Kerry Mills Barn Dance / words by Kerry Mills

Cover: drawing of Caucasian couples dancing in a barn; Publisher: F. A. Mills (New York)https://egrove.olemiss.edu/sharris_b/1090/thumbnail.jp

Serious limitations of the QTL/Microarray approach for QTL gene discovery

<p>Abstract</p> <p>Background</p> <p>It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed.</p> <p>Results</p> <p>Thirty-seven studies that have implemented the QTL/microarray approach in rodents were reviewed. About 30% of studies showed enrichment for QTL candidates, mostly in comparisons<b/> between congenic and background strains. Three studies led to the identification of an underlying <it>QTL </it>gene. To complement the literature results, a microarray experiment was performed using three mouse congenic strains isolating the effects of at least 25 biometric QTL. Results show that genes in the congenic donor regions were preferentially selected. However, within donor regions, the distribution of differentially expressed genes was homogeneous once gene density was accounted for. Genes within identical-by-descent (IBD) regions were less likely to be differentially expressed in chromosome 2, but not in chromosomes 11 and 17. Furthermore, expression of <it>QTL </it>regulated in <it>cis </it>(<it>cis </it>eQTL) showed higher expression in the background genotype, which was partially explained by the presence of single nucleotide polymorphisms (SNP).</p> <p>Conclusions</p> <p>The literature shows limited successes from the QTL/microarray approach to identify <it>QTL </it>genes. Our own results from microarray profiling of three congenic strains revealed a strong tendency to select <it>cis-</it>eQTL over <it>trans-</it>eQTL. IBD regions had little effect on rate of differential expression, and we provide several reasons why IBD should not be used to discard eQTL candidates. In addition, mismatch probes produced false <it>cis-</it>eQTL that could not be completely removed with the current strains genotypes and low probe density microarrays. The reviewed studies did not account for lack of coverage from the platforms used and therefore removed genes that were not tested. Together, our results explain the tendency to report QTL candidates as differentially expressed and indicate that the utility of the QTL/microarray as currently implemented is limited. Alternatives are proposed that make use of microarray data from multiple experiments to overcome the outlined limitations.</p

Intertwining technique for a system of difference Schroedinger equations and new exactly solvable multichannel potentials

The intertwining operator technique is applied to difference Schroedinger equations with operator-valued coefficients. It is shown that these equations appear naturally when a discrete basis is used for solving a multichannel Schroedinger equation. New families of exactly solvable multichannel Hamiltonians are found

Inhomogeneity of the intrinsic magnetic field in superconducting YBa2Cu3OX compounds as revealed by rare-earth EPR-probe

X-band electron paramagnetic resonance on doped Er3+ and Yb3+ ions in Y0.99(Yb,Er)0.01Ba2Cu3OX compounds with different oxygen contents in the wide temperature range (4-120)K have been made. In the superconducting species, the strong dependencies of the linewidth and resonance line position from the sweep direction of the applied magnetic field are revealed at the temperatures significantly below TC. The possible origins of the observed hysteresis are analyzed. Applicability of the presented EPR approach to extract information about the dynamics of the flux-line lattice and critical state parameters (critical current density, magnetic penetration depth, and characteristic spatial scale of the inhomogeneity) is discussedComment: 17 pages, 5 Figures. Renewed versio

Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses

Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p =.0002 for both). Anti-spike IgG correlated with lymphocyte count (r =.63; p =.002), and time from treatment (r =.56; p =.007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p =.03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p =.0008) and HC (p <.0001). Anti-spike IgG correlated with neutralization of the delta variant (r =.62, p <.0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p <.0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p =.004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant

Profiles and outcome of traditional healing practices for severe mental illnesses in two districts of Eastern Uganda

Background : The WHO estimates that more than 80% of African populations attend traditional healers for health reasons and that 40%–60% of these have some kind of mental illness. However, little is known about the profiles and outcome of this traditional approach to treatment. Objective : The purpose of this study was to describe the profiles and outcome of traditional healing practices for severe mental illnesses in Jinja and Iganga districts in the Busoga region of Eastern Uganda. Methods : Four studies were conducted. Study I used focus group discussions (FGDs) with case vignettes with local community members and traditional healers to explore the lay concepts of psychosis. Studies II and III concerned a cross-sectional survey of patients above 18 years at the traditional healer's shrines and study IV was made on a prospective cohort of patients diagnosed with psychosis in study III. Manual content analysis was used in study I; quantitative data in studies II, III, and IV were analyzed at univariate, bivariate, and multivariate levels to determine the association between psychological distress and socio-demographic factors; for study IV, factors associated with outcome were analyzed. One-way ANOVA for independent samples was the analysis used in Study IV. Results : The community gave indigenous names to psychoses (mania, schizophrenia, and psychotic depression) and had multiple explanatory models for them. Thus multiple solutions for these problems were sought. Of the 387 respondents, the prevalence of psychological distress was 65.1%, where 60.2% had diagnosable current mental illness, and 16.3% had had one disorder in their lifetime. Over 80% of patients with psychosis used both biomedical and traditional healing systems. Those who combined these two systems seemed to have a better outcome. All the symptom scales showed a percentage reduction of more than 20% at the 3- and 6-month follow-ups. Conclusion : Traditional healers shoulder a large burden of care of patients with mental health problems. This calls for all those who share the goal of improving the mental health of individuals to engage with traditional healers

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n=16) and baseball pitchers (n=16) were utilized as within-subject controlled models as they preferentially load their takeoff leg and leg contralateral to their throwing arm, respectively. Controls (n=15) were included, but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences, but less than pitchers. Pitchers had 5.8% (95% CI, 3.9–7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck, and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter, but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95%CI, 1.4–6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading, but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces, and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (i.e. fall onto the greater trochanter) raising questions as to how to better target these variables with PA