Miracle-dz/UniFAR-FTUs huggingface dataset:
Compartmentalization of the MAPK scaffold protein KSR1 modulates synaptic plasticity in hippocampal neurons

ERK1/2 is required for certain forms of synaptic plasticity, including the long‐term potentiation of synaptic strength. However, the molecular mechanisms regulating synaptically localized ERK1/2 signaling are poorly understood. Here, we show that the MAPK scaffold protein kinase suppressor of Ras 1 (KSR1) is directly phosphorylated by the downstream kinase ERK1/2. Quantitative Western blot analysis further demonstrates that expression of mutated, feedback‐deficient KSR1 promotes sustained ERK1/2 activation in HEK293 cells in response to EGF stimulation, compared to a more transient activation in control cells expressing wild‐type KSR1. Immunocytochemistry and confocal imaging of primary hippocampal neurons from newborn C57BL6 mice further show that feedback phosphorylation of KSR1 significantly reduces its localization to dendritic spines. This effect can be reversed by tetrodotoxin (1 μM) or PD184352 (2 μM) treatment, further suggesting that neuronal activity and phosphorylation by ERK1/2 lead to KSR1 removal from the postsynaptic compartment. Consequently, electrophysiological recordings in hippocampal neurons expressing wild‐type or feedback‐deficient KSR1 demonstrate that KSR1 feedback phosphorylation restricts the potentiation of excitatory postsynaptic currents. Our findings, therefore, suggest that feedback phosphorylation of the scaffold protein KSR1 prevents excessive ERK1/2 signaling in the postsynaptic compartment and thus contributes to maintaining physiological levels of synaptic excitability. —Canal, F. , Palygin, O. , Pankratov, Y. , Corrêa, S. A. L. , Müller, J. Compartmentalization of the MAPK scaffold protein KSR1 modulates synaptic plasticity in hippocampal neurons. FASEB J. 25, 2362–2372 (2011). www.fasebj. org
Malacoplakia and Spermatic Granuloma Complicating Vasectomy

Malacoplakia is a granulomatous disease with a histiocytic infiltrate containing calcified structures called Michaelis-Gutmann bodies. These structures are considered to represent an abnormal response to infection involving defective lysosomes and abnormal microbubular assembly. The disease most frequently involves urinary and genital tracts, but has also been described from most other organs. Here we present the first case of malacoplakia only involving the vas deferens.
Analysis of F2-isoprostanes in plasma of pregnant women by HPLC-MS/MS using a column packed with core-shell particles

Plasma F2-isoprostanes (F2-isoPs) are reliable biomarkers of oxidative stress. Several possible F2-isoPs are generated by the oxidation of arachidonic acid esterified in phospholipids. The separation of these isomers represents a technical challenge for rapid and selective determination. We have developed a HPLC-MS/MS method for the simultaneous determination of seven plasma F2-isoPs, namely 8-iso-15(R)-prostaglandin F2α (PGF2α), 8-iso-PGF2α, 15(R)-PGF2α, iPF2α-IV, iPF2α-VI, 5-iPF2α-VI, and (±)5-8,12-iso-iPF2α-VI. We have validated this method in plasma of pregnant women, a mild physiological oxidative stress known to increase F2-isoPs. Thus, plasma samples of women collected at the third trimester of pregnancy (n = 20) were subjected to alkaline hydrolysis followed by liquid-liquid extraction in order to extract total F2-isoPs. The F2-isoPs were separated within 16.5 min using a column packed with core-shell particles. The class VI isomers were the most abundant, accounting for 65% of the total level of all quantified F2-isoPs in plasma of pregnant women (P < 0.05). The 15(R)-PGF2α was the most abundant of the class III isomers quantified. This method allowed fast and selective separation of seven isomers from three different classes of F2-isoP regioisomers.
Online coupling of thin layer chromatography with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: synthesis and application of a new material for the identification of carbohydrates by thin layer chromatography/matrix free material enhanced laser desorption/ionization m

This article describes the online hyphenation of thin layer chromatography with matrix free material enhanced laser desorption/ionization mass spectrometry (mf-MELDI-MS), the preparation of new material for MELDI and application of this newly synthesized material using TLC/MELDI-MS for the analysis of carbohydrate reference standards and plant extracts. Samples included within these analyses are standard solutions of glucose, sucrose, raffinose and a plant extract of Quercus robur, which is used for its anti-inflammatory, anti-viral and anthelminitc properties in phytomedicine. A new material for mf-MELDI-MS is prepared by immobilizing bradykinin--a peptide, on silica gel coupled to 4-(3-triethoxysilylpropylureido)azobenzene. This modification enables the absorption of laser energy sufficient for desorption and ionization of low molecular weight molecules like carbohydrates and amino acids. The newly synthesized material delivered excellent results in respect to signal-to-noise (S/N) ratio (S/N ratio: >9/1) and sensitivity (limit of detection (LOD): lower to ng/microL). Hyphenation of TLC to MELDI-MS employing the novel developed material simultaneously as chromatographic and mass spectrometric sorbent was shown for the first time for the analysis of low molecular weight molecules like mono- and oligosaccharides.
Skeleton-free task-specific rapid upper limb ergonomie assessment using depth imaging sensors

Rapid upper body assessment (RULA) is, undoubtedly, one of the most frequently used ergonomic scoring sheets in different industries. The scoring is based on measuring joint angles during assembly tasks. However, the process is labour intensive and requires ergonomists to study hundreds of hours of videos to identify musculoskeletal disorders associated with different assembly tasks. In this paper we propose automating the process using depth imaging sensors such as Kinect and a random decision forest (RDF). The main contribution in this paper is relaxing the need to construct a skeleton and train the RDF on the whole posture at once at the price of training different RDFs for different tasks. The accuracy of the proposed method converges to 95%.
Cognitive Functions Buffer Age Differences in Technology Ownership

Background: Technology plays a major role in enhancing quality of life and everyday competence in old age. Mechanic and pragmatic cognitive functions are known to serve as resources when using technology in everyday life. Not much is known about the differential role of mechanic and pragmatic cognitive functions when moderating reduced technology ownership in old age. Objective: In this research, we explored whether perceptual speed or verbal fluency is more important for buffering age differences in technology ownership. We investigate possible moderation effects of cognitive functions relative to demographic characteristics, socioeconomic status, and household composition variables. Methods: We report findings based on a nationally representative German sample of 3,357 younger and older adults between 18 and 94 years of age (mean = 51.2, SD = 17.3). Interaction and relative importance analyses were conducted to examine the relative importance of perceptual speed and verbal fluency for the moderation of age differences in technology ownership across adulthood. Results: Findings suggest that perceptual speed (B = 0.0008, t = 6.23, p < 0.001) and verbal fluency (B = 0.0003, t = 2.70, p < 0.01) buffered age differences in technology ownership. The moderating role of perceptual speed remained robust (B = 0.0007, t = 5.48, p < 0.001) when including interactions of age with demographic, socioeconomic, and household composition variables; however, the interaction between age and verbal fluency was no longer significant (B = 0.0002, t = 1.82, p = 0.069). Relative importance analysis indicates that perceptual speed was the most important moderator of age differences (DW = 0.0121), whereas verbal fluency was less important for moderating the relation between age and technology ownership (DW = 0.0039). Conclusions: Mechanic and pragmatic cognitive functions may serve differently as moderators of the relation between age and technology ownership. Our findings suggest that perceptual speed was more important for buffering age differences in technology ownership than verbal fluency. Such findings underscore the relevance of information processing for the ownership of technological devices in late life.
A Comprehensive Structure-Function Comparison of Hepatitis C Virus Strain JFH1 and J6 Polymerases Reveals a Key Residue Stimulating Replication in Cell Culture across Genotypes

ABSTRACT The hepatitis C virus (HCV) genotype 2a isolate JFH1 represents the only cloned HCV wild-type sequence capable of efficient replication in cell culture as well as in vivo. Previous reports have pointed to NS5B, the viral RNA-dependent RNA polymerase (RdRp), as a major determinant for efficient replication of this isolate. To understand the contribution of the JFH1 NS5B gene at the molecular level, we aimed at conferring JFH1 properties to NS5B from the closely related J6 isolate. We created intragenotypic chimeras in the NS5B regions of JFH1 and J6 and compared replication efficiency in cell culture and RdRp activity of the purified proteins in vitro, revealing more than three independent mechanisms conferring the role of JFH1 NS5B in efficient RNA replication. Most critical was residue I405 in the thumb domain of the polymerase, which strongly stimulated replication in cell culture by enhancing overall de novo RNA synthesis. A structural comparison of JFH1 and J6 at high resolution indicated a clear correlation of a closed-thumb conformation of the RdRp and the efficiency of the enzyme at de novo RNA synthesis, in accordance with the proposal that I405 enhances de novo initiation. In addition, we identified several residues enhancing replication independent of RdRp activity in vitro. The functional properties of JFH1 NS5B could be restored by a few single-nucleotide substitutions to the J6 isolate. Finally, we were able to enhance the replication efficiency of a genotype 1b isolate with the I405 mutation, indicating that this mechanism of action is conserved across genotypes.
Effect of 2 Impression Techniques on the Dimensional Accuracy of Working Implant Prosthesis Models: An In Vitro Study

PurposeImplant impressions and working models form integrated precision systems for registration and transmission of clinical data. The components of implant systems have a dimensional tolerance capable of introducing inaccuracies in the impression, thus in the prosthetic framework. This article aimed at comparing 2 repositioning impression techniques: one using impression copings (conventional technique) and the other using the final abutments as impression copings (interceptive technique). Materials and MethodsTwo experimental models, one with 4 parallel implants and the other with 4 nonparallel implants, were used to make silicone impressions. Twenty impressions were made with the conventional technique, and a further 20 were made with the interceptive technique. Three-dimensional images acquired with a three-dimensional scanner were measured using a three-dimensional image analysis software, comparing models obtained from the impressions with the experimental models. Data were statistically analyzed by means of confidence intervals calculated with the mean (&agr; = 0.05), descriptive (box plot), and bivariate analyses. ResultsStatistic analysis highlighted significant differences among models obtained using both techniques: the interceptive technique generated working models with less distortion and variability. ConclusionsFor internal-connection implants, the interceptive technique provided significantly more precise working models than did the conventional technique.
Gram staining by physicians: an invaluable practice still seen in East Asia.

Figure 1. A devotee participating in a chakra puja Hindu religious ceremony in Sylhet, Bangladesh, 1978 tients with both Good syndrome and autoimmune conditions who receive immunosuppressive treatment, the risk of opportunistic infections will increase, and the clinical outcome will be poor. The case we describe suggests that physicians must weigh the efficacy of therapy and the increased risk of opportunistic infections before or during treatment of Good syndrome, especially for patients who need immunosuppressive treatment.
Perioperative Intravenous Ketamine Infusion for the Prevention of Persistent Post-amputation Pain: A Randomized, Controlled Trial

We hypothesized that perioperative ketamine administration would modify acute central sensitization following amputation and hence reduce the incidence and severity of persistent post-amputation pain (both phantom limb and stump pain). In a randomized, controlled trial, 45 patients undergoing above- or below-knee amputation received ketamine 0.5 mg.kg–1 or placebo as a pre-induction bolus followed by an intravenous infusion of ketamine 0.15 mg.kg–1.h–1 or normal saline for 72 hours postoperatively. Both groups received standardized general anaesthesia followed by patient-controlled intravenous morphine. The surface area of allodynia over the stump was mapped at days 3 and 6. Postamputation pain was assessed at days 3 and 6 and at 6 months postoperatively. We found no significant difference between groups in the surface area of stump allodynia or in morphine consumption. There was an unexplained, but significant, increase in the incidence of stump pain in the ketamine group at day 3. At six-month review, the incidence of phantom pain was 47% in the ketamine group and 71% in the control group. This did not reach statistical significance (P=0.28) as the power of the study was based on the search for a large treatment effect. The incidence of stump pain at six months was 47% in the ketamine group and 35% in the control group (P=0.72). There were no significant between-group differences in pain severity throughout the study period. Ketamine at the dose administered did not significantly reduce acute central sensitization or the incidence and severity of post-amputation pain.
Pollen germination activates the apical membrane-located RAC/ROP GTPase switch.

Pollen germination and tube growth underlie reproductive success in flowering plants. Pollen germination, whether occurring on the stigmatic surface of the pistil or under defined medium conditions in vitro, involves producing a polarized outgrowth that extends at the tip, producing a pollen tube. RAC/ROPs, the RHO GTPases of plants, are molecular switches that pivotally control the polarized pollen tube growth process. However, how RAC/ROP activities respond to conditions during germination and tube growth to signal the needed cellular events has not been examined.
Nonlinear Regression Improves Accuracy of Characterization of Multiplexed Mass Spectrometric Assays *

The need for assay characterization is ubiquitous in quantitative mass spectrometry-based proteomics. Among many assay characteristics, the limit of blank (LOB) and limit of detection (LOD) are two particularly useful figures of merit. LOB and LOD are determined by repeatedly quantifying the observed intensities of peptides in samples with known peptide concentrations and deriving an intensity versus concentration response curve. Most commonly, a weighted linear or logistic curve is fit to the intensity-concentration response, and LOB and LOD are estimated from the fit. Here we argue that these methods inaccurately characterize assays where observed intensities level off at low concentrations, which is a common situation in multiplexed systems. This manuscript illustrates the deficiencies of these methods, and proposes an alternative approach based on nonlinear regression that overcomes these inaccuracies. We evaluated the performance of the proposed method using computer simulations and using eleven experimental data sets acquired in Data-Independent Acquisition (DIA), Parallel Reaction Monitoring (PRM), and Selected Reaction Monitoring (SRM) mode. When the intensity levels off at low concentrations, the nonlinear model changes the estimates of LOB/LOD upwards, in some data sets by 20–40%. In absence of a low concentration intensity leveling off, the estimates of LOB/LOD obtained with nonlinear statistical modeling were identical to those of weighted linear regression. We implemented the nonlinear regression approach in the open-source R-based software MSstats, and advocate its general use for characterization of mass spectrometry-based assays.
Adaptive media playout buffer management for latency optimization of mobile live streaming

Media playout buffer is widely employed by today's streaming media player to cope with short-term network variation and achieve continuous playout. However, the playout buffer inevitably introduces additional latency, affecting mobile live streaming experience. In this paper, we propose a novel adaptive playout buffer management approach to dynamically optimize the buffer latency while to a great extent keeping playout continuity. We collect historical buffer level variation information, on the basis of which we estimate the buffer level variation range with a probabilistic model which can be implemented to a dynamic programming algorithm. According to this estimated range, we use adaptive media playout (AMP) scheme to adjust the buffer level on the fly. Experimental results show good tradeoff dynamically made by our proposed approach between buffer latency and playout interruption.
Convergent functional genomics of psychiatric disorders

Genetic and gene expression studies, in humans and animal models of psychiatric and other medical disorders, are becoming increasingly integrated. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit‐to‐disease way of extracting reproducible and biologically important signal, in contrast to the fit‐to‐cohort effect and limited reproducibility of human genetic analyses alone. With the advent of whole‐genome sequencing and the realization that a major portion of the non‐coding genome may contain regulatory variants, Convergent Functional Genomics (CFG) approaches are going to be essential to identify disease‐relevant signal from the tremendous polymorphic variation present in the general population. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer, cardiovascular diseases, and diabetes. © 2013 Wiley Periodicals, Inc.
Novel compound tetra-, dinucleotide microsatellite polymorphism in the tumor necrosis factor/lymphotoxin locus

A polymorphic (TGCG)n, tetranucleotide repeat was discovered juxtaposed to the (GT)n dinucleotide repeat that comprises the tumor necrosis factor a microsatellite (TNF) located telomeric to the tumor necrosis factor/lymphotoxin gene cluster. The degree of complexity of this compound tetra-,dinucleotide microsatellite consists of 16 potential alleles of combined length ranging from 24 to 54 bp. The pattern of frequencies of individual alleles belonging to the compound TNFa microsatellite was established from 52 healthy volunteers and was found to be highly heterogeneous. The data diverges significantly from previously published statistics that recognized only a simple variable dinucleotide tandem repeat. The newly recognized compound tetra-, dinucleotide TNFa microsatellite polymorphism establishes a more accurate genetic basis to explore potential linkage with disease susceptibility genes located within this region of the class III major histocompatibility complex. In addition, variable tumor necrosis factor and lymphotoxin production may reflect the more complex polymorphic nature of this microsatellite region. Finally, compound microsatellites probably exist elsewhere, throughout the human genome. Recognition of their presence may have a considerable impact on the validity of past and future microsatellite-based genetic analyses.
COMT: A common susceptibility gene in bipolar disorder and schizophrenia

A variety of psychiatric illnesses, including schizophrenia and bipolar disorder, have been reported in patients with microdeletion on chromosome 22q11—a region which includes the catechol‐O‐methyltransferase (COMT) gene. The variety of psychiatric manifestations in patients with the 22q11 microdeletion and the role of COMT in the degradation of catecholamine neurotransmitters may thus suggest a general involvement of the COMT gene in psychiatric diseases. We have previously reported on a significant association between a COMT haplotype and schizophrenia. In this study, we attempt to test for association between bipolar disorder and the polymorphisms implicated in schizophrenia. The association between COMT and bipolar disorder was tested by examining the allele and haplotype found to be associated with schizophrenia. A significant association between bipolar disorder and COMT polymorphisms was found. The estimated relative risk is greater in women, a result consistent with our previous findings in schizophrenia. We suggest that polymorphisms in the COMT gene may influence susceptibility to both diseases—and probably also a wider range of behavioral traits. © 2004 Wiley‐Liss, Inc.
Superficial siderosis of central nervous system with unknown cause: report of 2 cases and review of the literature

Abstract Objective: To report 2 cases of superficial siderosis of central nervous system (SS-CNS) and a review of the literature. Methods: We have analyzed the clinical data and relevant features of two patients with SS-CNS who were presented with ataxia and slurred speech. Both patients undertook blood tests, lumbar puncture, head CT (computer tomography) scans, and brain and spinal cord magnetic resonance (MR) scans. In addition, the first patient also undewent enhanced susceptibility-weighted angiography (ESWAN) and the second patient undertook susceptibility weighted imaging (SWI) scan. We searched PubMed with the keywords superficial siderosis and superficial siderosis of central nervous system, and selected publications that seemed appropriate. Results: A neurological examination revealed bilateral sensorineural hearing impairment in both the patients. Their past history was not significant to identify hemorrhage. Brain MR scans demonstrated typical hypointensity rimming at the brain surface on T2 weighted images. The patients were diagnosed with SS-CNS. Conclusion: SS-CNS should be highly suspected in patients with progressive sensorineural hearing loss, ataxia, and signs of pyramidal tracts, and MR scans of brain and whole spinal cord should be undertaken to confirm the diagnosis. Advanced MRI techniques such as SWI and ESWAN are helpful in making the diagnosis of SS-CNS. The cause of hemorrhage is not identified in most cases.