Checks and balances: the ocular response to infection.
Ontology highlight
ABSTRACT:
SUBMITTER: Callegan MC
PROVIDER: S-EPMC3073293 | biostudies-literature | 2010 Jul-Aug
REPOSITORIES: biostudies-literature
Publications
Bacterial corneal infections threaten vision. With the widespread use of contact lenses and the increasing number of vision-correction (refractive) surgeries, the number of bacterial corneal infection (keratitis) cases has dramatically increased over the past decade. These infections are often blinding, as bacteria multiply in the corneal epithelium and stroma, provoking inflammatory cell migration into the cornea, and ultimately damage or destruction of corneal tissue. ...[more]
Similar Datasets
Project description:Age-associated changes in the immune system including alterations in surface protein expression are thought to contribute to an increased susceptibility for autoimmune diseases. The balance between the expression of coinhibitory and costimulatory surface protein molecules, also known as immune checkpoint molecules, is crucial in fine-tuning the immune response and preventing autoimmunity. The activation of specific inhibitory signaling pathways allows cancer cells to evade recognition and destruction by the host immune system. The use of immune checkpoint inhibitors (ICIs) to treat cancer has proven to be effective producing durable antitumor responses in multiple cancer types. However, one of the disadvantages derived from the use of these agents is the appearance of inflammatory manifestations termed immune-related adverse events (irAEs). These irAEs are often relatively mild, but more severe irAEs have been reported as well including several forms of vasculitis. In this article, we argue that age-related changes in expression and function of immune checkpoint molecules lead to an unstable immune system, which is prone to tolerance failure and autoimmune vasculitis development. The topic is introduced by a case report from our hospital describing a melanoma patient treated with ICIs and who subsequently developed biopsy-proven giant cell arteritis. Following this case report, we present an in-depth review on the role of immune checkpoint pathways in the development and progression of autoimmune vasculitis and its relation with an aging immune system.
| S-EPMC5827159 | biostudies-literature
Project description:Recovering or threatened carnivore populations are often harvested to minimise their impact on human activities, such as livestock farming or game hunting. Increasingly, harvest quota decisions involve a set of scientific, administrative and political institutions operating at national and sub-national levels whose interactions and collective decision-making aim to increase the legitimacy of management and ensure population targets are met. In practice, however, assessments of how quota decisions change between these different actors and what consequences these changes have on population trends are rare.We combine a state-space population modelling approach with an analysis of quota decisions taken at both regional and national levels between 2007 and 2018 to build a set of decision-making models that together predict annual harvest quota values for Eurasian lynx (Lynx lynx) in Norway.We reveal a tendency for administrative decision-makers to compensate for consistent quota increases by political actors, particularly when the lynx population size estimate is above the regional target. Using population forecasts based on the ensemble of decision-making models, we show that such buffering of political biases ensures lynx population size remains close to regional and national targets in the long term.Our results go beyond the usual qualitative assessment of collaborative governance systems for carnivore management, revealing a system of checks and balances that, in the case of lynx in Norway, ensures both multi-stakeholder participation and sustainable harvest quotas. Nevertheless, we highlight important inter-regional differences in decision-making and population forecasts, the socio-ecological drivers of which need to be better understood to prevent future population declines. Synthesis and applications. Our work analyses the sequence of decisions leading to yearly quotas for lynx harvest in Norway, highlighting the collaborative and structural processes that together shape harvest sustainability. In doing so, we provide a predictive framework to evaluate participatory decision-making processes in wildlife management, paving the way for scientists and decision-makers to collaborate more widely in identifying where decision biases might lie and how institutional arrangements can be optimised to minimise them. We emphasise, however, that this is only possible if wildlife management decisions are documented and transparent.
| S-EPMC9306889 | biostudies-literature
Project description:Hematopoietic stem cells (HSC) sustain hematopoiesis throughout life, exiting dormancy to replenish homeostatic or acute cell loss in the peripheral blood. HSC activation is supported by PI3-Kinase/AKT/mTORC1 pathway, which promotes mitochondrial expansion, oxidative phosphorylation, and reactive oxygen species production. Activated HSCs must return to dormancy to prevent exhaustion and bone marrow failure, but the cell-intrinsic mechanisms underlying this transition are unknown. Here we identify an ERK-dependent, rate-limiting feedback mechanism that controls the fitness of the HSC compartment. We show that the MEK/ERK and PI3-Kinase pathways are synchronously deployed in HSC during emergency hematopoiesis, and that feedback phosphorylation of MEK1 by activated ERK is required to constrain AKT/mTORC1 activation. Genetic or chemical ablation of this feedback tilts the balance between HSC dormancy and activation, increasing the output of differentiated cells and accelerating HSC exhaustion. MEK inhibitors developed for cancer therapy may thus be useful to modulate HSC activation.
2018-05-28 | GSE112842 | GEO
Project description:Endophthalmitis is characterized by marked inflammation of intraocular fluids and tissues. Infective endophthalmitis may be categorized by the cause of the infection, which helps predict the underlying etiology and most likely causative organisms. The major category remains acute-onset postoperative endophthalmitis. Infective endophthalmitis is a clinical diagnosis but is confirmed by evaluation of intraocular fluid specimens. The Endophthalmitis Vitrectomy Study offered important guidelines for the initial management of endophthalmitis, and these guidelines remain relevant to this day. Prompt initiation of empiric broad-spectrum antimicrobial therapy is important in achieving best outcomes.
| S-EPMC5548375 | biostudies-other
Project description:This is a report of a Lagenidium sp. in a Thai patient who was diagnosed with severe keratitis that was unresponsive to antibacterial and antifungal drugs. Examination of a corneal biopsy specimen confirmed the presence of aseptate hyphae. The internal transcribed spacer DNA sequence of the strain isolated showed 97% identity with Lagenidium giganteum and other Lagenidium species.
| S-EPMC3719631 | biostudies-literature
Project description:Apoptosis and autophagy are two common forms of programmed cell death (PCD) used by host organisms to fight against virus infection. PCD in arthropod vectors can be manipulated by arboviruses, leading to arbovirus-vector coexistence, although the underlying mechanism is largely unknown. In this study, we find that coat protein (CP) of an insect-borne plant virus TYLCV directly interacts with a phosphatidylethanolamine-binding protein (PEBP) in its vector whitefly to downregulate MAPK signaling cascade. As a result, apoptosis is activated in the whitefly increasing viral load. Simultaneously, the PEBP4-CP interaction releases ATG8, a hallmark of autophagy initiation, which reduces arbovirus levels. Furthermore, apoptosis-promoted virus amplification is prevented by agonist-induced autophagy, whereas the autophagy-suppressed virus load is unaffected by manipulating apoptosis, suggesting that the viral load is predominantly determined by autophagy rather than by apoptosis. Our results demonstrate that a mild intracellular immune response including balanced apoptosis and autophagy might facilitate arbovirus preservation within its whitefly insect vector.
| S-EPMC8837789 | biostudies-literature
Project description:MicroRNAs (miRNAs) are small, non-coding, regulatory RNA molecules and constitute a newly recognized, important layer of gene-expression regulation at post-transcriptional levels. miRNAs quantitatively fine tune the expression of their downstream genes in a cell type- and developmental stage-specific fashion. miRNAs have been proven to play important roles in the normal development and function as well as in the pathogenesis of diseases in all tissues and organ systems. miRNAs have emerged as new therapeutic targets and biomarkers for treatment and diagnosis of various diseases. Although miRNA research in ocular infection remains in its early stages, a handful of pioneering studies have provided insight into the roles of miRNAs in the pathogenesis of parasitic, fungal, bacterial, and viral ocular infections. Here, we review the current status of research in miRNAs in several major ocular infectious diseases. We predict that the field of miRNAs in ocular infection will greatly expand with the discovery of novel miRNA-involved molecular mechanisms that will inform development of new therapies and identify novel diagnostic biomarkers.
| S-EPMC6780979 | biostudies-literature
Project description:Microfold cells (M cells) are responsible for antigen uptake to initiate immune responses in the gut-associated lymphoid tissue (GALT). Receptor activator of nuclear factor-κB ligand (RANKL) is essential for M cell differentiation. Follicle-associated epithelium (FAE) covers the GALT and is continuously exposed to RANKL from stromal cells underneath the FAE, yet only a subset of FAE cells undergoes differentiation into M cells. Here, we show that M cells express osteoprotegerin (OPG), a soluble inhibitor of RANKL, which suppresses the differentiation of adjacent FAE cells into M cells. Notably, OPG deficiency increases M cell number in the GALT and enhances commensal bacterium-specific immunoglobulin production, resulting in the amelioration of disease symptoms in mice with experimental colitis. By contrast, OPG-deficient mice are highly susceptible to Salmonella infection. Thus, OPG-dependent self-regulation of M cell differentiation is essential for the balance between the infectious risk and the ability to perform immunosurveillance at the mucosal surface.
| S-EPMC6957684 | biostudies-literature
Project description:ImportanceYellow fever virus (YFV) is a reemerging, potentially lethal arboviral disease that has been occurring recently in Africa and South America. Poor levels of immunization have facilitated the viral spread in southeastern Brazil, leading to an unprecedented outbreak that started in late 2016. Although human cases have been linked to sylvatic mosquitoes, the concern is that YFV may spread to urban centers infested with Aedes aegypti and Aedes albopictus mosquitoes and start a true urban cycle.ObjectiveTo describe the ocular findings in patients with acute YFV infection.Design, setting, participantsTwo adults with an acute YFV infection in southeastern Brazil underwent an ophthalmologic and ocular ultrasonographic examination in early 2018.Main outcomes and measuresOcular findings in patients with acute YFV infection.ResultsBoth patients presented with increased choroidal thickness bilaterally seen on ocular ultrasonography. A man in his late 50s who had not been vaccinated previously also presented with bilateral, midperipheral, 360° choroidal detachment and yellowish subretinal lesions. After clinical deterioration and liver transplant, the man died. A woman in her early 30s who had been vaccinated previously for YFV presented with increased retinal venous congestion bilaterally. She was discharged with mild conjunctival chemosis and icterus.Conclusions and relevanceThese reports describe different patterns of ocular findings associated with YFV acute infection. However, the exact mechanism involved in the retinal and choroidal findings remains unclear.
| S-EPMC6439724 | biostudies-literature
Project description:AimThe English NHS currently has a policy of providing Health Checks to all 40-74 year olds. Administered in primary care, they aim to identify patients at risk of a range of diseases, including diabetes and heart disease, and facilitate care. This study is the first to use observed data on the effectiveness of the Checks to consider whether they represent a cost-effective use of limited NHS resources.Subject and methodsUsing a publicly available evaluation tool we conducted an analysis of the Checks to establish the long-term cost and health-related outcomes of a cohort of patients. The primary focus of the analysis was to establish whether the impact of the Checks on BMI was sufficient to justify their cost.ResultsThe Checks were associated with a reduction in mean BMI of 0.27 (95% CI 0.20 to 0.34) compared to no Check. When applied to the evaluative tool, a small but positive QALY gain of 0.05 per participant was observed, coupled with a reduction in disease-related care costs of £170 ($210 USD). When the estimated cost per Check (£179, $220 USD) is taken into account, we estimate an incremental cost-effectiveness ratio of £900/QALY ($1109 USD/QALY).ConclusionsMuch of the criticism of the Health Checks has focussed on the relatively small average change in risk factors such as BMI. However, this analysis suggests that the significant health and cost-saving benefits from even a modest reduction in mean BMI, coupled with the low costs of the Checks, combine to result in a potentially highly cost-effective policy.
| S-EPMC5515950 | biostudies-literature