693 research outputs found

    Veteran\u27s Psychosocial Needs: How Higher Education Gets Impacted

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    The purpose of this study was to identify if institutions of higher learning were able to address the psychosocial needs of veteran students upon reintegration. This quantitative study asked the University of St. Thomas\u27s (UST) students to take part in an exploratory survey. Data was collected by sending out an anonymous survey via email where respondents (N=37) were requested to answer 11 questions in regards to their experience at UST and reintegrating into an institution of higher learning after military involvement. Findings showed veteran students attending UST feel their expectations have been met in an institution for higher learning. The findings also show that obstacles were experienced in adapting to life as a non-traditional college student making reintegrating a challenge. The results of this study report that institutions of higher learning, primarily UST, have the ability to assist their veteran students in beneficial ways. Also, this study identified that veteran students do need assistance in adjusting to civilian life, balancing subsystems (military, family, school subsystems), as well as succeeding in school. Veteran students at UST have identified skills the military has taught them to help them succeed even when an obstacle is present. This research highlights the needs veteran students at UST have but also highlights that they are still succeeding and moving forward while still struggling with reintegration obstacles

    Veteran’s Psychosocial Needs: How Higher Education Gets Impacted

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    The purpose of this study was to identify if institutions of higher learning were able to address the psychosocial needs of veteran students upon reintegration. This quantitative study asked the University of St. Thomas’s (UST) students to take part in an exploratory survey. Data was collected by sending out an anonymous survey via email where respondents (N=37) were requested to answer 11 questions in regards to their experience at UST and reintegrating into an institution of higher learning after military involvement. Findings showed veteran students attending UST feel their expectations have been met in an institution for higher learning. The findings also show that obstacles were experienced in adapting to life as a non-traditional college student making reintegrating a challenge. The results of this study report that institutions of higher learning, primarily UST, have the ability to assist their veteran students in beneficial ways. Also, this study identified that veteran students do need assistance in adjusting to civilian life, balancing subsystems (military, family, school subsystems), as well as succeeding in school. Veteran students at UST have identified skills the military has taught them to help them succeed even when an obstacle is present. This research highlights the needs veteran students at UST have but also highlights that they are still succeeding and moving forward while still struggling with reintegration obstacles

    Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes

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    Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific families and subfamilies of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate sustained interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to shaping 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution

    Tricuspid Valve Replacement in a Patient with a Leadless Cardiac Pacemaker: Current Guidelines and Recommendations for Perioperative Management

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    Leadless cardiac pacemakers were developed to reduce complications associated with conventional transvenous pacemakers. While this technology is still relatively new, devices are increasingly being implanted. The perioperative management of patients with these devices has been underreported; we thus seek to add to the limited body of knowledge of perioperative management of patients with leadless cardiac pacemakers. An elderly female patient with a Micra VR transcatheter pacing system leadless cardiac pacemaker placed for tachycardia-bradycardia syndrome with intermittent complete heart block was scheduled for elective tricuspid valve replacement for severe tricuspid regurgitation. Pacemaker interrogation was performed several hours prior to the scheduled surgery based on the electrophysiologist's availability; the device was kept in its programmed VVIR mode, and the base rate was increased from 60 to 80 beats per minute in anticipation of the upcoming surgery. Upon preoperative evaluation, the anesthesiologist asked that the electrophysiology team be placed on standby intraoperatively due to the concern that either oversensing in the setting of pacemaker dependence and/or undesirable tachycardia from rate-responsive pacing could occur. The surgeon used monopolar electrocautery for the duration of the cardiac surgery. Despite the patient having evidence of pacemaker dependence in the intensive care unit preoperatively, no electromagnetic interference leading to oversensing nor rate modulation was detected during intraoperative electrocardiographic and intraarterial invasive monitoring. Evidence-based guidelines regarding perioperative management specifically of leadless cardiac pacemakers do not exist. As these devices become more prevalent, further evaluation will be paramount to determine whether existing guidelines for perioperative management of conventional transvenous pacemakers apply

    INTEGRATE: Gene fusion discovery using whole genome and transcriptome data

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    While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use

    Partial collapse of the marine carbon pump after the Cretaceous-Paleogene boundary

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    The impact of an asteroid at the end of the Cretaceous caused mass extinctions in the oceans. A rapid collapse in surface to deep-ocean carbon isotope gradients suggests that transfer of organic matter to the deep sea via the biological pump was severely perturbed. However, this view has been challenged by the survival of deep-sea benthic organisms dependent on surface-derived food and uncertainties regarding isotopic fractionation in planktic foraminifera used as tracers. Here we present new stable carbon (δ13C) and oxygen (δ18O) isotope data measured on carefully selected planktic and benthic foraminifera from an orbitally dated deep-sea sequence in the southeast Atlantic. Our approach uniquely combines δ18O evidence for habitat depth of foraminiferal tracer species with species-specific δ13C eco-adjustments, and compares isotopic patterns with corresponding benthic assemblage data. Our results show that changes in ocean circulation and foraminiferal vital effects contribute to but cannot explain all of the observed collapse in surface to deep-ocean foraminiferal δ13C gradient. We conclude that the biological pump was weakened as a consequence of marine extinctions, but less severely and for a shorter duration (maximum of 1.77 m.y.) than has previously been suggested

    BreakTrans: Uncovering the genomic architecture of gene fusions

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    Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTran

    Retroviral DNA Integration: Viral and Cellular Determinants of Target-Site Selection

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    Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN) coding region into HIV (to make HIVmIN) caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN) further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag) displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I–hypersensitive sites (i.e., +/− 1 kb), and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins

    Integrated analysis of germline and somatic variants in ovarian cancer

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    We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyze germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2, and PALB2. Additionally, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B, and MLL3). Evidence for loss of heterozygosity was found in 100% and 76% of cases with germline BRCA1 and BRCA2 truncations respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 237 candidate functional germline truncation and missense variants, including 2 pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK, and MLL pathways
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