The Role of Molecular Microtubule Motors and the Microtubule Cytoskeleton in Stress Granule Dynamics

Stress granules (SGs) are cytoplasmic foci that appear in cells exposed to stress-induced translational inhibition. SGs function as a triage center, where mRNAs are sorted for storage, degradation, and translation reinitiation. The underlying mechanisms of SGs dynamics are still being characterized, although many key players have been identified. The main components of SGs are stalled 48S preinitiation complexes. To date, many other proteins have also been found to localize in SGs and are hypothesized to function in SG dynamics. Most recently, the microtubule cytoskeleton and associated motor proteins have been demonstrated to function in SG dynamics. In this paper, we will discuss current literature examining the function of microtubules and the molecular microtubule motors in SG assembly, coalescence, movement, composition, organization, and disassembly

Ozone and temperature trends

An update of the extensive reviews of the state of knowledge of measured ozone trends published in the Report of the International Ozone Trends Panel is presented. The update contains a review of progress since these reports, including reviewing of the ozone records, in most cases through March 1991. Also included are some new, unpublished reanalyses of these records including a complete reevaluation of 29 stations located in the former Soviet Union. The major new advance in knowledge of the measured ozone trend is the existence of independently calibrated satellite data records from the Total Ozone Mapping Spectrometer (TOMS) and Stratospheric Aerosol and Gas Experiment (SAG) instruments. These confirm many of the findings, originally derived from the Dobson record, concerning northern mid-latitude changes in ozone. We now have results from several instruments, whereas the previously reported changes were dependent on the calibration of a single instrument. This update will compare the ozone records from many different instruments to determine whether or not they provide a consistent picture of the ozone change that has occurred in the atmosphere. The update also briefly considers the problem of stratospheric temperature change. As in previous reports, this problem received significantly less attention, and the report is not nearly as complete. This area needs more attention in the future

Youth Single-Sport Specialization in Professional Baseball Players.

Background: An increasing number of youth baseball athletes are specializing in playing baseball at younger ages. Purpose: The purpose of our study was to describe the age and prevalence of single-sport specialization in a cohort of current professional baseball athletes. In addition, we sought to understand the trends surrounding single-sport specialization in professional baseball players raised within and outside the United States (US). Study Design: Cross-sectional study; Level of evidence, 3. Methods: A survey was distributed to male professional baseball athletes via individual team athletic trainers. Athletes were asked if and at what age they had chosen to specialize in playing baseball at the exclusion of other sports, and data were then collected pertaining to this decision. We analyzed the rate and age of specialization, the reasons for specialization, and the athlete\u27s perception of injuries related to specialization. Results: A total of 1673 professional baseball athletes completed the survey, representing 26 of the 30 Major League Baseball (MLB) organizations. Less than half (44.5%) of professional athletes specialized in playing a single sport during their childhood/adolescence. Those who reported specializing in their youth did so at a mean age of 14.09 ± 2.79 years. MLB players who grew up outside the US specialized at a significantly earlier age than MLB players native to the US (12.30 ± 3.07 vs 14.89 ± 2.24 years, respectively; Conclusion: This study challenges the current trends toward early youth sport specialization, finding that the majority of professional baseball athletes studied did not specialize as youth and that those who did specialize did so at a mean age of 14 years. With the potential cumulative effects of pitching and overhead throwing on an athlete\u27s arm, the trend identified in this study toward earlier specialization within baseball is concerning

Immunometabolism: Molecular mechanisms, diseases, and therapies 2018

Immunometabolism: Molecular mechanisms, diseases, and therapies 201

Pattern and Outcome of Chest Injuries at Bugando Medical Centre in Northwestern Tanzania.

Chest injuries constitute a continuing challenge to the trauma or general surgeon practicing in developing countries. This study was conducted to outline the etiological spectrum, injury patterns and short term outcome of these injuries in our setting. This was a prospective study involving chest injury patients admitted to Bugando Medical Centre over a six-month period from November 2009 to April 2010 inclusive. A total of 150 chest injury patients were studied. Males outnumbered females by a ratio of 3.8:1. Their ages ranged from 1 to 80 years (mean = 32.17 years). The majority of patients (72.7%) sustained blunt injuries. Road traffic crush was the most common cause of injuries affecting 50.7% of patients. Chest wall wounds, hemothorax and rib fractures were the most common type of injuries accounting for 30.0%, 21.3% and 20.7% respectively. Associated injuries were noted in 56.0% of patients and head/neck (33.3%) and musculoskeletal regions (26.7%) were commonly affected. The majority of patients (55.3%) were treated successfully with non-operative approach. Underwater seal drainage was performed in 39 patients (19.3%). One patient (0.7%) underwent thoracotomy due to hemopericardium. Thirty nine patients (26.0%) had complications of which wound sepsis (14.7%) and complications of long bone fractures (12.0%) were the most common complications. The mean LOS was 13.17 days and mortality rate was 3.3%. Using multivariate logistic regression analysis, associated injuries, the type of injury, trauma scores (ISS, RTS and PTS) were found to be significant predictors of the LOS (P < 0.001), whereas mortality was significantly associated with pre-morbid illness, associated injuries, trauma scores (ISS, RTS and PTS), the need for ICU admission and the presence of complications (P < 0.001). Chest injuries resulting from RTCs remain a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of RTCs is necessary to reduce the incidence of chest injuries in this region

The imposition of Cauchy data to the Teukolsky equation II: Numerical comparison with the Zerilli-Moncrief approach to black hole perturbations

We revisit the question of the imposition of initial data representing astrophysical gravitational perturbations of black holes. We study their dynamics for the case of nonrotating black holes by numerically evolving the Teukolsky equation in the time domain. In order to express the Teukolsky function Psi explicitly in terms of hypersurface quantities, we relate it to the Moncrief waveform phi_M through a Chandrasekhar transformation in the case of a nonrotating black hole. This relation between Psi and phi_M holds for any constant time hypersurface and allows us to compare the computation of the evolution of Schwarzschild perturbations by the Teukolsky and by the Zerilli and Regge-Wheeler equations. We explicitly perform this comparison for the Misner initial data in the close limit approach. We evolve numerically both, the Teukolsky (with the recent code of Ref. [1]) and the Zerilli equations, finding complete agreement in resulting waveforms within numerical error. The consistency of these results further supports the correctness of the numerical code for evolving the Teukolsky equation as well as the analytic expressions for Psi in terms only of the three-metric and the extrinsic curvature.Comment: 14 pages, 7 Postscript figures, to appear in Phys. Rev.

Copper and nanostructured anatase rutile and carbon coatings induce adaptive antibiotic resistance

Contaminated surfaces are vehicles for the spread of infectious disease-causing microorganisms. A strategy to prevent their spread is applying antimicrobial coatings to surfaces. Both nanostructured anatase rutile and carbon (NsARC), a TiO₂ formulation, and copper are examples of antimicrobial agents that are used in making or coating door handles and similar surfaces, to reduce microbial loads. Antimicrobial surfaces have been extensively tested for antimicrobial activity but not sublethal effects, such as exposure-associated multiple antibiotic resistance phenotypes usually caused by induction of efflux pump genes. The possibility of NsARC and copper inducing indicative efflux pump pathways was investigated by monitoring the expression of mScarlet fluorescent protein (FP) in two reporter strains of Escherichia coli. There was an increase in the expression of FP in the reporter strains exposed to NsARC and copper relative to the inert control composed of stainless steel. Furthermore we tested E. coli and Staphylococcus aureus following 8 h of exposure to NsARC for changes in resistance to selected antibiotics. E. coli that were exposed to NsARC became more susceptible to kanamycin but there was no significant change in susceptibility of S. aureus to any tested antibiotics. These findings suggests that even though NsARC and copper are antimicrobial, they also have some potential to cause unintended phenotypes

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

The close limit from a null point of view: the advanced solution

We present a characteristic algorithm for computing the perturbation of a Schwarzschild spacetime by means of solving the Teukolsky equation. We implement the algorithm as a characteristic evolution code and apply it to compute the advanced solution to a black hole collision in the close approximation. The code successfully tracks the initial burst and quasinormal decay of a black hole perturbation through 10 orders of magnitude and tracks the final power law decay through an additional 6 orders of magnitude. Determination of the advanced solution, in which ingoing radiation is absorbed by the black hole but no outgoing radiation is emitted, is the first stage of a two stage approach to determining the retarded solution, which provides the close approximation waveform with the physically appropriate boundary condition of no ingoing radiation.Comment: Revised version, published in Phys. Rev. D, 34 pages, 13 figures, RevTe

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

PurposeWe compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity.Methods and MaterialsWe reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity.ResultsAt 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742; nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction.ConclusionsSurvival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function