The proximity interactome of PML isoforms I and II under fatty acid stress.

Promyelocytic leukemia (PML) protein forms the scaffold for PML nuclear bodies (PML NB) that reorganize into Lipid-Associated PML Structures (LAPS) under fatty acid stress. We determined how the fatty acid oleate alters the interactome of PMLI or PMLII by expressing fusions with the ascorbate peroxidase APEX2 in U2OS cells. The resultant interactome included ESCRT and COPII transport protein nodes.

The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2.

During the last 30 years, an increasing number of cellular functions have been reported to be regulated by the lipid ceramide. The diversity in the ceramide structure, leading to tens of ceramide species and the discrete distribution based on subcellular topology, could explain the wide variety of functions attributed to this bioactive lipid. One of these pools of ceramide resides in the plasma membrane, and several works have suggested that an increase in plasma membrane ceramide (PMCer) in response to stimulation leads to cell death and modulates cell adhesion and migration.

Nuclear lipid droplets in Caco2 cells originate from nascent precursors and in situ at the nuclear envelope.

Intestinal epithelial cells convert excess fatty acids into triglyceride (TAG) for storage in cytoplasmic lipid droplets and secretion in chylomicrons. Nuclear lipid droplets (nLDs) are present in intestinal cells but their origin and relationship to cytoplasmic TAG synthesis and secretion is unknown. nLDs and related lipid-associated promyelocytic leukemia structures (LAPS) were abundant in oleate-treated Caco2 but less frequent in other human colorectal cancer cell lines and mouse intestinal organoids.

Lipid- and phospho-regulation of CTP:Phosphocholine Cytidylyltransferase α association with nuclear lipid droplets.

Fatty acids stored in triacylglycerol-rich lipid droplets are assembled with a surface monolayer composed primarily of phosphatidylcholine (PC). Fatty acids stimulate PC synthesis by translocating CTP:phosphocholine cytidylyltransferase (CCT) α to the inner nuclear membrane, nuclear lipid droplets (nLD) and lipid associated promyelocytic leukemia (PML) structures (LAPS). Huh7 cells were used to identify how CCTα translocation onto these nuclear structures are regulated by fatty acids and phosphorylation of its serine-rich P-domain.

Differential contributions of phosphotransferases CEPT1 and CHPT1 to phosphatidylcholine homeostasis and lipid droplet biogenesis.

The cytidine diphosphate-choline (Kennedy) pathway culminates with the synthesis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by choline/ethanolamine phosphotransferase 1 (CEPT1) in the endoplasmic reticulum (ER), and PC synthesis by choline phosphotransferase 1 (CHPT1) in the Golgi apparatus. Whether the PC and PE synthesized by CEPT1 and CHPT1 in the ER and Golgi apparatus has different cellular functions has not been formally addressed. Here, we used CRISPR editing to generate CEPT1-and CHPT1-KO U2OS cells to assess the differential contribution of the enzymes to feedback regulation of nuclear CTP:phosphocholine cytidylyltransferase (CCT)α, the rate-limiting enzyme in PC synthesis, and lipid droplet (LD) biogenesis.

Evaluation of different Maritime rapid environmental assessment procedures with a focus on acoustic performance.

Four different Marine Rapid Environmental Assessment (MREA) procedures are compared with a focus on underwater acoustic performance. Co-located oceanographic-acoustic data were collected during the summer of 2015 in the Northwestern Mediterranean in the framework of a sea trial led by the NATO Centre for Maritime Research and Experimentation. The data were used to link MREA procedures and ocean-acoustic validation in a seamless framework.

Analysis of ER-Phagy in Cancer Drug Resistance.

The ability of the cancer cells to survive hostile environment depends on their cellular stress response mechanisms. These mechanisms also help them to develop resistance to chemotherapies. Autophagy and more specifically organelle specific autophagy is one such adaptive mechanism that promotes drug resistance in cancer cells.

Cancer cells adapt FAM134B/BiP mediated ER-phagy to survive hypoxic stress.

In the tumor microenvironment, cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins largely in the endoplasmic reticulum (ER). Consequently, ER proteotoxicity elicits unfolded protein response (UPR) as an adaptive mechanism to resolve ER stress. In addition to canonical UPR, proteotoxicity also stimulates the selective, autophagy-dependent, removal of discrete ER domains loaded with misfolded proteins to further alleviate ER stress.

Efforts to advance underwater noise management in Canada: Introduction to the Marine Pollution Bulletin Special Issue.

This introduction to a special issue on approaches to managing underwater noise in Canada provides a brief overview of recent efforts to better understand and reduce anthropogenic underwater noise. Recent programs have aimed to increase understanding of anthropogenic noise in the habitats of highly endangered whales and have supported management actions such as vessel slow downs. Technical workshops have advanced the development of quiet ship design and associated technologies.

Ship noise management and the ORCA class of ships.

To support Transport Canada's projects to reduce underwater noise from shipping, Defence Research and Development Canada performed a series of experiments based on the Royal Canadian Navy's ORCA-Class training vessels. Sea trials measured onboard vibrations and underwater noise to support the development of a real-time prediction of propeller cavitation inception and underwater noise using only onboard sensors and to develop a database for assessing numerical predictions of underwater noise at the design stage. Based on these trials, it was noted that the noise impact of the vessel could be significantly reduced if the propeller cavitation inception speed could be increased.

The effective medium for a cylinder with cylindrical inclusions.

In this paper, the scattering from a fluid-filled (infinite length) cylinder is considered. This cylinder, C, has a different interior sound speed and density than the surrounding water. Within the cylinder's interior, there are a number of smaller cylinders, inclusions, with yet other sound speeds and densities.

Recalibrating the Department of National Defence approach to active sonar impact management.

Fielding a well-trained, combat-ready military, and observing Canada's responsibility as environmental stewards are at times conflicting priorities for the Department of National Defence (DND). As new low frequency sources are introduced into service, DND must review and update policies and procedures regarding the use of active sonar to minimize its impacts on marine mammals with an evidence-based approach. Risk is mitigated primarily through avoidance, which requires an understanding of marine mammal distribution in order to avoid the most sensitive species and their habitats.

Global Proximity Interactome of the Human Macroautophagy Pathway.

BioID: proximity-dependent biotin identification; GO: gene ontology; OSBPL: oxysterol binding protein like; VAPA: VAMP associated protein A; VAPB: VAMP associated protein B and C.

Tumor levels of the mediators of ErbB2-driven anoikis resistance correlate with breast cancer relapse in patients receiving trastuzumab-based therapies.

Purpose: Patients with ErbB2/Her2 oncoprotein-positive breast cancers often receive neoadjuvant therapies (NATs) containing the anti-ErbB2 antibody trastuzumab. Tumors that are still present after NATs are resected, and patients continue receiving trastuzumab. These cancers are associated with high relapse risk.

Correction to: Trastuzumab-induced upregulation of a protein set in extracellular vesicles emitted by ErbB2-positive breast cancer cells correlates with their trastuzumab sensitivity.

An amendment to this paper has been published and can be accessed via the original article.

Trastuzumab-induced upregulation of a protein set in extracellular vesicles emitted by ErbB2-positive breast cancer cells correlates with their trastuzumab sensitivity.

Background: ErbB2/HER2 oncoprotein often drives breast cancers (BCs) which are treated with the anti-ErbB2 antibody trastuzumab. The efficacy of trastuzumab-based metastatic BC therapies is routinely assessed by imaging studies. Trastuzumab typically becomes ineffective in the case of this disease and is then replaced by other drugs.

Dynamic Visual Noise Does Not Affect Memory for Fonts.

Dynamic visual noise (DVN) selectively impairs memory for some types of stimuli (e.g., colors, textures, concrete words), but not for others (e.

Truncated mutants of beta-glucosidase 2 (GBA2) are localized in the mitochondrial matrix and cause mitochondrial fragmentation.

The enzyme β-glucosidase 2 (GBA2) is clinically relevant because it is targeted by the drug miglustat (Zavesca®) and because it is involved in inherited diseases. Mutations in the GBA2 gene are associated with two neurological diseases on the ataxia-spasticity spectrum, hereditary spastic paraplegia 46 (SPG46) and Marinesco-Sjögren-like syndrome (MSS). To establish how GBA2 mutations give rise to neurological pathology, we have begun to investigate mutant forms of GBA2 encoded by disease-associated GBA2 alleles.

Correction to: Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson's disease.

The original article [1] contains an error in the y-axes of Fig. 8's sub-figures whereby 'CSF' is mistakenly mentioned instead of 'serum'.

Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson's disease.

Background: Haploinsufficiency in the Gaucher disease GBA gene, which encodes the lysosomal glucocerebrosidase GBA, and ageing represent major risk factors for developing Parkinson's disease (PD). Recently, more than fifty other lysosomal storage disorder gene variants have been identified in PD, implicating lysosomal dysfunction more broadly as a key risk factor for PD. Despite the evidence of multiple lysosomal genetic risks, it remains unclear how sphingolipid hydrolase activities, other than GBA, are altered with ageing or in PD.

Range-dependent impacts of ocean acoustic propagation on automated classification of transmitted bowhead and humpback whale vocalizations.

Significant effort has been made over the last few decades to develop automated passive acoustic monitoring (PAM) systems capable of classifying cetaceans at the species level. The utility of such systems depends on the systems' ability to operate across a wide range of ocean acoustic environments; however, anecdotal evidence suggests that site-specific propagation characteristics impact the performance of PAM systems. Variability in propagation characteristics leads to differences in how each cetacean vocalization is altered as it propagates along the source-receiver path.

Reduction in edge effects for small panels characterized by a parametric array source.

This study sought to explore effects of panel size on underwater acoustic transmission and reflection measurements made with a truncated parametric array source. The transmission loss (TL) and reflection loss spectra of aluminum panels of several different sizes were determined experimentally, and compared to predictions from plane wave theory in the 5-100 kHz frequency range. For the smallest panel size, there were significant discrepancies between experimental data and plane wave theory, which were attributed to contributions from edge-diffracted waves and interferences from the mounting fixture for the panel.

ErbB2-driven downregulation of the transcription factor Irf6 in breast epithelial cells is required for their 3D growth.

Background: The ability of solid tumor cells to resist anoikis, apoptosis triggered by cell detachment from the extracellular matrix (ECM), is thought to be critical for 3D tumor growth. ErbB2/Her2 oncoprotein is often overproduced by breast tumor cells and blocks their anoikis by partially understood mechanisms. In our effort to understand them better, we observed that detachment of nonmalignant human breast epithelial cells from the ECM upregulates the transcription factor Irf6.