1,813 research outputs found

    The longer your work hours, the worse your relationship? The role of selective optimization with compensation in the associations of working time with relationship satisfaction and self-disclosure in dual-career couples

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    This two-wave panel study investigates the associations between working time, selective optimization with compensation in private life and relationship outcomes (i.e. relationship satisfaction and self-disclosure) in dual-career couples. We propose that one partner’s selective optimization with compensation in private life either mediates or moderates the association of this partner’s working time and relationship outcomes (i.e. relationship satisfaction and self-disclosure). Moreover, we postulate the crossover (i.e. transmission) of relationship satisfaction and self-disclosure within the couple. To test these hypotheses, we conducted an online study with a time lag of six months, in which 285 dual-career couples took part. We found evidence for selective optimization with compensation in private life as a mediator: working time spent by partners in dual-career couples was associated with selective optimization with compensation in their private life that, in turn, predicted relationship satisfaction and self-disclosure. Results did not support the assumption that one partner’s selective optimization with compensation in private life moderates the association between working time and relationship satisfaction and self-disclosure. Relationship satisfaction, but not self-disclosure, crossed over within the couples. The results challenge the assumption that longer work hours have negative consequences for romantic relationships

    The electric dipole response of 76^{76}Se above 4 MeV

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    The dipole response of 3476^{76}_{34}Se in the energy range 4 to 9 MeV has been analyzed using a (γ,γ)(\vec\gamma,{\gamma}') polarized photon scattering technique, performed at the High Intensity γ\gamma-Ray Source facility, to complement previous work performed using unpolarized photons. The results of this work offer both an enhanced sensitivity scan of the dipole response and an unambiguous determination of the parities of the observed J=1 states. The dipole response is found to be dominated by E1E1 excitations, and can reasonably be attributed to a pygmy dipole resonance. Evidence is presented to suggest that a significant amount of directly unobserved excitation strength is present in the region, due to unobserved branching transitions in the decays of resonantly excited states. The dipole response of the region is underestimated when considering only ground state decay branches. We investigate the electric dipole response theoretically, performing calculations in a 3D cartesian-basis time-dependent Skyrme-Hartree-Fock framework.Comment: 20 pages, 18 figures, to be submitted to PR

    Region of hadron-quark mixed phase in hybrid stars

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    Hadron--quark mixed phase is expected in a wide region of the inner structure of hybrid stars. However, we show that the hadron--quark mixed phase should be restricted to a narrower region to because of the charge screening effect. The narrow region of the mixed phase seems to explain physical phenomena of neutron stars such as the strong magnetic field and glitch phenomena, and it would give a new cooling curve for the neutron star.Comment: to be published in Physical Review

    A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

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    Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

    KCC2 is required for the survival of mature neurons but not for their development

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    The K+/Cl- co-transporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl- levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors (GABAARs). In accordance with this, compromised KCC2 activity results in seizures, but whether such deficits directly contribute to the subsequent changes in neuronal structure and viability that lead to epileptogenesis, remains to be assessed. Canonical hyperpolarizing GABAAR currents develop postnatally which reflect a progressive increase in KCC2 expression levels and activity. To investigate the role that KCC2 plays in regulating neuronal viability and architecture we have conditionally ablated KCC2 expression in developing and mature neurons. Decreasing KCC2 expression in mature neurons resulted in the rapid activation of the extrinsic apoptotic pathway. Intriguingly, direct pharmacological inhibition of KCC2 in mature neurons was sufficient to rapidly induce apoptosis, an effect that was not abrogated via blockade of neuronal depolarization using Tetrodotoxin (TTX). In contrast, ablating KCC2 expression in immature neurons had no discernable effects on their subsequent development, arborization or dendritic structure. However, removing KCC2 in immature neurons was sufficient to ablate the subsequent postnatal development of hyperpolarizing GABAAR currents. Collectively, our results demonstrate that KCC2 plays a critical role in neuronal survival by limiting apoptosis, and mature neurons are highly sensitive to the loss of KCC2 function. In contrast, KCC2 appears to play a minimal role in mediating neuronal development or architecture

    A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

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    BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

    Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

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    Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system

    Efficacy of aerobic exercise and a prudent diet for improving selected lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials

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    Background Studies addressing the effects of aerobic exercise and a prudent diet on lipid and lipoprotein concentrations in adults have reached conflicting conclusions. The purpose of this study was to determine the effects of aerobic exercise combined with a prudent diet on lipid and lipoprotein concentrations in adults. Methods Studies were located by searching nine electronic databases, cross-referencing, and expert review. Two independent reviewers selected studies that met the following criteria: (1) randomized controlled trials, (2) aerobic exercise combined with diet recommendations (saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake ≥25 g/day in women and ≥35 grams per day in men), (3) intervention ≥4 weeks, (4) humans ≥18 years of age, (5) published studies, including dissertations and Master\u27s theses, (6) studies published in any language, (7) studies published between January 1, 1955 and May 1, 2009, (8) assessment of one or more of the following lipid and lipoprotein concentrations: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), ratio of TC to HDL-C, non-HDL-C, low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Two reviewers independently extracted all data. Random-effects models that account for heterogeneity and 95% confidence intervals were used to pool findings. Results Of the 1,401 citations reviewed, six studies representing 16 groups (8 intervention, 8 control) and up to 559 men and women (282 intervention, 277 control) met the criteria for analysis. Statistically significant intervention minus control reductions were found for TC (-15.5 mg/dl, 95% CI, -20.3 to -10.7), TC:HDL-C (-0.4 mg/dl, 95% CI, -0.7 to -0.2), LDL-C (-9.2 mg/dl, 95% CI, -12.7 to -5.8) and TG (-10.6 mg/dl, 95% CI, -17.2 to -4.0) but not HDL-C (-0.5 mg/dl, 95% CI, -4.0 to 3.1). Changes were equivalent to reductions of 7.5%, 6.6%, 7.2% and 18.2% respectively, for TC, TC:HDL-C, LDL-C and TG. Because of missing variance statistics, non-HDL-C was excluded. Conclusions Aerobic exercise combined with a prudent diet is highly efficacious for improving TC, TC:HDL-C, LDL-C and TG, but not HDL-C concentrations, in adults. However, additional studies are needed, including effectiveness studies using intention-to-treat analysis

    A Unique Modification of the Eukaryotic Initiation Factor 5A Shows the Presence of the Complete Hypusine Pathway in Leishmania donovani

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    Deoxyhypusine hydroxylase (DOHH) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (N€-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5A (eIF5A). We present here the molecular and structural basis of the function of DOHH from the protozoan parasite, Leishmania donovani, which causes visceral leishmaniasis. The L. donovani DOHH gene is 981 bp and encodes a putative polypeptide of 326 amino acids. DOHH is a HEAT-repeat protein with eight tandem repeats of α-helical pairs. Four conserved histidine-glutamate sequences have been identified that may act as metal coordination sites. A ∼42 kDa recombinant protein with a His-tag was obtained by heterologous expression of DOHH in Escherichia coli. Purified recombinant DOHH effectively catalyzed the hydroxylation of the intermediate, eIF5A-deoxyhypusine (eIF5A-Dhp), in vitro. L. donovani DOHH (LdDOHH) showed ∼40.6% sequence identity with its human homolog. The alignment of L. donovani DOHH with the human homolog shows that there are two significant insertions in the former, corresponding to the alignment positions 159-162 (four amino acid residues) and 174-183 (ten amino acid residues) which are present in the variable loop connecting the N- and C-terminal halves of the protein, the latter being present near the substrate binding site. Deletion of the ten-amino-acid-long insertion decreased LdDOHH activity to 14% of the wild type recombinant LdDOHH. Metal chelators like ciclopirox olamine (CPX) and mimosine significantly inhibited the growth of L. donovani and DOHH activity in vitro. These inhibitors were more effective against the parasite enzyme than the human enzyme. This report, for the first time, confirms the presence of a complete hypusine pathway in a kinetoplastid unlike eubacteria and archaea. The structural differences between the L. donovani DOHH and the human homolog may be exploited for structure based design of selective inhibitors against the parasite
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