Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression Analysis of Lrrk1, Lrrk2 and Lrrk2 Splice Variants in Mice

Missense mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are linked to autosomal dominant forms of Parkinson’s disease (PD). In order to get insights into the physiological role of Lrrk2, we examined the distribution of Lrrk2 mRNA and different splice variants in the developing murine embryo and the adult brain of Mus musculus. To analyse if the Lrrk2-paralog, Lrrk1, may have redundant functions in PD-development, we also compared Lrrk1 and Lrrk2 expression in the same tissues. Using radioactive in situ hybridization, we found ubiquitous expression of both genes at low level from embryonic stage E9.5 onward, which progressively increased up until birth. The developing central nervous system (CNS) displayed no prominent Lrrk2 mRNA signals at these time-points. However, in the entire postnatal brain Lrrk2 became detectable, showing strongest level in the striatum and the cortex of adult mice; Lrrk1 was only detectable in the mitral cell layer of the olfactory bulb. Thus, due to the non-overlapping expression patterns, a redundant function of Lrrk2 and Lrrk1 in the pathogenesis of PD seems to be unlikely. Quantification of Lrrk2 mRNA and protein level in several brain regions by real-time PCR and Western blot verified the striatum and cortex as hotspots of postnatal Lrrk2 expression. Strong expression of Lrrk2 is mainly found in neurons, specifically in the dopamine receptor 1 (DRD1a) and 2 (DRD2)-positive subpopulations of the striatal medium spiny neurons. Finally, we identified 2 new splice-variants of Lrrk2 in RNA-samples from various adult brain regions and organs: a variant with a skipped exon 5 and a truncated variant terminating in an alternative exon 42a. In order to identify the origin of these two splice variants, we also analysed primary neural cultures independently and found cell-specific expression patterns for these variants in microglia and astrocytes.
Syndecan and tenascin expression is induced by epithelial-mesenchymal interactions in embryonic tooth mesenchyme

Morphogenesis of embryonic organs is regulated by epithelial- mesenchymal interactions associating with changes in the extracellular matrix (ECM). The response of the cells to the changes in the ECM must involve integral cell surface molecules that recognize their matrix ligand and initiate transmission of signal intracellularly. We have studied the expression of the cell surface proteoglycan, syndecan, which is a matrix receptor for epithelial cells (Saunders, S., M. Jalkanen, S. O'Farrell, and M. Bernfield. J. Cell Biol. In press.), and the matrix glycoprotein, tenascin, which has been proposed to be involved in epithelial-mesenchymal interactions (Chiquet-Ehrismann, R., E. J. Mackie, C. A. Pearson, and T. Sakakura. 1986. Cell. 47:131-139) in experimental tissue recombinations of dental epithelium and mesenchyme. Our earlier studies have shown that in mouse embryos both syndecan and tenascin are intensely expressed in the condensing dental mesenchyme surrounding the epithelial bud (Thesleff, I., M. Jalkanen, S. Vainio, and M. Bernfield. 1988. Dev. Biol. 129:565-572; Thesleff, I., E. Mackie, S. Vainio, and R. Chiquet-Ehrismann. 1987. Development. 101:289-296). Analysis of rat-mouse tissue recombinants by a monoclonal antibody against the murine syndecan showed that the presumptive dental epithelium induces the expression of syndecan in the underlying mesenchyme. The expression of tenascin was induced in the dental mesenchyme in the same area as syndecan. The syndecan and tenascin positive areas increased with time of epithelial-mesenchymal contact. Other ECM molecules, laminin, type III collagen, and fibronectin, did not show a staining pattern similar to that of syndecan and tenascin. Oral epithelium from older embryos had lost its ability to induce syndecan expression but the presumptive dental epithelium induced syndecan expression even in oral mesenchyme of older embryos. Our results indicate that the expression of syndecan and tenascin in the tooth mesenchyme is regulated by epithelial-mesenchymal interactions. Because of their early appearance, syndecan and tenascin may be used to study the molecular regulation of this interaction. The similar distribution patterns of syndecan and tenascin in vivo and in vitro and their early appearance as a result of epithelial-mesenchymal interaction suggest that these molecules may be involved in the condensation and differentiation of dental mesenchymal cells.
Measurment of folding in surfaces of arbitrary size in human brain development

This paper describes a novel approach to in-vivo measurement of brain surface folding in clinically acquired neonatal MR image data. Specifically it addresses the problem of comparing folding of surfaces of arbitrary area. Most of the current measures of folding are not independent of the area of the surface from which they are derived. Therefore, applying them to whole brains or subregions of different sizes result in differences which may or may not reflect true differences in folding. In this paper we describe alternative approaches to deriving area independent measures. The measures were applied to twelve premature infants (age 28-37 weeks) from which cortical gray and white surfaces were extracted. Experimental results show that previous folding measures are sensitive to the size of the surface patch, and that the area independent measures proposed here provide significant improvements. Such a system provides a tool to allow the study of structural development in the neonatal brain within specific functional subregions, which may be critical in identifying later neurological impairment.
A Motion Aftereffect From Still Photographs Depicting Motion

A photograph of an action can convey a vivid sense of motion. Does the inference of motion from viewing a photograph involve the same neural and psychological representations used when one views physical motion? In this study, we tested whether implied motion is represented by the same direction-selective signals involved in the perception of real motion. We made use of the motion aftereffect, a visual motion illusion. Three experiments showed that viewing a series of static photographs with implied motion in a particular direction produced motion aftereffects in the opposite direction, as assessed with real-motion test probes. The transfer of adaptation from motion depicted in photographs to real motion demonstrates that the perception of implied motion activates direction-selective circuits that are also involved in processing real motion.
Assembly of N type Bi2(Te, Se)3 thermoelectric modules by low temperature bonding

Solid liquid interdiffusion technique is employed to attach N type Bi2(Te0·92Se0·08)3 thermoelectric material to alumina substrate. The surface finishes of the bonding surfaces for Bi2(Te0·92Se0·08)3 and alumina are Ni and Ag respectively. The bonding layer is pure Sn. The growth kinetic of intermetallic compounds and their microstructure evolution during aging at 200°C was established. The success of this bonding technique provides a cost effective way to assemble thermoelectric modules at a low temperature for higher temperature applications.
High temperature deformation and extended plasticity in Mg single crystals

The high temperature deformation behavior of Mg single crystals was precisely investigated using orientation imaging microscopy. For this purpose, Mg single crystals of various orientations were tensile tested in vacuum at temperatures between 473 and 673 K. A strain rate of 4.2 × 10−4 s−1 was employed. The elongations to fracture depended strongly on crystal orientation, the lowest fracture strains being associated with multiple slip. Single crystals in which single slip was activated exhibited extended ductilities corresponding to more than 1.5 in true strain. The strong orientation dependence of the ductility can also be correlated with the ease of occurrence of dynamic recrystallization (DRX), which took place in the multiple-slip specimens. The role of twinning in the initiation of DRX is also discussed.
Relationships Between Metabolic Syndrome and Other Baseline Factors and the Efficacy of Ezetimibe/Simvastatin and Atorvastatin in Patients With Type 2 Diabetes and Hypercholesterolemia

OBJECTIVE To investigate relationships between baseline factors and treatment-associated efficacy changes in type 2 diabetes. RESEARCH DESIGN AND METHODS Multivariable analyses of treatment response in 1,229 type 2 diabetic patients with hypercholesterolemia who received ezetimibe/simvastatin or atorvastatin in a randomized double-blind 6-week study. RESULTS Increasing age was related to improvements in all lipid assessments. Men had greater triglyceride and non-HDL cholesterol reductions than women, and black/Hispanic patients had less favorable lipid effects than other races/ethnicities. Increasing baseline LDL cholesterol was associated with improvements in most lipids; higher baseline non-HDL cholesterol with improved HDL cholesterol and triglycerides; higher baseline HDL cholesterol with greater non-HDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) reductions; and higher baseline hs-CRP with smaller LDL cholesterol, non-HDL cholesterol, and apolipoprotein B reductions. Patients with high baseline non-HDL cholesterol or triglycerides less frequently attained LDL cholesterol targets. Obesity was inversely related to HDL cholesterol and hs-CRP changes, and higher baseline A1C to smaller apolipoprotein B reductions. Metabolic syndrome was not a significant predictor. CONCLUSIONS Treatment responses in type 2 diabetic patients were related to baseline factors, although treatment effects (ezetimibe/simvastatin being more effective than atorvastatin) remained consistent. The presence of predictive factors should be considered in planning lipid-altering therapy.
Development of simulation model: An ethernet case study in heterogeneous environment

We present a novel approach for the measurement and estimation of network traffic utilization between network nodes in heterogeneous environment. We propose an enhanced equation to evaluate the performance of network interface via little law and queuing theories to improve the evaluation algorithm. To get accuracy results on the performance of simulation model, we verify and validate data from local area network (real network environment). We use network management tool to capture those data and Fluke Optiview device to generate traffic. As a result, this simulation model can provide a good approximation of the real traffic observed in the real network environment.
The Unique Dopamine/Ecdysteroid Receptor Modulates Ethanol-Induced Sedation in Drosophila

Steroids profoundly influence behavioral responses to alcohol by activating canonical nuclear hormone receptors and exerting allosteric effects on ion channels. Accumulating evidence has demonstrated that steroids can also trigger biological effects by directly binding G-protein-coupled receptors (GPCRs), yet physiological roles of such unconventional steroid signaling in controlling alcohol-induced behaviors remain unclear. The dopamine/ecdysteroid receptor (DopEcR) is a GPCR that mediates nongenomic actions of ecdysteroids, the major steroid hormones in insects. Here, we report that Drosophila DopEcR plays a critical role in ethanol-induced sedation. DopEcR mutants took longer than control flies to become sedated during exposure to ethanol, despite having normal ethanol absorption or metabolism. RNAi-mediated knockdown of DopEcR expression revealed that this receptor is necessary after eclosion, and is required in particular neuronal subsets, including cholinergic and peptidergic neurons, to mediate this behavior. Additionally, flies ubiquitously overexpressing DopEcR cDNA had a tendency to become sedated quickly upon ethanol exposure. These results indicate that neuronal subset-specific expression of DopEcR in adults is required for normal sedation upon exposure to ethanol. We also obtained evidence indicating that DopEcR may promote ethanol sedation by suppressing epidermal growth factor receptor/extracellular signal-regulated kinase signaling. Last, genetic and pharmacological analyses suggested that in adult flies ecdysone may serve as an inverse agonist of DopEcR and suppress the sedation-promoting activity of DopEcR in the context of ethanol exposure. Our findings provide the first evidence for the involvement of nongenomic G-protein-coupled steroid receptors in the response to alcohol, and shed new light on the potential roles of steroids in alcohol-use disorders. SIGNIFICANCE STATEMENT Alcohol abuse is an alarming personal and societal burden. The improvement of prevention and treatment strategies for alcohol-use disorders requires a better understanding of their biological basis. Steroid hormones profoundly affect alcohol-induced behaviors, but the contribution of their unconventional, nongenomic actions during these responses has not yet been elucidated. We found that Drosophila DopEcR, a unique G-protein-coupled receptor (GPCR) with dual specificity for dopamine and steroids, mediates noncanonical steroid actions to promote ethanol-induced sedation. Because steroid signaling and the behavioral response to alcohol are evolutionarily well conserved, our findings suggest that analogous mammalian receptors likely play important roles in alcohol-use disorders. Our work provides a foundation for further characterizing the function and mechanisms of action of nonclassical steroid GPCR signaling.
Optical Monitoring of BL Lacertae Object OJ 287: A 40 Day Period?

We present the results of our optical monitoring of the BL Lacertae object OJ 287 during the first half of 2005. The source did not show large-amplitude variations during this period and was in a relatively quiescent state. A possible period of 40 days was derived from its light curves in three BATC wave bands. A bluer-when-brighter chromatism was discovered, which is different from the extremely stable color during the outburst in 1994-1996. The different color behaviors imply different variation mechanisms in the two states. We then revisited the optical data on OJ 287 from the OJ-94 project and also found a probable period of 40 days in its optical variability during the late 1994 outburst. The results suggest that two components contribute to the variability of OJ 287 during its outburst state. The first component is the normal blazar variation. This component has an amplitude similar to that of the quiescent state and also may share a similar periodicity. The second component can be taken as a "low-frequency modulation" to the first component. It may be induced by the interaction of the assumed binary black holes in the center of this object. The 40 day period may be related to the helical structure of the magnetic field at the base of the jet or to the orbital motion close to the central primary black hole.
Identification and Functional Assessment of BCRP Polymorphisms in a Korean Population

The breast cancer resistance protein (BCRP) is a member of the ATP-binding cassette transporters. The aim of the present study was to identify genetic variants of BCRP in Koreans and to assess the functional consequences of BCRP polymorphisms. Twenty single nucleotide polymorphisms (SNP), including four nonsynonymous SNP, were identified by DNA sequencing of the BCRP gene in 92 Korean subjects. BCRP V12M, Q141K, P269S, and Q126Stop were detected at frequencies of 23, 28, 0.2, and 1.9%, respectively. These four coding variants were also screened in Chinese and Vietnamese subjects; the allelic frequencies among the three populations were compared; and predictions were made as to the potential frequency of each variant. In vitro functional analyses of the P269S protein and the promoter SNP –19031C>T (mutated in the hypoxia-inducible factor-1α binding site) were performed and compared with those of the wild type. P269S exhibited a 35 to 40% decrease in vesicular uptake of [3H]estrone-3-sulfate and [3H]methotrexate compared with the wild type. The promoter SNP –19031C>T did not affect BCRP promoter activity in either the presence or absence of chemical-induced hypoxic stress. Our results suggest that the P269S variant could be a functionally altered variant. Genotyping of this variant in clinical studies is needed to address its phenotypic role. Genetic polymorphisms of BCRP were found to be very common in Koreans, as well as in other ethnic groups. Comparative analyses among three Asian populations revealed different frequencies for the four functional BCRP variants.
Nucleoside binding site of Herpes simplex type 1 thymidine kinase analyzed by X‐ray crystallography

The crystal structures of the full‐length Herpes simplex virus type 1 thymidine kinase in its unligated form and in a complex with an adenine analogue have been determined at 1.9 Å resolution. The unligated enzyme contains four water molecules in the thymidine pocket and reveals a small induced fit on substrate binding. The structure of the ligated enzyme shows for the first time a bound adenine analogue after numerous complexes with thymine and guanine analogues have been reported. The adenine analogue constitutes a new lead compound for enzyme‐prodrug gene therapy. In addition, the structure of mutant Q125N modifying the binding site of the natural substrate thymidine in complex with this substrate has been established at 2.5 Å resolution. It reveals that neither the binding mode of thymidine nor the polypeptide backbone conformation is altered, except that the two major hydrogen bonds to thymidine are replaced by a single water‐mediated hydrogen bond, which improves the relative acceptance of the prodrugs aciclovir and ganciclovir compared with the natural substrate. Accordingly, the mutant structure represents a first step toward improving the virus‐directed enzyme‐prodrug gene therapy by enzyme engineering. Proteins 2000;41:545–553. © 2000 Wiley‐Liss, Inc.
Differences in Life-Histories Refute Ecological Equivalence of Cryptic Species and Provide Clues to the Origin of Bathyal Halomonhystera (Nematoda)

The discovery of morphologically very similar but genetically distinct species complicates a proper understanding of the link between biodiversity and ecosystem functioning. Cryptic species have been frequently observed to co-occur and are thus expected to be ecological equivalent. The marine nematode Halomonhystera disjuncta contains five cryptic species (GD1-5) that co-occur in the Westerschelde estuary. In this study, we investigated the effect of three abiotic factors (salinity, temperature and sulphide) on life-history traits of three cryptic H. disjuncta species (GD1-3). Our results show that temperature had the most profound influence on all life-cycle parameters compared to a smaller effect of salinity. Life-history traits of closely related cryptic species were differentially affected by temperature, salinity and presence of sulphides which shows that cryptic H. disjuncta species are not ecologically equivalent. Our results further revealed that GD1 had the highest tolerance to a combination of sulphides, high salinities and low temperatures. The close phylogenetic position of GD1 to Halomonhystera hermesi, the dominant species in sulphidic sediments of the Håkon Mosby mud volcano (Barent Sea, 1280 m depth), indicates that both species share a recent common ancestor. Differential life-history responses to environmental changes among cryptic species may have crucial consequences for our perception on ecosystem functioning and coexistence of cryptic species.
Intramembrane Proteolysis and Endoplasmic Reticulum Retention of Hepatitis C Virus Core Protein

ABSTRACT Hepatitis C virus (HCV) core protein is suggested to localize to the endoplasmic reticulum (ER) through a C-terminal hydrophobic region that acts as a membrane anchor for core protein and as a signal sequence for E1 protein. The signal sequence of core protein is further processed by signal peptide peptidase (SPP). We examined the regions of core protein responsible for ER retention and processing by SPP. Analysis of the intracellular localization of deletion mutants of HCV core protein revealed that not only the C-terminal signal-anchor sequence but also an upstream hydrophobic region from amino acid 128 to 151 is required for ER retention of core protein. Precise mutation analyses indicated that replacement of Leu139, Val140, and Leu144 of core protein by Ala inhibited processing by SPP, but cleavage at the core-E1 junction by signal peptidase was maintained. Additionally, the processed E1 protein was translocated into the ER and glycosylated with high-mannose oligosaccharides. Core protein derived from the mutants was translocated into the nucleus in spite of the presence of the unprocessed C-terminal signal-anchor sequence. Although the direct association of core protein with a wild-type SPP was not observed, expression of a loss-of-function SPP mutant inhibited cleavage of the signal sequence by SPP and coimmunoprecipitation with unprocessed core protein. These results indicate that Leu139, Val140, and Leu144 in core protein play crucial roles in the ER retention and SPP cleavage of HCV core protein.
Small fibre neuropathies

Purpose of reviewTo summarize the recent advances in aetiology, diagnostic assessment, and treatment of small fibre neuropathies. Recent findingsNew causes of small fibre neuropathy have been recognized and advances in neurophysiologic and neuropathologic techniques for investigating small fibres have been made, increasing the interest in this field. In particular, skin biopsy proved to be a sensitive method to diagnose small fibre neuropathy. It allows the detection of subclinical abnormalities of peripheral nerve function in patients with diabetes and tongue denervation in patients with burning mouth syndrome. This technique has also been used to demonstrate the neuroprotective effect of erythropoietin in experimental models of neuropathy. Among nonconventional neurophysiologic techniques for investigating small fibres, laser-evoked potential and contact heat-evoked potential stimulators have been developed and deserve particular interest. Several trials on neuropathic pain that is a typical feature of small fibre neuropathies have been performed and guidelines have recently been published. SummaryDetection of small fibre impairment allows earlier diagnosis of neuropathy and could be used as an outcome measure in future regenerative neuropathy trials. Standardization of skin biopsy can have an important impact on clinical practice and research. Further studies are needed to assess the reliability of current neurophysiologic techniques for testing small fibre function in peripheral neuropathies and the correlation with well established neuropathologic examination.
Ultra Low-energy Computing via Probabilistic Algorithms and Devices: CMOS Device Primitives and the Energy-Probability Relationship

This work is supported in part by DARPA under seedling contract #F30602-02-2-0124. Appeared in 2004 International Conference on Solid State Devices and Materials. “By 2010, the individual transistors in the circuits will be turned on or off by the addition or the removal of only eight electrons on the gate of a transistor, compared to about 1000 electrons today. The statistics of small numbers will become significant, and the ability to distinguish between zero and one in a digital circuit will be severely compromised. ” − J. Birnbaum and R. S. Williams [1]
Survey of Security and Privacy Issues of Internet of Things

This paper is a general survey of all the security issues existing in the Internet of Things (IoT) along with an analysis of the privacy issues that an end-user may face as a consequence of the spread of IoT. The majority of the survey is focused on the security loopholes arising out of the information exchange technologies used in Internet of Things. No countermeasure to the security drawbacks has been analyzed in the paper.