bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics, epigenetics and transgenerational transmission of obesity in children
Authors: Panera Nadia , Mandato Claudia , Crudele Annalisa , Bertrando Sara , Vajro Pietro , Alisi Anna
Published: November 2022

Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase of overweight and obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship of obesity with metabolic syndrome and several other comorbidities which do call for urgent workarounds. The usual ineffectiveness of present therapies and failure of prevention campaigns triggered overtime a number of research studies which have unveiled some relevant aspects of obesity genetic and epigenetic inheritable profiles. These findings are revealing extremely precious mainly to serve as a likely extra arrow to allow the clinician’s bow to achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy and lactation convincingly appears associated with several disorders in the offspring independently of the transmission of a purely genetic predisposition. Even the pre-conception direct exposure of either father or mother gametes to environmental factors can reprogram the epigenetic architecture of cells. Such phenomena lie behind the transfer of the obesity susceptibility to future generations through a mechanism of epigenetic inheritance. Moreover, a growing number of studies suggests that several environmental factors such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during pregnancy and the early postnatal period may play critical roles in programming childhood adipose tissue and obesity. A deeper understanding of how inherited genetics and epigenetics may generate an obesogenic environment at pediatric age might strengthen our knowledge about pathogenetic mechanisms and improve the clinical management of patients. Therefore, in this narrative review, we attempt to provide a general overview of the contribution of heritable genetic and epigenetic patterns to the obesity susceptibility in children, placing a particular emphasis on the mother-child dyad.
Screening of osteoporosis and sarcopenia in individuals aged 50 years and older at different altitudes in Yunnan province: Protocol of a longitudinal cohort study
Authors: Liu Xingli , Ma Cunwen , Wang Shiping , Liang Zhengrong , Yang Juntao , Zhou Jun , Shu Yi , He Zhengying , Zong Jilong , Wu Lizhi , Peng Peiqian , Su Yi , Gao Meng , Shen Kaiming , Zhao Hong , Ruan Jilu , Ji Shaoxuan , Yang Yunhui , Tang Taisong , Yang Zongfa , Luo Guangyin , Zeng Meng , Zhang Weiwan , He Bo , Cheng Xiaoguang , Wang Gang , Wang Ling , Lyu Liang
Published: November 2022

Introduction

Musculoskeletal system gradually degenerates with aging, and a hypoxia environment at a high altitude may accelerate this process. However, the comprehensive effects of high-altitude environments on bones and muscles remain unclear. This study aims to compare the differences in bones and muscles at different altitudes, and to explore the mechanism and influencing factors of the high-altitude environment on the skeletal muscle system.

Methods

This is a prospective, multicenter, cohort study, which will recruit a total of 4000 participants over 50 years from 12 research centers with different altitudes (50m~3500m). The study will consist of a baseline assessment and a 5-year follow-up. Participants will undergo assessments of demographic information, anthropomorphic measures, self-reported questionnaires, handgrip muscle strength assessment (HGS), short physical performance battery (SPPB), blood sample analysis, and imaging assessments (QCT and/or DXA, US) within a time frame of 3 days after inclusion. A 5-year follow-up will be conducted to evaluate the changes in muscle size, density, and fat infiltration in different muscles; the muscle function impairment; the decrease in BMD; and the osteoporotic fracture incidence. Statistical analyses will be used to compare the research results between different altitudes. Multiple linear, logistic regression and classification tree analyses will be conducted to calculate the effects of various factors (e.g., altitude, age, and physical activity) on the skeletal muscle system in a high-altitude environment. Finally, a provisional cut-off point for the diagnosis of sarcopenia in adults at different altitudes will be calculated.

Ethics and dissemination

The study has been approved by the institutional research ethics committee of each study center (main center number: KHLL2021-KY056). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.

Clinical Trial registration number

http://www.chictr.org.cn/index.aspx, identifier ChiCTR2100052153.
Genetic regulation of THBS1 methylation in diabetic retinopathy
Authors: Li Yaqi , Gong Chunmei , Xu Yuanfei , Liang Xiongshun , Chen Xiaoping , Hong Wenxu , Yan Junxia
Published: November 2022

Background

Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes mellitus (DM), but its pathological mechanism, especially the formation mechanism of new blood vessels remains unclear. Thrombospondin-1 (THBS1) is a potent endogenous inhibitor of angiogenesis and it was found over expressed in DR in our previous study. Our study aimed to determine whether overexpression of THBS1 is associated with its promoter methylation level, and whether methylation of THBS1 is regulated by genetic variants in DR.

Methods

Patients diagnosed with DR and DM patients without retinal problems were included in the case-control study. DNA methylation detection of THBS1 by bisulfite sequencing and genotyping of specific SNPs by MassARRAY analysis were performed in the patients recruited from 2019-2020. Real time quantitative PCR was performed to obtain mRNA expression of THBS1 in the patients recruited from August to October 2022. The differentially methylated CpG loci of THBS1 were identified by logistic regression, and associations between 13 SNPs and methylation levels of CpG loci were tested by methylation quantitative trait loci (meQTLs) analysis. Mediation analysis was applied to determine whether CpG loci were intermediate factors between meQTLs and DR.

Results

150 patients diagnosed with DR and 150 DM patients without retinal complications were enrolled in the first recruitment, seven DR patients and seven DM patients were enrolled in the second recruitment. The patients with DR showed promoter hypomethylation of THBS1 (P value = 0.002), and six out of thirty-nine CpG sites within two CpG islands (CGIs) showed hypomethylation(P value < 0.05). THBS1 mRNA expression in peripheral blood was significantly higher in DR patients than in DM patients. Five out of thirteen cis-meQTLs were identified to be associated with CpG sites: rs13329154, rs34973764 and rs5812091 were associated with cis-meQTLs of CpG-4 (P value=0.0145, 0.0095, 0.0158), rs11070177 and rs1847663 were associated with cis-meQTLs of CpG-2 and CpG-3 respectively (P value=0.0201, 0.0275). CpG-4 methylation significantly mediated the effect of the polymorphism rs34973764 on DR (B=0.0535, Boot 95%CI: 0.004~0.1336).

Conclusion

THBS1 overexpression is related to THBS1 hypomethylation in patients with DR. DNA methylation may be genetically controlled in DR.
Low carbon and economic dispatching of electric-gas integrated energy system with liquid storage carbon capture equipment
Authors: Hu Yang , Tang Ye , Wang Kaiyan , Yang Xiaoping
Published: November 2022

Because of the coupling of CO2 absorption and treatment, conventional carbon capture power plants lack the flexibility of power plant operation. This paper provides a liquid storage carbon capture power plant (LSCCPP) with solution storage, analyzes the “energy time-shift” features of the solution storage, and creates a joint operating model of the LSCCPP and Power to Gas(P2G) based on this. Taking into account the carbon market trading mechanism, this paper develops a low-carbon economic dispatch model for an integrated electric-gas energy system with the LSCCPP, with the goal of achieving the lowest overall system cost. Moreover, the proposed dispatch model is solved by transforming the model into a mixed-integer linear programing problem and calling CPLEX. Finally, a modified example system is used to demonstrate the validity of the proposed model. The results show that the suggested low-carbon dispatch model has a significant reference for enhancing the system’s use of wind power and accomplishing the low-carbon efficient functioning of the integrated electric-gas energy system.
PAS-based isotopologic analysis of highly concentrated methane
Authors: Bahr Marc-Simon , Wolff Marcus
Published: November 2022

Photoacoustic spectroscopy (PAS) is typically used for the detection of trace gases. In this way, mixtures of short-chain hydrocarbons such as methane, ethane or propane can be analyzed with detection limits in the range of parts per million (ppm) or parts per billion (ppb) or even below. However, there are a number of applications where highly concentrated mixtures need to be analyzed. In some cases even the isotopologic composition of certain hydrocarbons needs to be determined. Examples can be found in natural gas production and planetary research. We present PAS-based isotopologic analyses of two digit percentage-level methane concentrations in nitrogen. The investigation allows conclusions to be drawn about the extent to which PAS is suitable for an isotopologic analysis of undiluted natural gas-like mixtures.
Identification of immune-related signature for the prognosis and benefit of immunotherapy in triple-negative breast cancer
Authors: Sun Xiaorui , Zhang Tiansong
Published: November 2022

Background: There is a lack of biomarkers for predicting the efficacy of immunotherapy in triple-negative breast cancer (TNBC). Hence, we constructed an immune risk score (IRS) model to predict the prognosis of patients with TNBC and evaluate those who are sensitive to immunotherapy.

Methods: The ribonucleic acid (RNA) sequencing data, mutation data, and clinical information of TNBC patients were obtained from The Cancer Genome Atlas database. Data of immune-related genes were obtained from the Import and InnateDB databases. The IRS model was constructed using univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, and the predictive ability of the prognostic model was evaluated. Further external validation was performed using the Gene Expression Omnibus (GEO) databases GSE58812 and GSE135565. Data on the clinical characteristics, immune landscape, and immune checkpoint inhibitors used in different risk groups were analyzed. Finally, the drug sensitivity of the patients in the high- and low-risk groups was predicted.

Results: The prognostic risk score model comprised six genes: HSPA6, LCN1, ARTN, IL36G, BCL2A1, and CASP12. The area under the curve values at 1 year, 3 years, and 5 years were 0.835, 0.852, and 0.843, respectively, indicating that the model has a good potential for predicting the long-term survival of TNBC patients, which is consistent with the results of the GEO cohort. Compared with the high-risk group, the low-risk group had a better prognosis; more abundant immune-activated cell infiltrates, such as CD8+ T cells and CD4 memory-activated T cells, and a higher enrichment of immune-related signaling pathways, such as the cytokine receptor interaction, nucleotide oligomerization domain-like receptor signal pathway, T-cell receptor signal pathway, and B-cell receptor signaling pathway, were observed. In addition, the immune checkpoint encoding genes, such as CD274, CTLA4, PDCD1, and PDCD1LG2 were highly expressed in the low-risk group, which showed that this group was more likely to benefit from immunotherapy.

Conclusion: A new IRS gene feature was established to predict the patients’ prognosis and guide immunotherapy. Moreover, it was revealed that several potential therapeutic drugs can be used in high-risk patients who are unresponsive to immunotherapy.
Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages
Authors: Mendez-Cortina Yorjagis , Rodriguez-Perea Ana Lucía , Chvatal-Medina Mateo , Lopera Tulio Jose , Alvarez-Mesa Natalia , Rodas-Marín Jan Karlo , Moncada Diana Carolina , Rugeles Maria Teresa , Velilla Paula Andrea
Published: November 2022

Background

The COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up.

Methods

A cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively.

Results

Older age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts.

Conclusion

The humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.
Case report: Novel FHR2 variants in atypical Hemolytic Uremic Syndrome: A case study of a translational medicine approach in renal transplantation
Authors: Stea Emma Diletta , Skerka Christine , Accetturo Matteo , Pesce Francesco , Wiech Thorsten , Hartman Andrea , Pontrelli Paola , Conserva Francesca , Castellano Giuseppe , Zipfel Peter F. , Gesualdo Loreto
Published: November 2022

Atypical hemolytic–uremic syndrome (aHUS) is a severe thrombotic microangiopathy in which kidney involvement is common. aHUS can be due to either genetic or acquired abnormalities, with most abnormalities affecting the alternative complement pathway. Several genetic factors/alterations can drive the clinical presentation, therapeutic response, and risk of recurrence, especially recurrence following kidney transplantation. We report here the case of a 22-year-old man who developed a severe form of aHUS. Renal biopsy revealed thrombotic microangiopathy and features of chronic renal damage. Despite two eculizumab infusions, the patient remained dialysis dependent. Two novel rare variants, c.109G>A (p.E37K) and c.159 C>A (p.Y53*), were identified in the factor H-related 2 (FHR2) gene, and western blot analysis revealed a significant reduction in the level of FHR2 protein in the patient’s serum. Although FHR2 involvement in complement 3 glomerulopathy has been reported previously, a role for FRH2 as a complement modulator has not yet been definitively shown. In addition, no cases of aHUS in individuals with FHR2 variants have been reported. Given the role of FHRs in the complement system and the fact that this patient was a candidate for a kidney transplant, we studied the relevance of low FHR2 plasma levels through a set of functional in vitro assays. The aim of our work was to determine if low FHR2 plasma levels could influence complement control at the endothelial surface with a view to identifying a therapeutic approach tailored to this specific patient. Interestingly, we observed that low FHR2 levels in the patient’s serum could induce complement activation, as well as C5b–9 deposition on human endothelial cells, and affected cell morphology. As C5b–9 deposition is a prerequisite for endothelial cell damage, these results suggest that extremely low FHR2 plasma levels increase the risk of aHUS. Given their ability to reduce C5b–9 deposition, recombinant FHR2 and eculizumab were tested in vitro and found to inhibit hemolysis and endothelial cell surface damage. Both molecules showed effective and comparable profiles. Based on these results, the patient underwent a kidney transplant, and received eculizumab as induction and maintenance therapy. Five years after transplantation, the patient remains in good general health, with stable graft function and no evidence of disease recurrence. To our knowledge, this is first reported case of an aHUS patient carrying FHR2 mutations and provides an example of a translational therapeutic approach in kidney transplantation.
Analysis of herpesvirus infection and genome single nucleotide polymorphism risk factors in multiple sclerosis, Volga federal district, Russia
Authors: Lezhnyova Vera , Davidyuk Yuriy , Mullakhmetova Asia , Markelova Maria , Zakharov Alexander , Khaiboullina Svetlana , Martynova Ekaterina
Published: November 2022

Multiple sclerosis (MS) is a heterogeneous disease where herpesvirus infection and genetic predisposition are identified as the most consistent risk factors. Serum and blood samples were collected from 151 MS and 70 controls and used to analyze circulating antibodies for, and DNA of, Epstein Barr virus (EBV), human cytomegalovirus (HCMV), human herpes virus 6 (HHV6), and varicella zoster virus (VZV). The frequency of selected single nucleotide polymorphisms (SNPs) in MS and controls were studied. Herpesvirus DNA in blood samples were analyzed using qPCR. Anti-herpesvirus antibodies were detected by ELISA. SNPs were analyzed by the allele-specific PCR. For statistical analysis, Fisher exact test, odds ratio and Kruskall–Wallis test were used; p<0.05 values were considered as significant. We have found an association between circulating anti-HHV6 antibodies and MS diagnosis. We also confirmed higher frequency of A and C alleles in rs2300747 and rs12044852 of CD58 gene and G allele in rs929230 of CD6 gene in MS as compared to controls. Fatigue symptom was linked to AC and AA genotype in rs12044852 of CD58 gene. An interesting observation was finding higher frequency of GG genotype in rs12722489 of IL2RA and T allele in rs1535045 of CD40 genes in patient having anti-HHV6 antibodies. A link was found between having anti-VZV antibodies in MS and CC genotype in rs1883832 of CD40 gene.
A novel cuproptosis-related lncRNA signature predicts the prognosis and immune landscape in bladder cancer
Authors: Bai Yuchen , Zhang Qi , Liu Feng , Quan Jing
Published: November 2022

Background

Bladder cancer (BLCA) is one of the deadliest diseases, with over 550,000 new cases and 170,000 deaths globally every year. Cuproptosis is a copper-triggered programmed cell death and is associated with the prognosis and immune response of various cancers. Long non-coding RNA (lncRNA) could serve as a prognostic biomarker and is involved in the progression of BLCA.

Methods

The gene expression profile of cuproptosis-related lncRNAs was analyzed by using data from The Cancer Genome Atlas. Cox regression analysis and least absolute shrinkage and selection operator analysis were performed to construct a cuproptosis-related lncRNA prognostic signature. The predictive performance of this signature was verified by ROC curves and a nomogram. We also explored the difference in immune-related activity, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and drug sensitivity between the high- and low-risk groups.

Results

We successfully constructed a cuproptosis-related lncRNA prognostic signature for BLCA including eight lncRNAs (RNF139-AS1, LINC00996, NR2F2-AS1, AL590428.1, SEC24B-AS1, AC006566.1, UBE2Q1-AS1, and AL021978.1). Multivariate Cox analysis suggested that age, clinical stage, and risk score were the independent risk factors for predicting prognosis of BLCA. Further analysis revealed that this signature not only had higher diagnostic efficiency compared to other clinical features but also had a good performance in predicting the 1-year, 3-year, and 5-year overall survival rate in BLCA. Notably, BLCA patients with a low risk score seemed to be associated with an inflamed tumor immune microenvironment and had a higher TMB level than those with a high risk score. In addition, patients with a high risk score had a higher TIDE score and a higher half maximal inhibitory concentration value of many therapeutic drugs than those with a low risk score.

Conclusion

We identified a novel cuproptosis-related lncRNA signature that could predict the prognosis and immune landscape of BLCA.
Immunomodulatory effects of two recombinant arginine kinases in Sarcoptes Scabiei on host peripheral blood mononuclear cells
Authors: Xu Yanting , Xu Ziyi , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou
Published: November 2022

Background

As an important zoonotic parasitic disease with global distribution, scabies causes serious public health and economic problems. Arginine kinase (AK) is involved in cell signal transduction, inflammation, and apoptosis. Two AKs were identified in Sarcoptes scabiei, but their functions in the host immune response remain unclear.

Methods

rSsAK-1 and rSsAK-2 were expressed, purified, and immunolocalized. The effects of rSsAK-1 and rSsAK-2 on rabbit PBMC proliferation, apoptosis, and migration; Bcl-2, Bcl-xl, Fas, Bax, and NF-κB transcription levels; and IL-2, IFN-γ, IL-4, IL-10, TGF-β1, and IL-17 secretion were detected.

Results

rSsAK-1 and rSsAK-2 were cloned and expressed successfully. Both enzymes were ~57 kDa and contained 17-kDa tagged proteins, and had good catalytic activity and immunoreactivity. The proteins were located in the S. scabiei exoskeleton, chewing mouthparts, legs, stomach, and intestine. SsAK-1 and SsAK-2 were secreted in the pool and epidermis of the skin lesions, which may be involved in S. scabiei–host interaction. rSsAK-1 and rSsAK-2 significantly promoted cell proliferation, induced cell migration, inhibited apoptosis, and increased Bcl-2, Bcl-xl and NF-κB (p65) transcription levels concentration-dependently, and inhibited IL-2, IFN-γ, and IL-10 secretion and promoted IL-4 and IL-17 secretion.

Conclusion

rSsAK-1 and rSsAK-2 might increase Bcl-2 and Bcl-xl expression by activating the NF-κB signaling pathway to promote cell proliferation and inhibit apoptosis, which induced PBMC survival. By inducing PBMC migration to the infection site, rSsAK-1 and rSsAK-2 shifted the Th1/Th2 balance toward Th2 and changed the Th17/Treg balance, which indicated their immune role in S. scabiei allergic inflammation.
Challenges in diagnostic testing of nephritic factors
Authors: Michels Marloes A. H. M. , Volokhina Elena B. , van de Kar Nicole C. A. J. , van den Heuvel Lambertus P.W. J.
Published: November 2022

Nephritic factors (NeFs) are autoantibodies promoting the activity of the central enzymes of the complement cascade, an important first line of defense of our innate immune system. NeFs stabilize the complement convertase complexes and prevent their natural and regulator-mediated decay. They are mostly associated with rare complement-mediated kidney disorders, in particular with C3 glomerulopathy and related diseases. Although these autoantibodies were already described more than 50 years ago, measuring NeFs for diagnostic purposes remains difficult, and this also complicates our understanding of their clinical associations. In this review, we address the multifactorial challenges of NeF diagnostics. We describe the diseases NeFs are associated with, the heterogenic mechanisms of action of different NeF types, the different methods available in laboratories used for their detection, and efforts for standardization. Finally, we discuss the importance of proper NeF diagnostics for understanding the clinical impact of these autoantibodies in disease pathophysiology and for considering future complement-directed therapy.
Combinatorial depletions of G-protein coupled receptor kinases in immune cells identify pleiotropic and cell type-specific functions
Authors: Glaser Katharina M. , Tarrant Teresa K. , Lämmermann Tim
Published: November 2022

G-protein coupled receptor kinases (GRKs) participate in the regulation of chemokine receptors by mediating receptor desensitization. They can be recruited to agonist-activated G-protein coupled receptors (GPCRs) and phosphorylate their intracellular parts, which eventually blocks signal propagation and often induces receptor internalization. However, there is growing evidence that GRKs can also control cellular functions beyond GPCR regulation. Immune cells commonly express two to four members of the GRK family (GRK2, GRK3, GRK5, GRK6) simultaneously, but we have very limited knowledge about their interplay in primary immune cells. In particular, we are missing comprehensive studies comparing the role of this GRK interplay for (a) multiple GPCRs within one leukocyte type, and (b) one specific GPCR between several immune cell subsets. To address this issue, we generated mouse models of single, combinatorial and complete GRK knockouts in four primary immune cell types (neutrophils, T cells, B cells and dendritic cells) and systematically addressed the functional consequences on GPCR-controlled cell migration and tissue localization. Our study shows that combinatorial depletions of GRKs have pleiotropic and cell-type specific effects in leukocytes, many of which could not be predicted. Neutrophils lacking all four GRK family members show increased chemotactic migration responses to a wide range of GPCR ligands, whereas combinatorial GRK depletions in other immune cell types lead to pro- and anti-migratory responses. Combined depletion of GRK2 and GRK6 in T cells and B cells shows distinct functional outcomes for (a) one GPCR type in different cell types, and (b) different GPCRs in one cell type. These GPCR-type and cell-type specific effects reflect in altered lymphocyte chemotaxis in vitro and localization in vivo. Lastly, we provide evidence that complete GRK deficiency impairs dendritic cell homeostasis, which unexpectedly results from defective dendritic cell differentiation and maturation in vitro and in vivo. Together, our findings demonstrate the complexity of GRK functions in immune cells, which go beyond GPCR desensitization in specific leukocyte types. Furthermore, they highlight the need for studying GRK functions in primary immune cells to address their specific roles in each leukocyte subset.
C-Reactive Protein (CRP): A poor prognostic biomarker in COVID-19
Authors: Bouayed Mohamed Zakaria , Laaribi Ilyass , Chatar Charaf Eddine Mohammed , Benaini Iliass , Bouazzaoui Mohammed Amine , Oujidi Younes , Berrichi Samia , El Aidouni Ghizlane , Bkiyar Houssam , Abda Naima , Housni Brahim
Published: November 2022

Introduction

The COVID-19 pandemic continues to be rampant with considerable morbidity and mortality worldwide since its emergence in December 2019. Several studies have focused on identifying different predictive factors of poor prognosis, including biological markers, such as C Reactive Protein among others. The objective of our work was to determine whether the CRP levels on admission to the intensive care unit are predictive of an unfavorable evolution of patients with COVID-19 through the experience of the Anesthesia and Intensive Care Unit of the University Hospital of Oujda and to compare our results with those reported in the literature.

Methods

We conducted a retrospective, monocentric, descriptive and analytical study in the Department of Anesthesia and Intensive Care of the Mohammed VI University Hospital of Oujda, Morocco, between March 2020 and October 2021, including all critically ill patients admitted to the department during this period and meeting the inclusion criteria. The baseline admission CRP value was arbitrarily set at 100mg/d, thus conditioning the division of our patients into two groups (group 1: CRP < 100mg/L, group 2: CRP ≥ 100mg/L).

Results

Among our 1035 included patients, 291 patients with had a CRP<100mlg/L (group 1) and 744 presented a CRP level equal or superior to 100mg/L (group 2). Lung parenchymal involvement was more severe or even critical (CT involvement > 75%) in group 2 (60.8%) compared to group 1 (39.2%). In group 2, 79.8% of patients were mechanically ventilated, compared to 20.2% of patients in group 1. Finally, the mortality rate in patients with a CRP ≥ 100mg/l was 77.4%, compared with 22.6% for patients with a CRP < 100mg/l. These findings are all statistically highly significant (p<0.001)

Conclusion

Given the high contagiousness of the virus and the emergence of several variants, the management of the COVID-19 pandemic has focused more on prevention through vaccination against the virus, but also on an early identification of patients likely to evolve unfavorably for a personalized management.
The mitochondrial gene-CMPK2 functions as a rheostat for macrophage homeostasis
Authors: Arumugam Prabhakar , Chauhan Meghna , Rajeev Thejaswitha , Chakraborty Rahul , Bisht Kanika , Madan Mahima , Shankaran Deepthi , Ramalingam Sivaprakash , Gandotra Sheetal , Rao Vivek
Published: November 2022

In addition to their role in cellular energy production, mitochondria are increasingly recognized as regulators of the innate immune response of phagocytes. Here, we demonstrate that altering expression levels of the mitochondria-associated enzyme, cytidine monophosphate kinase 2 (CMPK2), disrupts mitochondrial physiology and significantly deregulates the resting immune homeostasis of macrophages. Both CMPK2 silenced and constitutively overexpressing macrophage lines portray mitochondrial stress with marked depolarization of their membrane potential, enhanced reactive oxygen species (ROS), and disturbed architecture culminating in the enhanced expression of the pro-inflammatory genes IL1β, TNFα, and IL8. Interestingly, the long-term modulation of CMPK2 expression resulted in an increased glycolytic flux of macrophages akin to the altered physiological state of activated M1 macrophages. While infection-induced inflammation for restricting pathogens is regulated, our observation of a total dysregulation of basal inflammation by bidirectional alteration of CMPK2 expression only highlights the critical role of this gene in mitochondria-mediated control of inflammation.
Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions
Authors: Yedigaryan Laura , Martínez-Sarrà Ester , Giacomazzi Giorgia , Giarratana Nefele , van der Veer Bernard K. , Rotini Alessio , Querceto Silvia , Grosemans Hanne , Cortés-Calabuig Álvaro , Salucci Sara , Battistelli Michela , Falcieri Elisabetta , Gijsbers Rik , Quattrocelli Mattia , Peng Koh Kian , De Waele Liesbeth , Buyse Gunnar M. , Derua Rita , Sampaolesi Maurilio
Published: November 2022

Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo, and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength, cross-sectional area, and fibrosis compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells.
Aquaculture over-optimism?
Authors: Sumaila U. Rashid , Pierruci Andrea , Oyinlola Muhammed A. , Cannas Rita , Froese Rainer , Glaser Sarah , Jacquet Jennifer , Kaiser Brooks A. , Issifu Ibrahim , Micheli Fiorenza , Naylor Rosamond , Pauly Daniel
Published: November 2022

The recent rapid growth in aquaculture production reported by the United Nations Food and Agriculture Organization may have inadvertently generated what we denote here as aquaculture over-optimism. An extreme form of this is the notion that we need not worry about sustaining wild fish stocks because we can meet the global need through farming. Here we investigate whether the recent growth in aquaculture production can be maintained, and we compare aquaculture production projections with the future need for fish to find out whether aquaculture over-optimism can be justified. We show relevant evidence suggesting that aquaculture growth rates in all the cases studied have already reached their peak and have begun declining. Also, our results indicate that without wild fish, the world will face a fish food shortage of about 71 million tonnes annually by 2030, and the aquaculture production growth rate would have to be 3 times current average projected production by the FAO, the World Bank and the OECD in 2030. Finally, the current geographical distribution of farmed fish production suggests that even if aquaculture over-optimism is physically, economically, technically and ecologically feasible, its socio-economic cost to low-income coastal countries could be devastating.
Advanced development and mechanism of sepsis-related acute respiratory distress syndrome
Authors: Gong Huankai , Chen Yao , Chen Meiling , Li Jiankang , Zhang Hong , Yan Shijiao , Lv Chuanzhu
Published: November 2022

The introduction of the Sepsis 3.0 guidelines in 2016 improved our understanding of sepsis diagnosis and therapy. Personalized treatment strategies and nursing methods for sepsis patients are recommended in the “Save Sepsis Campaign” in 2021. However, mortality in sepsis patients remains high. Patients with sepsis-related acute respiratory distress syndrome account for around 30% of them, with fatality rates ranging from 30 to 40%. Pathological specimens from individuals with sepsis-related ARDS frequently demonstrate widespread alveolar damage, and investigations have revealed that pulmonary epithelial and pulmonary endothelial injury is the underlying cause. As a result, the purpose of this work is to evaluate the mechanism and research progress of pulmonary epithelial and pulmonary endothelial damage in sepsis-related ARDS, which may provide new directions for future research, diagnosis, and therapy.
The effect of a spontaneous induction prophage, phi458, on biofilm formation and virulence in avian pathogenic Escherichia coli
Authors: Li Dezhi , Liang Wei , Hu Qingyue , Ren Jianluan , Xue Feng , Liu Qing , Tang Fang
Published: November 2022

Prophage sequences are present in most bacterial genomes and account for up to 20% of its host genome. Integration of temperate phages may have an impact on the expression of host genes, while some prophages could turn into the lytic cycle and affect bacterial host biological characteristics. We investigated the role of spontaneous induction prophages in avian pathogenic Escherichia coli (APEC), which is the causative agent of avian colibacillosis in poultry, and considered a potential zoonotic bacterium related to the fact it serves as an armory of extraintestinal pathogenic E. coli. We found that APEC strain DE458 had a high spontaneous induction rate in vivo and in vitro. The released phage particles, phi458, were isolated, purified, and sequenced, and the deletion mutant, DE458Δphi458, was constructed and characterized. Biofilm formation of DE458Δphi458 was strongly decreased compared to that of the wild-type strain (p < 0.01). In addition, while the addition of DNase (100 μg/ml) did not affect prophage release but could digest eDNA, it significantly reduced the biofilm production of DE458 biofilm to a level close to that of DE458Δphi458. Compared to DE458, the adhesion and invasion abilities of DE458Δphi458 increased by approximately 6–20 times (p < 0.05). The virulence of DE458Δphi458 was enhanced by approximately 10-fold in chickens based on a 50% lethal dose. Furthermore, avian infection assays showed that the bacterial loads of DE458Δphi458 in the lung and liver were increased by 16.5- and 10-fold (p < 0.05), respectively, compared with those of the WT strain. The qRT-PCR revealed that deletion of phi458 led to upregulation of type I fimbriate-related gene fimH and curli-related gene csgC by 3- and 2.8-fold, respectively (p < 0.01). Our study revealed that phi458 promoted biofilm formation by spontaneously inducing and decreasing virulence by repressing virulence genes.
Discovery and biosynthesis of macrophasetins from the plant pathogen fungus Macrophomina phaseolina
Authors: Yu Cui , Chen Lin , Gao Yang Le , Liu Jia , Li Pei Lin , Zhang Ming Liang , Li Qin , Zhang Huai Dong , Tang Man Cheng , Li Li
Published: November 2022

3-Decalinoyltetramic acids (DTAs) are a class of natural products with chemical diversity and potent bioactivities. In fungal species there is a general biosynthetic route to synthesize this type of compounds, which usually features a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) and a lipocalin-like Diels-Alderase (LLDAse). Using a synthetic biology approach, combining the bioinformatics analysis prediction and heterologous expression, we mined a PKS-NRPS and LLDAse encoding gene cluster from the plant pathogenic fungus Macrophomina phaseolina and characterized the cluster to be responsible for the biosynthesis of novel DTAs, macrophasetins. In addition, we investigated the biosynthesis of these compounds and validated the accuracy of the phylogeny-guided bioinformatics analysis prediction. Our results provided a proof of concept example to this approach, which may facilitate the discovery of novel DTAs from the fungal kingdom.
Identification of microRNA editing sites in three subtypes of leukemia
Authors: Xie Wenping , Yang Jun , Zhou Nan , Ding Hao , Zhou Guangchen , Wu Shuai , Guo Shiyong , Li Wanran , Zhang Lei , Yang Huaide , Mao Chunyi , Zheng Yun
Published: November 2022

Leukemia is an aberrant hyper-proliferation of immature blood cells that do not form solid tumors. The transcriptomes of microRNAs (miRNAs) of leukemia have been intensively explored. However, miRNA editing of leukemia has not been extensively studied. To identify miRNA editing patterns and explore their functional relevance in leukemia, we analyzed 200 small RNA sequencing profiles of three subtypes of leukemia and identified hundreds of miRNA editing sites in three subtypes of leukemia. Then, we compared the editing levels of identified miRNA editing sites in leukemia and normal controls. Many miRNAs were differential edited in different subtypes of leukemia. We also found the editing levels of 3′-A editing sites of hsa-mir-21-5p and hsa-mir-155-5p decreased in chronic lymphocytic leukemia patients with radiation treatments. By integrating PAR-CLIP sequencing profiles, we predicted the targets of original and edited miRNAs. One of the edited miRNA, hsa-let-7b_5c, with an additional cytosine at 5′ end of hsa-let-7b-5p, potentially targeted VBP1 and CTDSP1. CTDSP1 was significantly downregulated in T-ALL compared to normal controls, which might be originated from the hyperediting of hsa-let-7b-5p in T-ALL. Our study provides a comprehensive view of miRNA editing in three different subtypes of leukemia.
Frontal aslant tract in the non-dominant hemisphere: A systematic review of anatomy, functions, and surgical applications
Authors: Gallet Clémentine , Clavreul Anne , Bernard Florian , Menei Philippe , Lemée Jean-Michel
Published: November 2022

Knowledge of both the spatial organization and functions of white-matter fiber tracts is steadily increasing. We report here the anatomy and functions of the frontal aslant tract (FAT) in the non-dominant hemisphere (usually the right hemisphere). Despite the structural symmetry between the right and left FAT, these two tracts seem to display functional asymmetry, with several brain functions in common, but others, such as visuospatial and social cognition, music processing, shifting attention or working memory, more exclusively associated with the right FAT. Further studies are required to determine whether damage to the right FAT causes permanent cognitive impairment. Such studies will constitute the best means of testing whether this tract is a critical pathway that must be taken into account during neurosurgical procedures and the essential tasks to be incorporated into intraoperative monitoring during awake craniotomy.
Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination
Authors: Fekete Christopher D. , Nishiyama Akiko
Published: November 2022

Myelination is critical for fast saltatory conduction of action potentials. Recent studies have revealed that myelin is not a static structure as previously considered but continues to be made and remodeled throughout adulthood in tune with the network requirement. Synthesis of new myelin requires turning on the switch in oligodendrocytes (OL) to initiate the myelination program that includes synthesis and transport of macromolecules needed for myelin production as well as the metabolic and other cellular functions needed to support this process. A significant amount of information is available regarding the individual intrinsic and extrinsic signals that promote OL commitment, expansion, terminal differentiation, and myelination. However, it is less clear how these signals are made available to OL lineage cells when needed, and how multiple signals are integrated to generate the correct amount of myelin that is needed in a given neural network state. Here we review the pleiotropic effects of some of the extracellular signals that affect myelination and discuss the cellular processes used by the source cells that contribute to the variation in the temporal and spatial availability of the signals, and how the recipient OL lineage cells might integrate the multiple signals presented to them in a manner dialed to the strength of the input.
Inter-muscular networks of synchronous muscle fiber activation
Authors: Garcia-Retortillo Sergi , Ivanov Plamen Ch.
Published: November 2022

Skeletal muscles continuously coordinate to facilitate a wide range of movements. Muscle fiber composition and timing of activation account for distinct muscle functions and dynamics necessary to fine tune muscle coordination and generate movements. Here we address the fundamental question of how distinct muscle fiber types dynamically synchronize and integrate as a network across muscles with different functions. We uncover that physiological states are characterized by unique inter-muscular network of muscle fiber cross-frequency interactions with hierarchical organization of distinct sub-networks and modules, and a stratification profile of links strength specific for each state. We establish how this network reorganizes with transition from rest to exercise and fatigue—a complex process where network modules follow distinct phase-space trajectories reflecting their functional role in movements and adaptation to fatigue. This opens a new area of research, Network Physiology of Exercise, leading to novel network-based biomarkers of health, fitness and clinical conditions.
Kinetics and durability of transgene expression after intrastriatal injection of AAV9 vectors
Authors: Hollidge Bradley S. , Carroll Hayley B. , Qian Randolph , Fuller Madison L. , Giles April R. , Mercer Andrew C. , Danos Olivier , Liu Ye , Bruder Joseph T. , Smith Jared B.
Published: November 2022

Understanding the kinetics and durability of AAV-mediated transgene expression in the brain is essential for conducting basic neuroscience studies as well as for developing gene therapy approaches for CNS diseases. Here, we characterize and compare the temporal profile of transgene expression after bilateral injections into the mouse striatum of rAAV9 encoding GFP under the control of either a ubiquitous promoter (CAG), or the neuron-specific human synapsin (hSyn) and CamKII promoters. GFP protein expression with the CAG promoter was highest at 3 weeks, and then decreased to stable levels at 3 and 6 months. Surprisingly, GFP mRNA levels continued to increase from 3 weeks to 3 months, despite GFP protein expression decreasing during this time. GFP protein expression with hSyn increased more slowly, reaching a maximum at 3 months, which was equivalent to protein expression levels from CAG at that time point. Importantly, transgene expression driven by the hSyn promoter at 6 months was not silenced as previously reported, and GFP mRNA was continuing to rise even at the final 6-month time point. Thus, hSyn as a promoter for transgene expression demonstrates long-term durability but may require more time after vector administration to achieve steady-state levels. Because CAG had the highest GFP protein expression in our comparison, which was at 3 weeks post administration, the early kinetics of transgene expression from CAG was examined (1, 2, 5, and 10 days after injection). This analysis showed that GFP protein expression and GFP mRNA increased during the first 3 weeks after administration. Interestingly, vector DNA rapidly decreased 10-fold over the first 3 weeks following injection as it assembled into stable circular episomes and concatemers. Surprisingly, the processing of vector genomes into circular episomes and concatemers was continually dynamic up to 3 months after injection. These results provide novel insight into the dynamic processing of vector genomes and promoter-specific temporal patterns of transgene expression in the brain.
Animal models of developmental dyslexia
Authors: Galaburda Albert M.
Published: November 2022

As some critics have stated, the term “developmental dyslexia” refers to a strictly human disorder, relating to a strictly human capacity – reading – so it cannot be modeled in experimental animals, much less so in lowly rodents. However, two endophenotypes associated with developmental dyslexia are eminently suitable for animal modeling: Cerebral Lateralization, as illustrated by the association between dyslexia and non-righthandedness, and Cerebrocortical Dysfunction, as illustrated by the described abnormal structural anatomy and/or physiology and functional imaging of the dyslexic cerebral cortex. This paper will provide a brief review of these two endophenotypes in human beings with developmental dyslexia and will describe the animal work done in my laboratory and that of others to try to shed light on the etiology of and neural mechanisms underlying developmental dyslexia. Some thought will also be given to future directions of the research.