Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrathecal Injection of the &sfgr;1 Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression during the Induction Phase of Rodent Neuropathic Pain

Background: Selective blockade of spinal &sfgr;1 receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. Methods: Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-d-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. Results: BD1047 administered on postoperative days 0–5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-d-aspartate receptor subunit 1 expression and phosphorylation. Conclusions: These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.
Extrachromosomal DNA transformation of Caenorhabditis elegans

DNA was introduced into the germ line of the nematode Caenorhabditis elegans by microinjection. Approximately 10% of the injected worms gave rise to transformed progeny. Upon injection, supercoiled molecules formed a high-molecular-weight array predominantly composed of tandem repeats of the injected sequence. Injected linear molecules formed both tandem and inverted repeats as if they had ligated to each other. No worm DNA sequences were required in the injected plasmid for the formation of these high-molecular-weight arrays. Surprisingly, these high-molecular-weight arrays were extrachromosomal and heritable. On average 50% of the progeny of a transformed hermaphrodite still carried the exogenous sequences. In situ hybridization experiments demonstrated that approximately half of the transformed animals carried foreign DNA in all of their cells; the remainder were mosaic animals in which some cells contained the exogenous sequences while others carried no detectable foreign DNA. The presence of mosaic and nonmosaic nematodes in transformed populations may permit detailed analysis of the expression and function of C. elegans genes.
Global discovery of small RNAs in Yersinia pseudotuberculosis identifies Yersinia-specific small, noncoding RNAs required for virulence

A major class of bacterial small, noncoding RNAs (sRNAs) acts by base-pairing with mRNAs to alter the translation from and/or stability of the transcript. Our laboratory has shown that Hfq, the chaperone that mediates the interaction of many sRNAs with their targets, is required for the virulence of the enteropathogen Yersinia pseudotuberculosis. This finding suggests that sRNAs play a critical role in the regulation of virulence in this pathogen, but these sRNAs are not known. Using a deep sequencing approach, we identified the global set of sRNAs expressed in vitro by Y. pseudotuberculosis. Sequencing of RNA libraries from bacteria grown at 26 °C and 37 °C resulted in the identification of 150 unannotated sRNAs. The majority of these sRNAs are Yersinia specific, without orthologs in either Escherichia coli or Salmonella typhimurium. Six sRNAs are Y. pseudotuberculosis specific and are absent from the genome of the closely related species Yersinia pestis. We found that the expression of many sRNAs conserved between Y. pseudotuberculosis and Y. pestis differs in both timing and dependence on Hfq, suggesting evolutionary changes in posttranscriptional regulation between these species. Deletion of multiple sRNAs in Y. pseudotuberculosis leads to attenuation of the pathogen in a mouse model of yersiniosis, as does the inactivation in Y. pestis of a conserved, Yersinia-specific sRNA in a mouse model of pneumonic plague. Finally, we determined the regulon controlled by one of these sRNAs, revealing potential virulence determinants in Y. pseudotuberculosis that are regulated in a posttranscriptional manner.
A Novel Two-pore Domain K+ Channel, TRESK, Is Localized in the Spinal Cord*

To find a novel human ion channel gene we have executed an extensive search by using a human genome draft sequencing data base. Here we report a novel two-pore domain K+ channel, TRESK (TWIK-related spinal cord K+ channel). TRESK is coded by 385 amino acids and shows low homology (19%) with previously characterized two-pore domain K+ channels. However, the most similar channel is TREK-2 (two-pore domain K+ channel), and TRESK also has two pore-forming domains and four transmembrane domains that are evolutionarily conserved in the two-pore domain K+ channel family. Moreover, we confirmed that TRESK is expressed in the spinal cord. Electrophysiological analysis demonstrated that TRESK induced outward rectification and functioned as a background K+ channel. Pharmacological analysis showed TRESK to be inhibited by previously reported K+ channel inhibitors Ba2+, propafenone, glyburide, lidocaine, quinine, quinidine, and triethanolamine. Functional analysis demonstrated TRESK to be inhibited by unsaturated free fatty acids such as arachidonic acid and docosahexaenoic acid. TRESK is also sensitive to extreme changes in extracellular and intracellular pH. These results indicate that TRESK is a novel two-pore domain K+ channel that may set the resting membrane potential of cells in the spinal cord.
Structural Adaptations in a Membrane Enzyme That Terminates Endocannabinoid Signaling

Cellular communication in the nervous system is mediated by chemical messengers that include amino acids, monoamines, peptide hormones, and lipids. An interesting question is how neurons regulate signals that are transmitted by membrane-embedded lipids. Here, we report the 2.8 angstrom crystal structure of the integral membrane protein fatty acid amide hydrolase (FAAH), an enzyme that degrades members of the endocannabinoid class of signaling lipids and terminates their activity. The structure of FAAH complexed with an arachidonyl inhibitor reveals how a set of discrete structural alterations allows this enzyme, in contrast to soluble hydrolases of the same family, to integrate into cell membranes and establish direct access to the bilayer from its active site.
Effects of Substituting Granulin or a Granulin-Polyhedrin Chimera for Polyhedrin on Virion Occlusion and Polyhedral Morphology in Autographa californicaMultinucleocapsid Nuclear Polyhedrosis Virus

ABSTRACT Substitution of granulin from the Trichoplusia nigranulosis virus (TnGV) for polyhedrin of the Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) yielded a few very large (2 to 5 μm) cuboidal inclusions in the cytoplasm and nucleus of infected cells. These polyhedra lacked the beveled edges characteristic of wild-type AcMNPV polyhedra, contained fractures, and occluded few virions. Placing a nuclear localization signal (KRKK) in granulin directed more granulin to the nucleus and resulted in more structurally uniform cuboidal inclusions in which no virions were observed. A granulin-polyhedrin chimera produced tetrahedral occlusions with more virions than granulin inclusions but many fewer than wild-type polyhedra. Despite the unusual structure of the granulin and granulin-polyhedrin inclusions, they interacted with AcMNPV p10 fibrillar structures and electron-dense spacers that are precursors of the polyhedral calyx. The change in inclusion shape obtained with the granulin-polyhedrin chimera demonstrates that the primary amino acid sequence affects occlusion body shape, but the large cuboidal inclusions formed by granulin indicate that the amino acid sequence is not the only determinant. The failure of granulin or the granulin-polyhedrin chimera to properly occlude AcMNPV virions suggests that specific interactions occur between polyhedrin and other viral proteins which facilitate normal virion occlusion and occlusion body assembly and shape in baculoviruses.
Interactions Within Susceptible Hosts Drive Establishment of Genetically Distinct Variants of an Insect-Borne Pathogen

ABSTRACT Coinfections are common, leading to pathogen interactions during transmission and establishment in a host. However, few studies have tested the relative strengths of pathogen interactions in vectors and hosts that determine the outcome of infection. We tested interactions between two genetically distinct variants of the mealybug-transmitted Grapevine leafroll-associated virus 3. The transmission efficiency of each variant in single variant inoculations by two vector species was determined. The effects of vector species, a coinfected source, and simultaneous inoculation from multiple hosts to one host on variant establishment were examined. Within-vector interactions could have a role in transmission from hosts containing mixed infections, but not when vectors were moved from separate singly infected source plants to a single recipient plant. The invasive Planococcus ficus (Signoret) was a more efficient vector than Pseudococcus viburni (Signoret). Transmission efficiency of the two variants did not differ in single variant inoculations. Overall infections were the same whether from singly or coinfected source plants. In mixed inoculations, establishment of one variant was reduced. Mixed inoculations from two singly infected source plants resulted in fewer mixed infections than expected by chance. Therefore, the observed outcome was determined subsequent to host inoculation rather than in the vector. The outcome may be due to resource competition between pathogens. Alternatively apparent competition may be responsible; the pathogens' differential ability to overcome host defenses and colonize the host may determine the final outcome of new infections. Detailed knowledge of interactions between pathogens during transmission and establishment could improve understanding and management of disease spread.
Endothelial progenitor cells enhance blood–brain barrier permeability in subacute stroke

Objective To study the association among endothelial progenitor cells (EPCs), subacute blood–brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome. Methods We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at p < 0.05. Results We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816–0.986; p = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway. Conclusions The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke.
Stability analysis and Hopf bifurcation in a modified Leslie-Gower scheme prey predator system

A stage structured prey predator system with modified Leslie-Gower scheme is presented, where both maturation delay for prey and gestation delay for predator are considered. By analyzing the associated characteristic transcendental equation, combined dynamic effects of stage structure and double time delays on population dynamics are discussed, and regions of local stability around interior equilibrium are studied. According to Hopf bifurcation theorem for functional differential equations, existence of Hopf bifurcation around interior equilibrium is investigated as local stability switches. Existence of global continuation of periodic solutions bifurcating from the interior equilibrium is discussed by using a global Hopf bifurcation theorem for functional differential equations. Numerical simulations are provided to show consistency with theoretical analysis.
NK/T-Cell Lymphoma of the Nasal Cavity Causing Contralateral Dacryoadenitis

Abstract Purpose: To report a case of NK/T-cell lymphoma of the nasal cavity with contralateral lacrimal gland involvement. Methods: Observational case report. Results: A 39-year-old woman with a 5-month history of right fungal rhinosinusitis was referred to our hospital. A nasal mucosal biopsy performed before referral was consistent with Aspergillus sp. Despite surgical and parenteral antifungal treatment, the symptoms continued to deteriorate. On admission, the ophthalmic evaluation showed inflammation over the left lacrimal gland area. The fundus examination revealed bilateral subretinal infiltration. Computed tomography scans of the orbits and sinuses showed mucosal thickening of the right nasal mucosa and sinuses. There was heterogeneous enhancement and infiltration of the left lacrimal gland. Lacrimal gland biopsy and repeated biopsies of the nasal cavity and sinus tissue were performed. Immunohistopathology of the lacrimal glands and nasal mucosa showed extranodal nasal-type NK/T-cell lymphoma. The patient was treated with cyclophosphamide, vincristine, adriamycin, prednisolone (3 cycles), and intrathecal methotrexate. The patient developed sepsis and died 2 months after initiation of chemotherapy. Conclusion: Dacryoadenitis can be a clinical manifestation of NK/T-cell lymphoma. To our knowledge, this is the first reported case of nasal NK/T-cell lymphoma with contralateral dacryoadenitis.
Thrombopoietic potential and serial repopulating ability of murine hematopoietic stem cells constitutively expressing interleukin 11.

Based on transplantation studies with bone marrow cultured under various conditions, a role of interleukin 11 (IL-11) in the self-renewal and/or the differentiation commitment of hematopoietic stem cells has been indicated. To better evaluate the in vivo effects of IL-11 on stem/progenitor cell biology, lethally irradiated mice were serially transplanted with bone marrow cells transduced with a defective retrovirus, termed MSCV-mIL-11, carrying the murine IL-11 (mIL-11) cDNA and the bacterial neomycin phosphotransferase (neo) gene. High serum levels (i.e., > 1 ng/ml) of mIL-11 in all (20/20) primary and 86% (12/14) of secondary long-term reconstituted mice, as well as 86% (12/14) of tertiary recipients examined at 6 weeks posttransplant, demonstrated persistence of vector expression subsequent to transduction of bone marrow precursors functionally definable as totipotent hematopoietic stem cells. In agreement with results obtained with human IL-11 in other myeloablation models, ectopic mIL-11 expression accelerated recovery of platelets, neutrophils, and, to some extent, total leukocytes while preferentially increasing peripheral platelet counts in fully reconstituted mice. When analyzed 5 months posttransplant, tertiary MSCV-mIL-11 recipients had a significantly greater percentage of G418-resistant colony-forming cells in their bone marrow compared with control MSCV animals. Collectively, these data show that persistent stimulation of platelet production by IL-11 is not detrimental to stem cell repopulating ability; rather, they suggest that IL-11 expression in vivo may have resulted in enhanced maintenance of the most primitive hematopoietic stem cell compartment. The prolonged expression achieved by the MSCV retroviral vector, despite the presence of a selectable marker, contrasts with the frequent transcriptional extinction observed with other retroviral vectors carrying two genes. These findings have potentially important implications for clinical bone marrow transplantation and gene therapy of the hematopoietic system.
Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in Saccharomyces cerevisiae

We cloned GDH2, the gene that encodes the NAD-linked glutamate dehydrogenase in the yeast Saccharomyces cerevisiae, by purifying the enzyme, making polyclonal antibodies to it, and using the antibodies to screen a lambda gt11 yeast genomic library. A yeast strain with a deletion-disruption allele of GDH2 which replaced the wild-type gene grew very poorly with glutamate as a nitrogen source, but growth improved significantly when the strain was also provided with adenine or other nitrogenous compounds whose biosynthesis requires glutamine. Our results indicate that the NAD-linked glutamate dehydrogenase catalyzes the major, but not sole, pathway for generation of ammonia from glutamate. We also isolated yeast mutants that lacked glutamate synthase activity and present evidence which shows that normally NAD-linked glutamate dehydrogenase is not involved in glutamate biosynthesis, but that if the enzyme is overexpressed, it may function reversibly in intact cells.
Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific β1 Integrins*

Translocation of conventional protein kinases C (PKCs) to the plasma membrane leads to their specific association with transmembrane-4 superfamily (TM4SF; tetraspanin) proteins (CD9, CD53, CD81, CD82, and CD151), as demonstrated by reciprocal co-immunoprecipitation and covalent cross-linking experiments. Although formation and maintenance of TM4SF-PKC complexes are not dependent on integrins, TM4SF proteins can act as linker molecules, recruiting PKC into proximity with specific integrins. Previous studies showed that the extracellular large loop of TM4SF proteins determines integrin associations. In contrast, specificity for PKC association probably resides within cytoplasmic tails or the first two transmembrane domains of TM4SF proteins, as seen from studies with chimeric CD9 molecules. Consistent with a TM4SF linker function, only those integrins (α3β1, α6β1, and a chimeric “X3TC5” α3 mutant) that associated strongly with tetraspanins were found in association with PKC. We propose that PKC-TM4SF-integrin structures represent a novel type of signaling complex. The simultaneous binding of TM4SF proteins to the extracellular domains of the integrin α3 subunit and to intracellular PKC helps to explain why the integrin α3 extracellular domain is needed for both intracellular PKC recruitment and PKC-dependent phosphorylation of the α3 integrin cytoplasmic tail.
Eating habits, knowledge about cancer prevention and the HPLP scale in Turkish adolescents.

BACKGROUND Nutritional status and healthy lifestyle are important factors not only in cancer etiology but also for prevention efforts. A good nutritional status contributes to a healthy life with high economic, social and cultural level. Unhealthy eating habits are part of risky behavior seen from adolescence. The present study was therefore carried out to determine eating habits, level of knowledge about cancer prevention and behavior of a group of adolescents. METHODS Data were collected using questionnaire covering eating habits and knowledge of adolescents on prevention from cancer, and special scale (HPLP) to determine the related behavior. Three hundred sixty six of 390 students volunteered for study. RESULTS Eating habits and the level of cancer prevention knowledge were similar for both genders, except for the exercise issue. The mean total points of adolescents in the Health Promotion Behavior and Subscales was 113,63. While spiritual growth had the highest score in HPLP subscale, exercise had a minimal score. Exercise was the only HPLP subscale with a statistically significant difference between male and female genders. CONCLUSIONS Although they have some information, the adolescents surveyed did not have preventive skills relative to their practical life. In general in order to ensure cancer prevention and a healthy life style social, cultural and sportive activities should be encouraged and educational programmes supporting these goals should be designed and applied for all stages of life, starting in early childhood.
Parallel processing and parallel algorithms - theory and computation

From the Publisher: Parallel processing is a fast-growing technology that dominates many areas of computer science and engineering. This book progresses from theory to computation, exploring the fundamentals of parallelism and the relationship between parallel programming approaches, algorithms, and architectures. "This book is suitable for advanced undergraduate and first-year graduate students in computer science, as well as researchers in the area.
Social Media and Online Attention as an Early Measure of the Impact of Research in Solid Organ Transplantation

Introduction Traditional measures of the impact of published research, such as citation counts, are limited to measuring academic impact. The use of social media and other online tools as alternative measures of research impact is gaining popularity and used by leading medical journals. Methods MEDLINE was searched for articles published with subject headings relating to solid organ transplantation between August 1, 2011, and July 31, 2012. Citation data were retrieved from SCOPUS, and statistics regarding mentions in social media, social bookmarking sites, news outlets, and expert recommendation sites were retrieved from the data at www.altmetric. com. Data were analyzed for associations between alternative metric data and citation rates. Results The search retrieved 6,981 publications. Sixty-six percent of the articles had at least one citation. Mentions in social media were 19.3%, 13.1% had social bookmarks, 0.9% had expert recommendations, and online news outlets picked up eight articles. Significantly higher citation rates were associated with mention in social media, expert recommendation, social bookmarking, and for articles identified as meta-analyses, multicenter studies, randomized controlled trials, and reviews (all P<0.001). The odds of an article being highly cited were significantly increased by a mention in social media (odds ratio, 2.58; P<0.001). Qualitative analysis suggests that article topics discussed on social media are more likely to relate to the more controversial and emotive areas of transplantation. Discussion Social media and online attention act as early predictors of the impact of transplant research as measured by later citation rate. Blogging and expert recommendation, in particular, are associated with higher citation rates.