The blockade of endothelin A receptor protects astrocytes against hypoxic injury: common effects of BQ-123 anderythropoietin on the rejuvenation of the astrocyte population

In the present study the role of endothelin (ET) and its receptors (ETA-R and ETB-R) in cellular mechanisms underlying the resistance of astroglial cells to low oxygen level and development of hypoxia has been investigated. To define the influences of ET and its receptors on survival and on antigenic as well as morphologic differentiation of rat astroglial cells in normoxic (NC) and hypoxic culture (HC) the selective antagonists of ETA-R (BQ-123) and ETB-R (BQ-788) were used. Treatment of HC with BQ-123 caused an increase in cell number and inhibited the hypoxia-induced apoptosis by 37%. BQ-123 decreased the hypoxia-induced cytotoxicity in HC. These effects of BQ-123 were abolished in cultures simultaneously treated with BQ-123 and BQ-788. Administration of BQ-788 alone decreased the number of living cells in NC, but not in HC. The activity of caspase-3/-7 was not changed by exposure of NC and HC to BQ-788. The protection provided by BQ-123 to astroglial cells against cytotoxicity in NC and HC was similar to that of erythropoietin (EPO), a cytokine with established neuroprotective effects. The functional improvement of astroglial cells and slowing down of their differentiation under exposure to BQ-123, or EPO, or BQ-123 + EPO has been evidenced by an increased number of nestin+/glial fibrillary acidic protein-positive (GFAP+) astrocytes accompanied by decrease of nestin-/GFAP+ cells. The simultaneous treatment with BQ-123 and EPO additionally decreased the activities of caspase-3/-7 (64%) and release of LDH into the medium (94%). The benefits in the functional states of astrocytes obtained by combined treatment of HC with BQ-123 and EPO suggest a new therapeutic strategy in treatment of hypoxic brain injury.     

Family of hemorphins: co-relations between amino acid sequences and effects in cell cultures

Hemorphins, i.e. endogenous fragments of beta-globin chain segment (32-41) LVVYPWTQRY(F) suppress the growth of transformed murine fibroblasts L929 cell culture, the effect is due to cytotoxicity and inhibition of cell proliferation. The contribution of cytotoxicity depends on the presence of Leu(32): VV-hemorphins, except VV-hemorphin-4, exhibit cytotoxicity significantly higher than respective LVV-hemorphins. Decrease of cell number induced by hemorphins depend on the extent of N- and C-terminal degradation of hemorphins: VV-hemorphins in most cases are more active than LVV-, V-hemorphins, and hemorphins. In the group of VV-hemorphins the activity of VV-hemorphin-5 (valorphin) is significantly higher than of VV-hemorphin-7, VV-hemorphin-6, and VV-hemorphin-4, meaning that the presence of C-terminal Gln is important for suppressing of cell number. The amino acid sequence VVYPWTQ corresponding to valorphin was identified as important for manifestation of the both cytotoxic and antiproliferative effects.     

Marker-Dependent Recombination in T4 Bacteriophage. I. Outline of the Phenomenon and Evidence Suggesting a Mismatch Repair Mechanism

In standard crosses, some rIIB mutants of T4 phage were found to be susceptible to an extra recombination mechanism to which the other mutants were much less susceptible. The following observations were interpreted as evidence for the mismatch-repair nature of the phenomenon: (1) Marker-dependent recombination generates exclusively double exchanges at both sides of the marker. (2) Marker-dependent recombination is highly sensitive to DNA base sequence at the site of the marker and to that at the corresponding site on the chromosome of the other parent. (3) Within certain limits, the contribution of the marker-dependent mechanism to the total recombination frequency is distance-independent and thus constitutes a constant component.     

Dependence of 13C chemical shifts on the spatial interaction of protons,and its application in structural and conformational studies of oligo- and poly-saccharides

Regularities in the variation of chemical shifts and the glycosidation effects in the ¹³C-n.m.r. spectra of disaccharides were found to depend on the configuration at the anomeric centre of the glycosidating pyranose, and the absolute configuration of both pyranoses moieties. These empirical regularities are explained in terms of the spatial proton-proton interactions within the statistically averaged, or preferred, conformation near the glycosidic linkage. The applicability of these effects for the determination of the anomeric and absolute configuration and the sequence of pyranose residues in oligo- and poly-saccharides is discussed. The conformational properties of glycosidic linkages in disaccharides and disaccharide fragments of oligo- and poly-saccharides are compared on the basis of ¹³C-n.m.r. data.     

Distinct molecular mechanisms control levels of synaptic F‐actin

Polymerization of filamentous (F)‐actin at the neuronal synapse plays an important role in neuronal function. However, the regulatory mechanisms controlling the levels of synaptic actin remain incompletely understood. Here, I used established pharmacological blockers to acutely disrupt the function of actin polymerization machinery, then quantified their effect on synaptic F‐actin levels. Synaptic F‐actin was modestly decreased by inhibition of Arp2/3‐dependent actin branching. Blockade of formin‐dependent actin elongation resulted in an Arp2/3‐dependent increase in synaptic actin that could be mimicked by limited actin depolymerization. Limited actin depolymerization was also sufficient to reverse a decrease in synaptic F‐actin caused by prolonged blockade of synaptic NMDA‐type glutamate receptors. These results suggest that interplay between different actin polymerization pathways may regulate synaptic actin dynamics.     

A new species of Stenoloba Staudinger, 1892 from China (Lepidoptera,Noctuidae, Bryophilinae)

A new species of Stenoloba from the olivacea species group, Stenoloba solaris, sp. n. (Lepidoptera, Noctuidae), is described from Yunnan, China. Illustrations of the male holotype and its genitalia are provided. A diagnostic comparison is made with Stenoloba albistriata Kononenko & Ronkay, 2000, Stenoloba olivacea (Wileman, 1914), and Stenoloba benedeki Ronkay, 2001 (Fig. 4).Open in a separate windowFigures 1–5.Stenoloba spp. adults and biotope. 1 Stenoloba solaris, sp. n., male, holotypus, Yunnan, China (GBG/ZSM) 2 Stenoloba albistriata, male, paratypus, N. Vietnam (ZFMK) 3 Stenoloba olivacea, male, Taiwan (HNHM) 4 Stenoloba benedeki, male, paratypus, N. Vietnam (HNHM) 5 Type locality of Stenoloba solaris, sp. n. China, NW Yunnan, Lijiang/Zhongdian near Tuguancum, 27°29''700"N, 99°53''700"E.     

Synthesis and biological activity of 5-styryl and 5-phenethyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles

Syntheses, biological evaluation, and structure–activity relationships for a series of novel 5-styryl and 5-phenethyl analogs of dimebolin are disclosed. The novel derivatives and dimebolin share a broad spectrum of activities against therapeutically relevant targets. Among all synthesized derivatives, 2,8-dimethyl-5-[(Z)-2-phenylvinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and its 5-phenethyl analog are the most potent blockers of 5-HT₇, 5-HT₆, 5-HT_2C, Adrenergic α₂ and H₁ receptors. The general affinity rank order towards the studied receptors was Z-3(2) > 4(2) ? 4(3) ? dimebolin, all of them having highest affinities to 5-HT₇ receptors.     

Phylogeography of Y-chromosome haplogroup I reveals distinct domains of prehistoric gene flow in europe

To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia ~9,000 years ago.     

Cold adaptation in the phytopathogenic fungi causing snow molds

Snow molds are psychrophilic or psychrotrophic fungal pathogens of forage crops, winter cereals, and conifer seedlings. These fungi can grow and attack dormant plants at low temperatures under snow cover. In this review, we describe the biodiversity and physiological and biochemical characteristics of snow molds that belong to various taxa. Cold tolerance is one of the important factors related to their geographic distribution, because snow molds develop mycelia under snow cover and because they should produce intra- and extracellular enzymes active at low temperatures for growth and infection. Basidiomycetous snow molds produce extracellular antifreeze proteins. Their physiological significance is to keep the extracellular environment unfrozen. The psychrophilic ascomycete Sclerotia borealis shows normal mycelial growth under frozen conditions, which is faster than that on unfrozen media at optimal growth temperature. This fungus does not produce extracellular antifreeze proteins, but osmotic stress tolerance enables the fungus to grow at subzero temperatures. In conclusion, different taxa of snow molds have different strategies to adapt under snow cover.     

The Genographic Project public participation mitochondrial DNA database

The Genographic Project is studying the genetic signatures of ancient human migrations and creating an open-source research database. It allows members of the public to participate in a real-time anthropological genetics study by submitting personal samples for analysis and donating the genetic results to the database. We report our experience from the first 18 months of public participation in the Genographic Project, during which we have created the largest standardized human mitochondrial DNA (mtDNA) database ever collected, comprising 78,590 genotypes. Here, we detail our genotyping and quality assurance protocols including direct sequencing of the mtDNA HVS-I, genotyping of 22 coding-region SNPs, and a series of computational quality checks based on phylogenetic principles. This database is very informative with respect to mtDNA phylogeny and mutational dynamics, and its size allows us to develop a nearest neighbor-based methodology for mtDNA haplogroup prediction based on HVS-I motifs that is superior to classic rule-based approaches. We make available to the scientific community and general public two new resources: a periodically updated database comprising all data donated by participants, and the nearest neighbor haplogroup prediction tool.