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Yani Zhao, Pawel Dabrowski-Tumanski, Szymon Niewieczerzal, Joanna I Sulkowska
The folding of proteins with a complex knot is still an unresolved question. Based on representative members of Ubiquitin C-terminal Hydrolases (UCHs) that contain the 52 knot in the native state, we explain how UCHs are able to unfold and refold in vitro reversibly within the structure-based model. In particular, we identify two, topologically different folding/unfolding pathways and corroborate our results with experiment, recreating the chevron plot. We show that confinement effect of chaperonin or weak crowding greatly facilitates folding, simultaneously slowing down the unfolding process of UCHs, compared with bulk conditions...
March 16, 2018: PLoS Computational Biology
Size Zheng, Katherine S Shing, Muhammad Sahimi
In this paper, the second in a series devoted to molecular modeling of protein aggregation, a mesoscale model of proteins together with extensive discontinuous molecular dynamics simulation is used to study the phenomenon in a confined medium. The medium, as a model of a crowded cellular environment, is represented by a spherical cavity, as well as cylindrical tubes with two aspect ratios. The aggregation process leads to the formation of β sheets and eventually fibrils, whose deposition on biological tissues is believed to be a major factor contributing to many neuro-degenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis diseases...
March 14, 2018: Journal of Chemical Physics
Nancy A Scott, Taryn Vian, Jeanette L Kaiser, Thandiwe Ngoma, Kaluba Mataka, Elizabeth G Henry, Godfrey Biemba, Mary Nambao, Davidson H Hamer
BACKGROUND: The WHO recommends maternity waiting homes (MWH) as one intervention to improve maternal and newborn health. However, persistent structural, cultural and financial barriers in their design and implementation have resulted in mixed success in both their uptake and utilization. Guidance is needed on how to design a MWH intervention that is acceptable and sustainable. Using formative research and guided by a sustainability framework for health programs, we systematically collected data from key stakeholders and potential users in order to design a MWH intervention in Zambia that could overcome multi-dimensional barriers to accessing facility delivery, be acceptable to the community and be financially and operationally sustainable...
2018: PloS One
Michelle Wong, Esther Bejarano, Graeme Carvlin, Katie Fellows, Galatea King, Humberto Lugo, Michael Jerrett, Dan Meltzer, Amanda Northcross, Luis Olmedo, Edmund Seto, Alexa Wilkie, Paul English
Air pollution continues to be a global public health threat, and the expanding availability of small, low-cost air sensors has led to increased interest in both personal and crowd-sourced air monitoring. However, to date, few low-cost air monitoring networks have been developed with the scientific rigor or continuity needed to conduct public health surveillance and inform policy. In Imperial County, California, near the U.S./Mexico border, we used a collaborative, community-engaged process to develop a community air monitoring network that attains the scientific rigor required for research, while also achieving community priorities...
March 15, 2018: International Journal of Environmental Research and Public Health
Simon K Schnyder, Jürgen Horbach
Molecular dynamics simulations of interacting soft disks confined in a heterogeneous quenched matrix of soft obstacles show dynamics which is fundamentally different from that of hard disks. The interactions between the disks can enhance transport when their density is increased, as disks cooperatively help each other over the finite energy barriers in the matrix. The system exhibits a transition from a diffusive to a localized state, but the transition is strongly rounded. Effective exponents in the mean-squared displacement can be observed over three decades in time but depend on the density of the disks and do not correspond to asymptotic behavior in the vicinity of a critical point, thus, showing that it is incorrect to relate them to the critical exponents in the Lorentz model scenario...
February 16, 2018: Physical Review Letters
Chiho Watanabe, Miho Yanagisawa
Micrometric membrane confinements and macromolecular crowding of cytoplasm are key factors that regulate molecular diffusion in live cells. Previous studies have shown that macromolecular crowding delays molecular diffusion. However, the effect of cell-size confinement on diffusion in the crowding environment is yet to be elucidated. Using fluorescence correlation spectroscopy (FCS), we analyzed protein diffusion in microdroplets containing polymer solution covered with lipid membranes that mimic cells. As a result, we found that a synergistic condition of crowding and micrometric confinement results in accelerated protein diffusion on a sub-millisecond time scale...
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Huanchen Wang, Chunfang Gu, Ronda J Rolfes, Henning J Jessen, Stephen B Shears
Inositol pyrophosphates (PP-InsPs) are 'energetic' intracellular signals that are ubiquitous in animals, plant and fungi; structural and biochemical characterization of PP-InsP metabolic enzymes provides insight into their evolution, reaction mechanisms, and regulation. Here, we describe the 2.35 Å resolution structure of the catalytic core of Siw14, a 5-PP-InsP phosphatase from Saccharomyces cerevisiae, and a member of the protein tyrosinephosphatase (PTP) superfamily. Conclusions that we derive from structural data are supported by extensive site-directed mutagenesis and kinetic analyses, thereby attributing new functional significance to several key residues...
March 14, 2018: Journal of Biological Chemistry
Susan Williams, Mallory Schneider, Cory Wornell, Jennifer Langhinrichsen-Rohling
This study examined the relationship of students' perceptions of school safety and school avoidance related to feeling unsafe with predictor variables: bullying victimization, student/teacher/parent/administration relations, rule clarity and consistency, school physical environment (negative and positive), and student's belongingness. In a public high school sample ( n = 585), 24.7% of students felt unsafe and 14.4% avoided school due to feeling unsafe during the past month. Being female and experiencing bullying was associated with feeling unsafe...
January 1, 2018: Journal of School Nursing: the Official Publication of the National Association of School Nurses
Jeffrey W Jordan, Carolyn A Stalgaitis, John Charles, Patrick A Madden, Anjana G Radhakrishnan, Daniel Saggese
PURPOSE: Peer crowds are macro-level subcultures that share similarities across geographic areas. Over the past decade, dozens of studies have explored the association between adolescent peer crowds and risk behaviors, and how they can inform public health efforts. However, despite the interest, researchers have not yet reported on crowd size and risk levels from a representative sample, making it difficult for practitioners to apply peer crowd science to interventions. The current study reports findings from the first statewide representative sample of adolescent peer crowd identification and health behaviors...
February 1, 2018: Health Education & Behavior: the Official Publication of the Society for Public Health Education
Dennis de Coninck, Thomas H Schmidt, Jan-Gero Schloetel, Thorsten Lang
Plasma membrane proteins organize into structures named compartments, microdomains, rafts, phases, crowds, or clusters. These structures are often smaller than 100 nm in diameter. Despite their importance in many cellular functions, little is known about their inner organization. For instance, how densely are molecules packed? Being aware of the protein compaction may contribute to our general understanding of why such structures exist and how they execute their functions. In this study, we have investigated plasma membrane crowds formed by the amyloid precursor protein (APP), a protein well known for its involvement in Alzheimer's disease...
March 13, 2018: Biophysical Journal
Mimi Gao, Melanie Berghaus, Simone Möbitz, Vitor Schuabb, Nelli Erwin, Marius Herzog, Karin Julius, Christian Sternemann, Roland Winter
For over 50 years, it has been known that the mitosis of eukaryotic cells is inhibited already at high hydrostatic pressure conditions of 30 MPa. This effect has been attributed to the disorganization of microtubules, the main component of the spindle apparatus. However, the structural details of the depolymerization and the origin of the pressure sensitivity have remained elusive. It has also been a puzzle how complex organisms could still successfully inhabit extreme high-pressure environments such as those encountered in the depth of oceans...
March 13, 2018: Biophysical Journal
Anthony Banks, Sanbo Qin, Kevin L Weiss, Christopher B Stanley, Huan-Xiang Zhou
Conformational malleability allows intrinsically disordered proteins (IDPs) to respond agilely to their environments, such as nonspecifically interacting with in vivo bystander macromolecules (or crowders). Previous studies have emphasized conformational compaction of IDPs due to steric repulsion by macromolecular crowders, but effects of soft attraction are largely unexplored. Here we studied the conformational ensembles of the IDP FlgM in both polymer and protein crowders by small-angle neutron scattering...
March 13, 2018: Biophysical Journal
Hanh Ngo, Roberto Forero, David Mountain, Daniel Fatovich, Wing Nicola Man, Peter Sprivulis, Mohammed Mohsin, Sam Toloo, Antonio Celenza, Gerard Fitzgerald, Sally McCarthy, Ken Hillman
BACKGROUND: In 2009, the Western Australian (WA) Government introduced the Four-Hour Rule (FHR) program. The policy stated that most patients presenting to Emergency Departments (EDs) were to be seen and either admitted, transferred, or discharged within 4 hours. This study utilised de-identified data from five participating hospitals, before and after FHR implementation, to assess the impact of the FHR on several areas of ED functioning. METHODS: A state (WA) population-based intervention study design, using longitudinal data obtained from administrative health databases via record linkage methodology, and interrupted time series analysis technique...
2018: PloS One
Karen M Miernyk, Lisa R Bulkow, Benjamin D Gold, Michael G Bruce, Debby H Hurlburt, Patricia M Griffin, David L Swerdlow, Kim Cook, Thomas W Hennessy, Alan J Parkinson
BACKGROUND: Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection. METHODS: A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997...
March 14, 2018: Helicobacter
Michael Senske, Yao Xu, Alexander Bäumer, Sarah Schäfer, Hanna Wirtz, Janne Savolainen, Hermann Weingärtner, Martina Havenith
When comparing protein folding in vitro and in vivo significant differences have been found. This has been attributed to crowding and confinement effects. Using a combination of GHz- and THz-dielectric relaxation spectroscopy and MD simulations, we studied hydration dynamics and reviewed protein stability data inside sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and cetyltrimethylammonium bromide (CTAB) reverse micelles which are model systems for confinement. We find that water inside anionic AOT and cationic CTAB reverse micelles is characterized by a strong dielectric depolarization giving rise to a very low relative permittivity compared to an unconfined solution...
March 14, 2018: Physical Chemistry Chemical Physics: PCCP
Belinda M Craig, Ottmar V Lipp
Young adult participants are faster to detect young adult faces in crowds of infant and child faces than vice versa. These findings have been interpreted as evidence for more efficient attentional capture by own-age than other-age faces, but could alternatively reflect faster rejection of other-age than own-age distractors, consistent with the previously reported other-age categorization advantage: faster categorization of other-age than own-age faces. Participants searched for own-age faces in other-age backgrounds or vice versa...
March 13, 2018: British Journal of Psychology
Qing-Feng Wu, Xiao-Bing Wang, Peng-Xiang Shen, Jin-Quan Yu
Chiral mono- N -protected aminomethyl oxazoline (MPAO) ligands are found to promote enantioselective C-H arylation and vinylation of the cyclobutyl carboxylic acid derivatives via Pd(II)/Pd(IV) redox catalysis. This ligand scaffold overcame two important limitations of the previous MPAHA (mono- N -protected α-amino- O -methylhydroxamic acid) ligands-enabled asymmetric C-H activation/C-C coupling reactions of cyclic carboxylic amides through Pd(II)/Pd(0) catalysis: substrates containing α-hydrogen atoms are not compatible; vinylation has not been developed...
March 2, 2018: ACS Catalysis
Shawn M Ferguson
Lysosomes perform degradative functions that are important for all cells. However, neurons are particularly dependent on optimal lysosome function due to their extremes of longevity, size and polarity. Axons in particular exemplify the major spatial challenges faced by neurons in the maintenance of lysosome biogenesis and function. What impact does this have on the regulation and functions of lysosomes in axons? This review focuses on the mechanisms whereby axonal lysosome biogenesis, transport and function are adapted to meet neuronal demand...
March 9, 2018: Current Opinion in Neurobiology
A-G E Ausseil, J R Dymond, L Newstrom
Honey bees require nectar and pollen from flowers: nectar for energy and pollen for growth. The demand for nectar and pollen varies during the year, with more pollen needed in spring for colony population growth, and more nectar needed in summer to sustain the maximum colony size and collect surplus nectar stores for winter. Sufficient bee forage is therefore necessary to ensure a healthy bee colony. Land-use changes can reduce the availability of floral resources suitable for bees, thereby increasing the susceptibility of bees to other stressors such as disease and pesticides...
March 12, 2018: Ecological Applications: a Publication of the Ecological Society of America
Jens C Hegg, Jonathan Middleton, Ben Luca Robertson, Brian P Kennedy
The migration of Pacific salmon is an important part of functioning freshwater ecosystems, but as populations have decreased and ecological conditions have changed, so have migration patterns. Understanding how the environment, and human impacts, change salmon migration behavior requires observing migration at small temporal and spatial scales across large geographic areas. Studying these detailed fish movements is particularly important for one threatened population of Chinook salmon in the Snake River of Idaho whose juvenile behavior may be rapidly evolving in response to dams and anthropogenic impacts...
February 2018: Heliyon
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