753 research outputs found
Neutral forces acting on intragenomic variability shape the Escherichia coli regulatory network topology
Cis-regulatory networks (CRNs) play a central role in cellular decision
making. Like every other biological system, CRNs undergo evolution,
which shapes their properties by a combination of adaptive
and nonadaptive evolutionary forces. Teasing apart these forces is
an important step toward functional analyses of the different components
of CRNs, designing regulatory perturbation experiments,
and constructing synthetic networks. Although tests of neutrality
and selection based on molecular sequence data exist, no such tests
are currently available based on CRNs. In this work, we present
a unique genotype model of CRNs that is grounded in a genomic
context and demonstrate its use in identifying portions of the
CRN with properties explainable by neutral evolutionary forces
at the system, subsystem, and operon levels.We leverage our model
against experimentally derived data from Escherichia coli. The
results of this analysis show statistically significant and substantial
neutral trends in properties previously identified as adaptive
in originラdegree distribution, clustering coefficient, and motifsラ
within the E. coli CRN. Our model captures the tightly coupled genomeヨ
interactome of an organism and enables analyses of how
evolutionary events acting at the genome level, such as mutation,
and at the population level, such as genetic drift, give rise to neutral
patterns that we can quantify in CRNs
Perovskite-perovskite tandem photovoltaics with optimized bandgaps
We demonstrate four and two-terminal perovskite-perovskite tandem solar cells
with ideally matched bandgaps. We develop an infrared absorbing 1.2eV bandgap
perovskite, , that can deliver 14.8 %
efficiency. By combining this material with a wider bandgap
material, we reach monolithic two
terminal tandem efficiencies of 17.0 % with over 1.65 volts open-circuit
voltage. We also make mechanically stacked four terminal tandem cells and
obtain 20.3 % efficiency. Crucially, we find that our infrared absorbing
perovskite cells exhibit excellent thermal and atmospheric stability,
unprecedented for Sn based perovskites. This device architecture and materials
set will enable 'all perovskite' thin film solar cells to reach the highest
efficiencies in the long term at the lowest costs
Immersed boundary-finite element model of fluid-structure interaction in the aortic root
It has long been recognized that aortic root elasticity helps to ensure
efficient aortic valve closure, but our understanding of the functional
importance of the elasticity and geometry of the aortic root continues to
evolve as increasingly detailed in vivo imaging data become available. Herein,
we describe fluid-structure interaction models of the aortic root, including
the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the
sinotubular junction, that employ a version of Peskin's immersed boundary (IB)
method with a finite element (FE) description of the structural elasticity. We
develop both an idealized model of the root with three-fold symmetry of the
aortic sinuses and valve leaflets, and a more realistic model that accounts for
the differences in the sizes of the left, right, and noncoronary sinuses and
corresponding valve cusps. As in earlier work, we use fiber-based models of the
valve leaflets, but this study extends earlier IB models of the aortic root by
employing incompressible hyperelastic models of the mechanics of the sinuses
and ascending aorta using a constitutive law fit to experimental data from
human aortic root tissue. In vivo pressure loading is accounted for by a
backwards displacement method that determines the unloaded configurations of
the root models. Our models yield realistic cardiac output at physiological
pressures, with low transvalvular pressure differences during forward flow,
minimal regurgitation during valve closure, and realistic pressure loads when
the valve is closed during diastole. Further, results from high-resolution
computations demonstrate that IB models of the aortic valve are able to produce
essentially grid-converged dynamics at practical grid spacings for the
high-Reynolds number flows of the aortic root
Epigenetic DNA Methylation Mediating Octopus vulgaris Early Development: Effect of Essential Fatty Acids Enriched Diet
The common octopus, Octopus vulgaris, is a good candidate for aquaculture but a sustainable production is still unviable due to an almost total mortality during the paralarvae stage. DNA methylation regulates gene expression in the eukaryotic genome, and has been shown to exhibit plasticity throughout O. vulgaris life cycle, changing profiles from paralarvae to adult stages. This pattern of methylation could be sensitive to small alterations in nutritional and environmental conditions during the species early development, thus impacting on its health, growth and survival. In this sense, a full understanding of the epigenetic mechanisms operating during O. vulgaris development would contribute to optimizing the culture conditions for this species. Paralarvae of O. vulgaris were cultured over 28 days post-hatching (dph) using two different Artemia sp. based diets: control and a long chain polyunsaturated fatty acids (LC-PUFA) enriched diet. The effect of the diets on the paralarvae DNA global methylation was analyzed by Methyl-Sensitive Amplification Polymorphism (MSAP) and global 5-methylcytosine enzyme-linked immunosorbent assay (ELISA) approaches. The analysis of different methylation states over the time revealed a global demethylation phenomena occurring along O. vulgaris early development being directly driven by the age of the paralarvae. A gradual decline in methylated loci (hemimethylated, internal cytosine methylated, and hypermethylated) parallel to a progressive gain in non-methylated (NMT) loci toward the later sampling points was verified regardless of the diet provided and demonstrate a pre-established and well-defined demethylation program during its early development, involving a 20% of the MSAP loci. In addition, a differential behavior between diets was also observed at 20 dph, with a LC-PUFA supplementation effect over the methylation profiles. The present results show significant differences on the paralarvae methylation profiles during its development and a diet effect on these changes. It is characterized by a process of demethylation of the genome at the paralarvae stage and the influence of diet to favor this methylation loss.En prens
Imperfect distributed quantum phase estimation
In the near-term, the number of qubits in quantum computers will be limited to a few hundreds. Therefore, problems are often too large and complex to be run on quantum devices. By distributing quantum algorithms over different devices, larger problem instances can be run. This distributing however, often requires operations between two qubits of different devices. Using shared entangled states and classical communication, these operations between different devices can still be performed. In the ideal case of perfect fidelity, distributed quantum computing is a solution to achieving scalable quantum computers with a larger number of qubits. In this work we consider the effects on the output fidelity of a quantum algorithm when using noisy shared entangled states. We consider the quantum phase estimation algorithm and present two distribution schemes for the algorithm. We give the resource requirements for both and show that using less noisy shared entangled states results in a higher overall fidelity
Simultaneous determination of dopamine, uric acid and estriol in maternal urine samples based on the synergetic effect of reduced graphene oxide, silver nanowires and silver nanoparticles in their ternary 3D nanocomposite
A facile and efficient electrochemical biosensing platform based on screen printed carbon electrode (SPCE) modified with three-dimensional (3D) nanocomposite consists of reduced graphene oxide (RGO) with the insertion of silver nanowires (AgNWs) followed by the anchoring of silver nanoparticles (AgNPs) is constructed as RGO/AgNWs/AgNPs/SPCE for the simultaneous determination of dopamine (DA), uric acid (UA) and estriol (EST). The morphology characteristic and surface elemental composition of RGO/AgNWs/AgNPs nanocomposite are investigated by field-emission scanning electron microscope, transmission electron microscope and X-ray photoelectron spectroscope. Cyclic voltammetry, electrochemical impedance spectroscopy, linear sweep voltammetry and differential pulse voltammetry are utilized to explore the electrochemical performances of the constructed electrodes. Due to abundant active sites and excellent electrocatalytic activity of the nanocomposite, the RGO/AgNWs/AgNPs/SPCE sensor exhibits well-resolved oxidation peaks and enhanced oxidation peak currents in the ternary mixture of DA, UA and EST with respective linear response ranges of 0.6 to 50 μM, 1 to 100 μM and 1 to 90 μM and detection limits (S/N = 3) of 0.16 μM, 0.58 μM and 0.58 μM, respectively. Moreover, the constructed biosensor exhibits good selectivity, reproducibility and stability, and excellent performance in determining DA, UA and EST in synthetic urine samples with excellent recovery. The results reveal that the RGO/AgNWs/AgNPs nanocomposite is a promising candidate for advanced electrode material in electrochemical sensing field and possesses great application prospects in further sensing researches
Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice
<p>Abstract</p> <p>Background</p> <p>The mechanism by which HIV infection leads to a selective depletion of CD4 cells leading to immunodeficiency remains highly debated. Whether the loss of CD4 cells is a direct consequence of virus infection or bystander apoptosis of uninfected cells is also uncertain.</p> <p>Results</p> <p>We have addressed this issue in the humanized mouse model of HIV infection using a HIV variant with a point mutation in the gp41 region of the Env glycoprotein that alters its fusogenic activity. We demonstrate here that a single amino acid change (V38E) altering the cell-to-cell fusion activity of the Env minimizes CD4 loss in humanized mice without altering viral replication. This differential pathogenesis was associated with a lack of bystander apoptosis induction by V38E virus even in the presence of similar levels of infected cells. Interestingly, immune activation was observed with both WT and V38E infection suggesting that the two phenomena are likely not interdependent in the mouse model.</p> <p>Conclusions</p> <p>We conclude that Env fusion activity is one of the determinants of HIV pathogenesis and it may be possible to attenuate HIV by targeting gp41.</p
Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling
<p>Abstract</p> <p>Background</p> <p>Clock family genes encode transcription factors that regulate clock-controlled genes and thus regulate many physiological mechanisms/processes in a circadian fashion. Clock1 duplicates and copies of Clock3 and NPAS2-like genes were partially characterized (genomic sequencing) and mapped using family-based indels/SNPs in rainbow trout (RT)(<it>Oncorhynchus mykiss</it>), Arctic charr (AC)(<it>Salvelinus alpinus</it>), and Atlantic salmon (AS)(<it>Salmo salar</it>) mapping panels.</p> <p>Results</p> <p>Clock1 duplicates mapped to linkage groups RT-8/-24, AC-16/-13 and AS-2/-18. Clock3/NPAS2-like genes mapped to RT-9/-20, AC-20/-43, and AS-5. Most of these linkage group regions containing the Clock gene duplicates were derived from the most recent 4R whole genome duplication event specific to the salmonids. These linkage groups contain quantitative trait loci (QTL) for life history and growth traits (i.e., reproduction and cell cycling). Comparative synteny analyses with other model teleost species reveal a high degree of conservation for genes in these chromosomal regions suggesting that functionally related or co-regulated genes are clustered in syntenic blocks. For example, anti-müllerian hormone (amh), regulating sexual maturation, and ornithine decarboxylase antizymes (oaz1 and oaz2), regulating cell cycling, are contained within these syntenic blocks.</p> <p>Conclusions</p> <p>Synteny analyses indicate that regions homologous to major life-history QTL regions in salmonids contain many candidate genes that are likely to influence reproduction and cell cycling. The order of these genes is highly conserved across the vertebrate species examined, and as such, these genes may make up a functional cluster of genes that are likely co-regulated. CLOCK, as a transcription factor, is found within this block and therefore has the potential to cis-regulate the processes influenced by these genes. Additionally, clock-controlled genes (CCGs) are located in other life-history QTL regions within salmonids suggesting that at least in part, trans-regulation of these QTL regions may also occur via Clock expression.</p
Incidence rates of in-hospital carpal tunnel syndrome in the general population and possible associations with marital status
<p>Abstract</p> <p>Background</p> <p>Carpal tunnel syndrome (CTS) is a socially relevant condition associated with biomechanical risk factors. We evaluated age-sex-specific incidence rates of in-hospital cases of CTS in central/northern Italy and explored relations with marital status.</p> <p>Methods</p> <p>Seven regions were considered (overall population, 14.9 million) over 3–6-year periods between 1997 and 2002 (when out-of-hospital CTS surgery was extremely rare). Incidence rates of in-hospital cases of CTS were estimated based on 1) codified demographic, diagnostic and intervention data in obligatory discharge records from all Italian public/private hospitals, archived (according to residence) on regional databases; 2) demographic general population data for each region. We compared (using the χ<sub>score </sub>test) age-sex-specific rates between married, unmarried, divorced and widowed subsets of the general population. We calculated standardized incidence ratios (SIRs) for married/unmarried men and women.</p> <p>Results</p> <p>Age-standardized incidence rates (per 100,000 person-years) of in-hospital cases of CTS were 166 in women and 44 in men (106 overall). Married subjects of both sexes showed higher age-specific rates with respect to unmarried men/women. SIRs were calculated comparing married vs unmarried rates of both sexes: 1.59 (95% confidence interval [95% CI], 1.57–1.60) in women, and 1.42 (95% CI, 1.40–1.45) in men. As compared with married women/men, widows/widowers both showed 2–3-fold higher incidence peaks during the fourth decade of life (beyond 50 years of age, widowed subjects showed similar trends to unmarried counterparts).</p> <p>Conclusion</p> <p>This large population-based study illustrates distinct age-related trends in men and women, and also raises the question whether marital status could be associated with CTS in the general population.</p
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