Novartis

About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.

ERM is required for transcriptional control of the spermatogonial stem cell niche

Abstract: Division of spermatogonial stem cells1 produces daughter cells that either maintain their stem cell identity or undergo differentiation to form mature sperm. The Sertoli cell, the only somatic cell within seminiferous tubules, provides the stem cell niche through physical support and expression of surface proteins and soluble factors2,3. Here we show that the Ets related molecule4 (ERM) is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ-cell depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary Sertoli cells from ERM-deficient mice showed alterations in secreted factors known to regulate the haematopoietic stem cell niche. These results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.

The prebiotic effects of biscuits containing partially hydrolysed guar gum and fructo-oligosaccharides – a human volunteer study

Abstract: Prebiotics are non-digestible food ingredients that target selected groups of the human colonic microflora, thus having the ability to alter the composition towards a more 'beneficial' community, i.e. selectively increasing populations of bifidobacteria and/or lactobacilli. In the present study the prebiotic potential of partially hydrolysed guar gum (PHGG) and fructo-oligosaccharides (FOS) in a biscuit was assessed in human volunteers. Fluorescent in situ hybridization using oligonucleotide probes targeting Bacteroides spp., Bifidobacterium spp., Clostridium spp. and Lactobacillus-Enterococcus spp. were used for the bacteriology and total bacteria were enumerated using the fluorescent stain 4',6-diamidino-2-phenylindole. Thirty-one volunteers consumed daily either three experimental biscuits (providing a total (g/d) of 6.6 FOS and 3.4 PHGG) or three placebo biscuits for two 21-d crossover periods. Bifidobacteria significantly increased in number on ingestion of the experimental biscuits compared with pre-treatment and placebo population levels. Bifidobacterial numbers returned to pretreatment levels within 7 d of the cessation of intake of experimental biscuits. A correlation was observed between the initial faecal bifidobacterial numbers and the magnitude of bifidogenesis, with volunteers who possessed low initial population levels of bifidobacteria experiencing the greatest increase in bifidogenesis. No changes were observed in the other bacterial groups monitored during the trial. Thus, the prebiotic nature of FOS and PHGG was maintained in a final food product as evidenced from the selective increase in bifidobacterial numbers.

C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors.

Abstract: Assembly of fully functional GABA(B) receptors requires heteromerization of the GABA(B(1)) and GABA(B(2)) subunits. It is thought that GABA(B(1)) and GABA(B(2)) undergo coiled-coil dimerization in their cytoplasmic C termini and that assembly is necessary to overcome GABA(B(1)) retention in the endoplasmatic reticulum (ER). We investigated the mechanism underlying GABA(B(1)) trafficking to the cell surface. We identified a signal, RSRR, proximal to the coiled-coil domain of GABA(B(1)) that when deleted or mutagenized allows for surface delivery in the absence of GABA(B(2)). A similar motif, RXR, was recently shown to function as an ER retention/retrieval (ERR/R) signal in K(ATP) channels, demonstrating that G-protein-coupled receptors (GPCRs) and ion channels use common mechanisms to control surface trafficking. A C-terminal fragment of GABA(B(2)) is able to mask the RSRR signal and to direct the GABA(B(1)) monomer to the cell surface, where it is functionally inert. This indicates that in the heteromer, GABA(B(2)) participates in coupling to the G-protein. Mutagenesis of the C-terminal coiled-coil domains in GABA(B(1)) and GABA(B(2)) supports the possibility that their interaction is involved in shielding the ERR/R signal. However, assembly of heteromeric GABA(B) receptors is possible in the absence of the C-terminal domains, indicating that coiled-coil interaction is not necessary for function. Rather than guaranteeing heterodimerization, as previously assumed, the coiled-coil structure appears to be important for export of the receptor complex from the secretory apparatus.