Mccabeburke8741

The interplay between ferromagnetism and topological properties of electronic band structures leads to a precise quantization of Hall resistance without any external magnetic field. This so-called quantum anomalous Hall effect (QAHE) is born out of topological correlations, and is oblivious of low-sample quality. It was envisioned to lead towards dissipation-less and topologically protected electronics. However, no clear framework of how to design such an electronic device out of it exists. Here we construct an ultra-low power, non-volatile, cryogenic memory architecture leveraging the QAHE phenomenon. Our design promises orders of magnitude lower cell area compared with the state-of-the-art cryogenic memory technologies. We harness the fundamentally quantized Hall resistance levels in moiré graphene heterostructures to store non-volatile binary bits (1, 0). We perform the memory write operation through controlled hysteretic switching between the quantized Hall states, using nano-ampere level currents with opposite polarities. The non-destructive read operation is performed by sensing the polarity of the transverse Hall voltage using a separate pair of terminals. We custom design the memory architecture with a novel sensing mechanism to avoid accidental data corruption, ensure highest memory density and minimize array leakage power. Our design provides a pathway towards realizing topologically protected memory devices.The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.CRISPR/Cas9 gene editing is effective in manipulating genetic loci in mammalian cell cultures and whole fish but efficient platforms applicable to fish cell lines are currently limited. Our initial attempts to employ this technology in fish cell lines using heterologous promoters or a ribonucleoprotein approach failed to indicate genomic alteration at targeted sites in a tilapia brain cell line (OmB). For potential use in a DNA vector approach, endogenous tilapia beta Actin (OmBAct), EF1 alpha (OmEF1a), and U6 (TU6) promoters were isolated. The strongest candidate promoter determined by EGFP reporter assay, OmEF1a, was used to drive constitutive Cas9 expression in a modified OmB cell line (Cas9-OmB1). Cas9-OmB1 cell transfection with vectors expressing gRNAs driven by the TU6 promoter achieved mutational efficiencies as high as 81% following hygromycin selection. Mutations were not detected using human and zebrafish U6 promoters demonstrating the phylogenetic proximity of U6 promoters as critical when used for gRNA expression. Sequence alteration to TU6 improved mutation rate and cloning efficiency. In conclusion, we report new tools for ectopic expression and a highly efficient, economical system for manipulation of genomic loci and evaluation of their causal relationship with adaptive cellular phenotypes by CRISPR/Cas9 gene editing in fish cells.To date, an overwhelming number of preclinical studies have addressed acute treatment in mild TBI (mTBI) and repetitive mTBI (r-mTBI), whereas, in humans, there often exists a significant time gap between the injury and the first medical intervention. Our study focused on a delayed treatment with anatabine, an anti-inflammatory compound, in hTau mice using two different models of r-mTBI. The rationale for using two models of the same impact but different frequencies (5 hit mTBI over 9 days and 24 hit mTBI over 90 days) was chosen to address the heterogeneity of r-mTBI in clinical population. Following the last injury in each model, three months elapsed before the initiation of treatment. Anatabine was administered in drinking water for 3 months thereafter. Our data demonstrated that a 3-month delayed treatment with anatabine mitigated astrogliosis in both TBI paradigms but improved cognitive functions only in more-frequently-injured mice (24 hit mTBI). We also found that anatabine decreased the phosphorylation of tau protein and NFκB, which were increased after r-mTBI in both models. The ability of anatabine to suppress these mechanisms suggests that delayed treatment can be effective for clinical population of r-mTBI. The discrepancy between the two models with regard to changes in cognitive performance suggests that r-mTBI heterogeneity may influence treatment efficiency and should be considered in therapeutic development.In the complex process of homeostasis of phytohormones cytokinins (CKs), O-glucosylation catalyzed by specific O-glucosyltransferases represents one of important mechanisms of their reversible inactivation. The CK O-glucosyltransferases belong to a highly divergent and polyphyletic multigene superfamily of glycosyltransferases, of which subfamily 1 containing UDP-glycosyltransferases (UGTs) is the largest in the plant kingdom. It contains recently discovered O and P subfamilies present in higher plant species but not in Arabidopsis thaliana. The cis-zeatin O-glucosyltransferase (cisZOG) genes belong to the O subfamily encoding a stereo-specific O-glucosylation of cis-zeatin-type CKs. We studied different homologous genes, their domains and motifs, and performed a phylogenetic reconstruction to elucidate the plant evolution of the cisZOG gene. We found that the cisZOG homologs do not form a clear separate clade, indicating that diversification of the cisZOG gene took place after the diversification of the main angiosperm families, probably within genera or closely related groups. We confirmed that the gene(s) from group O is(are) not present in A. thaliana and is(are) also missing in the family Brassicaceae. However, cisZOG or its metabolites are found among Brassicaceae clade, indicating that remaining genes from other groups (UGT73-group D and UGT85-group G) are able, at least in part, to substitute the function of group O lost during evolution. This study is the first detailed evolutionary evaluation of relationships among different plant ZOGs within angiosperms.APOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.Pathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to produce RS, SI and control F1 offspring, respectively. Compared to controls, while paternal RS decreased anxiety-like behavior (ALB) in both female and male offspring, paternal SI increased ALB only in female offspring. Next-generation sequencing and bioinformatics using RS and SI female offspring identified 5 candidate anxiety-transmitting (CAT) genes; each showed a consistent pattern of DNA methylation from F0 spermatozoa through F1 blastocysts to fetal and adult hippocampi. Further analyses validated 4 CAT genes, demonstrated that paternal SI caused ALB differences between male and female offspring through modifying the CAT genes, and indicated a strong correlation between inflammation and ALB pathogenesis and an important function for intronic DNA methylation in regulating ALB-related genes. PRI-724 In conclusion, this study identified important CAT genes and suggested the possibility that stresses on males might alter offspring's ALB by modifying sperm DNA methylation.Cortisol is often measured as a marker for stress. Therefore, a profound validation of the time-lag between the stressor and the increase and peak in cortisol levels is needed. No study measured both the urinary and salivary cortisol time-lag after a psychological stressor. In this study, we used a frequent sampling study design to (1) describe the urinary and salivary cortisol pattern during a control day; and (2) characterize the induced excretion pattern of urinary and salivary cortisol after a psychological stressor in six zoo-housed bonobos. Liquid chromatography-tandem mass spectrometry was used to analyze 71 urine and 162 saliva samples collected on a control and a test day. We found that the time-lag between the stressor and the maximal cortisol concentration was similar in urine and saliva (160 min after the stressor). However, salivary cortisol after the stressor did show a faster and steeper increase than urinary cortisol. We also show inter-individual variation in the baseline and stress levels of cortisol, which should be considered in future cortisol studies.