Search results for "Moduli"

Genetic justification of severe COVID-19 using a rigorous algorithm

2021

Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (…

Defining Ewing and Ewing-like small round cell tumors (SRCT): The need for molecular techniques in their categorization and differential diagnosis. A…

2016

Abstract Background Differentiation of Ewing sarcoma family of tumors (ESFT) and Ewing-like tumors remains problematic. Certain ESFT with morphological and immunohistochemical (IHC) profiles lack the EWSR1-ETS transcript. To improve diagnostic accuracy we investigated the presence of several specific transcripts in 200 small round cell tumors (SRCT) displaying ESFT morphology and immunophenotype in which EWSR1 FISH analysis was non-informative or negative. Design 200 tumors (formalin-fixed, paraffin-embedded) were analyzed by RT-PCR. All tumors were tested for EWSR1-ETS , EWSR1 / WT1 , PAX3 / 7-FOX01 or SYT / SSX transcripts, and the negative tumors were subsequently analyzed for CIC / DUX4…

2019

Traumatic brain injury (TBI) can lead to impaired cognition and memory consolidation. The acute phase (24–48 h) after TBI is often characterized by neural dysfunction in the vicinity of the lesion, but also in remote areas like the contralateral hemisphere. Protein homeostasis is crucial for synaptic long-term plasticity including the protein degradation systems, proteasome and autophagy. Still, little is known about the acute effects of TBI on synaptic long-term plasticity and protein degradation. Thus, we investigated TBI in a controlled cortical impact (CCI) model in the motor and somatosensory cortex of mice ex vivo-in vitro. Late long-term potentiation (l-LTP) was induced by theta-burs…

Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.

2021

Heart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein ki…

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

2020

AbstractCoronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct…

Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

2017

Abstract Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1−/−) mice and PRG-1/LPA2–receptor double knockout (PRG-1−/−/LPA2−/−)…

Moduli spaces of rank two aCM bundles on the Segre product of three projective lines

2016

Let P^n be the projective space of dimension n on an algebraically closed field of characteristic 0 and F be the image of the Segre embedding of P^1xP^1xP^1 inside P^7. In the present paper we deal with the moduli spaces of locally free sheaves E on F of rank 2 with h^i(F,E(t))=0 for i=1,2 and each integer t.

Duality of moduli in regular toroidal metric spaces

2020

We generalize a result of Freedman and He [4, Theorem 2.5], concerning the duality of moduli and capacities in solid tori, to sufficiently regular metric spaces. This is a continuation of the work of the author and Rajala [12] on the corresponding duality in condensers. peerReviewed

Non-archimedean hyperbolicity and applications

2018

Inspired by the work of Cherry, we introduce and study a new notion of Brody hyperbolicity for rigid analytic varieties over a non-archimedean field $K$ of characteristic zero. We use this notion of hyperbolicity to show the following algebraic statement: if a projective variety admits a non-constant morphism from an abelian variety, then so does any specialization of it. As an application of this result, we show that the moduli space of abelian varieties is $K$-analytically Brody hyperbolic in equal characteristic zero. These two results are predicted by the Green-Griffiths-Lang conjecture on hyperbolic varieties and its natural analogues for non-archimedean hyperbolicity. Finally, we use …

Hemostatic Abnormalities in Patients With Severe Preeclampsia

2007

Preeclampsia is the most common medical disorder of pregnancy. Early onset preeclampsia is defined as presentation of hypertension and proteinuria before 34 weeks of gestation. Alterations of endothelial cells and fibrin deposition in microvasculature lead to enhanced activation of the coagulation cascade and impaired fibrinolysis associated with multiple organ dysfunctions. Plasma samples were obtained from 50 patients with severe preeclampsia before 34 weeks of gestation and in 61 patients with late preeclampsia. Factor VIIIR:Ag, fibrinogen, D-dimer, and thrombomodulin increased with advanced pregnancy. The platelet count is very important because of the close correlation with the activa…