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https://read.qxmd.com/read/30899214/molecular-mechanisms-of-synaptic-dysregulation-in-fragile-x-syndrome-and-autism-spectrum-disorders
#1
REVIEW
Michael Telias
Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment. FXS patient exhibit a high comorbidity rate with autism spectrum disorders (ASDs). This makes FXS a model disease for understanding how synaptic dysregulation alters neuronal excitability, learning and memory, social behavior, and more. Since 1991, with the discovery of fragile X mental retardation 1 (FMR1) as the sole gene that is mutated in FXS, thousands of studies into the function of the gene and its encoded protein FMR1 protein (FMRP), have been conducted, yielding important information regarding the pathophysiology of the disease, as well as insight into basic synaptic mechanisms that control neuronal networking and circuitry...
2019: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/30898416/multiple-autoimmune-disorders-in-aicardi-gouti%C3%A3-res-syndrome
#2
Debopam Samanta, Raghu Ramakrishnaiah, Shelley E Crary, Sukesh Sukumaran, Thomas A Burrow
BACKGROUND: Aicardi-Goutières syndrome is an early-onset encephalopathy with presumed immune pathogenesis caused by inherited defects in nucleic acid metabolism. It is a model disease to study systemic autoimmunity, and there are many clinical, genetic, and basic science considerations that underline a possible overlap between Aicardi-Goutières syndrome and systemic lupus erythematosus. RESULTS: We describe a 15-year-old girl with Aicardi-Goutières syndrome due to compound heterozygous pathogenic variants in SAMHD1 (sterile alpha motif domain and HD domain-containing protein 1)...
February 2, 2019: Pediatric Neurology
https://read.qxmd.com/read/30891151/crosstalk-between-gut-microbiota-and-antidiabetic-drug-action
#3
REVIEW
Yevheniia Kyriachenko, Tetyana Falalyeyeva, Oleksandr Korotkyi, Nataliia Molochek, Nazarii Kobyliak
Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease...
March 15, 2019: World Journal of Diabetes
https://read.qxmd.com/read/30890078/-interpretation-of-arterial-blood-gas-analysis
#4
Marek Nemec
Interpretation of Arterial Blood Gas Analysis Abstract. Arterial blood gas test is a common diagnostic method in clinical practice. It can detect the presence and identify the causes of acid-base and oxygenation disturbances. The correct interpretation of the results begins with a careful clinical evaluation of the patient and the knowledge of the basic principles of acid-base regulation. A systematic stepwise approach is recommended to find an accurate diagnosis and to better identify mixed acid-base disorders...
2019: Praxis
https://read.qxmd.com/read/30868786/association-of-non-alcoholic-fatty-liver-disease-with-serum-uric-acid
#5
Sarwat Abbasi, Nadia Haleem, Sara Jadoon, Amjad Farooq
BACKGROUND: Non-alcoholic fatty liver disorder is a clinicopathological condition, characterized by macro vesicular steatosis in hepatic cells and metabolic stress related disorders without other causes of chronic hepatic disease. Uric acid is basically a heterocyclic compound of hydrogen, carbon, oxygen and nitrogen. Uric acid is the metabolic end product of purine metabolism. Hyperuricemia is considered to be related with the causes responsible for the production of metabolic syndrome...
January 2019: Journal of Ayub Medical College, Abbottabad: JAMC
https://read.qxmd.com/read/30858092/lc-ms-ms-measurements-of-urinary-guanidinoacetic-acid-and-creatine-method-optimization-by-deleting-derivatization-step
#6
Rucheton Benoit, Mesli Samir, Julian Boutin, Amintas Samuel, Colombies Brigitte, Ducint Dominique, Redonnet-Vernhet Isabelle
BACKGROUND: Cerebral Creatine deficiency syndromes (CCDS) include three hereditary diseases affecting the metabolism of creatine (Cr): arginine glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency and disorders of creatine transporter. These pathologies cause a brain creatine deficiency responsible of non-specific neurological impairments with mental retardation. LC-MS/MS measurements of guanidinoacetic acid (GAA) and creatine in urine and plasma are an important screening test to identify the deficit...
March 8, 2019: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://read.qxmd.com/read/30790324/antiapoptosis-effect-of-zishen-prescription-to-increase-learning-and-memory-abilities-of-compound-alzheimer-s-disease-model-rats
#7
Zhiqiang Wei, Yu Zhang, Yan Chen, Xiaoshuang Xia, Boyu Zheng, Xugang Sun, Guangming Zhang, Ling Wang, Qi Zhang, Chen Xu, Shihe Jiang, Xiulian Li, Bingxin Xie, Xiaohui Liao, Zhu Ai, Xin Li
Alzheimer's disease (AD) is a neurodegenerative disease characterized progressive memory loss and cognitive impairment. In previous studies, the activities of extracts of Chinese medicinal herbs to treat brain function disorders caused by AD have already been reported. ZiShen prescription was a traditional Chinese medicine (TCM) compound prescription reformed for AD disease based on the basic theory of TCM. To explore the effect of ZiShen (kidney-reinforcing) prescription on the learning and memory abilities, we made compound AD model rats by injecting d-galactose and ibotenic acid into the abdominal cavity to damage both sides of the nucleus basalis of Meynert with ibotenic acid...
February 20, 2019: Journal of Cellular Biochemistry
https://read.qxmd.com/read/30769878/the-role-of-buffers-in-wild-type-hewl-amyloid-fibril-formation-mechanism
#8
Sandi Brudar, Barbara Hribar-Lee
Amyloid fibrils, highly ordered protein aggregates, play an important role in the onset of several neurological disorders. Many studies have assessed amyloid fibril formation under specific solution conditions, but they all lack an important phenomena in biological solutions-buffer specific effects. We have focused on the formation of hen egg-white lysozyme (HEWL) fibrils in aqueous solutions of different buffers in both acidic and basic pH range. By means of UV-Vis spectroscopy, fluorescence measurements and CD spectroscopy, we have managed to show that fibrillization of HEWL is affected by buffer identity (glycine, TRIS, phosphate, KCl-HCl, cacodylate, HEPES, acetate), solution pH, sample incubation (agitated vs...
February 14, 2019: Biomolecules
https://read.qxmd.com/read/30733478/fast-nmr-method-to-probe-solvent-accessibility-and-disordered-regions-in-proteins
#9
André F Faustino, Glauce M Barbosa, Micael Silva, Miguel A R B Castanho, Andrea T Da Poian, Eurico J Cabrita, Nuno C Santos, Fabio C L Almeida, Ivo C Martins
Understanding protein structure and dynamics, which govern key cellular processes, is crucial for basic and applied research. Intrinsically disordered protein (IDP) regions display multifunctionality via alternative transient conformations, being key players in disease mechanisms. IDP regions are abundant, namely in small viruses, allowing a large number of functions out of a small proteome. The relation between protein function and structure is thus now seen from a different perspective: as IDP regions enable transient structural arrangements, each conformer can play different roles within the cell...
February 7, 2019: Scientific Reports
https://read.qxmd.com/read/30733475/evolutionary-approach-of-intrinsically-disordered-cip-kip-proteins
#10
Muhamad Fahmi, Masahiro Ito
The mammalian CIP/KIP family proteins are intrinsically disordered proteins (IDPs) that can regulate various cellular processes. However, many reports have shown that IDPs generally evolve more rapidly than ordered proteins. Here, to elucidate the functional adaptability of CIP/KIP proteins in vertebrate, we analysed the rates of evolution in relation to their structural and sequence properties and predicted the post-translational modification based on the sequence data. The results showed that CIP/KIP proteins generally could maintain their function through evolution in the vertebrate...
February 7, 2019: Scientific Reports
https://read.qxmd.com/read/30714802/reduction-of-bdnf-results-in-gabaergic-neuroplasticity-dysfunction-and-contributes-to-late-life-anxiety-disorder
#11
Gongbei Zhu, Xiaofei Sun, Yun Yang, Yao Du, Yuhan Lin, Jianming Xiang, Ningna Zhou
The GABAergic neuroplasticity dysfunction (GND) has been proposed as a distinct pathology for late-life anxiety disorder (LLAD). Brain-derived neurotrophic factor (BDNF) is a critical signaling molecule that regulates the GABAergic neuroplasticity. This research was designed to explore our hypothesis that the reduction of BDNF along with aging could induce GND, which might contribute to LLAD, and application of exogenous BDNF might reverse LLAD by restoring the GABAergic neuroplasticity. We focused on the hippocampus because it is the neural core of mood regulation and can be affected by aging...
February 4, 2019: Behavioral Neuroscience
https://read.qxmd.com/read/30683917/hiv-induced-neuroinflammation-impact-of-par1-and-par2-processing-by-furin
#12
Vatsal Sachan, Robert Lodge, Koichiro Mihara, Josée Hamelin, Christopher Power, Benjamin B Gelman, Morley D Hollenberg, Éric A Cohen, Nabil G Seidah
HIV-associated neurocognitive disorders (HAND) is a syndrome defined by neurocognitive deficits that are driven by viral neurotoxins, cytokines, free radicals, and proteases expressed in the brain. This neurological disease has also been linked to activation of Protease-Activated Receptors 1 and 2 (PAR1,2). These receptors are highly expressed in the central nervous system and are upregulated in HAND. Secretory basic-amino-acid-specific Proprotein Convertases (PCs), which cleave precursor proteins at basic residues, are also induced in HAND...
January 25, 2019: Cell Death and Differentiation
https://read.qxmd.com/read/30682436/abnormal-empathy-like-pro-social-behaviour-in-the-valproic-acid-model-of-autism-spectrum-disorder
#13
Mellanie Fontes-Dutra, Gustavo Della-Flora Nunes, Julio Santos Terra, Walquíria Souza-Nunes, Guilherme Bauer-Negrini, Mauro Mozael Hirsch, Lily Green, Rudimar Riesgo, Carmem Gottfried, Victorio Bambini-Junior
Impairments in social behaviour are a defining feature of autism spectrum disorder (ASD). Individuals with ASD also usually present some difficulty to recognise or understand another person's feelings. Therefore, it is possible that altered empathy processing could hinder typical social interaction in ASD. Recently, robust paradigms confirmed that rodents show primordial forms of empathy-like behaviour. Therefore, in this work, we used one of these new protocols to test pro-social behaviour in the rat model of autism induced by Valproic Acid (VPA)...
January 22, 2019: Behavioural Brain Research
https://read.qxmd.com/read/30670178/establishment-of-a-%C3%AE-f508-cf-promyelocytic-cell-line-for-cystic-fibrosis-research-and-drug-screening
#14
Scott Jennings, Hang Pong Ng, Guoshun Wang
Cystic fibrosis (CF), one of the most common genetic disorders, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In spite of significant improvement in patient life expectancy, the disease remains lethal and incurable. Clinically, CF lung disease claims the most morbidity and mortality, characterized by chronic bacterial infection, persistent neutrophilic inflammation, and purulent small airway obstruction. Although all these manifestations are highly associated with neutrophils, the actual role of this phagocyte in the disease pathogenesis has not been fully appreciated...
January 2019: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://read.qxmd.com/read/30594987/3-d-printing-of-chitosan-calcium-phosphate-inks-rheology-interactions-and-characterization
#15
Silvia Stella Ramirez Caballero, Eduardo Saiz, Alexandra Montembault, Solène Tadier, Eric Maire, Laurent David, Thierry Delair, Laurent Grémillard
Bone substitute fabrication is of interest to meet the worldwide incidence of bone disorders. Physical chitosan hydrogels with intertwined apatite particles were chosen to meet the bio-physical and mechanical properties required by a potential bone substitute. A set up for 3-D printing by robocasting was found adequate to fabricate scaffolds. Inks consisted of suspensions of calcium phosphate particles in chitosan acidic aqueous solution. The inks are shear-thinning and consist of a suspension of dispersed platelet aggregates of dicalcium phosphate dihydrate in a continuous chitosan phase...
December 29, 2018: Journal of Materials Science. Materials in Medicine
https://read.qxmd.com/read/30579255/the-flavonoid-rich-fraction-from-rhizomes-of-smilax-glabra-roxb-ameliorates-renal-oxidative-stress-and-inflammation-in-uric-acid-nephropathy-rats-through-promoting-uric-acid-excretion
#16
Siwei Wang, Yuejuan Fang, Xinfen Yu, Lu Guo, Xiaoxi Zhang, Daozong Xia
Uric acid metabolic disorder is considered to be the main pathogenesis of uric acid nephropathy (UN). Smilax glabra Roxb. is a traditional Chinese herb which has been used in the treatment of gout, but the mechanism was unclear. In this study, we investigated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on uric acid nephropathy rats and its underlying mechanisms of promoting uric acid excretion. Sprague Dawley (SD) rats were induced by high purine diet (yeast pellets + adenine) for 5 weeks...
December 19, 2018: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/30559189/structure-of-the-lipoprotein-lipase-gpihbp1-complex-that-mediates-plasma-triglyceride-hydrolysis
#17
Gabriel Birrane, Anne P Beigneux, Brian Dwyer, Bettina Strack-Logue, Kristian Kølby Kristensen, Omar L Francone, Loren G Fong, Haydyn D T Mertens, Clark Q Pan, Michael Ploug, Stephen G Young, Muthuraman Meiyappan
Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries is bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in LPL or GPIHBP1 cause severe hypertriglyceridemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive. Inspired by our recent discovery that GPIHBP1's acidic domain preserves LPL structure and activity, we crystallized an LPL-GPIHBP1 complex and solved its structure...
December 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30536994/the-clinical-impact-of-exosomes-in-cardiovascular-disorders-from-basic-science-to-clinical-application
#18
REVIEW
Farzaneh Ghafarian, Mehran Pashirzad, Majid Khazaei, Majid Rezayi, Seyed Mahdi Hassanian, Gordon A Ferns, Amir Avan
Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of a valid biomarker that accurately predicts the risk of developing CVD, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, messenger RNAs, noncoding RNA, and nucleic acid contents that are important players in intercellular communication, and that act via long-range signals or cell-to-cell contact...
December 10, 2018: Journal of Cellular Physiology
https://read.qxmd.com/read/30447256/humble-beginnings-with-big-goals-small-molecule-soluble-epoxide-hydrolase-inhibitors-for-treating-cns-disorders
#19
REVIEW
Sydney Zarriello, Julian Tuazon, Sydney Corey, Samantha Schimmel, Mira Rajani, Anna Gorsky, Diego Incontri, Bruce D Hammock, Cesar V Borlongan
Soluble epoxide hydrolase (sEH) degrades epoxides of fatty acids including epoxyeicosatrienoic acid isomers (EETs), which are produced as metabolites of the cytochrome P450 branch of the arachidonic acid pathway. EETs exert a variety of largely beneficial effects in the context of inflammation and vascular regulation. sEH inhibition is shown to be therapeutic in several cardiovascular and renal disorders, as well as in peripheral analgesia, via the increased availability of anti-inflammatory EETs. The success of sEH inhibitors in peripheral systems suggests their potential in targeting inflammation in the central nervous system (CNS) disorders...
November 14, 2018: Progress in Neurobiology
https://read.qxmd.com/read/30446350/next-generation-sequencing-of-rna-reveals-novel-targets-of-resveratrol-with-possible-implications-for-canavan-disease
#20
Maja Dembic, Henriette S Andersen, Jean Bastin, Thomas K Doktor, Thomas J Corydon, Jörn Oliver Sass, Alexandra Lopes Costa, Fatima Djouadi, Brage S Andresen
Resveratrol (RSV) is a small compound first identified as an activator of sirtuin 1 (SIRT1), a key factor in mediating the effects of caloric restriction. Since then, RSV received great attention for its widespread beneficial effects on health and in connection to many diseases. RSV improves the metabolism and the mitochondrial function, and more recently it was shown to restore fatty acid β-oxidation (FAO) capacities in patient fibroblasts harboring mutations with residual enzyme activity. Many of RSV's beneficial effects are mediated by the transcriptional coactivator PGC-1α, a direct target of SIRT1 and a master regulator of the mitochondrial fatty acid oxidation...
October 22, 2018: Molecular Genetics and Metabolism
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