bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field trial of a probiotic bacteria and a chemical, chitosan, to protect bats from white-nose syndrome
Authors: Hoyt Joseph R. , Langwig Kate E. , White J. Paul , Kaarakka Heather M. , Redell Jennifer A. , Parise Katy L. , Frick Winifred F. , Foster Jeffrey T. , Kilpatrick A. Marm 
Published: March 2019

AbstractTools for reducing wildlife disease impacts are needed to conserve biodiversity. White-nose syndrome (WNS), caused by the fungusPseudogymnoascus destructans, has caused widespread declines in North American bat populations and threatens several species with extinction. Few tools exist for managers to reduce WNS impacts. We tested the efficacy of two treatments, a probiotic bacterium,Pseudomonas fluorescens, and a chemical, chitosan, to reduce impacts of WNS in two simultaneous experiments conducted with caged and free-flyingMyotis lucifugusbats at a mine in Wisconsin, USA. In the free-flying experiment, treatment withP. fluorescensincreased apparent overwinter survival five-fold compared to the control group (from 8.4% to 46.2%) by delaying emergence of bats from the site by 30 days. Apparent overwinter survival for free-flying chitosan-treated bats was 18.0%, which did not differ significantly from control bats. In the cage experiment, chitosan-treated bats had significantly higher survival until release on March 8 (53%) than control andP. fluorescens-treated bats (both 27%). However, these differences were likely due to within-cage disturbance and not reduced WNS impacts, because chitosan-treated bats actually had significantly higher UV-fluorescence (a measure of disease severity), and body mass, not infection intensity, predicted mortality. Further, few of the bats released from the cage experiment were detected emerging from the mine, indicating that the survival estimates at the time of release did not carryover to overwinter survival. These results suggest that treatment of bats may reduce WNS mortality, but additional measures are needed to prevent declines.
Tissue-specific Hi-C analyses of rice, foxtail millet and maize suggest non-canonical function of plant chromatin domains
Authors: Dong Pengfei , Tu Xiaoyu , Li Haoxuan , Zhang Jianhua , Grierson Donald , Li Pinghua , Zhong Silin 
Published: March 2019

AbstractChromatins are not randomly packaged in the nucleus and their organization plays important roles in transcription regulation. Usingin situHi-C, we have compared the 3D chromatin architectures of rice mesophyll and endosperm, foxtail millet bundle sheath and mesophyll, and maize bundle sheath, mesophyll and endosperm tissues. We have also profiled their DNA methylation, open chromatin, histone modification and gene expression to investigate whether chromatin structural dynamics are associated with epigenome features changes. We found that plant global A/B compartment partitions are stable across tissues, while local A/B compartment has tissue-specific dynamic that is associated with differential gene expression. Plant domains are largely stable across tissues, while rare domain border changes are often associated with gene activation. Genes inside plant domains are not conserved across species, and lack significant co-expression behavior unlike those in mammalian cells. When comparing synteny gene pairs, we found those maize genes involved in gene island chromatin loops have shorter genomic distances in smaller genomes without gene island loops such as rice and foxtail millet, suggesting that they have conserved functions. Our study revealed that the 3D configuration of the plant chromatin is also complex and dynamic with unique features that need to be further examined.
Solving High-Resolution Forward Problems for Extra- and Intracranial Neurophysiological Recordings Using Boundary Element Fast Multipole Method
Authors: Makarov Sergey N , Hämäläinen Matti , Okada Yoshio , Noetscher Gregory M , Ahveninen Jyrki , Nummenmaa Aapo 
Published: March 2019

AbstractWe present a general numerical approach for solving the forward problem in high-resolution. This approach can be employed in the analysis of noninvasive electroencephalography (EEG) and magnetoencephalography (MEG) as well as invasive electrocorticography (ECoG), stereoencephalography (sEEG), and local field potential (LFP) recordings. The underlying algorithm is our recently developed boundary element fast multipole method (BEM-FMM) that simulates anatomically realistic head models with unprecedented numerical accuracy and speed. This is achieved by utilizing the adjoint double layer formulation and zeroth-order basis functions in conjunction with the FMM acceleration. We present the mathematical formalism in detail and validate the method by applying it to the canonical multilayer sphere problem. The numerical error of BEM-FMM is 2-10 times lower while the computational speed is 1.5–20 times faster than those of the standard first-order FEM. We present four practical case studies: (i) evaluation of the effect of a detailed head model on the accuracy of EEG/MEG forward solution; (ii) demonstration of the ability to accurately calculate the electric potential and the magnetic field in the immediate vicinity of the sources and conductivity boundaries; (iii) computation of the field of a spatially extended cortical equivalent dipole layer; and (iv) taking into account the effect a fontanel for infant EEG source modeling and comparison of the results with a commercially available FEM. In all cases, BEM-FMM provided versatile, fast, and accurate high-resolution modeling of the electromagnetic field and has the potential of becoming a standard tool for modeling both extracranial and intracranial electrophysiological signals.
Identification of novel glycosylation events on human serum-derived Factor IX
Authors: Pegg Cassandra L. , Zacchi Lucia F. , Recinos Dinora Roche , Howard Christopher B. , Schulz Benjamin L. 
Published: March 2019

ABSTRACTHuman Factor IX is a highly post-translationally modified protein that is an important clotting factor in the blood coagulation cascade. Functional deficiencies in Factor IX result in the bleeding disorder haemophilia B, which is treated with plasma-derived or recombinant Factor IX concentrates. Here, we investigated the post-translational modifications of human serum-derived Factor IX and report previously undescribedO-linked monosaccharide compositions at serine 141 and a novel site of glycosylation. At serine 141 we observed two monosaccharide compositions, with HexNAc1Hex1NeuAc2dominant and a low level of HexNAc1Hex1NeuAc1. ThisO-linked site lies N-terminal to the first cleavage site for the activation peptide, an important region of the protein that is removed to activate Factor IX. The novel site is anN-linked site in the serine protease domain with low occupancy in a non-canonical consensus motif at asparagine 258, observed with a HexNAc4Hex5NeuAc2monosaccharide composition attached. This is the first reported instance of a site of modification in the serine protease domain. The description of these glycosylation events provides a basis for future functional studies and contributes to structural characterisation of native Factor IX for the production of effective therapeutic biosimilars and biobetters.
Thiostrepton hijacks pyoverdine receptors to inhibit growth ofPseudomonas aeruginosa
Authors: Ranieri Michael R. , Chan Derek C. K. , Yaeger Luke , Rudolph Madeleine , Karabelas-Pittman Sawyer , Abdo Hamdi , Chee Jessica , Harvey Hanjeong , Nguyen Uyen , Burrows Lori L. 
Published: March 2019

ABSTRACTPseudomonas aeruginosais a biofilm-forming opportunistic pathogen and intrinsically resistant to many antibiotics. In a high-throughput screen for molecules that modulate biofilm formation, we discovered that the thiopeptide antibiotic, thiostrepton (TS) - considered inactive against Gram-negative bacteria - stimulatedP. aeruginosabiofilm formation in a dose-dependent manner. This phenotype is characteristic of exposure to antimicrobial compounds at sub-inhibitory concentrations, suggesting that TS was active againstP. aeruginosa. Supporting this observation, TS inhibited growth of a panel of 96 multidrug-resistant (MDR)P. aeruginosaclinical isolates at low micromolar concentrations. TS also had activity againstAcinetobacter baumanniiclinical isolates. Expression of Tsr - a 23S rRNA-modifying methyltransferase - in trans conferred TS resistance, confirming that the drug acted via its canonical mode of action, inhibition of ribosome function. Deletion of oligopeptide permease systems used by other peptide antibiotics for uptake failed confer TS resistance. TS susceptibility was inversely proportional to iron availability, suggesting that TS exploits uptake pathways whose expression is increased under iron starvation. Consistent with this finding, TS activity againstP. aeruginosaandA. baumanniiwas potentiated by FDA-approved iron chelators deferiprone and deferasirox. Screening ofP. aeruginosamutants for TS resistance revealed that it exploits pyoverdine receptors FpvA and FpvB to cross the outer membrane. Our data show that the biofilm stimulation phenotype can reveal cryptic sub-inhibitory antibiotic activity, and that TS has activity against select multidrug resistant Gram-negative pathogens under iron-limited growth conditions, similar to those encountered at sites of infection.
Early changes in the urine proteome in a rat liver tumor model
Authors: Zhang Yameng , Gao Yufei , Gao Youhe 
Published: March 2019

AbstractUrine, as a potential biomarker source among the body fluids, can accumulate many changes in the body due to the lack of a mechanism to maintain a homeostatic state. Previous studies have demonstrated that proteomic technology can find many potential biomarkers to reflect different diseases in the urine. This study aims to detect early changes in the urinary proteome in a rat liver tumor model. The tumor model was established with the Walker-256 carcinosarcoma cell line (W256). Compared to before the injection, ninety-five differential proteins were significantly changed in the experimental rats. At day 3, twelve proteins were identified in the absence of pathological changes, and four of them were altered at all four time-points (B2MG, VCAM1, HA11, and LG3BP). Seven had previously been associated with liver cancer. At day 5, fifty-two differential proteins were identified. At day 7 and day 11, there was a significant decrease in the body weight of the rats, and tumor tissue was observed in the liver. Fifty-two and forty differential proteins were changed significantly at day 7 and day 11, respectively. Of the proteins that were identified at these three time-points, and twenty-four were reported to be associated with liver cancer. Comparing the differential urinary proteins and biological processes of liver tumor model with those in different models of W256 grown in other organs, specific differential protein patterns were found among the four models, which indicates that the differential urinary proteins can reflect the differences when the same tumor cell grown in different organs.SignificanceThis study demonstrated that (1) the rat liver tumor model caused early changes in urinary proteins may give new insight into the early diagnosis of liver cancer; (2) the same tumor cell grown in different organs can be reflected in differential urinary proteins.
DNA sequence differences are determinants of meiotic recombination outcome
Authors: Brown Simon D. , Mpaulo Samantha J. , Asogwa Mimi N. , Jézéquel Marie , Whitby Matthew C. , Lorenz Alexander 
Published: March 2019

AbstractMeiotic recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of meiotic recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. UsingSchizosaccharomyces pombe, we show that the distance between sequence polymorphisms across homologs has a strong impact on meiotic recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer recombination events were observed. In the immediate vicinity of DSBs, sequence polymorphisms affect the frequency of intragenic recombination events (gene conversions). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic recombination. A major regulator of this distance-dependent effect is the MutSα-MutLα complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.PreambleDue to a mistake during analysis of a batch of Sanger sequencing reactions for Supplementary Figure S1, we erroneously stated that we found evidence for intragenic crossovers. We now show that intragenic crossovers are less likely than we initially thought. We sincerely apologize for our mishap and any inconvenience it might have caused. However, this does not affect the main conclusions of our paper, just how some of our results are interpreted. This new manuscript version has been amended accordingly.
Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer
Authors: Kim Yoo-Ah , Wojtowicz Damian , Basso Rebecca Sarto , Sason Itay , Robinson Welles , Hochbaum Dorit S. , Leiserson Mark D.M. , Sharan Roded , Vandin Fabio , Przytycka Teresa M. 
Published: March 2019

AbstractStudies of cancer mutations typically focus on identifying cancer driving mutations. However, in addition to the mutations that confer a growth advantage, cancer genomes accumulate a large number of passenger somatic mutations resulting from normal DNA damage and repair processes as well as mutations triggered by carcinogenic exposures or cancer related aberrations of DNA maintenance machinery. These mutagenic processes often produce characteristic mutational patterns called mutational signatures. Understanding the etiology of the mutational signatures shaping a cancer genome is an important step towards understanding tumorigenesis. Considering mutational signatures as phenotypes, we asked two complementary questions (i) what are functional pathways whose geneexpressionprofiles are associated with mutational signatures, and (ii) what aremutated pathways(if any) that might underlie specific mutational signatures? We have been able to identify pathways associated with mutational signatures on both expression and mutation levels. In particular, our analysis provides novel insights into mutagenic processes in breast cancer by capturing important differences in the etiology of different APOBEC related signatures and the two clock-like signatures. These results are important for understanding mutagenic processes in cancer and for developing personalized drug therapies.
Analysis of single nucleotide variants in CRISPR-Cas9 edited zebrafish embryos shows no evidence of off-target inflation
Authors: Mooney Marie R , Davis Erica E , Katsanis Nicholas 
Published: March 2019

AbstractTherapeutic applications of CRISPR-Cas9 gene editing have spurred innovation in Cas9 enzyme engineering and single guide RNA (sgRNA) design algorithms to minimize potential off-target events. While recent work in rodents outlines favorable conditions for specific editing and uses a trio design to control for the contribution of natural genome variation, the potential for CRISPR-Cas9 to induce de novo mutations in vivo remains a topic of interest. In zebrafish, we performed whole exome sequencing (WES) on two generations of offspring derived from the same founding pair: 54 exomes from control and CRISPR-Cas9 edited embryos in the first generation (F0), and 16 exomes from the progeny of inbred F0 pairs in the second generation (F1). We did not observe an increase in the number of transmissible variants in edited individuals in F1, nor in F0 edited mosaic individuals, arguing that in vivo editing does not precipitate an inflation of deleterious point mutations.
Gut feelings begin in childhood: how the gut metagenome links to early environment, caregiving, and behavior
Authors: Flannery Jessica E , Stagaman Keaton , Burns Adam R , Hickey Roxana J , Roos Leslie E , Giuliano Ryan J , Fisher Philip A , Sharpton Thomas J 
Published: March 2019

ABSTRACTPsychosocial environments impact normative behavioral development in children, increasing the risk of problem behaviors and psychiatric disorders across the lifespan. Converging evidence demonstrates early normative development is affected by the gut microbiome, which itself can be altered by early psychosocial environments. Nevertheless, these relationships are poorly understood in childhood, particularly beyond peri- and postnatal microbial colonization. To determine the gut microbiome’s role in the associations between childhood adversity and behavioral development, we conducted a metagenomic investigation among cross-sectional sample of early school-aged children with a range of adverse experiences and caregiver stressors and relationships. Our results indicate that the taxonomic and functional composition of the gut microbiome links to behavioral dysregulation during a critical period of child development. Furthermore, our analysis reveals that both socioeconomic risk exposure and child behaviors associate with the relative abundances of specific taxa (e.g.,BacteroidesandBifidobacteriumspecies) as well as functional modules encoded in their genomes (e.g., monoamine metabolism) that have been linked to cognition and health. We also identified heretofore novel linkages between gut microbiota, their functions, and behavior. These findings hold important translational implications for developmental psychology and microbiome sciences alike, as they suggest that caregiver behavior might mitigate the impact of socioeconomic risk on the microbiome and modify the relationship between subclinical symptoms of behavioral dysregulation and the gut microbiome in early school-aged children.
Neural Correlates of Cognition in Primary Visual versus Neighboring Posterior Cortices during Visual Evidence-Accumulation-based Navigation
Authors: Koay Sue Ann , Thiberge Stephan Y. , Brody Carlos D. , Tank David W. 
Published: March 2019

SummaryStudies of perceptual decision-making have often assumed that the main role of sensory cortices is to provide sensory input to downstream processes that accumulate and drive behavioral decisions. We performed a systematic comparison of neural activity in primary visual (V1) to secondary visual and retrosplenial cortices, as mice performed a task where they should accumulate pulsatile visual cues through time to inform a navigational decision. Even in V1, only a small fraction of neurons had sensory-like responses to cues. Instead, in all areas neurons were sequentially active, and contained information ranging from sensory to cognitive, including cue timings, evidence, place/time, decision and reward outcome. Per-cue sensory responses were amplitude-modulated by various cognitive quantities, notably accumulated evidence. This inspired a multiplicative feedback-loop circuit hypothesis that proposes a more intricate role of sensory areas in the accumulation process, and furthermore explains a surprising observation that perceptual discrimination deviates from Weber-Fechner Law.Highlights / eTOC BlurbMice made navigational decisions based on accumulating pulsatile visual cuesThe bulk of neural activity in visual cortices was sequential and beyond-sensoryAccumulated pulse-counts modulated sensory (cue) responses, suggesting feedbackA feedback-loop neural circuit explains behavioral deviations from Weber’s LawIn a task where navigation was informed by accumulated pulsatile visual evidence, neural activity in visual cortices predominantly coded for cognitive variables across multiple timescales, including outside of a visual processing context. Even sensory responses to visual pulses were amplitude-modulated by accumulated pulse counts and other variables, inspiring a multiplicative feedback-loop circuit hypothesis that in turn explained behavioral deviations from Weber-Fechner Law.
A common tag nucleotide variant inMMP7promoter increases risk for hypertension via enhanced interactions with CREB transcription factor
Authors: Subramanian Lakshmi , Maghajothi Sakthisree , Singh Mrityunjay , Kesh Kousik , Ananthamohan Kalyani , Sharma Saurabh , Khullar Madhu , Victor Suma M. , Swarnakar Snehasikta , Asthana Shailendra , Mullasari Ajit S. , Mahapatra Nitish R. 
Published: March 2019

AbstractMMP7 (Matrilysin), a potent extracellular matrix degrading enzyme with wide substrate specificity, is emerging as a new regulator of cardiovascular diseases including coronary artery disease and atherosclerosis. However, potential contributions ofMMP7genetic variations to hypertension remain unknown. In this study, we first probed for the association of a tag single nucleotide polymorphism (SNP) in theMMP7gene promoter (-181A/G; rs11568818) with hypertension in an urban south Indian population (n=1517). The heterozygous A/G genotype showed a strong association with hypertension as compared to the A/A wild-type genotype (OR=1.641, 95% CI=1.276-2.109; p=1×10−4); AG genotype carriers also displayed significantly higher diastolic blood pressure and mean arterial pressure than AA genotype subjects. The study was replicated in a north Indian population (n=977) as well (OR=1.520, 95% CI =1.106-2.090; p=0.01). Transient transfection experiments usingMMP7promoter-luciferase reporter constructs revealed that the variant -181G allele conferred greater promoter activity than the -181A allele. Computational prediction and structure-based conformational and molecular dynamics simulation studies suggested higher binding affinity for the transcription factor CREB to the -181G promoter. In corroboration, over-expression/down-regulation of CREB and chromatin immunoprecipitation experiments provided convincing evidence for stronger binding of CREB with the -181G promoter. Further, the -181G promoter also displayed an enhanced response to hypoxia and epinephrine-treatment. The higher promoter activity of -181G allele also translated to increased MMP7 protein levels. Indeed,MMP7-181A/G heterozygous individuals displayed elevated plasma MMP7 levels which positively correlated with blood pressure. In conclusion, theMMP7A-181G promoter SNP increased expression of MMP7 under pathophysiological (such as hypoxic stress and catecholamine excess) conditions via increased interactions with the transcription factor CREB and enhanced the risk for hypertension in its carriers.