Genetic interactions contribute less than additive effects to quantitative trait variation in yeast.

Genetic mapping studies of quantitative traits typically focus on detecting loci that contribute additively to trait variation. Genetic interactions are often proposed as a contributing factor to trait variation, but the relative contribution of interactions to trait variation is a subject of debate. Here we use a very large cross between two yeast strains to accurately estimate the fraction of phenotypic variance due to pairwise QTL-QTL interactions for 20 quantitative traits. We find that this fraction is 9% on average, substantially less than the contribution of additive QTL (43%). Statistically significant QTL-QTL pairs typically have small individual effect sizes, but collectively explain 40% of the pairwise interaction variance. We show that pairwise interaction variance is largely explained by pairs of loci at least one of which has a significant additive effect. These results refine our understanding of the genetic architecture of quantitative traits and help guide future mapping studies

Establishment of a General Medicine Residency Training Program in Rural West Africa

Ghana, a developing country in West Africa, has major medical burdens in taking care of a large population with limited resources. Its three medical schools produce more than 200 graduates per year, but most emigrate to developed lands after training. Ghana is working to educate and retain locally trained physicians, but it is difficult to get them to work in rural settings where the need is greatest. This article details the establishment of a General Medicine residency at a 150-bed hospital in rural Ghana. Early training comprises 6 months each in Medicine, Surgery, OB/GYN, and Pediatrics; the hospital in Techiman also has a Surgery residency. House officers choose the program for more hands-on experience than they can get in larger centers. They perform many tasks, including surgery, sooner and more independently than do residents in developed countries. The training program includes a morning report, clinical teaching rounds, and rotations on in-patient wards and in the Emergency Department and clinics. Teaching focuses on history, physical examination, good communication, and proper follow-up, with rigorous training in the OR and some clinical research projects pertinent to Ghana. Trainees work hard and learn from one another, from a dedicated faculty, and by evaluating and treating very sick patients. Ghana’s rural residencies offer rigorous and attractive training, but it is too soon to tell whether this will help stem the “brain drain” of young physicians out of West Africa

The Medical System in Ghana

Ghana is a developing country in West Africa with a population of about 25 million. Medical illnesses in Ghana overlap with those in developed countries, but infection, trauma, and women’s health problems are much more prominent. Medical practice in rural Africa faces extremely limited resources, a multiplicity of languages (hundreds in Ghana), and presentation of severe illnesses at later stages than seen elsewhere. Despite these limitations, Ghana has established a relatively successful national medical insurance system, and the quality of medical practice is high, at least where it is available. Ghana also has a well-established and sophisticated administrative structure for the supervision of medical education and accreditation, but it has proven very difficult to extend medical training to rural areas, where health care facilities are particularly short of personnel. Physicians are sorely needed in rural areas, but there are few because of the working conditions and financial limitations. Hospital wards and clinics are crowded; time per patient is limited. This article details some of the differences between medical practice in Ghana and that in wealthier countries and how it functions with very limited resources. It also introduces the medical education and training system in Ghana. The following article describes an attempt to establish and maintain a residency training program in General Medicine in a rural area of Ghana

A comparison of brain gene expression levels in domesticated and wild animals

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30-75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.This work was funded by the Max Planck Society and a European Research Council grant (233297, TWOPAN) to SP. FWA is supported by a grant from the German Science Foundation (DFG grant AL 1525/1-1). MS was supported by a CAS young scientists fellowship (2009Y2BS12) and a National Science Foundation of China research grant (31010022). JAB-A is supported by fellowship (SFRH/BPD/65464/2009).Peer Reviewe

Early Stages of Gold and Silver Growth on α-MoTe2, β-MoTe2 and WTe2

The early stages of growth of gold and silver on (001) surfaces of α-MoTe2, β-MoTe2 and WTe2 were studied by means of scanning tunneling microscopy. Metals were deposited at room temperature at a rate of about one monolayer per minute. It is shown that, prior to the epitaxial growth of the noble metal, a local interaction between the impinging atoms and the substrate takes place. During this period the noble-metal atoms diffuse through vacancies in the top tellurium layer and occupy enlarged interstices in the chalcogen-metal-chalcogen sandwich layers, where they agglomerate into one-atom-thick islands. Their shape and size depend on the stress between them and the substrate, and they remain stable at room temperature

Genetics of single-cell protein abundance variation in large yeast populations

Many DNA sequence variants influence phenotypes by altering gene expression. Our understanding of these variants is limited by sample sizes of current studies and by measurements of mRNA rather than protein abundance. We developed a powerful method for identifying genetic loci that influence protein expression in very large populations of the yeast Saccharomyes cerevisiae. The method measures single-cell protein abundance through the use of green-fluorescent-protein tags. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci cluster at hotspot locations that influence multiple proteins - in some cases, more than half of those examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell physiology between yeast strains

All together now: findings from a PCORI workshop to align patient-reported outcomes in the electronic health record

In recent years, patient-reported outcomes have become increasingly collected and integrated into electronic health records. However, there are few cross-cutting recommendations and limited guidance available in this rapidly developing research area. Our goal is to report key findings from a 2013 Patient-Centered Outcomes Research Institute workshop on this topic and a summary of actions that followed from the workshop, and present resulting recommendations that address patient, clinical and research/quality improvement barriers to regular use. These findings provide actionable guidance across research and practice settings to promote and sustain widespread adoption of patient-reported outcomes across patient populations, healthcare settings and electronic health record systems

RELACIÓN ENTRE EL RENDIMIENTO ACADÉMICO DE LOS INGRESANTES Y EL ABANDONO DE LOS ESTUDIOS UNIVERSITARIOS: COMPARACIÓN ENTRE CARRERAS DE INGENIERÍA Y ECONOMICAS

La preocupación por orientar adecuadamente los recursos que se afectan a los programas de apoyo a los estudiantes de primer año de las carreras, nos llevó a trabajar intentando generar un modelo que sea capaz de determinar, anticipadamente, que estudiantes se encontrarían en situación de abandonar sus estudios. En una primera aplicación del modelo, se analizó la correlación entre el rendimiento académico y el abandono para diez cohortes de ingresantes, de las dos carreras de Ingeniería que ofrece la Universidad Nacional de Luján, observándose una significativa correlación entre el rendimiento académico del estudiante en el primer cuatrimestre y el abandono de los estudios durante el segundo, tercero y cuarto cuatrimestre. En este trabajo, presentamos los resultados que se alcanzaron al aplicar el mismo modelo a las diez cohortes, equivalentes, de estudiantes de las dos carreras del campo de las Ciencias Económicas que se ofrecen en la misma Institución: Licenciatura en Administración y Licenciatura en Comercio Internacional. Las principales conclusiones a las que arribamos es que el modelo se valida positivamente al cambiar el origen disciplinar de las carreras en las que se aplica. Por otra parte, existe mayor correlación entre el rendimiento académico en el primer cuatrimestre y el momento en que se abandonan los estudios para los estudiantes de carreras de Ciencias Económicas que la observada en los de Ingeniería. Se repite el fenómeno observado para las carreras de Ingeniería, de disminuir la correlación entre el rendimiento académico y el abandono para la cohorte 2002. También se detecta una diferencia significativa respecto de la moda para la cantidad de asignaturas aprobadas durante el primer cuatrimestre para las cuatro carreras

Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals