bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases
Authors: Kato Kazuki , Ahmad Sadeem , Zhu Zixiang , Young Janet M. , Mu Xin , Park Sehoon , Malik Harmit S. , Hur Sun 
Published: August 2020

AbstractRNA helicases and ubiquitin E3 ligases mediate many critical functions within cells, but their actions have been studied largely in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryo-electron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity-driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass-spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses thus reveal not only conserved substrates for TRIM proteins but also unexpectedly deep evolutionary connections between TRIM proteins and RNA helicases, thereby linking ubiquitin and RNA biology throughout animal evolution.
Estimating fecundity and density dependence from mark-recapture data for making population projections
Authors: Şen Bilgecan , Akçakaya H. Reşit 
Published: August 2020

AbstractForecasting changes in size and distributions of populations is at the forefront of ecological sciences in the 21stcentury. Such forecasts require robust estimators of fecundity, survival and density-dependence. While survival estimation is the main focus of mark-recapture modelling, fecundity and density dependence are rarely the subject of these models. Here, we demonstrate that these parameters can be simultaneously estimated in a Bayesian framework using only robust design mark-recapture data. Using simulated capture histories, we show that this framework (which we named CJS-pop) can estimate vital rates and their density dependence with little bias. When CJS-pop is applied to capture history data from Brown Creeper (Certhia americana), it provides estimates of fecundity that is expected from the breeding biology of this species. Finally, we illustrate that density dependence, even when estimated with uncertainty in the CJS-pop framework, regularizes population dynamics and reduces the frequent population extinctions and explosions observed under density-independent models. While CJS-pop as a whole is a useful addition to the current mark-recapture modelling toolbox, we argue that the independent components of this framework in estimating fecundity and density dependence can be integrated to other CJS frameworks, potentially creating models capable of population projections.
Cell growth model with stochastic gene expression helps understand the growth advantage of metabolic exchange and auxotrophy
Authors: Dutta Dibyendu , Saini Supreet 
Published: August 2020

AbstractDuring cooperative growth, microbes often experience higher fitness, due to sharing of resources by metabolic exchange and herd protection through biofilm structures. However, the trajectory of evolution of competitive species towards cooperation is not known. Moreover, existing models (based on optimisation of steady-state resources or fluxes) are often unable to explain the growth advantage for the cooperating species, even for simple reciprocally cross-feeding auxotrophic pairs. We present an abstracted model of cell growth that considers the stochastic burst-like gene expression of biosynthetic pathways of limiting biomass precursor metabolites, and directly connects their cellular levels to growth and division using a “metabolic sizer/adder” rule. Our model recapitulates Monod’s law and yields the experimentally observed right-skewed long-tailed distribution of cell doubling times. The model further predicts the growth effect of secretion and uptake of metabolites, by linking it to changes in the internal metabolite levels. The model also explains why auxotrophs may grow faster when provided the metabolite they cannot produce, and why a pair of reciprocally cross-feeding auxotrophs can grow faster than prototrophs. Overall, our framework allows us to predict the growth effect of metabolic interactions in microbial communities and also sets the stage to study the evolution of these interactions.ImportanceCooperative behaviours are highly prevalent in the wild, but we do not understand how it evolves. Metabolic flux models can demonstrate the viability of metabolic exchange as cooperative interactions, but steady-state growth models cannot explain why cooperators grow faster. We present a stochastic model that connects growth to the cell’s internal metabolite levels and quantifies the growth effect of metabolite exchange and auxotrophy. We show that a reduction in gene expression noise explains why cells that import metabolites or become auxotrophs can grow faster, and also why reciprocal cross-feeding of metabolites between complementary auxotrophs allow them to grow faster. Our framework can simulate the growth of interacting cells, which will enable us to understand the possible trajectories of the evolution of cooperationin silico.
Toxoplasma gondiiinfections are associated with boldness towards lions in wild hyena hosts
Authors: Gering Eben , Laubach Zachary M. , Weber Patricia , Hussey Gisela Soboll , Lehmann Kenna D. S. , Montgomery Tracy M. , Turner Julie W. , Perng Wei , Pioon Malit O. , Holekamp Kay E. , Getty Thomas 
Published: August 2020

AbstractToxoplasma gondiiis widely reported to manipulate the behavior of its non-definitive hosts in ways that promote lethal interactions with the parasite’s definitive feline hosts. Nonetheless, there is a lack of data on the association betweenT. gondiiinfection and costly behavioral interactions with felids in nature. Here, we report that three decades of field observations revealT. gondiiinfected hyena cubs approach lions more closely than uninfected peers and have higher rates of lion mortality. Our findings support the hypothesis thatT. gondii’smanipulation of host boldness is an extended phenotype that promotes parasite transmission from intermediate hosts to feline predators. While upregulating hyena boldness toward lions might achieve this, it may also reflect a collateral influence of manipulative traits that evolved in other hosts (e.g., rodents). In either case, our findings corroborate the potential impacts of a globally distributed and generalist parasite (T. gondii) on fitness-related interaction with felids in a wild host.One Sentence SummaryWild hyenas infected with the parasiteT. gondiishow evidence of costly behavioral manipulation when interacting with lions.
Underlying microevolutionary processes parallel macroevolutionary patterns in ancient Neotropical Mountains
Authors: Dantas-Queiroz Marcos Vinicius , da Costa Cacossi Tami , Leal Bárbara Simões Santos , Chaves Cleber Juliano Neves , Vasconcelos Thais N. C. , de Melo Versieux Leonardo , Palma-Silva Clarisse 
Published: August 2020

ABSTRACTAimThe exceptional species-richness associated with mountains worldwide is linked to the fragmented topography of these areas, responsible for constantly isolating populations during periods of climatic fluctuations. Consequently, endemism and spatial turnover in mountains are very high and few species are widespread among entire mountain ranges, precluding population-level studies that help understanding how macroevolutionary patterns were shaped. Here, we used the bromeliadVriesea oligantha, a species endemic to, but widespread in, one of the most species-rich ancient montane areas in the globe, the Espinhaco Range, to test how environmental changes over time may have acted on the evolutionary history of this taxon, contributing to understanding how montane macroevolutionary patterns were shaped. Through analyses of plastidial and nuclear DNA ofV. oligantha, we dated its origin and intraspecific diversification, and estimated the genetic diversity, structure and migration rates among populations. Using climatic and geographic variables, we modeled suitable areas for the present and the past, estimating corridors between isolated populations. We also used demographic analyses to estimate ancient population dynamics ofV. oligantha. Finally, we tested whether climatic variables or geographical distance explain the observed population structure. The origin and intraspecific diversification ofV. oliganthaare related to early climatic oscillations during the Plio-Pleistocene. This species has a high population structure due to its low pollen and seed dispersibility. The analysis of species distribution modeling estimated corridors between populations in the past, whereas the structure ofV. oligantharesults from both models of isolation by distance and isolation by environment. The phylogeographic patterns ofVriesea oliganthareflect previously recognized spatial and temporal macroevolutionary patterns in the Espinhaco Range, providing insights into how microevolutionary processes may have given rise to this astonishing mountain biodiversity.
A biophysical and structural analysis of DNA binding by oligomeric hSSB1 (NABP2/OBFC2B)
Authors: El-Kamand Serene , Jergic Slobodan , Lawson Teegan , Kariawasam Ruvini , Richard Derek J. , Cubeddu Liza , Gamsjaeger Roland 
Published: August 2020

AbstractThe oxidative modification of DNA can result in the loss of genome integrity and must be repaired to maintain overall genomic stability. We have recently demonstrated that human single stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) plays a crucial role in the removal of 8-oxo-7,8-dihydro- guanine (8-oxoG), the most common form of oxidative DNA damage. The ability of hSSB1 to form disulphide-bonded tetramers and higher oligomers in an oxidative environment is critical for this process. In this study, we have used nuclear magnetic resonance (NMR) spectroscopy and surface plasmon resonance (SPR) experiments to determine the molecular details of ssDNA binding by oligomeric hSSB1. We reveal that hSSB1 oligomers interact with single DNA strands containing damaged DNA bases; however, our data also show that oxidised bases are recognised in the same manner as undamaged DNA bases. We further demonstrate that oxidised hSSB1 interacts with ssDNA with a significantly higher affinity than its monomeric form confirming that oligomeric proteins such as tetramers can bind directly to ssDNA. NMR experiments provide evidence that oligomeric hSSB1 is able to bind longer ssDNA in both binding polarities using a distinct set of residues different to those of the related SSB fromEscherichia coli.
Chemokines as phosphatidylserine-bound ‘find-me’ signals in apoptotic cell clearance
Authors: Pontejo Sergio M. , Murphy Philip M. 
Published: August 2020

AbstractChemokines are positively charged cytokines that attract leukocytes by binding to anionic glycosaminoglycans (GAGs) on endothelial cells for efficient presentation to leukocyte G protein-coupled receptors (GPCRs). The atypical chemokine CXCL16 has been reported to also bind the anionic phospholipid phosphatidylserine (PS), but the biological relevance of this interaction remains poorly understood. Here we demonstrate that PS binding is in fact a widely shared property of chemokine superfamily members that, like GAG binding, induces chemokine oligomerization. PS is an essential phospholipid of the inner leaflet of the healthy cell plasma membrane but it is exposed in apoptotic cells to act as an ‘eat-me’ signal that promotes engulfment of dying cells by phagocytes. We found that chemokines can bind PS in pure form as well as in the context of liposomes and on the surface of apoptotic cells and extracellular vesicles released by apoptotic cells, which are known to act as ‘find-me’ signals that chemoattract phagocytes during apoptotic cell clearance. Importantly, we show that GAGs are severely depleted from the surface of apoptotic cells and that extracellular vesicles extracted from apoptotic mouse thymus bind endogenous thymic chemokines and activate cognate chemokine receptors. Together these results indicate that chemokines tethered to surface-exposed PS may be responsible for the chemotactic and find-me signal activity previously attributed to extracellular vesicles, and that PS may substitute for GAGs as the anionic scaffold that regulates chemokine oligomerization and presentation to GPCRs on the GAG-deficient membranes of apoptotic cells and extracellular vesicles. Here, we present a new mechanism by which extracellular vesicles, currently recognized as essential agents for intercellular communication in homeostasis and disease, can transport signaling cytokines.
Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome
Authors: Lago Sara , Cernilogar Filippo M. , Kazerani Maryam , Moreno Helena Domíniguez , Nadai Matteo , Schotta Gunnar , Richter Sara N. 
Published: August 2020

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization1-3. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity4,5. By G4 ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with high G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s strongly emerge as new epigenetic regulators of the transcription machinery.
MitoROS due to loss ofSlc4a11in corneal endothelial cells induces ER stress, lysosomal dysfunction and impairs autophagy
Authors: Shyam Rajalekshmy , Ogando Diego G. , Choi Moonjung , Bonanno Joseph A. 
Published: August 2020

AbstractRecent studies fromSlc4a11KO mice have identified mitochondrial dysfunction as a major contributor toward oxidative stress and cell death in Congenital Hereditary Endothelial Dystrophy. Here we asked if this stress activated autophagy in theSlc4a11KO cell line and in KO mouse endothelial tissue. Early indicators of autophagy, phospho-mTOR and LC3-II indicated activation, however P62 was elevated suggesting an impairment of autophagy flux. The activity and the number of lysosomes, the organelle responsible for the final degradation of autophagy substrates, were found to be reduced in the KO. In addition, the expression of the master regulator of lysosomal function and biogenesis, TFEB, was significantly reduced in the KO corneal endothelia. Also, we observed increased Unfolded Protein Response, as well as elevated expression of ER stress markers, BIP and CHOP. To test if lysosomal and ER stress stems from elevated mitochondrial ROS, we treatedSlc4a11KO corneal endothelial cells with the mitochondrial ROS quencher, MitoQ. MitoQ restored lysosomal enzymes as well as TFEB, reduced ER stress, and increased autophagy flux. MitoQ injections ofSlc4a11 KOmice decreased corneal edema, the major phenotype associated with CHED. We conclude that mitochondrial ROS causes ER stress and lysosomal dysfunction with impairment of autophagy inSlc4a11KO corneal endothelium. Our study is the first to identify the presence as well as cause of lysosomal dysfunction and ER stress in an animal model of CHED, and to characterize inter-organelle relationship in a corneal cell type.
Efficient generation of endogenous protein reporters for mouse preimplantation embryos
Authors: O’Hagan Dan , Ralston Amy 
Published: August 2020

SummaryFluorescent proteins and epitope tags can reveal protein localization in cells and animals. However, the large size of many tags hinders efficient genome targeting. Accordingly, many studies have relied on characterizing overexpressed proteins, which might not recapitulate endogenous protein activities. We present two approaches for higher throughput production of endogenous protein reporters. Our first approach makes use of a split fluorescent protein mNeonGreen2 (mNG2). Knock-in of a small portion of themNG2gene, in frame with gene coding regions of interest was highly efficient in embryos, eliminating the need to establish mouse lines. When complemented by the larger portion of themNG2gene, fluorescence was reconstituted and endogenous protein localization faithfully reported in living embryos. However, we report a threshold of detection using this approach. By contrast, the V5 epitope enabled high efficiency and higher sensitivity protein reporting. We describe complementary advantages and prospective applications of these two approaches.HighlightsSplit fluorescent protein for in vivo protein localization in living embryosV5 tagging for in vivo localization of low abundance proteinsBypassing the need for founder mouse lines for preimplantation studiesGuidelines and strategies for implementation and prospective applications
Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms
Authors: Cheong Alex , Johnson Chad , Wan Hanxiao , Liu Aiping , Kernien John , Gibson Angela , Nett Jeniel , Kalan Lindsay R. 
Published: August 2020

AbstractA hallmark of chronic infections are polymicrobial biofilms. The forces governing assembly and maturation of these microbial ecosystems are largely unexplored but the consequences on host response and clinical outcome can be significant. In the context of wound healing, formation of a biofilm and a stable microbial community structure is associated with impaired tissue repair resulting in a non-healing chronic wound. These types of wounds can persist for years simmering below the threshold of classical clinical infection or cycling through phases of recurrent infection. In the most severe outcome amputation of lower extremities may occur if spreading infection ensues. Here we take an ecological perspective to study priority effects and competitive exclusion on overall biofilm community structure in a three-membered community of microbes derived from a chronic wound. We find that priority effects occur across both biotic and abiotic substrates, and ecological interactions can alter both fungal physiology and host inflammatory response. We show that bacterial-competition occurs for binding to fungal structures, and some species trigger the yeast-hyphae switch, resulting in enhanced neutrophil killing and inflammation. Collectively, the results presented here facilitate our understanding of fungal-bacterial microbial community dynamics and their effects on, host-microbe interactions, pathogenesis, and ultimately, wound healing.
Auditory beat stimulation modulates memory-related single-neuron activity in the human medial temporal lobe
Authors: Derner M , Chaieb L , Dehnen G , Reber TP , Borger V , Surges R , Staresina BP , Mormann F , Fell J 
Published: August 2020

AbstractAuditory beats are composed of two sine waves using nearby frequencies, which can either be applied as a superposed signal to both ears or to each ear separately. In the first case, the beat sensation results from hearing an amplitude-modulated signal (monaural beat). In the second case, it is generated by phase-sensitive neurons in the brain stem (binaural beat). We investigated the effects of monaural and binaural 5 Hz beat stimulation on neural activity and memory performance in neurosurgical patients performing an associative recognition task. Previously, we had reported that these beat stimulation conditions modulated memory performance in opposite directions. Here, we analyzed data from a patient subgroup, in which microwires were implanted in the amygdala, hippocampus, entorhinal cortex and parahippocampal cortex. We identified neurons responding with firing rate changes to binaural versus monaural 5 Hz beat stimulation. In these neurons, we correlated the differences in firing rates for binaural versus monaural beats to the memory-related differences for remembered versus forgotten items and associations. In the left hemisphere for these neurons, we detected statistically significant negative correlations between firing rate differences for binaural versus monaural beats and remembered versus forgotten items/associations. Importantly, such negative correlations were also observed between beat stimulation-related firing rate differences in the baseline window and memory-related firing rate differences in the poststimulus windows. In line with concepts of homeostatic plasticity, we interpret our findings as indicating that beat stimulation is linked to memory performance via shifting baseline firing levels.
Regulation of Vacuole Morphology by PIEZO Channels in Spreading Earth Moss
Authors: Radin Ivan , Richardson Ryan A. , Weiner Ethan R. , Bascom Carlisle S. , Bezanilla Magdalena , Haswell Elizabeth S. 
Published: August 2020

AbstractThe perception of mechanical force is a fundamental property of most, if not all cells. PIEZO channels are plasma membrane-embedded mechanosensitive calcium channels that play diverse and essential roles in mechanobiological processes in animals1,2. PIEZO channel homologs are found in plants3,4, but their role(s) in the green lineage are almost completely unknown. Plants and animals diverged approximately 1.5 billion years ago, independently evolved multicellularity, and have vastly different cellular mechanics5. Here, we investigate PIEZO channel function in the mossPhyscomitrium patens, a representative of one of the first land plant lineages.PpPIEZO1 andPpPIEZO2 were redundantly required for normal growth, size, and shape of tip-growing caulonema cells. Both were localized to vacuolar membranes and facilitated the release of calcium into the cytosol in response to hypoosmotic shock. Loss-of-function (ΔPppiezo1/2) and gain-of-function (PpPIEZO2-R2508Kand-R2508H) mutants revealed a role for moss PIEZO homologs in regulating vacuole morphology. Our work here shows that plant and animal PIEZO homologs have diverged in both subcellular localization and in function, likely co-opted to serve different needs in each lineage. The plant homologs of PIEZO channels thus provide a compelling lens through which to study plant mechanobiology and the evolution of mechanoperceptive strategies in multicellular eukaryotes.