Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome

Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS.     

Presynaptic Adenosine A2 and N-Methyl-D-Aspartate Receptors Regulate Dopamine Synthesis in Rat Striatal Synaptosomes

Dopamine synthesis rate and cyclic AMP concentration were measured in synaptosomes prepared from rat striatum. Dopamine synthesis rate was decreased by the addition of either adenosine deaminase or 8-phenyltheophylline, an adenosine receptor blocker, and was increased by the addition of 2-chloroadenosine. The addition of L-glutamate in the absence of adenosine deaminase decreased both dopamine synthesis rate and cyclic AMP concentration; in the presence of adenosine deaminase, glutamate had no effect on basal dopamine synthesis, but enhanced K(+)-stimulated synthesis. Both these effects of glutamate were abolished in Ca2(+)-free medium or in the presence of 2-amino-5-phosphonovalerate, an N-methyl-D-aspartate (NMDA) receptor blocker. In Mg2(+)-free medium with adenosine deaminase, glutamate enhanced both basal and K(+)-stimulated synthesis. These results suggest that dopaminergic terminals have A2 adenosine receptors, whose activation can stimulate dopamine synthesis by a cyclic AMP-dependent mechanism, and NMDA receptors, which modulate dopamine synthesis by a Ca2(+)-dependent mechanism.     

EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy

Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.     

Plant–soil feedback during biological invasions: effect of litter decomposition from an invasive plant (Sphagneticola trilobata) on its native congener (S. calendulacea)

生物入侵过程中的植物-土壤反馈：一种入侵植物的凋落物分解对其本地近缘植物的影响 植物入侵可通过正或负的植物-土壤反馈效应改变土壤的生物和非生物性质,从而影响入侵栖息地的土壤理化性质。许多入侵物种的凋落物分解可增加土壤养分,降低本地植物多样性,并导致进一步的植物入侵。关于入侵植物凋落物在不同土壤类型及深度分解及反馈效应的研究依然很少。本研究旨在明确入侵植物南美蟛蜞菊(Sphagneticola trilobata)凋落物在不同土壤类型和不同土壤深度条件下的分解情 况及其对本地近缘植物蟛蜞菊(S. calendulacea)生理生长的影响。将装有南美蟛蜞菊凋落物的尼龙袋加入到不同深度(即0、2、4 和6 cm)的砂土、营养土和粘土中,经6个月的分解后,回收凋落物袋并计算分解速率,随后在凋落物分解处理后的土壤中种植本地蟛蜞菊,并在生长期结束时测量其生理生态指标。研究结果表明,所有处理土壤类型中,凋落物在土壤深度为2和4 cm处分解后显著增加了土壤养分,而对本 地蟛蜞菊的叶片叶绿素、叶氮含量等生长指标表现为负效应。因此,入侵植物南美蟛蜞菊凋落物分解对土壤养分表现为正的反馈效应,而对本地植物蟛蜞菊的生长表现为负效应。我们的研究结果还表明,入侵植物的凋落物分解对土壤和本地物种的影响还因凋落物分解所在的土壤深度而显著不同。未来的研究应侧重于入侵栖息地中更多本地和入侵物种的植物-土壤反馈效应,以及更多土壤类型和土壤深度的入侵植物凋落物效应。     

Assessment of genetic variation within Indian mustard (Brassica juncea) germplasm using random amplified polymorphic DNA markers

Genetic diversity among 45 Indian mustard (Brassica Juncea L.) genotypes comprising 37 germplasm collections, five advance breeding lines and three improved cultivars was investigated at the DNA level using the random amplified polymorphic DNA (RAPD) technique. Fifteen primers used generated a total of 92 RAPD fragments, of which 81 (88%) were polymorphic. Of these, 13 were unique to accession 'Pak85559'. Each primer produced four to nine amplified products with an average of 6.13 bands per primer. Based on pairwise comparisons of RAPD amplification products, Nei and Li's similarity coefficients were calculated to evaluate the relationships among the accessions. Pairwise similarity indices were higher among the oilseed accessions and cultivars showing narrow ranges of 0.77-0.99. An unweighted pair-group method with arithmetic averages cluster analysis based on these genetic similarities placed most of the collections and oilseed cultivars close to each other, showing a low level of polymorphism between the accessions used. However, the clusters formed by oilseed collections and cultivars were comparatively distinct from that of advanced breeding lines. Genetically, all of the accessions were classified into a few major groups and a number of individual accessions. Advanced breeding lines were relatively divergent from the rest of the accessions and formed independent clusters. Clustering of the accessions did not show any pattern of association between the RAPD markers and the collection sites. A low level of genetic variability of oilseed mustard was attributed to the selection for similar traits and horticultural uses. Perhaps close parentage of these accessions further contributed towards their little diversity. The study demonstrated that RAPD is a simple and fast technique to compare the genetic relationship and pattern of variation among the gene pool of this crop.     

Population Differences in Brain Morphology and Microstructure among Chinese,Malay, and Indian Neonates

We studied a sample of 75 Chinese, 73 Malay, and 29 Indian healthy neonates taking part in a cohort study to examine potential differences in neonatal brain morphology and white matter microstructure as a function of ethnicity using both structural T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We first examined the differences in global size and morphology of the brain among the three groups. We then constructed the T2-weighted MRI and DTI atlases and employed voxel-based analysis to investigate ethnic differences in morphological shape of the brain from the T2-weighted MRI, and white matter microstructure measured by fractional anisotropy derived from DTI. Compared with Malay neonates, the brains of Indian neonates’ tended to be more elongated in anterior and posterior axis relative to the superior-inferior axis of the brain even though the total brain volume was similar among the three groups. Although most anatomical regions of the brain were similar among Chinese, Malay, and Indian neonates, there were anatomical variations in the spinal-cerebellar and cortical-striatal-thalamic neural circuits among the three populations. The population-related brain regions highlighted in our study are key anatomical substrates associated with sensorimotor functions.     

Molecular characterization of Plasmodium vivax clinical isolates in Pakistan and Iran using pvmsp-1, pvmsp-3α and pvcsp genes as molecular markers

In this study, the diversity of Plasmodium vivax populations circulating in Pakistan and Iran has been investigated by using circumsporozoite protein (csp) and merozoite surface proteins 1 and 3α (msp-1 and msp-3α) genes as genetic markers. Infected P. vivax blood samples were collected from Pakistan (n = 187) and Iran (n = 150) during April to October 2008, and were analyzed using nested-PCR/RFLP and sequencing methods. Genotyping pvmsp-1 (variable block 5) revealed the presence of type 1, type 2 and recombinant type 3 allelic variants, with type 1 predominant, in both study areas. The sequence analysis of 33 P. vivax isolates from Pakistan and 30 from Iran identified 16 distinct alleles each, with one allele (R-8) from Iran which was not reported previously. Genotyping pvcsp gene also showed that VK210 type is predominant in both countries. Moreover, based on the size of amplified fragment of pvmsp-3α, three major types: type A (1800 bp), type B (1500 bp) and type C (1200 bp), were distinguished among the examined isolates that type A was predominant among Pakistani (72.7%) and Iranian (77.3%) parasites. PCR/RFLP products of pvmsp-3α with HhaI and AluI have detected 40 and 39 distinct variants among Pakistani and Iranian examined isolates, respectively. Based on these three studied genes, the rate of combined multiple genotypes were 30% and 24.6% for Pakistani and Iranian P. vivax isolates, respectively. These results indicate an extensive diversity in the P. vivax populations in both studies.     

Uncovering Atomic‐Scale Stability and Reactivity in Engineered Zinc Oxide Electrocatalysts for Controllable Syngas Production

In this study, scalable, flame spray synthesis is utilized to develop defective ZnO nanomaterials for the concurrent generation of H₂ and CO during electrochemical CO₂ reduction reactions (CO₂RR). The designed ZnO achieves an H₂/CO ratio of ≈1 with a large current density (j) of 40 mA cm^?2 during long‐term continuous reaction at a cell voltage of 2.6 V. Through in situ atomic pair distribution function analysis, the remarkable stability of these ZnO structures is explored, addressing the knowledge gap in understanding the dynamics of oxide catalysts during CO₂RR. Through optimization of synthesis conditions, ZnO facets are modulated which are shown to affect reaction selectivity, in agreement with theoretical calculations. These findings and insights on synthetic manipulation of active sites in defective metal‐oxides can be used as guidelines to develop active catalysts for syngas production for renewable power‐to‐X to generate a range of fuels and chemicals.     

Population diversity of Cistopus indicus inferred from mitochondrial DNA (Cytochrome b) variation from China and Vietnam

ABSTRACT

The octopus Cistopus indicus is an important target of cephalopod fisheries in China. It is widely distributed in the South Pacific and tropical Indian Ocean, from the South China Sea, the Philippines, Malaysia, to Indian and Pakistan seas. We collected specimens from five sites in China and Vietnam (Zhoushan, Wenzhou, Shacheng, Zhanjiang and Mangjie). A fragment of 675bp of cytochrome b (Cytb) was amplified from 95 individuals. A total of 27 haplotypes and 78 variable nucleotide sites was observed. High haplotype diversity and low nucleotide diversity were observed in all populations. The phylogenetic analysis separated these populations into two clades; one was composed of three populations (Zhoushan, Wenzhou and Shacheng), the other of two (Zhanjiang, Mangjie). AMOVA analysis detected that 4.67% of the genetic variation occurred within populations and 95.33% occurred among populations. FST values ranged from 0.014 to 0.993, highlighting the high genetic variation among the populations. Assuming a molecular clock with a rate of 2.15–2.6%/Ma for the Cytb gene, the two clades may have diverged 2.88–3.49 million years ago (Pliocene). Neutral evolution tests and mismatch distribution analysis suggested recent population expansion. The present results revealed valuable information for genetic assessment, management and conservation of this species.     

An Overview on the Toxicological Properties of Ionic Liquids toward Microorganisms

Ionic liquids (ILs), a class of materials with unique physicochemical properties, have been used extensively in the fields of chemical engineering, biotechnology, material sciences, pharmaceutics, and many others. Because ILs are very polar by nature, they can migrate into the environment with the possibility of inclusion in the food chain and bioaccumulation in living organisms. However, the chemical natures of ILs are not quintessentially biocompatible. Therefore, the practical uses of ILs must be preceded by suitable toxicological assessments. Among different methods, the use of microorganisms to evaluate IL toxicity provides many advantages including short generation time, rapid growth, and environmental and industrial relevance. This article reviews the recent research progress on the toxicological properties of ILs toward microorganisms and highlights the computational prediction of various toxicity models.