We propose a framework that combines variational immersed-boundary and arbitrary Lagrangian–Eulerian methods for fluid–structure interaction (FSI) simulation of a bioprosthetic heart valve implanted ...in an artery that is allowed to deform in the model. We find that the variational immersed-boundary method for FSI remains robust and effective for heart valve analysis when the background fluid mesh undergoes deformations corresponding to the expansion and contraction of the elastic artery. Furthermore, the computations presented in this work show that the arterial wall deformation contributes significantly to the realism of the simulation results, leading to flow rates and valve motions that more closely resemble those observed in practice.
There is a widely held and influential view that physical activity begins to decline at adolescence. This study aimed to identify the timing of changes in physical activity during childhood and ...adolescence.
Longitudinal cohort study (Gateshead Millennium Study) with 8 years of follow-up, from North-East England. Cohort members comprise a socioeconomically representative sample studied at ages 7, 9, 12 and 15 years; 545 individuals provided physical activity data at two or more time points. Habitual total volume of physical activity and moderate-to-vigorous intensity physical activity (MVPA) were quantified objectively using the Actigraph accelerometer over 5-7 days at the four time points. Linear mixed models identified the timing of changes in physical activity across the 8-year period, and trajectory analysis was used to identify subgroups with distinct patterns of age-related changes.
Four trajectories of change in total volume of physical activity were identified representing 100% of all participants: all trajectories declined from age 7 years. There was no evidence that physical activity decline began at adolescence, or that adolescent declines in physical activity were substantially greater than the declines during childhood, or greater in girls than boys. One group (19% of boys) had relatively high MVPA which remained stable between ages 7 and15 years.
Future policy and research efforts to promote physical activity should begin well before adolescence, and should include both boys and girls.
Gene expression during development and differentiation is regulated in a cell- and stage-specific manner by complex networks of intergenic and intragenic cis-regulatory elements whose numbers and ...representation in the genome far exceed those of structural genes. Using chromosome conformation capture, it is now possible to analyze in detail the interaction between enhancers, silencers, boundary elements and promoters at individual loci, but these techniques are not readily scalable. Here we present a high-throughput approach (Capture-C) to analyze cis interactions, interrogating hundreds of specific interactions at high resolution in a single experiment. We show how this approach will facilitate detailed, genome-wide analysis to elucidate the general principles by which cis-acting sequences control gene expression. In addition, we show how Capture-C will expedite identification of the target genes and functional effects of SNPs that are associated with complex diseases, which most frequently lie in intergenic cis-acting regulatory elements.
Celotno besedilo
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A series of reports over the last few years have indicated that a much larger portion of the mammalian genome is transcribed than can be accounted for by currently annotated genes, but the quantity ...and nature of these additional transcripts remains unclear. Here, we have used data from single- and paired-end RNA-Seq and tiling arrays to assess the quantity and composition of transcripts in PolyA+ RNA from human and mouse tissues. Relative to tiling arrays, RNA-Seq identifies many fewer transcribed regions ("seqfrags") outside known exons and ncRNAs. Most nonexonic seqfrags are in introns, raising the possibility that they are fragments of pre-mRNAs. The chromosomal locations of the majority of intergenic seqfrags in RNA-Seq data are near known genes, consistent with alternative cleavage and polyadenylation site usage, promoter- and terminator-associated transcripts, or new alternative exons; indeed, reads that bridge splice sites identified 4,544 new exons, affecting 3,554 genes. Most of the remaining seqfrags correspond to either single reads that display characteristics of random sampling from a low-level background or several thousand small transcripts (median length = 111 bp) present at higher levels, which also tend to display sequence conservation and originate from regions with open chromatin. We conclude that, while there are bona fide new intergenic transcripts, their number and abundance is generally low in comparison to known exons, and the genome is not as pervasively transcribed as previously reported.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Central nervous system-expressed long non-coding RNAs (lncRNAs) are often located in the genome close to protein coding genes involved in transcriptional control. Such lncRNA-protein coding gene ...pairs are frequently temporally and spatially co-expressed in the nervous system and are predicted to act together to regulate neuronal development and function. Although some of these lncRNAs also bind and modulate the activity of the encoded transcription factors, the regulatory mechanisms controlling co-expression of neighbouring lncRNA-protein coding genes remain unclear. Here, we used high resolution NG Capture-C to map the cis-regulatory interaction landscape of the key neuro-developmental Paupar-Pax6 lncRNA-mRNA locus. The results define chromatin architecture changes associated with high Paupar-Pax6 expression in neurons and identify both promoter selective as well as shared cis-regulatory-promoter interactions involved in regulating Paupar-Pax6 co-expression. We discovered that the TCF7L2 transcription factor, a regulator of chromatin architecture and major effector of the Wnt signalling pathway, binds to a subset of these candidate cis-regulatory elements to coordinate Paupar and Pax6 co-expression. We describe distinct roles for Paupar in Pax6 expression control and show that the Paupar DNA locus contains a TCF7L2 bound transcriptional silencer whilst the Paupar transcript can act as an activator of Pax6. Our work provides important insights into the chromatin interactions, signalling pathways and transcription factors controlling co-expression of adjacent lncRNAs and protein coding genes in the brain.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
is widely cultivated for medicinal, food, industrial, and recreational use, but much remains unknown regarding its genetics, including the molecular determinants of cannabinoid content. Here, we ...describe a combined physical and genetic map derived from a cross between the drug-type strain Purple Kush and the hemp variety "Finola." The map reveals that cannabinoid biosynthesis genes are generally unlinked but that aromatic prenyltransferase (
), which produces the substrate for THCA and CBDA synthases (THCAS and CBDAS), is tightly linked to a known marker for total cannabinoid content. We further identify the gene encoding CBCA synthase (
) and characterize its catalytic activity, providing insight into how cannabinoid diversity arises in cannabis.
and
(which determine the drug vs. hemp chemotype) are contained within large (>250 kb) retrotransposon-rich regions that are highly nonhomologous between drug- and hemp-type alleles and are furthermore embedded within ∼40 Mb of minimally recombining repetitive DNA. The chromosome structures are similar to those in grains such as wheat, with recombination focused in gene-rich, repeat-depleted regions near chromosome ends. The physical and genetic map should facilitate further dissection of genetic and molecular mechanisms in this commercially and medically important plant.
The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their ...pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.
The Human Transcription Factors Lambert, Samuel A.; Jolma, Arttu; Campitelli, Laura F. ...
Cell,
02/2018, Letnik:
172, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Transcription factors (TFs) recognize specific DNA sequences to control chromatin and transcription, forming a complex system that guides expression of the genome. Despite keen interest in ...understanding how TFs control gene expression, it remains challenging to determine how the precise genomic binding sites of TFs are specified and how TF binding ultimately relates to regulation of transcription. This review considers how TFs are identified and functionally characterized, principally through the lens of a catalog of over 1,600 likely human TFs and binding motifs for two-thirds of them. Major classes of human TFs differ markedly in their evolutionary trajectories and expression patterns, underscoring distinct functions. TFs likewise underlie many different aspects of human physiology, disease, and variation, highlighting the importance of continued effort to understand TF-mediated gene regulation.
Knowing how and where transcription factors bind to the genome is crucial for understanding how they control gene expression. This Review looks at how human TFs are identified and the ways they interact with DNA sequences.
Limited research has explored the links between sedentary behaviour, mental health and quality of life. This study examines objectively measured sedentary behaviour and perceived mental health and ...quality of life across week days and weekends.
42 adults (19M, 23F; mean age 38yrs (range 18-67) & BMI 24.8kg/m2 (range 18.7-33.8) wore an activPAL monitor 24h/day for one week and completed the Hospital Anxiety and Depression Scale (HADS) and SF12 Health Survey. Average weekday and weekend day sitting time was computed. Differences between sitting (Group 1 = <8hrs/day, Group 2 = 8-10 hrs/day, Group 3 = >10hrs/day) and components of the HADS and SF12 health survey were examined using an ANCOVA with a measure of physical activity (step count) included as a covariate.
Average sitting time on a weekday was 9hrs 29mins (range 5hrs 52mins to 12hrs 55mins) and 8hrs 59mins (range 4hrs, 07mins to 14hrs, 40mins) on a weekend day. There was a main effect (p<0.05) for weekday sitting time on total anxiety and depression (HADS) and mental health and vitality (SF12). Planned contrasts identified individuals in group 1 had lower anxiety and depression and higher mental health and vitality scores than individuals in groups 2 or 3 (p<0.05). No difference was found between individuals in group 2 and group 3 (p>0.05). No main effects were found for weekend sitting (p>0.05).
Weekday sitting time below 8 hours/day is associated with better perceived mental health and quality of life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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