Combinatorial Conflicting Homozygosity (CCH) analysis enables the rapid identification of shared genomic regions in the presence of multiple phenocopies.

The ability to identify regions of the genome inherited with a dominant trait in one or more families has become increasingly valuable with the wide availability of high throughput sequencing technology. While a number of methods exist for mapping of homozygous variants segregating with recessive traits in consanguineous families, dominant conditions are conventionally analysed by linkage analysis, which requires computationally demanding haplotype reconstruction from marker genotypes and, even using advanced parallel approximation implementations, can take substantial time, particularly for large pedigrees. In addition, linkage analysis lacks sensitivity in the presence of phenocopies (individuals sharing the trait but not the genetic variant responsible). Combinatorial Conflicting Homozygosity (CCH) analysis uses high density biallelic single nucleotide polymorphism (SNP) marker genotypes to identify genetic loci within which consecutive markers are not homozygous for different alleles. This allows inference of identical by descent (IBD) inheritance of a haplotype among a set or subsets of related or unrelated individuals

A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen

BACKGROUND: Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. METHODS: We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. RESULTS: We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. CONCLUSIONS: Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans

Conscious monitoring and control (reinvestment) in surgical performance under pressure.

Research on intraoperative stressors has focused on external factors without considering individual differences in the ability to cope with stress. One individual difference that is implicated in adverse effects of stress on performance is "reinvestment," the propensity for conscious monitoring and control of movements. The aim of this study was to examine the impact of reinvestment on laparoscopic performance under time pressure

Mosquito Abundance, Bed net Coverage and Other Factors Associated with Variations in Sporozoite Infectivity Rates in Four Villages of Rural Tanzania.

Entomological surveys are of great importance in decision-making processes regarding malaria control strategies because they help to identify associations between vector abundance both species-specific ecology and disease intervention factors associated with malaria transmission. Sporozoite infectivity rates, mosquito host blood meal source, bed net coverage and mosquito abundance were assessed in this study. A longitudinal survey was conducted in four villages in two regions of Tanzania. Malaria vectors were sampled using the CDC light trap and pyrethrum spray catch methods. In each village, ten paired houses were selected for mosquitoes sampling. Sampling was done in fortnight case and study was undertaken for six months in both Kilimanjaro (Northern Tanzania) and Dodoma (Central Tanzania) regions. A total of 6,883 mosquitoes were collected including: 5,628 (81.8%) Anopheles arabiensis, 1,100 (15.9%) Culex quinquefasciatus, 89 (1.4%) Anopheles funestus, and 66 (0.9%) Anopheles gambiae s.s. Of the total mosquitoes collected 3,861 were captured by CDC light trap and 3,022 by the pyrethrum spray catch method. The overall light trap: spray catch ratio was 1.3:1. Mosquito densities per room were 96.5 and 75.5 for light trap and pyrethrum spray catch respectively. Mosquito infectivity rates between villages that have high proportion of bed net owners and those without bed nets was significant (P < 0.001) and there was a significant difference in sporozoite rates between households with and without bed nets in these four villages (P < 0.001). Malaria remains a major problem in the study areas characterized as low transmission sites. Further studies are required to establish the annual entomological inoculation rates and to observe the annual parasitaemia dynamics in these communities. Outdoor mosquitoes collection should also be considered

Static non-reciprocity in mechanical metamaterials

Reciprocity is a fundamental principle governing various physical systems, which ensures that the transfer function between any two points in space is identical, regardless of geometrical or material asymmetries. Breaking this transmission symmetry offers enhanced control over signal transport, isolation and source protection. So far, devices that break reciprocity have been mostly considered in dynamic systems, for electromagnetic, acoustic and mechanical wave propagation associated with spatio-temporal variations. Here we show that it is possible to strongly break reciprocity in static systems, realizing mechanical metamaterials that, by combining large nonlinearities with suitable geometrical asymmetries, and possibly topological features, exhibit vastly different output displacements under excitation from different sides, as well as one-way displacement amplification. In addition to extending non-reciprocity and isolation to statics, our work sheds new light on the understanding of energy propagation in non-linear materials with asymmetric crystalline structures and topological properties, opening avenues for energy absorption, conversion and harvesting, soft robotics, prosthetics and optomechanics.Comment: 19 pages, 3 figures, Supplementary information (11 pages and 5 figures

Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine?

Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone therapy on the development of clinical signs, EEG, heart rate, respiration and AChE activity in blood and brain after soman poisoning. The model allowed the determination of the therapeutic effects at the short-term of obidoxime, atropine and physostigmine. Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1 mg/kg i.m.), whereas two higher doses (9 and 18 mg/kg) were less effective on most parameters. Addition of atropine at 0.03 and 3 mg/kg (i.m.) to the treatment did not improve the therapeutic effects of obidoxime alone. Physostigmine (0.8 mg/kg im) at 1 min after poisoning increased mortality. Two lower doses (0.1 and 0.3 mg/kg i.m.) showed improvements on all parameters but respiration. The middle dose was most effective in preventing seizure development and therefore assessed as the most efficacious dose. Combined treatment of obidoxime and physostigmine shortened the duration of seizures, if present, from up to 80 min to ~10–15 min. In practice, treatment will be employed when toxic signs appear, with the presence of high levels of AChE inhibition in both blood and brain. Administration of physostigmine at that moment showed to be redundant or even harmful. Therefore, treatment of OP poisoning with a carbamate, such as physostigmine, should be carefully re-evaluated

Isotope effect on the transition temperature TcT_c in Fe-based superconductors: the current status

The results of the Fe isotope effect (Fe-IE) on the transition temperature $T_c$ obtained up to date in various Fe-based high temperature superconductors are summarized and reanalyzed by following the approach developed in [Phys. Rev. B 82, 212505 (2010)]. It is demonstrated that the very controversial results for Fe-IE on $T_c$ are caused by small structural changes occurring simultaneously with the Fe isotope exchange. The Fe-IE exponent on $T_c$ [$\alpha_{\rm Fe}=-(\Delta T_c/T_c)/(\Delta M/M)$, $M$ is the isotope mass] needs to be decomposed into two components with the one related to the structural changes ($\alpha_{\rm Fe}^{\rm str}$) and the genuine (intrinsic) one ($\alpha_{\rm Fe}^{\rm int}$). The validity of such decomposition is further confirmed by the fact that $\alpha_{\rm Fe}^{\rm int}$ coincides with the Fe-IE exponent on the characteristic phonon frequencies $\alpha_{\rm Fe}^{\rm ph}$ as is reported in recent EXAFS and Raman experiments.Comment: 7 pages, 4 figures. The paper is partially based on the results published in [New J. Phys. 12, 073024 (2010) = arXiv:1002.2510] and [Phys. Rev. B 82, 212505 (2010) = arXiv:1008.4540

Conducting Health Research in Korean American Churches: Perspectives from Church Leaders

Korean Americans experience many challenges to obtaining adequate health care coverage and access to needed services. Because a large proportion of Korean Americans attend churches on a regular basis, churches may be a promising venue where health programs can be delivered. In order to gain an in-depth understanding of Korean American churches with respect to conducting future health intervention research, we conducted exploratory interviews and focus groups with 58 leaders from 23 Korean American churches and three community organizations. From these interviews and focus groups, we found that Korean churches and church leaders seek to meet a variety of social and health needs of their congregation and their surrounding community. Several leaders have stated that assisting with social and medical needs of their members is an important component of their current ministry. They described profound health needs of their congregations and have suggested various ways in which the university can partner with the local churches to help address these needs through research. Additionally, they described various resources churches can provide to researchers such as: their personal assistance, church volunteer base, church facility, and church network and contacts. Our findings suggest that Korean churches have a high potential to serve an important role in the health of Korean Americans. On the basis of the promising results of the present study, we are planning to conduct a cross sectional survey of Korean church leaders and members in Los Angeles County to substantiate our findings in a larger representative sample

ANKRD26 and Its Interacting Partners TRIO, GPS2, HMMR and DIPA Regulate Adipogenesis in 3T3-L1 Cells

Partial inactivation of the Ankyrin repeat domain 26 (Ankrd26) gene causes obesity and diabetes in mice and increases spontaneous and induced adipogenesis in mouse embryonic fibroblasts. However, it is not yet known how the Ankrd26 protein carries out its biological functions. We identified by yeast two-hybrid and immunoprecipitation assays the triple functional domain protein (TRIO), the G protein pathway suppressor 2 (GPS2), the delta-interacting protein A (DIPA) and the hyaluronan-mediated motility receptor (HMMR) as ANKRD26 interacting partners. Adipogenesis of 3T3-L1 cells was increased by selective down-regulation of Ankrd26, Trio, Gps2, Hmmr and Dipa. Furthermore, GPS2 and DIPA, which are normally located in the nucleus, were translocated to the cytoplasm, when the C-terminus of ANKRD26 was introduced into these cells. These findings provide biochemical evidence that ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenisis and identify new targets for the modulation of adipogenesis

Protective Efficacy of Menthol Propylene Glycol Carbonate Compared to N, N-diethyl-Methylbenzamide Against Mosquito Bites in Northern Tanzania.

The reduction of malaria parasite transmission by preventing human-vector contact is critical in lowering disease transmission and its outcomes. This underscores the need for effective and long lasting arthropod/insect repellents. Despite the reduction in malaria transmission and outcomes in Tanzania, personal protection against mosquito bites is still not well investigated. This study sought to determine the efficacy of menthol propylene glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination (blend), both in the laboratory and in the field against Anopheles gambiae s.l and Culex quinquefasciatus. In the laboratory evaluations, repellents were applied on one arm while the other arm of the same individual was treated with a base cream. Each arm was separately exposed in cages with unfed female mosquitoes. Repellents were evaluated either as a single dose or as a blend. Efficacy of each repellent was determined by the number of mosquitoes that landed and fed on treated arms as compared to the control or among them. In the field, evaluations were performed by human landing catches at hourly intervals from 18:00  hr to 01:00  hr. A total of 2,442 mosquitoes were collected during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66 (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar protective efficacy ranging from 92% to 100 for both single compound and blends. These findings indicate that MR08 has a similar protective efficacy as DEET for personal protection outside bed nets when used singly and in blends. Because of the personal protection provided by MR08, DEET and blends as topical applicants in laboratory and field situations, these findings suggest that, these repellents could be used efficiently in the community to complement existing tools. Overall, Cx. quinquefasciatus were significantly prevented from blood feeding compared to An. gambiae s.l. The incorporation of these topical repellents for protection against insect bites can be of additional value in the absence or presence of IRS and ITNs coverage. However, a combination of both the physical (bed nets) and the repellent should be used in an integrated manner for maximum protection, especially before going to bed. Additional research is needed to develop repellents with longer duration of protection