Insect growth‐reducing and antifeedant activity in Eastern North America hardwood species and bioassay‐guided isolation of active principles from Prunus serotina

1 Thirty extracts of wood and bark of hardwood trees from Eastern North America were examined for insect growth‐reducing activity in a bioassay with European corn borer, Ostrinia nubilalis, and an antifeedant bioassay with the rice weevil, Sitophilus oryzae. 2 Nine of the bark extracts and four of the wood extracts showed significant growth reducing effects at 0.5% in meridic diets, whereas only two bark extracts and one wood extract showed significant antifeedant effect at the same concentration. 3 Slower growing tree species were more biologically active than fast growing ones. Isolation of the bioactive compounds in one of the active species, Prunus serotina, showed that naringenin, its derivative methoxynaringenin, and eriodictyol were responsible for the antifeedant effects.     

Co-administration of APD668, a G protein-coupled receptor 119 agonist and linagliptin,a DPPIV inhibitor,prevents progression of steatohepatitis in mice fed on a high trans-fat diet

Non-Alcoholic SteatoHepatitis (NASH) is the more severe form of Non-Alcoholic Fatty Liver Disease (NAFLD) and is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, hepatocyte injury with or without fibrosis. Recently, GPR119 receptor has emerged as a novel therapeutic target for the treatment of dyslipidemia and non-alcoholic steatohepatitis. In the present study, we investigated the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor on the progression of steatohepatitis in mice fed on a high trans-fat diet. In this study, monotherapy with either APD668 or linagliptin caused a reduction in the levels of ALT, AST, glucose, cholesterol and epididymal fat mass but the effect was more pronounced upon treatment with combination of both drugs.On the other hand, combined treatment of APD668 with linagliptin demonstrated a non-significant additive effect in reduction of hepatic triglyceride (?78%) and cholesterol (?56%) compared to monotherapy groups. Moreover, co-administration of APD668 and linagliptin resulted in enhanced levels of active GLP-1 with additional benefit of significant synergistic decrease in body weight gain (?19%) in mice. We speculated that the enhanced effect observed with the combination treatment could be due to either 1) direct activation of GPR119 receptors present in liver and intestine or 2) enhanced active GLP-1 levels or 3) decreased degradation of GLP-1 in-vivo through DPPIV inhibition. Therefore, these findings clearly suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of non-alcoholic steatohepatitis.     

Development of an efficient,genotype independent plant regeneration and transformation protocol using cotyledonary nodes in safflower (<Emphasis Type="Italic">Carthamus tinctorius</Emphasis> L.)

Safflower is an important oilseed crop with a nutritionally desirable oil composition comprising low levels of saturated fatty acids and high levels of unsaturated fatty acids. In this study, a robust, genotype-independent plant regeneration protocol was developed for geographically diverse safflower genotypes, including one accession each from America, Australia, Egypt, Germany, Kazakhstan and three important Indian genotypes (Sharda, Bhima and PBNS-12). Use of cotyledonary nodes as explants resulted in genotype-independent regeneration on BAP (6-Benzylaminopurine), NAA (Naphthalene acetic acid) and ascorbic acid supplemented MS medium. Histological analysis revealed that multiple shoot apical meristems originated independently from peripheral cortical regions of explants. We developed a highly efficient in vitro micrografting method which enabled successful rooting of 85–90 % of regenerated shoots. An efficient genetic transformation system was also established for three Indian genotypes viz., Sharda, Bhima and PBNS-12 using the Agrobacterium strain, LBA4404 and phosphinothricin as the selection agent. This is the first report on use of phosphinothricin-based selection and cotyledonary nodes as explants for Agrobacterium-mediated transformation of safflower. Use of vacuum infiltration-assisted Agrobacterium infection and inclusion of a pre-culture step significantly increased transformation frequencies in all the three genotypes as seen by GUS assays on transformed calli. Genomic integration and transgene expression were confirmed by PCR, Southern hybridization and GUS assays. Most transgenic plants (90 %) exhibited a normal phenotype when grown under controlled conditions and produced viable seeds. This protocol would be useful for introduction of desirable traits in diverse genotypes of safflower.     

Prostate-specific antigen testing in Ontario: reasons for testing patients without diagnosed prostate cancer

BACKGROUND: The use of the prostate-specific antigen (PSA) test has been increasing rapidly in Canada since its introduction in 1988. The reasons for using the PSA test in patients without known prostate cancer are unclear. This paper reports on the first study in Canada to use physician records to assess the use of PSA testing. METHODS: A questionnaire was mailed to physicians attending 475 patients without diagnosed prostate cancer. The patients were randomly selected from 2 laboratory databases of PSA test records in the greater Toronto area during 1995. The physicians were asked to consult their patient records to avoid recall bias. Information obtained included physician''s specialty, patient''s age at time of PSA test and reason(s) for the test. RESULTS: There were 264 responses (56%), of which 240 (91%) were usable. Of these 240, 63% (95% confidence interval [Cl] 58%-70%) indicated that the test was conducted to screen for prostate cancer, 40% (95% Cl 34%-47%) said it was to investigate urinary symptoms, and 33% (95% Cl 27%-40%) responded that it was a follow-up to a medical procedure or drug therapy. More than one reason was permitted. Of 151 responses indicating screening as one reason for testing, 64% (95% Cl 56%-72%) stated that it was initiated by the patient, and 73% (95% Cl 65%-80%) stated that it was part of a routine examination. For 19%, both investigation of symptoms and screening asymptomatic patients were given as reasons for testing, and for another 19% both follow-up of a medical procedure and screening were given as reasons. Screening was recorded as a reason for testing far more commonly for patients seen by family physicians and general practitioners than for patients seen by urologists (67% v. 29%, p < 0.001). In contrast, the use of PSA testing to diagnose urinary symptoms was more common for patients seen by urologists than for those seen by family physicians and general practitioners (52% v. 37%, p = 0.044). No significant difference was found between physician groups in the use of PSA testing as a follow-up of a medical procedure (42% for urologists and 31% for family physicians and general practitioners). About 24% of the PSA test records were for patients younger than 50 and older than 70 years. PSA testing initiated by patients was more common in the practices of family physicians and general practitioners than in the practices of urologists (44% v. 13%, p < 0.001). INTERPRETATION: Screening for prostate cancer was the most common reason for PSA testing in our study group; it occurred most commonly in the family and general practice setting and was usually initiated by the patient. Differences in reasons for testing were identified by practice specialty. Although PSA screening for prostate cancer is sometimes recommended for men between 50 and 70 years of age, it is being conducted in men outside this age group.     

Active responses decrease impact forces at the hip and shoulder in falls to the side.

Active responses, such as using the arm to break the fall, may be an effective means of decreasing likelihood of injury in a fall and may help explain why only a small percentage of falls result in a fracture. We quantified the impact force at the hip and shoulder in falls to the side from a kneeling position under three conditions: (1) attempting to break the fall by using an arm; (2) falling with the body relaxed; and (3) falling with the body tensed. Subjects fell from a kneeling position onto a force platform array covered with foam padding and impact force data were recorded. The ground reaction force-time curve was generally bimodal due to sequential impacts of the hip and shoulder. Impact forces at the hip and shoulder were 12 and 16% less for the slap condition (p < 0.05) than for the tensed condition. The impact forces for the relaxed and tensed conditions were not significantly different, although impact forces tended to be less in the relaxed condition. We concluded that active responses reduce the impact forces experienced at the hip and shoulder in falls to the side. Decreased effectiveness of protective responses, due to increases in reaction time and decreases in strength with age, may help explain why so many hip fractures occur in the elderly but so few occur in younger people.     

Aggregation prone regions in human proteome: Insights from large‐scale data analyses

Protein aggregation leads to several burdensome human maladies, but a molecular level understanding of how human proteome has tackled the threat of aggregation is currently lacking. In this work, we survey the human proteome for incidence of aggregation prone regions (APRs), by using sequences of experimentally validated amyloid‐fibril forming peptides and via computational predictions. While approximately 30 human proteins are currently known to be amyloidogenic, we found that 260 proteins (～1% of human proteome) contain at least one experimentally validated amyloid‐fibril forming segment. Computer predictions suggest that more than 80% of the human proteins contain at least one potential APR and approximately two‐thirds (65%) contain two or more APRs; spanning 3–5% of their sequences. Sequence randomizations show that this apparently high incidence of APRs has been actually significantly reduced by unique amino acid composition and sequence patterning of human proteins. The human proteome has utilized a wide repertoire of sequence‐structural optimization strategies, most of them already known, to minimize deleterious consequences due to the presence of APRs while simultaneously taking advantage of their order promoting properties. This survey also found that APRs tend to be located near the active and ligand binding sites in human proteins, but not near the post translational modification sites. The APRs in human proteins are also preferentially found at heterotypic interfaces rather than homotypic ones. Interestingly, this survey reveals that APRs play multiple, often opposing, roles in the human protein sequence‐structure‐function relationships. Insights gained from this work have several interesting implications towards novel drug discovery and development. Proteins 2017; 85:1099–1118. © 2017 Wiley Periodicals, Inc.     

Changes in microbial community structure, methanogenesis and rumen fermentation in response to saponin-rich fractions from different plant materials

Aims:  Investigation of the effects of saponin-rich fractions on rumen fermentation, methane production and the microbial community.
Methods and Results:  Saponins were extracted from Carduus , Sesbania and Knautia leaves and fenugreek seeds. Two levels of saponin-rich fractions with a substrate were incubated using the Hohenheim gas method. Methane was measured using an infrared-based methane analyser and microbial communities using quantitative PCR. On addition of saponin-rich fractions, methane and short-chain fatty acid production was not affected. The protozoal counts decreased by 10–39%. Sesbania saponins decreased methanogen population by 78%. Decrease in ruminal fungal population (20–60%) and increase in Fibrobacter succinogenes (21–45%) and Ruminococcus flavefaciens (23–40%) were observed.
Conclusions:  The saponins evaluated possessed anti-protozoal activity; however, this activity did not lead to methane reduction. Fenugreek saponins seemed to have potential for increasing rumen efficiency. The saponins altered the microbial community towards proliferation of fibre-degrading bacteria and inhibition of fungal population.
Significance and Impact of the Study:  The uni-directional relationship between protozoal numbers and methanogenesis, as affected by saponins, is not obligatory. All saponins might not hold promise for decreasing methane production from ruminants.