New research examines how the aging brain prevents older adults from moving new memories into long-term storage, leading to “overnight forgetting.”
Posts Tagged ‘therapeutic’
This keeps older adults from ‘saving’ memories during sleep
Posted by Yasmin Anwar-UC Berkeley on December 18th, 2017
Posted in Physics, Science General, Technology 
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No Comments »Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer
Posted by Giannicola Genovese on February 8th, 2017
Malignant neoplasms evolve in response to changes in oncogenic signalling. Cancer cell plasticity in response to evolutionary pressures is fundamental to tumour progression and the development of therapeutic resistance. Here we determine the molecular and cellular mechanisms of cancer cell plasticity in a conditional oncogenic Kras mouse model of pancreatic ductal adenocarcinoma (PDAC), a malignancy that displays considerable phenotypic diversity and morphological heterogeneity. In this model, stochastic extinction of oncogenic Kras signalling and emergence of Kras-independent escaper populations (cells that acquire oncogenic properties) are associated with de-differentiation and aggressive biological behaviour. Transcriptomic and functional analyses of Kras-independent escapers reveal the presence of Smarcb1–Myc-network-driven mesenchymal reprogramming and independence from MAPK signalling. A somatic mosaic model of PDAC, which allows time-restricted perturbation of cell fate, shows that depletion of Smarcb1 activates the Myc network, driving an anabolic switch that increases protein metabolism and adaptive activation of endoplasmic-reticulum-stress-induced survival pathways. Increased protein turnover renders mesenchymal sub-populations highly susceptible to pharmacological and genetic perturbation of the cellular proteostatic machinery and the IRE1-α–MKK4 arm of the endoplasmic-reticulum-stress-response pathway. Specifically, combination regimens that impair the unfolded protein responses block the emergence of aggressive mesenchymal subpopulations in mouse and patient-derived PDAC models. These molecular and biological insights inform a potential therapeutic strategy for targeting aggressive mesenchymal features of PDAC.
Posted in Biology Tags: aggressive, aggressive mesenchymal, biological, Cancer, cancer cell plasticity, Cellular, Emergence, endoplasmic, Endoplasmic Reticulum, endoplasmic reticulum stress, Independent, Mesenchymal, mesenchymal subpopulations, molecular, network, Oncogenic, pancreatic, Perturbation, Plasticity, Populations, Protein, response, reticulum, reticulum stress, signalling, Stress, subpopulations, therapeutic No Comments »High-resolution crystal structure of the human CB1 cannabinoid receptor
Posted by Zhenhua Shao on November 16th, 2016
The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG), as well as the widely consumed plant (phyto)cannabinoid Δ9-tetrahydrocannabinol (THC)1. The cannabinoid receptors have been the targets of intensive drug discovery efforts owing to the therapeutic potential of modulators for controlling pain2, epilepsy3, obesity4, and other maladies. Although much progress has recently been made in understanding the biophysical properties of GPCRs, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. We used GPCR engineering and lipidic cubic phase (LCP) crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6 Å resolution. The extracellular surface of CB1, including the highly conserved membrane-proximal amino-terminal (N-terminal) region, is distinct from other lipid-activated GPCRs and forms a critical part of the ligand binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function, and will aid the design and optimization of cannabinoid system modulators for therapeutic ends.
Posted in Biology Tags: Cannabinoid, cannabinoid receptor, Modulators, pocket, receptor, Receptors, resolution, structure, terminal, therapeutic No Comments »Bacteria with ‘thermostats’ could bring drugs to your gut
Posted by Whitney Clavin-Caltech/JPL/NASA on November 15th, 2016
To fight cancer and other diseases of the gut, we could one day rely on […]
The post Bacteria with ‘thermostats’ could bring drugs to your gut appeared first on Futurity.
Posted in Biology, Health, Science General Tags: activate, activity, administered, all started with, altered, altered bacteria, and engineering took, Bacteria, bring drugs, called, Caltech, Cancer, Celsius, celsius bacteria, changes, chemical, Control, could bring, could bring drugs, create, degrees, Degrees Celsius, degrees celsius bacteria, demonstrated, designed, directed, Directed Evolution, disease, Doctors, engineered, engineered bacteria, engineering, Evolution, Express, fluorescent, fluorescent protein, foundation, genetic, Genetic Switches, genetically, genetically altered, genetically altered bacteria, gently, graduate, have shown that, instance, interest, Medicine, Microbes, Nature, patient, performance, piraner, Protein, Proteins, release, research, researchers, respond, Salmonella, Scientists, Shapiro, signal, started, started with what, studies, studies have shown, Switches, switching, Temperature, Temperature Changes, Temperatures, the engineered bacteria, the patient& 8217, theory, therapeutic, Therapy, thermal, thermal switches, these bacteria, Tumors, Ultrasound, what nature gave, with what nature No Comments »Ad26/MVA Therapeutic Vaccination with TLR7 Stimulation in SIV-Infected Rhesus Monkeys
Posted by Erica N. Borducchi on November 9th, 2016
The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of the HIV-1 cure field1,2. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy (ART). Here we show that Ad26/MVA3,4 therapeutic vaccination with toll-like receptor 7 (TLR7) stimulation improves virologic control and delays viral rebound following ART discontinuation in SIV-infected rhesus monkeys that initiated ART during acute infection. Ad26/MVA therapeutic vaccination resulted in a dramatic increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, as well as improved virologic control and delayed viral rebound following ART discontinuation. Cellular immune breadth correlated inversely with setpoint viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination with innate immune stimulation as a strategy aimed at an HIV-1 functional cure.
Posted in Biology Tags: Breadth, Cellular, cellular immune, Control, correlated, Discontinuation, following, immune, Immune Stimulation, infected, infected rhesus, infected rhesus monkeys, innate, innate immune, innate immune stimulation, Monkeys, mva therapeutic vaccination, Rebound, rebound following, reservoir, resulted, Rhesus, Rhesus Monkeys, siv infected rhesus, stimulation, the viral reservoir, therapeutic, therapeutic vaccination, therapeutic vaccination with, Vaccination, Viral Rebound, viral rebound following, viral reservoir, virologic, virologic control No Comments »
