79 research outputs found
Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem cell gene Sall4
<p>Abstract</p> <p>Background</p> <p>Sall4 is a key factor for the maintenance of pluripotency and self-renewal of embryonic stem cells (ESCs). Our previous studies have shown that Sall4 is a robust stimulator for human hematopoietic stem and progenitor cell (HSC/HPC) expansion. The purpose of the current study is to further evaluate how Sall4 may affect HSC/HPC activities in a murine system.</p> <p>Methods</p> <p>Lentiviral vectors expressing Sall4A or Sall4B isoform were used to transduce mouse bone marrow Lin-/Sca1+/c-Kit+ (LSK) cells and HSC/HPC self-renewal and differentiation were evaluated.</p> <p>Results</p> <p>Forced expression of Sall4 isoforms led to sustained <it>ex vivo </it>proliferation of LSK cells. In addition, Sall4 expanded HSC/HPCs exhibited increased <it>in vivo </it>repopulating abilities after bone marrow transplantation. These activities were associated with dramatic upregulation of multiple HSC/HPC regulatory genes including HoxB4, Notch1, Bmi1, Runx1, Meis1 and Nf-ya. Consistently, downregulation of endogenous Sall4 expression led to reduced LSK cell proliferation and accelerated cell differentiation. Moreover, in myeloid progenitor cells (32D), overexpression of Sall4 isoforms inhibited granulocytic differentiation and permitted expansion of undifferentiated cells with defined cytokines, consistent with the known functions of Sall4 in the ES cell system.</p> <p>Conclusion</p> <p>Sall4 is a potent regulator for HSC/HPC self-renewal, likely by increasing self-renewal activity and inhibiting differentiation. Our work provides further support that Sall4 manipulation may be a new model for expanding clinically transplantable stem cells.</p
Characterization of greater middle eastern genetic variation for enhanced disease gene discovery
The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics
Distribution and Preliminary Exposure Assessment of Bisphenol AF (BPAF) in Various Environmental Matrices around a Manufacturing Plant in China
Ionomeric membranes for proton exchange membrane fuel cell (PEMFC): sulfonated polysulfone associated with phosphatoantimonic acid
International audienceSulfonation of polysulfone strongly affects both protonic conductivity and lifetime of composite polyelectrolytes. Viscosimetric comparisons showed the effect of the sulfonating agent. Indeed, chlorosulfonic acid leads to chain cleavage while its trimethyl silyl ester does not affect the polymer backbone. Sampling aliquots allowed the sulfonation yield to be followed by 1H NMR. From this study, one might infer that the conversion should not exceed 70% of the theoretical yield. Viscosimetric measurements performed on the same aliquots demonstrated that, even after 72 h reaction time, chain cleavage did not occur. Filling of sulfonated polysulfone with 8% of phosphatoantimonic acid resulted in a conductivity trebling 0.06 versus 0.02 S cm−1 at 80°C and 98% of relative humidity (RH). Electrochemical performances, thermo-mechanical stability and low cost make this composite membrane an attractive material for proton exchange membrane fuel cell (PEMFC)
Cerebral folate deficiency: Analytical tests and differential diagnosis
Cerebral folate deficiency is typically defined as a deficiency of the major folate species 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) in the presence of normal peripheral total folate levels. However, it should be noted that cerebral folate deficiency is also often used to describe conditions where CSF 5-MTHF is low, in the presence of low or undefined peripheral folate levels. Known defects of folate transport are deficiency of the proton coupled folate transporter, associated with systemic as well as cerebral folate deficiency, and deficiency of the folate receptor alpha, leading to an isolated cerebral folate deficiency associated with intractable seizures, developmental delay and/or regression, progressive ataxia and choreoathetoid movement disorders. Inborn errors of folate metabolism include deficiencies of the enzymes methylenetetrahydrofolate reductase, dihydrofolate reductase and 5,10-methenyltetrahydrofolate synthetase. Cerebral folate deficiency is potentially a treatable condition and so prompt recognition of these inborn errors and initiation of appropriate therapy is of paramount importance. Secondary cerebral folate deficiency may be observed in other inherited metabolic diseases, including disorders of the mitochondrial oxidative phosphorylation system, serine deficiency, and pyridoxine dependent epilepsy. Other secondary causes of cerebral folate deficiency include the effects of drugs, immune response activation, toxic insults and oxidative stress. This review describes the absorption, transport and metabolism of folate within the body; analytical methods to measure folate species in blood, plasma and CSF; inherited and acquired causes of cerebral folate deficiency; and possible treatment options in those patients found to have cerebral folate deficiency. This article is protected by copyright. All rights reserved
On Physics of Optical Laser Light Scattering (OLLS) of an Industrial Polymer Which May Assist in Physics of Random Laser (RL) Investigation
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