4,4′-(o-Phenyl­enedioxy­dimethyl­ene)dipyridinium dinitrate

The cation of the salt, C18H18N2O2 2+·2NO3 −, lies about a twofold rotation axis. The pyridinium ring is almost coplanar with the phenyl­ene ring [dihedral angle between rings = 5.69 (9)°]. The crystal structure shows π–π stacking inter­actions [centroid–centroid distance = 3.70 (1) Å] between the pyridinium rings and the phenyl­ene rings, generating a linear chain structure. The cation also forms two N—H⋯O hydrogen bonds to two nitrate groups

Amyloid-like aggregates of neuronal tau induced by formaldehyde promote apoptosis of neuronal cells

BACKGROUND: The microtubule associated protein tau is the principle component of neurofibrillar tangles, which are a characteristic marker in the pathology of Alzheimer's disease; similar lesions are also observed after chronic alcohol abuse. Formaldehyde is a common environmental contaminant and also a metabolite of methanol. Although many studies have been done on methanol and formaldehyde intoxication, none of these address the contribution of protein misfolding to the pathological mechanism, in particular the effect of formaldehyde on protein conformation and polymerization. RESULTS: We found that unlike the typical globular protein BSA, the natively-unfolded structure of human neuronal tau was induced to misfold and aggregate in the presence of ~0.01% formaldehyde, leading to formation of amyloid-like deposits that appeared as densely staining granules by electron microscopy and atomic force microscopy, and bound the amyloid-specific dyes thioflavin T and Congo Red. The amyloid-like aggregates of tau were found to induce apoptosis in the neurotypic cell line SH-SY5Y and in rat hippocampal cells, as observed by Hoechst 33258 staining, assay of caspase-3 activity, and flow cytometry using Annexin V and Propidium Iodide staining. Further experiments showed that Congo Red specifically attenuated the caspase-3 activity induced by amyloid-like deposits of tau. CONCLUSION: The results suggest that low concentrations of formaldehyde can induce human tau protein to form neurotoxic aggregates, which could play a role in the induction of tauopathies

(Z)-N-{3-[(6-Chloro­pyridin-3-yl)meth­yl]-1,3-thia­zolidin-2-yl­idene}cyanamide

The asymmetric unit of the title compound, C10H9ClN4S, common name thia­cloprid, comprises two mol­ecules. In both mol­ecules, the thia­zolidine rings are almost planar (with r.m.s. deviations of 0.016 and 0.065 Å) and form dihedral angles of 73.36 (6) and 70.25 (8)° with the 2-chloro­pyridine rings. In the crystal, inter­molecular C—H⋯N hydrogen bonds links the mol­ecules into chains propagating in [01]

Intranasal immunization with a helper-dependent adenoviral vector expressing the codon-optimized fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in BALB/c mice

BACKGROUND: Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract. Currently, there is no clinically approved vaccine against RSV infection. Recent studies have shown that helper-dependent adenoviral (HDAd) vectors may represent effective and safe vaccine vectors. However, viral challenge has not been investigated following mucosal vaccination with HDAd vector vaccines. METHODS: To explore the role played by HDAd as an intranasally administered RSV vaccine vector, we constructed a HDAd vector encoding the codon optimized fusion glycoprotein (Fsyn) of RSV, designated HDAd-Fsyn, and delivered intranasally HDAd-Fsyn to mice. RESULTS: RSV-specific humoral and cellular immune responses were generated in BALB/c mice, and serum IgG with neutralizing activity was significantly elevated after a homologous boost with intranasal (i.n.) application of HDAd-Fsyn. Humoral immune responses could be measured even 14 weeks after a single immunization. Immunization with i.n. HDAd-Fsyn led to effective protection against RSV infection on challenge. CONCLUSION: The results indicate that HDAd-Fsyn can induce powerful systemic immunity against subsequent i.n. RSV challenge in a mouse model and is a promising candidate vaccine against RSV infection

A visible, targeted high-efficiency gene delivery and transfection strategy

<p>Abstract</p> <p>Background</p> <p>To enhance myocardial angiogenic gene expression, a novel gene delivery strategy was tested. Direct intramyocardial injection of an angiogenic gene with microbubbles and insonation were applied in a dog animal model. Dogs received one of the four different treatments in conjunction with either the enhanced green fluorescence protein (EGFP) gene or the hepatocyte growth factor (HGF) gene: gene with microbubbles (MB) and ultrasound (US); gene with US; gene with MB; or the gene alone.</p> <p>Results</p> <p>Distribution of MB and the gene in the myocardium was visualized during the experiment. Compared with the EGFP gene group, an average 14.7-fold enhancement in gene expression was achieved in the EGFP+MB/US group (P < 0.01). Compared with the HGF gene group, an average 10.7-fold enhancement in gene expression was achieved in the HGF+MB/US group (P < 0.01). In addition, capillary density increased from 20.8 ± 3.4/mm2 in the HGF gene group to 146.7 ± 31.4/mm2 in HGF+MB/US group (P < 0.01).</p> <p>Conclusions</p> <p>Thus, direct intramyocardial injection of an angiogenic gene in conjunction with microbubbles plus insonation synergistically enhances angiogenesis. This method offers an observable gene delivery procedure with enhanced expression efficiency of the delivered gene.</p

Biomedical Question Answering: A Survey of Approaches and Challenges

Automatic Question Answering (QA) has been successfully applied in various domains such as search engines and chatbots. Biomedical QA (BQA), as an emerging QA task, enables innovative applications to effectively perceive, access and understand complex biomedical knowledge. There have been tremendous developments of BQA in the past two decades, which we classify into 5 distinctive approaches: classic, information retrieval, machine reading comprehension, knowledge base and question entailment approaches. In this survey, we introduce available datasets and representative methods of each BQA approach in detail. Despite the developments, BQA systems are still immature and rarely used in real-life settings. We identify and characterize several key challenges in BQA that might lead to this issue, and discuss some potential future directions to explore.Comment: In submission to ACM Computing Survey

A novel variant of ER-alpha, ER-alpha36 mediates testosterone-stimulated ERK and Akt activation in endometrial cancer Hec1A cells

<p>Abstract</p> <p>Background</p> <p>Endometrial cancer is one of the most common gynecologic malignancies and its incidence has recently increased. Experimental and epidemiological data support that testosterone plays an important role in the pathogenesis of endometrial cancer, but the underlying mechanism has not been fully understood. Recently, we identified and cloned a variant of estrogen receptor (ER) alpha, ER-alpha36. The aim of the present study was to investigate the role of ER-alpha36 in testosterone carcinogenesis.</p> <p>Methods</p> <p>The cellular localization of ER-alpha36 was determined by immunofluorescence. Hec1A endometrial cancer cells (Hec1A/V) and Hec1A cells with siRNA knockdown of ER-alpha36 (Hec1A/RNAi) were treated with testosterone, ERK and Akt phosphorylation was assessed by Western blot analysis. Furthermore, the kinase inhibitors U0126 and LY294002 and the aromatase inhibitor letrozole were used to elucidate the pathway underlying testosterone-induced activities.</p> <p>Results</p> <p>Immunofluorescence shows that ER-alpha36 was localized on the plasma membrane of the both ER-alpha- and androgen receptor-negative endometrial cancer Hec1A cells. Testosterone induced ERK and Akt phosphorylation, which could be abrogated by ER-alpha 36 shRNA knockdown or the kinase inhibitors, U0126 and LY294002, and the aromatase inhibitor letrozole.</p> <p>Conclusion</p> <p>Testosterone induces ERK and Akt phosphorylation via the membrane-initiated signaling pathways mediated by ER-alpha36, suggesting a possible involvement of ER-alpha 36 in testosterone carcinogenesis.</p

Temporal and spatial distribution of phosphorus in the Xiangxi River

The phosphorus in water and sediment collected at different time from the Xiangxi River were analyzed. The results indicated that the phosphorus pollution have significant relations to human activities (especially the phosphorus industry). The concentrations of total-phosphorus (TP), total dissolved phosphorus (TDP) and dissolved phosphorus (DP) in Dec. 2004 were higher than those in Jul. 2005; the TP contents of sites 15 and 16 were much higher than others', the TP content of the largest site 16 was 1946.29 mg/kg in Dec. 2004 and 1756.11 mg/kg in Jul. 2005, respectively, which was much higher than the average (1497.51 mg/kg and 1369.38 mg/kg, respectively). The TP content in the sediment of the Xiangxi River was from 1179.53 mg/kg to 1851. 20 mg/kg. The TP contents of most sites except site 18, 19 and 20 were higher in Dec. 2004 than those in Jul. 2005. The aluminium-phosphorus (Al-P) content in the sediment was obviously higher in Jul. 2005 than that in Dec. 2004, which indicated that the stability of Al-P has a significant relation to the change of season