Ethyl 1-(6-chloro-3-pyridylmeth­yl)-5-methyl-1H-1,2,3-triazole-4-carboxyl­ate

In the title compound, C12H13ClN4O2, the triazole ring carries methyl and ethoxy­carbonyl groups, and is bound via a methyl­ene bridge to a chloro­pyridine unit. There is evidence for significant electron delocalization in the triazolyl system. Intra­molecular C—H⋯O and inter­molecular C—H⋯N hydrogen bonds stabilize the structure

Altered Brain Functional Hubs and Connectivity Underlie Persistent Somatoform Pain Disorder

This study investigated the degree of brain functional impairment in persistent somatoform pain disorder (PSPD) by examining changes in the patterns of brain functional hubs. Resting-state functional magnetic resonance imaging was performed in 21 PSPD patients with headache as the main symptom and 17 sex- and age-matched healthy controls. Degree centrality (DC) analysis as well as the connectivity among these hubs by functional connectivity (FC) analysis and Granger causality analysis (GCA) were performed to characterize abnormal brain networks in PSPD (Gaussian random field corrected: P < 0.001, Z > 3.09). The relationships between DC and connectivity and clinical parameters were also examined. DC values in the bilateral inferior occipital gyrus (IOG), bilateral calcarine fissure (CAL), and left paracentral lobule (PCL) and FC values of right IOG–left CAL, right IOG–right CAL, right IOG–left IOG, left CAL–right CAL, left CAL–left IOG, left CAL–left PCL, right CAL–left PCL, and left IOG–left PCL were lower in PSPD patients as compared to controls. A negative causal effect from the left CAL to the left paracentral lobule and a positive effect from the right CAL to the right IOG were observed in PSPD patients. Abnormal DC, FC, and signed-path coefficients in PSPD patients were negatively correlated with self-rating anxiety and depression scale scores. These results indicate that altered functional hubs and connectivity patterns in the somatosensory cortex may reflect emotional disturbance in PSPD patients

Arabidopsis NMD3 Is Required for Nuclear Export of 60S Ribosomal Subunits and Affects Secondary Cell Wall Thickening

NMD3 is required for nuclear export of the 60S ribosomal subunit in yeast and vertebrate cells, but no corresponding function of NMD3 has been reported in plants. Here we report that Arabidopsis thaliana NMD3 (AtNMD3) showed a similar function in the nuclear export of the 60S ribosomal subunit. Interference with AtNMD3 function by overexpressing a truncated dominant negative form of the protein lacking the nuclear export signal sequence caused retainment of the 60S ribosomal subunits in the nuclei. More interestingly, the transgenic Arabidopsis with dominant negative interference of AtNMD3 function showed a striking failure of secondary cell wall thickening, consistent with the altered expression of related genes and composition of cell wall components. Observation of a significant decrease of rough endoplasmic reticulum (RER) in the differentiating interfascicular fiber cells of the transgenic plant stems suggested a link between the defective nuclear export of 60S ribosomal subunits and the abnormal formation of the secondary cell wall. These findings not only clarified the evolutionary conservation of NMD3 functions in the nuclear export of 60S ribosomal subunits in yeast, animals and plants, but also revealed a new facet of the regulatory mechanism underlying secondary cell wall thickening in Arabidopsis. This new facet is that the nuclear export of 60S ribosomal subunits and the formation of RER may play regulatory roles in coordinating protein synthesis in cytoplasm and transcription in nuclei

3-Isopropyl-2-p-tol­yloxy-5,6,7,8-tetra­hydro-1-benzothieno[2,3-d]pyrimidin-4(3H)-one

In the title compound, C20H22N2O2S, the central thieno­pyrimidine ring system is essentially planar, with a maximum displacement of 0.023 (2) Å. The attached cyclo­hexene ring is disordered over two possible conformations, with an occupancy ratio of 0.776 (12):0.224 (12). Neither inter­molecular hydrogen-bonding inter­actions nor π–π stacking inter­actions are present in the crystal structure. The mol­ecular conformation and crystal packing are stabilized by three intra­molecular C—H⋯O hydrogen bonds and two C—H⋯π inter­actions

Clinical significance of Neutrophil gelatinase-associated lipocalin(NGAL) expression in primary rectal cancer

<p>Abstract</p> <p>Background</p> <p>Emerging evidence has demonstrated that Neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated in multiple malignancies, including oesophagus cancer, and plays a critical role in tumorigenesis and progression. However, till now, little is known about the role of NGAL in human rectal cancer. Its association with clinicopathologic characteristics and expression of MMP-9, one of its target genes, has not been reported systematically in rectal cancer. Therefore, to further determine the potential involvement of NGAL in rectal cancer, we have evaluated the expression level of NGAL mRNA by real time RT-PCR, and further elucidated the correlation of NGAL mRNA expression with clinicopathologic features and MMP-9 in rectal cancer.</p> <p>Methods</p> <p>100 paired samples of rectal cancer and adjacent normal tissues obtained from inpatients undergoing surgical operation were allocated into two groups (cancer group and control group). The mRNA expression of NGAL and MMP-9 was determined by real-time RT-PCR. The association between their expression and clinicopathological characteristics of rectal cancer were analysised.</p> <p>Results</p> <p>Among the 100 rectal cancers, 69 cases of NGAL mRNA up-regulation were observed. NGAL mRNA up-regulation was positively correlated with MMP-9 (<it>r</it>_s= 0.393, <it>p </it>< 0.001). In rectal cancer, NGAL mRNA overexpression was significantly associated with depth of invasion (<it>p </it>= 0.028), lymph node metastasis (<it>p </it>= 0.009), venous involvement (<it>p </it>= 0.023) and advanced pTNM stage (<it>p </it>= 0.011).</p> <p>Conclusion</p> <p>In human rectal cancer, NGAL mRNA expression was elevated. NGAL mRNA up-regulation was correlated significantly with tumor progression and MMP-9 mRNA overexpression in rectal cancer, suggesting a more aggressive phenotype. NGAL could be used for rectal cancer characterization.</p

Dissecting Genetic Networks Underlying Complex Phenotypes: The Theoretical Framework

Great progress has been made in genetic dissection of quantitative trait variation during the past two decades, but many studies still reveal only a small fraction of quantitative trait loci (QTLs), and epistasis remains elusive. We integrate contemporary knowledge of signal transduction pathways with principles of quantitative and population genetics to characterize genetic networks underlying complex traits, using a model founded upon one-way functional dependency of downstream genes on upstream regulators (the principle of hierarchy) and mutual functional dependency among related genes (functional genetic units, FGU). Both simulated and real data suggest that complementary epistasis contributes greatly to quantitative trait variation, and obscures the phenotypic effects of many ‘downstream’ loci in pathways. The mathematical relationships between the main effects and epistatic effects of genes acting at different levels of signaling pathways were established using the quantitative and population genetic parameters. Both loss of function and “co-adapted” gene complexes formed by multiple alleles with differentiated functions (effects) are predicted to be frequent types of allelic diversity at loci that contribute to the genetic variation of complex traits in populations. Downstream FGUs appear to be more vulnerable to loss of function than their upstream regulators, but this vulnerability is apparently compensated by different FGUs of similar functions. Other predictions from the model may account for puzzling results regarding responses to selection, genotype by environment interaction, and the genetic basis of heterosis