Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium tuberculosis.

Comparison of genome sequences from clinical isolates of Mycobacterium tuberculosis with phylogenetically-related pathogens Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium leprae reveals diversity amongst genes associated with vitamin B12-related metabolism. Diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (SNPs) with predicted impact on protein function and transcriptional regulation. Differences in the B12 synthesis pathway, methionine biosynthesis, fatty acid catabolism, and DNA repair and replication are consistent with adaptations to different environmental niches and pathogenic lifestyles.

BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.

B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and 2 suggested that activation of ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival. However, these inhibitors are now known to also inhibit MEK5, which activates the related MAP kinase ERK5.

Function and regulation of Rnd proteins in cortical projection neuron migration.

The mammalian cerebral cortex contains a high variety of neuronal subtypes that acquire precise spatial locations and form long or short-range connections to establish functional neuronal circuits. During embryonic development, cortical projection neurons are generated in the areas lining the lateral ventricles and they subsequently undergo radial migration to reach the position of their final maturation within the cortical plate. The control of the neuroblast migratory behavior and the coordination of the migration process with other neurogenic events such as cell cycle exit, differentiation and final maturation are crucial to normal brain development.

Neurogenesis in the embryonic and adult brain: same regulators, different roles.

Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans.

A unifying computational framework for stability and flexibility of arousal.

Arousal and consciousness flexibly adjust to salient cues, but remain stable despite noise and disturbance. Diverse, highly interconnected neural networks govern the underlying transitions of behavioral state; these networks are robust but very complex. Frameworks from systems engineering provide powerful tools for understanding functional logic behind component complexity.

Skeletal muscle pathology in Huntington's disease.

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a polyglutamine stretch within the huntingtin protein (HTT). The neurological symptoms, that involve motor, cognitive and psychiatric disturbances, are caused by neurodegeneration that is particularly widespread in the basal ganglia and cereberal cortex. HTT is ubiquitously expressed and in recent years it has become apparent that HD patients experience a wide array of peripheral organ dysfunction including severe metabolic phenotype, weight loss, HD-related cardiomyopathy and skeletal muscle wasting.

The conformation of enkephalin bound to its receptor: an "elusive goal" becoming reality.

The availability of solid state structures of opioid receptors has prompted us to reconsider a crucial question concerning bioactive peptides: can their conformation be studied without any knowledge of the structure of their receptors? The possibility of giving a meaningful answer to this query rests ultimately on the ease of dealing with the flexibility of bioactive peptides, and amongst them one of the most flexible bioactive peptides, enkephalin. All solution studies of enkephalin hint at an inextricable mixture of quasi isoenergetic conformers. In this study we refer to the only NMR work that yielded inter-residue NOEs, performed at very low temperature.

Glutamate and GABA as rapid effectors of hypothalamic "peptidergic" neurons.

Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx), are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters.

IL-22 Protects Against Liver Pathology and Lethality of an Experimental Blood-Stage Malaria Infection.

The host response following malaria infection depends on a fine balance between levels of pro-inflammatory and anti-inflammatory mediators resulting in the resolution of the infection or immune-mediated pathology. Whilst other components of the innate immune system contribute to the pro-inflammatory milieu, T cells play a major role. For blood-stage malaria, CD4(+) and γδ T cells are major producers of the IFN-γ that controls parasitemia, however, a role for TH17 cells secreting IL-17A and other cytokines, including IL-17F and IL-22 has not yet been investigated in malaria.