Extremely high frequencies of alpha-globin gene deletion in Madang and on Kar Kar Island, Papua New Guinea.

Extremely high frequencies of the deletion form of alpha(+)-thalassemia (-alpha/), as studied by the DNA mapping technique, were found in the population of Madang, a coastal province in the north of Papua New Guinea (PNG) and in the population of Kar Kar, an island situated near Madang. Ninety-seven percent of the population tested from Madang and 89% of that from Kar Kar Island were either alpha(+)-thalassemia heterozygotes or homozygotes. By contrast, no examples of the deletion form were detected in the Eastern Highlands of PNG. The haplotype frequencies of alpha(+)-thalassemia (-alpha/) in Madang and Kar Kar Island were found to be 81.33% and 66.67%, respectively. A more detailed analysis of the gene deletion revealed that in both populations 96% were of the 4.2 kilobase (kb) type and 4% were of the 3.7-kb type. Thus, this group is the only example in which the 4.2-kb deletion is predominant over 3.7-kb defect. The presence in high frequencies of alpha(+)-thalassemia in the coastal area of Madang and on the neighboring island, where malaria has long been holoendemic or hyperendemic, and its virtual absence from the nonmalarious highlands of PNG suggest the role of malaria as the selective factor in maintaining alpha(+)-thalassemia. If this selective pressure is still operating, and since alpha(+)-thalassemia has no apparent homozygous disadvantage, the abnormal haplotype (-alpha/) will be in the process of fixation in this population.     

Production of high-fructose syrup by a heat-fixed Lactobacillus sp.

A Lactobacillus sp. isolated from soil and capable of growing on xylose-containing medium exhibited high glucose isomerase activity. The enzyme was thermostable, stable toward dialysis, and activated by heat treatment. It did not show the presence of xylose or ribose isomerase activities; the K_m for glucose and xylose substrates were 0.48M and 0.513M, respectively. The heat treatment of ultrasonic crude extract gave insoluble fixed active glucose isomerase enzyme. The properties of free and immobilized enzyme in heat-fixed whole cells differed in many respects. The optimum temperature for enzyme activity changed from 70 to 85°C, the optimum substrate concentration changed from 1.0M to 2.4M, and the optimum pH from 7.4 to 6.0. Co²⁺ and Mg²⁺ ions activated the enzyme when used singly, but in combination they inhibited the enzyme and Mn²⁺ had no effect on the enzyme. Free and immobilized enzymes, when used in the used in the conversions of corn and bagasse hydrolysates to fructose, gave 58, 25.6%, and 50, 27.6% conversions, respectively. Immobilized enzyme retained a significant activity for more than 30 hr and was able to operate at higher glucose concentrations showing less products inhibition effect as compared to free enzyme. In the batch process it was able to operate for about eight cycles.     

Novel secopyrrolizidine alkaloids from Crotalaria verrucosa

Crotaverrine and O-acetylcrotaverrine, isolated from the seeds of C. verrucosa Linn., have been shown by spectroscopy and chemical evidence to be the macrocyclic diesters of otonecine and diastereoisomeric integerrinecic acid. Hitherto, diastereoisomeric integerrinecic acid esters were not known to occur in nature.     

Long-term platinum retention after treatment with cisplatin and oxaliplatin

Background  

The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin.     

Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis

Sepsis is a complex clinical syndrome resulting from a harmful host inflammatory response to infection. Chemokines and their receptors play a key role in the pathogenesis of sepsis. BX471 is a potent nonpeptide CC chemokine receptor-1 (CCR1) antagonist in both human and mouse. The aim of the present study was to evaluate the effect of prophylactic and therapeutic treatment with BX471 on cecal ligation and puncture-induced sepsis in the mouse and to investigate the underlying mechanisms. In sepsis induced by cecal ligation and puncture, treatment with BX471 significantly protected mice against lung and liver injury by attenuating MPO activity, an indicator of neutrophil recruitment in lungs and livers and attenuating lung and liver morphological changes in histological sections. Blocking CCR1 by BX471 also downregulated ICAM-1, P-selectin, and E-selectin expression at mRNA and protein levels in lungs and livers compared with placebo-treated groups. These findings suggest that blockage of CCR1 by specific antagonist may represent a promising strategy to prevent disease progression in sepsis.     

Construction of a Genetic Linkage Map and Identification of QTLs for Seed Weight and Seed Size Traits in Lentil (Lens culinaris Medik.)

Seed weight and seed size both are quantitative traits and have been considered as important components of grain yield, thus identification of quantitative trait loci (QTL) for seed traits in lentil (Lens culinaris) would be beneficial for the improvement of grain yield. Hence the main objective of this study was to identify QTLs for seed traits using an intraspecific mapping population derived from a cross between L. culinaris cv. Precoz (seed weight-5.1g, seed size-5.7mm) and L. culinaris cv. L830 (seed weight-2.2g, seed size-4mm) comprising 126 F₈-RILs. For this, two microsatellite genomic libraries enriched for (GA/CT) and (GAA/CTT) motif were constructed which resulted in the development of 501 new genomic SSR markers. Six hundred forty seven SSR markers (including 146 previously published) were screened for parental polymorphism and 219 (33.8%) were found to be polymorphic among the parents. Of these 216 were mapped on seven linkage groups at LOD4.0 spanning 1183.7cM with an average marker density of 5.48cM. Phenotypic data from the RILs was used to identify QTLs for the seed weight and seed size traits by single marker analysis (SMA) followed by composite interval mapping (CIM) which resulted in one QTL each for the 2 traits (qSW and qSS) that were co-localized on LG4 and explained 48.4% and 27.5% of phenotypic variance respectively. The current study would serve as a strong foundation for further validation and fine mapping for utilization in lentil breeding programs.     

Identification of a novel population of human cord blood cells with hema-topoietic and chondrocytic potential

With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin-CD45- ceils also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin^-CD45^-CD34^- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin^-CD45^-CD34^-differentiation into chondrocytes. Moreover, unlike CD34~ human hematopoietic stem cells, Lin^-CD45^-CD34^- cells were unable to proliferate or survive in liquid cultures, whereas single Lin^-CD45^-CD34^- cells were able to chimerize the inner cell mass (1CM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin-CD45-CD34^- cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.     

Molecular docking analysis of Clostridium perfringens beta toxin model with potential inhibitors from the ZINC database

Beta toxin from Clostridium perfringens after being secreted in gut is capable of causing necrotic enteritis in humans and several other animal species and does not respond to routinely used antibiotics. Therefore, there is a need to design an effective inhibitor for the Clostridium perfringens beta toxin (CPB) using cutting edge drug discovery technologies. Hence, potential CPB inhibitors were identified using computer aided screening of compounds from the ZINC database. Further, we document the molecular docking analysis of Clostridium perfringens beta toxin model (that revealed 4 binding pockets, A-D) with the identified potential inhibitors. We show that ZINC291192 [N-[(1-methylindol-3-yl) methyl eneamino]-7,10-dioxabicyclo[4.4.0]deca-2,4,11-triene-8- carboxamide] has optimal binding features with calculated binding energy of -10.38 kcal/mol and inhibition constant of 24.76 nM for further consideration.