Deletion of the WD40 domain of ATG16L1 exacerbates acute pancreatitis, abolishes LAP-like non-canonical autophagy and slows trypsin degradation.

The WD40 domain (WDD) of ATG16L1 plays a pivotal role in non-canonical autophagy. This study examined the role of recently identified LAP-like non-canonical autophagy (LNCA) in acute pancreatitis. LNCA involves rapid single-membrane LC3 conjugation to endocytic vacuoles in pancreatic acinar cells.

The infrared absorption spectrum of radioactive water isotopologue HO.

A room temperature line list for the HO radioactive isotopologue of the water molecule is computed using the variational nuclear-motion DVR3D program suite and an empirical high-precision potential energy function. The line list consists of rotation-vibrational energies and Einstein-A coefficients, covering a wide spectral range from 0 to 25000 cm and the total angular momenta J up to 30. Estimates of air-broadening coefficients are provided.

Influence of the Addition of Alumina Nanofibers on the Strength of Epoxy Resins.

The paper describes the effect of the addition of alumina nanofibers on the mechanical properties of the epoxy resin. Alumina nanofibers functionalized with epoxypropyl functional groups are used in this work. The dependence of the mechanical characteristics on the amount of the additive, as well as the features of its distribution in the material, is investigated.

Autophagy, Acute Pancreatitis and the Metamorphoses of a Trypsinogen-Activating Organelle.

Recent studies have highlighted the importance of autophagy and particularly non-canonical autophagy in the development and progression of acute pancreatitis (a frequent disease with considerable morbidity and significant mortality). An important early event in the development of acute pancreatitis is the intrapancreatic activation of trypsinogen, (i.e.

Features of Functionalization of the Surface of Alumina Nanofibers by Hydrolysis of Organosilanes on Surface Hydroxyl Groups.

Small additions of nanofiber materials make it possible to change the properties of polymers. However, the uniformity of the additive distribution and the strength of its bond with the polymer matrix are determined by the surface of the nanofibers. Silanes, in particular, allow you to customize the surface for better interaction with the matrix.

Data on the synergistic effect of a hybrid filler based on graphene nanoplates and multiwalled nanotubes for increasing the thermal conductivity of an epoxy composite.

The dataset contains raw files related to the manuscript "The synergistic effect of a hybrid filler based on graphene nanoplates and multiwalled nanotubes for increasing the thermal conductivity of an epoxy composite" (Shalygina T.A. et al.

Influence of the Filler Particles' Surface Morphology on the Polyurethane Matrix's Structure Formation in the Composite.

This article presents the surface morphology effect of silicon carbide (SiC) particles on the polyurethane binder's structure formation in a dispersed-filled composite. The difference in the morphology and surface relief of filler particles was ensured by the implementation of plasma chemical modification. As a result of this modification, the filler consisted of core-shell particles characterized by a SiC core and a carbon shell (SiC@C), as well as a carbon shell decorated with silicon nanoparticles (SiC@C/SiNP) or nanos (SiC@C/SiNW).

Data for determining the surface properties of carbon fiber in contact interaction with polymeric binders.

The data presented in this study are the supplementary materials related to the research paper "Determining the Surface Properties of Carbon Fiber in Contact Interaction with Polymeric Binders" (Voronina S.Yu. et al.

Knockout of the Mitochondrial Calcium Uniporter Strongly Suppresses Stimulus-Metabolism Coupling in Pancreatic Acinar Cells but Does Not Reduce Severity of Experimental Acute Pancreatitis.

Acute pancreatitis is a frequent disease that lacks specific drug treatment. Unravelling the molecular mechanisms of acute pancreatitis is essential for the development of new therapeutics. Several inducers of acute pancreatitis trigger sustained Ca increases in the cytosol and mitochondria of pancreatic acinar cells.

LAP-like non-canonical autophagy and evolution of endocytic vacuoles in pancreatic acinar cells.

Unlabelled: Activation of trypsinogen (formation of trypsin) inside the pancreas is an early pathological event in the development of acute pancreatitis. In our previous studies we identified the activation of trypsinogen within endocytic vacuoles (EVs), cellular organelles that appear in pancreatic acinar cells treated with the inducers of acute pancreatitis. EVs are formed as a result of aberrant compound exocytosis and subsequent internalization of post-exocytic structures.

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice.

Background And Aims: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression.

Methods: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5;Kras), and compared them with mice with only oncogenic Kras (controls).

FF-ATP Synthase Inhibitory Factor 1 in the Normal Pancreas and in Pancreatic Ductal Adenocarcinoma: Effects on Bioenergetics, Invasion and Proliferation.

FF-ATP synthase inhibitory factor 1 (IF1) inhibits the reverse mode of FF-ATP synthase, and therefore protects cellular ATP content at the expense of accelerated loss of mitochondrial membrane potential (ΔΨm). There is considerable variability in IF1 expression and its influence on bioenergetics between different cell types. High levels of IF1 in a number of cancers have been linked to increased glycolysis, resistance to cell death, increased migration and proliferation.

Intracellular rupture, exocytosis and actin interaction of endocytic vacuoles in pancreatic acinar cells: initiating events in acute pancreatitis.

Key Points: Giant trypsin-containing endocytic vacuoles are formed in pancreatic acinar cells stimulated with inducers of acute pancreatitis. F-actin envelops endocytic vacuoles and regulates their properties. Endocytic vacuoles can rupture and release their content into the cytosol of acinar cells.

Systemic histone release disrupts plasmalemma and contributes to necrosis in acute pancreatitis.

Background: Clinical and experimental acute pancreatitis feature histone release within the pancreas from innate immune cells and acinar cell necrosis. In this study, we aimed to detail the source of circulating histones and assess their role in the pathogenesis of acute pancreatitis.

Methods: Circulating nucleosomes were measured in patient plasma, taken within 24 and 48 h of onset of acute pancreatitis and correlated with clinical outcomes.

Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics.

Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below 40 nm and the membranes are connected by protein tethers. A number of molecular tools and technical approaches have been recently developed to visualise, modify and characterise properties of ER-PM junctions. The junctions serve as the platforms for lipid exchange between the organelles and for cell signalling, notably Ca(2+) and cAMP signalling.

Epithelial-mesenchymal transition, IP3 receptors and ER-PM junctions: translocation of Ca2+ signalling complexes and regulation of migration.

Disconnection of a cell from its epithelial neighbours and the formation of a mesenchymal phenotype are associated with profound changes in the distribution of cellular components and the formation of new cellular polarity. We observed a dramatic redistribution of inositol trisphosphate receptors (IP3Rs) and stromal interaction molecule 1 (STIM1)-competent endoplasmic reticulum-plasma membrane junctions (ER-PM junctions) when pancreatic ductal adenocarcinoma (PDAC) cells disconnect from their neighbours and undergo individual migration. In cellular monolayers IP3Rs are juxtaposed with tight junctions.

Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models.

Background & Aims: Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release-activated calcium modulator ORAI1 is the most abundant Ca(2+) entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice.

An efficient method is required to transfect non-dividing cells with genetically encoded optical probes for molecular imaging.

Genetically encoded fluorescent and bioluminescent reporters are now widely used for imaging and understanding of intracellular signaling in response to extracellular stimuli in real time in single living cells. Primary cultures are a valuable tool, and are often preferred over transformed or immortalized cell lines, since they are biologically more relevant and important in biomedical research and therapeutic development. To incorporate genetically encoded reporters into the primary culture of non-dividing cells, such as mouse or human pancreatic acinar cells, is not an easy task.

The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar cells.

The inducers of acute pancreatitis trigger a prolonged increase in the cytosolic Ca(2+) concentration ([Ca(2+)]c), which is responsible for the damage to and eventual death of pancreatic acinar cells. Vacuolization is an important indicator of pancreatic acinar cell damage. Furthermore, activation of trypsinogen occurs in the endocytic vacuoles; therefore the vacuoles can be considered as 'initiating' organelles in the development of the cell injury.

How to win ATP and influence Ca(2+) signaling.

This brief review discusses recent advances in studies of mitochondrial Ca(2+) signaling and considers how the relationships between mitochondria and Ca(2+) responses are shaped in secretory epithelial cells. Perhaps the more precise title of this review could have been "How to win ATP and influence Ca(2+) signaling in secretory epithelium with emphasis on exocrine secretory cells and specific focus on pancreatic acinar cells". But "brevity is a virtue" and the authors hope that many of the mechanisms discussed are general and applicable to other tissues and cell types.

Mitochondrial calcium in the life and death of exocrine secretory cells.

The remarkable recent discoveries of the proteins mediating mitochondrial Ca(2+) transport (reviewed in this issue) provide an exciting opportunity to utilise this new knowledge to improve our fundamental understanding of relationships between Ca(2+) signalling and bioenergetics and, importantly, to improve the understanding of diseases in which Ca(2+) toxicity and mitochondrial malfunction play a crucial role. Ca(2+) is an important activator of exocrine secretion, a regulator of the bioenergetics of exocrine cells and a contributor to exocrine cell damage. Exocrine secretory cells, exocrine tissues and diseases affecting exocrine glands (like Sjögren's syndrome and acute pancreatitis) will, therefore, provide worthy research areas for the application of this new knowledge of the Ca(2+) transport mechanisms in mitochondria.

Cellular geography of IP3 receptors, STIM and Orai: a lesson from secretory epithelial cells.

Pancreatic acinar cells exhibit a remarkable polarization of Ca2+ release and Ca2+ influx mechanisms. In the present brief review, we discuss the localization of channels responsible for Ca2+ release [mainly IP3 (inositol 1,4,5-trisphosphate) receptors] and proteins responsible for SOCE (store-operated Ca2+ entry). We also place these Ca2+-transporting mechanisms on the map of cellular organelles in pancreatic acinar cells, and discuss the physiological implications of the cellular geography of Ca2+ signalling.

Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells.

Background & Aims: Previous studies of pancreatic acinar cells characterized the effects of Ca(2+)-releasing secretagogues and substances, inducing acute pancreatitis on mitochondrial Ca(2+), transmembrane potential, and NAD(P)H, but dynamic measurements of the crucial intracellular adenosine triphosphate (ATP) levels have not been reported. Here we characterized the effects of these agents on ATP levels in the cytosol and mitochondria.

Methods: ATP levels were monitored using cytosolic- or mitochondrial-targeted luciferases.

Use of oligonucleotides conjugated to gold nanoparticles and streptavidin for amplification of optical biosensor signal during detection of telomeric repeats.

Hybridization of telomeric repeats with a complementary oligonucleotide probe was studied by the surface plasmon resonance method. Conjugation of the probe with streptavidin and gold nanoparticles was shown to amplify the signal at similar concentrations of this probe (by 60 and 300 times, respectively). Nanoparticles can be used for biosensor signal amplification in studying the telomerase activity of malignant cells.

Modulation of calcium signalling by mitochondria.

In this review we will attempt to summarise the complex and sometimes contradictory effects that mitochondria have on different forms of calcium signalling. Mitochondria can influence Ca(2+) signalling indirectly by changing the concentration of ATP, NAD(P)H, pyruvate and reactive oxygen species - which in turn modulate components of the Ca(2+) signalling machinery i.e.