208 research outputs found
Neurologic and Psychiatric Co-morbidity in Neuropsychiatry Training
Summary: Discusses a study on combined neuropsychiatry training for establishing competency in neuropsychiatry
T-cell libraries allow simple parallel generation of multiple peptide-specific human T-cell clones
Isolation of peptide-specific T-cell clones is highly desirable for determining the role of T-cells in human disease, as well as for the development of therapies and diagnostics. However, generation of monoclonal T-cells with the required specificity is challenging and time-consuming. Here we describe a library-based strategy for the simple parallel detection and isolation of multiple peptide-specific human T-cell clones from CD8+ or CD4+ polyclonal T-cell populations. T-cells were first amplified by CD3/CD28 microbeads in a 96U-well library format, prior to screening for desired peptide recognition. T-cells from peptide-reactive wells were then subjected to cytokine-mediated enrichment followed by single-cell cloning, with the entire process from sample to validated clone taking as little as 6 weeks. Overall, T-cell libraries represent an efficient and relatively rapid tool for the generation of peptide-specific T-cell clones, with applications shown here in infectious disease (EpsteinâBarr virus, influenza A, and Ebola virus), autoimmunity (type 1 diabetes) and cancer
Neuroleptanalgesia for acute abdominal pain: a systematic review
Background: Acute abdominal pain (AAP) comprises up to 10% of all emergency department (ED) visits. Current pain management practice is moving toward multi-modal analgesia
regimens that decrease opioid use.
Objective: This project sought to determine whether, in patients with AAP (population), does
administration of butyrophenone antipsychotics (intervention) compared to placebo, usual care,
or opiates alone (comparisons) improve analgesia or decrease opiate consumption (outcomes)?
Methods: A structured search was performed in Cochrane CENTRAL, CINAHL, Database of
Abstracts of Reviews of Effects, Directory of Open Access Journals, Embase, IEEE-Xplorer,
Latin American and Caribbean Health Sciences Literature, Magiran, PubMed, Scientific Information Database, Scopus, TĂĆBĂ°TAK ULAKBĂ°M, and Web of Science. Clinical trial registries
(ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform,
and Australian New Zealand Clinical Trials Registry), relevant bibliographies, and conference
proceedings were also searched. Searches were not limited by date, language, or publication
status. Studies eligible for inclusion were prospective randomized clinical trials enrolling
patients (age Ăąâ°Â„18 years) with AAP treated in acute care environments (ED, intensive care unit,
postoperative). The butyrophenone must have been administered either intravenously or intramuscularly. Comparison groups included placebo, opiate only, corticosteroids, non-steroidal
anti-inflammatory drugs, or acetaminophen.
Results: We identified 7,217 references. Six studies met inclusion criteria. One study assessed
ED patients with AAP associated with gastroparesis, whereas five studies assessed patients with
postoperative AAP: abdominal hysterectomy (n=4), sleeve gastrectomy (n=1). Three of four studies
found improvements in pain intensity with butyrophenone use. Three of five studies reported no
change in postoperative opiate consumption, while two reported a decrease. One ED study reported
no change in patient satisfaction, while one postoperative study reported improved satisfaction
scores. Both extrapyramidal side effects (n=3) and sedation (n=3) were reported as unchanged.
Conclusion: Based on available evidence, we cannot draw a conclusion on the efficacy or
benefit of neuroleptanalgesia in the management of patients with AAP. However, preliminary
data suggest that it may improve analgesia and decrease opiate consumption
Peptide cargo tunes a network of correlated motions in human leukocyte antigens
Most biomolecular interactions are typically thought to increase the (local) rigidity of a complex, for example, in drugâtarget binding. However, detailed analysis of specific biomolecular complexes can reveal a more subtle interplay between binding and rigidity. Here, we focussed on the human leucocyte antigen (HLA), which plays a crucial role in the adaptive immune system by presenting peptides for recognition by the αÎČ Tâcell receptor (TCR). The role that the peptide plays in tuning HLA flexibility during TCR recognition is potentially crucial in determining the functional outcome of an immune response, with obvious relevance to the growing list of immunotherapies that target the Tâcell compartment. We have applied highâpressure/temperature perturbation experiments, combined with molecular dynamics simulations, to explore the drivers that affect molecular flexibility for a series of different peptideâHLA complexes. We find that different peptide sequences affect peptideâHLA flexibility in different ways, with the peptide cargo tuning a network of correlated motions throughout the pHLA complex, including in areas remote from the peptideâbinding interface, in a manner that could influence Tâcell antigen discrimination
Molecular rules underpinning enhanced affinity binding of human T cell receptors engineered 2 for immunotherapy
Nonstimulatory peptide?MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling
First Results for Solar Soft X-ray Irradiance Measurements from the Third Generation Miniature X-Ray Solar Spectrometer
Three generations of the Miniature X-ray Solar Spectrometer (MinXSS) have
flown on small satellites with the goal "to explore the energy distribution of
soft X-ray (SXR) emissions from the quiescent Sun, active regions, and during
solar flares, and to model the impact on Earth's ionosphere and thermosphere".
The primary science instrument is the Amptek X123 X-ray spectrometer that has
improved with each generation of the MinXSS experiment. This third generation
MinXSS-3 has higher energy resolution and larger effective area than its
predecessors and is also known as the Dual-zone Aperture X-ray Solar
Spectrometer (DAXSS). It was launched on the INSPIRESat-1 satellite on 2022
February 14, and INSPIRESat-1 has successfully completed its 6-month prime
mission. The INSPIRESat-1 is in a dawn-dusk, Sun-Synchronous Orbit (SSO) and
therefore has 24-hour coverage of the Sun during most of its mission so far.
The rise of Solar Cycle 25 (SC-25) has been observed by DAXSS. This paper
introduces the INSPIRESat-1 DAXSS solar SXR observations, and we focus the
science results here on a solar occultation experiment and multiple flares on
2022 April 24. One key flare result is that the reduction of elemental
abundances is greatest during the flare impulsive phase and thus highlighting
the important role of chromospheric evaporation during flares to inject warmer
plasma into the coronal loops. Furthermore, these results are suggestive that
the amount of chromospheric evaporation is related to flare temperature and
intensity.Comment: 43 pages including 19-page Appendix A, 8 figures, 7 table
Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors
Evidence indicates that autoimmunity can be triggered by virus-specific CD8+ T cells that crossreact with self-derived peptide epitopes presented on the cell surface by major histocompatibility complex class I (MHCI) molecules. Identification of the associated viral pathogens is challenging because individual T-cell receptors can potentially recognize up to a million different peptides. Here, we generate peptide length-matched combinatorial peptide library (CPL) scan data for a panel of virus-specific CD8+ T-cell clones spanning different restriction elements and a range of epitope lengths. CPL scan data drove a protein database search limited to viruses that infect humans. Peptide sequences were ranked in order of likelihood of recognition. For all anti-viral CD8+ T-cell clones examined in this study, the index peptide was either the top-ranked sequence or ranked as one of the most likely sequences to be recognized. Thus, we demonstrate that anti-viral CD8+ T-cell clones are highly focused on their index peptide sequence and that âCPL-driven database searchingâ can be used to identify the inciting virus-derived epitope for a given CD8+ T-cell clone. Moreover, to augment access to CPL-driven database searching, we have created a publicly accessible webtool. Application of these methodologies in the clinical setting may clarify the role of viral pathogens in the etiology of autoimmune diseases
Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination
Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCRâCD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCRâCD3 complexes. We found that only TCRâCD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCRâpMHC affinity determined the density of TCRâCD3 clusters, which scaled with overall phosphorylation levels. Thus, TCRâCD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination
Recommended from our members
âBeing Yourselfâ in the Electronic Sweatshop: New Forms of Normative Control
This article extends research about high-commitment management practices in tightly controlled work environments typified by the call centre. One promising research avenue suggests that normative management systems in such contexts, involving âfunâ exercises and culture programmes, etc., are more about distracting employee attention away from other, more taxing controls. This article develops such an approach by exploring the specific nature and conditions of such distraction. An empirical study of a call centre in which employees were encouraged to âjust be themselvesâ (in relation to lifestyle differences, sexuality, diverse identities, etc.) reveals how the distractions are partly informed by the dysfunctions of existing technical, bureaucratic and conventional cultural controls, all of which homogenize workers. Furthermore, the new regime not only serves to distract employees, but proves instrumental in capturing their sociality, energy and âauthenticâ or ânon-workâ personalities as emotional labour. At the same time, it gives rise to some contestation and less individualistic forms of authenticity. These outcomes have wider implications for our understanding of worker autonomy in and around hybrid control systems
- âŠ