bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative metabolic analysis of orbital adipose/connective tissue in patients with thyroid-associated ophthalmopathy
Authors: Huang Jiancheng , Chen Meng , Liang Yu , Hu Yuxiang , Xia Weiyi , Zhang Yihan , Zhao Chen , Wu Lianqun
Published: November 2022

Objective

Thyroid-associated ophthalmopathy (TAO) is a disfiguring autoimmune disease, which destroys the structure of orbital tissues and even threatens vision. Metabolic reprograming is critical in autoimmune diseases; however, the metabolic basis of TAO remains to be clarified. Our study aimed to reveal the metabolic profile of TAO.

Methods

Orbital adipose/connective tissues from eleven TAO patients and twelve control subjects were collected during surgeries and analyzed with liquid chromatograph-mass spectrometer. Orthogonal partial least-squares discrimination analysis (OPLS-DA), variable importance in projection (VIP), heat map, and volcano plot were used to reveal metabolic profile in TAO. Pathway analysis and metabolites-gene analysis were utilized to explore potential metabolic metabolism in TAO.

Results

3038 metabolites were detected in samples from the TAO patients and the controls. OPLS-DA analysis of the metabolomics results showed two distinguished groups, demonstrating that TAO has a unique metabolome. Univariate tests identified 593 dysregulated metabolites (P < 0.05), including 367 increased metabolites and 226 decreased metabolites. Pathway analysis showed that changed metabolites were enriched in cholesterol metabolism, choline metabolism in cancer, fat digestion and absorption, regulation of lipolysis in adipocytes, and insulin resistance. In addition, metabolites-gene analysis illustrated that cholesterol metabolism was involved in the pathogenesis of TAO. Endoplasmic reticulum stress-related genes (ATF6, PERK, and IRE1α) expressions were higher in TAO orbital tissues than in control orbital tissues verified by western blot. Additionally, the expression level of diacylglycerol acyltransferase 1 (DGAT1), a key metabolic protein for triacylglycerol synthesis, was increased in orbital tissues of TAO detected by qRT-PCR, indicating disrupted cholesterol metabolism in TAO.

Conclusion

The present study demonstrated different metabolite profiles and potential metabolic mechanisms in TAO.
Influence of soil management for soybean production under microbial diversity in amazon soils
Authors: Cardenas-Alegria Oscar Victor , Dantas Carlos Willian Dias , Silva Guedes Lobato Elaine Maria , Da Silva Sandro Patroca , Moraes Cássia de Sousa , Cruz Ana Cecília Ribeiro , Ramos Rommel Thiago Jucá , Carneiro Adriana Ribeiro
Published: November 2022

The tropical Amazon has a unique biodiversity that has been affected by the development of pastures and economically important crops, such as soybeans. In the Amazon soil, the communities of microorganisms are diverse and act in different biogeochemical activities relevant to their adaptation to the environment. The assessment of changes in soil microorganism communities is essential to consider the impact of agribusiness action in one of the wealthiest regions in diversity in the world. Thus, the soil microbial diversity of the Amazon forest, the north region of Brazil, was evaluated regarding the influence of soybean farming with regions with periods of two and 14 years of exploitation, with regions of pasture and forest area, through the metagenomics approach with new generation sequencing technology, in addition, it was considered chemical characteristics such as pH value, organic matter content, macronutrients, micronutrients, and cations. High microbial diversity was identified at all collection sites and, despite this, bacterial, archaeal, and virus communities were very diverse between sites, with higher identification of Enterobacter cloacae and species of Pseudomonas, Pseudoplusia includens, Methanosarcina barkeri in the farmed and pasture, whose microbial diversity is influenced by the presence of cations and the interaction of organic matter with clay. It was evident that there is a change in the communities of native microorganisms for others adapted in the areas that had their vegetal cover eliminated.
Complete genome sequence analysis of a novel alkane-degrading bacterial strain, Acinetobacter vivianii KJ-1, and its diesel degradation ability
Authors: Zhang Yali , Song Fanyong , Wang Jianing , Zhao Qingqing , Zheng Liwen , Wang Zhenjie , Zhang Xinjian , Gao Yongchao , Chen Guanhong , Huang Yujie
Published: November 2022

With the increasing demand for diesel in various countries, the ecological pollution caused by the improper use, storage, and accidental leakage of diesel needs to be addressed urgently. As an environmentally friendly and cost-effective method, bioremediation generally uses various microorganisms to remove pollutants from the environment. Here, the strain KJ-1, obtained through an enrichment culture using n-dodecane from oil-contaminated soil near a gas station as the substrate, was identified as Acinetobacter vivianii according to its morphology, biochemistry, and molecular biology. The isolate KJ-1 was able to use diesel as a sole carbon source and more than 40% of diesel was degraded after 12 days of incubation with strain KJ-1 in mineral salts medium. The most suitable diesel concentration and nitrogen source concentrations were 4,140 mg/L and 350–700 mg/L, respectively, for diesel degradation and bacterial growth. The optimal initial pH and temperature for strain KJ-1 growth and diesel degradation were 6.5–8.0 and 20–37°C, respectively. To investigate the diesel-degrading mechanisms of this strain, the complete genome was sequenced and annotated. The complete genome consists of one chromosome with a total length of 3,927,757 base pairs and a G + C content of 41.5%. The genes related to the two-component regulatory system and alkane degradation were analyzed. In addition, two putative alkane monooxygenases were analyzed, and the protein sequences were characterized and compared with other AlkBs in Acinetobacter spp. using sequences downloaded from NCBI. The results demonstrated that A. vivianii KJ-1 may be particularly useful for future bioremediation of diesel-polluted soil.
Path of carbon emission reduction through land use pattern optimization under future scenario of multi-objective coordination
Authors: Dong Honghong , Huang Qing , Zhang Fangyi , Lu Xuehe , Zhang Qian , Cao Jianjun , Gen Ling , Li Ning
Published: November 2022

Land use change is one of the crucial factors affecting carbon emissions. The continuously increasing CO2 and global warming have raised concerns about carbon emission reduction in the process of urbanization. In this research, the Markov and multi-objective optimization models were conducted to predict the demands for land use in Nanjing in 2030 and 2060 under the natural growth (NG) and minimum carbon emission (MCE) scenarios to coordinate the needs of economic development, ecological protection and food security as well as the target of carbon emissions reduction in the future. The spatial distribution of land use simulated by the FLUS (Future Land Use Simulation) model was used to evaluate the effects of future land use on carbon emissions. The results showed that 1) The demands for each type of land use in the NG scenario were significantly different from those in the MCE scenario. Considering the goals of food security and ecological protection in the future, the total amount of cultivated land would not decrease in the MCE scenario, and the area of construction land was significantly smaller than that in the NG scenario. 2) The carbon emissions of Nanjing under the MCE scenario would decrease by 3.94 and 11.80 million tons in 2030 and 2060, respectively, accounting for 9.97% and 27.17% of the total carbon emissions. The optimization of land use patterns can effectively reduce carbon emissions in the process of urbanization.
Combining bulk stable H isotope (δ2H) measurements with fatty acid profiles to examine differential use of aquatic vs. terrestrial prey by three sympatric species of aerial insectivorous birds
Authors: Génier Corrine S. V. , Guglielmo Christopher G. , Hobson Keith A.
Published: November 2022

Aerial insectivorous songbirds such as swallows and martins have declined substantially in North America in recent decades. Aquatic-emergent insects provide more beneficial omega-3 fatty acids than terrestrial insects, and thus, diet quality is expected to vary among aerial insectivores with differential access to aquatic-emergent insects. We compared the stable hydrogen isotope (δ2H) values of feathers and bulk blood plasma fatty acids of nestling purple martins (Progne subis), tree swallows (Tachycineta bicolor), and barn swallows (Hirundo rustica), at lakeshore and inland sites near Lake Erie, Ontario, Canada. We found that diet quality differed between inland and lakeshore nesting habitats, but differences depended on species. Overall, purple martin and tree swallow nestlings had lower feather δ2H values, indicating a more aquatic-emergent diet, and lakeshore populations of both species had higher omega-3 fatty acid levels in their blood plasma compared to inland populations. Conversely, higher plasma levels of omega-6 fatty acids were found in inland birds. Tree swallows have a low omega-3 conversion efficiency from precursor substrates and so depend on aquatic subsidies to fulfill their nutritional needs. We suggest this may also be the case with purple martins. Barn swallows had the most positive feather δ2H values, regardless of proximity to the lakeshore, indicating a more terrestrial diet. However, barn swallow nestlings had consistently higher plasma omega-3 docosahexaenoic acid (DHA) regardless of nesting location, suggesting that barn swallows can efficiently convert omega-3 precursors into their beneficial elongated fatty acid chains. Our study indicates the benefit of combining plasma fatty acid compositional analyses with bulk feather δ2H values to decipher interspecific differences in adaptations to availability of aquatic-emergent insects.
Case report: Mild phenotype of a patient with vascular Ehlers–Danlos syndrome and COL3A1 duplication mutation without alteration in the [Gly-X-Y] repeat sequence
Authors: Hayashi Shujiro , Yamaguchi Tomomi , Kosho Tomoki , Igawa Ken
Published: November 2022

Background: Vascular-type Ehlers–Danlos syndrome (vEDS) is an autosomal dominant inherited disorder caused by a deficit in collagen III as a result of heterogeneous mutations in the α1 type III collagen gene (COL3A1). Patients with vEDS often experience the first major complications in their early 20s and >80% have at least one complication by their 40s, reducing their average life expectancy to 48 years. Most commonly, vEDS variants are heterozygous missense substitutions of a base-pair encoding a glycine (Gly) residue of the [Gly-X-Y] repeat of the COL3A1 protein. When a peptide chain derived from a mutant allele is present in the procollagen triple helical structure, the helical structure cannot be maintained. Therefore, typically, the mutated collagen peptide induces a dominant negative effect on procollagen production. We reported the case of a patient with vEDS and a unique novel duplication mutation without alteration in the [Gly-X-Y] triplet repeat sequence.

Case presentation: A 58-year-old man developed a sudden disorder of consciousness and abdominal pain and was consequently taken to a nearby hospital, where an intra-abdominal aneurysm was found, in addition to mild small joint hypermobility and acrogeria. There has been no history of spontaneous pneumothorax, dislocation, or subcutaneous hematoma. The analysis of genomic DNA from a blood sample identified a likely pathogenic in-frame duplication mutation in the COL3A1 gene coding region. Interestingly, this mutation is not expected to alter the [Gly-X-Y] triplet repeat sequence. We verified the mutation’s pathogenicity by performing an analysis of synthetic procollagen from cultured skin fibroblasts, electron microscopy, and mRNA expression analysis of unfolded protein response sensors for endoplasmic reticulum (ER) stress.

Conclusion: Although the clinical findings of the case were mild, when compared to typical vEDS, decreased α1 collagen III levels and morphological abnormalities of the collagenous bundles were observed in the patient samples when compared with the normal control samples. Our evidence supports the conclusion that this variant is pathogenic. However, unlike the common vEDS, ER stress was not observed, and the mild phenotype presentation was suggested to be due to the unique mutation, allowing the triple helical structure to be maintained to a certain extent.
Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis
Authors: Wang Yanchao , Zhou Wenjun , Chen Yan , He Dong , Qin Zhen , Wang Zhao , Liu Song , Zhou Lei , Su Jianwen , Zhang Chi
Published: November 2022

Osteoarthritis (OA) is a major cause of pain, disability, and social burden in the elderly throughout the world. Although many studies focused on the molecular mechanism of OA, its etiology remains unclear. Therefore, more biomarkers need to be explored to help early diagnosis, clinical outcome measurement, and new therapeutic target development. Our study aimed to retrieve the potential hub genes of osteoarthritis (OA) by weighted gene co-expression network analysis (WGCNA) and assess their clinical utility for predicting OA. Here, we integrated WGCNA to identify novel OA susceptibility modules and hub genes. In this study, we first selected 477 and 834 DEGs in the GSE1919 and the GSE55235 databases, respectively, from the Gene Expression Omnibus (GEO) website. Genes with p-value<0.05 and | log2FC | > 1 were included in our analysis. Then, WGCNA was conducted to build a gene co-expression network, which filtered out the most relevant modules and screened out 23 overlapping WGCNA-derived hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses elucidated that these hub genes were associated with cell adhesion molecules pathway, leukocyte activation, and inflammatory response. In addition, we conducted the protein–protein interaction (PPI) network in 23 hub genes, and the top four upregulated hub genes were sorted out (CD4, SELL, ITGB2, and CD52). Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789). After that, a single-sample gene set enrichment (ssGSEA) analysis was performed to discover immune cell infiltration in OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that those candidate genes were significantly upregulated in the OA groups compared with normal groups. We successfully constructed a co-expression network based on WGCNA and found out that OA-associated susceptibility modules and hub genes, which may provide further insight into the development of pre-symptomatic diagnosis, may contribute to understanding the molecular mechanism study of OA risk genes.
Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer’s disease
Authors: Zhang Qi , Chen Bishuang , Yang Ping , Wu Jipan , Pang Xinping , Pang Chaoyang
Published: November 2022

Alzheimer’s disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by β-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites (miRNA response elements, MREs), which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) and microRNAs (miRNAs) in Alzheimer’s disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer’s disease patients (GSE5281, GSE122603, GSE97760, GSE150693, GSE1297, and GSE161435). Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by MAPT and AP2M1, were identified by the mediation center algorithm, 34 miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs and mRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer’s disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer’s disease. Furthermore, the ncRNAs found here might become novel biomarkers and potential targets for the development of Alzheimer’s drugs.
GOLM1 is related to the inflammatory/immune nature of uveal melanoma and acts as a promising indicator for prognosis and immunotherapy response
Authors: Liang Xin , Yin Yu , Li Ning
Published: November 2022

Purpose: Inflammatory/immune-related features are associated with the immunotherapy and prognosis of uveal melanoma (UVM). In this study, we systematically analyzed the correlation between GOLM1 and the inflammatory/immune nature of UVM and explored its potential value in predicting prognosis and guiding immunotherapy for UVM patients.

Methods: A total of 143 UVM patients were enrolled in the current study. The differentially expressed genes between the GOLM1-low expression (LEXP) and GOLM1-high expression (HEXP) subgroups were calculated by the “limma” package and further annotated to reveal the key pathways by the “ClusterProfiler” package. Immunocyte infiltration was evaluated by single-sample gene set enrichment analysis, while the potential response to immunotherapy was realized by subclass mapping analysis. Moreover, tumor tissue sections from 23 UVM patients were collected and stained for GOLM1 (1:300; cat# DF8100, Affinity Biosciences), PD-L1 (1:250; cat# ab213524, Abcam), PD-1 (1:100; cat# ab52587, Abcam), CTLA-4 (1:300; cat# DF6793, Affinity Biosciences), and IFN-γ (1:300; cat# DF6045, Affinity Biosciences).

Results: We found that higher expression of GOLM1 correlated with an unfavorable prognosis in UVM patients. Multivariate Cox regression analysis suggested that GOLM1 served as a prognostic factor independent of clinicopathological parameters. Notably, we found that the expression of PD-1, PD-L1, IFN-γ, and CTLA4 was higher in the GOLM1-high subgroup than in the GOLM1-low expression subgroup at the mRNA level and was subsequently validated at the protein level by immunohistochemistry. Gene pattern and SubMap analyses confirmed the indicator role of GOLM1 in predicting immunotherapy response in UVM.

Conclusion: Taken together, GOLM1 is a novel prognostic marker, and it can be employed to predict the overall survival outcomes and treatment responses of anti-PD-1/PD-L1 and anti-CTLA4 therapies for UVM patients.
Detection and management of postpartum haemorrhage: Qualitative evidence on healthcare providers' knowledge and practices in Kenya, Nigeria, and South Africa
Authors: Akter Shahinoor , Forbes Gillian , Miller Suellen , Galadanci Hadiza , Qureshi Zahida , Fawcus Sue , Justus Hofmeyr G. , Moran Neil , Singata-Madliki Mandisa , Amole Taiwo Gboluwaga , Gwako George , Osoti Alfred , Thomas Eleanor , Gallos Ioannis , Mammoliti Kristie-Marie , Coomarasamy Arri , Althabe Fernando , Lorencatto Fabiana , Bohren Meghan A.
Published: November 2022

Background

Postpartum haemorrhage (PPH) is the leading cause of maternal death globally. Most PPH deaths can be avoided with timely detection and management; however, critical challenges persist. A multi-country cluster-randomised trial (E-MOTIVE) will introduce a clinical care bundle for early detection and first-response PPH management in hospital settings. This formative qualitative study aimed to explore healthcare providers' knowledge and practices of PPH detection and management after vaginal birth, to inform design and implementation of E-MOTIVE.

Methods

Between July 2020–June 2021, semi-structured qualitative interviews were conducted with 45 maternity healthcare providers (midwives, nurses, doctors, managers) of nine hospitals in Kenya, Nigeria, and South Africa. A thematic analysis approach was used.

Results

Four key themes were identified, which varied across contexts: in-service training on emergency obstetric care; limited knowledge about PPH; current approaches to PPH detection; and current PPH management and associated challenges. PPH was recognised as an emergency but understanding of PPH varied. Early PPH detection was limited by the subjective nature of visual estimation of blood loss. Lack of expertise on PPH detection and using visual estimation can result in delays in initiation of PPH management. Shortages of trained staff and essential resources, and late inter-hospital referrals were common barriers to PPH management.

Conclusion

There are critical needs to address context-specific barriers to early and timely detection and management of PPH in hospital settings. These findings will be used to develop evidence-informed implementation strategies, such as improved in-service training, and objective measurement of blood loss, which are key components of the E-MOTIVE trial (Trial registration: ClinicalTrials.gov: NCT04341662).
Integrated multi-omics reveals novel microbe-host lipid metabolism and immune interactions in the donkey hindgut
Authors: Li Yan , Ma Qingshan , Shi Xiaoyuan , Liu Guiqin , Wang Changfa
Published: November 2022

Evidence has shown that gut microbiota play a key role in host metabolism and health; however, little is known about the microbial community in the donkey hindgut as well as the interactions that occur between gut microbes and the host. This study aimed to explore the gut microbiome differences by analyzing the microbial community and differentially expressed genes (DEGs) related to lipid metabolism and the immune system along the donkey hindgut. The hindgut tissues (cecum, ventral colon, and dorsal colon) were separated, and the contents of each section were collected from six male donkeys for multi-omics analysis. There were significant differences in terms of dominant bacteria among the three sections, especially between the cecum and dorsal colon sites. For instance, species belonging to Prevotella and Treponema were most abundant in the cecum, while the Clostridiales_bacterium, Streptococcus_equinus, Ruminococcaceae_bacterium, etc., were more abundant in the dorsal colon. Apart from propionate, the concentrations of acetate, isobutyrate, valerate and isovalerate were all lower in the cecum than in the dorsal colon (p < 0.05). Furthermore, we identified some interesting DEGs related to lipid metabolism (e.g., ME1, MBOAT1, ACOX1, ACOX2 and LIPH) and the immune system (e.g., MUC3B, mucin-2-like, IL17RC, IL1R2, IL33, C1QA, and MMP9) between the cecum and dorsal colon and found that the PPAR pathway was mainly enriched in the cecum. Finally, we found a complex relationship between the gut microbiome and gene expression, especially with respect to the immune system, and combined with protein-protein interaction (PPI) data, suggesting that the PPAR pathway might be responsible, at least in part, for the role of the hindgut microbiota in the donkeys’ gut homeostasis. Our data provide an in-depth understanding of the interaction between the microbiota and function in the healthy equine hindgut and may also provide guidance for improving animal performance metrics (such as product quality) and equine welfare.
Evolutionary analyses of polymeric immunoglobulin receptor (pIgR) in the mammals reveals an outstanding mutation rate in the lagomorphs
Authors: Neves Fabiana , de Sousa-Pereira Patrícia , Melo-Ferreira José , Esteves Pedro J. , Pinheiro Ana
Published: November 2022

Background

The transcytosis of polymeric immunoglobulins, IgA and IgM, across the epithelial barrier to the luminal side of mucosal tissues is mediated by the polymeric immunoglobulin receptor (pIgR). At the luminal side the extracellular ligand binding region of pIgR, the secretory component (SC), is cleaved and released bound to dimeric IgA (dIgA), protecting it from proteolytic degradation, or in free form, protecting the mucosa form pathogens attacks. The pIgR was first cloned for rabbit in early 1980’s and since then has been described for all vertebrates, from fish to mammals. The existence of more than one functional pIgR alternative-spliced variant in the European rabbit, the complete pIgR as other mammals and a shorter pIgR lacking two SC exons, raised the question whether other lagomorphs share the same characteristics and how has thePIGRgene evolved in these mammals.

Results

To investigate these questions, we sequenced expressed pIgR genes for other leporid genus,Lepusspp., and obtained and aligned pIgR sequences from representative species of all mammalian orders. The obtained mammalian phylogeny, as well as the Bayesian inference of evolutionary rates and genetic distances, show that Lagomorpha pIgR is evolving at a higher substitution rate. Codon-based analyses of positive selection show that mammalian pIgR is evolving under strong positive selection, with strong incidence in the domains excised from the rabbit short pIgR isoform. We further confirmed that the hares also express the two rabbit pIgR isoforms.

Conclusions

The Lagomorpha pIgR unique evolutionary pattern may reflect a group specific adaptation. The pIgR evolution may be linked to the unusual expansion of IgA genes observed in lagomorphs, or to neofunctionalization in this group. Further studies are necessary to clarify the driving forces behind the unique lagomorph pIgR evolution.
Disruption of the HLA-E/NKG2X axis is associated with uncontrolled HIV infections
Authors: Romero-Martín Luis , Duran-Castells Clara , Olivella Mireia , Rosás-Umbert Míriam , Ruiz-Riol Marta , Sanchez Jorge , Hartigan-O´Connor Dennis , Mothe Beatriz , Olvera Àlex , Brander Christian
Published: November 2022

The contribution of the HLA-E/NKG2X axis in NK-mediated control of HIV infection remains unclear. We have studied the relationship between HLA-E expression and phenotypical as well as functional characteristics of NK cells, in the context of chronic HIV infection and in anin vitromodel of acute infection. High viremia in HIV+ individuals was related to increased HLA-E expression, and changes in NK subpopulations, especially a reduction of the CD56brightas well as an increase in adaptive NK subpopulation. Uncontrolled HIV infection was also characterized by a reversion of the NKG2A/NKG2C expression ratio and a loss of positive and negative regulation of NK mediated by HLA-E. This was reflected in a lower cytotoxic, degranulation and cytokine production capacity, especially in CD56brightand adaptive NK. In line with these results, HLA-E expression showed a positive correlation with viral growth inhibition in anin vitromodel of acute infection at day 7, which was lost after 14 days of culture. Using HLA-E expressing K562 cells, we determined that only one out of 11 described HIV-derived HLA-E epitopes increased HLA-E surface stability. In spite of that, eight of the 11 epitopes were capable of increasing degranulation and three drove differences in NK-cell mediated cell lysis or cytokine secretion. In conclusion, our results indicate that HLA-E molecules presenting HIV-derived epitopes may sensitize target cells for NK lysis in early HIV infection. However, prolonged exposure to elevated HLA-E expression levelsin vivomay lead to NK cell dysfunction and reduced viral control In chronic infection.
The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD
Authors: Astorga Jessica , Gasaly Naschla , Dubois-Camacho Karen , De la Fuente Marjorie , Landskron Glauben , Faber Klaas Nico , Urra Félix A. , Hermoso Marcela A.
Published: November 2022

Inflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for activating the inflammasome-mediated response. Mitochondrial alterations, such as reduced respiratory complex activities and reduced production of tricarboxylic acid (TCA) cycle intermediates (e.g., citric acid, fumarate, isocitric acid, malate, pyruvate, and succinate) have been described in in vitro and clinical studies. Under inflammatory conditions, mitochondrial architecture in intestinal epithelial cells is dysmorphic, with cristae destruction and high dynamin-related protein 1 (DRP1)-dependent fission. Likewise, these alterations in mitochondrial morphology and bioenergetics promote metabolic shifts towards glycolysis and down-regulation of antioxidant Nuclear erythroid 2-related factor 2 (Nrf2)/Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling. Although the mechanisms underlying the mitochondrial dysfunction during mucosal inflammation are not fully understood at present, metabolic intermediates and cholesterol may act as signals activating the NLRP3 inflammasome in IBD. Notably, dietary phytochemicals exhibit protective effects against cholesterol imbalance and mitochondrial function alterations to maintain gastrointestinal mucosal renewal in vitro and in vivo conditions. Here, we discuss the role of cholesterol and mitochondrial metabolism in IBD, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function.
Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP
Authors: Rico-Llanos Gustavo , Porras-Perales Óscar , Escalante Sandra , Vázquez-Calero Daniel B. , Valiente Lucía , Castillo María I. , Pérez-Tejeiro José Miguel , Baglietto-Vargas David , Becerra José , Reguera José María , Duran Ivan , Csukasi Fabiana
Published: November 2022

Inflammation is a central pathogenic feature of the acute respiratory distress syndrome (ARDS) in COVID-19. Previous pathologies such as diabetes, autoimmune or cardiovascular diseases become risk factors for the severe hyperinflammatory syndrome. A common feature among these risk factors is the subclinical presence of cellular stress, a finding that has gained attention after the discovery that BiP (GRP78), a master regulator of stress, participates in the SARS-CoV-2 recognition. Here, we show that BiP serum levels are higher in COVID-19 patients who present certain risk factors. Moreover, early during the infection, BiP levels predict severe pneumonia, supporting the use of BiP as a prognosis biomarker. Using a mouse model of pulmonary inflammation, we observed increased levels of cell surface BiP (cs-BiP) in leukocytes during inflammation. This corresponds with a higher number of neutrophiles, which show naturally high levels of cs-BiP, whereas alveolar macrophages show a higher than usual exposure of BiP in their cell surface. The modulation of cellular stress with the use of a clinically approved drug, 4-PBA, resulted in the amelioration of the lung hyperinflammatory response, supporting the anti-stress therapy as a valid therapeutic strategy for patients developing ARDS. Finally, we identified stress-modulated proteins that shed light into the mechanism underlying the cellular stress-inflammation network in lungs.
Differential expression of C5aR1 and C5aR2 in innate and adaptive immune cells located in early skin lesions of bullous pemphigoid patients
Authors: Emtenani Shirin , Holtsche Maike M. , Stahlkopf Richard , Seiler Daniel L. , Burn Timothy , Liu Huiqing , Parker Melissa , Yilmaz Kaan , Dikmen Hasan O. , Lang Markus Huber , Sadik Christian D. , Karsten Christian M. , van Beek Nina , Ludwig Ralf J. , Köhl Jörg , Schmidt Enno
Published: November 2022

Bullous pemphigoid (BP), the by far most frequent autoimmune subepidermal blistering disorder (AIBD), is characterized by the deposition of autoantibodies against BP180 (type XVII collagen; Col17) and BP230 as well as complement components at the dermal-epidermal junction (DEJ). The mechanisms of complement activation in BP patients, including the generation of C5a and regulation of its two cognate C5aRs, i.e., C5aR1 and C5aR2, are incompletely understood. In this study, transcriptome analysis of perilesional and non-lesional skin biopsies of BP patients compared to site-, age-, and sex-matched controls showed an upregulated expression of C5AR1, C5AR2, CR1, and C3AR1 and other complement-associated genes in perilesional BP skin. Of note, increased expressions of C5AR2 and C3AR1 were also observed in non-lesional BP skin. Subsequently, double immunofluorescence (IF) staining revealed T cells and macrophages as the dominant cellular sources of C5aR1 in early lesions of BP patients, while C5aR2 mainly expressed on mast cells and eosinophils. In addition, systemic levels of various complement factors and associated molecules were measured in BP patients and controls. Significantly higher plasma levels of C3a, CD55, and mannose-binding lectin-pathway activity were found in BP patients compared to controls. Finally, the functional relevance of C5aR1 and C5aR2 in BP was explored by two in vitro assays. Specific inhibition of C5aR1, resulted in significantly reduced migration of human neutrophils toward the chemoattractant C5a, whereas stimulation of C5aR2 showed no effect. In contrast, the selective targeting of C5aR1 and/or C5aR2 had no effect on the release of reactive oxygen species (ROS) from Col17-anti-Col17 IgG immune complex-stimulated human leukocytes. Collectively, this study delineates a complex landscape of activated complement receptors, complement factors, and related molecules in early BP skin lesions. Our results corroborate findings in mouse models of pemphigoid diseases that the C5a/C5aR1 axis is pivotal for attracting inflammatory cells to the skin and substantiate our understanding of the C5a/C5aR1 axis in human BP. The broad expression of C5aRs on multiple cell types critical for BP pathogenesis call for clinical studies targeting this axis in BP and other complement-mediated AIBDs.
Predicting non-native seaweeds global distributions: The importance of tuning individual algorithms in ensembles to obtain biologically meaningful results
Authors: Sainz-Villegas Samuel , de la Hoz Camino Fernández , Juanes José A. , Puente Araceli
Published: November 2022

Modelling non-native marine species distributions is still a challenging activity. This study aims to predict the global distribution of five widespread introduced seaweed species by focusing on two mains aspects of the ensemble modeling process: (1) Does the enforcement of less complex models (in terms of number of predictors) help in obtaining better predictions? (2) What are the implications of tuning the configuration of individual algorithms in terms of ecological realism? Regarding the first aspect, two datasets with different number of predictors were created. Regarding the second aspect, four algorithms and three configurations were tested. Models were evaluated using common evaluation metrics (AUC, TSS, Boyce index and TSS-derived sensitivity) and ecological realism. Finally, a stepwise procedure for model selection was applied to build the ensembles. Models trained with the large predictor dataset generally performed better than models trained with the reduced dataset, but with some exceptions. Regarding algorithms and configurations, Random Forest (RF) and Generalized Boosting Models (GBM) scored the highest metric values in average, even though, RF response curves were the most unrealistic and non-smooth and GBM showed overfitting for some species. Generalized Linear Models (GLM) and MAXENT, despite their lower scores, fitted smoother curves (especially at intermediate complexity levels). Reliable and biologically meaningful predictions were achieved. Inspecting the number of predictors to include in final ensembles and the selection of algorithms and its complexity have been demonstrated to be crucial for this purpose. Additionally, we highlight the importance of combining quantitative (based on multiple evaluation metrics) and qualitative (based on ecological realism) methods for selecting optimal configurations.
Diversity and metabolic potentials of microbial communities associated with pollinator and cheater fig wasps in fig-fig wasp mutualism system
Authors: Dong Yiyi , Zhang Zheng-Ren , Mishra Sandhya , Wong Adam Chun-Nin , Huang Jian-Feng , Wang Bo , Peng Yan-Qiong , Gao Jie
Published: November 2022

Microbial symbionts can influence a myriad of insect behavioral and physiological traits. However, how microbial communities may shape or be shaped by insect interactions with plants and neighboring species remains underexplored. The fig-fig wasp mutualism system offers a unique model to study the roles of microbiome in the interactions between the plants and co-habiting insects because a confined fig environment is shared by two fig wasp species, the pollinator wasp (Eupristina altissima and Eupristina verticillata) and the cheater wasp (Eupristina sp1 and Eupristina sp2). Here, we performed whole genome resequencing (WGS) on 48 individual fig wasps (Eupristina spp.) from Yunnan, China, to reveal the phylogenetic relationship and genetic divergence between pollinator and congeneric cheater wasps associated with the Ficus trees. We then extracted metagenomic sequences to explore the compositions, network structures, and functional capabilities of microbial communities associated with these wasps. We found that the cheaters and pollinators from the same fig species are sister species, which are highly genetically divergent. Fig wasps harbor diverse but stable microbial communities. Fig species dominate over the fig wasp genotype in shaping the bacterial and fungal communities. Variation in microbial communities may be partially explained by the filtering effect from fig and phylogeny of fig wasps. It is worth noting that cheaters have similar microbial communities to their sister pollinators, which may allow cheaters to coexist and gain resources from the same fig species. In terms of metabolic capabilities, some bacteria such as Desulfovibrio and Lachnospiraceae are candidates involved in the nutritional uptake of fig wasps. Our results provide novel insights into how microbiome community and metabolic functions may couple with the fig-wasp mutualistic systems.
A case report: Upper limb recovery from stroke related to SARS-CoV-2 infection during an intervention with a brain-computer interface
Authors: Carino-Escobar Ruben I. , Rodríguez-García Martín E. , Ramirez-Nava Ana G. , Quinzaños-Fresnedo Jimena , Ortega-Robles Emmanuel , Arias-Carrion Oscar , Valdés-Cristerna Raquel , Cantillo-Negrete Jessica
Published: November 2022

COVID-19 may increase the risk of acute ischemic stroke that can cause a loss of upper limb function, even in patients with low risk factors. However, only individual cases have been reported assessing different degrees of hospitalization outcomes. Therefore, outpatient recovery profiles during rehabilitation interventions are needed to better understand neuroplasticity mechanisms required for upper limb motor recovery. Here, we report the progression of physiological and clinical outcomes during upper limb rehabilitation of a 41-year-old patient, without any stroke risk factors, which presented a stroke on the same day as being diagnosed with COVID-19. The patient, who presented hemiparesis with incomplete motor recovery after conventional treatment, participated in a clinical trial consisting of an experimental brain-computer interface (BCI) therapy focused on upper limb rehabilitation during the chronic stage of stroke. Clinical and physiological features were measured throughout the intervention, including the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), the Modified Ashworth Scale (MAS), corticospinal excitability using transcranial magnetic stimulation, cortical activity with electroencephalography, and upper limb strength. After the intervention, the patient gained 8 points and 24 points of FMA-UE and ARAT, respectively, along with a reduction of one point of MAS. In addition, grip and pinch strength doubled. Corticospinal excitability of the affected hemisphere increased while it decreased in the unaffected hemisphere. Moreover, cortical activity became more pronounced in the affected hemisphere during movement intention of the paralyzed hand. Recovery was higher compared to that reported in other BCI interventions in stroke and was due to a reengagement of the primary motor cortex of the affected hemisphere during hand motor control. This suggests that patients with stroke related to COVID-19 may benefit from a BCI intervention and highlights the possibility of a significant recovery in these patients, even in the chronic stage of stroke.
The development of cortical processing of speech differs between children with cochlear implants and normal hearing and changes with parental singing
Authors: Torppa Ritva , Kuuluvainen Soila , Lipsanen Jari
Published: November 2022

Objective

The aim of the present study was to investigate speech processing development in children with normal hearing (NH) and cochlear implants (CI) groups using a multifeature event-related potential (ERP) paradigm. Singing is associated to enhanced attention and speech perception. Therefore, its connection to ERPs was investigated in the CI group.

Methods

The paradigm included five change types in a pseudoword: two easy- (duration, gap) and three difficult-to-detect (vowel, pitch, intensity) with CIs. The positive mismatch responses (pMMR), mismatch negativity (MMN), P3a and late differentiating negativity (LDN) responses of preschoolers (below 6 years 9 months) and schoolchildren (above 6 years 9 months) with NH or CIs at two time points (T1, T2) were investigated with Linear Mixed Modeling (LMM). For the CI group, the association of singing at home and ERP development was modeled with LMM.

Results

Overall, responses elicited by the easy- and difficult to detect changes differed between the CI and NH groups. Compared to the NH group, the CI group had smaller MMNs to vowel duration changes and gaps, larger P3a responses to gaps, and larger pMMRs and smaller LDNs to vowel identity changes. Preschoolers had smaller P3a responses and larger LDNs to gaps, and larger pMMRs to vowel identity changes than schoolchildren. In addition, the pMMRs to gaps increased from T1 to T2 in preschoolers. More parental singing in the CI group was associated with increasing pMMR and less parental singing with decreasing P3a amplitudes from T1 to T2.

Conclusion

The multifeature paradigm is suitable for assessing cortical speech processing development in children. In children with CIs, cortical discrimination is often reflected in pMMR and P3a responses, and in MMN and LDN responses in children with NH. Moreover, the cortical speech discrimination of children with CIs develops late, and over time and age, their speech sound change processing changes as does the processing of children with NH. Importantly, multisensory activities such as parental singing can lead to improvement in the discrimination and attention shifting toward speech changes in children with CIs. These novel results should be taken into account in future research and rehabilitation.
Non-coding RNA and n6-methyladenosine modification play crucial roles in neuropathic pain
Authors: Zhang Kexin , Li Pei , Jia Yuanyuan , Liu Ming , Jiang Jingjing
Published: November 2022

After peripheral nerve injury, pain signals are transmitted from primary sensory neurons in the dorsal root ganglion (DRG) to the central nervous system. Epigenetic modification affects neuropathic pain through alterations in the gene expression in pain-related areas and glial cell activation. Recent studies have shown that non-coding RNA and n6-methyladenosine (m6A) methylation modification play pivotal regulatory roles in the occurrence and maintenance of neuropathic pain. Dysregulation of the RNA m6A level via dynamic changes in methyltransferase and demethylase after central or peripheral nerve injury commonly regulates pain-associated genes, contributing to the induction and maintenance of neuropathic pain. The dynamic process has significant implications for the development and maintenance of neuropathic pain. However, the underlying mechanisms by which non-coding RNA and m6A RNA modification regulate neuropathic pain are not well-characterized. This article elucidates the multiple mechanisms of non-coding RNA and m6A methylation in the context of neuropathic pain, and summarizes its potential functions as well as recent advances.
Combining effect of camellia oil and squalene on hyperlipidemia-induced reproductive damage in male rats
Authors: Xu Qi , Luo Minhui , Cheng Gengjinsheng , Zhong Qi , Guo Yixing , Luo Jianghong
Published: November 2022

Introduction

Camellia oil (CO), a common edible oil in China, contains a variety of active ingredients. In this study, we explored the combining effect and optimal feeding time of CO and squalene on hyperlipemia-induced reproductive damage rats and probably provided supportive data for use of CO for health benefits.

Methods

We established the hyperlipidaemia-induced reproductive damage model, and then the successfully modeled rats were randomly classified into four groups including a model control (MC) group, a camellia oil (CO) group, a camellia oil + squalene (COS) group, and a sildenafil (SN) group, which were feeding with different subjects during days 30 and 60. The normal (NC) group was fed under the same conditions.

Results

Our results showed that compared with the MC group, the CO, COS, and SN groups could significantly decline the serum TG, TC and LDL-C levels, increase the serum testosterone levels, the sperm counts in epididymidis and organ coefficients of penises, and no pathological change in penis and testis at days 30 and 60. Compared with the pure CO, the mixture of CO and squalene could significantly enhance the effect of decreasing the concentrations of TG, TC, and LDL-C and increasing the serum testosterone level and sperm count of epididymal tail, and the results of day 30 were better than those of day 60.

Discussion

CO and squalene have a combining effect on lowering blood lipid, improving the level of testosterone and the number of epididymal tail sperm, and promoting the recovery of erectile and sexual function on hyperlipidemia-induced reproductive damage rats on day 30.