The 5300-year-old Helicobacter pylori genome of the Iceman.

The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The extant European population of H.

Oncogenic H-ras reprograms Madin-Darby canine kidney (MDCK) cell-derived exosomal proteins following epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenic process defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT is associated with increased aggressiveness, invasiveness, and metastatic potential in carcinoma cells. To assess the contribution of extracellular vesicles following EMT, we conducted a proteomic analysis of exosomes released from Madin-Darby canine kidney (MDCK) cells, and MDCK cells transformed with oncogenic H-Ras (21D1 cells).

The state of the human proteome in 2012 as viewed through PeptideAtlas.

The Human Proteome Project was launched in September 2010 with the goal of characterizing at least one protein product from each protein-coding gene. Here we assess how much of the proteome has been detected to date via tandem mass spectrometry by analyzing PeptideAtlas, a compendium of human derived LC-MS/MS proteomics data from many laboratories around the world. All data sets are processed with a consistent set of parameters using the Trans-Proteomic Pipeline and subjected to a 1% protein FDR filter before inclusion in PeptideAtlas.

Mitogen-activated protein kinase activity may not be necessary for the neuropathology of Niemann-Pick type C mice.

Hyperphosphorylation of neurofilament and tau, and formation of cytoskeletal lesions, are notable features of several human neurodegenerative diseases, including Niemann-Pick Disease Type C (NPC). Previous studies suggested that the MAPKs, extracellular signal regulated kinase 1 and 2 (ERK1/2) may play a significant role in this aspect of NPC. To test this idea, we treated npc mice with PD98059, a specific and potent inhibitor of MAPK activation.

Astrocyte-only Npc1 reduces neuronal cholesterol and triples life span of Npc1-/- mice.

Niemann-Pick type C (NPC) disease is an autosomal recessive, lethal neurodegenerative disorder. Although neurodegeneration of Purkinje cells in the mouse model (Npc1(-/-)) is thought to be autonomous, the basis of neuronal death in other regions of the brain remains elusive. We addressed this issue in vivo by using the glial fibrillary acidic protein (GFAP) promoter to direct astrocyte-specific, replacement expression of Npc1 in Npc1(-/-) mice.

Conditional neuronal simian virus 40 T antigen expression induces Alzheimer-like tau and amyloid pathology in mice.

A large body of evidence has shown the activation of a cohort of cell cycle regulators and the duplication of DNA in degenerating neurons of Alzheimer's disease (AD) brain. Activation of these regulators and duplication of chromosomes precede neurodegeneration and formation of neurofibrillary tangles (NFTs), one of the diagnostic lesions of AD. These findings, in combination with evidence for cell cycle regulation of amyloid precursor protein and tau, has led to the hypothesis that reentry into the cell cycle underlies AD pathogenesis.

p35/p25 is not essential for tau and cytoskeletal pathology or neuronal loss in Niemann-Pick type C disease.

Hyperactivation of the cyclin-dependent kinase 5 (cdk5), triggered by proteolytic conversion of its neuronal activator, p35, to a more potent byproduct, p25, has been implicated in Alzheimer's disease (AD), amyotrophic lateral sclerosis, and Niemann-Pick type C disease (NPC). This mechanism is thought to lead to the development of neuropathological hallmarks, i.e.

GTP-dependent secretion from neutrophils is regulated by Cdk5.

We have previously shown evidence for the existence of a calcium-independent, GTP-regulated mechanism of secretion from neutrophils, but this secretory mechanism remains to be fully elucidated. Cyclin-dependent kinase 5 (Cdk5), the various substrates of which include Munc18 and synapsin 1, has been implicated in neuronal secretion. Although the Cdk5 activator, p35, and Cdk5-p35 activity are primarily associated with neurons, we report here that p35 also exists in neutrophils and that an active Cdk5-p35 complex is present in these cells.

Decreased cyclin-dependent kinase 5 (cdk5) activity is accompanied by redistribution of cdk5 and cytoskeletal proteins and increased cytoskeletal protein phosphorylation in p35 null mice.

Cdk5/p35 has been implicated in cytoskeletal protein phosphorylation in normal brain and in many human neurodegenerative disorders. Yet, mouse models of cdk5/p35 hyperactivity have not yielded corresponding changes in cytoskeletal protein phosphorylation. To elucidate the relationship between p35, cdk5, and the neuronal cytoskeleton, we deleted the p35 gene in mice having a pure C57BL/6 background.

The cell cycle and human neurodegenerative disease.

The mechanism by which neurons die in human neurodegenerative diseases remains an enigma till today. Terminally differentiated neurons of normal brain are incapable of cell division. However, accumulating evidence has suggested that aberrant activation of the cell cycle in certain degenerative diseases leads to their demise.

Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1.

A low voltage-activated potassium current, IKL, is found in auditory neuron types that have low excitability and precisely preserve the temporal pattern of activity present in their presynaptic inputs. The gene Kcna1 codes for Kv1.1 potassium channel subunits, which combine in expression systems to produce channel tetramers with properties similar to those of IKL, including sensitivity to dendrotoxin (DTX).