Enhanced Synthesis of the Exopolysaccharide Ethapolan by Acinetobacter sp. 12S Grown on a Mixture of Substrates

Earlier, we found that the synthesis of the microbial exopolysaccharide (EPS) ethapolan by Acinetobacter sp. 12S can be enhanced by growing this bacterium on a mixture of ethanol and glucose It should be noted that the cultivation of Acinetobacter sp. 12S on the substrate mixture was accompanied by the enhancement of the synthesis of not only the EPS but also the biomass. The aim of this work was to maximize the transformation of the substrate carbon into EPS. Among the factors studied that may influence the transformation efficiency were the effect of the inoculum, the concentration of carbon and nitrogen sources in the medium, the nature of the energy-deficient substrate, and the availability of sodium ions. MATERIALS AND METHODS Strains. The two bacterial strains used in this work were Acinetobacter sp. 12S (the ethapolan producer described earlier Cultivation conditions. The strains were grown in a liquid mineral medium Cells for inoculation were grown on nutrient agar for 2 days or in mineral K + medium with (a) 0.5 vol % ethanol, (b) 0.5 wt % glucose, or (c) 0.5 vol % ethanol + 0.5 wt % glucose for 16-24 h (i.e., to the exponential growth phase). The inoculum was grown at the Abstract -Enhanced synthesis of the exopolysaccharide ethapolan by Acinetobacter sp. 12S was observed when the bacterium was grown on a mixture of two energetically nonequivalent substrates (ethanol and glucose) taken in a molar proportion of 3.1 : 1. The efficiency of carbon transformation into EPSs was maximum when sodium ions were absent in the medium, the concentration of nitrogen source was reduced to 0.3-0.45 g/l, and the inoculum was grown on ethanol. Such conditions provided an increase in the maximum specific growth rate and its attainment in earlier cultivation terms. Molasses as a substitution for glucose was inefficient. The activities of the key enzymes of C 2 metabolism in Acinetobacter sp. 12S cells grown on the substrate mixture were 1.1 to 1.7 times lower than they were during growth on ethanol alone. The activity of isocitrate lyase in cells grown on the substrate mixture declined to an even greater extent (by 4-7 times), indicating that the role of the glyoxylate cycle in such cells is insignificant. Key words : intensification of exopolysaccharide synthesis, mixed substrate, key enzymes of C 2 and C 6 metabolism

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections

Contains fulltext : 144469.pdf (publisher's version ) (Closed access)The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF(10) LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with high-grade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions

A preliminary investigation of materialism and impulsiveness as predictors of technological addictions among young adults

Background and aims: The primary objective of the present research is to investigate the drivers of technological addiction in college students — heavy users of Information and Communication Technology (ICT). The study places cell phone and instant messaging addiction in the broader context of consumption pathologies, investigating the influence of materialism and impulsiveness on these two technologies. Clearly, cell phones serve more than just a utilitarian purpose. Cell phones are used in public and play a vital role in the lives of young adults. The accessibility of new technologies, like cell phones, which have the advantages of portability and an ever increasing array of functions, makes their over-use increasingly likely. Methods: College undergraduates (N = 191) from two U.S. universities completed a paper and pencil survey instrument during class. The questionnaire took approximately 15–20 minutes to complete and contained scales that measured materialism, impulsiveness, and mobile phone and instant messaging addiction. Results: Factor analysis supported the discriminant validity of Ehrenberg, Juckes, White and Walsh's (2008) Mobile Phone and Instant Messaging Addictive Tendencies Scale. The path model indicates that both materialism and impulsiveness impact the two addictive tendencies, and that materialism's direct impact on these addictions has a noticeably larger effect on cell phone use than instant messaging. Conclusions: The present study finds that materialism and impulsiveness drive both a dependence on cell phones and instant messaging. As Griffiths (2012) rightly warns, however, researchers must be aware that one's addiction may not simply be to the cell phone, but to a particular activity or function of the cell phone. The emergence of multi-function smart phones requires that research must dig beneath the technology being used to the activities that draw the user to the particular technology

Клінічна анатомія і оперативна хірургія : навчально-методичний посібник до практичних занять лікарів-інтернів стоматологів

Навчально-методичний посібник із клінічної анатомії і оперативної хірургії для лікарів-інтернів стоматологів складено згідно з програмою і навчальним планом. У ньому послідовно викладені основні питання, які рекомендуються для розгляду на практичних заняттях, дані рекомендації щодо методології предмета. У кінці кожної теми наведено ситуаційні задачі та список літератури, яка рекомендується для використання під час самостійної підготовки лікарів-інтернів. Навчально-методичний посібник сприятиме підвищенню ефективності навчання інтернів-стоматологів. Він допоможе їм глибше вивчити предмет клінічної анатомії і оперативної хірургії, що має велике практичне значення в підготовці до лікувальної діяльності.The manual on clinical anatomy and operative surgery for dentist interns is compiled in accordance with the program and curriculum. It consistently sets out the main issues that are recommended for consideration in practical classes, gives recommendations on the methodology of the subject. At the end of each topic there are situational tasks and a list of literature that is recommended for use in self-training of interns. The manual will help increase the effectiveness of training of dental interns. It will help them to study more deeply the subject of clinical anatomy and operative surgery, which is of great practical importance in preparation for medical activities.Учебно-методическое пособие по клинической анатомии и оперативной хирургии для врачей-интернов стоматологов составлен согласно программе и учебным планом. В нем последовательно изложены основные вопросы, которые рекомендуются для рассмотрения на практических занятиях, даны рекомендации по методологии предмета. В конце каждой темы приведены ситуационные задачи и список литературы, рекомендуемой для использования во время самостоятельной подготовки врачей-интернов. Учебно-методическое пособие будет способствовать повышению эффективности обучения интернов-стоматологов. Он поможет им глубже изучить предмет клинической анатомии и оперативной хирургии, имеет большое практическое значение в подготовке к лечебной деятельности

Клінічна анатомія і оперативна хірургія

У підготовці лікаря акушера-гінеколога вивчення анатомо-фізіологічних, вікових і статевих особливостей будови передньо-бічної стінки живота необхідні для правильного розуміння перебігу патологічних процесів, проведення диференціальної діагностики, обґрунтування раціональних способів проведення лапаротомії. Гострий перитоніт, який може виникнути як ускладнення акушерсько-гінекологічної патології, і нині продовжує залишатися найчастішою причиною летальних випадків серед гострих хірургічних захворювань черевної порожнини. Гострі запальні захворювання, травматичні ушкодження, новоутвори, вади розвитку – досить поширена патологія органів черевної порожнини та малого тазу. Своєчасна диференціальна діагностика та їх успішне лікування можливі лише за умови детального знання лікарем клінічної анатомії очеревини і органів черевної порожнини.In the training of an obstetrician-gynecologist, the study of anatomical-physiological, age and sexual characteristics of the structure of the anterior-lateral abdominal wall is necessary for a correct understanding of pathological processes, differential diagnosis, justification of rational methods of laparotomy. Acute peritonitis, which can occur as a complication of obstetric and gynecological pathology, still continues to be the most common cause of death among acute surgical diseases of the abdominal cavity. Acute inflammatory diseases, traumatic injuries, tumors, malformations - a fairly common pathology of the abdominal cavity and pelvis. Timely differential diagnosis and their successful treatment are possible only if the doctor knows in detail the clinical anatomy of the peritoneum and abdominal organs.В подготовке врача акушера-гинеколога изучения анатомо-физиологических, возрастных и половых особенностей строения передне-боковой стенки живота необходимы для правильного понимания течения патологических процессов, проведение дифференциальной диагностики, обоснование рациональных способов проведения лапаротомии. Острый перитонит, который может возникнуть как осложнение акушерско-гинекологической патологии, и сейчас продолжает оставаться наиболее частой причиной летальных исходов среди острых хирургических заболеваний брюшной полости. Острые воспалительные заболевания, травматические повреждения, новообразования, пороки развития - достаточно распространенная патология органов брюшной полости и малого таза. Своевременная дифференциальная диагностика и их успешное лечение возможны только при условии детального знания врачом клинической анатомии брюшины и органов брюшной полости

Androgen Receptor Functional Analyses by High Throughput Imaging: Determination of Ligand, Cell Cycle, and Mutation-Specific Effects

Understanding how androgen receptor (AR) function is modulated by exposure to steroids, growth factors or small molecules can have important mechanistic implications for AR-related disease therapies (e.g., prostate cancer, androgen insensitivity syndrome, AIS), and in the analysis of environmental endocrine disruptors.We report the development of a high throughput (HT) image-based assay that quantifies AR subcellular and subnuclear distribution, and transcriptional reporter gene activity on a cell-by-cell basis. Furthermore, simultaneous analysis of DNA content allowed determination of cell cycle position and permitted the analysis of cell cycle dependent changes in AR function in unsynchronized cell populations. Assay quality for EC50 coefficients of variation were 5–24%, with Z' values reaching 0.91. This was achieved by the selective analysis of cells expressing physiological levels of AR, important because minor over-expression resulted in elevated nuclear speckling and decreased transcriptional reporter gene activity. A small screen of AR-binding ligands, including known agonists, antagonists, and endocrine disruptors, demonstrated that nuclear translocation and nuclear “speckling” were linked with transcriptional output, and specific ligands were noted to differentially affect measurements for wild type versus mutant AR, suggesting differing mechanisms of action. HT imaging of patient-derived AIS mutations demonstrated a proof-of-principle personalized medicine approach to rapidly identify ligands capable of restoring multiple AR functions.HT imaging-based multiplex screening will provide a rapid, systems-level analysis of compounds/RNAi that may differentially affect wild type AR or clinically relevant AR mutations

A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine.

Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels. In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed. Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa. Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits

Transcriptional Profiling of Chondrodysplasia Growth Plate Cartilage Reveals Adaptive ER-Stress Networks That Allow Survival but Disrupt Hypertrophy

Metaphyseal chondrodysplasia, Schmid type (MCDS) is characterized by mild short stature and growth plate hypertrophic zone expansion, and caused by collagen X mutations. We recently demonstrated the central importance of ER stress in the pathology of MCDS by recapitulating the disease phenotype by expressing misfolding forms of collagen X (Schmid) or thyroglobulin (Cog) in the hypertrophic zone. Here we characterize the Schmid and Cog ER stress signaling networks by transcriptional profiling of microdissected mutant and wildtype hypertrophic zones. Both models displayed similar unfolded protein responses (UPRs), involving activation of canonical ER stress sensors and upregulation of their downstream targets, including molecular chaperones, foldases, and ER-associated degradation machinery. Also upregulated were the emerging UPR regulators Wfs1 and Syvn1, recently identified UPR components including Armet and Creld2, and genes not previously implicated in ER stress such as Steap1 and Fgf21. Despite upregulation of the Chop/Cebpb pathway, apoptosis was not increased in mutant hypertrophic zones. Ultrastructural analysis of mutant growth plates revealed ER stress and disrupted chondrocyte maturation throughout mutant hypertrophic zones. This disruption was defined by profiling the expression of wildtype growth plate zone gene signatures in the mutant hypertrophic zones. Hypertrophic zone gene upregulation and proliferative zone gene downregulation were both inhibited in Schmid hypertrophic zones, resulting in the persistence of a proliferative chondrocyte-like expression profile in ER-stressed Schmid chondrocytes. Our findings provide a transcriptional map of two chondrocyte UPR gene networks in vivo, and define the consequences of UPR activation for the adaptation, differentiation, and survival of chondrocytes experiencing ER stress during hypertrophy. Thus they provide important insights into ER stress signaling and its impact on cartilage pathophysiology