MicroRNAs of Gallid and Meleagrid herpesviruses show generally conserved genomic locations and are virus-specific

AbstractMany herpesviruses, including Marek's disease viruses (MDV1 and MDV2), encode microRNAs. In this study, we report microRNAs of two related herpesviruses, infectious laryngotracheitis virus (ILTV) and herpesvirus of turkeys (HVT), as well as additional MDV2 microRNAs. The genome locations, but not microRNA sequences, are conserved among all four of these avian herpesviruses. Most are clustered in the repeats flanking the unique long region (I/TRL), except in ILTV which lacks these repeats. Two abundant ILTV microRNAs are antisense to the immediate early gene ICP4. A homologue of host microRNA, gga-miR-221, was found among the HVT microRNAs. Additionally, a cluster of HVT microRNAs was found in a region containing two locally duplicated segments, resulting in paralogous HVT microRNAs with 96–100% identity. The prevalence of microRNAs in the genomic repeat regions as well as in local repeats suggests the importance of genetic plasticity in herpesviruses for microRNA evolution and preservation of function

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

IFN-gamma Plays a Unique Role in Protection against Low Virulent Trypanosoma cruzi Strain

Background: T. cruzi strains have been divided into six discrete typing units (DTUs) according to their genetic background. These groups are designated T. cruzi I to VI. In this context, amastigotes from G strain (T. cruzi I) are highly infective in vitro and show no parasitemia in vivo. Here we aimed to understand why amastigotes from G strain are highly infective in vitro and do not contribute for a patent in vivo infection. Methodology/Principal Findings: Our in vitro studies demonstrated the first evidence that IFN-gamma would be associated to the low virulence of G strain in vivo. After intraperitoneal amastigotes inoculation in wild-type and knockout mice for TNF-alpha, Nod2, Myd88, iNOS, IL-12p40, IL-18, CD4, CD8 and IFN-gamma we found that the latter is crucial for controlling infection by G strain amastigotes. Conclusions/Significance: Our results showed that amastigotes from G strain are highly infective in vitro but did not contribute for a patent infection in vivo due to its susceptibility to IFN-gamma production by host immune cells. These data are useful to understand the mechanisms underlying the contrasting behavior of different T. cruzi groups for in vitro and in vivo infection.CAPES [3038.005295/2011-40]CAPESFAPEMIGFAPEMIG [APQ-00621-11]CNPqCNPqFAPESPFAPESP [10-50959-4

Opposing the toxic apartheid: The painted veil of the COVID‐19 pandemic, race and racism

This article is a personal reflection of how the coronavirus exposes ‘shocking’ levels of racism against us, and our vulnerability as Chinese women living in Britain. By reflecting our experiences of verbal and physical race‐based violence connected to coronavirus, we explore the fluidity of our racial identities, the taken‐for‐granted racial stereotypes and white privilege, and everyday racism in the UK. Can the vulnerable use vulnerability as an agent to shift the moment of helplessness? We contribute to the uncomfortable yet important debate on racism against Chinese women living in the UK through voicing up our embodied vulnerability as invisible and disempowered subjects to this viral anti‐Chinese racism. This is a form of resistance where we care for the racialized and marginalized others. In doing so, we lift the painted veil of the pandemic, race and racism to collectively combat racial inequalities

Peer support for frequent users of inpatient mental health care in Uganda: protocol of a quasi-experimental study.

BACKGROUND: Reducing readmissions among frequent users of psychiatric inpatient care could result in substantial cost savings to under-resourced mental health systems. Studies from high-income countries indicate that formal peer support can be an effective intervention for the reduction of readmissions among frequent users. Although in recent years formal peer support programmes have been established in mental health services in a few low- and middle-income countries (LMICs), they have not been rigorously evaluated. METHODS: This protocol describes a quasi-experimental difference-in-differences study conducted as part of a broader evaluation of the Brain Gain II peer support programme based at Butabika National Referral Hospital in Kampala, Uganda. The primary objective is to investigate whether frequent users of psychiatric inpatient care who have access to a peer support worker (PSW+) experience a greater reduction in rehospitalisation rates and number of days spent in hospital compared to those who do not have access to a peer support worker (PSW-). Frequent users, defined as adults diagnosed with either a mental disorder or epilepsy who have had three or more inpatient stays at Butabika over the previous 24 months, are referred to Brain Gain II by hospital staff on five inpatient wards. Frequent users who normally reside in a district where peer support workers currently operate (Kampala, Jinja, Wakiso and Mukono) are eligible for formal peer support and enter the PSW+ group. Participants in the PSW+ group are expected to receive at least one inpatient visit by a trained peer support worker before hospital discharge and three to six additional visits after discharge. Frequent users from other districts enter the PSW- group and receive standard care. Participants' admissions data are extracted from hospital records at point of referral and six months following referral. DISCUSSION: To the best of our knowledge, this will be the first quasi-experimental study of formal peer support in a LMIC and the first to assess change in readmissions, an outcome of particular relevance to policy-makers seeking cost-effective alternatives to institutionalised mental health care

The Simons Observatory: Characterizing the Large Aperture Telescope Receiver with Radio Holography

We present near-field radio holography measurements of the Simons Observatory Large Aperture Telescope Receiver optics. These measurements demonstrate that radio holography of complex millimeter-wave optical systems comprising cryogenic lenses, filters, and feed horns can provide detailed characterization of wave propagation before deployment. We used the measured amplitude and phase, at 4K, of the receiver near-field beam pattern to predict two key performance parameters: 1) the amount of scattered light that will spill past the telescope to 300K and 2) the beam pattern expected from the receiver when fielded on the telescope. These cryogenic measurements informed the removal of a filter, which led to improved optical efficiency and reduced side-lobes at the exit of the receiver. Holography measurements of this system suggest that the spilled power past the telescope mirrors will be less than 1% and the main beam with its near side-lobes are consistent with the nominal telescope design. This is the first time such parameters have been confirmed in the lab prior to deployment of a new receiver. This approach is broadly applicable to millimeter and sub-millimeter instruments.Comment: in proces

IL-17 Produced during Trypanosoma cruzi Infection Plays a Central Role in Regulating Parasite-Induced Myocarditis

Chagas disease is caused by the intracellular parasite Trypanosoma cruzi. This infection has been considered one of the most neglected diseases and affects several million people in the Central and South America. Around 30% of the infected patients develop digestive and cardiac forms of the disease. Most patients are diagnosed during the chronic phase, when the treatment is not effective. Here, we showed by the first time that IL-17 is produced during experimental T. cruzi infection and that it plays a significant role in host defense, modulating parasite-induced myocarditis. Applying this analysis to humans could be of great value in unraveling the elements involved in the pathogenesis of chagasic cardiopathy and could be used in the development of alternative therapies to reduce morbidity during the chronic phase of the disease, as well as clinical markers of disease progression. The understanding of these aspects of disease may be helpful in reducing the disability-adjusted life years (DALYs) and costs to the public health service in developing countries

Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer

A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent CNAs is key to advancing therapeutics because it is likely that these regions contain breast tumor ‘drivers’ (i.e., cancer causal genes). This study aims to characterize the genomic landscape of breast cancer CNAs and identify potential subtype-specific drivers using a large set of human breast tumors and genetically engineered mouse (GEM) mammary tumors. Using a novel method called SWITCHplus, we identified subtype-specific DNA CNAs occurring at a 15% or greater frequency, which excluded many well-known breast cancer-related drivers such as amplification of ERBB2, and deletions of TP53 and RB1. A comparison of CNAs between mouse and human breast tumors identified regions with shared subtype-specific CNAs. Additional criteria that included gene expression-to-copy number correlation, a DawnRank network analysis, and RNA interference functional studies highlighted candidate driver genes that fulfilled these multiple criteria. Numerous regions of shared CNAs were observed between human breast tumors and GEM mammary tumor models that shared similar gene expression features. Specifically, we identified chromosome 1q21-23 as a Basal-like subtype-enriched region with multiple potential driver genes including PI4KB, SHC1, and NCSTN. This step-wise computational approach based on a cross-species comparison is applicable to any tumor type for which sufficient human and model system DNA copy number data exist, and in this instance, highlights that a single region of amplification may in fact harbor multiple driver genes.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3476-2) contains supplementary material, which is available to authorized users