HLA antigen frequencies and Wegener's granulomatosis

Previous reports of an association between HLA tissue type and Wegener's granulomatosis are contradictory. By using for the first time a highly sensitive restriction fragment-length polymorphism (RFLP) analysis in addition to standard microcytotoxicity assays, the largest series yet investigated (41 patients) was tissue typed. No association was found between any specific HLA antigen and Wegener's granulomatosis. Although the condition appears to be immunologically mediated, this study indicates that the HLA antigens do not have a major role.

Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy

Background: Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN.

Methods: Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n = 718; controls: n = 749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate.

Results: A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P< 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing.

Conclusions: These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.© 2013 Kavanagh et al.; licensee BioMed Central Ltd.

Determination of Spontaneous Mutation Frequencies in Measles Virus under Nonselective Conditions

There is a paradox between the remarkable genetic stability of measles virus (MV) in the field and the high mutation rates implied by the frequency of the appearance of monoclonal antibody escape mutants generated when the virus is pressured to revert in vitro (S. J. Schrag, P. A. Rota, and W. J. Bellini, J. Virol. 73: 51-54, 1999). We established a highly sensitive assay to determine frequencies of various categories of mutations in large populations of wild-type and laboratory-adapted MVs using recombinant viruses containing an additional transcription unit (ATU) encoding enhanced green fluorescent protein (EGFP). Single and double mutations were made in the fluorophore of EGFP to ablate fluorescence. The frequencies of reversion mutants in the population were determined by measuring the appearance of fluorescence indicating a revertant virus. This allows mutation rates to be measured under nonselective conditions, as phenotypic reversion to fluorescence requires only either a single-or a double-nucleotide change and amino acid substitution, which does not affect the length of the nonessential reporter protein expressed from the ATU. Mutation rates in MV are the same for wild-type and laboratory-adapted viruses, and they are an order of magnitude lower than the previous measurement assessed under selective conditions. The actual mutation rate for MV is approximately 1.8 x 10(-6) per base per replication event. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Different frequencies of acupuncture for treatment for chronic low back pain: an-assessor blinded pilot randomised controlled trial.

OBJECTIVES:
To examine the feasibility of a main RCT to compare the effectiveness of two frequencies (2 versus 5 times/week) of acupuncture treatment for chronic low back pain (LBP).
METHODS:
Participants (n=30) with chronic LBP were randomised into two groups to receive 10 acupuncture treatments: Low Frequency Group, 2 times/week for five weeks (n=15); High Frequency Group, 5 times/week for two weeks (n=15). The following outcomes were measured blindly at baseline, 2 weeks, 5 weeks, 3 months and 1 year: pain on a VAS, functional disability using the RMDQ, quality of life using the Measure Yourself Medical Outcome Profile (MYMOP-2), psychological impact with the Coping Strategies Questionnaire (CSQ) and Pain Locus of Control (PLC) questionnaire. Two objective outcomes, the Shuttle Walk Test (SWT) and Lateral Trunk Flexibility (LTF), were also measured.
RESULTS:
The compliance rate was 100% for each group. Some of the measurements were shown to be sensitive (VAS, RMDQ, MYMOP-2 Wellbeing). 66-330 participants would be required for a fully powered non-inferiority trial. The groups were balanced at baseline for LBP and demographic characteristics. There were no significant differences between the groups in terms of any of the outcomes, at each follow-up time point. It was notable however that the clinically important improvement in terms of pain, functional disability, quality of life, and SWT in both groups was achieved within the first two weeks, which was maintained at one year follow-up.
CONCLUSIONS:
It is feasible to conduct a main RCT, to compare different frequencies of acupuncture for LBP, using sensitive measurements. Also the trend for early clinically important improvement within a minimum of four measurements is worthy of further study.

AMBIGUITIES IN ADSORBATE SITE ASSIGNMENT FROM VIBRATIONAL FREQUENCIES - A TLEED STRUCTURAL STUDY OF (2X1)CO-PD(110)

The structure of the (2 X 1)CO-Pd(110) surface phase has been determined by LEED intensity analysis. The CO molecule is found to be adsorbed in an atop site, tilted by 11-degrees +/- 4-degrees with respect to the surface normal, with a C-O bond length of 1.16 +/- 0.04 angstrom. Interestingly, the C-O vibrational frequency for this system (2003 cm-1) is virtually identical to the frequency observed for the (2 X 1)CO-Ni(110) surface phase (1998 cm-1) which a previous LEED study has shown involves bridge bound CO molecules. The result indicates that care must be taken in assigning site symmetries on the basis of C-O stretching frequencies alone.

Parametric study to extract bridge frequencies from the dynamic response of passing vehicles

A conventional way to identify bridge frequencies is utilizing vibration data measured directly from the bridge. A drawback with this approach is that the deployment and maintenance of the vibration sensors are generally costly and time-consuming. One way to cope with the drawback is an indirect approach utilizing vehicle vibrations while the vehicle passes over the bridge. In the indirect approach, however, the vehicle vibration includes the effect of road surface roughness, which makes it difficult to extract the bridge modal properties. One solution may be subtracting signals of two trailers towed by a vehicle to reduce the effect of road surface roughness. A simplified vehicle-bridge interaction model is used in the numerical simulation; the vehicle - trailer and bridge system are modeled as a coupled model. In addition, a laboratory experiment is carried out to verify results of the simulation and examine feasibility of the damage detection by the indirect method.

The effect of the 'Gait keeper' mutation in the DMRT3 gene on gaiting ability in Icelandic horses

A nonsense mutation in DMRT3 ('Gait keeper' mutation) has a predominant effect on gaiting ability in horses, being permissive for the ability to perform lateral gaits and having a favourable effect on speed capacity in trot. The DMRT3 mutant allele (A) has been found in high frequency in gaited breeds and breeds bred for harness racing, while other horse breeds were homozygous for the wild-type allele (C). The aim of this study was to evaluate further the effect of the DMRT3 nonsense mutation on the gait quality and speed capacity in the multigaited Icelandic horse and demonstrate how the frequencies of the A- and C- alleles have changed in the Icelandic horse population in recent decades. It was confirmed that homozygosity for the DMRT3 nonsense mutation relates to the ability to pace. It further had a favourable effect on scores in breeding field tests for the lateral gait tölt, demonstrated by better beat quality, speed capacity and suppleness. Horses with the CA genotype had on the other hand significantly higher scores for walk, trot, canter and gallop, and they performed better beat and suspension in trot and gallop. These results indicate that the AA genotype reinforces the coordination of ipsilateral legs, with the subsequent negative effect on the synchronized movement of diagonal legs compared with the CA genotype. The frequency of the A-allele has increased in recent decades with a corresponding decrease in the frequency of the C-allele. The estimated frequency of the A-allele in the Icelandic horse population in 2012 was 0.94. Selective breeding for lateral gaits in the Icelandic horse population has apparently altered the frequency of DMRT3 genotypes with a predicted loss of the C-allele in relatively few years. The results have practical implications for breeding and training of Icelandic horses and other gaited horse breeds.

Neolithic and Bronze age migration to Ireland and establishment of the insular Atlantic genome

The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.

Extracting bridge frequencies from dynamic responses of two passing vehicles

A conventional way to identify bridge frequencies is utilizing vibration data measured directly from the bridge. A drawback with this approach is that the deployment and maintenance of the vibration sensors are generally costly and time-consuming. One of the solutions is in a drive-by approach utilizing vehicle vibrations while the vehicle passes over the bridge. In this approach, however, the vehicle vibration includes the effect of road surface roughness, which makes it difficult to extract the bridge modal properties. This study aims to examine subtracting signals of two trailers towed by a vehicle to reduce the effect of road surface roughness. A simplified vehicle-bridge interaction model is used in the numerical simulation; the vehicle - trailer and bridge system are modeled as a coupled model. In addition, a laboratory experiment is carried out to verify results of the simulation and examine feasibility of the damage detection by the drive-by method.