scholarly journals An exclusive 42 amino acid signature in pp1ab protein provides insights into the evolutive history of the 2019 novel human‐pathogenic coronavirus (SARS‐CoV‐2)

2020 ◽  
Vol 92 (6) ◽  
pp. 688-692 ◽  
Author(s):  
Yair Cárdenas‐Conejo ◽  
Andrómeda Liñan‐Rico ◽  
Daniel Alejandro García‐Rodríguez ◽  
Sara Centeno‐Leija ◽  
Hugo Serrano‐Posada
Keyword(s):  
Amino Acid ◽  
History Of ◽  
Amino Acid Signature

Plasma-Free Amino Acid Profiling of Nasal Polyposis Patients

2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Free Amino Acid ◽  
Free Amino ◽  
Nasal Polyposis ◽  
Amino Acid Profile ◽  
Healthy Control Group ◽  
Control Group ◽  
Healthy Control ◽  
History Of

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.

scholarly journals Developing a machine learning model to identify protein–protein interaction hotspots to facilitate drug discovery

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10381
Author(s):  
Rohit Nandakumar ◽  
Valentin Dinu
Keyword(s):  
Machine Learning ◽  
Amino Acid ◽  
Drug Discovery ◽  
Structural Information ◽  
Learning Model ◽  
Protein Protein Interaction ◽  
Drug Molecules ◽  
Machine Learning Model ◽  
Disease Associations ◽  
History Of

Throughout the history of drug discovery, an enzymatic-based approach for identifying new drug molecules has been primarily utilized. Recently, protein–protein interfaces that can be disrupted to identify small molecules that could be viable targets for certain diseases, such as cancer and the human immunodeficiency virus, have been identified. Existing studies computationally identify hotspots on these interfaces, with most models attaining accuracies of ~70%. Many studies do not effectively integrate information relating to amino acid chains and other structural information relating to the complex. Herein, (1) a machine learning model has been created and (2) its ability to integrate multiple features, such as those associated with amino-acid chains, has been evaluated to enhance the ability to predict protein–protein interface hotspots. Virtual drug screening analysis of a set of hotspots determined on the EphB2-ephrinB2 complex has also been performed. The predictive capabilities of this model offer an AUROC of 0.842, sensitivity/recall of 0.833, and specificity of 0.850. Virtual screening of a set of hotspots identified by the machine learning model developed in this study has identified potential medications to treat diseases caused by the overexpression of the EphB2-ephrinB2 complex, including prostate, gastric, colorectal and melanoma cancers which are linked to EphB2 mutations. The efficacy of this model has been demonstrated through its successful ability to predict drug-disease associations previously identified in literature, including cimetidine, idarubicin, pralatrexate for these conditions. In addition, nadolol, a beta blocker, has also been identified in this study to bind to the EphB2-ephrinB2 complex, and the possibility of this drug treating multiple cancers is still relatively unexplored.

FIBRINOGEN BIRMINGHAM; A NEW CONGENITAL HETERODIMERIC DYSFIBRINOGENEMIA WITH DEFECTIVE FIBRINOPEPTIDE A RELEASE (Aα 16 Arg→His)

1987 ◽  
Author(s):  
K R Siebenlist ◽  
J T Prchal ◽  
M W Masesson
Keyword(s):  
Amino Acid ◽  
Amino Acid Analysis ◽  
Hplc Analysis ◽  
Biochemical Characterization ◽  
Clinical Manifestations ◽  
Severe Bleeding ◽  
Fibrinopeptide A ◽  
History Of ◽  
Bleeding Episodes

Aα 16 Arg→His substitutions are common forms of congenital dysfibrinogenemias. Clinical manifestations range from asymptomatic to moderate hemorrhagic tendencies. Biochemical characterization of one such heterozygotic individual (Fibrinogen Louisville, Galanakis, etal. Ann NY Acad Sci 408:644,1983) indicated that only homodimeric fibrinogen molecules (i.e., containing either normal or abnormal Aα chains) were present. We isolated fibrinogen from the plasma of a 23 year old patient with a history of easy bruising and several recent moderate to severe bleeding episodes. Coagulability with reptilase was 677 (65-70%; n=5) whereas with thrombin (Ha) it approached 100%, depending directly upon the time of incubation with enzyme. HPLC analysis of Ila-induced fibrinopeptide release demonstrated the presence of an abnormal A-peptide (A*), amounting to 50% of the total, which was released more slowly than the normal A-peptide (A). Amino acid analysis of A* demonstrated the absence of Arg and the presence of His. Carboxypeptidase digestion confirmed the structure of A* as Aα 16 Arg-→ His. The clot and the soluble clot liquor resulting from reptilase treatment were separated and each was then further treated with Ilato release A*. HPLC analysis indicated that 31% of the total A* present in the sample was associated with the reptilase clot and 697 remained in the clot liquor. This distribution of A* suggests that Fibrinogen Birmingham, unlike Fibrinogen Louisville, contains heterodimeric molecules that are incorporated into the reptilase clottable fraction. This finding is consistent with a process of random hepatic assembly of dimeric fibrinogen molecules in a heterozygotic individual.

A Novel Dysfibrinogenemia with Abnormal γ-Chain(Fibrinogen Nagoya).

1979 ◽  
Author(s):  
Junki Takamatsu ◽  
Kanji Oqata ◽  
Tadashi Kamiya ◽  
Katsuo Koie ◽  
Takagi Takashi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inhibitory Effect ◽  
Chain Structure ◽  
Japanese Family ◽  
Electrophoretic Mobilities ◽  
Sds Page ◽  
History Of ◽  
The Difference ◽  
Fibrin Monomers ◽  
Major Defect

Six individuals in 3 generations of Japanese family had prolonged thrombin clotting time, but no history of hemorrhagic or thrombotic disease. Very low fibrinogen levels were obtained by thrombin clottable protein, while immunological procedures gave normal values of fibrinogen. The serum contained 40-80μg/ml of unclottable fibrinogen related antigens. The patients’ plasma had an inhibitory effect on the fibrin formation in normal plasma. Major defect of this fibrinogen was a delayed aggregation of fibrin monomers.On CM-chromatography (CM-52) of the S-carboxymethylated fibrinogen, three different γ-chains, named γx, γL and γR, were separated. They did not differ in their electrophoretic mobilities in SDS-PAGE, but were distinguishable in PAGE containing 8M urea. Moreover, the amino acid compositions and tryptic peptide mappings of each chain revealed a little difference from those of normal fibrinogen γ chains, suggesting the difference in amino acid substitution or oligosaccharide chain structure.Based on these findings, we designated this fibrinogen as fibrinogen Nagoya; its possible identity without other dysfibrinogenemia has not been excluded.

Recurrent Dystonic Crisis and Rhabdomyolysis Treated with Dantrolene in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency

2020 ◽  
Vol 51 (03) ◽  
pp. 229-232
Author(s):  
J. Micallef ◽  
S. Stockler-Ipsiroglu ◽  
C.D. van Karnebeek ◽  
R. Salvarinova-Zivkovic ◽  
G. Horvath
Keyword(s):  
Amino Acid ◽  
Inborn Error ◽  
Autosomal Recessive ◽  
Global Developmental Delay ◽  
Acid Decarboxylase ◽  
First Year ◽  
Amino Acid Decarboxylase ◽  
History Of ◽  
First Year Of Life ◽  
Decarboxylase Deficiency

AbstractAromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive inborn error of metabolism in which several neurotransmitters including serotonin, dopamine, norepinephrine and epinephrine are deficient. Symptoms typically appear in the first year of life and include oculogyric crises and dystonia, hypotonia, and global developmental delay. Dystonia is of particular concern as a dystonic storm can ensue leading to rhabdomyolysis. Rhabdomyolysis can become life-threating and therefore its recognition and prompt management is of significant importance. Here we present two cases of patients with AADC deficiency and a history of dystonic crisis causing rhabdomyolysis. We hypothesize that in addition to the hypodopaminergic, a hypercholinergic state is contributing to the pathophysiology of dystonia in AADC deficiency, as well as to the associated rhabdomyolysis. We were able to prevent rhabdomyolysis in both patients with using Dantrolene and we suggest using a trial of this medication in cases of sustained dystonic crisis in AADC deficiency patients.

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