bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Universal Allosteric Mechanism for G Protein Activation
Authors: Knight Kevin M. , Ghosh Soumadwip , Campbell Sharon L. , Lefevre Tyler J. , Olsen Reid H. J. , Smrcka Alan V. , Valentin Natalie H. , Yin Guowei , Vaidehi Nagarajan , Dohlman Henrik G. 
Published: November 2020

SUMMARYG proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote GTP binding and the dissociation of Gα from the Gβγ subunits. Structural studies have revealed the molecular basis for subunit association with receptors, RGS proteins and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We used cell signaling assays, MD simulations, biochemistry and structural analysis to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This “G-R-E motif” secures GTP and, through an allosteric link, discharges the Gβγ dimer. Replacement of network residues prevents subunit dissociation, regardless of agonist or GTP binding. These findings reveal the molecular basis for the final committed step of G protein activation.HIGHLIGHTSReceptors promote GTP-GDP exchange and dissociation of G protein α and βγ subunitsWe find an allosteric network linking the γ phosphate of GTP with release of GβγThe network consists of a conserved Gly-Arg-Glu “activation triad”Triad mutations prevent subunit dissociation, regardless of agonist or GTP bindingTriad mutations are responsible for human endocrine and neurological disorders
α-Synuclein emerges as a potent regulator of VDAC-facilitated calcium transport
Authors: Rosencrans William M. , Aguilella Vicente M. , Rostovtseva Tatiana K. , Bezrukov Sergey M. 
Published: November 2020

AbstractWhen the Parkinson’s disease (PD) related neuronal protein, alpha-synuclein (αSyn), is added to the reconstituted mitochondrial voltage-dependent anion channel (VDAC), it reversibly and partially blocks VDAC conductance by its acidic C-terminal tail. Using single-molecule electrophysiology of reconstituted VDAC we now demonstrate that, at CaCl2concentrations below 150 mM, αSyn reverses the channel’s selectivity from anionic to cationic. Importantly, we find that the decrease in channel conductance upon its blockage by αSyn is hugely overcompensated by a favorable change in the electrostatic environment for calcium, making the blocked state orders-of-magnitude more selective for calcium and thus increasing its net flux. These findings reveal a new regulatory role of αSyn, with clear implications for both normal calcium signaling and PD-associated mitochondrial dysfunction.
The selective estrogen receptor modulator tamoxifen protects against subtle cognitive decline and early markers of injury twenty-four hours after hippocampal silent infarct
Authors: Finney Caitlin A. , Shvetcov Artur , Westbrook R. Frederick , Morris Margaret J. , Jones Nicole M. 
Published: November 2020

AbstractSilent infarcts (SI) are subcortical cerebral infarcts that occur in the absence of typical symptoms associated with ischemia but are linked to cognitive decline and the development of dementia. There are no approved treatments for SI, but one potential treatment is tamoxifen, a selective estrogen receptor modulator. While SI can have long-term consequences, it is critical to establish whether treatments are able to selectively target its early consequences, to avoid progression to complete injury. We induced SI in the dorsal hippocampal CA1 of rats and assessed whether tamoxifen is protective 24 hours later against cognitive deficits and injury responses to SI including gliosis, apoptosis, inflammation and changes in estrogen receptors (ERs). Hippocampal SI led to subtle cognitive impairment on the object place recognition task, an effect ameliorated by tamoxifen administration. SI did not lead to detectable hippocampal cell loss but did increase apoptosis, astrogliosis, microgliosis and inflammation. Tamoxifen protected against the effects of SI on all measures except microgliosis. SI also increased ERα and decreased ERβ in the hippocampus, which was again mitigated by tamoxifen. Exploratory data analyses using scatterplot matrices and principal component analysis indicated that the SI rats given tamoxifen were indistinguishable from sham controls. Further, SI rats were significantly different from all other groups, an effect produced by low levels of ERα and increased apoptosis, gliosis, inflammation, ERβ, and time spent with the unmoved object. The results demonstrate that tamoxifen is protective against the early cellular and cognitive consequences of hippocampal SI as early as 24 hours after injury. This effect is driven by mitigation of apoptosis, gliosis, and inflammation and normalization of ER levels in the CA1, leading to improved cognitive outcomes after hippocampal SI.
Distinct hydrogenotrophic bacteria are stimulated by elevated H2levels in upland and wetland soils
Authors: Xu Yongfeng , Teng Ying , Dong Xiyang , Wang Xiaomi , Zhang Chuwen , Ren Wenjie , Zhao Ling , Luo Yongming , Greening Chris 
Published: November 2020

AbstractBackgroundMolecular hydrogen (H2) is a major energy source supporting bacterial growth and persistence in soil ecosystems. While recent studies have uncovered mediators of atmospheric H2consumption, far less is understood about how soil microbial communities respond to elevated H2levels produced through natural or anthropogenic processes. Here we performed microcosm experiments to resolve how microbial community composition, capabilities, and activities change in upland (meadow, fluvo-aquic soil) and wetland (rice paddy, anthrosols soil) soils following H2supplementation (at mixing doses from 0.5 to 50,000 ppmv).ResultsGenome-resolved metagenomic profiling revealed that these soils harbored diverse bacteria capable of using H2as an electron donor for aerobic respiration (46 of the 196 MAGs from eight phyla) and carbon fixation (15 MAGs from three phyla). H2stimulated the growth of several of these putative hydrogenotrophs in a dose-dependent manner, though the lineages stimulated differed between the soils; whereas actinobacterial lineages encoding group 2a [NiFe]-hydrogenases grew most in the upland soils (i.e. Mycobacteriaceae, Pseudonocardiaceae), proteobacterial lineages harboring group 1d [NiFe]-hydrogenases were most enriched in wetland soils (i.e. Burkholderiaceae). Hydrogen supplementation also influenced the abundance of various other genes associated with biogeochemical cycling and bioremediation pathways to varying extents between soils. Reflecting this, we observed an enrichment of a hydrogenotrophicNoviherbaspirillumMAG capable of biphenyl hydroxylation in the wetland soils and verified that H2supplementation enhanced polychlorinated biphenyl (PCB) degradation in these soils, but not the upland soils.ConclusionsOur findings suggest that soils harbour different hydrogenotrophic bacteria that rapidly grow following H2exposure. In turn, this adds to growing evidence of a large and robust soil H2sink capable of counteracting growing anthropogenic emissions.
Effects of water content and mesh size on tea bag decomposition
Authors: Mori Taiki , Aoyagi Ryota , Taga Hiroki , Sakai Yoshimi 
Published: November 2020

AbstractThe tea bag method was developed to provide uniform litter bags that enable comparison of organic matter decomposition rates on a large scale. However, it remains uncertain whether tea bag decomposition in response to wetness is representative of that of natural litters. We performed incubation experiments to examine whether the effect of soil water on tea bag decomposition becomes inhibitory at higher water contents, as was demonstrated in natural leaf litters. In addition, we performed field studies in a mixed forest and cedar plantation in Japan to compare two litter bag mesh sizes: 0.25-mm mesh, the size previously used by a major manufacturer of tea bags (Lipton), and nonwoven bags with mesh sizes finer than 0.25 mm, which are currently produced by Lipton. Both green tea and rooibos tea exhibited higher decomposition rates at higher water contents, but decomposition was inhibited at the highest water content, consistent with conceptual models of natural litters. The nonwoven tea bags did not show lower decomposition rates, despite the finer mesh size. Rather, the nonwoven rooibos tea bags exhibited slightly higher decomposition rates than the 0.25-mm mesh bags in the cedar plantation, possibly due to a greater abundance of microorganisms that decompose litters in the nonwoven bags, due to the decrease in predation by mesofauna. Our findings provide essential information for future studies of tea bag decomposition.
Studying trajectories of multimorbidity: a systematic scoping review of longitudinal approaches and evidence
Authors: Cezard Genevieve , McHale Calum , Sullivan Frank , Bowles Juliana , Keenan Katherine 
Published: November 2020

ABSTRACTObjectivesMultimorbidity – the co-occurrence of at least two chronic diseases in an individual-is an important public health challenge in ageing societies. The vast majority of multimorbidity research takes a cross-sectional approach, but longitudinal approaches to understanding multimorbidity are an emerging research area, being encouraged by multiple funders. To support development in this research area, the aim of this study is to scope the methodological approaches and substantive findings of studies which have investigated longitudinal multimorbidity trajectories.DesignWe conducted a systematic search for relevant studies in four online databases (Medline, Scopus, Web of Science, and Embase) using pre-defined search terms and inclusion and exclusion criteria. The search was complemented by searching reference lists of relevant papers. From the selected studies we systematically extracted data on study methodology and findings, and summarised them in a narrative synthesis.ResultsWe identified 34 studies investigating multimorbidity longitudinally, all published in the last decade, and predominantly in high-income countries from the Global North. Longitudinal approaches employed included constructing change variables, multilevel regression analysis (e.g. growth curve modelling), longitudinal group-based methodologies (e.g. latent class modelling), analysing disease transitions, and visualisation techniques. Commonly identified risk factors for multimorbidity onset and progression were older age, higher socio-economic and area-level deprivation, overweight, and poorer health behaviours.ConclusionThe nascent research area employs a diverse range of longitudinal approaches that characterize accumulation and disease combinations, and to a lesser extent disease sequencing and progression. Gaps include understanding the long-term, life course determinants of different multimorbidity trajectories, and doing so in across diverse populations, including those from low and middle-income countries. This can provide a detailed picture of morbidity development, with important implications from a clinical and intervention perspective.STRENGTHS AND LIMITATIONS OF THE STUDYThis is the first systematic review to focus on studies that take a longitudinal, rather than cross-sectional, approach to multimorbidity.Systematic searches of online academic databases were performed using pre-defined search terms, as well as searching of reference lists, and this is reported using PRISMA guidelines.For selected papers, data was double extracted using standardised proformas to aid narrative synthesis.Due to the heterogeneity of the studies included, their weaknesses were described in the narrative synthesis, but we did not perform quality assessment using standardised tools.
Clustering of death receptor for apoptosis using nanoscale patterns of peptides
Authors: Wang Yang , Baars Igor , Fördös Ferenc , Högberg Björn 
Published: November 2020

AbstractThe nanoscale spatial organization of transmembrane tumor necrosis factor (TNF) receptors has been implied as a regulator of cellular fate. Accordingly, molecular tools that can induce specific arrangements of these receptors on cell surfaces would give us an opportunity to study these effects in detail. To achieve this, we introduce DNA origami nanostructures, that precisely scaffold the patterning of TNF-related apoptosis-inducing ligand (TRAIL)-mimicking peptides at nanoscale level. Stimulating human breast cancer cells with these patterns, we find that around 5 nm is the critical inter-ligand distance of hexagonally patterned peptides to induce death receptor clustering and a resulting apoptosis. We thus offer a strategy to reverse the non-efficacy of current ligand- and antibody-based methods for TNF superfamily (TNFRSF) activation.
A RNF12-USP26 amplification loop promotes germ cell specification and is disrupted in urogenital disorders
Authors: Segarra-Fas Anna , Bustos Francisco , Toth Rachel , Nardocci Gino , Findlay Greg M. 
Published: November 2020

SummaryUbiquitylation regulates all aspects of development, and components are frequently mutated in developmental disorders. Tonne-Kalscheuer Syndrome (TOKAS) is a X-linked multiple congenital anomaly disorder caused by mutations in the E3 ubiquitin ligase RNF12/RLIM and characterized by intellectual disability and urogenital abnormalities. However, the molecular underpinnings of TOKAS remain largely unknown. Here, we show that RNF12 catalytic activity relieves gene repression to drive a transcriptional program required for germ cell development and priming of pluripotent cells towards the germline. A major feature of the RNF12-dependent gametogenesis gene program is a transcriptional feed-forward loop featuring the deubiquitylaseUsp26/USP26.Usp26/USP26 induction stabilises RNF12 to amplify transcriptional responses, which is disrupted by RNF12 TOKAS mutations and USP26 variants identified in patients with fertility defects. In summary, we uncover remarkable synergy within a ubiquitylation cycle that controls expression of key genes required for germ cell development and is disrupted in patients with urogenital abnormalities.
The nature of mitotic forces in epithelial monolayers
Authors: Gupta Vivek K. , Nam Sungmin , Camuglia Jaclyn , Martin Judy Lisette , Sanders Erin Nicole , O’Brien Lucy Erin , Martin Adam C. , Kim Taeyoon , Chaudhuri Ovijit 
Published: November 2020

AbstractEpithelial cells undergo striking morphological changes during mitosis to ensure proper segregation of genetic and cytoplasmic materials. These morphological changes occur despite dividing cells being mechanically restricted by neighboring cells, indicating the need for extracellular force generation. While forces generated during mitotic rounding are well understood, forces generated after rounding remain unknown. Here, we identify two distinct stages of mitotic force generation that follow rounding: (1) protrusive forces along the mitotic axis that drive mitotic elongation, and (2) outward forces that facilitate post-mitotic re-spreading. Cytokinetic ring contraction of the mitotic cell, but not activity of neighboring cells, generates extracellular forces that propel mitotic elongation and also contribute to chromosome separation. Forces from mitotic elongation are observed in epithelia across many model organisms. Thus, forces from mitotic elongation represent a universal mechanism that powers mitosis in confining epithelia.
Sedimentary ancient DNA shows terrestrial plant richness continuously increased over the Holocene in northern Fennoscandia
Authors: Rijal Dilli P. , Heintzman Peter D. , Lammers Youri , Yoccoz Nigel G. , Lorberau Kelsey E. , Pitelkova Iva , Goslar Tomasz , Murguzur Francisco J.A. , Salonen J. Sakari , Helmens Karin F. , Bakke Jostein , Edwards Mary E. , Alm Torbjørn , Bråthen Kari A. , Brown Antony G. , Alsos Inger G. 
Published: November 2020

AbstractThe effects of climate change on species richness is debated but can be informed by the past. Here, we assess the impact of Holocene climate changes and nutrients on terrestrial plant richness across multiple sites from northern Fennoscandia using new sedimentary ancient DNA (sedaDNA) data quality control methods. We find that richness increased steeply during the rapidly warming Early Holocene. In contrast to findings from most pollen studies, we show that richness continued to increase through the Middle to Late Holocene even though temperature decreased, with the regional species pool only stabilizing during the last two millennia. Furthermore, overall increase in richness was greater in catchments with higher soil nutrient availability. We suggest that richness will rapidly increase with ongoing warming, especially at localities with high nutrient availability and even in the absence of increased human activity in the region, although delays of millennia may be expected.
Modeling of symbiotic bacterial biofilm growth with an example of theStreptococcus-Veillonellasp. system
Authors: Feng Dianlei , Neuweiler Insa , Nogueira Regina , Nackenhorst Udo 
Published: November 2020

AbstractWe present a multi-dimensional continuum mathematical model for modeling the growth of a symbiotic biofilm system. We take a dual-species namely, theStreptococcus - Veillonellasp. biofilm system as an example for numerical investigations. The presented model describes both the cooperation and competition between these species of bacteria. The coupled partial differential equations are solved by using an integrative finite element numerical strategy. Numerical examples are carried out for studying the evolution and distribution of the bio-components. The results demonstrate that the presented model is capable of describing the symbiotic behavior of the biofilm system. However, homogenized numerical solutions are observed locally. To study the homogenization behavior of the model, numerical investigations regarding on how random initial biomass distribution influences the homogenization process are carried out. We found that a smaller correlation length of the initial biomass distribution leads to faster homogenization of the solution globally, however, shows more fluctuated biomass profiles along the biofilm thickness direction. More realistic scenarios with bacteria in patches are also investigated numerically in this study.
TNF stimulation primarily modulates transcriptional burst size of NF-κB-regulated genes
Authors: Bass Victor L. , Wong Victor C. , Bullock M. Elise , Gaudet Suzanne , Miller-Jensen Kathryn 
Published: November 2020

AbstractCell-to-cell heterogeneity is a characteristic feature of the tumor necrosis factor (TNF)-stimulated inflammatory response mediated by the transcription factor NF-κB, motivating an exploration of the underlying sources of this noise. Here we combined single-transcript measurements with computational models to study transcriptional noise at six NF-κB-regulated inflammatory genes. In the basal state, NF-κB-target genes displayed an inverse correlation between mean and noise. TNF stimulation increased transcription while maintaining noise, except for the most repressed genes. By fitting transcript distributions to a two-state model of promoter activity, we found that TNF primarily stimulated transcription by increasing burst size while maintaining burst frequency. Burst size increases were associated with enrichment of initiated-but-paused RNA polymerase II at the promoter, and blocking the release of paused RNAPII with a small molecule inhibitor decreased TNF-stimulated burst size. Finally, we used a mathematical model to show that TNF positive feedback further amplified gene expression noise resulting from burst-size mediated transcription, leading to diverse TNF functional outputs. Our results reveal potential sources of noise underlying intercellular heterogeneity in the TNF-mediated inflammatory response.
Trees and their seed networks: the social dynamics of urban fruit trees and implications for genetic diversity
Authors: Rimlinger Aurore , Avana Marie-Louise , Awono Abdon , Chakocha Armel , Gakwavu Alexis , Lemoine Taïna , Marie Lison , Mboujda Franca , Vigouroux Yves , Johnson Vincent , Vinceti Barbara , Carrière Stéphanie M. , Duminil Jérôme 
Published: November 2020

AbstractTrees are a traditional component of urban spaces where they provide ecosystem services critical to urban wellbeing. In the Tropics, urban trees’ seed origins have rarely been characterized. Yet, understanding the social dynamics linked to tree planting is critical given their influence on the distribution of associated genetic diversity. This study examines elements of these dynamics (seed exchange networks) in an emblematic indigenous fruit tree species from Central Africa, the African plum tree (Dacryodes edulis, Burseraceae), within the urban context of Yaoundé. We further evaluate the consequences of these social dynamics on the distribution of the genetic diversity of the species in the city. Urban trees were planted predominantly using seeds sourced from outside the city, resulting in a level of genetic diversity as high in Yaoundé as in a whole region of production of the species. Debating the different drivers that foster the genetic diversity in planted urban trees, the study argued that cities and urban dwellers can unconsciously act as effective guardians of indigenous tree genetic diversity.
Seizing diminishing habitat conservation and restoration opportunities in the Tampa Bay, FL watershed: An urban estuary in recovery
Authors: Raulerson Gary E , Robison Douglas E , Beck Marcus W , Burke Maya C , Ries Thomas F , Saarinen Justin A , Sciarrino Christine M , Sherwood Edward T , Tomasko David A 
Published: November 2020

AbstractHabitat restoration efforts should integrate past trends, current status, expected climate change and coastal development impacts, remaining realistic opportunities, and resource management community capabilities. Integrating these concepts, a new target setting approach is being implemented in the Tampa Bay region with broad transferability potential. Past changes, as determined through a three-decade habitat change analysis and over forty years of habitat restoration experience in the region, has informed the new approach. It is also primarily focused on what is possible today and the projected needs for the future, rather than focusing on or attempting to replicate past ecological conditions. Likewise, this new paradigm accounts for persistent local and global stressors – especially watershed development, sea level rise, and climate change. As such, newly established numeric targets are “place-based,” meaning that they attempt to maximize the remaining restoration and conservation “opportunity areas” within the watershed. Lastly, the approach is comprehensive in that targets for the range of critical habitats, from subtidal to uplands, are now defined. This approach represents a general framework for addressing competing interests in planning for habitat restoration that could be applied in other coastal settings where sustainable urbanization practices are desired to co-exist with natural environments.