Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of the Type VI Secretion System in the Squid Symbiont Vibrio fischeri Requires the Transcriptional Regulator TasR and the Structural Proteins TssM and TssA

Interbacterial weapons like the T6SS are often located on mobile genetic elements, and their expression is highly regulated. We found that two conserved structural proteins are required for T6SS expression in Vibrio fischeri. ABSTRACT Bacteria have evolved diverse strategies to compete for a niche, including the type VI secretion system (T6SS), a contact-dependent killing mechanism. T6SSs are common in bacterial pathogens, commensals, and beneficial symbionts, where they affect the diversity and spatial structure of host-associated microbial communities. Although T6SS gene clusters are often located on genomic islands (GIs), which may be transferred as a unit, the regulatory strategies that promote gene expression once the T6SS genes are transferred into a new cell are not known. We used the squid symbiont Vibrio fischeri to identify essential regulatory factors that control expression of a strain-specific T6SS encoded on a GI. We found that a transcriptional reporter for this T6SS is active only in strains that contain the T6SS-encoding GI, suggesting the GI encodes at least one essential regulator. A transposon screen identified seven mutants that could not activate the reporter. These mutations mapped exclusively to three genes on the T6SS-containing GI that encode two essential structural proteins (a TssA-like protein and TssM) and a transcriptional regulator (TasR). Using T6SS reporters, reverse transcription-PCR (RT-PCR), competition assays, and differential proteomics, we found that all three genes are required for expression of many T6SS components, except for the TssA-like protein and TssM, which are constitutively expressed. Based on these findings, we propose a model whereby T6SS expression requires conserved structural proteins, in addition to the essential regulator TasR, and this ability to self-regulate may be a strategy to activate T6SS expression upon transfer of T6SS-encoding elements into a new bacterial host. IMPORTANCE Interbacterial weapons like the T6SS are often located on mobile genetic elements, and their expression is highly regulated. We found that two conserved structural proteins are required for T6SS expression in Vibrio fischeri. These structural proteins also contain predicted GTPase and GTP binding domains, suggesting their role in promoting T6SS expression may involve sensing the energetic state of the cell. Such a mechanism would provide a direct link between T6SS activation and cellular energy levels, providing a “checkpoint” to ensure the cell has sufficient energy to build such a costly weapon. Because these regulatory factors are encoded within the T6SS gene cluster, they are predicted to move with the genetic element to activate T6SS expression in a new host cell.
Growth of passive oxide films on iron and titanium under non-stationary state

Abstract Growth of passive oxides on iron and titanium under the non-stationary state was studied during constant current density (CD) oxidation and potential sweep oxidation. Increase and decrease of the thickness of the passive oxide film were determined from the relation between dissolution and growth CDs. By using rotating Fe disc-Pt ring electrode, the CDs of the dissolution from the oxide to solution and the growth of the passive oxide on iron were simultaneously measured. From the ratio of the growth CD to the dissolution CD and the pH dependence of the growth CD, a possible mechanism was discussed. Next, the growth of passive oxides on iron in pH 8.4 borate solution and on titanium in 0.1 m sulfuric acid solution during the potential sweep oxidation was examined by using three-parameter ellipsometry. Oxide growth was initially delayed when the sweep in the positive direction was started, and then the oxide film linearly grew with the potential increase. It was found that the oxide growth rate influenced the properties of the oxide film. The electric field in the oxide film during the non-stationary growth was discussed, concerned with the CD of the oxide film formation.
Contraceptive choice as risk reduction? The relevance of local violence for women’s uptake of sterilization in Colombia

Altered childbearing behaviour has been observed in many settings of violent conflict, but few studies have addressed fertility control. This is the first study to investigate empirically the relationship between local conflict and uptake of sterilization, the only contraceptive method that reflects a definitive stop to childbearing. The study is based on Colombia, a middle-income, low-fertility, and long-term conflict setting. It builds on a mixed methods approach, combining survey and conflict data with expert interviews. Fixed effects regressions show that local conflict is generally associated with an increased sterilization uptake. The interviews suggest that women may opt for sterilization when reversible methods become less accessible because of ongoing violence. Since sterilization is a relatively available contraceptive option in Colombia, it may represent a risk-aversion strategy for women who have completed their fertility goals. These findings can enlighten research and programmes on fertility and family planning in humanitarian contexts.
Soft law and individual responsibility: a review of the Swedish policy response to COVID-19

Abstract Sweden's coronavirus disease 2019 (COVID-19) response, initially based largely on voluntary measures, has evoked strong reactions nationally and internationally. In this study, we describe Sweden's national policy response with regard to the general public, the community and the health care system, with a focus on how the response changed from March 2020 to June 2021. A number of factors contributed to Sweden's choice of policy response, including its existing legal framework, independent expert agencies and its decentralized, multi-level health care governance system. Challenges to the health- and elder care system during the pandemic, such as the need to increase intensive care- and testing capacity, and to ensure the safety of the elderly were addressed largely at the regional and local levels, with national authorities assuming a primarily coordinative role. Although the overall response based on voluntary compliance has persisted, the national government started to take a more prominent role in public messaging, and in enacting legally binding restrictions during subsequent waves of the pandemic. This study illustrates that not only policy responses, but also the fundamental structure of the health- and elder care system and its governance should be considered when evaluating the impact of the COVID-19 pandemic.
Exploring Transgender and Gender Diverse Young Adult Tobacco Use

ABSTRACT Aside from prevalence estimates and comparisons to heterosexual and presumed cisgender (i.e., not transgender) samples, little is known about transgender and gender diverse (TGD) young adult tobacco use. This study explored reasons and contexts TGD young adults used a variety of tobacco products through 25 one-on-one semi-structured qualitative interviews in 2018. Thematic analysis yielded four themes: (1) smoking in response to anxiety, depression, or stress, (2) social smoking, (3) accepting smoking-related norms, and (4) appealing aspects of tobacco. The first three themes contained elements specifically tied to TGD identity; the final theme related to perceptions of tobacco unrelated to identity. Findings suggest reasons for smoking that are unique to TGD young adults, who frequently reported smoking cigarettes as a coping response to an amalgam of stressors. Accounting for unique stressors related to TGD identity will assist in developing culturally relevant interventions to reduce the disproportionate tobacco burden in TGD communities.
Human hepatoma cell line hep-t2

PURPOSE: A human hepatoma cell line HEP-T2 is provided, which is useful for study on the effects of HBV(hepatitis B virus) infection on the development of cancer, so that cancer metastasis can be inhibited. CONSTITUTION: The human hepatoma cell line HEP-T2 (KCTC 10398BP) transformed with HBV(hepatitis B virus) is provided, wherein the HEP-T2 (KCTC 10398BP) secretes HBV virus particles in the culture medium; the HEP-T2 (KCTC 10398BP) improves the activity of glucose transferring enzymes GnT(N-acetylglucosaminyltransferase)-III and GnT-V; the HEP-T2 (KCTC 10398BP) improves the activity of metalloprotein decomposing enzymes MMP(matrix metalloproteinase)-2 and MMP-9; and the HEP-T2 (KCTC 10398BP) inhibits the activity of selective MMP inhibitors TIMP(matrix metalloproteinase)-1 and TIMP-3.
Detection of potentially pathogenic Arcobacter spp. in Bangkok canals and the Chao Phraya River.

The management of pathogenic bacteria in waterways is a public health issue. Here, we investigated the concentrations of potentially pathogenic bacteria, Arcobacter spp. and Campylobacter spp. , and Escherichia coli, by quantifying species-specific genes in surface water samples from canals and the Chao Phraya River from June 2017 to June 2018 in Bangkok, Thailand. We assessed the relationship between the specific bacterial concentrations, water quality, and seasonal changes. Arcobacter spp. were detected at high density in all samples and showed seasonal fluctuations according to analyses based on 16S rDNA and the invasion gene ciaB. High levels of 16S rDNA and dut gene of E. coli were detected in the polluted drainage canals. A high correlation was observed between E. coli and chemical and biochemical oxygen demand (COD and BOD), suggesting that untreated domestic wastewater was the source of the E. coli. In contrast, Arcobacter spp. were detected with high density even in water samples with relatively low COD, suggesting that Arcobacter spp. are more likely than E. coli to survive in the water environment. The analysis of 16S rDNA and ciaB gene sequence analyses indicated that the Arcobacter spp. isolated from the drainage canals were A. butzleri and A. cryaerophilus.
Population Genomics of emm4 Group A Streptococcus Reveals Progressive Replacement with a Hypervirulent Clone in North America

Severe invasive infections caused by group A Streptococcus (GAS) result in substantial morbidity and mortality in children and adults worldwide. Previously, GAS clonal strain replacement has been attributed to acquisition of exogenous DNA leading to novel virulence gene acquisition or increased virulence gene expression. ABSTRACT Clonal replacement is a major driver for changes in bacterial disease epidemiology. Recently, it has been proposed that episodic emergence of novel, hypervirulent clones of group A Streptococcus (GAS) results from acquisition of a 36-kb DNA region leading to increased expression of the cytotoxins Nga (NADase) and SLO (streptolysin O). We previously described a gene fusion event involving the gene encoding the GAS M protein (emm) and an adjacent M-like protein (enn) in the emm4 GAS population, a GAS emm type that lacks the hyaluronic acid capsule. Using whole-genome sequencing of a temporally and geographically diverse set of 1,126 isolates, we discovered that the North American emm4 GAS population has undergone clonal replacement with emergent GAS strains completely replacing historical isolates by 2017. Emergent emm4 GAS strains contained a handful of small genetic variations, including the emm-enn gene fusion, and showed a marked in vitro growth defect compared to historical strains. In contrast to other previously described GAS clonal replacement events, emergent emm4 GAS strains were not defined by acquisition of exogenous DNA and had no significant increase in transcript levels of nga and slo toxin genes via RNA sequencing and quantitative real-time PCR analysis relative to historic strains. Despite the in vitro growth differences, emergent emm4 GAS strains were hypervirulent in mice and ex vivo growth in human blood compared to historical strains. Thus, these data detail the emergence and dissemination of a hypervirulent acapsular GAS clone defined by small, endogenous genetic variation, thereby defining a novel model for GAS strain replacement. IMPORTANCE Severe invasive infections caused by group A Streptococcus (GAS) result in substantial morbidity and mortality in children and adults worldwide. Previously, GAS clonal strain replacement has been attributed to acquisition of exogenous DNA leading to novel virulence gene acquisition or increased virulence gene expression. Our study of type emm4 GAS identified emergence of a hypervirulent GAS clade defined by variation in endogenous DNA content and lacking augmented toxin gene expression relative to replaced strains. These findings expand our understanding of the molecular mechanisms underlying bacterial clonal emergence.
Sources of Infection Among Confirmed Cases of COVID-19 in Jeju Province, Korea

Objectives Jeju Province in Korea reported 627 coronavirus disease 2019 (COVID-19) cases between January 20, 2020, and March 31, 2021. This study analyzed the sources of infection among confirmed cases in Jeju Province, a self-governed island. Methods The sources of infection were broadly categorized as follows: (1) infections from overseas (confirmed patients who reported travel overseas or contact with overseas travelers); (2) infections from outside Jeju Province (confirmed patients who had visited other provinces or had contact with individuals who had traveled to other provinces in Korea); and (3) unknown sources of infection (confirmed patients who were infected following contact with an infected person whose source of infection was unknown). The chi-square test was used to analyze the differences in the distributions of related variables for each source of infection. Results Of the 627 confirmed cases, 38 (6.1%) were infections from overseas sources, 199 (31.7%) were from outside of Jeju Province, and 390 (62.2%) were from unknown sources. Jeju Province had no cases with an unknown source of infection during the first and second waves of the nationwide outbreak. Conclusions Infections from overseas sources could be blocked from spreading to local communities in Jeju Province by conducting screening at the airport, along with the preemptive suspension of visa-free entry. In addition, considering the scale of the nationwide outbreak, measures must be established to delay outbreaks from unknown sources of infection caused by sources outside Jeju Province.
Loss of Septation Initiation Network (SIN) kinases blocks tissue invasion and unlocks echinocandin cidal activity against Aspergillus fumigatus

Although considered effective treatment for many yeast fungi, the therapeutic efficacy of the echinocandin class of antifungals for invasive aspergillosis (IA) is limited. Recent studies suggest intense kinase- and phosphatase-mediated echinocandin adaptation in A. fumigatus. To identify A. fumigatus protein kinases required for survival under echinocandin stress, we employed CRISPR/Cas9-mediated gene targeting to generate a protein kinase disruption mutant library in a wild type genetic background. Cell wall and echinocandin stress screening of the 118 disruption mutants comprising the library identified only five protein kinase disruption mutants displaying greater than 4-fold decreased echinocandin minimum effective concentrations (MEC) compared to the parental strain. Two of these mutated genes, the previously uncharacterized A. fumigatus sepL and sidB genes, were predicted to encode protein kinases functioning as core components of the Septation Initiation Network (SIN), a tripartite kinase cascade that is necessary for septation in fungi. As the A. fumigatus SIN is completely uncharacterized, we sought to explore these network components as effectors of echinocandin stress survival. Our data show that mutation of any single SIN kinase gene caused complete loss of hyphal septation and increased susceptibility to cell wall stress, as well as widespread hyphal damage and loss of viability in response to echinocandin stress. Strikingly, mutation of each SIN kinase gene also resulted in a profound loss of virulence characterized by lack of tissue invasive growth. Through the deletion of multiple novel regulators of hyphal septation, we show that the non-invasive growth phenotype is not SIN-kinase dependent, but likely due to hyphal septation deficiency. Finally, we also find that echinocandin therapy is highly effective at eliminating residual tissue burden in mice infected with an aseptate strain of A. fumigatus. Together, our findings suggest that inhibitors of septation could enhance echinocandin-mediated killing while simultaneously limiting the invasive potential of A. fumigatus hyphae.
Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes

Chronic infection with HCV is manifested by dysregulation of innate immune responses and impaired T cell function at multiple levels. These changes may impact susceptibility to other infections, responsiveness to antiviral therapies, vaccine responsiveness, and development of complications such as hepatocellular carcinoma. Highly effective direct-acting antiviral (DAA) therapy has revolutionized the management of chronic HCV, with expected cure rates exceeding 95%. DAA treatment represents a unique opportunity to investigate to what extent elimination of viral replication and chronic antigen stimulation can restore immunologic phenotype. In this study we interrogated the global transcriptional profile of isolated peripheral blood T cells before, during and after IFN-free DAA therapy using single-cell mRNA sequencing. Our results demonstrate that T cells mapped at single-cell resolution have dramatic transcriptomic changes early after initiation of DAA and many of these changes are sustained after completion of DAA therapy. Specifically, we see a significant reduction in transcripts associated with innate immune activation and interferon signaling such as ISG15, ISG20, IFIT3, OAS and MX1 in many different T cell subsets. Furthermore, we find an early upregulation of a gene involved in suppression of immune activation, DUSP1, in circulating T cells. Conclusion: This study provides the first in-depth transcriptomic analysis at the single-cell level of patients undergoing DAA therapy, demonstrating that IFN-free antiviral therapy in chronic HCV infection induces hitherto unrecognized shifts in innate immune and interferon signaling within T cell populations early, during, and long-term after treatment. The present study provides a rich data source to explore the effects of DAA treatment on bulk T cells.
Tumor necrosis factor‐α expression aberration of M1/M2 macrophages in adult high‐functioning autism spectrum disorder

The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor‐α (TNF‐α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF‐α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF‐α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF‐α expression in M1 macrophages and the TNF‐α expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF‐α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF‐α expression in cultured macrophages may improve the understanding of ASD pathobiology.
A rare variant Klinefelter syndrome seen 40 years later: 47,X,del(Xq24),Y

Patients with Klinefelter syndrome (KS) show a typically 47,XXY karyotype; however, some variations have been observed, including 47,XX,der(Y), 46,XY/47,XXY, 48,XXXY, 48,XXYY, and mosaicism or structural sex chromosome abnormalities in some patients. In the literature, a rare KS variant, 47,X,del(Xq),Y karyotype, was reported in only a few cases prior to 1981. A 40‐year‐old man (IV‐3) was referred to our department due to infertility. His phenotype did not differ from the classic KS phenotype. He had two siblings (1‐male; 1‐female). His brother (IV‐5) had mental retardation and died one year earlier at age 32. Additionally, his sister (IV‐2) also had a history of infertility due to her husband's azoospermia. His mother had a history of 12 miscarriages. Karyotype analysis revealed the 47,X,del(Xq24),Y karyotype, and no deletions were seen in the AZF and SRY regions. We thought this chromosomal abnormality in the patient might have resulted from X‐autosome translocation in one of his parents since his mother had recurrent pregnancy loss and his sibling had mental retardation. However, we could not confirm it due to his parents were not alive. This study shows the first case of a long‐arm X‐chromosome deletion after a long period and reviews current knowledge concerning variant KS (deletion Xq).
Age dependent response to T4 overtreatment and recovery on systemic and organ level.

Thyroid hormone (TH) metabolism and cellular TH action are influenced by ageing. To investigate response to thyroxine (T4) overtreatment, a kinetic study was conducted in young and aged mice with chronic hyperthyroidism and hormone withdrawal. Five and 22 months old male mice were treated with T4 or PBS over 5 weeks, followed by observation for up to 12 days. Serial analysis was performed for thyroid function parameters, transcript levels of TH target genes, deiodinase type 1 (DIO1) activity as well as serum lipids at 12, 24, 72, 144, 216 and 288h after cessation of T4 administration. Higher FT3 concentrations and higher renal DIO1 activities were noted in aged mice 12h after T4 withdrawal and marked thyroid stimulating hormone elevation was found in aged mice after 12 days compared to respective controls. A biphasic expression pattern occurred for TH target genes in all organs and a hypothyroid organ state was observed at the end of study, despite normalization of TH serum concentrations after 72h. In line with this, mirror image kinetics were detected for serum cholesterol and triglycerides in aged and young mice. Recovery from TH overtreatment in mice involves short and medium-term adaption of TH metabolism on systemic and organ level. Increased renal DIO1 activity may contribute to higher T3 concentrations and prolonged thyrotoxicosis followed by hypothyroidism in an aged mouse organism. Translation of these findings in the clinical setting seems warranted and may lead to a better management of hyperthyroidism and prevention of T4 overtreatment in aged patients.