Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases

<p>Abstract</p> <p>Background</p> <p>Hepato-biliary tract lithiasis is common and present either as pain or as asymptomatic on abdominal ultrasonography for other causes. Although the DNA of <it>Helicobacter </it>species are identified in the gallbladder bile, tissue or stones analyzed from these cases, still a causal relationship could not be established due to different results from different geographical parts.</p> <p>Methods</p> <p>A detailed search of pubmed and pubmedcentral was carried out with key words <it>Helicobacter </it>and gallbladder, gallstones, hepaticolithiasis, cholelithiasis and choledocholithiasis, benign biliary diseases, liver diseases. The data was entered in a data base and meta analysis was carried out. The analysis was carried out using odds ratio and a fixed effect model, 95% confidence intervals for odds ratio was calculated. Chi square test for heterogeneity was employed. The overall effect was calculated using Z test.</p> <p>Results</p> <p>A total of 12 articles were identified. One study used IgG for diagnosis while others used the PCR for Ure A gene, 16 S RNA or Cag A genes. A couple of studies used culture or histopathology besides the PCR. The cumulative results show a higher association of <it>Helicobacter </it>with chronic liver diseases (30.48%), and stone diseases (42.96%)(OR 1.77 95% CI 1.2–2.58; Z = 2.94, p = 0.003), the effect of each could not be identified as it was difficult to isolate the effect of helicobacter due to mixing of cases in each study.</p> <p>Conclusion</p> <p>The results of present meta analysis shows that there is a slight higher risk of cholelithiasis and benign liver disease (OR 1.77), however due to inherent inability to isolate the effect of stone disease from that of other benign lesions it is not possible to say for sure that <it>Helicobacter </it>has a casual relationship with benign biliary disease or stone disease or both.</p

Bootstrapping the energy flow in the beginning of life.

This paper suggests that the energy flow on which all living structures depend only started up slowly, the low-energy, initial phase starting up a second, slightly more energetic phase, and so on. In this way, the build up of the energy flow follows a bootstrapping process similar to that found in the development of computers, the first generation making possible the calculations necessary for constructing the second one, etc. In the biogenetic upstart of an energy flow, non-metals in the lower periods of the Periodic Table of Elements would have constituted the most primitive systems, their operation being enhanced and later supplanted by elements in the higher periods that demand more energy. This bootstrapping process would put the development of the metabolisms based on the second period elements carbon, nitrogen and oxygen at the end of the evolutionary process rather than at, or even before, the biogenetic even

Ionic liquids at electrified interfaces

Until recently, “room-temperature” (<100–150 °C) liquid-state electrochemistry was mostly electrochemistry of diluted electrolytes(1)–(4) where dissolved salt ions were surrounded by a considerable amount of solvent molecules. Highly concentrated liquid electrolytes were mostly considered in the narrow (albeit important) niche of high-temperature electrochemistry of molten inorganic salts(5-9) and in the even narrower niche of “first-generation” room temperature ionic liquids, RTILs (such as chloro-aluminates and alkylammonium nitrates).(10-14) The situation has changed dramatically in the 2000s after the discovery of new moisture- and temperature-stable RTILs.(15, 16) These days, the “later generation” RTILs attracted wide attention within the electrochemical community.(17-31) Indeed, RTILs, as a class of compounds, possess a unique combination of properties (high charge density, electrochemical stability, low/negligible volatility, tunable polarity, etc.) that make them very attractive substances from fundamental and application points of view.(32-38) Most importantly, they can mix with each other in “cocktails” of one’s choice to acquire the desired properties (e.g., wider temperature range of the liquid phase(39, 40)) and can serve as almost “universal” solvents.(37, 41, 42) It is worth noting here one of the advantages of RTILs as compared to their high-temperature molten salt (HTMS)(43) “sister-systems”.(44) In RTILs the dissolved molecules are not imbedded in a harsh high temperature environment which could be destructive for many classes of fragile (organic) molecules

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Expression of heat shock protein (Hsp90) paralogues is regulated by amino acids in skeletal muscle of Atlantic salmon

Heat shock proteins 90 (Hsp90) have an essential role in sarcomere formation and differentiation in skeletal muscle and also act as molecular chaperones during protein folding impacting a wide range of physiological processes. We characterised and provided a phylogenetically consistent nomenclature for the complete repertoire of six Hsp90 paralogues present in duplicated salmonid fish genomes (Hsp90α1a, Hsp90α1b, Hsp90α2a, Hsp90α2b, Hsp90ß1a and Hsp90ß1b). The expression of paralogues in fast skeletal muscle was investigated using in vivo fasting-feeding experiments and primary myogenic cultures. Fasted juvenile Atlantic salmon (Salmo salar) showed a transient 2 to 8-fold increase in the expression of all 4 Hsp90α paralogues within 24h of satiation feeding. Hsp90α1a and hsp90α1b also showed a pronounced secondary increase in expression after 10 days, concomitant with muscle differentiation and the expression of myogenin and sarcomeric proteins (mlc2, myhc). Hsp90ß1b was constitutively expressed whereas Hsp90ß1a expression was downregulated 10-fold between fasted and fed individuals. Hsp90α1a and Hsp90α1b were upregulated 10 to 15-fold concomitant with myotube formation and muscle differentiation in vitro whereas other Hsp90 paralogues showed no change in expression. In cells starved of amino acid (AA) and serum for 72h the addition of AA, but not insulin-like growth factor 1, increased phosphorylation of mTor and expression of all 4 hsp90α paralogues and associated co-chaperones including hsp30, tbcb, pdia4, pdia6, stga and fk504bp1, indicating a general activation of the protein folding response. In contrast, Hsp90ß1a expression in vitro was unresponsive to AA treatment indicating that some other as yet uncharacterised signal(s) regulate its expression in response to altered nutritional state.Publisher PDFPeer reviewe