Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons*

The molecular mechanisms underlying migraine pain remain unclear and probably require sustained facilitation in pain-sensing P2X3 receptors gated by extracellular ATP in nociceptive sensory neurons. The major migraine mediator calcitonin generelated peptide (CGRP) is known to sensitize P2X3 receptors to increase impulse flow to brainstem trigeminal nuclei. This process is mediated via changes in the expression and function of P2X3 receptors initially through enhanced trafficking and, later, perhaps through augmented synthesis of P2X3 receptors. To clarify the mechanisms responsible for CGRP-evoked long lasting alterations in P2X3 receptors, we used as a model mouse trigeminal ganglion neurons in culture. CGRP activated Ca2+-calmodulin-dependent kinase II, which became localized to the perimembrane region and neuronal processes, a phenomenon already apparent after 30 min and accompanied by a parallel increase in cAMP-response element-binding protein (CREB) phosphorylation and nuclear translocation. These effects triggered increased P2X3 receptor transcription and were prevented by expressing a dominant negative form of CREB. Increased P2X3 receptor synthesis was partly mediated by endogenous brain-derived neurotrophic factor (BDNF) because of its block by anti-BDNF antibodies and mimicry by exogenous BDNF. Immunocytochemistry experiments indicated distinct subpopulations of BDNF- or CGRP-sensitive trigeminal neurons with only partial overlap. The present data indicate a novel mechanism for enhancing P2X3 receptor expression and function in trigeminal sensory neurons by CGRP via CREB phosphorylation. BDNF was an intermediate to extend the sensitizing effect of CGRP also to CGRP-insensitive neurons. This combinatorial action could serve as a powerful process to amplify and prolong pain mediated by P2X3 receptors.
The Differential Requirement for Cyclin-Dependent Kinase Activities Distinguishes Two Functions of Herpes Simplex Virus Type 1 ICP0

ABSTRACT Herpes simplex virus type 1 (HSV-1) ICP0 directs the degradation of cellular proteins associated with nuclear structures called ND10, a function thought to be closely associated with its broad transactivating activity. Roscovitine (Rosco), an inhibitor of cyclin-dependent kinases (cdks), inhibits the replication of HSV-1, HSV-2, human cytomegalovirus, varicella-zoster virus, and human immunodeficiency virus type 1 by inhibiting specific steps or activities of viral regulatory proteins, indicating the broad and pleiotropic effects that cdks have on the replication of these viruses. We previously demonstrated that Rosco inhibits the transactivating activity of ICP0. In the present study, we asked whether Rosco also affects the ability of ICP0 to direct the degradation of ND10-associated proteins. For this purpose, WI-38 cells treated with cycloheximide (CHX) were mock infected or infected with wild-type HSV-1 or an ICP0− mutant (7134). After release from the CHX block, the infections were allowed to proceed for 2 h in the presence or absence of Rosco at a concentration known to inhibit ICP0's transactivating activity. The cells were then examined for the presence of ICP0 and selected ND10-associated antigens (promyelocytic leukemia antigen [PML], sp100, hDaxx, and NDP55) by immunofluorescence. Staining for the ND10-associated antigens was detected in ≤20% of KOS-infected cells in the presence or absence of Rosco, demonstrating that Rosco-sensitive kinases are not required for ICP0's ability to direct the dispersal or degradation of these antigens. In contrast, >90% of 7134- and mock-infected cells stained positive for all ND10-associated antigens in the presence or absence of Rosco. Similar results were obtained with a non-ND10-associated antigen, DNA-PKcs, a known target of ICP0-directed degradation. The results of the PML and DNA-PKcs immunofluorescence studies correlated with a decrease in the levels of these proteins as determined by Western blotting. Thus, the differential requirement for Rosco-sensitive cdk activities distinguishes ICP0's ability to direct the dispersal or degradation of cellular proteins from its transactivating activity.
A Review of the Use of Practice Theory in Information Systems Research

Traditional theories are reaching their limits in explaining new phenomena of IT-enabled work practices. Practice theory is considered a contemporary and promising theoretical lens to overcome such limitations. This paper presents intermediate results from a review of practice theory use in IS research. Our review shows that IS scholars have increasingly become interested in practice theory. This concerns the understanding of how actors and materials are embedded in and enact patterns of social practice. It is a fundamentally different type of theory compared to traditional IS theories. Practice theory builds on non-dualist philosophy (tradition of European-continental philosophy), and proposes practical rationality (theory should be based on practice, not vice versa). Due to such properties, IS scholars are sometimes confused about the nature, philosophical roots, and general applicability of practice theory. In this paper, we discuss what practice theory is (central concepts), where practice theory comes from (intellectually, historically), in which areas (of IS research) it has been used, and where and how the use and development of practice theory in IS may be further improved going forward. This discussion is based on a review of seminal practice theory research and a structured review of mainstream IS outlets.
Identification, Localization, and Regulation of Expression of the UL24 Protein of Herpes Simplex Virus Type 1

ABSTRACT The UL24 gene of herpes simplex virus type 1 is conserved across many herpesviruses, but its protein product has not been identified. We expressed the UL24 gene in insect cells from a recombinant baculovirus and used the resulting protein to raise a rat antiserum. In immunoblotting experiments, this antiserum recognized a 30-kDa protein in lysates from infected cells. The identity of this species as UL24 was confirmed by using a virus encoding a truncated form of UL24. On the basis of biochemical fractionation of infected cells, UL24 appeared to be predominantly nucleus associated, especially at later times in infection. Although certain UL24 transcripts exhibit early kinetics, UL24 protein accumulated at later times in infection and levels were decreased sixfold in the presence of the viral DNA synthesis inhibitor phosphonoacetic acid; thus, UL24 was expressed with leaky-late kinetics. The entire UL24 open reading frame is encoded by mRNAs with two different 5′ ends. A mutation that eliminates the more abundant transcripts that originate at the first transcription start site resulted in a 10-fold reduction in the level of UL24 expressed but did not eliminate expression. Thus, the less abundant transcripts originating at the second transcription start site can evidently be translated, although transcripts originating at the first start site appear to be the major contributors to the expression of UL24. We conclude that UL24 is a bona fide herpes simplex virus type 1 protein that associates primarily with nuclei and whose expression is regulated at multiple levels.
Iron-Sulfur Cluster Biosynthesis

The biogenesis of iron-sulfur [Fe-S] clusters requires the coordinated delivery of both iron and sulfide. Sulfide is provided by cysteine desulfurases that use l-cysteine as sulfur source. So far, the physiological iron donor has not been clearly identified. CyaY, the bacterial ortholog of frataxin, an iron binding protein thought to be involved in iron-sulfur cluster formation in eukaryotes, is a good candidate because it was shown to bind iron. Nevertheless, no functional in vitro studies showing an involvement of CyaY in [Fe-S] cluster biosynthesis have been reported so far. In this paper we demonstrate for the first time a specific interaction between CyaY and IscS, a cysteine desulfurase participating in iron-sulfur cluster assembly. Analysis of the iron-loaded CyaY protein demonstrated a strong binding of Fe3+ and a weak binding of Fe2+ by CyaY. Biochemical analysis showed that the CyaY-Fe3+ protein corresponds to a mixture of monomer, intermediate forms (dimer-pentamers), and oligomers with the intermediate one corresponding to the only stable and soluble iron-containing form of CyaY. Using spectroscopic methods, this form was further demonstrated to be functional in vitro as an iron donor during [Fe-S] cluster assembly on the scaffold protein IscU in the presence of IscS and cysteine. All of these results point toward a link between CyaY and [Fe-S] cluster biosynthesis, and a possible mechanism for the process is discussed.
The Quest for Content: How User-Generated Links can Facilitate Online Exploration

Online content and products are presented as product networks, in which nodes are product pages linked by hyperlinks. These links are typically algorithmically induced recommendations based on aggregated data. Recently, websites have begun to offer social networks and user-generated links alongside the product network, creating a dual-network structure. The authors investigate the role of this dual-network structure in facilitating content exploration. They analyze YouTube's dual network and show that user pages have unique structural properties and act as content brokers. Next, the authors show that random rewiring of the product network cannot replicate this brokering effect. They present seven Internet studies in which participants browsing a YouTube-based website are exposed to different conditions of recommendations. The first set of studies shows that exposure to the dual network results in a more efficient (time to desirable outcome) and more effective (average product rating, overall satisfaction) exploration process. The next set of studies extends the previous ones to include dynamic structures, in which the network changes as a function of time or in response to participants' satisfaction. Furthermore, the results are replicated using data from another content site.
Shift-accumulator ALU centric JPEG2000 5/3 lifting based discrete wavelet transform architecture

This paper presents a novel (low arithmetic unit count) hardware architecture for performing lifting-based JPEG2000's 5/3 Discrete Wavelet Transform (DWT). The architecture is built around parallel Shift-Accumulator Arithmetic Logic Units (ALUs) which can encode (with implicit embedded extension) up to five levels of transformation. The proposed architecture, which consists of three adders, two subtractor-adders and five shifters, has a significantly lower hardware count compared to the architectures proposed by K. Andra et. al. (2002) and C-J. Lian et. al. (2001). In addition, the architecture has an efficient memory organisation, which uses lesser amount of embedded memory for processing and buffering. In this paper, we present the architecture and demonstrate that it closely adheres to the JPEG2000's specification while reducing the hardware requirements and hence area and power consumption.
Postsynaptic GABA(B) Receptors Contribute to the Termination of Giant Depolarizing Potentials in CA3 Neonatal Rat Hippocampus

During development, hippocampal CA3 network generates recurrent population bursts, so-called Giant Depolarizing Potentials (GDPs). GDPs are characterized by synchronous depolarization and firing of CA3 pyramidal cells followed by afterhyperpolarization (GDP-AHP). Here, we explored the properties of GDP-AHP in CA3 pyramidal cells using gramicidin perforated patch clamp recordings from neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of whether CA3 pyramidal cells fire action potentials (APs) or remain silent during GDPs. However, the amplitude of GDP-AHP increased with the number of APs the cells fired during GDPs. The reversal potential of the GDP-AHP was close to the potassium equilibrium potential. During voltage-clamp recordings, current-voltage relationships of the postsynaptic currents activated during GDP-AHP were characterized by reversal near the potassium equilibrium potential and inward rectification, similar to the responses evoked by the GABA(B) receptor agonists. Finally, the GABA(B) receptor antagonist CGP55845 strongly reduced GDP-AHP and prolonged GDPs, eventually transforming them to the interictal and ictal-like discharges. Together, our findings suggest that the GDP-AHP involves two mechanisms: (i) postsynaptic GABA(B) receptor activated potassium currents, which are activated independently on whether the cell fires or not during GDPs; and (ii) activity-dependent, likely calcium activated potassium currents, whose contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We propose that these two complementary inhibitory postsynaptic mechanisms cooperate in the termination of GDP.
Colossal Magnetoresistance and Phase Separation in Magnetic Semiconductors

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Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

Nusslock R, Almeida JRC, Forbes EE, Versace A, Frank E, LaBarbara EJ, Klein CR, Phillips ML. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disord 2012: 14: 249–260. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.
Novel Electrochemiluminescence Immunoassay Exclusively for Full‐length Parathyroid Hormone during Treatment with Cinacalcet for Secondary Hyperparathyroidism

A novel, electrochemiluminescence immunoassay that exclusively measures full‐length parathyroid hormone (PTH), called Elecsys PTH (1–84) assay, is currently under development for clinical use. We measured serum PTH levels using this novel assay, as well as the Elecsys Intact PTH assay and the Whole PTH immunoradiometric assay, in 53 hemodialysis patients who participated in a 52‐week clinical trial of cinacalcet. At baseline, serum PTH (1–84) levels measured with the Elecsys PTH (1–84) assay and those with the Whole PTH assay were comparable, and both values were significantly lower than Elecsys Intact PTH levels. After 52 weeks of cinacalcet treatment, Elecsys PTH (1–84) levels and Whole PTH levels decreased significantly by 56% and 60% from baseline, respectively. These results indicate that the Elecsys PTH (1–84) assay provides comparable data to the Whole PTH assay for monitoring parathyroid function in patients receiving hemodialysis. Introduction of this novel automated immunoassay would provide more widespread measurements of full‐length PTH (1–84) in clinical practice.
Word Alignment Based on Bilingual Bracketing

In this paper, an improved word alignment based on bilingual bracketing is described. The explored approaches include using Model-1 conditional probability, a boosting strategy for lexicon probabilities based on importance sampling, applying Parts of Speech to discriminate English words and incorporating information of English base noun phrase. The results of the shared task on French-English, Romanian-English and Chinese-English word alignments are presented and discussed.
Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors

Imatinib is used to treat chronic myelogenous leukemia (CML), but resistance develops in all phases of this disease. The purpose of the present study was to identify the mode of resistance of newly derived imatinib-resistant (IM-R) and PD166326-resistant (PD-R) CML cells. IM-R and PD-R clones exhibited an increase in viability and a decrease in caspase activation in response to various doses of imatinib and PD166326, respectively, as compared with parental K562 cells. Resistance involved neither mutations in BCR-ABL nor increased BCR-ABL, MDR1 or Lyn expression, all known modes of resistance. To gain insight into the resistance mechanisms, we used pangenomic microarrays and identified 281 genes modulated in parental versus IM-R and PD-R cells. The gene signature was similar for IM-R and PD-R cells, accordingly with the cross-sensitivity observed for both inhibitors. These genes were functionally associated with pathways linked to development, cell adhesion, cell growth, and the JAK-STAT cascade. Especially relevant were the increased expression of the tyrosine kinases AXL and Fyn as well as CD44 and HMGA2. Small interfering RNA experiments and pharmacologic approaches identified FYN as a candidate for resistance to imatinib. Our findings provide a comprehensive picture of the transcriptional events associated with imatinib and PD166326 resistance and identify Fyn as a new potential target for therapeutic intervention in CML. [Mol Cancer Ther 2009;8(7):1924–33]
Heat and Moisture Transfer Through Nonwoven Fabrics

The geometric moisture diffusivity model developed by this research indicates that fiber volume fraction and shape coefficient are the most important structural parameters affecting water vapor diffusivity through nonhydrophilic nonwoven fabrics. Water vapor diffusivity decreases with increasing fiber volume fraction and decreases as the flatness of the fiber cross section increases. Although structural properties such as fiber fineness and fabric thickness affect optical porosity, their effect on water vapor diffusivity through nonhygroscopic nonwoven materials is small.
Edge Influence on Forest Structure and Composition in Fragmented Landscapes

Abstract: Although forest edges have been studied extensively as an important consequence of fragmentation, a unifying theory of edge influence has yet to be developed. Our objective was to take steps toward the development of such a theory by (1) synthesizing the current knowledge of patterns of forest structure and composition at anthropogenically created forest edges, (2) developing hypotheses about the magnitude and distance of edge influence that consider the ecological processes influencing these patterns, and (3) identifying needs for future research. We compiled data from 44 published studies on edge influence on forest structure and composition in boreal, temperate, and tropical forests. Abiotic and biotic gradients near created forest edges generate a set of primary responses to edge creation. Indirect effects from these primary responses and the original edge gradient perpetuate edge influence, leading to secondary responses. Further changes in vegetation affect the edge environment, resulting in ongoing edge dynamics. We suggest that the magnitude and distance of edge influence are a direct function of the contrast in structure and composition between adjacent communities on either side of the edge. Local factors such as climate, edge characteristics, stand attributes, and biotic factors affect patch contrast. Regional factors define the context within which to assess the ecological significance of edge influence (the degree to which the edge habitat differs from interior forest habitat). Our hypotheses will help predict edge influence on structure and composition in forested ecosystems, an important consideration for conservation. For future research on forest edges in fragmented landscapes, we encourage the testing of our hypotheses, the use of standardized methodology, complete descriptions of study sites, studies on other types of edges, synthesis of edge influence on different components of the ecosystem, and investigations of edges in a landscape context.
Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study)

Background Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. Objective To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Methods Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Results Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. Conclusions We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years.