Resistant Host Responses to Ten California Populations of Meloidogyne incognita

Resistant and susceptible cultivars of tomato, lima beans, cotton, and alfalfa were tested with 10 populations of Meloidogyne incognita from different California locations. Nine of the populations differed in aggressiveness on the nine cultivars tested. Two populations were especially aggressive toward resistant tomato cultivars.     

Antibiotics present and future

Here we make a brief survey of the present state of antibiotic research and use. We also describe a novel antibiotic that contains a basic peptide covalently bound to a morpholino oligonucleotide.     

Sufficient intake of high amylose cornstarch maintains high colonic hydrogen production for 24 h in rats

Colonic hydrogen (H₂) can suppress oxidative stress and damage in the body. We examined the minimum requirement of high amylose cornstarch (HAS) to maintain high colonic H₂ production for 24 h. Ileorectostomized and sham-operated rats were fed a control diet supplemented with or without 20% HAS for 7 days. Colonic starch utilization was determined. Next, rats were fed the control diet with or without 10% or 20% HAS for 14 or 28 days, respectively. Breath and flatus H₂ excretion for 24 h was measured. 1.04 g of resistant fraction in HAS was utilized for 24 h by colonic bacteria. High H₂ excretion was not maintained for 24 h in rats fed the 10% HAS diet, from which only 0.89 g of resistant starch was estimated to be delivered. High colonic H₂ production for 24 h would be maintained by delivering more HAS to the large intestine than is utilized.     

Antibacterial potential of hGlyrichin encoded by a human gene

Emerging multidrug‐resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero‐immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin‐resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42–60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero‐immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Discovery and optimization of novel pyridines as highly potent and selective glycogen synthase kinase 3 inhibitors

Glycogen synthase kinase-3 plays an essential role in multiple biochemical pathways in the cell, particularly in regards to energy regulation. As such, Glycogen synthase kinase-3 is an attractive target for pharmacological intervention in a variety of disease states, particularly non-insulin dependent diabetes mellitus. However, due to homology with other crucial kinases, such as the cyclin-dependent protein kinase CDC2, developing compounds that are both potent and selective is challenging. A novel series of derivatives of 5-nitro-N2-(2-(pyridine-2ylamino)ethyl)pyridine-2,6-diamine were synthesized and have been shown to potently inhibit glycogen synthase kinase-3 (GSK3). Potency in the low nanomolar range was obtained along with remarkable selectivity. The compounds activate glycogen synthase in insulin receptor-expressing CHO-IR cells and in primary rat hepatocytes, and have acceptable pharmacokinetics and pharmacodynamics to allow for oral dosing. The X-ray co-crystal structure of human GSK3-β in complex with compound 2 is reported and provides insights into the structural determinants of the series responsible for its potency and selectivity.     

Roles of the two type II NADH dehydrogenases in the survival of Mycobacterium tuberculosis in vitro

Most bacteria are able to generate sufficient amounts of ATP from substrate level phosphorylation, thus rendering the respiratory oxidative phosphorylation non-critical. In mycobacteria, including Mycobacterium tuberculosis, ATP generation by oxidative phosphorylation is an essential process. Of the two types of NADH dehydrogenases (type I and type II), the type II NADH dehydrogenase (Ndh) which is inhibited by phenothiazines has been thought to be essential. In M. tuberculosis there are two Ndh isozymes (Ndh and NdhA) coded by ndh and ndhA genes respectively. Ndh and NdhA share a high degree of amino acid similarity. Both the enzymes have been shown to be enzymatically active and are inhibited by phenothiazines, suggesting a functional similarity between the two. We attempted gene knockout of ndh and ndhA genes in wild type and merodiploid backgrounds. It was found that ndh gene cannot be inactivated in a wild type background, though it was possible to do so when an additional copy of ndh was provided. This showed that in spite of its apparent functional equivalence, NdhA cannot complement the loss of Ndh in M. tuberculosis. We also showed that NdhA is not essential in M. tuberculosis as the ndhA gene could be deleted in a wild type strain of M. tuberculosis without causing any adverse effects in vitro. RT-PCR analysis of in vitro grown M. tuberculosis showed that ndhA gene is actively transcribed. This study suggests that despite being biochemically similar, Ndh and NdhA play different roles in the physiology of M. tuberculosis.     

油菜田看麦娘对高效氟吡甲禾灵产生抗药性的生理响应

采用种子检测法,鉴定了对除草剂高效氟吡甲禾灵产生抗药性的看麦娘(Alopecu-rus aequalis Sobol.)生物型JXRII。为探讨看麦娘对高效氟吡甲禾灵产生抗性的生理反应,以敏感生物型JJSII为对比,喷施高效氟吡甲禾灵后,测定抗药生物型和敏感生物型几个重要生理指标变化情况的差异。结果表明:高效氟吡甲禾灵处理下,JJSII的叶片电解质泄漏率、MDA含量极显著上升,叶绿素、类胡萝卜素含量下降;JXRII叶片的电解质渗漏率、MDA含量、叶绿素、类胡萝卜素均与对照无显著差异;高效氟吡甲禾灵处理下,JJSII的GSH含量在处理后就开始逐渐下降,JXRII的GSH含量始终高于对照;二者可溶性糖含量均增加,敏感生物型JJSII可溶性糖含量增加的幅度远远大于抗性生物型JXRII;这2种群体经除草剂胁迫下,除草剂对敏感性生物型的生理变化影响大,抗性生物型表现为一定的生理适应性。