Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease-causing mutation in α-actinin-4 promotes podocyte detachment through maladaptation to periodic stretch

Significance Point mutations in α-actinin-4 (ACTN4) cause a form of kidney disease in humans. Although we know these mutations affect kidney podocytes, the mechanism by which they lead to podocyte dysfunction remains unclear. Here, we show that homozygous mutant Actn4 podocytes developed irrecoverable reductions in their contraction and irreparable disruptions in their actin cytoskeletons when subjected to periodic stretch. This maladaptive response is akin to failure of a brittle material under deformation. Our results clarify the mechanism by which mutations in ACTN4 leave the podocyte more vulnerable to detachment in the progression of kidney disease. α-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network. How this resilience is built and dynamically regulated in the podocyte, and the cause of its failure in ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS-causing point mutant Actn4 knockin mice, we report responses to periodic stretch. While WT cells largely maintained their F-actin cytoskeleton and contraction, mutant cells developed extensive and irrecoverable reductions in these same properties. This difference was attributable to both actin material changes and a more spatially correlated intracellular stress in mutant cells. When stretched cells were further challenged using a cell adhesion assay, mutant cells were more likely to detach. Together, these data suggest a mechanism for mutant podocyte dysfunction and loss in FSGS—it is a direct consequence of mechanical responses of a cytoskeleton that is brittle.
Altered white matter integrity in adolescent binge drinkers.

BACKGROUND White matter integrity has been found to be compromised in adult alcoholics, but it is unclear when in the course of alcohol exposure white matter abnormalities become apparent. This study assessed microstructural white matter integrity among adolescent binge drinkers with no history of an alcohol use disorder. METHODS We used diffusion tensor imaging to examine fractional anisotropy (FA), a measure of directional coherence of white matter tracts, among teens with (n = 14) and without (n = 14) histories of binge drinking but no history of alcohol use disorder, matched on age, gender, and education. RESULTS Binge drinkers had lower FA than controls in 18 white matter areas (clusters > or =27 contiguous voxels, each with p < 0.01) throughout the brain, including the corpus callosum, superior longitudinal fasciculus, corona radiata, internal and external capsules, and commissural, limbic, brainstem, and cortical projection fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in 6 of these regions was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations. CONCLUSIONS Binge drinking adolescents demonstrated widespread reductions of FA in major white matter pathways. Although preliminary, these results could indicate that infrequent exposure to large doses of alcohol during youth may compromise white matter fiber coherence.
A Prospective Study Analyzing One‐Year Multidimensional Outcomes in Living Lung Transplant Donors

The success of living‐donor lobar lung transplantation (LDLLT) largely depends on donor outcome; but to date, no authors have studied health‐related quality of life (HRQOL) of donors. We prospectively evaluated multidimensional outcomes before and 1 year after donor lobectomies. Patient‐reported HRQOL, dyspnea, psychological status and sleep quality, and physiological pulmonary function were determined. All donors were alive without any limitations in their activities of daily living after 1 year. Postoperative pulmonary function was better than the estimated preoperative values; but, with respect to HRQOL, four of the eight subscales of the Medical Outcomes Study 36‐item short form (SF‐36) deteriorated significantly after donation. In addition, dyspnea assessed by the modified Medical Research Council scale also worsened significantly. In contrast, postoperative anxiety assessed by the Hospital Anxiety and Depression Scale significantly improved from baseline. The donors whose recipients died reported lower SF‐36 scores with worsening sleep quality measured by Pittsburgh Sleep Quality Index. Thus, although postoperative pulmonary functions in donors were preserved, their HRQOL and dyspnea deteriorated postoperatively. Moreover, HRQOL and sleep quality were impaired in recipients who experienced poor outcomes. To capture the comprehensive outcomes in LDLLT donors after donation, patient‐reported outcomes should be analyzed separately from physiological outcomes.
Deficiencies in extrusion of the second polar body due to high calcium concentrations during in vitro fertilization in inbred C3H/He mice

Summary Successful in vitro fertilization (IVF) of all inbred strains of laboratory mice has not yet been accomplished. We have previously shown that a high calcium concentration improved IVF in various inbred mice. However, we also found that in cumulus-free ova of C3H/He mice such IVF conditions significantly increased the deficiency of extrusion of the second polar body (PBII) in a dose-dependent manner (2% at 1.71 mM and 29% at 6.84 mM, P < 0.05) and that PBII extrusion was affected by high calcium levels at 2–3 h post-insemination. While developmental competence of ova without PBII extrusion to blastocysts after 96 h culture was not affected, a significant reduction in the nuclear number of the inner cell mass was observed in blastocyst fertilized under high calcium condition. We also examined how high calcium concentration during IVF affects PBII extrusion in C3H/He mice. Cumulus cells cultured under high calcium conditions showed a significantly alleviated deficient PBII extrusion. This phenomenon is likely to be specific to C3H/He ova because deficient PBII extrusion in reciprocal fertilization between C3H and BDF1 gametes was observed only in C3H/He ova. Sperm factor(s) was still involved in deficient PBII extrusion due to high calcium concentrations, as this phenomenon was not observed in ova activated by ethanol. The cytoskeletal organization of ova without PBII extrusion showed disturbed spindle rotation, incomplete formation of contractile ring and disturbed localization of actin, suggesting that high calcium levels affect the anchoring machinery of the meiotic spindle. These results indicate that in C3H/He mice high calcium levels induce abnormal fertilization, i.e. deficient PBII extrusion by affecting the cytoskeletal organization, resulting in disturbed cytokinesis during the second meiotic division. Thus, use of high calcium media for IVF should be avoided for this strain.
Patrones altitudinales en la diversidad de coleópteros y hormigas epígeos del noroeste de la Patagonia argentina

Se estudio la influencia de factores metodologicos y biologicos sobre los patrones altitudinales en la diversidad de artropodos, con enfasis en coleopteros y hormigas. A escala global, un meta-analisis de 109 gradientes publicados mostro que el patron altitudinal en la riqueza de especies de artropodos tiene multiples formas, aunque la percepcion del patron puede estar influida por el metodo empleado para identificar la forma y la calidad de los datos. A escala local, un estudio de campo realizado en cinco montanas, en el noroeste de la Patagonia argentina, mostro cambios altitudinales en la composicion de ensambles de especies de coleopteros y hormigas asociados a distintas variables ambientales y una subdivision fina de los ambientes. Los patrones altitudinales en la riqueza de especies y abundancia de individuos difirieron sustancialmente entre coleopteros y hormigas. Se confirmo la alta diversidad de coleopteros, y la baja diversidad de hormigas. Ambos taxa mostraron la dominancia de pocas especies muy abundantes y muchas especies raras. Distintos factores ambientales explicaron variaciones locales en la diversidad en distintos ambientes del gradiente altitudinal, y afectaron de manera diferencial a coleopteros y hormigas.
Characterising the castration‐resistant prostate cancer population: a systematic review

Background: Castration‐resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. However, characterisation of the disease epidemiology is hampered by use of varying terminology, definition and disease management. The aim of this review was to conduct a systematic review to provide greater clarity on the sum of the available epidemiologic evidence and to guide future research into the disease prevalence, progression, characteristics and outcome.
Nonlinear dynamical law governs magnetic field induced changes in lymphoid phenotype

The results of many different types of animal and human studies dealing with the biological effects of exposure to low frequency electromagnetic fields (EMFs) have consistently been both positive and negative. We addressed the question of why this pattern had occurred so commonly in biological studies involving exposure to EMFs and hypothesized that it stemmed from the prevalent use of a linear model to characterize what are inherently nonlinear input–output relationships. The hypothesis was tested by analyzing biological data using a novel statistical procedure that could be adjusted to detect either nonlinear or linear effects. The reliability of the procedure was established using positive and negative controls and by comparison with the results obtained from sampling a known nonlinear system. In four independent experiments, male and female mice were exposed continuously to 0.1 or 0.5 mT, 60 Hz, for 175 days, and the effect on 20 immune parameters was measured using flow cytometry and functional assays. In each experiment, EMF exposure resulted in statistically significant changes in lymphoid phenotype when and only when the response of the animals to the fields was analyzed as if it were governed by nonlinear laws. Our results suggest that the pattern of inconsistency in the EMF bioeffects studies is an artifact resulting from an incorrect choice of the conceptual model for the relation between the field and the biological effect it causally determines. Bioelectromagnetics 22:529–546, 2001. © 2001 Wiley‐Liss, Inc.
Strategies to manage antifungal drug resistance

Introduction: Invasive fungal infections continue to cause significant morbidity and mortality in immunocompromised hosts. From more than half a million deaths from cryptococcosis in sub-Saharan Africa to an unchanging death rate from invasive candidiasis, despite three antifungal classes of drugs, insights into better strategies to reduce therapeutic failures or resistance are needed. Areas covered: This review examines the issues around antifungal drug resistance from both a basic description of the failures and how they are detected to the variety of issues that need to be addressed to help prevent failures for successful management. The reader will gain an understanding of the clinical complexities in this patient population for management of invasive fungal infections. Throughout the review, principles of management are given along with some specific clinical examples to illustrate the issues and frame the knowledge base. From this discussion it is hoped that the clinician can use the insights provided to manage individual patients and find links to the evidence-based material that support its conclusions. Also, this review specifically identifies the limitations of present management and directs clinicians to gather additional information and provide even better treatment strategies. Expert opinion : Invasive fungal infections are life-threatening complications of serious underlying diseases. Their management can be complicated by both direct and clinical drug resistance and by understanding these possibilities and correcting them; most patients can be successfully managed with present antifungal drugs if the underlying diseases can be controlled.
Buried objects localization in presence of correlated signals

In this paper a MUSIC algorithm for locating buried cylindrical shells using the scattering field at a wideband frequency is developed. The algorithm presented here modifies the conventional direction finding array precessing techniques, it uses the spatial complexities of the fields combined to the focusing operator to decorrelate the signals that allows us to estimate both the range and the bearing of the objects in the region of interest. Finally, the performances of the proposed method are validated on simulated data and experimental data recorded during an underwater acoustics experiments
Incidence and prognostic significance of right bundle branch block complicating acute myocardial infarction.

The incidence and hospital courseofacute myocardial infarction wereobserved among randomly selected 560 patients. The mean age of the patients was 53 +/- 6.67 years with male-female ratio 2.6:1. The incidence of right bundle branch block (RBBB) was 15% (84 out of 560 patients). New RBBB, old RBBB and RBBB of indeterminate age were observed in 33 (39.25%), 23 (27.40%) and 28 (33.25%) cases respectively. RBBB was isolated in 50 (60%) cases and bi-fascicular in remaining 34 (40%) cases. The rate of use of thrombolytic was greater in RBBB group than non-RBBB group (52% vs 30.67%, P < 0.05). The complications were more frequently observed in patients with RBBB: in-hospital mortality, 27.40% vs 10.90% (P < 0.01); use of temporary pacemaker, 15% vs 9% (P < 0.05); and heart failure, 50% vs 35% (P < 0.05). In sub-group analysis, in-hospital mortality rate was higher among bi-fascicular group than isolated RBBB group (P < 0.05). Thus it appeared from the results that the incidence of RBBB is relatively common i.e. 15% over all (84 out of 560) and 5.90% new (33 out of 560) and despite greater use of thrombolytics, some specific in-hospital complications were significantly higher in patients with RBBB than without, RBBB.
Experiences of a patient‐initiated self‐monitoring service in inflammatory arthritis: A qualitative exploration†

OBJECTIVES The aim of the present study was to explore patients' experience of a patient-initiated self-monitoring service for people with rheumatoid or psoriatic arthritis who are on methotrexate. METHODS The study took the form of qualitative semi-structured interviews, embedded within a randomized controlled trial. Twelve participants who were randomly assigned to the intervention arm were interviewed. Interviews digitally, transcribed verbatim and analysed using inductive thematic analysis. The study received full National Health Service ethics approval from Camden and Islington Community Local Research Ethics Committee (Ref. 09/H0722/91). RESULTS Analysis revealed five key themes. Participants described usual care as burdensome and an inefficient use of time, particularly those in employment. Being able to self-monitor and initiate their own care increased patients' knowledge about their illness and its treatment, and enabled them to gain a sense of control and ownership over their arthritis. They appreciated the personalized nature of the new service, which allowed them to be seen at a time and by a method more appropriate to their needs. There were, however, some concerns about fidelity to the service protocol, confusion about the lack of consistency between symptoms and laboratory results, and anxiety about self-monitoring. CONCLUSIONS Overall, participants were positive about the new service, in comparison with usual care, valuing its tailored approach and empowering effects. Further work is needed to ensure adherence to the service protocol and address anxieties around self-monitoring prior to any widespread implementation of the service.
Isolation and characterization of resident macrophages from the smooth muscle layers of murine small intestine

Abstract Macrophages within the murine tunica muscularis were isolated and cultured for physiological studies. Following dispersion, macrophages were identified by phagocytotic activity of fluorescein isothiocyanate (FITC)‐dextran. Immediately following isolation, macrophages were rounded and possessed fluorescent granula but developed a ramified shape after 3–4 days in culture. Resident and cultured macrophages were immunopositive for F4/80 and I‐Ad/I‐Ed. Greater than 90% of F4/80 positive cultured cells were FITC‐dextran positive. Macrophages had resting membrane potentials (RMP) of −33.3 ± 1.5 mV after 1 day in culture, which increased to −53.9 ± 4.4 mV after 3–4 days. The change in RMP was associated with the development of an inward rectifying K+ current, and a decrease in a voltage‐dependent, inactivating outward current. After 3–4 days in culture the inflammatory mediated substances adenosine triphosphate (ATP), platelet‐activating factor and bacterial lipopolysaccharide induced increases in cytoplasmic Ca2+ ([Ca2+]i). Forskolin suppressed the ATP‐induced increase in [Ca2+]i. Macrophages exhibited oxidative bursts, measured by oxidation of dihydrorhodamine‐123 to rhodamine‐123. Oxidative bursts coincided with a reduction in intracellular pH. Macrophages expressed a proton conductance that may participate in pH maintenance during reactive oxygen production. These results suggest that resident macrophages in the intestine may play a role in the immunological protection of the gut.
The homeobox gene BREVIPEDICELLUS is a key regulator of inflorescence architecture in Arabidopsis

Flowering plants display a remarkable range of inflorescence architecture, and pedicel characteristics are one of the key contributors to this diversity. However, very little is known about the genes or the pathways that regulate pedicel development. The brevipedicellus (bp) mutant of Arabidopsis thaliana displays a unique phenotype with defects in pedicel development causing downward-pointing flowers and a compact inflorescence architecture. Cloning and molecular analysis of two independent mutant alleles revealed that BP encodes the homeodomain protein KNAT1, a member of the KNOX family. bp-1 is a null allele with deletion of the entire locus, whereas bp-2 has a point mutation that is predicted to result in a truncated protein. In both bp alleles, the pedicels and internodes were compact because of fewer cell divisions; in addition, defects in epidermal and cortical cell differentiation and elongation were found in the affected regions. The downward-pointing pedicels were produced by an asymmetric effect of the bp mutation on the abaxial vs. adaxial sides. Cell differentiation, elongation, and growth were affected more severely on the abaxial than adaxial side, causing the change in the pedicel growth angle. In addition, bp plants displayed defects in cell differentiation and radial growth of the style. Our results show that BP plays a key regulatory role in defining important aspects of the growth and cell differentiation of the inflorescence stem, pedicel, and style in Arabidopsis.
Greater Activation of Secondary Motor Areas Is Related to Less Arm Use After Stroke

Background. Past studies have identified reorganization of brain activity in relation to motor outcome through standardized laboratory measures, which are quantifiable surrogates for arm use in real life. In contrast, accelerometers can provide a real-life estimate of arm and hand usage. Methods. Ten persons with chronic, subcortical stroke and 10 healthy controls of similar age performed a squeeze motor task at 40% maximum voluntary contraction during functional magnetic resonance imaging (fMRI). Use of the upper extremity was quantified over 3 consecutive days using wrist accelerometers. Correlations were performed between arm use and peak percent signal change (PSC) during grasp force production in 6 regions of interest (ROIs): bilateral primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM). Results. Results demonstrate that in healthy controls, PSC across all ROIs did not show a relationship between arm use and brain activation during force production. In contrast, after stroke, contralesional PM and M1 showed a significant (P ≤ .05) correlation between increasing activation and decreasing paretic arm use, whereas ipsilesional PM showed a significant correlation ( P ≤ .05) between increasing activation and decreasing nonparetic arm use. Conclusions. The results of this pilot study demonstrate a negative relationship between brain activation and actual arm use after stroke. Larger studies using accelerometers that can detect amount and types of movement may offer further insight into brain reorganization and rehabilitation interventions.
Nanoscale Pt(0) particles prepared in imidazolium room temperature ionic liquids: synthesis from an organometallic precursor, characterization, and catalytic properties in hydrogenation reactions.

The reaction of Pt(2)(dba)(3) (dba = bis-dibenzylidene acetone) dispersed in room temperature 1-n-butyl-3-methylimidazolium (BMI) hexafluorophosphate ionic liquid with molecular hydrogen (4 atm) at 75 degrees C leads to stable and isolable nanometric Pt(0) particles. The X-ray diffraction analysis (XRD) of the material indicated that it is constituted of Pt(0). Transmission electron microscopy (TEM) analysis of the particles dispersed in the ionic liquid shows the formation of [Pt(0)](n) nanoparticles of 2.0-2.5 nm in diameter. A detailed examination of the nanoparticles imbibed in the ionic liquid and their environment shows an interaction of the BMI.PF(6) ionic liquid with the Pt(0) nanoparticles. The isolated [Pt(0)](n) nanoparticles can be redispersed in the ionic liquid or in acetone or used in solventless conditions for liquid-liquid biphasic, homogeneous, or heterogeneous hydrogenation of alkenes and arenes under mild reaction conditions (75 degrees C and 4 atm). The recovered platinum nanoparticles can be reused as a solid or redispersed in the ionic liquid several times without any significant loss in catalytic activity.
Tissue reactions to sutures in the presence and absence of anti-infective therapy.

BACKGROUND In the oral cavity, sutures are placed within tissues of high vascularity in a moist environment with infectious potential. The objective of this study was to evaluate tissue reactions at silk and expanded polytetrafluoroethylene (ePTFE) sutures in the presence and absence of anti-infective therapy (AT). METHODS Thirty-six sutures were placed within the mandibular keratinized gingiva in six Beagle dogs. Each animal received one braided silk (4-0) and one ePTFE (CV-5) suture in contra-lateral jaw quadrants at 14, 7, and 3 days prior to biopsy. Three animals received daily AT including topical 2% chlorhexidine solution and a systemic broad-spectrum antibiotic. Biopsy specimens allowed histometric analysis of tissue reactions along the central part of the suture loop including the area of perisutural epithelium, ratio inflammatory cells (ICs)/epithelial cells and IC/fibroblasts, and presence/absence of bacterial plaque in the suture track. RESULTS A perisutural epithelial sheath was forming within 3 days. The cross-sectional area of the epithelium increased with time for both suture materials (p=0.003) but was particularly pronounced for the silk sutures in the absence of AT. Clusters of IC were present in the perisutural connective tissue and epithelium. Over time, a more prominent increase in IC/fibroblasts was evident for the silk sutures in the absence of AT. The pooled material revealed a significantly higher IC/fibroblast ratio for silk compared with ePTFE sutures (p=0.017). Bacterial plaque influx was detected in 6/9 silk and 0/9 ePTFE suture channels in the presence, and 6/6 and 3/6 suture channels, respectively, in the absence of AT. CONCLUSIONS AT may reduce biofilm formation and inflammation along the suture track. Braided silk, however, elicits more severe tissue reactions than ePTFE regardless of infection control.