CISD2 counteracts the inhibition of ER-mitochondrial calcium transfer by anti-apoptotic BCL-2.

CISD2, a 2Fe2S cluster domain-containing protein, is implicated in Wolfram syndrome type 2, longevity and cancer. CISD2 is part of a ternary complex with IP receptors (IPRs) and anti-apoptotic BCL-2 proteins and enhances BCL-2's anti-autophagic function. Here, we examined how CISD2 impacted the function of BCL-2 in apoptosis and in controlling IPR-mediated Ca signaling.

A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome.

Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration.

ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome.

Wolfram syndrome is a rare genetic disease caused by mutations in the WFS1 or CISD2 gene. A primary defect in Wolfram syndrome involves poor ER Ca handling, but how this disturbance leads to the disease is not known. The current study, performed in primary neurons, the most affected and disease-relevant cells, involving both Wolfram syndrome genes, explains how the disturbed ER Ca handling compromises mitochondrial function and affects neuronal health.

Loss of INPP5K attenuates IP-induced Ca responses in the glioblastoma cell line U-251 MG cells.

INPP5K (inositol polyphosphate 5-phosphatase K) is an endoplasmic reticulum (ER)-resident enzyme that acts as a phosphoinositide (PI) 5-phosphatase, capable of dephosphorylating various PIs including PI 4,5-bisphosphate (PI(4,5)P), a key phosphoinositide found in the plasma membrane. Given its ER localization and substrate specificity, INPP5K may play a role in ER-plasma membrane contact sites. Furthermore, PI(4,5)P serves as a substrate for phospholipase C, an enzyme activated downstream of extracellular agonists acting on Gq-coupled receptors or tyrosine-kinase receptors, leading to IP production and subsequent release of Ca from the ER, the primary intracellular Ca storage organelle.

The ER-mitochondria interface, where Ca and cell death meet.

Endoplasmic reticulum (ER)-mitochondria contact sites are crucial to allow Ca flux between them and a plethora of proteins participate in tethering both organelles together. Inositol 1,4,5-trisphosphate receptors (IPRs) play a pivotal role at such contact sites, participating in both ER-mitochondria tethering and as Ca-transport system that delivers Ca from the ER towards mitochondria. At the ER-mitochondria contact sites, the IPRs function as a multi-protein complex linked to the voltage-dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane, via the chaperone glucose-regulated protein 75 (GRP75).

Dysregulated Ca Homeostasis as a Central Theme in Neurodegeneration: Lessons from Alzheimer's Disease and Wolfram Syndrome.

Calcium ions (Ca) operate as important messengers in the cell, indispensable for signaling the underlying numerous cellular processes in all of the cell types in the human body. In neurons, Ca signaling is crucial for regulating synaptic transmission and for the processes of learning and memory formation. Hence, the dysregulation of intracellular Ca homeostasis results in a broad range of disorders, including cancer and neurodegeneration.

Uniting the divergent Wolfram syndrome-linked proteins WFS1 and CISD2 as modulators of Ca signaling.

Mutations in (which encodes Wolframin, WFS1) and (which encodes CDGSH iron sulfur domain 2) result in Wolfram syndrome (WS), a rare genetic disorder that starts with juvenile diabetes and progresses to neurological dysfunction. WFS1 and CISD2 belong to different protein families with distinct properties. Despite differences between WFS1 and CISD2, loss-of-function mutations in these proteins result in similar disease phenotypes, suggesting that they have convergent roles.

A Practical Tool for Family Assessment Based on the Social Relations Model.

An empirically based family assessment can help family therapists understand how a family functions. In systemic therapy a family is seen as a dynamic system in which the family members form interdependent subsystems. The Social Relations Model (SRM) is a useful tool to study such interdependence within a family.

Balancing ER-Mitochondrial Ca Fluxes in Health and Disease.

Organelles cooperate with each other to control cellular homeostasis and cell functions by forming close connections through membrane contact sites. Important contacts are present between the endoplasmic reticulum (ER), the main intracellular Ca-storage organelle, and the mitochondria, the organelle responsible not only for the majority of cellular ATP production but also for switching on cell death processes. Several Ca-transport systems focalize at these contact sites, thereby enabling the efficient transmission of Ca signals from the ER toward mitochondria.

Factor Score Regression With Social Relations Model Components: A Case Study Exploring Antecedents and Consequences of Perceived Support in Families.

The family social relations model (SRM) is applied to identify the sources of variance in interpersonal dispositions in families, but the antecedents or consequences of those sources are rarely investigated. Simultaneous modeling of the SRM with antecedents or consequences using structural equation modeling (SEM) allows to do so, but may become computationally prohibitive in small samples. We therefore consider two factor score regression (FSR) methods: regression and Bartlett FSR.

Preliminary Results of the Adoption and Application of the Integrated Comprehensive Care Bundle Care Program When Treating Patients with Chronic Obstructive Pulmonary Disease.

Background: St. Joseph's Health System has implemented an integrated comprehensive care bundle care (ICC) program with the hopes that it would improve patients' care while reducing overall costs. The aim of this analysis was to evaluate the performance of the ICC program within patients admitted with chronic pulmonary obstructive disease (COPD).

A mildly inducible and selective cross-link methodology for RNA duplexes.

We here report on the furan oxidation methodology for interstrand cross-linking of RNA duplexes, which have a different structure and are more stiff, reactive and labile than their DNA counterparts. Through this mildly inducible approach, natural unmodified RNA can be selectively cross-linked in high yield. The method therefore has direct applications in the increasing number of RNA based technologies.

Emergency reversal of oral anticoagulation through PPSB-SD: the fastest procedure in Belgium.

Objective: To corroborate results obtained in The Netherlands with PPSB-SD, showing a safe acute reversal of anticoagulation within 15 minutes of administration.

Material And Methods: PPSB-SD is a concentrate prothrombin complex containing a relatively constant high level of vitamin K-dependant coagulation factors II, VII, IX and X. PPSB-SD was administered to 14 patients treated with oral anticoagulants, according the patient's weight, the initial and the target INR (< 2.

Contact dermatitis caused by airborne agents. A review and case reports.

A general review is given of airborne-induced contact dermatoses, particularly of the irritant and allergenic types. Because the reports in the literature often omit the term airborne, 12 volumes of Contact Dermatitis (January 1975-July 1985) were screened, and the cases cited were classified in function of the anamnesis, lesion locations, causative irritants and allergens, and other factors. The present article also discusses differential diagnoses, in particular with regard to contact dermatitis of the face, ears, and neck.

Pustular reactions to hexafluorosilicate in foam rubber.

A case is reported of a foam rubber carrier with pustular lesions on the arms, wrists, thighs and trunk. Scratch and patch testing with the foam rubber components was negative. Animal testing revealed sodium hexafluorosilicate (Na2SiF6), one of the ingredients of the foam rubber, to be a pustulogen on previously damaged skin.