851 research outputs found
PRECIS: Protein reports engineered from concise information in SWISS-PROT
Motivation: There have been several endeavours to address the problem of annotating sequence data computationally, but the task is non-trivial and few tools have emerged that gather useful information on a given sequence, or set of sequences, in a simple and convenient manner. As more genome projects bear fruit, the mass of uncharacterized sequence data accumulating in public repositories grows ever larger. There is thus a pressing need for tools to support the process of automatic analysis and annotation of newly determined sequences. With this in mind, we have developed PRECIS, which automatically creates protein reports from sets of SWISS-PROT entries, collating results into structured reports, detailing known biological and medical information, literature and database cross-references, and relevant keywords. Availability: The software is accessible online at: http://www.bioinf.man.ac.uk/cgi-bin/dbbrowser/precis/blast_precis.cg
Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity
Background
Salivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number variation (CNV) at AMY1 on salivary amylase protein production are less well understood. The amylase gene cluster is highly structured with a fundamental difference between odd and even AMY1 copy number haplotypes. In this study, we aimed to explore, in samples from 119 unrelated individuals, not only the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity but also whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes.
Results
AMY1 copy number was significantly correlated with the variation observed in salivary amylase production (11.7% of variance, P < 0.0005) and enzyme activity (13.6% of variance, P < 0.0005) but did not explain the majority of observed variation between individuals. AMY1-odd and AMY1-even haplotypes showed a different relationship between copy number and expression levels, but the difference was not statistically significant (P = 0.052).
Conclusions
Production of salivary amylase is correlated with AMY1 CNV, but the majority of interindividual variation comes from other sources. Long-range haplotype structure may affect expression, but this was not significant in our data
Surface Scaling Analysis of a Frustrated Spring-network Model for Surfactant-templated Hydrogels
We propose and study a simplified model for the surface and bulk structures
of crosslinked polymer gels, into which voids are introduced through templating
by surfactant micelles. Such systems were recently studied by Atomic Force
Microscopy [M. Chakrapani et al., e-print cond-mat/0112255]. The gel is
represented by a frustrated, triangular network of nodes connected by springs
of random equilibrium lengths. The nodes represent crosslinkers, and the
springs correspond to polymer chains. The boundaries are fixed at the bottom,
free at the top, and periodic in the lateral direction. Voids are introduced by
deleting a proportion of the nodes and their associated springs. The model is
numerically relaxed to a representative local energy minimum, resulting in an
inhomogeneous, ``clumpy'' bulk structure. The free top surface is defined at
evenly spaced points in the lateral (x) direction by the height of the topmost
spring, measured from the bottom layer, h(x). Its scaling properties are
studied by calculating the root-mean-square surface width and the generalized
increment correlation functions C_q(x)= . The surface is
found to have a nontrivial scaling behavior on small length scales, with a
crossover to scale-independent behavior on large scales. As the vacancy
concentration approaches the site-percolation limit, both the crossover length
and the saturation value of the surface width diverge in a manner that appears
to be proportional to the bulk connectivity length. This suggests that a
percolation transition in the bulk also drives a similar divergence observed in
surfactant templated polyacrylamide gels at high surfactant concentrations.Comment: 17 pages RevTex4, 10 imbedded eps figures. Expanded discussion of
multi-affinit
Accurate measurement of gene copy number for human alpha-defensin DEFA1A3
Background:
Multi-allelic copy number variants include examples of extensive variation between individuals in the copy number of important genes, most notably genes involved in immune function. The definition of this variation, and analysis of its impact on function, has been hampered by the technical difficulty of large-scale but accurate typing of genomic copy number. The copy-variable alpha-defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10 copies per diploid genome, and presents considerable challenges for accurate high-throughput typing.
Results:
In this study, we developed two paralogue ratio tests and three allelic ratio measurements that, in combination, provide an accurate and scalable method for measurement of DEFA1A3 gene number. We combined information from different measurements in a maximum-likelihood framework which suggests that most samples can be assigned to an integer copy number with high confidence, and applied it to typing 589 unrelated European DNA samples. Typing the members of three-generation pedigrees provided further reassurance that correct integer copy numbers had been assigned. Our results have allowed us to discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy number in European samples.
Conclusions:
We have developed an accurate and robust method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and associated SNPs in Genome-Wide Association Study SNP data provides no evidence that alpha-defensin copy number is a strong risk factor for phenotypes such as Crohn’s disease, type I diabetes, HIV progression and multiple sclerosis
Folate/homocysteine phenotypes and MTHFR 677C>T genotypes are associated with serum levels of monocyte chemoattractant protein- 1
Cystic Fibrosis Foundation and European Cystic Fibrosis Society Survey of cystic fibrosis mental health care delivery
Background: Psychological morbidity in individuals with cystic fibrosis (CF) and their caregivers is common. The Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) Guidelines Committee on Mental Health sought the views of CF health care professionals concerning mental health care delivery.
Methods: An online survey which focused on the current provision and barriers to mental health care was distributed to CF health care professionals.
Results: Of the 1454 respondents, many did not have a colleague trained in mental health issues and 20% had no one on their team whose primary role was focused on assessing or treating these issues. Insufficient resources and a lack of competency were reported in relation to mental health referrals. Seventy-three percent of respondents had no experience with mental health screening. Of those who did, they utilized 48 different, validated scales.
Conclusions: These data have informed the decision-making, dissemination and implementation strategies of the Mental Health Guidelines Committee sponsored by the CFF and ECFS
A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA
AbstractThe neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of fatal recessively inherited neurodegenerative diseases of humans and animals characterised by common clinical signs and pathology. These include blindness, ataxia, dementia, behavioural changes, seizures, brain and retinal atrophy and accumulation of fluorescent lysosome derived organelles in most cells. A number of different variants have been suggested and seven different causative genes identified in humans (CLN1, CLN2, CLN3, CLN5, CLN6, CLN8 and CTSD). Animal models have played a central role in the investigation of this group of diseases and are extremely valuable for developing a better understanding of the disease mechanisms and possible therapeutic approaches. Ovine models include flocks of affected New Zealand South Hampshires and Borderdales and Australian Merinos. The ovine CLN6 gene has been sequenced in a representative selection of these sheep. These investigations unveiled the mutation responsible for the disease in Merino sheep (c.184C>T; p.Arg62Cys) and three common ovine allelic variants (c.56A>G, c.822G>A and c.933_934insCT). Linkage analysis established that CLN6 is the gene most likely to cause NCL in affected South Hampshire sheep, which do not have the c.184C>T mutation but show reduced expression of CLN6 mRNA in a range of tissues as determined by real-time PCR. Lack of linkage precludes CLN6 as a candidate for NCL in Borderdale sheep
Small Corrections to the Tunneling Phase Time Formulation
After reexamining the above barrier diffusion problem where we notice that
the wave packet collision implies the existence of {\em multiple} reflected and
transmitted wave packets, we analyze the way of obtaining phase times for
tunneling/reflecting particles in a particular colliding configuration where
the idea of multiple peak decomposition is recovered. To partially overcome the
analytical incongruities which frequently rise up when the stationary phase
method is adopted for computing the (tunneling) phase time expressions, we
present a theoretical exercise involving a symmetrical collision between two
identical wave packets and a unidimensional squared potential barrier where the
scattered wave packets can be recomposed by summing the amplitudes of
simultaneously reflected and transmitted wave components so that the conditions
for applying the stationary phase principle are totally recovered. Lessons
concerning the use of the stationary phase method are drawn.Comment: 14 pages, 3 figure
The Exact Correspondence between Phase Times and Dwell Times in a Symmetrical Quantum Tunneling Configuration
The general and explicit relation between the phase time and the dwell time
for quantum tunneling or scattering is investigated. Considering a symmetrical
collision of two identical wave packets with an one-dimensional barrier, here
we demonstrate that these two distinct transit time definitions give connected
results where, however, the phase time (group delay) accurately describes the
exact position of the scattered particles. The analytical difficulties that
arise when the stationary phase method is employed for obtaining phase
(traversal) times are all overcome. Multiple wave packet decomposition allows
us to recover the exact position of the reflected and transmitted waves in
terms of the phase time, which, in addition to the exact relation between the
phase time and the dwell time, leads to right interpretation for both of them.Comment: 11 pages, 2 figure
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