bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiseptic Agents Elicit Short-Term, Personalized and Body Site-Specific Shifts in Resident Skin Bacterial Communities
Authors: SanMiguel Adam J. , Meisel Jacquelyn S. , Horwinski Joseph , Zheng Qi , Bradley Charles W. , Grice Elizabeth A. 
Published: December 2017

ABSTRACTDespite critical functions in cutaneous health and disease, it is unclear how resident skin microbial communities are altered by topical antimicrobial interventions commonly used in personal and clinical settings. Here we show that acute exposure to antiseptic treatments elicits rapid but short-term depletion of microbial community diversity and membership. Thirteen subjects were enrolled in a longitudinal treatment study to analyze the effects of topical treatments (ethanol, povidone-iodine, chlorhexidine, water) on the skin microbiome at two skin sites of disparate microenvironment: forearm and back. Treatment effects were highly dependent on personalized and body site-specific colonization signatures, which concealed community dynamics at the population level when not accounted for in this analysis. The magnitude of disruption was influenced by the identity and abundance of particular bacterial inhabitants. Lowly abundant members of the skin microbiota were more likely to be displaced, and subsequently replaced by the most abundant taxa prior to treatment. Members of the skin commensal family Propionibactericeae were particularly resilient to treatment, suggesting a distinct competitive advantage in the face of disturbance. These results provide insight into the stability and resilience of the skin microbiome, while establishing the impact of topical antiseptic treatment on skin bacterial dynamics and community ecology.
To be a Grid Cell: Shuffling procedures for determining “Gridness”
Authors: Barry C. , Burgess N. 
Published: December 2017

AbstractGrid cells in freely behaving mammals are defined by the strikingly regular periodic spatial distribution of their firing. The standard method of identification calculates the “Gridness” of the spatial firing pattern, with significance being defined relative to the 95th percentile of a null distribution of the Gridness values found after randomly permuting spike times relative to behaviour. We determined the false-positive rate by applying the method to simulated firing with irregular spatially inhomogeneity (i.e. randomly distributed Gaussian patches). We found surprisingly high false positive rates (potentially approaching 20%), which were strongly dependent on the type of Gridness measure used and the number of spatial fields in the synthetic data. This likely reflects the spatial homogeneity of the distributions of spikes after shuffling compared to the inhomogeneous synthetic data. However, false positive rates were reduced (generally below 8%), and less dependent on other factors, when an alternative spatial field shuffling method was used to generate the null Gridness distribution. For comparison, we analysed single unit recordings made using tetrodes implanted into rat medial entorhinal cortex for the purpose of finding grid cells. We found 24% of active neurons were classified as grid cells via spike shuffling and 22% via field shuffling. These results, and the potentially high false-positive rate when classifying cells with patchy but irregular firing as grid cells, indicate that the proportion of cells with regular grid-like firing patterns can be over-estimated by standard methods.
Assembly-free and alignment-free sample identification using genome skims
Authors: Sarmashghi Shahab , Bohmann Kristine , P. Gilbert M. Thomas , Bafna Vineet , Mirarab Siavash 
Published: December 2017

AbstractThe ability to quickly and inexpensively describe taxonomic diversity is critical in this era of rapid climate and biodiversity changes. The currently preferred molecular technique, barcoding, has been very successful, but is based on short organelle markers. Recently, an alternative genome-skimming approach has been proposed: low-pass sequencing (100Mb – several Gb per sample) is applied to voucher and/or query samples, and marker genes and/or organelle genomes are recovered computationally. The current practice of genome-skimming discards the vast majority of the data because the low coverage of genome-skims prevents assembling the nuclear genomes. In contrast, we suggest using all unassembled reads directly, but existing methods poorly support this goal. We introduce a new alignment-free tool, Skmer, to estimate genomic distances between the query and each reference genome-skim using the k-mer decomposition of reads. We test Skmer on a large set of insect and bird genomes, sub-sampled to create genome-skims. Skmer shows great accuracy in estimating genomic distances, identifying the closest match in a reference dataset, and inferring the phylogeny. The software is publicly available on https://github.com/shahab-sarmashghi/Skmer.git
Is there association between APOE e4 genotype and structural brain ageing phenotypes, and does that association increase in older age in UK Biobank? (N = 8,395)
Authors: Lyall Donald M. , Cox Simon R. , Lyall Laura M. , Celis-Morales Carlos , Cullen Breda , Mackay Daniel F. , Ward Joey , Strawbridge Rona J. , McIntosh Andrew M. , Sattar Naveed , Smith Daniel J. , Cavanagh Jonathan , Deary Ian J. , Pell Jill P. 
Published: December 2017

AbstractApolipoprotein (APOE) e4 genotype is a purported risk factor for accelerated cognitive ageing and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N=8,395). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95 confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive ageing.
Complex multicellularity in fungi: evolutionary convergence, single origin, or both?
Authors: Nagy László G. , Krizsán Krisztina 
Published: December 2017

AbstractComplex multicellularity comprises the most advanced level of organization evolved on Earth. It has evolved only a few times in metazoans, green plants, brown and red algae and fungi. Compared to other lineages, the evolution of multicellularity in fungi follows different principles; both simple and complex multicellularity evolved via unique mechanisms not seen in other lineages. In this article we review ecological, paleontological, developmental and genomic aspects of complex multicellularity in fungi and discuss the general principles of the evolution of complex multicellularity in light of its fungal manifestations. Fungi represent the only lineage in which complex multicellularity shows signatures of convergent evolution: it appears 8-12 distinct fungal lineages, which show a patchy phylogenetic distribution, yet share some of the genetic mechanisms underlying complex multicellular development. To mechanistically explain the patchy distribution of complex multicellularity across the fungal tree of life we identify four key observations that need to be considered: the large number of apparently independent complex multicellular clades; the lack of documented phenotypic homology between these; the universal conservation of gene circuits regulating the onset of complex multicellular development; and the existence of clades in which the evolution of complex multicellularity is coupled with limited gene family diversification. We discuss how these patterns and known genetic aspects of fungal development can be reconciled with the genetic theory of convergent evolution to explain its pervasive occurrence in across the fungal tree of life.
Terrestrial effects of moderately nearby supernovae
Authors: Melott Adrian L. , Thomas Brian C. 
Published: December 2017

AbstractRecent data indicate one or more moderately nearby supernovae in the early Pleistocene, with additional events likely in the Miocene. This has motivated more detailed computations, using new information about the nature of supernovae and the distances of these events to describe in more detail the sorts of effects that are indicated at the Earth. This short communication/review is designed to describe some of these effects so that they may possibly be related to changes in the biota around these times.SummaryIt has been known for some time that moderately nearby supernovae may have substantial effects on the Earth. Events at ˜150 light years will happen on average every few Myr, but will tend to happen in groups, with long periods between with no events. The effects of cosmic rays from such events appears to be greater than estimated previously. Ozone depletion and the increase of hazardous UVB continues to be important, but new effects come to the fore. Muon irradiation on the ground and hundreds of meters down into the ocean will increase cancer and mutation rates, the differences being most notable in terrestrial megafauna and benthic organisms. Typically larger organisms live long enough to develop cancer; in microorganisms the primary effects would be associated with mutation rates. Atmospheric ionization in the troposphere will greatly increase lightning rates, with a concomitant increase in the rate of wildfires.
White Matter Hyperintensities and Cognitive Decline in de Novo Parkinson’s Disease Patients
Authors: Dadar Mahsa , Zeighami Yashar , Yau Yvonne , Fereshtehnejad Seyed-Mohammad , Maranzano Josefina , Postuma Ronald B. , Dagher Alain , Collins D. Louis 
Published: December 2017

AbstractObjectiveWhite Matter Hyperintensities (WMHs) are associated with cognitive decline in normative aging and Alzheimer’s disease. However, the pathogenesis of cognitive decline in Parkinson’s disease (PD) is not directly related to vascular causes, and therefore the role of WMHs in PD remains unclear. If WMH has a higher impact on cognitive decline in PD, vascular pathology should be assessed and treated with a higher priority in this population. Here we investigate whether WMH leads to increased cognitive decline in PD, and if these effects relate to cortical thinningMethodsTo investigate the role of WMHs in PD, it is essential to study recently-diagnosed/non-treated patients.De novoPD patients and age-matched controls (NPD=365,NControl=174) with FLAIR/T2-weighted scans at baseline were selected from Parkinson’s Progression Markers Initiative (PPMI). WMHs and cortical thickness were measured to analyse the relationship between baseline WMHs and future cognitive decline (follow-up:4.09±1.14 years) and cortical thinning (follow-up:1.05±0.10 years).ResultsHigh WMH load (WMHL) at baseline in PD was associated with increased cognitive decline, significantly more than i) PDs with low WMHL and ii) controls with high WMHL. Furthermore, PD patients with higher baseline WMHL showed more cortical thinning in right frontal lobe than subjects with low WMHL. Cortical thinning of this region also predicted decline in performance on a cognitive test.InterpretationPresence of WMHs inde novoPD patients predicts greater future cognitive decline and cortical thinning than in normal aging. Recognizing WMHs as a potential predictor of cognitive deficit in PD provides an opportunity for timely interventions.
Diversity and evolution of the emerging Pandoraviridae family
Authors: Legendre Matthieu , Fabre Elisabeth , Poirot Olivier , Jeudy Sandra , Lartigue Audrey , Alempic Jean-Marie , Beucher Laure , Philippe Nadège , Bertaux Lionel , Labadie Karine , Couté Yohann , Abergel Chantal , Claverie Jean-Michel 
Published: December 2017

AbstractWith DNA genomes up to 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infectingPandoravirusesremained the most spectacular viruses since their description in 2013. Our isolation of three new strains from distant locations and environments allowed us to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses, led to the discovery of many non-coding transcripts while significantly reducing the former set of predicted protein-coding genes. We found that the Pandoraviridae exhibit an open pan genome, the enormous size of which is not adequately explained by gene duplications or horizontal transfers. As most of the strain specific genes have no extant homolog and exhibit statistical features comparable to intergenic regions, we suggests thatde novogene creation is a strong component in the evolution of the giant Pandoravirus genomes.
Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH
Authors: Nadtochiy Sergiy M. , Wang Yves T. , Nehrke Keith , Munger Joshua , Brookes Paul S. 
Published: December 2017

ABSTRACTStimulation of the cytosolic NAD+ dependent deacetylase SIRT1 is cardioprotective against ischemia-reperfusion (IR) injury. NAD+ precursors including nicotinamide mononucleotide (NMN) are thought to induce cardioprotection via SIRT1. Herein, while NMN protected perfused hearts against IR (functional recovery: NMN 42±7% vs. vehicle 11±3%), this protection was insensitive to the SIRT1 inhibitor splitomicin (recovery 47±8%). Although NMN-induced cardioprotection was absent in Sirt3-/- hearts (recovery 9±5%), this was likely due to enhanced baseline injury in Sirt3-/- (recovery 6±2%), since similar injury levels in WT hearts also blunted the protective efficacy of NMN. Considering alternative cardiac effects of NMN, and the requirement of glycolysis for NAD+, we hypothesized NMN may confer protection via direct stimulation of cardiac glycolysis. In primary cardiomyocytes, NMN induced cytosolic and extracellular acidification and elevated lactate. In addition, [U-13C]glucose tracing in intact hearts revealed that NMN stimulated glycolytic flux. Consistent with a role for glycolysis in NMN-induced protection, hearts perfused without glucose (palmitate as fuel source), or hearts perfused with galactose (no ATP from glycolysis) exhibited no benefit from NMN (recovery 11±4% and 15±2% respectively). Acidosis during early reperfusion is known to be cardioprotective (i.e., acid post-conditioning), and we also found that NMN was cardioprotective when delivered acutely at reperfusion (recovery 39±8%). This effect of NMN was not additive with acidosis, suggesting overlapping mechanisms. We conclude that the acute cardioprotective benefits of NMN are mediated via glycolytic stimulation, with the downstream protective mechanism involving enhanced ATP synthesis during ischemia and/or enhanced acidosis during reperfusion.
Resolving the Full Spectrum of Human Genome Variation using Linked-Reads
Authors: Marks Patrick , Garcia Sarah , Barrio Alvaro Martinez , Belhocine Kamila , Bernate Jorge , Bharadwaj Rajiv , Bjornson Keith , Catalanotti Claudia , Delaney Josh , Fehr Adrian , Fiddes Ian T. , Galvin Brendan , Heaton Haynes , Herschleb Jill , Hindson Christopher , Holt Esty , Jabara Cassandra B. , Jett Susanna , Keivanfar Nikka , Kyriazopoulou-Panagiotopoulou Sofia , Lek Monkol , Lin Bill , Lowe Adam , Mahamdallie Shazia , Maheshwari Shamoni , Makarewicz Tony , Marshall Jamie , Meschi Francesca , O’keefe Chris , Ordonez Heather , Patel Pranav , Price Andrew , Royall Ariel , Ruark Elise , Seal Sheila , Schnall-Levin Michael , Shah Preyas , Williams Stephen , Wu Indira , Xu Andrew Wei , Rahman Nazneen , MacArthur Daniel , Church Deanna M. 
Published: December 2017

AbstractLarge-scale population based analyses coupled with advances in technology have demonstrated that the human genome is more diverse than originally thought. To date, this diversity has largely been uncovered using short read whole genome sequencing. However, standard short-read approaches, used primarily due to accuracy, throughput and costs, fail to give a complete picture of a genome. They struggle to identify large, balanced structural events, cannot access repetitive regions of the genome and fail to resolve the human genome into its two haplotypes. Here we describe an approach that retains long range information while harnessing the advantages of short reads. Starting from only ∼1ng of DNA, we produce barcoded short read libraries. The use of novel informatic approaches allows for the barcoded short reads to be associated with the long molecules of origin producing a novel datatype known as ‘Linked-Reads’. This approach allows for simultaneous detection of small and large variants from a single Linked-Read library. We have previously demonstrated the utility of whole genome Linked-Reads (lrWGS) for performing diploid, de novo assembly of individual genomes (Weisenfeld et al. 2017). In this manuscript, we show the advantages of Linked-Reads over standard short read approaches for reference based analysis. We demonstrate the ability of Linked-Reads to reconstruct megabase scale haplotypes and to recover parts of the genome that are typically inaccessible to short reads, including phenotypically important genes such as STRC, SMN1 and SMN2. We demonstrate the ability of both lrWGS and Linked-Read Whole Exome Sequencing (lrWES) to identify complex structural variations, including balanced events, single exon deletions, and single exon duplications. The data presented here show that Linked-Reads provide a scalable approach for comprehensive genome analysis that is not possible using short reads alone.
A deep mutational scan of an acidic activation domain
Authors: Staller Max V. , Holehouse Alex S. , Swain-Lenz Devjanee , Das Rahul K. , Pappu Rohit V. , Cohen Barak A. 
Published: December 2017

AbstractTranscriptional activation domains are intrinsically disordered peptides with little primary sequence conservation. These properties have made it difficult to identify the sequence features that define activation domains. For example, although acidic activation domains were discovered 30 years ago, we still do not know what role, if any, acidic residues play in these peptides. To address this question we designed a rational mutagenesis scheme to independently test four sequence features theorized to control the strength of activation domains: acidity (negative charge), hydrophobicity, intrinsic disorder, and short linear motifs. To test enough mutants to deconvolve these four features we developed a method to quantify the activities of thousands of activation domain variants in parallel. Our results with Gcn4, a classic acidic activation domain, suggest that acidic residues in particular regions keep two hydrophobic motifs exposed to solvent. We also found that the specific activity of the Gcn4 activation domain increases during amino acid starvation. Our results suggest that Gcn4 may have evolved to have low activity but high inducibility. Our results also demonstrate that high-throughput rational mutation scans will be powerful tools for unraveling the properties that control how intrinsically disordered proteins function.
Inhibition of Glyoxalase 1 reduces alcohol self-administration in dependent and nondependent rats
Authors: de Guglielmo Giordano , Conlisk Dana E. , Barkley-Levenson Amanda M. , Palmer Abraham A. , George Olivier 
Published: December 2017

AbstractPrevious studies showed that the glyoxalase 1 (Glo1) gene modulates anxiety-like behavior, seizure susceptibility, depression-like behavior, and alcohol drinking in the drinking-in-the-dark paradigm in nondependent mice. Administration of the small-molecule GLO1 inhibitor S-bromobenzylglutathione cyclopentyl diester (pBBG) decreased alcohol drinking in nondependent mice, suggesting a possible therapeutic strategy. However, the preclinical therapeutic efficacy of pBBG in animal models of alcohol dependence remains to be demonstrated. We tested the effect of pBBG (7.5 and 25 mg/kg) on operant alcohol self-administration in alcohol-dependent and nondependent rats. Wistar rats were trained to self-administer 10% alcohol (v/v) and made dependent by chronic intermittent passive exposure to alcohol vapor for 5 weeks. Pretreatment with pBBG dose-dependently reduced alcohol self-administration in both nondependent and dependent animals, without affecting water self-administration. pBBG treatment was more effective in dependent rats than in nondependent rats. These data extend previous findings that implicated Glo1 in alcohol drinking in nondependent mice by showing even more profound effects in alcohol-dependent rats. These results suggest that the pharmacological inhibition of GLO1 is a relevant therapeutic target for the treatment of alcohol use disorders.HighlightsAlcohol use disorder (AUD) places an enormous burden on society, and there is an urgent need for new druggable targets.Glo1 inhibition by pBBG dose-dependently reduces alcohol self-administration in both nondependent and dependent animals.pBBG treatment is more effective in reducing alcohol intake in dependent rats than in nondependent rats.
Prioritizing Parkinson’s Disease genes using population-scale transcriptomic data
Authors: Li Yang I , Wong Garrett , Humphrey Jack , Raj Towfique 
Published: December 2017

AbstractGenome-wide association studies (GWAS) have identified over41susceptibility loci associated with late-onset Parkinson’s Disease (PD) but identifying putative causal genes and the underlying mechanisms remains challenging. To address this, we leveraged large-scale transcriptomic datasets to prioritize genes that are likely to affect PD. We found29gene associations in peripheral monocytes, and44gene associations whose expression or differential splicing in prefrontal cortex is associated with PD. This includes many novel genes but also known associations such as MAPT, for which we found that variation in exon3splicing explains the common genetic association. Genes identified in our analyses are more likely to interact physically with known PD genes and belong to the same or related pathways including lysosomal and innate immune function. Overall, our study provides a strong foundation for further mechanistic studies that will elucidate the molecular drivers of PD.