Chromosomes with two centromeres provide a unique opportunity to study chromosome breakage and DNA repair using completely endogenous cellular machinery. Using a conditional transcriptional promoter to control the second centromere, we are able to activate the dicentric chromosome and follow the appearance of DNA repair products. We find that the rate of appearance of DNA repair products resulting from homology-based mechanisms exceeds the expected rate based on their limited centromere homology (340 bp) and distance from one another (up to 46.
View Article and Find Full Text PDFA key feature of chromosome segregation is the ability to sense tension between sister kinetochores. DNA between sister kinetochores must be packaged in a way that sustains tension propagation from one kinetochore to its sister, approximately 1 micron away. A molecular bottlebrush consisting of a primary axis populated with a crowded array of side chains provides a means to build tension over length scales considerably larger than the stiffness of the individual elements, that is, DNA polymer.
View Article and Find Full Text PDFDNA double-strand breaks arise in vivo when a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two centromeres attached to opposite spindle pole bodies. Repair of the DSBs generates phenotypic diversity due to the range of monocentric derivative chromosomes that arise. To explore whether DSBs may be differentially repaired as a function of their spatial position in the chromosome, we have examined the structure of monocentric derivative chromosomes from cells containing a suite of dicentric chromosomes in which the distance between the two centromeres ranges from 6.
View Article and Find Full Text PDFThe revolution in understanding higher order chromosome dynamics and organization derives from treating the chromosome as a chain polymer and adapting appropriate polymer-based physical principles. Using basic principles, such as entropic fluctuations and timescales of relaxation of Rouse polymer chains, one can recapitulate the dominant features of chromatin motion observed in vivo. An emerging challenge is to relate the mechanical properties of chromatin to more nuanced organizational principles such as ubiquitous DNA loops.
View Article and Find Full Text PDFExperiential background can influence how individuals respond to affective interpersonal information. For formerly depressed individuals, sad facial expressions are presumably salient. If so, when performing affectively neutral daily tasks, these individuals would find peripheral sad faces particularly distracting, and thus, they might shift their attention from them.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2018
De novo kinetochore assembly, but not template-directed assembly, is dependent on COMA, the kinetochore complex engaged in cohesin recruitment. The slowing of replication fork progression by treatment with phleomycin (PHL), hydroxyurea, or deletion of the replication fork protection protein Csm3 can activate de novo kinetochore assembly in COMA mutants. Centromere DNA looping at the site of de novo kinetochore assembly can be detected shortly after exposure to PHL.
View Article and Find Full Text PDFPurpose: Formal agreement studies on interpretation of the videofluoroscopic swallowing study (VFSS) procedure among speech-language pathologists, radiology house officers, and staff radiologists have not been pursued. Each of these professions participates in the procedure, interprets the examination, and writes separate reports on the findings. The aim of this study was to determine reliability of interpretation between and within the disciplines and to determine if structured training improved reliability.
View Article and Find Full Text PDFXMAP215/Dis1 family proteins are potent microtubule polymerases, critical for mitotic spindle structure and dynamics. While microtubule polymerase activity is driven by an N-terminal tumor overexpressed gene (TOG) domain array, proper cellular localization is a requisite for full activity and is mediated by a C-terminal domain. Structural insight into the C-terminal domain's architecture and localization mechanism remain outstanding.
View Article and Find Full Text PDFJAMA Otolaryngol Head Neck Surg
December 2017
Importance: There is a dearth of research examining the associations between cognitive function and quality of life (QoL) in patients with head and neck cancer (HNC), despite much research examining QoL and some research examining cognitive function in this population.
Objective: To identify the associations between cognitive functioning and QoL in patients prior to treatment for HNC within a multidisciplinary care team.
Design, Setting, And Participants: Case series with planned data collection of cognitive function, QoL, and psychosocial variables at an urban Midwest academic medical center including 83 patients with a diagnosis of HNC between August 2015 and December 2016 who underwent a pretreatment assessment with a clinical health psychologist and a speech and language pathologist.
Regions of highly repetitive DNA, such as those found in the nucleolus, show a self-organization that is marked by spatial segregation and frequent self-interaction. The mechanisms that underlie the sequestration of these sub-domains are largely unknown. Using a stochastic, bead-spring representation of chromatin in budding yeast, we find enrichment of protein-mediated, dynamic chromosomal cross-links recapitulates the segregation, morphology and self-interaction of the nucleolus.
View Article and Find Full Text PDFChromatin exhibits increased mobility on DNA damage, but the biophysical basis for this behavior remains unknown. To explore the mechanisms that drive DNA damage-induced chromosome mobility, we use single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models of chromatin chains. Telomeres become mobilized from sites on the nuclear envelope and the pericentromere expands after exposure to DNA-damaging agents.
View Article and Find Full Text PDFPurpose: To identify risk factors that may lead to the development of dysphagia after combined anterior and posterior (360°) cervical fusion surgery.
Methods: A single center, retrospective analysis of patients who had same-day, 360° fusion at Henry Ford Hospital between 2008 and 2012 was performed. Variables analyzed included demographics, medical co-morbidities, levels fused, and degree of dysphagia.
This study investigated associations between maternal and paternal emotion coaching and the self-regulation skills of kindergarten and first-grade children. Participants were 54 children categorized as either aggressive/rejected or low aggressive/popular by peer reports. Findings indicated a statistical trend for fathers of low aggressive/popular children to engage in more emotion coaching than fathers of aggressive/rejected children.
View Article and Find Full Text PDFThe β-sitosterol concentration in pulp and paper mill effluents is typically greater than that of other phytosterols and has been shown to cause a variety of effects in fish. The authors exposed fathead minnow (Pimephales promelas) to low (22 ± 0.93 µg/L), medium-low (70 ± 2.
View Article and Find Full Text PDFWe exposed fathead minnows (Pimephales promelas to 7 concentrations of effluents from pulp mills at 4 Long-Term Receiving Water Study (LTRWS) sites. The primary objective of these investigations was to determine the potential for toxicity, particularly on fish reproduction, of the pulp mill effluents using laboratory tests. These tests were performed as LTRWS fish community assessments were being completed, thus results of the laboratory fish reproduction tests could be compared to in-stream fish community measurements.
View Article and Find Full Text PDFWatershed characteristics, study streams, sample sites, mills, and mill effluents are provided for 4 streams included in a long-term study to assess potential effects of pulp and paper mill effluents on US receiving waters. The study streams are Codorus Creek (Pennsylvania, USA), Leaf River (Mississippi, USA) and McKenzie and Willamette rivers (Oregon, USA) and were chosen to represent a blend of mill process types, effluent concentrations, and coldwater/warmwater stream systems. The described effluent quality, water quality, and habitat data sets encompass the initial 7 to 8 y of a study anticipated to continue >10 y and provide a backdrop to a series of articles describing periphyton, macroinvertebrate, and fish community properties in these same streams.
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