Solving the 100 Swiss Francs Problem

Sturmfels offered 100 Swiss Francs in 2005 to a conjecture, which deals with a special case of the maximum likelihood estimation for a latent class model. This paper confirms the conjecture positively

Dexmedetomidine inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascades

NOD-like receptor 3 (NLRP3) plays critical roles in the initiation of inflammasome-mediated inflammation in microglia, thus becomes an important therapeutic target of Alzheimer’s disease (AD). Dexmedetomidine (Dex), a new type of clinical anesthetic agent, shows anti-inflammatory properties and inhibits postoperative cognitive dysfunction in AD patients. The present study was aimed to investigate effect of Dex on NLRP3 activity in activated microglia and reveal the underlying mechanisms. The human microglia clone 3 (HMC3) cells were exposed to 100 ng/ml LPS and 5 mM ATP, in the presence and absence of doses of Dex. Data from ELISA and Western blot assays showed that Dex abrogated the promoting effects of LPS/ATP on the release of pro-inflammatory cytokines including IL-1ß and IL-18 in the cell medium and the expression of NLRP3 and its downstream target caspase-1 in HMC3 cells. Furthermore, the present study found that exposure of HMC3 cells to LPS/ATP increased nuclear protein levels of transcription factor c-Fos, but treatment with Dex reversed the increase in c-Fos, as indicated by Western blot and immunofluorescence measures. Luciferase reported assay revealed that c-Fos can bind to the promoter region of NLRP3 gene and positively regulate the expression. These results suggest that Dex inhibiting c-Fos nuclear protein levels promoted by LPS/ATP blocks the up-regulation of NLRP3. This suggestion is supported by co-immunoprecipitation and PCR studies, in which Dex decreased the amount of c-Fos that binds to NLRP3 under the stimulation of LPS/ATP. The present study revealed that Dex inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascades, which adds new understanding of the anti-inflammatory mechanism of Dex

Urbanization Further Intensifies Short-Duration Rainfall Extremes in a Warmer Climate

Abstract Intensification of short-duration rainfall extremes contributes to increased urban flood risk. Yet, it remains unclear how upper-tail rainfall statistics could change with regional warming. Here, we characterize the non-stationarity of rainfall extremes over durations of 1?24 hr for the rapidly developing coastal megalopolis of the Greater Bay Area, China. Using high-resolution, multi-source, merged and gridded data we observe greater increases in rainfall intensities over the north-central part of the region compared with the southern coastal region. Our results show, for the first time, that urbanization nonlinearly increases rainfall intensities at different durations and return periods. Over short durations (≤3-hr) and short return periods (2-yr), urban areas have the greatest scaling rates (≥19.9%/°C). However, over longer durations (≥9-hr) rural areas have greater scaling rates, with a lower degree of dependency on both durations and return periods

Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells.</p> <p>Methods</p> <p>We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID₅₀assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods.</p> <p>Results</p> <p>Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice.</p> <p>Conclusions</p> <p>These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.</p

Identification of flavone phytoalexins and a pathogen-inducible flavone synthase II gene (SbFNSII) in sorghum

Following inoculation with the anthracnose pathogen Colletotrichum sublineolum, seedlings of the sorghum resistant cultivar SC748-5 showed more rapid and elevated accumulation of luteolin than the susceptible cultivar BTx623. On the other hand, apigenin was the major flavone detected in infected BTx623 seedlings. Luteolin was demonstrated to show stronger inhibition of spore germination of C. sublineolum than apigenin. Because of their pathogen-inducible and antifungal nature, both flavone aglycones are considered sorghum phytoalexins. The key enzyme responsible for flavone biosynthesis has not been characterized in monocots. A sorghum pathogen-inducible gene encoding a cytochrome P450 protein (CYP93G3) in the uncharacterized CYP93G subfamily was identified. Transgenic expression of the P450 gene in Arabidopsis demonstrated that the encoded protein is a functional flavone synthase (FNS) II in planta. The sorghum gene was then termed SbFNSII. It is a single-copy gene located on chromosome 2 and the first FNSII gene characterized in a monocot. Metabolite analysis by liquid chromatography–tandem mass spectrometry (LC-MS/MS) in precursor ion scan mode revealed the accumulation of 2-hydroxynaringenin and 2-hydroxyeriodictyol hexosides in the transgenic Arabidopsis plants. Hence, SbFNSII appears to share a similar catalytic mechanism with the licorice and Medicago truncatula FNSIIs (CYP93B subfamily) by converting flavanones to flavone through the formation of 2-hydroxyflavanones

Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion

Angiogenesis is increasingly recognized as an important prognosticator associated with the progression of lymphoma and as an attractive target for novel modalities. We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. Global gene expression profiles of microdissected endothelium from lymphoma and reactive lymph nodes revealed that T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) was preferentially expressed in lymphoma-derived endothelial cells (ECs). Clinically, the level of Tim-3 in B cell lymphoma endothelium was closely correlated to both dissemination and poor prognosis. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization, and providing protective immunity. In a lymphoma mouse model, Tim-3–expressing ECs promoted the onset, growth, and dissemination of lymphoma by inhibiting activation of CD4+ T cells and Th1 polarization. Our findings strongly argue that the lymphoma endothelium is not only a vessel system but also a functional barrier facilitating the establishment of lymphoma immune tolerance. These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases

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