831 research outputs found
Motif-guided sparse decomposition of gene expression data for regulatory module identification
<p>Abstract</p> <p>Background</p> <p>Genes work coordinately as gene modules or gene networks. Various computational approaches have been proposed to find gene modules based on gene expression data; for example, gene clustering is a popular method for grouping genes with similar gene expression patterns. However, traditional gene clustering often yields unsatisfactory results for regulatory module identification because the resulting gene clusters are co-expressed but not necessarily co-regulated.</p> <p>Results</p> <p>We propose a novel approach, motif-guided sparse decomposition (mSD), to identify gene regulatory modules by integrating gene expression data and DNA sequence motif information. The mSD approach is implemented as a two-step algorithm comprising estimates of (1) transcription factor activity and (2) the strength of the predicted gene regulation event(s). Specifically, a motif-guided clustering method is first developed to estimate the transcription factor activity of a gene module; sparse component analysis is then applied to estimate the regulation strength, and so predict the target genes of the transcription factors. The mSD approach was first tested for its improved performance in finding regulatory modules using simulated and real yeast data, revealing functionally distinct gene modules enriched with biologically validated transcription factors. We then demonstrated the efficacy of the mSD approach on breast cancer cell line data and uncovered several important gene regulatory modules related to endocrine therapy of breast cancer.</p> <p>Conclusion</p> <p>We have developed a new integrated strategy, namely motif-guided sparse decomposition (mSD) of gene expression data, for regulatory module identification. The mSD method features a novel motif-guided clustering method for transcription factor activity estimation by finding a balance between co-regulation and co-expression. The mSD method further utilizes a sparse decomposition method for regulation strength estimation. The experimental results show that such a motif-guided strategy can provide context-specific regulatory modules in both yeast and breast cancer studies.</p
Fabrication of ciprofloxacin loaded alginate/cockle shell powder nanobiocomposite bone scaffold
Orthopedic implant infection is one of the most challenging issues in bone tissue engineering industry. Hence, local delivery of antibiotics incorporated into a fabricated bone scaffold possibly provides a more rapid bacteria inhibitory effect. In this study, pure ciprofloxacin loaded alginate/cockle shell powder nanobiocomposite bone scaffolds are fabricated with 5 wt% and 10 wt% ciprofloxacin respectively and tested for drug encapsulation, drug release and antibacterial properties towards common implant infecting bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa). Results from the studies showed a low drug encapsulation and drug release regardless of the concentration of drugs loaded with no significant differences noted (p<0.05). However, bacterial inhibition studies through direct contact and using eluted samples from drug release studies showed some inhibitory effects towards the growth of both bacterial strains tested. These findings were further justified with microscopy observations on biofilm and bacterial colony formation. Mineralization studies conducted additionally indicated that the scaffolds characteristics was not compromised due to drug loading. Although pure ciprofloxacin may not be the most suitable antibiotic to be incorporated into the nanobiocomposite bone scaffold, the study did provide some insight to the possible use of the scaffold for future drug delivery applications
Phase Transition in a One-Dimensional Extended Peierls-Hubbard Model with a Pulse of Oscillating Electric Field: I. Threshold Behavior in Ionic-to-Neutral Transition
Photoinduced dynamics of charge density and lattice displacements is
calculated by solving the time-dependent Schr\"odinger equation for a
one-dimensional extended Peierls-Hubbard model with alternating potentials for
the mixed-stack organic charge-transfer complex, TTF-CA. A pulse of oscillating
electric field is incorporated into the Peierls phase of the transfer integral.
The frequency, the amplitude, and the duration of the pulse are varied to study
the nonlinear and cooperative character of the photoinduced transition. When
the dimerized ionic phase is photoexcited, the threshold behavior is clearly
observed by plotting the final ionicity as a function of the increment of the
total energy. Above the threshold photoexcitation, the electronic state reaches
the neutral one with equidistant molecules after the electric field is turned
off. The transition is initiated by nucleation of a metastable neutral domain,
for which an electric field with frequency below the linear absorption peak is
more effective than that at the peak. When the pulse is strong and short, the
charge transfer takes place on the same time scale with the disappearance of
dimerization. As the pulse becomes weak and long, the dimerization-induced
polarization is disordered to restore the inversion symmetry on average before
the charge transfer takes place to bring the system neutral. Thus, a
paraelectric ionic phase is transiently realized by a weak electric field. It
is shown that infrared light also induces the ionic-to-neutral transition,
which is characterized by the threshold behavior.Comment: 24 pages, 11 figure
Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function
Abuse of alcohol is a major clinical problem with far- reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol- related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast- induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet- induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol- related behavior in other species.Flies fed a high yeast diet consume more nutrients, have decreased levels of internal ethanol when exposed to ethanol vapor and require longer exposure to ethanol to become sedated (ie, increased ST50). Our studies implicate serotonergic neurons as key regulators of nutrient consumption and therefore, the effect of dietary yeast on ethanol sedation in flies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/1/adb12779.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/2/adb12779_am.pd
Arachis hypogaea gene expression atlas for fastigiata subspecies of cultivated groundnut to accelerate functional and translational genomics applications
Spatio-temporal and developmental stage-specific transcriptome analysis plays a crucial role in
systems biology-based improvement of any species. In this context, we report here the Arachis
hypogaea gene expression atlas (AhGEA) for the world’s widest cultivated subsp. fastigiata based
on RNA-seq data using 20 diverse tissues across five key developmental stages. Approximately
480 million paired-end filtered reads were generated followed by identification of 81 901
transcripts from an early-maturing, high-yielding, drought-tolerant groundnut variety, ICGV
91114. Further, 57 344 genome-wide transcripts were identified with ≥1 FPKM across different
tissues and stages. Our in-depth analysis of the global transcriptome sheds light into complex
regulatory networks namely gravitropism and photomorphogenesis, seed development, allergens
and oil biosynthesis in groundnut. Importantly, interesting insights into molecular basis of
seed development and nodulation have immense potential for translational genomics research.
We have also identified a set of stable expressing transcripts across the selected tissues, which
could be utilized as internal controls in groundnut functional genomics studies. The AhGEA
revealed potential transcripts associated with allergens, which upon appropriate validation could
be deployed in the coming years to develop consumer-friendly groundnut varieties. Taken
together, the AhGEA touches upon various important and key features of cultivated groundnut
and provides a reference for further functional, comparative and translational genomics research
for various economically important traits
Effects of Lattice and Molecular Phonons on Photoinduced Neutral-to-Ionic Transition Dynamics in Tetrathiafulvalene--Chloranil
For electronic states and photoinduced charge dynamics near the neutral-ionic
transition in the mixed-stack charge-transfer complex
tetrathiafulvalene--chloranil (TTF-CA), we review the effects of Peierls
coupling to lattice phonons modulating transfer integrals and Holstein
couplings to molecular vibrations modulating site energies. The former
stabilizes the ionic phase and reduces discontinuities in the phase transition,
while the latter stabilizes the neutral phase and enhances the discontinuities.
To reproduce the experimentally observed ionicity, optical conductivity and
photoinduced charge dynamics, both couplings are quantitatively important. In
particular, strong Holstein couplings to form the highly-stabilized neutral
phase are necessary for the ionic phase to be a Mott insulator with large
ionicity. A comparison with the observed photoinduced charge dynamics indicates
the presence of strings of lattice dimerization in the neutral phase above the
transition temperature.Comment: 9 pages, 7 figures, accepted for publication in J. Phys. Soc. Jp
The problem of a metal impurity in an oxide: ab-initio study of electronic and structural properties of Cd in Rutile TiO2
In this work we undertake the problem of a transition metal impurity in an
oxide. We present an ab-initio study of the relaxations introduced in TiO2 when
a Cd impurity replaces substitutionally a Ti atom. Using the Full-Potential
Linearized-Augmented-Plane-Wave method we obtain relaxed structures for
different charge states of the impurity and computed the electric-field
gradients (EFGs) at the Cd site. We find that EFGs, and also relaxations, are
dependent on the charge state of the impurity. This dependence is very
remarkable in the case of the EFG and is explained analyzing the electronic
structure of the studied system. We predict fairly anisotropic relaxations for
the nearest oxygen neighbors of the Cd impurity. The experimental confirmation
of this prediction and a brief report of these calculations have recently been
presented [P.R.L. 89, 55503 (2002)]. Our results for relaxations and EFGs are
in clear contradiction with previous studies of this system that assumed
isotropic relaxations and point out that no simple model is viable to describe
relaxations and the EFG at Cd in TiO2 even approximately.Comment: 11 pages, 8 figures, Revtex 4, published in Physical Review
Dissection of the genetic basis of oil content in Chinese peanut cultivars through association mapping
Background: Peanut is one of the primary sources for vegetable oil worldwide, and enhancing oil content is the
main objective in several peanut breeding programs of the world. Tightly linked markers are required for faster
development of high oil content peanut varieties through genomics-assisted breeding (GAB), and association
mapping is one of the promising approaches for discovery of such associated markers.
Results: An association mapping panel consisting of 292 peanut varieties extensively distributed in China was
phenotyped for oil content and genotyped with 583 polymorphic SSR markers. These markers amplified 3663 alleles
with an average of 6.28 alleles per locus. The structure, phylogenetic relationship, and principal component analysis
(PCA) indicated two subgroups majorly differentiating based on geographic regions. Genome-wide association analysis
identified 12 associated markers including one (AGGS1014_2) highly stable association controlling up to 9.94%
phenotypic variance explained (PVE) across multiple environments. Interestingly, the frequency of the favorable alleles
for 12 associated markers showed a geographic difference. Two associated markers (AGGS1014_2 and AHGS0798) with
6.90–9.94% PVE were verified to enhance oil content in an independent RIL population and also indicated selection
during the breeding program.
Conclusion: This study provided insights into the genetic basis of oil content in peanut and verified highly associated
two SSR markers to facilitate marker-assisted selection for developing high-oil content breeding peanut varieties
A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting
BACKGROUND: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance. METHODS: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping. RESULTS: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96. CONCLUSIONS: A simple decision rule based on data readily obtainable in the setting of patients' first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement.published_or_final_versio
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