Women and Employment

Presents results of the 1998 research project 'The Status of Women & Men in the Czech Republic' (N = 1,000 respondents ages 20-60), inspired by the need to obtain information on the circumstances of enforcement of European Union (EU) legislation on equal opportunities in the Czech Republic in connection with its application for EU membership. The public perception & consciousness of equal opportunities are investigated in terms of pay, access to employment, promotion, & vocational training, as well as legal knowledge concerning employment. Reconciling family & working life is the crucial problem in the Czech Republic, as in other countries. It can be understood as a result of both modernization & the special national situation that has resulted from the social & economic transition. Comparison of conditions of women's employment with their professional expectations & satisfaction reveals the social determination of these, as well as some stereotypes in understanding men's & women's roles that influence women's position in the labor market

Host–microbiome intestinal interactions during early life: considerations for atopy and asthma development

Purpose of review: The body's largest microbial community, the gut microbiome, is in contact with mucosal surfaces populated with epithelial, immune, endocrine and nerve cells, all of which sense and respond to microbial signals. These mutual interactions have led to a functional coevolution between the microbes and human physiology. Examples of coadaptation are anaerobes Bifidobacteria and Bacteroides, which have adjusted their metabolism to dietary components of human milk, and infant immune development, which has evolved to become reliant on the presence of beneficial microbes. Current research suggests that specific composition of the early-life gut microbiome aligns with the maturation of host immunity. Disruptions of natural microbial succession patterns during gut colonization are a consistent feature of immune-mediated diseases, including atopy and asthma. Recent findings: Here, we catalog recent birth cohorts documenting associations between immune dysregulation and microbial alterations, and summarize the evidence supporting the role of the gut microbiome as an etiological determinant of immune-mediated allergic diseases. Summary: Ecological concepts that describe microbial dynamics in the context of the host environment, and a portray of immune and neuroendocrine signaling induced by host–microbiome interactions, have become indispensable in describing the molecular role of early-life microbiome in atopy and asthma susceptibility

Creep behaviour and microstructure changes of model cast Ni-Cr-W-C alloys

AbstractA comparative study of creep and microstructural properties of two model cast Ni-Cr-W-C alloys (Alloys A and B) resistant to high-temperature oxidation with different contents of Cr, W, Zr and Fe was performed. Uniaxial tensile creep tests were carried out at temperatures from 1023 to 1273K and at the applied stresses ranged from 20 to 250MPa. Creep tests were followed by microstructural and fractographic investigations. A mutual comparison between the creep characteristics of the alloys under comparable creep loading conditions shows that the alloy B with higher contents of tungsten and zirconium is more creep resistant as that of the Alloy A at lower temperatures. It is suggested that the alloy A and B earn their creep strength from the combination of solid solution hardening and precipitation hardening. However, it is difficult to quantify each contribution to the overall creep strength. Possible reason for the different consequence of strengthening effects is discussed

Functional Age-Related Changes Within the Human Auditory System Studied by Audiometric Examination

Age related hearing loss (presbycusis) is one of the most common sensory deficits in the aging population. The main subjective ailment in the elderly is the deterioration of speech understanding, especially in a noisy environment, which cannot solely be explained by increased hearing thresholds. The examination methods used in presbycusis are primarily focused on the peripheral pathologies (e.g., hearing sensitivity measured by hearing thresholds), with only a limited capacity to detect the central lesion. In our study, auditory tests focused on central auditory abilities were used in addition to classical examination tests, with the aim to compare auditory abilities between an elderly group (elderly, mean age 70.4 years) and young controls (young, mean age 24.4 years) with clinically normal auditory thresholds, and to clarify the interactions between peripheral and central auditory impairments. Despite the fact that the elderly were selected to show natural age-related deterioration of hearing (auditory thresholds did not exceed 20 dB HL for main speech frequencies) and with clinically normal speech reception thresholds (SRTs), the detailed examination of their auditory functions revealed deteriorated processing of temporal parameters [gap detection threshold (GDT), interaural time difference (ITD) detection] which was partially responsible for the altered perception of distorted speech (speech in babble noise, gated speech). An analysis of interactions between peripheral and central auditory abilities, showed a stronger influence of peripheral function than temporal processing ability on speech perception in silence in the elderly with normal cognitive function. However, in a more natural environment mimicked by the addition of background noise, the role of temporal processing increased rapidly

Mutations in topoisomerase IIβ result in a B cell immunodeficiency.

B cell development is a highly regulated process involving multiple differentiation steps, yet many details regarding this pathway remain unknown. Sequencing of patients with B cell-restricted immunodeficiency reveals autosomal dominant mutations in TOP2B. TOP2B encodes a type II topoisomerase, an essential gene required to alleviate topological stress during DNA replication and gene transcription, with no previously known role in B cell development. We use Saccharomyces cerevisiae, and knockin and knockout murine models, to demonstrate that patient mutations in TOP2B have a dominant negative effect on enzyme function, resulting in defective proliferation, survival of B-2 cells, causing a block in B cell development, and impair humoral function in response to immunization

Combinational Spinal GAD65 Gene Delivery and Systemic GABA-Mimetic Treatment for Modulation of Spasticity

receptor agonist), while effective in modulating spasticity is associated with major side effects such as general sedation and progressive tolerance development. The goal of the present study was to assess if a combined therapy composed of spinal segment-specific upregulation of GAD65 (glutamate decarboxylase) gene once combined with systemic treatment with tiagabine (GABA uptake inhibitor) will lead to an antispasticity effect and whether such an effect will only be present in GAD65 gene over-expressing spinal segments.Adult Sprague-Dawley (SD) rats were exposed to transient spinal ischemia (10 min) to induce muscle spasticity. Animals then received lumbar injection of HIV1-CMV-GAD65 lentivirus (LVs) targeting ventral α-motoneuronal pools. At 2–3 weeks after lentivirus delivery animals were treated systemically with tiagabine (4, 10, 20 or 40 mg/kg or vehicle) and the degree of spasticity response measured. In a separate experiment the expression of GAD65 gene after spinal parenchymal delivery of GAD65-lentivirus in naive minipigs was studied. Spastic SD rats receiving spinal injections of the GAD65 gene and treated with systemic tiagabine showed potent and tiagabine-dose-dependent alleviation of spasticity. Neither treatment alone (i.e., GAD65-LVs injection only or tiagabine treatment only) had any significant antispasticity effect nor had any detectable side effect. Measured antispasticity effect correlated with increase in spinal parenchymal GABA synthesis and was restricted to spinal segments overexpressing GAD65 gene.These data show that treatment with orally bioavailable GABA-mimetic drugs if combined with spinal-segment-specific GAD65 gene overexpression can represent a novel and highly effective anti-spasticity treatment which is associated with minimal side effects and is restricted to GAD65-gene over-expressing spinal segments

Promoting remyelination through cell transplantation therapies in a model of viral-induced neurodegenerative disease.

Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Several United States Food and Drug Administration-approved therapies exist that impede activated lymphocytes from entering the CNS thereby limiting new lesion formation in patients with relapse-remitting forms of MS. However, a significant challenge within the field of MS research is to develop effective and sustained therapies that allow for axonal protection and remyelination. In recent years, there has been increasing evidence that some kinds of stem cells and their derivatives seem to be able to mute neuroinflammation as well as promote remyelination and axonal integrity. Intracranial infection of mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in immune-mediated demyelination and axonopathy, making this an excellent model to interrogate the therapeutic potential of stem cell derivatives in evoking remyelination. This review provides a succinct overview of our recent findings using intraspinal injection of mouse CNS neural progenitor cells and human neural precursors into JHMV-infected mice. JHMV-infected mice receiving these cells display extensive remyelination associated with axonal sparing. In addition, we discuss possible mechanisms associated with sustained clinical recovery. Developmental Dynamics 248:43-52, 2019. © 2018 Wiley Periodicals, Inc

Molecular mechanism of central nervous system repair by the Drosophila NG2 homologue kon-tiki:Drosophila NG2 in CNS repair

Neuron glia antigen 2 (NG2)–positive glia are repair cells that proliferate upon central nervous system (CNS) damage, promoting functional recovery. However, repair is limited because of the failure of the newly produced glial cells to differentiate. It is a key goal to discover how to regulate NG2 to enable glial proliferation and differentiation conducive to repair. Drosophila has an NG2 homologue called kon-tiki (kon), of unknown CNS function. We show that kon promotes repair and identify the underlying mechanism. Crush injury up-regulates kon expression downstream of Notch. Kon in turn induces glial proliferation and initiates glial differentiation by activating glial genes and prospero (pros). Two negative feedback loops with Notch and Pros allow Kon to drive the homeostatic regulation required for repair. By modulating Kon levels in glia, we could prevent or promote CNS repair. Thus, the functional links between Kon, Notch, and Pros are essential for, and can drive, repair. Analogous mechanisms could promote CNS repair in mammals

Ablation of NG2 Proteoglycan Leads to Deficits in Brown Fat Function and to Adult Onset Obesity

Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O2 consumption and CO2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator (PGC)1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes