102,958 research outputs found
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Análisis de genes situados en el haplotipo H1 de la región 17q21 y de genes involucrados en la fosforilación de "tau" en la parálisis supranuclear progresiva
No full text[spa] INTRODUCCIÓN: La parálisis supranuclear progresiva (PSP) se caracteriza por el depósito anormal de proteína tau hiperfosforilada en ganglios basales y tronco cerebral. Su etiología es desconocida y el único factor de riesgo genético conocido es su asociación con el haplotipo H1, que engloba un conjunto de polimorfismos en la región 17q21 incluyendo el gen tau y genes flanqueantes. Este haplotipo podría actuar modulando la expresión o el "splicing" de tau, pero existen otros genes candidatos importantes para la función neuronal o relacionados con la función de tau como saitohin, NIK y CRHR1 en esta región, o kinasas implicadas en la fosforilación de tau como GSK-3beta, en otras regiones. OBJETIVOS: Investigar el efecto de polimorfismos y mutaciones de los genes saitohin, CRHR1, región 3'-UTR de tau y GSK-3β sobre el riesgo de desarrollar PSP, y analizar la expresión de CRHR1 en el cerebro de pacientes fallecidos con PSP.METODOLOGÍA: Pacientes con criterios de PSP probable y controles sanos reclutados por la Unidad de Trastornos del Movimiento del Hospital Clínic. Se secuenció la región 3'UTR de tau, diseñando primers específicos, y la región codificante de saitohin en 3 PSP y se genotipó el polimorfismo Q7R en 57 PSP y 83 controles usando métodos previamente descritos. Se secuenció la región codificante de NIK en 3 PSP con métodos previamente descritos y se genotipó el polimorfismo 2839G/C en 40 PSP y 35 controles mediante el enzima de restricción HphI. Se cuantificó la expresión génica de CRHR1 en globus pallidus con PCR a tiempo real en 12 PSP, 10 Alzheimer, 5 pacientes con enfermedad cerebrovascular y 6 controles. Se secuenció la región codificante de CRHR1 en 2 PSP y se genotipó el polimorfismo -16C/T en 40 PSP y 51 controles mediante SSCP. Se genotipó el polimorfismo -50T/C de GSK-3beta en 93 PSP y 125 controles. Los análisis estadísticos se hicieron con el programa SPSS 11.5, usando el test chi-cuadrado para comparar las frecuencias genotípicas y alélicas y el test de Kruskal-Wallis para la comparación de los niveles de expresión génica.RESULTADOS: No se hallaron mutaciones en la región 3'-UTR de tau ni en la región codificante de los genes saitohin, NIK y CRHR1. El genotipo QQ de saitohin fue más frecuente en PSP que en controles (91.2% vs 47%) y cosegregaba con el genotipo CC del polimorfismo G(-221)C del promotor de tau. No se hallaron diferencias entre PSP y controles en la frecuencia genotípica del polimorfismo de NIK. La expresión de mRNA de CRHR1 en globus pallidus fue similar en PSP y el resto de sujetos. El genotipo CC del polimorfismo de CRHR1 fue más frecuente en PSP que en controles (80% vs 53%). El genotipo CC del polimorfismo-50 T/C de GSK-3-betafue algo menos frecuente (p=0.048) y el alelo T más frecuente (p=0.033) en PSP que en controles, y no se detectó interacción con el haplotipo H1/H1.CONCLUSIONES: Nuestros resultados no apoyan que la región 3'UTR de tau presente variantes génicas que puedan explicar el riesgo proporcionado por el haplotipo H1 para sufrir PSP. El genotipo QQ de saitohin y el genotipo CC del polimorfismo de CRHR1 están asociados a PSP en nuestra población y forman parte del haplotipo H1. El gen NIK no está incluído en el haplotipo H1 y no incrementa el riesgo de PSP. La ausencia de mutaciones y de alteración en la expresión génica en ganglios basales no apoya un papel funcional del gen CRHR1 en la PSP. El alelo T del polimorfismo -50T/C GSK-3β está sobrerepresentado en PSP y podría ser un factor de riesgo adicional independiente del haplotipo H1; alternativamente, el genotipo CC podría ser un factor protector.[eng] Progressive supranuclear palsy (PSP) is characterised by abnormal deposition of hyperphosphorylated tau protein in basal ganglia and brainstem. The only known genetic risk factor is the H1 haplotype in the tau gene region, but there are other candidate genes related to tau or neuronal function like saitohin, NIK and CRHR1 in this region or tau-kinases like GSK-3beta in other regions. The aim of this work was to analyse variations of these genes and CRHR1 brain expression in PSP. Patients and controls were recruited by the Hospital Clínic Movement Disorders Unit. Sequencing of tau-3'UTR region and coding region of saitohin were performed in 3 PSP patients, and the Q7R saitohin polymorphism was genotyped in 57 PSP and 83 controls. The coding region of NIK was sequenced in 3 PSP and the 2839G/C polymorphism was genotyped in 40 PSP and 35 controls. CRHR1 gene expression was quantified in globus pallidus using real-time PCR in 12 PSP, 10 Alzheimer, 5 stroke patients and 6 controls. The coding region of CRHR1 was sequenced in 2 PSP and the -16C/T polymorphism was genotyped in 40 PSP and 51 controls. The GSK-3beta -50T/C polymorphism was genotyped in 83 PSP and 125 controls. Genotype and allelic frequencies were compared using the chi-square test and gene expression levels with the Kruskal-Wallis test. No mutations were found. The saitohin QQ genotype and the CRHR1 CC genotype were more frequent in PSP than in controls (91.2% vs 47%; 80% vs 53%), and the NIK genotype frequencies were similar. CRHR1 mRNA expression in globus pallidus was similar in PSP and the rest of subjects. The T allele of the GSK-3polymorphism was more frequent in PSP than in controls (p=0.033), and no interaction was detected with the H1/H1 haplotype. Our results do not support a role of tau-3'UTR and CRHR1 in PSP. The saitohin and CRHR1 polymorphisms are associated with PSP in the context of the H1 haplotype. The NIK gene is not included in the H1 haplotype and does not increase the risk of PSP. GSK-3β genetic variations could be an additional genetic risk factor indepedent of the H1 haplotype
Advances in Immunotherapy for the Treatment of Cutaneous T-Cell Lymphoma
No full textAri Pelcovits,1,2 Thomas A Ollila,1,2 Adam J Olszewski1,2 1Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA; 2Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USACorrespondence: Adam J Olszewski, Department of Medicine, Alpert Medical School of Brown University, Rhode Island Hospital, George Building, Ste 310, 593 Eddy St, Providence, RI, 02903, USA, Tel +1-401-444-2269, Fax +1-401-444-4184, Email [email protected]: Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach to management. The most common subtype is mycosis fungoides, in which local disease has an excellent prognosis and is often managed with topical therapy alone. More extensive cutaneous involvement as well as involvement of lymph nodes and the peripheral blood (Sezary syndrome) require systemic therapies. Recent years have brought an expansion of therapeutic options, specifically with immune-based approaches that were developed using the knowledge gained regarding the biology and molecular pathology of CTCL. Previous systemic therapies such as retinoids, histone deacetylase inhibitors, and chemotherapeutic agents come with significant toxicity and only short-term response. Newer agents such as mogamulizumab and brentuximab vedotin use a targeted immune-based approach leading to longer periods of response with less systemic toxicity. While still in its infancy, the use of immune checkpoint inhibitors such as nivolumab and pembrolizumab appears promising, and while their current clinical application is limited, early data suggest possible future areas for research of immune manipulation to treat CTCL. Herein, we review these novel immune-based treatment strategies, their superiority over prior systemic options, and the ongoing need for further research and clinical trial enrollment.Keywords: cutaneous T-cell lymphoma, Sézary syndrome, immunotherapy, brentuximab vedoti
Strategic Manipulation of Empirical Tests
No full textTheories can be produced by experts seeking a reputation for having knowledge. Hence, a tester could anticipate that theories may have been strategically produced by uninformed experts who want to pass an empirical test. We show that, with no restriction on the domain of permissible theories, strategic experts cannot be discredited for an arbitrary but given number of periods, no matter which test is used (provided that the test does not reject the actual data-generating process). Natural ways around this impossibility result include 1) assuming that unbounded data sets are available and 2) restricting the domain of permissible theories (opening the possibility that the actual data-generating process is rejected out of hand). In both cases, it is possible to dismiss strategic experts, but only to a limited extent. These results show significant limits on what data can accomplish when experts produce theories strategically.Testing Strategic Experts
A living presence of the Holy Spirit in the movements of the Church
No full textThe phenomenon of the action of the Holy Spirit has accompanied the Church throughout her history. After the Second Vatican Council, a special influence of the Holy Spirit is noted in the initiated new prayer movements and communities. This study aims to show the functioning of small communities, the mechanisms of personal and group activities that contribute to deepening the faith of believers.ks. dr hab. MIECZYSŁAW OLSZEWSKI – doktor habilitowany z zakresu teologii pastoralnej. Emerytowany profesor Akademii Katolickiej w Warszawie. Autor wielu publikacji z dziedziny teologii pastoralnej, teologii pastoralnej Kościołów Wschodnich i bibliotekarstwa.Papieski Wydział Teologiczny w WarszawieJan Paweł II, Redemptor hominis u początku papieskiej posługi (4 III 1979).Jan Paweł II, Catechesi tradendae o katechizacji w naszych czasach (16 X 1979).Edward D. O’Connor, Ruch charyzmatyczny w Kościele Katolickim, Warszawa 1984.N. Glatzel, Gemeindebildung und Gemeindestruktur. Ein Beitrag der christlichen Sozialwissenschaften zu einer Kernfrage des christlichen Lebens, Muenchen-Paderborn-Wien 1976, s. 111 (Abhandlungen zur Sozialethik, 14).P. Grieger, L’animazione comunitaria, Rzym 1976.P. Grieger, La creativita: strumento del rinnovamento. Applicazioni comunitarie, Rzym 1977.M. Olszewski, Ks. Stanisław Szczepura pierwszym opiekunem Odnowy w Duchu Świętym w Archidiecezji Białostockiej, [w:] W służbie Kościoła, (red.) Z. T. Klimaszewski, Białystok 2011.J. Przybyłowski, Duszpasterstwo grupowe w kontekście zadań wychowawczych, „Teologia Praktyczna” 5(2004).6879
The breath of the Holy Spirit in the Church
No full text„The Holy Spirit blows where he wants,” that is everyone who believes can receive the gifts of the Holy Spirit. This endowment of the Holy Spirit, ordinary as well as the extraordinary one takes place from the very beginning of the existence of the Church of Christ and became evident in its history, and is being revealed in the formation of various movements at present. One of them is Renewal in the Holy Spirit Movement. It is a special gift of God, a special breath of the Holy Spirit for the today’s Church, operating in diffi cult Times. It is therefore an extraordinary gift for believers and today’s world.ks. dr hab. MIECZYSŁAW OLSZEWSKI – dr habilitowany z zakresu teologii pastoralnej, wykładowca na Papieskim Wydziale Teologicznym w Warszawie oraz w Studium Teologii w Białymstoku, członek Rady Wydziału PWTW. Autor licznych publikacji z dziedziny teologii pastoralnej oraz teologii pastoralnej Kościołów Wschodnich i publikacji z dziedziny bibliotekarstwa.Papieski Wydział Teologiczny w WarszawieBolczyk H., Działalność ruchów katolickich w Polsce, [w:] Wiosna Ruchów. Materiały z I Kongresu ruchów katolickich 3-4 czerwca, A. Schulz (opr.), Warszawa [1994].Krzysteczko H., W małej grupie religijnej. Wpływ przynależności do małej grupy religijnej na poczucie uczestnictwa w życiu społecznym. Studium pastoralne, Katowice 2003.Mariański J., Zmieniająca się religijność w – i poza Kościołem w Polsce, „Wrocławskie Wiadomości Kościelne”, LIV(2001) nr 2.Olszewski M., Ks. Stanisław Szczepura pierwszym opiekunem Odnowy w Duchu Świętym w Archidiecezji Białostockiej, [w:] W służbie Kościoła, Z. T. Klimaszewski (red.), Białystok 2011, s. 210.Orędzie Jana Pawła II z okazji 30-lecia ruchu Wiara i Światło, „Wrocławskie Wiadomości Kościelne”, LIV(2001) nr 2, s. 121-122.O’Connor E. D., Ruch charyzmatyczny w Kościele Katolickim, Warszawa 1984.Sowa T., Obchody 50-lecia Odnowy w Duchu Świętym, https://ekai/warszawa-obchody-50-lecia-odnowy-w-duchu-swietm/?print=1Święcicki J., Ruchy i Stowarzyszenia Katolickie wiosną Kościoła, Niedziela.pl [13.06.2017].Załęcki P., Wspólnota religijna jako grupa pierwotna, Kraków 1997.122-130312213
Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract
No full textBackground: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments. Methods: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum. Results: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors. Conclusions: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions. © 2012 Badiali et al.; licensee BioMed Central Ltd
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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