Apoptosis during arenavirus infection: mechanisms and evasion strategies

In recent years there has been a greatly increased interest in the interactions of arenaviruses with the apoptotic machinery, and particularly the extent to which these interactions may be an important contributor to pathogenesis. Here we summarize the current state of our knowledge on this subject and address the potential for interplay with other immunological mechanisms known to be regulated by these viruses. We also compare and contrast what is known for arenavirus-induced apoptosis with observations from other segmented hemorrhagic fever viruses.     

Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics

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Improved Optics in Monolithic Perovskite/Silicon Tandem Solar Cells with a Nanocrystalline Silicon Recombination Junction

Perovskite/silicon tandem solar cells are increasingly recognized as promi­sing candidates for next‐generation photovoltaics with performance beyond the single‐junction limit at potentially low production costs. Current designs for monolithic tandems rely on transparent conductive oxides as an intermediate recombination layer, which lead to optical losses and reduced shunt resistance. An improved recombination junction based on nanocrystalline silicon layers to mitigate these losses is demonstrated. When employed in monolithic perovskite/silicon heterojunction tandem cells with a planar front side, this junction is found to increase the bottom cell photocurrent by more than 1 mA cm^?2. In combination with a cesium‐based perovskite top cell, this leads to tandem cell power‐conversion efficiencies of up to 22.7% obtained from J–V measurements and steady‐state efficiencies of up to 22.0% during maximum power point tracking. Thanks to its low lateral conductivity, the nanocrystalline silicon recombination junction enables upscaling of monolithic perovskite/silicon heterojunction tandem cells, resulting in a 12.96 cm² monolithic tandem cell with a steady‐state efficiency of 18%.     

Adenosine enhances cisplatin sensitivity in human ovarian cancer cells

Ovarian cancer is the deadliest gynecologic cancer due to lack of early effective diagnosis and development of resistance to platinum-based chemotherapy. Several studies reported that adenosine concentrations are higher in tumor microenvironment than in non-tumor tissue. This finding inspired us to study the role of adenosine in ovarian cancer cells and to investigate if adenosine pathways offer new treatment options urgently needed to prevent or overcome chemoresistance. The ovarian cancer cell lines HEY, A2780, and its cisplatin-resistant subline A2780CisR were used in this study. Expression and functional activity of adenosine receptors were investigated by RT-PCR, Western blotting, and cAMP assay. A1 and A2B adenosine receptors were expressed and functionally active in all three cell lines. Adenosine showed moderate cytotoxicity (MTT-IC₅₀ values were between 700 and 900 μM) and induced apoptosis in a concentration-dependent manner by increasing levels of sub-G1 and cleaved PARP. Apoptosis was diminished by QVD-OPh, confirming caspase-dependent induction of apoptosis. Forty-eight hours pre-incubation of adenosine prior to cisplatin significantly enhanced cisplatin-induced cytotoxicity in a synergistic manner and increased apoptosis. SLV320 or PSB603, selective A1 and A2B antagonists, was not able to inhibit adenosine-induced increase in cisplatin cytotoxicity or apoptosis whereas dipyridamole, a nucleoside transporter inhibitor, completely abrogated both effects. Mechanistically, adenosine increased pAMPK and reduced pS6K which was prevented by dipyridamole. In conclusion, application of adenosine prior to cisplatin could be a new therapeutic option to increase the potency of cisplatin in a synergistic manner and thus overcome platinum resistance in ovarian cancer.     

Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VIIa, participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VIIa molecule, namely, 10 gamma-carboxylated, N-terminally located glutamic acid residues, 1 beta-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VIIa as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VIIa. By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradations, the protein backbone of recombinant factor VIIa was found to be identical with human factor VIIa. Neither recombinant factor VIIa nor human plasma factor VIIa was found to contain beta-hydroxyaspartic acid. In human plasma factor VIIa, the 10 N-terminally located glutamic acid residues were found to be fully gamma-carboxylated whereas 9 full and 1 partial gamma-carboxylated residues were found in the corresponding positions of the recombinant factor VIIa molecule. Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VIIa. In the recombinant factor VIIa, asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VIIa and human plasma factor VIIa.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Sphingolipid Receptor S1PR2 Is a Receptor for Nogo-A Repressing Synaptic Plasticity

Nogo-A is a membrane protein of the central nervous system (CNS) restricting neurite growth and synaptic plasticity via two extracellular domains: Nogo-66 and Nogo-A-Δ20. Receptors transducing Nogo-A-Δ20 signaling remained elusive so far. Here we identify the G protein-coupled receptor (GPCR) sphingosine 1-phosphate receptor 2 (S1PR2) as a Nogo-A-Δ20-specific receptor. Nogo-A-Δ20 binds S1PR2 on sites distinct from the pocket of the sphingolipid sphingosine 1-phosphate (S1P) and signals via the G protein G₁₃, the Rho GEF LARG, and RhoA. Deleting or blocking S1PR2 counteracts Nogo-A-Δ20- and myelin-mediated inhibition of neurite outgrowth and cell spreading. Blockade of S1PR2 strongly enhances long-term potentiation (LTP) in the hippocampus of wild-type but not Nogo-A^−/− mice, indicating a repressor function of the Nogo-A/S1PR2 axis in synaptic plasticity. A similar increase in LTP was also observed in the motor cortex after S1PR2 blockade. We propose a novel signaling model in which a GPCR functions as a receptor for two structurally unrelated ligands, a membrane protein and a sphingolipid. Elucidating Nogo-A/S1PR2 signaling platforms will provide new insights into regulation of synaptic plasticity.