YsxC, an essential protein in Staphylococcus aureus crucial for ribosome assembly/stability

<p>Abstract</p> <p>Background</p> <p>Bacterial growth and division requires a core set of essential proteins, several of which are still of unknown function. They are also attractive targets for the development of new antibiotics. YsxC is a member of a family of GTPases highly conserved across eubacteria with a possible ribosome associated function.</p> <p>Results</p> <p>Here, we demonstrate by the creation of a conditional lethal mutant that <it>ysxC </it>is apparently essential for growth in <it>S. aureus</it>. To begin to elucidate YsxC function, a translational fusion of YsxC to the CBP-ProteinA tag in the staphylococcal chromosome was made, enabling Tandem Affinity Purification (TAP) of YsxC-interacting partners. These included the ribosomal proteins S2, S10 and L17, as well as the ^β' subunit of the RNA polymerase. YsxC was then shown to copurify with ribosomes as an accessory protein specifically localizing to the 50 S subunit. YsxC depletion led to a decrease in the presence of mature ribosomes, indicating a role in ribosome assembly and/or stability in <it>S. aureus</it>.</p> <p>Conclusions</p> <p>In this study we demonstrate that YsxC of <it>S. aureus </it>localizes to the ribosomes, is crucial for ribosomal stability and is apparently essential for the life of <it>S. aureus</it>.</p

Supramolecular structure in the membrane of Staphylococcus aureus

The fundamental processes of life are organized and based on common basic principles. Molecular organizers, often interacting with the membrane, capitalize on cellular polarity to precisely orientate essential processes. The study of organisms lacking apparent polarity or known cellular organizers (e.g., the bacterium Staphylococcus aureus) may enable the elucidation of the primal organizational drive in biology. How does a cell choose from infinite locations in its membrane? We have discovered a structure in the S. aureus membrane that organizes processes indispensable for life and can arise spontaneously from the geometric constraints of protein complexes on membranes. Building on this finding, the most basic cellular positioning system to optimize biological processes, known molecular coordinators could introduce further levels of complexity. All life demands the temporal and spatial control of essential biological functions. In bacteria, the recent discovery of coordinating elements provides a framework to begin to explain cell growth and division. Here we present the discovery of a supramolecular structure in the membrane of the coccal bacterium Staphylococcus aureus, which leads to the formation of a large-scale pattern across the entire cell body; this has been unveiled by studying the distribution of essential proteins involved in lipid metabolism (PlsY and CdsA). The organization is found to require MreD, which determines morphology in rod-shaped cells. The distribution of protein complexes can be explained as a spontaneous pattern formation arising from the competition between the energy cost of bending that they impose on the membrane, their entropy of mixing, and the geometric constraints in the system. Our results provide evidence for the existence of a self-organized and nonpercolating molecular scaffold involving MreD as an organizer for optimal cell function and growth based on the intrinsic self-assembling properties of biological molecules

Shrinking the lymphatic filariasis map of Ethiopia: reassessing the population at risk through nationwide mapping

BACKGROUND Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. METHODOLOGY/PRINCIPAL FINDING A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. CONCLUSIONS We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale

Surfactant-free purification of membrane protein complexes from bacteria: application to the staphylococcal penicillin-binding protein complex PBP2/PBP2a

Surfactant-mediated removal of proteins from biomembranes invariably results in partial or complete loss of function and disassembly of multi-protein complexes. We determined the capacity of styrene-co-maleic acid (SMA) co-polymer to remove components of the cell division machinery from the membrane of drug-resistant staphylococcal cells. SMA-lipid nanoparticles solubilized FtsZ-PBP2-PBP2a complexes from intact cells, demonstrating the close physical proximity of these proteins within the lipid bilayer. Exposure of bacteria to (-)-epicatechin gallate, a polyphenolic agent that abolishes β-lactam resistance in staphylococci, disrupted the association between PBP2 and PBP2a. Thus, SMA purification provides a means to remove native integral membrane protein assemblages with minimal physical disruption and shows promise as a tool for the interrogation of molecular aspects of bacterial membrane protein structure and function

Cortical Surface Diffusion Generative Models

Cortical surface analysis has gained increased prominence, given its potential implications for neurological and developmental disorders. Traditional vision diffusion models, while effective in generating natural images, present limitations in capturing intricate development patterns in neuroimaging due to limited datasets. This is particularly true for generating cortical surfaces where individual variability in cortical morphology is high, leading to an urgent need for better methods to model brain development and diverse variability inherent across different individuals. In this work, we proposed a novel diffusion model for the generation of cortical surface metrics, using modified surface vision transformers as the principal architecture. We validate our method in the developing Human Connectome Project (dHCP), the results suggest our model demonstrates superior performance in capturing the intricate details of evolving cortical surfaces. Furthermore, our model can generate high-quality realistic samples of cortical surfaces conditioned on postmenstrual age(PMA) at scan.Comment: 4 page

The global atlas of podoconiosis.

The world stands on the edge of an historic public health success with the imminent eradication of dracunculiasis (guinea-worm disease) and polio. Since the World Health Assembly called for the eradication of dracunculiasis in 1986 and poliomyelitis in 1988, astonishing progress has been made. In 2016, only 25 human cases of dracunculiasis were reported from three countries, transmission of wild poliovirus was found in only three countries, and 37 cases of polio were reported worldwide. In addition to these achievements, there has been progress in the elimination of the little-known disease podoconiosis (endemic non-filarial elephantiasis)

Coating carbon nanotubes with a polystyrene-based polymer protects against pulmonary toxicity

BACKGROUND: carbon nanotubes (CNT) can have adverse effects on health. Therefore, minimizing the risk associated with CNT exposure is of crucial importance. The aim of this work was to evaluate if coating multi-walled CNT (MWCNT) with polymers could modify their toxicity, thus representing a useful strategy to decrease adverse health effects of CNT. We used industrially-produced MWCNT uncoated (NT1) or coated (50/50 wt%) with acid-based (NT2) or polystyrene-based (NT3) polymer, and exposed murine macrophages (RAW 264.7 cell line) or Balb/c mice by intratracheal administration. Biological experiments were performed both in vitro and in vivo, examining time- and dose-dependent effects of CNT, in terms of cytotoxicity, expression of genes and proteins related to oxidative stress, inflammation and tissue remodeling, cell and lung tissue morphology (optical and transmission electron microscopy), and bronchoalveolar lavage fluid content analysis.RESULTS: extensive physico-chemical characterization of MWCNT was performed, and showed, although similar dimensions for the 3 MWCNT, a much smaller specific surface area for NT2 and NT3 as compared to NT1 (54.1, 34 and 227.54 m(2)/g respectively), along with different surface characteristics. MWCNT-induced cytotoxicity, oxidative stress, and inflammation were increased by acid-based and decreased by polystyrene-based polymer coating both in vitro in murine macrophages and in vivo in lung of mice monitored for 6 months.CONCLUSIONS: these results demonstrate that coating CNT with polymers, without affecting their intrinsic structure, may constitute a useful strategy for decreasing CNT toxicity, and may hold promise for improving occupational safety and that of general the user

Unwind: Interactive Fish Straightening

The ScanAllFish project is a large-scale effort to scan all the world's 33,100 known species of fishes. It has already generated thousands of volumetric CT scans of fish species which are available on open access platforms such as the Open Science Framework. To achieve a scanning rate required for a project of this magnitude, many specimens are grouped together into a single tube and scanned all at once. The resulting data contain many fish which are often bent and twisted to fit into the scanner. Our system, Unwind, is a novel interactive visualization and processing tool which extracts, unbends, and untwists volumetric images of fish with minimal user interaction. Our approach enables scientists to interactively unwarp these volumes to remove the undesired torque and bending using a piecewise-linear skeleton extracted by averaging isosurfaces of a harmonic function connecting the head and tail of each fish. The result is a volumetric dataset of a individual, straight fish in a canonical pose defined by the marine biologist expert user. We have developed Unwind in collaboration with a team of marine biologists: Our system has been deployed in their labs, and is presently being used for dataset construction, biomechanical analysis, and the generation of figures for scientific publication