Exploring the Efficacy of miR-33 Antagonism in Promoting Regression of Intracranial Atherosclerosis in an Nonhuman Primate Model

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we successfully induced measurable ICAS, providing a unique opportunity to investigate underlying mechanisms and potential therapeutic strategies for ICAS regression. This study presents a robust NHP model of ICAS development and explores the potential of miR-33 antagonism for promoting atherosclerosis regression. Mouse studies have shown that inhibiting miR-33a can stabilize or regress atherosclerosis in extracranial arteries, but their translatability is limited. To address this, we employed an NHP model that closely mimics human miR-33a and miR-33b expression and atherosclerosis development. Our investigation aims to assess the effectiveness of miR-33 antagonism in promoting ICAS regression in 61 NHPs, using histological characterization and digital pathology techniques to evaluate ICAS morphology and composition. Surprisingly, our results showed no histological evidence supporting the efficacy of miR-33 antagonism in improving ICAS regression measures. This study significantly contributes to our understanding of ICAS and its potential treatment strategies by establishing a reliable animal model for ICAS development. However, further investigation is required to determine the role of miR-33 antagonism in atherosclerosis regression. These findings have important implications for future research and the development of therapeutic strategies to improve brain health and function while reducing the burden of ICAS on stroke and vascular cognitive impairment

Blood Digestion in the Mosquito, Anopheles stephensi Liston (Diptera: Culicidae): Activity and Distribution of Trypsin, Aminopeptidase, and α-Glucosidase in the Midgut

The activities of trypsin, aminopeptidase, and α-glucosidase were studied in the whole midgut, anterior and posterior midgut, and posterior midgut lumen and epithelium of the mosquito Anopheles stephensi Liston. Trypsin activity was restricted entirely to the posterior midgut lumen. No trypsin activity was found before the blood meal, but activity increased continuously up to 30 h after feeding, and subsequently returned to baseline levels by 60 h. Aminopeptidase was active in anterior and posterior midgut regions before and after feeding. In whole midguts, activity rose from a baseline of ≍3 enzyme units (EU) per midgut to a maximum of 12 EU at 30 h after the blood meal, subsequently falling to baseline levels by 60 h. A similar cycle of activity was observed in the posterior midgut and posterior midgut lumen, whereas aminopeptidase in the posterior midgut epithelium decreased in activity during digestion. Aminopeptidase in the anterior midgut was maintained at a constant low level, showing no significant variation with time after feeding, α-glucosidase was active in anterior and posterior midguts before and at all times after feeding. In whole midgut homogenates, α-glucosidase activity increased slowly up to 18 h after the blood meal, then rose rapidly to a maximum at 30 h after the blood meal, whereas the subsequent decline in activity was less predictable. All posterior midgut activity was restricted to the posterior midgut lumen. Depending upon the time after feeding, >25% of the total midgut activity of α-glucosidase was located in the anterior midgut. The enzyme distributions are consistent with described structural models for digestion in mosquitoes. After blood meal ingestion, proteases are active only in the posterior midgut. Trypsin is the major primary hydrolytic protease and is secreted into the posterior midgut lumen without activation in the posterior midgut epithelium. Aminopeptidase activity is also luminal in the posterior midgut, but cellular aminopeptidases are required for peptide processing in both anterior and posterior midguts. α-glucosidase activity is elevated in the posterior midgut after feeding in response to the blood meal, whereas activity in the anterior midgut is consistent with a nectarprocessing role for this midgut regio

Организация ремонта МТП в условиях ООО «Октябрьское» Зонального района, Алтайского края

Дипломный проект состоит из ___ страниц машинописного текста. Представленная работа состоит из пяти частей, количество использованной литературы – 20 источников. Графический материал представлен на 6 листах формата А1. Ключевые слова: организация, сельскохозяйственное предприятие, ремонтная мастерская, техническое обслуживание, ремонт, технологический процесс, автомобиль, трактор, технологическое оборудование, конструкции, технологические расчеты. В разделе объект и методы исследования приведена характеристика предприятия и обоснование выбора темы выпускной работы. В разделе расчеты и аналитика представлены необходимые расчеты для организация технического обслуживания и ремонта в ремонтной мастерской и подобрано необходимое оборудование по участкам. В разделе «Социальная ответственность» выявлены опасные и вредные факторы, а так же мероприятия по их ликвидации. В разделе «Финансовый менеджмент, ресурсоэффективность и ресурсосбережение» приведена экономическая оценка проектных решений. Выпускная квалификационная работа выполнена в текстовом редакторе Мicrosoft Word 7XP и графическом редакторе КОМПАС 16.0 3D.The degree project consists of ____ pages of typewritten text. This work consists of five parts, the number of references - 20 sources. The graphic material presented on 7 sheets of A1 format. Keywords: organization, agricultural enterprise, repair shop, maintenance, repair, manufacturing process, track, tractor, process equipment design, technological calculations. In the object and research methods, see the enterprise characteristics and justification of choice of theme of master's work. In the calculations and analysis are presented the necessary calculations for the organization of maintenance and repair in the repair shop and pick up the necessary equipment areas. In the "Social Responsibility" found dangerous and harmful factors, as well as measures for their elimination. In the "Financial management, resource efficiency and resource conservation" for the economic assessment of design solutions. Final qualifying work is done in a text editor and the Microsoft Corporation Word 7XP 16.0 KOMPAS 3D graphic editor

Optimizing RNA structures by sequence extensions using RNAcop

A key aspect of RNA secondary structure prediction is the identification of novel functional elements. This is a challenging task because these elements typically are embedded in longer transcripts where the borders between the element and flanking regions have to be defined. The flanking sequences impact the folding of the functional elements both at the level of computational analyses and when the element is extracted as a transcript for experimental analysis. Here, we analyze how different flanking region lengths impact folding into a constrained structure by computing probabilities of folding for different sizes of flanking regions. Our method, RNAcop (RNA context optimization by probability), is tested on known and de novo predicted structures. In vitro experiments support the computational analysis and suggest that for a number of structures, choosing proper lengths of flanking regions is critical. RNAcop is available as web server and stand-alone software via http://rth.dk/resources/rnacop

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE

Integration of all FSSIM components within SEAMLESS-IF and a stand alone Graphical User Interface for FSSIM

Agricultural and Food Policy, Environmental Economics and Policy, Farm Management, Land Economics/Use,