bluuebunny/crossref_metadata_2025_split huggingface dataset:
LSP1-myosin1e bi-molecular complex regulates focal adhesion dynamics and cell migration
Authors: Schäringer Katja , Maxeiner Sebastian , Schalla Carmen , Rütten Stephan , Zenke Martin , Sechi Antonio 
Published: February 2020

AbstractSeveral cytoskeleton-associated proteins and signalling pathways work in concert to regulate actin cytoskeleton remodelling, cell adhesion and migration. We have recently demonstrated that the bi-molecular complex between the leukocyte-specific protein 1 (LSP1) and myosin1e controls actin cytoskeleton remodelling during phagocytosis. In this study, we show that LSP1 down regulation severely impairs cell migration, lamellipodia formation and focal adhesion dynamics in macrophages. Inhibition of the interaction between LSP1 and myosin1e also impairs these processes resulting in poorly motile cells, which are characterised by few and small lamellipodia. Furthermore, cells in which LSP1-myosin1e interaction is inhibited are typically associated with inefficient focal adhesion turnover. Collectively, our findings show that the LSP1-myosin1e bimolecular complex plays a pivotal role in the regulation of actin cytoskeleton remodelling and focal adhesion dynamics required for cell migration.
Deep neural networks identify context-specific determinants of transcription factor binding affinity
Authors: Zheng An , Lamkin Michael , Wu Cynthia , Su Hao , Gymrek Melissa 
Published: February 2020

AbstractTranscription factors (TFs) bind DNA by recognizing highly specific DNA sequence motifs, typically of length 6-12bp. A TF motif can occur tens of thousands of times in the human genome, but only a small fraction of those sites are actually bound. Despite the availability of genome-wide TF binding maps for hundreds of TFs, predicting whether a given motif occurrence is bound and identifying the influential context features remain challenging. Here we present a machine learning framework leveraging existing convolutional neural network architectures and state of the art model interpretation techniques to identify, visualize, and interpret context features most important for determining binding activity for a particular TF. We apply our framework to predict binding at motifs for 38 TFs in a lymphoblastoid cell line and achieve superior classification performance compared to existing frameworks. We compute importance scores for context regions at single base pair resolution and uncover known and novel determinants of TF binding. Finally, we demonstrate that important context bases are under increased purifying selection compared to nearby bases and are enriched in disease-associated variants identified by genome-wide association studies.
Genomic and transcriptomic analyses reveal a tandem amplification unit of 11 genes and mutations of mismatch repair genes in methotrexate-resistant HT-29 cells
Authors: Kim Ahreum , Shin Jong-Yeon , Seo Jeong-Sun 
Published: February 2020

AbstractDHFRgene amplification is present in methotrexate (MTX)-resistant colon cancer cells and acute lymphoblastic leukemia. However, little is known aboutDHFRgene amplification due to difficulties in quantifying amplification size and recognizing the repetitive rearrangements involved in the process. In this study, we have proposed an integrative framework to characterize the amplified region by using a combination of single-molecule real time sequencing, next-generation optical mapping, and chromosome conformation capture (Hi-C). Amplification of theDHFRgene was optimized to generate homogenously amplified patterns. The amplification units of 11 genes, from theDHFRgene to theATP6AP1Lgene position on chromosome 5 (~2.2Mbp), and a twenty-fold tandemly amplified region were verified using long-range genome and RNA sequencing data. In doing so, a novel inversion at the start and end positions of the amplified region as well as frameshift insertions in most of theMSHandMLHgenes were detected. These might stimulate chromosomal breakage and cause the dysregulation of mismatch repair pathways. Using Hi-C technology, high adjusted interaction frequencies were detected on the amplified unit and unsuspected position on 5q, which could have a complex network of spatial contacts to harbor gene amplification. Characterizing the tandem gene-amplified unit and genomic variants as well as chromosomal interactions on intra-chromosome 5 can be critical in identifying the mechanisms behind genomic rearrangements. These findings may give new insight into the mechanisms underlying the amplification process and evolution of drug resistance.
Localized prediction of glutamate from whole-brain functional connectivity of the pregenual anterior cingulate cortex
Authors: Martens Louise , Kroemer Nils B. , Teckentrup Vanessa , Colic Lejla , Palomero-Gallagher Nicola , Li Meng , Walter Martin 
Published: February 2020

AbstractLocal measures of neurotransmitters provide crucial insights into neurobiological changes underlying altered functional connectivity in psychiatric disorders. However, non-invasive neuroimaging techniques such as magnetic resonance spectroscopy (MRS) may cover anatomically and functionally distinct areas, such asp32andp24of the pregenual anterior cingulate cortex (pgACC). Here, we aimed to overcome this low spatial specificity of MRS by predicting local glutamate and GABA based on functional characteristics and neuroanatomy, using complementary machine learning approaches. Functional connectivity profiles of pgACC areap32predicted pgACC glutamate better than chance (R2= .324) and explained more variance compared to areap24using both elastic net and partial least squares regression. In contrast, GABA could not be robustly predicted. To summarize, machine learning helps exploit the high resolution of fMRI to improve the interpretation of local neurometabolism. Our augmented multimodal imaging analysis can deliver novel insights into neurobiology by using complementary information.
Gut Microbiome Pattern Reflects Healthy Aging and Predicts Extended Survival in Humans
Authors: Wilmanski Tomasz , Diener Christian , Rappaport Noa , Patwardhan Sushmita , Wiedrick Jack , Lapidus Jodi , Earls John C. , Zimmer Anat , Glusman Gustavo , Robinson Max , Yurkovich James T. , Kado Deborah M. , Cauley Jane A. , Zmuda Joseph , Lane Nancy E. , Magis Andrew T. , Lovejoy Jennifer C. , Hood Leroy , Gibbons Sean M. , Orwoll Eric S. , Price Nathan 
Published: February 2020

AbstractThe gut microbiome has important effects on human health, yet its importance in human aging remains unclear. Using two independent cohorts comprising 4582 individuals across the adult lifespan we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique with age. This uniqueness pattern is strongly associated with gut microbial amino acid derivatives circulating within the bloodstream, many of which have been previously identified as longevity biomarkers. At the latest stages of human life, two distinct patterns emerge wherein individuals in good health show continued microbial drift toward a unique compositional state, while the same drift is absent in individuals who perform worse on a number of validated health measures. The identified healthy aging pattern is characterized by an overall depletion of core genera found across most humans - primarily a depletion in the nearly ubiquitous genusBacteroides. Consistently, retaining a highBacteroidesdominance into extreme age, or, equivalently, having a low gut microbiome uniqueness score, predicts decreased survival in a four-year follow-up. Our comprehensive analysis identifies the gut microbiome as a novel component of healthy aging, with important implications for the world’s growing older population.
Crosstalk between invadopodia and the extracellular matrix
Authors: Iizuka Shinji , Leon Ronald P. , Gribbin Kyle P. , Zhang Ying , Navarro Jose , Smith Rebecca , Devlin Kaylyn , Wang Lei G. , Gibbs Summer L. , Korkola James , Nan Xiaolin , Courtneidge Sara A. 
Published: February 2020

ABSTRACTThe scaffold protein Tks5α is required for invadopodia-mediated cancer invasion bothin vitroandin vivo. We have previously also revealed a role for Tks5 in tumor cell growth using three-dimensional (3D) culture model systems and mouse transplantation experiments. Here we use both 3D and high-density fibrillar collagen (HDFC) culture to demonstrate that native type I collagen, but not a form lacking the telopeptides, stimulated Tks5-dependent growth, which was dependent on the DDR collagen receptors. We used microenvironmental microarray (MEMA) technology to determine that laminin, collagen I, fibronectin and tropoelastin also stimulated invadopodia formation. A Tks5α-specific monoclonal antibody revealed its expression both on microtubules and at invadopodia. High- and super-resolution microscopy of cells in and on collagen was then used to place Tks5α at the base of invadopodia, separated from much of the actin and cortactin, but coincident with both matrix metalloprotease and cathepsin proteolytic activity. Inhibition of the Src family kinases, cathepsins or metalloproteases all reduced invadopodia length but each had distinct effects on Tks5α localization. These studies highlight the crosstalk between invadopodia and extracellular matrix components, and reveal the invadopodium to be a spatially complex structure.
In vivo repair of a protein underlying a neurological disorder by programmable RNA editing
Authors: Sinnamon John R , Kim Susan Y , Fisk Jenna R , Song Zhen , Nakai Hiroyuki , Jeng Sophia , McWeeney Shannon K , Mandel Gail 
Published: February 2020

AbstractRNA base editing is gaining momentum as an approach to repair mutations, but its application to neurological disease has not been established. We have succeeded in directed transcript editing of a pathological mutation in a mouse model of the neurodevelopmental disease, Rett syndrome. Specifically, we directed editing of a guanosine to adenosine mutation in RNA encoding Methyl CpG Binding Protein 2 (MECP2). Repair was mediated by injecting the hippocampus of juvenile Rett mice with an adeno-associated virus expressing both an engineered enzyme containing the catalytic domain of Adenosine Deaminase Acting on RNA 2 and aMecp2targeting guide. After one month, 50% ofMecp2RNA was recoded in three different hippocampal neuronal subtypes, and the ability of MeCP2 protein to associate with heterochromatin was similarly restored to 50% of wild-type levels. This study represents the firstin vivoprogrammable RNA editing applied to a model of neurological disease.
Frequency-specific suppression of locomotor components by thewhite+gene inDrosophila melanogasteradult flies
Authors: Xiao Chengfeng , Qiu Shuang 
Published: February 2020

AbstractThe classic eye-color genewhite+(w+) inDrosophila melanogaster(fruitfly) has unexpected behavioral consequences. Howw+affect locomotion of adult flies is largely unknown. Here, we show thatw+selectively suppresses locomotor components at relatively high frequencies (> 0.1 Hz). The wildtype Canton-S male flies walked intermittently in circular arenas while the white-eyedw1118flies walked continuously. Through careful control of genetic and cytoplasmic backgrounds, we found thatw+was associated with intermittent walking.w+-carrying male flies had smaller median values of path length per second (PPS) and reduced 5-min path length compared withw1118-carrying males. Additionally, flies carrying 2-4 genomic copies of mini-white+(mw+) showed reduced median PPSs and decreased 5-min path length compared withw1118flies, and the suppression was dependent on the copy number of mw+. Fourier transform of the time series (i.e. PPSs over time) indicated thatw+/mw+specifically suppressed the locomotor components at relatively high frequencies (> 0.1 Hz). Lastly, the downregulation ofw+in neurons but not glial cells resulted in an increased percentage of high-frequency locomotor components. We concluded thatw+suppressed the locomotion of adult flies by selectively reducing the high-frequency locomotor components.
Necrosignaling: Cell death triggers antibiotic survival pathways in bacterial swarms
Authors: Bhattacharyya Souvik , Walker David M. , Harshey Rasika M. 
Published: February 2020

SummarySwarming is form of collective bacterial motion enabled by flagella on the surface of semi-solid media1. Many bacterial species exhibit non-genetic adaptive resistance to a broad range of antibiotics only when swarming (SR)2-4. While the swarming population as a whole survives antibiotic challenge, it nonetheless sustains considerable cell death5. In this study focused mainly on E. coli, an initial analysis of antibiotic-induced killing patterns of swarm vs planktonic cells indicated that death of a sub-population is beneficial to the swarm in promoting SR. Introduction of pre-killed cells into a swarm indeed enhanced SR, allowing us to purify the SR factor from killed cells, and to establish that cell death is directly involved in SR. The SR-enhancing factor was identified to be AcrA, a periplasmic component of a tripartite RND efflux pump6, of which the outer membrane component TolC is shared by multiple drug efflux pumps7. We show that AcrA stimulates drug efflux in live cells by interacting with TolC from the outside. This stimulus acts as a signal to activate efflux in the short term, and to induce the expression of other classes of efflux pumps in the long term, amplifying the response and establishing SR. We call this phenomenon ‘necrosignaling’, and show the existence of species-specific necrosignaling in both Gram-positive and Gram-negative bacteria. Our results have implications for the adaptive resistance of other surface-associated bacterial collectives such as biofilms. Given that such resistance is known to be an incubator for evolving genetic resistance8, our findings may also be relevant to chemotherapy-resistant cancers.
The Taste of Blood in Mosquitoes
Authors: Jové Veronica , Gong Zhongyan , Hol Felix J.H. , Zhao Zhilei , Sorrells Trevor R. , Carroll Thomas S. , Prakash Manu , McBride Carolyn S. , Vosshall Leslie B. 
Published: February 2020

SUMMARYBlood-feeding mosquitoes survive by feeding on nectar for metabolic energy, but to develop eggs, females require a blood meal.Aedes aegyptifemales must accurately discriminate between blood and nectar because detection of each meal promotes one of two mutually exclusive feeding programs characterized by distinct sensory appendages, meal sizes, digestive tract targets, and metabolic fates. We investigated the role of the syringe-like blood-feeding appendage, the stylet, and discovered that sexually dimorphic stylet neurons are the first to taste blood. Using pan-neuronal GCaMP calcium imaging, we found that blood is detected by four functionally distinct classes of stylet neurons, each tuned to specific blood components associated with diverse taste qualities. Furthermore, the stylet is specialized to detect blood over nectar. Stylet neurons are insensitive to nectar-specific sugars and responses to glucose, the sugar found in both blood and nectar, depend on the presence of additional blood components. The distinction between blood and nectar is therefore encoded in specialized neurons at the very first level of sensory detection in mosquitoes. This innate ability to recognize blood is the basis of vector-borne disease transmission to millions of people world-wide.
Candidate stress biomarkers for queen failure diagnostics
Authors: McAfee Alison , Milone Joseph , Chapman Abigail , Foster Leonard J , Pettis Jeffery S , Tarpy David R 
Published: February 2020

AbstractBackgroundQueen failure is a persistent problem in beekeeping operations, but in the absence of overt symptoms it is often difficult, if not impossible, to ascertain the root cause. Stressors like heat-shock, cold-shock, and sublethal pesticide exposure can reduce stored sperm viability and lead to cryptic queen failure. Previously, we suggested candidate protein markers indicating heat-shock in queens, which we investigate further here, and tested new stressors to identify additional candidate protein markers.ResultsWe found that heat-shocking queens for upwards of one hour at 40 °C was necessary to induce significant changes in the two strongest candidate heat-shock markers, and that relative humidity significantly influenced the degree of activation. In blind heat-shock experiments, we tested the efficiency of these markers at assigning queens to their respective treatment groups and found that one marker was sufficient to correctly assign queens 75% of the time. Finally, we compared cold-shocked queens at 4 °C and pesticide-exposed queens to controls to identify candidate markers for these additional stressors, and compared relative abundances of all markers to queens designated as ‘healthy’ and ‘failing’ by beekeepers.ConclusionsThis work offers some of the first steps towards developing molecular diagnostic tools to aid in determining cryptic causes of queen failure. Further work will be necessary to determine how long after the stress event a marker’s expression remains changed and how accurate these could be in the field.
Bambara Groundnut Rhizobacteria Antimicrobial and Biofertilization Potential
Authors: Ajilogba Caroline F. , Babalola Olubukola O. , Adebola Patrick , Adeleke Rasheed 
Published: February 2020

AbstractBambara groundnut, an underutilized crop has been proved to be an indigenous crop in Africa with the potential for food security. The rhizosphere of Bambara groundnut like other legumes contains several important bacteria that have not been explored for their plant growth-promoting properties. The aim of this research was to determine the potentials of rhizobacteria from Bambara groundnut soil samples as either biofertilizer or biocontrol agents or both to help provide sustainable agriculture in Africa and globally. Analyses of Bambara groundnut rhizospheric soil samples included chemical analysis such as nitrogen content analysis using extractable inorganic nitrogen method as well as cation exchangeable capacity using ammonium acetate method. Plant growth-promoting properties of isolated rhizobacteria tested include indole acetic acid, hydrogen cyanide, phosphate solubilization, 1-aminocyclopropane-1-carboxylate and ammonia production activities using standard methods. In addition, antifungal assay dual culture method was used to analyze the biocontrol properties of the isolates. Phylogenetic analysis using 16S rRNA was also carried out on the isolates. Isolated rhizobacteria from bambara groundnut rhizosphere were cultured. All the isolates were able to produce ammonia and 1-aminocyclopropane-1-carboxylate while 4.65%, 12.28% and 27.91% produced Hydrogen cyanide, Indole acetic acid and solubilized phosphate respectively, making them important targets as biocontrol and biofertilizer agents. The growth ofFusarium graminearumwas suppressedin vitroby 6.98% of the isolates. Plant growth promoting activities of rhizobacteria from bambara groundnut rhizosphere reveals that it has great potentials in food security as biofertilizer and biocontrol agent against fungal and bacterial pathogens.
Jekyll or Hyde? The genome (and more) ofNesidiocoris tenuis, a zoophytophagous predatory bug that is both a biological control agent and a pest
Authors: Ferguson K. B. , Visser S. , Dalíková M. , Provazníková I. , Urbaneja A. , Pérez-Hedo M. , Marec F. , Werren J. H. , Zwaan B. J. , Pannebakker B. A. , Verhulst E. C. 
Published: February 2020

AbstractNesidiocoris tenuis(Reuter) is an efficient predatory biological control agent used throughout the Mediterranean Basin in tomato crops but regarded as a pest in northern European countries. Belonging to the family Miridae, it is an economically important insect yet very little is known in terms of genetic information – no published genome, population studies, or RNA transcripts. It is a relatively small and long-lived diploid insect, characteristics that complicate genome sequencing. Here, we circumvent these issues by using a linked-read sequencing strategy on a single femaleN. tenuis. From this, we assembled the 355 Mbp genome and delivered anab initio, homology-based, and evidence-based annotation. Along the way, the bacterial “contamination” was removed from the assembly, which also revealed potential symbionts. Additionally, bacterial lateral gene transfer (LGT) candidates were detected in theN. tenuisgenome. The complete gene set is composed of 24,688 genes; the associated proteins were compared to other hemipterans (Cimex lectularis,Halyomorpha halys, andAcyrthosiphon pisum), resulting in an initial assessment of unique and shared protein clusters. We visualised the genome using various cytogenetic techniques, such as karyotyping, CGH and GISH, indicating a karyotype of 2n=32 with a male-heterogametic XX/XY system. Additional analyses include the localization of 18S rDNA and unique satellite probes via FISH techniques. Finally, population genomics via pooled sequencing further showed the utility of this genome. This is one of the first mirid genomes to be released and the first of a mirid biological control agent, representing a step forward in integrating genome sequencing strategies with biological control research.
High school Internship Program in Integrated Mathematical Oncology (HIP IMO) – five-year experience at Moffitt Cancer Center
Authors: Enderling Heiko , Altrock Philipp M. , Andor Noemi , Basanta David , Brown Joel S. , Gatenby Robert A. , Marusyk Andriy , Rejniak Katarzyna A. , Silva Ariosto , Anderson Alexander R.A. 
Published: February 2020

AbstractModern cancer research, and the wealth of data across multiple spatial and temporal scales, has created the need for researchers that are well-versed in the life sciences (cancer biology, developmental biology, immunology), medical sciences (oncology) and natural sciences (mathematics, physics, engineering, computer sciences). College undergraduate education is traditionally provided in disciplinary silos, which creates a steep learning curve at the graduate and postdoctoral levels that increasingly bridge multiple disciplines. Numerous colleges have begun to embrace interdisciplinary curricula, but students who double-major in mathematics (or other quantitative sciences) and biology (or medicine) remain scarce. We identified the need to educate junior and senior high school students about integrating mathematical and biological skills, through the lens of mathematical oncology, to better prepare students for future careers at the interdisciplinary interface. The High school Internship Program in Integrated Mathematical Oncology (HIP IMO) at Moffitt Cancer Center has so far trained 59 students between 2015 and 2019. We report here on the program structure, training deliverables, curriculum, and outcomes. We hope to promote such interdisciplinary educational activities early in a student’s career.