Provider: Czech digital library/Česká digitální knihovna - Institution: Academy of Sciences Library/Knihovna Akademie věd ČR - Data provided by Europeana Collections- Travinné ekosystémy jsou ...významnou součástí středoevropské krajiny. Polopřirozená travinná společenstva dnes tvoří v Evropě místa s vysokou biodiverzitou, jsou velmi náchylná k degradaci a k jejich efektivní ochraně je nutné znát vlivy různých typů managementu. Neodmyslitelnými obyvateli těchto ekosystémů jsou také zástupci rovnokřídlého hmyzu (Orthoptera), kteří zde hrají důležitou roli v potravní síti. Zároveň jsou vhodným indikátorem změn stanovištních podmínek, a to zejména struktury vegetace, čehož lze využít při zjišťování dopadů různých managementových opatření. Jedním z nejběžnějších a zároveň pro hmyz nejméně vhodných typů péče je dnes mechanizovaná seč. Nevhodná péče o travinné ekosystémy může ovlivňovat druhovou bohatost jak v měřítku lokálním tak i v měřítku krajiny. Snížení negativního dopadu seče ve prospěch biodiverzity lze docílit několika způsoby - např. zmírněnou intenzitou zásahu, a to posunutím nebo vynecháním první seče, nebo ponecháním neposečených ploch.- Oto Kaláb.- Grasslands are an important part of the Central European landscape. Seminatural grasslands are considered to be biodiversity hotspots in Europe, with high conservation value. However, they are very unstable, and for their effective conservation it is necessary to know how different management systems affect the progression of the ecosystem. Orthopterans play an important role in the food web and they are also a good indicator of changes in habitat conditions, particularly in the vegetation structure, which can be used in determining the impact of different types of conservation management. Nowadays, one of the most common and least insect-friendly type of care is mechanized hay harvesting. Improper care can affect the species richness (both, on the local and landscape scale). The negative impact of mowing can be reduced in favour of biodiversity in several ways, as described (e.g., mitigating the intensity of the process by delaying or omitting the first mowing, or leaving uncut refuges).- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic ...compounds inhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, making this a promising target for therapeutic intervention. To understand the mode of inhibition and provide insight into the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61 inhibited by the Mycobacterium ulcerans exotoxin mycolactone via electron cryo-microscopy. Unexpectedly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedging open the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively transport substrate proteins implies that signal peptides and transmembrane domains pass through the site occupied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhibitors and reveals novel features of translocon function and dynamics.
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•The inhibited Sec translocon adopts a conformation optimal for substrate engagement•The inhibitor mycolactone wedges open the lateral gate of Sec61α•Mycolactone blocks the path taken by the signal peptide during engagement•Resistance mutations are likely to operate by modulating translocon dynamics
Gérard et al. determine the structure of the mammalian Sec translocon in an inhibited state. Mycolactone holds the translocon in a conformation optimal for substrate engagement, wedging open the cytosolic side of the lateral gate, while also blocking the path taken by the signal peptide during engagement.
Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still ...unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD). Here, we used a newly identified Sec61 blocker, mycolactone, to analyze Sec61's contribution to antigen cross-presentation, ERAD, and transport of internalized antigens into the cytosol. As shown previously in other cell types, mycolactone prevented protein import into the ER of DCs. Mycolactone-mediated Sec61 blockade also potently suppressed both antigen cross-presentation and direct presentation of synthetic peptides to CD8
T cells. In contrast, it did not affect protein export from the ER lumen or from endosomes into the cytosol, suggesting that the inhibition of cross-presentation was not related to either of these trafficking pathways. Proteomic profiling of mycolactone-exposed DCs showed that expression of mediators of antigen presentation, including MHC class I and β2 microglobulin, were highly susceptible to mycolactone treatment, indicating that Sec61 blockade affects antigen cross-presentation indirectly. Together, our data suggest that the defective translocation and subsequent degradation of Sec61 substrates is the cause of altered antigen cross-presentation in Sec61-blocked DCs.
Self-complementing split fluorescent proteins (FPs) have been widely used for protein labeling, visualization of subcellular protein localization, and detection of cell-cell contact. To expand this ...toolset, we have developed a screening strategy for the direct engineering of self-complementing split FPs. Via this strategy, we have generated a yellow-green split-mNeonGreen2
that improves the ratio of complemented signal to the background of FP
-expressing cells compared to the commonly used split GFP
; as well as a 10-fold brighter red-colored split-sfCherry2
. Based on split sfCherry2, we have engineered a photoactivatable variant that enables single-molecule localization-based super-resolution microscopy. We have demonstrated dual-color endogenous protein tagging with sfCherry2
and GFP
, revealing that endoplasmic reticulum translocon complex Sec61B has reduced abundance in certain peripheral tubules. These new split FPs not only offer multiple colors for imaging interaction networks of endogenous proteins, but also hold the potential to provide orthogonal handles for biochemical isolation of native protein complexes.Split fluorescent proteins (FPs) have been widely used to visualise proteins in cells. Here the authors develop a screen for engineering new split FPs, and report a yellow-green split-mNeonGreen2 with reduced background, a red split-sfCherry2 for multicolour labeling, and its photoactivatable variant for super-resolution use.
Selenium is a fascinating element that has a long history, most of which documents it as a deleterious element to health. In more recent years, selenium has been found to be an essential element in ...the diet of humans, all other mammals, and many other life forms. It has many health benefits that include, for example, roles in preventing heart disease and certain forms of cancer, slowing AIDS progression in HIV patients, supporting male reproduction, inhibiting viral expression, and boosting the immune system, and it also plays essential roles in mammalian development. Elucidating the molecular biology of selenium over the past 40 years generated an entirely new field of science which encompassed the many novel features of selenium. These features were (1) how this element makes its way into protein as the 21st amino acid in the genetic code, selenocysteine (Sec); (2) the vast amount of machinery dedicated to synthesizing Sec uniquely on its tRNA; (3) the incorporation of Sec into protein; and (4) the roles of the resulting Sec-containing proteins (selenoproteins) in health and development. One of the research areas receiving the most attention regarding selenium in health has been its role in cancer prevention, but further research has also exposed the role of this element as a facilitator of various maladies, including cancer.
This paper comments on the some mistakes which have been observed in Tripathi et al. (2023) 1. We have specifically pointed out the following mistakes of Tripathi et al. (2023) 1.
i) Presented (41, ...32) SEC-DAEC-TAEC H-matrix in Fig. 3 of Tripathi et al. (2023) 1.
ii) Presented error detection and correction coverage in Table 6 of Tripathi et al. (2023) 1.
The corrected versions of the above mentioned mistakes have been presented in this paper. Also the FPGA-based synthesis result of corrected encoder and decoder circuits based on the corrected (41, 32) H-matrix have been presented here.
This study examines the tax avoidance behavior of firms prior to the issuance, and following the resolution, of SEC tax comment letters. We find that firms that appear to engage in greater tax ...avoidance are more likely to receive a tax-related SEC comment letter. We also find that firms receiving a tax-related SEC comment letter, relative to firms receiving a non-tax comment letter, subsequently decrease their tax avoidance behavior consistent with an increase in expected tax costs. Additionally, we document evidence consistent with other firms that do not receive a comment letter reacting to multiple publicly disclosed tax-related comment letters within their industry by lowering their reported GAAP ETR, consistent with an indirect effect of regulatory scrutiny on certain types of tax avoidance.
ABSTRACT
This study explores close US congressional elections involving politicians who have influence over the SEC to examine the effect of firms' political connections on their financial reporting. ...This question is important in understanding the overall effect of political connections on financial reporting. Our difference‐in‐differences tests reveal no evidence that firms experiencing a relative increase in political connections report more opportunistically after close elections in anticipation of preferential treatment by the SEC in its enforcement actions. In contrast, we find evidence that these firms report less opportunistically in response to an increase in their connections with SEC‐influential politicians. Further tests show that our findings are unlikely to be driven by capital market pressure, managerial equity incentives, or corporate governance. Overall, our results are consistent with political connections mitigating opportunistic reporting through enhanced scrutiny by the SEC of politically connected firms' financial reporting. Our findings provide new insights into the interactions among political connections, SEC oversight, and financial reporting by showing how politically connected firms alter their financial reporting in anticipation of differential treatment by the SEC.
RÉSUMÉ
Les relations politiques mènent‐elles à des rapports financiers plus opportunistes ou moins opportunistes? Données issues d'élections serrées mettant en cause des politiciens ayant une influence sur la SEC
La présente étude se penche sur des élections serrées au Congrès des États‐Unis auxquelles se sont présentés des politiciens qui ont de l'influence auprès de la Securities and Exchange Commission (SEC) pour examiner l'effet des relations politiques des sociétés sur leurs rapports financiers. Cette question est importante pour comprendre l'effet global des liens politiques sur la communication d'information financière. Nos tests menés selon la méthode des doubles différences ne révèlent aucune donnée indiquant que les sociétés qui connaissent une augmentation relative de leurs liens politiques préparent leurs rapports de façon plus opportuniste après des élections serrées en vue d'obtenir un traitement de faveur dans le cadre des mesures d'exécution prises par la SEC. À l'inverse, nous trouvons des éléments indiquant que ces firmes produisent des rapports moins opportunistes à la suite d'un accroissement de leurs liens avec des politiciens ayant une influence sur la SEC. d'autres tests indiquent que nos résultats ne sont pas susceptibles d'être dictés par la pression des marchés financiers, les primes sous forme d'actions accordées aux gestionnaires ou la gouvernance d'entreprise. Globalement, nos résultats reflètent le fait que les relations politiques des sociétés réduisent le caractère opportuniste de leurs rapports financiers en raison de la surveillance accrue de la SEC à l'égard des rapports financiers des sociétés ayant des liens politiques. Ils fournissent de nouvelles perspectives sur les interactions entre les relations politiques, la surveillance exercée par la SEC et la production de rapports financiers en montrant de quelle façon les sociétés entretenant des relations politiques modifient la production de leurs rapports financiers en prévision d'un traitement différent de la part de la SEC.
The endoplasmic reticulum (ER) is a nexus for mRNA localization and translation, and recent studies have demonstrated that ER-bound ribosomes also play a transcriptome-wide role in regulating ...proteome composition. The Sec61 translocon (SEC61) serves as the receptor for ribosomes that translate secretory/integral membrane protein-encoding mRNAs, but whether SEC61 also serves as a translation site for cytosolic protein-encoding mRNAs remains unknown. Here, using a BioID proximity-labeling approach in HEK293T Flp-In cell lines, we examined interactions between ER-resident proteins and ribosomes in vivo. Using in vitro analyses, we further focused on bona fide ribosome interactors (i.e. SEC61) and ER proteins (ribophorin I, leucine-rich repeat–containing 59 (LRRC59), and SEC62) previously implicated in associating with ribosomes. We observed labeling of ER-bound ribosomes with the SEC61β and LRRC59 BioID reporters, comparatively modest labeling with the ribophorin I reporter, and no labeling with the SEC62 reporter. A biotin pulse-chase/subcellular fractionation approach to examine ribosome exchange at the SEC61β and LRRC59 sites revealed that, at steady state, ribosomes at these sites comprise both rapid- and slow-exchanging pools. Global translational initiation arrest elicited by the inhibitor harringtonine accelerated SEC61β reporter-labeled ribosome exchange. RNA-Seq analyses of the mRNAs associated with SEC61β- and LRRC59-labeled ribosomes revealed both site-enriched and shared mRNAs and further established that the ER has a transcriptome-wide role in regulating proteome composition. These results provide evidence that ribosomes interact with the ER membrane via multiple modes and suggest regulatory mechanisms that control global proteome composition via ER membrane-bound ribosomes.
Many proteins must translocate through the protein-conducting Sec61 channel in the eukaryotic endoplasmic reticulum membrane or the SecY channel in the prokaryotic plasma membrane
. Proteins with ...highly hydrophobic signal sequences are first recognized by the signal recognition particle (SRP)
and then moved co-translationally through the Sec61 or SecY channel by the associated translating ribosome. Substrates with less hydrophobic signal sequences bypass the SRP and are moved through the channel post-translationally
. In eukaryotic cells, post-translational translocation is mediated by the association of the Sec61 channel with another membrane protein complex, the Sec62-Sec63 complex
, and substrates are moved through the channel by the luminal BiP ATPase
. How the Sec62-Sec63 complex activates the Sec61 channel for post-translational translocation is not known. Here we report the electron cryo-microscopy structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting both with cytosolic loops in the C-terminal half of Sec61 and transmembrane segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp70
. Our structure shows how the Sec61 channel is activated for post-translational protein translocation.
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