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Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion
Transposon mutagenesis has been applied to a hyper-invasive clinical isolate of Campylobacter jejuni, 01/51. A random transposon mutant library was screened in an in vitro assay of invasion and 26 mutants with a significant reduction in invasion were identified. Given that the invasion potential of C. jejuni is relatively poor compared to other enteric pathogens, the use of a hyper-invasive strain was advantageous as it greatly facilitated the identification of mutants with reduced invasion. The location of the transposon insertion in 23 of these mutants has been determined; all but three of the insertions are in genes also present in the genome-sequenced strain NCTC 11168. Eight of the mutants contain transposon insertions in one region of the genome (âź14 kb), which when compared with the genome of NCTC 11168 overlaps with one of the previously reported plasticity regions and is likely to be involved in genomic variation between strains. Further characterization of one of the mutants within this region has identified a gene that might be involved in adhesion to host cells
Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells.
SummaryIncreasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of âdisallowedâ genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans
Building Research Supervision and Training across Australian Universities
`Building Research Supervision and Training in Australian Universities was undertaken with the aims of identifying existing higher degree research supervisor training provisions; identifying current and future needs of supervisors and making recommendations that assist universities in their ongoing development of effective higher degree research supervisor training
Effects of Epistasis and Pleiotropy on Fitness Landscapes
The factors that influence genetic architecture shape the structure of the
fitness landscape, and therefore play a large role in the evolutionary
dynamics. Here the NK model is used to investigate how epistasis and pleiotropy
-- key components of genetic architecture -- affect the structure of the
fitness landscape, and how they affect the ability of evolving populations to
adapt despite the difficulty of crossing valleys present in rugged landscapes.
Populations are seen to make use of epistatic interactions and pleiotropy to
attain higher fitness, and are not inhibited by the fact that valleys have to
be crossed to reach peaks of higher fitness.Comment: 10 pages, 6 figures. To appear in "Origin of Life and Evolutionary
Mechanisms" (P. Pontarotti, ed.). Evolutionary Biology: 16th Meeting 2012,
Springer-Verla
Using false discovery rates to benchmark SNP-callers in next-generation sequencing projects
This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Sequence alignments form the basis for many comparative and population genomic studies. Alignment tools provide a range of accuracies dependent on the divergence between the sequences and the alignment methods. Despite widespread use, there is no standard method for assessing the accuracy of a dataset and alignment strategy after resequencing. We present a framework and tool for determining the overall accuracies of an input read dataset, alignment and SNP-calling method providing an isolate in that dataset has a corresponding, or closely related reference sequence available. In addition to this tool for comparing False Discovery Rates (FDR), we include a method for determining homozygous and heterozygous positions from an alignment using binomial probabilities for an expected error rate. We benchmark this method against other SNP callers using our FDR method with three fungal genomes, finding that it was able achieve a high level of accuracy. These tools are available at http://cfdr.sourceforge.net/.R.A.F. was funded by the Natural Environment Research Council (NERC). D.A.H. and M.C.F. were supported by the Wellcome Trust. No additional external funding received for this study
Intoxication, criminal offences and suicide attempts in a group of South African problem drinkers
Background. Incidence rates of crime and alcohol abuse in South Africa are unacceptably high. Research suggests a relationship between alcohol and both crime and suicide. This study aims to add to the information base on this topic in South Africa.Methods. This is a cross-sectional record study of criminal offences and suicide attempts in 269 admissions to an alcohol rehabilitation unit in the Western Cape. Types of criminal offences and suicide attempts are described. Relationships are sought between crime, violent crime and suicide attempts on the one hand, and demographic and alcohol-related variables on the other.Results. One hundred and four subjects (39%) had criminal convictions, the majority of which were committed while the subjects were intoxicated. The commonest alcoholrelated crimes were driving-related (17% of subjects) and crimes of violence (15%). Male gender, younger age at initiation of drinking, and earlier onset of problem drinking were significantly associated with criminal behaviour. Violent crime was associated with earlier onset of initial, regular and problem drinking, and maternal alcohol abuse. Suicide attempts (24% of subjects) were associated with female gender, white racial group, not being in a marital relationship, younger current age and early age of problem drinking.Conclusions. There was an association between intoxication and both violent crime and suicide attempts. The importance of population studies and the need for intervention programmes aimed at teenagers who are drinking, are emphasised
Chemical characteristics of Pacific tropospheric air in the region of the Intertropical Convergence Zone and South Pacific Convergence Zone
The Pacific Exploratory Mission (PEM)-Tropics provided extensive aircraft data to study the atmospheric chemistry of tropospheric air in Pacific Ocean regions, extending from Hawaii to New Zealand and from Fiji to east of Easter Island. This region, especially the tropics, includes some of the cleanest tropospheric air of the world and, as such, is important for studying atmospheric chemical budgets and cycles. The region also provides a sensitive indicator of the global-scale impact of human activity on the chemistry of the troposphere, and includes such important features as the Pacific "warm pool," the Intertropical Convergence Zone (ITCZ), the South Pacific Convergence Zone (SPCZ), and Walker Cell circulations. PEM-Tropics was conducted from August to October 1996. The ITCZ and SPCZ are major upwelling regions within the South Pacific and, as such, create boundaries to exchange of tropospheric air between regions to the north and south. Chemical data obtained in the near vicinity of the ITCZ and the SPCZ are examined. Data measured within the convergent zones themselves are not considered. The analyses show that air north and south of the convergent zones have different chemical signatures, and the signatures are reflective of the source regions and transport histories of the air. Air north of the ITCZ shows a modest urban/industrialized signature compared to air south of the ITCZ. The chemical signature of air south of the SPCZ is dominated by combustion emissions from biomass burning, while air north of the SPCZ is relatively clean and of similar composition to ITCZ south air. Chemical signature differences of air north and south of the zones are most pronounced at altitudes below 5 km, and, as such, show that the ITCZ and SPCZ are effective low-altitude barriers to the transport of tropospheric air. At altitudes of 8 to 10 km, chemical signatures are less dissimilar, and air backward trajectories (to 10 days) show cross-convergent-zone flow. At altitudes below about 5 km, little cross-zonal flow is observed. Chemical signatures presented include over 30 trace chemical species including ultrafine, fine, and heated-fine (250°C) aerosol. Copyright 1999 by the American Geophysical Union
Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients
Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes
An Empirical Planetesimal Belt Radius-Stellar Luminosity Relation
Resolved observations of millimetre-sized dust, tracing larger planetesimals,
have pinpointed the location of 26 Edgeworth-Kuiper belt analogs. We report
that a belt's distance to its host star correlates with the star's
luminosity , following with a low
intrinsic scatter of 17%. Remarkably, our Edgeworth-Kuiper belt in the
Solar System and the two CO snow lines imaged in protoplanetary disks lie close
to this - relation, suggestive of an intrinsic relationship
between protoplanetary disk structures and belt locations. To test the effect
of bias on the relation, we use a Monte Carlo approach and simulate
uncorrelated model populations of belts. We find that observational bias could
produce the slope and intercept of the - relation, but is unable
to reproduce its low scatter. We then repeat the simulation taking into account
the collisional evolution of belts, following the steady state model that fits
the belt population as observed through infrared excesses. This significantly
improves the fit by lowering the scatter of the simulated -
relation; however, this scatter remains only marginally consistent with the one
observed. The inability of observational bias and collisional evolution alone
to reproduce the tight relationship between belt radius and stellar luminosity
could indicate that planetesimal belts form at preferential locations within
protoplanetary disks. The similar trend for CO snow line locations would then
indicate that the formation of planetesimals and/or planets in the outer
regions of planetary systems is linked to the volatility of their building
blocks, as postulated by planet formation models
The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein
The folding pathway and rate coefficients of the folding of a knotted protein
are calculated for a potential energy function with minimal energetic
frustration. A kinetic transition network is constructed using the discrete
path sampling approach, and the resulting potential energy surface is
visualized by constructing disconnectivity graphs. Owing to topological
constraints, the low-lying portion of the landscape consists of three distinct
regions, corresponding to the native knotted state and to configurations where
either the N- or C-terminus is not yet folded into the knot. The fastest
folding pathways from denatured states exhibit early formation of the
N-terminus portion of the knot and a rate-determining step where the C-terminus
is incorporated. The low-lying minima with the N-terminus knotted and the
C-terminus free therefore constitute an off-pathway intermediate for this
model. The insertion of both the N- and C-termini into the knot occur late in
the folding process, creating large energy barriers that are the rate limiting
steps in the folding process. When compared to other protein folding proteins
of a similar length, this system folds over six orders of magnitude more
slowly.Comment: 19 page
- âŚ