689 research outputs found
Fine-scale time-lapse analysis of the biphasic, dynamic behaviour of the two Vibrio cholerae chromosomes
Using fluorescent repressor-operator systems in live cells, we investigated the dynamic behaviour of chromosomal origins in Vibrio cholerae, whose genome is divided between two chromosomes. We have developed a method of analysing fine-scale motion in the curved co-ordinate system of vibrioid bacteria. Using this method, we characterized two different modes of chromosome behaviour corresponding to periods between segregation events and periods of segregation. Between segregation events, the origin positions are not fixed but rather maintained within ellipsoidal caged domains, similar to eukaryotic interphase chromosome territories. These domains are approximately 0.4 ”m wide and 0.6 ”m long, reflecting greater restriction in the short axis of the cell. During segregation, movement is directionally biased, speed is comparable between origins, and cell growth can account for nearly 20% of the motion observed. Furthermore, the home domain of each origin is positioned by a different mechanism. Specifically, the oriCI domain is maintained at a constant actual distance from the pole regardless of cell length, while the oriCII domain is maintained at a constant relative position. Thus the actual position of oriCII varies with cell length. While the gross behaviours of the two origins are distinct, their fine-scale dynamics are remarkably similar, indicating that both experience similar microenvironments
Mapping of interaction sites of the Schizosaccharomyces pombe protein Translin with nucleic acids and proteins: a combined molecular genetics and bioinformatics study
Translin is a single-stranded RNA- and DNA-binding protein, which has been highly conserved in eukaryotes, from man to Schizosaccharomyces pombe. TRAX is a Translin paralog associated with Translin, which has coevolved with it. We generated structural models of the S. pombe Translin (spTranslin), based on the solved 3D structure of the human ortholog. Using several bioinformatics computation tools, we identified in the equatorial part of the protein a putative nucleic acids interaction surface, which includes many polar and positively charged residues, mostly arginines, surrounding a shallow cavity. Experimental verification of the bioinformatics predictions was obtained by assays of nucleic acids binding to amino acid substitution variants made in this region. Bioinformatics combined with yeast two-hybrid assays and proteomic analyses of deletion variants, also identified at the top of the spTranslin structure a region required for interaction with spTRAX, and for spTranslin dimerization. In addition, bioinformatics predicted the presence of a second protein-protein interaction site at the bottom of the spTranslin structure. Similar nucleic acid and protein interaction sites were also predicted for the human Translin. Thus, our results appear to generally apply to the Translin family of proteins, and are expected to contribute to a further elucidation of their functions
Pre-trauma verbal ability at five years of age and the risk of post-traumatic stress disorder in adult males and females
Previous studies have shown that high cognitive ability, measured in childhood and prior to the experience of traumatic events, is protective of PTSD development. Our aim was to test if the association between pre-trauma verbal ability ascertained at 5 years with DSM-IV lifetime post-traumatic stress disorder (PTSD) at 21 years was subject to effect modification by gender, trauma type or prior behaviour problems. Using a prospective birth cohort of young Australians, we found that both trauma type and behaviour problems did not change the association between cognitive ability and PTSD. During multivariate analysis, testing for the interactive effect of gender revealed that verbal ability was linearly and inversely associated with PTSD in females only, with those in the lowest verbal ability quintile having strongly increased odds of PTSD (OR = 3.89: 95% Cl; 1.50, 10.10) compared with those in the highest quintile. A graph of the interaction revealed lower verbal ability placed females, but not males, at an increased risk of PTSD. Our results indicate that lower verbal ability in early childhood is a vulnerability factor for PTSD in females but not in males, and may constitute a gender-specific risk factor responsible for part of the increased risk of PTSD found in females compared with males. (C) 2012 Elsevier Ltd. All rights reserved
Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine
Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base
Six weeks of home enteral nutrition versus standard care after esophagectomy or total gastrectomy for cancer: study protocol for a randomized controlled trial
Background: Each year approximately 3000 patients in the United Kingdom undergo surgery for esophagogastric
cancer. Jejunostomy feeding tubes, placed at the time of surgery for early postoperative nutrition, have been
shown to have a positive impact on clinical outcomes in the short term. Whether feeding out of hospital is of
benefit is unknown. Local experience has identified that between 15 and 20% of patients required ârescueâ
jejunostomy feeding for nutritional problems and weight loss while at home. This weight loss and poor nutrition
may contribute to the detrimental effect on the overall quality of life (QoL) reported in these patients.
Methods/Design: This randomized pilot and feasibility study will provide preliminary information on the routine
use of jejunostomy feeding after hospital discharge in terms of clinical benefits and QoL. Sixty participants
undergoing esophagectomy or total gastrectomy will be randomized to receive either a planned program of six
weeks of home jejunostomy feeding after discharge from hospital (intervention) or treatment-as-usual (control). The
intention of this study is to inform a multi-centre randomized controlled trial. The primary outcome measures will
be recruitment and retention rates at six weeks and six months. Secondary outcome measures will include disease
specific and general QoL measures, nutritional parameters, total and oral nutritional intake, hospital readmission
rates, and estimates of healthcare costs. Up to 20 participants will also be enrolled in a qualitative sub-study that will
explore participantsâ and carersâ experiences of home tube feeding.
The results will be disseminated by presentation at surgical, gastroenterological and dietetic meetings and
publication in appropriate peer review journals. A patient-friendly lay summary will be made available on the
University of Leicester and the University Hospitals of Leicester NHS Trust websites. The study has full ethical and
institutional approval and started recruitment in July 2012.
Trial registration: UKClinical Research Network ID #12447 (Main study); UKCRN ID#13361 (Qualitative sub study);
ClinicalTrials.gov #NCT01870817 (First registered 28 May 2013
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy
We measure the energy emitted by extensive air showers in the form of radio
emission in the frequency range from 30 to 80 MHz. Exploiting the accurate
energy scale of the Pierre Auger Observatory, we obtain a radiation energy of
15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV
arriving perpendicularly to a geomagnetic field of 0.24 G, scaling
quadratically with the cosmic-ray energy. A comparison with predictions from
state-of-the-art first-principle calculations shows agreement with our
measurement. The radiation energy provides direct access to the calorimetric
energy in the electromagnetic cascade of extensive air showers. Comparison with
our result thus allows the direct calibration of any cosmic-ray radio detector
against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI.
Supplemental material in the ancillary file
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