Bystander Attenuation Of Neuronal And Astrocyte Intercellular Communication By Murine Cytomegalovirus Infection Of Glia

Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in primary cultures of brain. These cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. Using ratiometric fura-2 digital calcium imaging of \u3e8,000 neurons and glia, we found that MCMV-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and ATP, and to high potassium levels. Cultured neurons with no sign of MCMV infection showed attenuated synaptic signaling after infection of the underlying astrocyte substrate, and intercellular communication between astrocytes with no sign of infection was reduced by the presence of infected glia. These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells

Molecular layer-by-layer re-stacking of MoS2–In2Se3 by electrostatic means: assembly of a new layered photocatalyst

2D-layered transition metal chalcogenides are useful semiconductors for a wide range of opto-electronic applications. Their similarity as layered structures offers exciting possibility to modify their electronic properties by creating new heterojunction assemblies from layer-by-layer restacking of individual monolayer sheets, however, the lack of specific interaction between these layers could induce phase segregation. Here, we employed a chemical method using n-BuLi to exfoliate MoS2 and In2Se3 into their monolayer-containing colloids in solution. The bulky Se atoms can be selectively leached from In2Se3 during Li treatment which gives positively charged surface monolayers in neutral pH whereas the strong polarization of Mo–S with moderate S leaching gives a negatively charged surface. Specific interlayer electrostatic attraction during their selective assembly gives a controllable atomic AB-type of layer stacking as supported by EXAFS, STEM with super-EDX mapping, TAS/TRPL and DFT calculations. Using this simple but inexpensive bottom-up solution method, a new photocatalyst assembled from layers for photo water splitting can be tailor-made with high activity

Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host\u27s response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14-15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual\u27s recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4-5, 2019

Correction to: Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.

Following publication of the original article [1], the author reported that an author name, Roberta Zappasodi, was missed in the authorship list

Photocrosslinked sustained release biodegradable preformed implants for ocular drug delivery

The thesis investigates the challenges associated with topical ocular formulations for prolonged treatment of various anterior ocular conditions due to limitations such as rapid elimination in the eye's biological environment. To overcome these challenges, researchers explore the use of photocrosslinked biodegradable implants composed of poly(ethylene glycol) diacrylate (PEGDA), poly(ethylene glycol) methacrylate (PEGMA), and poly(lactic-co-glycolic acid) (PLGA). These hydrogel-based implants demonstrate versatility in delivering small molecule drugs, including timolol maleate, latanoprost, and dexamethasone, for conditions like glaucoma and posterior segment inflammation. The study comprehensively characterises these implants, assessing swelling properties, network parameters, mechanical strength, in vitro drug release profiles, biocompatibility, degradation patterns, and the impact of sterilisation. The findings suggest the potential of photocrosslinked biodegradable implants as a promising approach for sustained and tailored drug delivery to the eye over extended periods.Thesis is embargoed until 31 July 2029.<br/

A retrospective review of the multidisciplinary management of medullary thyroid cancer: eligibility for systemic therapy

Abstract Background Medullary thyroid carcinoma (MTC) accounts for 1-2% of all thyroid cancers. The clinical course of metastatic disease can be indolent. Our aim was to characterize the natural history of disease to evaluate the true proportion of patients who would be eligible for the currently available systemic therapies. Methods The British Columbia Cancer Agency (BCCA) provides cancer care to a population of 4.6 million. A retrospective chart review was conducted of all patients with MTC referred to the BCCA from 1991 to 2013. Clinical characteristics, pathology, treatment and outcome data were collected. Relapse free survival and overall survival was determined for patients based on staging at the time of diagnosis. Results Of the 98 patients referred to the BCCA during the study period, inherited mutations were found in 6% though 60% did not undergo genetic testing. Based on clinical SEER staging at diagnosis 50% had localized disease, 38% regional, and 12% had distant metastasis. 77% had complete surgical resection of which 25% received adjuvant radiation therapy. Five year relapse free survival (RFS) for localized and regional disease was 75% and 66%, respectively (p = 0.006). Initial treatment of 23 patients with locally unresectable and metastatic disease predominantly involved multiple modalities. Of the 37 patients with relapsed or metastatic MTC only 7 (19%) patients received one or more course of chemotherapy for metastatic disease: 1 temsirolimus, 2 adriamycin, 3 sunitinib, 3 sorafenib, and 3 vandetanib. Five year OS based on clinical SEER stage: localized 93%, regional 72% and distant 33% (p < 0.001). Conclusion Localized and regional MTC treatment patterns reflect multidisciplinary management based on disease characteristics. Patients with distant disease had poor outcomes with 28% of patients dying from disease. In our cohort the minority of patients ultimately received systemic therapy due to timing and lack of TKI availability

Bystander Attenuation of Neuronal and Astrocyte Intercellular Communication by Murine Cytomegalovirus Infection of Glia▿

Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in primary cultures of brain. These cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. Using ratiometric fura-2 digital calcium imaging of >8,000 neurons and glia, we found that MCMV-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and ATP, and to high potassium levels. Cultured neurons with no sign of MCMV infection showed attenuated synaptic signaling after infection of the underlying astrocyte substrate, and intercellular communication between astrocytes with no sign of infection was reduced by the presence of infected glia. These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells