The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Building a collaborative Psychological Science: Lessons Learned from ManyBabies 1

The field of infancy research faces a difficult challenge: Some questions require samples that are simply too large for any 1 lab to recruit and test. ManyBabies aims to address this problem by forming large-scale collaborations on key theoretical questions in developmental science, while promoting the uptake of Open Science practices. Here, we look back on the first project completed under the ManyBabies umbrella—ManyBabies 1—which tested the development of infant-directed speech preference. Our goal is to share the lessons learned over the course of the project and to articulate our vision for the role of large-scale collaborations in the field. First, we consider the decisions made in scaling up experimental research for a collaboration involving 100+ researchers and 70+ labs. Next, we discuss successes and challenges over the course of the project, including the following: protocol design and implementation, data analysis, organisational structures and collaborative workflows, securing funding, and encouraging broad participation in the project. Finally, we discuss the benefits we see both in ongoing ManyBabies projects and in future large-scale collaborations in general, with a particular eye toward developing best practices and increasing growth and diversity in infancy research and psychological science in general. Throughout the article, we include first-hand narrative experiences to illustrate the perspectives of researchers playing different roles within the project. Although this project focused on the unique challenges of infant research, many of the insights we gained can be applied to large-scale collaborations across the broader field of psychology

Mouse Estrous Cycle Identification Tool and Images

The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J), agouti (CByB6F1/J) and albino (BALB/cByJ). When all 4 stages (proestrus, estrus, metestrus, and diestrus) need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology

Predictors of Ips confusus Outbreaks During a Record Drought in Southwestern USA: Implications for Monitoring and Management

In many ecosystems the effects of disturbance can be cryptic and disturbance may vary in subtle spatiotemporal ways. For instance, we know that bark beetle outbreaks are more frequent in temperate forests during droughts; however, we have little idea about why they occur in some locations and not others. Understanding biotic and abiotic factors promoting bark beetle outbreaks can be critical to predicting and responding to pest outbreaks. Here we address the environmental factors which are associated with Ips confusus outbreaks during the 2002 widespread drought within the distribution range of pinyon pine woodlands in Arizona. We used univariate statistics to test if whether tree characteristics, other herbivores, stand properties, soil type, wind, and topography were associated with I. confusus outbreak, and logistic regression to create a predictive model for the outbreaks. We found that I. confusus attacks occur in low elevation stands on steeper slopes, where favorable winds for I. confusus dispersion occur. I. confusus select larger trees, in high density stands with understory shrubs that exhibit phenotypic traits characteristic of resistance to stem-boring moths. The model was highly accurate, and explained 95% of the variability in occurrence (98% of the absences and 95% of the presences). Accurate prediction of the impacts of disturbance allow us to anticipate, minimize or mitigate for and eventually counteract its effects, especially those affecting diversity and ecosystem function. Identification of outbreak risk areas can guide regional and national management towards the reduction of infestation risk and enhancing conservation of pinyon-juniper woodlands

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta

Osteogenesis imperfecta (OI) comprises a group of inherited disorders characterized by bone fragility and increased susceptibility to fractures. Historically, the laboratory confirmation of the diagnosis OI rested on cultured dermal fibroblasts to identify decreased or abnormal production of abnormal type I (pro)collagen molecules, measured by gel electrophoresis. With the discovery of COL1A1 and COL1A2 gene variants as a cause of OI, sequence analysis of these genes was added to the diagnostic process. Nowadays, OI is known to be genetically heterogeneous. About 90% of individuals with OI are heterozygous for causative variants in the COL1A1 and COL1A2 genes. The majority of remaining affected individuals have recessively inherited forms of OI with the causative variants in the more recently discovered genes CRTAP, FKBP10, LEPRE1,PLOD2, PPIB, SERPINF1, SERPINH1 and SP7, or in other yet undiscovered genes. These advances in the molecular genetic diagnosis of OI prompted us to develop new guidelines for molecular testing and reporting of results in which we take into account that testing is also used to ‘exclude' OI when there is suspicion of non-accidental injury. Diagnostic flow, methods and reporting scenarios were discussed during an international workshop with 17 clinicians and scientists from 11 countries and converged in these best practice guidelines for the laboratory diagnosis of OI

Mobility and other predictors of hospitalization for urinary tract infection: a retrospective cohort study

Abstract Background Many hospitalizations for residents of skilled nursing facilities are potentially avoidable. Factors that could prevent hospitalization for urinary tract infection (UTI) were investigated, with focus on patient mobility. Methods A retrospective cohort study was conducted using 2003–2004 data from the Centers for Medicare and Medicaid Services. The study included 408,192 residents of 4267 skilled nursing facilities in California, Florida, Michigan, New York, and Texas. The patients were followed over time, from admission to the skilled nursing facility to discharge or, for those who were not discharged, for 1 year. Cox proportional hazards regression was conducted with hospitalization for UTI as the outcome. Results The ability to walk was associated with a 69% lower rate of hospitalization for UTI. Maintaining or improving walking ability over time reduced the risk of hospitalization for UTI by 39% to 76% for patients with various conditions. For residents with severe mobility problems, such as being in a wheelchair or having a missing limb, maintaining or improving mobility (in bed or when transferring) reduced the risk of hospitalization for UTI by 38% to 80%. Other potentially modifiable predictors included a physician visit at the time of admission to the skilled nursing facility (Hazard Ratio (HR), 0.68), use of an indwelling urinary catheter (HR, 2.78), infection with Clostridium difficile or an antibiotic-resistant microorganism (HR, 1.20), and use of 10 or more medications (HR, 1.31). Patient characteristics associated with hospitalization for UTI were advancing age, being Hispanic or African-American, and having diabetes mellitus, renal failure, Parkinson's disease, dementia, or stroke. Conclusion Maintaining or improving mobility (walking, transferring between positions, or moving in bed) was associated with a lower risk of hospitalization for UTI. A physician visit at the time of admission to the skilled nursing facility also reduced the risk of hospitalization for UTI.http://deepblue.lib.umich.edu/bitstream/2027.42/112369/1/12877_2008_Article_125.pd

Functional Characterization of CLPTM1L as a Lung Cancer Risk Candidate Gene in the 5p15.33 Locus

Cleft Lip and Palate Transmembrane Protein 1-Like (CLPTM1L), resides in a region of chromosome 5 for which copy number gain has been found to be the most frequent genetic event in the early stages of non-small cell lung cancer (NSCLC). This locus has been found by multiple genome wide association studies to be associated with lung cancer in both smokers and non-smokers. CLPTM1L has been identified as an overexpressed protein in human ovarian tumor cell lines that are resistant to cisplatin, which is the only insight thus far into the function of CLPTM1L. Here we find CLPTM1L expression to be increased in lung adenocarcinomas compared to matched normal lung tissues and in lung tumor cell lines by mechanisms not exclusive to copy number gain. Upon loss of CLPTM1L accumulation in lung tumor cells, cisplatin and camptothecin induced apoptosis were increased in direct proportion to the level of CLPTM1L knockdown. Bcl-xL accumulation was significantly decreased upon loss of CLPTM1L. Expression of exogenous Bcl-xL abolished sensitization to apoptotic killing with CLPTM1L knockdown. These results demonstrate that CLPTM1L, an overexpressed protein in lung tumor cells, protects from genotoxic stress induced apoptosis through regulation of Bcl-xL. Thus, this study implicates anti-apoptotic CLPTM1L function as a potential mechanism of susceptibility to lung tumorigenesis and resistance to chemotherapy

The fitness consequences of inbreeding in natural populations and their implications for species conservation – a systematic map

Background: Threatened species often have small and isolated populations where mating among relatives can result in inbreeding depression increasing extinction risk. Effective management is hampered by a lack of syntheses summarising the magnitude of, and variation in inbreeding depression. Here we describe the nature and scope of the literature examining phenotypic/fitness consequences of inbreeding, to provide a foundation for future syntheses and management. Methods: We searched the literature for articles documenting the impact of inbreeding in natural populations. Article titles, abstracts and full-texts were assessed against a priori defined criteria, and information relating to study design, quality and other factors that may influence inbreeding responses (e.g. population size) was extracted from relevant articles. Results: The searches identified 11457 articles, of which 614 were assessed as relevant and included in the systematic map (corresponding to 703 distinct studies). Most studies (663) assessed within-population inbreeding resulting from self-fertilisation or consanguineous pairings, while 118 studies assessed among-population inbreeding due to drift load. Plants were the most studied taxon (469 studies) followed by insects (52 studies) and birds (43 studies). Most studies investigated the effects of inbreeding on components of fitness (e.g. survival or fecundity; 648 studies) but measurements were typically under laboratory/greenhouse conditions (486 studies). Observations were also often restricted to the first inbred generation (607 studies) and studies frequently lacked contextual information (e.g. population size). Conclusions: Our systematic map describes the scope and quality of the evidence describing the phenotypic consequences of inbreeding. The map reveals substantial evidence relating to inbreeding responses exists, but highlights information is still limited for some aspects, including the effects of multiple generations of inbreeding. The systematic map allowed us to define several conservation-relevant questions, where sufficient data exists to support systematic reviews, e.g. How do inbreeding responses vary with population size? However, we found that such syntheses are likely to be constrained by incomplete reporting of critical contextual information. Our systematic map employed the same rigorous literature assessment methods as systematic review, including a novel survey of study quality and thus provides a robust foundation to guide future research and syntheses seeking to inform conservation decision-making

Siderophore production by Bacillus megaterium : effect of growth-phase and cultural conditions

Siderophore production by Bacillus megaterium was detected, in an iron-deficient culture medium, during the exponential growth phase, prior to the sporulation, in the presence of glucose; these results suggested that the onset of siderophore production did not require glucose depletion and was not related with the sporulation. The siderophore production by B. megaterium was affected by the carbon source used. The growth on glycerol promoted the very high siderophore production (1,182 μmol g−1 dry weight biomass); the opposite effect was observed in the presence of mannose (251 μmol g−1 dry weight biomass). The growth in the presence of fructose, galactose, glucose, lactose, maltose or sucrose, originated similar concentrations of siderophore (546–842 μmol g−1 dry weight biomass). Aeration had a positive effect on the production of siderophore. Incubation of B. megaterium under static conditions delayed and reduced the growth and the production of siderophore, compared with the incubation in stirred conditions.The authors thank Porto University/Totta Bank for their financial support through the project "Microbiological production of chelating agents" (Ref: 180). The authors also thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grants Strategic project-LA23/2013-2014 (IBB) and PEST-C/EQB/LA0006/2011 (REQUIMTE). Manuela D. Machado gratefully acknowledges the postdoctoral (SFRH/BPD/72816/2010) grant from FCT