Facile solution-phase synthesis of γ-Mn3O4 hierarchical structures

<p>Abstract</p> <p>Background</p> <p>A lot of effort has been focused on the integration of nanorods/nanowire as building blocks into three-dimensional (3D) complex superstructures. But, the development of simple and effective methods for creating novel assemblies of self-supported patterns of hierarchical architectures to designed materials using a suitable chemical method is important to technology and remains an attractive, but elusive goal.</p> <p>Results</p> <p>The hierarchical structure of Mn₃O₄with radiated spherulitic nanorods was prepared via a simple solution-based coordinated route in the presence of macrocycle polyamine, hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene (CT) with the assistance of thiourea as an additive.</p> <p>Conclusion</p> <p>This approach opens a new and facile route for the morphogenesis of Mn₃O₄material and it might be extended as a novel synthetic method for the synthesis of other inorganic semiconducting nanomaterials such as metal chalcogenide semiconductors with novel morphology and complex form, since it has been shown that thiourea can be used as an effective additive and the number of such water-soluble macrocyclic polyamines also makes it possible to provide various kinds of ligands for different metals in homogeneous water system.</p

A sequence-based genetic linkage map as a reference for Brassica rapa pseudochromosome assembly

<p>Abstract</p> <p>Background</p> <p><it>Brassica rapa </it>is an economically important crop and a model plant for studies concerning polyploidization and the evolution of extreme morphology. The multinational <it>B. rapa </it>Genome Sequencing Project (BrGSP) was launched in 2003. In 2008, next generation sequencing technology was used to sequence the <it>B. rapa </it>genome. Several maps concerning <it>B. rapa </it>pseudochromosome assembly have been published but their coverage of the genome is incomplete, anchoring approximately 73.6% of the scaffolds on to chromosomes. Therefore, a new genetic map to aid pseudochromosome assembly is required.</p> <p>Results</p> <p>This study concerns the construction of a reference genetic linkage map for <it>Brassica rapa</it>, forming the backbone for anchoring sequence scaffolds of the <it>B. rapa </it>genome resulting from recent sequencing efforts. One hundred and nineteen doubled haploid (DH) lines derived from microspore cultures of an F1 cross between a Chinese cabbage (<it>B. rapa </it>ssp. <it>pekinensis</it>) DH line (Z16) and a rapid cycling inbred line (L144) were used to construct the linkage map. PCR-based insertion/deletion (InDel) markers were developed by re-sequencing the two parental lines. The map comprises a total of 507 markers including 415 InDels and 92 SSRs. Alignment and orientation using SSR markers in common with existing <it>B. rapa </it>linkage maps allowed ten linkage groups to be identified, designated A01-A10. The total length of the linkage map was 1234.2 cM, with an average distance of 2.43 cM between adjacent marker loci. The lengths of linkage groups ranged from 71.5 cM to 188.5 cM for A08 and A09, respectively. Using the developed linkage map, 152 scaffolds were anchored on to the chromosomes, encompassing more than 82.9% of the <it>B. rapa </it>genome. Taken together with the previously available linkage maps, 183 scaffolds were anchored on to the chromosomes and the total coverage of the genome was 88.9%.</p> <p>Conclusions</p> <p>The development of this linkage map is vital for the integration of genome sequences and genetic information, and provides a useful resource for the international <it>Brassica </it>research community.</p

A Meta-Analysis of Caspase 9 Polymorphisms in Promoter and Exon Sequence on Cancer Susceptibility

BACKGROUND: Caspases are important regulators and executioners in apoptosis pathway and have been defined as either tumor suppressors or oncogenes. Polymorphisms in promoter and exon of caspase 9 were shown to confer genetic susceptibility to multiple cancers, but the results were inconsistent. To accomplish a more precise estimation of the relationship, a meta-analysis was performed. METHODOLOGY/PRINCIPAL FINDINGS: We assessed published studies of the association between caspase 9 polymorphisms and cancer risk from nine studies with 5,528 subjects for rs4645978, six studies with 2,403 subjects for rs105276 and two studies for rs4645981. Overall meta-analysis indicated that no evidence of an association between rs4645978 and cancers was found. Through the stratified analysis, statistically significant reduced cancer risks were observed among Caucasians (AG vs AA: OR = 0.81, 95% CI = 0.66-0.99, P(heterogeneity) = 0.150 and the dominant model: OR = 0.86, 95% CI = 0.75-0.99, P(heterogeneity) = 0.290) and prostate cancer. As for rs105276, Ex5+32G>A polymorphism was found with protective effect in overall meta-analysis (AA vs GG: OR = 0.75, 95% CI = 0.60-0.92, P(heterogeneity) = 0.887; A vs G: OR = 0.85, 95% CI = 0.77-0.95, P(heterogeneity) = 0.739 and the recessive model: OR = 0.68, 95% CI = 0.56-0.82, P(heterogeneity) = 0.309) and Asians group. While for rs4645981, a statistically significant increase in risk of lung cancer was shown in Asians (T vs C: OR = 1.23, 95% CI = 1.07-1.42, P(heterogeneity) = 0.399 and the dominant model: OR = 1.22, 95% CI = 1.04-1.43, P(heterogeneity) = 0.660). CONCLUSIONS/SIGNIFICANCE: Our meta-analysis suggests that the caspase 9 rs4645978 most likely contributes to decreased susceptibility to cancer in Caucasians and prostate cancer. The A allele of rs105276 might be a protective factor for cancer, especially for Asians. However, it seems that rs4645981 confers increased susceptibility to lung cancer in Asians

Structural Basis of Enzymatic Activity for the Ferulic Acid Decarboxylase (FADase) from Enterobacter sp. Px6-4

Microbial ferulic acid decarboxylase (FADase) catalyzes the transformation of ferulic acid to 4-hydroxy-3-methoxystyrene (4-vinylguaiacol) via non-oxidative decarboxylation. Here we report the crystal structures of the Enterobacter sp. Px6-4 FADase and the enzyme in complex with substrate analogues. Our analyses revealed that FADase possessed a half-opened bottom β-barrel with the catalytic pocket located between the middle of the core β-barrel and the helical bottom. Its structure shared a high degree of similarity with members of the phenolic acid decarboxylase (PAD) superfamily. Structural analysis revealed that FADase catalyzed reactions by an “open-closed” mechanism involving a pocket of 8×8×15 Å dimension on the surface of the enzyme. The active pocket could directly contact the solvent and allow the substrate to enter when induced by substrate analogues. Site-directed mutagenesis showed that the E134A mutation decreased the enzyme activity by more than 60%, and Y21A and Y27A mutations abolished the enzyme activity completely. The combined structural and mutagenesis results suggest that during decarboxylation of ferulic acid by FADase, Trp25 and Tyr27 are required for the entering and proper orientation of the substrate while Glu134 and Asn23 participate in proton transfer

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors

BACKGROUND: Nonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). However, the mechanism in which these factors control embryonic brain development is not clear. RESULT: We found that RBM8a is critical for proliferation and differentiation in cortical neural progenitor cells (NPCs). RBM8a is highly expressed in the subventricular zone (SVZ) of the early embryonic cortex, suggesting that RBM8a may play a role in regulating NPCs. RBM8a overexpression stimulates embryonic NPC proliferation and suppresses neuronal differentiation. Conversely, knockdown of RBM8a in the neocortex reduces NPC proliferation and promotes premature neuronal differentiation. Moreover, overexpression of RBM8a suppresses cell cycle exit and keeps cortical NPCs in a proliferative state. To uncover the underlying mechanisms of this phenotype, genome-wide RNAseq was used to identify potential downstream genes of RBM8a in the brain, which have been implicated in autism and neurodevelopmental disorders. Interestingly, autism and schizophrenia risk genes are highly represented in downstream transcripts of RBM8a. In addition, RBM8a regulates multiple alternative splicing genes and NMD targets that are implicated in ASD. Taken together, this data suggests a novel role of RBM8a in the regulation of neurodevelopment. CONCLUSIONS: Our studies provide some insight into causes of mental illnesses and will facilitate the development of new therapeutic strategies for neurodevelopmental illnesses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13064-015-0045-7) contains supplementary material, which is available to authorized users