Identification of domain boundaries within the N‐termini of TAP1 and TAP2 and their importance in tapasin binding and tapasin‐mediated increase in peptide loading of MHC class I

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141680/1/imcb200564.pd

The influence of employment social support for risk and prognosis in nonspecific back pain: a systematic review and critical synthesis

PURPOSE: To examine the influence of employment social support type (e.g. co-worker, supervisor, general support) on risk of occurrence of low back pain, and prognosis (e.g. recovery, return to work status) for those who have low back pain. METHODS: Systematic search of seven databases (MEDLINE, Embase, PsychINFO, CINAHL, IBSS, AMED and BNI) for prospective or case-control studies reporting findings on employment social support in populations with nonspecific back pain. Data extraction and quality assessment were carried out on included studies. A systematic critical synthesis was carried out on extracted data. RESULTS: Thirty-two articles were included that describe 46 findings on the effect of employment social support on risk of and prognosis of back pain. Findings show that there is no effect of co-worker, supervisor or general work support on risk of new onset back pain. Weak effects of employment support were found for recovery and return to work outcomes; greater levels of co-worker support and general work support were found to be associated with less time to recovery or return to work. CONCLUSIONS: The evidence suggests that the association between employment support and prognosis may be subject to influence from wider concepts related to the employment context. This review discusses these wider issues and offers directions for future research

Tracing the dynamic life story of a Bronze Age Female

YesAncient human mobility at the individual level is conventionally studied by the diverse application of suitable techniques (e.g. aDNA, radiogenic strontium isotopes, as well as oxygen and lead isotopes) to either hard and/or soft tissues. However, the limited preservation of coexisting hard and soft human tissues hampers the possibilities of investigating high-resolution diachronic mobility periods in the life of a single individual. Here, we present the results of a multidisciplinary study of an exceptionally well preserved circa 3.400-year old Danish Bronze Age female find, known as the Egtved Girl. We applied biomolecular, biochemical and geochemical analyses to reconstruct her mobility and diet. We demonstrate that she originated from a place outside present day Denmark (the island of Bornholm excluded), and that she travelled back and forth over large distances during the final months of her life, while consuming a terrestrial diet with intervals of reduced protein intake. We also provide evidence that all her garments were made of non-locally produced wool. Our study advocates the huge potential of combining biomolecular and biogeochemical provenance tracer analyses to hard and soft tissues of a single ancient individual for the reconstruction of high-resolution human mobility.The Danish National Research Foundation; The Carlsberg Foundation, L'Oreal Denmark-UNESCO; The ERC agreement no. 26944

Resection in the popliteal fossa for metastatic melanoma

BACKGROUND: Traditionally metastatic melanoma of the distal leg and the foot metastasize to the lymph nodes of the groin. Sometimes the first site of nodal disease can be the popliteal fossa. This is an infrequent event, with rare reports in literature and when it occurs, radical popliteal node dissection must be performed. CASE PRESENTATION: We report a case of a 36-year old man presented with diagnosis of 2 mm thick, Clark's level II-III, non ulcerated melanoma of the left heel, which developed during the course of the disease popliteal node metastases, after a superficial and deep groin dissection for inguinal node involvement. Five months after popliteal lymph node dissection he developed systemic disease, therefore he received nine cycles of dacarbazine plus fotemustine. To date (56 months after prior surgery and 11 months after chemotherapy) he is alive with no evidence of disease. CONCLUSION: In case of groin metastases from melanoma of distal lower extremities, clinical and ultrasound examination of ipsilateral popliteal fossa is essential. When metastatic disease is found, radical popliteal dissection is the standard of care. Therefore knowledge of anatomy and surgical technique about popliteal lymphadenectomy are required to make preservation of structures that if injured, can produce a permanent, considerable disability

Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

Optical and near-infrared observations of the Fried Egg Nebula

Context. The fate of a massive star during the latest stages of its evolution is highly dependent on its mass-loss rate and geometry and therefore knowing the geometry of the circumstellar material close to the star and its surroundings is crucial. Aims. We aim to provide insight into the nature (i.e. geometry, rates) of mass-loss episodes, and in particular, the connection between the observed asymmetries due to the mass lost in a fast wind or during a previous, prodigious mass-losing phase. In this context, yellow hypergiants offer a good opportunity to study mass-loss events. Methods. We analysed a large set of optical and near-infrared data in spectroscopic and photometric, spectropolarimetric, and interferometric (GRAVITY/VLTI) modes, towards the yellow hypergiant IRAS 17163−3907. We used X-shooter optical observations to determine the spectral type of this yellow hypergiant and we present the first model-independent, reconstructed images of IRAS 17163−3907 at these wavelengths tracing milli-arcsecond scales. Lastly, we applied a 2D radiative transfer model to fit the dereddened photometry and the radial profiles of published diffraction-limited VISIR images at 8.59 μm, 11.85 μm, and 12.81 μm simultaneously, adopting a revised distance determination using Gaia Data Release 2 measurements. Results. We constrain the spectral type of IRAS 17163−3907 to be slightly earlier than A6Ia (Teff ∼ 8500 K). The interferometric observables around the 2 μm window towards IRAS 17163−3907 show that the Brγ emission appears to be more extended and asymmetric than the Na I and the continuum emission. Interestingly, the spectrum of IRAS 17163−3907 around 2 μm shows Mg II emission that is not previously seen in other objects of its class. In addition, Brγ shows variability in a time interval of four months that is not seen towards Na I. Lastly, in addition to the two known shells surrounding IRAS 17163−3907, we report on the existence of a third hot inner shell with a maximum dynamical age of only 30 yr. Conclusions. The 2 μm continuum originates directly from the star and not from hot dust surrounding the stellar object. The observed spectroscopic variability of Brγ could be a result of variability in the mass-loss rate. The interpretation of the presence of Na I emission at closer distances to the star compared to Brγ has been a challenge in various studies. To address this, we examine several scenarios. We argue that the presence of a pseudo-photosphere, which was traditionally considered to be the prominent explanation, is not needed and that it is rather an optical depth effect. The three observed distinct mass-loss episodes are characterised by different mass-loss rates and can inform theories of mass-loss mechanisms, which is a topic still under debate both in theory and observations. We discuss these in the context of photospheric pulsations and wind bi-stability mechanisms

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Infectious Disease Ontology

Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain