Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and liver abscess. This pathogen possesses a two-stage life cycle consisting of an environmentally stable cyst and a ...pathogenic amoeboid trophozoite. Since infection is acquired by ingestion of cysts from contaminated food and water, this parasite is prevalent in underdeveloped countries. A reptilian pathogen, Entamoeba invadens, which can encyst in culture, has long served as a surrogate to study stage conversion. In the host,
species must manage stress, including nutrient deprivation and host immune pressure. In many systems, the stress response is characterized by downregulation of translation, which is initiated by the phosphorylation of eukaryotic initiation factor-2 alpha (eIF2α). In mammalian cells, this phosphorylation is carried out by a family of eIF2α kinases. A canonical eIF2α translational control system exists in
species; however, no eIF2α kinases have been characterized. In this study, we identified two eIF2α kinases in
, EiIF2K-A and EiIF2K-B. Their identity as eIF2α kinases was validated using a heterologous yeast system. We used an RNA interference (RNAi) trigger-mediated silencing system to reduce expression of EiIF2K-A, which also reduced expression of EiIF2K-B. Parasites with decreased kinase expression exhibited decreased phosphorylation of eIF2α and increased sensitivity to oxidative stress. Diminished kinase expression also correlated with an increased rate of encystation, a decreased rate of excystation, and an increase in several virulence functions, erythrophagocytosis and adhesion to host cells. Taken together, these data suggest that EiIF2K-A and EiIF2K-B are authentic eIF2α kinases that may regulate the
stress response.
Entamoeba histolytica is a human pathogen that causes dysentery and affects millions of people worldwide. This parasite possesses a two-stage life cycle: an environmentally stable cyst and the pathogenic trophozoite. Cysts are ingested from contaminated food and water; thus, this parasite in prevalent in underdeveloped countries. Current therapies commonly cause adverse side effects; therefore, new treatments are needed. In the host,
experiences stress brought on, in part, by the host immune system. Understanding stage conversion and the stress response of this pathogen may lead to new drug therapies. Using the model organism
, we identified two kinases similar to those involved in stress and stage conversion in other systems. We determined that these kinases may regulate the oxidative stress response, stage conversion, and virulence. This work is significant, as it will inform future studies on the life cycle and pathogenicity of
species.
Abstract
The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes ...are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival.
Impacts caused to freshwater reservoirs by human activities have increased in tropical and subtropical regions in the last decades. We studied the effects of land use on the physicochemical ...properties of water and their effects on larval Odonata diversity in a subtropical lagoon. During 1 year, physicochemical variables were measured, and Odonata larvae were collected in 8 sites (4 in the urbane zone and 4 in the more conserved rural zone) with different land uses that cover the entire periphery of the lagoon. Physicochemically, no clustering of samples from urban and rural zones or by site was observed, rather clustering reflected temporal patterns. A total of 28 species were found and some of them showed a differential distribution between both zones, and between the 8 sites and collectings. The highest diversity was recorded in the rural zone. The site with domestic waste discharges had the lowest diversity and it showed high concentrations of nitrates and ammonium. We conclude that the effect of land use in this lagoon is still incipient on Odonata diversity. The diversion and treatment of urban waters and proper land management are recommended to ensure the maintenance of Odonata diversity.
Multisystemic inflammatory syndrome (MIS-C) is an inflammatory condition temporally associated with COVID-19 in children; nevertheless, the clinical and immunologic spectrum of MIS-C is ...heterogeneous, and its long-term effects are unknown. During the period of August 2020 to December 2021, a total of 52 MIS-C cases were confirmed in pediatric patients from the Hospital del Niño DIF Hidalgo, diagnosed using criteria from the World Health Organization. All patients had serologic IgG confirmation of SARS-CoV2, the mean age of the patients was 7 years, and 94% of the patients did not have a previous underlying disease. In addition to the presentation of lymphopenia, neutropenia, and thrombocytopenia, elevations in D-dimer and ferritin levels were observed in all patients. There was clinical improvement with intravenous gamma globulin and corticosteroid treatment.
Promotion of biomedical research along with the development of evidence-based prevention policies have been suggested as an effective way to reduce environmental risks for children's health in Latin ...America. However, there is little information on the current state of childhood environmental health research, which might help identify its strengths and limitations, as well as to design a strategy to improve the future of child environmental health research in the region.
To describe the current state of environmental health research on children exposed to environmental pollutants in Latin America.
We performed a comprehensive search of published peer-reviewed environmental health articles (1994-2014), dealing with the exposure of Latin American children to chemical compounds. We described the type of studies and their research topics, and identified networks of co-authors. We also analyzed the relationship between research funding sources and the impact factor (IF) of the journal where research was published.
The average number of publications was about 20 per year. Mexico and Brazil produced almost 70% of the 409 identified papers. The most studied contaminant was lead, but research on this element has declined since 2005. Retrospective studies were the most frequent, and also showed a decreasing trend. Most studies did not assess health effects. Four groups of leading investigators and two collaboration models for scientific production were identified. Except for Mexico, there was very little collaboration with North American and European countries. Compared to articles that did not report financial support, those that received international funding had on average an IF around 7, and those with national funding reached a mean IF near 3.
There is a limited number of publications and insufficient collaboration between Latin-American scientists. It is necessary to identify strategies to stimulate South-South-North alliances and strengthen the scarce research on the environmental health of children in the region.
The COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a ...function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.
In a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 - June 2021. Participants completed a baseline survey about the pandemic, including open-ended questions about the effects of the pandemic, what was helping them navigate, and how it impacted T1D management. Hemoglobin A1c (A1c) was extracted from clinical records. Free text responses were analyzed using an inductive content approach. Survey responses and A1c were summarized using descriptive statistics and associations were assessed by Chi-squared tests.
Adolescents (n=122) were 56% female. 11% of adolescents reported diagnosis of COVID-19 and 12% had a family member/other important person die from COVID-19 complications. Adolescents described Social Relationships, Personal Health/Safety Practices, Mental Health, Family Relationships, and School to be primary areas affected by COVID-19. Helpful resources included: Learned Skills/Behaviors, Social Support/Community, and Meaning-Making/Faith. Among participants indicating that the pandemic had an impact on their T1D management (n=35), the most commonly described areas were: Food, Self-Care, Health/Safety, Diabetes Appointments, and Exercise. Compared to adolescents who reported minimal difficulty managing T1D during the pandemic (71%), those reporting moderate to extreme difficulty (29%) were more likely to have A1C ≥ 8% (80%
43%, p<.01).
Results underscore the pervasive impact of COVID-19 on teens with T1D across multiple major life domains. Their coping strategies aligned with stress, coping, and resilience theories and suggest resilient responses in the face of stress. Despite experiencing pandemic-related stressors in many areas, diabetes-related functioning was relatively protected for most teens, highlighting their diabetes-specific resilience. Discussing the pandemic impact on T1D management may be an important focus for clinicians, especially for adolescents with diabetes distress and above-target A1C.
The chemical synthesis of gold nanoparticles (NP) by using gold (III) chloride trihydrate (HAuCl∙3H₂O) and sodium citrate as a reducing agent in aqueous conditions at 100 °C is presented here. Gold ...nanoparticles areformed by a galvanic replacement mechanism as described by Lee and Messiel. Morphology of gold-NP was analyzed by way of high-resolution transmission electron microscopy; results indicate a six-fold icosahedral symmetry with an average size distribution of 22 nm. In order to understand the mechanical behaviors, like hardness and elastic moduli, gold-NP were subjected to nanoindentation measurements-obtaining a hardness value of 1.72 GPa and elastic modulus of 100 GPa in a 3-5 nm of displacement at the nanoparticle's surface.
Voices of chemical biology Davis, B; Backus, K; Winter, G ...
Nature chemical biology,
01/2021, Letnik:
17, Številka:
1
Journal Article
Recenzirano
We asked a collection of chemical biologists, “What is the most exciting frontier area in chemical biology and what key technology is needed to advance knowledge and applications in this area?” and ...reveal some of the perspectives we received.
We announce the draft genome sequence of three Gram-negative bacteria isolated from coral tissues affected with the black band disease (BBD), identified with the NCBI's Assembly Database accession ...numbers: MBQF, MAYB and MBQE. These genome drafts constitute an useful tool for the characterisation of these bacteria and for the understanding of the relationship between the microbial consortia associated with the disease and the onset and progression of the pathology.
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