Ibrutinib pharmacokinetics in B-lymphoproliferative disorders discloses exposure-related incidence of hypertension.

Objective: Ibrutinib has been the first Bruton tyrosine kinase inhibitor (BTKi) authorized for the treatment of B-cell lymphoproliferative disorders (B-LPDs). Numerous publications have confirmed the efficacy of this orally administrated drug in chemo-free regimens for B-LPDs. They also reported several adverse events (AE) associated with ibrutinib treatment.

Acceptability of "DIDE", a mobile application designed at facilitating care adherence of patients with substance use disorder.

Background: Attrition continues to be a major hurdle for addiction treatment. Through the prism of the attachment theory, this phenomenon can be understood as a manifestation of the patient's insecure attachment style, needing a highly-responsive care delivery. We developed an electronic health mobile application, co-designed with patients, aimed at helping healthcare teams respond to their patients' needs, and fostering adherence to care.

Calcineurin-Dependent Homeostatic Response of Muscle Cells upon Prolonged Activation of Acetylcholine Receptors.

Pharmacological adaptation is a common phenomenon observed during prolonged drug exposure and often leads to drug resistance. Understanding the cellular events involved in adaptation could provide new strategies to circumvent this resistance issue. We used the nematode to analyze the adaptation to levamisole, an ionotropic acetylcholine receptor agonist, used for decades to treat nematode parasitic infections.

Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors.

Objective: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML).

Methods: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. One-year follow-up data were analyzed to determine clinical outcomes and safety profile.

Peacefull: A French mindfulness-based intervention for adolescents with chronic pain a feasibility study.

Introduction: Pediatric chronic pain can lead to serious consequences in terms of daily functioning and global quality of life. Mindfulness-based intervention (MBI) approaches that emphasize accepting rather than controlling pain have gained increasing attention in adults with chronic pain. The effectiveness of MBIs for chronic pain in the pediatric population remains unknown.

An extracellular scaffolding complex confers unusual rectification upon an ionotropic acetylcholine receptor in .

Biophysical properties of ligand-gated receptors can be profoundly modified by auxiliary subunits or by the lipid microenvironment of the membrane. Hence, it is sometimes challenging to relate the properties of receptors reconstituted in heterologous expression systems to those of their native counterparts. Here we show that the properties of levamisole-sensitive acetylcholine receptors (L-AChRs), the ionotropic acetylcholine receptors targeted by the cholinergic anthelmintic levamisole at neuromuscular junctions, can be profoundly modified by their clustering machinery.

DAF-2/insulin IGF-1 receptor regulates motility during aging by integrating opposite signaling from muscle and neuronal tissues.

During aging, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In Caenorhabditis elegans, mutants of the insulin-IGF-1 receptor DAF2/IIRc represent a paradigm of healthy aging, as their increased lifespan is accompanied by a delay in age-related loss of motility. Here, we investigated the DAF-2/IIRc-dependent relationship between longevity and motility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2/IIRc.

Remodeling of Ca signaling in cancer: Regulation of inositol 1,4,5-trisphosphate receptors through oncogenes and tumor suppressors.

The calcium ion (Ca) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca transport systems. Inositol 1,4,5-trisphosphate (IP) receptors (IPRs) are IP-activated Ca release channels located on the endoplasmic reticulum (ER).

Preclinical Testing of a Combination Stone Basket and Ureteral Balloon to Extract Ureteral Stones.

We have developed the Peralta Stone Extraction System to increase the safety of ureteral stone extraction. The device combines a nitinol stone basket and low-pressure balloon into a single device. After visualization, the stone is captured in the tipless nitinol basket and enveloped by a low-pressure balloon.

Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins.

IRBIT [inositol 1,4,5-trisphosphate receptor (IPR) binding protein released with inositol 1,4,5-trisphosphate (IP)] is a multifunctional protein that regulates several target molecules such as ion channels, transporters, polyadenylation complex, and kinases. Through its interaction with multiple targets, IRBIT contributes to calcium signaling, electrolyte transport, mRNA processing, cell cycle, and neuronal function. However, the regulatory mechanism of IRBIT binding to particular targets is poorly understood.

IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact.

IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP)-binding pocket of the IP receptor (IPR), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IPR in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation.

IRBIT Interacts with the Catalytic Core of Phosphatidylinositol Phosphate Kinase Type Iα and IIα through Conserved Catalytic Aspartate Residues.

Phosphatidylinositol phosphate kinases (PIPKs) are lipid kinases that generate phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a critical lipid signaling molecule that regulates diverse cellular functions, including the activities of membrane channels and transporters. IRBIT (IP3R-binding protein released with inositol 1,4,5-trisphosphate) is a multifunctional protein that regulates diverse target proteins. Here, we report that IRBIT forms signaling complexes with members of the PIPK family.

Crystal structures of Na2SeO4·1.5H2O and Na2SeO4·10H2O.

The crystal structures of Na2SeO4·1.5H2O (sodium selenate sesquihydrate) and Na2SeO4·10H2O (sodium selenate deca-hydrate) are isotypic with those of Na2CrO4·1.5H2O and Na2 XSeO4·10H2O (X = S, Cr), respectively.

The Bcl-2 homolog Nrz inhibits binding of IP3 to its receptor to control calcium signaling during zebrafish epiboly.

Members of the Bcl-2 protein family regulate mitochondrial membrane permeability and also localize to the endoplasmic reticulum where they control Ca(2+) homeostasis by interacting with inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs). In zebrafish, Bcl-2-like 10 (Nrz) is required for Ca(2+) signaling during epiboly and gastrulation. We characterized the mechanism by which Nrz controls IP3-mediated Ca(2+) release during this process.

Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish.

Bcl-2 proteins are acknowledged as key regulators of programmed cell death. However, increasing data suggest additional roles, including regulation of the cell cycle, metabolism and cytoskeletal dynamics. Here we report the discovery and characterization of a new Bcl-2-related multidomain apoptosis accelerator, Bcl-wav, found in fish and frogs.

TIF1γ requires sumoylation to exert its repressive activity on TGFβ signaling.

TIF1γ, a new regulator of TGFβ signaling, inhibits the Smad4-mediated TGFβ response by interaction with Smad2/3 or ubiquitylation of Smad4. We have shown that TIF1γ participates in TGFβ signaling as a negative regulator of Smad4 during the TGFβ-induced epithelial-to-mesenchymal transition (EMT) in mammary epithelial cells, and during terminal differentiation of mammary alveolar epithelial cells and lactation. We demonstrate here that TIF1γ is sumoylated and interacts with Ubc9, the only known SUMO-conjugating enzyme.

Non-apoptotic roles of Bcl-2 family: the calcium connection.

The existence of the bcl-2 (B-cell lymphoma-2) gene was reported nearly 30 years ago. Yet, Bcl-2 family group of proteins still surprises us with their structural and functional diversity. Since the discovery of the Bcl-2 family of proteins as one of the main apoptosis judges, the precise mechanism of their action remains a hot topic of intensive scientific research and debates.

Cytoskeleton dynamics in early zebrafish development: A matter of phosphorylation?

Early morphogenic movements are an important feature of embryonic development in vertebrates. During zebrafish gastrulation, epiboly progression is driven by the coordinated remodeling of the YSL microtubule network and F-actin cables. We recently described the implication of Nrz, an anti-apoptotic Bcl-2 homolog, in the control of the YSL cytoskeleton dynamics.

The yolk cell of the zebrafish blastula harbors functional apoptosis machinery.

We recently described the implication of the Bcl-2 related antiapoptotic Nrz protein during early zebrafish development. Nrz knock-down induces calcium-dependent cytoskeleton remodeling leading to margin constriction and premature embryo lethality. In the YSL, nrz knock-down embryos exhibit some typical features of apoptosis such as mitochondrial transmembrane potential loss and cytochrome c release.

The apoptotic regulator Nrz controls cytoskeletal dynamics via the regulation of Ca2+ trafficking in the zebrafish blastula.

Bcl-2 family members are key regulators of apoptosis. Their involvement in other cellular processes has been so far overlooked. We have studied the role of the Bcl-2 homolog Nrz in the developing zebrafish.