Dynamic light scattering study on phase separation of a protein-water mixture: Application on cold cataract development in the ocular lens

We present a detailed dynamic light scattering study on the phase separation in the ocular lens emerging during cold cataract development. Cold cataract is a phase separation effect that proceeds via spinodal decomposition of the lens cytoplasm with cooling. Intensity auto-correlation functions of the lens protein content are analyzed with the aid of two methods providing information on the populations and dynamics of the scattering elements associated with cold cataract. It is found that the temperature dependence of many measurable parameters changes appreciably at the characteristic temperature ~16+1 oC which is associated with the onset of cold cataract. Extending the temperature range of this work to previously inaccessible regimes, i.e. well below the phase separation or coexistence curve at Tcc, we have been able to accurately determine the temperature dependence of the collective and self-diffusion coefficient of proteins near the spinodal. The analysis showed that the dynamics of proteins bears some resemblance to the dynamics of structural glasses where the apparent activation energy for particle diffusion increases below Tcc indicating a highly cooperative motion. Application of ideas developed for studying the critical dynamics of binary protein/solvent mixtures, as well as the use of a modified Arrhenius equation, enabled us to estimate the spinodal temperature Tsp of the lens nucleus. The applicability of dynamic light scattering as a non-invasive, early-diagnostic tool for ocular diseases is also demonstrated in the light of the findings of the present paper

Research of microdeformation and stress in details of agricultural machines by implementing holography

The article presents theoretical and experimental studies of microstrains and stresses in the details of agricultural machines by the implementation of holography. В статье представлены теоретические и экспериментальные исследования микродеформаций и напряжений в деталях сельскохозяйственных машин с применением голографии

"Language breathes life" - Barngarla community perspectives on the wellbeing impacts of reclaiming a dormant Australian Aboriginal language

Traditional languages are a key element of Indigenous peoples’ identity, cultural expression, autonomy, spiritual and intellectual sovereignty, and wellbeing. While the links between Indigenous language loss and poor mental health have been demonstrated in several settings, little research has sought to identify the potential psychological benefits that may derive from language reclamation. The revival of the Barngarla language on the Eyre Peninsula, South Australia, offers a unique opportunity to examine whether improvements in mental health and social and emotional wellbeing can occur during and following the language reclamation process. This paper presents findings from 16 semi-structured interviews conducted with Barngarla community members describing their own experienced or observed mental health and wellbeing impacts of language reclamation activities. Aligning with a social and emotional wellbeing framework from an Aboriginal and Torres Strait Islander perspective, key themes included connection to spirituality and ancestors; connection to Country; connection to culture; connection to community; connection to family and kinship; connection to mind and emotions; and impacts upon identity and cultural pride at an individual level. These themes will form the foundation of assessment of the impacts of language reclamation in future stages of the project.Leda Sivak, Seth Westhead, Emmalene Richards, Stephen Atkinson, Jenna Richards, Harold Dare, Ghil, ad Zuckermann, Graham Gee, Michael Wright, Alan Rosen, MichaelWalsh, Ngiare Brown and Alex Brow

Выбор метода лечения симптоматической инфравезикальной обструкции У пациентов С доброкачественной гиперплазией предстательной железы, перенесших трансплантацию почки

St. Petersburg, Russian Federation The paper presents a comparative assessment of different methods of treating symptomatic bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH) who underwent kidney transplantation (KT).Статья посвящена сравнительной оценке различных методов лечения симптоматической инфравезикальной обструкции (ИВО) у пациентов с доброкачественной гиперплазией предстательной железы (ДГПЖ), перенесших трансплантацию почки (ТП)

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

Sprouty2 and Spred1-2 Proteins Inhibit the Activation of the ERK Pathway Elicited by Cyclopentenone Prostanoids

Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA1 and 15d-PGJ2. Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA1-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators

Результаты радикальной простатэктомии при лечении местно-распространенного рака предстательной железы: клинические наблюдения

Background. Radical prostatectomy in treatment of locally advanced prostate cancer is currently recommended as one of the stages of multimodal therapy. Despite this, the expediency of surgical intervention remains a subject of discussion: based on the results of their own research, supporters of surgical tactics for treatment of locally advanced prostate cancer point to the effectiveness and relative safety of radical prostatectomy, opponents point to the high probability of a positive surgical edge associated with the operation, local tumor recurrence, lymphogenic metastasis, and formation of distant metastases.Aim. To evaluate the outcomes of laparoscopic radical prostatectomy performed in combination with expanded pelvic lymphadenectomy in treatment of prostate adenocarcinoma T3a–3bN0M0.Materials and methods. The perioperative, functional, and oncological results of surgical treatment of patients with locally advanced prostate cancer (n = 32) aged between 46 years to 71 years were analyzed. The follow-up period averaged 9–36 months (median 13 months).Results. Mean total duration of surgical intervention and mean volume of intraoperative blood loss were 182.69 ± 3.99 minutes and 253.06 ± 9.80 ml, respectively. Overestimation of the clinical stage of the disease, according to histological examination of the surgical material, was observed in 6.3 % of patients. After the intervention, the function of urinary retention was preserved and did not require correction in 65.6 % of men. In all patients 6 months after the operation, the urinary volume, maximum and mean urine flow rates were normalized, and there was a trend toward a decrease in the post-void residual volume. During the entire follow-up period, there were no signs of biochemical relapse in 78.1 % of patients. None of the participants dropped out of the study due to death.Conclusion. Over the last 20 years in specialized medical periodicals, author teams from various countries have shown the immediate and remote (follow-up period from 3 to 20 years) outcomes of radical surgical treatment of locally advanced prostate cancer in at least 80,000 patients in total, while the criterion for exclusion from research was adjuvant therapy. The authors’ conclusions indicate the effectiveness and relative safety of surgical treatment of locally advanced prostate cancer, as well as the importance of extended pelvic lymphadenectomy, which allows to optimize the tactics of adjuvant therapy if necessary. The results of our own observations are completely comparable with the literature data. Currently, scientific research is continuing with the aim of improving the outcomes of surgical treatment of locally advanced prostate cancer, in particular clarifying the role of individual prognostic factors, improving prediction techniques and choosing a rational scheme of treatment measures. Введение. Радикальная простатэктомия при лечении местно-распространенного рака предстательной железы в настоящее время рекомендована в качестве одного из этапов мультимодальной терапии. Целесообразность оперативного вмешательства остается предметом дискуссии. На основании результатов собственных исследований сторонники хирургической тактики лечения местно-распространенного рака предстательной железы указывают на эффективность и относительную безопасность радикальной простатэктомии, противники – на ассоциированную с операцией высокую вероятность положительного хирургического края, локального рецидивирования о пухоли, лимфогенного метастазирования и формирования отдаленных метастазов.Цель исследования – оценка результатов лапароскопической радикальной простатэктомии, проводившейся в комплексе с расширенной тазовой лимфаденэктомией, при лечении аденокарциномы предстательной железы Т3а–3bN0M0.Материалы и методы. Рассмотрены периоперационные, функциональные и онкологические результаты хирургического лечения больных местно-распространенным раком предстательной железы (n = 32) в возрасте от 46 до 71 года. Период наблюдения составил 9–36 мес (медиана 13 мес).Результаты. Общая продолжительность хирургического вмешательства и объем интраоперационной кровопотери составили в среднем 182,69 ± 3,99 мин и 253,06 ± 9,80 мл соответственно. Завышение клинической стадии заболевания по данным гистологического исследования операционного материала наблюдалось у 6,3 % больных. После вмешательства функция удержания мочи была сохранена и не требовала коррекции у 65,6 % мужчин. У всех пациентов через 6 мес после операции были нормализованы объем мочеиспускания, его максимальная и средняя скорости, появилась тенденция к уменьшению объема остаточной мочи. За все время наблюдения признаки формирования биохимического рецидива отсутствовали у 78,1 % пациентов. Ни один из участников не выбыл из исследования по причине смерти.Заключение. За последние 20 лет в специальной медицинской периодике авторскими коллективами из разных стран показаны ближайшие и отдаленные (период наблюдения от 3 до 20 лет) результаты радикального хирургического лечения местно-распространенного рака предстательной железы не менее чем у 80 тыс. пациентов в совокупности, при этом критерием исключения из исследований являлось проведение адъювантной терапии. Выводы авторов свидетельствуют об эффективности и относительной безопасности оперативного лечения местно-распространенного рака предстательной железы, а также о значимости расширенной тазовой лимфаденэктомии, позволяющей оптимизировать тактику адъювантной терапии при ее необходимости. Результаты наших наблюдений полностью сопоставимы с данными литературы. В настоящее время продолжаются научные изыскания, направленные на улучшение результатов хирургического лечения местно-распространенного рака предстательной железы, в частности на уточнение роли отдельных прогностических факторов, совершенствование методов прогнозирования  и выбора рациональной схемы лечебных мероприятий