Hepatocyte RXRalpha deficiency in matured and aged mice: impact on the expression of cancer-related hepatic genes in a gender-specific manner

<p>Abstract</p> <p>Background</p> <p>The occurrence of liver cancer is higher in males than in females, and the incidence increases during aging. Signaling pathways regulated by retinoid × receptor α (RXRα) are involved in hepatocellular carcinogenesis. The phenotype of hepatocyte RXRα deficient mice is different between genders. To explore the impact of hepatocyte RXRα deficiency on gender-dependent hepatic gene expression, we compared the expression profiles of cancer-related genes in 6 and 24 month old male and female mice.</p> <p>Results</p> <p>In 6 month old mice, male mutant mice showed more cancer-related genes with alteration in mRNA levels than females did (195 vs. 60). In aged mice (24 month), female mutant mice showed greater deviation in mRNA expression levels of cancer-related genes than their male counterparts (149 vs. 82). The genes were classified into five categories according to their role in carcinogenesis: apoptosis, metastasis, cell growth, stress, and immune respnse. In each category, dependent upon age and gender, the genes as well as the number of genes with altered mRNA levels due to RXRα deficiency varies.</p> <p>Conclusion</p> <p>The change in hepatic cancer-related gene expression profiles due to RXRα deficiency was gender- and age-dependent. The alteration of mRNA levels of cancer-related genes implied that aberrant RXRα signaling could potentially increase the risk of liver cancer and that retinoid signaling might contribute to gender- and age-associated liver cancer incidence.</p

Autonomous Light Management in Flexible Photoelectrochromic Films Integrating High Performance Silicon Solar Microcells

Commercial smart window technologies for dynamic light and heat management in building and automotive environments traditionally rely on electrochromic (EC) materials powered by an external source. This design complicates building-scale installation requirements and substantially increases costs for applications in retrofit construction. Self-powered photoelectrochromic (PEC) windows are an intuitive alternative wherein a photovoltaic (PV) material is used to power the electrochromic device, which modulates the transmission of the incident solar flux. The PV component in this application must be sufficiently transparent and produce enough power to efficiently modulate the EC device transmission. Here, we propose Si solar microcells (μ-cells) that are i) small enough to be visually transparent to the eye, and ii) thin enough to enable flexible PEC devices. Visual transparency is achieved when Si μ-cells are arranged in high pitch (i.e. low-integration density) form factors while maintaining the advantages of a single-crystalline PV material (i.e., long lifetime and high performance). Additionally, the thin dimensions of these Si μ-cells enable fabrication on flexible substrates to realize these flexible PEC devices. The current work demonstrates this concept using WO₃ as the EC material and V₂O₅ as the ion storage layer, where each component is fabricated via sol-gel methods that afford improved prospects for scalability and tunability in comparison to thermal evaporation methods. The EC devices display fast switching times, as low as 8 seconds, with a modulation in transmission as high as 33%. Integration with two Si μ-cells in series (affording a 1.12 V output) demonstrates an integrated PEC module design with switching times of less than 3 minutes, and a modulation in transmission of 32% with an unprecedented EC:PV areal ratio

Embryological staging of the Zebra Finch, Taeniopygia guttata

Zebra Finches (Taeniopygia guttata) are the most commonly used laboratory songbird species, yet their embryological development has been poorly characterized. Most studies to date apply Hamburger and Hamilton stages derived from chicken development; however, significant differences in development between precocial and altricial species suggest that they may not be directly comparable. We provide the first detailed description of embryological development in the Zebra Finch under standard artificial incubation. These descriptions confirm that some of the features used to classify chicken embryos into stages are not applicable in an altricial bird such as the Zebra Finch. This staging protocol will help to standardize future studies of embryological development in the Zebra Finch. J. Morphol. 274:1090-1110, 2013. (c) 2013 Wiley Periodicals, Inc

Autonomous Light Management in Flexible Photoelectrochromic Films Integrating High Performance Silicon Solar Microcells

Commercial smart window technologies for dynamic light and heat management in building and automotive environments traditionally rely on electrochromic (EC) materials powered by an external source. This design complicates building-scale installation requirements and substantially increases costs for applications in retrofit construction. Self-powered photoelectrochromic (PEC) windows are an intuitive alternative wherein a photovoltaic (PV) material is used to power the electrochromic device, which modulates the transmission of the incident solar flux. The PV component in this application must be sufficiently transparent and produce enough power to efficiently modulate the EC device transmission. Here, we propose Si solar microcells (μ-cells) that are i) small enough to be visually transparent to the eye, and ii) thin enough to enable flexible PEC devices. Visual transparency is achieved when Si μ-cells are arranged in high pitch (i.e. low-integration density) form factors while maintaining the advantages of a single-crystalline PV material (i.e., long lifetime and high performance). Additionally, the thin dimensions of these Si μ-cells enable fabrication on flexible substrates to realize these flexible PEC devices. The current work demonstrates this concept using WO₃ as the EC material and V₂O₅ as the ion storage layer, where each component is fabricated via sol-gel methods that afford improved prospects for scalability and tunability in comparison to thermal evaporation methods. The EC devices display fast switching times, as low as 8 seconds, with a modulation in transmission as high as 33%. Integration with two Si μ-cells in series (affording a 1.12 V output) demonstrates an integrated PEC module design with switching times of less than 3 minutes, and a modulation in transmission of 32% with an unprecedented EC:PV areal ratio

A Practical Stereo Depth System for Smart Glasses

We present the design of a productionized end-to-end stereo depth sensing system that does pre-processing, online stereo rectification, and stereo depth estimation with a fallback to monocular depth estimation when rectification is unreliable. The output of our depth sensing system is then used in a novel view generation pipeline to create 3D computational photography effects using point-of-view images captured by smart glasses. All these steps are executed on-device on the stringent compute budget of a mobile phone, and because we expect the users can use a wide range of smartphones, our design needs to be general and cannot be dependent on a particular hardware or ML accelerator such as a smartphone GPU. Although each of these steps is well studied, a description of a practical system is still lacking. For such a system, all these steps need to work in tandem with one another and fallback gracefully on failures within the system or less than ideal input data. We show how we handle unforeseen changes to calibration, e.g., due to heat, robustly support depth estimation in the wild, and still abide by the memory and latency constraints required for a smooth user experience. We show that our trained models are fast, and run in less than 1s on a six-year-old Samsung Galaxy S8 phone's CPU. Our models generalize well to unseen data and achieve good results on Middlebury and in-the-wild images captured from the smart glasses.Comment: Accepted at CVPR202

Cryo-EM and molecular docking shows myosin-S1 loop 4 contacts actin and tropomyosin on thin filaments

The motor protein, myosin, drives muscle and non-muscle motility by binding to and moving along actin of thin filaments. Myosin-binding to actin also modulates interactions of the regulatory protein, tropomyosin, on thin filaments, and conversely tropomyosin affects myosin-binding to actin. Insight into this reciprocity will facilitate a molecular level elucidation of tropomyosin regulation of myosin interaction with actin in muscle contraction, and in turn, promote better understanding non-muscle cell motility. Indeed, experimental approaches, such as fiber diffraction, cryo-electron microscopy and 3D reconstruction, have long been used to define regulatory interaction of tropomyosin and myosin on actin at a structural level. However, their limited resolution has not proven sufficient to determine tropomyosin and myosin contacts at an atomic-level and thus to fully substantiate possible functional contributions. To overcome this deficiency, we have followed a hybrid approach by performing new cryo-EM reconstruction of myosin-S1‒decorated F-actin-tropomyosin together with atomic-scale protein-protein docking of tropomyosin to the EM models. Here, cryo-EM data were derived from filaments reconstituted with α1-actin, cardiac αα-tropomyosin, and masseter muscle β-myosin complexes; masseter myosin, which shares sequence identity with β-cardiac myosin-heavy chain, was used because of its stability in vitro. The data were used to build an atomic model of the tropomyosin cable that fits onto the actin filament between the tip of the myosin head and a cleft on the innermost edge of actin subunits. The docking and atomic scale fitting showed multiple discrete interactions of myosin loop 4 and acidic residues on successive 39 to 42 residue-long tropomyosin pseudo-repeats. The contacts between S1 and tropomyosin on actin appear to compete with and displace ones normally found between actin and tropomyosin on myosin-free thin filaments in relaxed muscle, thus restructuring the filament during myosin-induced activation

Transcriptomic analysis of mRNA expression and alternative splicing during mouse sex determination

Mammalian sex determination hinges on sexually dimorphic transcriptional programs in developing fetal gonads. A comprehensive view of these programs is crucial for understanding the normal development of fetal testes and ovaries and the etiology of human disorders of sex development (DSDs), many of which remain unexplained. Using strand-specific RNA-sequencing, we characterized the mouse fetal gonadal transcriptome from 10.5 to 13.5 days post coitum, a key time window in sex determination and gonad development. Our dataset benefits from a greater sensitivity, accuracy and dynamic range compared to microarray studies, allows global dynamics and sex-specificity of gene expression to be assessed, and provides a window to non-transcriptional events such as alternative splicing. Spliceomic analysis uncovered female-specific regulation of Lef1 splicing, which may contribute to the enhanced WNT signaling activity in XX gonads. We provide a user-friendly visualization tool for the complete transcriptomic and spliceomic dataset as a resource for the field

Using social cognitive career theory to understand why students choose to study computer science

The aim of this research is to use Social Cognitive Career Theory (SCCT) to identify and understand reasons why students choose to study Computer Science (CS) at university. SCCT focuses on students’ prior experience, social support, self-efficacy and outcome expectation. The research is part motivated by the desire to increase female participation rates in CS, particularly in the UK. Policymakers can use the factors that both females and males identify as influencing their choice of studying CS to enhance the experiences of all students prior to coming to university, but female students in particular. The study uses a semi-structured interview with 17 mixed gender subjects currently studying CS at three Scottish universities. The findings are that social support from family, teachers, friends and mentors is a particularly important factor in choosing to study CS, especially for female subjects. The career paths offered by a CS degree is another major factor, not just the potential jobs, but also the general value of a CS education and the potential to make useful contributions to society. School education appeared to have limited influence, though exposure to problem solving, programming, online self-learning and internships are positive influences. The stereotypical view of CS students as ‘geeks’ is outdated and unhelpful – it is more appropriate to see them as ‘analytical’ or ‘over-achievers’. Subjects make many suggestions for improving the CS education provided at school, especially to make it more attractive to females, including: make it compulsory, teach it earlier, include more programming and problem solving, and increase the visibility of female exemplars and role models

Converging and Differential Brain Phospholipid Dysregulation in the Pathogenesis of Repetitive Mild Traumatic Brain Injury and Alzheimer’s Disease

Repetitive mild traumatic brain injury (rmTBI) is a major epigenetic risk factor for Alzheimer’s disease (AD). The precise nature of how rmTBI leads to or precipitates AD pathology is currently unknown. Numerous neurological conditions have shown an important role for dysfunctional phospholipid metabolism as a driving factor for the pathogenesis of neurodegenerative diseases. However, the precise role in rmTBI and AD remains elusive. We hypothesized that a detailed phospholipid characterization would reveal profiles of response to injury in TBI that overlap with age-dependent changes in AD and thus provide insights into the TBI-AD relationship. We employed a lipidomic approach examining brain phospholipid profiles from mouse models of rmTBI and AD. Cortex and hippocampal tissue were collected at 24 h, 3, 6, 9, and 12 months post-rmTBI, and at ages representing ‘pre’, ‘peri’ and ‘post’ onset of amyloid pathology (i.e., 3, 9, 15 months-old). Total levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), LysoPE, and phosphatidylinositol (PI), including their monounsaturated, polyunsaturated and saturated fatty acid (FA) containing species were significantly increased at acute and/or chronic time points post-injury in both brain regions. However, levels of most phospholipid species in PS1/APP mice were nominal in the hippocampus, while in the cortex, levels were significantly decreased at ages post-onset of amyloid pathology. Sphingomyelin and LysoPC levels showed coincidental trends in our rmTBI and AD models within the hippocampus, an increase at acute and/or chronic time points examined. The ratio of arachidonic acid (omega-6 FA) to docosahexaenoic acid (omega-3 FA)-containing PE species was increased at early time points in the hippocampus of injured versus sham mice, and in PS1/APP mice there was a coincidental increase compared to wild type littermates at all time points. This study demonstrates some overlapping and diverse phospholipid profiles in rmTBI and AD models. Future studies are required to corroborate our findings in human post-mortem tissue. Investigation of secondary mechanisms triggered by aberrant downstream alterations in bioactive metabolites of these phospholipids, and their modulation at the appropriate time-windows of opportunity could help facilitate development of novel therapeutic strategies to ameliorate the neurodegenerative consequences of rmTBI or the potential triggering of AD pathogenesis by rmTBI