bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of public-initiated COVID-19 risk communication on individual NPI practices
Authors: Tefera Yifokire , Kumie Abera , Hailemariam Damen , Wakuma Samson , Abegaz Teferi , Yirsaw Shibabaw 
Published: March 2023

AbstractBackgroundNon-Pharmaceutical Interventions (NPI) are the most widely recognized public health measures practiced globally to prevent the spread of Covid-19 transmission. The effectiveness of NPIs is dependent on the type, a combination of applied interventions, and the level of compliance of the NPIs. The expected outcome of behavioral practices varies relative to the behavioral intervention duration.ObjectivesThis study aimed to assess the trend of community compliance to NPIs and with its level of variation with the place of residence and sociodemographic characteristics of people.MethodsA weekly non-participatory field survey on an individual’s NPI practice was observed from October 2020 to July 2021, for a total of 39 weeks. The survey covered all the regions; 14 regional and capital cities. Data collection for the 3 NPI behaviors (mask use, hand hygiene, and physical distance was and managed weekly at eight public service locations using the Open Data Kit (ODK) tool.ResultsMore than 180,000 individuals were observed for their NPI practice; on average 5,000 observations in a week. About 43% of the observation was made from Addis Ababa, 56% were male participants and the middle age group (18-50 years) accounts for 75%. The overall level of NPI compliance had a peak around the 26th– 30thweeks then decline the rest of the weeks. Respiratory hygiene had the highest compliance whereas hand hygiene had the least 41% and 4%, respectively. There was a significant difference between capital city and regional city residents by their level of NPI compliance. Females comply more than males, and individuals had increased NPI compliance while at the bank service and workplaces compared to while in the transport services at p<0.001.ConclusionThe overall community compliance with NPI practice showed a declining trend in Ethiopia but increased compliance was also observed following the implementation of government-initiated public measures. Therefore, public-initiated risk communication and public advocacy programs for the prevention of Covid-19 should be strengthened.
Lipid nanodiscs as a template for high-resolution cryo-EM structures of peripheral membrane proteins
Authors: Cannon Kevin S. , Sarsam Reta D. , Tedamrongwanish Tanita , Zhang Kevin , Baker Richard W. 
Published: March 2023

AbstractPeripheral membrane proteins are ubiquitous throughout cell biology and are required for a variety of cellular processes such as signal transduction, membrane trafficking, and autophagy. Transient binding to the membrane has a profound impact on protein function, serving to induce conformational changes and alter biochemical and biophysical parameters by increasing the local concentration of factors and restricting diffusion to two dimensions. Despite the centrality of the membrane in serving as a template for cell biology, there are few reported high-resolution structures of peripheral membrane proteins bound to the membrane. We analyzed the utility of lipid nanodiscs to serve as a template for cryo-EM analysis of peripheral membrane proteins. We tested a variety of nanodiscs and we report a 3.3 Å structure of the AP2 clathrin adaptor complex bound to a 17-nm nanodisc, with sufficient resolution to visualize a bound lipid head group. Our data demonstrate that lipid nanodiscs are amenable to high-resolution structure determination of peripheral membrane proteins and provide a framework for extending this analysis to other systems.
The nucleolar aberrancies that drive ribosome impairment induced by RNA binding proteins are hallmarks of aging
Authors: Aguilar-Garrido Pedro , Velasco-Estévez María , Navarro-Aguadero Miguel Ángel , Hernandez-Sanchez María , Malaney Prerna , Zhang Xiaroui , Aitken Marisa J. L. , Otero-Sobrino Alvaro , Ibañez-Navarro Marta , Ortiz-Ruiz Alejandra , Megias Diego , Pérez-Martínez Manuel , Mata Gadea , Gomez Jesús , Dominguez Orlando , Graña-Castro Osvaldo , Caleiras Eduardo , de Andres Paloma Jimena , Rodriguez Sandra , Torres Raúl , Sirozh Oleksandra , Lafarga Vanesa , Martinez-Lopez Joaquín , Post Sean M. , Gallardo Miguel 
Published: March 2023

AbstractThe nucleolus is a dynamic structure where ribosome subunits are produced. Indeed, nucleoli respond to any change in cellular homeostasis by altering the rate of ribosome biogenesis, thus working as a stress sensor. Therefore, an imbalance in ribosome biogenesis promotes changes in morphology and function and can evoke a nucleolar stress response. Changes in the structure and composition of nucleoli impair ribosome biogenesis and have been described as nucleolar stress, a mechanism related to aging and cancer.Here, we show the role of the RNA binding protein Hnrnpk in nucleolar dynamics and ribosome function. Hnrnpk is a ribonucleoprotein in charge of escorting nascent transcripts to its processing and nuclear export to ribosomes. When Hnrnpk is overexpressed, the nucleolus is altered and shows stress-like phenotype, with accumulation and delocalization of components such as Ncl, driving ribosome biogenesis impairment and halting protein translation.Nucleolin haploinsufficiency is correlated with enlarged nucleoli, increased ribosome components and translation and induces a reduction in lifespan. Thus, gain of Ncl generated by Hnrnpk overexpression can cause ribosome biogenesis defects associated with ribosome impairment leading to ribosomopathies and bone marrow failure syndrome.Aging and bone marrow failure share common biological hallmarks. Indeed, Hnrnpk overexpression and nucleolar stress trigger cell cycle arrest and senescence of the cells, a feature of both processes.Together, these findings support the idea that nucleolar abnormalities contribute to ribosome impairment, thus triggering the onset of hematopoiesis and the aging process. Here, we decipher a novel master regulator of this mechanism: Hnrnpk.
Tmem178 negatively regulates IL-1β production through inhibition of the NLRP3 inflammasome
Authors: Khanna Kunjan , Yan Hui , Mehra Muneshwar , Rohatgi Nidhi , Mbalaviele Gabriel , Faccio Roberta 
Published: March 2023

AbstractObjectiveInflammasomes modulate the release of bioactive IL-1β. Excessive IL-1β levels are detected in patients with systemic juvenile idiopathic arthritis (sJIA) and cytokine storm syndrome (CSS) with mutated and unmutated inflammasome components, raising questions on the mechanisms of IL-1β regulation in these disorders.MethodsTo investigate how the NLRP3 inflammasome is modulated in sJIA, we focused on Tmem178, a negative regulator of calcium levels in macrophages, and measured IL-1β and caspase-1 activation in wild-type (WT) andTmem178-/-macrophages following calcium chelators, silencing of Stim1, a component of store-operated calcium entry (SOCE), or by expressing a Tmem178 mutant lacking Stim1 binding site. Mitochondrial function in both genotypes was assessed by measuring oxidative respiration, mitochondrial reactive oxygen species (mtROS), and mitochondrial damage. CSS development was analyzed inPerforin-/-/Tmem178-/-mice infected with LCMV in which inflammasome or IL-1 signaling was pharmacologically inhibited. HumanTMEM178andIL-1Btranscripts were analyzed in a dataset of peripheral blood monocytes from healthy controls and active sJIA patients.ResultsTMEM178levels are reduced in monocytes from sJIA patients while IL-1B show increased levels. Accordingly,Tmem178-/-macrophages produce elevated IL-1β compared to WT cells. The elevated intracellular calcium levels following SOCE activation inTmem178-/-macrophages induce mitochondrial damage, release mtROS, and ultimately, promote NLRP3 inflammasome activation.In vivo, inhibition of inflammasome or IL-1 neutralization prolongsTmem178-/-mouse survival to LCMV-induced CSS.ConclusionDownregulation of Tmem178 levels may represent a new biomarker to identify sJIA/CSS patients that could benefit from receiving drugs targeting inflammasome signaling.
Deciphering dermal fibroblast behavior in 3D bioprinted dermis contructs
Authors: Chastagnier Laura , el-Kholti Naima , Essayan Lucie , Thomann Céline , Courtial Edwin-Joffrey , Marquette Christophe , Petiot Emma 
Published: March 2023

AbstractIn recent years, numerous strategies have emerged to answer the growing demand for graftable tissues. Tissue engineering andin-vitroproduction are one of them. Among all the engineered tissues, skin is one of the most advanced. Nevertheless, biofabrication of graftable and fully functional skin substitutes is still far from being reached. Skin reconstruction, particularly dermis, necessitates cultivation and maturation for several weeks (> 3 weeks) to recover the tissue’s composition and functions, which prevent its transfer to clinical applications. Thus, several strategies, including 3D bioprinting, have been explored to accelerate these productions. In the present study, based on the successful application of 3D bioprinting achieved by our group for skin reconstruction in 21 days, we propose to detail the biological behaviors and maturation phases occurring in the bioprinted skin construct thanks to a descriptive approach transferred from the bioprocess field. The aim is to comprehensively characterize dermis construct maturation phases (cell proliferation and ECM secretion) to master later the interdependent and consecutive mechanisms involved inin-vitroproduction. Thus, standardized quantitative techniques were deployed to describe 3D bioprinted dermis proliferation and maturation phases. Then, in a second step, various parameters potentially impacting the dermis reconstruction phases were evaluated to challenge our methodology and reveal the biological behavior described (fibroblast proliferation and migration, cell death, ECM remodeling with MMP secretion). The parameters studied concern the bioprinting practice including various printed geometries, bioink formulations and cellular physiology in relation with their nutritional supplementation with selected medium additives.
A Msp1-containing complex removes orphaned proteins in the mitochondrial outer membrane of trypanosomes
Authors: Gerber Markus , Suppanz Ida , Oeljeklaus Silke , Niemann Moritz , Käser Sandro , Warscheid Bettina , Schneider André , Dewar Caroline E. 
Published: March 2023

AbstractThe AAA-ATPase Msp1 extracts mislocalized outer membrane proteins and thus contributes to mitochondrial proteostasis. Using pull down experiments we show that trypanosomal Msp1 localizes to both glycosomes and the mitochondrial outer membrane, where it forms a stable complex with four outer membrane proteins. The trypanosome-specific pATOM36 mediates complex assembly of a-helically anchored mitochondrial outer membrane proteins such as protein translocase subunits. Inhibition of their assembly triggers a pathway that results in the proteasomal digestion of unassembled substrates. Using inducible single, double and triple RNAi cell lines combined with proteomic analyses we demonstrate that not only Msp1 but also the trypanosomal homolog of the AAA-ATPase VCP are implicated in this quality control pathway. Moreover, in the absence of VCP three out of the four Msp1-interacting mitochondrial proteins are required for efficient proteasomal digestion of pATOM36 substrates suggesting they act in concert with Msp1. pATOM36 is a functional analogue of the yeast MIM complex and possibly of human MTCH2 suggesting that similar mitochondrial quality control pathways linked to Msp1 might also exist in yeast and humans.
SIN3 acts in distinct complexes to regulate the germline transcriptional program inC. elegans
Authors: Caron M. , Robert V. , Gely L. , Adrait A. , Pakulska V. , Couté Y. , Chevalier M. , Riedel C.G. , Bedet C. , Palladino F. 
Published: March 2023

AbstractThe SIN3 transcriptional coregulator influences gene expression through multiple interactions that include histone deacetylases (HDACs). Haploinsufficiency and mutations in SIN3 are the underlying cause of Witteveen-Kolk syndrome and related intellectual disability (ID)/autism syndromes, emphasizing its key role in development. However, little is known about the diversity of its interactions and functions in developmental processes. Here we show that loss of SIN-3, the single SIN3 homologue inCaenorhabditis elegans, results in maternal effect sterility associated with deregulation of the germline transcriptome, including desilencing of X-linked genes. We identify at least two distinct SIN3 complexes containing specific HDACs, and show that they differentially contribute to fertility. Single cell smFISH reveals that insin-3mutants, the X chromosome becomes re-expressed prematurely and in a stochastic manner in individual germ cells. Furthermore, we identify histone residues whose acetylation increases in the absence of SIN3. Together, this work provides a powerful framework for thein vivostudy of SIN3 and associated proteins.
Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells
Authors: Morgun Eva , Zhu Jennifer , Almunif Sultan , Bobbala Sharan , Aguilar Melissa S. , Wang Junzhong , Conner Kathleen , Cui Yongyong , Cao Liang , Seshadri Chetan , Scott Evan A. , Wang Chyung-Ru 
Published: March 2023

AbstractMycobacterium tuberculosis(Mtb) infection elicits both protein and lipid antigen-specific T cell responses. However, the incorporation of lipid antigens into subunit vaccine strategies and formulations has been underexplored, and the characteristics of vaccine-induced Mtb lipid-specific memory T cells have remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to unconventional T cell subsets. These MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting that MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized the enhanced stability of bicontinuous nanospheres (BCN) to efficiently encapsulate MA forin vivodelivery to MA-specific T cells, both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary administration of MA-loaded BCN (MA-BCN) elicited MA-specific T cell responses in humanized CD1 transgenic mice. Simultaneous delivery of MA and Ag85B within BCN activated both MA- and Ag85B-specific T cells. Notably, pulmonary vaccination with MA-Ag85B-BCN resulted in the persistence of MA, but not Ag85B, within alveolar macrophages in the lung. Vaccination of MA-BCN through intravenous or subcutaneous route, or with attenuated Mtb likewise reproduced MA persistence. Moreover, MA-specific T cells in MA-BCN-vaccinated mice differentiated into a T follicular helper-like phenotype. Overall, the BCN platform allows for the dual encapsulation andin vivoactivation of lipid and protein antigen-specific T cells and leads to persistent lipid depots that could offer long-lasting immune responses.
Landing force reveals new form of motion-induced sound camouflage in a wild predator
Authors: Schalcher Kim , Milliet Estelle , Séchaud Robin , Bühler Roman , Almasi Bettina , Potier Simon , Becciu Paolo , Roulin Alexandre , Shepard Emily L. C. 
Published: March 2023

ABSTRACTPredator-prey arms races have led to the evolution of finely-tuned disguise strategies. While the theoretical benefits of predator camouflage are well established, no study has yet been able to quantify its consequences for hunting success in natural conditions. We used high-resolution movement data to quantify how barn owls (Tyto alba) conceal their approach when using a sit-and-wait strategy. We hypothesized that hunting barn owls would modulate their landing force, potentially reducing noise levels in the vicinity of prey. Analysing 87,957 landings by 163 individuals equipped with GPS tags and accelerometers, we show that barn owls reduce their landing force as they approach their prey, and that landing force predicts the success of the following hunting attempt. Landing force also varied with the substrate, being lowest on man-made poles in field boundaries. The physical environment therefore affects the capacity for sound camouflage, providing an unexpected link between predator-prey interactions and land-use. Finally, hunting strike forces in barn owls were the highest recorded in any bird, relative to body mass, highlighting the range of selective pressures that act on landings and the capacity of these predators to modulate their landing force. Overall, our results provide the first measurements of landing force in a wild setting, revealing a new form of motion-induced sound camouflage and its link to hunting success.
The FSGS disease gene product and nuclear pore protein NUP205 regulates nuclear localization and activity of the transcriptional regulators YAP and TAZ in podocytes
Authors: Ester Lioba , Cabrita Inês , Ventzke Michel , Christodoulou Marita , Fabretti Francesca , Benzing Thomas , Habbig Sandra , Schermer Bernhard 
Published: March 2023

ABSTRACTBackgroundMutations in genes encoding nuclear pore proteins (NUPs) cause steroid-resistant nephrotic syndrome (SRNS) and focal and segmental glomerulosclerosis (FSGS). The mechanisms of how NUP deficiency may cause podocyte dysfunction and failure of the kidney filtration barrier are elusive. The tightly controlled activity of the transcriptional effectors of the evolutionarily conserved Hippo pathway YAP and TAZ is essential for podocyte homeostasis. Here we analyze the role of NUPs in controlling YAP/TAZ nuclear import and activity in podocytes.MethodsWe used quantitative label-free mass spectrometry to characterize the YAP/TAZ interactomes in podocytes, particularly identifying NUP interactions. Moreover, we specifically studied NUP205 in controlling YAP/TAZ nuclear import and YAP/TAZ-dependent target gene expression.ResultsHere we identify the disease-causing nuclear pore proteins NUP107, NUP133, NUP205, and XPO5 as components of YAP and TAZ protein complexes in podocytes. We demonstrate that NUP205 is essential for YAP/TAZ nuclear import. The nuclear interaction of YAP/TAZ with TEAD1 and their transcriptional activity were dependent on NUP205 expression. Furthermore, we identify a feedback regulatory mechanism that controls YAP activity depending on TAZ-mediated NUP205 expression.ConclusionThis study links the disease protein NUP205 with the activity of the transcriptional regulators and Hippo effectors YAP and TAZ and suggests a pathogenic role of YAP/TAZ-deregulation in podocytes in patients withNUP205mutations. Moreover, this study suggests an important role of YAP/TAZ signaling in human FSGS.SIGNIFICANCE STATEMENTUnderstanding the interference of signaling pathways in genetic diseases is essential to finally develop tailored treatment strategies. The increasing number of pathogenic variants causing focal-segmental glomerulosclerosis (FSGS) comprises genes encoding for proteins of the nuclear-cytoplamic shuttling machinery. We here found several of these proteins in an unbiased interactome analysis of the Hippo signaling effector proteins YAP and TAZ in podocytes, pointing to a connection between nucleoporins and the Hippo pathway. Further analyses confirmed that NUP205 is essential for correct YAP/TAZ shuttling; depletion of NUP205 resulted in cytoplasmic retention and inactivation of YAP/TAZ. We suggest the nuclear pore and hippo signaling as a pathogenic module in FSGS.
The pleiotropic functions of Pri smORF peptides synchronise leg development regulators
Authors: Markus Damien , Pelletier Aurore , Boube Muriel , Port Filip , Boutros Michael , Payre François , Obermayer Benedikt , Zanet Jennifer 
Published: March 2023

AbstractThe last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed inDrosophilaimaginal leg discs. Thanks to a functional screen in legs, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri. Since we identified its target Ubr3 in the epidermis andpriwas known to control leg development through misunderstood mechanisms, we investigated the role of Ubr3 in mediatingprifunction in legs. We found thatpriplay several roles during leg development both in patterning and in cell survival. At larval pupal transition, Pri peptides cooperate with Ubr3 to insure cell survival and leg morphogenesis. Earlier, during larval stage,priactivates independently of Ubr3 tarsal transcriptional programs and Notch and EGFR signalling pathways. Our results highlight Ubr3 dependent and independent functions of Pri peptides and their pleiotropy. Moreover, we reveal that the smORF peptide family is a reservoir of overlooked developmental regulators, displaying distinct molecular functions and orchestrating leg development.Summary statementPri smORF peptides activate multiple actors regulating signalling pathways, transcription and apoptosis by distinct mechanisms to insure tarsal patterning and epithelial morphogenesis during leg development.
Tld1 is a novel regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation
Authors: Speer Natalie Ortiz , Braun R. Jay , Reynolds Emma Grace , Brudnicka Alicja , Swanson Jessica M.J. , Henne W. Mike 
Published: March 2023

AbstractCells store lipids in the form of triglyceride (TG) and sterol-ester (SE) in lipid droplets (LDs). Distinct pools of LDs exist, but a pervasive question is how proteins localize to and convey functions to LD subsets. Here, we show the yeast protein YDR275W/Tld1 (for TG-associated LD protein 1) localizes to a subset of TG-containing LDs, and reveal it negatively regulates lipolysis. Mechanistically, Tld1 LD targeting requires TG, and is mediated by two distinct hydrophobic regions (HRs). Molecular dynamics simulations reveal Tld1’s HRs interact with TG on LDs and adopt specific conformations on TG-rich LDs versus SE-rich LDs in yeast and human cells. Tld1-deficient yeast display no defect in LD biogenesis, but exhibit elevated TG lipolysis dependent on lipase Tgl3. Remarkably, over-expression of Tld1, but not LD protein Pln1/Pet10, promotes TG accumulation without altering SE pools. Finally, we find Tld1-deficient cells display altered LD mobilization during extended yeast starvation. We propose Tld1 senses TG-rich LDs and regulates lipolysis on LD subpopulations.
Bacterial cGAS senses a viral RNA to initiate immunity
Authors: Banh Dalton V. , Roberts Cameron G. , Amador Adrian Morales , Brady Sean F. , Marraffini Luciano A. 
Published: March 2023

ABSTRACTCBASS immunity protects prokaryotes from viral (phage) attack through the production of cyclic dinucleotides which activate effector proteins that trigger the death of the infected host. How bacterial cyclases recognize phage infection is not known. Here we show that staphylococcal phages produce a highly structured 400-nt RNA, termedCBASS-activatingbacteriophage RNA (cabRNA), that binds to a positively charged surface of the CdnE03 cyclase and promotes the synthesis of the cyclic dinucleotide cGAMP. Phages that escape CBASS immunity harbor mutations that lead to the generation of a longer form of the cabRNA that cannot activate CdnE03. Since the mammalian cyclase OAS1 also binds viral dsRNA during the interferon response, our results reveal a conserved mechanism for the activation of innate antiviral defense pathways.