309 research outputs found

    Identification of quantitative trait loci controlling root and shoot traits associated with drought tolerance in a lentil (Lens culinaris Medik.) recombinant inbred line population

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    Drought is one of the major abiotic stresses limiting lentil productivity in rainfed production systems. Specific rooting patterns can be associated with drought avoidance mechanisms that can be used in lentil breeding programs. In all, 252 co-dominant and dominant markers were used for Quantitative Trait Loci (QTL) analysis on 132 lentil recombinant inbred lines based on greenhouse experiments for root and shoot traits during two seasons under progressive drought-stressed conditions. Eighteen QTLs controlling a total of 14 root and shoot traits were identified. A QTL-hotspot genomic region related to a number of root and shoot characteristics associated with drought tolerance such as dry root biomass, root surface area, lateral root number, dry shoot biomass and shoot length was identified. Interestingly, a QTL (QRSratioIX-2.30) related to root-shoot ratio, an important trait for drought avoidance, explaining the highest phenotypic variance of 27.6 and 28.9% for the two consecutive seasons, respectively, was detected. This QTL was closed to the co-dominant SNP marker TP6337 and also flanked by the two SNP TP518 and TP1280. An important QTL (QLRNIII-98.64) related to lateral root number was found close to TP3371 and flanked by TP5093 and TP6072 SNP markers. Also, a QTL (QSRLIV-61.63) associated with specific root length was identified close to TP1873 and flanked by F7XEM6b SRAP marker and TP1035 SNP marker. These two QTLs were detected in both seasons. Our results could be used for marker-assisted selection in lentil breeding programs targeting root and shoot characteristics conferring drought avoidance as an efficient alternative to slow and labor-intensive conventional breeding methods

    Disrupted network architecture of the resting brain in attention‐deficit/hyperactivity disorder

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    Background Attention‐deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders of childhood. Neuroimaging investigations of ADHD have traditionally sought to detect localized abnormalities in discrete brain regions. Recent years, however, have seen the emergence of complementary lines of investigation into distributed connectivity disturbances in ADHD. Current models emphasize abnormal relationships between default network—involved in internally directed mentation and lapses of attention—and task positive networks, especially ventral attention network. However, studies that comprehensively investigate interrelationships between large‐scale networks in ADHD remain relatively rare. Methods Resting state functional magnetic resonance imaging scans were obtained from 757 participants at seven sites in the ADHD‐200 multisite sample. Functional connectomes were generated for each subject, and interrelationships between seven large‐scale brain networks were examined with network contingency analysis. Results ADHD brains exhibited altered resting state connectivity between default network and ventral attention network [ P  < 0.0001, false discovery rate (FDR)‐corrected], including prominent increased connectivity (more specifically, diminished anticorrelation) between posterior cingulate cortex in default network and right anterior insula and supplementary motor area in ventral attention network. There was distributed hypoconnectivity within default network ( P  = 0.009, FDR‐corrected), and this network also exhibited significant alterations in its interconnections with several other large‐scale networks. Additionally, there was pronounced right lateralization of aberrant default network connections. Conclusions Consistent with existing theoretical models, these results provide evidence that default network‐ventral attention network interconnections are a key locus of dysfunction in ADHD. Moreover, these findings contribute to growing evidence that distributed dysconnectivity within and between large‐scale networks is present in ADHD. Hum Brain Mapp 35:4693–4705, 2014 . © 2014 Wiley Periodicals, Inc .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107992/1/hbm22504.pd

    Purification of a monoclonal antibody using a novel high-capacity multimodal cation exchange nonwoven membrane

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    A high-capacity, multimodal cation exchange (MMC) chromatographic membrane was developed by conjugating a multimodal ligand – 2-mercaptopyridine-3-carboxylic acid (MPCA) – on a polybutylene terepthalate (PBT) nonwoven fabric. The membrane features an equilibrium binding capacity of ≈ 1000 mg of human polyclonal IgG (IgG) per g of membrane and dynamic binding capacities (DBC10%) ranging from 77.5 to 115.1 mg/mL (residence times of 1 and 5 min, respectively); these values are 2-to-3-fold higher than those of commercial MMC adsorbents. The effects of buffer composition, pH, conductivity on the binding behavior of the MMC-MPCA membrane were investigated in detail. As a moderate cation exchange binder, MPCA enables effective protein elution using buffers with mild pH (8.0–9.0) and conductivity (≈13 mS/cm), thus circumventing the harsh conditions often needed in multimodal chromatography. The MMC-MPCA membrane was evaluated for product capture in bind-and-elute mode on a Chinese hamster ovary (CHO) cell culture harvest containing therapeutic monoclonal antibodies, using commercial multimodal (Capto MMC and MX-Trp-650M) and affinity (AF-rProtein A HC-650F) resins as controls. The MMC-MPCA membrane outperformed the multimodal resins in terms of binding capacity as well as clearance of host cell proteins (HCPs) and aggregates. The membrane was then evaluated by polishing the mAb from a Protein A eluate in bind-and-elute mode. The MMC-MPCA membrane reduced the level of high molecular weight components from 11% to 4% and the HCP content from 1319.7 ppm to 48.7 ppm (LRV of 1.4). Most notably, proteomics analysis of the product demonstrated the clearance of a significant fraction of persistent, high-risk HCPs from the Protein A eluate

    Cemented total hip replacement in patients under 55 years:Good results in 104 hips followed up for ≄22 years

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    Background and purpose — About 86,000 total hip replacements (THR) have been registered in patients under 55 years in the National Joint Registry of England and Wales (NJR). The use of uncemented implants has increased, despite their outcomes not having been proven to be significantly better than cemented implants in this registry. We determined the implant survivorship and functional outcomes of cemented THR in patients under 55 years at a minimum follow-up of 22 years. Patients and methods — 104 hips in 100 patients were included in this prospective study. Functional outcome was assessed using the Harris Hip Score and radiographs were assessed for implant failure and “at risk” of failure. Kaplan–Meier survivorship analysis was performed. Results — 89% of hips showed good to excellent results at final follow-up with a mean Harris Hip Score of 88 at a mean follow-up of 25 years. Revision was performed in 3/104 hips. 14 acetabular components and 4 femoral components were “at risk” of failure. The survivorship at minimum 22 years with revision for any reason as the end-point was 97% (95% CI 95–98). Interpretation — Cemented hip replacements perform well in young patients with good long-term functional and radiographic outcomes

    The Global Durum Wheat Panel (GDP): An International Platform to Identify and Exchange Beneficial Alleles

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    Representative, broad and diverse collections are a primary resource to dissect genetic diversity and meet pre-breeding and breeding goals through the identification of beneficial alleles for target traits. From 2,500 tetraploid wheat accessions obtained through an international collaborative effort, a Global Durum wheat Panel (GDP) of 1,011 genotypes was assembled that captured 94-97% of the original diversity. The GDP consists of a wide representation of Triticum turgidum ssp. durum modern germplasm and landraces, along with a selection of emmer and primitive tetraploid wheats to maximize diversity. GDP accessions were genotyped using the wheat iSelect 90K SNP array. Among modern durum accessions, breeding programs from Italy, France and Central Asia provided the highest level of genetic diversity, with only a moderate decrease in genetic diversity observed across nearly 50 years of breeding (1970-2018). Further, the breeding programs from Europe had the largest sets of unique alleles. LD was lower in the landraces (0.4 Mbp) than in modern germplasm (1.8 Mbp) at r 2 = 0.5. ADMIXTURE analysis of modern germplasm defined a minimum of 13 distinct genetic clusters (k), which could be traced to the breeding program of origin. Chromosome regions putatively subjected to strong selection pressure were identified from fixation index (F st ) and diversity reduction index (DRI) metrics in pairwise comparisons among decades of release and breeding programs. Clusters of putative selection sweeps (PSW) were identified as co-localized with major loci controlling phenology (Ppd and Vrn), plant height (Rht) and quality (gliadins and glutenins), underlining the role of the corresponding genes as driving elements in modern breeding. Public seed availability and deep genetic characterization of the GDP make this collection a unique and ideal resource to identify and map useful genetic diversity at loci of interest to any breeding program

    The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes.

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    Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared to controls. Here, we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioural symptoms. PTSD patients (n=49), with (n=13) and without (n=36) the dissociative subtype, and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared to the PTSD-DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception -implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.Neuropsychopharmacology accepted article preview online, 19 March 2015. doi:10.1038/npp.2015.79

    Trauma-related emotions and radical acceptance in dialectical behavior therapy for posttraumatic stress disorder after childhood sexual abuse

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    Background: Posttraumatic Stress Disorder (PTSD) related to childhood sexual abuse (CSA) is often associated with a wide range of trauma-related aversive emotions such as fear, disgust, sadness, shame, guilt, and anger. Intense experience of aversive emotions in particular has been linked to higher psychopathology in trauma survivors. Most established psychosocial treatments aim to reduce avoidance of trauma-related memories and associated emotions. Interventions based on Dialectical Behavior Therapy (DBT) also foster radical acceptance of the traumatic event. Methods: This study compares individual ratings of trauma-related emotions and radical acceptance between the start and the end of DBT for PTSD (DBT-PTSD) related to CSA. We expected a decrease in trauma-related emotions and an increase in acceptance. In addition, we tested whether therapy response according to the Clinician Administered PTSD-Scale (CAPS) for the DSM-IV was associated with changes in trauma-related emotions and acceptance. The data was collected within a randomized controlled trial testing the efficacy of DBT-PTSD, and a subsample of 23 women was included in this secondary data analysis. Results: In a multilevel model, shame, guilt, disgust, distress, and fear decreased significantly from the start to the end of the therapy whereas radical acceptance increased. Therapy response measured with the CAPS was associated with change in trauma-related emotions. Conclusions: Trauma-related emotions and radical acceptance showed significant changes from the start to the end of DBT-PTSD. Future studies with larger sample sizes and control group designs are needed to test whether these changes are due to the treatment. Trial registration: ClinicalTrials.gov, number NCT0048100
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