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https://www.readbyqxmd.com/read/28821400/alzheimer-s-disease-as-oligomeropathy
#1
REVIEW
Kenjiro Ono
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid β-protein (Aβ) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, Aβ has been suggested to be responsible for the pathogenesis of AD (the amyloid hypothesis). Aβ molecules tend to aggregate to form oligomers, protofibrils, and mature fibrils. Although mature fibrils in the final stage have been thought to be the cause of AD pathogenesis, recent studies using synthetic Aβ peptides, a cell culture model, Aβ precursor protein transgenic mice models, and human samples, such as cerebrospinal fluids and postmortem brains of AD patients, suggest that pre-fibrillar forms (oligomers of Aβ) are more deleterious than are extracellular fibril forms...
August 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28820467/aquaporin-4-functionality-and-virchow-robin-space-water-dynamics-physiological-model-for-neurovascular-coupling-and-glymphatic-flow
#2
REVIEW
Tsutomu Nakada, Ingrid L Kwee, Hironaka Igarashi, Yuji Suzuki
The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28819550/effects-of-storage-temperature-on-airway-exosome-integrity-for-diagnostic-and-functional-analyses
#3
Rosario Maroto, Yingxin Zhao, Mohammad Jamaluddin, Vsevolod L Popov, Hongwang Wang, Madumali Kalubowilage, Yueqing Zhang, Jonathan Luisi, Hong Sun, Christopher T Culbertson, Stefan H Bossmann, Massoud Motamedi, Allan R Brasier
Background: Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim: We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods: Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or -80°C...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28817096/time-resolved-study-of-nanomorphology-and-nanomechanic-change-of-early-stage-mineralized-electrospun-poly-lactic-acid-fiber-by-scanning-electron-microscopy-raman-spectroscopy-and-atomic-force-microscopy
#4
Mengmeng Wang, Yin Cai, Bo Zhao, Peizhi Zhu
In this study, scanning electron microscopy (SEM), Raman spectroscopy and high-resolution atomic force microscopy (AFM) were used to reveal the early-stage change of nanomorphology and nanomechanical properties of poly(lactic acid) (PLA) fibers in a time-resolved manner during the mineralization process. Electrospun PLA nanofibers were soaked in simulated body fluid (SBF) for different periods of time (0, 1, 3, 5, 7 and 21 days) at 10 °C, much lower than the conventional 37 °C, to simulate the slow biomineralization process...
August 17, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28814668/injury-induced-actin-cytoskeleton-reorganization-in-podocytes-revealed-by-super-resolution-microscopy
#5
Hani Y Suleiman, Robyn Roth, Sanjay Jain, John E Heuser, Andrey S Shaw, Jeffrey H Miner
The architectural integrity of tissues requires complex interactions, both between cells and between cells and the extracellular matrix. Fundamental to cell and tissue homeostasis are the specific mechanical forces conveyed by the actomyosin cytoskeleton. Here we used super-resolution imaging methods to visualize the actin cytoskeleton in the kidney glomerulus, an organized collection of capillaries that filters the blood to make the primary urine. Our analysis of both mouse and human glomeruli reveals a network of myosin IIA-containing contractile actin cables within podocyte cell bodies and major processes at the outer aspects of the glomerular tuft...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814497/extracellular-acid-base-balance-and-ion-transport-between-body-fluid-compartments
#6
REVIEW
Julian L Seifter, Hsin-Yun Chang
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment...
September 2017: Physiology
https://www.readbyqxmd.com/read/28812111/syndrome-of-inappropriate-anti-diuresis-induces-volume-dependent-hypercalciuria
#7
J Grellier, A Jaafar, A Martin, M El Alaoui, C Lebely, I Tack, M Vallet
Hyponatremia is associated with bone demineralization. We hypothesized that, during hyponatremia, calciuria and calcium balance depend on volemic status. We evaluated calciuria in patients with hyponatremia, secondary to SIAD or hypovolemia. Patients with SIAD exhibited a volemic expansion that was associated with hypercalciuria. Calciuria was proportional to markers of volemia. INTRODUCTION: Chronic mild hyponatremia has been associated with bone demineralization of unknown mechanisms...
August 15, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28811641/joint-inflammation-related-citrullination-of-functional-arginines-in-extracellular-proteins
#8
Kalle H Sipilä, Vipin Ranga, Pekka Rappu, Markku Mali, Laura Pirilä, Ilona Heino, Johanna Jokinen, Jarmo Käpylä, Mark S Johnson, Jyrki Heino
We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811499/the-role-of-dermcidin-isoform-2-in-the-occurrence-and-severity-of-diabetes
#9
Suman Bhattacharya, Md Mobidullah Khan, Chandradipa Ghosh, Sarbashri Bank, Smarajit Maiti
Diabetes is now epidemic worldwide. Several hundred-million peoples are presently suffering from this disease with other secondary-disorders. Stress, hypertension, sedentary life-style, carbohydrate/lipid metabolic-disorders due to genetic or environmental factors attributes to type-1 and/or type-2 diabetes. Present investigation demonstrates that stress-induced protein dermcidin isoform-2 (DCN-2) which appears in the serum of diabetic-patients play a key-role in this disease pathogenesis/severity. DCN-2 suppresses insulin production-release from liver/pancreas...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810844/effect-of-tolvaptan-on-renal-handling-of-water-and-sodium-gfr-and-central-hemodynamics-in-autosomal-dominant-polycystic-kidney-disease-during-inhibition-of-the-nitric-oxide-system-a-randomized-placebo-controlled-double-blind-crossover-study
#10
Safa Al Therwani, My Emma Sofie Malmberg, Jeppe Bakkestroem Rosenbaek, Jesper Noergaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis. Nitric oxide (NO) stimulates natriuresis and diuresis, but its role is unknown during tolvaptan treatment in ADPKD. METHODS: Eighteen patients with ADPKD received tolvaptan 60 mg or placebo in a randomized, placebo-controlled, double blind, crossover study. L-NMMA (L-NG-monomethyl-arginine) was given as a bolus followed by continuous infusion during 60 min...
August 15, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28808131/intercellular-communication-via-the-comx-inducing-peptide-xip-of-streptococcus-mutans
#11
Justin Kaspar, Simon A M Underhill, Robert C Shields, Adrian Reyes, Suzanne Rosenzweig, Stephen J Hagen, Robert A Burne
Gram-positive bacteria utilize exported peptides to coordinate genetic and physiological processes required for biofilm formation, stress responses and ecological competitiveness. One example is activation of natural genetic competence by ComR and the comX-inducing peptide (XIP) in Streptococcus mutans Although the competence pathway can be activated by addition of synthetic XIP in defined medium, the hypothesis that XIP is able to function as an intercellular signal molecule has not been rigorously tested...
August 14, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#12
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807994/a-novel-computational-model-predicts-key-regulators-of-chemokine-gradient-formation-in-lymph-nodes-and-site-specific-roles-for-ccl19-and-ackr4
#13
Mohammad Jafarnejad, David C Zawieja, Bindi S Brook, Robert J B Nibbs, James E Moore
The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807683/nano-sized-drug-carriers-extravasation-intratumoral-distribution-and-their-modeling
#14
Joseph W Nichols, Yu Sakurai, Hideyoshi Harashima, You Han Bae
Navigating intratumoral drug distribution has proven to be one of the most challenging aspects of drug delivery. The barriers are significant and varied; increased diffusional distances, elevated interstitial fluid pressure, regions of dense extracellular matrix and high cell density, and overall heterogeneity. Such a long list imposes significant requirements on nano-sized carriers. Unfortunately, other capabilities are eclipsed by the distribution requirements. A drug can do no good until it reaches its target...
August 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28806983/profiling-of-metalloprotease-activities-in-cerebrospinal-fluids-of-patients-with-neoplastic-meningitis
#15
Catharina Conrad, Kristina Dorzweiler, Miles A Miller, Douglas A Lauffenburger, Herwig Strik, Jörg W Bartsch
BACKGROUND: Neoplastic invasion into leptomeninges and subarachnoid space, resulting in neoplastic meningitis (NM) is a fatal complication of advanced solid and hematological neoplasms. Identification of malignant involvement of the cerebrospinal fluid (CSF) early in the disease course has crucial prognostic and therapeutic implications, but remains challenging. As indicators of extracellular matrix (ECM) degradation and breakdown of the blood-brain-barrier, Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloproteases (ADAMs) are potential analytes for cerebral pathophysiology and metastatic dissemination of tumor cells into the CSF...
August 14, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28805874/microfluidic-modeling-of-the-biophysical-microenvironment-in-tumor-cell-invasion
#16
Yu Ling Huang, Jeffrey E Segall, Mingming Wu
Tumor cell invasion, whether penetrating through the extracellular matrix (ECM) or crossing a vascular endothelium, is a critical step in the cancer metastatic cascade. Along the way from a primary tumor to a distant metastatic site, tumor cells interact actively with the microenvironment either via biomechanical (e. g. ECM stiffness) or biochemical (e.g. secreted cytokines) signals. Increasingly, it is recognized that the tumor microenvironment (TME) is a critical player in tumor cell invasion. A main challenge for the mechanistic understanding of tumor cell-TME interactions comes from the complexity of the TME, which consists of extracellular matrices, fluid flows, cytokine gradients and other cell types...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28804598/a-rigorous-method-to-enrich-for-exosomes-from-brain-tissue
#17
Laura J Vella, Benjamin J Scicluna, Lesley Cheng, Emma G Bawden, Colin L Masters, Ching-Seng Ang, Nicholas Willamson, Catriona McLean, Kevin J Barnham, Andrew F Hill
Extracellular vesicles, including exosomes, are released by all cells, including those of the nervous system. Capable of delivering lipid, protein and nucleic acids to both nearby and distal cells, exosomes have been hypothesized to play a role in progression of many diseases of the nervous system. To date, most analyses on the role of these vesicles in the healthy and diseased state have relied on studying vesicles from in vitro sources, such as conditioned cell culture media, or body fluids. Here we have taken a critical approach to the enrichment and characterization of exosomes from human frontal cortex...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28803831/localization-of-connexin-43-gap-junctions-and-hemichannels-in-tanycytes-of-adult-mice
#18
Anett Szilvásy-Szabó, Edina Varga, Zsuzsa Beliczai, Ronald M Lechan, Csaba Fekete
Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes...
August 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28803541/ion-exchange-chromatography-purification-of-extracellular-vesicles
#19
Maja Kosanović, Bojana Milutinović, Sanja Goč, Ninoslav Mitić, Miroslava Janković
Despite numerous studies, isolating pure preparations of extracellular vesicles (EVs) has proven challenging. Here, we compared ion-exchange chromatography (IEC) to the widely used sucrose density gradient (SDG) centrifugation method for the purification of EVs. EVs in bulk were isolated from pooled normal human amniotic fluid (AF) by differential centrifugation followed by IEC or sucrose density gradient separation. The purity of the isolated EVs was evaluated by electrophoresis and lectin blotting/immuno blotting to monitor the distribution of total proteins, different EVs markers, and selected N-glycans...
August 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28803246/biofunctional-ionic-doped-calcium-phosphates-silk-fibroin-composites-for-bone-tissue-engineering-scaffolding
#20
S Pina, R F Canadas, G Jiménez, M Perán, J A Marchal, R L Reis, J M Oliveira
The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attention, owing to their ability to promote cell adhesion, proliferation, and extracellular matrix production, which promote new bone growth. Here, we present novel biofunctional scaffolds for bone regeneration composed of silk fibroin (SF) and β-tricalcium phosphate (β-TCP) and incorporating Sr, Zn, and Mn, which were successfully developed using salt-leaching followed by a freeze-drying technique...
August 12, 2017: Cells, Tissues, Organs
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