The use of referential expressions in structuring discourse

Referential expressions that refer to entities that occur in a text differ in lexical specificity. It is claimed that if these anaphoric expressions are more specific than necessary for their identificational function, they not only relate the current information to the intended referent, but also contribute to the expression of the thematic structure of the discourse and to the comprehension of the thematic structure. In two controlled production experiments, it is demonstrated that thematic shifts are produced when one has to make use of such an overspecified expression, and that overspecified referential expressions are produced when one has to formulate a thematic shift. In two comprehension experiments, using a probe recognition technique, it is shown that an overspecified referential expression decreases the availability of information contained in a sentence that precedes the overspecification. This finding is interpreted in terms of the thematic structuring function of referential expressions in the understanding of discourse

Evidence for trans-cis isomerization of the p-coumaric acid chromophore as the photochemical basis of the photocycle of photoactive yellow protein

AbstractAnalysis of the chromophore p-courmaix acid, extracted from the ground state and the long-lived blue-shifted photocycle intermediate of photoactive yellow protein, shows that the chromophore is reversibly converted from the trans to the cis configuration, while progressing through the photocycle. The detection of the trans and cis isomers was carried out by high performance capillary zone electrophoresis and further substained by 1H NMR spectroscopy. The data presented here establish the photo-isomerization of the vinyl double bond in the chromophore yellow protein, a eubacterial photosensory protein. A similar isomerization process occurs in the structurally very different sensory rhodopsins, offering an explanation for the strong spectroscopic similarities between photoactive yellow protein and the sensory rhodopsins. This is the first demonstration of light-induced isomerization of a chromophore double bond as the photochemical basis for photosensing in the domain of Bacteria

Short communication:Supplementation of fructo-oligosaccharides does not improve insulin sensitivity in heavy veal calves fed different sources of carbohydrates

Heavy veal calves (4–6 mo old) often develop problems with insulin sensitivity. This could lead to metabolic disorders and impaired animal growth performance. Studies in various animal species have shown that the supplementation of short-chain fructo-oligosaccharides (scFOS) can improve insulin sensitivity. We therefore studied the effects of scFOS supplementation on insulin sensitivity in heavy veal calves. Forty male Holstein-Friesian calves (BW = 190 ± 2.9 kg; age = 162 ± 1.4 d at the start of the trial) were fed either a control milk replacer (MR) diet or a diet in which one-third of the lactose was replaced by glucose, fructose, or glycerol for 10 wk prior to the start of the trial. At the start of the trial, calves were subjected to a frequently sampled intravenous glucose tolerance test to assess whole-body insulin sensitivity (muscle and hepatic insulin sensitivity). Calves within each dietary treatment group were ranked based on their insulin sensitivity value. Half of the calves received scFOS (12 mg/kg of BW) with the MR for 6 wk (supplementation was equally distributed over the insulin sensitivity range). Subsequently, a second frequently sampled intravenous glucose tolerance test was conducted to assess the effect of scFOS. In addition, fasting plasma levels of glucose, insulin, triglycerides, and cholesterol were determined to calculate the quantitative insulin sensitivity check index and triglyceride:high-density lipoprotein cholesterol ratio (fasting indicators of insulin sensitivity). Whole-body insulin sensitivity was low at the start of the trial and remained low in all groups [1.0 ± 0.1 and 0.8 ± 0.1 (mU/L)−1 · min−1 on average, respectively]. Supplementation of scFOS did not improve insulin sensitivity in any of the treatment groups. The quantitative insulin sensitivity check index and the triglyceride:high-density lipoprotein cholesterol ratio also did not differ between scFOS and non-scFOS calves and averaged 0.326 ± 0.003 and 0.088 ± 0.004, respectively, at the end of the trial. We conclude that scFOS supplementation does not improve insulin sensitivity in heavy veal calves regardless of the carbohydrate composition of the MR. This is in contrast to other animals (e.g., dogs and horses), where scFOS supplementation did improve insulin sensitivity. The absence of an effect of scFOS might be related to the dosage or to metabolic differences between ruminants and nonruminants. Increasing evidence indicates that dietary interventions in veal calves have little or no effect on insulin sensitivity, possibly because of low levels of insulin sensitivity

Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Snake Venom Toxins.

Animal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in snake venoms. The venoms of , , and , which are known for their potent haemotoxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combinations of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming

Diet Quality and Upper Gastrointestinal Cancers Risk:A Meta-Analysis and Critical Assessment of Evidence Quality

We aimed to assess the effect of a high-quality diet on the risk of upper gastrointestinal cancer and to evaluate the overall quality of our findings by searching PubMed, EMBASE, Web of Science, Cochrane, and the references of related articles to February 2020. Two reviewers independently retrieved the data and performed the quality assessments. We defined the highest-quality diet as that with the lowest Diet Inflammatory Index category and the highest Mediterranean Diet Score category. Overall odds ratios and 95% confidence intervals were estimated for upper gastrointestinal cancer risk comparing the highest- versus lowest-diet quality. A random-effects meta-analysis was then applied with Review Manager, and the quality of the overall findings was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. The highest-quality diets were significantly associated with reduced risk of upper gastrointestinal cancers, achieving odds ratios of 0.59 (95% confidence interval: 0.48-0.72) for the Diet Inflammatory Index, pooling the findings from nine studies, and 0.72 (95% confidence interval: 0.61-0.88) for the Mediterranean Diet Score, pooling the findings from 11 studies. We observed a minimum of 69% heterogeneity in the pooled results. The pooled results were graded as low quality of evidence. Although it may be possible to offer evidence-based general dietary advice for the prevention of upper gastrointestinal cancers, the evidence is currently of insufficient quality to develop dietary recommendations

A refined radio-telemetry technique to monitor right ventricle or pulmonary artery pressures in rats: a useful tool in pulmonary hypertension research

Implantable radio-telemetry methodology, allowing for continuous recording of pulmonary haemodynamics, has previously been used to assess effects of therapy on development and treatment of pulmonary hypertension. In the original procedure, rats were subjected to invasive thoracic surgery, which imposes significant stress that may disturb critical aspects of the cardiovascular system and delay recovery. In the present study, we describe and compare the original trans-thoracic approach with a new, simpler trans-diaphragm approach for catheter placement, which avoids the need for surgical invasion of the thorax. Satisfactory overall success rates up to 75% were achieved in both approaches, and right ventricular pressures and heart and respiratory rates normalised within 2 weeks. However, recovery was significantly faster in trans-diaphragm than in trans-thoracic operated animals (6.4 ± 0.5 vs 9.5 ± 1.1 days, respectively; p < 0.05). Stable right ventricular pressures were recorded for more than 4 months, and pressure changes, induced by monocrotaline or pulmonary embolisms, were readily detected. The data demonstrate that right ventricular telemetry is a practicable procedure and a useful tool in pulmonary hypertension research in rats, especially when used in combination with echocardiography. We conclude that the described trans-diaphragm approach should be considered as the method of choice, for it is less invasive and simpler to perform