bluuebunny/crossref_metadata_2025 huggingface dataset:
Etiology of end-stage liver cirrhosis impacts hepatic natural killer cell heterogenicity
Authors: Maretti-Mira Ana C. , Salomon Matthew P. , Hsu Angela M. , Dara Lily , Golden-Mason Lucy
Published: March 2023

The natural killer (NK) cell population is a critical component of the innate immune compartment of the liver, and its functions are deeply affected by the surrounding environment. In the late stage of fibrosis, NK cells become dysfunctional, but the influence of disease etiology on NK cell behavior during cirrhosis remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterized the hepatic NK cells from end-stage cirrhotic livers from subjects with non-alcoholic steatohepatitis (NASH), chronic hepatitis C infection (HCV) and primary sclerosing cholangitis (PSC). Here, we show that although NK cells shared similar dysfunctions, the disease etiology impacts hepatic NK cell heterogeneity. Therapeutical strategies targeting NK cells for the prevention or treatment of fibrosis should consider liver disease etiology in their design.
Development of a dual vaccine against East Coast fever and lumpy skin disease
Authors: Whittle Leah , Chapman Ros , Douglass Nicola , Jaffer Mohamed , Margolin Emmanuel , Rybicki Edward , Williamson Anna-Lise
Published: March 2023

East Coast fever is an acute bovine disease caused by the apicomplexan parasite Theileria parva and is regarded as one of the most important tick-vectored diseases in Africa. The current vaccination procedure has many drawbacks, as it involves the use of live T. parva sporozoites. As a novel vaccination strategy, we have constructed the recombinant lumpy skin disease virus (LSDV) named LSDV-SODis-p67HA-BLV-Gag, encoding a modified form of the T. parva p67 surface antigen (p67HA), as well as the bovine leukemia virus (BLV) gag gene for the formation of virus-like particles (VLPs) to potentially enhance p67 immunogenicity. In place of the native sequence, the chimeric p67HA antigen has the human tissue plasminogen activator signal sequence and the influenza hemagglutinin A2 transmembrane domain and cytoplasmic tail. p67HA was detected on the surface of infected cells, and VLPs comprising BLV Gag and p67HA were produced. We also show that higher multiple bands observed in western blot analysis are due to glycosylation of p67. The two vaccines, pMExT-p67HA (DNA) and LSDV-SODis-p67HA-BLV-Gag, were tested for immunogenicity in mice. p67-binding antibodies were produced by vaccinated animals, with higher titers detected in mice vaccinated with the recombinant LSDV. This candidate dual vaccine warrants further testing in cattle.
Breakthrough infections due to SARS-CoV-2 Delta variant: relation to humoral and cellular vaccine responses
Authors: Buscot Matthieu , Cremoni Marion , Graça Daisy , Brglez Vesna , Courjon Johan , Allouche Jonathan , Teisseyre Maxime , Boyer Laurent , Barrière Jérôme , Chamorey Emmanuel , Carles Michel , Seitz-Polski Barbara
Published: March 2023

Introduction

COVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood.

Methods

Here, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease.

Results

In this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form.

Discussion

Knowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters.

Trial registration numbers

https://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.
Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization
Authors: Hou Tianzhichao , Dai Huajie , Wang Qi , Hou Yanan , Zhang Xiaoyun , Lin Hong , Wang Shuangyuan , Li Mian , Zhao Zhiyun , Lu Jieli , Xu Yu , Chen Yuhong , Gu Yanyun , Zheng Jie , Wang Tiange , Wang Weiqing , Bi Yufang , Ning Guang , Xu Min
Published: March 2023

Objectives

Our aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.

Methods

We extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.

Results

Two taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.

Conclusions

Gut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.
MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla via targeting IFIT2 in apical periodontitis
Authors: Hu Jing , Huang Xia , Zheng Liwen , Zhang Yuxin , Zeng Huan , Nie Li , Pang Xiaoxiao , Zhang Hongmei
Published: March 2023

Introduction

Periapical alveolar bone loss is the common consequence of apical periodontitis (AP) caused by persistent local inflammation around the apical area. Human stem cells from apical papilla (hSCAPs) play a crucial role in the restoration of bone lesions during AP. Studies have recently identified the critical role of microRNAs (miRNAs) involved in AP pathogenesis, but little is known about their function and potential molecular mechanism, especially in the osteogenesis of hSCAPs during AP. Here, we investigated the role of clinical sample-based specific miRNAs in the osteogenesis of hSCAPs.

Methods

Differential expression of miRNAs were detected in the periapical tissues of normal and patients with AP via transcriptomic analysis, and the expression of miR-199a-5p was confirmed by qRT-PCR. Treatment of hSCAPs with miR-199a-5p mimics while loaded onto beta-tricalcium phosphate (β-TCP) ceramic particle scaffold to explore its effect on osteogenesis in vivo. RNA binding protein immunoprecipitation (RIP) and Luciferase reporter assay were conducted to identify the target gene of miR-199a-5p.

Results

The expression of miR-199a-5p was decreased in the periapical tissues of AP patients, and miR-199a-5p mimics markedly enhanced cell proliferation and osteogenic differentiation of hSCAPs, while miR-199a-5p antagomir dramatically attenuated hSCAPs osteogenesis. Moreover, we identified and confirmed Interferon Induced Protein with Tetratricopeptide Repeats 2 (IFIT2) as a specific target of miR-199a-5p, and silencing endogenous IFIT2 expression alleviated the inhibitory effect of miR-199a-5p antagomir on the osteogenic differentiation of hSCAPs. Furthermore, miR-199a-5p mimics transfected hSCAPs loaded onto beta-tricalcium phosphate (β-TCP) scaffolds induced robust subcutaneous ectopic bone formation in vivo.

Discussion

These results strengthen our understanding of predictors and facilitators of the key AP miRNAs (miR-199a-5p) in bone lesion repair under periapical inflammatory conditions. And the regulatory networks will be instrumental in exploring the underlying mechanisms of AP and lay the foundation for future regenerative medicine based on dental mesenchymal stem cells.
Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines
Authors: Puri Munish , Miranda-Hernandez Socorro , Subbian Selvakumar , Kupz Andreas
Published: March 2023

Tuberculosis (TB) remains one of the most lethal infectious diseases globally. The only TB vaccine approved by the World Health Organization, Bacille Calmette-Guérin (BCG), protects children against severe and disseminated TB but provides limited protection against pulmonary TB in adults. Although several vaccine candidates have been developed to prevent TB and are undergoing preclinical and clinical testing, BCG remains the gold standard. Currently, BCG is administered as an intradermal injection, particularly in TB endemic countries. However, mounting evidence from experimental animal and human studies indicates that delivering BCG directly into the lungs provides enhanced immune responses and greater protection against TB. Inhalation therapy using handheld delivery devices is used for some diseases and allows the delivery of drugs or vaccines directly into the human respiratory tract. Whether this mode of delivery could also be applicable for live attenuated bacterial vaccines such as BCG or other TB vaccine candidates remains unknown. Here we discuss how two existing inhalation devices, the mucosal atomization device (MAD) syringe, used for influenza vaccines, and the Respimat® Soft Mist™ inhaler, used for chronic obstructive pulmonary disease (COPD) therapy, could be repurposed for mucosal delivery of live attenuated TB vaccines. We also outline the challenges and outstanding research questions that will require further investigations to ensure usefulness of respiratory delivery devices that are cost-effective and accessible to lower- and middle-income TB endemic countries.
Case report: Schnitzler-like syndrome without monoclonal gammopathy
Authors: Wesselmann Anna Sophie , Künstner Axel , Fähnrich Anke , Rose Christian , Lamprecht Peter , Busch Hauke , Ludwig Ralf J. , Recke Andreas
Published: March 2023

Schnitzler syndrome is a rare autoinflammatory disorder characterized by urticarial rash, joint pain, recurrent fever, leucocytosis, elevated C-reactive protein (CRP) and serum amyloid A (SAA), and monoclonal IgM or IgG gammopathy. According to the Strasbourg criteria, both urticarial rash and gammopathy are mandatorily required for the diagnosis of Schnitzler’s syndrome. However, incomplete variants lacking either skin symptoms or monoclonal gammopathy have also been described. Here, we report a case in which the diagnosis of Schnitzler-like syndrome was made despite the absence of gammopathy, based on neutrophilic dermal inflammation, episodic and excessive increase in inflammatory parameters, and prompt response to anakinra, a soluble IL1 receptor antagonist (sIL-1RA). In addition, we detected neutrophil epitheliotropism, which is highly suggestive of autoinflammatory disease. Using whole-exome sequencing, we were unable to find a causative pathogenic mutation but did find several mutations possibly related to the inflammatory processes in this patient. This and other cases highlight that the existing Strasbourg criteria are too strict to capture Schnitzler-like syndromes that may respond well and rapidly to IL1 inhibition. Recurrent episodes of disease with normalization of inflammatory symptoms in the interval, rapid response to anakinra, and neutrophilic epitheliotropism in a lesional skin biopsy may help confirm the diagnosis of Schnitzler-like syndrome.
Characterisation of the pro-inflammatory cytokine signature in severe COVID-19
Authors: Hawerkamp Heike C. , Dyer Adam H. , Patil Neha D. , McElheron Matt , O’Dowd Niamh , O’Doherty Laura , Mhaonaigh Aisling Ui , George Angel M. , O’Halloran Aisling M. , Reddy Conor , Kenny Rose Anne , Little Mark A. , Martin-Loeches Ignacio , Bergin Colm , Kennelly Sean P. , Donnelly Seamas C. , Bourke Nollaig M. , Long Aideen , Sui Jacklyn , Doherty Derek G. , Conlon Niall , Cheallaigh Cliona Ni , Fallon Padraic G.
Published: March 2023

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19.
Cytokine concentration in peripheral blood of patients with colorectal cancer
Authors: Li Wenchang , Chen Fangqian , Gao Han , Xu Zhuoqing , Zhou Yu , Wang Shenjie , Lv Zeping , Zhang Yuchen , Xu Zifeng , Huo Jianting , Zhao Jingkun , Zong Yaping , Feng Wenqing , Shen Xiaohui , Wu Zhiyuan , Lu Aiguo
Published: March 2023

Introduction

The role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared.

Methods

Peripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples.

Results

In peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1β, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis.

Discussion

Different types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.
Malpighian tubules of Rhodnius prolixus: More than post-prandial diuresis
Authors: Orchard Ian , Al-Dailami Areej N. , Leyria Jimena , Lange Angela B.
Published: March 2023

Rhodnius prolixus, a major vector of Chagas disease, may be considered the model upon which the foundations of insect physiology and biochemistry were built. It is an obligate blood feeder in which the blood meal triggers growth, development and reproduction. The blood meal also triggers a post-prandial diuresis to maintain osmotic homeostasis. In R. prolixus, as with other insects, the Malpighian tubules play a critical role in this diuresis, and much has been learned about diuresis in R. prolixus, and in other model insects. But the post-genomic era has brought new insights, identifying functions quite apart from diuresis for Malpighian tubules. Indeed, microarrays, transcriptomes, and proteomics have revealed the major roles that Malpighian tubules play in immunity, detoxification, pesticide resistance, and in tolerance to overall stress. This is particularly relevant to R. prolixus since gorging on blood creates several challenges in addition to osmotic balance. Xenobiotics may be present in the blood or toxins may be produced by metabolism of blood; and these must be neutralized and excreted. These processes have not been well described at the molecular level for Malpighian tubules of R. prolixus. This paper will review the involvement of Malpighian tubules in immunity and detoxification, identifying new aspects for Malpighian tubule physiology of R. prolixus by virtue of a transcriptome analysis. The transcriptome analysis indicates the potential of Malpighian tubules of R. prolixus to mount a robust innate immune response, and to contribute to antioxidant production and heme detoxification.
Moderate relative size of covered and non-covered structures of artificial reef enhances the sheltering effect on reef fish
Authors: Zhang Yue , Sun Tao , Ding Gang , Yu Daode , Yang Wei , Sun Qianzhao , Wang Xiaoling , Lin Haiying
Published: March 2023

Identifying the relationship between fish aggregations and artificial reefs (ARs) is important for optimizing reef structures and protecting marine resources subjected to external disturbance. Yet, knowledge remains limited of how the distribution of fish is affected by shelter availability provided by different AR structures. Here, we tested the effects of two structural attributes on the distribution of a benthic juvenile reef fish (fat greenling, Hexagrammos otakii). We used a laboratory mesocosm experiment with a simplified reef unit that was made of covered structure and non-covered structure. The covered structure was defined as the area inside ARs that provided effective shelter. The non-covered structure was defined as the area along the edge of ARs, which attracts fish but has lower sheltering effects. Four scenarios of two orthogonal structural attributes contained in a reef unit were implemented: size of covered structure (small shelter versus large shelter) and size of non-covered structure (small edge versus large edge), forming three size ratios of shelters to edges (low, medium, and high). The sheltering effects of the four scenarios were evaluated based on changes to the distribution patterns of fish under disturbance. We found that the reef with a large shelter had a better sheltering effect than the reef with a small shelter, but was limited by its small edge, especially when fish density was high. In contrast, the sheltering effect of the reef with a small shelter was limited by its large edge compared to the small edge. Thus, a moderate shelter-edge ratio enhanced the ability of juvenile fat greenling to elude external disturbance. Our findings highlight the importance of quantifying how the structural composition of reefs affects fish distributions, providing guidance to optimize AR structures.
Sea-level trend variability in the Mediterranean during the 1993–2019 period
Authors: Meli Matteo , Camargo Carolina M. L. , Olivieri Marco , Slangen Aimée B. A. , Romagnoli Claudia
Published: March 2023

Sea-level change is one of the most concerning climate change and global warming consequences, especially impacting coastal societies and environments. The spatial and temporal variability of sea level is neither linear nor globally uniform, especially in semi-enclosed basins such as the Mediterranean Sea, which is considered a hot spot regarding expected impacts related to climate change. This study investigates sea-level trends and their variability over the Mediterranean Sea from 1993 to 2019. We use gridded sea-level anomaly products from satellite altimetry for the total observed sea level, whereas ocean temperature and salinity profiles from reanalysis were used to compute the thermosteric and halosteric effects, respectively, and the steric component of the sea level. We perform a statistical change point detection to assess the spatial and temporal significance of each trend change. The linear trend provides a clear indication of the non-steric effects as the dominant drivers over the entire period at the Mediterranean Sea scale, except for the Levantine and Aegean sub-basins, where the steric component explains the majority of the sea-level trend. The main changes in sea-level trends are detected around 1997, 2006, 2010, and 2016, associated with Northern Ionian Gyre reversal episodes, which changed the thermohaline properties and water mass redistribution over the sub-basins.
Machine vision system for digital twin modeling of composite structures
Authors: Döbrich Oliver , Brauner Christian
Published: March 2023

Although the structural design of composite structures has already been carried out on a virtual level, composite mechanical properties remain sensitive to fiber orientation and therefore to the quality and reliability of the production process. Considering both manual single-unit manufacturing and advanced mass-unit fabrication, requirements on the production quality may differ, but certainty on the achieved result is crucial. A digital twin model, deterministically derived from produced parts, can be transferred into a virtual simulation environment to check for potential deviations of fiber alignment, resulting from variations in source material or composite production. Transferring that deterministic information into a virtual simulation environment allows for an estimation of the part’s structural potential despite any possible deviations by carrying out numerical simulation predictions on that model. This step of quality assessment can help reduce scrap parts by relying on simulation data that may demonstrate the feasibility of parts despite the containment of deviations with an otherwise uncertain impact. Therefore, further steps toward digitalization of the composite production process chain, especially on the characterization of the production quality, are aspired. In this contribution, a vision system based on a Microsoft Azure Kinect RGB-D camera is introduced which is used to digitalize the composite preform configuration from machine vision data by evaluating the achieved local fiber orientation as result of the complex preform draping process by digital image processing. A digital workflow is introduced that enables to feed the captured real-world data back into a digital environment where numerical simulations with the “as-built” fiber orientation can be carried out. The obtained results are used for assessing production quality and composite performance in the presence of possible deviations. The system, which consists of a camera array of consumer grade, can acquire real-world data and then transfer the data into a virtual environment.
The “adult inactivity triad” in patients with chronic kidney disease: A review
Authors: Zhang Fan , Yin Xiaojing , Huang Liuyan , Zhang Huachun
Published: March 2023

Background

The “pediatric inactivity triad” framework consists of three complex, interrelated conditions influencing physical inactivity and associated health risks. Evidence on the beneficial effects of physical activity in adults with chronic kidney disease (CKD) continues to grow, but few studies have explored the complex interactions behind inactivity in this population.

Results

Based on the “pediatric inactivity triad” framework and prior research, we would like to propose a new concept, the “adult inactivity triad” in CKD, including (1) exercise deficit disorder, (2) sarcopenia, and (3) physical illiteracy. Individuals can shift from “adult inactivity triad” to “adult activity triad” and move at different rates and directions along the arrows in each of the three components.

Conclusion

This review explores and summarizes previous research on the three main adult inactivity triad components in the chronic kidney disease population.
Relationship of environmental factors in pond water and dynamic changes of gut microbes of sea bass Lateolabrax japonicus
Authors: Zhu Zheng , Xu Yu-Min , Liang Jun-Han , Huang Wei , Chen Jin-Ding , Wu Si-Ting , Huang Xiao-Hong , Huang You-Hua , Zhang Xiao-Yang , Sun Hong-Yan , Qin Qi-Wei
Published: March 2023

The effect of structure of gut microbes on the health of host has attracted increasing attention. Sea bass Lateolabrax japonicus is an important farmed fish in China. The relationship of the dynamic changes of intestinal bacterial communities in L. japonicus and the cultural water environment is very important for healthy culture. Here, the diversity and abundance of the gut microbial communities of L. japonicus were evaluated during the culture using 16S rRNA Illumina sequencing. Both the opportunistic pathogens Aeromonas (1.68%), Vibrio (1.59%), and Acinetobacter (1.22%); and the potential probiotics Lactobacillus (2.27%), Bacillus (1.16%), and Lactococcus (0.37%) were distributed in the gut of L. japonicus. The increasing concentration of nitrogen of water environments with the increase of culture time significantly correlated with shifts in the microbial community structure: 40.04% of gut microbial changes due to nitrogen concentration. Higher concentrations of nitrogen showed a significantly negative correlation with intestinal probiotics in L. japonicus. The results indicate that the abundance of intestinal bacteria of L. japonicus is mainly driven by the changes of environmental factors (e.g., nitrogen), and it’s very important that the linking environmental parameters with bacterial data of guts could be used as an early warning indicator in L. japonicus heath culture.
Antimicrobial resistance and genomic characterization of Salmonella enterica isolates from chicken meat
Authors: Alzahrani Khaloud O. , AL-Reshoodi Fahad M. , Alshdokhi Elaf A. , Alhamed Ashwaq S. , Al Hadlaq Meshari A. , Mujallad Mohammed I. , Mukhtar Lenah E. , Alsufyani Amani T. , Alajlan Abdullah A. , Al Rashidy Malfi S. , Al Dawsari Mashan J. , Al-Akeel Saleh I. , AL-Harthi Meshari H. , Al Manee Abdulaziz M. , Alghoribi Majed F. , Alajel Suliman M.
Published: March 2023

This study investigated genotypic and phenotypic antimicrobial resistance profiles, phylogenic relatedness, plasmid and virulence composition of 39 Salmonella enterica strains isolated from chicken meat samples using whole genome sequencing (WGS) technology. Four distinct serotypes were identified; Salmonella Minnesota (16/39, 41%), Salmonella Infantis (13/39, 33.3%), Salmonella Enteritidis (9/39, 23.1%), and one isolate was detected for Salmonella Kentucky (1/39, 2.6%), with sequence types (STs) as followed: ST548, ST32, ST11, and ST198, respectively. Phenotypic resistance to tetracycline (91.2%), ampicillin (82.4%), sulfisoxazole (64.7%), and nalidixic acid (61.6%) was the most observed. Resistome analysis revealed the presence of resistance genes to aminoglycosides, β-lactamase, sulfonamides, trimethoprim, phenicol, lincosamide, macrolides, and tetracyclines. Plasmidome showed the presence of eight incompatibility groups, including IncA/C2, IncFIB(K)_1_Kpn3, Col440I_1, IncR, IncX1, IncI1_1_Alpha, IncFIB(S)/IncFII(S), IncHI2/IncHI2A, IncX2 and ColpVC plasmids across the 39 genomes. Three resistance genes, sul2, tetA and blaCMY-2, were predicted to be located on IncA/C2 plasmid in S. Minnesota isolates, whereas all S. Infantis isolates were positive to IncFIB(K)_1_Kpn3 plasmid that carries blaCTX-M-65 gene. Eleven Salmonella pathogenicity islands and up to 131 stress and/or virulence genes were identified in the evaluated genomes. Phylogenetic analysis showed four phylogroups that were consistent with the identified ST profiles with a high level of inter-diversity between isolates. This is the first genomic characterization of Salmonella isolates from retail chicken meat in Saudi Arabia using WGS technology. The availability of Salmonella genomes from multiple geographic locations, including Saudi Arabia, would be highly beneficial in future source-tracking, especially during epidemiological surveillance and outbreak investigations.
Host genetics and gut microbiota composition: Baseline gut microbiota composition as a possible prognostic factor for the severity of COVID-19 in patients with familial Mediterranean fever disease
Authors: Tsaturyan Vardan , Manvelyan Anahit , Balayan Marine , Harutyunyan Natalya , Pepoyan Elya , Torok Tamas , Chikindas Michael , Pepoyan Astghik
Published: March 2023

Background

It is known that the gut microbiome of a healthy person affects the process of COVID-19 after getting infected with SARS-CoV-2 virus. It is also believed that colchicine can alleviate the severity of COVID-19.

Objective

Current investigations aimed to evaluate the associations between the baseline gut microbiota composition of healthy and Familial Mediterranean fever (FMF) - carrier Armenian men populations, and the severity of the COVID-19 disease after their infection with the SARS-CoV-2. The study has a purpose of answering three core questions: i. Do the characteristics of gut microbiome of Armenians affect the course of COVID-19 severity? ii. How does the COVID-19 disease course on go for FMF patients who have been taking colchicine as a medication over the years after getting infected with SARS-CoV-2? iii. Is there an initial gut micribiota structure pattern for non-FMF and FMF patients in the cases when COVID-19 appears in mild form?

Methods

The gut microbiota composition in non-FMF and FMF patients before the first infection (mild and moderate course of COVID-19) was considered. COVID-19 was diagnosed by SARS-CoV-2 nucleic acid RT-PCR in nasopharyngeal swab and/or sputum.

Results

The number of patients with male FMF with mild COVID-19 was approximately two times higher than that of non-FMF male subjects with COVID-19. In addition, an association of COVID-19 disease severity with the baseline gut Prevotella, Clostridium hiranonis, Eubacterium biforme, Veillonellaceae, Coprococcus, and Blautia diversities in the non-FMF and FMF populations were revealed by us, which can be used as risk/prognostic factor for the severity of COVID-19.
Metagenomic analyses of a microbial assemblage in a subglacial lake beneath the Vatnajökull ice cap, Iceland
Authors: Vannier Pauline , Farrant Gregory K. , Klonowski Alexandra , Gaidos Eric , Thorsteinsson Thorsteinn , Marteinsson Viggó þór
Published: March 2023

Skaftárkatlar are two subglacial lakes located beneath the Vatnajökull ice cap in Iceland associated with geothermal and volcanic activity. Previous studies of these lakes with ribosomal gene (16S rDNA) tag sequencing revealed a limited diversity of bacteria adapted to cold, dark, and nutrient-poor waters. In this study, we present analyses of metagenomes from the lake which give new insights into its microbial ecology. Analyses of the 16S rDNA genes in the metagenomes confirmed the existence of a low-diversity core microbial assemblage in the lake and insights into the potential metabolisms of the dominant members. Seven taxonomic genera, Sulfuricurvum, Sulfurospirillum, Acetobacterium, Pelobacter/Geobacter, Saccharibacteria, Caldisericum, and an unclassified member of Prolixibacteraceae, comprised more than 98% of the rDNA reads in the library. Functional characterisation of the lake metagenomes revealed complete metabolic pathways for sulphur cycling, nitrogen metabolism, carbon fixation via the reverse Krebs cycle, and acetogenesis. These results show that chemolithoautotrophy constitutes the main metabolism in this subglacial ecosystem. This assemblage and its metabolisms are not reflected in enrichment cultures, demonstrating the importance of in situ investigations of this environment.
The core fungal microbiome of banana (Musa spp.)
Authors: Birt Henry W. G. , Pattison Anthony B. , Skarshewski Adam , Daniells Jeff , Raghavendra Anil , Dennis Paul G.
Published: March 2023

Here, we report a metabarcoding (ITS2) study to define the common core fungal microbiome (mycobiome) of healthy Musa spp. (bananas and plantains). To identify a list of 21 core fungal taxa, we first characterised the effects of edaphic conditions and host genotype – two factors that are likely to differ between farms – on the diversity of fungal communities in bulk soil and seven plant compartments. This experiment facilitated shortlisting of core ‘candidates’, which were then elevated to full core status if also found to frequent a wide-range of field-grown Musa spp. and exhibit hub-like characteristics in network analyses. Subsequently, we conducted a meta-analysis of eleven publicly available datasets of Musa spp. associated fungi demonstrating that the core fungi identified in our study have close relatives in other countries. The diversity and composition of mycobiomes differed between plant compartments and soils, but not genotypes. The core mycobiome included Fusarium oxysporum and its relatives, which dominated all plant compartments, as well as members of the Sordariomycetes, Dothideomycetes, and Mortierellomycota. Our study provides a robust list of common core fungal taxa for Musa spp. Further studies may consider how changes in the frequencies and activities of these taxa influence host fitness and whether they can be managed to improve banana production.
Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice
Authors: Wu Xiao , Li Run-Feng , Lin Zheng-Shi , Xiao Chuang , Liu Bin , Mai Kai-Lin , Zhou Hong-Xia , Zeng De-You , Cheng Sha , Weng Yun-Ceng , Zhao Jin , Chen Rui-Feng , Jiang Hai-Ming , Chen Li-Ping , Deng Ling-Zhu , Xie Pei-Fang , Yang Wei-Min , Xia Xue-Shan , Yang Zi-Feng
Published: March 2023

Background

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood.

Methods

We developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman’s rank correlation coefficient test.

Results

Coinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated.

Conclusion

Coinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.
Recent advances in understanding neuronal diversity and neural circuit complexity across different brain regions using single-cell sequencing
Authors: Xing Yu , Zan Chunfang , Liu Lu
Published: March 2023

Neural circuits are characterized as interconnecting neuron networks connected by synapses. Some kinds of gene expression and/or functional changes of neurons and synaptic connections may result in aberrant neural circuits, which has been recognized as one crucial pathological mechanism for the onset of many neurological diseases. Gradual advances in single-cell sequencing approaches with strong technological advantages, as exemplified by high throughput and increased resolution for live cells, have enabled it to assist us in understanding neuronal diversity across diverse brain regions and further transformed our knowledge of cellular building blocks of neural circuits through revealing numerous molecular signatures. Currently published transcriptomic studies have elucidated various neuronal subpopulations as well as their distribution across prefrontal cortex, hippocampus, hypothalamus, and dorsal root ganglion, etc. Better characterization of brain region-specific circuits may shed light on new pathological mechanisms involved and assist in selecting potential targets for the prevention and treatment of specific neurological disorders based on their established roles. Given diverse neuronal populations across different brain regions, we aim to give a brief sketch of current progress in understanding neuronal diversity and neural circuit complexity according to their locations. With the special focus on the application of single-cell sequencing, we thereby summarize relevant region-specific findings. Considering the importance of spatial context and connectivity in neural circuits, we also discuss a few published results obtained by spatial transcriptomics. Taken together, these single-cell sequencing data may lay a mechanistic basis for functional identification of brain circuit components, which links their molecular signatures to anatomical regions, connectivity, morphology, and physiology. Furthermore, the comprehensive characterization of neuron subtypes, their distributions, and connectivity patterns via single-cell sequencing is critical for understanding neural circuit properties and how they generate region-dependent interactions in different context.
Control of circadian rhythm on cortical excitability and synaptic plasticity
Authors: Lodovichi Claudia , Ratto Gian Michele
Published: March 2023

Living organisms navigate through a cyclic world: activity, feeding, social interactions are all organized along the periodic succession of night and day. At the cellular level, periodic activity is controlled by the molecular machinery driving the circadian regulation of cellular homeostasis. This mechanism adapts cell function to the external environment and its crucial importance is underlined by its robustness and redundancy. The cell autonomous clock regulates cell function by the circadian modulation of mTOR, a master controller of protein synthesis. Importantly, mTOR integrates the circadian modulation with synaptic activity and extracellular signals through a complex signaling network that includes the RAS-ERK pathway. The relationship between mTOR and the circadian clock is bidirectional, since mTOR can feedback on the cellular clock to shift the cycle to maintain the alignment with the environmental conditions. The mTOR and ERK pathways are crucial determinants of synaptic plasticity and function and thus it is not surprising that alterations of the circadian clock cause defective responses to environmental challenges, as witnessed by the bi-directional relationship between brain disorders and impaired circadian regulation. In physiological conditions, the feedback between the intrinsic clock and the mTOR pathway suggests that also synaptic plasticity should undergo circadian regulation.
Accurate few-shot object counting with Hough matching feature enhancement
Authors: He Zhiquan , Zheng Donghong , Wang Hengyou
Published: March 2023

Introduction

Given some exemplars, few-shot object counting aims to count the corresponding class objects in query images. However, when there are many target objects or background interference in the query image, some target objects may have occlusion and overlap, which causes a decrease in counting accuracy.

Methods

To overcome the problem, we propose a novel Hough matching feature enhancement network. First, we extract the image feature with a fixed convolutional network and refine it through local self-attention. And we design an exemplar feature aggregation module to enhance the commonality of the exemplar feature. Then, we build a Hough space to vote for candidate object regions. The Hough matching outputs reliable similarity maps between exemplars and the query image. Finally, we augment the query feature with exemplar features according to the similarity maps, and we use a cascade structure to further enhance the query feature.

Results

Experiment results on FSC-147 show that our network performs best compared to the existing methods, and the mean absolute counting error on the test set improves from 14.32 to 12.74.

Discussion

Ablation experiments demonstrate that Hough matching helps to achieve more accurate counting compared with previous matching methods.
Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study
Authors: Liguori Claudio , Santamarina Estevo , Strzelczyk Adam , Rodríguez-Uranga Juan Jesús , Shankar Rohit , Rodríguez-Osorio Xiana , Auvin Stéphane , Bonanni Paolo , Trinka Eugen , McMurray Rob , Sáinz-Fuertes Ricardo , Villanueva Vicente
Published: March 2023

Introduction

The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.

Methods

Thispost-hocanalysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.

Results

The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%;p= 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%;p< 0.001), focal seizures (65.0% vs. 36.8%;p< 0.001) and GTCS (83.7% vs. 67.2%;p< 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p< 0.001]; focal seizures, 29.4% vs. 8.7% [p< 0.001]; GTCS, 69.0% vs. 48.1% [p< 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%;p< 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%;p= 0.031).

Discussion

This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.
Potential molecular mechanisms of Erlongjiaonang action in idiopathic sudden hearing loss: A network pharmacology and molecular docking analyses
Authors: Zhao He , Wang Yan , Xu Cong , Li Guangjin , Song Yuwan , Qiu Jingjing , Cui Limei , Song Xicheng , Yang Yujuan , Sun Yan
Published: March 2023

Background

Idiopathic sudden hearing loss (ISHL) is characterized by sudden unexplainable and unilateral hearing loss as a clinically emergent symptom. The use of the herb Erlongjiaonang (ELJN) in traditional Chinese medicine is known to effectively control and cure ISHL. This study explored the underlying molecular mechanisms using network pharmacology and molecular docking analyses.

Method

The Traditional Chinese Medicine System Pharmacological database and the Swiss Target Prediction database were searched for the identification of ELJN constituents and potential gene targets, respectively, while ISHL-related gene abnormality was assessed using the Online Mendelian Inheritance in Man and Gene Card databases. The interaction of ELJN gene targets with ISHL genes was obtained after these databases were cross-screened, and a drug component–intersecting target network was constructed, and the gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction networks were analyzed. Cytoscape software tools were used to map the active components–crossover target–signaling pathway network and screened targets were then validated by establishing molecular docking with the corresponding components.

Result

Erlongjiaonang contains 85 components and 250 corresponding gene targets, while ISHL has 714 disease-related targets, resulting in 66 cross-targets. The bioinformatical analyses revealed these 66 cross-targets, including isorhamnetin and formononetin on NOS3 expression, baicalein on AKT1 activity, and kaempferol and quercetin on NOS3 and AKT1 activity, as potential ELJN-induced anti-ISHL targets.

Conclusion

This study uncovered potential ELJN gene targets and molecular signaling pathways in the control of ISHL, providing a molecular basis for further investigation of the anti-ISHL activity of ELJN.