Tangled1: A Microtubule Binding Protein Required for the Spatial Control of Cytokinesis in Maize

Spatial control of cytokinesis in plant cells depends on guidance of the cytokinetic apparatus, the phragmoplast, to a cortical “division site” established before mitosis. Previously, we showed that the Tangled1 (Tan1) gene of maize is required for this process during maize leaf development (Cleary, A.L., and L.G. Smith. 1998. Plant Cell. 10:1875–1888.). Here, we show that the Tan1 gene is expressed in dividing cells and encodes a highly basic protein that can directly bind to microtubules (MTs). Moreover, proteins recognized by anti-TAN1 antibodies are preferentially associated with the MT-containing cytoskeletal structures that are misoriented in dividing cells of tan1 mutants. These results suggest that TAN1 protein participates in the orientation of cytoskeletal structures in dividing cells through an association with MTs

Genome-Wide Association Study for Maize Leaf Cuticular Conductance Identifies Candidate Genes Involved in the Regulation of Cuticle Development.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (g c) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of g c of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with g c were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and β-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of g c in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of g c and have the potential to help breeders more effectively develop drought-tolerant maize for target environments

Gene Birth, Death, Modification, Poaching, Crippling, Dimorphism and Culling: The Challenge for Genomics

This brief survey covers the main events in the evolution of eukaryotic genes in broad brush style. It concentrates on regulatory DNA, an area that has been relatively neglected, and where we believe that the present case-by-case analysis is likely to be supplemented by more general, genomics-based methods. It is biased towards immunology, in part because the immune system relies heavily on polymorphism of regulatory DNA to provide flexibility and in part because of our own field of interest. It gives a central place to recent work that has shown how analysis of electronic genomes can be used to trace gene duplication and its consequences. It mentions cellular systems that offer models for the study of evolution of regulatory DNA on a small scale. It alludes to the unanswered question of how genomes adjust their overall size

Change in health-related quality of life in the context of pediatric obesity interventions: A meta-analytic review.

Objective: To quantitatively characterize change in health-related quality of life (HRQoL) in the context of behavioral (n = 16), surgical (n = 5), and pharmacological (n = 1) interventions for pediatric overweight and obesity. A secondary goal was to examine the relationship between change in HRQoL and change in body mass index (ΔBMI) by treatment type. The amount of weight loss necessary to observe a minimally clinically important difference (MCID) in HRQoL was determined. Method: Data were gathered from studies reporting on weight change and ΔHRQoL over the course of obesity interventions (N = 22) in youths (N = 1,332) with average ages between 7.4 and 16.5 years (M = 12.2). An overall effect size was calculated for ΔHRQoL. Moderation analyses were conducted using analysis of variance and weighted regression. MCID analyses were conducted by converting HRQoL data to standard error of measurement units. Results: The overall effect size for ΔHRQoL in the context of pediatric obesity interventions was medium (g = 0.51). A significant linear relationship was detected between ΔBMI and ΔHRQoL (R2 = 0.87). This relationship was moderated by treatment type, with medical (i.e., surgical) interventions demonstrating a stronger relationship. Results indicated that it takes a change of 0.998 BMI units to detect true change in HRQoL. Conclusion: This study provides the first known quantitative examination of changes in HRQoL associated with weight loss in pediatric interventions. Medical interventions appear to offer a more substantial increase in HRQoL per unit of BMI change. These results offer a concrete weight loss goal for noticing positive effects in daily life activities. (PsycINFO Database Record (c) 2016 APA, all rights reserved

De novoframeshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies

BACKGROUND: Currently, diagnosis of affected individuals with rare genetic disorders can be lengthy and costly, resulting in a diagnostic odyssey and in many patients a definitive molecular diagnosis is never achieved despite extensive clinical investigation. The recent advent and use of genomic medicine has resulted in a paradigm shift in the clinical molecular genetics of rare diseases and has provided insight into the causes of numerous rare genetic conditions. In particular, whole exome and genome sequencing of families has been particularly useful in discovering de novo germline mutations as the cause of both rare diseases and complex disorders. CASE PRESENTATION: We present a six year old, nonverbal African American female with microcephaly, autism, global developmental delay, and metopic craniosynostosis. Exome sequencing of the patient and her two parents revealed a heterozygous two base pair de novo deletion, c.1897_1898delCA, p.Gln633ValfsX13 in ASXL3, predicted to result in a frameshift at codon 633 with substitution of a valine for a glutamine and introduction of a premature stop codon. CONCLUSIONS: We provide additional evidence that, truncating and frameshifting mutations in the ASXL3 gene are the cause of a newly recognized disorder characterized by severe global developmental delay, short stature, microcephaly, and craniofacial anomalies. Furthermore, we expand the knowledge about disease causing mutations and the genotype-phenotype relationships in ASXL3 and provide evidence that rare, nonsynonymous, damaging mutations are not associated with developmental delay or microcephaly

"Happy to Close?": The relationship between surgical experience and incisional hernia rates following abdominal wall closure in colorectal surgery

Aim Incisional hernia (IH) is a common complication of colorectal surgery, affecting up to 30% of patients at 2 years. Given the associated morbidity and high recurrence rates after attempted repair of IH, emphasis should be placed on prevention. There is an association between surgeon volume and outcomes in hernia surgery, yet there is little evidence regarding impact of the seniority of the surgeon performing abdominal wall closure on IH rate. The aim of our study was to assess the rates of IH at 1 year following abdominal wall closure between junior and senior surgeons in patients undergoing elective colorectal surgery. Methods This was an exploratory analysis of patients who underwent elective surgery for colorectal cancer between 2014–2018 as part of the Hughes Abdominal Repair Trial (HART), a prospective, multicentre randomised control trial comparing abdominal wall closure methods. Grade of surgeon performing abdominal closure was categorised into “trainee” and “consultant” and compared to IH rate at one year. Results A total of 663 patients were included in this retrospective analysis of patients in the HART trial. The rate of IH in patients closed by trainees was 20%, compared to 12% in those closed by consultants (p = <0.001). When comparing closure methods, IH rates were significantly higher in the Hughes closure arm between trainees and consultants (20% vs. 12%, p = 0.032), but not high enough in the mass closure arm to reach statistical significance (21% vs. 13%, p = 0.058). On multivariate analysis, age (p = 0.036, OR: 1.02, 95% CI: 1.00–1.04), Male sex (p = 0.049, OR: 1.61, 95% CI: 1.00–2.59) and closure by a trainee (p = 0.006, OR: 1.85, 95% CI: 1.20–2.85) were identified as risk factors for developing IH. Conclusion Patients who undergo abdominal wall closure by a surgeon in training have an increased risk of developing IH when compared to those closed by a consultant. Further work is needed to determine the impact of supervised and unsupervised trainees on IH rates, but abdominal wall closure should be regarded as a training opportunity in its own righ

Florida\u27s Mystery Coral-Killer Identified

An unusual coral disease appeared on the Florida Reef Tract in June 1995. It was distinct in its microbiology, its pattern of tissue degradation, the species susceptible to it, and its regional distribution. Symptoms included a sharp line between healthy and diseased tissue, as occurs with other coral diseases, but the pathogen responsible for the new outbreak seemed more virulent, affected a wider variety of species, and destroyed tissue much more rapidly than these other \u27line\u27 or \u27band\u27 diseases. We have identified the pathogen responsible for this new disease as a new species of Sphingomonas

Modeling Kelvin wave cascades in superfluid helium

We study two different types of simplified models for Kelvin wave turbulence on quantized vortex lines in superfluids near zero temperature. Our first model is obtained from a truncated expansion of the Local Induction Approximation (Truncated-LIA) and it is shown to possess the same scalings and the essential behaviour as the full Biot-Savart model, being much simpler than the later and, therefore, more amenable to theoretical and numerical investigations. The Truncated-LIA model supports six-wave interactions and dual cascades, which are clearly demonstrated via the direct numerical simulation of this model in the present paper. In particular, our simulations confirm presence of the weak turbulence regime and the theoretically predicted spectra for the direct energy cascade and the inverse wave action cascade. The second type of model we study, the Differential Approximation Model (DAM), takes a further drastic simplification by assuming locality of interactions in k-space via using a differential closure that preserves the main scalings of the Kelvin wave dynamics. DAMs are even more amenable to study and they form a useful tool by providing simple analytical solutions in the cases when extra physical effects are present, e.g. forcing by reconnections, friction dissipation and phonon radiation. We study these models numerically and test their theoretical predictions, in particular the formation of the stationary spectra, and closeness of numerics for the higher-order DAM to the analytical predictions for the lower-order DAM

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments