Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)–dependent model ...of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expression by myeloid cells, but did not require neutrophil extracellular trap formation involving peptidyl arginine deiminase 4. In contrast to C3−/− mice, C5-deficient mice had no apparent defect in platelet activation in vitro, and vessel wall platelet deposition and initial hemostasis in vivo. However, fibrin formation, the exposure of negatively charged phosphatidylserine (PS) on adherent leukocytes, and clot burden after 48 hours were significantly reduced in C5−/− mice compared with wild-type controls. These results delineate that C3 plays specific roles in platelet activation independent of formation of the terminal complement complex and provide in vivo evidence for contributions of complement-dependent membrane perturbations to prothrombotic TF activation on myeloid cells.
•Myeloid cell TF-dependent venous thrombosis is under control of PDI and the complement cascade.•C5 deficiency reduces fibrin formation and leukocyte PS exposure with normal platelet deposition in flow-restricted vessels.
The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver ...failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.
Convergence of local supermartingales Larsson, Martin; Ruf, Johannes
Annales de l'I.H.P. Probabilités et statistiques,
11/2020, Letnik:
56, Številka:
4
Journal Article
According to the U.S. Census Bureau, 89% of American households have a computer with internet access capability.7 The widespread adoption of technology now supports the potential conduct of virtual ...focus groups, which may benefit participants with geographical barriers to in-person participation. ...adaptations for Institutional Review Board (IRB)-related processes must be made to assure protection of participants in research. ...written materials that are normally distributed during in-person focus groups for discussions must be prepared differently for virtual group participants. For virtual focus groups, the co-moderator has the new responsibilities of admitting and organizing patients in the virtual waiting room, muting participants who may be unintentionally distracting others and resolving technical problems during the meeting. ...in the virtual setting, the co-moderator acts as technology support for potential problems during the session.
Neurocysticercosis is almost exclusively caused by Taenia solium tapeworms. We describe a case of neurocysticercosis in Switzerland caused by infection with Taenia martis, the marten tapeworm, and ...review all 5 published cases of human infection with the marten tapeworm. In epidemiologically nonplausible cases of neurocysticercosis, zoonotic spillover infections should be suspected.
Urinary tract malformations constitute the most frequent cause of chronic renal failure in the first two decades of life. Branchio-otic (BO) syndrome is an autosomal dominant developmental disorder ...characterized by hearing loss. In branchio-oto-renal (BOR) syndrome, malformations of the kidney or urinary tract are associated. Haploinsufficiency for the human gene EYA1, a homologue of the Drosophila gene eyes absent (eya), causes BOR and BO syndromes. We recently mapped a locus for BOR/BO syndrome (BOS3) to human chromosome 14q23.1. Within the 33-megabase critical genetic interval, we located the SIX1, SIX4, and SIX6 genes, which act within a genetic network of EYA and PAX genes to regulate organogenesis. These genes, therefore, represented excellent candidate genes for BOS3. By direct sequencing of exons, we identified three different SIX1 mutations in four BOR/BO kindreds, thus identifying SIX1 as a gene causing BOR and BO syndromes. To elucidate how these mutations cause disease, we analyzed the functional role of these SIX1 mutations with respect to protein-protein and protein-DNA interactions. We demonstrate that all three mutations are crucial for Eya1-Six1 interaction, and the two mutations within the homeodomain region are essential for specific Six1-DNA binding. Identification of SIX1 mutations as causing BOR/BO offers insights into the molecular basis of otic and renal developmental diseases in humans.
Aggregation of alpha-synuclein (α-syn) is central in Parkinson’s disease as well as in other synucleinopathies. Recent evidence suggests that not only intracellular aggregation of α-syn plays an ...important role for disease pathogenesis but also cell-to-cell propagation of α-syn seems to significantly contribute to pathological changes in synucleinopathies. In this mini-review we summarize current aspects of spreading of α-syn between brain cell types and its role in pathology.
The article is concerned with the existence of positive solutions of a semi-linear elliptic system defined in a cylinder
Ω
=
Ω
′
×
(
0
,
a
)
⊂
R
n
, where
Ω
′
⊂
R
n
-
1
is a bounded and smooth ...domain. The system couples a superlinear equation defined in the whole cylinder
Ω
with another superlinear (or linear) equation defined at the bottom of the cylinder
Ω
′
×
{
0
}
. Possible applications for such systems are interacting substances (gas in the cylinder and fluid at the bottom) or competing species in a cylindrical habitat (insects in the air and plants on the ground). We provide a priori
L
∞
bounds for all positive solutions of the system when the nonlinear terms satisfy certain growth conditions. It is interesting that due to the structure of the system our growth restrictions are weaker than those of the pioneering result by Brezis–Turner for a single equation. Using the a priori bounds and topological arguments, we prove the existence of positive solutions for these particular semi-linear elliptic systems.
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