Identification of drought-responsive genes in roots of upland rice (Oryza sativa L)

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Mapping the Human Memory B Cell and Serum Neutralizing Antibody Responses to Dengue Virus Serotype 4 Infection and Vaccination

ABSTRACT The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses responsible for dengue fever and dengue hemorrhagic fever. People exposed to DENV develop antibodies (Abs) that strongly neutralize the serotype responsible for infection. Historically, infection with DENV serotype 4 (DENV4) has been less common and less studied than infections with the other three serotypes. However, DENV4 has been responsible for recent large and sustained epidemics in Asia and Latin America. The neutralizing antibody responses and the epitopes targeted against DENV4 have not been characterized in human infection. In this study, we mapped and characterized epitopes on DENV4 recognized by neutralizing antibodies in people previously exposed to DENV4 infections or to a live attenuated DENV4 vaccine. To study the fine specificity of DENV4 neutralizing human antibodies, B cells from two people exposed to DENV4 were immortalized and screened to identify DENV-specific clones. Two human monoclonal antibodies (MAbs) that neutralized DENV4 were isolated, and their epitopes were finely mapped using recombinant viruses and alanine scan mutation array techniques. Both antibodies bound to quaternary structure epitopes near the hinge region between envelope protein domain I (EDI) and EDII. In parallel, to characterize the serum neutralizing antibody responses, convalescence-phase serum samples from people previously exposed to primary DENV4 natural infections or a monovalent DENV4 vaccine were analyzed. Natural infection and vaccination also induced serum-neutralizing antibodies that targeted similar epitope domains at the EDI/II hinge region. These studies defined a target of neutralizing antigenic site on DENV4 targeted by human antibodies following natural infection or vaccination. IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever and dengue hemorrhagic fever. People exposed to primary DENV infections develop long-term neutralizing antibody responses, but these principally recognize only the infecting serotype. An effective vaccine against dengue should elicit long-lasting protective antibody responses to all four serotypes simultaneously. We and others have defined antigenic sites on the envelope (E) protein of viruses of dengue virus serotypes 1, 2, and 3 targeted by human neutralizing antibodies. The epitopes on DENV4 E protein targeted by the human neutralizing antibodies and the mechanisms of serotype 4 neutralization are poorly understood. Here, we report the properties of human antibodies that neutralize dengue virus serotype 4. People exposed to serotype 4 infections or a live attenuated serotype 4 vaccine developed neutralizing antibodies that bound to similar sites on the viral E protein. These studies have provided a foundation for developing and evaluating DENV4 vaccines

Histological Examination in Obtaining a Diagnosis in Patients with Lymphadenopathy in Lima, Peru.

The differential diagnosis for lymphadenopathy is wide and clinical presentations overlap, making obtaining an accurate diagnosis challenging. We sought to characterize the clinical and radiological characteristics, histological findings, and diagnoses for a cohort of patients with lymphadenopathy of unknown etiology. 121 Peruvian adults with lymphadenopathy underwent lymph node biopsy for microbiological and histopathological evaluation. Mean patient age was 41 years (Interquartile Range 26-52), 56% were males, and 39% were HIV positive. Patients reported fever (31%), weight loss (23%), and headache (22%); HIV infection was associated with fever (P < 0.05) and gastrointestinal symptoms (P < 0.05). Abnormalities were reported in 40% of chest X-rays (N = 101). Physicians suspected TB in 92 patients (76%), lymphoma in 19 patients (16%), and other malignancy in seven patients (5.8%). Histological diagnoses (N = 117) included tuberculosis (34%), hyperplasia (27%), lymphoma (13%), and nonlymphoma malignancy (14%). Hyperplasia was more common (P < 0.001) and lymphoma less common (P = 0.005) among HIV-positive than HIV-negative patients. There was a trend toward reduced frequency of caseous necrosis in samples from HIV-positive than HIV-negative TB patients (67 versus 93%, P = 0.055). The spectrum of diagnoses was broad, and clinical and radiological features correlated poorly with diagnosis. On the basis of clinical features, physicians over-diagnosed TB, and under-diagnosed malignancy. Although this may not be inappropriate in resource-limited settings where TB is the most frequent easily treatable cause of lymphadenopathy, diagnostic delays can be detrimental to patients with malignancy. It is important that patients with lymphadenopathy undergo a full diagnostic work-up including sampling for histological evaluation to obtain an accurate diagnosis

APROVEITAMENTO DO SUBPRODUTO DO PROCESSAMENTO DE PUPUNHA E AVALIAÇÃO DOS COMPOSTOS FENÓLICOS

Introdu&ccedil;&atilde;o e objetivos: A pupunheira (Bactris gasipaes Kunth), &eacute; uma palmeira cultivada, principalmente, para produ&ccedil;&atilde;o de palmito. A industrializa&ccedil;&atilde;o gera grande quantidade de subprodutos, que cont&ecirc;m quantidades significativas de nutrientes e compostos importantes na alimenta&ccedil;&atilde;o. Seu aproveitamento &eacute; uma alternativa para diminuir o impacto ambiental e aumentar rentabilidade. Os fen&oacute;licos s&atilde;o compostos importantes, sua quantifica&ccedil;&atilde;o revela o poder antioxidante, qualidade do alimento e dos potenciais benef&iacute;cios &agrave; sa&uacute;de. O objetivo deste estudo, foi avaliar o teor de fen&oacute;licos totais do subproduto de pupunha in natura e de sua farinha. Metodologia: As bainhas residuais resultantes do processamento do palmito de pupunha, foram obtidas em ind&uacute;stria de palmito. O preparo da farinha foi realizado de acordo com o proposto por Simas et al. (2010)1, com modifica&ccedil;&otilde;es. O conte&uacute;do de fen&oacute;licos totais dos extratos foi determinado de acordo com o m&eacute;todo de Zielinski e Kozlowska (2000)2. Os resultados foram submetidos a an&aacute;lise de varian&ccedil;a em Software SISVAR&reg;, utilizando o Teste de Tuckey e o de t-Student, a 5% de signific&acirc;ncia. Resultados e discuss&otilde;es: Os resultados dos fen&oacute;licos totais das bainhas in natura, revelam que os extratos et&eacute;reo, etan&oacute;lico e aquoso, apresentaram concentra&ccedil;&otilde;es vari&aacute;veis de polifen&oacute;is e diferiram estatisticamente (p&lt;0,05). O extrato aquoso no res&iacute;duo in natura e na farinha (191,72 e 192,44 mg EAG.100g-1 amostra) apresentaram maiores teores de fen&oacute;licos, e foram diferentes estatisticamente (p&lt;0,05). Destaca-se, ainda, o extrato etan&oacute;lico da farinha e do res&iacute;duo in natura (192,37 e 191,15 mg EAG.100g-1 amostra), ao contr&aacute;rio do extrato et&eacute;reo (190,99 e 191,97 mg EAG.100g-1 amostra, respectivamente). Conclus&otilde;es: A bainha residual de pupunha in natura possui quantidade significativa de compostos fen&oacute;licos, e o processamento aplicado para a obten&ccedil;&atilde;o de farinha promove a manuten&ccedil;&atilde;o deste conte&uacute;do

A 46,XX testicular disorder of sex development caused by a Wilms’ tumour Factorâ 1 (WT1) pathogenic variant

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146930/1/cge13459_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146930/2/cge13459.pd

Insights into HLA-Restricted T Cell Responses in a Novel Mouse Model of Dengue Virus Infection Point toward New Implications for Vaccine Design

The frequency of dengue virus (DENV) infection has increased dramatically in the last few decades, and the lack of a vaccine has led to significant morbidity and mortality worldwide. To date, a convenient murine system to study human T cell responses to DENV has not been available. Mice transgenic for human leukocyte antigens (HLA) are widely used to model human immune responses and it has been shown that mouse-passaged DENV is able to replicate to significant levels in IFN-α/βR−/− mice. To cover a wide range of HLA phenotypes, we backcrossed IFN-α/βR−/− mice with HLA A*0201, A*0101, A*1101, B*0702 and DRB1*0101 transgenic mice. A DENV proteome-wide screen identified a total of 42 epitopes across all HLA-transgenic IFN-α/βR−/− strains tested. In contrast only 8 of these elicited responses in the corresponding IFN-α/βR+/+ mice. We were able to identify T cell epitopes from 9 out of the 10 DENV proteins. However, the majority of responses were derived from the highly conserved nonstructural proteins NS3 and NS5. The relevance of this model is further demonstrated by the fact that most of the epitopes identified in our murine system are also recognized by PBMC from DENV exposed human donors, and a dominance of HLA B*0702 restricted responses has been detected in both systems. Our results provide new insights into HLA-restricted T cell responses against DENV, and we herein describe a novel murine model, which allows the investigation of T cell-mediated immune mechanisms relevant to vaccine design

Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume

() and () form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy however their genomic location has impeded formal analysis. Using genome-editing, we generated mutants for and and found single mutants indistinguishable from wildtype whereas / double mutants display heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of , and expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for Hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirm cardiac jelly expansion in / double mutants. Finally, knockdown rescues the expansion of expression and cardiac jelly in double mutants. This definitively shows that and function redundantly during cardiac development to restrict gene expression to the AVC, preventing excessive cardiac jelly synthesis in the atrial chamber

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL