The Role of Adipocytes and Adipocyte‐Like Cells in the Severity of COVID‐19 Infections

Coronavirus disease‐2019 (COVID‐19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis. In this Perspective, we argue that adipocytes and adipocyte‐like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to SARS‐CoV‐2. Expression of angiotensin‐converting enzyme 2 (the functional receptor for SARS‐CoV) is upregulated in adipocytes of patients with obesity and diabetes, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID‐19 infections. Similar to the recently established adipocyte‐myofibroblast transition, pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of pulmonary fibrosis. This may significantly increase the severity of the local response to SARS‐CoV‐2 in the lung. To reduce the severity and mortality associated with COVID‐19, we propose to probe for the clinical response to thiazolidinediones, peroxisome proliferator activated receptor γ agonists that are well‐known antidiabetic drugs. Thiazolidinediones are able to stabilize lipofibroblasts in their “inactive” state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.     

Low Genetic Diversity in Wide-Spread Eurasian Liver Fluke Opisthorchis felineus Suggests Special Demographic History of This Trematode Species

Opisthorchis felineus or Siberian liver fluke is a trematode parasite (Opisthorchiidae) that infects the hepato-biliary system of humans and other mammals. Despite its public health significance, this wide-spread Eurasian species is one of the most poorly studied human liver flukes and nothing is known about its population genetic structure and demographic history. In this paper, we attempt to fill this gap for the first time and to explore the genetic diversity in O. felineus populations from Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Analysis of marker DNA fragments from O. felineus mitochondrial cytochrome c oxidase subunit 1 and 3 (cox1, cox3) and nuclear rDNA internal transcribed spacer 1 (ITS1) sequences revealed that genetic diversity is very low across the large geographic range of this species. Microevolutionary processes in populations of trematodes may well be influenced by their peculiar biology. Nevertheless, we suggest that lack of population genetics structure observed in O. felineus can be primarily explained by the Pleistocene glacial events and subsequent sudden population growth from a very limited group of founders. Rapid range expansion of O. felineus through Asian and European territories after severe bottleneck points to a high dispersal potential of this trematode species.     

TRAIL receptor and CD95 signal to mitochondria via FADD,caspase-8/10, Bid,and Bax but differentially regulate events downstream from truncated Bid

The death receptor ligand TRAIL arouses much interest for clinical application. We found that TRAIL receptor could induce cytochrome c (Cyt c) release from mitochondria in cells that failed to respond to CD95. Therefore, we examined whether these two closely related death receptors use different intermediates to convey the apoptotic signal to mitochondria. Dominant negative FADD, FLIP(L), or a Bid mutant lacking cleavage sites for caspase-8/10 completely inhibited Cyt c release in response to either receptor. Depletion of Bid from TRAIL- or CD95-activated cytosols blocked their capacity to mediate Cyt c release from mitochondria in vitro, whereas Bax depletion reduced it. We conclude that FADD, caspase-8/10, and caspase-cleaved Bid are required for TRAIL receptor and CD95 signaling to mitochondria, whereas Bax is a common accessory. In vitro, caspase-8 treatment of cytosol from CD95-resistant cells permitted generation of truncated Bid and its association with mitochondria. However, this cytosol impaired the ability of truncated Bid to liberate Cyt c from exogenous mitochondria. We conclude that the TRAIL receptor can bypass or neutralize the activity of cytosolic factor that blocks truncated Bid function. This may benefit the capacity of TRAIL to break apoptosis resistance in tumor cells.     

O-mannosylation precedes and potentially controls the N-glycosylation of a yeast cell wall glycoprotein

Secretory proteins in yeast are N- and O-glycosylated while they enter the endoplasmic reticulum. N-glycosylation is initiated by the oligosaccharyl transferase complex and O-mannosylation is initiated by distinct O-mannosyltransferase complexes of the protein mannosyl transferase Pmt1/Pmt2 and Pmt4 families. Using covalently linked cell-wall protein 5 (Ccw5) as a model, we show that the Pmt4 and Pmt1/Pmt2 mannosyltransferases glycosylate different domains of the Ccw5 protein, thereby mannosylating several consecutive serine and threonine residues. In addition, it is shown that O-mannosylation by Pmt4 prevents N-glycosylation by blocking the hydroxy amino acid of the single N-glycosylation site present in Ccw5. These data prove that the O- and N-glycosylation machineries compete for Ccw5; therefore O-mannosylation by Pmt4 precedes N-glycosylation.     

Quantitative measurement of cell migration using time-lapse videomicroscopy and non-linear system analysis

Epithelial cells of the mammary gland possess the inherent capacity to form epithelial monolayers in vitro. This requires coordination of cell migration, cell-cell contact formation, and cell proliferation. Using time-lapse phase contrast videomicroscopy we have observed mammary gland epithelial cells over different time scales. We show the generation of a complete polarized epithelial monolayer in real-time, starting from a few cells. We subsequently concentrated on the early stages of this process by tracking epithelial cells during phases of polarized migration. We performed migration analysis using fractal measures. With this technology the structure of seemingly random processes not accessible to the usual methods of linear analysis can be measured. As a control and proof of principle approach we applied infection of cells with an adenoviral vector, which is used as a gene targeting vector for many applications. Infection markedly influenced the patterns of migratory behavior. We, therefore, believe that time-lapse videomicroscopy in combination with fractal analysis can contribute to differential characterization of distinct cellular migration patterns. This will be useful in situations of long-term alterations in cell culture systems.     

Higher Lipoprotein (a) Levels Are Associated with Better Pulmonary Function in Community-Dwelling Older People – Data from the Berlin Aging Study II

Reduced pulmonary function and elevated serum cholesterol levels are recognized risk factors for cardiovascular disease. Currently, there is some controversy concerning relationships between cholesterol, LDL-cholesterol, HDL-cholesterol, serum triglycerides and lung function. However, most previous studies compared patients suffering from chronic obstructive pulmonary disease (COPD) with healthy controls, and only a small number examined this relationship in population-based cohorts. Moreover, lipoprotein a [Lp(a)], another lipid parameter independently associated with cardiovascular diseases, appears not to have been addressed at all in studies of lung function at the population level. Here, we determined relationships between lung function and several lipid parameters including Lp(a) in 606 older community-dwelling participants (55.1% women, 68±4 years old) from the Berlin Aging Study II (BASE-II). We found a significantly lower forced expiration volume in 1 second (FEV1) in men with low Lp(a) concentrations (t-test). This finding was further substantiated by linear regression models adjusting for known covariates, showing that these associations are statistically significant in both men and women. According to the highest adjusted model, men and women with Lp(a) levels below the 20^th percentile had 217.3ml and 124.2ml less FEV1 and 239.0ml and 135.2ml less FVC, respectively, compared to participants with higher Lp(a) levels. The adjusted models also suggest that the known strong correlation between pro-inflammatory parameters and lung function has only a marginal impact on the Lp(a)-pulmonary function association. Our results do not support the hypothesis that higher Lp(a) levels are responsible for the increased CVD risk in people with reduced lung function, at least not in the group of community-dwelling older people studied here.     

Historical geography of pearl harvesting and current status of populations of freshwater pearl mussel Margaritifera margaritifera (L.) in the western part of Northern European Russia

This paper summarises data on the occurrence of freshwater pearl mussel Margaritifera margaritifera in the western part of Northern European Russia adjacent to White Sea, Barents Sea, Onega Lake and Ladoga Lake basins. Also, this article provides an overview of the literature-based data and archive materials on the history of pearl harvesting. We include a list of rivers of Northwestern Russia, where pearls were harvested during the period of the sixteenth to twentieth centuries. The pearl mussel populations at the present time exist in at least 24 water streams in Northwestern Russia. Many of these populations are in high abundance and are able to reproduce normally. Data on the status of populations are given in this paper. Data indicate that the pearl mussel population in Russia contains >143.5 million individuals, but this estimation is certainly undervalued. Timber floating (timber floating is the transport of timber on waterways), hydro-engineering construction, pollution of rivers by industrial wastes and introduction of alien species, as well as a reduction in host fish species numbers can all be cited as the main factors that transformed the ecosystems inhabited by pearl mussel of Northern Russia. In addition, methods used in the Russian Federation for decreasing the anthropogenic load on pearl mussel populations were considered.     

Studies of the silencing of baculovirus DNA binding protein

Baculovirus DNA binding protein (DBP) binds preferentially single-stranded DNA in vitro and colocalizes with viral DNA replication sites. Here, its putative role as viral replication factor has been addressed by RNA interference. Silencing of DBP in Autographa californica multiple nucleopolyhedrovirus-infected cells increased expression of LEF-3, LEF-4, and P35. In contrast, expression of the structural genes coding for P39 and polyhedrin was suppressed while expression of genes coding for P10 and GP64 was unaffected. In the absence of DBP, viral DNA replication sites were formed, indicating replication of viral DNA. Electron microscopy studies, however, revealed a loss of formation of polyhedra and virus envelopment, suggesting that the primary role of DBP is viral formation rather than viral DNA replication.