bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic Genetic Aberrations in Benign Breast Disease and the Risk of Subsequent Breast Cancer
Authors: Zeng Zexian , Vo Andy , Li Xiaoyu , Shidfar Ali , Saldana Paulette , Xuei Xiaoling , Luo Yuan , Khan Seema A. , Clare Susan E. 
Published: April 2019

AbstractIt is largely unknown how the risk of development of breast cancer is transduced by somatic genetic alterations. To address this lacuna of knowledge and acknowledging that benign breast disease (BBD) is an established risk factor for breast cancer, we established a case-control study: The Benign Breast & Cancer Risk (BBCAR) Study. Cases are women with BBD who developed subsequent invasive breast cancer (IBC) at least 3 years after the biopsy and controls are women with BBD who did not develop IBC (median follow-up 16.6 years). We selected 135 cases and individually matched controls (1:2) to cases based on age and type of benign disease: non-proliferative or proliferation without atypia. Whole exome sequencing was performed on DNA from the benign lesions and from subsets with available germline DNA or tumor DNA. Although the number of cases and controls with copy number variation data is limited, several amplifications and deletions are exclusive to the cases. In addition to two known mutational signatures, a novel signature was identified that is significantly (p=0.007) associated with triple negative breast cancer. The somatic mutation rate in benign lesions is similar to that of invasive breast cancer and does not differ between cases and controls. Two mutated genes are significantly associated with time to the diagnosis of breast cancer, and mutations shared between the benign biopsy tissue and the breast malignancy for the ten cases for which we had matched pairs were identified. BBD tissue is a rich source of clues to breast oncogenesis.One Sentence SummaryGenetic aberrations in benign breast lesions distinguish breast cancer cases from controls and predict cancer risk.
Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain
Authors: Li Hui-quan , Spitzer Nicholas C. 
Published: April 2019

AbstractPhysical exercise promotes motor skill learning in normal individuals and those with neurological disorders but its mechanism of action is unclear. We found that one week of voluntary wheel running enhances the acquisition of motor skills in adult mice. One week of running also induces switching from ACh to GABA expression in neurons in the caudal pedunculopontine nucleus (cPPN). The switching neurons make projections to the substantia nigra (SN), ventral tegmental area (VTA) and ventrolateral-ventromedial nuclei of the thalamus (VL-VM), which regulate acquisition of motor skills. Use of viral vectors to override transmitter switching blocks the beneficial effect of running on motor skill learning. We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a new target for clinical treatment of movement disorders.
The user’s guide to comparative genomics with EnteroBase, including case studies on transmissions of micro-clades ofSalmonella, the phylogeny of ancient and modernYersinia pestisgenomes, and the core genomic diversity of allEscherichia
Authors: Zhou Zhemin , Alikhan Nabil-Fareed , Mohamed Khaled , Fan Yulei ,   the Agama Study Group, Achtman Mark 
Published: April 2019

AbstractEnteroBase is an integrated software environment which supports the identification of global population structures within several bacterial genera that include pathogens. Here we provide an overview on how EnteroBase works, what it can do, and its future prospects. EnteroBase has currently assembled more than 300,000 genomes from Illumina short reads fromSalmonella, Escherichia, Yersinia, Clostridiodes, Helicobacter, Vibrio, andMoraxella, and genotyped those assemblies by core genome Multilocus Sequence Typing (cgMLST). Hierarchical clustering of cgMLST sequence types allows mapping, a new bacterial strain to predefined population structures at multiple levels of resolution within a few hours after uploading its short reads. Case study 1 illustrates this process for local transmissions ofSalmonella entericaserovar Agama between neighboring social groups of badgers and humans. EnteroBase also supports SNP calls from both genomic assemblies and after extraction from metagenomic sequences, as illustrated by case study 2 which summarizes the microevolution ofYersinia pestisover the last 5,000 years of pandemic plague. EnteroBase can also provide a global overview of the genomic diversity within an entire genus, as illustrated by case study 3 which presents a novel, global overview of the population structure of all of the species, subspecies and clades withinEscherichia.
A High Dose Tango Intervention for People with Parkinson’s disease (PwPD)
Authors: Rabinovich Débora B. , Garreto Nélida , Arakaki Tomoko , DeSouza Joseph FX 
Published: April 2019

AbstractBackgroundDance has been used extensively to help supplement ongoing therapies for people with PD, most commonly on a weekly or biweekly basis. A daily dose, however, may provide additional benefits. This study examines the dose effect of a dance intervention delivered within a clinic for movement disorders in which PwPD are paired with experienced studio tango dancers.ObjectiveThe current study aims to examine the dose effects of daily dance for PwPD on motor and non-motor functions directly within a movement disorders clinic.Designwithin-subject, pre-post-intervention, mixed-methods evaluation including UPDRS III.SettingThe intervention was held at the Movement Disorders Department of a General Hospital in Buenos Aires, Argentina over two-weeks.SubjectsThe class had 21 people in total attendance per class. Two were expert tango dancers and instructors, nine were advanced tango dancers (volunteers), two were caregivers and eight were people with mild and moderate severity [Hoehn and Yahr (H&Y) scale 1-2] idiopathic Parkinson’s disease.InterventionTen dance lessons, each 90-minutes daily within a two-week period.Outcome measuresThe Movement Disorders Society Unified Parkinson’s Disease Rating Scale (UPDRS) part III was used for pre- and post-motor assessment. Psychological questionnaires, a Likert scale examining symptoms, and a pictorial scale were used to assess non-motor aspects. Semi-structured interviews were conducted to assess the impact of the dance intervention on participants’ experience.ResultsOur study found a significant 18% amelioration in motor symptoms as measured by UPDRS III. We also found improvements on activities of daily living (ADL), sleep, Psychological Needs variables - post high dose dance intervention in Likert Scale.ConclusionsA high dose short-term tango intervention for PwPD improved motor and non-motor aspects of PD such as ADL and sleep with high levels of adherence (97.5%) and enjoyment reported by participants. This dance intervention also improved participant’s perception of their own skills. The frequency or dosage of dance in rehabilitation suggests that an increased dose from once per week to 5 times per week can ameliorate many symptoms of PD and could be used as a short-term intervention.
A glycosaminoglycan extract from Portunus pelagicus inhibits BACE1, the β secretase implicated in Alzheimer’s disease
Authors: Mycroft-West Courtney J. , Cooper Lynsay C. , Devlin Anthony J. , Procter Patricia , Guimond Scott Eric , Guerrini Marco , Fernig David G. , Lima Marcelo A. , Yates Edwin A. , Skidmore Mark A. 
Published: April 2019

AbstractTherapeutic options for Alzheimer’s disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer’s disease-relevant β-secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer’s disease is largely precluded by its potent anticoagulant activity. Furthermore, ongoing concerns regarding the use of mammalian sourced heparins, primarily due to prion diseases and religious beliefs, hinder the deployment of alternative heparin based therapeutics. A marine-derived, heparan sulphate-containing glycosaminoglycan extract isolated from the crabPortunus pelagicus, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC50= 1.85 μg.mL-1(R2= 0.94) and 2.43 μg.mL-1(R2= 0.93), respectively) possessing highly attenuated anticoagulant activities. The results from several structural techniques suggest that the interactions between BACE1 and the extract fromP. pelagicusare complex and distinct from those of heparin.
Raven Calls Indicate Sender’s Neural State
Authors: Huang Zixuan , Wang Zhilong , Xie Jun , Mirt Greg , Yan Chengying , Zhong Jing , Deng Xianli , Liu Fangfang , Zhou Chunlin , Xu Fan 
Published: April 2019

AbstractVocal communication accounts for dominantly percentage within animal species. The information of vocal samples contains not only the amplitude of objects, but also the emotional states behind it. However, to extract the emotion state behind the sound remains controversial. Here we introduce an artificial network method, the Back Propagation Neural Network, BPNN, to classify the emotional states behind the sound. The results disclosed the behaviour categories, including alarm, flight, begging and singing which has been successfully classified. This artificial intelligence classification may aid us to distinguish the ecological categories via animal vocal communication and to discover its significance of evolution and nature.
Pan-genomic and Polymorphic Driven Prediction of Antibiotic Resistance inElizabethkingia
Authors: Naidenov Bryan , Willyerd Karyn , Lim Alexander , Torres Nathanial J , Johnson William L. , Hwang Hong Jin , Hoyt Peter , Gustafson John , Chen Charles 
Published: April 2019

AbstractTheElizabethkingiaare a genetically diverse genus of emerging pathogens that exhibit multidrug resistance to a range of common antibiotics. Two representative species,Elizabethkingia bruunianaandElizabethkingia meningoseptica, were phenotypically tested to determine minimum inhibitory concentrations for five antibiotics. Ultra-long read sequencing with Oxford Nanopore Technologies and subsequentde novoassembly produced complete, gapless circular genomes for each strain. Alignment based annotation with Prokka identified 5,480 features inE. bruunianaand 5,203 features inE. meningoseptica, where none of these identified genes or gene combinations corresponded to observed phenotypic resistance values. Pan-genomic analysis, performed with an additional 19Elizabethkingiastrains, identified a core-genome size of 2,658,537 bp, 32 uniquely identifiable intrinsic chromosomal antibiotic resistance core-genes and 77 antibiotic resistance pan-genes. Using core-SNPs and pan-genes in combination with six machine learning algorithms, binary classification of clindamycin and vancomycin resistance achieved f1 scores of 0.94 and 0.84 respectively. Performance on the more challenging multiclass problem for fusidic acid, rifampin and ciprofloxacin resulted in f1 scores of 0.70, 0.75 and 0.54 respectively.
CXCL5-mediated recruitment of neutrophils into the peritoneal cavity ofGdf15-deficient mice protects against abdominal sepsis
Authors: Santos Isa , Colaço Henrique G. , Neves-Costa Ana , Seixas Elsa , Velho Tiago R. , Pedroso Dora , Barros André , Martins Rui , Carvalho Nuno , Payen Didier , Weis Sebastian , Yi Hyon-Seung , Shong Minho , Moita Luís Ferreira 
Published: April 2019

AbstractSepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth-differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15 and thatGdf15-deficient animals are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.
Two-Color Spatial Cumulant Analysis Detects Heteromeric Interactions between Membrane Proteins
Authors: Foust D.J. , Godin A.G. , Ustione A. , Wiseman P.W. , Piston D.W. 
Published: April 2019

AbstractFluorescence fluctuation spectroscopy (FFS) can be used to measure the aggregation of fluorescently labeled molecules and is typically performed using time series data. Spatial intensity distribution analysis (SpIDA) and fluorescence moment image analysis (FMIA) are established tools for measuring molecular brightnesses from single-color images collected with laser scanning microscopes. We have extended these tools for analysis of two-color images to resolve heteromeric interactions between molecules labeled with spectrally distinct chromophores. We call these new methods two-color SpIDA (2c-SpIDA) and two-color spatial cumulant analysis (2c-SpCA). To implement these techniques on a hyperspectral imaging system, we developed a spectral shift filtering (SSF) technique to remove artifacts due to intrinsic crosstalk between detector bins. We determined that 2c-SpCA provides better resolution from samples containing multiple fluorescent species, hence this technique was carried forward to study images of living cells. We used fluorescent heterodimers labeled with EGFP and mApple to quantify the effects of resonance energy transfer and incomplete maturation of mApple on brightness measurements. We show that 2c-SpCA can detect the interaction between two components of trimeric G-protein complexes. Thus 2c-SpCA presents a robust and computationally expedient means of measuring heteromeric interactions in cellular environments.Statement of SignificanceFluorescence fluctuation spectroscopy (FFS) techniques determine biophysical parameters from samples containing fluorescently labeled biomolecules by considering the statistical nature of fluorescent signals measured with photodetectors. The present study introduces two-color spatial cumulant analysis (2c-SpCA) to the canon of FFS techniques. 2c-SpCA analyzes pixel-value data of two-color images collected with laser scanning fluorescence microscopes. We show that 2c-SpCA can determine several biophysical parameters in living cells including Forster resonance energy transfer efficiency, the dark state fraction of fluorescent proteins, and heteromerization between distinctly labeled proteins. In comparison to existing techniques, 2c-SpCA requires very few image frames for analysis, minimal computations, and can be applied to images of fixed tissue samples.
Response of Bat Activity to Land-Cover and Land-Use Change in Savannas is Scale-, Season-, and Guild-Specific
Authors: Shapiro Julie Teresa , Monadjem Ara , Röder Timo , McCleery Robert A. 
Published: April 2019

AbstractTropical savannas are biomes of global importance that are under severe pressure from anthropogenic change, including land-cover and land-use change. Bats, the second-most diverse group of mammals, are critical to ecosystem functioning, but may be vulnerable to such anthropogenic stresses. However, there is little information on the response of savanna bats to land-cover and land-use change, especially in Africa. This limits our ability to develop conservation strategies for bats and maintain the ecosystem functions and services they provide in this biome. Using acoustic monitoring, we measured how guild-specific (aerial, edge, and clutter forager) bat activity responded to both fine-scale metrics of vegetation structure and landscape-scale metrics of land-cover composition and configuration across the wet and dry seasons in a savanna in southern Africa undergoing rapid land-cover and land-use change. We found that all three guilds responded more strongly to landscape metrics than fine-scale vegetation structure, although the specific metrics varied between guilds. Aerial and edge bats responded most strongly to the percent savanna cover and savanna fragmentation in both seasons while clutter bats responded to percent rural cover in the wet season and percent water cover in the dry. All three guilds responded more strongly to the landscape in the dry season than the wet season. Our results show it is possible to conserve bats, and the ecosystem services they can provide, in savannas undergoing anthropogenic land-use and land-cover change but strategies to do so must consider foraging guild, large spatial scales, and seasonal variation in bat activity.HighlightsBats in savannas respond to land-cover and land-use change on large spatial scalesLandscape had a greater influence on bat activity in the dry season than the wetAerial and edge forager activity responded to savanna cover and fragmentationClutter forager activity was best explained by rural and water coverMinimizing fragmentation and maintaining water promotes bat activity in modified savannas
Rapid 3D enhanced resolution microscopy reveals the dynamics of cortical dendritic spinules
Authors: Zaccard CR , Myczek K , Martin-de-Saavedra MD , Penzes P 
Published: April 2019

SummaryDendritic spinules are thin, membranous protrusions formed by neuronal dendritic spines that are not adequately resolved by diffraction-limited light microscopy. Hence, our understanding of spinules is inferred predominantly from fixed-tissue electron microscopy (EM). Super-resolution modalities have enabled live-cell nanoscopic imaging, but their utility for fast, time-lapse, volumetric imaging has been restricted. Herein, we utilized rapid structured illumination microscopy (SIM) and ‘enhanced resolution’ confocal microscopy to study spatiotemporal spinule dynamics in live cultured cortical pyramidal neurons. Spinules on mushroom spines typically recurred at the same topographical locations and most were short-lived, originating near simple post-synaptic densities (PSDs), while a subset was long-lived and elongated, emerging from complex PSDs. Ca2+ puncta within spinules synchronized with spine head transients and Ca2+ depletion drastically decreased spinule number. Moreover, we uncovered evidence of differential Ca2+-mediated regulation of short-lived and long-lived spinules. Thus, we identified unique spinule classes divergent in lifespan, dynamics, morphology, relationship to the PSD, and regulation. These data suggest distinct synaptic functions of spinule classes, informing future studies, while demonstrating a new application for enhanced resolution microscopy.
Optimizing oleaginous yeast cell factories for flavonoids and hydroxylated flavonoids biosynthesis
Authors: Lv Yongkun , Koffas Mattheos , Zhou Jingwen , Xu Peng 
Published: April 2019

AbstractPlants possess myriads of secondary metabolites with a broad spectrum of health-promoting benefits. Up to date, plant extraction is still the primary route to produce high-value natural products, which inherently suffers from economics and scalability issues. Heterologous production in microbial host is considered as a feasible approach to overcoming these limitations. Flavonoid and its hydroxylated derivatives represent a diversified family of bioactive compounds, most prominently known as antioxidant and anti-aging agents. Oleaginous yeast is rich in hydrophobic lipid bodies and spatially-organized organelles, which provides the ideal environment for the regioselectivity and stereoselectivity of many plant-specific enzymes. In this report, we validated thatY. lipolyticais a superior platform for heterologous production of high-value flavonoids and hydroxylated flavonoids. By modular construction and characterization, we determined the rate-limiting steps for efficient flavonoids biosynthesis inY. lipolytica. We evaluated various precursor pathways and unleashed the metabolic potential ofY. lipolyticato produce flavonoids, including the supply of acetyl-CoA, malonyl-CoA and chorismate. Coupled with the optimized chalcone synthase module and the hydroxylation module, our engineered strain produced 252.4 mg/L naringenin, 134.2 mg/L eriodictyol and 110.5 mg/L taxifolin from glucose. Collectively, these findings demonstrate our ability to harness oleaginous yeast as microbial workhorse to expand nature’s biosynthetic potential, enabling us to bridge the gap between drug discovery and natural product manufacturing.
A Rab GTPase protein FvSec4 is necessary for fumonisin B1 biosynthesis and virulence inFusarium verticillioides
Authors: Yan Huijuan , Huang Jun , Zhang Huan , Shim Won Bo 
Published: April 2019

AbstractRab GTPases are responsible for a variety of membrane trafficking and vesicular transportation in fungi. But the role of Rab GTPases inFusarium verticillioides, one of the key corn pathogens worldwide, remains elusive. These Small GTPases in fungi, particularly those homologous toSaccharomyces cerevisiaeSec4, are known to be associated with protein secretion, vesicular trafficking, secondary metabolism and pathogenicity. Here, we characterized the molecular functions of FvSec4 by generating a null mutant and learned that it is important for vegetative growth, hyphal branching, and conidiation. Interestingly, the mutation did not impair the expression of key conidiation-related genes. Meanwhile, the mutant did not show any defect in sexual development, including perithecia production. GFP-FvSec4 localized to growing hyphal tips, and raised the possibility that FvSec4 is involved in protein trafficking and endocytosis. The mutant exhibited defect in corn stalk rot virulence and also significant alteration of fumonisn B1 production. The mutation led to more sensitivity to oxidative and cell wall stress agents, and defects in carbon utilization. Gene complementation fully restored the defects in the mutant demonstrating that FvSec4 plays important role in these functions. Taken together, our data indicate that FvSec4 plays important roles inF. verticillioideshyphal development, virulence, mycotoxin production and stresses response. Further study is needed to characterize whether the mutation in FvSec4 leads to altered vesicle trafficking and protein secretion, which ultimately impactF. verticillioidesphysiology and virulence.