Flax (Linum usitatissimum) is an ancient crop that is widely cultivated as a source of fiber, oil and medicinally relevant compounds. To accelerate crop improvement, we performed whole‐genome shotgun ...sequencing of the nuclear genome of flax. Seven paired‐end libraries ranging in size from 300 bp to 10 kb were sequenced using an Illumina genome analyzer. A de novo assembly, comprised exclusively of deep‐coverage (approximately 94× raw, approximately 69× filtered) short‐sequence reads (44–100 bp), produced a set of scaffolds with N50 = 694 kb, including contigs with N50 = 20.1 kb. The contig assembly contained 302 Mb of non‐redundant sequence representing an estimated 81% genome coverage. Up to 96% of published flax ESTs aligned to the whole‐genome shotgun scaffolds. However, comparisons with independently sequenced BACs and fosmids showed some mis‐assembly of regions at the genome scale. A total of 43 384 protein‐coding genes were predicted in the whole‐genome shotgun assembly, and up to 93% of published flax ESTs, and 86% of A. thaliana genes aligned to these predicted genes, indicating excellent coverage and accuracy at the gene level. Analysis of the synonymous substitution rates (Ks) observed within duplicate gene pairs was consistent with a recent (5–9 MYA) whole‐genome duplication in flax. Within the predicted proteome, we observed enrichment of many conserved domains (Pfam‐A) that may contribute to the unique properties of this crop, including agglutinin proteins. Together these results show that de novo assembly, based solely on whole‐genome shotgun short‐sequence reads, is an efficient means of obtaining nearly complete genome sequence information for some plant species.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A new heteroleptic iridium complex demonstrated low cytotoxicity and near-infrared excitation (via two-photon absorption) for target-specific in vitro Golgi imaging in various cell lines (HeLa and ...A549 cells) with two-photon absorption cross section (~350 GM) in DMSO.
Dysregulation of microRNA (miRNA) expression in various tissues and body fluids has been demonstrated to be associated with several diseases, including Type 2 Diabetes mellitus (T2D). Here, we ...compare miRNA expression profiles in different tissues (pancreas, liver, adipose and skeletal muscle) as well as in blood samples from T2D rat model and highlight the potential of circulating miRNAs as biomarkers of T2D. In parallel, we have examined the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients.
Employing miRNA microarray and stem-loop real-time RT-PCR, we identify four novel miRNAs, miR-144, miR-146a, miR-150 and miR-182 in addition to four previously reported diabetes-related miRNAs, miR-192, miR-29a, miR-30d and miR-320a, as potential signature miRNAs that distinguished IFG and T2D. Of these microRNAs, miR-144 that promotes erythropoiesis has been found to be highly up-regulated. Increased circulating level of miR-144 has been found to correlate with down-regulation of its predicted target, insulin receptor substrate 1 (IRS1) at both mRNA and protein levels. We could also experimentally demonstrate that IRS1 is indeed the target of miR-144.
We demonstrate that peripheral blood microRNAs can be developed as unique biomarkers that are reflective and predictive of metabolic health and disorder. We have also identified signature miRNAs which could possibly explain the pathogenesis of T2D and the significance of miR-144 in insulin signaling.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the past decade, an association has been discovered between MCC and either ...integration of the Merkel cell polyomavirus, which likely drives tumorigenesis, or somatic mutations owing to ultraviolet-induced DNA damage. Both virus-positive and virus-negative MCCs are immunogenic, and inhibition of the programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in treating patients with metastatic MCC; however, not all patients have a durable response to immunotherapy. Despite these rapid advances in the understanding and management of patients with MCC, many basic, translational and clinical research questions remain unanswered. In March 2018, an International Workshop on Merkel Cell Carcinoma Research was held at the US National Cancer Institute, at which academic, government and industry experts met to identify the highest-priority research questions. Here, we review the biology and treatment of MCC and report the consensus-based recommendations agreed upon during the workshop.
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NUK, OILJ, SBMB, UL, UM, UPUK
The association of the intrinsic optical and biophysical properties of cells to homeostasis and pathogenesis has long been acknowledged. Defining these label-free cellular features obviates the need ...for costly and time-consuming labelling protocols that perturb the living cells. However, wide-ranging applicability of such label-free cell-based assays requires sufficient throughput, statistical power and sensitivity that are unattainable with current technologies. To close this gap, we present a large-scale, integrative imaging flow cytometry platform and strategy that allows hierarchical analysis of intrinsic morphological descriptors of single-cell optical and mass density within a population of millions of cells. The optofluidic cytometry system also enables the synchronous single-cell acquisition of and correlation with fluorescently labeled biochemical markers. Combined with deep neural network and transfer learning, this massive single-cell profiling strategy demonstrates the label-free power to delineate the biophysical signatures of the cancer subtypes, to detect rare populations of cells in the heterogeneous samples (10-5), and to assess the efficacy of targeted therapeutics. This technique could spearhead the development of optofluidic imaging cell-based assays that stratify the underlying physiological and pathological processes based on the information-rich biophysical cellular phenotypes.
An optofluidic imaging cytometry strategy that hierarchically analyzes single-cell biophysical morphology beyond millions of cells at high sensitivity and specificity.
Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is ...widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.
► Epilepsy is one consequence of excess protein synthesis in the Fmr1−/y mouse ► Lovastatin inhibits Ras-ERK1/2 and normalizes protein synthesis ► Lovastatin prevents epileptogenesis in the Fmr1−/y mouse ► Lovastatin, approved for human use, is potentially disease modifying in FXS
Osterweil et al. show that lovastatin, a widely prescribed HMG-CoA reductase inhibitor (statin), can correct multiple pathological changes in the mouse model of fragile X syndrome, including the induction of epilepsy (epileptogenesis).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Existing studies on health-related quality of life (HRQoL) mainly covered single growth stages of childhood or adolescence and did not report on the trends in the relationships of HRQoL with sleep ...duration, physical activity, and screen time. This study aimed to establish the population norm of HRQoL in children and adolescents aged 6-17 years and examine the associations of screen time, sleep duration, and physical activity with HRQoL in this population.
We conducted a large-scale cross-sectional population-based survey study of Hong Kong children and adolescents aged 6 to 17 years. A representative sample of students were interviewed to assess their HRQoL using PedsQL and EQ-5D-Y-5L. Multivariable homoscedastic Tobit regression with linear form or restricted cubic spline of predictors was used to analyze the associations between screen time, sleep duration, and HRQoL. Multiple imputation by chained equations was performed to deal with missing data.
A total of 7555 respondents (mean age 11.5, SD 3.2; 55.1% female) were sampled. Their EQ VAS scores, PedsQL physical summary scores, and psychosocial summary scores were positively correlated with sleep duration and moderate/vigorous activity but was negatively correlated with screen time.
Children and adolescents who had longer exposure to screen, shorter sleep duration, and lower physical activity levels appeared to have poorer HRQoL as assessed by PedsQL and EQ-5D-Y-5L. Advice and guidance on screen time allocation for children and adolescents should be provided at the levels of school, community, and family.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Restrictive COVID-19 measures can have significant mental health impacts, particularly on young people. How such measures may influence day-to-day momentary affect, nonetheless, remains to be ...explored. Experience sampling data were collected from 165 young people (aged 15–24) as part of a larger epidemiological youth mental health study in Hong Kong. We examined the impact of one of the most stringent COVID-19 measures – dine-in restrictions – on momentary positive and negative affect and current contexts and activities of these young people. The effects of a milder form of COVID-19 measure – school suspension – were separately examined. Multilevel analysis revealed that those in the dine-in ban group, compared to dining-as-usual, showed significantly reduced momentary positive affect (
β
= −0.17,
SE
= 0.06,
p
= 0.003). Its effect remained significant even when accounting for baseline depressive and anxiety symptoms and socioeconomic status (
β
= −0.15,
SE
= 0.05,
p
= 0.008). The effect of dine-in ban on reduced momentary positive affect was found specifically when participants were in indoor locations (e.g., home, office), alone, and engaged in passive leisure activities. This pattern was not observed when participants were at school or at other outdoor locations, with friends, or engaged in active leisure activities. No significant effect of school suspension on momentary affect was observed. More severe COVID-19 measures, such as dine-in ban, can have significant impacts on the momentary positive affect of young people. Certain contexts and activities may offer protection against the consequences of COVID-19 measures. The current findings may help to inform future designs of mental health interventions and public health policies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aberrant Notch activation has been implicated in multiple malignancies and the identification of NOTCH receptors and related pathways is critical for targeted therapy. In this study, we aim to ...delineate the most prominent dysregulated NOTCH receptor and comprehensively reveal its deregulation in gastric cancer (GC). In the four Notch members, NOTCH3 was found uniformly upregulated and associated with poor clinical outcomes in multiple GC datasets. siRNA-mediated NOTCH3 knockdown demonstrated antitumor effects by suppressing cell proliferation, inhibiting monolayer formation, and impairing cell invasion abilities. Its depletion also induced early and late apoptosis. NOTCH3 was confirmed to be a direct target of two tumor suppressor microRNAs (miRNAs), namely miR-491-5p and miR-875-5p. The activation of NOTCH3 is partly due to the silence of these two miRNAs. Through RNA-seq profiling and functional validation, PHLDB2 was identified as a potent functional downstream modulator for NOTCH3 in gastric carcinogenesis. PHLDB2 expression demonstrated a positive correlation with NOTCH3, but was negatively correlated with miR-491-5p. Akt-mTOR was revealed as the downstream signaling of PHLDB2. The NOTCH3-PHLDB2-Akt co-activation was found in 33.7% GC patients and the activation of this axis predicted poor clinical outcome. GC cells treated with siNOTCH3, siPHLDB2, miR-491-5p, miR-875-5p, were more sensitive to Cisplatin and 5-FU. Taken together, the NOTCH3-PHLDB2-Akt cascade plays oncogenic role in gastric carcinogenesis and serves as a therapeutic target. Our study provided insights into Notch-mediated underlying molecular mechanisms and implied translational potential.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In a phase 3 randomized trial, 199 patients with type 1 hepatorenal syndrome were assigned to receive the vasoconstrictor terlipressin plus albumin and 101 to receive placebo plus albumin. Renal ...function was better with terlipressin than with placebo; however, mortality was not lower, and terlipressin was associated with adverse events, including respiratory failure.
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