no viral respiratory vaccination (CON), 2) intranasal, trivalent, MLV respiratory vaccine in addition to a parenteral BVDV type I and II vaccine (INT), and 3) parenteral, pentavalent, MLV respiratory vaccination against the same agents (INJ). Calves (n = 525) arrived in 5 truckload blocks and were stratified by body weight, sex, and presence of a pre-existing identification ear-tag. A total of 600 nasal swab samples were selected for DNA extraction and subsequent 16S rRNA gene sequencing to characterize the microbiome of the upper respiratory tract. Nasal swabs collected on d 28 from healthy cattle were used to evaluate the impact of vaccination on upper respiratory tract (URT) microbial communities.

Results

Firmicutes were less abundant in INT calves (n = 114; P < 0.05) and this difference was attributed to decreased relative abundance (RA) of Mycoplasma spp. (P = 0.04). Mannheimia and Pasteurella had lower RA in INT (P < 0.05). The microbiome in healthy animals on d 28 had increased Proteobacteria (largely Moraxella spp.) and decreased Firmicutes (comprised almost exclusively of Mycoplasma spp.) compared to animals that were treated for or died from BRD (P < 0.05). Cattle that died had a greater RA of Mycoplasma spp. in their respiratory microbiome on d 0 (P < 0.02). Richness was similar on d 0 and 28, but diversity increased for all animals on d 28 (P>0.05).
Novel leaderless bacteriocin geobacillin 6 from thermophilic bacterium Parageobacillus thermoglucosidasius
Authors: Koniuchovaitė Ana , Petkevičiūtė Akvilė , Bernotaitė Emilija , Gricajeva Alisa , Gegeckas Audrius , Kalėdienė Lilija , Kaunietis Arnoldas
Published: June 2023

Bacterial resistance to conventional antibiotics has urged us to develop alternative strategies against bacterial pathogens. Moreover, a demand for food products containing no chemical preservatives has led us to search for new alternative technologies for food preservation. Bacteriocins – ribosomally synthesized antimicrobial peptides – have been proposed as a new alternative to conventional antibiotics or chemicals for food preservation. This study describes biosynthesis and characterization of a novel leaderless bacteriocin, geobacillin 6, which was identified in the thermophilic bacterium Parageobacillus thermoglucosidasius. Its amino acid sequence shows low similarity to other bacteriocins and it is the first leaderless-type bacteriocin identified in thermophilic bacteria. Based on structure assessment, the bacteriocin forms a multi-helix bundle. Geobacillin 6 exhibits a relatively narrow antimicrobial spectrum, it is active in the μM range and against Gram-positive bacteria, mostly thermophilic species closely related to the producer strain. Bacteriocin demonstrates stability over pH 3–11 and is highly thermostable, retaining 100% of its activity after incubation at 95°C for 6 h. Geobacillin 6 has potential in the food industry and biotechnological processes where contamination with thermophilic bacteria is undesirable.
Polymorphisms and NIHL: a systematic review and meta-analyses
Authors: Wang Lu , Wang HanYu , Xiang Feng , Xiang YuLu , Xiong Feng , Zhang QinXiu
Published: June 2023

Background

Noise-induced hearing loss (NIHL) has always been a global public health problem, which is related to noise exposure and genetic factors. Many researchers have tried to identify the polymorphisms that cause different individuals' susceptibility to NIHL. We conducted a meta-analysis of the most frequently studied polymorphisms to identify those genes that may be associated with NIHL and may provide value in risk prevention.

Methods

PubMed, China National Knowledge Infrastructure (CNKI) database, Embase, Wang Fang, Web of Science and Cochrane library were searched, and qualified studies on the correlation between polymorphism and NIHL susceptibility were screened, and then polymorphisms cited in at least three studies were selected for meta-analysis. Fixed- or random-effects models were used to calculate odds ratios and 95% confidence intervals. Statistical I2 tests and sensitivity analyses were used to detect interstudy heterogeneity and test the statistical stability of overall estimates, respectively. Egger's tests were applied to detect publication bias among included studies. All of the above analyses were performed using stata 17.0.

Results

64 genes were initially selected and introduced in 74 papers. Among them, 10 genes (and 25 polymorphisms) have been reported in more than 3 papers. Twenty five polymorphisms participated in the meta-analysis. Of the 25 polymorphisms, only 5 were significantly associated with the risk of AR: rs611419 (GRHL2) polymorphism and rs3735715 polymorphism (GRHL2), rs208679 polymorphism (CAT), rs3813346 polymorphism (EYA4) were significantly associated with the susceptibility of NIHL, rs2227956 polymorphism (HSP70) was significantly associated with the susceptibility of white population NIHL, and the remaining 20 gene polymorphisms were not significantly associated with NIHL.

Conclusion

We found polymorphisms that are valuable for the prevention of NIHL and polymorphisms that are not related to NIHL. This is the first step to establish an effective risk prediction system for the population, especially for high-risk groups, which may help us better identify and prevent the occurrence of NIHL. In addition, our research results contribute to the in-depth exploration of NIHL.

Systematic review registration

https://inplasy.com/inplasy-2023-6-0003/, identifier INPLASY202360003.
A blended neurostimulation protocol to delineate cortico-muscular and spino-muscular dynamics following neuroplastic adaptation
Authors: Stefanovic Filip , Martinez Julian A. , Saleem Ghazala T. , Sisto Sue Ann , Miller Michael T. , Achampong Yaa A. , Titus Albert H.
Published: June 2023

In this paper we propose a novel neurostimulation protocol that provides an intervention-based assessment to distinguish the contributions of different motor control networks in the cortico-spinal system. Specifically, we use a combination of non-invasive brain stimulation and neuromuscular stimulation to probe neuromuscular system behavior with targeted impulse-response system identification. In this protocol, we use an in-house developed human-machine interface (HMI) for an isotonic wrist movement task, where the user controls a cursor on-screen. During the task, we generate unique motor evoked potentials based on triggered cortical or spinal level perturbations. Externally applied brain-level perturbations are triggered through TMS to cause wrist flexion/extension during the volitional task. The resultant contraction output and related reflex responses are measured by the HMI. These movements also include neuromodulation in the excitability of the brain-muscle pathway via transcranial direct current stimulation. Colloquially, spinal-level perturbations are triggered through skin-surface neuromuscular stimulation of the wrist muscles. The resultant brain-muscle and spinal-muscle pathways perturbed by the TMS and NMES, respectively, demonstrate temporal and spatial differences as manifested through the human-machine interface. This then provides a template to measure the specific neural outcomes of the movement tasks, and in decoding differences in the contribution of cortical- (long-latency) and spinal-level (short-latency) motor control. This protocol is part of the development of a diagnostic tool that can be used to better understand how interaction between cortical and spinal motor centers changes with learning, or injury such as that experienced following stroke.