bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Mapping in Autohexaploid Sweet Potato with Low-coverage NGS-based Genotyping Data
Authors: Yamamoto Eiji , Shirasawa Kenta , Kimura Takumi , Monden Yuki , Tanaka Masaru , Isobe Sachiko 
Published: October 2019

AbstractNext-generation sequencing (NGS)-based genotyping methods can generate numerous genetic markers in a single experiment and have contributed to plant genetic mapping. However, the benefits of NGS-based methods are limited in autopolyploids as their genetic segregation mode is complex. Moreover, autopolyploids have large genomes and require abundant sequencing data to obtain sufficient genetic markers. There are several methods for genetic mapping in autopolyploids. These approaches may be impractical for plant genetic studies as they require large amounts of data and are not cost-effective. In the present study, we propose a simple strategy for genetic mapping of polyploids in a cost-effective manner. The allele dosage probabilities calculated from NGS read counts were used in association analyses to detect loci associated with specific phenotypes. This approach is superior to conventional methods of determining allele dosage, which usually result in the filtering of many genetic markers with low read depth. The validity of the strategy was demonstrated using real phenotype data from autohexaploid sweet potato populations to detect genetic loci for both qualitative and quantitative traits, the latter of which required the use of allele dosage probabilities for the detection of loci. We demonstrate that this proposed method is useful with reasonable NGS read counts.
The Influence of Ecosystem and Phylogeny on Tropical Tree Crown Size and Shape
Authors: Shenkin Alexander , Bentley Lisa Patrick , Oliveras Imma , Salinas Norma , Adu-Bredu Stephen , Marimon Ben Hur , Marimon Beatriz , Peprah Theresa , Choque Efrain Lopez , Rodriguez Lucio Trujillo , Clemente Arenas Edith Rosario , Adonteng Christian , Seidu John , Passos Fabio Barbosa , Reis Simone Matias , Blonder Benjamin , Silman Miles , Enquist Brian J. , Asner Gregory P. , Malhi Yadvinder 
Published: October 2019

1ABSTRACTThe sizes and shapes of tree crowns are of fundamental importance in ecology, yet understanding the forces that determine them remains elusive. A cardinal question facing ecologists is the degree to which general and non-specific versus ecological and context-dependent processes are responsible for shaping tree crowns. Here, we test this question for the first time across diverse tropical ecosystems. Using trees from 20 plots varying in elevation, precipitation, and ecosystem type (savanna-forest transitions) across the paleo- and neo-tropics, we test the relationship between crown dimensions and tree size. By analyzing these scaling relationships across environmental gradients, biogeographic regions, and phylogenetic distance, we extend Metabolic Scaling Theory (MST) predictions to include how local selective pressures shape variation in crown dimensions. Across all sites, we find strong agreement between mean trends and MST predictions for the scaling of crown size and shape, but large variation around the mean. While MST explained approximately half of the observed variation in tree crown dimensions, we find that local, ecosystem, and phylogenetic predictors account for the half of the residual variation. Crown scaling does not change significantly across regions, but does change across ecosystem types, where savanna tree crowns grow more quickly with tree size than forest tree crowns. Crowns of legumes were wider and larger than those of other taxa. Thus, while MST can accurately describe the central tendency of tree crown size, local ecological conditions and evolutionary history appear to modify the scaling of crown shape. Importantly, our extension of MST incorporating these differences accounts for the mechanisms driving variation in the scaling of crown dimensions across the tropics. These results are critical when scaling the function of individual trees to larger spatial scales or incorporating the size and shape of tree crowns in global biogeochemical models.
CUB domain-containing protein 1 controls HGF responses by integrating Src and Met–STAT3 signaling
Authors: Kajiwara Kentaro , Sugihara Atsuya , Aoki Kazuhiro , Okuzaki Daisuke , Matsumoto Kunio , Okada Masato 
Published: October 2019

AbstractHepatocyte growth factor (HGF) controls various biological responses, including morphogenesis, organ regeneration, and cancer invasion, by activating its receptor, Met. However, the mechanisms that precisely control diverse Met signaling remain unclear. Here, we identified CUB domain-containing protein 1 (CDCP1) as a crucial element of HGF signaling. In MDCK cysts, HGF induced Src activation via CDCP1 upregulation, and CDCP1 ablation abrogated HGF responses, i.e., extended invasive cell protrusions and promoted cell growth/proliferation. Mechanistically, CDCP1 upregulation promoted Src recruitment into lipid rafts to activate Met-associated STAT3. In breast cancer cells in which Met and CDCP1 were co-upregulated, CDCP1 knockdown suppressed HGF-induced cell invasion. Furthermore,in vivoanalysis showed that CDCP1 ablation suppressed compensatory renal growth by attenuating Met–STAT3 signaling. These findings demonstrate that CDCP1 plays a crucial role in controlling HGF responses by integrating Src and Met-STAT3 signaling, and provide new insights into the regulatory mechanisms underlying the multifaceted functions of HGF.
The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding
Authors: Hughes Kevin R , Schofield Z , Dalby MJ , Caim S , Chalklen L , Bernuzzi F , Alcon-Giner C , Le Gall G , Watson AJM , Hall LJ 
Published: October 2019

AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances ofStreptococcus,EscherichiaandEnterococcusand increased primary bile acids. In contrast, older mice were dominated byCandidatusArthromitus,AlistipesandLachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.
Estimating the power of sequence covariation for detecting conserved RNA structure
Authors: Rivas Elena , Clements Jody , Eddy Sean R. 
Published: October 2019

AbstractPairwise sequence covariations are a signal of conserved RNA secondary structure. We describe a method for distinguishing when lack of covariation signal can be taken as evidence against a conserved RNA structure, as opposed to when a sequence alignment merely has insufficient variation to detect covariations. We find that alignments for several long noncoding RNAs previously shown to lack covariation support do have adequate covariation detection power, providing additional evidence against their proposed conserved structures.
Conifers exhibit a characteristic inactivation of auxin to maintain tissue homeostasis
Authors: Brunoni Federica , Collani Silvio , Casanova-Saéz Rubén , Šimura Jan , Karady Michal , Schmid Markus , Ljung Karin , Bellini Catherine 
Published: October 2019

SummaryDynamic regulation of the levels of the natural auxin, indol-3-acetic acid (IAA), is essential to coordinate most of the physiological and developmental processes and responses to environmental changes. Oxidation of IAA is a major pathway to control auxin concentrations in Arabidopsis and, along with IAA conjugation, to respond to perturbation of IAA homeostasis. However, these regulatory mechanisms are still poorly investigated in conifers. To reduce this gap of knowledge, we investigated the different contribution of the IAA inactivation pathways in conifers.Mass spectrometry-based quantification of IAA metabolites under steady state conditions and after perturbation was investigated to evaluate IAA homeostasis in conifers. Putative Picea abies GH3 genes (PaGH3) were identified by a comprehensive phylogenetic analysis including Arabidopsis and basal land plants. Auxin-inducible PaGH3 genes were identified by expression analysis and their IAA-conjugating activity was explored.Compared to Arabidopsis, oxidative and conjugative pathways differentially contribute to reduce IAA levels in conifers. We demonstrated that the oxidation pathway plays a marginal role in controlling IAA homeostasis in spruce. On the other hand, an excess of IAA rapidly activates GH3-mediated irreversible conjugation pathways.Taken together, these data indicate that a diversification of IAA inactivation mechanisms evolved specifically in conifers.
Landmark-Based Navigation Instructions Improve Incidental Spatial Knowledge Acquisition in Real-World Environments
Authors: Wunderlich Anna , Gramann Klaus 
Published: October 2019

AbstractThe repeated use of navigation assistance systems leads to decreased processing of the environment. Previous studies demonstrated that auditory augmentation of landmarks in navigation instructions can improve incidental spatial knowledge acquisition when driving a single route through an unfamiliar virtual environment. Based on these results, three experiments were conducted to investigate the generalizability and ecological validity of incidental spatial knowledge acquisition by landmark augmentation in navigation instructions.In the first experiment, spatial knowledge acquisition was tested after watching an interactive video showing the navigation of a real-world urban route. A second experiment investigated incidental spatial knowledge acquisition during assisted navigation when participants walked through the same real-world, urban environment. The third experiment tested the acquired spatial knowledge two weeks after an assisted pedestrian navigation phase through the real-world.All experiments demonstrated better performance in a cued-recall task for participants navigating with landmark-based navigation instructions as compared to standard instructions. Different levels of information provided with landmark-based instructions impacted landmark recognition dependent on the delay between navigation and test. The results replicated an improved landmark and route knowledge when using landmark-based navigation instructions emphasizing that auditory landmark augmentation enhances incidental spatial knowledge acquisition, and that this enhancement can be generalized to real-life settings.This research is paving the way for navigation assistants that, instead of impairing spatial knowledge acquisition, incidentally foster the acquisition of landmark and route knowledge during every-day navigation.
Compensatory replacement of the BigH1 variant histone by canonical H1 supports normal embryonic development in Drosophila
Authors: Li Kaili K. , Han Dongsheng , Chen Fang , Li Ruihao , Zhou Bing-Rui , Bai Yawen , Yuan Kai , Rong Yikang S. 
Published: October 2019

SummaryHistone variants carry specific functions in addition to those fulfilled by their canonical counterparts. Variants of the linker Histone H1 are prevalent in vertebrates and based on the pattern of their expression, many are presumed to function during germline and the earliest zygotic stages of development. While the existence of multiple H1 variants has hampered their study in vertebrates, a single variant, BigH1, was identified in Drosophila, promising to accelerate our understanding of the biological functions of H1 and H1 variants. Here we uncovered evidence for a compensatory activity that loads maternal H1 onto BigH1-devoid chromatin. Remarkably, this H1-based chromatin state is fully functional in supporting normal embryonic development, suggesting that H1 carries the essential function of the BigH1 molecule under the same developmental context. In addition, we discovered that this compensatory replacement of BigH1 with H1 might be limited to rapidly cycling cells in early embryos.
Cargo-free scaffold implant recruits metastatic cancer cells via lung-mimicking myeloid cell S100A8/A9 axis
Authors: Wang Jing , Hall Matthew S. , Bushnell Grace G. , Orbach Sophia M. , Raghani Ravi M. , Zhang Yining , Decker Joseph T. , Morris Aaron H. , Kandagatla Pridvi , Jeruss Jacqueline S. , Shea Lonnie D. 
Published: October 2019

AbstractPre-metastatic niches in distant tissue facilitate metastasis from the primary tumor. Cargo-free porous polymer scaffolds implanted in tumor-bearing mice act as synthetic metastatic niches recruiting metastasizing cancer cells. Herein, we investigated the mechanisms by which these implants attract cancer cells from circulation. Scaffolds attract cancer cells in part via S100A8/A9 secreted by Gr1+ myeloid cells in a mechanism that mimics lung metastasis. Further, cancer cells attracted to the scaffold have a lung-tropic gene expression signature regardless of their tissue of origin. The scaffold implant reduces metastasis to the lung suggesting otherwise lung-tropic cancer cells are diverted to the scaffold. The suppression of metastatic spread by the scaffold suggests this mechanism may be exploited for novel therapies, and may broadly influence the design of scaffold-based drug delivery system for anti-cancer therapy.
Vagus nerve stimulation increases vigor to work for rewards
Authors: Neuser Monja P. , Teckentrup Vanessa , Kühnel Anne , Hallschmid Manfred , Walter Martin , Kroemer Nils B. 
Published: October 2019

AbstractInteroceptive feedback transmitted via the vagus nerve plays a vital role in motivation by tuning actions according to physiological needs. Whereas vagus nerve stimulation (VNS) reinforces actions and enhances dopamine transmission in animals, motivational effects elicited by VNS in humans are still largely elusive. Here, we applied non-invasive transcutaneous auricular VNS (taVNS) on the left or the right ear using a randomized cross-over design (vs. sham). During stimulation, 81 healthy participants had to exert effort to earn food or monetary rewards. We reasoned that taVNS enhances motivation and tested whether it does so by increasing prospective benefits (i.e., vigor) or reducing costs of action (i.e., maintenance) compared to sham stimulation. In line with preclinical studies, taVNS generally enhanced invigoration of effort (p = .004, Bayes factor, BF10 = 7.34), whereas stimulation on the left side primarily facilitated vigor for food rewards (left taVNS: Stimulation × Reward Type, p =.003, BF10 = 11.80). In contrast, taVNS did not affect effort maintenance (ps ≥ .09, BF10 < 0.52). Critically, during taVNS, vigor declined less steeply with decreases in wanting (Δb = −.046, p = .031) indicating a boost in the drive to work for rewards. Collectively, our results suggest that taVNS enhances reward-seeking by boosting vigor, not effort maintenance and that the side of the stimulation affects generalization beyond food reward. We conclude that taVNS may enhance the pursuit of prospective rewards which may pave new avenues for treatment of motivational deficiencies.
Effects of irrigation scheduling and different irrigation methods on onion and water productivity in Tigray, northern Ethiopia
Authors: Haile Gebremedhin Gebremeskel , Gebremicael T.G. , Kifle Mulubrehan , Gebremedhin Teferi 
Published: October 2019

AbstractEfficient irrigation water use can meet its objective if irrigated agriculture is managed properly in regions where water is limited. A two-year (2016-2017) field experiments were conducted in the semiarid areas of Tigray in northern Ethiopia to evaluate irrigation scheduling with different irrigation methods. The experiments were carried out to identify their contribution for enhancing onion and water productivity in water-stressed irrigation schemes of Korir and Hatset sites. Six factorial treatments comprising of three levels of irrigation methods (furrow, basin and flood) and two levels of irrigation scheduling (fixed interval and farmer’s practices) were evaluated with three replications. The agronomic and irrigation parameters were subjected to separate level-wise comparison followed by the factorial interaction effects. The results showed that the fixed irrigation interval, basin irrigation method and their factorial combinations showed better performances and produced a higher yield and water productivity. On average, 263.85 q/ha and 281 q/ha of onion were obtained under the basin irrigation method and basin irrigation with fixed irrigation interval (T2) at both sites and seasons. For the T2, 6.27 and 6.06 kg/m3 of water productivity (WP) and 4.39 and 4.24 kg/m3 of irrigation water productivity (IWP) were obtained at Korir and Hatset sites, respectively showing higher results as compared to other treatment combinations. Moreover, the basin irrigation method produces higher marketable onion bulbs that are essential for onion producers to earn maximum profit from selling and enhance their livelihoods. Treatments comprising basin method and fixed interval showed better onion and water productivity in the water-limited irrigation schemes of Tigray. Hence, focusing on enhanced irrigation scheduling techniques and irrigation methods are important for effective agricultural water management. Farmers, irrigation experts, water resources managers and decision-makers are suggested to use these techniques to save the limited water resources and increase agricultural productivity.
Loss of AKAP1 triggers Drp1 dephosphorylation-mediated mitochondrial fission and loss in retinal ganglion cells
Authors: Edwards Genea , Perkins Guy A. , Kim Keun-Young , Kong YeEun , Lee Yonghoon , Choi Soo-Ho , Liu Yujia , Skowronska-Krawczyk Dorota , Weinreb Robert N. , Zangwill Linda , Strack Stefan , Ju Won-Kyu 
Published: October 2019

AbstractImpairment of mitochondrial structure and function is strongly linked to glaucoma pathogenesis. Despite the widely appreciated disease relevance of mitochondrial dysfunction and loss, the molecular mechanisms underlying mitochondrial fragmentation and metabolic stress in glaucoma are poorly understood. We demonstrate here that glaucomatous retinal ganglion cells (RGCs) show loss of A-kinase anchoring protein 1 (AKAP1), activation of calcineurin (CaN) and reduction of dynamin-related protein 1 (Drp1) phosphorylation at serine 637 (Ser637). These findings suggest that AKAP1-mediated phosphorylation of Drp1 at Ser637 has a critical role in RGC survival in glaucomatous neurodegeneration. Male mice lacking AKAP1 show increases of CaN and total Drp1 level, as well as a decrease of Drp1 phosphorylation at Ser637 in the retina. Ultrastructural analysis of mitochondria shows that loss of AKAP1 triggers mitochondrial fragmentation and loss, as well as mitophagosome formation in RGCs. Loss of AKAP1 deregulates oxidative phosphorylation (OXPHOS) complexes (Cxs) by increasing CxII and decreasing CxIII-V, leading to metabolic and oxidative stress. Also, loss of AKAP1 decreases Akt phosphorylation at Serine 473 (Ser473) and threonine 308 (Thr308) and activates the Bim/Bax signaling pathway in the retina. These results suggest that loss of AKAP1 has a critical role in RGC dysfunction by decreasing Drp1 phosphorylation at Ser637, deregulating OXPHOS, decreasing Akt phosphorylation at Ser473 and Thr308, and activating the Bim/Bax pathway in glaucomatous neurodegeneration. Thus, we propose that overexpression of AKAP1 or modulation of Drp1 phosphorylation at Ser637 are potential therapeutic strategies for neuroprotective intervention in glaucoma and other mitochondria-related optic neuropathies.
Machine and deep learning single-cell segmentation and quantification of multi-dimensional tissue images
Authors: McKinley Eliot T , Roland Joseph T , Franklin Jeffrey L , Macedonia Mary Catherine , Vega Paige N , Shin Susie , Coffey Robert J , Lau Ken S 
Published: October 2019

AbstractIncreasingly, highly multiplexedin situtissue imaging methods are used to profile protein expression at the single-cell level. However, a critical limitation is a lack of robust cell segmentation tools applicable for sections of tissues with a complex architecture and multiple cell types. Using human colorectal adenomas, we present a pipeline for cell segmentation and quantification that utilizes machine learning-based pixel classification to define cellular compartments, a novel method for extending incomplete cell membranes, quantification of antibody staining, and a deep learning-based cell shape descriptor. We envision that this method can be broadly applied to different imaging platforms and tissue types.
Early hippocampal hyperexcitability followed by disinhibition in a mouse model of Dravet syndrome
Authors: Almog Yael , Brusel Marina , Anderson Karen , Rubinstein Moran 
Published: October 2019

AbstractDravet syndrome (Dravet) epilepsy begins with febrile seizures followed by worsening to refractory seizures, with some improvement and stabilization toward adolescence. The neuronal basis of Dravet is debatable, with evidence favoring reduced inhibition or enhanced excitation. Focusing on the firing properties of hippocampal CA1 pyramidal neurons and oriens-lacunosum moleculare (O-LM) interneurons, we provide a comprehensive analysis of the activity of both cell types through the febrile, worsening and stabilization stages. Our data indicate a temporary increase in the excitability of CA1 pyramidal neurons during the febrile stage, which is fully reversed by the onset of spontaneous seizures. In contrast, reduced function of O-LM interneurons persisted from the febrile through the stabilization stages, with the greatest impairment of excitability occurring during the worsening stage. Thus, both excitatory and inhibitory neurons contribute to Dravet, indicating complex and reciprocal pathophysiological neuronal changes during the different stages of the disease.Graphical abstract