Relation between the space flight-induced frequency of dominant lethal mutations and the level of allozyme heterozygosity in Drosophila melanogaster populations

Currently, the treatment of falciparum malaria is seriously compromised by spreading drug resistance. We studied the effects of camptothecin, a potent and specific topoisomerase I inhibitor, on erythrocytic malaria parasites in vitro. In Plasmodium falciparum, camptothecin trapped protein-DNA complexes, inhibited nucleic acid biosynthesis, and was cytotoxic. These results provide proof for the concept that topoisomerase I is a vulnerable target for new antimalarial drug development.     

Diffusion coefficients in the lateral intercellular spaces of Madin-Darby canine kidney cell epithelium determined with caged compounds

The diffusion coefficients of two caged fluorescent dyes were measured in free solution and in the lateral intercellular spaces (LIS) of cultured Madin-Darby canine kidney (MDCK) cells after photoactivation by illumination with a continuous or pulsed UV laser. Both quantitative video imaging and a new photometric method were utilized to determine the rates of diffusion of the caged fluorescent dyes: 8-((4,5-dimethoxy-2-nitrobenzyl)oxy)pyrene-1,3,6-trisulfonic acid (DMNB-HPTS) and (4,5-dimethoxy-2-nitrobenzyl) fluorescein dextran (10,000 MW) (DMNB-caged fluorescein dextran). The diffusion coefficients at 37 degrees C in free solution were 3.3 x 10(-6) cm2/s (HPTS) and 0.98 x 10(-6) cm2/s (10,000 MW dextran). Diffusion of HPTS within nominally linear stretches of the LIS of MDCK cells grown on glass coverslips was indistinguishable from that in free solution, whereas dextran showed a 1.6 +/- 0.5-fold reduction in diffusivity. Measurements of HPTS diffusion within the LIS of multicellular regions also exhibited a diffusivity comparable to the free solution value. The restriction to diffusion of the dextran within the LIS may be due to molecular hindrance.     

Phosphatidylinositol 3-kinase-gamma activates Bruton's tyrosine kinase in concert with Src family kinases

Bruton's tyrosine kinase (Btk) is essential for normal B lymphocyte development and function. The activity of Btk is partially regulated by transphosphorylation within its kinase domain by Src family kinases at residue Tyr-551 and subsequent autophosphorylation at Tyr-223. Activation correlates with Btk association with cellular membranes. Based on specific loss of function mutations, the Btk pleckstrin homology (PH) domain plays an essential role in this activation process. The Btk PH domain can bind in vitro to several lipid end products of the phosphatidylinositol 3-kinase (PI 3-kinase) family including phosphatidylinositol 3,4,5-trisphosphate. Activation of Btk as monitored by elevation of phosphotyrosine content and a cellular transformation response was dramatically enhanced by coexpressing a weakly activated allele of Src (E378G) and the two subunits of PI 3-kinase-gamma. This activation correlates with new sites of phosphorylation on Btk identified by two-dimensional phosphopeptide mapping. Activation of Btk was dependent on the catalytic activity of all three enzymes and an intact Btk PH domain and Src transphosphorylation site. These combined data define Btk as a downstream target of PI 3-kinase-gamma and Src family kinases.     

Risk of human immunodeficiency virus infection among pregnant crack cocaine users in a rural community

OBJECTIVE: To investigate why women who use crack cocaine are at increased risk of human immunodeficiency virus (HIV) infection. METHODS: One thousand one hundred fifty-two (99.7%) of 1155 consecutive prenatal patients attending a rural public health clinic were interviewed about drug use and sexual practices and tested for HIV infection and other sexually transmitted diseases. RESULTS: Fifty-one (4.7%) of 1096 pregnant women reported ever using crack cocaine, but only five (10%) of the crack cocaine users had ever injected drugs. Eighteen (35%) of the crack users were HIV infected compared with 22 (2%) of the 1045 women who reported never using crack (odds ratio 25, 95% confidence interval 12-52; P < .001). Crack users were more likely to have had a known HIV-infected sex partner, exchanged sex for money or drugs, and tested positive for syphilis than were non-crack users (for each comparison, P < .001). Before using crack, 18% of crack users had exchanged sex for money or drugs and 8% had averaged three or more sex partners per month; in contrast, after beginning to use crack, 76% of crack users exchanged sex for money or drugs and 63% averaged three or more sex partners per month (for both comparisons, P < .001). Crack users who were not HIV infected were more likely to have almost always used condoms and/or had fewer than three sex partners per month than were HIV-infected crack users (P < .01). CONCLUSION: Women who reported using crack cocaine were at an increased risk of HIV infection because crack use was associated with a significant increase in unprotected sexual contact.     

Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene

Iraqi-Jewish optic atrophy plus is an autosomal recessive condition characterized by infantile optic atrophy, an early onset movement disorder, and 3-methylglutaconic aciduria. Other features include spastic paraplegia, mild ataxia, mild cognitive deficiency and dysarthria. This disorder was identified in inbred Iraqi-Jewish kindreds in which relationships between most of the affected individuals were unknown. In this study we identify linkage to chromosome 19q13.2-q13.3 by using a DNA pooling strategy to perform a genome wide screen followed by a high density search for shared segments among affected individuals in candidate regions identified in the initial genome wide screen. A significantly high positive lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. The existence of multiple recombinant individuals indicates the disease interval can be further narrowed with additional markers. Linkage disequilibrium was seen in six polymorphic markers across a 1 Mb interval. This region is well characterized and contains several candidate genes.     

计算机辅助设计大大简化了功率因素变换器的设计

由于能源调节的持续增长，电源变得越来越复杂。人们意识到需要一个更简单的方式进行设计时，出现了计算机辅助设计工具。这篇文章就论述了此工具如何很快产生一个连续导通模式升压功率因素校正设计的优势。全部设计已经得到证实，并且会提供一些相关的公式。     

The role of apitherapy in the combined treatment of patients with chronic nonspecific lung diseases]

The authors suggest that apitherapy should be used in the treatment of patients with chronic non-specific pulmonary diseases (ChNPD) in order that it might be more effective. Apitherapeutic complex (bee venom and bee keeping apiculture produce) has been applied to the treatment of 104 ChNPD patients. High effectiveness of apitherapy in a combined treatment of ChNPD patients was demonstrated as was their stimulating and normalizing influence on the function of the adrenals.     

The etiological and pathogenetic characteristics of duodenal peptic ulcer in adolescents

Studied by endoscopy were 100 adolescents with diagnosed duodenal ulcer, as were 100 essentially healthy subjects and 90 ones of the same age presenting with primary chronic gastroduodenitis together with 60 adults who had duodenal ulcer. The following items were etiologic risk factors for duodenal ulcer, if combined, in the above adolescent series: Frequent episodes nervous of tension, hereditary predisposition and helicobacteriosis. In juveniles with duodenal ulcer, secretion and motility of the stomach appeared to be subjected to changes to a higher degree than it was in adult subjects with duodenal ulcer, while functions of the psychovegetative and immune systems were found to be less changeable in the former. In adolescents presenting with duodenal ulcer and primary chronic gastroduodenitis, the etiologic risk factors and pathogenetic changes were found out to be identical.