Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair.     

C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance.     

Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1)

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.     

Improved inhibitory activities against tumor-cell migration and invasion by 15-benzylidene substitution derivatives of andrographolide

In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure–activity relationships were studied. Compared to 1, compounds 8a–8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs.     

Phylogeography of Sophora davidii (Leguminosae) across the ‘Tanaka‐Kaiyong Line’, an important phytogeographic boundary in Southwest China

The ‘Tanaka‐Kaiyong Line’ (TKL) is a major phytogeographic boundary in Southwest China, separating East Asia's Sino‐Himalayan and Sino‐Japanese Floras. However, little is known about the importance of this boundary in promoting intraspecific phylogeographic subdivision and divergence. Using chloroplast (cpDNA) and nuclear‐intron (nDNA) sequence data, we reconstructed the population history of Sophora davidii, a drought‐tolerant riparian shrub widely distributed on either side of the TKL. Specifically, we aimed at testing two long‐standing explanations for possible vicariant events across the TKL: (i) Late Pliocene (c. 3 Ma) geological uplift of the eastern Qinghai‐Tibetan Plateau (QTP) or (ii) a sharp environmental gradient associated with the establishment of different monsoon regimes on either side of the TKL during the (Late) Pleistocene. Our genealogical analyses detected a major west–east split in cpDNA, geographically largely consistent with the TKL, and dated to c. 1.28 Ma (95% HPD: 0.21–2.96 Ma), hence postdating the latest phase of eastern QTP uplift. Furthermore, integrating cpDNA phylogeographic patterns with mismatch analyses, we found multiple refugial isolation and long‐term demographic stability of populations in the west (Hengduan Mountain Range) compared with extensive range expansions in the east, possibly during the last glacial period(s) and followed by differentiation into regional sublineages (southeast: Yunnan‐Guizhou Plateau vs. northeast: Qinling Mts./Loess Plateau). Although nuclear differentiation was less marked, the geographical pattern of nDNA haplotypes provided some further indication of the species' eastward expansion, possibly from source populations located just east of the TKL (lower Jinshajiang region). Overall, the present data reject the geological (tectonic) explanation for the TKL and, instead, provide supportive evidence for its role as a climatically driven barrier to present‐day plant dispersal. In addition, our study highlights changing temperatures and vegetation types during the last glacial period(s), along with aspects of regional topography, to be important determinants of the glacial eastward expansion of S. davidii. In consequence, our study lends support to a ‘glacial out‐of‐Hengduan Mts’. hypothesis for the xerophytic‐riparian flora of Southwest China, which in turn is inconsistent with the traditional view of the TKL as a ‘classical’ vicariant‐biogeographic boundary.     

Impact of GC content on gene expression pattern in chicken

Background

GC content varies greatly between different genomic regions in many eukaryotes. In order to determine whether this organization named isochore organization influences gene expression patterns, the relationship between GC content and gene expression has been investigated in man and mouse. However, to date, this question is still a matter for debate. Among the avian species, chicken (Gallus gallus) is the best studied representative with a complete genome sequence. The distinctive features and organization of its sequence make it a good model to explore important issues in genome structure and evolution.

Methods

Only nuclear genes with complete information on protein-coding sequence with no evidence of multiple-splicing forms were included in this study. Chicken protein coding sequences, complete mRNA sequences (or full length cDNA sequences), and 5^′ untranslated region sequences (5^′ UTR) were downloaded from Ensembl and chicken expression data originated from a previous work. Three indices i.e. expression level, expression breadth and maximum expression level were used to measure the expression pattern of a given gene. CpG islands were identified using hgTables of the UCSC Genome Browser. Correlation analysis between variables was performed by SAS Proprietary Software Release 8.1.

Results

In chicken, the GC content of 5^′ UTR is significantly and positively correlated with expression level, expression breadth, and maximum expression level, whereas that of coding sequences and introns and at the third coding position are negatively correlated with expression level and expression breadth, and not correlated with maximum expression level. These significant trends are independent of recombination rate, chromosome size and gene density. Furthermore, multiple linear regression analysis indicated that GC content in genes could explain approximately 10% of the variation in gene expression.

Conclusions

GC content is significantly associated with gene expression pattern and could be one of the important regulation factors in the chicken genome.     

原生质体融合技术选育分解草酸乳酸菌菌株的研究

将具有草酸分解能力的乳双歧杆菌和具有耐氧特性的嗜酸乳杆菌进行原生质体融合,其最佳条件为:50%的PEG6000,融合温度30℃,融合时间为7 min,CaCl2浓度为0.02 mol/L,MgCl2浓度为0.5 mol/L,在此条件下融合率可达7.6%。从中筛选出同时具有耐氧特性和草酸分解能力的融合子,草酸分解率为13.4%。     

Polyphyly of the Padus group of Prunus (Rosaceae) and the evolution of biogeographic disjunctions between eastern Asia and eastern North America

Prunus subgenus Padus is a group with a wide distribution in temperate eastern Asia and eastern North America with one species extending to Europe and one to Central America. Phylogenetic relationships of subgenus Padus were reconstructed using sequences of nuclear ribosomal ITS, and plastid ndhF gene, and rps16 intron and rpl16 intron. Prunus subgenus Padus is shown to be polyphyletic. Taxa of subgenus Padus and subgenus Laurocerasus are highly intermixed in both the ITS and the plastid trees. The results support two disjunctions between eastern North America and Eurasia within the Padus group. One disjunction is between Prunus virginiana of eastern North America and P. padus of Eurasia, estimated to have diverged at 2.99 (95 % HPD 0.59–6.15)–4.1 (95 % HPD 0.63–8.59) mya. The other disjunction is between P. serotina and its Asian relatives. The second disjunction may have occurred earlier than the former one, but the age estimate is difficult due to the unresolved phylogenetic position of the P. serotina complex.     

MicroRNAs Involved in Skeletal Muscle Differentiation

MicroRNAs (miRNAs) negatively regulate gene expression by promoting degradation of target mRNAs or inhibiting their translation. Previous studies have expanded our understanding that miRNAs play an important role in myogenesis and have a big impact on muscle mass, muscle fiber type and muscle-related diseases. The muscle-specific miRNAs, miR-206, miR-1 and miR-133, are among the most studied and best characterized miRNAs in skeletal muscle differentiation. They have a profound influence on multiple muscle differ-entiation processes, such as alternative splicing, DNA synthesis, and cell apoptosis. Many non-muscle-specific miRNAs are also required for the differentiation of muscle through interaction with myogenic factors. Studying the regulatory mechanisms of these miRNAs in muscle differentiation will extend our knowledge of miRNAs in muscle biology and will improve our understanding of the myogenesis regulation.     

Pulmonary Tuberculosis Incidence and Risk Factors in Rural Areas of China: A Cohort Study

The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies.