Targeted Disruption of the Low-Affinity Leukemia Inhibitory Factor-Receptor Gene Causes Placental, Skeletal, Neural and Metabolic Defects and Results in Perinatal Death

The low-affinity receptor for leukemia inhibitory factor (LIFR)* interacts with gp130 to induce an intracellular signal cascade, The LIFR-gp130 heterodimer is implicated in the function of diverse systems, Normal placentation is disrupted in LIFR mutant animals, which leads to poor intrauterine nutrition but allows fetuses to continue to term. Fetal bone volume is reduced greater than three-fold and the number of osteoclasts is increased six-fold, resulting in severe osteopenia of perinatal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of glycogen, indicating a metabolic disorder. Hematologic and primordial germ cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth

MiR-128 Inhibits Tumor Growth and Angiogenesis by Targeting p70S6K1

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating glioma tumor angiogenesis via miR-128/p70S6K1 axis, and miR-128 may serve as a potential therapeutic target in glioma in the future

Spatial and seasonal distributions of carbonaceous aerosols over China

Author name used in this publication: S. C. LeeAuthor name used in this publication: S. H. Qi2007-2008 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

MiR-223 Suppresses Cell Proliferation by Targeting IGF-1R

To study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3′UTR(3′untranslated region) of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3′UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R

Community health needs assessment with precede-proceed model: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Community health services in China have developed over the last few decades. In order to use limited health resources more effectively, we conducted a community health needs assessment. This aimed to provide an understanding of the community's health problems and the range of potential factors affecting risk behaviours for the priority health problems.</p> <p>Methods</p> <p>We used the precede-proceed model for the needs assessment. Triangulation of data, methods and researchers were employed in data collection.</p> <p>Results</p> <p>Main findings include: cardiovascular diseases (CVDs) were identified as the priority health problems in the study communities; risk factors associated with CVDs included smoking, physical inactivity and unhealthy eating behaviours, particularly amongst male residents with low education level; factors negatively affecting behaviours were classified into predisposing factors (limited knowledge, beliefs and lack of perceived needs), enabling factors (limited access to health promotion activities, unawareness of health promotion, lack of work-site and school health promotion, absence of health promotion related policy) and reinforcing factors (culture). Policies and organization were not perfect; there were limited staff skilled in providing health promotion in the community.</p> <p>Conclusion</p> <p>CVDs were identified by the communities as priority health problems. Future health programs should focus on smoking, physical inactivity and unhealthy eating behaviours. Behaviour change strategies should take predisposing factors, enabling factors and reinforcing factors into consideration. Policies, organization and human resource need strengthening.</p

An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways

Developmenrt of EST-SSR and genomic-SSR markers to assess genetic diversity in Jatropha Curcas L.

<p>Abstract</p> <p>Background</p> <p><it>Jatropha curcas L. </it>has attracted a great deal of attention worldwide, regarding its potential as a new biodiesel crop. However, the understanding of this crop remains very limited and little genomic research has been done. We used simple sequence repeat (SSR) markers that could be transferred from <it>Manihot esculenta </it>(cassava) to analyze the genetic relationships among 45 accessions of <it>J. curcas </it>from our germplasm collection.</p> <p>Results</p> <p>In total, 187 out of 419 expressed sequence tag (EST)-SSR and 54 out of 182 genomic (G)-SSR markers from cassava were polymorphic among the <it>J. curcas </it>accessions. The EST-SSR markers comprised 26.20% dinucleotide repeats, 57.75% trinucleotide repeats, 7.49% tetranucleotide repeats, and 8.56% pentanucleotide repeats, whereas the majority of the G-SSR markers were dinucleotide repeats (62.96%). The 187 EST-SSRs resided in genes that are involved mainly in biological and metabolic processes. Thirty-six EST-SSRs and 20 G-SSRs were chosen to analyze the genetic diversity among 45 <it>J. curcas </it>accessions. A total of 183 polymorphic alleles were detected. On the basis of the distribution of these polymorphic alleles, the 45 accessions were classified into six groups, in which the genotype showed a correlation with geographic origin. The estimated mean genetic diversity index was 0.5572, which suggests that our <it>J. curcas </it>germplasm collection has a high level of genetic diversity. This should facilitate subsequent studies on genetic mapping and molecular breeding.</p> <p>Conclusion</p> <p>We identified 241 novel EST-SSR and G-SSR markers in <it>J. curcas</it>, which should be useful for genetic mapping and quantitative trait loci analysis of important agronomic traits. By using these markers, we found that the intergroup gene diversity of <it>J. curcas </it>was greater than the intragroup diversity, and that the domestication of the species probably occurred partly in America and partly in Hainan, China.</p