Evaluation of possible preventive activity of Elaeagnus angustifolia L. against osteoporosis, an in vivo study

Evaluation of possible preventive activity of Elaeagnus angustifolia L. against osteoporosis, an in vivo study</p

SAPrIm, a semi-automated protocol for mid-throughput immunopeptidomics

Human leukocyte antigen (HLA) molecules play a crucial role in directing adaptive immune responses based on the nature of their peptide ligands, collectively coined the immunopeptidome. As such, the study of HLA molecules has been of major interest in the development of cancer immunotherapies such as vaccines and T-cell therapies. Hence, a comprehensive understanding and profiling of the immunopeptidome is required to foster the growth of these personalised solutions. We herein describe SAPrIm, an Immunopeptidomics tool for the Mid-Throughput era. This is a semi-automated workflow involving the KingFisher platform to isolate immunopeptidomes using anti-HLA antibodies coupled to a hyper-porous magnetic protein A microbead, a variable window data independent acquisition (DIA) method and the ability to run up to 12 samples in parallel. Using this workflow, we were able to concordantly identify and quantify ~400 - 13000 unique peptides from 5e5 - 5e7 cells, respectively. Overall, we propose that the application of this workflow will be crucial for the future of immunopeptidome profiling, especially for mid-size cohorts and comparative immunopeptidomics studies

A subset of HLA-I peptides are not genomically templated: evidence for cis- and trans-spliced peptide ligands

The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy

Most viral peptides displayed by class I MHC on infected cells are immunogenic

CD8+ T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8+ T cell responses.This work was supported by a Project Grant from the National Health and Medical Research Council Australia (NHMRC) (APP1084283) (to D.C.T., A.W.P., and N.P.C.); an NHMRC Senior Research Fellowship (APP1104329) (to D.C.T.); an NHMRC Principal Research Fellowship (APP1137739) (to A.W.P.); and a Viertel Fellowship, ARC Future Fellowship, and NHMRC Program Grant (APP1071916) (to N.L.L.G.)

Solving the spliced-peptides mystery by using machine learning techniques

Peptides bind to Human Leukocyte Antigens (p-HLA) and present on the cell surface work like a messenger to reports what is happening in the cell to the immune system. p-HLA derives from the intracellular proteins digestion. If a peptide sequence presented from a mutated region of the proteome (which could be the cause of cancer), then the immune system recognize the peptide on the cell surface and kills the tumor cell. For a long time, scientist believed that HLA-peptides, drive from just cutting proteins to small peptides by an enzyme called proteasome. However, recently it is discovered that proteasome not only cuts the proteins to peptides but also paste the resulted small peptides together and make new peptides called as “spliced peptides” which don’t have any template in the proteome. Understanding the rules of cutting and pasting peptides and prediction of spliced peptides sequences is a critical challenge in the “cancer vaccine design” field. We believe by using our empirical data and machine learning techniques; it is possible to discover splicing rules and ultimately predict spliced peptides sequences

To Investigate or Not to Investigate? Researchers' Views on Unexplored Atmospheric Light Phenomena

For hundreds of years, scientists have been studying light, which is used nowadays to explore the universe and cure diseases. Here, we present the results of a survey indicating a significant support from a subset of the academic community to investigate rare, unusual and unexplained atmospheric light phenomena that have historically been unexplored by scientists—the transient luminous phenomena in the valley of Hessdalen in Norway in particular. We propose that stable, long-term funding, and thorough investigation of poorly understood and/or unexplored luminous phenomena occurring in the low atmosphere could lead to the creation of new inter-disciplinary research programs in multiple universities, and ultimately, to important fundamental discoveries in the field of atmospheric science, photonics and beyond.ISSN:2296-646

A first dataset toward a standardized community-driven global mapping of the human immunopeptidome

We present the first standardized HLA peptidomics dataset generated by the immunopeptidomics community. The dataset is composed of native HLA class I peptides as well as synthetic HLA class II peptides that were acquired in data-dependent acquisition mode using multiple types of mass spectrometers. All laboratories used the spiked-in landmark iRT peptides for retention time normalization and data analysis. The mass spectrometric data were deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier http://www.ebi.ac.uk/pride/archive/projects/PXD001872. The generated data were used to build HLA allele-specific peptide spectral and assay libraries, which were stored in the SWATHAtlas database. Data presented here are described in more detail in the original eLife article entitled ‘An open-source computational and data resource to analyze digital maps of immunopeptidomes’. Keywords: Immunology, HLA, Peptidomics, Mass spectrometr

Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT) was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA) induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l), epinephrine (20 μmol/l), collagen(0.19 mg/ ml) and arachidonic acid (0.5mg/ ml) was measured by Light Transmittance Aggregometry (LTA) in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg) a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding). No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method

Hot And Cold: An Old Theory With Modern Applications

The use of traditional medicine as an important part of complementary/alternative medicine spread nowadays all around the world. Something that is due to the lack of effectiveness of modern medicine in treating some disease especially chronic disease. Since one of the most important theories beside traditional medicine is the concept of “temperaments” and this is very close to the concept of personalized medicine, which is taken into consideration nowadays. It is important to investigate what really temperament is and also reach a precise meaning and criteria for determining it. For reviewing all the researches that have been done on temperaments till today, the most popular database like PubMed, Scopus, Google scholar, science direct and etc. were searched for keywords Hot and cold, temperaments, hot and cold medicine, hot and cold nature, hot and cold parameters till September 2015. The results show that there are some physiological and metabolic criteria, genes and networks and metabolite that contribute in determining the temperaments not only in body but also in disease, foods and drugs. Despite the presence of all these detailed data the lack of a comprehensive practical criteria for temperament is still obvious, so we try to gather all data to reach that in its best way.</p

Sphygmology of Ibn Sina, a message for future

Sphygmology is a 2000-year-old method that is still used in some traditional medicine systems, mainly Iranian, Chinese and Ayurveda. Ibn Sina is one of the most popular physicians in the history of Sphygmology, who had made great contributions to this method, but few meticulous studies have been made on his concepts. In this article, his standpoints on Pulsology are studied. Ibn Sina has mentioned 10 parameters for pulse palpation, and 13 compound pulses, as well. Besides, some pulse patterns applicable for differentiating similar diseases have been introduced. Nowadays some concepts on pulse patterns, such as pulse change in sleep and pregnancy have been studied; but unfortunately many of the ideas on Pulsology have not yet been examined. Sphygmology, as an accessible and inexpensive means, having a substantial diagnosis yield, has been accepted by the people since its rise, and its development over centuries ago. Although some new instruments have been innovated, which can measure different parameters of pulse, yet sphygmology can be one of the most commonly usable diagnostic methods in future, not only applicable by cardiologists but also by all the physicians