Dietary gangliosides rescue GM3 synthase deficiency outcomes in mice accompanied by neurogenesis in the hippocampus.

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GM3SD) causes an absence of GM3 and all downstream biosynthetic derivatives, including all the a-, b-, c-series gangliosides, commonly found in neural tissues. The affected individuals manifest with severe irritability, intractable seizures, hearing loss, blindness, and profound intellectual disability.

Assessing the suitability of three proxy sources for the development of detectors of special nuclear materials.

Numerous techniques and equipment have been developed to provide a capability for the detection of special nuclear materials (SNM), but due to the necessary security measures surrounding these materials alternate, or proxy, neutron sources are often utilised in their stead. In this paper we report the neutron and gamma pulse shape discrimination response of plastic scintillator to mixed neutron/gamma beams produced from two radionuclide neutron sources, and also from an SNM source of weapons-grade plutonium. We discuss the suitability of using radionuclide sources, with appropriate shielding configurations as proxy sources for SNM.

Loss of Dynamin 2 GTPase function results in microcytic anaemia.

In a dominant mouse ethylnitrosurea mutagenesis screen for genes regulating erythropoiesis, we identified a pedigree with a novel microcytic hypochromia caused by a V235G missense mutation in Dynamin 2 (Dnm2). Mutations in Dnm2, a GTPase, are highly disease-specific and have been implicated in four forms of human diseases: centronuclear myopathy, Charcot-Marie Tooth neuropathy and, more recently, T-cell leukaemia and Hereditary Spastic Paraplegia, but red cell abnormalities have not been reported to date. The V235G mutation lies within a crucial GTP nucleotide-binding pocket of Dnm2, and resulted in defective GTPase activity and incompatibility with life in the homozygous state.

SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3) domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD).

Altered transcription of murine genes induced in the small bowel by administration of probiotic strain Lactobacillus rhamnosus HN001.

Lactobacillus rhamnosus HN001 is a probiotic strain reported to increase resistance to epithelium-adherent and -invasive intestinal pathogens in experimental animals. To increase understanding of the relationship between strain HN001 and the bowel, transcription of selected genes in the mucosa of the murine small bowel was measured. Mice previously naive to lactobacilli (Lactobacillus-free mice) were examined after daily exposure to HN001 in drinking water.

Unique secreted-surface protein complex of Lactobacillus rhamnosus, identified by phage display.

Proteins are the most diverse structures on bacterial surfaces; hence, they are candidates for species- and strain-specific interactions of bacteria with the host, environment, and other microorganisms. Genomics has decoded thousands of bacterial surface and secreted proteins, yet the function of most cannot be predicted because of the enormous variability and a lack of experimental data that would allow deduction of function through homology. Here, we used phage display to identify a pair of interacting extracellular proteins in the probiotic bacterium Lactobacillus rhamnosus HN001.

FRQ-interacting RNA helicase mediates negative and positive feedback in the Neurospora circadian clock.

The Neurospora circadian oscillator comprises FREQUENCY (FRQ) and its transcription activator, the White Collar Complex (WCC). Repression of WCC's transcriptional activity by FRQ via negative feedback is indispensable for clock function. An unbiased genetic screen that targeted mutants with defects in negative feedback regulation yielded a fully viable arrhythmic strain bearing a novel allele of FRQ-interacting RNA helicase (frh), an essential gene that encodes a putative exosome component protein.

Direct selection and phage display of a Gram-positive secretome.

Surface, secreted and transmembrane protein-encoding open reading frames, collectively the secretome, can be identified in bacterial genome sequences using bioinformatics. However, functional analysis of translated secretomes is possible only if many secretome proteins are expressed and purified individually. We have now developed and applied a phage display system for direct selection, identification, expression and purification of bacterial secretome proteins.

Functionality of probiotics - potential for product development.

It is becoming increasingly accepted by consumers that live lactic acid bacteria do exert health benefits when eaten. In addition, it is also becoming recognised that not all probiotic bacteria are equal. It is now no longer just a question of providing sufficient numbers of viable bacteria in a product; industry must also provide proof of efficacy for each strain.

Light and clock expression of the Neurospora clock gene frequency is differentially driven by but dependent on WHITE COLLAR-2.

Visible light is thought to reset the Neurospora circadian clock by acting through heterodimers of the WHITE COLLAR-1 and WHITE COLLAR-2 proteins to induce transcription of the frequency gene. To characterize this photic entrainment we examined frq expression in constant light, under which condition the mRNA and protein of this clock gene were strongly induced. In continuous illumination FRQ accumulated in a highly phosphorylated state similar to that seen at subjective dusk, the time at which a step from constant light to darkness sets the clock.