Neue Formen vonAsperula scutellaris Vis. und ihre morphologisch-geographische und klimatische Bedeutung

Zusammenfassung Die ArtAsperula scutellaris Vis. wurde diagnostisch erweitert und genauer präzisiert. Sie zerfällt in folgende Sippen: die typische Form ssp.illyrica Korica, welche zwei Varietäten umfaßt (var.veleensis Korica und var.montenegrina Korica), und ssp.ramiflora Korica mit einer Varietät (var.albanica Korica).Asperula scutellaris Vis. ist ein mediterran-illyrischer Endem und einer der bemerkenswertesten Vertreter der jugoslawischen und albanischen Karstflora. Im mittleren Teil Albaniens tritt sie auch auf Serpentinen auf.In pflanzengeographischem Sinn sind vier Entwicklungsgebiete dieser Art zu unterscheiden: das Entwicklungsgebiet der Veleplanina in der Herzegowina (var.veleensis), das montenegrinische Entwicklungsgebiet (var.montenegrina) mit dem ursprünglichen Ausbildungszentrum in der weiteren Umgebung der Stadt Cetinje, endlich das nordalbanische Entwicklungsgebiet im Stromgebiet der Flüsse Cijevna und Drim. Diese drei Gebiete sind von submediterranem Charakter, das mittelalbanische Entwicklungsgebiet in der Gegend des Flusses Shkumbi (var.albanica) weist dagegen einen mediterranisch-submediterranischen Charakter auf.Auf Grund der festgestellten Tatsachen des heutigen Standes der Verbreitung der einzelnen Sippen dieser Art sowie auf Grund der charakteristischen geomorphologischen und klimatischen Differenzen zwischen den monomorphen Sippen (ssp.illyrica), welche an die Küstenteile des beschriebenen Areals gebunden sind, und den polymorphen Übergangsformen der submediterranen Sippen, welche in den kontinentalen Teilen des Areals überwiegen (submediterrane klimatische Einflüsse), folgt, daß die typischen Formen (ssp.illyrica) im submediterranen Gebiet phylogenetisch nicht mit jenen des mediterranen Gebietes identisch sind.     

Theoretical investigations on circular and chain-like hydrogen bonded structures found in two crystal forms of α-cyclodextrin hexahydrate: Models for hydration and water clusters

Hydration of macromolecules and the structure of water of crystallization are not understood in detail because in these complex systems. H-atoms cannot be located and the hydrogen bonding schemes are not known. X-ray and neutron diffraction studies on a hydrated oligosaccharide, α-cyclodextrin 6H₂O, ((C₆H₁₀O₅)₆·6H₂O), crystals forms A and B, gave insight into the chain-like and circular arrangement of hydrogen bonds. In the circles, homodromic (unidirectional) and antidromic (counter-running) orientation of five to six hydrogen bounds is observed. PCILO calculations showed that homodromic circles and chains are approx. 8% per hydrogen bond more stable than antidromic circles, that the changes in electronic charges on H and O atoms are greater in homo than in antidromic systems and that the dipole moments are only approx. 3 D in the homodromic circles but 6–8 D in chain-like and antidromic arrangement. These results have been interpreted in terms of cooperative effect. Circular systems are considered as structural elements in hydration shells of macromolecules and in the assembly of ‘flickering’ water clusters.     

New evidence that the antiestrogen binding site may be a novel growth-promoting histamine receptor (?H3) which mediates the antiestrogenic and antiproliferative effects of tamoxifen

Using as a probe [3H]-DPPE (N,N-diethyl-2-[(4-phenylmethyl)phenoxy]ethanamine HCl), a novel compound selective for the antiestrogen binding site (AEBS), new evidence is presented that this site could be a growth-promoting histamine receptor of a type not previously described (?H3). In the rat uterus, DPPE alone at a concentration of 4 mg/kg acts as an estrogen antagonist, unlike TAM alone which is a partial estrogen agonist. In the presence of exogenous estradiol, both TAM and DPPE are partial antagonists. This suggests that the "antiestrogenic" effects of tamoxifen are mediated through AEBS/?H3 while the estrogenic effects are mediated through ER.     

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h ² in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk.     

Molecular profile of the NF‐κB signalling pathway in human colorectal cancer

The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF‐κB signalling pathway. The characterization of the NF‐κB expression profile in CRC is an important topic since the suppression of NF‐κB represents a potential therapeutic approach. In this study, we assessed the expression levels of 84 NF‐κB‐related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case–control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR‐182‐5p was upregulated in T compared with PT, whereas miR‐10b‐5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF‐ κB pathway.