DichroCalc: Improvements in Computing Protein Circular Dichroism Spectroscopy in the Near-Ultraviolet

A fully quantitative theory connecting protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. The web server DichroCalc (http://comp.chem.nottingham.ac.uk/dichrocalc) allows one to compute from first principles the electronic circular dichroism spectrum of a (modeled or experimental) protein structure or ensemble of structures. The regular, repeating, chiral nature of secondary structure elements leads to intense bands in the far-ultraviolet (UV). The near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, realized through the consideration of the vibrational structure of the electronic transitions of aromatic side chains. The improvements have been assessed over a set of diverse proteins. We illustrate them using bovine pancreatic trypsin inhibitor and present a new, detailed analysis of the interactions which are most important in determining the near-UV circular dichroism spectrum.     

Transcriptional mechanisms regulating alveolar epithelial cell-specific CCL5 secretion in pulmonary tuberculosis

CCL5 (or RANTES (regulated upon activation, normal T cell expressed and secreted)) recruits T lymphocytes and monocytes. The source and regulation of CCL5 in pulmonary tuberculosis are unclear. Infection of the human alveolar epithelial cell line (A549) by Mycobacterium tuberculosis caused no CCL5 secretion and little monocyte secretion. Conditioned medium from tuberculosis-infected human monocytes (CoMTB) stimulated significant CCL5 secretion from A549 cells and from primary alveolar, but not upper airway, epithelial cells. Differential responsiveness of small airway and normal human bronchial epithelial cells to CoMTB but not to conditioned medium from unstimulated human monocytes was specific to CCL5 and not to CXCL8. CoMTB induced CCL5 mRNA accumulation in A549 cells and induced nuclear translocation of nuclear factor kappaB (NFkappaB) subunits p50, p65, and c-rel at 1 h; nuclear binding of activator protein (AP)-1 (c-Fos, FosB, and c-Jun) at 4-8 h; and binding of NF-interleukin (IL)-6 at 24 h. CCL5 promoter-reporter analysis using deletion and site-specific mutagenesis constructs demonstrated a key role for AP-1, NF-IL-6, and NFkappaB in driving CoMTB-induced promoter activity. The IL-1 receptor antagonist inhibited A549 and small airway epithelial cell CCL5 secretion, gene expression, and promoter activity. CoMTB contained IL-1beta, and recombinant IL-1beta reproduced CoMTB effects. Monocyte alveolar, but not upper airway, epithelial cell networks in pulmonary tuberculosis cause AP-1-, NF-IL-6-, and NFkappaB-dependent CCL5 secretion. IL-1beta is the critical regulator of tuberculosis-stimulated CCL5 secretion in the lung.     

Molecular Investigation of Outer Membrane Channel Genes Among Multidrug Resistance Clinical Pseudomonas Aeruginosa Isolates

Background:Multidrug resistance Pseudomonas aeruginosa (MDRPA) is most important issue in healthcare setting. It can secrete many virulence effector proteins via its secretion system type (T1SS-T6SS). They are using them as conductor for delivering the effector proteins outside to begins harmful effect on host cell increasing pathogenicity, competition against other microorganism and nutrient acquisition.Methods:The study include investigation of 50 isolates of MDRPA for transport secretion system and resistance for antibiotics. Molecular diagnosis using P. aeruginosa specific primer pairs, investigation of AprF, HasF, XcpQ, HxcQ, PscC, CdrB, CupB3, and Hcp using specific primer pairs by PCR were also performed.Results:The results revealed high resistance to beta lactam antibiotics (78% for ceftazidime, 78% for cefepime and 46% for piperacillin) can indicate possessing of isolates for beta lactamases and this confirmed by dropping resistance to piperacillin to 16% when combined with tazobactam. Also, the results shown the ability of MDRPA for pyocyanin biosynthesis using the system of genes.Conclusion:The current study conclude that all isolates of P. aeruginosa were highly virulent due to their possessing of all transport secretion system to deliver different effector proteins with possible harmful effects of these proteins.Key Words: Drug resistance, MDR, Efflux pump, Pseudomonas aeruginosa     

Tritium nuclear magnetic resonance spectroscopy. Part VI. Tritiated steroid hormones

The regio- and stereo-specificity of the labelling in a series of tritiated steroid hormones has been examined by ³H n.m.r., which also yields quantitative information on the distribution of the tritium between the labelled sites. Complete analysis is thus readily achieved non-destructively. Hydrogen chemical shifts for various skeletal sites are provided for the first time. The specificity of the methods of labelling steroids with tritium by catalytic reduction, catalysed exchange, and tritiodehalogenation are discussed.     

Comparative Study of New Biomarkers in Iraqi DM2 with and without Complications

Background:Recent research indicates that persistent inflammatory responses may contribute to the rise of diabetic nephropathy (DN) and diabetic cardiovascular disease (DCVD) in type 2 diabetes mellitus patients (DM2). Numerous molecules associated with inflammation and angiogenesis have been implicated in the development and progression of DN and DCVD, respectively.Methods:The subjects were separated into five groups: healthy controls (n= 25), type 2 diabetes mellitus patients (n= 30), type 2 diabetes mellitus patients with nephropathy DN (n= 30), and type 2 diabetes mellitus patients with cardiovascular disease DCVD (n= 30). The blood levels of irisin, IL-8, HbA1C, urea, and creatinine were determined.Results:In current study there was high significant increased irisin levels (p< 0.001) in DN patients than other groups and a high significant decreased IL-8 level in DCVD.DiscussionSerum IL-8 and irisin levels may serve as early indicators of DM2 problems (DN, DCVD).Key Words: DM2, DN, DCVD, HbA1C, IL-8, Irisin     

Effective extracellular vesicles in glioma: Focusing on effective ncRNA exosomes and immunotherapy methods for treatment

This comprehensive article explores the complex field of glioma treatment, with a focus on the important roles of non-coding RNAsRNAs (ncRNAs) and exosomes, as well as the potential synergies of immunotherapy. The investigation begins by examining the various functions of ncRNAs and their involvement in glioma pathogenesis, progression, and as potential diagnostic biomarkers. Special attention is given to exosomes as carriers of ncRNAs and their intricate dynamics within the tumor microenvironment. The exploration extends to immunotherapy methods, analyzing their mechanisms and clinical implications in the treatment of glioma. By synthesizing these components, the article aims to provide a comprehensive understanding of how ncRNAs, exosomes, and immunotherapy interact, offering valuable insights into the evolving landscape of glioma research and therapeutic strategies.