Miracle-dz/UniFAR-FTUs huggingface dataset:
The Set1 complex is dimeric and acts with Jhd2 demethylation to convey symmetrical H3K4 trimethylation

Epigenetic modifications can maintain or alter the inherent symmetry of the nucleosome however the mechanisms that deposit and/or propagate symmetry or asymmetry are not understood. Here we report that yeast Set1C/COMPASS is dimeric and consequently symmetrically trimethylates histone 3 lysine 4 (H3K4me3) on promoter nucleosomes. Mutation of the dimer interface to make Set1C monomeric abolished H3K4me3 on most promoters. The most active promoters, particularly those involved in the oxidative phase of the yeast metabolic cycle, displayed H3K4me2, which is normally excluded from active promoters, and a subset of these also displayed H3K4me3. In wild-type yeast, deletion of the sole H3K4 demethylase, Jhd2, has no effect. However in monomeric Set1C yeast, Jhd2 deletion increased H3K4me3 levels on the H3K4me2 promoters. Notably, the association of Set1C with the elongating polymerase was not perturbed by monomerisation. These results imply that symmetrical H3K4 methylation is an embedded consequence of Set1C dimerism and that Jhd2 demethylates asymmetric H3K4me3. Consequently, rather than methylation and demethylation acting in opposition as logic would suggest, a dimeric methyltransferase and monomeric demethylase co-operate to eliminate asymmetry and focus symmetrical H3K4me3 onto selected nucleosomes. This presents a new paradigm for the establishment of epigenetic detail.
Lifetime socioeconomic circumstances and chronic pain in later adulthood: findings from a British birth cohort study

Objectives To investigate associations between a range of different indicators of socioeconomic position (SEP: occupational class, education, household overcrowding and tenure, and experience of financial hardship) across life and chronic widespread and regional pain (CWP and CRP) at age 68. Design Prospective birth cohort; the Medical Research Council National Survey of Health and Development. Setting England, Scotland and Wales. Participants Up to 2378 men and women who have been followed-up since birth in 1946 to age 68. Primary outcome measures On the basis of their self-report of pain at age 68, participants were classified as: CWP (American College of Rheumatology criteria), CRP (pain of at least 3 months’ duration but that does not meet the definition of CWP), other pain (<3 months in duration) or no pain. Results At age 68, the prevalence of CWP was 13.3% and 7.8% in women and men, respectively, and that of CRP was 32.3% and 28.7% in women and men, respectively. There was no clear evidence that indicators of SEP in childhood or later adulthood were associated with pain. Having experienced (vs not) financial hardship and being a tenant (vs owner-occupier) in earlier adulthood were both associated with an increased risk of CWP; for example, moderate hardship adjusted relative risk ratio (RRRadj) 2.32 (95% CI: 1.19 to 4.52) and most hardship RRRadj 4.44 (95% CI: 2.02 to 9.77). Accumulation of financial hardship across earlier and later adulthood was also associated with an increased risk of CWP. Conclusions Consideration of socioeconomic factors in earlier adulthood may be important when identifying targets for intervention to prevent CWP in later life.
Analog Integrated Current Drivers for Bioimpedance Applications: A Review

An important component in bioimpedance measurements is the current driver, which can operate over a wide range of impedance and frequency. This paper provides a review of integrated circuit analog current drivers which have been developed in the last 10 years. Important features for current drivers are high output impedance, low phase delay, and low harmonic distortion. In this paper, the analog current drivers are grouped into two categories based on open loop or closed loop designs. The characteristics of each design are identified.
Association Between the Elasticity of Hip Muscles and the Hip Migration Index in Cerebral Palsy

Cerebral palsy (CP) increases the risk of hip displacement during childhood. Abnormal hip muscle forces have been proposed as the predisposing factors. In CP, the amount of hip displacement is commonly evaluated by the Reimers hip migration index (MI) on an anteroposterior pelvic radiograph. To the best of our knowledge, the association between the elasticity of hip muscles measured by shear wave elastography and the MI has not been studied yet. Herein, we aimed to analyze the correlation between the elasticity of hip muscles and the MI.
A Highlight-Generation Method for Rendering Translucent Objects

The acquisition of translucent objects has become a very common task thanks to the progress of 3D scanning technology. Since the characteristic soft appearance of translucent objects is due to subsurface scattering, the details are naturally left out in this appearance. For objects that have complex shapes, this lack of detail is obviously more prominent. In this paper, we propose a method to preserve the details of surface geometry by adding highlight effects. In generating highlight effects, our method employs a local orthonormal frame and combines, in a novel way, the incoming and outgoing light in approximating the subsurface scattering process. When the incident illuminant direction changes from nearly overhead to nearly horizontal, our method effectively preserves complex surface geometry details in the appearance of translucent materials. Through experiments, we show that our method can store surface features as well as maintain the translucency of the original materials and even enhance the perception of translucency. By numerically comparing the generated highlight effects with those generated by the traditional Bidirectional Reflectance Distribution Function (BRDF) models with different bandwidth parameters, we demonstrate the validity of our proposed method.
Phosphosugar Stress in Bacillus subtilis: Intracellular Accumulation of Mannose 6-Phosphate Derepressed the glcR-phoC Operon from Repression by GlcR

Bacillus subtilis has different stress response systems to cope with external and internal stressors. Here, we investigated how B. subtilis deals with the high intracellular concentration of phosphosugars as an internal stressor. The results indicated the derepression of an operon consisting of a repressor (GlcR) and a phosphatase (PhoC). Further analysis revealed that this operon is not a phosphosugar stress response system. The substrate specificity of PhoC may indicate a connection between the glcR-phoC operon and pathways in which glycerol 3-phosphate and ribose 5-phosphate are utilized, such as membrane biosynthesis and teichoic acid elongation. ABSTRACT Bacillus subtilis phosphorylates sugars during or after their transport into the cell. Perturbation in the conversion of intracellular phosphosugars to the central carbon metabolites and accumulation of phosphosugars can impose stress on the cells. In this study, we investigated the effect of phosphosugar stress on B. subtilis. Preliminary experiments indicated that the nonmetabolizable analogs of glucose were unable to impose stress on B. subtilis. In contrast, deletion of manA encoding mannose 6-phosphate isomerase (responsible for conversion of mannose 6-phosphate to fructose 6-phosphate) resulted in growth arrest and bulged cell shape in the medium containing mannose. Besides, an operon encoding a repressor (GlcR) and a haloic acid dehalogenase (HAD)-like phosphatase (PhoC; previously YwpJ) were upregulated. Integration of the PglcR-lacZ cassette into different mutational backgrounds indicated that PglcR is induced when (i) a manA-deficient strain is cultured with mannose or (ii) when glcR is deleted. GlcR repressed the transcription of glcR-phoC by binding to the σA-type core elements of PglcR. An electrophoretic mobility shift assay showed no interaction between mannose 6-phosphate (or other phosphosugars) and the GlcR-PglcR DNA complex. PhoC was an acid phosphatase mainly able to dephosphorylate glycerol 3-phosphate and ribose 5-phosphate. Mannose 6-phosphate was only weakly dephosphorylated by PhoC. Since deletion of glcR and phoC alone or in combination had no effect on the cells during phosphosugar stress, it is assumed that the derepression of glcR-phoC is a side effect of phosphosugar stress in B. subtilis. IMPORTANCE Bacillus subtilis has different stress response systems to cope with external and internal stressors. Here, we investigated how B. subtilis deals with the high intracellular concentration of phosphosugars as an internal stressor. The results indicated the derepression of an operon consisting of a repressor (GlcR) and a phosphatase (PhoC). Further analysis revealed that this operon is not a phosphosugar stress response system. The substrate specificity of PhoC may indicate a connection between the glcR-phoC operon and pathways in which glycerol 3-phosphate and ribose 5-phosphate are utilized, such as membrane biosynthesis and teichoic acid elongation.
Exploring factors that influence the integration of HIVST with HCT using a qualitative comparative cross-over design in KwaZulu-Natal, South Africa

ABSTRACT The World Health Organization recommends using HIV self-testing (HIVST) to improve HIV testing coverage by integrating self-testing for HIV into public domain primary healthcare (PHC) clinics in areas with a high burden of HIV. However, an understanding of the relationship and interaction between HIVST and the standard HIV counselling and testing (HCT), the primary HIV testing approach within public PHC clinics, is limited. We therefore sought to compare experiences of people seeking an HIV test, specifically, how HIVST can be used to enhance HCT when introduced together. A cross-over study design was used wherein participants were randomly exposed to either HCT followed by HIVST or HIVST followed by HCT. Semi-structured interviews were conducted at the baseline, and after each testing exposure. Forty volunteers were enrolled and 119 interviews were completed. Although a higher preference for HIVST was reported, a symbiotic relationship between HIVST and HCT was identified, where benefits of one testing approach overcame barriers of the other. Introducing HIVST as an additional testing approach with HCT within PHC facilities in South Africa could positively influence HIV testing given their complementary relationship. HIVST and HCT should accommodate HIV testing situations among HIV testing naïve and repeat testing populations.
Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models

Significance Multiple myeloma is a deadly disease for which new therapies are urgently needed. B cell maturation antigen (BCMA) is an excellent target for therapy of myeloma because it is a lineage restricted differentiation protein that is expressed on myeloma cells and plasma cells but not on essential organs. We have produced recombinant immunotoxins that target and kill myeloma cells expressing BCMA. We have examined two mouse models of myeloma and show that the anti-BCMA immunotoxins produce long-term complete regressions in both models. These data support further preclinical development of these agents. Multiple myeloma (MM) is a B cell malignancy for which new treatments are urgently needed. The B cell maturation antigen (BCMA) is a lineage-restricted differentiation protein highly expressed on myeloma. Recombinant immunotoxins (RITs) are proteins composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. We previously treated H929 myeloma s.c. tumors with anti-BCMA immunotoxins, very active on killing cultured cells, and observed tumor growth inhibition but not complete tumor responses. To determine if immunotoxins were more active against cells growing in the bone marrow (BM), the normal location of myeloma cells, we developed a BM mouse model that is more relevant to human disease. H929 cells were transfected with luciferase and GFP, enriched by flow, recycled through the BM of a mouse, and injected IV into nonobese diabetic scid γ mice (NSG) mice. A second myeloma mouse model used the MM.1S-GFP-luc cell line. Mice were treated IV with immunotoxins, and the tumor burden was assessed using bioluminescence imaging. We achieved complete durable remissions when treating mice with H929-GFP-luc cells with anti-BCMA RITs both leptomycin B-75 (LMB-75) [anti-BCMA-disulfide-stabilized (ds)-Fv-PE24] (where PE represents Pseudomonas exotoxin A) or LMB-70 (anti-BCMA-Fab-PE24) given every other day for 5-d (QOD×5) doses beginning on day 4 or day 8. Mice were disease free at 3 months; untreated mice became moribund around day 40. We also achieved long-term responses using the MM.1S-GFP-luc myeloma cell line. Treatment with an 1.5 mg/kg LMB-75 QOD×5 anti-BCMA RIT beginning on day 4 caused the complete disappearance of tumors for 80 days. To summarize, LMB-75 and LMB-70, our anti-BCMA RITs, induced complete durable responses in two myeloma models.
TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival

Significance Zn2+, Mg2+, and Ca2+ are the most abundant divalent metals in mammals. Different categories of cation-selective channels and transporters are thought to control the levels of individual metals in a cell-specific manner. However, the mechanisms responsible for the organismal balance of these minerals are poorly understood. Using genetic mouse models together with biophysical and biochemical analysis, we show that the channel-kinase TRPM7 is a master regulator of the organismal balance of divalent cations. TRPM7 activity is primarily required in the intestine, while TRPM7 function in the kidney—commonly thought to be essential—is expendable. Hence, against current thinking, organismal balance of multiple divalent cations predominantly relies on a common gatekeeper, TRPM7, rather than on individual specialized channels/transporters. Zn2+, Mg2+, and Ca2+ are essential minerals required for a plethora of metabolic processes and signaling pathways. Different categories of cation-selective channels and transporters are therefore required to tightly control the cellular levels of individual metals in a cell-specific manner. However, the mechanisms responsible for the organismal balance of these essential minerals are poorly understood. Herein, we identify a central and indispensable role of the channel-kinase TRPM7 for organismal mineral homeostasis. The function of TRPM7 was assessed by single-channel analysis of TRPM7, phenotyping of TRPM7-deficient cells in conjunction with metabolic profiling of mice carrying kidney- and intestine-restricted null mutations in Trpm7 and animals with a global “kinase-dead” point mutation in the gene. The TRPM7 channel reconstituted in lipid bilayers displayed a similar permeability to Zn2+ and Mg2+. Consistently, we found that endogenous TRPM7 regulates the total content of Zn2+ and Mg2+ in cultured cells. Unexpectedly, genetic inactivation of intestinal rather than kidney TRPM7 caused profound deficiencies specifically of Zn2+, Mg2+, and Ca2+ at the organismal level, a scenario incompatible with early postnatal growth and survival. In contrast, global ablation of TRPM7 kinase activity did not affect mineral homeostasis, reinforcing the importance of the channel activity of TRPM7. Finally, dietary Zn2+ and Mg2+ fortifications significantly extended the survival of offspring lacking intestinal TRPM7. Hence, the organismal balance of divalent cations critically relies on one common gatekeeper, the intestinal TRPM7 channel.
Impact of The Affordable Care Act’s Elimination of Cost-Sharing on the Guideline-Concordant Utilization of Cancer Preventive Screenings in the United States Using Medical Expenditure Panel Survey

Currently available evidence regarding the association of the Affordable Care Act’s (ACA) elimination of cost-sharing and the utilization of cancer screenings is mixed. We determined whether the ACA’s zero cost-sharing policy affected the guideline-concordant utilization of cancer screenings, comparing adults (≥21 years) from 2009 with 2011–2014 data from the Medical Expenditure Panel Survey. Study participants were categorized as: 21–64 years with any private insurance, ≥65 years with Medicare only, and 21–64 years uninsured, with a separate sample for each type of screening test. Adjusted weighted prevalence and prevalence ratios (PR (95%CI)) were estimated. In 2014 (vs. 2009), privately-insured women reported 2% (0.98 (0.97–0.99)) and 4% (0.96 (0.93–0.99)) reduction in use of Pap tests and mammography, respectively. Privately-insured non-Hispanic Asian women had 16% (0.84 (0.74–0.97)) reduction in mammography in 2014 (vs. 2009). In 2011 (vs. 2009), privately-insured and Medicare-only men reported 9% (1.09 (1.03–1.16)) and 13% (1.13 (1.02–1.25)) increases in colorectal cancer (CRC) screenings, respectively. Privately-insured women reported a 6–7% rise in 2013–2014 (vs. 2009), and Hispanic Medicare beneficiaries also reported 40–44%, a significant rise in 2011–2014 (vs. 2009), in the utilization of CRC screenings. While the guideline-concordant utilization of Pap tests and mammography declined in the post-ACA period, the elimination of cost-sharing appeared to have positively affected CRC screenings of privately-insured males, females, and Hispanic Medicare-only beneficiaries. Greater awareness about the zero cost-sharing policy may help in increasing the uptake of cancer screenings.
The Psychology of Smartphone: The Development of the Smartphone Impact Scale (SIS)

Smartphones are changing lives in a number of ways. However, the psychological literature has primarily focused on smartphone overuse, neglecting the impacts that are not strictly related to problematic use. The present research was aimed to develop a comprehensive self-report scale that accounts for the cognitive, affective, social, and behavioral impacts of smartphones in everyday life—the Smartphone Impact Scale (SIS). Study 1 (N = 407) yielded a preliminary version of the scale, which was refined in Study 2 (N = 601). The SIS is a 26-item scale that measures seven dimensions of smartphone impact. Results revealed meaningful associations between its subscales, psychosocial constructs, and daily usage of smartphones and apps. The SIS broadens the view of human–smartphone interaction by extending the concept of problematic smartphone use to further dimensions (e.g., emotion regulation) and introducing a proper measurement of underinvestigated smartphone impacts (e.g., tasks support). The implications of each SIS subscale are discussed.
Sex hormones modulate pathogenic processes in experimental traumatic brain injury

Clinical and animal studies have revealed sex‐specific differences in histopathological and neurological outcome after traumatic brain injury (TBI). The impact of perioperative administration of sex steroid inhibitors on TBI is still elusive. Here, we subjected male and female C57Bl/6N mice to the controlled cortical impact (CCI) model of TBI and applied pharmacological inhibitors of steroid hormone synthesis, that is, letrozole (LET, inhibiting estradiol synthesis by aromatase) and finasteride (FIN, inhibiting dihydrotestosterone synthesis by 5α‐reductase), respectively, starting 72 h prior CCI, and continuing for a further 48 h after CCI. Initial gene expression analyses showed that androgen (Ar) and estrogen receptors (Esr1) were sex‐specifically altered 72 h after CCI. When examining brain lesion size, we found larger lesions in male than in female mice, but did not observe effects of FIN or LET treatment. However, LET treatment exacerbated neurological deficits 24 and 72 h after CCI. On the molecular level, FIN administration reduced calpain‐dependent spectrin breakdown products, a proxy of excitotoxicity and disturbed Ca2+ homeostasis, specifically in males, whereas LET increased the reactive astrocyte marker glial fibrillary acid protein specifically in females. Examination of neurotrophins (brain‐derived neurotrophic factor, neuronal growth factor, NT‐3) and their receptors (p75NTR, TrkA, TrkB, TrkC) revealed CCI‐induced down‐regulation of TrkB and TrkC protein expression, which was reduced by LET in both sexes. Interestingly, FIN decreased neuronal growth factor mRNA expression and protein levels of its receptor TrkA only in males. Taken together, our data suggest a sex‐specific impact on pathogenic processes in the injured brain after TBI. Sex hormones may thus modulate pathogenic processes in experimental TBI.
A 3D quantitative imaging biomarker in pre-treatment MRI predicts overall survival after stereotactic radiation therapy of patients with a singular brain metastasis

Background Brain metastases (BM) are the most frequent intracranial malignant tumor. Various prognostic factors facilitate the prediction of survival; however, few have become tools for clinical use. Purpose To investigate the role of three-dimensional (3D) quantitative tissue enhancement in pre-treatment cranial magnetic resonance imaging (MRI) as a radiomic biomarker for survival (OS) in patients with singular BM treated with stereotactic radiation therapy (SRT). Material and Methods In this retrospective study, 48 patients (27 non-small cell lung cancer and 21 melanoma) with singular BM treated with SRT, were analyzed. Contrast-enhanced MRI scans of the neurocranium were used for quantitative image analyses. Segmentation-based 3D quantification was performed to measure the enhancing tumor volume. A cut-off value of 68.61% of enhancing volume was used to stratify the cohort into two groups (≤68.61% and > 68.61%). Univariable and multivariable cox regressions were used to analyze the prognostic factors of OS and intracranial progression-free survival (iPFS). Results The level of enhancing tumor volume achieved statistical significance in univariable and multivariable analysis for OS (univariable: P = 0.005, hazard ratio [HR] = 0.375, 95% confidence interval [CI] = 0.168–0.744; multivariable: P = 0.006, HR = 0.376, 95% CI = 0.186–0.757). Patients with high-level enhancement (>68.61% enhancing lesion volume) survived significantly longer (4.9 vs. 10.2 months) and showed significantly longer iPFS rates (univariable: P < 0.001, HR = 0.046, 95% CI = 0.009–0.245). Conclusions Patients with lesions that show a higher percentage of enhancement in pre-treatment MRI demonstrated improved iPFS and OS compared to those with mainly hypo-enhancing lesions. Lesion enhancement may be a radiomic marker, useful in prognostic indices for survival prediction, in patients with singular BM.
3D Porous Amorphous γ-CrOOH on Ni Foam as Bifunctional Electrocatalyst for Overall Water Splitting.

The development of novel and highly efficient bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is an ongoing challenge. The Cr3+ cation has a special electronic configuration (t32ge0g), which facilitates charge transfer and electron capture. However, Cr-based materials applied on water-splitting electrocatalysis is still a research void up to now. Herein, a novel amorphous γ-CrOOH was developed as a bifunctional electrocatalyst toward overall water splitting for the first time. It shows extraordinary HER activity with an ultralow overpotential of only 149 mV at 50 mA cm-2. Meantime, there is a small overpotential of 334 mV at 50 mA cm-2 for the OER. Importantly, the bifunctional electrocatalyst for overall water-splitting electrocatalysis can work with a cell voltage of merely 1.56 V at 10 mA cm-2. Amorphous γ-CrOOH has effectively enhanced the intrinsic electrochemical activity via density functional theoretical calculations. Therefore, this work not only provides a new method for preparation of amorphous γ-CrOOH but also expands the types of catalysts for water splitting.