The Parkinson\u27s Disease Protein α-Synuclein Disrupts Cellular Rab Homeostasis

α-Synuclein (α-syn), a protein of unknown function, is the most abundant protein in Lewy bodies, the histological hallmark of Parkinson\u27s disease (PD). In yeast α-syn inhibits endoplasmic reticulum (ER)-to-Golgi (ER→Golgi) vesicle trafficking, which is rescued by overexpression of a Rab GTPase that regulates ER→Golgi trafficking. The homologous Rab1 rescues α-syn toxicity in dopaminergic neuronal models of PD. Here we investigate this conserved feature of α-syn pathobiology. In a cell-free system with purified transport factors α-syn inhibited ER→Golgi trafficking in an α-syn dose-dependent manner. Vesicles budded efficiently from the ER, but their docking or fusion to Golgi membranes was inhibited. Thus, the in vivo trafficking problem is due to a direct effect of α-syn on the transport machinery. By ultrastructural analysis the earliest in vivo defect was an accumulation of morphologically undocked vesicles, starting near the plasma membrane and growing into massive intracellular vesicular clusters in a dose-dependent manner. By immunofluorescence/immunoelectron microscopy, these clusters were associated both with α-syn and with diverse vesicle markers, suggesting that α-syn can impair multiple trafficking steps. Other Rabs did not ameliorate α-syn toxicity in yeast, but RAB3A, which is highly expressed in neurons and localized to presynaptic termini, and RAB8A, which is localized to post-Golgi vesicles, suppressed toxicity in neuronal models of PD. Thus, α-syn causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

System Engineering Paper

The Iowa State University team, Team LunaCY, is composed of the following sub-teams: the main student organization, the Lunabotics Club; a senior mechanical engineering design course, ME 415; a senior multidisciplinary design course, ENGR 466; and a senior design course from Wartburg College in Waverly, Iowa. Team LunaCY designed and fabricated ART-E III, Astra Robotic Tractor- Excavator the Third, for the team's third appearance in the NASA Lunabotic Mining competition. While designing ART-E III, the team had four main goals for this year's competition:to reduce the total weight of the robot, to increase the amount of regolith simulant mined, to reduce dust, and to make ART-E III autonomous. After many designs and research, a final robot design was chosen that obtained all four goals of Team LunaCY. A few changes Team LunaCY made this year was to go to the electrical, computer, and software engineering club fest at Iowa State University to recruit engineering students to accomplish the task of making ART-E III autonomous. Team LunaCY chose to use LabView to program the robot and various sensors were installed to measure the distance between the robot and the surroundings to allow ART-E III to maneuver autonomously. Team LunaCY also built a testing arena to test prototypes and ART-E III in. To best replicate the competition arena at the Kennedy Space Center, a regolith simulant was made from sand, QuickCrete, and fly ash to cover the floor of the arena. Team LunaCY also installed fans to allow ventilation in the arena and used proper safety attire when working in the arena . With the additional practice in the testing arena and innovative robot design, Team LunaCY expects to make a strong appearance at the 2012 NASA Lunabotic Mining Competition.

Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant

(BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype.Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation

Evidence for the η_b(1S) Meson in Radiative Υ(2S) Decay

We have performed a search for the η_b(1S) meson in the radiative decay of the Υ(2S) resonance using a sample of 91.6 × 10^6 Υ(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E_γ = 609.3^(+4.6)_(-4.5)(stat)±1.9(syst) MeV, corresponding to an η_b(1S) mass of 9394.2^(+4.8)_(-4.9)(stat) ± 2.0(syst) MeV/c^2. The branching fraction for the decay Υ(2S) → γη_b(1S) is determined to be [3.9 ± 1.1(stat)^(+1.1)_(-0.9)(syst)] × 10^(-4). We find the ratio of branching fractions B[Υ(2S) → γη_b(1S)]/B[Υ(3S) → γη_b(1S)]= 0.82 ± 0.24(stat)^(+0.20)_(-0.19)(syst)

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Thermotolerance and molecular chaperone function of the small heat shock protein HSP20 from hyperthermophilic archaeon, Sulfolobus solfataricus P2

Small heat shock proteins are ubiquitous in all three domains (Archaea, Bacteria and Eukarya) and possess molecular chaperone activity by binding to unfolded polypeptides and preventing aggregation of proteins in vitro. The functions of a small heat shock protein (S.so-HSP20) from the hyperthermophilic archaeon, Sulfolobus solfataricus P2 have not been described. In the present study, we used real-time polymerase chain reaction analysis to measure mRNA expression of S.so-HSP20 in S. solfataricus P2 and found that it was induced by temperatures that were substantially lower (60°C) or higher (80°C) than the optimal temperature for S. solfataricus P2 (75°C). The expression of S.so-HSP20 mRNA was also up-regulated by cold shock (4°C). Escherichia coli cells expressing S.so-HSP20 showed greater thermotolerance in response to temperature shock (50°C, 4°C). By assaying enzyme activities, S.so-HSP20 was found to promote the proper folding of thermo-denatured citrate synthase and insulin B chain. These results suggest that S.so-HSP20 promotes thermotolerance and engages in chaperone-like activity during the stress response