Search results for "BOX"
showing 10 items of 2676 documents
The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates
2017
16 páginas, 7 figuras, 2 tablas
Evolving Notch polyQ tracts reveal possible solenoid interference elements.
2016
ABSTRACTPolyglutamine (polyQ) tracts in regulatory proteins are extremely polymorphic. As functional elements under selection for length, triplet repeats are prone to DNA replication slippage and indel mutations. Many polyQ tracts are also embedded within intrinsically disordered domains, which are less constrained, fast evolving, and difficult to characterize. To identify structural principles underlying polyQ tracts in disordered regulatory domains, here I analyze deep evolution of metazoan Notch polyQ tracts, which can generate alleles causing developmental and neurogenic defects. I show that Notch features polyQ tract turnover that is restricted to a discrete number of conserved “polyQ …
CitA (citrate) and DcuS (C4-dicarboxylate) sensor kinases in thermophilic Geobacillus kaustophilus and Geobacillus thermodenitrificans
2015
The thermophilic Geobacillus thermodenitrificans and Geobacillus kaustophilus are able to use citrate or C4-dicarboxylates like fumarate or succinate as the substrates for growth. The genomes of the sequenced Geobacillus strains (nine strains) each encoded a two-component system of the CitA family. The sensor kinase of G. thermodenitrificans (termed CitAGt) was able to replace CitA of Escherichia coli (CitAEc) in a heterologous complementation assay restoring expression of the CitAEc-dependent citC-lacZ reporter gene and anaerobic growth on citrate. Complementation was specific for citrate. The sensor kinase of G. kaustophilus (termed DcuSGk) was able to replace DcuSEc of E. coli. It respon…
Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo
2016
Summary - The realization that nuclear distribution of DNA, RNA, and proteins differs between cell types and developmental stages suggests that nuclear organization serves regulatory functions. Understanding the logic of nuclear architecture and how it contributes to differentiation and cell fate commitment remains challenging. Here, we use soft X-ray tomography (SXT) to image chromatin organization, distribution, and biophysical properties during neurogenesis in vivo. Our analyses reveal that chromatin with similar biophysical properties forms an elaborate connected network throughout the entire nucleus. Although this interconnectivity is present in every developmental stage, differentiati…
Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation
2017
MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR- 29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b…
Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APPNL-G-F/NL-G-F mouse model
2020
Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Neuropathological processes, including the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, and neuroinflammation, lead to cognitive impairment at middle and eventually later stages of AD progression. Over the last decade, focused efforts have explored repurposed drug approaches for AD pathophysiological mechanisms. Recently, auranofin, an anti-inflammatory drug, was shown to have therapeutic potential in a number of diseases in addition to rheumatoid arthritis. Surprisingly, no data regarding the effects of auranofin on cognitive deficits in AD mice or the influence of auranofin on Aβ pathology and n…
Immunohistochemical analysis of NKX2.2, ETV4, and BCOR in a large series of genetically confirmed Ewing sarcoma family of tumors
2017
Ewing sarcoma is an aggressive neoplasm of pediatric and adolescent patients. Immunohistochemistry (IHC) can be used to support the morphologic diagnosis of Ewing sarcoma family of tumors (ESFT) in a convincing clinical/radiological context. Although neither NKX2.2 nor CD99 alone are entirely specific, when combined, the diagnostic specificity is high. The aim of the present study was to investigate the IHC expression of NKX2.2, ETV4 and BCOR in a large series of genetically confirmed ESFT. The results for CD99 and CAV-1 immunoreactivity, and the histological and fusion gene subtypes were retrieved from our previous study. NKX2.2 demonstrated moderate or strong nuclear positivity in 91.2% o…
Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity.
2020
The memory CD8 T-cell pool must select for clones that bind immunodominant epitopes with high affinity to efficiently counter reinfection. At the same time, it must retain a level of clonal diversity to allow recognition of pathogens with mutated epitopes. How the level of diversity within the memory pool is controlled is unclear, especially in the context of a selective drive for antigen affinity. We find that preservation of clones that bind the activating antigen with low affinity depends on expression of the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the prosurvival protein…
Resveratrol shifts energy metabolism to increase lipid oxidation in healthy old mice.
2019
Abstract Objectives The objective of this work was to determine the specific mechanisms by which resveratrol inhibits lipogenesis and stimulates lipolysis. Methods Twelve male mice were individually introduced into a metabolic cage for 24 h to measure basal metabolic rate, prior to intervention. They were randomly divided into two groups, resveratrol (RSV) and control (C), and administered resveratrol intraperitoneally or vehicle, respectively, for two consecutive days. After 24 h, the metabolic energy expenditure was again determined for 24 h, before mice were sacrificed. Protein and gene expression of different enzymes related to metabolism in the hepatic tissue, adipose tissue and gastro…
A systematic variant screening in familial cases of congenital heart defects demonstrates the usefulness of molecular genetics in this field
2016
International audience; The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvula…