Antigenic mapping of a human λ light chain: Correlation with three dimensional structure

Although the amino acid sequence and three-dimensional structure of human immunoglobulin light chains have been known for more than 15 years, the location of antigenic markers characteristic of chains has not been determined. Here, we use a set of synthetic overlapping peptides to completely model the sequence of the chain Mcg and test these for the binding or rabbit and goat antisera specific for chain determinants. We assess peptide contributions to -antigenic reactivity and also to identify a portion of C-region where conformational factors contribute to the antigenicity. Specific determinants occur both in the constant and variable (first and third framework) domains of the molecule. The fourth framework of the variable region, a segment specified by the joining gene, is also recognized and cross-reacts antigenically with the homologous region of T cell receptor chains. Major specific determinants are localized in the N- and C-terminal segments, which are linear and devoid of major conformational folding. Other segments that are strongly antigenic, such as the third framework of the V region (residue 78–93) and a segment of the constant region (residues 177–192), show strong conformational dependence in antigenicity.     

Comparative bioinformatics analysis and abiotic stress responses of expansin proteins in Cucurbitaceae members: watermelon and melon

Protoplasma - Watermelon and melon are members of the Cucurbitaceae family including economically significant crops in the world. The expansin protein family, which is one of the members of the...     

Structure-Activity Relationship of Methyl 4-Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S-transferase (GST) are two glutathione-related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4-aminobenzoate derivatives on GR and GST were examined in vitro. GR and GST were isolated from human erythrocytes with 7.63 EU/mg protein and 5.66 EU/mg protein specific activity, respectively. It was found that compound 1 (methyl 4-amino-3-bromo-5-fluorobenzoate with K_i value of 0.325±0.012 μM) and compound 5 (methyl 4-amino-2-nitrobenzoate with K_i value of 92.41±22.26 μM) inhibited GR and GST stronger than other derivatives. Furthermore, a computer-aided method was used to predict the binding affinities of derivatives, ADME characteristics, and toxicities. Derivatives 4 (methyl 4-amino-2-bromobenzoate) and 6 (methyl 4-amino-2-chlorobenzoate) were estimated to have the lowest binding energies into GR and GST receptors, respectively according to results of in silico studies.     

Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Design,in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas ( 1 – 16 ) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives ( 17 – 32 ). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC₅₀=8.09±0.58 μM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.     

Focus: Preventive Medicine: Pre-Participation Screening of Athletes: Primary Health Care Physicians’ Knowledge,Experience, and Approach in Turkey

Pre-participation screening (PPS) is crucial for assessing the competitive athletes since their risk of sudden death is higher than non-athletes. In Turkey, PPS is performed at the primary health care setting by primary care physicians (PCPs) who are family medicine specialists (FMSs) or general practitioners (GPs). Although there are national guidelines, there is no legal regulation for this process. This study aims to evaluate PCPs’ knowledge, experience, and approach about PPS. We prepared an online survey for PCPs and used non-probabilistic sampling. PPS attitudes and practices were analyzed and compared according to factors such as experience, education, and being GP or FMS. Of the 214 PCPs included in the study, 39.3% were female. The mean age was 44.9 years (SD:8.88). The average work experience was 7.9 years. Most participants were aware of their authorization to perform PPS (89.7%) and had previously prepared it (90.2%). However, 6.5% of them felt confident in performing PPS. Only 13.1% were aware of the guidelines. Almost 25% of the participants stated being informed about the subject at some part of their career, but this did not affect the confidence or referral decisions. In addition to medical history and physical examination, further testing was considered necessary by 96.3% of the participants. Significantly more tests were ordered by GPs than FMSs (p=0.026 and p=0.011, respectively). The accurate referral decision ratio was 59.3%, without difference between FMSs and GPs (p=0.216). We found that awareness of the guidelines was low among PCPs who lack confidence in PPS. These factors collectively increased the tendency for unnecessary further testing and referral. Therefore, the PPS implementation into medical school and residency curriculums and national legal regulation for the process is a necessity in Turkey.     

Effects of stocking density during live transportation on haematological parameters of Siberian sturgeon (Acipenser baerii,Brandt, 1869)

In this study, we investigated the effects of different stocking densities water quality and blood parameters during the transportation of the Siberian sturgeon (Acipenser baerii). Experiments were carried out in high-density polyethylene tank with three different stocking densities (50, 100 and 150 kg/m³) for 20 h. Ammonium nitrogen (NH₄-N) and nitrite nitrogen (NO₂-N) were measured in the water samples. The erythrocyte, leucocyte, haematocrit (HCT), haemoglobin (Hb), cortisol, and sodium ion (Na⁺) were measured in blood samples. Ammonium nitrogen and nitrite nitrogen concentrations in the water have increased in parallel with the stocking density depending on the time. In the highest stocking density, the maximum levels of NH₄-N and NO₂-N at the 16^th h reached 2.64 mg/L and 4.74 mg/L, respectively. Erythrocyte, leucocyte, HCT, and Hb values did not differ significantly between the experimental groups (p > .05). The results showed that fish could be transported safely for 20 h in 15℃ water temperature at 50 kg/m³ stocking density; however, stocking density of 100 kg/m³ and over could threaten fish welfare and health as from 16^th h.     

Effect of methylenetetrahydrofolate reductase gene polymorphisms and oxidative stress in silent brain infarction

Ischemic infarctions occur under the influence of genetic and environmental factors. In our study, the role of ischemia-modified albumin and thiol balance, which are new markers in determining oxidative damage together with MTHFR gene polymorphisms and homocysteine levels, in the development of SBI was investigated. White matter lesions in the magnetic resonance imaging (MRI) results of the patients were evaluated according to the Fazekas scale and divided into groups (Grade 0, 1, 2, and 3). Homocysteine, folate, B12, IMA, total thiol, and native thiol were measured by biochemical methods. The polymorphisms in MTHFR genes were investigated by the RT-PCR method. According to our results, a significant difference was found between the groups in age, homocysteine, folate, IMA, total thiol, and native thiol parameters (p?<?0.05). When we compared the groups in terms of genotypes of the C677T gene, we found a significant difference in TT genotype between grades 0/3 and 1/3 (p?<?0.05). We determined that homocysteine and IMA levels increased and folate levels decreased in CC/TT and CT/TT genotypes in the C677T gene (p?<?0.05). Considering our results, the observation of homocysteine and IMA changes at the genotype level of the MTHFR C677T gene and between the groups, and the deterioration of thiol balance between the groups suggested that these markers can be used in the diagnosis of silent brain infarction.

     

IMMOBILIZATION OF BOVINE CATALASE ONTO MAGNETIC NANOPARTICLES

The scope of this study is to achieve carrier-bound immobilization of catalase onto magnetic particles (Fe₃O₄ and Fe₂O₃NiO₂ · H₂O) to specify the optimum conditions of immobilization. Removal of H₂O₂ and the properties of immobilized sets were also investigated. To that end, adsorption and then cross-linking methods onto magnetic particles were performed. The optimum immobilization conditions were found for catalase: immobilization time (15 min for Fe₃O₄; 10 min for Fe₂O₃NiO₂ · H₂O), the initial enzyme concentration (1 mg/mL), amount of magnetic particles (25 mg), and glutaraldehyde concentration (3%). The activity reaction conditions (optimum temperature, optimum pH, pH stability, thermal stability, operational stability, and reusability) were characterized. Also kinetic parameters were calculated by Lineweaver–Burk plots. The optimum pH values were found to be 7.0, 7.0, and 8.0 for free enzyme, Fe₃O₄-immobilized catalases, and Fe₂O₃NiO₂ · H₂O-immobilized catalases, respectively. All immobilized catalase systems displayed the optimum temperature between 25 and 35°C. Reusability studies showed that Fe₃O₄-immobilized catalase can be used 11 times with 50% loss in original activity, while Fe₂O₃NiO₂ · H₂O-immobilized catalase lost 67% of activity after the same number of uses. Furthermore, immobilized catalase systems exhibited improved thermal and pH stability. The results transparently indicate that it is possible to have binding between enzyme and magnetic nanoparticles.