MicroRNAs (miRNAs) participate in most aspects of cellular differentiation and homeostasis, and consequently have roles in many pathologies, including cancer. These small non-coding RNAs exert their ...effects in the context of complex regulatory networks, often made all the more extensive by the inclusion of transcription factors as their direct targets. In recent years, the increased availability of gene expression data and the development of methodologies that profile miRNA targets en masse have fuelled our understanding of miRNA functions, and of the sources and consequences of miRNA dysregulation. Advances in experimental and computational approaches are revealing not just cancer pathways controlled by single miRNAs but also intermeshed regulatory networks controlled by multiple miRNAs, which often engage in reciprocal feedback interactions with the targets that they regulate.
We present a self-consistent, absolute isochronal age scale for young ( ≲ 200 Myr), nearby ( ≲ 100 pc) moving groups in the solar neighbourhood based on homogeneous fitting of semi-empirical ...pre-main-sequence model isochrones using the τ2 maximum-likelihood fitting statistic of Naylor & Jeffries in the M
V
, V − J colour–magnitude diagram. The final adopted ages for the groups are as follows:
$149^{+51}_{-19}\,\rm {Myr}$
for the AB Dor moving group, 24 ± 3 Myr for the β Pic moving group (BPMG),
$45^{+11}_{-7}\,\rm {Myr}$
for the Carina association,
$42^{+6}_{-4}\,\rm {Myr}$
for the Columba association, 11 ± 3 Myr for the η Cha cluster, 45 ± 4 Myr for the Tucana–Horologium moving group (Tuc–Hor), 10 ± 3 Myr for the TW Hya association and
$22^{+4}_{-3}\,\rm {Myr}$
for the 32 Ori group. At this stage we are uncomfortable assigning a final, unambiguous age to the Argus association as our membership list for the association appears to suffer from a high level of contamination, and therefore it remains unclear whether these stars represent a single population of coeval stars. Our isochronal ages for both the BPMG and Tuc–Hor are consistent with recent lithium depletion boundary (LDB) ages, which unlike isochronal ages, are relatively insensitive to the choice of low-mass evolutionary models. This consistency between the isochronal and LDB ages instils confidence that our self-consistent, absolute age scale for young, nearby moving groups is robust, and hence we suggest that these ages be adopted for future studies of these groups. Software implementing the methods described in this study is available from http://www.astro.ex.ac.uk/people/timn/tau-squared/.
As we continue to find new regulatory roles for RNAs, a theme is emerging in which regulation may not be mediated through the actions of a specific RNA, as one typically thinks of a regulator and ...target, but rather through the collective nature of many RNAs, each contributing a small degree of the regulatory load. This mechanism has been termed "crowd-control" and may apply broadly to miRNAs and to RNAs that bind and regulate protein activity. This provides an alternative way of thinking about how RNAs can act as biological regulators and has repercussions, both for the understanding of biological systems, and for the interpretation of results in which individual members of the "crowd" can replicate the effects of the crowd when overexpressed, but are not individually significant biological regulators.
In this cluster-randomized trial conducted in Indonesia, deployment of mosquitoes infected with the
w
Mel strain of
Wolbachia pipientis
resulted in fewer symptomatic, virologically confirmed dengue ...infections and hospitalizations among residents.
There is an increasing demand for flexible, skin-attachable, and wearable strain sensors due to their various potential applications. However, achieving strain sensors with both high sensitivity and ...high stretchability is still a grand challenge. Here, we propose highly sensitive and stretchable strain sensors based on the reversible microcrack formation in composite thin films. Controllable parallel microcracks are generated in graphite thin films coated on elastomer films. Sensors made of graphite thin films with short microcracks possess high gauge factors (maximum value of 522.6) and stretchability (ε ≥ 50%), whereas sensors with long microcracks show ultrahigh sensitivity (maximum value of 11 344) with limited stretchability (ε ≤ 50%). We demonstrate the high performance strain sensing of our sensors in both small and large strain sensing applications such as human physiological activity recognition, human body large motion capturing, vibration detection, pressure sensing, and soft robotics.
The development of deep sequencing has enabled the identification of novel microRNAs (miRNAs), leading to a growing appreciation for the fact that individual miRNAs can be heterogeneous in length ...and/or sequence. These variants, termed isomiRs, can be expressed in a cell-specific manner, and numerous recent studies suggest that at least some isomiRs may affect target selection, miRNA stability, or loading into the RNA-induced silencing complex (RISC). Reports indicating differential functionality for isomiRs are currently confined to several specific variants, and although isomiRs are common, their broader biological significance is yet to be fully resolved. Here we review the growing body of evidence suggesting that isomiRs have functional differences, of which at least some appear biologically relevant, and caution researchers to take miRNA isoforms into consideration in their experiments.
We investigate the relationship of diabetes knowledge, diabetes management self-efficacy and diabetes self-management with blood glucose control among people with Thai type 2 diabetes mellitus (T2D). ...Seven hundred outpatients from diabetes clinics from large university and small community hospitals in two provinces of Thailand (Khon Kaen and Bangkok) were interviewed to evaluate their diabetes knowledge (DK), diabetes management self-efficacy (DMSE) and diabetes self-management (DSM). In addition, patient medical records were accessed to obtain other patient characteristics including patients' HbA1c levels. Bivariate and multivariable logistic regression modelling was conducted and unadjusted and adjusted odds ratios obtained, respectively. Over half (52.4%) of the patients in our sample failed to control their blood glucose (HbA1c > 7%). All three psychometric measures (DK, DMSE and DSM) were identified as associated with blood glucose control in the bivariate analysis (ORDK(unadj) = 0.89, 95%CI: 0.82, 0.96; ORDSM(unadj) = 1.64, 95%CI: 1.46, 1.82; ORDMSE(unadj) = 2.84; 95%CI: 2.43, 3.32). However, after mutual adjustment and adjustment for other patient characteristics, of the three psychometric measures, only diabetes management self-efficacy remained associated with blood glucose control (ORDMSE(adj) = 2.67; 95%CI: 2.20, 3.25). Diabetes management self-efficacy is shown to be strongly associated with blood glucose control in the Thai Type 2 diabetes population. Current early diabetes interventions in Thailand tend to focus on disease knowledge. A stronger emphasis on enhancing patients' disease management self-efficacy in these interventions is likely to lead to substantial improvement in both diabetes self-management and blood glucose control, thereafter reducing the risk, or prolonging the development, of chronic diabetes complications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human Mitochondrial Transcriptome Mercer, Tim R; Neph, Shane; Dinger, Marcel E ...
Cell,
08/2011, Letnik:
146, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The human mitochondrial genome comprises a distinct genetic system transcribed as precursor polycistronic transcripts that are subsequently cleaved to generate individual mRNAs, tRNAs, and rRNAs. ...Here, we provide a comprehensive analysis of the human mitochondrial transcriptome across multiple cell lines and tissues. Using directional deep sequencing and parallel analysis of RNA ends, we demonstrate wide variation in mitochondrial transcript abundance and precisely resolve transcript processing and maturation events. We identify previously undescribed transcripts, including small RNAs, and observe the enrichment of several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI footprinting, we establish the global profile of DNA-binding protein occupancy across the mitochondrial genome at single-nucleotide resolution, revealing regulatory features at mitochondrial transcription initiation sites and functional insights into disease-associated variants. This integrated analysis of the mitochondrial transcriptome reveals unexpected complexity in the regulation, expression, and processing of mitochondrial RNA and provides a resource for future studies of mitochondrial function (accessed at http://mitochondria.matticklab.com).
The pathogenesis of dengue Whitehorn, Jamie; Simmons, Cameron P
Vaccine,
09/2011, Letnik:
29, Številka:
42
Journal Article
Recenzirano
Odprti dostop
Abstract Dengue is an important cause of childhood and adult morbidity in Asian and Latin American countries and its geographic footprint is growing. The clinical manifestations of dengue are the ...expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. The virulence of the virus plus the flavivirus infection history, age, gender and genotype of the host all appear to help shape the severity of infection. Similarly, the characteristics of the innate and acquired host immune response subsequent to infection are also likely determinants of outcome. This review summarises recent developments in the understanding of dengue pathogenesis and their relevance to dengue vaccine development.
A Candidate Dengue Vaccine Walks a Tightrope Simmons, Cameron P
New England journal of medicine/The New England journal of medicine,
09/2015, Letnik:
373, Številka:
13
Journal Article
Recenzirano
Odprti dostop
The most advanced candidate vaccine against dengue viruses, called CYD-TDV, is progressing toward potential registration and review by the World Health Organization (WHO) in 2016. CYD-TDV is a ...formulation of four chimeric yellow fever 17D vaccine viruses, each one engineered to express the surface envelope and prM (membrane) proteins from one of the four serotypes of dengue virus. The surface envelope protein is a target of virus-neutralizing antibodies. The safety and efficacy of CYD-TDV after the administration of three doses over a 12-month period was recently measured in two pediatric phase 3 trials in Latin America
1
and Southeast Asia.
2
The . . .
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