Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization.

Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation.

Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models.

The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models.

Small molecule ligand docking to genotype specific bundle structures of hepatitis C virus (HCV) p7 protein.

The genome of hepatitis C virus encodes for an essential 63 amino acid polytopic protein p7 of most likely two transmembrane domains (TMDs). The protein is identified to self-assemble thereby rendering lipid membranes permeable to ions. A series of small molecules such as adamantanes, imino sugars and guanidinium compounds are known to interact with p7.

Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells.

Unlabelled: Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control.

Helicobacter pylori HP0231 Influences Bacterial Virulence and Is Essential for Gastric Colonization.

The Dsb protein family is responsible for introducing disulfide bonds into nascent proteins in prokaryotes, stabilizing the structure of many proteins. Helicobacter pylori HP0231 is a Dsb-like protein, shown to catalyze disulfide bond formation and to participate in redox homeostasis. Notably, many H.

Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9).

Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.

Monoclinic sphere packings. I. Invariant, univariant and bivariant lattice complexes.

All homogeneous sphere packings were derived that refer to the two invariant, the four univariant and the three bivariant lattice complexes belonging to the monoclinic crystal system. In total, sphere packings of 29 types have been found. Only for five types is the maximal inherent symmetry of their sphere packings monoclinic whereas the inherent symmetry is orthorhombic for nine types, tetragonal for five types, hexagonal for six types and cubic for four types.

Integrated sequence and immunology filovirus database at Los Alamos.

The Ebola outbreak of 2013-15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount.

Asymmetric dynamics of ion channel forming proteins - Hepatitis C virus (HCV) p7 bundles.

Protein p7 of hepatitis C virus (HCV) is a short 63 amino acid membrane protein which homo-oligomerises in the lipid membrane to form ion and proton conducting bundles. Two different genotypes (GTs) of p7, 1a and 5a, are used to simulate hexameric bundles of the protein embedded in a fully hydrated lipid bilayer during 400 ns molecular dynamics (MD) simulations. Whilst the bundle of GT 1a is based on a fully computational derived structure, the bundle of GT 5a is based on NMR spectroscopic data.

How did life survive Earth's great oxygenation?

Life on Earth originated and evolved in anoxic environments. Around 2.4 billion-years-ago, ancestors of Cyanobacteria invented oxygenic photosynthesis, producing substantial amounts of O2 as a byproduct of phototrophic water oxidation.

Real-Time Manganese Phase Dynamics during Biological and Abiotic Manganese Oxide Reduction.

Manganese oxides are often highly reactive and easily reduced, both abiotically, by a variety of inorganic chemical species, and biologically during anaerobic respiration by microbes. To evaluate the reaction mechanisms of these different reduction routes and their potential lasting products, we measured the sequence progression of microbial manganese(IV) oxide reduction mediated by chemical species (sulfide and ferrous iron) and the common metal-reducing microbe Shewanella oneidensis MR-1 under several endmember conditions, using synchrotron X-ray spectroscopic measurements complemented by X-ray diffraction and Raman spectroscopy on precipitates collected throughout the reaction. Crystalline or potentially long-lived phases produced in these experiments included manganese(II)-phosphate, manganese(II)-carbonate, and manganese(III)-oxyhydroxides.

Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients.

Confronting Ebola as a Sexually Transmitted Infection.

The unprecedented Ebola outbreak that devastated West Africa evolved within months from a regional outbreak to a global public health emergency. While the rate of confirmed cases declined dramatically, sporadic clusters of Ebola virus disease (EVD) continue well beyond the double incubation period of 42 days used to declare a nation Ebola-free. At the same time, evidence that the virus persists in genital fluids and can be sexually transmitted, along with the potential for lingering virus in other body compartments to permit recrudescence of EVD, has shaken our thinking of what it takes to achieve lasting control of an Ebola epidemic.

Patch formation of a viral channel forming protein within a lipid membrane--Vpu of HIV-1.

Ion channels and their viral companions are defined by their quaternary structure. The individual sub-units have to assemble into homo- or hetero-oligomers. Using Vpu of HIV-1, a putative viral channel forming protein (VCP), as a test case, the formation of a quaternary structure is monitored using coarse grained molecular dynamics (CGMD) simulations.

Viral channel forming proteins--How to assemble and depolarize lipid membranes in silico.

Viral channel forming proteins (VCPs) have been discovered in the late 70s and are found in many viruses to date. Usually they are small and have to assemble to form channels which depolarize the lipid membrane of the host cells. Structural information is just about to emerge for just some of them.

Characterization of Multisubstituted Corticotropin Releasing Factor (CRF) Peptide Antagonists (Astressins).

CRF mediates numerous stress-related endocrine, autonomic, metabolic, and behavioral responses. We present the synthesis and chemical and biological properties of astressin B analogues {cyclo(30-33)[D-Phe(12),Nle(21,38),C(α)MeLeu(27,40),Glu(30),Lys(33)]-acetyl-h/r-CRF(9-41)}. Out of 37 novel peptides, 17 (2, 4, 6-8, 10, 11, 16, 17, 27, 29, 30, 32-36) and 16 (3, 5, 9, 12-15, 18, 19, 22-26, 28, 31) had k(i) to CRF receptors in the high picomolar and low nanomole ranges, respectively.

Interaction of ions with the luminal sides of wild-type and mutated skeletal muscle ryanodine receptors.

Ryanodine receptors (RyRs) are the largest known ion channels, and are of central importance for the release of Ca(2+) from the sarco/endoplasmic reticulum (SR/ER) in a variety of cells. In cardiac and skeletal muscle cells, contraction is triggered by the release of Ca(2+) into the cytoplasm and thus depends crucially on correct RyR function. In this work, in silico mutants of the RyR pore were generated and MD simulations were conducted to examine the impact of the mutations on the Ca(2+) distribution.

Operational Head-on Beam-Beam Compensation with Electron Lenses in the Relativistic Heavy Ion Collider.

Head-on beam-beam compensation has been implemented in the Relativistic Heavy Ion Collider in order to increase the luminosity delivered to the experiments. We discuss the principle of combining a lattice for resonance driving term compensation and an electron lens for tune spread compensation. We describe the electron lens technology and its operational use.

Quantitative analysis of CagA type IV secretion by Helicobacter pylori reveals substrate recognition and translocation requirements.

Bacterial type IV secretion systems are protein transporters with a remarkable diversity of substrates and substrate recognition mechanisms. Type IV-secreted proteins often contain C-terminal secretion signals, but may also require other regions for recognition as secretory substrates, or for full secretion efficiency. For example, type IV secretion of CagA, a major pathogenicity factor of the human gastric pathogen Helicobacter pylori, depends on a C-terminal signal and on N-terminal protein regions.

Draft Genome Sequence of Levilinea saccharolytica KIBI-1, a Member of the Chloroflexi Class Anaerolineae.

We report the draft genome sequence of Levilinea saccharolytica KIBI-1, a facultative anaerobic member of the Chloroflexi class Anaerolineae. While L. saccharolytica was characterized as an obligate anaerobe, genome analysis provides evidence for the presence of both aerobic respiration and partial denitrification pathways.

Draft Genome Sequence of Leptolinea tardivitalis YMTK-2, a Mesophilic Anaerobe from the Chloroflexi Class Anaerolineae.

We present the draft genome sequence of Leptolinea tardivitalis YMTK-2, a member of the Chloroflexi phylum. This organism was initially characterized as a strictly anaerobic nonmotile fermenter; however, genome analysis demonstrates that it encodes for a flagella and might be capable of aerobic respiration.