TAR DNA-binding protein 43 (TDP-43) is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we report ...that lipopolysaccharide (LPS)-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α) increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T) transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
E-commerce has become a booming market for wildlife trafficking, as online platforms are increasingly more accessible and easier to navigate by sellers, while still lacking adequate supervision. ...Artificial intelligence models, and specifically deep learning, have been emerging as promising tools for the automated analysis and monitoring of digital online content pertaining to wildlife trade. Here, we used and fine-tuned freely available artificial intelligence models (i.e., convolutional neural networks) to understand the potential of these models to identify instances of wildlife trade. We specifically focused on pangolin species, which are among the most trafficked mammals globally and receiving increasing trade attention since the COVID-19 pandemic. Our convolutional neural networks were trained using online images (available from iNaturalist, Flickr and Google) displaying both traded and non-traded pangolin settings. The trained models showed great performances, being able to identify over 90 % of potential instances of pangolin trade in the considered imagery dataset. These instances included the showcasing of pangolins in popular marketplaces (e.g., wet markets and cages), and the displaying of commonly traded pangolin parts and derivates (e.g., scales) online. Nevertheless, not all instances of pangolin trade could be identified by our models (e.g., in images with dark colours and shaded areas), leaving space for further research developments. The methodological developments and results from this exploratory study represent an advancement in the monitoring of online wildlife trade. Complementing our approach with other forms of online data, such as text, would be a way forward to deliver more robust monitoring tools for online trafficking.
to map the existing knowledge on nursing ethical decision making in the physical restraint of hospitalised adults. (1) Background: physical restraint is a technique that conditions the free movement ...of the body, with risks and benefits. The prevalence of physical restraint in healthcare suffers a wide variation, considering the environment or pathology, and it raises ethical issues that hinders decision making. This article intends to analyse and discuss this problem, starting from a literature review that will provoke a grounded discussion on the ethical and legal aspects. Inclusion criteria are: studies on physical restraint (C) and ethical nursing decision making (C) in hospitalized adults (P); (2) methods: a three-step search strategy was used according to the JBI. The databases consulted were CINAHL Plus with Full Text (EBSCOhost), MEDLINE Full Text (EBSCOhost), Nursing and Allied Health Collection: Comprehensive and Cochrane Database of Systematic Reviews (by Cochrane Library, RCAAP and Google Scholar. All articles were analysed by two independent reviewers; (3) results: according to the inclusion criteria, 18 articles were included. The categories that influence ethical decision in nursing are: consequence of the decision, the context, the nature of the decision in terms of its complexity, the principles of the ethical decision in nursing, ethical issues and universal values; (4) conclusions: the findings of this review provide evidence that there is extensive knowledge regarding nursing ethical decision making in adult physical restriction, also, it is considered an ethical issue with many associated assumptions. In this article we aim to confront all these issues from a legal perspective.
SARS-CoV-2 pandemic has forced frequent testing of populations. It is necessary to identify the most cost-effective strategies for the detection of COVID-19 outbreaks. Nasopharyngeal samples have ...been used for SARS-CoV-2 detection but require a healthcare professional to collect the sample and cause discomfort and pain to the individual. Saliva has been suggested as an appropriate fluid for the diagnosis of COVID-19. We have investigated the possibility of using pools of saliva samples to detect SARS-CoV-2 in symptomatic and asymptomatic patients. Two hundred and seventy-nine saliva samples were analyzed through RT-PCR of Envelope, Nucleocapsid and Open Reading Frame 1ab genes. Reproducibility assays showed an almost perfect agreement as well as high sensitivity (96.6%), specificity (96.8%), positive predicted value (96.6%), and negative predicted value (96.8%). The average Cycle Threshold of the genes detected was 29.7. No significant differences (p > 0.05) were detected when comparing the cycle threshold average of two consecutive reactions on the same positive saliva samples. Saliva samples have a higher median viral load (32.6) than in nasopharyngeal samples (28.9), although no significant differences were detected (p > 0.05). Saliva-pool samples allowed effective SARS-CoV-2 screening, with a higher sensibility (96.9%) on 10-sample pools than in 20-sample pools (87.5%). Regardless of pools size specificity was high (99.9%) and an almost perfect agreement was observed. Our strategy was successfully applied in population wide testing of more than 2000 individuals, showing that it is possible to use pooled saliva as diagnostic fluid for SARS-CoV-2 infection.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cyphomandra betacea (tamarillo) is a tree that produces edible, highly nutritional fruits. In tamarillo, somatic embryogenesis (SE) is achieved through a two-step process starting with the formation ...of an embryogenic tissue on an auxin-rich medium and further development of embryos, following tissue transfer to an auxin-free medium. During the induction stage, both embryogenic (EC) and nonembryogenic calli (NEC) arise from the same explant (immature leaves or mature zygotic embryos) in the presence of either picloram or 2,4-dichlorophenoxyacetic acid. In an attempt to find somatic embryogenic-specific proteins, a comparative analysis of the proteome of tamarillo’s EC and NEC was performed. Analysis of 2-DE gels revealed ca. 150 differentially expressed proteins, from which 22 have been identified by LC–MS/MS. Proteins exclusively or predominantly expressed in EC included metabolism-related proteins, such as enolases or treonine synthases, and also heat-shock and ribosomal proteins. Pathogenesis-related proteins were found mainly in NEC. A number of additional differentially expressed proteins involved in various functional categories were also identified. A quantitative real time PCR (qPCR) analysis revealed no significant differences at the mRNA level for 11 differentially expressed proteins, with exception of the pathogenesis-related proteins that were up-regulated in NEC. This seems to indicate that a posttranscriptional control might be responsible for the proteomic differences detected.
E-cadherin and P-cadherin are major contributors to cell–cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes during development, and in ...maintaining integrity and homeostasis in adult tissues. It is now generally accepted that alterations in these two molecules are observed during tumour progression of most carcinomas. Genetic or epigenetic alterations in E- and P-cadherin-encoding genes (CDH1 and CDH3, respectively), or alterations in their proteins expression, often result in tissue disorder, cellular de-differentiation, increased invasiveness of tumour cells and ultimately in metastasis. In this review, we will discuss the major properties of E- and P-cadherin molecules, its regulation in normal tissue, and their alterations and role in cancer, with a specific focus on gastric and breast cancer models.
Glioblastoma multiforme (GBM) is a highly heterogeneous malignant tumor. Recent data suggests the presence of a hierarchical organization within the GBM cell population that involves cancer cells ...with stem‐like behavior, capable of repopulating the tumor and contributing to its resistance to therapy. Tumor stem cells are thought to reside within a vascular niche that provides structural and functional support. However, most GBM studies involve isolated tumor cells grown under various culture conditions. Here, we use a novel three‐dimensional organotypic “explant” system of surgical GBM specimens that preserves cytoarchitecture and tumor stroma along with tumor cells. Notch inhibition in explants results in decreased proliferation and self‐renewal of tumor cells but is also associated with a decrease in endothelial cells. When endothelial cells are selectively eliminated from the explants via a toxin conjugate, we also observed a decrease in self‐renewal of tumor stem cells. These findings support a critical role for tumor endothelial cells in GBM stem cell maintenance, mediated at least in part by Notch signaling. The explant system further highlighted differences in the response to radiation between explants and isolated tumor neurospheres. Combination treatment with Notch blockade and radiation resulted in a substantial decrease in proliferation and in self‐renewal in tumor explants while radiation alone was less effective. This data suggests that the Notch pathway plays a critical role in linking angiogenesis and cancer stem cell self‐renewal and is thus a potential therapeutic target. Three‐dimensional explant systems provide a novel approach for the study of tumor and microenvironment interactions. STEM Cells 2010;28:1019–1029
Amino acids are crucial nutrients involved in several cellular and physiological processes, including fertilization and early embryo development. In particular, Leucine and Arginine have been shown ...to stimulate implantation, as lack of both in a blastocyst culture system is able to induce a dormant state in embryos. The aim of this work was to evaluate the effects of Leucine and Arginine withdrawal on pluripotent mouse embryonic stem cell status, notably, their growth, self-renewal, as well as glycolytic and oxidative metabolism. Our results show that the absence of both Leucine and Arginine does not affect mouse embryonic stem cell pluripotency, while reducing cell proliferation through cell-cycle arrest. Importantly, these effects are not related to Leukemia Inhibitory Factor (LIF) and are reversible when both amino acids are reconstituted in the culture media. Moreover, a lack of these amino acids is related to a reduction in glycolytic and oxidative metabolism and decreased protein translation in mouse embryonic stem cells (mESCs), while maintaining their pluripotent status.
Hormonal variations are known to influence the course of multiple sclerosis (MS).
We aimed to evaluate the impact of menopause in MS course, including disease activity and disability progression.
We ...conducted a retrospective longitudinal cohort study including all women, older than 44, post-menopausal, with a diagnosis of MS at least 1 year before menopause. We evaluated the impact of menopause in MS course comparing clinical and radiologic outcomes within 5 years before and after menopause. We repeated the analysis in subgroups of patients without disease-modifying treatment (DMT) change or co-morbidities diagnosed during the observation period, considering that those factors might also impact MS outcomes.
Thirty-seven women, with a mean age at the time of menopause of 49.8 (±4.06) years were included in the analysis. Within 5 years following menopause, we observed a decrease in the annualized relapse rate (0.37 ± 0.35 pre-menopause vs. 0.08 ± 0.18 post-menopause, p < 0.001) compared with the same period before menopause, while the EDSS progression rate remained stable (0.13 ± 0.24 EDSS point/year pre-menopausal vs. 0.13 ± 0.18 post-menopause, p = 0.935). EDSS progression events frequency was similar before and after the menopause (37.8 vs. 48.6%, respectively, p = 0.424). These observations persisted in patients' subgroups without DMT switch or co-morbidities.
Following menopause, we observed a reduction in the relapse rate, but the disability progression continued at a similar rate, compared to the pre-menopausal period. These observations persisted in the subgroup of patients without changes in DMT or co-morbidities diagnosed during the observation period.
Online digital data from media platforms have the potential to complement biodiversity monitoring efforts. We propose a strategy for integrating these data into current biodiversity datasets in light ...of the Kunming-Montreal Global Biodiversity Framework.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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