Miracle-dz/UniFAR-FTUs huggingface dataset:
Proximity labeling reveals an extensive steady-state stress granule interactome and insights to neurodegeneration

Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form in response to proteotoxic stress. Although SGs are distinct from aggregates observed in neurodegenerative disorders, they share protein components. We used APEX-mediated proximity labeling combined with quantitative mass spectrometry and high-throughput imaging to identify >100 previously unknown SG proteins in human cells, about 10% of which localize to SGs in a cell type- or stress type-dependent manner. Supporting a link between SG proteins and neurodegeneration, we demonstrate aberrant SG composition and subcellular distribution in iPSC-derived motor neurons from ALS patients, and identify several known and previously unidentified SG proteins that modify toxicity of mutant FUS and TDP-43 overexpression in Drosophila. We show that even in an unstressed steady-state, SG proteins form a densely-connected protein interaction network (PIN) and propose a model in which existing RNPs coalesce rapidly into microscopically visible granules that can act as gateways to pathological protein aggregation. Highlights APEX proximity labeling of dynamic RNP granules identifies over 100 novel SG proteins SG proteins form a densely-connected protein interaction network in unstressed cells Systematic immunofluorescence analysis reveals stress- and cell type-specific SG composition ALS motor neurons contain SGs with distinct content and subcellular distribution
rpoD Gene Pyrosequencing for the Assessment of Pseudomonas Diversity in a Water Sample from the Woluwe River

ABSTRACT A water sample from a noncontaminated site at the source of the Woluwe River (Belgium) was analyzed by culture-dependent and -independent methods. Pseudomonas isolates were identified by sequencing and analysis of the rpoD gene. Culture-independent methods consisted of cloning and pyrosequencing of a Pseudomonas rpoD amplicon from total DNA extracted from the same sample and amplified with selective rpoD gene primers. Among a total of 14,540 reads, 6,228 corresponded to Pseudomonas rpoD gene sequences by a BLAST analysis in the NCBI database. The selection criteria for the reads were sequences longer than 400 bp, an average Q 40 value greater than 25, and >85% identity with a Pseudomonas species. Of the 6,228 Pseudomonas rpoD sequences, 5,345 sequences met the established criteria for selection. Sequences were clustered by phylogenetic analysis and by use of the QIIME software package. Representative sequences of each cluster were assigned by BLAST analysis to a known Pseudomonas species when the identity with the type strain was greater than or equal to 96%. Twenty-six species distributed among 12 phylogenetic groups or subgroups within the genus were detected by pyrosequencing. Pseudomonas stutzeri, P. moraviensis, and P. simiae were the only cultured species not detected by pyrosequencing. The predominant phylogenetic group within the Pseudomonas genus was the P. fluorescens group, as determined by culture-dependent and -independent analyses. In all analyses, a high number of putative novel phylospecies was found: 10 were identified in the cultured strains and 246 were detected by pyrosequencing, indicating that the diversity of Pseudomonas species has not been fully described.
Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression.

OBJECTIVE Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission. METHOD We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6, and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS Improvement occurred in a majority of the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109 patients; paroxetine: 64.9% of 103 patients). Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs. NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine. After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine, almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course. CONCLUSION Our results strongly suggest that early improvement predicts later stable response with high sensitivity. These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment.
Cellular and Mitochondrial Effects of Alcohol Consumption

Alcohol dependence is correlated with a wide spectrum of medical, psychological, behavioral, and social problems. Acute alcohol abuse causes damage to and functional impairment of several organs affecting protein, carbohydrate, and fat metabolism. Mitochondria participate with the conversion of acetaldehyde into acetate and the generation of increased amounts of NADH. Prenatal exposure to ethanol during fetal development induces a wide spectrum of adverse effects in offspring, such as neurologic abnormalities and pre- and post-natal growth retardation. Antioxidant effects have been described due to that alcoholic beverages contain different compounds, such as polyphenols as well as resveratrol. This review analyzes diverse topics on the alcohol consumption effects in several human organs and demonstrates the direct participation of mitochondria as potential target of compounds that can be used to prevent therapies for alcohol abusers.
Vaccination against lethal coronavirus-induced encephalitis with a synthetic decapeptide homologous to a domain in the predicted peplomer stalk

A surface probability method was used to select a decapeptide homologous to residues 993 to 1002 of the peplomer protein E2 of murine hepatitis virus strain JHM, a neurotropic coronavirus. This sequence of amino acids corresponded to a minor peak on a hydrophilicity plot. Immunization of mice with the chemically synthesized peptide coupled to keyhole limpet hemocyanin elicited high levels of neutralizing antibody and protected against lethal virus challenge. Protection correlated with a critical level of antipeptide antibody, which could be reached after a single inoculation. These results suggest that an appropriate antibody response to a highly restricted, surface-exposed domain of this viral protein is critical in determining the outcome of infection of the central nervous system. This sequence is located in the C-terminal fifth of the E2 peplomers, between two predicted coiled-coil structures.
ChronicleDB

Reactive security monitoring, self-driving cars, the Internet of Things (IoT), and many other novel applications require systems for both writing events arriving at very high and fluctuating rates to persistent storage as well as supporting analytical ad hoc queries. As standard database systems are not capable of delivering the required write performance, log-based systems, key-value stores, and other write-optimized data stores have emerged recently. However, the drawbacks of these systems are a fair query performance and the lack of suitable instant recovery mechanisms in case of system failures. In this article, we present ChronicleDB, a novel database system with a storage layout tailored for high write performance under fluctuating data rates and powerful indexing capabilities to support a variety of queries. In addition, ChronicleDB offers low-cost fault tolerance and instant recovery within milliseconds. Unlike previous work, ChronicleDB is designed either as a serverless library to be tightly integrated in an application or as a standalone database server. Our results of an experimental evaluation with real and synthetic data reveal that ChronicleDB clearly outperforms competing systems with respect to both write and query performance.
Regulatory volume decrease in perfused proximal nephron: evidence for a dumping of cell K+.

We utilized the microscopic and morphometric procedures described in the preceding paper to examine the role of a swelling-activated dumping of K-salt in the reversal of hyposmotic cell swelling in the perfused proximal nephron. The rate of the regulatory volume decrease that follows cell swelling in dilute solutions was reduced by two maneuvers that attenuate the K+ chemical potential difference across the basolateral membrane; inhibiting the Na+-K+ pump (e.g., with ouabain) and raising the peritubular K+ concentration. The rate of the regulatory volume decrease was also inhibited by peritubular quinine, which blocks K channels and volume regulation for a number of mammalian cells. Additionally, exposure to hyposmotic solutions resulted in a sustained and quinine-sensitive increase in the apparent permeability of the basolateral membrane to K+ salt, which was monitored qualitatively as the rate of cell volume change that was induced by a perturbation in the peritubular K+ concentration. The simplest interpretation of these results is that the reversal of hyposmotic cell swelling in the proximal nephron is referable at least in part to a swelling-activated loss of K-salt and water from the cells.
A Classroom Experiment in Monetary Policy Title for running header : A Classroom Experiment in Monetary Policy

We propose a classroom experiment implementing a simple version of a New Keynesian model suitable for courses in intermediate macroeconomics and money and banking. Students play as either the central bank or members of the private sector. The central banker sets interest rates to meet either twin objectives for inflation and the output gap or to meet only an inflation target. In both settings, private sector agents are concerned with correctly forecasting the inflation rate. We show that an experiment implementing this setup is feasible and yields results that enhance understanding of the New Keynesian model of monetary policy. We propose alternative versions where the central bank is replaced by a policy rule and we provide suggestions for discussing the experimental results with students.
Smaller Hippocampus Volume Is Associated with Short Variant of 5-HTTLPR Polymorphism in Medication-Free Major Depressive Disorder Patients

Aim: Serotonin is known for its importance in the pathophysiology of major depressive disorder. Although the hippocampus is one of the key regions in which neurogenesis occurs, and serotonin plays an important role in neurogenesis, results of studies that investigate effect of the 5-HTTLPR polymorphism on hippocampal volumes in major depressive disorder are inconclusive. Method: We looked for a relationship between the 5-HTTLPR polymorphism and hippocampal volumes in 44 depressed patients (mean age ± SD 33.6 ± 9.5 years) and 43 healthy controls (30.4 ± 6.7 years). Region of interest analysis was conducted on the images acquired via MRI. Results: Although hippocampal volumes were similar in healthy and patient groups, there was a significant interaction between genotype and diagnosis on hippocampus volumes. Post-hoc ANCOVA showed that hippocampal volumes of S/S homozygous depressed patients were smaller compared to healthy controls in both hemispheres. Conclusion: The 5-HTTLPR polymorphism has an effect on hippocampal volumes of depressed patients, which is apparent only in S/S genotype. It seems that decreased neurogenesis by effects of reduced serotoninergic transmission may be responsible for smaller hippocampal volumes observed in S/S homozygous depressed patients.
Microtubules in Plasmodium falciparum merozoites and their importance for invasion of erythrocytes

Plasmodium falciparum merozoites have an array of 2–3 subpellicular microtubules, designated f-MAST. We have previously shown that colchicine inhibits merozoite invasion of erythrocytes, indicating a microtubular involvement in this process. Colchicine inhibition of invasion was reduced by the Taxol®-stabilization of merozoite microtubules prior to colchicine exposure. Immunofluorescence assays showed that the number and length of f-MASTs were reduced in colchicine-treated merozoites, confirming that microtubules were the target of colchicine inhibition. The dinitroaniline drugs, trifluralin and pendimethalin, were shown by immunofluorescence to depolymerize the f-MAST and both drugs were inhibitory in invasion assays. These results demonstrate that the integrity of the f-MAST is important for successful invasion. Fluorescence imaging demonstrated the alignment of mitochondria to f-MAST, suggesting that mitochondrial transport might be perturbed in merozoites with disorganized f-MAST. Depolymerizing mt in late-stage schizonts did not affect the allocation of mitochondria to merozoites.
Faculty teaching practices and perceptions of institutional attitudes toward teaching at eight engineering schools

All engineering faculty members in the eight universities that comprise the SUCCEED Coalition were surveyed about their use of a variety of instructional methods and their perceptions about attitudes toward teaching on their campuses. The results provide a unique snapshot of engineering education at a transitional moment in its history. The same survey will be administered two years and four years from now. The results should provide an indication of the degree to which the SUCCEED faculty development program is meeting its objectives, which are to promote facility adoption of proven instructional methods and materials and to improve institutional support for effective teaching.
Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation

ABSTRACT The molecular mechanisms associated with rabies virus (RV) virulence are not fully understood. In this study, the RV Flury low-egg-passage (LEP) and high-egg-passage (HEP) strains were used as models to explore the attenuation mechanism of RV. The results of our studies confirmed that the R333Q mutation in the glycoprotein (GR333Q) is crucial for the attenuation of Flury RV in mice. The R333Q mutation is stably maintained in the HEP genome background but not in the LEP genome background during replication in mouse brain tissue or cell culture. Further investigation using chimeric viruses revealed that the polymerase L gene determines the genetic stability of the GR333Q mutation during replication. Moreover, a recombinant RV containing the LEP G protein with the R333Q mutation and the HEP L gene showed significant attenuation, genetic stability, enhancement of apoptosis, and immunogenicity. These results indicate that attenuation of the RV Flury strain results from the coevolution of G and L elements and provide important information for the generation of safer and more effective modified live rabies vaccine.
Biodiesel Blend Level Detection Using Ultraviolet Absorption Spectra

Biodiesel is often blended with regular U.S. No. 2 diesel. The blending level influences engine performance, emissions, and fuel cold-flow properties. In this article, ultraviolet (UV) absorption spectroscopy is presented as a reliable and affordable technology for blend level detection based on the absorbance patterns of the aromatic compounds in the proposed spectrum. Blends of biodiesel from six different feedstocks and U.S. No. 2 diesels from five different sources were used to test the robustness of the method. Since the absorbance of undiluted samples was too high to measure reliably, the samples were diluted with n-heptane. It was found that the feedstock and alcohol used (methyl or ethyl) did not make a significant difference in the absorbance of diluted biodiesel in the 245 to 305 nm range, while absorbance from 254 to 281 nm was correlated with blend level with R2 > 0.99. It was also observed that if the absorbance of the diesel source was known, then a single wavelength could be used to detect the biodiesel blend level. However, a single wavelength was inadequate when the diesel source was unknown because of variation in the level of aromatics in diesel fuel. Absorbances at 265, 273, and 280 nm were used to calculate the absorbance index, which was found to be independent of the diesel fuel used. Using three wavelengths captured the shape information of the absorbance curve and eliminated the variation from the aromatics content. The root mean square error in determining blend level with this method was estimated to be 2.88%, and the R2 for the linear model was 0.99. The method worked well with biodiesel from the different feedstocks tested in this research and was independent of the diesel fuel used.
Identification of a Gene Cluster for the Biosynthesis of a Long, Galactose-Rich Exopolysaccharide in Lactobacillus rhamnosus GG and Functional Analysis of the Priming Glycosyltransferase

ABSTRACT Cell surface polysaccharides have an established role as virulence factors in human bacterial pathogens. Less documented are the biosynthesis and biological functions of surface polysaccharides in beneficial bacteria. We identified a gene cluster that encodes the enzymes and regulatory and transporter proteins for the different steps in the biosynthesis of extracellular polysaccharides (EPS) of the well-documented probiotic strain Lactobacillus rhamnosus GG. Subsequent mutation of the welE gene, encoding the priming glycosyltransferase within this cluster, and comparative phenotypic analyses of wild-type versus mutant strains confirmed the specific function of this gene cluster in the biosynthesis of high-molecular-weight, galactose-rich heteropolymeric EPS molecules. The phenotypic analyses included monomer composition determination, estimation of the polymer length of the isolated EPS molecules, and single-molecule force spectroscopy of the surface polysaccharides. Further characterization of the welE mutant also showed that deprivation of these long, galactose-rich EPS molecules results in an increased adherence and biofilm formation capacity of L. rhamnosus GG, possibly because of less shielding of adhesins such as fimbria-like structures.
Analysis of Complications and Recurrences of Aneurysm Coiling with Special Emphasis on the Stent-Assisted Technique

BACKGROUND AND PURPOSE: Stent-assisted coiling has expanded the treatment of intracranial aneurysms. With the use of continuously compiled data, we reviewed the role and drawbacks of stent-assisted coiling. MATERIALS AND METHODS: We compiled data from consecutive patients from 2003–2012 who underwent coiling, with or without stent assistance. Clinical and angiographic results were analyzed retrospectively. RESULTS: Of 1815 saccular aneurysms in 1505 patients, 323 (17.8%) were treated with stents (299 procedures) and 1492 (82.2%) without stents (1400 procedures). Procedure-related complications occurred in 9.4% with stents versus 5.6% without stents (P = .016, relative risk 1.5; 95% CI, 1.1–2.7). Ischemic complications were more frequent in the stent group than in the no-stent group (7.0% versus 3.5%; P = .005; relative risk, 1.7; 95% CI 1.2–2.5), as were hemorrhagic complications (2.3% versus 1.9%, P = .64). Procedure-induced mortality occurred in 2.7% (8/299) with stents versus 1.1% (15/1400) without stents (P = .029; relative risk, 2.0; 95% CI, 1.1–3.5). Logistic regression analysis identified wide-neck aneurysms as the most significant independent predictor of complications. A total of 64.1% (207/323) of aneurysms treated with stents and 70.3% (1049/1492) treated without stents have been followed, disclosing angiographic recurrence in 15.5% (32/207) versus 35.5% (372/1049), respectively (P < .0001). Logistic regression analysis showed that the presence of a stent was the most important factor for the reduction of angiographic recurrence (P < .0001; relative risk, 2.3; 95% CI, 1.6–3.3). CONCLUSIONS: The stent-assisted coiling technique is associated with a significant decrease in recurrences but a significant increase in complications. The treatment of wide-neck aneurysms remains hazardous.
Lobbying Competition Over Trade Policy

Competition between opposing lobbies is an important factor in the endogenous determination of trade policy. This paper investigates empirically the consequences of lobbying competition between upstream and downstream producers for trade policy. The theoretical structure underlying the empirical analysis is the well-known Grossman-Helpman model of trade policy determination, modified suitably to account for the cross-sectoral use of inputs in production (itself a quantitatively significant phenomenon with around 50 percent of manufacturing output being used by other sectors rather than in final consumption). Data from more than 40 countries are used in our analysis. Our empirical results validate the predictions of the theoretical model with lobbying competition. Importantly, accounting for lobbying competition also alters substantially estimates of the "welfare-mindedness" of governments in setting trade policy.
Heterogeneity: we can't live with it, and we can't live without it

As hard as it is to believe now, it was permissible not long ago to sell a prescription drug (in the USA) without providing evidence that it worked; all that was needed was evidence it was safe. Then, Kefauver–Harris changed everything. Acting largely in response to the thalidomide tragedy, Estes Kefauver, a senator from Tennessee, and representative Oren Harris from Arkansas introduced the amendment that now bears their names. The amendment required convincing evidence of efficacy, as well as safety, before a drug could be brought to market.1 It was signed into law by John F Kennedy on 10 October 1962. The effect of Kefauver–Harris on clinical practice is unequivocal; its effect on the shaping of clinical evidence has been less obvious. Although it would be hard to prove a strong cause–effect relation between enactment of the amendment and emergence of controlled trials as the evidentiary ‘gold standard,’ the timing is right. Reports of controlled trials that meet reasonable methodological standards began to enter the medical literature in 1948, but their numbers were small until 1966—just a few years after Kefauver–Harris—at which point their …