bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary Response to Resource Deprivation: Parallelism and Nonmonotonicity
Authors: Behringer Megan G. , Ho Wei-Chin , Miller Samuel F. , Meraz John C. , Boyer Gwyneth F. , Lynch Michael 
Published: December 2019

AbstractEstablishing reliable frameworks for predicting unknown outcomes from empirical observations is of great interest to ecologists and evolutionary biologists. Strong predictability in evolutionary responses has been previously demonstrated by the repeated observation of similar phenotypes or genotypes across multiple natural or experimental populations in analogous environments. However, the degree to which evolutionary outcomes can be predicted across environmental gradients, or in fluctuating environments, remains largely unexplored. Presumably, the phenotypic evolution in an intermediate environment could be interpolated from the evolved phenotypes observed in two extreme environments, but this assumption remains to be fully tested. Here, we report on the experimental evolution ofEscherichia coliunder three nutritional transfer periods: every day, every 10 days, and every 100 days, representing increasing severity in feast/famine cycles. After 900 days of experimental evolution, populations experiencing intermediate durations of starvation had evolved longer times to reach maximum growth rate, smaller colony sizes, higher biofilm formation, and higher mutation rates than populations evolving in the other environmental extremes. Because the intermediately starved populations exhibit significantly high molecular parallelism, these distinct phenotypes are likely due to non-monotonic deterministic forces instead of increased stochastic forces commonly associated with fluctuating environments. Our results demonstrate novel complexities associated with evolutionary predictability across environmental gradients and highlight the risk of using interpolation in evolutionary biology.
MrDNA: A multi-resolution model for predicting the structure and dynamics of nanoscale DNA objects
Authors: Maffeo Christopher , Aksimentiev Aleksei 
Published: December 2019

AbstractAlthough the field of structural DNA nanotechnology has been advancing with an astonishing pace,de novodesign of complex 3D nanostructures remains a laborious and time-consuming process. One reason for that is the need for multiple cycles of experimental characterization to elucidate the effect of design choices on the actual shape and function of the self-assembled objects. Here, we demonstrate a multi-resolution simulation framework,mrdna, that, in 30 minutes or less, can produce an atomistic-resolution structure of an arbitrary DNA nanostructure with accuracy on par with that of a cryo-electron microscopy (cryo-EM) reconstruction. We demonstrate fidelity of ourmrdnaframework through direct comparison of the simulation results with the results of cryo-EM reconstruction of multiple 3D DNA origami objects. Furthermore, we show that our approach can characterize an ensemble of conformations adopted by dynamic DNA nanostructures, the equilibrium structure and dynamics of DNA objects constructed using a self-assembly principle other than origami, i.e., wireframe DNA objects, and to study the properties of DNA objects under a variety of environmental conditions, such as applied electric field. Implemented as an open source Python package, our framework can be extended by the community and integrated with DNA design and molecular graphics tools.
Standardized Effect Sizes and Image-Based Meta-Analytical Approaches for fMRI Data
Authors: Bossier Han , Nichols Thomas E. , Moerkerke Beatrijs 
Published: December 2019

AbstractScientific progress is based on the ability to compare opposing theories and thereby develop consensus among existing hypotheses or create new ones. We argue that data aggregation (i.e. combine data across studies or research groups) for neuroscience is an important tool in this process. An important prerequisite is the ability to directly compare fMRI results over studies. In this paper, we discuss how an observed effect size in an fMRI data-analysis can be transformed into a standardized effect size. We demonstrate how these enable direct comparison and data aggregation over studies. Furthermore, we also discuss the influence of key parameters in the design of an fMRI experiment (such as number of scans and the sample size) on (statistical) properties of standardized effect sizes. In the second part of the paper, we give an overview of two approaches to aggregate fMRI results over studies. The first corresponds to extending the two-level general linear model approach as is typically used in individual fMRI studies with a third level. This requires the parameter estimates corresponding to the group models from each study together with estimated variances and meta-data. Unfortunately, there is a risk of running into unit mismatches when the primary studies use different scales to measure the BOLD response. To circumvent, it is possible to aggregate (unitless) standardized effect sizes which can be derived from summary statistics. We discuss a general model to aggregate these and different approaches to deal with between-study heterogeneity. Furthermore, we hope to further promote the usage of standardized effect sizes in fMRI research.
Skill Acquisition is Enhanced by Reducing Trial-To-Trial Repetition
Authors: Vleugels Lore WE , Swinnen Stephan P , Hardwick Robert M 
Published: December 2019

ABSTRACTDeveloping approaches to improve motor skill learning is of considerable interest across multiple disciplines. Previous research has typically shown that repeating the same action on consecutive trials enhances short-term performance, but has detrimental effects on longer term skill acquisition. However, most prior research has contrasted the effects of repetition only at the block level; here we examined the effects of repeating individual trials embedded in a larger randomized block a feature that is often overlooked when generating random trial orders in learning tasks. With four days of practice, a “Minimal Repeats Group”, who rarely experienced repeating stimuli on consecutive trials during training improved to a greater extent than a “Frequent Repeats Group”, who were frequently presented with repeating stimuli on consecutive trials during training. Our results extend the previous finding of the beneficial effects of random as compared to blocked practice on performance, showing that reduced trial-to-trial repetition during training is favorable with regards to skill learning. This research highlights that limiting the number of repeats on consecutive trials is a simple behavioral manipulation that can enhance the process of skill learning. Data/analysis code and supplementary materials available at https://osf.io/p3278/NEW & NOTEWORTHYNumerous studies have shown that performing different sub-tasks across consecutive blocks of trials enhances learning. Here we examined whether the same effect would occur on a trial-to-trial level. Our Minimal Repeats Group, who primarily responded to different stimuli on consecutive trials, learned more than our Frequent Repeats Group, who frequently responded to the same stimulus on consecutive trials. This shows that minimizing trial-to-trial repetition is a simple and easily applicable manipulation that can enhance learning.
Estimation of Genetic Diversity in Genus Mentha Collected From Azad Jammu And Kashmir, Pakistan
Authors: Abasi Fozia , Ahmad Israr , khan Sami Ullah , Ahmad Khawaja Shafique , Ulfat Aneela , Khurshid Rubab 
Published: December 2019

ABSTRACTMints are perennial aromatic herbs used both for medicinal and aromatic purposes. Flora of Pakistan has reported six species of genus Mentha. Taxonomy of genus Mentha is more complex and confusing due to inter specific hybridization. The present research is the first documented report from Pakistan for the purpose to dissect Mentha specimens using molecular tools. A total of 17 SCoT and SSR markers used to dissect genetic diversity among 41 Mentha specimens. The results revealed substantial variation among Mentha specimens. The molecular data analyzed through NTSYS and Power marker software’s. Dendrogram constructed on the base of similarity coefficients generated using weighted pair group method of arithmetic means (UPGMA) recorded high level of polymorphism. Polymorphic Information Content (PIC) for molecular markers recorded in the range of 5-8. Mean genetic distance (GD) was estimated in the range from 0.35% to 100%. The minimum and maximum GD recorded in one combination each as P2-P4 and M41-P10. The present study was explored the efficiency of SCoT and SSR markers for evaluating the genetic diversity of medicinal plants. The present research was concluded that both morphological and molecular dendrogram determined considerable level of diversity among Mentha species. Furthermore, specific primers and DNA chloroplast technology could be needed for further molecular analysis to refine the data more up to varietal level.
Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons
Authors: Maldonado Paloma P , Nuno-Perez Alvaro , Kirchner Jan , Hammock Elizabeth , Gjorgjieva Julijana , Lohmann Christian 
Published: December 2019

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns.In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+(SST) interneurons specifically. Accordingly, silencing SST+neurons pharmacogenetically fully blocked oxytocin’s effect on inhibitionin vitroas well its effect on spontaneous activity patternsin vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.
Comparing current noise in biological and solid-state nanopores
Authors: Fragasso A. , Schmid S. , Dekker C. 
Published: December 2019

AbstractNanopores bear great potential as single-molecule tools for bioanalytical sensing and sequencing, due to their exceptional sensing capabilities, high-throughput, and low cost. The detection principle relies on detecting small differences in the ionic current as biomolecules traverse the nanopore. A major bottleneck for the further progress of this technology is the noise that is present in the ionic current recordings, because it limits the signal-to-noise ratio and thereby the effective time resolution of the experiment. Here, we review the main types of noise at low and high frequencies and discuss the underlying physics. Moreover, we compare biological and solid-state nanopores in terms of the signal-to-noise ratio (SNR), the important figure of merit, by measuring free translocations of a short ssDNA through a selected set of nanopores under typical experimental conditions. We find that SiNx solid-state nanopores provide the highest SNR, due to the large currents at which they can be operated and the relatively low noise at high frequencies. However, the real game-changer for many applications is a controlled slowdown of the translocation speed, which for MspA was shown to increase the SNR >160-fold. Finally, we discuss practical approaches for lowering the noise for optimal experimental performance and further development of the nanopore technology.
Systemic Treatment with Nicotinamide Riboside is Protective in Three Mouse Models of Retinal Degeneration
Authors: Zhang Xian , Henneman Nathaniel F. , Girardot Preston E. , Sellers Jana T. , Chrenek Micah A. , Li Ying , Wang Jiaxing , Brenner Charles , Nickerson John M. , Boatright Jeffrey H. 
Published: December 2019

AbstractPurpose: The retina is highly metabolically active, suggesting that metabolic dysfunction could underlie many retinal degenerative diseases. Nicotinamide adenine dinucleotide (NAD+) is a cofactor and a co-substrate in several cellular energetic metabolic pathways. Maintaining NAD+ levels may be therapeutic in retinal disease since retinal NAD+ levels decline with age and during retinal damage or degeneration. The purpose of this study was to investigate whether systemic treatment with nicotinamide riboside (NR), a NAD+ precursor, is protective in disparate models of retinal damage or degeneration.MethodsThree mouse models of retinal degeneration were tested: an albino mouse model of light-induced retinal degeneration (LIRD) and two models of retinitis pigmentosa (RP), including a mouse line deficient in interphotoreceptor binding protein (IRBP) gene expression (IRBP KO), and a naturally-occuring cGMP phosphodiesterase 6b mutant mouse model of RP (the Pde6brd10 mouse). Mice were intraperitoneally (IP) injected with PBS or NR at various times relative to damage or degeneration onset. One to two weeks later, retinal function was assessed by electroretinograms (ERGs) and retinal morphology was assessed by optical coherence tomography (OCT). Afterwards, retina sections were H&E stained for morphological analysis or by terminal deoxynucleiotidyl transferase dUTP nick and labeling (TUNEL). Retinal NAD+/NADH levels were enzymatically assayed.ResultsThe retinal degeneration models exhibited significantly suppressed retinal function, and where examined, severely disrupted photoreceptor cell layer and significantly decreased numbers of nuclei and increased accumulation of DNA breaks as measured by TUNEL-labeled cells in the outer nuclear layer (ONL). These effects were prevented by various NR treatment regimens. IP treatment with NR also resulted in increased levels of NAD+ in retina.ConclusionsThis is the first study to report protective effects of NR treatment in mouse models of retinal degeneration. The positive outcomes in several models, coupled with human tolerance to NR dosing, suggest that maintaining retinal NAD+ via systemic NR treatment should be further explored for clinical relevance.
Abundant expression of maternal siRNAs is a conserved feature of seed development
Authors: Grover Jeffrey W. , Burgess Diane , Kendall Timmy , Baten Abdul , Pokhrel Suresh , King Graham J. , Meyers Blake C. , Freeling Michael , Mosher Rebecca A. 
Published: December 2019

AbstractSmall RNAs are abundant in plant reproductive tissues, especially 24-nt short interfering (si)RNAs. Most 24-nt siRNAs are dependent on RNA Pol IV and RDR2, and establish DNA methylation at thousands of genomic loci in a process called RNA-directed DNA methylation (RdDM). In Brassica rapa, RdDM is required in the maternal sporophyte for successful seed development. Here we demonstrate that a small number of siRNA loci account for over 90% of siRNA expression during B. rapa seed development. These loci exhibit unique characteristics with regard to their copy number and association with genomic features, but they resemble canonical 24-nt siRNA loci in their dependence on RNA Pol IV/RDR2 and role in RdDM. These loci are expressed in ovules before fertilization and in the seed coat, embryo, and endosperm following fertilization. We observed a similar pattern of 24-nt siRNA expression in diverse angiosperms despite rapid sequence evolution at siren loci. In the endosperm, siren siRNAs show a marked maternal bias, and siren expression in maternal sporophytic tissues is required for siren siRNA accumulation. Together these results demonstrate that seed development occurs under the influence of abundant maternal siRNAs that might be transported to, and function in, filial tissues.Abstract Figure
Integrative analysis and machine learning based characterization of single circulating tumor cells
Authors: Iyer Arvind , Gupta Krishan , Sharma Shreya , Hari Kishore , Lee Yi Fang , Ramalingam Neevan , Yap Yoon Sim , West Jay , Bhagat Ali Asgar , Subramani Balaram Vishnu , Sabuwala Burhanuddin , Tan Tuan Zea , Thiery Jean Paul , Jolly Mohit Kumar , Ramalingam Naveen , Sengupta Debarka 
Published: December 2019

ABSTRACTWe collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic systems for label-free enrichment of CTCs.
The Phlebotomus papatasi transcriptomic response to trypanosomatid-contaminated blood is robust but non-specific
Authors: Sloan Megan A. , Sadlova Jovana , Lestinova Tereza , Sanders Mandy J. , Cotton James A. , Volf Petr , Ligoxygakis Petros 
Published: December 2019

AbstractLeishmaniasis, caused by parasites of the genus Leishmania, is a disease that effects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control, require a better understanding of the key step for transmission namely, the establishment of infection inside the fly. In this work we wanted to identify fly transcriptomic signatures associated with infection success or failure. We used next generation sequencing to describe the transcriptome of the sand fly Phlebotomus papatasi when fed with blood alone or with blood containing one of three trypanosomatids: Leishmania major, Leishmania donovani and Herpetomonas muscarum: a parasite not transmitted to humans. Of these, only L. major was able to successfully establish an infection in P. papatasi. However, the transcriptional signatures observed were not specific to success or failure of infection but a generalised response to the blood meal. This implies that sand flies perceive Leishmania as just a feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment.Authors summaryLeishmania are parasites that cause leishmaniasis, a group of serious diseases that affect millions of people, mainly across the subtropics and tropics. They are transmitted to humans by phlebotomine sand flies. However, despite establishment in the insect’s midgut being key to transmission, early infection events inside the insect are still unclear. Here, we study the gene expression response of the insect vector to a Leishmania parasite that is able to establish infection (L. major) one that is unable to do so (L. donovani) as well as one that is not a natural parasite of sand flies (Herpetomonas muscarum). We found that responses following any of the infected blood meals was very similar to uninfected blood meal. However, changes post-blood meal from day 1 to day 9 were dramatic. As a blood feeding insect can accumulate three times its weight in one blood meal, this seems to be the most important physiological change rather than the presence of the parasite. The latter might be just one in a number of microbes the insect encounters. This result will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.
A FIJI Macro for quantifying pattern in extracellular matrix
Authors: Wershof Esther , Park Danielle , Barry David J , Jenkins Robert P , Rullan Antonio , Wilkins Anna , Roxanis Ioannis , Anderson Kurt I , Bates Paul A , Sahai Erik 
Published: December 2019

AbstractDiverse extracellular matrix patterns are observed in both normal and pathological tissue. However, most current tools for quantitative analysis focus on a single aspect of matrix patterning. Thus, an automated pipeline that simultaneously quantifies a broad range of metrics and enables a comprehensive description of varied matrix patterns is needed. To this end we have developed an ImageJ plugin called TWOMBLI, which stands for The Workflow Of Matrix BioLogy Informatics. TWOMBLI is designed to be quick, versatile and easy-to-use particularly for non-computational scientists. TWOMBLI can be downloaded from https://github.com/wershofe/TWOMBLI together with detailed documentation. Here we present an overview of the pipeline together with examples from a wide range of contexts where matrix patterns are generated.
Short-term management earnings forecasts and earnings management through real activities manipulation
Authors: Luo Bing 
Published: December 2019

Purpose
The purpose of this paper is to investigate the association between managers’ short-term, quarterly earnings forecast characteristics and earnings management through real activities manipulation.

Design/methodology/approach
Using a propensity-score matched sample from 2000 to 2015, the author examines whether, compared to non-issuers, firms issuing short-term earnings forecasts exhibit abnormal levels of earnings management through the manipulation of real activities such as acceleration of sales, changes in shipment schedules and delaying R&D and maintenance expenditures.

Findings
The finding of this study suggests that firms actually engage in less real activities manipulation when they provide short-term management earnings forecasts. This result does not support the practitioners’ criticism that providing short-term management earnings forecasts increases earnings management. Instead, it suggests that providing management earnings forecasts can reduce information asymmetry between managers and external shareholders, thereby constraining managers’ opportunistic behaviors.

Originality/value
Practitioners have expressed concerns that issuing earnings forecasts may foster managerial myopia, therefore, increasing earnings management. However, recent empirical study found evidence that management earnings forecast mitigates accrual-based earnings management, which is inconsistent with practitioners’ view. This study hence aims to provide timely evidence to this debate by examining the relation between management earnings forecasts and real activities manipulation.