bluuebunny/crossref_metadata_2025_split huggingface dataset:
NO GAMETOPHORES 2is a novel regulator of the 2D to 3D growth transition in the mossPhyscomitrium patens
Authors: Moody Laura A. , Kelly Steven , Clayton Roxaana , Weeks Zoe , Emms David M. , Langdale Jane A. 
Published: July 2020

SUMMARYThe colonization of land by plants was one of the most transformative events in the history of life on Earth. The transition from water, which coincided with and was likely facilitated by the evolution of 3-dimensional (3D) growth, enabled the generation of morphological diversity on land. In many plants, the transition from 2-dimensional (2D) to 3D growth occurs during embryo development. However, in the early divergent mossPhyscomitrium patens(formerlyPhyscomitrella patens), 3D growth is preceded by an extended filamentous phase that can be maintained indefinitely. Here, we describe the identification of the cytokinin-responsiveNO GAMETOPHORES 2(PpNOG2) gene, which encodes a shikimate o- hydroxycinnamoyltransferase. In mutants lackingPpNOG2function, transcript levels ofCLAVATAandSCARECROWgenes are significantly reduced, excessive gametophore initial cells are produced, and buds undergo premature developmental arrest. Our results suggest that PpNOG2 functions in the ascorbic acid pathway leading to cuticle formation, and that NOG2-related genes were co-opted into the lignin biosynthesis pathway after the divergence of bryophytes and vascular plants. We present a revised model of 3D growth in which PpNOG2 comprises part of a feedback mechanism that is required for the modulation of gametophore initial cell frequency. We also propose that the 2D to 3D growth transition inP. patensis underpinned by complex auxin-cytokinin crosstalk that is regulated, at least in part, by changes in flavonoid metabolism.
Inference and analysis of cell-cell communication using CellChat
Authors: Jin Suoqin , Guerrero-Juarez Christian F. , Zhang Lihua , Chang Ivan , Myung Peggy , Plikus Maksim V. , Nie Qing 
Published: July 2020

AbstractUnderstanding global communications among cells requires accurate representation of cell-cell signaling links and effective systems-level analyses of those links. We constructed a database of interactions among ligands, receptors and their cofactors that accurately represents known heteromeric molecular complexes. Based on mass action models, we then developed CellChat, a tool that is able to quantitively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data. CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches. Through manifold learning and quantitative contrasts, CellChat classifies signaling pathways and delineates conserved and context-specific pathways across different datasets. Applications of CellChat to several mouse skin scRNA-seq datasets for embryonic development and adult wound healing shows its ability to extract complex signaling patterns, both previously known as well as novel. Our versatile and easy-to-use toolkit CellChat and a web-based Explorer (http://www.cellchat.org/) will help discover novel intercellular communications and build a cell-cell communication atlas in diverse tissues.
The role of Vitamin C in the energy supply of cells Hypothetical structure for energy transformation
Authors: Hunyady János 
Published: July 2020

SummaryThe present paper represents a hypothetical structure, the structure for energy transformation (SET), which might be responsible for the proper energy transformation steps leading to the continuous production of H+and ATP in living cells. We predict that the electron flow is realized through the electron flow device (EFD). We suppose that there are several versions of the SET. Two of them are described below [Structure of Aerobic Glycolysis (SET-AG) and Structure of Oxidative Phosphorylation (SET-OP)]. The hypothesis is based on the atom properties of the protonated adenine molecule and the docking computations of molecular mechanics involved, suggesting that two ascorbate molecules may occupy the empty NADPH pocket, preferably binding to the adenine binding site. We hypothesize that the adenine originates from uric acid (UA), resulting in an ATP-UA-ADP-ATP-UA cycle. It would also mean that UA is one of the oxygen sources in aerobic glycolysis.We also suppose that the EFD contains the well-known molecules of the Nicotinamide Adenine Dinucleotide (NAD) and Flavin Adenine Dinucleotide (FAD) supplemented with two additional UA-originated adenine molecules, two L-ascorbic acids, and two D-glucose molecules. Based on all this, we surmise that a tetra adenine octo phosphate ring (TAR) exists, in which the UA originated adenine molecules form a ring. The molecules are linked to each other through the N7-C2 and C8-N1 atoms of the adenine molecules by H2PO4e-molecules. The four N10 atoms of the adenine molecules bind one flavin, one nicotinamide, and two L-ascorbic acid molecules. Six D-glucose molecules complete one Unit of the structure. Both Fe-S and cytochrome clusters, as well as dehydrogenases, ensure the continuous operation of the Unit. The synchronized function of the three-stoke, three twin-cylinder engine results in continuous energy, ATP, and H+production. Eukaryotic cells are equipped with the SET-AG and the SET-OP; thus, they can live in an anoxic and oxygenized environment. It is hoped that the SET concept developed here will help the better understanding the way of action regarding the cancer treatment with Vitamin C or glucose deprivation.
Endogenous zebrafish proneural Cre drivers generated by CRISPR/Cas9 short homology directed targeted integration
Authors: Almeida Maira P. , Welker Jordan M. , Ekker Stephen C. , Clark Karl J. , Essner Jeffrey J. , McGrail Maura 
Published: July 2020

AbstractThe Cre/loxrecombinase system has been widely used for spatiotemporal control of gene expression in animal model systems, however, efficient methods to isolate zebrafish Cre drivers that reliably recapitulate endogenous gene expression patterns are needed. Here, we apply CRISPR/Cas9 targeting to integrate a 2A-Cre recombinase transgene with 48bp homology arms into proneural genesascl1b,olig2andneurod1. We observed high rates of germline transmission ranging from 10%-100% (2/20olig2; 1/5neurod1; 3/3ascl1b). The transgenic linesTg(ascl1b-2A-Cre)is75,Tg(olig2-2A-Cre)is76, andTg(neurod1-2A-Cre)is77expressed functional Cre recombinase in the expected proneural cell populations. The results demonstrate Cre recombinase expression is driven by the native promoter and regulatory elements of the targeted genes. This approach provides a straightforward, efficient, and cost-effective method to generate cell type specific zebrafish Cre drivers whose spatial and temporal restricted expression mimics endogenous genes, surmounting the challenges associated with promoter BAC cloning and transposon mediated transgenesis.
Neurovascular-modulation
Authors: Khadka Niranjan , Bikson Marom 
Published: July 2020

AbstractNeurovascular-modulation is based on two principles that derive directly from brain vascular ultra-structure, namely an exceptionally dense capillary bed (BBB length density: 972 mm/mm3) and a blood-brain-barrier (BBB) resistivity (ρ~ 1×105Ω.m) much higher than brain parenchyma/interstitial space (ρ~ 4 Ω.m) or blood (ρ~ 1 Ω.m). Principle 1: Electrical current crosses between the brain parenchyma (interstitial space) and vasculature, producing BBB electric fields (EBBB) that are > 400x of the average parenchyma electric field (ĒBRAIN), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λBBB) and wall thickness (dth-BBB): analytical solution for maximum BBB electric field (EABBB) is given as: (ĒBRAIN× λBBB) / dth-BBB. Direct vascular stimulation suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Boosting metabolic capacity impacts all forms of neuromodulation, including those applying intensive stimulation or driving neuroplasticity. Boosting interstitial fluid clearance has broad implications as a treatment for neurodegenerative disease including Alzheimer’s disease. Principle 2: Electrical current in the brain parenchyma is distorted around brain vasculature, amplifying neuronal polarization. Specifically, vascular ultra-structure produces ~50% modulation of the average parenchyma electric field (ĒBRAIN) over the ~40 μm inter-capillary distance. The divergence of EBRAIN(activating function) is thus ~100 kV/m2per unit average parenchyma electric field (ĒBRAIN). This impacts all forms of neuromodulation, including Deep Brain Stimulation (DBS), Spinal Cord Stimulation (SCS), Transcranial Magnetic Stimulation (TMS), Electroconvulsive Therapy (ECT), and transcranial electrical stimulation (tES) techniques such a transcranial Direct Current Stimulation (tDCS). Specifically, whereas spatial profile of EBRAINalong neurons is traditionally assumed to depend on macroscopic anatomy, it instead depends on local vascular ultra-structure.
Topoisomerase 1 dependent R-loop deficiency drives accelerated replication and genomic instability
Authors: Sarni Dan , Shtrikman Alon , Oren Yifat S. , Kerem Batsheva 
Published: July 2020

AbstractDNA replication is a complex process that is tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here we show that increased topoisomerase 1 (TOP1) expression induces aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids (R-loops). Degradation of R-loops by overexpression of RNaseH1 also accelerates replication and generates DNA damage. Furthermore, upregulation of TOP1 by activation of the mutated HRAS oncogene leads to fork acceleration and DNA damage in pre-senescent cells. In these cells, restoration of TOP1 expression level or mild replication inhibition rescues the perturbed replication and reduces DNA damage. These findings highlight the importance of TOP1 equilibrium in the regulation of R-loop homeostasis to ensure faithful DNA replication and genome integrity.
Ranking the direct threats to biodiversity in sub-Saharan Africa
Authors: Leisher Craig , Robinson Nathaniel , Brown Matthew , Kujirakwinja Deo , Schmitz Mauricio Castro , Wieland Michelle , Wilkie David 
Published: July 2020

AbstractSub-Saharan Africa benefits from large investments in biodiversity conservation, yet there is no prioritization of the many direct threats to biodiversity available to inform organizations developing sub-Saharan or sub-regional conservation strategies. Consequently, regional investments by funders of biodiversity conservation such as international conservation organizations, foundations, and bilateral and multilateral donors may be suboptimal. To identify the priority threats to biodiversity in sub-Saharan Africa, we classified the direct threats to biodiversity using standardized threats categories and triangulated data from a Delphi consensus of sub-Saharan Africa biodiversity experts, known threats to IUCN Red-listed sub-Saharan African species, and National Biodiversity Strategy and Action Plans from 47 sub-Saharan African countries. After ranking the threats from each source and averaging the rankings, we find that the highest threats are: annual and perennial crops (non-timber); logging and wood harvesting (natural forests); fishing and harvesting aquatic resources (marine and freshwater); and hunting and collecting terrestrial animals. Within the sub-regions of sub-Saharan Africa there is considerable variation. The highest ranked threat in Central Africa is hunting. In East Africa, it is agriculture. In Southern Africa, it is invasive non-native/alien species, and in West Africa, agriculture and logging are tied as the highest threats. There are known ways to address all of these threats, and concentrating investments on these threats while accounting for unique socio-ecological contexts across sub-Saharan Africa is essential for the sustained conservation of biodiversity.
Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19
Authors: Bell Lucy CK , Meydan Cem , Kim Jacob , Foox Jonathan , Butler Daniel , Mason Christopher E. , Shapira Sagi D. , Noursadeghi Mahdad , Pollara Gabriele 
Published: July 2020

SummaryDysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokinesin vivoare urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1β and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood, but is not associated with severity of COVID-19 disease, length of stay or mortality. We propose that IL-1β and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activityin vivo, aiding quantification of the biological effects of immunomodulatory therapies in COVID-19.
ABCB-mediated auxin transport in outer root tissues regulates lateral root spacing inArabidopsis
Authors: Chen Jian , Hu Yangjie , Hao Pengchao , Zhang Yuqin , Roth Ohad , Njo Maria F. , Sterck Lieven , Hu Yun , Zhao Yunde , Geisler Markus , Shani Eilon , Beeckman Tom , Vanneste Steffen 
Published: July 2020

AbstractRoot branching is an important strategy to explore efficiently large volumes of soil. To economize this process, lateral roots (LR) are formed along the growing root at discrete positions that are instructed by oscillating auxin signals derived from the lateral root cap (LRC). This assumes that auxin moves from the LRC across multiple layers to accumulate in the pericycle. Here, we identified, using gene silencing and CRISPR based approaches, a group of five genetically linked, closely related ABCBs that control LR spacing by modulating the amplitude of the auxin oscillation. The transporters localize to the plasma membrane and reveal significant auxin export activity. These ABCBs are mainly expressed in the LRC and epidermis where they contribute to auxin transport towards the root oscillation zone. Our findings highlight the importance of auxin transport in the outer tissues of the root meristem to regulate LR spacing.
Oestrogen promotes innate immune evasion ofCandida albicansthrough inactivation of the alternative complement system
Authors: Kumwenda Pizga , Cottier Fabien , Keevan Ben , Gallagher Hannah , Tsai Hung-Ji , Hall Rebecca A. 
Published: July 2020

AbstractGender is a risk factor for several infections that, for many pathogens, has been linked to sex hormones impacting host immunity and directly affecting microbial virulence.Candida albicansis a commensal of the urogenital tract and the predominant cause of vulvovaginal candidiasis (VVC). Factors that increase circulatory oestrogen levels like pregnancy, the use of oral contraceptives, and hormone replacement therapy predispose women to VVC, but the reasons for this are largely unknown. Here, we investigate how adaptation ofC. albicansto oestrogen impacts the fungal host-pathogen interaction. Physiologically relevant concentrations of oestrogen promoted fungal virulence by enablingC. albicansto avoid the actions of the innate immune system. Oestrogen-induced innate immune evasion was mediated via inhibition of opsonophagocytosis through enhanced acquisition of the human complement regulatory protein, Factor H, on the fungal cell surface. Oestrogen induced accumulation of Factor H was dependent on the fungal cell surface protein Gpd2, with oestrogen dependent derepression ofGPD2being mediated via a non-canonical signalling pathway involving Ebp1 and Bcr1. Therefore, we propose that, in addition to affecting the antifungal potential of vaginal epithelial cells, elevated oestrogen levels predispose women to VVC by directly enhancing fungal pathogenicity through the inactivation of complement. The discovery of this new hormone sensing pathway might pave the way in explaining gender biases associated with fungal infections and may provide an alternative approach to improving women’s health.
Whole-genome sequencing of multiple isolates ofPuccinia triticinareveals asexual lineages evolving by recurrent mutations
Authors: Fellers John P. , Sakthikumar Sharadha , He Fei , McRell Katie , Bakkeren Guus , Cuomo Christina A. , Kolmer James A. 
Published: July 2020

ABSTRACTBackgroundThe wheat leaf rust fungus,Puccinia triticinaErikss. is a worldwide pathogen of tetraploid durum and hexaploid wheat. Many races ofP. triticinadiffer for virulence to specific leaf rust resistance genes and are found in most wheat-growing regions of the world. Wheat cultivars with effective leaf rust resistance exert selection pressure onP. triticinapopulations for virulent race types. The objectives of this study were to examine whole-genome sequence data of 121P. triticinaisolates and to gain insight into race evolution. The collection included isolates comprising many different race phenotypes collected worldwide from common wheat in the U.S. and the European Union together with isolates from durum wheat. One isolate from the wild wheat relativeAegilops speltoides,and two fromAe. cylindricawere also included for comparison.ResultsBased on 121,907 variants identified relative to the reference race 1-1 genome, the isolates were clustered into 11 major lineages with 100% bootstrap support. The isolates were also grouped based on variation in approximately 1400 secreted resistance interactor candidate proteins. In gene-coding regions, all groups had high ratios of non-synonymous to synonymous mutations and nonsense to readthrough mutations.ConclusionsBased on total variation or variation in the secreted protein genes, isolates grouped the same indicating that variants were distributed across the entire genome. Our results suggest that recurrent mutation and selection play a major role in differentiation within the clonal lineages.
Increasing cell-free gene expression yields from linear templates inEscherichia coliandVibrio natriegensextracts by using DNA-binding proteins
Authors: Zhu Bo , Gan Rui , Cabezas Maria D. , Kojima Takaaki , Nicol Robert , Jewett Michael C. , Nakano Hideo 
Published: July 2020

AbstractIn crude extract-based cell-free protein synthesis (CFPS), DNA templates are transcribed and translated into functional proteins. Although linear expression templates (LETs) are less laborious and expensive to generate, plasmid templates are often desired over PCR-generated LETs due to increased stability and protection against exonucleases present in the extract of the reaction. Here we demonstrate that addition of a dsDNA-binding protein to the CFPS reaction, termed single-chain Cro protein (scCro), achieves terminal protection of LETs. This CroP-LET (scCro-basedProtection ofLET) method effectively increases sfGFP expression levels from LETs inEscherichia coliCFPS reactions by 6-fold. Our yields are comparable to other strategies that provide chemical and enzymatic DNA stabilization inE. coliCFPS. Notably, we also report that the CroP-LET method successfully enhanced yields in CFPS platforms derived from non-model organisms. Our results show that CroP-LET increased sfGFP yields by 18-fold in theVibrio natriegensCFPS platform. With the fast-expanding applications of CFPS platforms, this method provides a practical and generalizable solution to protect linear expression DNA templates.
Expectancy changes the self-monitoring of voice identity
Authors: Johnson Joseph F. , Belyk Michel , Schwartze Michael , Pinheiro Ana P. , Kotz Sonja A. 
Published: July 2020

ABSTRACTSelf-voice attribution can become difficult when voice characteristics are ambiguous, and functional magnetic resonance imagines (fMRI) investigations of such ambiguity are sparse. We utilized voice-morphing (self-other) to manipulate (un-)certainty in self-voice attribution in a button-press paradigm. This allowed investigating how levels of self-voice certainty alter brain activation in regions monitoring voice identity areas and unexpected changes in voice playback quality. FMRI results confirm a self-voice suppression effect in the right anterior superior temporal gyrus (aSTG) when self-voice attribution was unambiguous. Although the right inferior frontal gyrus (IFG) was more active during self-generated voice compared to when passively-heard, the putative role of this region in detecting unexpected self-voice changes was not confirmed. Further research on the link between right aSTG and IFG is required and may establish a threshold monitoring voice identity in action. The current results have implications for a better understanding of an altered experience of self-voice feedback leading to auditory verbal hallucinations.
STAT3 but not STAT5 contributes to the protective effect of electro-acupuncture against myocardial ischemia/reperfusion injury
Authors: Guo Hui-Hui , Jing Xin-Yue , Chen Hui , Xu Hou-Xi , Zhu Bing-Mei 
Published: July 2020

AbstractLate remote ischemia preconditioning (RIPC) and electro-acupuncture (EA) have both been suggested to reduce injury caused by myocardial ischemia/reperfusion (I/R). Our previous study has found that cardioprotection in RIPC is STAT5-dependent. Here, we aim to observe the effects of electro-acupuncture pretreatment (EAP) on I/R in the presence or absence of STAT5 in mice and investigate whether the protection of EAP is in a STAT5-dependent manner. In this study, EAP decreased myocardial infarction size (IS) /total area (TA) and rate of cardiomyocyte apoptosis. STAT5 was activated by EAP in theStat5fl/flmice but not in theStat5-cKOmice, whereas, STAT3 was activated by EAP only in theStat5-cKObut not in theStat5fl/flmice. Differentially expressed genes (DEGs) regulated by EAP in theStat5fl/fland theStat5-cKOmice were quite distinct, indicating that EAP may activate IL-6/STAT3 signal in the absence ofStat5, and that EAP-induced cardioprotection against myocardial I/R injury was correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling. Our results, for the first time, demonstrated that the protective effect of EAP was attributed to, but not dependent on, STAT5.