bluuebunny/crossref_metadata_2025 huggingface dataset:
Convective boundary mixing in low- and intermediate-mass stars – I. Core properties from pressure-mode asteroseismology
Authors: Angelou George C , Bellinger Earl P , Hekker Saskia , Mints Alexey , Elsworth Yvonne , Basu Sarbani , Weiss Achim
Published: February 2020

Convective boundary mixing (CBM) is ubiquitous in stellar evolution. It is a necessary ingredient in the models in order to match observational constraints from clusters, binaries, and single stars alike. We compute ‘effective overshoot’ measures that reflect the extent of mixing and which can differ significantly from the input overshoot values set in the stellar evolution codes. We use constraints from pressure modes to infer the CBM properties of Kepler and CoRoT main-sequence and subgiant oscillators, as well as in two radial velocity targets (Procyon A and α Cen A). Collectively, these targets allow us to identify how measurement precision, stellar spectral type, and overshoot implementation impact the asteroseismic solution. With these new measures, we find that the ‘effective overshoot’ for most stars is in line with physical expectations and calibrations from binaries and clusters. However, two F-stars in the CoRoT field (HD 49933 and HD 181906) still necessitate high overshoot in the models. Due to short mode lifetimes, mode identification can be difficult in these stars. We demonstrate that an incongruence between the radial and non-radial modes drives the asteroseismic solution to extreme structures with highly efficient CBM as an inevitable outcome. Understanding the cause of seemingly anomalous physics for such stars is vital for inferring accurate stellar parameters from TESS data with comparable timeseries length.
Magnetic field structure of the Galactic plane from differential analysis of interstellar polarization
Authors: Zenko Tetsuya , Nagata Tetsuya , Kurita Mikio , Kino Masaru , Nishiyama Shogo , Matsunaga Noriyuki , Nakajima Yasushi
Published: February 2020

A new method for measuring the global magnetic field structure of the Galactic plane is presented. We have determined the near-infrared polarization of field stars around 52 Cepheids found in recent surveys toward the Galactic plane. The Cepheids are located at the galactic longitudes $-10^{\circ} \le l \le +10.^{\!\!\!\circ }5$ and latitudes $-0.^{\!\!\!\circ }22\le b \le +0.^{\!\!\!\circ }45$, and their distances are mainly in the range of 10 to 15 kpc from the Sun. Simple classification of the sightlines is made with the polarization behavior vs. $H-K_{\mathrm{S}}$ color of field stars, and typical examples of three types are presented. Then, division of the field stars in each line of sight into (a) foreground, (b) bulge, and (c) background is made with the Gaia DR2 catalog, the peak of the $H-K_{\mathrm{S}}$ color histogram, and $H-K_{\mathrm{S}}$ colors consistent with the distance of the Cepheid in the center, respectively. Differential analysis between them enables us to examine the magnetic field structure more definitely than just relying on the $H-K_{\mathrm{S}}$ color difference. In one line of sight, the magnetic field is nearly parallel to the Galactic plane and well aligned all the way from the Sun to the Cepheid position on the other side of the Galactic center. Contrary to our preconceived ideas, however, sightlines having such well-aligned magnetic fields in the Galactic plane are rather small in number. At least 36 Cepheid fields indicate random magnetic field components are significant. Two Cepheid fields indicate that the magnetic field orientation changes more than $45^{\circ }$ in the line of sight. The polarization increase per color change $\Delta P/\Delta (H-K_{\mathrm{S}})$ varies from region to region, reflecting the change in the ratio of the magnetic field strength and the turbulence strength.
Thermal-viscous instability in tilted accretion disks: A possible application to IW Andromeda-type dwarf novae
Authors: Kimura Mariko , Osaki Yoji , Kato Taichi , Mineshige Shin
Published: February 2020

IW And stars are a subgroup of dwarf novae characterized by repetition of the intermediate brightness state with oscillatory variations terminated by brightening. This group of dwarf novae is also known to exhibit a wide variety even within one system in long-term light curves, including the usual dwarf-nova outbursts, Z Cam-type standstills, and so on, besides the typical IW And-type variations mentioned above. Following recent observations suggesting that some IW And stars seem to have tilted disks, we have investigated how the thermal-viscous instability works in tilted accretion disks in dwarf novae and whether it could reproduce the essential features of the light curves in IW And stars. By adopting various simplifying assumptions for tilted disks, we have performed time-dependent one-dimensional numerical simulations of a viscous disk by taking into account various mass supply patterns to the disk; that is, the gas stream from the secondary star flows not only to the outer edge of the disk but also to the inner portions of the disk. We find that tilted disks can achieve a new kind of accretion cycle, in which the inner disk almost always stays in the hot state while the outer disk repeats outbursts, thereby reproducing alternating mid-brightness intervals with dips and brightening, which are quite reminiscent of the most characteristic observational light variations of IW And stars. Further, we have found that our simulations produce diverse light variations, depending on different mass supply patterns even without time variations in mass transfer rates. This could explain the wide variety in long-term light curves of IW And stars.
Clinical profile and outcome of patients with Crimean Congo haemorrhagic fever: a hospital based observational study from Rajasthan, India
Authors: Tripathi Swapnil , Bhati Rajendra , Gopalakrishnan Maya , Bohra Gopal Krishna , Tiwari Sarika , Panda Samhita , Sahay Rima R , Yadav Pragya D , Nag Vijaya Lakshmi , Garg Mahendra Kumar
Published: February 2020

Background

Crimean Congo haemorrhagic fever (CCHF) is an emerging zoonotic infection with high mortality. Nosocomial spread is described secondary to body fluid contact.

Methods

Patients meeting the case definition for viral haemorrhagic fever (VHF) from August to November 2019 were tested for CCHF after ruling out dengue, malaria, scrub typhus and leptospirosis in a tertiary teaching hospital in western Rajasthan, India. Diagnosis was confirmed using both quantitative reverse transcription polymerase chain reaction and immunoglobulin M/immunoglobulin G enzyme-linked immunosorbent assay for all patients. All hospital contacts were line listed and tested and symptomatic high-risk contacts received ribavirin post-exposure prophylaxis. Cohorting, personal protective equipment use and hand washing were employed to prevent nosocomial spread.

Results

Four patients tested positive for CCHF. We encountered uncommon initial presentations involving motor weakness and supraventricular tachycardia. Elevated serum lactate dehydrogenase and creatinine kinase were useful in clinical diagnosis. Only one patient survived despite ribavirin therapy. There was zero nosocomial transmission. A partial segment of nucleocapsid of amplified CCHF virus was 99.62% identical to the Afghanistan and Oman strains.

Conclusions

The distribution of CCHF appears to be expanding, with CCHF emerging as endemic in Rajasthan, India. In this setting of high mortality, hand washing and PPE use prevented nosocomial transmission.
Linguistic structure and meaning organize neural oscillations into a content-specific hierarchy
Authors: Kaufeld Greta , Bosker Hans Rutger , Alday Phillip M. , Meyer Antje S. , Martin Andrea E.
Published: February 2020

Neural oscillations track linguistic information during speech comprehension (e.g., Ding et al., 2016; Keitel et al., 2018), and are known to be modulated by acoustic landmarks and speech intelligibility (e.g., Zoefel & VanRullen, 2015). But, it is unclear what information (e.g., timing, rhythm, or content) the brain utilizes to generate linguistic structure and meaning beyond the information that is present in the physical stimulus. We used electroencephalography (EEG) to investigate whether oscillations are modulated by linguistic content over and above the speech stimulus’ rhythmicity and temporal distribution. We manipulated the presence of semantic and syntactic information apart from the timescale of their occurrence, and controlled for the acoustic-prosodic and lexical-semantic information in the signal. EEG was recorded while 29 adult native speakers of all genders listened to naturally-spoken Dutch sentences, jabberwocky controls with a sentence-like prosodic rhythm and morphemes, word lists with lexical content but no phrase structure, and backwards acoustically-matched controls. Mutual information (MI) analysis revealed sensitivity to linguistic content: Phase MI was highest for sentences at the phrasal (0.8-1.1 Hz) and lexical timescale (1.9-2.8 Hz), suggesting that the delta-band is modulated by lexically-driven combinatorial processing beyond prosody, and that linguistic content (i.e., structure and meaning) organizes the phase of neural oscillations beyond the timescale and rhythmicity of the stimulus. This pattern is consistent with neurophysiologically-inspired models of language comprehension (Martin, 2016, 2020; Martin & Doumas, 2017) where oscillations encode endogenously-generated linguistic content over and above exogenous or stimulus-driven timing and rhythm information.

Significance Statement

Biological systems like the brain encode their environment not only by reacting in a series of stimulus-driven responses, but by combining stimulus-driven information with endogenous, internally-generated, inferential knowledge and meaning. Understanding language from speech is the human benchmark for this. Much research focusses on the purely stimulus-driven response, but here, we focus on the goal of language behavior: conveying structure and meaning. To that end, we use naturalistic stimuli that contrast acoustic-prosodic and lexical-semantic information to show that, during spoken language comprehension, oscillatory modulations reflect computations related to inferring structure and meaning from the acoustic signal. Our experiment provides the first evidence to date that compositional structure and meaning organize the oscillatory response, above and beyond acoustic and lexical controls.
Transcriptome analysis of hippocampal subfields identifies gene expression profiles associated with long-term active place avoidance memory
Authors: Harris Rayna M. , Kao Hsin-Yi , Alarcón Juan Marcos , Fenton André A. , Hofmann Hans A.
Published: February 2020

The hippocampus plays a critical role in storing and retrieving spatial information. By targeting the dorsal hippocampus and manipulating specific “candidate” molecules using pharmacological and genetic manipulations, we have previously discovered that long-term active place avoidance memory requires transient activation of particular molecules in dorsal hippocampus. These molecules include amongst others, the persistent kinases Ca-calmodulin kinase II (CaMKII) and the atypical protein kinase C isoform PKCι/λfor acquisition of the conditioned behavior, whereas persistent activation of the other atypical PKC, protein kinase M zeta (PKMζ) is necessary for maintaining the memory for at least a month. It nonetheless remains unclear what other molecules and their interactions maintain active place avoidance long-term memory, and the candidate molecule approach is both impractical and inadequate to identify new candidates since there are so many to survey. Here we use a complementary approach to identify candidates by transcriptional profiling of hippocampus subregions after formation of the long-term active place avoidance memory. Interestingly, 24-h after conditioning and soon after expressing memory retention, immediate early genes were upregulated in the dentate gyrus but not Ammon’s horn of the memory expressing group. In addition to determining what genes are differentially regulated during memory maintenance, we performed an integrative, unbiased survey of the genes with expression levels that covary with behavioral measures of active place avoidance memory persistence. Gene Ontology analysis of the most differentially expressed genes shows that active place avoidance memory is associated with activation of transcription and synaptic differentiation in dentate gyrus but not CA3 or CA1, whereas hypothesis-driven candidate molecule analyses identified insignificant changes in the expression of many LTP-associated molecules in the various hippocampal subfields, nor did they covary with active place avoidance memory expression, ruling out strong transcriptional regulation but not translational regulation, which was not investigated. These findings and the data set establish an unbiased resource to screen for molecules and evaluate hypotheses for the molecular components of a hippocampus-dependent, long-term active place avoidance memory.
The effect of healthy aging on change detection and sensitivity to predictable sturcture in crowded acoustic scenes
Authors: de Kerangal Mathilde , Vickers Deborah , Chait Maria
Published: February 2020

The auditory system plays a critical role in supporting our ability to detect abrupt changes in our surroundings. Here we study how this capacity is affected in the course of healthy ageing. Artifical acoustic ‘scenes’, populated by multiple concurrent streams of pure tones (‘sources’) were used to capture the challenges of listening in complex acoustic environments. Two scene conditions were included: REG scenes consisted of sources characterized by a regular temporal structure. Matched RAND scenes contained sources which were temporally random. Changes, manifested as the abrupt disappearance of one of the sources, were introduced to a subset of the trials and participants (‘young’ group N=41, age 20-38 years; ‘older’ group N=41, age 60-82 years) were instructed to monitor the scenes for these events. Previous work demonstrated that young listeners exhibit better change detection performance in REG scenes, reflecting sensitivity to temporal structure. Here we sought to determine: (1) Whether ‘baseline’ change detection ability (i.e. in RAND scenes) is affected by age. (2) Whether aging affects listeners’ sensitivity to temporal regularity. (3) How change detection capacity relates to listeners’ hearing and cognitive profile. The results demonstrated that healthy aging is associated with reduced sensitivity to abrupt scene changes in RAND scenes but that performance does not correlate with age or standard audiological measures such as pure tone audiometry or speech in noise performance. Remarkably older listeners’ change detection performance improved substantially (up to the level exhibited by young listeners) in REG relative to RAND scenes. This suggests that the capacity to extract and track the regularity associated with scene sources, even in crowded acoustic environments, is relatively preserved in older listeners.
Multi-scale planning helps resolve global conservation needs with regional priorities
Authors: Rinnan D. Scott , Sica Yanina , Ranipeta Ajay , Wilshire John , Jetz Walter
Published: February 2020

Area-based conservation through reserves or other measures is vital for preserving biodiversity and its functions for future generations1–5, but its effective implementation suffers from a lack of both spatial detail necessary for management practices6and transparency around national responsibilities that might underpin cross-national support mechanisms7. Here we implement a conservation prioritization2,8framework that accounts for spatial data limitations yet offers actionable guidance at a 1km resolution. Our multi-scale linear optimization approach delineates globally the areas required to meet area-based conservation targets for all ~32 000 described terrestrial vertebrate species, while offering flexibility in decision management to meet different local conservation objectives. Roughly 30.4% of land is sufficient to meet conservation targets for all species, of which 60.1% is either already protected9or has minimal human modification10. However, the remaining 39.9% of human-modified areas need to be managed or restored in some form to ensure the long-term survival for over half of species. This burden of area-based conservation is distributed very unevenly among countries, and, without a process that explicitly addresses geopolitical inequity, meeting species conservation targets would require disproportionately large commitments from poorer countries (i.e., lower GNI). Our analysis provides baseline information for a potential intergovernmental and stakeholder contribution mechanism in service of a globally shared goal of sustaining biodiversity. Future updates and extensions to this global priority map have the potential to guide local and national advocacy and actions with a data-driven approach to support global conservation outcomes.
The nucleus accumbens core is necessary to scale fear to degree of threat
Authors: Ray Madelyn H. , Russ Alyssa N. , Walker Rachel A. , McDannald Michael A.
Published: February 2020

Fear is adaptive when the level of the response rapidly scales to degree of threat. Using a discrimination procedure consisting of danger, uncertainty and safety cues, we have found rapid fear scaling (within two seconds of cue presentation) in male rats. Here we examined a possible role for the nucleus accumbens core (NAcc) in the acquisition and expression of fear scaling. In experiment 1, male Long Evans rats received bilateral sham or neurotoxic NAcc lesions, recovered and underwent fear discrimination. NAcc-lesioned rats were generally impaired in scaling fear to degree of threat, and specifically impaired in rapid uncertainty-safety discrimination. In experiment 2, male Long Evans rats received NAcc transduction with halorhodopsin or a control fluorophore. After fear scaling was established, the NAcc was illuminated during cue or control periods. NAcc-halorhodopsin rats receiving cue illumination were specifically impaired in rapid uncertainty-safety discrimination. The results reveal a general role for the NAcc in scaling fear to degree of threat, and a specific role in rapid discrimination of uncertain threat and safety.

Significance Statement

Rapidly discriminating cues for threat and safety is essential for survival and impaired threat-safety discrimination is a hallmark of stress and anxiety disorders. In two experiments, we induced nucleus accumbens core (NAcc) dysfunction in rats receiving fear discrimination consisting of cues for danger, uncertainty and safety. Permanent NAcc dysfunction, via neurotoxic lesion, generally disrupted the ability to scale fear to degree of threat, and specifically impaired one component of scaling: rapid discrimination of uncertain threat and safety. Reversible NAcc dysfunction, via optogenetic inhibition, specifically impaired rapid discrimination of uncertain threat and safety. The results reveal that the NAcc is essential to scale fear to degree of threat, and is a plausible source of dysfunction in stress and anxiety disorders.
Unexplained Repeated Pregnancy Loss is Associated with Altered Perceptual and Brain Responses to Men’s Body-Odor
Authors: Rozenkrantz Liron , Weissgross Reut , Weiss Tali , Ravrebi Inbal , Frumin Idan , Shushan Sagit , Gorodisky Lior , Reshef Netta , Holzman Yael , Pinchover Liron , Endevelt-Shapira Yaara , Mishor Eva , Furman-Haran Edna , Carp Howard , Sobel Noam
Published: February 2020

In theBruce effect, pregnant mice remember the odor of the fathering male, and miscarry in response to the odor of a male stranger. Humans experience a high rate of unexplained spontaneous miscarriage. Could it be that a portion of these miscarriages reflect a Bruce-like effect? Given ethical constraints on a direct test, we instead probed for circumstantial evidence in women with repeated pregnancy loss (RPL). Consistent with a Bruce-like effect, women with RPL remembered the body-odor of their spouse, but controls could not. Also consistent with a Bruce-like effect, body-odor from a stranger man caused increased activity in the hypothalamus of women experiencing RPL, yet decreased activity in the hypothalamus of women controls. Finally, RPL was associated with reduced olfactory-bulb volume. Although not causal, these observations link RPL with an altered behavioral and brain response to men’s body-odor, implicating the olfactory system in this poorly understood or managed condition.
Visual mental imagery engages the left fusiform gyrus, but not the early visual cortex: a meta-analysis of neuroimaging evidence
Authors: Spagna Alfredo , Hajhajate Dounia , Liu Jianghao , Bartolomeo Paolo
Published: February 2020

The dominant neural model of visual mental imagery (VMI) stipulates that memories from the medial temporal lobe acquire sensory features in early visual areas. However, neurological patients with damage restricted to the occipital cortex typically show perfectly vivid VMI, while more anterior damages extending into the temporal lobe, especially in the left hemisphere, often cause VMI impairments. Here we present two major results reconciling neuroimaging findings in neurotypical subjects with the performance of brain-damaged patients: (1) a large-scale metaanalysis of 46 fMRI studies, of which 27 investigated specifically visual mental imagery, revealed that VMI engages fronto-parietal networks and a well-delimited region in the left fusiform gyrus. (2) A Bayesian analysis showing no evidence for imagery-related activity in early visual cortices. We propose a revised neural model of VMI that draws inspiration from recent cytoarchitectonic and lesion studies, whereby fronto-parietal networks initiate, modulate, and maintain activity in a core temporal network centered on the fusiform imagery node, a high-level visual region in the left fusiform gyrus.
Assessing performance of pathogenicity predictors using clinically-relevant variant datasets
Authors: Gunning Adam C , Fryer Verity , Fasham James , Crosby Andrew H , Ellard Sian , Baple Emma , Wright Caroline F
Published: February 2020

Purpose

Pathogenicity predictors are an integral part of genomic variant interpretation but, despite their widespread usage, an independent validation of performance using a clinically-relevant dataset has not been undertaken.

Methods

We derive two validation datasets: an “open” dataset containing variants extracted from publicly-available databases, similar to those commonly applied in previous benchmarking exercises, and a “clinically-representative” dataset containing variants identified through research/diagnostic exome and diagnostic panel sequencing. Using these datasets, we evaluate the performance of three recently developed meta-predictors, REVEL, GAVIN and ClinPred, and compare their performance against two commonly usedin silicotools, SIFT and PolyPhen-2.

Results

Although the newer meta-predictors outperform the older tools, the performance of all pathogenicity predictors is substantially lower in the clinically-representative dataset. Using our clinically-relevant dataset, REVEL performed best with an area under the ROC of 0.81. Using a concordance-based approach based on a consensus of multiple tools reduces the performance due to both discordance between tools and false concordance where tools make common misclassification. Analysis of tool feature usage may give an insight into the tool performance and misclassification.

Conclusion

Our results support the adoption of meta-predictors over traditionalin silicotools, but do not support a consensus-based approach as recommended by current variant classification guidelines.
Unbalanced Sample Size Introduces Spurious Correlations to Genome-wide Heterozygosity Analyses
Authors: Liu Li , Caselli Richard J
Published: February 2020

Excess of heterozygosity (H) is a widely used measure of genetic diversity of a population. As high-throughput sequencing and genotyping data become readily available, it has been applied to investigating the associations of genome-wide genetic diversity with human diseases and traits. However, these studies often report contradictory results. In this paper, we present a meta-analysis of five whole-exome studies to examine the association of H scores with Alzheimer’s disease. We show that the mean H score of a group is not associated with the disease status, but is associated with the sample size. Across all five studies, the group with more samples has a significantly lower H score than the group with fewer samples. To remove potential confounders in empirical data sets, we perform computer simulations to create artificial genomes controlled for the number of polymorphic loci, the sample size and the allele frequency. Analyses of these simulated data confirm the negative correlation between the sample size and the H score. Furthermore, we find that genomes with a large number of rare variants also have inflated H scores. These biases altogether can lead to spurious associations between genetic diversity and the phenotype of interest. Based on these findings, we advocate that studies shall balance the sample sizes when using genome-wide H scores to assess genetic diversities of different populations, which helps improve the reproducibility of future research.
DoesDrosophila sechelliaescape parasitoid attack by feeding on a toxic resource?
Authors: Salazar-Jaramillo Laura , Wertheim Bregje
Published: February 2020

Host shifts can drastically change the selective pressures that animals experience from their environment.Drosophila sechelliais a species restricted to the Seychelles islands, where it specialized on the fruitMorinda citrifolia(noni). This fruit is known to be toxic to closely relatedDrosophilaspecies, includingD. melanogasterandD. simulans, releasingD. sechelliafrom interspecific competition when breeding on this substrate. Previously, we showed thatD. sechelliais unable to mount an effective immunological response against wasp attack, while the closely-related species can defend themselves from parasitoid attack by melanotic encapsulation. We hypothesized that this inability constitutes a trait loss due to a reduced risk of parasitoid attack in noni. Here we present a field study aimed to test the hypothesis that specialization on noni has releasedD. sechelliafrom the antagonistic interaction with its larval parasitoids. Our results from the field survey indicate thatD. sechelliawas found in ripe noni, whereas anotherDrosophilaspecies,D. malerkotliana, was present in unripe and rotting stages. Parasitic wasps of the speciesLeptopilina boulardiemerged from rotten noni, whereD. malerkotlianawas the most abundant host. These results indicate that the specialization ofD. sechelliaon noni has indeed drastically altered its ecological interactions, leading to a relaxation in the selection pressure to maintain parasitoid resistance.
Transcranial Photobiomodulation with Near-Infrared Light from Childhood to Elderliness: Simulation of Dosimetry
Authors: Yuan Yaoshen , Cassano Paolo , Pias Matthew , Fang Qianqian
Published: February 2020

Significance

Major depressive disorder (MDD) affects over 40 million US adults in their lifetimes. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for anatomical head and brain changes due to aging.

Aim

We study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Caxrlo (MC) simulations and age-dependent brain atlases ranging between 5 to 85 years of age.

Approach

Age-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3-F4 and Fp1-Fpz-Fp2 in the EEG 10-20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions – dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) – are quantified.

Results

An overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extra-cerebral tissues (ECT) and energy deposition, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3-F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1-Fpz-Fp2 position.

Conclusion

Quantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the needs for personalized and age-adaptive t-PBM treatment planning.
Abstract sequential task control is facilitated by practice and embedded motor sequences
Authors: Trach Juliana E. , McKim Theresa H. , Desrochers Theresa M.
Published: February 2020

Everyday task sequences, such as cooking, contain overarching goals (completing the meal), sub-goals (prepare vegetables), and motor actions (chopping). Such tasks generally are considered hierarchical because superordinate levels (e.g., goals) affect performance at subordinate levels (e.g., sub-goals and motor actions). However, there is debate as to whether this hierarchy is “strict” with unidirectional, top-down influences, and it is unknown if and how practice affects performance at the superordinate levels. To investigate these questions, we manipulated practice with sequences at the goal and motor action levels using an abstract, or non-motor, task sequence paradigm (Desrochers et al., 2015; Schneider & Logan, 2006). In three experiments, participants performed memorized abstract task sequences composed of simple tasks (e.g., color/shape judgements), where some contained embedded motor response sequences. We found that practice facilitated performance and reduced control costs for abstract task sequences and subordinate tasks. The interrelation was different between the hierarchical levels, demonstrating a strict relationship between abstract task sequence goals and sub-goals and a non-strict relationship between sub-goal and motor response levels. Under some conditions, the motor response level influenced the abstract task sequence level in a non-strict manner. Further, manipulating the presence or absence of a motor sequence after learning indicated that these effects were not the result of an integrated representation produced by practice. These experiments provide evidence for a mixed hierarchical model of task sequences and insight into the distinct roles of practice and motor processing in efficiently executing task sequences in daily life.
Development of a Murine Model of Pyogenic Flexor Tenosynovitis
Authors: Qiu Bowen , Cobb Justin , Loiselle Alayna , Ketonis Constantinos
Published: February 2020

Background

To demonstrate the plausibility of a murine model of pyogenic flexor tenosynovitis.

Methods

2μL of sterile PBS or bioluminescent Xen29Staphylococcus aureuswas administered to the tendon sheath of 36 male C57BL/6J mice. The infectious course was monitored by bioluminescence (BLI) signal via IVIS imaging and recording of weight change. The infected hind paws were harvested at four time points: 24 hours, 72 hours, 1 week and 2 weeks for histopathology using Alcian Blue hematoxylin staining. Two-way ANOVA with Sidak’s multiple comparison test was used for statistical analysis.

Results

The infected cohort displayed significantly elevated bioluminescent values, reductions in weight, and exhibited swelling of the infected digit throughout the course of infection. By day 7 most infected mice saw a substantial decrease in BLI signal intensity, however two infected mice exhibited persistent BLI intensity through day 14. Histopathology of the infected cohort showed tissue disorganization and the presence of a cellular infiltrate in and around the flexor tendon sheath.

Conclusions

A murine model of pyogenic flexor tenosynovitis is possible. Further optimization of the model offers an experimental platform for investigation of the pathophysiology of pyogenic flexor tenosynovitis.

Clinical Relevance

This animal model can be utilized in order to elucidate the basic molecular/cellular mechanisms of pyogenic flexor tenosynovitis while simultaneously evaluating novel therapeutic strategies.
STRIDER: Steric hindrance estimator
Authors: Prasad Patro L Ponoop , Rathinavelan Thenmalarchelvi
Published: February 2020

In silicomodeling plays a vital role in thede novodesigning and docking of biomacromolecules as well as in exploring their conformational dynamics. Additionally, it has a major role in acquiring the structural insights from the parameters derived from the experimental techniques such as cryo-electron microscopy. Steric hindrance is one of the important measures to validate the accuracy of the constructed model. A web user interface (WUI) namely, STRIDER (steric hindranceestimator) (www.iith.ac.in/strider/) can estimate and report pairwise inter- and intra- molecular steric hindrances using the van der Waals radius of 117 elements through a user interactive interface. STRIDER also identifies and reports the coordination number of 64 metals along with their interacting pattern in an interactive mode. STRIDER can analyze an ensemble of conformers, wherein, multiple conformers are used to circumvent sampling issue in flexible docking, understand protein folding and facilitate structure based virtual screening. Further, it generates a pymol session file that can be used for offline analysis. As STRIDER simply requires the Cartesian coordinates of the given molecule in protein data bank format, any chemical structure can be an input.

Availability

It can be freely accessible through:www.iith.ac.in/strider/without any registration.

Theme Of the Concept
Spatial inter-centromeric interactions facilitated the emergence of evolutionary new centromeres
Authors: Guin Krishnendu , Chen Yao , Mishra Radha , Muzaki Siti Rawaidah B. M. , Thimmappa Bhagya C. , O’Brien Caoimhe E. , Butler Geraldine , Sanyal Amartya , Sanyal Kaustuv
Published: February 2020

Centromeres ofCandida albicansform on unique and different DNA sequences but a closely related species,Candida tropicalis, possesses homogenized inverted repeat (HIR)-associated centromeres. To investigate the mechanism of centromere-type transition, we improved the fragmented genome assembly and constructed a chromosome-level genome assembly ofC. tropicalisby employing PacBio sequencing, chromosome conformation capture sequencing (3C-seq), chromoblot, and genetic analysis of engineered aneuploid strains. Further, we analyzed the 3D genome organization using 3C-seq data, which revealed spatial proximity among the centromeres as well as telomeres of seven chromosomes inC. tropicalis. Intriguingly, we observed evidence of inter-centromeric translocations in the common ancestor ofC. albicansandC. tropicalis. Identification of putative centromeres in closely relatedCandida sojae, Candida viswanathiiandCandida parapsilosisindicates loss of ancestral HIR-associated centromeres and establishment of evolutionary new centromeres (ENCs) inC. albicans. We propose that spatial proximity of the homologous centromere DNA sequences facilitated karyotype rearrangements and centromere type transitions in human pathogenic yeasts of the CUG-Ser1 clade.
Augmenting Vascular Disease Diagnosis by Vasculature-aware Unsupervised Learning
Authors: Wang Yong , Ji Mengqi , Jiang Shengwei , Wang Xukang , Wu Jiamin , Duan Feng , Fan Jingtao , Huang Laiqiang , Ma Shaohua , Fang Lu , Dai Qionghai
Published: February 2020

Vascular diseases are among the leading causes of death and threaten human health worldwide. Imaging examination of vascular pathology with reduced invasiveness is challenging due to the intrinsic vasculature complexity and the non-uniform scattering from bio-tissues. Here, we report VasNet, a vasculature-aware unsupervised learning algorithm that augments pathovascular recognition from small sets of unlabeled fluorescence and digital subtraction angiography (DSA) images. The VasNet adopts the multi-scale fusion strategy with a domain adversarial neural network (DANN) loss function that induces biased pattern reconstruction, by strengthening the features relevant to the retinal vasculature reference while weakening the irrelevant features. VasNet delivers outputs of “Structure + X”, where X refers to multi-dimensional features such as blood flows, the distinguishment of blood dilation and its suspicious counterparts, and the dependence of new pattern emergence on a disease progression, which may assist the discovery of novel diagnostics. Therefore, explainable imaging output from VasNet and other algorithm extensions hold the promise to revolutionize the practice of medical diagnosis, as it improves performance while reduces the cost on human expertise, equipment exquisite and time consumption.
Sparse latent factor regression models for genome-wide and epigenome-wide association studies
Authors: Jumentier Basile , Caye Kevin , Heude Barbara , Lepeule Johanna , François Olivier
Published: February 2020

Association of phenotypes or exposures with genomic and epigenomic data faces important statistical challenges. One of these challenges is to account for variation due to unobserved confounding factors, such as individual ancestry or cell-type composition in tissues. This issue can be addressed with penalized latent factor regression models, where penalties are introduced to cope with high dimension in the data. If a relatively small proportion of genomic or epigenomic markers correlate with the variable of interest, sparsity penalties may help to capture the relevant associations, but the improvement over non-sparse approaches has not been fully evaluated yet. Here, we present least-squares algorithms that jointly estimate effect sizes and confounding factors in sparse latent factor regression models. In simulated data, sparse latent factor regression models generally achieved higher statistical performance than other sparse methods, including the least absolute shrinkage and selection operator (LASSO) and a Bayesian sparse linear mixed model (BSLMM). In generative model simulations, statistical performance was slightly lower (while being comparable) to non-sparse methods, but in simulations based on empirical data, sparse latent factor regression models were more robust to departure from the model than the non-sparse approaches. We applied sparse latent factor regression models to a genome-wide association study of a flowering trait for the plantArabidopsis thalianaand to an epigenome-wide association study of smoking status in pregnant women. For both applications, sparse latent factor regression models facilitated the estimation of non-null effect sizes while overcoming multiple testing issues. The results were not only consistent with previous discoveries, but they also pinpointed new genes with functional annotations relevant to each application.
Snow Microbiome Functional Analyses Reveal Novel Microbial Metabolism of Complex Organic Compounds
Authors: Zhu Chengsheng , Miller Maximilian , Lusskin Nicholas , Bergk Pinto Benoît , Maccario Lorrie , Haggblom Max , Vogel Timothy , Larose Catherine , Bromberg Yana
Published: February 2020

Microbes active in extremely cold environments are not as well explored as those of other extreme environments. Studies have revealed a substantial microbial diversity and identified cold-specific microbiome molecular functions. We analyzed the metagenomes and metatranscriptomes of twenty snow samples collected during early and late spring in Svalbard, Norway using our computational read-based microbiome function annotation tool, mi-faser. Our results revealed a more diverse microbiome functional capacity and activity in the early compared to in the late spring samples. The dissimilarity between the metagenomes and metatranscriptomes of the same samples was also significantly higher in the early spring. These findings suggest that early spring samples may contain a larger fraction of DNA of dormant organisms, while late spring samples reflect a new community that is metabolically active. We additionally showed that the abundance of the sequencing reads mapping to the fatty acid synthesis-related microbial pathways was significantly positively correlated with organic acid levels, in both our late spring metagenomes and metatranscriptomes. Moreover, the geraniol degradation pathway and the styrene degradation pathway read abundances correlated and inversely correlated, respectively, with the organic acid levels. These results suggest a possible nutrient switch. Our study thus highlights the activity of microbial degradation pathways of complex organic compounds previously unreported at low temperatures.
SCRINSHOT, a spatial method for single-cell resolution mapping of cell states in tissue sections
Authors: Sountoulidis Alexandros , Liontos Andreas , Nguyen Hong Phuong , Firsova Alexandra B. , Fysikopoulos Athanasios , Qian Xiaoyan , Seeger Werner , Sundström Erik , Nilsson Mats , Samakovlis Christos
Published: February 2020

Changes in cell identities and positions underlie tissue development and disease progression. Although, single-cell mRNA sequencing (scRNA-Seq) methods rapidly generate extensive lists of cell-states, spatially resolved single-cell mapping presents a challenging task. We developed SCRINSHOT (SingleCellResolutionINSituHybridizationOnTissues), a sensitive, multiplex RNA mapping approach. Direct hybridization of padlock probes on mRNA is followed by circularization with SplintR ligase and rolling circle amplification (RCA) of the hybridized padlock probes. Sequential detection of RCA-products using fluorophore-labeled oligonucleotides profiles thousands of cells in tissue sections. We evaluated SCRINSHOT specificity and sensitivity on murine and human organs. SCRINSHOT quantification of marker gene expression shows high correlation with published scRNA-Seq data over a broad range of gene expression levels. We demonstrate the utility of SCRISHOT by mapping the locations of abundant and rare cell types along the murine airways. The amenability, multiplexity and quantitative qualities of SCRINSHOT facilitate single cell mRNA profiling of cell-state alterations in tissues under a variety of native and experimental conditions.
Familial primary ovarian insufficiency associated with aSYCE1point mutation: Defective meiosis elucidated in humanized mice
Authors: Hernández-López Diego , Geisinger Adriana , Trovero María Fernanda , Santiñaque Federico F. , Brauer Mónica , Folle Gustavo A. , Benavente Ricardo , Rodríguez-Casuriaga Rosana
Published: February 2020

Objective

To investigate if nonsense mutationSYCE1c.613C˃T-found in women with familial primary ovarian insufficiency (POI)- is actually responsible for infertility, and to elucidate the involved molecular mechanisms.

Design

As most fundamental mammalian oogenesis events occur during the embryonic phase, thus hindering the study of POI’s etiology/pathogeny in infertile women, we have used CRISPR/Cas9 technology to generate a mouse model line with an equivalent genome alteration (humanized mice).

Setting

Academic research laboratories.

Interventions

We present the characterization of the biallelic mutant mice phenotype, compared to wild type and monoallelic littermates.

Animals

Studies were conducted employing the generated humanized mice. All studies were performed for both genders, except otherwise stated.

Main outcome measures

reproductive capability by fertility tests; gonadal histological analysis; evaluation of chromosome synapsis and synaptonemal complex (SC) assembly by immunolocalizations; protein studies by Western blotting; transcript quantification by RT-qPCR.

Results

The studied mutation proved to be the actual cause of the infertile phenotype, both in female and male mice homozygous for the change, confirming infertility of genetic origin with a recessive mode of inheritance. The mechanisms that lead to infertility are related to chromosome synapsis defects; no putative truncated SYCE1 protein was observed, andSyce1transcript was hardly detected in biallelic mutants.

Conclusions

We present for the first time the generation of humanized mice to study the actual consequences of a SC component mutation found in women with familial POI. By this approach we could confirm the suspected etiology, and shed light on the underlying molecular mechanism.
Translate the untranslated: excising as a novel post-splicing event
Authors: Panteleev Dmitry Y. , Reshetnikov Roman V. , Samoylenkova Nadezhda S. , Pustogarov Nikolay A. , Pavlova Galina V.
Published: February 2020

Maturing of a messenger RNA (mRNA) is a multi-way process producing mRNA variants through diverse splicing events, alternative polyadenylation, RNA editing, etc. Studying posttranscriptional processing of human cold-inducible RNA binding protein (CIRBP), we discovered yet another mechanism that could be added to this list. We named it excising, and it consists of low-accuracy post-splicing deletion of sequence regions of variable length. The main features of the excising process and putative members of corresponding multiprotein machinery were described with a series of cloning vectors and RNA-pulldown assay. Our results highlight a possible role of U-rich stretches and the proteins targeting such motifs in the discovered process. The discovered mechanism suggests the potential translation of 3’-untranslated regions, which may be an adjuvant way of CIRBP activity inhibition or generation of structural and functional diversity.
Large extracellular vesicles can be characterised by multiplex labelling using imaging flow cytometry
Authors: Johnson Suzanne M , Banyard Antonia , Smith Christopher , Mironov Aleksandr , McCabe Martin G
Published: February 2020

Extracellular vesicles (EVs) are heterogeneous in size (30nm-10µm), content (lipid, RNA, DNA, protein) and potential function(s). Many isolation techniques routinely discard the large EVs at the early stages of small EV or exosome isolation protocols. We describe here a standardised method to isolate large EVs and examine EV marker expression and diameter using imaging flow cytometry.

Methods

We describe step-wise isolation and characterisation of a subset of large EVs from the medulloblastoma cell line UW228-2 assessed by fluorescent light microscopy, transmission electron microscopy (TEM) and TRPS. Viability of parent cells was assessed by Annexin V exposure by flow cytometry. Imaging flow cytometry (Imagestream Mark II) identified EVs by direct fluorescent membrane labelling with Cell Mask Orange (CMO) in conjunction with EV markers. A stringent gating algorithm based on side scatter and fluorescence intensity was applied and expression of EV markers CD63, CD9 and LAMP 1 assessed.

Results

UW228-2 cells prolifically release EVs of up to 6 µm. We show that the Imagestream Mark II imaging flow cytometer allows robust and reproducible analysis of large EVs, including assessment of diameter. We also demonstrate a correlation between increasing EV size and co-expression of markers screened.

Conclusions

We have developed a labelling and stringent gating strategy which is able to explore EV marker expression (CD63, CD9 and LAMP1) on individual EVs within a widely heterogeneous population. Taken together data presented here strongly support the value of exploring large EVs in clinical samples for potential biomarkers, useful in diagnostic screening and disease monitoring.
In Vitro Assessment of Antioxidant activity, Antimicrobial, and cytotoxicity of ultrasound-assisted acetone extracts of Plectranthus amboinicus
Authors: Ye Xian-wen , Deng Ya-ling , Xia Lan-ting , Ren Hong-min , Zhang Jin-lian
Published: February 2020

Disclaimer statement

The authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.