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Beatrice Ballarin, Michael Tymianski
Stroke creates a complex interplay of multiple signaing pathways including excitotoxicity, ionic imbalance, inflammation, oxidative stress and apoptosis. There are very few treatments that have been shown to be beneficial in acute stroke. Recent findings have provided insights into the pathophysiology and mechanisms of ischemic stroke, complementing the traditional glutamate hypothesis: the molecular interaction between PSD95 and GluN2B has been identified as a culprit in stroke-mediated excitotoxicity, leading to the discovery of NA-1, a peptide that disrupts that interaction, as a potent neuroprotective agent for the treatment of acute stroke...
March 22, 2018: Acta Pharmacologica Sinica
Saqib Hussain Ansari, Syed Omair Adil, Tahir Sultan Shamsi, Kashif Ali, Ali Akbar, Mirza Tasawer
AIM AND OBJECTIVES: Acute biochemical changes, hepatotoxicity, nephrotoxicity and frequency of infections are common in diffuse large B-cell Lymphoma patients undergoing Cyclophosphamide, hydroxyrubicin, Oncovin (Vincristine) Prednisolone (CHOP) and Rituximab plus CHOP chemo cycles. Eventually, it leads to prolong hospital stay and suspending the next chemotherapy cycles. Changes in biochemical profile and immunosuppressant effects correlated with dose intensity ratio, the findings of this study will be helpful in choices for the physician to discontinue therapy or delaying treatment...
March 20, 2018: Current Drug Safety
Andrea Becerra-Calixto, Rafael Posada-Duque, Gloria Patricia Cardona-Gómez
Astrocytes play metabolic and structural support roles and contribute to the integrity of the blood-brain barrier (BBB), linking communication between neurons and the endothelium. Cyclin-dependent kinase 5 (CDK5) likely exerts a dual effect on the endothelium and astrocytes due to its involvement in migration and angiogenesis; the overactivation of CDK5 is associated with dysfunction in glutamate recapture and hypoxia. Recently, we proposed that CDK5-targeted astrocytes facilitate the recovery of neurological and motor function in transplanted ischemic rats...
March 22, 2018: Molecular Neurobiology
David Curtis, Leda Coelewij, Shou-Hwa Liu, Jack Humphrey, Richard Mott
A previous study of exome-sequenced schizophrenia cases and controls reported an excess of singleton, gene-disruptive variants among cases, concentrated in particular gene sets. The dataset included a number of subjects with a substantial Finnish contribution to ancestry. We have reanalysed the same dataset after removal of these subjects and we have also included non-singleton variants of all types using a weighted burden test which assigns higher weights to variants predicted to have a greater effect on protein function...
March 21, 2018: Behavior Genetics
Paolo Bollella, Yuya Hibino, Kenji Kano, Lo Gorton, Riccarda Antiochia
We report on the influence of pH and monovalent/divalent cations on the catalytic current response, internal electron transfer (IET), and structure of fructose dehydrogenase (FDH) by using amperometry, spectrophotometry, and circular dichroism (CD). Amperometric measurements were performed on graphite electrodes, onto which FDH was adsorbed and the effect on the response current to fructose was investigated when varying the pH and the concentrations of divalent/monovalent cations in the contacting buffer. In the presence of 10 mM CaCl2 , a current increase of up to ≈ 240% was observed, probably due to an intra-complexation reaction between Ca2+ and the aspartate/glutamate residues found at the interface between the dehydrogenase domain and the cytochrome domain of FDH...
March 22, 2018: Analytical and Bioanalytical Chemistry
Mitul A Mehta, Anne Schmechtig, Vasileia Kotoula, Juliet McColm, Kimberley Jackson, Claire Brittain, Sitra Tauscher-Wisniewski, Bruce J Kinon, Paul D Morrison, Thomas Pollak, Timothy Mant, Steven C R Williams, Adam J Schwarz
BACKGROUND: Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system...
March 21, 2018: Psychopharmacology
Siobhan A Turner, Qinxi Ma, Mihaela Ola, Kontxi Martinez de San Vicente, Geraldine Butler
Fungi can use a wide variety of nitrogen sources. In the absence of preferred sources such as ammonium, glutamate, and glutamine, secondary sources, including most other amino acids, are used. Expression of the nitrogen utilization pathways is very strongly controlled at the transcriptional level. Here, we investigated the regulation of nitrogen utilization in the pathogenic yeast Candida parapsilosis . We found that the functions of many regulators are conserved with respect to Saccharomyces cerevisiae and other fungi...
March 2018: MSphere
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
Chunxiao Qi, Xiaoming Ji, Guoliang Zhang, Yunxiao Kang, Yuanxiang Huang, Rui Cui, Shuangcheng Li, Huixian Cui, Geming Shi
The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopaminergic system and the elevated levels of serotonin in the nucleus accumbens, without affecting the levels of glutamate, γ-aminobutyric acid, norepinephrine and histamine in the caudate putamen and nucleus accumbens of PND21 and PND49 rats...
March 21, 2018: Journal of Endocrinology
Thomas V Riley, Deirdre A Collins, Rina Karunakaran, Maria Abdul Kahar, Ariza Adnan, Siti Asma Hassan, Nadiah Hanim Zainul, Fr Mohammed Rustam, Z Abd Wahab, Ramliza Ramli, Yeong Yeh Lee, Hamimah Hassan
Accumulating evidence shows a high prevalence of Clostridium difficile in Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigated C. difficile infection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A/B were performed on diarrhoeal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates of C. difficile characterised by PCR ribotyping and detection of toxin genes...
March 21, 2018: Journal of Clinical Microbiology
Nada Assi, Duncan C Thomas, Michael Leitzman, Magdalena Stepien, Veronique Chajes, Thierry Philip, Paolo Vineis, Christina Bamia, Marie-Christine Boutron-Ruault, Torkjel M Sandanger, Amaia Molinuevo, Hendriek C Boshuizen, Anneli Sundkvist, Tilman Kühn, Ruth C Travis, Kim Overvad, Elio Riboli, Marc J Gunter, Augustin Scalbert, Mazda Jenab, Pietro Ferrari, Vivian Viallon
BACKGROUND: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within EPIC where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. METHODS: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls...
March 21, 2018: Cancer Epidemiology, Biomarkers & Prevention
Ewelina Bratek, Apolonia Ziembowicz, Elzbieta Salinska
Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible experimental therapies, the induction of ischemic tolerance is promising. Recent investigations have shown that activation of group II metabotropic glutamate receptors (mGluR2/3) can provide neuroprotection against H-I, but the mechanism of this effect is not clear...
March 17, 2018: Brain Sciences
Kate S Collison, Angela Inglis, Sherin Shibin, Soad Saleh, Bernard Andres, Rosario Ubungen, Jennifer Thiam, Princess Mata, Futwan A Al-Mohanna
RATIONALE: Aspartame (L-aspartyl phenylalanine methyl ester) is a non-nutritive sweetener (NNS) approved for use in more than 6000 dietary products and pharmaceuticals consumed by the general public including adults and children, pregnant and nursing mothers. However a recent prospective study reported a doubling of the risk of being overweight amongst 1-year old children whose mothers consumed NNS-sweetened beverages daily during pregnancy. We have previously shown that chronic aspartame (ASP) exposure commencing in utero may detrimentally affect adulthood adiposity status, glucose metabolism and aspects of behavior and spatial cognition, and that this can be modulated by developmental N-methyl-D-aspartate receptor (NMDAR) blockade with the competitive antagonist CGP 39551 (CGP)...
2018: PloS One
Germano Guerra, Angela Lucariello, Angelica Perna, Laura Botta, Antonio De Luca, Francesco Moccia
BACKGROUND: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+ -dependent manner throughout peripheral vasculature...
March 21, 2018: International Journal of Molecular Sciences
Wuxing Dong, Alison C Todd, Angelika Bröer, Sarah R Hulme, Stefan Bröer, Brian Billups
Astrocytes are glial cells that have an intimate physical and functional association with synapses in the brain. One of their main roles is to recycle the neurotransmitters glutamate and gamma-aminobutyric acid (GABA), as a component of the glutamate/GABA-glutamine cycle. They perform this function by sequestering neurotransmitters and releasing glutamine via the neutral amino acid transporter SNAT3. In this way, astrocytes regulate the availability of neurotransmitters and subsequently influence synaptic function...
March 21, 2018: International Journal of Molecular Sciences
Sawsan Aboul-Fotouh, Mohamed Habib, Tarek Asaad, Samar K Kassim, Mohamed H Ghanem
Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression...
March 20, 2018: Behavioural Pharmacology
Hojun Sung, Hyun Sik Kim, June-Young Lee, Woorim Kang, Pil Soo Kim, Dong-Wook Hyun, Euon Jung Tak, Mi-Ja Jung, Ji-Hyun Yun, Min-Soo Kim, Na-Ri Shin, Tae Woong Whon, Jeong Rae Rho, Sun Duk Park, Hyung Eun Shim, Jin-Woo Bae
A Gram-stain-positive, facultatively aerobic, spore-forming, oxidase-positive, catalase- and DNase-negative, rod-shaped and motile bacterial strain, AR23208T , was isolated from the gut of a cinereous vulture (Aegypius monachus), collected at Seoul Grand Park Zoo (Republic of Korea). Strain AR23208T grew optimally at 25-30 °C, at pH 7 and in the absence of NaCl. Phylogenetic analysis revealed that strain AR23208T shared 98.2 and 97.1 % 16S rRNA gene sequence similarity with Tumebacillus algifaecis THMBR28T and Tumebacilluslipolyticus NIO-S10T , respectively...
March 21, 2018: International Journal of Systematic and Evolutionary Microbiology
Mindy Elizabeth Hair, Adrianna I Mathis, Erica K Brunelle, Lenka Halámková, Jan Halámek
Sweat is a biological fluid present on the skin surface of every individual and is known to contain amino acids as well as other low molecular weight compounds. Each individual is inherently different from one another based on certain factors including, but not limited to, his/her genetic make-up, environment, and lifestyle. As such, the biochemical composition of each person greatly differs. The concentrations of the biochemical content within an individual's sweat are largely controlled by metabolic processes within the body that fluctuate regularly based on attributes such as age, gender, and activity levels...
March 21, 2018: Analytical Chemistry
G V Ponomarev, T V Lalayan, S A Dambinova, A A Skoromets
The study aimed at assessing the level of glutamate receptors antibodies (Abs) in blood serum and cerebrospinal fluid (CSF) of patients with spinal cord ischemia along with traditional diagnostic approaches. MATERIAL AND METHODS: Forty patients with spinal cord ischemia (10 with spinal stroke and 30 with subacute and chronic course of the disease) were enrolled. After exclusion of some participants, 27 patients continued the study. Comparison groups included 30 patients with ischemic stroke and 30 patients with radiculopathy...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Pranjul Mishra, Na-Rae Lee, Meiyappan Lakshmanan, Minsuk Kim, Byung-Gee Kim, Dong-Yup Lee
BACKGROUND: Recently, there have been several attempts to produce long-chain dicarboxylic acids (DCAs) in various microbial hosts. Of these, Yarrowia lipolytica has great potential due to its oleaginous characteristics and unique ability to utilize hydrophobic substrates. However, Y. lipolytica should be further engineered to make it more competitive: the current approaches are mostly intuitive and cumbersome, thus limiting its industrial application. RESULTS: In this study, we proposed model-guided metabolic engineering strategies for enhanced production of DCAs in Y...
March 19, 2018: BMC Systems Biology
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