Use of a random coefficient regression (RCR) model to estimate growth parameters

We used a random coefficient regression (RCR) model to estimate growth parameters for the time series of observed serum glucose levels in the Replicate 1 of the Genetic Analysis Workshop 13 simulated data. For comparison, a two time-point interval was also selected and the slope between these two observations was calculated. This process yielded four phenotypes: the RCR growth phenotype, a two time-point slope phenotype, and Time 1 and Time 2 serum glucose level phenotypes. These four phenotypes were used for linkage analyses on simulated chromosomes 5, 7, 9, and 21, those chromosomes that contained loci affecting the growth course for serum glucose levels. The linkage analysis of the RCR-derived phenotype showed overwhelming evidence for linkage at one locus (LOD 65.78 on chromosome 5), while showing elevated but nonsignificant LOD scores for two other loci (LOD 1.25 on chromosome 7, LOD 1.10 on chromosome 9), and no evidence of linkage for the final locus. The two time-point slope phenotype showed evidence for linkage at one locus (LOD 4.16 on chromosome 5) but no evidence for linkage at any of the other loci. A parallel cross-sectional approach, using as input phenotypes the endpoints of the two-point slope phenotype, gave strong linkage results for the major locus on chromosome 5 (maximal LOD scores of 17.90 and 27.24 for Time 1 and Time 2, respectively) while showing elevated but nonsignificant linkage results on chromosome 7 (maximal LOD scores of 1.71 and 1.48) and no evidence for linkage at the two remaining loci. The RCR growth parameter showed more power to detect linkage to the major locus than either the cross-sectional or two-point slope approach, but the cross-sectional approach gave a higher maximal LOD score for one of the minor loci.     

Hemorrhagic Fever with Renal Syndrome Complicated by Orchitis

Hemorrhagic fever with renal syndrome (HFRS) is a disease caused by viruses of the family Bunyaviridae,genus Hantavirus.HFRS from Dobrava virus (DOBV) is a seldom reported disease in Albania.Clinically HFRS is manifested as mild,moderate,or severe.Therefore,the number of cases of Hantavirus' infection may be underestimated,and should be included in the differential diagnosis of many acute infections,hematologic diseases,acute abdominal diseases and renal diseases complicated by acute renal failure.We report...     

Quantitative Trait Loci for Metabolic Syndrome in the Hypertension Genetic Epidemiology Network Study

As part of the Hypertension Genetic Epidemiology Network study, genome scans were performed in two ethnicities on the categorical metabolic syndrome (MetS). Genome scans were performed also on the factor scores produced by factor analysis (quantitative MetS). Heritabilities were highest for the obesity‐insulin (INS) factor and lowest for blood pressure (BP) and central obesity. Seventeen unique putative quantitative trait loci (QTLs) yielded logarithm of the odds ratio (LOD) scores in excess of 1.7, 8 for blacks and 9 for whites. Important QTL findings in whites included an LOD score of 3.19 on chromosome 15q15 for the BP factor, 3.08 on chromosome 8p23 for the lipids‐INS factor, and 3.07 on chromosome 3p26 for the obesity‐INS factor. In blacks, after excluding type 2 diabetics, important QTLs were identified, including an LOD score of 2.77 on 13p12 for the obesity‐INS factor and 2.63 on chromosome 11q24 for the lipids‐INS factor. Categorical MetS had lower results than quantitative MetS. Notably, several loci identified overlap with those identified in other studies for a single or group of traits. The most promising candidate loci on 11q24 for lipids‐INS and 13p12 for obesity‐INS in blacks, 8p23 for lipids‐INS, 14q24 for obesity‐INS, and 15q15 for BP in whites warrant further investigation.     

Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae

A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N′-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N′-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N′-(β-cyanoethyl)-N′-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N′-(β-cyanoethyl)-N′-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3).Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.     

Microsatellite linkage analysis, single-nucleotide polymorphisms, and haplotype associations with ECB21 in the COGA data

This study, part of the Genetic Analysis Workshop 14 (GAW14), explored real Collaborative Study on the Genetics of Alcoholism data for linkage and association mapping between genetic polymorphisms (microsatellite and single-nucleotide polymorphisms (SNPs)) and beta (16.5-20 Hz) oscillations of the brain rhythms (ecb21). The ecb21 phenotype underwent the statistical adjustments for the age of participants, and for attaining a normal distribution. A total of 1,000 subjects' available phenotypes were included in linkage analysis with microsatellite markers. Linkage analysis was performed only for chromosome 4 where a quantitative trait locus with 5.01 LOD score had been previously reported. Previous findings related this location with the gamma-aminobutyric acid type A (GABAA) receptor. At the same location, our analysis showed a LOD score of 2.2. This decrease in the LOD score is the result of a drastic reduction (one-third) of the available GAW14 phenotypic data. We performed SNP and haplotype association analyses with the same phenotypic data under the linkage peak region on chromosome 4. Seven Affymetrix and two Illumina SNPs showed significant associations with ecb21 phenotype. A haplotype, a combination of SNPs TSC0044171 and TSC0551006 (the latter almost under the region of GABAA genes), showed a significant association with ecb21 (p = 0.015) and a relatively high frequency in the sample studied. Our results affirmed that the GABA region has potential of harboring genes that contribute quantitatively to the beta oscillation of the brain rhythms. The inclusion of the remaining 614 subjects, which in the GAW14 had missing data for the ecb21, can improve the strength of the associations as they have already shown that they contribute quite important information in the linkage analysis.     

Two classes of 5S rDNA unit arrays of the silver fir, Abies alba Mill.: structure, localization and evolution

The structure and organization of the 5S ribosomal DNA units of the silver fir, Abies alba Mill., as well as their position in the chromosome complement were investigated. PCR amplification of the gene and nontranscribed spacer region, sequence analysis and Southern hybridization, using a homologous probe, detected DNA sequences of approximately 550 bp and 700 bp. Sequence analysis of the spacers revealed that the difference in length between the sequences occurred in the middle spacer region as a result of the amplification of a 75-bp sequence of the short unit class, which is organized in four 54- to 68-bp tandem repeats in the long spacer unit. The 5S rDNA transcribed region is 120 bp long and shows high sequence similarity with other gymnosperm species. The comparative analysis of 5 and 3 flanking sequences of 5S rRNA genes of silver fir and other gymnosperms indicates that A. alba spacer units have the same rate of evolution and are more closely related to Larix and Pseudotsuga than to Pinus and Picea. Southern hybridization and fluorescence in situ hybridization of metaphase chromosomes of A. alba suggest that the short and long spacer units are organized as separate tandem arrays at two chromosomal loci on chromosomes V and XI.     

Hemorrhagic fever with renal syndrome complicated by orchitis

Hemorrhagic fever with renal syndrome (HFRS) is a disease caused by viruses of the family Bunyaviridae,genus Hantavirus.HFRS from Dobrava virus (DOBV) is a seldom reported disease in Albania.Clinically HFRS is manifested as mild,moderate,or severe.Therefore,the number of cases of Hantavirus'infection may be underestimated,and should be included in the differential diagnosis of many acute infections,hematologic diseases,acute abdominal diseases and renal diseases complicated by acute renal failure.We report here an atypical presentation of HFRS from Dobrava virus complicated by orchitis with a positive outcome.     

Cks85A and Skp2 interact to maintain diploidy and promote growth in Drosophila

The Cks or Suc1 proteins are highly conserved small proteins that play remarkably diverse roles in the cell cycle. All Cks homologues have the ability to associate with Cyclin dependent kinases (Cdks) and in many cases this interaction has been shown to be important for function. Here we characterize the null and RNAi knockdown phenotype of the Drosophila Cks1 (Cks85A) gene. Cks85A is essential for viability in Drosophila. Cks85A null animals have reduced overall growth and this correlates with reduced ploidy and impaired DNA replication in endoreplicating cells. Interestingly, Cks85A is also required for the maintenance of diploidy in mitotically cycling cells. The requirement for Cks85A in growth is similar to that of the mammalian Cks1, which was found to interact with the SCF^Skp2 ubiquitin ligase. We identified the Drosophila Skp2 gene and generated null alleles. Comparison of these mutants to null mutants for Cks85A reveals a remarkably similar dual requirement in growth and in maintenance of diploidy. We find that Cks85A interacts directly with the SCF^Skp2 ubiquitin ligase and genetic evidence indicates that this is its major molecular function. The closely related Cks30A cannot interact with the SCF^Skp2 and cannot functionally compensate for loss of Cks85A. We also find that the critical growth promoting and diploidy maintaining functions of Cks85A and Skp2 are independent of known SCF^Skp2 substrates, p27 and Cdt1, indicating that other critical substrates remain to be identified.