Sperm glycocalyx is altered during epididymitis as a consequence of bacterial infection

In mammals, glycoconjugates (e.g. O-glycans, three major classes of N-glycans) coat the surface of sperm. Terminal sialic acid residues and/or fucose act immunosuppressive and facilitate the survival in the female reproductive organs. Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in human. In men, pathogens can also spread to the genital tract via the continuous ductal system eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis, however, fertility of patients can be permanently impaired. Since premature acrosome reaction was observed in an UPEC epididymitis mouse model and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. We found a massive redecoration of sperm N-glycans, especially hyposialylation, along with an acrosome reaction induced in vitro. In UPEC elicited acute epididymitis in mouse, a substantial loss of N-acetylneuraminic acid (Neu5Ac) residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. Lectin staining suggested that infection reduced substantially alpha2,6-linked Neu5AC in mouse epididymis and sperm. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli associated epididymitis concurrent with premature acrosome reaction. In vitro, such an UPEC induced Neu5Ac release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after premature acrosome reaction during acute epididymitis.Bei Säugetieren sind Spermatozoen mit Glycokonjugaten (z. B. O-Glykane, drei Hauptklassen von N-Glykanen) dekoriert. Diese besitzen immunsuppressive Eigenschaften. Vor allem N-terminale Neuraminsäuren und/oder Fucose schützen die Spermien vor Immunangriffen in weiblichen Reproduktionstrakt. Durch uropathogene Escherichia coli (UPEC) hervorgerufene Harnwegsinfektionen gehören zu den häufigsten Infektionen des Menschen. Bei Männern können sich Krankheitserreger auch kanalikulär in den Genitaltrakt ausbreiten und eine bakterielle Prostatitis und/oder Epididymo-Orchitis hervorrufen. Eine Antibiotika-Behandlung eradiziert in der Regel die Krankheitserreger bei akuter Epididymitis, dennoch kann es zu einer dauerhaften Beeinträchtigung der Fruchtbarkeit der betroffenen Männer kommen. Eine massive Redekoration der N-Glycane auf Spermien, insbesondere ein starker Verlust an Sialinsäure (Hyposialylation), ist mit einer experimenell-induzierten acrosomalen Reaktion assoziiert. Da bereits eine vorzeitige acrosomale Reaktion in einem UPEC-induzierten Epididymitis-Mausmodell beobachtet wurde, und zudem Sialidasen auf der Spermienoberfläche vermutlich durch Proteasen des Akrosoms aktiviert werden können, war es das Ziel dieser Arbeit zu untersuchen, ob Veränderungen des Sialoms im Nebenhoden bei der Epididymitis auftreten. Ein substantieller Verlust an N-Acetylneuraminsäure (Neu5Ac)-Resten wurde in epididymalen Spermatozoen und Epithelzellen der UPEC-induzierten akuten Epididymitis der Maus mittels kombinierter Laser-Mikrodissektion/HPLC-ESI-MS-Analyse nachgewiesen. Lektin-Färbungen lassen vermuten, dass die Infektion zu einer deutlichen Verminderung der alpha2,6-verknüpften Neu5Ac im Nebenhoden und in den luminalen Spermien führt. Unterstützend wurde bei Männern mit einer kürzlich diagnostizierten E. coli-assoziierten Epididymitis eine deutliche Verringerung der gebundenen Sialinsäurereste an der Oberfläche der Spermien zusammen mit einer vorzeitigen acrosomalen Reaktion dokumentiert. Die UPEC-induzierte Neu5Ac-Freisetzung aus menschlichen Spermien konnte in vitro wirksam durch einen Sialidase-Inhibitor gehemmt werden. Diese Ergebnisse legen eine wesentliche Umgestaltung der Glykokalyx von Spermatozoen und epididymalen Epithelzellen durch endogene Sialidasen nach vorzeitiger Akrosomenreaktion während der akuten Epididymitis nahe

Carbon nanotubes micro-arrays: characterization and application in biosensing of free proteins and label-free capture of breast cancer cells

Circulating tumor cells (CTCs) are cells released into the bloodstream from primary tumors and are suspected to be one of the main causes behind metastatic spreading of cancer. The ability to capture and analyze circulating tumor cells in clinical samples is of great interest in prevailing patient prognosis and clinical management of cancer. Carbon nanotubes, individual rolled-up graphene sheets, have emerged as exciting materials for probing the biomolecular interactions. With diameter of about 1 nm, they can attach themselves to cell surface receptors through specific antibodies and hold a great potential for diagnostic cellular profiling. Carbon nanotubes can be either semiconducting or metallic, and the electronic properties of either type rivals the best known materials. Small size of nanotubes and the ability to functionalize their surface using 1-Pyrenebutanoic Acid, Succinimidyl Ester (PASE), enables a versatile probe for developing a platform for capture and analysis of cancer biomarkers and circulating tumor cells. Although nanotubes have previously been used to electrically detect a variety of molecules and proteins, here for the first time we demonstrate the label free capture of spiked breast cancer cells using ultra-thin carbon nanotube film micro-array devices in a drop of buffy coat and blood. A new statistical approach of using Dynamic Time Warping (DTW) was used to classify the electrical signatures with 90% sensitivity and 90% specificity in blood. These results suggest such label free devices could potentially be useful for clinical capture and further analysis of circulating tumor cells. This thesis will go in-depth the properties of carbon nanotubes, device fabrication and characterization methodologies, functionalization protocols, and experiments in buffy coats and in blood. Combination of nano and biological materials, functionalization protocols and advanced statistical classifiers can potentially enable clinical translation of such devices in the future

The Role of Religious Concepts in the Nastaliq Inscriptions of Safavid Monuments

Problem Definition: The usage of inscriptions in the Safavid monuments has been expanded and diverse, and the initial study of these works shows that the Safavid artists often used Thuluth and Kufic inscriptions to write religious themes and Nastaliq for non-religious inscriptions. However, this is not certain as Nastaliq inscriptions that contain religious themes exist.Objective: The present research has been carried out with the aim of identifying and categorizing the religious themes used in Safavid Nastaliq inscriptions. In other words, the main question of this research is that what is the status of religious themes in the Nastaliq inscriptions during the Safavid dynasty?Research Method: This research follows a descriptive and analytical method. The research data are based on library studies and field findings. The case studies are belonging to the Safavid era in Iran, with all historical monuments being considered in this period. In this research, all available samples were studied and after collecting data, the religious themes used in the samples were classified.Results: The results of this investigation, based on the study of the contents of about 250 Nastaliq inscriptions in 140 Safavid monument, indicate that 33 of them contain religious themes (about 13%). In other words, about 87% of Nastaliq inscriptions contain non-religious themes. In addition, the results indicate that the religious themes used are as follows: praying phrases (14 items in 19 works), Quranic verses (4 verses in 9 cases), and Hadith (2 hadiths in 5 inscriptions). Also, among the Nastaliq religious inscriptions in Safavid era, the most frequent is the prayer of "Nad Ali" (4 items) and the Hadith "Madinat al-Ilm" (I am the city of the knowledge and Ali is its entranceway) (3 items), which confirms and emphasizes the existence of Shiite tendencies in the formation of the mentioned works

Quantum spin operator of the photon

All elementary particles in nature can be classified as fermions with half-integer spin and bosons with integer spin. Within quantum electrodynamics (QED), even though the spin of the Dirac particle is well defined, there exist open questions on the quantized description of spin of the gauge field particle -- the photon. Here, we discover the quantum operators for the spin angular momentum (SAM) $\boldsymbol{S}_{M}=(1/c)\int d^{3}x\boldsymbol{\pi}\times\boldsymbol{A}$ and orbital angular momentum (OAM) $\boldsymbol{L}_{M}=-(1/c)\int d^{3}x\pi^{\mu}\boldsymbol{x}\times\boldsymbol{\nabla}A_{\mu}$ of the photon, where $\pi^{\mu}$ is the conjugate canonical momentum of the gauge field $A_{\mu}$. Using relativistic field theory, we reveal a perfect symmetry between the angular momentum commutation relations for Dirac fields and Maxwell fields. Our work resolves the long-standing questions on the decomposition of orbital and spin angular momentum of the photon with applications in quantum optics, topological photonics as well as nanophotonics and also has important ramifications for the spin structure of nucleons.Comment: 7 pages, 1 figure, 3 tables and a supplementary materia

Non-convex Quadratic Programming Using Coherent Optical Networks

We investigate the possibility of solving continuous non-convex optimization problems using a network of interacting quantum optical oscillators. We propose a native encoding of continuous variables in analog signals associated with the quadrature operators of a set of quantum optical modes. Optical coupling of the modes and noise introduced by vacuum fluctuations from external reservoirs or by weak measurements of the modes are used to optically simulate a diffusion process on a set of continuous random variables. The process is run sufficiently long for it to relax into the steady state of an energy potential defined on a continuous domain. As a first demonstration, we numerically benchmark solving box-constrained quadratic programming (BoxQP) problems using these settings. We consider delay-line and measurement-feedback variants of the experiment. Our benchmarking results demonstrate that in both cases the optical network is capable of solving BoxQP problems over three orders of magnitude faster than a state-of-the-art classical heuristic.Comment: 10 pages, 5 figure

Educational analysis on the pathology of the Civil Service Management Law with emphasis on the prevailing systemic approach to various areas of human resource management in government organizations in Iran

The purpose of this study is to examine the pathology of the Civil Service Management Law by emphasizing the prevailing systemic approach to various areas of human resource management in government organizations in Iran. The method of this research is descriptive-survey. Statistical samples were selected through quota and judgmental sampling. First, the interview was conducted with a statistical sample and then with the Delphi method of three stages and exploratory factor analysis. The classification of injuries in the Civil Service Law was performed according to the system characteristics in seven categories. The results showed that pathology has been studied in terms of generalization characteristics such as lack of systems, severe bureaucracy and neglect of the environment. This factor can be divided into four categories of recruitment, employment and supply and maintenance of human resources. Other pathologies include ignoring the environment despite extensive communication. According to the results we can said that Civil service management law for various reasons such as inflexibility, uncoordinated subsystems, static, non-dependence and interaction of subsystems, etc. has led to various consequences in the input and output sections of the system in the administrative system of government organizations

Educational analysis on the pathology of the Civil Service Management Law with emphasis on the prevailing systemic approach to various areas of human resource management in government organizations in Iran

The purpose of this study is to examine the pathology of the Civil Service Management Law by emphasizing the prevailing systemic approach to various areas of human resource management in government organizations in Iran. The method of this research is descriptive-survey. Statistical samples were selected through quota and judgmental sampling. First, the interview was conducted with a statistical sample and then with the Delphi method of three stages and exploratory factor analysis. The classification of injuries in the Civil Service Law was performed according to the system characteristics in seven categories. The results showed that pathology has been studied in terms of generalization characteristics such as lack of systems, severe bureaucracy and neglect of the environment. This factor can be divided into four categories of recruitment, employment and supply and maintenance of human resources. Other pathologies include ignoring the environment despite extensive communication. According to the results we can said that Civil service management law for various reasons such as inflexibility, uncoordinated subsystems, static, non-dependence and interaction of subsystems, etc. has led to various consequences in the input and output sections of the system in the administrative system of government organizations