bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide Identification, Expression, and Functional Analysis of MdMSI Genes in Apples (Malus domestica Borkh.)
Authors: Wang Daru , Wang Xun , Zhang Chunling , Yang Kuo , Wang Xinjie , Cui Jianying , Liu Dandan , You Chunxiang
Published: March 2022

The multicopy suppressor of IRA (MSI) is a subfamily of WD40 repeat proteins, which is widely involved in plant growth and development. In order to explore the function of MdMSI members in abiotic stress, we identified eight MSI gene family members from the Malus × domestica reference genome. They were distributed on six chromosomes, and they had similar secondary and tertiary structures. We found a variety of regulatory elements in response to hormones and abiotic stress in MdMSI promoters. Through qRT-PCR analysis, it was revealed that MdMSIs were expressed in all tissues, especially in roots. The analysis results also revealed that the expression of MdMSIs was induced in varying degrees under salt, drought stress, and ABA treatments. Furthermore, we obtained the overexpression of MdMSI1-1 transgenic apple calli and Arabidopsis. The overexpression of MdMSI1-1 in calli and Arabidopsis played a negative regulatory role in salt stress response. Our work laid a foundation for further verifying the function of MSI genes under abiotic stress in apples.
seGMM: A New Tool for Gender Determination From Massively Parallel Sequencing Data
Authors: Liu Sihan , Zeng Yuanyuan , Wang Chao , Zhang Qian , Chen Meilin , Wang Xiaolu , Wang Lanchen , Lu Yu , Guo Hui , Bu Fengxiao
Published: March 2022

In clinical genetic testing, checking the concordance between self-reported gender and genotype-inferred gender from genomic data is a significant quality control measure because mismatched gender due to sex chromosomal abnormalities or misregistration of clinical information can significantly affect molecular diagnosis and treatment decisions. Targeted gene sequencing (TGS) is widely recommended as a first-tier diagnostic step in clinical genetic testing. However, the existing gender-inference tools are optimized for whole genome and whole exome data and are not adequate and accurate for analyzing TGS data. In this study, we validated a new gender-inference tool, seGMM, which uses unsupervised clustering (Gaussian mixture model) to determine the gender of a sample. The seGMM tool can also identify sex chromosomal abnormalities in samples by aligning the sequencing reads from the genotype data. The seGMM tool consistently demonstrated >99% gender-inference accuracy in a publicly available 1,000-gene panel dataset from the 1,000 Genomes project, an in-house 785 hearing loss gene panel dataset of 16,387 samples, and a 187 autism risk gene panel dataset from the Autism Clinical and Genetic Resources in China (ACGC) database. The performance and accuracy of seGMM was significantly higher for the targeted gene sequencing (TGS), whole exome sequencing (WES), and whole genome sequencing (WGS) datasets compared to the other existing gender-inference tools such as PLINK, seXY, and XYalign. The results of seGMM were confirmed by the short tandem repeat analysis of the sex chromosome marker gene, amelogenin. Furthermore, our data showed that seGMM accurately identified sex chromosomal abnormalities in the samples. In conclusion, the seGMM tool shows great potential in clinical genetics by determining the sex chromosomal karyotypes of samples from massively parallel sequencing data with high accuracy.
Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity
Authors: Duan Tianhao , Du Yang , Xing Changsheng , Wang Helen Y. , Wang Rong-Fu
Published: March 2022

Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host’s defense against infectious diseases, autoimmune diseases, and cancer.
Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects
Authors: Shafer Paul , Kelly Lauren M. , Hoyos Valentina
Published: March 2022

To redirect T cells against tumor cells, T cells can be engineeredex vivoto express cancer-antigen specific T cell receptors (TCRs), generating products known as TCR-engineered T cells (TCR T). Unlike chimeric antigen receptors (CARs), TCRs recognize HLA-presented peptides derived from proteins of all cellular compartments. The use of TCR T cells for adoptive cellular therapies (ACT) has gained increased attention, especially as efforts to treat solid cancers with ACTs have intensified. In this review, we describe the differing mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs. We describe the classes of cancer antigens recognized by current TCR T therapies and discuss both classical and emerging pre-clinical strategies for antigen-specific TCR discovery, enhancement, and validation. Finally, we review the current landscape of clinical trials for TCR T therapy and discuss what these current results indicate for the development of future engineered TCR approaches.
Characterization of Macrophage-Like Cells in Retinal Vein Occlusion Using En Face Optical Coherence Tomography
Authors: Zeng Yunkao , Zhang Xiongze , Mi Lan , Gan Yuhong , Su Yongyue , Li Miaoling , Yang Ruijun , Zhang Yining , Wen Feng
Published: March 2022

Purpose

To investigate the clinical features of a macrophage-like cell (MLC) obtained by en face optical coherence tomography (OCT) in retinal vein occlusion (RVO).

Methods

The study involved 36 patients with treatment-naïve unilateral acute RVO, including 21 branch RVO (BRVO) and 15 central RVO. Vessel density and macular thickness were quantified using OCT angiography. A 3-μm en face OCT slab on the inner limiting membrane in the optic nerve head (ONH) region or macular region was used to visualize the MLCs. The MLCs were binarized and quantified using a semiautomated method. The unaffected fellow eyes served as the control group.

Results

The morphology of MLCs appeared larger and plumper in RVO eyes. The mean MLC density in the ONH and macular regions was 2.46 times and 2.86 times higher than their fellow eyes, respectively (p < 0.001). The macular MLC density of the occlusive region was significantly lower than that of the unaffected region in BRVO (p = 0.01). The ONH and macular MLC densities in the non-perfused region were significantly lower than those in the perfused region in all RVO eyes (p < 0.001). The ONH MLC density in RVO eyes was negatively correlated with radial peripapillary capillary vessel density (r = −0.413, p = 0.012). Both ONH and macular MLC densities were positively correlated with macular thickness (r = 0.505, p = 0.002; r = 0.385, p = 0.02, respectively).

Conclusion

The increased density and changes of morphology characterized by OCT may indicate generalized activation and aggregation of MLCs in RVO. More MLCs are recruited in the perfused region rather than the non-perfused region. RVO eyes with a higher density of MLCs tend to suffer from the thicker macula.
IRF4b and IRF8 Negatively Regulate RLR-Mediated NF-κB Signaling by Targeting MITA for Degradation in Teleost Fish
Authors: Yan Xiaolong , Zhao Xueyan , Zhou Ming , Sun Yuena , Xu Tianjun
Published: March 2022

Mediator of IRF3 activation (MITA) is a significant signal adaptor in the retinoic acid-inducible gene-I like receptor (RLR) signaling pathway and plays an important role in the innate immune system. As a transcription factor, nuclear factor kappa B (NF-κB) can be available in many signaling pathways including the RLR signaling pathway and relative to biological processes like immune responses. In this study, it is determined that IRF4b and IRF8 can have a negative effect on NF-κB signaling pathway mediated by MITA in fish. Firstly, it is found that IRF4b and IRF8 have an inhibitory function on MITA-mediated NF-κB signaling pathway. It is interesting that IRF4b and IRF8 have similar functions to achieve precise downregulated and the degradation of MITA through the ubiquitin-proteasome pathway. IRF is taken as the core domain of IRF4b or IRF8 for the downregulation to MITA. This study provides data on MITA-mediated NF-κB signaling pathway in teleost fish and provides new insights into the regulatory mechanism in fish immune system.
Sustained Actions in Combating Neglected Tropical Diseases during the COVID-19 Pandemic: Lessons Learned From the Leprosy Program in the Hyper-Endemic Area in Papua Province, Indonesia
Authors: Krismawati Hana , Rochman Mohhamad Fadjri , Oktavian Antonius , Diana Aly
Published: March 2022

In 2020 we witnessed the global pandemic of COVID-19. Papua, Indonesia announced the first case of COVID-19 on 7 March 2020, and reached 41,137 positive cases with a total of 1,183 fatality cases in August 2021. In the midst of the effort to handle COVID-19, this area of hyper-endemic tropical diseases, including leprosy, has also had to cope with these established problems. Some leprosy indicators have shown decreased performance. The new case detection rate (NCDR) per 100,000 population in Papua Province decreased from 45.36 in 2019 to 29.75 in December 2020. Grade 2 disability (G2D) proportion amongst the new cases increased from 9.0% in 2019 to 11.4% in 2020. There was a 27% decrease of the proportion of child leprosy, following the decrease of elementary school surveys from 6.1% in 2019 to only 1.0% in 2020. Although precautions should be taken, it should be done to minimalize impacts not only for the current pandemic, but also the existing neglected tropical diseases (NTDs). The central government should optimize their functions as a control system to maintain standard services and to monitor the local health authority. The current guidelines regarding implementation of NTD programs during the COVID-19 pandemic should be evaluated and revised, and followed by adequate explanation and proper training to accommodate better services. Emphasis on prevention and early detection should be considered as the main way forward to strengthen the health system.
Evaluating the Hatchery Program of a Highly Exploited Shrimp Stock (Fenneropenaeus chinensis) in a Temperate Marine Ecosystem
Authors: Xing Lei , Chen Yong , Tanaka Kisei R. , Barrier Nicolas , Ren Yiping
Published: March 2022

Hatchery programs are commonly used to enhance fishery stocks, while the efforts to minimize potential negative ecological impacts have grown in recent years. In China, Fenneropenaeus chinensis is a fast-growing, short-lived shrimp species with a high commercial value. F. chinensis fishery is heavily dependent on the hatchery program. We evaluated the trade-off between economic profits and ecological impacts of F. chinensis hatchery program in the Jiaozhou Bay of China. The total length of released individuals was 1.4 cm. The results showed that artificially released F. chinensis individuals experienced high predation pressure during the first 2 weeks. The economic profit peaked when 198 million individuals were released. The modeled hatchery program yielded a lower proportion of individuals with the increasing amount of F. chinensis release. The temporally uniform hatchery release was more efficient than other hatchery release scenarios (e.g., increasing the released amount year by year) in a long-term hatchery program. F. chinensis had the negative impacts on two large predatory fishes. Large fishes recovered at a slower rate than small fishes after the F. chinensis release stopped. Reducing fishing pressure could offset negative impacts of F. chinensis release on large fishes. The study indicates that the effectiveness of F. chinensis release cannot be enhanced by simply increasing the released amount. A long-term F. chinensis hatchery program with a large released amount may present additional challenges for managing natural resources in an ecosystem context.
PEAC: An Ultrasensitive and Cost-Effective MRD Detection System in Non-small Cell Lung Cancer Using Plasma Specimen
Authors: Xu Jianping , Pu Yue , Lin Rui , Xiao Shanshan , Fu Yingxue , Wang Tao
Published: March 2022

Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA (cfDNA), has emerged as a promising marker in targeted therapy, immunotherapy, and minimal residual disease (MRD) monitoring in postsurgical patients. However, ctDNA level in early-stage cancers and postsurgical patients is very low, which posed many technical challenges to improve the detection rate and sensitivity, especially in the clinical practice of MRD detection. These challenges usually include insufficient DNA input amount, limit of detection (LOD), and high experimental costs. To resolve these challenges, we developed an ultrasensitive ctDNA MRD detection system in this study, namely PErsonalized Analysis of Cancer (PEAC), to simultaneously detect up to 37 mutations, which account for 70–80% non-small cell lung cancer (NSCLC) driver mutations from low plasma sample volume and enables LOD of 0.01% at a single-site level. We demonstrated the high performance achieved by PEAC on both cfDNA reference standards and clinical plasma samples from three NSCLC patient cohorts. For cfDNA reference standards, PEAC achieved a specificity of 99% and a sensitivity of 87% for the mutations at 0.01% allele fraction. In the second cohort, PEAC showed 100% concordance rate between ddPCR and Next-generation sequencing (NGS) among 29 samples. In the third cohort, 22 of 59 patients received EGFR TKI treatment. Among them, three in four patients identified low level actionable gene mutations only by PEAC had partial responses after targeted therapy, demonstrating high ctDNA detection ability of PEAC. Overall, the developed PEAC system can detect the majority of NSCLC driver mutations using 8–10 ml plasma samples, and has the advantages of high detection sensitivity and lower costs compared with the existing technologies such as ddPCR and NGS. These advantages make the PEAC system quite appropriate for ctDNA and MRD detection in early-stage NSCLC and postsurgical recurrence monitoring.
Collapsing Glomerulopathy: A Review by the Collapsing Brazilian Consortium
Authors: Cutrim Érico Murilo Monteiro , Neves Precil Diego Miranda de Meneses , Campos Marcos Adriano Garcia , Wanderley Davi Campos , Teixeira-Júnior Antonio Augusto Lima , Muniz Monique Pereira Rêgo , Ladchumananandasivam Francisco Rasiah , Gomes Orlando Vieira , Vasco Rafael Fernandes Vanderlei , Brito Dyego José de Araújo , Lages Joyce Santos , Salgado-Filho Natalino , Guedes Felipe Leite , de Almeida José Bruno , Magalhães Marcelo , Araújo Stanley de Almeida , Silva Gyl Eanes Barros
Published: March 2022

Collapsing glomerulopathy (CG) is a clinicopathologic entity characterized by segmentar or global collapse of the glomerulus and hypertrophy and hyperplasia of podocytes. The Columbia classification of 2004 classified CG as a histological subtype of focal segmental glomerulosclerosis (FSGS). A growing number of studies have demonstrated a high prevalence of CG in many countries, especially among populations with a higher proportion of people with African descent. The present study is a narrative review of articles extracted from PubMed, Medline, and Scielo databases from September 1, 2020 to December 31, 2021. We have focused on populational studies (specially cross-sectional and cohort articles). CG is defined as a podocytopathy with a distinct pathogenesis characterized by strong podocyte proliferative activity. The most significant risk factors for CG includeAPOL1gene mutations and infections with human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. CG typically presents with more severe symptoms and greater renal damage. The prognosis is notably worse than that of other FSGS subtypes.
Prevalence of Psychosomatic and Genitourinary Syndrome Among Menopausal Women: A Systematic Review and Meta-Analysis
Authors: Nik Hazlina Nik Hussain , Norhayati Mohd Noor , Shaiful Bahari Ismail , Nik Muhammad Arif Nik Ahmad
Published: March 2022

Introduction

The menopausal transition represents the passage from reproductive to non-reproductive life and is characterized by a number of menstrual disturbances. We systematically reviewed the evidence on the prevalence of psychosomatic and genitourinary syndrome among menopausal women and compared the risk of symptoms between premenopausal, perimenopausal, and post-menopausal women.

Methods

We performed a systematic search in MEDLINE, CINAHL, and ScienceDirect through March 2021. Case series/reports, conference papers and proceedings, articles available only in abstract form, editorial reviews, letters of communication, commentaries, systematic reviews, and qualitative studies were excluded. Two reviewers independently extracted and assessed the quality of data using the Joanna Briggs Institute Meta-Analysis. The outcomes were assessed with random-effects model using the Review Manager software.

Results

In total, 29 studies had a low risk of bias and were included in the review. Our findings showed that the pooled prevalence of somatic symptoms in post-menopausal women (52.6%) was higher than in the premenopausal and perimenopausal stages (34.6 and 39.5%, respectively). There was a low prevalence of psychological symptoms in premenopausal women (28.4%). The genitourinary syndrome was highest among post-menopausal women (55.1%), followed by perimenopausal (31.9%) and premenopausal (19.2%) women.

Conclusion

Post-menopausal women have a higher risk of experiencing menopausal symptoms particularly genitourinary syndrome than premenopausal and perimenopausal women. It is pertinent for healthcare professionals to evaluate the symptoms in order to provide them with a better quality of life.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235958
Glucose-Potentiated Amikacin Killing of Cefoperazone/Sulbactam Resistant Pseudomonas aeruginosa
Authors: Tang Xi-kang , Su Yu-bin , Ye Hui-qing , Dai Zhen-yuan , Yi Huan , Yang Ke-xin , Zhang Tian-tuo , Chen Zhuang-gui
Published: March 2022

Multidrug-resistant Pseudomonas aeruginosa has become one of global threat pathogens for human health due to insensitivity to antibiotics. Recently developed reprogramming metabolomics can identify biomarkers, and then, the biomarkers were used to revert the insensitivity and elevate antibiotic-mediated killing. Here, the methodology was used to study cefoperazone/sulbactam (SCF)-resistant P. aeruginosa (PA-RSCF) and identified reduced glycolysis and pyruvate cycle, a recent clarified cycle providing respiratory energy in bacteria, as the most key enriched pathways and the depressed glucose as one of the most crucial biomarkers. Further experiments showed that the depression of glucose was attributed to reduction of glucose transport. However, exogenous glucose reverted the reduction to elevate intracellular glucose via activating glucose transport. The elevated glucose fluxed to the glycolysis, pyruvate cycle, and electron transport chain to promote downstream proton motive force (PMF). Consistently, exogenous glucose did not promote SCF-mediated elimination but potentiated aminoglycosides-mediated killing since aminoglycosides uptake is PMF-dependent, where amikacin was the best one. The glucose-potentiated amikacin-mediated killing was effective to both lab-evolved PA-RSCF and clinical multidrug-resistant P. aeruginosa. These results reveal the depressed glucose uptake causes the reduced intracellular glucose and expand the application of metabolome-reprogramming on selecting conventional antibiotics to achieve the best killing efficacy.
The Infection of the Japanese Encephalitis Virus SA14-14-2 Strain Induces Lethal Peripheral Inflammatory Responses in IFNAR Deficiency Mice
Authors: Liu Juan , Jing Wenxian , Fang Yongxiang , He Xiaobing , Chen Guohua , Jia Huaijie , Wang Jingyu , Jing Zhizhong
Published: March 2022

The Japanese encephalitis virus (JEV) is a leading cause of mosquito-borne viral encephalitis worldwide. Clinical symptoms other than encephalitis, on the other hand, are substantially more prevalent with JEV infection, demonstrating the relevance of peripheral pathophysiology. We studied the peripheral immunopathogenesis of JEV using IFNAR deficient (IFNAR–/–) mice infected with the SA14-14-2 strain under the BSL-2. The body weight and survival rate of infected-IFNAR–/–mice decreased significantly. Infected-IFNAR–/–mice’s liver and spleen demonstrated obvious tissue damage and inflammatory cell infiltration. There was also extensive viral replication in the organs. IFN-α/β protein expression was dramatically elevated in peripheral tissues and serum, although the related interferon-stimulated genes (ISGs) remained low in the spleen and liver of infected-IFNAR–/–animals. Consistently, the differentially expressed genes (DEGs) analysis using RNA-sequencing of spleens showed inflammatory cytokines upregulation, such as IL-6, TNF-α, and MCP-1, and IFN-γ associated cytokine storm. The infiltration of macrophages and neutrophils in the spleen and liver of SA14-14-2-infected IFNAR–/– mice was dramatically elevated. However, there was no significant difference in tissue damage, viral multiplication, or the production of IFNα/β and inflammatory cytokines in the brain. Infection with the JEV SA14-14-2 strain resulted in a lethal peripheral inflammatory response and organ damage without encephalitis in IFNAR–/– mice. Our findings may help shed light on the peripheral immunopathogenesis associated with clinical JEV infection and aid in developing treatment options.
Clinico-Genomic Analysis Reiterates Mild Symptoms Post-vaccination Breakthrough: Should We Focus on Low-Frequency Mutations?
Authors: Kanakan Akshay , Mehta Priyanka , Devi Priti , Saifi Sheeba , Swaminathan Aparna , Maurya Ranjeet , Chattopadhyay Partha , Tarai Bansidhar , Das Poonam , Jha Vinita , Budhiraja Sandeep , Pandey Rajesh
Published: March 2022

Vaccine development against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been of primary importance to contain the ongoing global pandemic. However, studies have demonstrated that vaccine effectiveness is reduced and the immune response is evaded by variants of concern (VOCs), which include Alpha, Beta, Delta, and, the most recent, Omicron. Subsequently, several vaccine breakthrough (VBT) infections have been reported among healthcare workers (HCWs) due to their prolonged exposure to viruses at healthcare facilities. We conducted a clinico-genomic study of ChAdOx1 (Covishield) VBT cases in HCWs after complete vaccination. Based on the clinical data analysis, most of the cases were categorized as mild, with minimal healthcare support requirements. These patients were divided into two sub-phenotypes based on symptoms: mild and mild plus. Statistical analysis showed a significant correlation of specific clinical parameters with VBT sub-phenotypes. Viral genomic sequence analysis of VBT cases revealed a spectrum of high- and low-frequency mutations. More in-depth analysis revealed the presence of low-frequency mutations within the functionally important regions of SARS-CoV-2 genomes. Emphasizing the potential benefits of surveillance, low-frequency mutations, D144H in the N gene and D138Y in the S gene, were observed to potentially alter the protein secondary structure with possible influence on viral characteristics. Substantiated by the literature, our study highlights the importance of integrative analysis of pathogen genomic and clinical data to offer insights into low-frequency mutations that could be a modulator of VBT infections.
Population Differences and Host Species Predict Variation in the Diversity of Host-Associated Microbes in Hydra
Authors: Taubenheim Jan , Miklós Máté , Tökölyi Jácint , Fraune Sebastian
Published: March 2022

Most animals co-exist with diverse host-associated microbial organisms that often form complex communities varying between individuals, habitats, species and higher taxonomic levels. Factors driving variation in the diversity of host-associated microbes are complex and still poorly understood. Here, we describe the bacterial composition of field-collected Hydra, a freshwater cnidarian that forms stable associations with microbial species in the laboratory and displays complex interactions with components of the microbiota. We sampled Hydra polyps from 21 Central European water bodies and identified bacterial taxa through 16S rRNA sequencing. We asked whether diversity and taxonomic composition of host-associated bacteria depends on sampling location, habitat type, host species or host reproductive mode (sexual vs. asexual). Bacterial diversity was most strongly explained by sampling location, suggesting that the source environment plays an important role in the assembly of bacterial communities associated with Hydra polyps. We also found significant differences between host species in their bacterial composition that partly mirrored variations observed in lab strains. Furthermore, we detected a minor effect of host reproductive mode on bacterial diversity. Overall, our results suggest that extrinsic (habitat identity) factors predict the diversity of host-associated bacterial communities more strongly than intrinsic (species identity) factors, however, only a combination of both factors determines microbiota composition in Hydra.
Mutation of rpoB Shifts the Nutrient Threshold Triggering Myxococcus Multicellular Development
Authors: Eisner Sabrina A. , Velicer Gregory J. , Yu Yuen-Tsu N.
Published: March 2022

The ability to perceive and respond to environmental change is essential to all organisms. In response to nutrient depletion, cells of the soil-dwelling δ-proteobacterium Myxococcus xanthus undergo collective morphogenesis into multicellular fruiting bodies and transform into stress-resistant spores. This process is strictly regulated by gene networks that incorporate both inter- and intracellular signals. While commonly studied M. xanthus reference strains and some natural isolates undergo development only in nutrient-poor conditions, some lab mutants and other natural isolates commit to development at much higher nutrient levels, but mechanisms enabling such rich medium development remain elusive. Here we investigate the genetic basis of rich medium development in one mutant and find that a single amino acid change (S534L) in RpoB, the β-subunit of RNA polymerase, is responsible for the phenotype. Ectopic expression of the mutant rpoB allele was sufficient to induce nutrient-rich development. These results suggest that the universal bacterial transcription machinery bearing the altered β-subunit can relax regulation of developmental genes that are normally strictly controlled by the bacterial stringent response. Moreover, the mutation also pleiotropically mediates a tradeoff in fitness during vegetative growth between high vs. low nutrient conditions and generates resistance to exploitation by a developmental cheater. Our findings reveal a previously unknown connection between the universal transcription machinery and one of the most behaviorally complex responses to environmental stress found among bacteria.
Emergence of Progressive Mutations in SARS-CoV-2 From a Hematologic Patient With Prolonged Viral Replication
Authors: Garcia-Vidal Carolina , Iglesias-Caballero María , Puerta-Alcalde Pedro , Mas Vicente , Cuesta-Chasco Genoveva , Garcia-Pouton Nicole , Varona Sarai , Pozo Francisco , Vázquez-Morón Sonia , Marcos Maria Angeles , Soriano Alex , Casas Inmaculada ,   HEMATOCOVID19-Researchers Group
Published: March 2022

We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed.
Lysine Methylation Modulates the Interaction of Archaeal Chromatin Protein Cren7 With DNA
Authors: Ding Niannian , Chen Yuanyuan , Chu Yindi , Zhong Cheng , Huang Li , Zhang Zhenfeng
Published: March 2022

Cren7 and Sis7d, two chromatin proteins from Sulfolobus islandicus, undergo extensive methylations at multiple lysine residues to various extents. Whether this highly conserved protein serves an epigenetic role in the regulation of the structure and function of the chromosome remains unclear. In the present study, we show that methylation significantly affects Cren7, but not Sis7d, in the ability to bind DNA and to constrain negative DNA supercoils. Strikingly, methylated Cren7 was significantly less efficient in forming oligomers or mediating intermolecular DNA bridging. Single-site substitution mutation with glutamine reveals that methylation of the four lysine residues (K24, K31, K42, and K48) of Cren7 at the protein-DNA interface, which are variably conserved among Cren7 homologues from different branches of the Crenarchaeota, influenced Cren7-DNA interactions in different manners. We suggest that dynamic methylation of Cren7 may represent a potential epigenetic mechanism involved in the chromosomal regulation in crenarchaea.
The Phlorizin-Degrading Bacillus licheniformis XNRB-3 Mediates Soil Microorganisms to Alleviate Apple Replant Disease
Authors: Duan Yanan , Zhao Lei , Jiang Weitao , Chen Ran , Zhang Rong , Chen Xuesen , Yin Chengmiao , Mao Zhiquan
Published: March 2022

In this study, an endophytic phlorizin-degrading Bacillus licheniformis XNRB-3 was isolated from the root tissue of healthy apple trees, and its control effect on apple replant disease (ARD) and how it alleviates the pathogen pressure via changes in soil microbiomes were studied. The addition of strain XNRB-3 in Fusarium infested soils significantly reduced the number of pathogens in the soil, thus resulting in a lower disease incidence, and the relative control effect on Fusarium oxysporum reached the highest of 66.11%. The fermentation broth can also protect the roots of the plants from Fusarium oxysporum, Fusarium moniliforme, Fusarium proliferatum, and Fusarium solani infection. These antagonistic effects were further validated using an in vitro assay in which the pathogen control was related to growth and spore germination inhibition via directly secreted antimicrobial substances and indirectly affecting the growth of pathogens. The secreted antimicrobial substances were identified using gas chromatography-mass spectrometry (GC-MS) technology. Among them, alpha-bisabolol and 2,4-di-tert-butylphenol had significant inhibitory effects on many planted pathogenic fungi. Butanedioic acid, monomethyl ester, and dibutyl phthalate promoted root development of Arabidopsis plants. Strain XNRB-3 has multifarious plant growth promoting traits and antagonistic potential. In pot and field experiments, the addition of strain XNRB-3 significantly promoted the growth of plants, and the activity of enzymes related to disease resistance [superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)] was also significantly enhanced. It also reduced the abundance of four species of Fusarium and the content of phenolic acids in the rhizosphere soil, improved soil microbial community structure and nutritional conditions, and increased soil microbial diversity and activity, as well as the soil enzyme activity. The above results indicated that B. licheniformis XNRB-3 could be developed into a promising biocontrol and plant-growth-promoting agent.
Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design
Authors: Ferrell Kia C. , Johansen Matt D. , Triccas James A. , Counoupas Claudio
Published: March 2022

Mycobacterium abscessus is a member of the non-tuberculous mycobacteria (NTM) group, responsible for chronic infections in individuals with cystic fibrosis (CF) or those otherwise immunocompromised. While viewed traditionally as an opportunistic pathogen, increasing research into M. abscessus in recent years has highlighted its continued evolution into a true pathogen. This is demonstrated through an extensive collection of virulence factors (VFs) possessed by this organism which facilitate survival within the host, particularly in the harsh environment of the CF lung. These include VFs resembling those of other Mycobacteria, and non-mycobacterial VFs, both of which make a notable contribution in shaping M. abscessus interaction with the host. Mycobacterium abscessus continued acquisition of VFs is cause for concern and highlights the need for novel vaccination strategies to combat this pathogen. An effective M. abscessus vaccine must be suitably designed for target populations (i.e., individuals with CF) and incorporate current knowledge on immune correlates of protection against M. abscessus infection. Vaccination strategies must also build upon lessons learned from ongoing efforts to develop novel vaccines for other pathogens, particularly Mycobacterium tuberculosis (M. tb); decades of research into M. tb has provided insight into unconventional and innovative vaccine approaches that may be applied to M. abscessus. Continued research into M. abscessus pathogenesis will be critical for the future development of safe and effective vaccines and therapeutics to reduce global incidence of this emerging pathogen.
Biological Sulfate Reduction in Deep Subseafloor Sediment of Guaymas Basin
Authors: Nagakura Toshiki , Schubert Florian , Wagner Dirk , Kallmeyer Jens ,   IODP Exp. 385 Shipboard Scientific Party
Published: March 2022

Sulfate reduction is the quantitatively most important process to degrade organic matter in anoxic marine sediment and has been studied intensively in a variety of settings. Guaymas Basin, a young marginal ocean basin, offers the unique opportunity to study sulfate reduction in an environment characterized by organic-rich sediment, high sedimentation rates, and high geothermal gradients (100–958°C km−1). We measured sulfate reduction rates (SRR) in samples taken during the International Ocean Discovery Program (IODP) Expedition 385 using incubation experiments with radiolabeled 35SO42− carried out at in situ pressure and temperature. The highest SRR (387 nmol cm−3 d−1) was recorded in near-surface sediments from Site U1548C, which had the steepest geothermal gradient (958°C km−1). At this site, SRR were generally over an order of magnitude higher than at similar depths at other sites (e.g., 387–157 nmol cm−3 d−1 at 1.9 mbsf from Site U1548C vs. 46–1.0 nmol cm−3 d−1 at 2.1 mbsf from Site U1552B). Site U1546D is characterized by a sill intrusion, but it had already reached thermal equilibrium and SRR were in the same range as nearby Site U1545C, which is minimally affected by sills. The wide temperature range observed at each drill site suggests major shifts in microbial community composition with very different temperature optima but awaits confirmation by molecular biological analyses. At the transition between the mesophilic and thermophilic range around 40°C–60°C, sulfate-reducing activity appears to be decreased, particularly in more oligotrophic settings, but shows a slight recovery at higher temperatures.
Virulence Determinants in Staphylococcus aureus Clones Causing Osteomyelitis in Italy
Authors: Pimentel de Araujo Fernanda , Pirolo Mattia , Monaco Monica , Del Grosso Maria , Ambretti Simone , Lombardo Donatella , Cassetti Tiziana , Gargiulo Raffaele , Riccobono Eleonora , Visca Paolo , Pantosti Annalisa
Published: March 2022

Staphylococcus aureus is the most common pathogen causing osteomyelitis (OM). The aim of this study was to explore the clonal complex (CC) distribution and the pattern of virulence determinants of S. aureus isolates from OM in Italy. Whole-genome sequencing was performed on 83 S. aureus isolates from OM cases in six hospitals. Antibiotic susceptibility tests showed that 30.1% of the isolates were methicillin-resistant S. aureus (MRSA). The most frequent CCs detected were CC22, CC5, CC8, CC30, and CC15, which represent the most common lineages circulating in Italian hospitals. MRSA were limited in the number of lineages (CC22, CC5, CC8, and CC1). Phylogenetic analysis followed the sequence type-CC groupings and revealed a non-uniform distribution of the isolates from the different hospitals. No significant difference in the mean number of virulence genes carried by MRSA or MSSA isolates was observed. Some virulence genes, namely cna, fib, fnbA, coa, lukD, lukE, sak, and tst, were correlated with the CC. However, different categories of virulence factors, such as adhesins, exoenzymes, and toxins, were frequently detected and unevenly distributed among all lineages. Indeed, each lineage carried a variable combination of virulence genes, likely reflecting functional redundancy, and arguing for the importance of those traits for the pathogenicity in OM. In conclusion, no specific genetic trait in the most frequent lineages could explain their high prevalence among OM isolates. Our findings highlight that CCs detected in OM isolates follow the epidemiology of S. aureus infections in the country. It is conceivable that any of the most common S. aureus CC can cause a variety of infections, including OM.
Force-Generation by the Trans-Envelope Tol-Pal System
Authors: Webby Melissa N. , Williams-Jones Daniel P. , Press Cara , Kleanthous Colin
Published: March 2022

The Tol-Pal system spans the cell envelope of Gram-negative bacteria, transducing the potential energy of the proton motive force (PMF) into dissociation of the TolB-Pal complex at the outer membrane (OM), freeing the lipoprotein Pal to bind the cell wall. The primary physiological role of Tol-Pal is to maintain OM integrity during cell division through accumulation of Pal molecules at division septa. How the protein complex couples the PMF at the inner membrane into work at the OM is unknown. The effectiveness of this trans-envelope energy transduction system is underscored by the fact that bacteriocins and bacteriophages co-opt Tol-Pal as part of their import/infection mechanisms. Mechanistic understanding of this process has been hindered by a lack of structural data for the inner membrane TolQ-TolR stator, of its complexes with peptidoglycan (PG) and TolA, and of how these elements combined power events at the OM. Recent studies on the homologous stators of Ton and Mot provide a starting point for understanding how Tol-Pal works. Here, we combine ab initio protein modeling with previous structural data on sub-complexes of Tol-Pal as well as mutagenesis, crosslinking, co-conservation analysis and functional data. Through this composite pooling of in silico, in vitro, and in vivo data, we propose a mechanism for force generation in which PMF-driven rotary motion within the stator drives conformational transitions within a long TolA helical hairpin domain, enabling it to reach the TolB-Pal complex at the OM.
Characterization of Two Novel Toti-Like Viruses Co-infecting the Atlantic Blue Crab, Callinectes sapidus, in Its Northern Range of the United States
Authors: Zhao Mingli , Xu Lan , Bowers Holly , Schott Eric J.
Published: March 2022

The advancement of high throughput sequencing has greatly facilitated the exploration of viruses that infect marine hosts. For example, a number of putative virus genomes belonging to the Totiviridae family have been described in crustacean hosts. However, there has been no characterization of the most newly discovered putative viruses beyond description of their genomes. In this study, two novel double-stranded RNA (dsRNA) virus genomes were discovered in the Atlantic blue crab (Callinectes sapidus) and further investigated. Sequencing of both virus genomes revealed that they each encode RNA dependent RNA polymerase proteins (RdRps) with similarities to toti-like viruses. The viruses were tentatively named Callinectes sapidus toti-like virus 1 (CsTLV1) and Callinectes sapidus toti-like virus 2 (CsTLV2). Both genomes have typical elements required for −1 ribosomal frameshifting, which may induce the expression of an encoded ORF1–ORF2 (gag-pol) fusion protein. Phylogenetic analyses of CsTLV1 and CsTLV2 RdRp amino acid sequences suggested that they are members of two new genera in the family Totiviridae. The CsTLV1 and CsTLV2 genomes were detected in muscle, gill, and hepatopancreas of blue crabs by real-time reverse transcription quantitative PCR (RT-qPCR). The presence of ~40 nm totivirus-like viral particles in all three tissues was verified by transmission electron microscopy, and pathology associated with CsTLV1 and CsTLV2 infections were observed by histology. PCR assays showed the prevalence and geographic range of these viruses, to be restricted to the northeast United States sites sampled. The two virus genomes co-occurred in almost all cases, with the CsTLV2 genome being found on its own in 8.5% cases, and the CsTLV1 genome not yet found on its own. To our knowledge, this is the first report of toti-like viruses in C. sapidus. The information reported here provides the knowledge and tools to investigate transmission and potential pathogenicity of these viruses.
Neurons Release Injured Mitochondria as “Help-Me” Signaling After Ischemic Stroke
Authors: Gao Li , Liu Fan , Hou Pin-Pin , Manaenko Anatol , Xiao Zhi-Peng , Wang Fei , Xu Tian-Le , Hu Qin
Published: March 2022

Mitochondrial dysfunction has been regarded as one of the major contributors of ischemic neuronal death after stroke. Recently, intercellular mitochondrial transfer between different cell types has been widely studied and suggested as a potential therapeutic approach. However, whether mitochondria are involved in the neuron-glia cross-talk following ischemic stroke and the underlying mechanisms have not been explored yet. In this study, we demonstrated that under physiological condition, neurons release few mitochondria into the extracellular space, and the mitochondrial release increased when subjected to the challenges of acidosis, hydrogen peroxide (H2O2), N-methyl-D-aspartate (NMDA), or glutamate. Acidosis reduced the mitochondrial basal respiration and lowered the membrane potential in primary-cultured mouse cortical neurons. These defective mitochondria were prone to be expelled to the extracellular space by the injured neurons, and were engulfed by adjacent astrocytes, leading to increased astrocytic expressions of mitochondrial Rho GTPase 1 (Miro 1) and mitochondrial transcription factor A (TFAM) at mRNA level. In mice subjected to transient focal cerebral ischemia, the number of defective mitochondria in the cerebrospinal fluid increased. Our results suggested that the neuron-derived mitochondria may serve as a “help-me” signaling and mediate the neuron-astrocyte cross-talk following ischemic stroke. Promoting the intercellular mitochondrial transfer by accelerating the neuronal releasing or astrocytic engulfing might be a potential and attractive therapeutic strategy for the treatment of ischemic stroke in the future.
The Olfactory Tract: Basis for Future Evolution in Response to Rapidly Changing Ecological Niches
Authors: Whitlock Kathleen E. , Palominos M. Fernanda
Published: March 2022

Within the forebrain the olfactory sensory system is unique from other sensory systems both in the projections of the olfactory tract and the ongoing neurogenic potential, characteristics conserved across vertebrates. Olfaction plays a crucial role in behaviors such as mate choice, food selection, homing, escape from predators, among others. The olfactory forebrain is intimately associated with the limbic system, the region of the brain involved in learning, memory, and emotions through interactions with the endocrine system and the autonomic nervous system. Previously thought to lack a limbic system, we now know that teleost fishes process emotions, have exceptional memories, and readily learn, behaviors that are often associated with olfactory cues. The association of neuromodulatory hormones, and more recently, the immune system, with odor cues underlies behaviors essential for maintenance and adaptation within natural ecological niches. Increasingly anthropogenic perturbations affecting ecosystems are impacting teleost fishes worldwide. Here we examine the role of the olfactory tract as the neural basis for the integration of environmental cues and resulting behaviors necessary for the regulation of biotic interactions that allow for future adaptation as the climate spins out of control.
Thyroid Function Affects the Risk of Post-stroke Depression in Patients With Acute Lacunar Stroke
Authors: Guo Jianglong , Wang Jinjing , Xia Yue , Jiang Shiyi , Xu Pengfei , Tao Chunrong , Sun Wen , Liu Xinfeng
Published: March 2022

Objective

This study aimed to investigate whether thyroid function profiles are associated with post-stroke depression (PSD) and evaluate the mediation effect of cerebral small vessel disease (cSVD) on the association of thyroid function profiles and PSD in patients with acute ischemic lacunar stroke.

Methods

In this study, 372 patients with confirmed acute ischemic lacunar stroke within 3 days of onset were consecutively recruited. Serum levels of thyroid hormones and thyroid antibodies were detected on admission. Lacunar infarcts, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. The severity of depression was scored with the 24-item Hamilton Depression Scale in the hospital after a week of stroke onset. Multivariate regression was utilized to analyze the association of thyroid function profiles and PSD. Mediation analysis was employed to evaluate the effect of cSVD on the association of thyroid function profiles and PSD.

Results

A total of 87 (23.4%) participants were diagnosed with depression after stroke. Serum thyroid-stimulating hormone (TSH) levels were significantly higher in patients with PSD than in those without PSD, while free triiodothyronine (FT3) and free thyroxine (FT4) were not significantly different between the two groups. After adjusting for potential confounders, serum TSH levels were positively associated with the risk of PSD (OR = 1.228; 95% CI: 1.053–1.431, p = 0.009). A similar association was also found between the total cSVD burden score and PSD (OR = 2.137; 95% CI: 1.634–2.793, p < 0.001). Further mediation analysis indicated that 26.37% of the association between TSH and PSD was mediated by cSVD.

Conclusions

Serum TSH levels on admission can probably predict depression after acute ischemic lacunar stroke.