bluuebunny/crossref_metadata_2025_split huggingface dataset:
High diversity of type I polyketide genes in Bacidia rubella as revealed by the comparative analysis of 23 lichen fungal genomes
Authors: Gerasimova Julia , Beck Andreas , Werth Silke , Resl Philipp 
Published: February 2022

AbstractFungi involved in lichen symbioses produce a large array of different secondary metabolites. The high diversity of those substances has been known for decades and are often considered characteristic for taxonomical delimitation in lichen-forming fungi. Polyketides, the most common secondary metabolites, are synthesized by the Type I Polyketide synthases (TI-PKS) comprised of different enzymatic domains. We present a phylogenetic overview of Type I PKS genes recovered from the de-novo sequenced genome of Bacidia rubella in the context of additional twenty-one fungal genomes from the largest radiation of lichen-forming Ascomycetes (Lecanoromycetes) as well as the lichen-forming Eurotiomycete, Endocarpon pusillum. Using de-novo gene prediction and functional annotation combined with a phylogenetic analysis, we provide insights into the biosynthetic potential and PKS gene diversity of lichen-forming fungi. We discuss genes predicted in the lichen-forming fungal genomes in relation to previously characterized PKS genes from other fungi and bacteria. Our results reveal a high number of biosynthetic gene clusters and their gene domain composition. PKS gene content outnumbers known secondary substances produced by the lichen-forming fungi. We were able to assign putative functions to several of those PKS genes in silico, based on similarity to already characterized genes. In particular, we identified a putative PKS23 gene of Bacidia rubella, producing the common lichen substance atranorin. However, we also found that several lichen-forming fungi still possess homologs of different biosynthetic genes without producing the corresponding substances in detectable amounts. Although many PKSs remain without functional assignments in our analysis, our findings highlight that genes from lichen-forming fungi represent an untapped source of novel polyketide compounds. However, additional experimental approaches are necessary to link biosynthetic genes and secondary metabolites with confidence.
Gi/o protein–coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na+/K+ ATPase activation
Authors: Dickerson Matthew T. , Dadi Prasanna K. , Zaborska Karolina E. , Nakhe Arya Y. , Schaub Charles M. , Dobson Jordyn R. , Wright Nicole M. , Lynch Joshua C. , Scott Claire F. , Jacobson David A. 
Published: February 2022

ABSTRACTGi/o protein-coupled receptors (Gi/o-GPCRs) limit pancreatic islet insulin secretion by decreasing β-cell Ca2+ entry, which is essential for maintenance of glucose homeostasis. However, the Gi/o-GPCR signaling mechanism that mediates inhibition of human islet hormone secretion has not been identified. Here we demonstrate that Gi/o-GPCRs cause hyperpolarization of the β-cell membrane potential through activation of Na+/K+ ATPases (NKAs) in mouse and human islets. Stimulation of Gi/o-coupled somatostatin or α2-adrenergic receptors induced oscillations in β-cell NKA activity, which resulted in islet Ca2+ fluctuations. Selective induction of β-cell Gi/o signaling with a chemogenetic Gi/o-GPCR also activated NKAs and initiated islet Ca2+ oscillations, suggesting that β-cell Gi/o-GPCRs tune pulsatile insulin secretion. Furthermore, intra-islet paracrine activation of β-cell Gi/o-GPCR signaling and NKAs by δ-cell somatostatin secretion slowed Ca2+ oscillations, which decreased insulin secretion. Gi/o-GPCR-mediated oscillations in β-cell membrane potential and Ca2+ were dependent on NKA phosphorylation by Src tyrosine kinases; an effect that was mimicked by stimulating islet insulin receptor tyrosine kinases. Whereas β-cell NKA function was completely inhibited by cAMP-dependent PKA activation. Taken together, these data reveal that NKA-mediated hyperpolarization of β-cell membrane potential serves as the primary and conserved mechanism for Gi/o-GPCR control of electrical excitability, Ca2+ handling, and insulin secretion.
Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2
Authors: Ai Liangxia , Li Yafei , Zhou Li , Yao Wenrong , Zhang Hao , Hu Zhaoyu , Han Jinyu , Wu Junmiao , Wang Weijie , Xu Pan , Wang Ruiyue , Li Zhangyi , Li Zhouwang , Wei Chengliang , Chen Haobo , Liang Jianqun , Guo Ming , Huang Zhixiang , Wang Xin , Zhang Zhen , Xiang Wenjie , Xu Lianqiang , Lv Bin , Peng Peiqi , Zhang Shangfeng , Ji Xuhao , Luo Huiyi , Chen Nanping , Chen Jianping , Lan Ke , Hu Yong 
Published: February 2022

AbstractAdvanced mRNA vaccines play vital roles against SARS-CoV-2. However, due to their poor stability, most current mRNA delivery platforms need to be stored at -20°C or -70°C, which severely limits their distribution. Herein, we present lyophilized SARS-CoV-2 mRNA-lipid nanoparticle vaccines, which can be stored at room temperature with long-term thermostability. In the invivoDelta virus challenge experiment, lyophilized Delta variant mRNA vaccine successfully protected mice from infection and cleared the virus. Lyophilized omicron mRNA vaccine enabled to elicit both potent humoral and cellular immunity. In booster immunization experiments in mice and old monkeys, lyophilized omicron mRNA vaccine could effectively increase the titers of neutralizing antibodies against wild-type coronavirus and omicron variants. In humans, lyophilized omicron mRNA vaccine as a booster shot could also engender excellent immunity and had less severe adverse events. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity, and significantly improved their accessibility, particularly in remote regions.
Sulfide toxicity as key control on anaerobic oxidation of methane in eutrophic coastal sediments
Authors: Martins Paula Dalcin , de Monlevad João P. R. C. , Lenstra Wytze K. , Wallenius Anna J. , Echeveste Medrano Maider J. , Hermans Martijn , Slomp Caroline P. , Welte Cornelia U. , Jetten Mike S. M. , van Helmond Niels A.G.M. 
Published: February 2022

AbstractCoastal zones account for significant global marine methane emissions to the atmosphere. In coastal ecosystems, the tight balance between microbial methane production and oxidation in sediments prevents most methane from escaping to the water column. Anthropogenic activities, causing eutrophication and bottom water deoxygenation, could disrupt this balance in the microbial methane cycle and lead to increased methane release from coastal sediments. Here, we combined microbiological and biogeochemical analyses of sediments from three sites along a bottom water redox gradient (oxic-hypoxic-euxinic) in the eutrophic Stockholm Archipelago to investigate the impact of anthropogenically-induced redox shifts on microbial methane cycling. At both the hypoxic and euxinic site, sediments displayed a stronger depletion of terminal electron acceptors at depth and a shoaling of the sulfate-methane transition zone in comparison to the oxic site. Porewater methane and sulfide concentrations and potential methane production rates were also higher at the hypoxic and euxinic site. Analyses of metagenome-assembled genomes and 16S rRNA gene profiling indicated that methanogens became more abundant at the hypoxic and euxinic site, while anaerobic methane-oxidizing archaea (ANME), present in low coverage at the oxic site, increased at the hypoxic site but virtually disappeared at the euxinic site. A 98% complete genome of an ANME-2b Ca. Methanomarinus archaeon had genes encoding a complete reverse methanogenesis pathway, several multiheme cytochromes, and a sulfite reductase predicted to detoxify sulfite. Based on these results, we infer that sulfide exposure at the euxinic site led to toxicity in ANME, which, despite the abundance of substrates at this site, could no longer thrive. These mechanistic insights imply that the development of euxinia, driven by eutrophication, could disrupt the coastal methane biofilter, leading to increased benthic methane release and potential increased methane emissions from coastal zones to the atmosphere.
Causes, temporal trends and the effects of urbanisation on admissions of wild raptors to rehabilitation centres in England and Wales
Authors: Panter Connor T. , Allen Simon , Backhouse Nikki , Mullineaux Elizabeth , Rose Carole-Ann , Amar Arjun 
Published: February 2022

ABSTRACTData from wildlife rehabilitation centres can provide on-the-ground records of causes of raptor morbidity and mortality, allowing threat patterns to be explored throughout time and space. We provide an overview of native raptor admissions to four wildlife rehabilitation centres (WRCs) in England and Wales, quantifying the main causes of morbidity and mortality, trends over time and whether certain causes were more common in more urbanised areas between 2001-2019. Throughout the study period 14 raptor species were admitted totalling 3305 admission records. The Common Buzzard (Buteo buteo;31%) and Tawny Owl (Strix aluco; 29%) were most numerous. Relative to the proportion of breeding individuals in Britain & Ireland, Peregrine Falcons (Falco peregrinus), Little Owls (Athene noctua) and Western Barn Owls (Tyto alba) were over-represented in the admissions data by 103%, 73% and 69%, respectively. Contrastingly Northern Long-eared Owls (Asio otus), Western Marsh Harriers (Circus aeruginosus) and Merlin (Falco columbarius) were under-represented by 187%, 163% and 126%, respectively. Across all species, vehicle collisions were the most frequent anthropogenic admission cause (22%) and orphaned young birds (10%) were most frequent natural admission cause. Mortality rate was highest for infection/parasite admissions (90%), whereas orphaned birds experienced lowest mortality rates (16%). For one WRC, there was a notable decline in admissions over the study period. Red Kite (Milvus milvus) admissions increased over time, whereas Common Buzzard and Common Kestrel admissions declined. There were significant declines in the relative proportion of persecution and metabolic admissions, and an increase in orphaned young birds. Urban areas were positively associated with persecution, building collisions and unknown trauma admissions, whereas vehicle collisions were associated with more rural areas. Many threats persist for raptors in England and Wales, however, have not changed substantially over the past two decades. Threats associated with urban areas, such as building collisions, may increase over time in line with human population growth and subsequent urban expansion.
Morphological profiling of environmental chemicals enables efficient and untargeted exploration of combination effects
Authors: Rietdijk Jonne , Aggarwal Tanya , Georgieva Polina , Lapins Maris , Carreras-Puigvert Jordi , Spjuth Ola 
Published: February 2022

AbstractEnvironmental chemicals are commonly studied one at a time, and there is a need to advance our understanding of the effect of exposure to their combinations. Here we apply high-content microscopy imaging of cells stained with multiplexed dyes (Cell Painting) to profile the effects of Cetyltrimethylammonium bromide (CTAB), Bisphenol A (BPA), and Dibutyltin dilaurate (DBTDL) exposure on four human cell lines; both individually and in all combinations. We show that morphological features can be used with multivariate data analysis to discern between exposures from individual compounds, concentrations, and combinations. CTAB and DBTDL induced concentration-dependent morphological changes across the four cell lines, and BPA exacerbated morphological effects when combined with CTAB and DBTDL. Combined exposure to CTAB and BPA induced changes on the ER, Golgi apparatus, nucleoli and cytoplasmic RNA in one of the cell lines. Different responses between cell lines indicate that multiple cell types are needed when assessing combination effects. The rapid and relatively low-cost experiments combined with high information content makes Cell Painting an attractive methodology for future studies of combination effects. All data in the study is made publicly available on Figshare.HighlightsAssessment of combination effects of BPA, CTAB and DBTDL on four human cell linesMorphological profiling/Cell Painting captures dose and combination dependent effectsBPA exacerbated morphological effects when combined with CTAB and DBTDL.Cell models of diverse origin are needed when profiling environmental chemicals
Feasibility of enhancing carbon sequestration and stock capacity in temperate and boreal European forests via changes to management regimes
Authors: Dalmonech D. , Marano G. , Amthor J.S. , Cescatti A. , Lindner M. , Trotta C. , Collalti A. 
Published: February 2022

AbstractForest management practices might act as nature-based methods to remove CO2from the atmosphere and slow anthropogenic climate change and thus support an EU forest-based climate change mitigation strategy. However, the extent to which diversified management actions could lead to quantitatively important changes in carbon sequestration and stocking capacity at the tree level remains to be thoroughly assessed. To that end, we used a state-of-the-science bio-geochemically based forest growth model to simulate effects of multiple forest management scenarios on net primary productivity (NPP) and potential carbon woody stocks (pCWS) under twenty scenarios of climate change in a suite of observed and virtual forest stands in temperate and boreal European forests. Previous modelling experiments indicated that the capacity of forests to assimilate and store atmospheric CO2in woody biomass is already being attained under business-as-usual forest management practices across a range of climate change scenarios. Nevertheless, we find that on the long-term, with increasing atmospheric CO2concentration and warming, managed forests show both higher productivity capacity and a larger potential pool size of stored carbon than unmanaged forests as long as thinning and tree harvesting are of moderate intensity.
Chemometrics-based evaluation on effect of sonication, contact time and solvent-to-solid ratio on total phenolics and flavonoids, fatty acids and antibacterial potency of Carica papaya seed against S. enteritidis, B. cereus, V. vulnificus and P. mirabilis
Authors: Abdullah Sani Muhamad Shirwan 
Published: February 2022

AbstractThis study was aimed on extraction optimization of antibacterial agent from Carica papaya seed against S. enteritidis, B. cereus, V. vulnificus and P. mirabilis as affected by sonication-assisted extraction (SAE), contact time (CT) and solid-to-solvent ratio (SSR). The principal component analysis (PCA) and individual evaluation approaches identified that no SAE, 8 CT and 1:10 SSR was the best treatment with the highest antibacterial potency. The PCA identified no SAE, 8 CT, and 1:5 SSR as the second-beat treatment. The yield, total phenolic compound (TPC), C18:1n9t and C16:1 fatty acids (FAs) in no SAE, 8 CT and 1:10 SSR treatment inhibited the growth of B. cereus, V. vulnificus and P. mirabilis while C21:0 and C15:0 in 30 min SAE, 8 CT and 1:2 SSR inhibited the S. enteritidis growth. The yield, TPC, C18:1n9t and C16:1 FAs, and C6:0 and C24:1n9, C20:1, C4:0 and C20:0 FAs had antagonistic effects on B. cereus, V. vulnificus and P. mirabilis growths. The C21:0, C15:0, C6:0 and C13:0, and C23:0, C20:0 and C11:0 FAs had antagonistic effects on S. enteritidis growth. The PCA also denoted that the MIC50 and MIC0 had a higher variation than MIC; hence, the former variables were better to use in PCA.
A pore-forming β-trefoil lectin with specificity for the tumor-related glycosphingolipid Gb3
Authors: Notova Simona , Bonnardel François , Rosato Francesca , Siukstaite Lina , Schwaiger Jessica , Bovin Nicolai , Varrot Annabelle , Römer Winfried , Lisacek Frédérique , Imberty Anne 
Published: February 2022

AbstractLectins are efficient multivalent glycan receptors, deciphering the glyco-code on cell surfaces. The β-trefoil fold, characterized by three lobe-shaped repeats, is adopted by several classes of lectins, often associated with other domains having enzymatic or toxic activity. Based on the UniLectin3D database classification, the sequence signature of trefoil lobes was defined and used to predict 44714 lectins from 4497 species. Among them, SaroL-1 from the lower eukaryote Salpingoeca rosetta was predicted to contain both β-trefoil and aerolysin-like pore-forming domain. Recombinant SaroL-1 binds to galactose and derivatives, with a stronger affinity for cancer-related α-galactosylated epitopes such as glycosphingolipid Gb3 embedded in giant unilamellar vesicles or cell membranes. Crystal structures in complex with Gb3 trisaccharide and GalNAc show similarity with pore-forming toxins. Recognition of the αGal epitope on glycolipids was necessary for hemolysis of rabbit erythrocytes and toxicity on cancer cells through carbohydrate-dependent pore-formation.
Structural basis of human IL-18 sequestration by the decoy receptor IL-18 binding protein (IL-18BP) in inflammation and tumor immunity
Authors: Detry Sammy , Andries Julie , Bloch Yehudi , Gabay Cem , Clancy Danielle , Savvides Savvas N. 
Published: February 2022

AbstractHuman Interleukin-18 (IL-18) is an omnipresent pro-inflammatory cytokine of the IL-1 family with central roles in autoimmune and inflammatory diseases, and serving as a staple biomarker in the evaluation of inflammation in physiology and disease, including the inflammatory phase in COVID-19. The sequestration of IL-18 by its soluble decoy receptor IL-18 Binding Protein (IL-18BP) is critical to the regulation of IL-18 activity. Since an imbalance in expression and circulating levels of IL-18 is associated with disease, structural insights into how IL-18BP outcompetes binding of IL-18 by its cognate cell-surface receptors would be highly desirable. However, the structure of human IL-18BP in complex with IL-18 had remained elusive. Here, we elucidate the sequestration mechanism of human IL-18 mediated by IL-18BP based on the crystal structure of the IL-18:IL-18BP complex. These detailed structural snapshots reveal the interaction landscape leading to the ultra-high affinity of IL-18BP towards IL-18 and identify substantial differences with respect to previously characterized complexes of IL-18 with IL-18BP of viral origin. Furthermore, our structure captured a fortuitous higher-order assembly between IL-18 and IL-18BP coordinated by a disulfide-bond distal to the binding surface connecting IL-18 and IL-18BP molecule from different complexes, resulting in a novel complex with 2:2 stoichiometry. This tetrapartite assembly was found to restrain IL-18 activity more effectively than the canonical 1:1 complex. Collectively, our findings will provide a framework for innovative structure-driven therapeutic strategies and further functional interrogation of IL-18 in physiology and disease.Significance statementElevated levels of interleukin-18 (IL-18) have long been implicated in numerous inflammatory diseases while also displaying potent anti-tumoral activities. Recent research on COVID-19 has now underscored the role of IL-18 and IL-18 binding protein (IL-18BP), a soluble receptor serving to regulate IL-18 activity, as key players in viral immunity and as promising biomarkers and predictors of disease severity. In this work, we present detailed structural insights into how human IL-18 and IL-18BP interact thereby completing the structural repertoire of IL-18 in complex with its cognate human receptors and viral decoy receptors. Our findings will support structure-based efforts to either disrupt or enhance the interactions of IL-18 with its cognate receptors for therapeutic purposes.
Fentanyl reinstatement to discriminative cues after conflict in sign- and goal-tracking rats
Authors: Martin David A. , Keefer Sara E. , Calu Donna J. 
Published: February 2022

AbstractRationaleDiscriminative stimuli (DS) are cues that predict reward availability. DS are resistant to extinction and motivate drug seeking even after long periods of abstinence. Previous studies have demonstrated that sign tracking (ST) and goal tracking (GT) individual differences in Pavlovian approach to food cues predict distinct vulnerabilities to CS and DS reinstatement of cocaine seeking, respectively. Compared to goal-trackers, sign-trackers show heightened CS relapse even after electric barrier induced abstinence. We do not know whether DS relapse persists after electric barrier induced abstinence, or whether tracking-related relapse vulnerabilities generalize to models of opioid relapse.ObjectivesWe sought to determine if DS-induced reinstatement of fentanyl seeking persists in the presence of reduced adverse consequences after electric barrier-induced abstinence. We also aimed to determine whether tracking differences predict the magnitude of DS-induced reinstatement of fentanyl seeking after electric barrier-induced abstinence.MethodsFirst we used Pavlovian lever autoshaping (PLA) training to determine sign-, goal- and intermediate tracking groups in male and female Sprague Dawley rats. We then trained rats in a DS model of intermittent fentanyl self-administration, and extinguished drug seeking by imposing an electric barrier of increasing intensity. We then measured the level of DS-induced reinstatement in the presence of a reduced electric barrier intensity.ResultsWe report that DS produce large increases in fentanyl seeking after electric barrier induced abstinence. Contrary to our expectations, the magnitude of the DS induced reinstatement effect was not related to tracking group.ConclusionsDiscriminative stimuli powerfully motivate opioid seeking, despite continued aversive consequences. Individual differences in Pavlovian approach do not predict the level of DS reinstatement to fentanyl seeking after conflict induced abstinence.
OzTracs: Optical Osmolality Reporters Engineered from Mechanosensitive Ion Channels
Authors: Kleist Thomas J. , Lin I Winnie , Xu Sophia , Maksaev Grigory , Sadoine Mayuri , Haswell Elizabeth S. , Frommer Wolf B. , Wudick Michael M. 
Published: February 2022

ABSTRACTInteractions between physical forces and membrane proteins underpin many forms of environmental sensation and acclimation. Microbes survive sudden osmotic stresses with the help of mechanically gated ion channels and osmolyte transporters. Plant mechanosensitive ion channels have been shown to function in defense signaling. Here, we engineered genetically encoded osmolality sensors (OzTracs) by fusing green fluorescent protein spectral variants to the mechanosensitive ion channels MscL from E. coli or MSL10 from A. thaliana. When expressed in yeast cells, OzTrac sensors reported osmolality changes as a proportional change in emission ratio of the two fluorescent protein domains. Live-cell imaging revealed accumulation of fluorescent sensors in internal aggregates presumably derived from the endomembrane system. Thus, OzTrac sensors serve as osmolality-dependent reporters through an indirect mechanism, such as effects on molecular crowding or fluorophore solvation.