Abstract
PLEs (phage-inducible chromosomal island-like elements) are phage parasites integrated into the chromosome of epidemic Vibrio cholerae. In response to infection by its viral host ICP1, PLE ...excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism, PLE prevents ICP1 from transitioning to rolling circle replication (RCR), a prerequisite for efficient packaging of the viral genome. Here, we characterize a PLE-encoded nuclease, NixI, that blocks phage development likely by nicking ICP1’s genome as it transitions to RCR. NixI-dependent cleavage sites appear in ICP1’s genome during infection of PLE(+) V. cholerae. Purified NixI demonstrates in vitro nuclease activity specifically for sites in ICP1’s genome and we identify a motif that is necessary for NixI-mediated cleavage. Importantly, NixI is sufficient to limit ICP1 genome replication and eliminate progeny production, representing the most inhibitory PLE-encoded mechanism revealed to date. We identify distant NixI homologs in an expanded family of putative phage parasites in vibrios that lack nucleotide homology to PLEs but nonetheless share genomic synteny with PLEs. More generally, our results reveal a previously unknown mechanism deployed by phage parasites to limit packaging of their viral hosts’ genome and highlight the prominent role of nuclease effectors as weapons in the arms race between antagonizing genomes.
Lay Summary
Parasites of viruses, often referred to as satellites, are found in all domains of life and have been co-opted for host defense across diverse virus-host systems multiple independent times. This study describes the mechanism by which such an element prevents a bacterial virus (a ‘phage’) from otherwise infecting Vibrio cholera and related bacteria. The study is of broad interest to investigators with interests in phage-host interactions and microbial genetics.
The P2X7 receptor has recently been described as a marker for lung alveolar epithelial type I cells. Here, we demonstrate both the expression of P2X7 protein and its partition into lipid rafts in the ...mouse lung alveolar epithelial cell line E10. A significant degree of colocalization was observed between P2X7 and the raft marker protein Caveolin‐1; also, P2X7 protein was associated with caveolae. A marked reduction in P2X7 immunoreactivity was observed in lung sections prepared from Caveolin‐1‐knockout mice, indicating that Caveolin‐1 expression was required for full expression of P2X7 protein. Indeed, suppression of Caveolin‐1 protein expression in E10 cells using short hairpin RNAs resulted in a large reduction in P2X7 protein expression. Our data demonstrate a potential interaction between P2X7 protein and Caveolin‐1 in lipid rafts, and provide a basis for further functional and biochemical studies to probe the physiologic significance of this interaction.
Multiple studies have reported the prevalence of posttraumatic stress disorder (PTSD) in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans; however, these studies have been ...limited to populations who use the Department of Veterans Affairs (VA) for health care, specialty clinic populations, or veterans who deployed. The 3 aims of this study were to report weighted prevalence estimates of a positive screen for PTSD among OEF/OIF and nondeployed veterans, demographic subgroups, and VA health care system users and nonusers. The study analyzed data from the National Health Study for a New Generation of U.S. Veterans, a large population‐based cohort of OEF/OIF and OEF/OIF‐era veterans. The overall weighted prevalence of a positive screen for PTSD in the study population was 13.5%: 15.8% among OEF/OIF veterans and 10.9% in nondeployed veterans. Among OEF/OIF veterans, there was increased risk of a positive screen for PTSD among VA health care users (OR = 2.71), African Americans (OR = 1.61), those who served in the Army (OR = 2.67), and those on active duty (OR = 1.69). The same trend with decreased magnitude was observed in nondeployed veterans. PTSD is a significant public health problem in OEF/OIF‐era veterans, and should not be considered an outcome solely related to deployment.
Resumen
Spanish s by the Asociación Chilena de Estrés Traumático (ACET)
Varios estudios han reportado la prevalencia de trastorno por estrés post‐traumático (TEPT) en veteranos de las Operaciones de Libertad Duradera y Libertad Iraquí (OLD/OLI); sin embargo, estos estudios se han limitado a poblaciones que usan el sistema de salud del Departamento de Asuntos Veteranos (AV), especialmente poblaciones clínicas, o veteranos que fueron enviados a la Guerra. Los 3 objetivos de este estudio fueron reportar estimaciones de la prevalencia ponderada para un chequeo positivo de TEPT entre los subgrupos demográficos OLD/OLI y los veteranos no enviados a la Guerra, y los usuarios y no usuarios del Sistema de salud de AV. El estudio analizó los datos del Estudio Nacional de Salud para una Nueva Generación de Veteranos Norteamericanos, basado en una cohorte de una gran población de veteranos de OLD/OLI y de la era OLD/OLI. La prevalencia total ponderada de un chequeo positivo para TEPT en la población de estudio fue de 13.5%: 15.8% entre los veteranos OLD/OLI y 10.9% en los veteranos no enviados a la Guerra. Entre los veteranos OLD/OLI, hubo un mayor riesgo de chequeo positivo para TEPT en los usuarios del Sistema de salud AV OR=2.71), afroamericanos (OR=1.61), aquellos que sirvieron a la Armada (OR=2.67) y en servicio activo (OR=1.69). La misma tendencia con una menor magnitud se observa en veteranos no enviados a la Guerra. El TEPT es un problema de salud pública significativo en los veteranos de la era OLD/OLI y no debería ser considerado una consecuencia exclusiva de relacionada al despliegue a zona de Guerra.
抽象
Traditional and Simplified Chinese s by AsianSTSS
標題：大型人口世代的OEF/OIF和OEF/OIF年代退役軍中PTSD正篩查的患病率。
撮要：我們有很多維持和平和伊拉克自由行動(OEF/OIF)退役兵創傷後壓力症(PTSD)的流行率研究。但這些研究局限在退役軍人部門(VA)使用醫療服務人羣、專科診所病人或被調配老兵。本研究有3個目的：報告OEF/OIF和未調派退役兵、人口子組別、和VA醫療服務使用者/非使用者中有PTSD正篩查的加權患病率估量。一個OEF/OIF和OEF/OIF時代退役兵的大型人口世代研究，即美國全國新生代退役兵健康研究數據作分析。PTSD正篩查的綜合加權患病率是13.5%，OEF/OIF退役軍是15.8%，而非調派退役兵則為10.9%。在OEF/OIF退役兵中，VA醫療服務使用者(OR=2.71) 、非裔美國人(OR=1.61) 、在陸軍中曾服役者(OR=2.67)和現役士兵(OR=1.69)都有較高PTSD正篩查風險。但非調派者有相同趨勢但減退幅度。PTSD在OEF/OIF年代退役軍中是顯著的公共健康問題，而非只與調派任務有關係。
标题：大型人口世代的OEF/OIF和OEF/OIF年代退役军中PTSD正筛查的患病率。
撮要：我们有很多维持和平和伊拉克自由行动(OEF/OIF)退役兵创伤后压力症(PTSD)的流行率研究。但这些研究局限在退役军人部门(VA)使用医疗服务人羣、专科诊所病人或被调配老兵。本研究有3个目的：报告OEF/OIF和未调派退役兵、人口子组别、和VA医疗服务使用者/非使用者中有PTSD正筛查的加权患病率估量。一个OEF/OIF和OEF/OIF时代退役兵的大型人口世代研究，即美国全国新生代退役兵健康研究数据作分析。PTSD正筛查的综合加权患病率是13.5%，OEF/OIF退役军是15.8%，而非调派退役兵则为10.9%。在OEF/OIF退役兵中，VA医疗服务使用者(OR=2.71) 、非裔美国人(OR=1.61) 、在陆军中曾服役者(OR=2.67)和现役士兵(OR=1.69)都有较高PTSD正筛查风险。但非调派者有相同趋势但减退幅度。PTSD在OEF/OIF年代退役军中是显著的公共健康问题，而非只与调派任务有关系。
Abstract
Phage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found in Vibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, ...replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robust replication of the PLE genome, relatively few transducing units are produced. We investigated if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage. Replication of PLE was necessary for interference of ICP1 DNA replication, but replication of a minimalized PLE replicon was not sufficient for ICP1 DNA replication interference. Despite restoration of ICP1 DNA replication, non-replicating PLE remained broadly inhibitory against ICP1. These results suggest that PLE DNA replication is one of multiple mechanisms contributing to ICP1 restriction.
Bone morphogenetic proteins (Bmps) are key regulators of dorsoventral (DV) patterning. Within the ectoderm, Bmp activity has been shown to inhibit neural development, promote epidermal ...differentiation and influence the specification of dorsal neurons and neural crest. In this study, we examine the patterning of neural tissue in mutant zebrafish embryos with compromised Bmp signalling activity. We find that although Bmp activity does not influence anteroposterior (AP) patterning, it does affect DV patterning at all AP levels of the neural plate. Thus, we show that Bmp activity is required for specification of cell fates around the margin of the entire neural plate, including forebrain regions that do not form neural crest. Surprisingly, we find that Bmp activity is also required for patterning neurons at all DV levels of the CNS. In swirl/bmp2b(â) (swr(â)) embryos, laterally positioned sensory neurons are absent whereas more medial interneuron populations are hugely expanded. However, in somitabun(â) (sbn(â)) embryos, which probably retain higher residual Bmp activity, it is the sensory neurons and not the interneurons that are expanded. Conversely, in severely Bmp depleted embryos, both interneurons and sensory neurons are absent and it is the most medial neurons that are expanded. These results are consistent with there being a gradient of Bmp-dependent positional information extending throughout the entire neural and non-neural ectoderm.
The purinergic receptor P2X7 represents an ATP-gated ionotropic receptor with a selective localization in alveolar epithelial type I cells of the lung. Despite the involvement of the receptor in ...inflammatory processes of the lung, it is not established whether this receptor plays a specific role in the alveolar epithelial cell biology. There is evidence that P2X7 receptor influences Wnt/β-catenin signalling pathways in alveolar epithelial cells under conditions of injury. Here, we investigated the expression of GSK-3β, a potent protein kinase involved in alveolar epithelial barrier functions, and of tight junction molecules occludin, claudin-4 and claudin-18 in wild-type and P2X7
−/−
mice. Western blot analysis, immunohistochemistry and quantitative real-time RT-PCR revealed a remarkable increase in claudin-18 mRNA and protein in lungs of P2X7
−/−
mice animals. Furthermore, alveolar epithelial cells from P2X7
−/−
animals showed decreased levels of GSK-3β protein and its inactive form GSK-3β (pS9). Conversely, claudin-18 knockout mice exhibited decreased P2X7 mRNA transcript abundance as measured by mRNA expression microarray and quantitative PCR. Our data are consistent with the hypothesis that P2X7R contributes to alveolar epithelial barrier function through effects on GSK-3β. Furthermore, these data suggest a potential reciprocal regulation of claudin-18 and P2X7R in the alveolar epithelium.
Background: Studies on the incidence of COVID-19 among persons with HIV (PWH) present varied results. Few studies have investigated the impact of COVID-19 infection on health and socioeconomic ...factors or COVID-19 stigma. We sought to measure the incidence and severity of COVID-19 infection among a cohort of PWH, characterize associated risk factors and impact, and document perceptions of COVID-19-related stigma. Methods: Data for this cross-sectional study come from the COVID-19 survey of participants in the DC Cohort longitudinal study from October 30, 2020 through December 31, 2022. Survey results were linked to electronic health records, including HIV labs and COVID test results. We conducted analyses comparing demographic, socioeconomic, HIV measures, and stigma among those with and without self-reported COVID-19. Results: Out of 1,972 survey respondents, 17% self-reported COVID-19 infection, with greatest incidence in the Omicron wave of the pandemic. We found statistically significant differences by age, employment status, essential worker status, education, and household income. Longer duration of HIV diagnosis was associated with greater incidence of COVID-19. PWH who were overweight or obese had greater incidence of COVID-19 compared to those who were not. Over 40% of PWH with COVID-19 reported experiencing at least one form of COVID-19-related stigma. Conclusion: We observed a high incidence of COVID-19 infection among PWH in DC. Further, a substantial proportion of PWH with COVID-19 reported experiencing COVID-19 related stigma. These findings add to the existing literature on COVID-19 co-infection among PWH and highlight the need for awareness and support for those experiencing COVID-19 stigma.
•A PI-RADS Score Calculator may significantly fasten the reporting process in Prostate MRI.•Increased PI-RADS v2.1 reporting speed does not translate into lower diagnostic accuracy.•Particularly ...non-expert radiologists may profit in terms of prostate MRI reporting efficiency.
To evaluate the value of a browser-based PI-RADS Score Calculator (PCalc) compared to MRI reporting using the official PI-RADS v2.1 document (PDoc) for non-specialized radiologists in terms of reporting efficiency, interrater agreement and diagnostic accuracy for detection of clinically significant prostate cancer (PCa).
Between 09/2013 and 04/2015, 100 patients (median age, 64.8; range 47.5−78.2) who underwent prostate-MRI at a 3 T scanner and who received transperineal prostate mapping biopsy within <6 months were included in this retrospective study. Two non-specialized radiology residents (R1, R2) attributed a PI-RADS version 2.1 score for the most suspect (i. e. index) lesion (i) using the original PI-RADS v2.1 document only and after a 6-week interval (ii) using a browser-based PCalc. Reading time was measured. Reading time differences were assessed using Wilcoxon signed rank test. Intraclass-correlation Coefficient (ICC) was used to assess interrater agreement (IRA). Parameters of diagnostic accuracy and ROC curves were used for assessment of lesion-based diagnostic accuracy.
Cumulative reading time was 32:55 (mm:ss) faster when using the PCalc, the difference being statistically significant for both readers (p < 0.05). The difference in IRA between the image sets (ICC 0.55 0.40, 0.68) and 0.75 0.65, 0.82 for the image set with PDoc and PCalc, respectively) was not statistically significant. There was no statistically significant difference in lesion-based diagnostic accuracy (AUC 0.83 0.74, 0.92 and 0.82 95 %CI: 0.74, 0.91) for images assessed with PDoc as compared to PCalc (AUC 0.82 0.74, 0.91 and 0.74 95 %CI: 0.64, 0.83) for R1 and R2, respectively.
Non-specialized radiologists may increase reading speed in prostate MRI with the help of a browser-based PI-RADS Score Calculator compared to reporting using the official PI-RADS v2.1 document without impairing interreader agreement or lesion-based diagnostic accuracy for detection of clinically significant PCa.
The Nodal and Hedgehog signaling pathways influence dorsoventral patterning at all axial levels of the CNS, but it remains largely unclear how these pathways interact to mediate patterning. Here we ...show that, in zebrafish, Nodal signaling is required for induction of the homeobox genes
nk2.1a in the ventral diencephalon and
nk2.1b in the ventral telencephalon. Hedgehog signaling is also required for telencephalic
nk2.1b expression but may not be essential to establish diencephalic
nk2.1a expression. Furthermore, Shh does not restore ventral diencephalic development in embryos lacking Nodal activity. In contrast, Shh does restore telencephalic
nk2.1b expression in the absence of Nodal activity, suggesting that Hedgehog signaling acts downstream of Nodal activity to pattern the ventral telencephalon. Thus, the Nodal pathway regulates ventral forebrain patterning through both Hedgehog signaling-dependent and -independent mechanisms.
•Image quality is similar for different body phased-array receive coil setups.•An 18-channel body phased-array receive coil setup achieved good image quality.•60-channel body phased-array receive ...coil setup slightly improves SNR in T2W images.
To evaluate the influence of body phased-array (BPA) receive coil setups on signal-to-noise ratio (SNR) and image quality (IQ) in prostate MRI.
This prospective study evaluated axial T2-weighted images (T2W-TSE) and DWI of the prostate in ten healthy volunteers with 18-channel (18CH), 30-channel and 60-channel (60CH) BPA receive coil setups. SNR and ADC values were assessed in the peripheral and transition zones (TZ). Two radiologists rated IQ features. Differences in qualitative and quantitative image features between BPA receive coil setups were compared. After correction for multiple comparisons, p-values <0.004 for quantitative and p-values <0.017 for qualitative image analysis were considered statistically significant.
Significantly higher SNR was found in T2W-TSE images in the TZ using 60CH BPA compared to 18CH BPA coil setups (15.20 ± 4.22 vs. 7.68 ± 2.37; p = 0.001). There were no significant differences between all other quantitative (T2W-TSE, p = 0.007−0.308; DWI, p = 0.024−0.574) and qualitative image features (T2W-TSE, p = 0.083–1.0; DWI, p = 0.046–1.0).
60CH BPA receive coil setup showed marginal SNR improvement in T2W-TSE images. Good IQ could be achieved with 18CH BPA coil setups.
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