Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

Significance Dysfunction of mitochondria, the powerhouses of living cells, favors the onset of human diseases, namely neurodegenerative diseases, cardiovascular pathologies, and cancer. Actually, respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 during the insulin-induced neuroprotection response following a brain ischemic injury. Here, we report that the decrease in neuronal death could be directly ascribed to changes in mitochondrial metabolism—including lower production of reactive oxygen species—and cell homeostasis induced by cytochrome c phosphorylation. Our findings thus provide the basis for understanding the molecular mechanism and potential use of phosphomimetic species of cytochrome c, thereby yielding new opportunities to develop more efficient therapies against acute pathologies. Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome c mutant, which was generated by site-specific incorporation at position 97 of p-carboxymethyl-l-phenylalanine using the evolved tRNA synthetase method. We found that the point mutation does not alter the overall folding and heme environment of cytochrome c, but significantly affects the entire oxidative phosphorylation process. In fact, the electron donation rate of the mutant heme protein to cytochrome c oxidase, or complex IV, within respiratory supercomplexes was higher than that of the wild-type species, in agreement with the observed decrease in reactive oxygen species production. Direct contact of cytochrome c with the respiratory supercomplex factor HIGD1A (hypoxia-inducible domain family member 1A) is reported here, with the mutant heme protein exhibiting a lower affinity than the wild-type species. Interestingly, phosphomimetic cytochrome c also exhibited a lower caspase-3 activation activity. Altogether, these findings yield a better understanding of the molecular basis for mitochondrial metabolism in acute diseases, such as brain ischemia, and thus could allow the use of phosphomimetic cytochrome c as a neuroprotector with therapeutic applications.
Concepts toward directing human astroplasticity to promote neuroregeneration

Astrocytes exhibit dynamic and complex reactions to various insults. Recently, investigations into the transitions that occur during cellular specification, differentiation, maturation, and disease responses have provided insights into understanding the mechanisms that underlie these altered states of reactivity and function. Here we summarize current concepts in how astrocyte state transitions, termed astroplasticity, are regulated, as well as how this affects neural circuit function through extracellular signaling. We postulate that a promising future approach toward enhancing functional repair after injury and disease would be to steer astrocytes away from an inhibitory response and toward one that is beneficial to neuroplasticity and neuroregeneration. Toward this goal, we discuss emerging biotechnological advancements, with a focus on human pluripotent stem cell bioengineering, which has high potential for effective manipulation and control of astroplasticity. Highlights include innovations in cellular transdifferentiation techniques, nanomedicine, organoid and three‐dimensional (3D) spheroid microcircuit development, and the use of biomaterials to influence the extracellular environment. Current barriers and future applications are also summarized in order to augment the design of future preclinical trials aimed toward astrocyte‐targeted neuroregeneration with a concept termed astrocellular therapeutics. Developmental Dynamics 248:21–33, 2019. © 2018 Wiley Periodicals, Inc.
Murine type VII collagen distorts outcome in human skin graft mouse model for dystrophic epidermolysis bullosa

Human skin graft mouse models are widely used to investigate and develop therapeutic strategies for the severe generalized form of recessive dystrophic epidermolysis bullosa (RDEB), which is caused by biallelic null mutations in COL7A1 and the complete absence of type VII collagen (C7). Most therapeutic approaches are focused on reintroducing C7. Therefore, C7 and anchoring fibrils are widely used as readouts in therapeutic research with skin graft models. In this study, we investigated the expression pattern of human and murine C7 in a grafting model, in which human skin is reconstituted out of in vitro cultured keratinocytes and fibroblasts. The model revealed that murine C7 was deposited in both human healthy control and RDEB skin grafts. Moreover, we found that murine C7 is able to form anchoring fibrils in human grafts. Therefore, we advocate the use of human‐specific antibodies when assessing the reintroduction of C7 using RDEB skin graft mouse models.
Comparison of hemagglutination inhibition, single radial hemolysis, virus neutralization assays, and ELISA to detect antibody levels against seasonal influenza viruses

The immunological response to influenza vaccine and/or natural infection is evaluated by serological techniques, the most common being hemagglutination inhibition (HI), single radial hemolysis (SRH), and virus neutralization assays, which is commonly used in a micro‐neutralization (MN) format. ELISA is not officially required; however, this assay is able to measure different class‐specific antibodies. The four assays identify different sets or subsets of antibodies.
Analysis of DNA methylation alterations in rice seeds induced by different doses of carbon-ion radiation

Abstract To investigate the mechanism underlying differences in biological effects induced by low- versus high-dose heavy-ion radiation (HIR) in rice plants, two-dimensional gel electrophoresis (2-DE) coupled with methylation-sensitive amplification polymorphism (MSAP) analysis were used to check the expression changes in rice leaf proteome profiles and the changes in DNA methylation after exposure of seeds to ground-based carbon-ion radiation at various cumulative doses (0, 0.01, 0.02, 0.1, 0.2, 1, 2, 5 or 20 Gy; 12C6+; energy, 165 MeV/u; mean linear energy transfer, 30 KeV/μm). In this study, principal component analysis (PCA) and gene ontology (GO) functional analysis of differentially expressed proteins of rice at tillering stage showed that proteins expressed in rice samples exposed to 0.01, 0.02, 0.1, 0.2 or 1 Gy differed from those exposed to 2, 5 or 20 Gy. Correspondingly, the proportion of hypermethylation was higher than that of hypomethylation at CG sites following low-dose HIR (LDR; 0.01, 0.2 or 1 Gy), whereas this was reversed at high-dose HIR (HDR; 2, 5 or 20 Gy). The hypomethylation changes tended to occur at CHG sites with both low- and high-dose HIR. Furthermore, sequencing of MSAP variant bands indicated that the plants might activate more metabolic processes and biosynthetic pathways on exposure to LDR, but activate stress resistance on exposure to HDR. This study showed that radiation induced different biological effects with low- and high-dose HIR, and that this may have been caused by different patterns of hyper- and hypomethylation at the CG sites.
Nonheavy Drinking and Worsening of Noninvasive Fibrosis Markers in Nonalcoholic Fatty Liver Disease: A Cohort Study

The effect of modest alcohol consumption on fibrosis progression in the general population with nonalcoholic fatty liver disease (NAFLD) remains unclear. We examined the association of nonheavy alcohol consumption with worsening of noninvasive fibrosis indices in a large‐scale, low‐risk population with NAFLD. A cohort study was performed in 58,927 Korean adults with NAFLD and low fibrosis scores who were followed for a median of 4.9 years. Non‐, light, and moderate drinkers were defined as 0 g/day, 1‐9.9 g/day, and 10‐29.9 g/day (10‐19.9 g/day for women), respectively. Progression from low to intermediate or high probability of advanced fibrosis was assessed using noninvasive indices including NAFLD fibrosis score (NFS) and Fibrosis‐4 Index (FIB‐4). A parametric proportional hazards model was used to estimate the multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). During 347,925.4 person‐years of follow‐up, 5,630 subjects with low FIB‐4 progressed to intermediate or high FIB‐4. The multivariable‐adjusted HRs (95% CI) for worsening of FIB‐4 comparing light and moderate drinkers with nondrinkers were 1.06 (0.98‐1.16) and 1.29 (1.18‐1.40), respectively. Similarly, using NFS, corresponding HRs (95% CI) comparing light and moderate drinkers with nondrinkers were 1.09 (1.02‐1.16) and 1.31 (1.23‐1.40), respectively. Furthermore, the association of moderate drinkers with worsening of either FIB‐4 or NFS remained significant after introducing alcohol use and confounders treated as time‐varying covariates. Conclusion: In this large‐scale cohort of young and middle‐aged individuals with NAFLD, nonheavy alcohol consumption, especially moderate alcohol consumption, was significantly and independently associated with worsening of noninvasive markers of fibrosis, indicating that even moderate alcohol consumption might be harmful.
Cosmetics and ocular allergy

Purpose of review The purpose of this review was to explore recent developments in the study of ocular cosmetics, as they pertain to adverse reactions that can be attributed to them. Recent findings Immunologically mediated adverse reactions to cosmetics are most commonly the result of sensitization to preservatives, fragrances and dyes used in these products. Metals such as nickel, cobalt, chromium and lead are used in products such as eye shadows and eye liners as well as toy makeup sets in amounts greater than the recommended amount of 1 ppm. Cosmetics make up the majority of fragrance-induced contact dermatitis. Recently, a free smartphone app was developed by American Contact Dermatitis Society that holds promise in better enabling patients to utilize their patch test data while shopping for cosmetics. Summary Both immediate and delayed hypersensitivity reactions linked to cosmetics are often the result of sensitization to preservatives, fragrances and additives in the products themselves. Despite significant advances in our understanding of these reactions, further research will be necessary to elucidate the mechanisms behind these reactions and bring this knowledge to the bedside as to improve patient care with potential cosmetic-based related allergic disorders.
A PTAS for $\ell_p$-Low Rank Approximation

A number of recent works have studied algorithms for entrywise $\ell_p$-low rank approximation, namely algorithms which given an $n \times d$ matrix $A$ (with $n \geq d$), output a rank-$k$ matrix $B$ minimizing $\|A-B\|_p^p=\sum_{i,j} |A_{i,j} - B_{i,j}|^p$. We show the following: On the algorithmic side, for $p \in (0,2)$, we give the first $n^{\text{poly}(k/\epsilon)}$ time $(1+\epsilon)$-approximation algorithm. For $p = 0$, there are various problem formulations, a common one being the binary setting for which $A\in\{0,1\}^{n\times d}$ and $B = U \cdot V$, where $U\in\{0,1\}^{n \times k}$ and $V\in\{0,1\}^{k \times d}$. There are also various notions of multiplication $U \cdot V$, such as a matrix product over the reals, over a finite field, or over a Boolean semiring. We give the first PTAS for what we call the Generalized Binary $\ell_0$-Rank-$k$ Approximation problem, for which these variants are special cases. Our algorithm runs in time $(1/\epsilon)^{2^{O(k)}/\epsilon^{2}} \cdot nd \cdot \log^{2^k} d$. For the specific case of finite fields of constant size, we obtain an alternate algorithm with time $n \cdot d^{\text{poly}(k/\epsilon)}$. On the hardness front, for $p \in (1,2)$, we show under the Small Set Expansion Hypothesis and Exponential Time Hypothesis (ETH), there is no constant factor approximation algorithm running in time $2^{k^{\delta}}$ for a constant $\delta > 0$, showing an exponential dependence on $k$ is necessary. For $p = 0$, we observe that there is no approximation algorithm for the Generalized Binary $\ell_0$-Rank-$k$ Approximation problem running in time $2^{2^{\delta k}}$ for a constant $\delta > 0$. We also show for finite fields of constant size, under the ETH, that any fixed constant factor approximation algorithm requires $2^{k^{\delta}}$ time for a constant $\delta > 0$.
Highly Efficient and Reusable Montmorillonite/Fe3O4/Humic Acid Nanocomposites for Simultaneous Removal of Cr(VI) and Aniline

Recyclable nanomaterials are in great need to develop clean technology for applications in the removal of water contaminants. In this work, easily separable montmorillonite/Fe3O4/humic acid (MFH) nanocomposites were fabricated through a facile hydrothermal route. It was found the adsorption ability and stability of MFH was significantly enhanced due to the synergistic effects between montmorillonite, Fe3O4 nanoparticles and humic acid. The MFH nanocomposites are highly efficient and recyclable as they can remove at least 82.3% of Cr(VI) and 95.1% of aniline in six consecutive runs. The adsorption mechanism was investigated by analyzing the kinetic parameters of pseudo first-order, pseudo second-order, and intraparticle diffusion models and describing the equilibrium isotherms of Langmuir and Freundlich models. Results indicated different adsorption mechanisms of Cr(VI) and aniline by MFH. The readily synthesized MFH nanocomposites can act as effective and practical materials for environmental applications.
Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium

Introduction: Magnesium is an essential mineral involved in a range of key biochemical pathways. Several magnesium supplements are present on the market and their degree of bioavailability differs depending on the form of magnesium salt used. Aquamin-Mg is a natural source of magnesium, containing 72 additional trace minerals derived from the clean waters off the Irish coast. However, the in vitro bioaccessibility and bioavailability of Aquamin-Mg in comparison with other supplement sources of magnesium has yet to be tested. Method: Aquamin-Mg, magnesium chloride (MgCl2) and magnesium oxide (MgO) were subjected to gastrointestinal digestion according to the harmonized INFOGEST in vitro digestion method and in vitro bioavailability tested using the Caco-2 cell model. Magnesium concentration was measured by atomic absorption spectrophotometry (AAS). Results: Magnesium recovery from both Aquamin-Mg and MgCl2 was greater than for MgO. Magnesium from all three sources was transported across the epithelial monolayer with Aquamin-Mg displaying a comparable profile to the more bioavailable MgCl2. Conclusions: Our data support that magnesium derived from a marine-derived multimineral product is bioavailable to a significantly greater degree than MgO and displays a similar profile to the more bioavailable MgCl2 and may offer additional health benefits given its multimineral profile.
An engineered novel lentivector specifically transducing dendritic cells and eliciting robust HBV-specific CTL response by upregulating autophagy in T cells

ABSTRACT Dendritic cells (DCs) play a predominant role in initiating cell immune responses. Here we generated a DC-targeting lentiviral vector (LVDC-UbHBcAg-LIGHT) and evaluated its capacity to elicit HBV-specific cytotoxic T lymphocyte (CTL) responses. DC-SIGN-mediated specific transduction using this construct was confirmed in DC-SIGN-expressing 293T cells and ex vivo-cultured bone marrow cells. LVDC-UbHBcAg-LIGHT-loaded DCs were highly effective in inducing HBV-specific CTLs. Mechanistic studies demonstrated autophagy blocking led to a significant increase in apoptosis and obvious inhibition of CD8 + T cells entry into S-phase, correspondingly attenuated LVDC-UbHBcAg-LIGHT-loaded DC-induced T cell responses. This observation was supported by accumulation of pro-apoptotic proteins and the main negative cell cycle regulator-CDKN1B that otherwise would be degraded in activated T cells where autophagy preferentially occured. Our findings revealed an important role of autophagy in the activation of T cells and suggested LVDC-UbHBcAg-LIGHT may potentially be used as a therapeutic strategy to combat persistent HBV infection with higher security.
Gold Nanocage-Based Electrochemical Sensing Platform for Sensitive Detection of Luteolin

A simple and sensitive electrochemical sensor was developed for the detection of tracelevels of luteolin. The sensoris based on a novel type of chemically modified electrode: gold nanocage (AuNCs)-modified carbon ionic liquid electrode (CILE). To construct this electrochemical sensing platform for luteolin, CILE is initially prepared by using 1-hexylpyridinium hexafluorophosphate as the binder and then AuNCs are coated on the surface of CILE to fabricate AuNCs-modified CILE (AuNCs/CILE). Electrochemical studies have shown that AuNCs/CILE can exhibit enhanced electrocatalytic activity toward the redox reaction of luteolin, therefore, the redox peak current of luteolin can be greatly improved, resulting in the high sensitivity of the developed sensor. Under the optimal conditions, the oxidation peak currents of the sensor increase linearly with an increase in the luteolin concentration in a range from 1 to 1000 nM with a detection limit of 0.4 nM, which is lower than those of most reported electrochemical luteolin sensors. Moreover, the reproducibility, precision, selectivity, and stability of this sensor are excellent. Finally, the sensing system was applied to the analysis of luteolin-spiked drug samples and the recovery in all cases was 95.0–96.7%, indicating the potential application of this simple, facile, and sensitive sensing system in pharmaceutical analysis.
The interplay between permanent pacemaker implantation and mortality in patients treated by transcatheter aortic valve implantation: A systematic review and meta‐analysis

Previous implantation of a permanent pacemaker (PPM) is common among patients undergoing transcatheter aortic valve implantation (TAVI). Moreover, onset of conduction disturbances needing new PPM implantation after TAVI is frequent. The interplay of pre‐existing and new‐PPM on mortality after TAVI remains controversial.
Staphylococcus aureus bacteremia in a secondary level Spanish hospital: clinical implications of high vancomycin MIC

ABSTRACT Background One of the most controversial issues in recent years has been the clinical significance of high vancomycin MIC in Staphylococcus aureus bacteremia. The aim of this study was to elucidate the clinical implication that this parameter has in the staphylococcal bacteremia of a second level hospital. Material and methods Retrospective descriptive study between January 2014 and September 2016 with 138 records from the blood culture Severo Ochoa University Hospital registry. A total of 98 cases were finally analized. Microbiological analysis of vancomycin MIC was performed using micro dilution technique. Results The mean age was 71.4 ± 12.45 and 63.26% of the patients had a Charlson index ≥6. A 30.61% were carriers of a venous central catheter. The most frequent source was venous central catheter (26.53%). There were 14.24% metastatic events. Global mortality rate at 30 days was 25.51%. The 43.87% of strains had a vancomycin MIC ≥ 2 mg/L. High vancomycin MIC was significantly associated with persistent bacteremia (OR 3.12 [1.13-8.93]), maintaining this statistical significance in methicillin-resistant S. aureus (MRSA) group (p =0.001) but no in methicillin-susceptible S. aureus (MSSA) group (p = 0.13). Persistent bacteremia was also significantly related with permanent catheter carriers (OR 4.18 [1.38-12.61]), peripheric catheter source (OR 5.18 [1.13-8.93]) and metastatic complications (OR 3.82 [1.03-12.81]). There was no significant association between high vancomycin MIC and mortality. Conclusions High vancomycin MIC may be useful in daily clinical practice as a marker of poor clearance of S. aureus bacteremia, specially when is due to MRSA strains.
No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B

Background & aims It has yet to be firmly established whether host IFNL3 (IL28B) genotype influences interferon responsiveness in patients with chronic hepatitis B. We investigated associations between single-nucleotide polymorphisms (SNPs) in the IFNL3 region and response to peginterferon alfa-2a in 701 patients enrolled in three large, randomized, international studies. Methods Responses were defined as hepatitis B surface antigen (HBsAg) loss and/or hepatitis B e antigen (HBeAg) seroconversion plus hepatitis B virus (HBV) DNA <2000 IU/ml in HBeAg-positive patients, and HBsAg loss and/or HBV DNA <2000 IU/ml in HBeAg-negative patients (24 weeks after end of treatment). Associations between treatment response and the number of copies of the poor-response allele at three SNPs (rs8099917, rs12980275, rs12979860) were explored with logistic regression models in Asian and white patients. Results The HBeAg-positive and -negative populations comprised 465 (92% Asian, 50% HBV genotype C) and 236 (79% Asian, 41% HBV genotype C) patients, respectively, and had respective response rates of 26% and 47%. The IFNL3 genotype was strongly associated with ethnicity. There was no association between IFNL3 genotype and treatment response in HBeAg-positive or -negative patients. Independent predictors of treatment response were: sex, HBV DNA level and alanine aminotransferase level in HBeAg-positive Asian patients; age in HBeAg-negative Asian patients; and HBV DNA in HBeAg-negative white patients. Conclusions This is the largest analysis to date of associations between IFNL3 genotype and peginterferon response in patients with chronic hepatitis B. The data suggest that IFNL3 polymorphism is not a major determinant of the response to peginterferon alfa-2a in either HBeAg-positive or HBeAg-negative patients.
Whole Genome Sequence of the Parasitoid Wasp Microplitis demolitor That Harbors an Endogenous Virus Mutualist

Microplitis demolitor (Hymenoptera: Braconidae) is a parasitoid used as a biological control agent to control larval-stage Lepidoptera and serves as a model for studying the function and evolution of symbiotic viruses in the genus Bracovirus. Here we present the M. demolitor genome (assembly version 2.0), with a genome size of 241 Mb, and a N50 scaffold and contig size of 1.1 Mb and 14 Kb, respectively. Using RNA-Seq data and manual annotation of genes of viral origin, we produced a high-quality gene set that includes 18,586 eukaryotic and 171 virus-derived protein-coding genes. Bracoviruses are dsDNA viruses with unusual genome architecture, in which the viral genome is integrated into the wasp genome and is comprised of two distinct components: proviral segments that are amplified, circularized, and packaged into virions for export into the wasp’s host via oviposition; and replication genes. This genome assembly revealed that at least two scaffolds contain both nudivirus-like genes and proviral segments, demonstrating that at least some of these components are near each other in the genome on a single chromosome. The updated assembly and annotation are available in several publicly accessible databases; including the National Center for Biotechnology Information and the Ag Data Commons. In addition, all raw sequence data available for M. demolitor have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the ‘microgastroid complex’), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes.