Influence of Plasminogen Activator Inhibitor Type 1 on Choroidal Neovascularization

peer reviewedHigh levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss, and current therapies are limited. PAI-1 has recently been shown to be essential for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice prevented the development of subretinal choroidal angiogenesis induced by laser photocoagulation. When systemic and local PAI-1 expression was achieved by intravenous injection of a replication-defective adenoviral vector expressing human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored. These observations demonstrate the proangiogenic activity of PAI-1 not only in tumoral models, but also in choroidal experimental neovascularization sharing similarities with human AMD. They identify therefore PAI-1 as a potential target for therapeutic ocular anti-angiogenic strategies

Scalable Coupling of Deep Learning with Logical Reasoning

In the ongoing quest for hybridizing discrete reasoning with neural nets, there is an increasing interest in neural architectures that can learn how to solve discrete reasoning or optimization problems from natural inputs. In this paper, we introduce a scalable neural architecture and loss function dedicated to learning the constraints and criteria of NP-hard reasoning problems expressed as discrete Graphical Models. Our loss function solves one of the main limitations of Besag's pseudo-loglikelihood, enabling learning of high energies. We empirically show it is able to efficiently learn how to solve NP-hard reasoning problems from natural inputs as the symbolic, visual or many-solutions Sudoku problems as well as the energy optimization formulation of the protein design problem, providing data efficiency, interpretability, and \textit{a posteriori} control over predictions.Comment: 10 pages, 2 figures, 6 tables. Published in IJCAI'2023 proceeding

Impact of Belgian COVID-19 lockdown restrictions on autistic individuals' socio-communicative behaviors and their parents' quality of life

Background In the spring of 2020, Belgian authorities enforced a full lockdown period to contain the spread of the SARS-CoV-2 virus. This lockdown drastically disrupted the daily life of autistic individuals’ and that of their families. In the midst of these extraordinary circumstances, we assessed the impact of social restrictions on autistic individuals’ behavior and their parents’ or caregivers’ quality of life; we also sought to identify individual characteristics that may influence such changes. Methods We designed an online survey targeting caregivers living with an autistic child or adult. The questionnaire included 125 five-point Likert questions which targeted changes in families’ quality of life and in autistic individuals’ behavior, as well as factors likely to influence the extent and direction of these changes. Results We collected data from 209 French-speaking Belgian respondents. Respondents reported that the lockdown brought about a higher frequency of nonfunctional socio-communicative behaviors, as well as a decrease in families’ quality of life. Parents who had less access to respite care experienced a steeper decrease in their quality of life. Autistic individuals with comorbidities, and whose parents had less access to respite care and implemented fewer rules at home during lockdown were more likely to display nonfunctional socio-communicative behaviors. Conclusion COVID-19 lockdown restrictions had a negative impact on both autistic individuals and their parents

Investigaciones experimentales sobre la accion fisiológica y terapéutica de la Pancreatina

Copia digital : Junta de Castilla y León. Conserjería de Cultura y Turismo, 201

Is Counseling Ready for Rational Suicide? A Study of Perceived Competence

Many counselors believe suicidal ideation in a terminally ill client can be rational (Rogers et al, 2001). One hundred and fifty-three counselors rated their perceived competence to counsel individuals who are rationally suicidal. Data were analyzed with non-parametric statistics. Findings suggest participants with more education, more years of service, and more experience with terminally ill clients rated themselves more competent to work with rationally suicidal clients. Implications for counselors and counselor educators are discussed

Analysis by in Situ Hybridization of Cells Expressing mRNA for Tumor-Necrosis Factor in the Developing Thymus of Mice

We have used in situ hybridization to investigate the expression of TNF-α genes by thymic cells during fetal development in mice. In 14-day-old fetal thymuses, very scarce cells produce TNF-α mRNA. A second phase of cytokine gene expression starts on day 16. The density of positive cells progressively increases up to day 20. Thymuses at 15 days of gestation and after birth do not express detectable cytokine mRNA. In an attempt to identify the nature of the TNF-α mRNA-producing cells, acid phosphatase activity, which is characteristic of the macrophage lineage, was studied in the same thymuses. Acid phosphatase-positive cells only appear on day 15. Their frequency increases up to birth. However, no correlation can be established between acid phosphatase—and TNFα mRNA— positive cells. The results indicate that a small subset of thymic cells is responsible for TNF-α mRNA production during ontogeny: These cells are not yet identified. The possible role of TNF-α in thymic ontogeny is discussed

Leptin Reverts Pro-Apoptotic and Antiproliferative Effects of α-Linolenic Acids in BCR-ABL Positive Leukemic Cells: Involvement of PI3K Pathway

It is suspected that bone marrow (BM) microenvironmental factors may influence the evolution of chronic myeloid leukaemia (CML). In this study, we postulated that adipocytes and lipids could be involved in the progression of CML. To test this hypothesis, adipocytes were co-cultured with two BCR-ABL positive cell lines (PCMDS and K562). T cell (Jurkat) and stroma cell (HS-5) lines were used as controls. In the second set of experiments, leukemic cell lines were treated with stearic, oleic, linoleic or α-linolenic acids in presence or absence of leptin. Survival, proliferation, leptin production, OB-R isoforms (OB-Ra and OB-Rb), phosphoinositide 3-kinase (PI3k) and BCL-2 expression have been tested after 24h, 48h and 72h of treatment. Our results showed that adipocytes induced a decrease of CML proliferation and an increase in lipid accumulation in leukemic cells. In addition, CML cell lines induced adipocytes cell death. Chromatography analysis showed that BM microenvironment cells were full of saturated (SFA) and monounsaturated (MUFA) fatty acids, fatty acids that protect tumor cells against external agents. Stearic acid increased Bcl-2 expression in PCMDS, whereas oleic and linoleic acids had no effects. In contrast, α-linolenic acid decreased the proliferation and the survival of CML cell lines as well as BCL-2 and OB-R expression. The effect of α-linolenic acids seemed to be due to PI3K pathway and Bcl-2 inhibition. Leptin production was detected in the co-culture medium. In the presence of leptin, the effect of α-linolenic acid on proliferation, survival, OB-R and BCl-2 expression was reduced

Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

Abstract Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment