Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension

To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy.status: publishe

A Novel Tau Antibody Detecting the First Amino-Terminal Insert Reveals Conformational Differences Among Tau Isoforms

International audienceAs human Tau undergoes pathologically relevant post-translational modifications when expressed in yeast, the use of humanized yeast models for the generation of novel Tau monoclonal antibodies has previously been proven to be successful. In this study, human Tau2N4R-ΔK280 purified from yeast was used for the immunization of mice and subsequent selection of high affinity Tau-specific monoclonal antibodies. The characterization of four novel antibodies in different Tau model systems yielded a phosphorylation-dependent antibody (15A10), an antibody directed to the first microtubule-binding repeat domain (16B12), a carboxy-terminal antibody (20G10) and an antibody targeting an epitope on the hinge of the first and second amino-terminal insert (18F12). The latter was found to be conformation-dependent, suggesting structural differences between the Tau splicing isoforms and allowing insight in the roles played by the amino-terminal inserts. As this monoclonal antibody also has the capacity to detect tangle-like structures in different transgenic Tau mice and neurofibrillary tangles in brain sections of patients diagnosed with Alzheimer's disease, we also tested the diagnostic potential of 18F12 in a pilot study and found this monoclonal antibody to have the ability to discriminate Alzheimer's disease patients from control individuals based on increased Tau levels in the cerebrospinal fluid

A Novel Tau Antibody Detecting the First Amino-Terminal Insert Reveals Conformational Differences Among Tau Isoforms

As human Tau undergoes pathologically relevant post-translational modifications when expressed in yeast, the use of humanized yeast models for the generation of novel Tau monoclonal antibodies has previously been proven to be successful. In this study, human Tau2N4R-ΔK280 purified from yeast was used for the immunization of mice and subsequent selection of high affinity Tau-specific monoclonal antibodies. The characterization of four novel antibodies in different Tau model systems yielded a phosphorylation-dependent antibody (15A10), an antibody directed to the first microtubule-binding repeat domain (16B12), a carboxy-terminal antibody (20G10) and an antibody targeting an epitope on the hinge of the first and second amino-terminal insert (18F12). The latter was found to be conformation-dependent, suggesting structural differences between the Tau splicing isoforms and allowing insight in the roles played by the amino-terminal inserts. As this monoclonal antibody also has the capacity to detect tangle-like structures in different transgenic Tau mice and neurofibrillary tangles in brain sections of patients diagnosed with Alzheimer's disease, we also tested the diagnostic potential of 18F12 in a pilot study and found this monoclonal antibody to have the ability to discriminate Alzheimer's disease patients from control individuals based on increased Tau levels in the cerebrospinal fluid.status: Published onlin

The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling

Loss of ER Ca2+ homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca2+. Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca2+ fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts. Following ER-Ca2+ store depletion, the PERK-FLNA interaction drives the expansion of ER-PM juxtapositions by regulating F-actin-assisted relocation of the ER-associated tethering proteins Stromal Interaction Molecule 1 (STIM1) and Extended Synaptotagmin-1 (E-Syt1) to the PM. Cytosolic Ca2+ elevation elicits rapid and UPR-independent PERK dimerization, which enforces PERK-FLNA-mediated ER-PM juxtapositions. Collectively, our data unravel an unprecedented role of PERK in the regulation of ER-PM appositions through the modulation of the actin cytoskeleton.publisher: Elsevier articletitle: The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling journaltitle: Molecular Cell articlelink: http://dx.doi.org/10.1016/j.molcel.2017.01.020 content_type: article copyright: © 2017 Elsevier Inc.status: publishe

Closing schools for SARS-CoV-2: a pragmatic rapid recommendation

Background: In Belgium, schools closed during the first lockdown in March 2020, with a partial reopening in May. They fully reopened in September. During the summer, infections started to increase in the general population, speeding up in September. Some measures were taken to limit social contacts but those were insufficient to mitigate the exponential rise of infections in October. Children were still receiving all lessons at school at that time and it was questioned whether this position was tenable. We systematically compared the benefits and harms of closing primary and secondary schools and developed a&nbsp;recommendation. Methods: A multidisciplinary panel, including school pupils and teachers, educational experts, clinicians and researchers, produced this recommendation in compliance with the standards for trustworthy rapid guidelines. The recommendation is based on data collected through national surveillance or studies from Belgium, and supported by a rapid literature&nbsp;review. Results: Closing schools during the first lockdown probably resulted in a large learning delay and possibly led to more cases of child abuse. We are uncertain about the effect on the infection rate, hospitalisations, transmission rates, mental health of children, teachers and parents. The panel concluded that the balance of benefits and harms of closing schools clearly shifts against closing schools. Detrimental effects are even worse for vulnerable children. This recommendation is affected by the local virus&nbsp;circulation. Conclusion: The guideline panel issues a strong recommendation against closing schools when the virus circulation is low to moderate, and a weak recommendation against closing schools when the virus circulation is high. It does not apply when the school system cannot function due to lack of teachers, too many children who are at home or a shortage of support services. As the results of international studies are consistent with Belgian study results, this recommendation may also be relevant&nbsp;internationally.</p

The ER stress sensor PERK coordinates ER-plasma membrane contact site formation through interaction with filamin-A and F-actin remodeling

Loss of ER Ca2+ homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca2+. Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca2+ fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts. Following ER-Ca2+ store depletion, the PERK-FLNA interaction drives the expansion of ER-PM juxtapositions by regulating F-actin-assisted relocation of the ER-associated tethering proteins Stromal Interaction Molecule 1 (STIM1) and Extended Synaptotagmin-1 (E-Syt1) to the PM. Cytosolic Ca2+ elevation elicits rapid and UPR-independent PERK dimerization, which enforces PERK-FLNA-mediated ER-PM juxtapositions. Collectively, our data unravel an unprecedented role of PERK in the regulation of ER-PM appositions through the modulation of the actin cytoskeleton