Chemoenzymatic Probes for Detecting and Imaging Fucose-α(1-2)-galactose Glycan Biomarkers

The disaccharide motif fucose-α(1-2)-galactose (Fucα(1-2)Gal) is involved in many important physiological processes, such as learning and memory, inflammation, asthma, and tumorigenesis. However, the size and structural complexity of Fucα(1-2)Gal-containing glycans have posed a significant challenge to their detection. We report a new chemoenzymatic strategy for the rapid, sensitive detection of Fucα(1-2)Gal glycans. We demonstrate that the approach is highly selective for the Fucα(1-2)Gal motif, detects a variety of complex glycans and glycoproteins, and can be used to profile the relative abundance of the motif on live cells, discriminating malignant from normal cells. This approach represents a new potential strategy for biomarker detection and expands the technologies available for understanding the roles of this important class of carbohydrates in physiology and disease

Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative proteomics

The addition of the monosaccharide beta-N-acetyl-D-glucosamine to proteins (O-GlcNAc glycosylation) is an intracellular, post-translational modification that shares features with phosphorylation. Understanding the cellular mechanisms and signaling pathways that regulate O-GlcNAc glycosylation has been challenging because of the difficulty of detecting and quantifying the modification. Here, we describe a new strategy for monitoring the dynamics of O-GlcNAc glycosylation using quantitative mass spectrometry-based proteomics. Our method, which we have termed quantitative isotopic and chemoenzymatic tagging (QUIC-Tag), combines selective, chemoenzymatic tagging of O-GlcNAc proteins with an efficient isotopic labeling strategy. Using the method, we detect changes in O-GlcNAc glycosylation on several proteins involved in the regulation of transcription and mRNA translocation. We also provide the first evidence that O-GlcNAc glycosylation is dynamically modulated by excitatory stimulation of the brain in vivo. Finally, we use electron-transfer dissociation mass spectrometry to identify exact sites of O-GlcNAc modification. Together, our studies suggest that O-GlcNAc glycosylation occurs reversibly in neurons and, akin to phosphorylation, may have important roles in mediating the communication between neurons

Despertar la curiosidad por la química desde la Universidad

En este trabajo se presentará la experiencia realizada a partir de la visita a la exposición “¿Dónde está la química?”, por parte de estudiantes de secundaria, ciclos formativos y bachillerato. Esta exposición se ha programado desde la Escola Universitària Politècnica de Manresa de la Universitat Politècnica de Catalunya, con el objetivo de acercar a los estudiantes de este nivel al conocimiento y, más que nada, a la curiosidad por el mundo de la química. Se expondrá en primer lugar el material que se presenta en la exposición, así como los resultados obtenidos en una encuesta realizada a los asistentes una vez concluida la visita, y en segundo lugar se presentarán las conclusiones obtenidas de la valoración indicada.Peer ReviewedPostprint (published version

Mediators Between Job Stress and Health Quality of Life Among Adults with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal affliction that affects millions around the globe, impacting health-related quality of life (HRQoL). The biopsychosocial model, Folkman and Lazarus’ transactional model of stress, Leventhal’s common sense model of self-regulation health and illness, and Bronfenbrenner’s human ecology theory are relevant to conceptualize interactions among environmental factors, biopsychosocial responses, and health-related quality of life (HRQoL). This quantitative, cross-sectional, complex correlational study sought to provide more understanding of how and whether IBS symptoms of pain, cognitive functioning, and interpersonal functioning serve as mediators between work stress and HRQoL. A total of 133 English-speaking volunteers from online IBS support groups completed an online survey containing a demographic questionnaire, the IBS-36, the Overall Anxiety Severity and Impairment Scale (OASIS), the Modified Illness Perceptions Questionnaire (M-IPQ), and the Workplace Organization Indices (WOI). Mediational analyses were performed using the Hayes Process method. While the study failed to reject the null hypothesis, it provided suggestions for further research into relationships between work stress and HRQoL among individuals who experience IBS. Studies in this area have positive social change because they provide information to individuals diagnosed with IBS, health providers, academic researchers, and employers concerning relationships of symptoms and severity of IBS to workplace stress and emotional well-being of individuals with IBS. This awareness may promote workplace interventions, such as training management on job accommodations and support for these employees

Mediators Between Job Stress and Health Quality of Life Among Adults with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal affliction that affects millions around the globe, impacting health-related quality of life (HRQoL). The biopsychosocial model, Folkman and Lazarus’ transactional model of stress, Leventhal’s common sense model of self-regulation health and illness, and Bronfenbrenner’s human ecology theory are relevant to conceptualize interactions among environmental factors, biopsychosocial responses, and health-related quality of life (HRQoL). This quantitative, cross-sectional, complex correlational study sought to provide more understanding of how and whether IBS symptoms of pain, cognitive functioning, and interpersonal functioning serve as mediators between work stress and HRQoL. A total of 133 English-speaking volunteers from online IBS support groups completed an online survey containing a demographic questionnaire, the IBS-36, the Overall Anxiety Severity and Impairment Scale (OASIS), the Modified Illness Perceptions Questionnaire (M-IPQ), and the Workplace Organization Indices (WOI). Mediational analyses were performed using the Hayes Process method. While the study failed to reject the null hypothesis, it provided suggestions for further research into relationships between work stress and HRQoL among individuals who experience IBS. Studies in this area have positive social change because they provide information to individuals diagnosed with IBS, health providers, academic researchers, and employers concerning relationships of symptoms and severity of IBS to workplace stress and emotional well-being of individuals with IBS. This awareness may promote workplace interventions, such as training management on job accommodations and support for these employees

Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation

O-GlcNAcylated proteins are abundant in the brain and are associated with neuronal functions and neurodegenerative diseases. Although several studies have reported the effects of aberrant regulation of O-GlcNAcylation on brain function, the roles of O-GlcNAcylation in synaptic function remain unclear. To understand the effect of aberrant O-GlcNAcylation on the brain, we used Oga+/- mice which have an increased level of O-GlcNAcylation, and found that Oga+/- mice exhibited impaired spatial learning and memory. Consistent with this result, Oga+/- mice showed a defect in hippocampal synaptic plasticity. Oga heterozygosity causes impairment of both long-term potentiation and long-term depression due to dysregulation of AMPA receptor phosphorylation. These results demonstrate a role for hyper-O-GlcNAcylation in learning and memory.ope

Structural basis of nuclear import of flap endonuclease 1 (FEN1)

Flap endonuclease 1 (FEN1) is a member of the nuclease family and is structurally conserved from bacteriophages to humans. This protein is involved in multiple DNA-processing pathways, including Okazaki fragment maturation, stalled replication-fork rescue, telomere maintenance, long-patch base-excision repair and apoptotic DNA fragmentation. FEN1 has three functional motifs that are responsible for its nuclease, PCNA-interaction and nuclear localization activities, respectively. It has been shown that the C-terminal nuclear localization sequence (NLS) facilitates nuclear localization of the enzyme during the S phase of the cell cycle and in response to DNA damage. To determine the structural basis of the recognition of FEN1 by the nuclear import receptor importin alpha, the crystal structure of the complex of importin alpha with a peptide corresponding to the FEN1 NLS was solved. Structural studies confirmed the binding of the FEN1 NLS as a classical bipartite NLS; however, in contrast to the previously proposed (KRKX8KKK367)-K-354 sequence, it is the (354)KRX(10)KKAK(369) sequence that binds to importin alpha. This result explains the incomplete inhibition of localization that was observed on mutating residues (KKK367)-K-365. Acidic and polar residues in the X-10 linker region close to the basic clusters play an important role in binding to importin alpha. These results suggest that the basic residues in the N-terminal basic cluster of bipartite NLSs may play roles that are more critical than those of the many basic residues in the C-terminal basic cluster

Adjectival and Adverbial Modification:The View from Modern Type Theories

In this paper we present a study of adjectival/adverbial modification using modern type theories (MTTs), i.e. type theories within the tradition of Martin-Lof. We present an account of various issues concerning adjectival/adverbial modification and argue that MTTs can be used as an adequate language for interpreting NL semantics. MTTs are not only expressive enough to deal with a range of modification phenomena, but are furthermore well-suited to perform reasoning tasks that can be easily implemented (e.g. in proof-assistants) given their proof-theoretic nature. In MTT-semantics, common nouns are interpreted as types rather than predicates. Therefore, in order to capture the semantics of adjectives adequately, one needs to meet the challenge of modeling CNs modified by adjectives as types. To explicate that this can be done successfully, we first look at the mainstream classification of adjectives, i.e. intersective, subsective and non-subsective adjectives. There, we show that the rich type structure available in MTTs, along with a suitable subtyping framework, offers an adequate mechanism to model these cases. In particular, this modelling naturally takes care of the characterising inferences associated with each class of adjectives. Then, more advanced issues on adjectival modification are discussed: (a) degree adjectives, (b) comparatives and (c) multidimensional adjectives. There, it is shown that the use of indexed types can be usefully applied in order to deal with these cases. In the same vein, the issue of adverbial modification is discussed. We study two general typings for sentence and VP adverbs respectively. It is shown that the rich type structure in MTTs further provides useful organisational mechanisms in giving formal semantics for adverbs. In particular, we discuss the use of -types to capture the veridicality/non-veridicality distinction and further discuss cases of intensional adverbs using the type theoretic notion of context (i.e. without resorting to intensional typing). We also look at manner, subject and speech act adverbials and propose solutions using MTTs. Finally, we show that the current proof technology can help mechanically check the associated inferences. A number of our proposals concerning adjectival and adverbial modification have been formalised in the proof assistant Coq and many of the associated inference patterns are checked to be correctly captured

A mutant O-GlcNAcase enriches Drosophila developmental regulators

YesProtein O-GlcNAcylation is a reversible post-translational modification of serines/threonines on nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is essential for early embryogenesis. Drosophila melanogaster OGT/supersex combs (sxc) is a polycomb gene, null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities of the O-GlcNAcylated proteins involved, and the underlying mechanisms linking these phenotypes to embryonic development, are poorly understood. Identification of O-GlcNAcylated proteins from biological samples is hampered by the low stoichiometry of this modification and limited enrichment tools. Using a catalytically inactive bacterial O-GlcNAcase mutant as a substrate trap, we have enriched the O-GlcNAc proteome of the developing Drosophila embryo, identifying, amongst others, known regulators of Hox genes as candidate conveyors of OGT function during embryonic development.Wellcome Trust Investigator Award (110061); MRC grant (MC_UU_12016/5); and Royal Society Research Grant

Learning and Challenges of University Extension. Systematization of an Experience in the University Teaching Staff of Physical Education (UNLU)

El presente trabajo tiene el objetivo de sistematizar diversas propuestas de Extensión universitaria llevadas a cabo en el Profesorado de Educación Física dependiente de la Universidad Nacional de Luján. A lo largo del escrito se recuperan las características y aprendizajes fruto de estas propuestas. Se describen los orígenes de cada una de las iniciativas y se realiza un encuadre historizando el recorrido. También se hace referencia a las variantes y modificaciones que fueron necesarios diseñar ante la emergencia sanitaria producto de la pandemia por el covid-19. Por último, se propone revisitar las acciones y proyectos desde las voces de los y las estudiantes a fin de identificar aportes de las experiencias para sus recorridos de formación y desafíos aún pendientes.The present work aims to systematize various proposals for University Extension carried out in the Physical Education Faculty dependent on the National University of Luján. Throughout the writing, the characteristics and learnings resulting from these proposals are recovered. The origins of each of the initiatives are described and a framing is made historicizing the route. Reference is also made to the variants and modifications that it was necessary to design in the face of the health emergency resulting from the Covid-19 pandemic. Finally, it is proposed to revisit the actions and projects from the voices of the students in order to identify contributions from the experiences for their training journeys and challenges still pending.Facultad de Periodismo y Comunicación Socia