High and low affinity carbohydrate ligands revealed for murine SIGN-R1 by carbohydrate array and cell binding approaches, and differing specificities for SIGN-R3 and langerin

The number of receptors of the \u27C-type\u27 lectin family is greater than previously thought with a considerable proportion on cells (dendritic cells and macrophages) critical for innate immunity. Establishing that they bind carbohydrates, unravelling and comparing details of their ligands is crucial for understanding the molecular basis of the cell-cell and cell-pathogen interactions that they mediate. Here we use carbohydrate arrays as a new approach to discovering the ligands of three recently described C-type lectin-type receptors on antigen-presenting cells: murine SIGN-R1, SIGN-R3 and langerin. The arrays encompass an extensive panel including polysaccharides, glycoproteins, oligosaccharides and monosaccharides. These are probed with soluble forms of the receptors (IgG-Fc chimeras). The dominant specificities found for SIGN-R1 and SIGN-R3 are mannose- and fucose-related, as expressed on high mannose type N-glycans and Lewisa/b/Lewisx/y-type sequences, respectively, with subtle differences between the receptors. The dominant specificity for langerin is unique so far: a Lewisx-related sequence with sulfate at position 6 of the terminal galactose. The polysaccharide dextran, known from classical studies to elicit a T-independent response, and whose cellular uptake has been shown recently to be mediated by membrane-associated SIGN-R1, gave no binding signals with the soluble form of the protein. We highlight here the additional need for cell-based assays for detecting biologically relevant low affinity ligands, for we show with SIGN-R1-transfected cells that dextran is such a low affinity ligand for SIGN-R1 that binding is detectable only with the cell membrane-associated receptor. But there is a close relationship between dextran recognition and mannose/fucose recognition, with dextran- and mannose-conjugates co-localizing in intracellular compartments. © 2004 The Japanese Society for Immunology

The Power of the Web in Cancer Drug Discovery and Clinical Trial Design: Research without a Laboratory?

The discovery of effective cancer treatments is a key goal for pharmaceutical companies. However, the current costs of bringing a cancer drug to the market in the USA is now estimated at $1 billion per FDA approved drug, with many months of research at the bench and costly clinical trials. A growing number of papers highlight the use of data mining tools to determine associations between drugs, genes or protein targets, and possible mechanism of actions or therapeutic efficacy which could be harnessed to provide information that can refine or direct new clinical cancer studies and lower costs. This report reviews the paper by R.J. Epstein, which illustrates the potential of text mining using Boolean parameters in cancer drug discovery, and other studies which use alternative data mining approaches to aid cancer research

Do College Students with ADHD have Expressive Writing Difficulties as Do Children with ADHD?

This study analyzed the expressive writing of college students. Twenty-two ADHD students and 22 controls were asked to write a story based on a picture story and a personal challenge. The texts were compared based on several qualitative and quantitative parameters. The results show that students in both groups presented similar text quality. Out of six qualitative parameters only one was statistically different between the two groups: ADHD students performed worse in adequacy, but only in the picture task. Students writings were also investigated using corpus based analysis. This analysis showed that ADHD students used less unusually frequent words in the picture story but more in the challenge task. Taken together the findings indicate no significant difference in expressive writing between ADHD and non ADHD college students. An explanation to this result is that college students with ADHD may have passed the filter of prior education

Service-learning through historical dissemination via Wikipedia

[EN] This paper focuses on an educational experience based on the incorporation of the service-learning methodology in two university courses of Contemporary History. The objective of the service-learning practice was for students to generate knowledge with social impact while collaborating with extra-academic social agents (such as the associations Ecologistas en Acción and the Historical Memory Association "Los Barracones"). The idea was, therefore, to combine the development of competencies inherent to the historical discipline with the performance of a service to the community. Thus, this paper is based on the data collected (surveys and evaluations) over the course of a semester to carry out a descriptive multi-case study. This has made it possible to accurately assess the development of the experience in the courses involved. Based on group work and interaction with social agents, students wrote five Wikipedia entries and developed curricular competencies included in the curriculum or their syllabus. Satisfaction with their participation in the service-learning experience was evident, but there was also room for improvement in group functioning, workload and quality of interactions with social agents. Although data suggests that service-learning can be a useful methodology for the teaching-learning process of Contemporary History, it also reveals that its effects could be more satisfactory if a series of modifications are made to the experience described here.[ES] Este trabajo se centra en una experiencia educativa basada en incorporar la metodología del aprendizaje-servicio (ApS) en dos asignaturas universitarias de historia contemporánea. El fin era lograr que los estudiantes generasen conocimiento con impacto social al mismo tiempo que colaboraban con agentes sociales extraacadémicos (como Ecologistas en Acción o la Asociación de Memoria Histórica “Los Barracones”). Se perseguía, por tanto, reunir la adquisición de competencias propias de la disciplina histórica con la realización de un servicio a la comunidad. Así, este texto parte de los datos recogidos (encuestas y evaluaciones) a lo largo de un semestre para realizar un estudio multicaso de carácter descriptivo. Ello ha permitido evaluar de forma precisa el desarrollo de la experiencia en las asignaturas implicadas. A partir del trabajo en grupo y de la interacción con los agentes sociales, los estudiantes redactaron cinco entradas en Wikipedia y desarrollaron competencias curriculares de sus guías docentes. El grado de satisfacción quedó patente, pero también se abrió espacio a la mejora en el funcionamiento de los grupos, la carga de trabajo y la calidad de las interacciones con los agentes sociales. Aunque los datos apuntan a que el aprendizaje-servicio podría ser una metodología útil para el proceso de enseñanza-aprendizaje de la historia contemporánea, también revela que sus efectos podrían resultar más satisfactorios en caso de realizar una serie de modificaciones en la experiencia que aquí se presenta.Toledo Machado, L.; Pérez Del Puerto, Á.; López-De-Arana Prado, E.; Llinares Galustian, M.; Toboso Sánchez, MP.; Aramburuzabala Higuera, MP. (2023). Aprendizaje-servicio mediante la divulgación histórica a través de Wikipedia. REDU. Revista de Docencia Universitaria. 21(2):9-26. https://doi.org/10.4995/redu.2023.1814592621

T-regulatory cell modulation: the future of cancer immunotherapy?

T-regulatory cells suppress anti-tumour immunity in cancer patients and in murine tumour models. Furthermore, their activity is likely to have an effect on the effectiveness of immunotherapeutic treatments for cancer. Here we describe the current status of developing clinical strategies for modulating Treg activity in cancer patients

HES1 in immunity and cancer

Hairy and enhancer of split homolog-1 (HES1) is a part of an extensive family of basic helix-loop-helix (bHLH) proteins and plays a crucial role in the control and regulation of cell cycle, proliferation, cell differentiation, survival and apoptosis in neuronal, endocrine, T-lymphocyte progenitors as well as various cancers. HES1 is a transcription factor which is regulated by the NOTCH, Hedgehog and Wnt signalling pathways. Aberrant expression of these pathways is a common feature of cancerous cells. There appears to be a fine and complicated crosstalk at the molecular level between the various signalling pathways and HES1, which contributes to its effects on the immune response and cancers such as leukaemia. Several mechanisms have been proposed, including an enhanced invasiveness and metastasis by inducing epithelial mesenchymal transition (EMT), in addition to its strict requirement for tumour cell survival. In this review, we summarize the current biology and molecular mechanisms as well as its use as a clinical target in cancer therapeutics

Sulfotransferases of Two Specificities Function in the Reconstitution of High Endothelial Cell Ligands for L-selectin

L-selectin, a lectin-like receptor, mediates rolling of lymphocytes on high endothelial venules (HEVs) in secondary lymphoid organs by interacting with HEV ligands. These ligands consist of a complex of sialomucins, candidates for which are glycosylation- dependent cell adhesion molecule 1 (GlyCAM-1), CD34, and podocalyxin. The ligands must be sialylated, fucosylated, and sulfated for optimal recognition by L-selectin. Our previous structural characterization of GlyCAM-1 has demonstrated two sulfation modifications, Gal-6-sulfate and GlcNAc-6-sulfate in the context of sialyl Lewis x. We now report the cloning of a Gal-6-sulfotransferase and a GlcNAc-6-sulfotransferase, which can modify GlyCAM-1 and CD34. The Gal-6-sulfotransferase shows a wide tissue distribution. In contrast, the GlcNAc-6-sulfotransferase is highly restricted to HEVs, as revealed by Northern analysis and in situ hybridization. Expression of either enzyme in Chinese hamster ovary cells, along with CD34 and fucosyltransferase VII, results in ligand activity, as detected by binding of an L-selectin/IgM chimera. When coexpressed, the two sulfotransferases synergize to produce strongly enhanced chimera binding