Search Results (9)

Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer’s disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroserpin (Serpini1), a serine protease inhibitor expressed in neurons which selectively inhibits extracellular tissue-type plasminogen activator (tPA)/plasmin and plays a neuroprotective role during ischemic brain injury. Abnormal function of this protein has been implicated in several conditions including stroke, glaucoma, AD, and familial encephalopathy with neuroserpin inclusion bodies (FENIB). Here, we explore the potential biochemical roles of Serpini1 by comparing proteome changes between neuroserpin-deficient (NS^−/−) and control mice, in the retina (RE), optic nerve (ON), frontal cortex (FC), visual cortex (VC), and cerebellum (CB). To achieve this, a multiple-plex quantitative proteomics approach using isobaric tandem mass tag (TMT) technology was employed followed by functional enrichment and protein–protein interaction analysis. We detected around 5000 proteins in each tissue and a pool of 6432 quantified proteins across all regions, resulting in a pool of 1235 differentially expressed proteins (DEPs). Principal component analysis and hierarchical clustering highlighted similarities and differences in the retina compared to various brain regions, as well as differentiating NS^−/− proteome signatures from control samples. The visual cortex revealed the highest number of DEPs, followed by cerebellar regions. Pathway analysis unveiled region-specific changes, including visual perception, focal adhesion, apoptosis, glutamate receptor activation, and supramolecular fiber organization in RE, ON, FC, VC, and CB, respectively. These novel findings provide comprehensive insights into the region-specific networking of Serpini1 in the central nervous system, further characterizing its potential role as a neuroprotective agent. Data are available via ProteomeXchange with identifier PXD046873. Full article

Background: Low-quality tumoral surgical excision is the major relapse factor in rectal cancer. If the surgery is highly difficult, the quality of the resection might be compromised. In the literature, it is described how low pelvic dimensions can make this type of surgery difficult. The main aim was to study the influence of pelvic measures in surgical difficulty on the patients submitted to tumoral surgical resection with curative intent. Methods: A retrospective, observational and analytic study was conducted. A total of 73 patients over a period of 3 years were included. Demographic and surgical data, as well as measurements of the pelvis taken from MRI, were collected. An univariate and multivariate analysis was performed. Results: 11 (15.1%) patients were classified as having highly difficult surgeries. All 11 patients were male. Significant differences were found between groups regarding gender (p = 0.013), transverse diameter of the pelvis (p < 0.001), interspinal distance (p = 0.014) and intertuberous distance (p < 0.001). The logistic regression revealed that a small transverse diameter (O.R. 0.919, 95% I.C. 0.846–0.999, p = 0.047) increases the degree of difficulty of the surgery. Conclusions: Male patients with a small pelvic measurement deserve a thorough surgical plan that predicts a quality resection. Full article

The ILA Study Group began its work by identifying guiding principles that should frame and inform state practices with respect to children in migration. These principles included, but were not limited to, non-discrimination; the best interests of the child; the right to life, survival, and development; the right of the child to express their views on all matters affecting them; and the right to an effective remedy. The Study Group identified some of the most common rights violations for children in migration such as arbitrary age assessment practices; inadequate and age-inappropriate reception policies and facilities; and immigration detention of children and other coercive practices. The Study Group undertook a multidisciplinary approach by summarizing the research documenting the harmful effects of these practices on child health and well-being. It surveyed (1) treaties and international instruments that might recognize a right or remedy for children on the move; (2) regional and international fora where the claims of children could be heard; and (3) the growing body of regional and international jurisprudence upholding the rights of children in migration. Finally, it identified gaps in the international and regional frameworks and formulated recommendations as to how to ensure children in migration are able to enforce their rights and access justice. Full article

Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood. To shed light on ROS induced downstream pathological events, we employed a tandem mass tag (TMT) labelling-based quantitative mass-spectrometric approach to determine proteome changes in 661W photoreceptor cells following oxidative stress induction via the application of different concentrations of H₂O₂ at different time points. Overall, 5920 proteins were identified and quantified, and 450 differentially expressed proteins (DEPs) were identified, which were altered in a dose and time dependent manner in all treatment groups compared to the control group. These proteins were involved in several biological pathways, including spliceosome and ribosome response, activated glutathione metabolism, decreased ECM-receptor interaction, oxidative phosphorylation, abnormally regulated lysosome, apoptosis, and ribosome biogenesis. Our results highlighted ECM receptor interaction, oxidative phosphorylation and spliceosome pathways as the major targets of oxidative stress that might mediate vascular dysfunction and cellular senescence. Full article

Cannabis (Cannabis sativa), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheimer’s disease (AD), multiple sclerosis (MS), Parkinson’s disease, schizophrenia and glaucoma; these have prompted changes in medicinal cannabis legislation. The relaxation of legal restrictions and increased socio-cultural acceptance has led to its increase in both medicinal and recreational usage. Several biochemically active components of cannabis have a range of effects on the biological system. There is an urgent need for more research to better understand the molecular and biochemical effects of cannabis at a cellular level, to understand fully its implications as a pharmaceutical drug. Proteomics technology is an efficient tool to rigorously elucidate the mechanistic effects of cannabis on the human body in a cell and tissue-specific manner, drawing conclusions associated with its toxicity as well as therapeutic benefits, safety and efficacy profiles. This review provides a comprehensive overview of both in vitro and in vivo proteomic studies involving the cellular and molecular effects of cannabis and cannabis-derived compounds. Full article

Animal welfare can be represented by an array of indicators. There is, however, increasing demand for concise welfare assessments that can be easily communicated and compared. Previous methods to aggregate welfare assessments have focused on livestock systems and produced a single welfare score, which may not represent all aspects of welfare. We propose an aggregation method for the recently developed Equid Assessment Research and Scoping (EARS) welfare assessment tool that results in grades for five welfare categories: housing conditions, working conditions, health, nutrition, and behavior. We overcome the problems associated with existing approaches by using a single aggregation method (decision trees) that incorporates the most important welfare indicators in a single step. The process aims to identify equids with the poorest welfare and aid decision-making when allocating resources. We demonstrate its application using a case study of over 6000 equids across Europe and Asia, where equids in India and Pakistan had the poorest welfare status in terms of health (respiratory disease and open wounds) and behavior (signs of fear and distress, and limb tethering practices). We recommend identification of the specific causes of these issues, using either existing detailed welfare data or through issue-specific assessments by an appropriate professional, to guide the development of appropriate interventions and, ultimately, improve equid welfare. Full article

The assessment of animal welfare poses numerous challenges, yet an emerging approach is the consolidation of existing knowledge into new frameworks which can offer standardised approaches to welfare assessment across a variety of contexts. Multiple tools exist for measuring the welfare of equids, but such tools have typically been developed for specific contexts. There is no ‘one size fits all’ which means that resulting datasets are generally non-comparable, creating a barrier to knowledge-sharing and collaboration between the many organisations working to improve equid welfare around the globe. To address this, we developed the Equid Assessment, Research and Scoping (EARS) tool, which incorporates pre-existing validated welfare assessment methods alongside new welfare indicators to deliver a larger and more comprehensive series of welfare indicators than currently exists, creating a single resource that can be used to assess equid welfare in any context. We field-trialled three welfare assessment protocols within the EARS tool, and applied these to welfare assessment of equids in a variety of contexts across nineteen countries. The EARS tool proved a useful, versatile and rapid method for collecting welfare assessment data and we collected 7464 welfare assessments in a period of fifteen months. We evaluate the EARS tool and provide ideas for future development. Full article

This research work uses a simplified approach to combine location information from a beacon’s propagation signal interaction with a mobile device sensor (accelerometer and gyroscope) with local building information to give real-time location and guidance to a user inside a building. This is an interactive process with visualisation information that can help user’s orientation inside unknown buildings and the data stored from different users can provide useful information about users’ movements inside a public building. Beacons installed on the building at specific pre-defined positions emit signals that give a geographic position with an associated imprecision, related with Bluetooth’s range. This uncertainty is handled by building layout and users’ movement in a developed system that maps users’ position, gives guidance, and stores user movements. This system is based on an App (Find Me!) for Android OS (Operating System) which captures the Bluetooth Low Energy (BLE) signal coming from the beacon(s) and shows, through a map, the location of the user’s smartphone and guide him to the desired destination. Also, the beacons can deliver relevant context information. The application was tested by a panel of new and habitual campus users against traditional wayfinding alternatives yielding navigation times about 30% smaller, respectively. Full article

Resveratrol is a plant-derived polyphenol that has been widely studied for its putative health promoting effects. Many of those studies have been conducted in cell culture, in supra-physiological levels of oxygen and glucose. Resveratrol interacts with reactive oxygen species (ROS) as an antioxidant or pro-oxidant. Resveratrol affects the expression and activities of ROS-producing enzymes and organelles. It is therefore important to consider how cell culture conditions might determine the effects of resveratrol on cultured cells. We determined the effects of resveratrol on cell growth, hydrogen peroxide production, and mitochondrial network characteristics in C2C12 mouse myoblasts and PC3 human prostate cancer cells under conditions of physiological (5%) and supra-physiological (18%) oxygen, and normo- (5 mM) and hyper-glycemia (25 mM). Interestingly, most effects of resveratrol on the parameters measured here were dependent upon prevailing oxygen and glucose levels during the experiment. Many of the effects of resveratrol on cell growth, hydrogen peroxide production, and mitochondrial network characteristics that were seen in 25 mM glucose and/or 18% oxygen were absent under the physiologically relevant conditions of 5 mM glucose with 5% oxygen. These findings emphasize the importance of using physiologically meaningful starting conditions for cell-culture experiments with resveratrol and indeed any manipulation affecting ROS metabolism and mitochondria. Full article