scholarly journals D-Serine in Neuropsychiatric Disorders: New Advances

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Andrea R. Durrant ◽  
Uriel Heresco-Levy
Keyword(s):  
Amino Acid ◽  
First Generation ◽  
Neuropsychiatric Disorders ◽  
Depression And Anxiety ◽  
Proof Of Concept ◽  
Glycine Site ◽  
Pharmacological Manipulation ◽  
Treatment Refractory ◽  
Dependent Processes ◽  
Major Drug

D-Serine (DSR) is an endogenous amino acid involved in glia-synapse interactions that has unique neurotransmitter characteristics. DSR acts as obligatory coagonist at the glycine site associated with the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) and has a cardinal modulatory role in major NMDAR-dependent processes including NMDAR-mediated neurotransmission, neurotoxicity, synaptic plasticity, and cell migration. Since either over- or underfunction of NMDARs may be involved in the pathophysiology of neuropsychiatric disorders; the pharmacological manipulation of DSR signaling represents a major drug development target. A first generation of proof-of-concept animal and clinical studies suggest beneficial DSR effects in treatment-refractory schizophrenia, movement, depression, and anxiety disorders and for the improvement of cognitive performance. A related developing pharmacological strategy is the indirect modification of DSR synaptic levels by use of compounds that alter the function of main enzymes responsible for DSR production and degradation. Accumulating data indicate that, during the next decade, we will witness important advances in the understanding of DSR role that will further contribute to elucidating the causes of neuropsychiatric disorders and will be instrumental in the development of innovative treatments.

scholarly journals Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoto Kamagata ◽  
Rika Chiba ◽  
Ichiro Kawahata ◽  
Nanako Iwaki ◽  
Saori Kanbayashi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Electrostatic Interactions ◽  
Amyloid Fibrils ◽  
Droplet Formation ◽  
Liquid Droplets ◽  
Proof Of Concept ◽  
Aggregate Formation ◽  
Fused In Sarcoma ◽  
Dynamics Simulations

AbstractLiquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggregation. The protocol essentially involves investigation of 19 amino acid additives and polymerization of the identified amino acids. As a proof of concept, we applied this protocol to fused in sarcoma (FUS). First, we evaluated 19 amino acid additives for an FUS solution and identified Arg and Tyr as suppressors of droplet formation. Molecular dynamics simulations suggested that the Arg additive interacts with specific residues of FUS, thereby inhibiting the cation–π and electrostatic interactions between the FUS molecules. Second, we observed that Arg polymers promote FUS droplet formation, unlike Arg monomers, by bridging the FUS molecules. Third, we found that the Arg additive suppressed solid aggregate formation of FUS, while Arg polymer enhanced it. Finally, we observed that amyloid-forming peptides induced the conversion of FUS droplets to solid aggregates of FUS. The developed protocol could be used for the primary design of peptides controlling liquid droplets and aggregates of proteins.

scholarly journals Amino acid and mineral composition of milk from local Ukrainian cows and their crossbreedings with Brown Swiss and Montbeliarde breeds

2018 ◽  
Vol 43 (3) ◽  
pp. 238 ◽  
Author(s):  
A. A. Borshch ◽  
A.V. Borshch ◽  
M.M. Lutsenko ◽  
S.V. Merzlov ◽  
L.T. Kosior ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mineral Composition ◽  
Milk Protein ◽  
First Generation ◽  
Essential Amino Acids ◽  
Technological Properties ◽  
Crossbred Cows ◽  
Brown Swiss ◽  
Pure Breed ◽  
Dairy Breed

The aim of this study was to analyze the mineral composition of milk, the amino acid composition of milk protein, and the productivity per 305 days of lactation in crossbred cows compared to pure-breed local Ukrainian analogues. The research was conducted at cows of the Ukrainian Black-Spotted (UBS) dairy breed and crossbred cows of the first-generation obtained as a result of crossing with Brown Swiss breed and at cows of the Ukrainian Red-Spotted (URS) dairy breed and crossbred cows of the first-generation obtained by crossing of the URS dairy breed with Montbeliarde breed. In both farms there were two groups of pure-breed and crossbred cows-analogues. The mineral composition of milk and its technological properties in crossbred cows were higher compared to the pure-breed analogues. The fat content of milk crossbred cows exceeded by 0.08-0.16%, protein exceeded by 0.15-0.22%, and the main trace elements include Ca and P – by 2.66-8.83 and 2.12-7.81 mg/100 g of milk, respectively. Milk protein of crossbred cows was marked by a more balanced composition of essential amino acids (EAAs) and their ratio suitable for processing. The amount of EAAs in 100 g of milk protein of crossbred cows was 3.11-6.25% higher compared to local analogues. Crossbred cows dominated pure-breed analogues by the mineral composition of milk. The authors recommend the use of Montbeliarde or Brown Swiss breeds in commercial herds to improve the technological properties of milk.

scholarly journals Self-Dividing Micelles: A Mechanistic Look with Evolutionary and Clinical Implications

2021 ◽  
pp. 8-20
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Laboratory Testing ◽  
Prebiotic Chemistry ◽  
Clinical Implications ◽  
Proof Of Concept ◽  
Mass Spec ◽  
First Time ◽  
Division Mechanism ◽  
Viable Treatment

Micellar therapy has become a usefully viable treatment arm in various fields, ranging from oncology to bioimaging. As such, research leading to any improvements or adaptations in administration and techniques can have far-reaching consequences. Potential aspects of prebiotic chemistry may also be explored in such research as well. To that end, proof-of-concept experiments were performed to elucidate a possible mechanism of action for prebiotic protocell division. Representative potentially prebiotically plausible biomolecules, i.e., a fatty acid, amino acid, and nucleotide were mixed and heated in water and subjected to microscopic examination for observation of possible self-division and laboratory testing for the presence of polypeptides and polynucleotides (Biuret, MALDI mass-spec, etc.) with and without the presence of nucleotide. The results are presented for the first time here and a mechanism is proposed that best fits the data obtained. The evolutionary, e.g., prebiotic biomolecular cooperativity, and clinical, e.g., potential antineoplastic micellar/vesicular therapy, ramifications are discussed as well. Keywords: Micelle; Liposome; Protocell; MRNA; Self-division; Mechanism; Solid tumors

scholarly journals Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

2013 ◽  
Vol 16 (8) ◽  
pp. 958-965 ◽  
Author(s):  
Scott A. Irwin ◽  
Alana Iglewicz ◽  
Richard A. Nelesen ◽  
Jessica Y. Lo ◽  
Connie H. Carr ◽  
...  
Keyword(s):  
Hospice Care ◽  
Depression And Anxiety ◽  
Proof Of Concept ◽  
Open Label ◽  
Oral Ketamine ◽  
Treatment Of Depression

scholarly journals Dietary Inositol Reduces Fearfulness and Avoidance in Laying Hens

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 938
Author(s):  
Eugenia Herwig ◽  
Henry L. Classen ◽  
Carrie L. Walk ◽  
Mike Bedford ◽  
Karen Schwean-Lardner
Keyword(s):  
Amino Acid ◽  
Crude Protein ◽  
Laying Hens ◽  
Skin Lesions ◽  
Depression And Anxiety ◽  
Daily Mortality ◽  
Novel Object

Myo-inositol (inositol) affects memory, and the incidence of depression and anxiety in mammals. An experiment was designed to determine if pure inositol (0.16%), or high levels of phytase (3000 FTU/kg) affect the behaviour of fully beaked Lohmann LSL lite hens fed amino acid sufficient (19% crude protein (CP)) and deficient diets (16% CP), from 19 to 59 weeks of age. The data collected included live-scan behaviour observations and novel object (NO) tests (both at 1, 10 and 40 weeks of the trial); heterophil-to-lymphocyte (H/L) ratios (week 1 and week 40 of the trial); end of trial feather cover, and comb and skin lesions; and daily mortality. Reducing CP increased sitting by 2.5%. Inositol, but not phytase, reduced the latency to peck at the NO by 300 sec. Inositol reduced vent feather cover by 12% and tended to increase mortality by 13%. No effects on H/L ratio, and comb or skin lesions were found. In conclusion, regardless of the source, inositol reduced vent feather cover, while it tended to increase mortality. Only pure inositol reduced fearfulness in laying hens.

Maternal l-proline supplementation during gestation alters amino acid and polyamine metabolism in the first generation female offspring of C57BL/6J mice

Amino Acids ◽  
2019 ◽  
Vol 51 (5) ◽  
pp. 805-811 ◽  
Author(s):  
Ning Liu ◽  
Zhaolai Dai ◽  
Yunchang Zhang ◽  
Hai Jia ◽  
Jiangqing Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
First Generation ◽  
Female Offspring ◽  
Polyamine Metabolism ◽  
Generation Female
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