Notes

Cytogenomic depiction of a signifiant novo 4q34.1 removal in a girl along with gentle dysmorphic features along with a coagulation dysfunction.
4E-BP (eIF4E-BP) represses translation initiation by binding to the 5' cap-binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, cancer, neuronal activity, and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used HyperTRIBE (targets of RNA binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in both Drosophila and mammals under conditions known to activate 4E-BP. The protein associates with specific mRNAs, and ribosome profiling data show that mTOR inhibition changes the translational efficiency of 4E-BP TRIBE targets more substantially compared to nontargets. In both systems, these targets have specific motifs and are enriched in translation-related pathways, which correlate well with the known activity of 4E-BP and suggest that it modulates the binding specificity of eIF4E and contributes to mTOR translational specificity.Quantum Monte Carlo (QMC) methods are the gold standard for studying equilibrium properties of quantum many-body systems. However, in many interesting situations, QMC methods are faced with a sign problem, causing the severe limitation of an exponential increase in the runtime of the QMC algorithm. In this work, we develop a systematic, generally applicable, and practically feasible methodology for easing the sign problem by efficiently computable basis changes and use it to rigorously assess the sign problem. Our framework introduces measures of non-stoquasticity that-as we demonstrate analytically and numerically-at the same time provide a practically relevant and efficiently computable figure of merit for the severity of the sign problem. Complementing this pragmatic mindset, we prove that easing the sign problem in terms of those measures is generally an NP-complete task for nearest-neighbor Hamiltonians and simple basis choices by a reduction to the MAXCUT-problem.Cigarette smoking, the leading cause of chronic obstructive pulmonary disease (COPD), has been implicated as a risk factor for severe disease in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we show that mice with lung epithelial cell-specific loss of function of Miz1, which we identified as a negative regulator of nuclear factor κB (NF-κB) signaling, spontaneously develop progressive age-related changes resembling COPD. Furthermore, loss of Miz1 up-regulates the expression of Ace2, the receptor for SARS-CoV-2. Concomitant partial loss of NF-κB/RelA prevented the development of COPD-like phenotype in Miz1-deficient mice. Miz1 protein levels are reduced in the lungs from patients with COPD, and in the lungs of mice exposed to chronic cigarette smoke. Our data suggest that Miz1 down-regulation-induced sustained activation of NF-κB-dependent inflammation in the lung epithelium is sufficient to induce progressive lung and airway destruction that recapitulates features of COPD, with implications for COVID-19.Ultraconformable strain gauge can be applied directly to human skin for continuous motion activity monitoring, which has seen widespread application in interactive robotics, human motion detection, personal health monitoring, and therapeutics. However, the development of an on-skin strain gauge that can detect human body motions over a long period of time without disturbing the natural skin movements remains a challenge. Here, we present an ultrathin and durable nanomesh strain gauge for continuous motion activity monitoring that minimizes mechanical constraints on natural skin motions. The device is made from reinforced polyurethane-polydimethylsiloxane (PU-PDMS) nanomeshes and exhibits excellent sustainability, linearity, and durability with low hysteresis. Its thinness geometry and softness provide minimum mechanical interference on natural skin deformations. During speech, the nanomesh-attached face exhibits skin strain mapping comparable to that of a face without nanomeshes. We demonstrate long-term facial stain mapping during speech and the capability for real-time stable full-range body movement detection.Protein persulfidation (protein-SSH) is a previously unidentified type of modification found in both eukaryotic and prokaryotic cells in recent years. Although a few persulfidated proteins have been identified, analyzing protein persulfidation from a proteomic level is still a big challenge. ProPerDP is a persulfidation detection method recently reported in Science Advances. The authors claimed that this method could specifically detect persulfidated proteins of cell lysate with minor false-positive hits; hence, it could be used for proteomic-level analysis of protein persulfidation. Semaxanib concentration However, when using this method for Escherichia coli cell lysate analysis, we found that the percentage of false-positive hit was >90%. We performed a systematic study on this method and discovered that iodoacetyl-PEG2-biotin tag mislabeling is the reason causing this low specificity. We concluded that the ProPerDP method is completely inadequate for persulfidation analysis. The previous findings based on the ProPerDP method need to be reinvestigated.Two-dimensional (2D) polymers hold great promise in the rational materials design tailored for next-generation applications. However, little is known about the grain boundaries in 2D polymers, not to mention their formation mechanisms and potential influences on the material's functionalities. Using aberration-corrected high-resolution transmission electron microscopy, we present a direct observation of the grain boundaries in a layer-stacked 2D polyimine with a resolution of 2.3 Å, shedding light on their formation mechanisms. We found that the polyimine growth followed a "birth-and-spread" mechanism. Antiphase boundaries implemented a self-correction to the missing-linker and missing-node defects, and tilt boundaries were formed via grain coalescence. Notably, we identified grain boundary reconstructions featuring closed rings at tilt boundaries. Quantum mechanical calculations revealed that boundary reconstruction is energetically allowed and can be generalized into different 2D polymer systems. We envisage that these results may open up the opportunity for future investigations on defect-property correlations in 2D polymers.
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