Functional omics of ORP7 in primary endothelial cells.

Background: Many members of the oxysterol-binding protein-related protein (ORP) family have been characterized in detail over the past decades, but the lipid transport and other functions of ORP7 still remain elusive. What is known about ORP7 points toward an endoplasmic reticulum and plasma membrane-localized protein, which also interacts with GABA type A receptor-associated protein like 2 (GABARAPL2) and unlipidated Microtubule-associated proteins 1A/1B light chain 3B (LC3B), suggesting a further autophagosomal/lysosomal association. Functional roles of ORP7 have been suggested in cholesterol efflux, hypercholesterolemia, and macroautophagy.

Long-term outcomes of extracapsular tonsillectomy in the treatment of obstructive sleep apnoea in adults.

Background: Tonsillectomy is an effective treatment option for obstructive sleep apnoea in selected adult patients, but there has been a lack of long-term follow-up data.

Objectives: To analyse the long-term outcomes of extracapsular tonsillectomy in the treatment of obstructive sleep apnoea in adults, with the longest follow-up periods to date.

Materials And Methods: We recruited adults who had undergone extracapsular tonsillectomy because of obstructive sleep apnoea between 2004 and 2018 in the Hospital District of Southwest Finland.

Real-time measurement of metals in submicron aerosols with particle-into-liquid sampler combined with micro-discharge optical emission spectroscopy.

The paper presents a novel technique for quantifying trace metals in aerosol samples in real time. Airborne metals were continuously collected for one week near the Baltic Sea in Finland using a particle-into-liquid sampler (PILS). The collected liquid samples were analyzed for metals using micro-discharge optical emission spectroscopy (µDOES).

Cholesterol binding to VCAM-1 promotes vascular inflammation.

Hypercholesterolemia has long been implicated in endothelial cell (EC) dysfunction, but the mechanisms by which excess cholesterol causes vascular pathology are incompletely understood. Here we used a cholesterol-mimetic probe to map cholesterol-protein interactions in primary human ECs and discovered that cholesterol binds to and stabilizes the adhesion molecule VCAM-1. We show that accessible plasma membrane (PM) cholesterol in ECs is acutely responsive to inflammatory stimuli and that the nonvesicular cholesterol transporter Aster-A regulates VCAM-1 stability in activated ECs by controlling the size of this pool.

Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex.

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex.

Getting to Grips with the Oxysterol-Binding Protein Family - a Forty Year Perspective.

This review discusses how research around the oxysterol-binding protein family has evolved. We briefly summarize how this protein family, designated OSBP-related (ORP) or OSBP-like (OSBPL) proteins, was discovered, how protein domains highly conserved among family members between taxa paved the way for understanding their mechanisms of action, and how insights into protein structural and functional features help to understand their versatility as lipid transporters. We also discuss questions and future avenues of research opened by these findings.

IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts.

Background: Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms.

HiHo-AID2: boosting homozygous knock-in efficiency enables robust generation of human auxin-inducible degron cells.

Recent developments in auxin-inducible degron (AID) technology have increased its popularity for chemogenetic control of proteolysis. However, generation of human AID cell lines is challenging, especially in human embryonic stem cells (hESCs). Here, we develop HiHo-AID2, a streamlined procedure for rapid, one-step generation of human cancer and hESC lines with high homozygous degron-tagging efficiency based on an optimized AID2 system and homology-directed repair enhancers.

Development of primary reference facilities and measurement comparison of standard artifacts for the bidirectional transmittance distribution function.

To determine the bidirectional transmittance distribution function (BTDF) of diffusely transmitting materials, two new primary facilities have been developed at the Physikalisch-Technische Bundesanstalt (PTB) and Aalto University (Aalto). A detailed description of both facilities and the different approaches used are presented in this paper. The performance of both facilities is compared by determining the BTDF of two different diffuser types in both in-plane and out-of-plane bidirectional geometries at four different wavelengths in the visible spectral range.

ATPase activity of DFCP1 controls selective autophagy.

Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction.

Intracellular Cholesterol Trafficking.

Cholesterol is an essential lipid species of mammalian cells. Cells acquire it through synthesis in the endoplasmic reticulum (ER) and uptake from lipoprotein particles. Newly synthesized cholesterol is efficiently distributed from the ER to other organelles via lipid-binding/transfer proteins concentrated at membrane contact sites (MCSs) to reach the -Golgi network, endosomes, and plasma membrane.

Cholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols.

Cellular cholesterol can be metabolized to its fatty acid esters, cholesteryl esters (CEs), to be stored in lipid droplets (LDs). With triacylglycerols (TGs), CEs represent the main neutral lipids in LDs. However, while TG melts at ~4 °C, CE melts at ~44 °C, raising the question of how CE-rich LDs form in cells.

Terahertz radiation detection with a cantilever-based photoacoustic sensor.

We report the photoacoustic (PA) response in the terahertz (THz) range by employing a detection process actuated with a silicon cantilever pressure sensor and a carbon-based radiation absorber. The detection relies on the mechanical response of the cantilever, when the volume of the carrier gas inside the PA cell expands with the heat produced by the radiation absorber. The detector interferometrically monitors the movement of the cantilever sensor to generate the PA signal.

The Sonic Meanings of the Life and Death of My Disabled Brother: Listening as a Method for Qualitative Research.

Long neglected listening is an underdeveloped element in western epistemology in general and in qualitative research in particular. However, recent developments in philosophy, sound art, anthropology, and qualitative research open promising pathways for mastering listening as a method and metaphor of inquiry also in health research, where understanding multiple layers of emotionally challenging experiences is crucial, yet often elusive. Through a sonic analysis of autobiographical data about life, death, and my disabled brother, I will try to demonstrate how paying attention to listening and sounds in research can add evolving layers of meaning to the data gathering and analyzing processes.

Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignancies and potentially curable only with radical surgical resection at early stages. The tumor microenvironment has been shown to be central to the development and progression of PDAC. A better understanding of how early human PDAC metabolically communicates with its environment and differs from healthy pancreas could help improve PDAC diagnosis and treatment.

M1 Macrophages Induce Protumor Inflammation in Melanoma Cells through TNFR-NF-κB Signaling.

The tumor microenvironment, with distinctive cell types and a complex extracellular matrix has a tremendous impact on cancer progression. In this study, we investigated the effects of proinflammatory (M1) and immunosuppressive (M2) macrophages on hyaluronan (HA) matrix formation and inflammatory response in melanoma cells. Proinflammatory factors secreted from M1 macrophages stimulated the formation of a thick pericellular HA matrix in melanoma cells due to upregulation of HA synthase 2 (HAS2).

Multiparametric platform for profiling lipid trafficking in human leukocytes.

Systematic insight into cellular dysfunction can improve understanding of disease etiology, risk assessment, and patient stratification. We present a multiparametric high-content imaging platform enabling quantification of low-density lipoprotein (LDL) uptake and lipid storage in cytoplasmic droplets of primary leukocyte subpopulations. We validate this platform with samples from 65 individuals with variable blood LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH) and non-FH subjects.

DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion.

Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined.

Optical power detector with broad spectral coverage, high detectivity, and large dynamic range.

Optical power measurements are needed in practically all technologies based on light. Here, we report a general-purpose optical power detector based on the photoacoustic effect. Optical power incident on the detector's black absorber produces an acoustic signal, which is further converted into an electrical signal using a silicon-cantilever pressure transducer.

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes.

Deficiency of the endoplasmic reticulum (ER) protein seipin results in generalized lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin-deficient patient cells. A subset of seipin is enriched at ER-mitochondria contact sites (MAMs) in human and mouse cells and localizes in the vicinity of calcium regulators SERCA2, IP3R, and VDAC.

High Performance Predictable Quantum Efficient Detector Based on Induced-Junction Photodiodes Passivated with SiO/SiN.

We performed a systematic study involving simulation and experimental techniques to develop induced-junction silicon photodetectors passivated with thermally grown SiO and plasma-enhanced chemical vapor deposited (PECVD) SiN thin films that show a record high quantum efficiency. We investigated PECVD SiN passivation and optimized the film deposition conditions to minimize the recombination losses at the silicon-dielectric interface as well as optical losses. Depositions with varied process parameters were carried out on test samples, followed by measurements of minority carrier lifetime, fixed charge density, and optical absorbance and reflectance.

Cholesterol transport in the late endocytic pathway: Roles of ORP family proteins.

Oxysterol-binding protein (OSBP) homologues, designated ORP or OSBPL proteins, constitute one of the largest families of intracellular lipid-binding/transfer proteins (LTP). This review summarizes the mounting evidence that several members of this family participate in the machinery facilitating cholesterol trafficking in the late endocytic pathway. There are indications that OSBP, besides acting as a cholesterol/phosphatidylinositol 4-phosphate (PI4P) exchanger at the endoplasmic reticulum (ER)-trans-Golgi network (TGN) membrane contact sites (MCS), also exchanges these lipids at ER-lysosome (Lys) contacts, increasing Lys cholesterol content.

Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis.

Cholesterol biosynthetic intermediates, such as lanosterol and desmosterol, are emergent immune regulators of macrophages in response to inflammatory stimuli or lipid overloading, respectively. However, the participation of these sterols in regulating macrophage functions in the physiological context of atherosclerosis, an inflammatory disease driven by the accumulation of cholesterol-laden macrophages in the artery wall, has remained elusive. Here, we report that desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis, serving as a key molecule integrating cholesterol homeostasis and immune responses in macrophages.

Specific subdomain localization of ER resident proteins and membrane contact sites resolved by electron microscopy.

The endoplasmic reticulum (ER) is a large, single-copy, membrane-bound organelle that comprises an elaborate 3D network of diverse structural subdomains, including highly curved tubules, flat sheets, and parts that form contacts with nearly every other organelle. The dynamic and complex organization of the ER poses a major challenge on understanding how its functioning - maintenance of the structure, distribution of its functions and communication with other organelles - is orchestrated. In this study, we resolved a unique localization profile within the ER network for several resident ER proteins representing a broad range of functions associated with the ER using immuno-electron microscopy and calculation of a relative labeling index (RLI).

LED-Based Photoacoustic NO Sensor with a Sub-ppb Detection Limit.

A high-sensitivity light-emitting diode (LED)-based photoacoustic NO sensor is demonstrated. Sensitive photoacoustic gas sensors based on incoherent light sources are typically limited by background noise and drifts due to a strong signal generated by light absorbed at the photoacoustic cell walls. Here, we reach a sub-ppb detection limit and excellent stability using cantilever-enhanced photoacoustic detection and perform a two-channel relative measurement.