Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA

The juice of fresh leaves of Catharanthus roseus Linn. reduces blood glucose in normal and alloxan diabetic rabbits

BACKGROUND: The leaf juice or water decoction of Catharanthus roseus L. (Apocyanaceae) is used as a folk medicine for the treatment of diabetes all over the world. In the present investigation, the leaf juice of C. roseus has been evaluated for its hypoglycemic activity in normal and alloxan-induced diabetic rabbits. METHODS: The blood glucose lowering activity of the leaf juice was studied in normal and alloxan-induced (100 mg/kg, i.v.) diabetic rabbits, after oral administration at doses of 0.5, 0.75 and 1.0 ml/kg body weight. Blood samples were collected from the marginal ear vein before and also at 4, 6, 8, 10, 12, 16, 18, 20 & 24 h after drug administration and blood glucose was analyzed by Nelson-Somogyi's method using a visible spectrophotometer. The data was compared statistically by using Student's t-test. RESULTS: The leaf juice of C. roseus produced dose-dependent reduction in blood glucose of both normal and diabetic rabbits and comparable with that of the standard drug, glibenclamide. The results indicate a prolonged action in reduction of blood glucose by C. roseus and the mode of action of the active compound(s) of C. roseus is probably mediated through enhance secretion of insulin from the β-cells of Langerhans or through extrapancreatic mechanism. CONCLUSIONS: The present study clearly indicated a significant antidiabetic activity with the leaf juice of Catharanthus roseus and supports the traditional usage of the fresh leaves by Ayurvedic physicians for the control of diabetes

Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis

Background Approximately 50% of systemic lupus erythematosus (SLE) patients develop nephritis, which is among the most severe and frequent complications of the disease and a leading cause of morbidity and mortality. Despite intensive research, there are still no reliable lupus nephritis (LN) markers in clinical use that can assess renal damage and activity with a high sensitivity and specificity. To this end, the aim of this study was to identify new clinically relevant tissue-specific protein biomarkers and possible underlying molecular mechanisms associated with renal involvement in SLE, using mass spectrometry (MS)-based proteomics. Methods Kidneys were harvested from female triple congenic B6.NZMsle1/sle2/sle3 lupus mice model, and the respective sex- and age-matched C57BL/6 control mice at 12, 24 and 36 weeks of age, representing pre-symptomatic, established and end-stage LN, respectively. Proteins were extracted from kidneys, purified, reduced, alkylated and digested by trypsin. Purified peptides were separated by liquid chromatography and analysed by high-resolution MS. Data were processed by the Progenesis QIp software, and functional annotation analysis was performed using DAVID bioinformatics resources. Immunofluorescence and multiple reaction monitoring (MRM) MS methods were used to confirm prospective biomarkers in SLE mouse strains as well as human serum samples. Results Proteomic profiling of kidney tissues from SLE and control mice resulted in the identification of more than 3800 unique proteins. Pathway analysis revealed a number of dysregulated molecular pathways that may be mechanistically involved in renal pathology, including phagosome and proximal tubule bicarbonate reclamation pathways. Proteomic analysis supported by human transcriptomic data and pathway analysis revealed Coronin-1A, Ubiquitin-like protein ISG15, and Rho GDP-dissociation inhibitor 2, as potential LN biomarkers. These results were further validated in other SLE mouse strains using MRM-MS. Most importantly, experiments in humans showed that measurement of Coronin-1A in human sera using MRM-MS can segregate LN patients from SLE patients without nephritis with a high sensitivity (100%) and specificity (100%). Conclusions These preliminary findings suggest that serum Coronin-1A may serve as a promising non-invasive biomarker for LN and, upon validation in larger cohorts, may be employed in the future as a screening test for renal disease in SLE patients

Immune Modulation by Adjuvants Combined with Diphtheria Toxoid Administered Topically in BALB/c Mice After Microneedle Array Pretreatment

Purpose. In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. Methods. TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-administrated with lipopolysaccharide (LPS), Quil A, CpG oligo deoxynucleotide (CpG) or cholera toxin (CT) as adjuvant. The immunogenicity was evaluated by measuring serum IgG subtype titers and neutralizing antibody titers. Results. TCI with microneedle array pretreatment resulted in a 1,000-fold increase of DT-specific serum IgG levels as compared to TCI. The immune response was further improved by co-administration of adjuvants, showing a progressive increase in serum IgG titers when adjuvanted with LPS, Quil A, CpG and CT. IgG titers of the CT-adjuvanted group reached levels comparable to those obtained after DTalum subcutaneous injection. The IgG1/IgG2a ratio of DT-specific antibodies decreased in the following sequence: plain DT, Quil A, CT and CpG, suggesting that the immune response was skewed towards the Th1 direction. Conclusions. The potency and the quality of the immune response against DT administered by microneedle array mediated TCI can be modulated by co-administration of adjuvants. KEY WORDS: cholera toxin; CpG; diphtheria toxoid; microneedle array; transcutaneous immunization

Nanoparticles of Selenium as Species with Stronger Physiological Effects in Sheep in Comparison with Sodium Selenite

The present study was designed to compare the effects of nano red selenium and sodium selenite on the antioxidative activities of neutrophils and the hematological parameters in sheep. Fifteen sheep were randomly allocated into three groups. Groups 1 and 2 received selenium nanoparticles orally at 1 mg/kg and sodium selenite at 1 mg Se/kg for 10 consecutive days; group 3 served as the control. To assess the degrees of oxidative stress and of lipid peroxidation of the cellular membranes, the levels of thiobarbituric acid reactive substances (TBARS) were determined in serum samples that were collected at different supplementation intervals, i.e., after 0, 10, 20, and 30 days. In addition, hematological parameters in the serum samples were measured by routine procedures. It was found that TBARS levels in groups 1 and 2 were significantly higher on days 20 and 30 compared to the basal level on day 0. It was also found that on day 30, the TBARS activities in both treated groups were significantly higher than those of the controls (P < 0.05). These findings may explain the seemingly paradoxical effects of supplemental selenium on the indicators of oxidative stress, as the levels of TBARS were generally expected to decrease in the presence of selenium. There were no significant differences between the PCV and RBC values in the three groups. The white blood cell count (WBC) in group 1 showed a significant increase on days 20 and 30 in comparison with the control group. However, in group 2, there was a significant increase of the WBC value just on day 20 in comparison with the control group. Also, there were significant increases of the neutrophil counts and significant decreases of the lymphocyte counts on day 10 in group 1, in comparison with those in group 2 and controls, and on days 20 and 30 in groups 1 and 2 in comparison with those in the control group

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Background - Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods - We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results - We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions - A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits

The role of rewards and demands in burnout among surgical nurses

Job rewards have both, an intrinsic and an extrinsic motivational potential, and lead to employees’ development as well as help them to achieve work goals. Rewards can balance job demands and protect from burnout. Due to changes on the labour market, new studies are needed. The aim of our study was to examine the role of demands and individual rewards (and their absence) in burnout among surgical nurses. Materials and Methods: The study was conducted in 2009 and 2010 with 263 nurses who worked in surgical wards and clinics in hospitals in Southern Poland. The hypotheses were tested by the use of measures of demands and rewards (Effort-Reward Imbalance Questionnaire by Siegrist) and burnout syndrome (Maslach Burnout Inventory). A cross-sectional, correlational study design was applied. Results: Nurses experienced the largest deficiencies in salary and prestige. Exhaustion was explained by stronger demands and lack of respect (large effect). Depersonalization was explained by stronger demands, lack of respect and greater job security (medium effect). Reduced personal achievement was explained by more demands and greater job security (small effect). Conclusions: Excessive demands and lack of esteem are key reasons for burnout among surgical nurses. Job security can increase burnout when too many resources are invested and career opportunities do not appear. These results may help to improve human resource management in the healthcare sector

Ouabain Stimulates a Na+/K+-ATPase-Mediated SFK-Activated Signalling Pathway That Regulates Tight Junction Function in the Mouse Blastocyst

The Na+/K+-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na+/K+-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS)-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK) members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and YES protein were localized throughout preimplantation development. Treatment of mouse morulae with the SFK inhibitors PP2 and SU6656 for 18 hours resulted in a reversible blockade of progression to the blastocyst stage. Blastocysts treated with 10−3 M ouabain for 2 or 10 minutes and immediately immunostained for phosphorylation at SRC tyr418 displayed reduced phosphorylation while in contrast blastocysts treated with 10−4 M displayed increased tyr418 fluorescence. SFK inhibition increased and SFK activation reduced trophectoderm tight junction permeability in blastocysts. The results demonstrate that SFKs are expressed during preimplantation development and that SFK activity is required for blastocyst formation and is an important mediator of trophectoderm tight junction permeability

Dissection of genetic associations with language-related traits in population-based cohorts

Recent advances in the field of language-related disorders have led to the identification of candidate genes for specific language impairment (SLI) and dyslexia. Replication studies have been conducted in independent samples including population-based cohorts, which can be characterised for a large number of relevant cognitive measures. The availability of a wide range of phenotypes allows us to not only identify the most suitable traits for replication of genetic association but also to refine the associated cognitive trait. In addition, it is possible to test for pleiotropic effects across multiple phenotypes which could explain the extensive comorbidity observed across SLI, dyslexia and other neurodevelopmental disorders. The availability of genome-wide genotype data for such cohorts will facilitate this kind of analysis but important issues, such as multiple test corrections, have to be taken into account considering that small effect sizes are expected to underlie such associations