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1.
Aiming to study the early stages of type 1 diabetes phenotype, before insulitis appears, we measured insulin autoantibodies (IAA) between 3 and 5 wk of age in the NOD mouse (early-IAA (E-IAA)). We report that IAA are found as early as at 3 wk of age, at weaning, and their expression is a quantal phenotype. Maternal autoantibody status influences this early phenotype, because animals of litters issued from IAA-positive ante partum mothers develop E-IAA with a significantly higher incidence than animals issued from IAA-negative mothers. These E-IAA represent synthesized rather than transplacental autoantibodies, as evidenced by higher levels in many offspring compared with maternal IAA, and negative as well as positive offspring in the same litters and it correlates with early diabetes onset, defining the first autoimmune window in diabetes pathogenesis. Therefore, autoimmune processes leading to type 1 diabetes initiate early in life, are influenced by maternal autoantibody status, and can be revealed by the presence of IAA. Our data suggest that the mechanisms responsible for the breakdown of self-tolerance are subjected not only to genetic predisposition, but also to the physiological status of the mother. Pathological progression to autoimmunity is marked by the presence of immunological windows relating early steps with final disease onset.  相似文献   
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The aim of the present study was to identify a collection of 35 Cupriavidus isolates at the species level and to examine their capacity to nodulate and fix N(2). These isolates were previously obtained from the root nodules of two promiscuous trap species, Phaseolus vulgaris and Leucaena leucocephala, inoculated with soil samples collected near Sesbania virgata plants growing in Minas Gerais (Brazil) pastures. Phenotypic and genotypic methods applied for this study were SDS-PAGE of whole-cell proteins, and 16S rRNA and gyrB gene sequencing. To confirm the ability to nodulate and fix N(2), the presence of the nodC and nifH genes was also determined, and an experiment was carried out with two representative isolates in order to authenticate them as legume nodule symbionts. All 35 isolates belonged to the betaproteobacterium Cupriavidus necator, they possessed the nodC and nifH genes, and two representative isolates were able to nodulate five different promiscuous legume species: Mimosa caesalpiniaefolia, L. leucocephala, Macroptilium atropurpureum, P. vulgaris and Vigna unguiculata. This is the first study to demonstrate that C. necator can nodulate legume species.  相似文献   
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Learning is crucial to the survival of organisms across their life span, including during embryonic development. We set out to determine when learning becomes possible in amphibian development by exposing spotted salamander (Ambystoma maculatum) embryos to chemical stimuli from a predator (Ambystoma opacum), nonpredator (Lithobates clamitans), or control at developmental stages 16–21 or 36–38 (Harrison 1969 ). Once exposures were completed and embryos hatched, we recorded the number of movements and time spent moving of individuals in both groups and all treatments. There was no significant difference in number of movements or time spent moving among any of the treatments. The groups that were exposed to predator stimuli and a blank control at stages 36–38 were also tested to determine whether there was a difference in refuge preference or difference in survivorship when exposed to a predator (marbled salamander). There was no difference in survival or refuge preference between individuals; however, all individuals preferred vegetated over open areas regardless of treatment type. We discuss hypotheses for the absence of embryonic learning in this species and suggest it may be the result of the intensity of the predator–prey interaction between the predator, large marbled salamander larvae, and the prey, spotted salamander larvae.  相似文献   
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The main aim of this study was to evaluate the specificity of three commonly used 16S rRNA gene-based polymerase chain reaction (PCR) primer sets for bacterial community analysis of samples contaminated with eukaryotic DNA. The specificity of primer sets targeting the V3, V3-V5, and V6-V8 hypervariable regions of the 16S rRNA gene was investigated in silico and by community fingerprinting of human and fish intestinal samples. Both in silico and PCR-based analysis revealed cross-reactivity of the V3 and V3-V5 primers with the 18S rRNA gene of human and sturgeon. The consequences of this primer anomaly were illustrated by denaturing gradient gel electrophoresis (DGGE) profiling of microbial communities in human feces and mixed gut of Siberian sturgeon. DGGE profiling indicated that the cross-reactivity of 16S rRNA gene primers with nontarget eukaryotic DNA might lead to an overestimation of bacterial biodiversity. This study has confirmed previous sporadic indications in literature indicating that several commonly applied 16S rRNA gene primer sets lack specificity toward bacteria in the presence of eukaryotic DNA. The phenomenon of cross-reactivity is a potential source of systematic error in all biodiversity studies where no subsequent analysis of individual community amplicons by cloning and sequencing is performed.  相似文献   
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Artificial wombs are already in development that have the potential to radically alter how we perceive the developing fetus and the role of pregnancy in society. That this technology would allow greater visibility of gestation than ever before also highlights the risk that artificial wombs will be used to further restrict women’s reproductive liberty and access to abortion. This article uses Paul Lauritzen’s theory of “visual bioethics” to explore the ethical significance of images of the developing fetus and how artificial wombs might best be visually designed and integrated into society.  相似文献   
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Introduction

We examined the prevalence of substance use disorders among homeless and vulnerably housed persons in three Canadian cities and its association with unmet health care needs and access to addiction treatment using baseline data from the Health and Housing in Transition Study.

Methods

In 2009, 1191 homeless and vulnerably housed persons were recruited in Vancouver, Toronto, and Ottawa, Canada. Interviewer administered questionnaires collected data on socio-demographics, housing history, chronic health conditions, mental health diagnoses, problematic drug use (DAST-10≥6), problematic alcohol use (AUDIT≥20), unmet physical and mental health care needs, addiction treatment in the past 12 months. Three multiple logistic regression models were fit to examine the independent association of substance use with unmet physical health care need, unmet mental health care need, and addiction treatment.

Results

Substance use was highly prevalent, with over half (53%) screening positive for the DAST-10 and 38% screening positive for the AUDIT. Problematic drug use was 29%, problematic alcohol use was lower at 16% and 7% had both problematic drug and alcohol use. In multiple regression models for unmet need, we found that problematic drug use was independently associated with unmet physical (adjusted odds ratio [AOR] 1.95; 95% confidence interval [CI] 1.43–2.64) and unmet mental (AOR 3.06; 95% CI 2.17–4.30) health care needs. Problematic alcohol use was not associated with unmet health care needs. Among those with problematic substance use, problematic drug use was associated with a greater likelihood of accessing addiction treatment compared to those with problematic alcohol use alone (AOR 2.32; 95% CI 1.18–4.54).

Conclusions

Problematic drug use among homeless and vulnerably housed individuals was associated with having unmet health care needs and accessing addiction treatment. Strategies to provide comprehensive health services including addiction treatment should be developed and integrated within community supported models of care.  相似文献   
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