Selenium is regulated in the body to maintain vital selenoproteins and to avoid toxicity. When selenium is limiting, cells utilize it to synthesize the selenoproteins most important to them, creating ...a selenoprotein hierarchy in the cell. The liver is the central organ for selenium regulation and produces excretory selenium forms to regulate whole-body selenium. It responds to selenium deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is distributed to tissues in relation to their expression of the Sepp1 receptor apolipoprotein E receptor-2, creating a tissue selenium hierarchy.
N
-terminal Sepp1 forms are taken up in the renal proximal tubule by another receptor, megalin. Thus, the regulated whole-body pool of selenium is shifted to needy cells and then to vital selenoproteins in them to supply selenium where it is needed, creating a whole-body selenoprotein hierarchy.
Sonic hedgehog (Shh) expression during limb development is crucial for specifying the identity and number of digits. The spatial pattern of Shh expression is restricted to a region called the zone of ...polarizing activity (ZPA), and this expression is controlled from a long distance by the cis-regulator ZRS. Here, members of two groups of ETS transcription factors are shown to act directly at the ZRS mediating a differential effect on Shh, defining its spatial expression pattern. Occupancy at multiple GABPα/ETS1 sites regulates the position of the ZPA boundary, whereas ETV4/ETV5 binding restricts expression outside the ZPA. The ETS gene family is therefore attributed with specifying the boundaries of the classical ZPA. Two point mutations within the ZRS change the profile of ETS binding and activate Shh expression at an ectopic site in the limb bud. These molecular changes define a pathogenetic mechanism that leads to preaxial polydactyly (PPD).
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► ETS factors bind to the Shh enhancer, ZRS, to specify spatial expression in the limb ► ETS1 and GABPα bind to multiple sites to define the expression domain boundary ► ETV4 and ETV5 bind to inhibit expression outside that spatial domain ► Mutations that change the ETS binding profile cause limb abnormalities
A long-range limb-specific enhancer controls Sonic hedgehog expression in a spatiotemporally restricted manner. Lettice et al. identify ETS-binding sites within this enhancer that mediate antagonistic interactions between different ETS transcription factor clades. Mutations in the enhancer that change the balance of power between ETS factors cause limb abnormalities.
Extant research on parental involvement in education has been conducted largely without respect to which parent is involved. The implicit assumption is that family-school relationship frameworks ...function similarly for fathers and mothers. Although there is a growing body of research examining fathers' involvement in education, this assumption has not been tested. In this meta-analysis, we examined the relative strength of the association between educational involvement of fathers versus mothers and achievement of school-age children (kindergarten to 12th grade). The association of involvement with achievement over time (i.e., longitudinal studies) was stronger than for cross-sectional studies. Parental involvement in education was positively associated with student achievement and the relation between involvement and achievement was equally strong for fathers and mothers, although mothers' mean levels of involvement were higher than fathers'. Moderator analyses across the different types of involvement suggested that school-based involvement and intellectual enrichment at home was more strongly related to achievement for mothers than for fathers, although there were no differences in mean levels of involvement.
Around 1 in 10 of all cancer cases occur in adults of reproductive age. Cancer and its treatments can cause long-term effects, such as loss of fertility, which can lead to poor emotional adjustment. ...Unmet information needs are associated with higher levels of anxiety. US research suggests that many oncologists do not discuss fertility. Very little research exists about fertility information provision in the United Kingdom. This study aimed to explore current knowledge, practice and attitudes among oncologists in the United Kingdom regarding fertility preservation in patients of child-bearing age.
A national online survey of 100 oncologists conducted online via medeconnect, a company which has exclusive access to the doctors.net.uk membership of GMC registered doctors.
Oncologists saw fertility preservation (FP) as mainly a women's issue, and yet only felt knowledgeable about sperm storage, not other methods of FP; 87% expressed a need for more information. Most reported discussing the impact of treatment on fertility with patients, but only 38% reported routinely providing patients with written information, and 1/3 reported they did not usually refer patients who had questions about fertility to a specialist fertility service. Twenty-three per cent had never consulted any FP guidelines. The main barriers to initiating discussions about FP were lack of time, lack of knowledge, perceived poor success rates of FP options, poor patient prognosis and, to a lesser extent, if the patient already had children, was single, or could not afford FP treatment.
The findings from this study suggest a deficiency in UK oncologist's knowledge about FP options and highlights that the provision of information to patients about FP may be sub-optimal. Oncologists may benefit from further education, and further research is required to establish if patients perceive a need for further information about FP options.
COVID-19 has presented challenges and opportunities for telehealth delivery of behavioral health care to diverse populations and those with chronic illness such as diabetes.
Abstract
Conspiracy ...theories have been proliferating during the COVID-19 pandemic. Evidence suggests that belief in conspiracy theories undermines engagement in pro-health behaviors and support for public health policies. Moreover, previous work suggests that inoculating messages from opinion leaders that expose conspiracy theories as false before people are exposed to them can help to prevent belief in new conspiracies. Goals of this study were to: (a) explore associations between COVID-19 conspiracy beliefs with SARS-CoV-2 vaccine intentions, cooperation with public health recommendations, and support for public health policies among U.S. adults and (b) investigate trusted sources of COVID-19 information to inform strategies to address conspiracy beliefs. A cross-sectional, online survey was conducted with 845 U.S. adults in April 2020. Data were analyzed using analyses of variance and multivariable regressions. One-third (33%) of participants believed one or more conspiracies about COVID-19. Participants who believed conspiracies reported that their intentions to vaccinate were 3.9 times lower and indicated less support for COVID-19 public health policies than participants who disbelieved conspiracies. There were no differences in cooperation with public health recommendations by conspiracy belief endorsement in the multivariable regression analysis. Although there were some key differences in trusted sources of COVID-19 information, doctor(s) were the most trusted source of information about COVID-19 overall with 90% of participants trusting doctor(s). Doctor(s) may play a role in addressing COVID-19 conspiracy theories before people are exposed to them to promote COVID-19 prevention efforts.
A fundamental hypothesis for the evolution and maintenance of ornamental traits is that ornaments convey information to choosing females about the quality of prospective mates. A diverse array of ...ornaments (e.g., colors, morphological features, and behaviors) has been associated with a wide range of measures of individual quality, but decades of study of such indicator traits have failed to produce general mechanisms of honest signaling. Here, I propose that efficiency of cellular respiration, as a product of mitochondrial function, underlies the associations between ornamentation and performance for a broad range of traits across taxa. A large biomedical literature documents the fundamental biochemical links between oxidative phosphorylation (OXPHOS) and the production of reactive oxygen species (ROS), the process of metabolism, the function of the immune system, the synthesis of proteins, and the development and function of the nervous system. The production of virtually all ornaments whose expressions have been demonstrated to be condition-dependent is directly affected by the efficiency of cellular respiration, suggesting that the signaling of respiratory efficiency may be the primary function of such traits. Furthermore, the production of ornaments links to stress-response systems, including particularly the neuroendocrine system, through mitochondrial function, thereby makes ornamental traits effective signals of the capacity to withstand environmental perturbations. The identification of a unifying mechanism of honest signaling holds the potential to connect many heretofore-disparate fields of study related to stress and ornamentation, including neuroendocrinology, respiratory physiology, metabolic physiology, and immunology.
Chaotic Dirac Billiard in Graphene Quantum Dots Ponomarenko, L.A; Schedin, F; Katsnelson, M.I ...
Science (American Association for the Advancement of Science),
04/2008, Letnik:
320, Številka:
5874
Journal Article
Recenzirano
Odprti dostop
The exceptional electronic properties of graphene, with its charge carriers mimicking relativistic quantum particles and its formidable potential in various applications, have ensured a rapid growth ...of interest in this new material. We report on electron transport in quantum dot devices carved entirely from graphene. At large sizes (>100 nanometers), they behave as conventional single-electron transistors, exhibiting periodic Coulomb blockade peaks. For quantum dots smaller than 100 nanometers, the peaks become strongly nonperiodic, indicating a major contribution of quantum confinement. Random peak spacing and its statistics are well described by the theory of chaotic neutrino billiards. Short constrictions of only a few nanometers in width remain conductive and reveal a confinement gap of up to 0.5 electron volt, demonstrating the possibility of molecular-scale electronics based on graphene.
The psychiatric disorders autism and schizophrenia have a strong genetic component, and copy number variants (CNVs) are firmly implicated. Recurrent deletions and duplications of chromosome 16p11.2 ...confer a high risk for both diseases, but the pathways disrupted by this CNV are poorly defined. Here we investigate the dynamics of the 16p11.2 network by integrating physical interactions of 16p11.2 proteins with spatiotemporal gene expression from the developing human brain. We observe profound changes in protein interaction networks throughout different stages of brain development and/or in different brain regions. We identify the late mid-fetal period of cortical development as most critical for establishing the connectivity of 16p11.2 proteins with their co-expressed partners. Furthermore, our results suggest that the regulation of the KCTD13-Cul3-RhoA pathway in layer 4 of the inner cortical plate is crucial for controlling brain size and connectivity and that its dysregulation by de novo mutations may be a potential determinant of 16p11.2 CNV deletion and duplication phenotypes.
•Rare high-risk CNVs for psychiatric disorders have unique spatiotemporal signatures•Dynamic 16p11.2 protein interaction network reveals changes during brain development•The late mid-fetal period is critical for establishing 16p11.2 network connectivity•KCTD13-Cul3-RhoA pathway may be dysregulated by gene-damaging mutations
Deletions and duplications of chromosome 16p11.2 confer a high risk for neuropsychiatric diseases. By integrating the physical interactions of 16p11.2 proteins with spatiotemporal gene expression, Lin et al. implicate the KCTD13-Cul3-RhoA pathway as being crucial for controlling brain size and connectivity.
Work-family research frequently focuses on the conflict experienced by working mothers. Using data from the National Study of the Changing Workforce (N = 1,314), this study also examined work-family ...facilitation and working fathers. Ecological systems, family stress, family resilience, and sex role theories were used to organize the data and create hypotheses. Work-to-family facilitation was positively related to job satisfaction and life satisfaction, and negatively related to individual stress. Family-to-work facilitation was positively related to marital satisfaction, family satisfaction, and life satisfaction, and negatively related to organizational commitment. Working fathers reported long work hours (49 hours/week), major involvement in household responsibilities (46 hours/week), and a work culture less supportive of their family life than working mothers reported. However, working fathers reported less work-family conflict, less individual stress, and greater family satisfaction, marital satisfaction, and life satisfaction than working mothers. The results support including facilitation and gender in future work-family research.
Upon heterologous overexpression, many proteins misfold or aggregate, thus resulting in low functional yields. Human acetylcholinesterase (hAChE), an enzyme mediating synaptic transmission, is a ...typical case of a human protein that necessitates mammalian systems to obtain functional expression. We developed a computational strategy and designed an AChE variant bearing 51 mutations that improved core packing, surface polarity, and backbone rigidity. This variant expressed at ∼2,000-fold higher levels in E. coli compared to wild-type hAChE and exhibited 20°C higher thermostability with no change in enzymatic properties or in the active-site configuration as determined by crystallography. To demonstrate broad utility, we similarly designed four other human and bacterial proteins. Testing at most three designs per protein, we obtained enhanced stability and/or higher yields of soluble and active protein in E. coli. Our algorithm requires only a 3D structure and several dozen sequences of naturally occurring homologs, and is available at http://pross.weizmann.ac.il.
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•A new computational method is used to stabilize five recalcitrant proteins•Designed variants show higher expression and stability with unmodified function•A designed human acetylcholinesterase variant expresses solubly in bacteria•The method is fully automated and implemented on a webserver
Heterologous expression of proteins and their mutants often results in misfolding and aggregation. Goldenzweig et al. (2016) developed an automated algorithm for protein stabilization requiring minimal experimental testing; for instance, the five tested variants of human acetylcholinesterase showed ≥100-fold higher soluble bacterial expression and higher melting temperatures than wild-type.
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