Variation in complement factor 3 is associated with risk of age-related macular degeneration

The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample.     

Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.     

A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

Wnt-beta-catenin signaling initiates taste papilla development

Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning.     

Research and Reflection: Potential Impact on the Professional Development of Undergraduate Occupational Therapy Students

In occupational therapy education in South Africa, community service (CS) focuses learning opportunities during fieldwork placements. CS therefore enabled the researcher to utilise successive small scale research projects to guide learning of students during fieldwork while simultaneously developing the occupational therapy service at a residential care facility. This community setting provided a powerful environment through which research, in combination with opportunities for reflection, contributed to nurturing skills needed by these future health professionals. A technical action research (AR) approach incorporated AR cycles and opportunities for structured reflection. Therefore situations were created for the students to embrace experiential learning. Experiential learning in the form of anticipatory reflection, reflection-in-action, reflection on reflection and retrospective reflection impacted on the quality of the students’ work. Besides encouraging unique leaning opportunities for students when engaging in research during their fieldwork placement, engagement in AR cycles simultaneously improved service delivery to residents in the facility. Key benefits of this investigation were that fieldwork education utilising AR cycles within a CS situation promoted students to identify voids in their theoretical background as well as practice skills; to apply reflective practice that could contribute to their personal and professional development; and to utilize learning opportunities optimally. Despite positive gains showed by this study, the role of power relations between the researcher as fieldwork educator and the students prohibited the AR cycles from being more emancipatory in nature and should be addressed in follow-up studies.     

Performance analysis of optimal channel estimation and multiuser detection in a randomly-spread CDMA channel

<正> This paper analyzes performance of optimal channel estimation and multiuser detection(MUD) in a block-fading code-division multiple-access (CDMA) channel on the assumptions of randomspreading and large-system limit,by using the replica method developed in statistical mechanics.The authors find that the asymptotic spectral efficiency of the linear minimum mean-squared error(LMMSE) MUD which was proposed and analyzed by Evans and Tse in 2000 is indistinguishable fromthat of the optimal MUD for small system loads.Our results imply that performance of MUD scarcelyimproves even if one spends more computational cost than that of the LMMSE MUD,i.e.,at most thecube of the number of users,on the above-described conditions.