Elevated expression of human bHLH factor ATOH7 accelerates cell cycle progression of progenitors and enhances production of avian retinal ganglion cells.

The production of vertebrate retinal projection neurons, retinal ganglion cells (RGCs), is regulated by cell-intrinsic determinants and cell-to-cell signaling events. The basic-helix-loop-helix (bHLH) protein Atoh7 is a key neurogenic transcription factor required for RGC development. Here, we investigate whether manipulating human ATOH7 expression among uncommitted progenitors can promote RGC fate specification and thus be used as a strategy to enhance RGC genesis. Using the chicken retina as a model, we show that cell autonomous expression of ATOH7 is sufficient to induce precocious RGC formation and expansion of the neurogenic territory. ATOH7 overexpression among neurogenic progenitors significantly enhances RGC production at the expense of reducing the progenitor pool. Furthermore, forced expression of ATOH7 leads to a minor increase of cone photoreceptors. We provide evidence that elevating ATOH7 levels accelerates cell cycle progression from S to M phase and promotes cell cycle exit. We also show that ATOH7-induced ectopic RGCs often exhibit aberrant axonal projection patterns and are correlated with increased cell death during the period of retinotectal connections. These results demonstrate the high potency of human ATOH7 in promoting early retinogenesis and specifying the RGC differentiation program, thus providing insight for manipulating RGC production from stem cell-derived retinal organoids

Molecular cloning, expression profiling, and yeast complementation of 19 β-tubulin cDNAs from developing cotton ovules

Microtubules are a major structural component of the cytoskeleton and participate in cell division, intracellular transport, and cell morphogenesis. In the present study, 795 cotton tubulin expressed sequence tags were analysed and 19 β-tubulin genes (TUB) cloned from a cotton cDNA library. Among the group, 12 cotton TUBs (GhTUBs) are reported for the first time here. Transcription profiling revealed that nine GhTUBs were highly expressed in elongating fibre cells as compared with fuzzless-lintless mutant ovules. Treating cultured wild-type cotton ovules with exogenous phytohormones showed that individual genes can be induced by different agents. Gibberellin induced expression of GhTUB1 and GhTUB3, ethylene induced expression of GhTUB5, GhTUB9, and GhTUB12, brassinosteroids induced expression of GhTUB1, GhTUB3, GhTUB9, and GhTUB12, and lignoceric acid induced expression of GhTUB1, GhTUB3, and GhTUB12. When GhTUBs were transformed into the Saccharomyces cerevisiae inviable mutant, tub2, which is deficient in β-tubulin, one ovule-specific and eight of nine fibre-preferential GhTUBs rescued this lethality. This study suggests that the proteins encoded by cotton GhTUBs are involved during cotton fibre development

Adult restoration of Shank3 expression rescues selective autistic-like phenotypes

Because autism spectrum disorders are neurodevelopmental disorders and patients typically display symptoms before the age of three, one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigate the developmental requirement of Shank3 in mice, a prominent monogenic autism gene that is estimated to contribute to approximately 1% of all autism spectrum disorder cases. SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of post synaptic density macromolecular signalling complex. Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic-like behaviours including anxiety, social interaction deficits, and repetitive behaviour. We generated a novel Shank3 conditional knock-in mouse model, and show that re-expression of the Shank3 gene in adult mice led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provide behavioural evidence that certain behavioural abnormalities including social interaction deficit and repetitive grooming behaviour could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results reveal the profound effect of post-developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain.National Institutes of Health (U.S.) (Grant R01MH097104

The 2 micron plasmid purloins the yeast cohesin complex: a mechanism for coupling plasmid partitioning and chromosome segregation?

The yeast 2 micron plasmid achieves high fidelity segregation by coupling its partitioning pathway to that of the chromosomes. Mutations affecting distinct steps of chromosome segregation cause the plasmid to missegregate in tandem with the chromosomes. In the absence of the plasmid stability system, consisting of the Rep1 and Rep2 proteins and the STB DNA, plasmid and chromosome segregations are uncoupled. The Rep proteins, acting in concert, recruit the yeast cohesin complex to the STB locus. The periodicity of cohesin association and dissociation is nearly identical for the plasmid and the chromosomes. The timely disassembly of cohesin is a prerequisite for plasmid segregation. Cohesin-mediated pairing and unpairing likely provides a counting mechanism for evenly partitioning plasmids either in association with or independently of the chromosomes

Cardiac Biomarkers Predicting MACE in Patients Undergoing Noncardiac Surgery: A Meta-Analysis

Objective: The present meta-analysis was aimed to systematically evaluate the effectiveness and accuracy of brain natriuretic peptide (BNP), cardiac troponin (cTn), high sensitive C reactive protein (hs-CRP) and CRP for predicting postoperative major adverse cardiovascular events (MACE) in patients undergoing noncardiac surgery.Methods: A total of 26 relevant studies with 7,877 participants were collected from five databases, namely PubMed, Embase, China National Knowledge Infrastructure (CNKI), CQVIP and the Wanfang Database until August 10, 2018. And the Review Manager Version 5.3 and Stata/SE 12 software were used for data syntheses in the meta-analysis.Results: Strong relationships of BNP/NT-proBNP, cTnI/cTnT and hs-CRP with MACE were detected in patients undergoing noncardiac surgery, and the five biomarkers all increased the risk of MACE. Compared to normal levels, elevated BNP/NT-proBNP could increase the MACE risk by almost 4-fold [RR:3.92, 95%CI: 3.23–4.75, P < 0.001]; elevated BNP corresponded to a 4.5-fold risk [RR:4.57, 95%CI: 3.37–6.20, P < 0.001]; elevated NT-proBNP led to a 3-fold higher risk [RR:3.48, 95%CI: 2.71–4.46, P < 0.001]. Comparing with normal levels of cTnI/cTnT, increased cTnI/cTnT was associated with nearly 5-fold more higher risk of MACE [RR:5.52, 95%CI: 4.62–6.58, P < 0.001]; elevated cTnI faced a 5-fold risk [RR:5.21, 95%CI: 3.96–6.86, P < 0.001]; elevated cTnT resulted in nearly 6-fold higher risk [RR:5.73, 95%CI: 4.55–7.22, P < 0.001]. The elevation of hs-CRP was associated with nearly 4-fold higher risk of MACE in comparison with normal concentration [RR:3.73, 95%CI: 2.63–5.30, P < 0.001].Conclusion: According to the results of our meta-analysis, the elevations of BNP/NT-proBNP, cTnI/cTnT, and hs-CRP, pre-operation or post-operation immediately, can predict much higher risk of postoperative MACE in patients undergoing noncardiac surgery

Chaotic Bayesian optimal prediction method and its application in hydrological time series

AbstractThe embedding dimension and the number of nearest neighbors are very important parameters in the prediction of chaotic time series. To reduce the prediction errors and the uncertainties in the determination of the above parameters, a new chaos Bayesian optimal prediction method (CBOPM) is proposed by choosing optimal parameters in the local linear prediction method (LLPM) and improving the prediction accuracy with Bayesian theory. In the new method, the embedding dimension and the number of nearest neighbors are combined as a parameter set. The optimal parameters are selected by mean relative error (MRE) and correlation coefficient (CC) indices according to optimization criteria. Real hydrological time series are taken to examine the new method. The prediction results indicate that CBOPM can choose the optimal parameters adaptively in the prediction process. Compared with several LLPM models, the CBOPM has higher prediction accuracy in predicting hydrological time series