Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabotropic Glutamate Receptor 5 Modulates Nociceptive Plasticity via Extracellular Signal-Regulated Kinase–Kv4.2 Signaling in Spinal Cord Dorsal Horn Neurons

Metabotropic glutamate receptors (mGluRs) play important roles in the modulation of nociception. The group I mGluRs (mGlu1 and mGlu5) modulate nociceptive plasticity via activation of extracellular signal-regulated kinase (ERK) signaling. We reported recently that the K+ channel Kv4.2 subunit underlies A-type K+ currents in the spinal cord dorsal horn and is modulated by the ERK signaling pathway. Kv4.2-mediated A-type currents are important determinants of dorsal horn neuronal excitability and central sensitization that underlies hypersensitivity after tissue injury. In the present study, we demonstrate that ERK-mediated phosphorylation of Kv4.2 is downstream of mGlu5 activation in spinal cord dorsal horn neurons. Activation of group I mGluRs inhibited Kv4.2-mediated A-type K+ currents and increased neuronal excitability in dorsal horn neurons. These effects were mediated by activation of mGlu5, but not mGlu1, and were dependent on ERK activation. Analysis of Kv4.2 phosphorylation site mutants clearly identified S616 as the residue responsible for mGlu5–ERK-dependent modulation of A-type currents and excitability. Furthermore, nociceptive behavior induced by activation of spinal group I mGluRs was impaired in Kv4.2 knock-out mice, demonstrating that, in vivo, modulation of Kv4.2 is downstream of mGlu5 activation. Altogether, our results indicate that activation of mGlu5 leads to ERK-mediated phosphorylation and modulation of Kv4.2-containing potassium channels in dorsal horn neurons. This modulation may contribute to nociceptive plasticity and central sensitization associated with chronic inflammatory pain conditions.
Inequality and Insurgency: A Statistical Study of South Vietnam

Tocqueville referred to the behavior of the French peasantry during the Revolution as a wonder of history. The centers of revolution, he noted, were the very districts in which social reform and progress had been most visible, whereas resistance to revolution sprang up in areas where the old order had been most completely retained.
Walking in the neighbourhood: Performing social citizenship in dementia

The proliferation of community-based activity programs for people with dementia suggests an appetite for new approaches to support quality of life and well-being for this population. Such groups also have potential to promote social citizenship, although this remains poorly understood. This article presents findings from a subset of data from an ethnographic study of a community-based program for people with young onset dementia; it focuses on Paul’s Club and the experiences of 12–15 members who are physically healthy, with moderate to moderately severe dementia. Analysis suggests how aspects of social citizenship are constructed and revealed through the Club’s everyday practice of walking in the neighbourhood. Three major themes emerged: Keeping the focus off dementia; Creating a place of belonging; and Claiming a place in the community. How the group balances consideration of members’ vulnerability and agency is discussed, and the article concludes with implications for future practice and research initiatives.
Mycobacterium caprae infection in humans

Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, causes tuberculosis (TB) in man and animals. Some features distinguish M. caprae from its epidemiological twin, Mycobacterium bovis: M. caprae is evolutionarily older, accounts for a smaller burden of zoonotic TB and is not globally distributed, but primarily restricted to European countries. M. caprae occurs only in a low proportion of human TB cases and this proportion may even decrease, if progress toward eradication of animal TB in Europe continues. So why bother, if M. caprae is not an enigma for diagnostic TB tests and if resistance against first-line drugs is a rarity with M. caprae? This ‘European’ pathogen of zoonotic TB asks interesting questions regarding the definition of a species. The latter, seemingly only an academic question, particularly requires and challenges the collaboration between human and veterinary medicine.
Favorable outcome after 1-year treatment of childhood T-cell lymphoma/T-cell acute lymphoblastic leukemia.

BACKGROUND For T-malignancies in children a poor prognosis is reported. In these malignancies a combination of lymphoma and leukemia is commonly seen at presentation and most patients are treated according to protocols for acute lymphoblastic leukemia (ALL). These protocols are often designed for the majority of ALL cases, i.e., progenitor-B-ALL. In pediatric lymphoblastic non-Hodgkin's lymphoma without bone marrow infiltration various protocols have been used. The most frequently reported regimens show variable survival rates between 40 and 75%. PATIENTS AND METHODS From 1989 we have treated 32 consecutive patients with T-cell malignancies, irrespective of localization, with a protocol consisting of a 4-agent induction treatment followed by high doses of methotrexate, and cytosine-arabinoside and intensified bleomycin, adriamycin, cyclophosphamide, vin cristin, prednisone (BACOP) courses. Treatment duration for each patient was 1 year. Twenty-one of the 32 patients had stage IV disease. Follow-up ranged from 1.6 to 7.6 years (median 4.2 years). RESULTS Overall event-free survival (EFS) was 72%, while in those with stage IV disease it was 67%. No therapy-related deaths occurred. Neither stage, initial leukocyte value, mediastinal involvement, bone marrow involvement, nor the presence of CD1, CD3, CD4, CD8, or CD10 epitopes was prognostically significant. Evaluation of toxicity revealed a minimal decrease of carbon monoxide diffusion and cardiac shortening fraction. CONCLUSION A relatively short but intensive chemotherapy can be used in T-cell malignancies. The EFS is satisfying, but larger studies are needed.
Skills, Tasks, and Occupational Choice

This paper seeks to quantify two important sources of workers’ wage growth - skill accumulation and occupational human capital - by constructing and estimating a structural occupational choice model. Accumulated skills are assumed to be more transferable between jobs that utilize similar tasks. Unlike previous work, I allow task usage to vary not only by occupation, but also by hierarchical level within an occupation. Furthermore, I separately estimate the impacts of occupation-specic and occupationlevel specic
Contractual Farming Arrangements, Quality Control, Incentives, and Distribution Failure in Kenya's Smallholder Horticulture: A Multivariate Probit Analysis

ABSTRACT With the rapid growth of horticultural value chains, the use of contractual farming arrangements, strategies of quality control (farm audits/crop rejections), pricing incentives, and distribution efficiencies (crop collection arrangements) are increasingly breaking market barriers, for example, private standards, certification, traceability, and supply reliability in developing countries. Cognizant of market access, farm produce value, sustainable production, and reduction of postharvest losses, this paper investigated whether farm size, schooling, producer price, farm visits, and social capital networks condition these strategies. The results show that use of written contracts is conditioned by farm sizes, more extension, and number of producer groups (PGs) while farm certification is positively predicted by farm sizes, more extension, number of sellers in the village and seasons with the same buyer. However, certification is less responsive to producer prices. Crop rejections are predicted to be less depending on a farmer's education, number of PGs, and the producer price but are more likely to increase the more the number of sellers. Further, the results show that a forward pricing incentive is highly correlated with higher producer prices, more extension, and number of seasons with the same buyer. Finally, uncollected produce at harvest is likely to decrease with farm sizes, more education and extension, higher producer price, number of PGs, and seasons with the same buyer but is more likely to increase the higher the number of sellers. Implications are made. [EconLit citations: L14; Q13].
Variants of Base Excision Repair Genes MUTYH, PARP1 and XRCC1 in Alzheimer's Disease Risk

Background: Many clinical studies have shown that oxidative stress pathways and the efficiency of the oxidative DNA damage base excision repair (BER) system are associated with the pathogenesis of Alzheimer's disease (AD). Reduced BER efficiency may result from polymorphisms of BER-related genes. In the present study, we examine whether single nucleotide polymorphisms (SNPs) of BER genes are associated with increased risk of AD. Methods: SNP genotyping was carried out on DNA isolated from peripheral blood mononuclear cells obtained from 120 patients with AD and 110 healthy volunteers. Samples were genotyped for the presence of BER-related SNPs, i.e. XRCC1-rs1799782, rs25487; MUTYH-rs3219489, and PARP1-rs1136410. Results: We found a positive association between AD risk and the presence of G/A genotype variant of the XRCC1 rs25487 polymorphism [odds ratio (OR) = 3.762, 95% CI: 1.793-7.891]. The presence of the A/A genotype of this polymorphism reduced the risk of AD (OR = 0.485, 95% CI: 0.271-0.870). In cases of the PARP1 gene rs1136410 polymorphism, we observed that the T/C variant increases (OR = 4.159, 95% CI: 1.978-8.745) while the T/T variant reduces risk (OR = 0.240, 95% CI: 0.114-0.556) of AD. Conclusions: We conclude that BER gene polymorphisms may play an important role in the etiology of AD. Diagnosing the presence or absence of particular genetic variants may be an important marker of AD. Further research on a larger population is needed. There is also a need to examine polymorphisms of other BER in the context of AD risk.
Automatic Bone Age Measurement Using Computerized Image Analysis

In 1992 we described a computer-assisted method for assigning Tanner-Whitehouse RUS skeletal maturity scores to hand-wrist radiographs. An operator positions each epiphysis in turn beneath a video camera, views the image on the computer screen and corrects the position of the radiograph by matching to templates of the TW stages displayed on the screen. The process is then automatic; the computer, not the operator, rates the bone. The image is digitized and then represented by a large number of mathematical coefficients. These coefficients are then compared to those generated by each stage of the TW standards, and the closest match is sought. Since the comparison is quantitative the system produces continuous stage scores instead of the old discrete ones such as B, C, D, etc. Thus in longitudinal data a much smoother progression of skeletal maturity scores with age is achieved. The reliability of the computer-assisted skeletal age score (CASAS) is considerably greater than that of the usual manual method. Differences between duplicate readings of a bone by a single observer average about 0.25 stage, and reach 1.0 stage or more only in about 3% of instances, compared with 15-20% characteristic of manual ratings.
Monoclonal antibody-defined epitope map of expressed rubella virus protein domains

An expanded library of murine monoclonal antibodies (MAbs) was generated by infecting BALB/C mice with the Therien strain of rubella virus (RV) and selecting secreting hybrids by enzyme-linked immunosorbent assay (ELISA) using purified virion targets. A panel of plasmids containing specified RV cDNA fragments was also constructed by using a variety of strategies with pGE374- and pGE374-derived expression vectors. Hybrid RecA-RV-beta-galactosidase (LacZ)- or RecA-RV-truncated LacZ-containing proteins collectively representing the entire open reading frame of the structural proteins of RV were overexpressed in Escherichia coli. Bacterial lysates were then probed by ELISA with selected MAbs and by immunoblot following separation by electrophoresis under denaturing conditions. With this approach, MAbs that appeared to react with linear determinants defined epitopes localized within the following domains: MAbs C-1, C-2, and C-8 bind epitopes within the predicted amino-terminal 21 amino acids of the capsid region C9 to C29; MAb C-9 binds to a domain bounded by C64 and C97; MAbs E2-1 through E2-6 bind to the E2 glycoprotein backbone region from E2(1) to E2(115); MAbs E1-18 and E1-20 bind to the E1 glycoprotein region from E1(202) to E1(283). MAb E1-18 neutralizes RV infectivity; MAb E1-20 neutralizes infectivity and modestly inhibits hemagglutination. Analyses with selected synthetic peptides have confirmed several of the molecular domains deduced with the expressed proteins. These plasmid constructions and peptides have proven useful in beginning to unravel the molecular organization of several antigenic sites of this human pathogen.
The Core of Aggregative Cooperative Games with Externalities

Abstract This paper analyzes cooperative games with externalities generated by aggregative normal form games. We construct the characteristic function of a coalition S for various coalition formation rules and we examine the corresponding cores. We first show that the γ$$\gamma $$-core is non-empty provided each player’s payoff decreases in the sum of all players’ strategies. We generalize this result by showing that if S believes that the outside players form at least l(s)=n−s−(s−1)$$l(s) = n - s - (s - 1)$$ coalitions, then S has no incentive to deviate from the grand coalition and the corresponding core is non-empty (where n is the number of players in the game and s the number of members of S). We finally consider the class of linear aggregative games (Martimort and Stole 2010). In this case, if S believes that the outsiders form at least lˆ(s)=ns−1$$\widehat l(s) = {n \over s} - 1$$ coalitions [where lˆ(s)≤l(s)$$\widehat l(s) \le l(s)$$] a core non-emptiness result holds again.
Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients.

PURPOSE To evaluate the prognostic significance of DNA mismatch repair (MMR) status in a large series of stage II and III colorectal cancer patients. The relationship among MMR status, adjuvant chemotherapy, and clinical outcome was also investigated. PATIENTS AND METHODS The study included 718 patients with colorectal adenocarcinoma (393 stage II and 325 stage III) who underwent curative surgical resection. MMR status was determined by immunohistochemical analysis of MLH1 and MSH2 expression. Microsatellite instability (MSI) was assessed in 363 patients using mononucleotide and dinucleotide markers. RESULTS One hundred fourteen (15.9%) carcinomas showed abnormal MMR protein (MMRP) expression (96 MLH1 negative and 18 MSH2 negative) and were classified as MMRP negative, whereas 604 tumors demonstrated normal MLH1/MSH2 immunoreactivity (MMRP positive). MLH1/MSH2 expression was closely related to MSI status (P < .001) and several clinicopathologic features. Patients with MMRP-negative carcinomas demonstrated a marked reduction in the risk of cancer-related death with respect to patients with MMRP-positive tumors (hazard ratio, 0.2579; 95% CI, 0.1289 to 0.5159). A better clinical outcome for patients with MMRP-negative tumors was observed in both stage II (P = .0006) and stage III (P = .0052) disease. In stage III disease, the survival advantage conferred by MMRP-negative tumors was more evident among patients treated with surgery alone than among patients who received adjuvant chemotherapy. A nonsignificant trend for survival benefit from adjuvant chemotherapy was observed among patients with MMRP-positive carcinomas but not among those with MMRP-negative carcinomas. CONCLUSION Immunohistochemical testing for MLH1/MSH2 expression provides useful prognostic information for the management of stage II and III colorectal cancer patients.
Characterization of the Influence of Semen-Derived Enhancer of Virus Infection on the Interaction of HIV-1 with Female Reproductive Tract Tissues

ABSTRACT The majority of human immunodeficiency virus type 1 (HIV-1) transmission events occur in women when semen harboring infectious virus is deposited onto the mucosal barriers of the vaginal, ectocervical, and endocervical epithelia. Seminal factors such as semen-derived enhancer of virus infection (SEVI) fibrils were previously shown to greatly enhance the infectivity of HIV-1 in cell culture systems. However, when SEVI is intravaginally applied to living animals, there is no effect on vaginal transmission. To define how SEVI might function in the context of sexual transmission, we applied HIV-1 and SEVI to intact human and rhesus macaque reproductive tract tissues to determine how it influences virus interactions with these barriers. We show that SEVI binds HIV-1 and sequesters most virions to the luminal surface of the stratified squamous epithelium, significantly reducing the number of virions that penetrated the tissue. In the simple columnar epithelium, SEVI was no longer fibrillar in structure and was detached from virions but allowed significantly deeper epithelial virus penetration. These observations reveal that the action of SEVI in intact tissues is very different in the anatomical context of sexual transmission and begin to explain the lack of stimulation of infection observed in the highly relevant mucosal transmission model. IMPORTANCE The most common mode of HIV-1 transmission in women occurs via genital exposure to the semen of HIV-infected men. A productive infection requires the virus to penetrate female reproductive tract epithelial barriers to infect underlying target cells. Certain factors identified within semen, termed semen-derived enhancers of virus infection (SEVI), have been shown to significantly enhance HIV-1 infectivity in cell culture. However, when applied to the genital tracts of living female macaques, SEVI did not enhance virus transmission. Here we show that SEVI functions very differently in the context of intact mucosal tissues. SEVI decreases HIV-1 penetration of squamous epithelial barriers in humans and macaques. At the mucus-coated columnar epithelial barrier, the HIV-1/SEVI interaction is disrupted. These observations suggest that SEVI may not play a significant stimulatory role in the efficiency of male-to-female sexual transmission of HIV.
Diffusion tensor imaging findings suggestive of white matter alterations in a canine model of mucopolysaccharidosis type I

Purpose We investigated fractional anisotropy (FA) and radial diffusivity (RD) in a canine model of mucopolysaccharidosis (MPS). We hypothesized that canines affected with MPS would exhibit decreased FA and increased RD values when compared to unaffected canines, a trend that has been previously described in humans with white matter diseases. Methods Four unaffected canines and two canines with MPS were euthanized at 18 weeks of age. Their brains were imaged using high-resolution diffusion tensor imaging (DTI) on a 7T small-animal magnetic resonance imaging system. One hundred regions of interest (ROIs) were placed in each of four white matter regions: anterior and posterior regions of the internal capsule (AIC and PIC, respectively) and anterior and posterior regions of the centrum semiovale (ACS and PCS, respectively). For each specimen, average FA and RD values and associated 95% confidence intervals were calculated from 100 ROIs for each brain region. Results For each brain region, the FA values in MPS brains were consistently lower than in unaffected dogs, and the RD values in MPS dogs were consistently higher, supporting our hypothesis. The confidence intervals for affected and unaffected canines did not overlap in any brain region. Conclusion FA and RD values followed the predicted trend in canines affected with MPS, a trend that has been described in humans with lysosomal storage and dysmyelinating diseases. These findings suggest that the canine model parallels MPS in humans, and further indicates that quantitative DTI analysis of such animals may be suitable for future study of disease progression and therapeutic response in MPS.
Identification of the Human Rhinovirus Serotype 1A Binding Site on the Murine Low-Density Lipoprotein Receptor by Using Human-Mouse Receptor Chimeras

ABSTRACT Human rhinovirus serotype 1A (HRV1A) binds more strongly to the mouse low-density lipoprotein receptor (LDLR) than to the human homologue (M. Reithmayer, A. Reischl, L. Snyers, and D. Blaas, J. Virol. 76:6957-6965, 2002). Here, we used this fact to determine the binding site of HRV1A by replacing selected ligand binding modules of the human receptor with the corresponding ligand binding modules of the mouse receptor. The chimeric proteins were expressed in mouse fibroblasts deficient in endogenous LDLR and LDLR-related protein, both used by minor group HRVs for cell entry. Binding was assessed by virus overlay blots, by immunofluorescence microscopy, and by measuring cell attachment of radiolabeled virus. Replacement of ligand binding repeat 5 of the human LDLR with the corresponding mouse sequence resulted in a substantial increase in HRV1A binding, whereas substitution of repeats 3 and 4 was without effect. Replacement of human receptor repeats 1 and 2 with the murine homologues also increased virus binding. Finally, murine receptor modules 1, 2, and 5 simultaneously introduced into the human receptor resulted in HRV1A binding indistinguishable from mouse wild-type receptor. Thus, repeats 1 and/or 2 and repeat 5 are involved in HRV1A attachment. Changing CDGGPD in the acidic cluster of module 5 in the human receptor to CDGEAD present in the mouse receptor led to substantially increased binding of HRV1A, indicating an important role of the glutamate residue in HRV1A recognition.
"Usually I like school PE, but..." : school physical education described in Internet discussion forums

Lauritsalo, Kirsti ”Usually I like school PE, but. ” School physical education described in Internet discussion forums Jyväskylä: University of Jyväskylä, 2014, p. (Studies in Sport, Physical Education and Health ISSN 0356-1070; 207) ISBN 978-951-39-5725-4 (nid.) ISBN 978-951-39-5726-1 (PDF) Diss. The aim of this study was to enrich the existing picture of school physical education (PE) by investigating messages on the topic of school PE posted on Internet discussion forums, that is, by listening to people’s voices online. The study addressed three main research questions: (1) How is school PE described in Internet discussion forums? (2) What factors underlie the various opinions on school PE in Finnish schools expressed in Internet discussion forums? (3) What factors, mentioned in the messages, seem to lead towards engagement in or alienation from school PE? The data collected for this study comprised two data sets, for which the collection protocol was identical. Data I were collected from Internet discussion forums during a randomly chosen week number 15 in April 2007, data II similarly in 2012. The data were collected using a GoogleTM search engine with the broad term “koululiikunta” [“school PE” in Finnish] and the first 200 hits were taken for consideration. The data were analyzed using qualitative content analysis and Carlson’s (1995) model was applied to the data classification. The main finding was that the messages posted on the Internet discussion forums studied here referred to negative experiences more frequently, and sometimes with more vehement expressions of dislike of school PE, than has been previously reported in PE studies. The discussion forum messages mainly concerned extrinsic factors, in particular teachers, curriculum and the class environment. Emotions linked to school PE were most often mentioned among the intrinsic factors in the messages. The findings indicate that students’ voices should be more closely listened to by teachers and teacher educators. They need to be more aware of the feelings that PE arouses in order to develop school PE and learning environments that all students can enjoy and which will encourage the adoption of a physically active lifestyle.