bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA regulation of BMP signaling; cross-talk between endothelium and vascular smooth muscle cells
Authors: Watterston Charlene , Zeng Lei , Onabadejo Abidemi , Childs Sarah J 
Published: August 2018

AbstractVascular smooth muscle cells (vSMC) are essential to the integrity of blood vessels, and therefore an attractive target of therapeutics aimed at improving vascular function. Smooth muscle cells are one of the few cell types that maintain plasticity and can switch phenotypes from differentiated (contractile) to de-differentiated (synthetic) and vice versa. As small regulatory transcripts, miRNAs act as genetic ‘fine tuners’ of posttranscriptional events and can act as genetic switches promoting phenotypic switching. The microRNAmiR26atargets the BMP signalling effector,smad1. We show that loss ofmiR26leads to hemorrhage (a loss of vascular stability)in vivo, suggesting altered vascular differentiation. Reduction inmiR26alevels increasessmad1mRNA and phospho-Smad1 (pSmad1) levels. We show that increasing BMP signalling by overexpression ofsmad1also leads to hemorrhage and that normalization of Smad1 levels through double knockdown ofmiR26andsmad1rescues hemorrhage suggesting a direct relationship betweenmiR26andsmad1and vascular stability. Using a BMP genetic reporter and pSmad1 staining we show that the effect ofmiR26on vascular instability is non-autonomous; BMP signalling is active in embryonic endothelial cells, but not in smooth muscle cells. Nonetheless, increased BMP signalling due to loss ofmiR26results in an increase inacta2-expressing smooth muscle cell numbers and promotes a differentiated smooth muscle morphology. Taken together our data suggests thatmiR26modulates BMP signalling in endothelial cells and indirectly promotes a differentiated smooth muscle phenotype. Our data also suggests that crosstalk from BMP-responsive endothelium to smooth muscle is important for its differentiation.
Basalin: an evolutionary unconstrained protein revealed via a conserved role in basal plate function
Authors: Dean Samuel , Moreira-Leite Flavia , Gull Keith 
Published: August 2018

AbstractMost motile flagella have an axoneme that contains nine outer microtubule doublets and a central pair (CP) of microtubules. The CP is thought to coordinate the flagellar beat and defects in CP projections are associated with loss of motility and human disease. In most cilia, the CP nucleate near a ‘basal plate’ at the distal end of the transition zone (TZ). Here, we show that the trypanosome TZ protein ‘basalin’ is essential for building the basal plate, and its loss is associated with inefficient recruitment of CP assembly factors to the TZ, loss of the CP and flagellum paralysis. Guided by synteny, we identified highly divergent basalin orthologs in the genomes of related Leishmania species. Basalins are predicted to be highly unstructured, suggesting that they may act as ‘hubs’ facilitating many protein-protein interactions. This raises the general concept that proteins involved in cytoskeletal functions and apparently appearing organism-specific, may have highly divergent and cryptic orthologs in other species.
Widespread methane formation byCyanobacteriain aquatic and terrestrial ecosystems
Authors: Bižić-Ionescu M. , Klintzsch T. , Ionescu D. , Hindiyeh M. Y. , Günthel M. , Muro-Pastor A.M. , Eckert W. , Keppler F. , Grossart H-P 
Published: August 2018

AbstractEvidence is accumulating to challenge the paradigm that biogenic methanogenesis, traditionally considered a strictly anerobic process, is exclusive toArchaea. Here we demonstrate that Cyanobacteria living in marine, freshwater and terrestrial environments produce methane at substantial rates under light and dark oxic and anoxic conditions, forming a link between light driven primary productivity and methane production in globally relevant group of phototrophs. Biogenic methane production was enhanced during oxygenic photosynthesis and directly attributed to the cyanobacteria by applying stable isotope labelling techniques. We suggest that formation of methane byCyanobacteriamay contribute to methane accumulation in oxygen-saturated surface waters of marine and freshwater ecosystems. Moreover, in these environments, cyanobacterial blooms already do, and might further occur more frequently during future global warming and thus have a direct feedback on climate change. We further highlight that cyanobacterial methane production not only affects recent and future global methane budgets, but also has implications for inferences on Earth’s methane budget for the last 3.5 billion years, when this phylum is thought to have first evolved.
Incorporating in-source fragment information improves metabolite identification accuracy in untargeted LC-MS datasets
Authors: Seitzer Phillip M. , Searle Brian C. 
Published: August 2018

[ABSTRACT]In-source fragmentation occurs as a byproduct of electrospray ionization. We find that ions produced as a result of in-source fragmentation often match fragment ions produced during MS/MS fragmentation and we take advantage of this phenomenon in a novel algorithm to analyze LC-MS metabolomics datasets. Our approach organizes co-eluting MS1 features into a single peak group and then identifies in-source fragments among co-eluting features using MS/MS spectral libraries. We tested our approach using previously published data of verified metabolites, and compared the results to features detected by other mainstream metabolomics tools. Our results indicate that considering in-source fragment information as a part of the identification process increases annotation quality, allowing us to leverage MS/MS data in spectrum libraries even if MS/MS scans were not collected.
Structural basis of Toxoplasma gondii Perforin-Like Protein 1 membrane interaction and activity during egress
Authors: Guerra Alfredo J. , Zhang Ou , Bahr Constance M. E. , Huynh My-Hang , DelProposto James , Brown William C. , Wawrzak Zdzislaw , Koropatkin Nicole M. , Carruthers Vern B. 
Published: August 2018

AbstractIntracellular pathogens must egress from the host cell to continue their infectious cycle. Apicomplexans are a phylum of intracellular protozoans that have evolved members of the membrane attack complex and perforin (MACPF) family of pore forming proteins to disrupt cellular membranes for traversing cells during tissue migration or egress from a replicative vacuole following intracellular reproduction. Previous work showed that the apicomplexan Toxoplasma gondii secretes a perforin-like protein (TgPLP1) that contains a C-terminal Domain (CTD) which is necessary for efficient parasite egress. However, the structural basis for CTD membrane binding and egress competency remained unknown. Here, we present evidence that TgPLP1 CTD prefers binding lipids that are abundant in the inner leaflet of the lipid bilayer. Additionally, solving the high-resolution crystal structure of the TgPLP1 APCβ domain within the CTD reveals an unusual double-layered β-prism fold that resembles only one other protein of known structure. Three direct repeat sequences comprise subdomains, with each constituting a wall of the β-prism fold. One subdomain features a protruding hydrophobic loop with an exposed tryptophan at its tip. Spectrophotometric measurements of intrinsic tryptophan fluorescence are consistent with insertion of the hydrophobic loop into a target membrane. Using CRISPR/Cas9 gene editing we show that parasite strains bearing mutations in the hydrophobic loop, including alanine substitution of the tip tryptophan, are equally deficient in egress as a strain lacking TgPLP1 altogether. Taken together our findings suggest a crucial role for the hydrophobic loop in anchoring TgPLP1 to the membrane to support its cytolytic activity and egress function.Author SummaryToxoplasma gondii has a complex life cycle that involves active invasion of the host cell, the formation of a replicative compartment, and egress from the replicative niche. T. gondii encodes a pore-forming protein, TgPLP1, that contains a C-terminal domain that is crucial for efficient exit from both the parasite containing vacuole and the host cell. However, the mechanism by which TgPLP1 recognizes and binds to the appropriate membrane is unclear. Here we use a combination of biochemistry, structural biology, and parasitology to identify the a preference of TgPLP1 for specific lipids and show that a loop within the structure of the C-terminal domain inserts into the membrane and is necessary for egress from the parasite containing vacuole. Our study sheds light into the determinants of membrane binding in TgPLP1 which may inform the overall mechanism of pore formation in similar systems
Regulation of tensile stress in response to external forces coordinates epithelial cell shape transitions with organ growth and elongation
Authors: Balaji Ramya , Weichselberger Vanessa , Classen Anne-Kathrin 
Published: August 2018

AbstractThe role of actomyosin contractility at epithelial adherens junctions has been extensively studied. However, little is known about how external forces are integrated to establish epithelial cell and organ shapein vivo. We use theDrosophilafollicle epithelium to investigate how tension at adherens junctions is regulated to integrate external forces arising from changes in germline size and shape. We find that overall tension in the epithelium decreases despite pronounced growth of enclosed germline cells, suggesting that the epithelium relaxes to accommodate growth. However, we find local differences in adherens junction tension correlate with apposition to germline nurse cells or the oocyte. We demonstrate that medial Myosin II coupled to corrugating adherens junctions resists nurse cell-derived forces and thus maintains apical surface areas and cuboidal cell shapes. Furthermore, medial reinforcement of the apical surface ensures cuboidal-to-columnar cell shape transitions and imposes circumferential constraints on nurse cells guiding organ elongation. Our study provides insight into how tension within an adherens junction network integrates growth of a neighbouring tissue, mediates cell shape transitions and channels growth into organ elongation.
PIRD: Pan immune repertoire database
Authors: Zhang Wei , Wang Longlong , Liu Ke , Wei Xiaofeng , Yang Kai , Du Wensi , Wang Shiyu , Guo Nannan , Ma Chuanchuan , Luo Lihua , Wu Jinghua , Lin Liya , Yang Fan , Gao Fei , Wang Xie , Li Tao , Zhang Ruifang , Saksena Nitin K. , Yang Huanming , Wang Jian , Fang Lin , Hou Yong , Xu Xun , Liu Xiao 
Published: August 2018

ABSTRACTMotivationT and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database.ResultsWe developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including fromHomo sapiensand other species. In addition to data storage, PIRD also provides functions of data visualisation and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD.Availability and ImplementationPIRD can be freely accessed athttps://db.cngb.org/pird.
Molecular noise of innate immunity shapes bacteria-phage ecologies
Authors: Ruess Jakob , Pleška Maroš , Guet Câlin C , Tkačik Gašper 
Published: August 2018

AbstractMathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their steady state population size, with the first strategy favoring simple and the second strategy favoring complex bacterial innate immunity.
Evidence of Müller glia conversion into retina ganglion cells using Neurogenin2
Authors: Melo Guimarães Roberta Pereira de , Landeira Bruna Soares , Coelho Diego Marques , Ferreira Golbert Daiane Cristina , Silveira Mariana S. , Linden Rafael , Melo Reis Ricardo A. de , Costa Marcos R. 
Published: August 2018

AbstractMacular Degeneration, Glaucoma, and Retinitis Pigmentosa are all leading causes of irreversible visual impairment in the elderly, affecting hundreds of millions of patients. Müller glia cells (MGC), the main type of glia found in the vertebrate retina, can resume proliferation in the adult injured retina and contribute to tissue repair. Also, MGC can be genetically reprogrammed through the expression of the transcription factor (TF) Achaete-scute homolog 1 (ASCL1) into induced neurons (iNs), displaying key hallmarks of photoreceptors, bipolar and amacrine cells, which may contribute to regenerate the damaged retina. Here, we show that the TF neurogenin 2 (NEUROG2) is also sufficient to lineage-reprogram MGC into iNs. The efficiency of MGC lineage conversion by NEUROG2 is similar to that observed after expression of ASCL1. However, reprogramming efficiency is affected by previous exposure to EGF and FGF2 during the expansion of MGC population. Transduction of either Neurog2 or Ascl1 led to the upregulation of key retina neuronal genes in MGC-derived iNs, but only NEUROG2 induced a consistent increase in the expression of putative retinal ganglion cell (RGC) genes. In vivo electroporation of Neurog2 in the neonatal retina also induced a shift in the generation of retinal cell subtypes, favoring the differentiation RGCs at the expense of MGCs. Altogether, our data indicate that Neurog2 induces lineage conversion of MGCs into RGC-like iNs.
Frequency-specific brain dynamics related to prediction during language comprehension
Authors: Armeni Kristijan , Willems Roel M. , van den Bosch Antal , Schoffelen Jan-Mathijs 
Published: August 2018

AbstractThe brain’s remarkable capacity to process spoken language virtually in real time requires fast and efficient information processing machinery. In this study, we investigated how frequency-specific brain dynamics relate to models of probabilistic language prediction during auditory narrative comprehension. We recorded MEG activity while participants were listening to auditory stories in Dutch. Using trigram statistical language models, we estimated for every word in a story its conditional probability of occurrence. On the basis of word probabilities, we computed how unexpected the current word is given its context (word perplexity) and how (un)predictable the current linguistic context is (word entropy). We then evaluated whether source-reconstructed MEG oscillations at different frequency bands are modulated as a function of these language processing metrics. We show that theta-band source dynamics are increased in high relative to low entropy states, likely reflecting lexical computations. Beta-band dynamics are increased in situations of low word entropy and perplexity possibly reflecting maintenance of ongoing cognitive context. These findings lend support to the idea that the brain engages in the active generation and evaluation of predicted language based on the statistical properties of the input signal.
Enhanced Stability of Non-Canonical NPC2 in the symbiosome supports coral-algal symbiosis
Authors: Hambleton Elizabeth A. , Jones Victor A.S. , Maegele Ira , vaskoff David K , Sachsenheimer Timo , Guse Annika 
Published: August 2018

AbstractCnidarians such as reef-building corals depend upon nutrient transfer from intracellular symbionts, but the mechanisms and evolution of this process remain unknown. Homologues of the conserved cholesterol binder Niemann-Pick Type C2 (NPC2) in cnidarians are implicated in the transfer of sterol from symbionts. Here, we show that symbionts transfer bulk sterols to the host, host sterol utilization is plastic, and pharmacological inhibition of sterol trafficking disrupts symbiosis. Having undergone an anthozoan-specific expansion, “non-canonical” NPC2s respond to symbiosis and accumulate over time at the lysosomal-like organelle in which the symbiont resides (“symbiosome”). We demonstrate that both a non- and canonicalAiptasiaNPC2 bind symbiont-produced sterols, yet only the non-canonical homologue exhibits increased stability at low pH. We propose that symbiotic cnidarians adapted pre-existing cholesterol-trafficking machinery to function in the highly acidic symbiosome environment, allowing corals to dominate nutrient-poor shallow tropical seas worldwide.
The Pemphigus Vulgaris antigen desmoglein-3 suppresses p53 function via the YAP-Hippo pathway
Authors: Rehman Ambreen , Cai Yang , Hünefeld Christian , Jedličková Hana , Huang Yunying , Teh M Teck , Uttagomol Jutamas , Kang Angray , Warnes Gary , Ahmad Usama , Harwood Catherine , Bergamaschi Daniele , Parkinson Eric Kenneth , Röcken Martin , Hart Ian , Wan Hong 
Published: August 2018

AbstractDesmoglein-3 (Dsg3), the Pemphigus Vulgaris (PV) antigen (PVA), plays an essential role in keratinocyte cell-cell adhesion and regulates various signaling pathways implicated in the pathogenesis the PV blistering disease. We show here that expression of Dsg3 may directly influence p53, a key transcription factor governing the response to cellular stress. Dsg3 depletion caused increased p53 and apoptosis, an effect that was further enhanced by UV and mechanical strain and reversed by Dsg3 gain-of-function studies. Analysis in Dsg3-/- mouse skin confirmed increased p53/p21/caspase-3 compared to Dsg3+/- control in vivo. This Dsg3-p53 pathway involved YAP since Dsg3 forms a complex with YAP and regulates its expression and localization. Analysis of PV patient samples detected increased p53/YAP with diffuse cytoplasmic and/or nuclear staining in cells surrounding blisters. Treatment of keratinocytes with PV sera evoked pronounced p53/YAP expression. Collectively, our findings establish a novel role for Dsg3 as an anti-stress protein, via suppression of p53 function, suggesting that this pathway, involving YAP-Hippo control of skin homeostasis, is disrupted in PV.
Hemagglutinin stalk-reactive antibodies interfere with influenza virus neuraminidase activity by steric hindrance
Authors: Chen Yao-Qing , Lan Linda Yu-Ling , Huang Min , Henry Carole , Wilson Patrick C. 
Published: August 2018

Abstract:Hemagglutinin (HA) stalk-reactive antibodies are the basis of several current “one-shot” universal influenza vaccine efforts because they protect against a wide spectrum of influenza virus strains. The appreciated mechanism of protection by HA-stalk antibodies is to inhibit HA stalk reconfiguration, blocking viral fusion and entry. This study shows that HA stalk-reactive antibodies also inhibit neuraminidase (NA) enzymatic activity, prohibiting viral egress. NA inhibition (NI) is evident for an attached substrate but not for unattached small molecule cleavage of sialic acid. This suggests that the antibodies inhibit NA enzymatic activity through steric hindrance, thus limiting NA access to sialic acids when adjacent to HA on whole virions. Consistently, F(ab’)2 fragments that occupy reduced area without loss of avidity or disrupted HA/NA interactions show significantly reduced NI activity. Notably, HA stalk binding antibodies lacking NI activity were unable to neutralize viral infection via microneutralization assays. This work suggests that NI activity is an important component of HA-stalk antibody mediated protection.SummaryThis study reports a new mechanism of protection that is mediated by influenza hemagglutinin-stalk reactive antibodies: inhibition of neuraminidase activity by steric hindrance, blocking access of neuraminidase to sialic acids when it is abutted next to hemagglutinin on whole virions.
Cold trapped - Correcting locomotion dependent observation biases in thermal preference ofDrosophila
Authors: Giraldo Diego , Adden Andrea K. , Kuhlemann Ilyas , Gras Heribert , Geurten Bart R. H. 
Published: August 2018

AbstractSensing environmental temperatures is essential for the survival of ectothermic organisms. InDrosophila,two methodologies are used to study temperature preferences (TP) and the genes involved in thermosensation: two-choice assays and temperature gradients. Whereas two-choice assays reveal a relative TP, temperature gradients can identify the absolute Tp. One drawback of gradients is that small ectothermic animals are susceptible to cold-trapping: a physiological inability to move at the cold area of the gradient. Often cold-trapping cannot be avoided, biasing the resulting TPto lower temperatures. Two mathematical models were previously developed to correct for cold-trapping. These models, however, focus on group behaviour which can lead to overestimation of cold-trapping due to group aggregation. Here we present a mathematical model that estimates the behaviour of individualDrosophilain temperature gradients. The model takes the spatial dimension and temperature difference of the gradient into account, as well as the rearing temperature of the flies. Furthermore, it allows quantifying cold-trapping, reveals true TP, and differentiates between temperature preference and tolerance. Online simulation is hosted athttp://igloo.uni-goettingen.de. The code can be accessed athttps://github.com/zerotonin/igloo.