bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in error-based and reward-based human motor learning is associated with entorhinal volume
Authors: de Brouwer Anouk J. , Rashid Mohammad R. , Flanagan J. Randall , Poppenk Jordan , Gallivan Jason P. 
Published: May 2020

AbstractError-based and reward-based processes are critical for motor learning, and are thought to be mediated via distinct neural pathways. However, recent behavioral work in humans suggests that both learning processes are supported by cognitive strategies and that these contribute to individual differences in motor learning ability. While it has been speculated that medial temporal lobe regions may support this strategic component to learning, direct evidence is lacking. Here we first show that faster and more complete learning during error-based visuomotor adaptation is associated with better learning during reward-based shaping of reaching movements. This result suggests that strategic processes, linked to faster and better learning, drive individual differences in both error-based and reward-based motor learning. We then show that right entorhinal cortex volume was larger in good learning individuals—classified across both motor learning tasks—compared to their poorer learning counterparts. This suggests that strategic processes underlying both error- and reward-based learning are linked to neuroanatomical differences in entorhinal cortex.Significance StatementWhile it is widely appreciated that humans vary greatly in their motor learning abilities, little is known about the processes and neuroanatomical bases that underlie these differences. Here, using a data-driven approach, we show that individual variability in error-based and reward-based motor learning is tightly linked, and related to the use of cognitive strategies. We further show that structural differences in entorhinal cortex predict this intersubject variability in motor learning, with larger entorhinal volumes being associated with better overall error-based and reward-based learning. Together, these findings provide support for the notion that the ability to recruit strategic processes underlies intersubject variability in both error-based and reward-based learning, which itself may be linked to structural differences in medial temporal regions.
Competition delays multi-drug resistance evolution during combination therapy
Authors: Berríos-Caro Ernesto , Gifford Danna R. , Galla Tobias 
Published: May 2020

ABSTRACTCombination therapies have shown remarkable success in preventing the evolution of resistance to multiple drugs, including HIV, tuberculosis, and cancer. Nevertheless, the rise in drug resistance still remains an important challenge. The capability to accurately predict the emergence of resistance, either to one or multiple drugs, may help to improve treatment options. Existing theoretical approaches often focus on exponential growth laws, which may not be realistic when scarce resources and competition limit growth. In this work, we study the emergence of single and double drug resistance in a model of combination therapy of two drugs. The model describes a sensitive strain, two types of single-resistant strains, and a double-resistant strain. We compare the probability that resistance emerges for three growth laws: exponential growth, logistic growth without competition between strains, and logistic growth with competition between strains. Using mathematical estimates and numerical simulations, we show that between-strain competition only affects the emergence of single resistance when resources are scarce. In contrast, the probability of double resistance is affected by between-strain competition over a wider space of resource availability. This indicates that competition between different resistant strains may be pertinent to identifying strategies for suppressing drug resistance, and that exponential models may overestimate the emergence of resistance to multiple drugs. A by-product of our work is an efficient strategy to evaluate probabilities of single and double resistance in models with multiple sequential mutations. This may be useful for a range of other problems in which the probability of resistance is of interest.
Theory and Simulations of condensin mediated loop extrusion in DNA
Authors: Takaki Ryota , Dey Atreya , Shi Guang , Thirumalai D. 
Published: May 2020

ABSTRACTCondensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE), we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the available experimental data quantitatively, and suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity. Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~ 50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE.
The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition
Authors: Dadar Mahsa , Camicioli Richard , Duchesne Simon , Collins D. Louis ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2020

ABSTRACTINTRODUCTIONCognitive decline in Alzheimer’s disease is associated with amyloid-β accumulation, neurodegeneration and cerebral small vessel disease, but the temporal relationships between these factors is not well established.METHODSData included white matter hyperintensity (WMH) load, grey matter (GM) atrophy and Alzheimer’s Disease Assessment Scale-Cognitive-Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1-42) for 461 participants from the Alzheimer’s Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships between baseline WMH, GM, and Aβ1-42 to changes in WMH, GM, Aβ1-42, and cognition at one-year follow-up.RESULTSBaseline WMHs and Aβ1-42 predicted WMH increase and GM atrophy. Baseline WMHs, GM, and Aβ1-42 predicted worsening cognition. Only baseline Aβ1-42 predicted change in Aβ1-42.DISCUSSIONBaseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1-42 predicted WMH increase, suggesting a potential role of amyloid in WM damage.Research in ContextSystematic Review: Both amyloid β and neurodegeneration are primary pathologies in Alzheimer’s disease. White matter hyperintensities (indicative of presence of cerebrovascular disease) might also be part of the pathological changes in Alzheimer’s. However, the temporal relationship between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline is still unclear.Interpretation: Our results establish a potential temporal order between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline, showing that white matter hyperintensities precede neurodegeneration and cognitive decline. The results provide some evidence that amyloid β deposition, in turn, precedes accumulation of white matter hyperintensities.Future Directions: The current findings reinforce the need for future longitudinal investigations of the mechanisms through which white matter hyperintensities impact the aging population in general and Alzheimer’s disease patients, in particular.
A Study of Coronary Artery Disease in the Left Circumflex Artery via Artificial Vessel Restoration
Authors: Paulraj Akhil , Liu Fei 
Published: May 2020

AbstractDiagnosis, risk analysis, and treatment of coronary artery disease (CAD) can be improved with a better understanding of cardiovascular flows. Numerical simulations can assist in achieving this understanding. The objective of this study is to compare the dynamics of blood flow in a diseased left circumflex artery (LCX) and its artificially restored counterpart representing its healthy state. This comparison is made to identify flow characteristics in the restored vessel that contribute to the development of CAD. The diseased LCX geometry was derived from computed tomography angiography data. The stenosed region of the diseased LCX was repaired by manually redefining cross-sections of the vessel, creating the restored geometry. To account for inaccuracies, variations of the restored LCX were made by dilating the repaired surface. Numerical simulations were conducted on all geometries and the results were compared. Alongside expected low wall shear stress, a region of high vorticity was present in all of the restored vessels near the location where CAD developed in the diseased vessel. Therefore, this research suggests that flow vorticity is relevant in assessing the risk for CAD, potentially improving the accuracy of non-invasive, computational diagnosis. Such improvements can also help avoid unnecessary invasive diagnosis methods and minimize risk.
Identifying Mangrove-Coral Habitats in the Florida Keys
Authors: Kellogg Christina A. , Moyer Ryan P. , Jacobsen Mary , Yates Kimberly K. 
Published: May 2020

AbstractCoral reefs are degrading due to many synergistic stressors. Recently there have been a number of global reports of corals occupying mangrove habitats that provide a supportive environment or refugium for corals, sheltering them by reducing stressors such as oxidative light stress and low pH. This study used satellite imagery and manual ground-truthing surveys to search for mangrove-coral habitats in the Florida Keys and then collected basic environmental parameters (temperature, salinity, dissolved oxygen, pHNBS, turbidity) at identified sites using a multi-parameter water quality sonde. Two kinds of mangrove-coral habitats were found in both the Upper and Lower Florida Keys: (1) prop-root corals, where coral colonies were growing directly on (and around) mangrove prop roots, and (2) channel corals, where coral colonies were growing in mangrove channels under the shade of the mangrove canopy, at deeper depths and not in as close proximity to the mangroves. Coral species found growing on and directly adjacent to prop roots includedPorites porites(multiple morphs),Siderastrea radiansandFavia fragum. Channel coral habitats predominantly hostedS. radiansand a fewS. siderea, although single colonies ofSolenastrea bournoniandStephanocoenia interseptawere observed. Circumstantial evidence suggests additional coral communities existed on mangrove shorelines of oceanside and backcountry islands until destroyed, likely by Hurricane Irma. These mangrove-coral habitats may be climate refugia for corals and could be included in ecosystem management plans and considered for their applications in coral restoration, for example, as a source of adapted genetic resources, places to support growth and acclimation of coral outplants, or natural laboratories to test survival of different genotypes.
How good are predictions of the effects of selective sweeps on levels of neutral diversity?
Authors: Charlesworth Brian 
Published: May 2020

ABSTRACTSelective sweeps are thought to play a significant role in shaping patterns of variability across genomes; accurate predictions of their effects are, therefore, important for understanding these patterns. A commonly used model of selective sweeps assumes that alleles sampled at the end of a sweep, and that fail to recombine with wild-type haplotypes during the sweep, coalesce instantaneously, leading to a simple expression for sweep effects on diversity. It is shown here that there can be a significant probability that a pair of alleles sampled at the end of a sweep coalesce during the sweep before a recombination event can occur, reducing their expected coalescent time below that given by the simple approximation. Expressions are derived for the expected reductions in pairwise neutral diversities caused by both single and recurrent sweeps in the presence of such within-sweep coalescence, although the effects of multiple recombination events during a sweep are only treated heuristically. The accuracies of the resulting expressions were checked against the results of simulations. For even moderate ratios of the recombination rate to the selection coefficient, the simple approximation can be substantially inaccurate. The selection model used here can be applied to favorable mutations with arbitrary dominance coefficients, to sex-linked loci with sex-specific selection coefficients, and to inbreeding populations. Using the results from this model, the expected differences between the levels of variability on X chromosomes and autosomes with selection at linked sites are discussed, and compared with data on a population ofDrosophila melanogaster.
Functional Characterization offer-ts, a Temperature-Sensitive FERONIA Mutant Allele That Alters Root Hair Growth
Authors: Kim Daewon , Yang Jiyuan , Gu Fangwei , Park Sung Jin , Combs Jonathon , Adams Alexander , Mayes Heather B. , Bahk Jeong Dong , Nielsen Erik 
Published: May 2020

ABSTRACTIn plants, root hairs undergo a highly-polarized form of cell expansion called tip-growth, in which cell wall deposition is restricted to the root hair apex. In order to identify essential cellular components that might have been missed in earlier genetic screens we identified conditional temperature sensitive (ts) root hair mutants by EMS mutagenesis. Here we describe one of these mutants,fer-ts(feronia-temperaturesensitive). Mutantfer-tsseedlings grew normally at normal temperatures (20°C), but failed to form root hairs at elevated temperatures (30°C). Map based-cloning and whole genome sequencing revealed thatfer-tsresulted from a G41S substitution in the extracellular domain ofFERONIA(FER). A functional fluorescent fusion of FER containing thefer-tsmutation localized to plasma membranes, but was subject to enhanced protein turnover at elevated temperatures. While tip-growth was rapidly inhibited by addition of RALF1 peptides in both wild-type andfer-tsmutants at normal temperatures, root elongation offer-tsseedlings was resistant to added RALF1 peptide at elevated temperatures. Additionally, at elevated temperaturesfer-tsseedlings displayed altered ROS accumulation upon auxin treatment and phenocopied constitutivefermutant responses to a variety of plant hormone treatments. Molecular modeling and sequence comparison with other CrRLK1L receptor family members revealed that the mutated glycine infer-tsis highly conserved, but is not located in the recently characterized RALF23 and LORELI-LIKE-GLYCOPROTEIN (LLG2) binding domains, perhaps suggesting thatfer-tsphenotypes may not be directly due to loss of binding to RALF1 peptides.
Fast computational optimization of TMS coil placement for individualized electric field targeting
Authors: Gomez Luis J. , Dannhauer Moritz , Peterchev Angel V. 
Published: May 2020

AbstractBackgroundDuring transcranial magnetic stimulation (TMS) a coil placed on the scalp is used to non-invasively modulate activity of targeted brain networks via a magnetically induced electric field (E-field). Ideally, the E-field induced during TMS is concentrated on a targeted cortical region of interest (ROI).ObjectiveTo improve the accuracy of TMS we have developed a fast computational auxiliary dipole method (ADM) for determining the optimum coil position and orientation. The optimum coil placement maximizes the E-field along a predetermined direction or, alternatively, the overall E-field magnitude in the targeted ROI. Furthermore, ADM can assess E-field uncertainty resulting from precision limitations of TMS coil placement protocols.MethodADM leverages the electromagnetic reciprocity principle to compute rapidly the TMS induced E-field in the ROI by using the E-field generated by a virtual constant current source residing in the ROI. The framework starts by solving for the conduction currents resulting from this ROI current source. Then, it rapidly determines the average E-field induced in the ROI for each coil position by using the conduction currents and a fast-multipole method. To further speed-up the computations, the coil is approximated using auxiliary dipoles enabling it to represent all coil orientations for a given coil position with less than 600 dipoles.ResultsUsing ADM, the E-fields generated in an MRI-derived head model when the coil is placed at 5,900 different scalp positions and 360 coil orientations per position (over 2.1 million unique configurations) can be determined in under 15 minutes on a standard laptop computer. This enables rapid extraction of the optimum coil position and orientation as well as the E-field variation resulting from coil positioning uncertainty.ConclusionADM enables the rapid determination of coil placement that maximizes E-field delivery to a specific brain target. This method can find the optimum coil placement in under 15 minutes enabling its routine use for TMS. Furthermore, it enables the fast quantification of uncertainty in the induced E-field due to limited precision of TMS coil placement protocols, enabling minimization and statistical analysis of the E-field dose variability.HighlightsAuxiliary dipole method (ADM) optimizes TMS coil placement in under 8 minutesOptimum coil position is up to 14 mm away from conventional targetingOptimum coil orientation is typically near normal to the sulcal wallTMS induced E-field is less sensitive to orientation than position errors
Odor mixture perception: can molecular complexity be a factor determining elemental or configural perception?
Authors: Hamakawa Masayuki , Ishikawa Hiroya , Kikuchi Yumika , Tamura Kaori , Okamoto Tsuyoshi 
Published: May 2020

AbstractOdor mixtures can evoke smells that differ from those of their individual odor components. Research has revealed the existence of two perceptual modes, in which a mixture can be perceived as either the original smells of its individual components (elemental) or as a novel smell (configural). However, the factors underlying the perceptual transformation that occurs when smelling a mixture versus its original components remain unclear. Therefore, the present study aimed to identify the properties of odorants that affect olfactory perception of odor mixtures, focusing on the structural complexity of an odorant. We conducted psychophysical experiments in which different groups of participants were instructed to provide olfactory perceptual descriptions of low-, medium-, and high-complexity odor mixtures or components, respectively. To investigate the perceptual modes induced by the mixtures, we compared the participants’ evaluations between mixtures and components via two types of analyses. First, we compared each olfactory description following quantification via principal component analysis. We then compared data based on seven major olfactory perceptual groups. We observed that odor mixtures composed of low-complexity odorants were perceived as relatively novel smells with regard to both minor (olfactory descriptions) and major (perceptual community) odor qualities than medium- and high-complexity mixtures. Such information may further our understanding of the olfactory perceptual modes of odor mixtures.
Human Endogenous Retrovirus K Rec forms a regulatory loop with MITF that opposes the progression of melanoma to an invasive stage
Authors: Singh Manvendra , Cai Huiqiang , Bunse Mario , Feschotte Cédric , Izsvák Zsuzsanna 
Published: May 2020

AbstractThe HML2 subfamily of HERV-K (henceforth HERV-K) represents the most recently endogenized retrovirus in the human genome. While the products of certain HERV-K genomic copies are expressed in normal tissues, they are upregulated in a number of pathological conditions, including various tumours. It remains unclear whether HERV-K(HML2)-encoded products overexpressed in cancer contribute to disease progression or are merely by-products of tumorigenesis. Here, we focus on the regulatory activities of the Long Terminal Repeats (LTR5_Hs) of HERV-K and on the potential role of the HERV-K-encoded Rec in melanoma. Our regulatory genomics analysis of LTR5_Hs loci indicates that Melanocyte Inducing Transcription Factor (MITF) binds to a canonical E-box motif (CA(C/T)GTG) within these elements inproliferativetype of melanoma, and that depletion of MITF results in reduced HERV-K expression. In turn, experimentally depleting Rec in aproliferativemelanoma cell line leads to lower mRNA levels of MITF and its predicted target genes. Furthermore, Rec knockdown leads to an upregulation of epithelial-to-mesenchymal associated genes and to an enhanced invasion phenotype ofproliferativemelanoma cells. Together these results suggest the existence of a regulatory loop between MITF and Rec that may modulate the transition fromproliferativetoinvasivestages of melanoma. Because HERV-K(HML2) elements are restricted to hominoid primates, these findings might explain certain species-specific features of melanoma progression and point to some limitations of animal models in melanoma studies.
One enzyme reverse transcription qPCR using Taq DNA polymerase
Authors: Bhadra Sanchita , Maranhao Andre C. , Ellington Andrew D. 
Published: May 2020

ABSTRACTTaq DNA polymerase, one of the first thermostable DNA polymerases to be discovered, has been typecast as a DNA-dependent DNA polymerase commonly employed for PCR. However, Taq polymerase belongs to the same DNA polymerase superfamily as the Molony murine leukemia virus reverse transcriptase and has in the past been shown to possess reverse transcriptase activity. We report optimized buffer and salt compositions that promote the reverse transcriptase activity of Taq DNA polymerase, and thereby allow it to be used as the sole enzyme in TaqMan RT-qPCR reactions. We demonstrate the utility of Taq-alone RT-qPCR reactions by executing CDC SARS-CoV-2 N1, N2, and N3 TaqMan RT-qPCR assays that could detect as few as 2 copies/µL of input viral genomic RNA.