KSR1, a key scaffold protein for the MAPK pathway, facilitates ERK activation upon growth factor stimulation. We recently demonstrated that KSR1 binds the Ca-binding protein calmodulin (CaM), thereby providing an intersection between KSR1-mediated and Ca signaling. In this study, we set out to generate a KSR1 point mutant with reduced Ca/CaM binding in order to unravel the functional implications of their interaction.
View Article and Find Full Text PDFBackground: Cerebellar intracerebral hemorrhage (ICH) is associated with poor functional prognosis and high mortality. Surgical evacuation has been proposed to improve outcome. The purpose of this review was to determine the benefit of surgical evacuation of cerebellar ICH and to establish guidelines for when it should be performed.
View Article and Find Full Text PDFThe Hippo signaling pathway is a master regulator of organ size and tissue homeostasis. Hippo integrates a broad range of cellular signals to regulate numerous processes, such as cell proliferation, differentiation, migration and mechanosensation. Ca is a fundamental second messenger that modulates signaling cascades involved in diverse cellular functions, some of which are also regulated by the Hippo pathway.
View Article and Find Full Text PDFThe scaffold protein IQGAP1 assembles multiprotein signaling complexes to influence biological functions. Cell surface receptors, particularly receptor tyrosine kinases and G-protein coupled receptors, are common IQGAP1 binding partners. Interactions with IQGAP1 modulate receptor expression, activation, and/or trafficking.
View Article and Find Full Text PDFThe GDT1 family is broadly spread and highly conserved among living organisms. GDT1 members have functions in key processes like glycosylation in humans and yeasts and photosynthesis in plants. These functions are mediated by their ability to transport ions.
View Article and Find Full Text PDFThe scaffold protein IQGAP1 associates with over 150 interactors to influence multiple biological processes. The molecular mechanisms that underly spatial and temporal regulation of these interactions, which are crucial for proper cell functions, remain poorly understood. The receptor tyrosine kinase MET phosphorylates IQGAP1 on Tyr.
View Article and Find Full Text PDFBackground: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients.
Methods: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM).
The small GTPase Cdc42 is an integral component of the cytoskeleton, and its dysregulation leads to pathophysiological conditions, such as cancer. Binding of Cdc42 to the scaffold protein IQGAP1 stabilizes Cdc42 in its active form. The interaction between Cdc42 and IQGAP1 enhances migration and invasion of cancer cells.
View Article and Find Full Text PDFMedicine (Baltimore)
October 2022
Introduction: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries.
View Article and Find Full Text PDFThe Hippo signaling pathway regulates tissue growth and cell fate, and its dysregulation can induce tumorigenesis. When Hippo is activated by cell-cell contact, extracellular signals, or cell polarity among others, the large tumor suppressor 1 (LATS1) kinase catalyzes inhibitory phosphorylation of the transcriptional coactivator Yes-associated protein (YAP) to maintain YAP in the cytoplasm or promote its degradation. Separately, calmodulin is a Ca-dependent protein that modulates the activity of target proteins and regulates several signaling cascades; however, its potential role in the Hippo pathway has not been identified.
View Article and Find Full Text PDFPotocki-Schaffer syndrome includes multiple exostoses, parietal foramina, and variable developmental delay/intellectual disability. It is associated with a heterozygous deletion of the 11p12p11.2 region.
View Article and Find Full Text PDFStudy Design: Retrospective observational survey-based study.
Introduction: In France, intracranial aneurysm (IA) patients are managed by neurosurgeons and by interventional neuroradiologists. The growth of endovascular treatment led us to reflect on the role of neurosurgeons in the management of patients with IA.
Background: Cerebral arteriovenous malformations (AVMs) are rare, with incidence of 1.12-1.42 cases per 100,000 person-years (Ozpinar et al.
View Article and Find Full Text PDFStudy Design: Observational retrospective survey-based study.
Introduction: Intracranial aneurysms (IA) can be treated with microsurgery or by endovascular treatments (EVT). EVT have taken an increasingly important part in IA management; the ability of neurosurgical teams to perform such surgery as well as the quality of their training is being questioned.
Superoxide dismutases (SODs) act as a primary defence against reactive oxygen species (ROS) by converting superoxide anion radicals (O ) into molecular oxygen (O) and hydrogen peroxide (HO). Members of this enzyme family include CuZnSODs, MnSODs, FeSODs, and NiSODs, depending on the nature of the cofactor that is required for proper activity. Most eukaryotes, including yeast, possess CuZnSOD and MnSOD.
View Article and Find Full Text PDFThe yeast has been perceived over decades as a highly valuable model organism for the investigation of ion homeostasis. Indeed, many of the genes and biological systems that function in yeast ion homeostasis are conserved throughout unicellular eukaryotes to humans. In this context, measurement of the yeast cellular ionic content provides information regarding yeast response to gene deletion or exposure to chemicals for instance.
View Article and Find Full Text PDFThe Uncharacterized Protein Family 0016 (UPF0016) gathers poorly studied membrane proteins well conserved through evolution that possess one or two copies of the consensus motif Glu-x-Gly-Asp-(Arg/Lys)-(Ser/Thr). Members are found in many eukaryotes, bacteria and archaea. The interest for this protein family arose in 2012 when its human member TMEM165 was linked to the occurrence of Congenital Disorders of Glycosylation (CDGs) when harbouring specific mutations.
View Article and Find Full Text PDFObjective: The aim of this study was to define whether rapidly reallocating health care workers not experienced with PP for performing PP in ICU is feasible and safe.
Summary Background Data: In the setting of severe acute respiratory distress syndrome (ARDS), the use of prone and supine positioning procedures (PP) has been associated with improved oxygenation resulting in decreased mortality. Nevertheless, applying PP is time consuming for ICU staffs that are at risk of mental of physical exhaustion, especially with the constant surge of admitted COVID-19 patients with severe ARDS.
Background: Extracranial-to-intracranial bypass surgery is a well-established technique that has been practiced for over 50 years. Since then, numerous technical variants have developed nationally and internationally.
Objective: Based on a survey, to collect information on cerebrovascular bypass surgeons and their background, surgical volume, and technical steps of extracranial-to-intracranial bypasses with focus on superficial temporal artery to middle cerebral artery (STA-MCA) bypass.
Cases of congenital disorders of glycosylation (CDG) have been associated with specific mutations within the gene encoding the human Golgi TMEM165 (transmembrane protein 165), belonging to UPF0016 (uncharacterized protein family 0016), a family of secondary ion transporters. To date, members of this family have been reported to be involved in calcium, manganese, and pH homeostases. Although it has been suggested that TMEM165 has cation transport activity, direct evidence for its Ca- and Mn-transporting activities is still lacking.
View Article and Find Full Text PDFBackground: Population aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment.
Methods: This study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment.
The biological importance of manganese lies in its function as a key cofactor for numerous metalloenzymes and as non-enzymatic antioxidant. Due to these two essential roles, it appears evident that disturbed manganese homeostasis may trigger the development of pathologies in humans. In this context, yeast has been extensively used over the last decades to gain insight into how cells regulate intra-organellar manganese concentrations and how human pathologies may be related to disturbed cellular manganese homeostasis.
View Article and Find Full Text PDFIntroduction: Moyamoya angiopathy (MMA) is a progressive steno-occlusive disease of the distal internal carotid arteries mainly described in Asia. It induces the development of collateral vascular networks to reduce chronic cerebral hypoperfusion. Symptoms depend on the patient's age in Asia: children are at greater risk of transient or constituted ischemic events, whereas adults are more exposed to hemorrhagic stroke.
View Article and Find Full Text PDFBackground: Current aging of the population with good physiological status and the increasing incidence of subarachnoid hemorrhage (SAH) in elderly patients has enhanced the benefit of treatment in terms of independence and long-term quality of life (QoL).
Methods: From November 1, 2008 to October 30, 2012, 351 patients aged 70 years or older with aneurysmal SAH underwent adapted treatment: endovascular coiling (EV) for 228 (65%) patients, microsurgical clipping (MS) for 75 (29.3%) or conservative treatment for 48 (13.