Conserved missense variant in ALDH1A3 ortholog impairs fecundity in C. elegans

Accumulating evidence demonstrates that mutations in ALDH1A3 (the aldehyde dehydrogenase 1 family, member A3) are associated with developmental defects. The ALDH1A3 enzyme catalyzes retinoic acid biosynthesis and is essential to patterning and neuronal differentiation in the development of embryonic nervous system. Several missense mutations in ALDH1A3 have been identified in family studies of autosomal recessive microphthalmia, autism spectrum disorder, and other neurological disorders. However, there has been no evidence from animal models that verify the functional consequence of missense mutations in ALDH1A3. Here, we introduced the equivalent of the ALDH1A3 C174Y variant into the Caenorhabditis elegans ortholog, alh-1, at the corresponding locus. Mutant animals with this missense mutation exhibited decreased fecundity by 50% compared to wild-type animals, indicating disrupted protein function. To our knowledge, this is the first ALDH1A3 C174Y missense model, which might be used to elucidate the effects of ALDH1A3 C174Y missense mutation in the retinoic acid signaling pathway during development

Superconducting order parameter in nonmagnetic borocarbides RNi2B2C (R = Y, Lu) probed by point-contact Andreev reflection spectroscopy

We report on the measurements of the superconducting order parameter in the nonmagnetic borocarbides LuNi2B2C and YNi2B2C. Andreev conductance spectra are obtained from nanoscale metallic junctions on single crystal surfaces prepared along three major crystallographic orientations: [001], [110], and [100]. The gap values extracted by the single-gap Blonder-Tinkham-Klapwijk model follow the theoretical predictions as a function of temperature and magnetic field and exhibit a small anisotropy with no indication of proposed gap nodes along the [100] and [010] directions. These observations are robust and reproducible among all the measurements on two different sets of LuNi2B2C crystals and one set of YNi2B2C crystals. We suggest that the possible gap nodes in the [100] direction may be masked by two effects: different gap anisotropy across multiple Fermi surfaces, as reported in the recent photoemission spectroscopy, and the large tunneling cone. Our results provide a consistent picture of the superconducting gap structure in these materials, addressing the controversy particularly in the reported results of point-contact Andreev reflection spectroscopy

Exercise Training Increases Parietal Lobe Cerebral Blood Flow in Chronic Stroke: An Observational Study

Exercise is increasingly recommended as an essential component of stroke rehabilitation, yet uncertainty remains with respect to its direct effect on the cerebral vasculature. The current study first demonstrated the repeatability of pseudo-continuous arterial spin labeling (ASL) magnetic resonance imaging (MRI) in older adults with stroke, and then investigated the change in cerebrovascular function following a 6-month cardiovascular rehabilitation program. In the repeatability study, 12 participants at least 3 months post-stroke underwent two ASL imaging scans 1 month apart. In the prospective observational study, eight individuals underwent ASL imaging and aerobic fitness testing before and after a 6-month cardiovascular rehabilitation program. Cerebral blood flow (CBF) and the spatial coefficient of variation of CBF (sCoV) were quantified to characterize tissue-level perfusion and large cerebral artery transit time properties, respectively. In repeat scanning, intraclass correlation (ICC) indicated moderate test-retest reliability for global gray matter CBF (ICC = 0.73) and excellent reliability for sCoV (ICC = 0.94). In the observational study, gray matter CBF increased after training (baseline: 40 ± 13 vs. 6-month: 46 ± 12 ml·100 g−1·min−1, P = 0.036). The greatest change occurred in the parietal lobe (+18 ± 12%). Gray matter sCoV, however, did not change following training (P = 0.31). This study provides preliminary evidence that exercise-based rehabilitation in chronic stroke enhances tissue-level perfusion, without changing the relative hemodynamic properties of the large cerebral arteries

Oxidative stress predicts depressive symptom changes with omega-3 fatty acid treatment in coronary artery disease patients

AbstractBackgroundAntidepressant efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment in coronary artery disease (CAD) patients remains unpredictable. N-3 PUFA can mitigate oxidative stress, which is common in CAD and may contribute to depressive symptoms. This study investigated whether greater pre-treatment oxidative stress, measured by the ratios of late-stage lipid peroxidation markers (malondialdehyde [MDA], 4-hydroxy-2-nonenal [4-HNE], and 8-isoprostane [8-ISO]) to an early-stage marker (lipid hydroperoxides [LPH]), predicted n-3 PUFA antidepressant benefits in CAD.MethodsThis was a secondary analysis of CAROTID (CAD Randomized Omega-3 Trial in Depression, NCT00981383). Patient demographics and medical characteristics were collected. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D). Patients were then randomized to receive either 1.9g/day n-3 PUFA or placebo for 12weeks, after which HAM-D scores were reassessed. Baseline LPH, 4-HNE, 8-ISO, MDA and n-3 PUFA concentrations were analysed from fasting blood.ResultsSeventy-nine patients (age=61.1±8.5, 76% male, HAM-D=7.5±6.1) were included (n=45 placebo, n=34 n-3 PUFA). In the n-3 PUFA group, higher baseline ratios of MDA/LPH (primary analysis: F1,33=6.20, beta=−0.35, p=0.018), 4-HNE/LPH (exploratory analysis: F1,33=5.35, beta=−0.32, p=0.027), and 8-ISO/LPH (exploratory analysis: F1,33=6.10, beta=−0.33, p=0.019), indicating higher oxidative stress, were associated with greater depressive symptom improvement. In each model, higher baseline EPA+DHA concentrations independently predicted depressive symptom improvement with n-3 PUFA (MDA/LPH: F1,33=11.05, p=0.002; 4-HNE/LPH: F1,33=11.36, p=0.002; 8-ISO/LPH: F1,33=13.15, p=0.001). No associations were observed in the placebo group.Conclusionsn-3 PUFA may be more likely to improve depressive symptoms in CAD patients with pre-treatment evidence of oxidative stress

Zee Model Confronts SNO Data

We reexamine the solution of the minimal Zee model by comparing with the data of the SNO experiment, and conclude that the model is strongly disfavored but not yet excluded by the observations. Two extensions of the Zee model are briefly discussed both of which introduce additional freedom and can accommodate the data.Comment: 16 pages LaTeX including 7 figure

Stresses in cement mantles of hip replacements: effect of femoral implant sizes, body mass index and bone quality

The effects of femoral prosthetic heads of diameters 22 and 28 mm were investigated on the stability of reconstructed hemi-pelves with cement mantles of thicknesses 1-4 mm and different bone qualities. Materialise medical imaging package and I-Deas finite element (FE) software were used to create accurate geometry of a hemi-pelvis from CT-scan images. Our FE results show an increase in cement mantle stresses associated with the larger femoral head. When a 22 mm femoral head is used on acetabulae of diameters 56 mm and above, the probability of survivorship can be increased by creating a cement mantle of at least 1 mm thick. However, when a 28 mm femoral head is used, a cement mantle thickness of at least 4 mm is needed. Poor bone quality resulted in an average 45% increase in the tensile stresses of the cement mantles, indicating resulting poor survivorship rate

Making Maps Of The Cosmic Microwave Background: The MAXIMA Example

This work describes Cosmic Microwave Background (CMB) data analysis algorithms and their implementations, developed to produce a pixelized map of the sky and a corresponding pixel-pixel noise correlation matrix from time ordered data for a CMB mapping experiment. We discuss in turn algorithms for estimating noise properties from the time ordered data, techniques for manipulating the time ordered data, and a number of variants of the maximum likelihood map-making procedure. We pay particular attention to issues pertinent to real CMB data, and present ways of incorporating them within the framework of maximum likelihood map-making. Making a map of the sky is shown to be not only an intermediate step rendering an image of the sky, but also an important diagnostic stage, when tests for and/or removal of systematic effects can efficiently be performed. The case under study is the MAXIMA data set. However, the methods discussed are expected to be applicable to the analysis of other current and forthcoming CMB experiments.Comment: Replaced to match the published version, only minor change

Meta-heuristically seeded genetic algorithm for independent job scheduling in grid computing

Grid computing is an infrastructure which connects geographically distributed computers owned by various organizations allowing their resources, such as computational power and storage capabilities, to be shared, selected, and aggregated. Job scheduling problem is one of the most difficult tasks in grid computing systems. To solve this problem efficiently, new methods are required. In this paper, a seeded genetic algorithm is proposed which uses a meta-heuristic algorithm to generate its initial population. To evaluate the performance of the proposed method in terms of minimizing the makespan, the Expected Time to Compute (ETC) simulation model is used to carry out a number of experiments. The results show that the proposed algorithm performs better than other selected techniques

TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination

SummarySystems biological analysis of immunity to the trivalent inactivated influenza vaccine (TIV) in humans revealed a correlation between early expression of TLR5 and the magnitude of the antibody response. Vaccination of Trl5−/− mice resulted in reduced antibody titers and lower frequencies of plasma cells, demonstrating a role for TLR5 in immunity to TIV. This was due to a failure to sense host microbiota. Thus, antibody responses in germ-free or antibiotic-treated mice were impaired, but restored by oral reconstitution with a flagellated, but not aflagellated, strain of E. coli. TLR5-mediated sensing of flagellin promoted plasma cell differentiation directly and by stimulating lymph node macrophages to produce plasma cell growth factors. Finally, TLR5-mediated sensing of the microbiota also impacted antibody responses to the inactivated polio vaccine, but not to adjuvanted vaccines or the live-attenuated yellow fever vaccine. These results reveal an unappreciated role for gut microbiota in promoting immunity to vaccination