The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle

Daily behavioral and physiological rhythms are linked to circadian oscillations of clock genes in the brain and periphery that are synchronized by the master clock in the suprachiasmatic nucleus. In addition, there are a number of inputs that can influence circadian oscillations in clock gene expression in a tissue-specific manner. Here we identify an influence on the circadian oscillation of the clock protein PER2, endogenous changes in ovarian steroids, within two nuclei of the limbic forebrain: the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. We show that the daily rhythm of PER2 expression within these nuclei but not in the suprachiasmatic nucleus, dentate gyrus, or basolateral amygdala is blunted in the metestrus and diestrus phases of the estrus cycle. The blunting of the PER2 rhythm at these phases of the cycle is abolished by ovariectomy and restored by phasic estrogen replacement suggesting that fluctuations in estrogen levels or their sequelae are necessary to produce these effects. The finding that fluctuations in ovarian hormones have area-specific effects on clock gene expression in the brain introduces a new level of organizational complexity in the control of circadian rhythms of behavior and physiology

Development of products with Shiitake mushroom: chemical, physical and sensory characterization

Shiitake mushrooms are much appreciated and therefore their production has increased. However, an important quantity of by-products and residues, are also generated and which are considered as waste materials. In this way, the aim of this work was to develop new foods incorporating shiitake mushrooms that do not comply with standards for commercialization, thus providing additional sources of income for the farmers. For this, a filling with mushroom was produced for rissoles and pies, and the final products were analysed for their chemical composition, colour, texture and sensorial attributes. The results showed that the shiitake products presented an interesting chemical composition, rich in protein and minerals, and poor in salt. It was also observed that the frying operation induced more colour changes in the rissoles than the oven baking of the pies. The textural measurements indicated that the rissoles were much softer when compared to the pies, being also more cohesive and elastic. The sensory panel attributed high scores to both products (around 4.5, on a scale from 1 to 5), thus indicating that these may constitute an additional source of income to the farmers and at the same time reducing waste.info:eu-repo/semantics/publishedVersio

Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

Abstract\ud \ud \ud \ud Background\ud Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood.\ud \ud \ud \ud Methods\ud At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data.\ud \ud \ud \ud Results\ud As expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered.\ud \ud \ud \ud Conclusions\ud In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels.The authors are thankful to Ruither Carolino for hormonal determinations, to Felipe Hiroshi Saito and Silvia Sakamoto for technical assistance, to Fernanda Pereira Lima for her help with animal care, and to CAPES for financial support

Pregnancy and Maternal Behavior Induce Changes in Glia, Glutamate and Its Metabolism within the Cingulate Cortex

An upregulation of the astrocytic proteins GFAP and bFGF within area 2 of the cingulate cortex (Cg2) occurs within 3 hours of parturition in rats. These changes are the result of an interaction between hormonal state and maternal experience and are associated with increased dendritic spine density in this area. Here, we examined whether this upregulation of astrocytic proteins generalized to other glial markers and, in particular those associated with glutamate metabolism. We chose glial markers commonly used to reflect different aspects of glial function: vimentin, like GFAP, is a marker of intermediate filaments; glutamine synthetase (GS), and S-100beta, are used as markers for mature astrocytes and GS has also been used as a specific marker for glutamatergic enzymatic activity. In addition, we examined levels of proteins associated with glutamine synthetase, glutamate, glutamine and two excitatory amino acid transporters found in astrocytes, glt-1 and glast. S100beta immunoreactivity did not vary with reproductive state in either Cg2 or MPOA suggesting no change in the number of mature astrocytes across these conditions. Vimentin-ir did not differ across groups in Cg2, but expression of this protein decreased from Day 1 postpartum onwards in the MPOA. By contrast, GS-ir was increased within 24 h postpartum in Cg2 but not MPOA and similarly to GFAP and bFGF this upregulation of GS resulted from an interaction between hormonal state and maternal experience. Within Cg2, upregulation of GS was not accompanied by changes in the astrocytic glutamatergic transporters, glt-1 and glast, however, an increase in both glutamate and glutamine proteins were observed within the Cg2 of postpartum animals. Together, these changes suggest postpartum upregulation of glutamatergic activity and metabolism within Cg2 that is stimulated by pregnancy hormones and maternal experience

Nepotism, employees’ competencies and firm performance in the tourism sector: A dual multivariate and Qualitative Comparative Analysis approach

© 2018 Elsevier Ltd The paper identifies the critical competencies affecting Egyptian travel agents’ performance while assessing the negative influence of nepotism on such competencies. To address this aim, the study uses a holistic dual approach employing a multivariate technique using Partial Least Squares Structural Equation Modelling (PLS-SEM) and a configuration method through a fuzzy-set Qualitative Comparative Analysis (fsQCA). Based on a sample of 500 travel agents’ employees, the results show that: (1) none of the competencies is sufficient to drive travel agents’ performance, (2) two distinct configurations of employee competencies are likely to result in high performance, and (3) nepotism has a direct negative influence on some of these competencies. The study holds important implications for both theory and practice

Mind the gap: A process model for diagnosing barriers to key account management implementation

Today, many firms develop and implement key account management (KAM) programs to manage the relationships with strategically important customers. The implementation of KAM programs requires the configuration of special activities, actors, and resources dedicated to key accounts, which poses major challenges for managerial practice. Firms often underestimate the fundamental organizational change required for a successful implementation of KAM. The objective of this article is to advance extant knowledge on KAM by developing a framework that outlines essential processes to assess and diagnose barriers to KAM implementation. In our article, we integrate extant knowledge on KAM organization and enactment, and we propose a four-step process model that links the concepts of embeddedness, differentiation, integration, and alignment. In addition, we illustrate our model in a case study analysis with a large-scale European industrial company. The findings of our study allow us to derive avenues for further research on KAM implementation as well as implications for management practice

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia