Regulatory job stressors and their within-person relationships with ego depletion: The roles of state anxiety, self-control effort, and job autonomy

AbstractOur research aimed at disentangling the underlying processes of the adverse relationship between regulatory job stressors and ego depletion. Specifically, we analyzed whether state anxiety and self-control effort would mediate the within-person relationships of time pressure, planning and decision-making, and emotional dissonance with ego depletion. In addition, we also tested potential attenuating effects of situational job autonomy on the adverse effects of regulatory job stressors on state anxiety, self-control effort, and ego depletion. Based on an experience sampling design, we gathered a sample of 97 eldercare workers who provided data on 721 experience-sampling occasions. Multilevel moderated serial mediation analyses revealed that time pressure and emotional dissonance, but not planning and decision-making, exerted significant serial indirect effects on ego depletion via state anxiety and self-control effort. Finally, we found conditional serial indirect effects of all three regulatory job stressors on ego depletion as a function of job autonomy. Theoretical implications for scholarly understanding of coping with regulatory job stressors are discussed

Suv39h-Mediated Histone H3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin

AbstractBackground: Histone H3 lysine 9 (H3-K9) methylation and DNA methylation are characteristic hallmarks of mammalian heterochromatin. H3-K9 methylation was recently shown to be a prerequisite for DNA methylation in Neurospora crassa and Arabidopsis thaliana. Currently, it is unknown whether a similar dependence exists in mammalian organisms.Results: Here, we demonstrate a physical and functional link between the Suv39h-HP1 histone methylation system and DNA methyltransferase 3b (Dnmt3b) in mammals. Whereas in wild-type cells Dnmt3b interacts with HP1α and is concentrated at heterochromatic foci, it fails to localize to these regions in Suv39h double null (dn) mouse embryonic stem (ES) cells. Consistently, the Suv39h dn ES cells display an altered DNA methylation profile at pericentric satellite repeats, but not at other repeat sequences. In contrast, H3-K9 trimethylation at pericentric heterochromatin is not impaired in Dnmt1 single- or Dnmt3a/Dnmt3b double-deficient ES cells. We also show that pericentric heterochromatin is not transcriptionally inert and can give rise to transcripts spanning the major satellite repeats.Conclusions: These data demonstrate an evolutionarily conserved pathway between histone H3-K9 methylation and DNA methylation in mammals. While the Suv39h HMTases are required to direct H3-K9 trimethylation and Dnmt3b-dependent DNA methylation at pericentric repeats, DNA methylation at centromeric repeats occurs independent of Suv39h function. Thus, our data also indicate a more complex interrelatedness between histone and DNA methylation systems in mammals. Both methylation systems are likely to be important in reinforcing the stability of heterochromatic subdomains and thereby in protecting genome integrity

High mobility SiMOSFETs fabricated in a full 300mm CMOS process

The quality of the semiconductor–barrier interface plays a pivotal role in the demonstration of high quality reproducible quantum dots for quantum information processing. In this work, we have measured SiMOSFET Hall bars on undoped Si substrates in order to investigate the device quality. For devices fabricated in a full complementary metal oxide semiconductor (CMOS) process and of very thin oxide below a thickness of 10 nm, we report a record mobility of 17.5 × 103 cm2 V−1 s−1 indicating a high quality interface, suitable for future qubit applications. We also study the influence of gate materials on the mobilities and discuss the underlying mechanisms, giving insight into further material optimization for large scale quantum processors

A Small-Molecule Probe of the Histone Methyltransferase G9a Induces Cellular Senescence in Pancreatic Adenocarcinoma

Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also named euchromatin histone methyltransferase 2 (EHMT2)) catalyzes methylation of lysine 9 on histone H3 (H3K9), a modification linked to aberrant silencing of tumor-suppressor genes, among others. Here, we report the discovery of a novel histone methyltransferase inhibitor, BRD4770. This compound reduced cellular levels of di- and trimethylated H3K9 without inducing apoptosis, induced senescence, and inhibited both anchorage-dependent and -independent proliferation in the pancreatic cancer cell line PANC-1. ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology.Chemistry and Chemical Biolog

Low charge noise quantum dots with industrial CMOS manufacturing

Silicon spin qubits are among the most promising candidates for large scale quantum computers, due to their excellent coherence and compatibility with CMOS technology for upscaling. Advanced industrial CMOS process flows allow wafer-scale uniformity and high device yield, but off the shelf transistor processes cannot be directly transferred to qubit structures due to the different designs and operation conditions. To therefore leverage the know-how of the micro-electronics industry, we customize a 300mm wafer fabrication line for silicon MOS qubit integration. With careful optimization and engineering of the MOS gate stack, we report stable and uniform quantum dot operation at the Si/SiOx interface at milli-Kelvin temperature. We extract the charge noise in different devices and under various operation conditions, demonstrating a record-low average noise level of 0.61 ${\mu}$eV/${\sqrt{Hz}}$ at 1 Hz and even below 0.1 ${\mu}$eV/${\sqrt{Hz}}$ for some devices and operating conditions. By statistical analysis of the charge noise with different operation and device parameters, we show that the noise source can indeed be well described by a two-level fluctuator model. This reproducible low noise level, in combination with uniform operation of our quantum dots, marks CMOS manufactured MOS spin qubits as a mature and highly scalable platform for high fidelity qubits.Comment: 22 pages, 13 figure

Customization options in consumer health information materials on type-2 diabetes mellitus—an analysis of modifiable features in different types of media

IntroductionThe understanding of health-related information is essential for making informed decisions. However, providing health information in an understandable format for everyone is challenging due to differences in consumers’ health status, disease knowledge, skills, and preferences. Tailoring health information to individual needs can improve comprehension and increase health literacy.ObjectiveThe aim of our research was to analyze the extent to which consumers can customize consumer health information materials (CHIMs) for type-2 diabetes mellitus through various media types.MethodsWe conducted a comprehensive search for various CHIMs across various media types, such as websites, apps, videos, and printed or printable forms. A representative sample of CHIMs was obtained for analysis through blocked randomization across the various media types. We conducted a quantitative content analysis to determine the frequency of user-centered customization options. Cross-comparisons were made to identify trends and variations in modifiable features among the media.ResultsIn our representative sample of 114 CHIMs, we identified a total of 24 modifiable features, which we grouped into five main categories: (i) language, (ii) text, (iii) audiovisual, (iv) presentation, and (v) medical content. Videos offered the most customization opportunities (95%), while 47% of websites and 26% of apps did not allow users to tailor health information. None of the printed or printable materials provided the option to customize the information. Overall, 65% of analyzed CHIMs did not allow users to tailor health information according to their needs.ConclusionOur results show that CHIMs for type-2 diabetes mellitus could be significantly improved by providing more customization options for users. Further research is needed to investigate the effectiveness and usability of these options to enhance the development and appropriate provision of modifiable features in health information

Microscale thermophoresis quantifies biomolecular interactions under previously challenging conditions

Item does not contain fulltextMicroscale thermophoresis (MST) allows for quantitative analysis of protein interactions in free solution and with low sample consumption. The technique is based on thermophoresis, the directed motion of molecules in temperature gradients. Thermophoresis is highly sensitive to all types of binding-induced changes of molecular properties, be it in size, charge, hydration shell or conformation. In an all-optical approach, an infrared laser is used for local heating, and molecule mobility in the temperature gradient is analyzed via fluorescence. In standard MST one binding partner is fluorescently labeled. However, MST can also be performed label-free by exploiting intrinsic protein UV-fluorescence. Despite the high molecular weight ratio, the interaction of small molecules and peptides with proteins is readily accessible by MST. Furthermore, MST assays are highly adaptable to fit to the diverse requirements of different biomolecules, such as membrane proteins to be stabilized in solution. The type of buffer and additives can be chosen freely. Measuring is even possible in complex bioliquids like cell lysate allowing close to in vivo conditions without sample purification. Binding modes that are quantifiable via MST include dimerization, cooperativity and competition. Thus, its flexibility in assay design qualifies MST for analysis of biomolecular interactions in complex experimental settings, which we herein demonstrate by addressing typically challenging types of binding events from various fields of life science

Target 2035-update on the quest for a probe for every protein

Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. The challenge of translating the wealth of new knowledge from genomics into new medicines is that proteins, and not genes, are the primary executers of biological function. Therefore, much of how biology works in health and disease must be understood through the lens of protein function. Accordingly, a subset of human proteins has been at the heart of research interests of scientists over the centuries, and we have accumulated varying degrees of knowledge about approximately 65% of the human proteome. Nevertheless, a large proportion of proteins in the human proteome (∼35%) remains uncharacterized, and less than 5% of the human proteome has been successfully targeted for drug discovery. This highlights the profound disconnect between our abilities to obtain genetic information and subsequent development of effective medicines. Target 2035 is an international federation of biomedical scientists from the public and private sectors, which aims to address this gap by developing and applying new technologies to create by year 2035 chemogenomic libraries, chemical probes, and/or biological probes for the entire human proteome