Cell migration affects all morphogenetic processes and contributes to numerous diseases, including cancer and cardiovascular disease. For most cells in most environments, movement begins with ...protrusion of the cell membrane followed by the formation of new adhesions at the cell front that link the actin cytoskeleton to the substratum, generation of traction forces that move the cell forwards and disassembly of adhesions at the cell rear. Adhesion formation and disassembly drive the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin II activity, and therefore adhesion dynamics.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
N
-acetylcytidine (ac
C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA
. However, the distribution, ...dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac
C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac
C at single-nucleotide resolution. In human and yeast mRNAs, ac
C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac
C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac
C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac
C and its potential thermoadaptive role. Our studies quantitatively define the ac
C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease
.
The novel coronavirus and associated Coronavirus Disease 2019 (COVID-19) is rapidly spreading throughout the world, with robust growth in the United States. Its drastic impact on the global ...population and international health care is swift, evolving, and unpredictable. The effects on orthopaedic surgery departments are predominantly indirect, with widespread cessation of all nonessential orthopaedic care. Although this is vital to the system-sustaining measures of isolation and resource reallocation, there is profound detriment to orthopaedic training programs.
In the face of new pressures on the finite timeline on an orthopaedic residency, the Emory University School of Medicine Department of Orthopaedics has devised a 5-pronged strategy based on the following: (1) patient and provider safety, (2) uninterrupted necessary care, (3) system sustainability, (4) adaptability, and (5) preservation of vital leadership structures.
Our 5 tenants support a 2-team system, whereby the residents are divided into cycling "active-duty" and "working remotely" factions. In observation of the potential incubation period of viral symptoms, phase transitions occur every 2 weeks with strict adherence to team assignments. Intrateam redundancy can accommodate potential illness to ensure a stable unit of able residents. Active duty residents participate in in-person surgical encounters and virtual ambulatory encounters, whereas remotely working residents participate in daily video-conferenced faculty-lead, case-based didactics and pursue academic investigation, grant writing, and quality improvement projects. To sustain this, faculty and administrative 2-team systems are also in place to protect the leadership and decision-making components of the department.
The novel coronavirus has decimated the United States healthcare system, with an unpredictable duration, magnitude, and variability. As collateral damage, orthopaedic residencies are faced with new challenges to provide care and educate residents in the face of safety, resource redistribution, and erosion of classic learning opportunities. Our adaptive approach aims to be a generalizable tactic to optimize our current landscape.
The immunogenicity of a bivalent mRNA vaccine with both ancestral and omicron BA.1 sequences elicited higher neutralization titers against BA.1 than did the ancestral strain–specific vaccine.
Herein, we report an approach to produce levoglucosenone (LGO) from cellulose in yields up to 51% under mild reaction conditions (170-230 °C; 5-20 mM H
2
SO
4
) using polar, aprotic solvents such as ...tetrahydrofuran (THF). LGO can be used to make a wide variety of chemicals from biomass. The water content and solvent used in the reaction system control the product distribution. LGO is produced from the dehydration of levoglucosan (LGA). LGA is produced from cellulose depolymerization. Increasing the water content leads to the production of 5-hydroxymethyl furfural (HMF), obtaining a maximum HMF yield of 30%.
Herein, we report an approach to produce levoglucosenone (LGO) from cellulose in yields up to 51% under mild reaction conditions (170-230 °C; 5-20 mM H
2
SO
4
) using polar, aprotic solvents such as tetrahydrofuran (THF).
Recent advances in metabolic engineering have allowed for the production of a wide array of molecules via biocatalytic routes. The high selectivity of biocatalysis to remove functionality from ...biomass can be used to produce platform molecules that are suitable for subsequent upgrading over heterogeneous catalysts. Accordingly, the more robust continuous processing allowed by chemical catalysis could be leveraged to upgrade biologically derived platform molecules to produce direct or functional replacements for petroleum products. Herein, we highlight recent results that utilize a combination of chemical and biological catalysis, and using the perspective of heterogeneous chemical catalysis, we identify challenges that need to be addressed to bridge the gap between the two catalytic approaches. Specifically, studies are required to address the effects on catalyst performance of impurities that originate during bioprocessing. In addition, new generations of heterogeneous catalysts are required for stable operation under liquid phase reaction conditions in the presence of biogenic impurities. Finally, the design and syntheses of new catalysts are required to tailor the active sites and the environment around these sites to achieve selective conversion of the functional groups present in biologically derived platform molecules.
The Fate of FDA Postapproval Studies Woloshin, Steven; Schwartz, Lisa M; White, Brian ...
The New England journal of medicine,
09/2017, Letnik:
377, Številka:
12
Journal Article
Recenzirano
The Food and Drug Administration often requires postapproval studies to address issues such as optimal dosing, potential long-term side effects, and use in children or to confirm a drug’s clinical ...benefit. But many of these studies aren’t completed on time, if at all.
Wildlife-vehicle collisions are one of the main causes of mortality for wild mammals and birds in the UK. Here, using a dataset of 54,000+ records collated by a citizen science roadkill recording ...scheme between 2014-2019, we analyse and present temporal patterns of wildlife roadkill of the 19 most commonly reported taxa in the UK (84% of all reported roadkill). Most taxa (13 out of 19) showed significant and consistent seasonal variations in road mortality and fitted one of two seasonal patterns; bimodal or unimodal: only three species (red fox Vulpes vulpes, European polecat Mustela putorius and Reeves' muntjac deer Muntiacus reevesi) showed no significant seasonality. Species that increase movement in spring and autumn potentially have bimodal patterns in roadkill due to the increase in mate-searching and juvenile dispersal during these respective time periods (e.g. European badger Meles meles). Unimodal patterns likely represent increased mortality due to a single short pulse in activity associated with breeding (e.g. birds) or foraging (e.g. grey squirrels Sciurus carolinensis in autumn). Importantly, these patterns also indicate periods of increased risk for drivers, potentially posing a greater threat to human welfare. In addition to behaviour-driven annual patterns, abiotic factors (temperature and rainfall) explained some variance in roadkill. Notably, high rainfall was associated with decreased observations of two bird taxa (gulls and Eurasian magpies Pica pica) and European rabbit Oryctolagus cuniculus. By quantifying seasonal patterns in roadkill, we highlight a significant anthropogenic impact on wild species, which is important in relation to conservation, animal welfare, and human safety.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ergonomics researchers and practitioners use many techniques to assess risk. The Rapid Entire Body Assessment (REBA) is a common tool used to facilitate the measurement and evaluation of the risks ...associated with working postures as a part of ergonomic workload. However, little work has been reported regarding the reliability of REBA reporting.
This study assesses the reliability of this commonly used tool for research and practice.
The study was conducted as part of the larger Safe Workload Ergonomic Exposure Project (SWEEP), which is a University of Minnesota research initiative for custodians. For this effort, a secondary data analysis was conducted on data collected during a study of custodians’ exposures to risks of musculoskeletal disorders. Eight observers used the REBA tool to sequentially evaluate tasks performed two times in succession by the same individual.
This study reports high intra-rater reliability (ICC = 0.925) for REBA raw scores and moderate inter-rater reliability (IRR) (Fleiss kappa = 0.54) for a categorical scoring of REBA.
A moderate amount of IRR was found, and a standardized training and calibration protocol is proposed as a potential means to improve intra- and inter-rater reliability.
•Eight observers used the REBA tool to sequentially evaluate tasks performed two times in succession by the same individual.•High intra-rater reliability (ICC = 0.925) was found for REBA raw scores.•Moderate inter-rater reliability (Fleiss kappa = 0.54) was found for a categorical scoring of REBA.
With the increased use of small self-complementary adeno-associated viral (AAV) vectors, the design of compact promoters becomes critical for packaging and expressing larger transgenes under ...ubiquitous or cell-specific control. In a comparative study of commonly used 800-bp cytomegalovirus (CMV) and chicken β-actin (CBA) promoters, we report significant differences in the patterns of cell-specific gene expression in the central and peripheral nervous systems. The CMV promoter provides high initial neural expression that diminishes over time. The CBA promoter displayed mostly ubiquitous and high neural expression, but substantially lower expression in motor neurons (MNs). We report the creation of a novel hybrid form of the CBA promoter (CBh) that provides robust long-term expression in all cells observed with CMV or CBA, including MNs. To develop a short neuronal promoter to package larger transgenes into AAV vectors, we also found that a 229-bp fragment of the mouse methyl-CpG-binding protein-2 (MeCP2) promoter was able to drive neuron-specific expression within the CNS. Thus the 800-bp CBh promoter provides strong, long-term, and ubiquitous CNS expression whereas the MeCP2 promoter allows an extra 570-bp packaging capacity, with low and mostly neuronal expression within the CNS, similar to the MeCP2 transcription factor.
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