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https://www.readbyqxmd.com/read/29452157/hypertrophic-cardiomyopathy-mutation-r58q-in-the-myosin-regulatory-light-chain-perturbs-thick-filament-based-regulation-in-cardiac-muscle
#1
Thomas Kampourakis, Saraswathi Ponnam, Malcolm Irving
Hypertrophic cardiomyopathy (HCM) is frequently linked to mutations in the protein components of the myosin-containing thick filaments leading to contractile dysfunction and ultimately heart failure. However, the molecular structure-function relationships that underlie these pathological effects remain largely obscure. Here we chose an example mutation (R58Q) in the myosin regulatory light chain (RLC) that is associated with a severe HCM phenotype and combined the results from a wide range of in vitro and in situ structural and functional studies on isolated protein components, myofibrils and ventricular trabeculae to create an extensive map of structure-function relationships...
February 13, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29451895/metabolic-enzyme-cost-explains-variable-trade-offs-between-microbial-growth-rate-and-yield
#2
Meike T Wortel, Elad Noor, Michael Ferris, Frank J Bruggeman, Wolfram Liebermeister
Microbes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29451805/loss-and-formation-of-malodorous-volatile-sulfhydryl-compounds-during-wine-storage
#3
Gal Y Kreitman, Ryan J Elias, David W Jeffery, Gavin L Sacks
Volatile sulfur compounds (VSCs), particularly low molecular weight sulfhydryls like hydrogen sulfide (H 2 S) and methanethiol (MeSH), are often observed in wines with sulfurous off-aromas. Recent work has shown both H 2 S and MeSH can increase up to a few µM (> 40 µg/L) during anoxic storage, but the identity of the latent sources of these sulfhydryls is still disputed. This review critically evaluates the latent precursors and pathways likely to be responsible for the loss and formation of these sulfhydryls during wine storage based on the existing enology literature as well as studies from food chemistry, geochemistry, biochemistry, and synthetic chemistry...
February 16, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29449457/the-activity-of-thalamic-nucleus-reuniens-is-critical-for-memory-retrieval-but-not-essential-for-the-early-phase-of-off-line-consolidation
#4
Hao Mei, Nikos K Logothetis, Oxana Eschenko
Spatial navigation depends on the hippocampal function, but also requires bidirectional interactions between the hippocampus (HPC) and the prefrontal cortex (PFC). The cross-regional communication is typically regulated by critical nodes of a distributed brain network. The thalamic nucleus reuniens (RE) is reciprocally connected to both HPC and PFC and may coordinate the information flow within the HPC-PFC pathway. Here we examined if RE activity contributes to the spatial memory consolidation. Rats were trained to find reward following a complex trajectory on a crossword-like maze...
March 2018: Learning & Memory
https://www.readbyqxmd.com/read/29446868/the-amyloid-polymorphism-in-the-protein-folding-and-aggregation-energy-landscape
#5
Raffaele Mezzenga, Jozef Adamcik
Protein folding (and misfolding) is of paramount importance to an extraordinary vast class of fields, spanning from biochemistry to biology, medicine, biophysics and statistical thermodynamics. The folding process involves a large number of steps and conformations in which the folding protein samples different thermodynamic states characterized by local minima and activation energies in between. The kinetically trapped on- or off-pathway intermediates identifying the relative minima are metastable folding intermediates towards the lowest absolute energy minima, which have been postulated to be the natively folded state for the regime in which the intramolecular interactions dominate, and the amyloid status for the regime where intermolecular interactions rule...
February 15, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29445344/invertebrate-trehalose-6-phosphate-synthase-gene-genetic-architecture-biochemistry-physiological-function-and-potential-applications
#6
REVIEW
Bin Tang, Su Wang, Shi-Gui Wang, Hui-Juan Wang, Jia-Yong Zhang, Shuai-Ying Cui
The non-reducing disaccharide trehalose is widely distributed among various organisms. It plays a crucial role as an instant source of energy, being the major blood sugar in insects. In addition, it helps countering abiotic stresses. Trehalose synthesis in insects and other invertebrates is thought to occur via the trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) pathways. In many insects, the TPP gene has not been identified, whereas multiple TPS genes that encode proteins harboring TPS/OtsA and TPP/OtsB conserved domains have been found and cloned in the same species...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29444113/effects-of-protein-protein-interactions-and-ligand-binding-on-the-ion-permeation-in-kcnq1-potassium-channel
#7
Horia Jalily Hasani, Aravindhan Ganesan, Marawan Ahmed, Khaled H Barakat
The voltage-gated KCNQ1 potassium ion channel interacts with the type I transmembrane protein minK (KCNE1) to generate the slow delayed rectifier (IKs) current in the heart. Mutations in these transmembrane proteins have been linked with several heart-related issues, including long QT syndromes (LQTS), congenital atrial fibrillation, and short QT syndrome. Off-target interactions of several drugs with that of KCNQ1/KCNE1 ion channel complex have been known to cause fatal cardiac irregularities. Thus, KCNQ1/KCNE1 remains an important avenue for drug-design and discovery research...
2018: PloS One
https://www.readbyqxmd.com/read/29443498/spectrally-resolved-and-functional-super-resolution-microscopy-via-ultrahigh-throughput-single-molecule-spectroscopy
#8
Rui Yan, Seonah Moon, Samuel J Kenny, Ke Xu
As an elegant integration of the spatial and temporal dimensions of single-molecule fluorescence, single-molecule localization microscopy (SMLM) overcomes the diffraction-limited resolution barrier of optical microscopy by localizing single molecules that stochastically switch between fluorescent and dark states over time. While this type of super-resolution microscopy (SRM) technique readily achieves remarkable spatial resolutions of ∼10 nm, it typically provides no spectral information. Meanwhile, current scanning-based single-location approaches for mapping the positions and spectra of single molecules are limited by low throughput and are difficult to apply to densely labeled (bio)samples...
February 14, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29440911/should-frail-older-adults-be-in-long-term-care-facilities
#9
Liv Wergeland Sørbye, Sidsel Sverdrup, Birgit Brunborg Pay
Aim: Home-based nursing care is relatively easy to access in Norway compared to the rest of Europe, and the threshold for applying for assistance is relatively low. The aim of the present study was to analyze factors that enable frail older adults to live in their own homes, with a low level of care burden stress. Methodology: In 2015 and 2016, eight municipalities from different parts of Norway participated in a cross-sectional study. The quantitative part of the project consisted of assessing care of 71 older adults, aged ≥80 years, using a geriatric comprehensive assessment...
2018: Journal of Multidisciplinary Healthcare
https://www.readbyqxmd.com/read/29440406/chimeric-antigen-receptor-t-cells-form-nonclassical-and-potent-immune-synapses-driving-rapid-cytotoxicity
#10
A J Davenport, R S Cross, K A Watson, Y Liao, W Shi, H M Prince, P A Beavis, J A Trapani, M H Kershaw, D S Ritchie, P K Darcy, P J Neeson, M R Jenkins
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29436633/microarray-analysis-for-the-identification-of-specific-proteins-and-functional-modules-involved-in-the-process-of-hepatocellular-carcinoma-originating-from-cirrhotic-liver
#11
Wufeng Fan, Guangming Ye
In order to identify the potential pathogenesis of hepatocellular carcinoma (HCC) developing from cirrhosis, a microarray‑based transcriptome profile was analyzed. The GSE63898 expression profile was downloaded from the Gene Expression Omnibus database, which included data from 228 HCC tissue samples and 168 cirrhotic tissue samples. The Robust Multi‑array Average in the Affy package of R was used for raw data processing and Student's t‑test was used to screen differentially expressed genes (DEGs). An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the protein‑protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape...
February 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29433357/transferrin-and-octaarginine-modified-dual-functional-liposomes-with-improved-cancer-cell-targeting-and-enhanced-intracellular-delivery-for-the-treatment-of-ovarian-cancer
#12
Pranali Deshpande, Aditi Jhaveri, Bhushan Pattni, Swati Biswas, Vladimir Torchilin
Off-target effects of drugs severely limit cancer therapy. Targeted nanocarriers are promising to enhance the delivery of therapeutics to tumors. Among many approaches for active tumor-targeting, arginine-rich cell penetrating peptides (AR-CPP) and ligands specific to target over-expressed receptors on cancer-cell surfaces, are popular. Earlier, we showed that the attachment of an AR-CPP octaarginine (R8) to the surface of DOXIL® (Doxorubicin encapsulated PEGylated liposomes) improved cytoplasmic and nuclear DOX delivery that enhanced the cytotoxic effect in vitro and improved therapeutic efficacy in vivo...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29432815/targeting-the-ras-dependent-chemoresistance-the-warburg-connection
#13
REVIEW
Roberto Serna-Blasco, Marta Sanz-Álvarez, Óscar Aguilera, Jesús García-Foncillas
RAS protein family members (KRAS4A, KRAS4B, HRAS and NRAS) function as GDP-GTP-regulated on-off switches, which regulate cytoplasmic-nuclear signaling networks ruling diverse normal cellular processes. Constitutive activating mutations in RAS genes are found in up to 30% of human cancers, and remarkably, the oncogenic Ras mutations and mutations in other components of Ras/MAPK signaling pathways seem to be mutually exclusive in most tumors, pointing out that deregulation of Ras-dependent signaling is an essential requirement for tumorigenesis...
February 9, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29432770/rna-seq-analysis-during-the-life-cycle-of-cryptosporidium-parvum-reveals-significant-differential-gene-expression-between-proliferating-stages-in-the-intestine-and-infectious-sporozoites
#14
Christoph Lippuner, Chandra Ramakrishnan, Walter U Basso, Marc W Schmid, Michal Okoniewski, Nicholas C Smith, Michael Hässig, Peter Deplazes, Adrian B Hehl
Cryptosporidium parvum is a major cause of diarrhoea in humans and animals. There are no vaccines and few drugs available to control C. parvum. In this study, we used RNA-Seq to compare gene expression in sporozoites and intracellular stages of C. parvum to identify genes likely to be important for successful completion of the parasite's life cycle and, thereby, possible targets for drugs or vaccines. We identified 3774 protein-encoding transcripts in C. parvum. Applying a stringent cut-off of eight fold for determination of differential expression, we identified 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites...
February 9, 2018: International Journal for Parasitology
https://www.readbyqxmd.com/read/29432300/dopamine-modulates-striatal-response-to-reward-and-punishment-in-patients-with-parkinson-s-disease-a-pharmacological-challenge-fmri-study
#15
Miklos Argyelan, Mohammad Herzallah, Wataru Sako, Ivana DeLucia, Deepak Sarpal, An Vo, Toni Fitzpatrick, Ahmed A Moustafa, David Eidelberg, Mark Gluck
It is well established that Parkinson's disease leads to impaired learning from reward and enhanced learning from punishment. The administration of dopaminergic medications reverses this learning pattern. However, few studies have investigated the neural underpinnings of these cognitive processes. In this study, using fMRI, we tested a group of Parkinson's disease patients on and off dopaminergic medications and matched healthy individuals. All individuals completed an fMRI cognitive task that dissociates feedback learning from reward versus punishment...
February 9, 2018: Neuroreport
https://www.readbyqxmd.com/read/29430828/microwave-assisted-regeneration-of-single-walled-carbon-nanotubes-from-carbon-fragments
#16
Dewu Lin, Shuchen Zhang, Zhe Zheng, Wenping Hu, Jin Zhang
Direct growth of chirality-controlled single-walled carbon nanotubes (SWNTs) with metal catalyst free strategy, like cloning or epitaxial growth, has suffered from the low efficiency. The underlying problem is the activation of seed edge. Here an unexpectedly efficient microwave-assisted pathway to regenerate SWNTs from carbon fragments on SiO2 /Si substrate is demonstrated via Raman spectroscopy and atomic force microscope (AFM) characterization. In this attempt, microwave irradiation provides fast heating to remove polar groups bonded to carbon nanotubes and reduce the spontaneous closure of tubes' open ends...
February 12, 2018: Small
https://www.readbyqxmd.com/read/29428223/angiotensin-1-7-ameliorates-6-hydroxydopamine-lesions-in-hemiparkinsonian-rats-through-activation-of-mas-receptor-pi3k-akt-bdnf-pathway-and-inhibition-of-angiotensin-ii-type-1-receptor-nf-%C3%AE%C2%BAb-axis
#17
Mostafa A Rabie, Mai A Abd El Fattah, Noha N Nassar, Hanan S El-Abhar, Dalaal M Abdallah
MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, improved motor performance and muscle coordination. On the molecular level, Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a positive feedback upregulates MASR...
February 8, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29427801/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-introduction
#18
REVIEW
Mario Fernández-Ruiz, Yolanda Meije, Oriol Manuel, Hamdi Akan, Jordi Carratalà, José María Aguado, Julie Delaloye
BACKGROUND: The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for non-specialized clinicians. AIMS: The present Consensus Document is an initiative of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) aimed at analyzing, from an Infectious Diseases perspective, the safety of targeted and biological therapies. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 7, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29422643/rna-seq-transcriptome-analysis-of-breast-cancer-cell-lines-under-shikonin-treatment
#19
Kuo-Hua Lin, Ming-Yii Huang, Wei-Chung Cheng, Shu-Chi Wang, Shih-Hua Fang, Hung-Pin Tu, Chia-Cheng Su, Yung-Li Hung, Po-Len Liu, Chi-Shuo Chen, Yu-Ting Wang, Chia-Yang Li
Shikonin is a naphthoquinone isolated from the dried root of Lithospermum erythrorhizon, an herb used in Chinese medicine. Although several studies have indicated that shikonin exhibits antitumor activity in breast cancer, the mechanism of action remains unclear. In the present study, we performed transcriptome analysis using RNA-seq and explored the mechanism of action of shikonin in regulating the growth of different types of breast cancer cells. The IC50 of shikonin on MCF-7, SKBR-3 and MDA-MB-231 cells were 10...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29422442/pallidal-deep-brain-stimulation-modulates-excessive-cortical-high-%C3%AE-phase-amplitude-coupling-in-parkinson-disease
#20
Mahsa Malekmohammadi, Nicholas AuYong, Joni Ricks-Oddie, Yvette Bordelon, Nader Pouratian
OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are equally efficacious in the management of Parkinson disease (PD). Studies of STN-DBS have revealed a therapeutic reduction in excessive cortical β-γ phase-amplitude coupling (PAC). It is unclear whether this is specific to STN-DBS and potentially mediated by modulation of the hyperdirect pathway or if it is a generalizable mechanism seen with DBS of other targets. Moreover, it remains unclear how cortical signals are differentially modulated by movement versus therapy...
January 31, 2018: Brain Stimulation
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