Do TNF-alpha-insensitive cancer cells escape alpha-tubulin nitrotyrosination?

TNF-alpha induces tumor-selective cytotoxicity in certain cancers, but many tumors are resistant to the effects of this inflammatory cytokine. This brief hypothesis outlines my views that nitric oxide-mediated alpha-tubulin posttranslational nitrotyrosination may be a major mechanism through which TNF-alpha exerts its cytotoxic effects on cancer cells. Additionally, I propose that tumor cells that are resistant to the effects of TNF-alpha may be so because of suppressed levels of "tubulin tyrosine ligase," which is responsible for the posttranslational tyrosination of alpha-tubulin.     

Metal Halide Perovskites for Solar‐to‐Chemical Fuel Conversion

This review article presents and discusses the recent progress made in the stabilization, protection, improvement, and design of halide perovskite‐based photocatalysts, photoelectrodes, and devices for solar‐to‐chemical fuel conversion. With the target of water splitting, hydrogen iodide splitting, and CO₂ reduction reactions, the strategies established for halide perovskites used in photocatalytic particle‐suspension systems, photoelectrode thin‐film systems, and photovoltaic‐(photo)electrocatalysis tandem systems are organized and introduced. Moreover, recent achievements in discovering new and stable halide perovskite materials, developing protective and functional shells and layers, designing proper reaction solution systems, and tandem device configurations are emphasized and discussed. Perspectives on the future design of halide perovskite materials and devices for solar‐to‐chemical fuel conversion are provided. This review may serve as a guide for researchers interested in utilizing halide perovskite materials for solar‐to‐chemical fuel conversion.     

Phencyclidine (PCP) blocks glutamate-activated postsynaptic currents

Phencyclidine (PCP) was tested on the metathoracic tibialis muscles of Locusta migratoria. In physiological solution, the peak amplitude of the excitatory postsynaptic currents (EPSCs) evoked by nerve stimulation was linearly related to membrane potential between -50 and -150 mV. The decay time constant of the EPSC (tau EPSC) was exponentially dependent on voltage and decreased with hyperpolarization. The membrane potential change required to produce an e-fold change in tau EPSC was 315 mV. PCP (5-40 microM) produced a concentration-dependent depression of both EPSC peak amplitude and tau EPSC. A slight nonlinearity in the current-voltage relationship could be discerned at high concentrations of PCP. The shortening of the decay time constant of EPSC (tau EPSC) occurred without significant change in the voltage sensitivity observed under control conditions. Under all experimental conditions, the decay of the EPSCs remained a single exponential of time. Fluctuation analysis indicated that 5 microM PCP shortens the lifetime of the glutamate-activated channels by 25.7 +/- 3%. PCP (10-80 microM) did not induced desensitization of the glutamate receptors. These results suggest that PCP interacts with the open conformation of ion channels activated by the glutamate receptor.     

Synthesis and receptor binding studies of halogenated N,N-dialkylel-(2-phenyl-1H-indol-3-yl)glyoxylamides to visualize peripheral benzodiazepine receptors with SPECT or PET

A library of halogenated 2-arylindolyl-3-oxocarboxamides was prepared to develop radioligands to visualize cerebral PBR by SPECT and PET imaging. In vitro evaluation showed that most of the synthesized compounds were selective,high-affinity PBR ligands with adequate lipophilicity (log D7.4 in the range of 1.6-2.4). The iodinated derivative 11 (Ki = 2.6 nM) and the fluorinated analog 26 (Ki = 6.2 nM) displayed higher affinity than reference compounds.     

Characterization of the antigenicity of the formiminotransferase-cyclodeaminase in type 2 autoimmune hepatitis

Human formiminotransferase-cyclodeaminase (hFTCD) is the autoantigen recognized by anti-liver cytosol type 1 (LC1) autoantibodies in type 2 autoimmune hepatitis (AIH) patients. In rats, this octameric protein is localized on the Golgi apparatus and binds brain microtubules (MTs) and vimentin. Subcellular localization of human formiminotransferase-cyclodeaminase and its implication in the pathogenesis of autoimmune hepatitis are unknown. Localization of the human formiminotransferase-cyclodeaminase in human hepatocytes was done using indirect immunofluorescence and subcellular fractionations followed by in vitro binding techniques. The formiminotransferase-cyclodeaminase antigen at two distinct locations in hepatocytes, free in the cytosol and associated with the Golgi membranes are recognized by anti-liver cytosol type 1 autoantibodies. The human formiminotransferase-cyclodeaminase binds reversibly to the Golgi membranes and this complex formation is increased by anti-liver cytosol type 1 autoantibodies. Finally, human formiminotransferase-cyclodeaminase does not interact with liver-specific cytoskeleton proteins. Anti-liver cytosol type 1 autoantibodies are directed against the mature high molecular form of human formiminotransferase-cyclodeaminase. Therefore, the subcellular location of the protein may influence the production of autoantibodies and their role in the pathogenesis of type 2 autoimmune hepatitis. This antigen-driven response does not appear to be facilitated or enhanced by a possible interaction between human formiminotransferase-cyclodeaminase and hepatocyte cytoskeleton proteins.     

新疆罗布泊小河墓地居民的口腔健康与饮食

小河墓地是新疆罗布泊地区一处重要的早期青铜时代墓地。本文主要对该墓地出土颅骨所附牙齿的磨耗程度及牙结石沉积状况进行了观察、量化统计和分析,同时也对该人群其他的口腔疾病如根尖脓肿、颞下颌关节病变、生前牙齿脱落等做了简单的统计,以期从古病理学的角度获取当时居民的口腔健康、食物类型和饮食习惯等信息。本研究发现:1)小河人群的牙齿磨耗程度远远高于对比组的古代居民,其上腭圆枕及颞下颌关节炎出现率较高,存在牙齿崩裂现象,且其前后部牙齿磨耗差异不大。这一方面说明其食物加工技术比较落后,食物粗糙坚硬;另一方面小河居民的经济生活方式和食物构成都比较复杂,不同的食物对前部和后部牙齿磨耗的程度造成了不同的影响;此外,小河人群风沙肆虐的生活环境也对其严重牙齿磨耗的形成产生了一定影响。2)小河人群异常严重的牙结石沉积归功于其高蛋白质和碳水化合物的饮食,以及生活用水的水质。3)统计分析发现两性存在上、下颌犬齿的磨耗差异,而这一情况可能暗示了在家庭手工业方面存在男女分工的现象。     

DNA polymerase beta

Mammalian DNA polymerase beta(beta-pol) is a single polypeptide chain enzyme of 39kDa. beta-pol has enzymatic activities appropriate for roles in base excision repair and other DNA metabolism events involving gap-filling DNA synthesis. Many crystal structures of beta-pol complexed with dNTP and DNA substrates have been solved, and mouse fibroblast cell lines deleted in the beta-pol gene have been examined. These approaches have enhanced our understanding of structural and functional aspects of beta-pol's role in protecting genomic DNA.     

ASSIST Applicability Scoring of Surgical trials. An Investigator-reported aSsessment Tool

Context

We aimed to develop a new tool for assessing and depicting the applicability of the results of surgical randomized controlled trials (RCTs) from the trial investigators'' perspective.

Methods

We identified all items related to applicability by a systematic methodological review, and then a sample of surgeons used these items in a web-based survey to evaluate the applicability of their own trial results. For each applicability item, participants had to indicate on a numerical scale that was simplified as a three-item scale: 1) items essential to consider, 2) items requiring attention, and 3) items inconsequential to the applicability of the results of their own RCT to clinical practice. For the final tool, we selected only items that were rated as being essential or requiring attention for at least 25% of the trials evaluated. We propose a specific process to construct the tool and to depict applicability in a graph. We identified all investigators of published and registered ongoing RCTs assessing surgery and invited them to participate in the web-based survey.

Results

148 surgeons assessed applicability for their own trial and participated in the process of item selection. The final tool contains 22 items (4 dedicated to patients, 5 to centers, 5 to surgeons and 8 to the intervention). We proposed a straightforward process of constructing the graphical tool: 1) a multidisciplinary team of investigators or other care providers participating in the trial could independently assess each item, 2) a consensus method could be used, and 3) the investigators could depict their assessment of the applicability of the trial results in 4 graphs related to patients, centers, surgeons and the intervention.

Conclusions

This investigator-reported assessment tool could help readers define under what conditions they could reasonably apply the results of a surgical RCT to their clinical practice.     

Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene

The transformer (tra) gene regulates female somatic sexual differentiation and has no known function in males. It gives rise to two sizes of RNA, one non-sex-specific and one female-specific. These two RNAs are shown to be present throughout the life cycle, and related by the use of alternative first intron splice acceptor sites. The non-sex-specific RNA has a 73 base first intron, while that in the female-specific RNA is 248 bases. The non-sex-specific RNA has no long open reading frame, while the female-specific RNA has a single long open reading frame beginning at the first AUG. Substitution of a heat shock promoter for the tra promoter still leads to female-specific differentiation of otherwise tra-females. We suggest a mechanism by which Sex-lethal controls itself and tra.