17 research outputs found

    Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

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    Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.Children’s Discovery InstituteMarch of Dimes Birth Defects FoundationNational Institute of General Medical Sciences (U.S.) (grant T32 GM081739)Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study)Sigrid Jusélius FoundationSigne and Anne Gyllenberg FoundationAcademy of FinlandVanderbilt University (Turner-Hazinski grant award

    Leadership = Communication? The relations of leaders' communication styles with leadership styles, knowledge sharing and leadership outcomes

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    Purpose: The purpose of this study was to investigate the relations between leaders' communication styles and charismatic leadership, human-oriented leadership (leader's consideration), task-oriented leadership (leader's initiating structure), and leadership outcomes. Methodology: A survey was conducted among 279 employees of a governmental organization. The following six main communication styles were operationalized: verbal aggressiveness, expressiveness, preciseness, assuredness, supportiveness, and argumentativeness. Regression analyses were employed to test three main hypotheses. Findings: In line with expectations, the study showed that charismatic and human-oriented leadership are mainly communicative, while task-oriented leadership is significantly less communicative. The communication styles were strongly and differentially related to knowledge sharing behaviors, perceived leader performance, satisfaction with the leader, and subordinate's team commitment. Multiple regression analyses showed that the leadership styles mediated the relations between the communication styles and leadership outcomes. However, leader's preciseness explained variance in perceived leader performance and satisfaction with the leader above and beyond the leadership style variables. Implications: This study offers potentially invaluable input for leadership training programs by showing the importance of leader's supportiveness, assuredness, and preciseness when communicating with subordinates. Originality/value: Although one of the core elements of leadership is interpersonal communication, this study is one of the first to use a comprehensive communication styles instrument in the study of leadership. © 2009 The Author(s)

    Creation of a library of induced pluripotent stem cells from Parkinsonian patients

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    Induced pluripotent stem cells (iPSCs) are becoming an important source of pre-clinical models for research focusing on neurodegeneration. They offer the possibility for better understanding of common and divergent pathogenic mechanisms of brain diseases. Moreover, iPSCs provide a unique opportunity to develop personalized therapeutic strategies, as well as explore early pathogenic mechanisms, since they rely on the use of patients' own cells that are otherwise accessible only post-mortem, when neuronal death-related cellular pathways and processes are advanced and adaptive. Neurodegenerative diseases are in majority of unknown cause, but mutations in specific genes can lead to familial forms of these diseases. For example, mutations in the superoxide dismutase 1 gene lead to the motor neuron disease amyotrophic lateral sclerosis (ALS), while mutations in the SNCA gene encoding for alpha-synuclein protein lead to familial Parkinson's disease (PD). The generations of libraries of familial human ALS iPSC lines have been described, and the iPSCs rapidly became useful models for studying cell autonomous and non-cell autonomous mechanisms of the disease. Here we report the generation of a comprehensive library of iPSC lines of familial PD and an associated synucleinopathy, multiple system atrophy (MSA). In addition, we provide examples of relevant neural cell types these iPSC can be differentiated into, and which could be used to further explore early disease mechanisms. These human cellular models will be a valuable resource for identifying common and divergent mechanisms leading to neurodegeneration in PD and MSA
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