884 research outputs found
Unwrapping of DNA-protein complexes under external stretching
A DNA-protein complex modelled by a semiflexible chain and an attractive
spherical core is studied in the situation when an external stretching force is
acting on one end monomer of the chain while the other end monomer is kept
fixed in space. Without stretching force, the chain is wrapped around the core.
By applying an external stretching force, unwrapping of the complex is induced.
We study the statics and the dynamics of the unwrapping process by computer
simulation and simple phenomenological theory. We find two different scenarios
depending on the chain stiffness: For a flexible chain, the extension of the
complex scales linearly with the external force applied. The sphere-chain
complex is disordered, i.e. there is no clear winding of the chain around the
sphere. For a stiff chain, on the other hand, the complex structure is ordered,
which is reminiscent to nucleosome. There is a clear winding number and the
unwrapping process under external stretching is discontinuous with jumps of the
distance-force curve. This is associated to discrete unwinding processes of the
complex. Our predictions are of relevance for experiments, which measure
force-extension curves of DNA-protein complexes, such as nucleosome, using
optical tweezers.Comment: 8 pages, 7 figure
Axial turbulent flow in a circular pipe containing a fixed eccentric core
The turbulent flow of air through a circular pipe containing a fixed eccentric core was investigated at one air flow and one fixed eccentricity
How does torsional rigidity affect the wrapping transition of a semiflexible chain around a spherical core?
We investigated the effect of torsional rigidity of a semiflexible chain on
the wrapping transition around a spherical core, as a model of nucleosome, the
fundamental unit of chromatin. Through molecular dynamics simulation, we show
that the torsional effect has a crucial effect on the chain wrapping around the
core under the topological constraints. In particular, the torsional stress (i)
induces the wrapping/unwrapping transition, and (ii) leads to a unique complex
structure with an antagonistic wrapping direction which never appears without
the topological constraints. We further examine the effect of the stretching
stress for the nucleosome model, in relation to the unique characteristic
effect of the torsional stress on the manner of wrapping
All-or-none switching of transcriptional activity on single DNA molecules caused by a discrete conformational transition
Recently, it has been confirmed that long duplex DNA molecules with sizes
larger than several tens of kilo-base pairs (kbp), exhibit a discrete
conformational transition from an elongated coil state to a compact globule
state upon the addition of various kinds of chemical species that usually
induce DNA condensation. In this study, we performed a single-molecule
observation on a large DNA, Lambda ZAP II DNA (ca. 41 kbp), in a solution
containing RNA polymerase and substrates along with spermine, a tetravalent
cation, at different concentrations, by use of fluorescence staining of both
DNA and RNA. We found that transcription, or RNA production, is completely
inhibited in the compact state, but is actively performed in the unfolded coil
state. Such an all-or-none effect on transcriptional activity induced by the
discrete conformational transition of single DNA molecules is discussed in
relation to the mechanism of the regulation of large-scale genetic activity.Comment: 14 pages, 2 figure
Orientational correlations in confined DNA
We study how the orientational correlations of DNA confined to nanochannels
depend on the channel diameter D by means of Monte Carlo simulations and a
mean-field theory. This theory describes DNA conformations in the
experimentally relevant regime where the Flory-de Gennes theory does not apply.
We show how local correlations determine the dependence of the end-to-end
distance of the DNA molecule upon D. Tapered nanochannels provide the necessary
resolution in D to study experimentally how the extension of confined DNA
molecules depends upon D. Our experimental and theoretical results are in
qualitative agreement.Comment: Revised version including supplemental material, 7 pages, 8 figure
The BRG1 transcriptional coregulator
The packaging of genomic DNA into chromatin, often viewed as an impediment to the transcription process, plays a fundamental role in the regulation of gene expression. Chromatin remodeling proteins have been shown to alter local chromatin structure and facilitate recruitment of essential factors required for transcription. Brahma-related gene-1 (BRG1), the central catalytic subunit of numerous chromatin-modifying enzymatic complexes, uses the energy derived from ATP-hydrolysis to disrupt the chromatin architecture of target promoters. In this review, we examine BRG1 as a major coregulator of transcription. BRG1 has been implicated in the activation and repression of gene expression through the modulation of chromatin in various tissues and physiological conditions. Outstanding examples are studies demonstrating that BRG1 is a necessary component for nuclear receptor-mediated transcriptional activation. The remodeling protein is also associated with transcriptional corepressor complexes which recruit remodeling activity to target promoters for gene silencing. Taken together, BRG1 appears to be a critical modulator of transcriptional regulation in cellular processes including transcriptional regulation, replication, DNA repair and recombination
Scottish Firefighters Occupational Cancer and Disease Mortality Rates: 2000-2020
Background
Increased mortality from cancers and other diseases has been reported in USA, Canadian, and Nordic firefighters. However, UK firefighters are understudied.
Aims
To determine whether UK firefighters suffer increased mortality from cancers and other diseases when compared with the general population.
Methods
Mortality from cancer and other diseases in Scottish male firefighters between 2000 and 2020 was compared with the general Scottish male population and expressed as standardized mortality ratios (SMRs) (with 95% confidence intervals, CI).
Results
Significant overall excess cancer mortality was found for Scottish firefighters compared with the general population (SMR 1.61, CI 1.42-1.81). Scottish firefighters were nearly three times more likely to die of malignant neoplasms (unspecified sites) (SMR 2.71, CI 1.71-4.00). Excess cancer mortality was also found for several site-specific cancers, including prostate (SMR 3.80, CI 2.56-5.29), myeloid leukaemia (SMR 3.17, CI 1.44-5.58), oesophagus (SMR 2.42, CI 1.69-3.29) and urinary system (kidney and bladder) (SMR 1.94, CI 1.16-2.91). Mortality from neoplasms of unknown behaviour was over six times greater in Scottish firefighters (SMR 6.37, CI 2.29-12.49). Additionally, significantly higher mortality was found for: acute ischaemic heart diseases (SMR 5.27, CI 1.90-10.33), stroke (SMR 2.69, CI 1.46-4.28), interstitial pulmonary diseases (SMR 3.04, CI 1.45-5.22), renal failure (SMR 3.28, CI 1.18-6.44) and musculoskeletal system diseases (SMR 5.64, CI 1.06-13.83).
Conclusions
UK firefighters suffer significant excess mortality from cancer and other diseases when compared with the general population. Preventative health monitoring and presumptive legislation are urgently required to protect UK firefighters’ health
Mental health of UK firefighters
Exposure to trauma, high-stress situations, and disrupted sleep are well known risk factors affecting firefighters’ mental health. Little is known about the association between firefighters’ exposure to fire contaminants and mental health disorders. The UK Firefighter Contamination Survey assessed firefighters’ health and capacity for occupational exposure to contaminants. Participants were invited to anonymously complete its 64 questions online. Logistic regression analyses assessed the associations between self-reported mental health disorders and proxies of contaminant exposure. Results found that firefighters who notice soot in their nose/throat for more than a day after attending fires (Odds Ratio (OR) = 1.8, 1.4–2.4), and those who remain in their personal protective equipment (PPE) for over 4 h after fires (OR = 1.9, 1.2–3.1), were nearly twice as likely to report mental health disorders. Significantly increased odds ratios for all three outcomes of interest (anxiety, depression and/or any mental health disorders) were also found among firefighters who take PPE home to clean. Sleeping problems were reported by 61% of firefighters. These firefighters were 4.2 times more likely to report any mental health disorder (OR = 4.2, 3.7–4.9), 2.9 times more likely to report anxiety (OR = 2.9, 2.4–3.5) and 2.3 times more likely to report depression (OR = 2.3, 1.9–2.8) when compared to firefighters who did not report sleep issues. Effective decontamination measures within UK Fire and Rescue Services, together with firefighters’ wellness, may play a crucial role in protecting firefighters’ mental health
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