Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells.

Lipid raft membrane compartmentalization and membrane-associated guanylate kinase (MAGUK) family molecular scaffolds function in establishing cell polarity and organizing signal transducers within epithelial cell junctions and neuronal synapses. Here, we elucidate a role for the MAGUK protein, Dlgh1, in polarized T cell synapse assembly and T cell function. We find that Dlgh1 translocates to the immune synapse and lipid rafts in response to T cell receptor (TCR)/CD28 engagement and that LckSH3-mediated interactions with Dlgh1 control its membrane targeting. TCR/CD28 engagement induces the formation of endogenous Lck-Dlgh1-Zap70-Wiskott-Aldrich syndrome protein (WASp) complexes in which Dlgh1 acts to facilitate interactions of Lck with Zap70 and WASp. Using small interfering RNA and overexpression approaches, we show that Dlgh1 promotes antigen-induced actin polymerization, synaptic raft and TCR clustering, nuclear factor of activated T cell activity, and cytokine production. We propose that Dlgh1 coordinates TCR/CD28-induced actin-driven T cell synapse assembly, signal transduction, and effector function. These findings highlight common molecular strategies used to regulate cell polarity, synapse assembly, and transducer organization in diverse cellular systems

Outcomes of 23-gauge pars plana vitrectomy in combined scleral buckling and vitrectomy for complex rhegmatogenous retinal detachments

Rhegmatogenous retinal detachments associated with proliferative vitreoretinopathy, giant retinal tears, ocular trauma, proliferative diabetic retinopathy, or necrotizing retinitis are considered more complex than those without these factors. The aim of the current review is to address the surgical outcomes and complications of 23-gauge pars plana vitrectomy with scleral buckling (23GPPV/SB) for repair of these complex retinal detachments. This retrospective study involved 54 eyes of 53 patients who underwent 23GPPV/SB between July 2007 and September 2009. Preoperative diagnosis, surgical technique, preoperative and postoperative visual acuities, intraoperative and postoperative complications, and anatomic reattachment rates were examined. Fifty-four eyes of 53 patients were reviewed in this study and indications for surgery varied. Mean logarithm of the minimal angle of resolution (logMAR) pre- and post-operative visual acuities were 1.166 (20/293) and 0.780 (20/120), respectively, which led to a statistically significant improvement in logMAR (P=0.0165). Single operation and final reattachment rates were 87% (47 of 54 eyes) and 100%, respectively. Postoperative complications included choroidal effusion/hemorrhage (14.8%, 8 of 54 eyes) and vitreous hemorrhage (11.1%, 6 of 54 eyes). Other more infrequent complications included hyphema (9.3%, 5 of 54 eyes), hypotony (5.6%, 3 of 54 eyes) and ocular hypertension > 35 mmHg (3.7%, 2 of 54 eyes). A total of 31.5% (17 of 54 eyes) of patients had a complication in the postoperative time period, but 58.8% of these resolved spontaneously without requiring an intervention. 23GPPV/SB may be considered for complex retinal detachment repair with good anatomic reattachment rates, but with relatively high complication rates

Tumor Growth Enhances Cross-Presentation Leading to Limited T Cell Activation without Tolerance

Using a tumor model of spontaneously arising insulinomas expressing a defined tumor-associated antigen, we investigated whether tumor growth promotes cross-presentation and tolerance of tumor-specific T cells. We found that an advanced tumor burden enhanced cross-presentation of tumor-associated antigens to high avidity tumor-specific T cells, inducing T cell proliferation and limited effector function in vivo. However, contrary to other models, tumor-specific T cells were not tolerized despite a high tumor burden. In fact, in tumor-bearing mice, persistence and responsiveness of adoptively transferred tumor-specific T cells were enhanced. Accordingly, a potent T cell–mediated antitumor response could be elicited by intravenous administration of tumor-derived peptide and agonistic anti-CD40 antibody or viral immunization and reimmunization. Thus, in this model, tumor growth promotes activation of high avidity tumor-specific T cells instead of tolerance. Therefore, the host remains responsive to T cell immunotherapy

Big Data and AI – A transformational shift for government: So, what next for research?

Big Data and artificial intelligence will have a profound transformational impact on governments around the world. Thus, it is important for scholars to provide a useful analysis on the topic to public managers and policymakers. This study offers an in-depth review of the Policy and Administration literature on the role of Big Data and advanced analytics in the public sector. It provides an overview of the key themes in the research field, namely the application and benefits of Big Data throughout the policy process, and challenges to its adoption and the resulting implications for the public sector. It is argued that research on the subject is still nascent and more should be done to ensure that the theory adds real value to practitioners. A critical assessment of the strengths and limitations of the existing literature is developed, and a future research agenda to address these gaps and enrich our understanding of the topic is proposed

Glossary of methods and terms used in analytical spectroscopy (IUPAC Recommendations 2019)

Recommendations are given concerning the terminology of concepts and methods used in spectroscopy in analytical chemistry, covering nuclear magnetic resonance spectroscopy, atomic spectroscopy, and vibrational spectroscopy. © 2021 IUPAC and De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: http://creativecommons.org/licenses/by-nc-nd/4.0/ 2021

Evaluation of the clinical value of bone metabolic parameters for the screening of osseous metastases compared to bone scintigraphy

BACKGROUND: Bone metastases are common in many types of cancer. As screening methods different imaging modalities are available. A new approach for the screening of osseous metastases represents the measurement of bone metabolic markers. Therefore aim of this study was to evaluate the usefulness of the determination of bone metabolic markers aminoterminal propeptide of type I procollagen (PINP, osteoblastic activity) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP, osteoclastic activity) for the detection of bone metastases associated with other malignancies. METHODS: 88 patients aged 21 – 82 years with malignant tumors were prospectively studied. The serum concentrations of PINP and ICTP were measured and compared to the results of bone scintigraphy, radiological bone series, CT, MRI and clinical follow-up. RESULTS: Osseous metastases were found in 21 patients. 19 of them were correctly identified by bone scintigraphy (sensitivity: 90%). For bone metabolic markers results were as follows: ICTP sensitivity: 71%, specificity: 42%; PINP sensitivity: 24%, specificity: 96%. CONCLUSIONS: As markers of bone metabolism PINP and ICTP showed low sensitivity and/or specificity for the detection of osseous metastases. The presented markers did not seem to be sufficient enough to identify patients with bone metastases or to replace established screening methods