Proteomics: a subcellular look at spermatozoa

<p>Abstract</p> <p>Background</p> <p>Male-factor infertility presents a vexing problem for many reproductively active couples. Many studies have focused on abnormal sperm parameters. Recent advances in proteomic techniques, especially in mass spectrometry, have aided in the study of sperm and more specifically, sperm proteins. The aim of this study was to review the current literature on the various proteomic techniques, and their usefulness in diagnosing sperm dysfunction and potential applications in the clinical setting.</p> <p>Methods</p> <p>Review of PubMed database. Key words: spermatozoa, proteomics, protein, proteome, 2D-PAGE, mass spectrometry.</p> <p>Results</p> <p>Recently employed proteomic methods, such as two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and differential in gel electrophoresis, have identified numerous sperm-specific proteins. They also have provided a further understanding of protein function involved in sperm processes and for the differentiation between normal and abnormal states. In addition, studies on the sperm proteome have demonstrated the importance of post-translational modifications, and their ability to bring about physiological changes in sperm function. No longer do researchers believe that in order for them to elucidate the biochemical functions of genes, mere knowledge of the human genome sequence is sufficient. Moreover, a greater understanding of the physiological function of every protein in the tissue-specific proteome is essential in order to unravel the biological display of the human genome.</p> <p>Conclusion</p> <p>Recent advances in proteomic techniques have provided insight into sperm function and dysfunction. Several multidimensional separation techniques can be utilized to identify and characterize spermatozoa. Future developments in bioinformatics can further assist researchers in understanding the vast amount of data collected in proteomic studies. Moreover, such advances in proteomics may help to decipher metabolites which can act as biomarkers in the detection of sperm impairments and to potentially develop treatment for infertile couples.</p> <p>Further comprehensive studies on sperm-specific proteome, mechanisms of protein function and its proteolytic regulation, biomarkers and functional pathways, such as oxidative-stress induced mechanisms, will provide better insight into physiological functions of the spermatozoa. Large-scale proteomic studies using purified protein assays will eventually lead to the development of novel biomarkers that may allow for detection of disease states, genetic abnormalities, and risk factors for male infertility. Ultimately, these biomarkers will allow for a better diagnosis of sperm dysfunction and aid in drug development.</p

Mucosal melanoma of nasal cavity and paranasal sinus

Mucosal melanoma of the nasal cavity and paranasal sinuses is seldom encountered in routine ENT practice. These tumors have poor prognosis owing to higher rates of locoregional recurrence and distant metastasis. Various treatment modalities have been employed over time but the ideal treatment approach still remains an open issue. This article presents some commonly accepted guidelines in treating these rare mucosal neoplasms

Two-dimensional differential in-gel electrophoresis-based proteomics of male gametes in relation to oxidative stress

Objective: To identify the relative abundance of proteins in pooled reactive oxygen species (ROS)-positive (ROSþ) and ROS-negative (ROSÀ) semen samples with the use of two-dimensional differential in-gel electrophoresis (2D-DIGE). Design: Spermatozoa suspensions from ROSþ and ROSÀ groups by 2D-DIGE analysis. Setting: Tertiary hospital. Patient(s): 20 donors and 32 infertile men. Intervention(s): Seminal ejaculates evaluated for semen and proteomic analysis. Main Outcome Measure(s): Semen samples from 20 donors and 32 infertile men were pooled, divided into ROSþ and ROSÀ groups based on the cutoff value of &lt;20 relative light units/s/10 6 sperm and frozen. From each pooled group, spermatozoa were labeled with Cy3/Cy5 fluorescent dye. Duplicate 2D-DIGE gels were run. Image analysis was performed with the use of Decider software. Protein spots exhibiting R1.5-fold difference in intensity were excised from the preparatory gel and identified by liquid chromatographymass spectrometry. Data were analyzed with the use of Sequest and Blast programs. Result(s): A total of 1,343 protein spots in gel 1 (ROSÀ) and 1,265 spots in gel 2 (ROSþ) were detected. The majority of protein spots had similar expression, with 31 spots were differentially expressed. Six spots were significantly decreased and 25 increased in the ROSÀ sample compared with the ROSþ sample. Conclusion(s): Significantly different expression of protective proteins against oxidative stress was found in ROSÀcompared with ROSþ samples. These differences may explain the role of oxidation species in the pathology of male infertility. (Fertil Steril Ò 2013;99:1216-26. Ó2013 by American Society for Reproductive Medicine.

Quantum singular oscillator as a model of two-ion trap: an amplification of transition probabilities due to small time variations of the binding potential

Following the paper by M. Combescure [Ann. Phys. (NY) 204, 113 (1990)], we apply the quantum singular time dependent oscillator model to describe the relative one dimensional motion of two ions in a trap. We argue that the model can be justified for low energy excited states with the quantum numbers $n\ll n_{max}\sim 100$, provided that the dimensionless constant characterizing the strength of the repulsive potential is large enough, $g_*\sim 10^5$. Time dependent Gaussian-like wave packets generalizing odd coherent states of the harmonic oscillator, and excitation number eigenstates are constructed. We show that the relative motion of the ions, in contradistinction to its center of mass counterpart, is extremely sensitive to the time dependence of the binding harmonic potential, since the large value of $g_*$ results in a significant amplification of the transition probabilities between energy eigenstate even for slow time variations of the frequency.Comment: 19 pages, LaTeX, 5 eps-figures, to appear on Phys. Rev. A, one reference correcte

Expression and role of PAICS, a de novo purine biosynthetic gene in prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/1/pros23533_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/2/pros23533.pd

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine Derivatives Acting as Acid Pump Antagonists

A quantitative structure-activity relationship (QSAR) and molecular docking study has been performed on a series of heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine derivatives acting as acid pump antagonists in order to have a better understanding of the mechanism of H+/K+-ATPase inhibition. The QSAR study shows a significant correlation of activity with Global Topological Charge Indices (GTCI) of the compounds and the hydrophobic constant of some substituents, indicating that the charge transfer within the molecule and the hydrophobic property of some substituents will be the controlling factor of the activity of these compounds and that there can be dispersion interaction between the molecules and the receptor, where some substituents may have hydrophobic interaction, too. Based on this correlation some new compounds with higher potency have been predicted and their docking study has been performed to see if they can have better interaction with the receptor. The ADME properties of these predicted compounds have also been reported that follow Lipinski’s rule of five