scholarly journals Sulfated K5 Escherichia coli Polysaccharide Derivatives as Wide-Range Inhibitors of Genital Types of Human Papillomavirus

2008 ◽  
Vol 52 (4) ◽  
pp. 1374-1381 ◽  
Author(s):  
David Lembo ◽  
Manuela Donalisio ◽  
Marco Rusnati ◽  
Antonella Bugatti ◽  
Maura Cornaglia ◽  
...  

ABSTRACT Genital human papillomaviruses (HPV) represent the most common sexually transmitted agents and are classified into low or high risk by their propensity to cause genital warts or cervical cancer, respectively. Topical microbicides against HPV may be a useful adjunct to the newly licensed HPV vaccine. A main objective in the development of novel microbicides is to block HPV entry into epithelial cells through cell surface heparan sulfate proteoglycans. In this study, selective chemical modification of the Escherichia coli K5 capsular polysaccharide was integrated with innovative biochemical and biological assays to prepare a collection of sulfated K5 derivatives with a backbone structure resembling the heparin/heparan biosynthetic precursor and to test them for their anti-HPV activity. Surface plasmon resonance assays revealed that O-sulfated K5 with a high degree of sulfation [K5-OS(H)] and N,O-sulfated K5 with a high [K5-N,OS(H)] or low [K5-N,OS(L)] sulfation degree, but not unmodified K5, N-sulfated K5, and O-sulfated K5 with low levels of sulfation, prevented the interaction between HPV-16 pseudovirions and immobilized heparin. In cell-based assays, K5-OS(H), K5-N,OS(H), and K5-N,OS(L) inhibited HPV-16, HPV-18, and HPV-6 pseudovirion infection. Their 50% inhibitory concentration was between 0.1 and 0.9 μg/ml, without evidence of cytotoxicity. These findings provide insights into the design of novel, safe, and broad-spectrum microbicides against genital HPV infections.

Author(s):  
B. Herman ◽  
M.R. Pillai ◽  
S. Halabi ◽  
A. McKalip ◽  
A. Periasamy ◽  
...  

The development of quantitative optical microscopy has led to the ability to obtain accurate, highly sensitive spatial and temporal measurements of cell structure and function as well as the detection of low levels of pathogenic agents. One application of this capability has been in studies examining the role of high risk Human Papillomaviruses (HPV) in cervical cancer. Cervical cancer is the second most prevalent cancer in women worldwide, and epidemiological studies have strongly implicated the sexually transmitted HPV as a causative agent. So far, approximately 70 different genotypes have been identified, and those types associated with genital lesions have been classified as either “low-risk” or “high-risk” based on their association with benign or malignant lesions. The “high-risk” HPVs, such as HPV-16 and 18, have been found in approximately 84% of cervical carcinomas and are associated with cervical dysplasia and cervical intraepithelial neoplasia (CIN). HPV-16 is the most prevalent high-risk genotype and is present in about 50% of all genital lesions.


2020 ◽  
Vol 75 (3) ◽  
pp. 189-195
Author(s):  
Vladislav I. Krasnopolsky ◽  
Nina V. Zarochentseva ◽  
Ksenia V. Krasnopolskaya ◽  
Yulia N. Bashankaeva ◽  
Varvara S. Kuzmicheva

The purpose of the review a synthesis of research data on the role of human papillomavirus infection in the reproductive health of women and men. Key Points. Human papillomavirus (HPV) is one of the most common sexually transmitted viruses worldwide. According to the World Health Organization, HPV is the main cause of the development of HPV-associated diseases among both women and men. Viruses are subdivided into HPV with low carcinogenic risk, which cause benign warts, and HPV with high carcinogenic risk, which cause cancer. Different types of human papillomaviruses depending on their characteristic tropism, are divided into skin and mucous types. Viral infection in men leads to a decrease in the quality of sperm (for example, asthenozoospermia) due to apoptosis in sperm cells and due to the development of antisperm immunity. A negative viral effect on the fertility of women is manifested in an increase in the frequency of spontaneous miscarriages and a premature rupture of the amniotic membranes during pregnancy. There is evidence that HPV decreases the number of trophoblastic cells and abnormal trophoblastic-endometrial adhesion is also observed. In trophoblastic cells transfected with high-risk HPV, the level of apoptosis increases. HPV vaccination is safe, and the results show not only protection against HPV-associated diseases in women and men, but also a reduction of gestational complications, reduced preterm birth rates and the protection of newborns from infection.


2020 ◽  
Author(s):  
Lucian Chan ◽  
Garrett Morris ◽  
Geoffrey Hutchison

The calculation of the entropy of flexible molecules can be challenging, since the number of possible conformers grows exponentially with molecule size and many low-energy conformers may be thermally accessible. Different methods have been proposed to approximate the contribution of conformational entropy to the molecular standard entropy, including performing thermochemistry calculations with all possible stable conformations, and developing empirical corrections from experimental data. We have performed conformer sampling on over 120,000 small molecules generating some 12 million conformers, to develop models to predict conformational entropy across a wide range of molecules. Using insight into the nature of conformational disorder, our cross-validated physically-motivated statistical model can outperform common machine learning and deep learning methods, with a mean absolute error ≈4.8 J/mol•K, or under 0.4 kcal/mol at 300 K. Beyond predicting molecular entropies and free energies, the model implies a high degree of correlation between torsions in most molecules, often as- sumed to be independent. While individual dihedral rotations may have low energetic barriers, the shape and chemical functionality of most molecules necessarily correlate their torsional degrees of freedom, and hence restrict the number of low-energy conformations immensely. Our simple models capture these correlations, and advance our understanding of small molecule conformational entropy.


1993 ◽  
Vol 27 (3-4) ◽  
pp. 267-270 ◽  
Author(s):  
M. T. Augoustinos ◽  
N. A. Grabow ◽  
B. Genthe ◽  
R. Kfir

A fluorogenic β-glucuronidase assay comprising membrane filtration followed by selective enumeration on m-FC agar at 44.5°C and further confirmation using tlie 4-metliylumbelliferyl-β-D-glucuronide (MUG) containing medium was evaluated for the detection of Escherichia coli in water. A total of 200 typical blue and non-typical blue colonies were isolated from sea and fresh water samples using initial selective enumeration on m-FC agar. Pure cultures of the selected colonies were further tested using the MUG assay and identified using the API 20E method. Of the colonies tested which were shown to be positive using the MUG assay 99.4% were Escherichia coli. The results of this study indicate the combination of the m-FC method followed by the MUG assay to be highly efficient for the selection and confirmation of E. coli from a wide range of environmental waters.


Author(s):  
Samuel K. Cohn, Jr.

By exploring the wide range of names given to the ‘new’ sexually transmitted disease—the Great Pox—this chapter dispels notions held for two centuries or more. Instead, no tit-for-tat-naming war among nations accused of carrying the disease ensued. The ‘French disease’ alone became standard in medical texts, but not among commoners and not after the late sixteenth century for physicians. The chapter challenges a second truism of the historiography: that naming meant blaming. Although the disease was named after the French, no laws or pogroms ensued against them or any other ‘other’. However, physicians increasingly identified humans as the essential carriers of this new disease and became concerned with tracking human contacts. By the end of the sixteenth century, medical texts had renamed it the territorially neutral lues venerea. Coincidently, with the rise of this new name, blame placed on women, the poor, and victims of the disease increased.


2018 ◽  
Vol 16 (05) ◽  
pp. 362-368 ◽  
Author(s):  
Federica Sullo ◽  
Agata Polizzi ◽  
Stefano Catanzaro ◽  
Selene Mantegna ◽  
Francesco Lacarrubba ◽  
...  

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.


Electronics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 715
Author(s):  
Alexander Schäfer ◽  
Gerd Reis ◽  
Didier Stricker

Virtual Reality (VR) technology offers users the possibility to immerse and freely navigate through virtual worlds. An important component for achieving a high degree of immersion in VR is locomotion. Often discussed in the literature, a natural and effective way of controlling locomotion is still a general problem which needs to be solved. Recently, VR headset manufacturers have been integrating more sensors, allowing hand or eye tracking without any additional required equipment. This enables a wide range of application scenarios with natural freehand interaction techniques where no additional hardware is required. This paper focuses on techniques to control teleportation-based locomotion with hand gestures, where users are able to move around in VR using their hands only. With the help of a comprehensive study involving 21 participants, four different techniques are evaluated. The effectiveness and efficiency as well as user preferences of the presented techniques are determined. Two two-handed and two one-handed techniques are evaluated, revealing that it is possible to move comfortable and effectively through virtual worlds with a single hand only.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Blazej Slazak ◽  
Klara Kaltenböck ◽  
Karin Steffen ◽  
Martyna Rogala ◽  
Priscila Rodríguez-Rodríguez ◽  
...  

AbstractCyclotides are cyclic peptides produced by plants. Due to their insecticidal properties, they are thought to be involved in host defense. Violets produce complex mixtures of cyclotides, that are characteristic for each species and variable in different environments. Herein, we utilized mass spectrometry (LC–MS, MALDI-MS), transcriptomics and biological assays to investigate the diversity, differences in cyclotide expression based on species and different environment, and antimicrobial activity of cyclotides found in violets from the Canary Islands. A wide range of different habitats can be found on these islands, from subtropical forests to dry volcano peaks at high altitudes. The islands are inhabited by the endemic Viola palmensis, V. cheiranthifolia, V. anagae and the common V. odorata. The number of cyclotides produced by a given species varied in plants from different environments. The highest diversity was noted in V. anagae which resides in subtropical forest and the lowest in V. cheiranthifolia from the Teide volcano. Transcriptome sequencing and LC–MS were used to identify 23 cyclotide sequences from V. anagae. Cyclotide extracts exhibited antifungal activities with the lowest minimal inhibitory concentrations noted for V. anagae (15.62 μg/ml against Fusarium culmorum). The analysis of the relative abundance of 30 selected cyclotides revealed patterns characteristic to both species and populations, which can be the result of genetic variability or environmental conditions in different habitats. The current study exemplifies how plants tailor their host defense peptides for various habitats, and the usefulness of cyclotides as markers for chemosystematics.


2021 ◽  
Vol 9 (5) ◽  
pp. 890
Author(s):  
Pietro Tedesco ◽  
Fortunato Palma Esposito ◽  
Antonio Masino ◽  
Giovanni Andrea Vitale ◽  
Emiliana Tortorella ◽  
...  

Extremophilic microorganisms represent a unique source of novel natural products. Among them, cold adapted bacteria and particularly alpine microorganisms are still underexplored. Here, we describe the isolation and characterization of a novel Gram-positive, aerobic rod-shaped alpine bacterium (KRL4), isolated from sediments from the Karuola glacier in Tibet, China. Complete phenotypic analysis was performed revealing the great adaptability of the strain to a wide range of temperatures (5–40 °C), pHs (5.5–8.5), and salinities (0–15% w/v NaCl). Genome sequencing identified KRL4 as a member of the placeholder genus Exiguobacterium_A and annotation revealed that only half of the protein-encoding genes (1522 of 3079) could be assigned a putative function. An analysis of the secondary metabolite clusters revealed the presence of two uncharacterized phytoene synthase containing pathways and a novel siderophore pathway. Biological assays confirmed that the strain produces molecules with antioxidant and siderophore activities. Furthermore, intracellular extracts showed nematocidal activity towards C. elegans, suggesting that strain KRL4 is a source of anthelmintic compounds.


2000 ◽  
Vol 275 (35) ◽  
pp. 27311-27315
Author(s):  
Nigel Hodson ◽  
Gary Griffiths ◽  
Nicola Cook ◽  
Meraj Pourhossein ◽  
Eva Gottfridson ◽  
...  

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