Phenomenological model of diffuse global and regional atrophy using finite-element methods

The main goal of this work is the generation of ground-truth data for the validation of atrophy measurement techniques, commonly used in the study of neurodegenerative diseases such as dementia. Several techniques have been used to measure atrophy in cross-sectional and longitudinal studies, but it is extremely difficult to compare their performance since they have been applied to different patient populations. Furthermore, assessment of performance based on phantom measurements or simple scaled images overestimates these techniques' ability to capture the complexity of neurodegeneration of the human brain. We propose a method for atrophy simulation in structural magnetic resonance (MR) images based on finite-element methods. The method produces cohorts of brain images with known change that is physically and clinically plausible, providing data for objective evaluation of atrophy measurement techniques. Atrophy is simulated in different tissue compartments or in different neuroanatomical structures with a phenomenological model. This model of diffuse global and regional atrophy is based on volumetric measurements such as the brain or the hippocampus, from patients with known disease and guided by clinical knowledge of the relative pathological involvement of regions and tissues. The consequent biomechanical readjustment of structures is modelled using conventional physics-based techniques based on biomechanical tissue properties and simulating plausible tissue deformations with finite-element methods. A thermoelastic model of tissue deformation is employed, controlling the rate of progression of atrophy by means of a set of thermal coefficients, each one corresponding to a different type of tissue. Tissue characterization is performed by means of the meshing of a labelled brain atlas, creating a reference volumetric mesh that will be introduced to a finite-element solver to create the simulated deformations. Preliminary work on the simulation of acquisition artefa- - cts is also presented. Cross-sectional and

Parallel processing in immune networks

In this work we adopt a statistical mechanics approach to investigate basic, systemic features exhibited by adaptive immune systems. The lymphocyte network made by B-cells and T-cells is modeled by a bipartite spin-glass, where, following biological prescriptions, links connecting B-cells and T-cells are sparse. Interestingly, the dilution performed on links is shown to make the system able to orchestrate parallel strategies to fight several pathogens at the same time; this multitasking capability constitutes a remarkable, key property of immune systems as multiple antigens are always present within the host. We also define the stochastic process ruling the temporal evolution of lymphocyte activity, and show its relaxation toward an equilibrium measure allowing statistical mechanics investigations. Analytical results are compared with Monte Carlo simulations and signal-to-noise outcomes showing overall excellent agreement. Finally, within our model, a rationale for the experimentally well-evidenced correlation between lymphocytosis and autoimmunity is achieved; this sheds further light on the systemic features exhibited by immune networks.Comment: 21 pages, 9 figures; to appear in Phys. Rev.

Genome-Wide Detection of SNP Markers Associated with Four Physiological Traits in Groundnut (Arachis hypogaea L.) Mini Core Collection

In order to integrate genomics in breeding and development of drought-tolerant groundnut genotypes, identification of genomic regions/genetic markers for drought surrogate traits is essential. We used 3249 diversity array technology sequencing (DArTSeq) markers for a genetic analysis of 125 ICRISAT groundnut mini core collection evaluated in 2015 and 2017 for genome-wide marker-trait association for some physiological traits and to determine the magnitude of linkage disequilibrium (LD). Marker-trait association (MTA) analysis, probability values, and percent variation modelled by the markers were calculated using the GAPIT package via the KDCompute interface. The LD analysis showed that about 36% of loci pairs were in significant LD (p 0.2) and 3.14% of the pairs were in complete LD. The MTAs studies revealed 20 significant MTAs (p < 0.001) with 11 markers. Four MTAs were identified for leaf area index, 13 for canopy temperature, one for chlorophyll content and two for normalized difference vegetation index. The markers explained 20.8% to 6.6% of the phenotypic variation observed. Most of the MTAs identified on the A subgenome were also identified on the respective homeologous chromosome on the B subgenome. This could be due to a common ancestor of the A and B genome which explains the linkage detected between markers lying on different chromosomes. The markers identified in this study can serve as useful genomic resources to initiate marker-assisted selection and trait introgression of groundnut for drought tolerance after further validation

Single Cell Analysis of Lymph Node Tissue from HIV-1 Infected Patients Reveals that the Majority of CD4⁺ T-cells Contain One HIV-1 DNA Molecule

Genetic recombination contributes to the diversity of human immunodeficiency virus (HIV-1). Productive HIV-1 recombination is, however, dependent on both the number of HIV-1 genomes per infected cell and the genetic relationship between these viral genomes. A detailed analysis of the number of proviruses and their genetic relationship in infected cells isolated from peripheral blood and tissue compartments is therefore important for understanding HIV-1 recombination, genetic diversity and the dynamics of HIV-1 infection. To address these issues, we used a previously developed single-cell sequencing technique to quantify and genetically characterize individual HIV-1 DNA molecules from single cells in lymph node tissue and peripheral blood. Analysis of memory and naïve CD4+ T cells from paired lymph node and peripheral blood samples from five untreated chronically infected patients revealed that the majority of these HIV-1-infected cells (>90%) contain only one copy of HIV-1 DNA, implying a limited potential for productive recombination in virus produced by these cells in these two compartments. Phylogenetic analysis revealed genetic similarity of HIV-1 DNA in memory and naïve CD4+ T-cells from lymph node, peripheral blood and HIV-1 RNA from plasma, implying exchange of virus and/or infected cells between these compartments in untreated chronic infection

A case of polyarteritis nodosa limited to the right calf muscles, fascia, and skin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Limited polyarteritis nodosa is a rare benign disease that usually responds well to systemic corticosteroid treatment. We report a case limited to calf muscles, fascia, and skin treated with local corticosteroid therapy directed to the affected areas by ultrasound guidance.</p> <p>Case presentation</p> <p>A 36-year-old Caucasian woman presented with a 10-month history of progressive right calf pain and swelling, which were unresponsive to treatment with non-steroidal anti-inflammatory drugs and physiotherapy. An examination revealed a swollen tender right calf with indurated overlying skin. Laboratory investigations showed an erythrocyte sedimentation rate of 24 mm/hour and a C-reactive protein of 15 mg/dl. Full blood count, renal profile, and creatinine kinase level were normal. A full autoantibody screen and hepatitis B and C serology results were negative. A chest X-ray was unremarkable. Magnetic resonance imaging of the right leg revealed increased signal intensity in T2-weighted images and this was suggestive of extensive inflammatory changes of the gastrocnemius muscle and, to a lesser extent, the soleus muscle. There were marked inflammatory changes throughout the gastrocnemius muscle and the subcutaneous tissue circumferentially around the right lower leg. A biopsy of affected skin, muscle, and fascia showed histopathological features consistent with polyarteritis nodosa, including small-vessel vasculitis with fibrinoid changes in the vessel wall and intense perivascular and focal mural chronic inflammatory changes. Our patient declined treatment with oral steroids. She received a course of ultrasound-guided injections of steroid (Depo-Medrone, methylprednisolone) in the involved muscle area and commenced maintenance azathioprine with a good response.</p> <p>Conclusions</p> <p>Limited polyarteritis nodosa is rare and affects middle-aged individuals. In most cases, treatment with moderate- to high-dose corticosteroids gives symptomatic relief within one week. Resistant cases require treatment with cytotoxics or intravenous immunoglobulins. This case demonstrates response to local targeted steroid therapy as an alternative to systemic steroids.</p

Genetic trends for yield and key agronomic traits in pre-commercial and commercial maize varieties between 2008 and 2020 in Uganda

Estimating genetic gains is vital to optimize breeding programs for increased efficiency. Genetic gains should translate into productivity gains if returns to investments in breeding and impact are to be realized. The objective of this study was to estimate genetic gain for grain yield and key agronomic traits in pre-commercial and commercial maize varieties from public and private breeding programs tested in (i) national performance trials (NPT), (ii) era trial and, (iii) compare the trends with the national average. The study used (i) historical NPT data on 419 improved maize varieties evaluated in 23 trials at 6-8 locations each between 2008 and 2020, and (ii) data from an era trial of 54 maize hybrids released between 1999 and 2020. The NPT data was first analyzed using a mixed model and resulting estimate for each entry was regressed onto its first year of testing. Analysis was done over all entries, only entries from National Agricultural Research Organization (NARO), International Maize and Wheat Improvement Center (CIMMYT), or private seed companies. Estimated genetic gain was 2.25% or 81 kg ha-1 year-1 from the NPT analysis. A comparison of genetic trends by source indicated that CIMMYT entries had a gain of 1.98% year-1 or 106 kg ha-1 year-1. In contrast, NARO and private sector maize entries recorded genetic gains of 1.30% year-1 (59 kg ha-1 year-1) and 1.71% year-1 (79 kg ha-1 year-1), respectively. Varieties from NARO and private sector showed comparable mean yields of 4.56 t ha-1 and 4.62 t ha-1, respectively, while hybrids from CIMMYT had a mean of 5.37 t ha-1. Era analysis indicated significant genetic gain of 1.69% year-1 or 55 kg ha-1 year-1, while a significant national productivity gain of 1.48% year-1 (37 kg ha-1 year-1) was obtained. The study, thus, demonstrated the importance of public-private partnerships in development and delivery of new genetics to farmers in Uganda

Arsenite efflux is not enhanced in the arsenate-tolerant phenotype of Holcus lanatus

P>Arsenate tolerance in Holcus lanatus is achieved mainly through suppressed arsenate uptake. We recently showed that plant roots can rapidly efflux arsenite to the external medium. Here, we tested whether arsenite efflux is a component of the adaptive arsenate tolerance in H. lanatus. Tolerant and nontolerant phenotypes were exposed to different arsenate concentrations with or without phosphate for 24 h, and arsenic (As) speciation was determined in nutrient solutions, roots and xylem sap. At the same arsenate exposure concentration, the nontolerant phenotype took up more arsenate and effluxed more arsenite than the tolerant phenotype. However, arsenite efflux was proportional to arsenate uptake and was not enhanced in the tolerant phenotype. Within 2-24 h, most (80-100%) of the arsenate taken up was effluxed to the medium as arsenite. About 86-95% of the As in the roots and majority of the As in xylem sap (c. 66%) was present as arsenite, and there were no significant differences between phenotypes. Arsenite efflux is not adaptively enhanced in the tolerant phenotype H. lanatus, but it could be a basal tolerance mechanism to greatly decrease cellular As burden in both phenotypes. Tolerant and nontolerant phenotypes had a similar capacity to reduce arsenate in roots. New Phytologist (2009) 183: 340-348doi: 10.1111/j.1469-8137.2009.02841.x