bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalization in data-driven models of primary visual cortex
Authors: Lurz Konstantin-Klemens , Bashiri Mohammad , Willeke Konstantin , Jagadish Akshay K. , Wang Eric , Walker Edgar Y. , Cadena Santiago A. , Muhammad Taliah , Cobos Erick , Tolias Andreas S. , Ecker Alexander S. , Sinz Fabian H.
Published: October 2020

Abstract

Deep neural networks (DNN) have set new standards at predicting responses of neural populations to visual input. Most such DNNs consist of a convolutional network (core) shared across all neurons which learns a representation of neural computation in visual cortex and a neuron-specific readout that linearly combines the relevant features in this representation. The goal of this paper is to test whether such a representation is indeed generally characteristic for visual cortex, i.e. gener-alizes between animals of a species, and what factors contribute to obtaining such a generalizing core. To push all non-linear computations into the core where the generalizing cortical features should be learned, we devise a novel readout that reduces the number of parameters per neuron in the readout by up to two orders of magnitude compared to the previous state-of-the-art. It does so by taking advantage of retinotopy and learns a Gaussian distribution over the neuron’s receptive field po-sition. With this new readout we train our network on neural responses from mouse primary visual cortex (V1) and obtain a gain in performance of 7% compared to the previous state-of-the-art network. We then investigate whether the convolutional core indeed capturesgeneralcortical features by using the core in transfer learning to a different animal. When transferring a core trained on thousands of neurons from various animals and scans we exceed the performance of training directly on that animal by 12%, and outperform a commonly used VGG16 core pre-trained on imagenet by 33%. In addition, transfer learning with our data-driven core is more data-efficient than direct training, achieving the same performance with only 40% of the data. Our model with its novel readout thus sets a new state-of-the-art for neural response prediction in mouse visual cortex from natural images, generalizes between animals, and captures better characteristic cortical features than current task-driven pre-training approaches such as VGG16.
Steric Interactions at Gln154 in ZEITLUPE Induce Reorganization of the LOV Domain Dimer Interface
Authors: Pudasaini Ashutosh , Green Robert , Song Young Hun , Blumenfeld Abby , Karki Nischal , Imaizumi Takato , Zoltowski Brian D.
Published: October 2020

Plants measure light, quality, intensity, and duration to coordinate growth and development with daily and seasonal changes in environmental conditions, however, the molecular details linking photochemistry to signal transduction remain incomplete. Two closely related Light, Oxygen, or Voltage (LOV) domain containing photoreceptor proteins ZEITLUPE (ZTL) and FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) divergently regulate the protein stability of circadian clock and photoperiodic flowering components to mediate daily and seasonal development. Using structural approaches, we identified that mutations at the Gly46 position led to global rearrangements of the ZTL dimer interface. Specifically, introduction of G46S and G46A variants that mimic equivalent residues found in FKF1 induce a 180° rotation about the dimer interface that is coupled to ordering of N- and C-terminal signaling elements. These conformational changes hinge upon rotation of a C-terminal Gln residue analogous to that present in light-state structures of ZTL. The results presented herein, confirm a divergent signaling mechanism within ZTL that deviates from other members of the LOV superfamily and suggests that mechanisms of signal transduction in LOV proteins may be fluid across the LOV protein family.
Fat Mass Regain in Middle-Aged Mice after Sleeve Gastrectomy is divergent from plasma leptin levels
Authors: Emiliano Ana BF , He Ying , Higuchi Sei , Nemr Rabih , Lopatinsky Natalie , Schwartz Gary J.
Published: October 2020

Background

Some degree of weight regain is typically observed in human patients who undergo Sleeve Gastrectomy (SG), even if the majority of them do not return to their presurgical body weight. Although the majority of bariatric surgery patients are middle aged, most preclinical models of bariatric surgery utilize juvenile male mice. A long-term characterization of the response of mature, wild type, obese male mice to SG has not been performed.

Methods

Eight-month old C57bl/6J obese male mice were randomized to undergo SG, sham surgery without caloric restriction (SH) or sham surgery with caloric restriction to match body weight to the SG group (SWM). Body weight, body composition and glucose tolerance were matched at baseline. Mice were followed for 60 days following their respective surgeries.

Results

SG mice had a more pronounced percent weight loss than the SH group in the first post-operative month (p<0.05), along with fat mass loss (p<0.01). By the second post-operative month, the SG group started to regain fat mass, although it continued to be statistically lower than the SH group (p<0.05). Cumulative food intake was significantly lower in the SG group compared to SH group only in the first post-operative week (p<0.05), with both groups having similar cumulative food intake thereafter (p>0.05). SWM group had a significantly lower cumulative food intake throughout the study, except for week 1 (p<0.01). Glucose tolerance was only demonstrably better in the SG group compared to SH group at 8 weeks post-operatively (p<0.01). Plasma leptin was significantly lower in the SG group compared to both SWM and SH groups group by the second post-operative month (p<0.01), in spite of SG’s increasing fat mass accumulation. In the second post-operative month, both FGF-21 and GDF-15 were increased in the SH group compared to the SG and SWM groups (p<0.05), while there was no difference in plasma insulin among the three groups. Heat production was surprisingly higher in the SH group compared to the other two groups (p<0.05), even though brown adipose tissue Peroxisome Proliferator-Activated Receptor Gamma (PPARg) and Cidea mRNA expression were significantly higher in SG and SWM compared to SH (p<0.01). There was no change in BAT UCP-1 mRNA expression among the groups (p>0.05). There was also no change in fecal lipid content among the groups (p>0.05).

Conclusions

SG in obese, middle aged male mice leads is accompanied by fat mass regain in the second post-operative month, while plasma leptin levels continue to be significantly lower. This raises the question of whether the observed fat mass regain consists mostly of visceral adipose tissue.
Taxonomic revision of the threatened African genusPseudohydrosmeEngl. (Araceae), withP. ebo, a new, Critically Endangered species from Ebo, Cameroon
Authors: Cheek Martin , Tchiengue Barthelemy , van der Burgt Xander
Published: October 2020

This is the first revision in nearly 130 years of the African genusPseudohydrosme, formerly considered endemic to Gabon. Sister toAnchomanes, Pseudohydrosmeis distinct fromAnchomanesbecause of its 2–3-locular ovary (not unilocular), peduncle concealed by cataphylls at anthesis and far shorter than the spathe (not exposed, far exceeding the spathe), stipitate fruits and viviparous (vegetatively apomictic) roots (not sessile, roots non-viviparous). Three species, one new to science, are recognised, in two sections. Although doubt has previously been cast on the value of recognisingPseudohydrosme buettneri, of Gabon, it is here accepted and maintained as a distinct species in the monotypic section,Zyganthera. However, it is considered to be probably globally extinct.Pseudohydrosme gabunensis, type species of the genus, also Gabonese, is maintained in Sect.Pseudohydrosmetogether withPseudohydrosme ebo sp.nov. of the Ebo Forest, Littoral, Cameroon, the first addition to the genus since the nineteenth century, and which extends the range of the genus 450 km north from Gabon, into the Cross-Sanaga biogeographic area. The discovery ofPseudohydrosme eboresulted from a series of surveys for conservation management in Cameroon, and triggered this paper. All three species ofPseudohydrosmeare morphologically characterised, their habitat and biogeography discussed, and their extinction risks are respectively assessed as Critically Endangered (Possibly Extinct), Endangered and Critically Endangered using the IUCN standard. Clearance of forest habitat for logging, followed by agriculture or urbanisation are major threats. One of the species may occur in a formally protected areas and is also cultivated widely but infrequently in Europe and the USA for its spectacular inflorescences.
A model for learning based on the joint estimation of stochasticity and volatility
Authors: Piray Payam , Daw Nathaniel D.
Published: October 2020

Previous research has stressed the importance of uncertainty for controlling the speed of learning, and of how such control depends on the learner inferring the noise properties of the environment, especially volatility: the speed of change. However, learning rates are jointly determined by the comparison between volatility and a second factor, moment-to-momentstochasticity. Yet much previous research has focused on simplified cases corresponding to estimation of either factor alone. Here, we introduce a new learning model, in which both factors are learned simultaneously from experience. By considering the full problem of joint estimation, we highlight a set of previously unappreciated issues, arising from the mutual interdependence of inference about volatility and stochasticity. This interdependence both complicates and enriches the interpretation of previous results, such as those thought to implicate volatility in psychiatric conditions. This provides a novel mechanism for understanding pathological learning in amygdala damage and anxiety disorders.
Auditory Steady-State Responses During And After A Stimulus: Cortical Sources, and the Influence of Attention and Musicality
Authors: Manting Cassia Low , Gulyas Balazs , Ullén Fredrik , Lundqvist Daniel
Published: October 2020

The auditory steady-state response (ASSR) is an oscillatory brain response generated by periodic auditory stimuli and originates mainly from the temporal auditory cortices. Recent data show that while the auditory cortices are indeed strongly activated by the stimulus when it is present (ON ASSR), the anatomical distribution of ASSR sources involves also parietal and frontal cortices, indicating that the ASSR is a more complex phenomenon than previously believed. Furthermore, while the ASSR typically continues to oscillate even after the stimulus has stopped (OFF ASSR), very little is known about the characteristics of the OFF ASSR and how it compares to the ON ASSR. Here, we assessed whether the OFF and ON ASSR powers are modulated by the stimulus properties (i.e. volume and pitch), selective attention, as well as individual musical sophistication. We also investigated the cortical source distribution of the OFF ASSR using a melody tracking task, in which attention was directed between uniquely amplitude-modulated melody streams that differed in pitch. The ON and OFF ASSRs were recorded with magnetoencephalography (MEG) on a group of participants varying from low to high degree of musical sophistication. Our results show that the OFF ASSR is distinctly different from the ON ASSR in nearly every aspect. While the ON ASSR was modulated by the stimulus properties and selective attention, the OFF ASSR was not influenced by any of these factors. Furthermore, while the ON ASSR was generated primarily from temporal sources, the OFF ASSR originated mainly from the frontal cortex. These findings challenge the notion that the OFF ASSR is merely a continuation of the ON ASSR. Rather, they suggest that the OFF ASSR is an internally-driven signal that develops from an initial sensory processing state (ON ASSR), with both types of ASSRs clearly differing in cortical representation and character. Furthermore, our results show that the ON ASSR power was enhanced by selective attention at cortical sources within each of the bilateral frontal, temporal, parietal and insular lobes. Finally, the ON ASSR proved sensitive to musicality, demonstrating positive correlations between musical sophistication and ASSR power, as well as with the degree of attentional ASSR modulation at the left and right parietal cortices. Taken together, these results show new aspects of the ASSR response, and demonstrate its usefulness as an effective tool for analysing how selective attention interacts with individual abilities in music perception.
Clinical and immunoserological status 12 weeks after infection with COVID-19: prospective observational study
Authors: Santis Lucía Valiente-De , Pérez-Camacho Inés , Sobrino Beatriz , González Gracia Eugenia , Ruíz-Mesa Juan Diego , Plata Antonio , Márquez-Gómez Ignacio , Delgado-Fernández Marcial , Castaño Manuel , Oñate Francisco , Orihuela Francisco , Palop Begoña , María Reguera José
Published: October 2020

Objectives

to undertake a multidisciplinary follow-up at 12 weeks after an acute episode of COVID-19 to assess the functional status, persistence of symptoms and immunoserological situation.

Methods

this prospective, observational, single-centre study included outpatients reviewed 12 weeks after an acute infection with SARS-CoV-2. The clinical evaluation included data about the acute episode and epidemiological and clinical variables. The patients were classified as symptomatic or asymptomatic depending on the persistence or otherwise of symptoms. All the patients underwent a full blood test and serology for SARS-CoV-2, as well as imaging tests and spirometry if needed.

Results

The mean age of the 108 patients was 55.5 (SD: 15.4) years and 27.8% were health-care workers; 75.9% presented some type of symptoms, with dyspnoea being the most common. A D-dimer >500 ng/mL was detected in 32 (31.4%) patients. All the patients had antibodies against SARS-CoV-2. Being a health-care worker was associated with symptom persistence, with age ≥65 years being a protective factor.

Conclusions

The persistence of symptoms in patents with COVID is usual 12 weeks after the acute episode, especially in patients <65 years and health-care workers. All our patients had developed antibodies by 12 weeks.
Suicide and mental health during the COVID-19 pandemic in Japan
Authors: Ueda Michiko , Nordström Robert , Matsubayashi Tetsuya
Published: October 2020

Background

The coronavirus disease (COVID-19) pandemic is an unprecedented public health crisis, but its effect on suicide deaths is little understood.

Methods

We analyzed data from monthly suicide statistics between January 2017 and October 2020 and from online surveys on mental health filled out by the general population in Japan.

Results

Compared to the last three years (2017-2019), the number of suicide deaths was lower than average during the initial phase of the pandemic but exceeded the past trend starting in July 2020. The source of the increase was mainly female suicides whose numbers increased by approximately 70% in October 2020 (IRR: 1.695, 95% CI: 1.558-1.843). The largest increase was found among young women (less than 40 years of age). Our survey data indicated that the status of mental health among young women has been deteriorating in recent months, and that young female workers were more likely than any other group to have experienced a job or income loss, suggesting adverse economic conditions surrounding some of these individuals.

Conclusions

Our results indicate that continuous monitoring of mental health, particularly that of the most vulnerable populations identified in this study, and appropriate suicide prevention efforts are necessary during the COVID-19 pandemic.
Sars-Cov-2 in Argentina: Following Virus Spreading Using Granger Causality
Authors: Larrosa Juan M.C.
Published: October 2020

There is a debate in Argentina on how COVID-19 outbreak in one district ends up infecting its neighbor districts. This contribution aims to use tools of time series analysis for understanding processes of contagious through regions. I use VAR and Granger causality for testing neighbor spreading via sequential rate of contagion. Results show that in the case of Argentina, contagion began in the capital city of Buenos Aires and then spread to its hinterland via specific districts. Once interior districts were infected a positive feedback dynamics emerge creating regions of high reproducibility of the virus where interventions may be focus in the very near future. This specific use of time series analysis may provide a tool for tracing infectiousness along regions that may help to anticipate infection and then for intervening for reducing the problems derived by the disease.
Real-world effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: results of a target trial emulation using observational data from a nationwide healthcare system in Peru
Authors: Soto-Becerra Percy , Culquichicón Carlos , Hurtado-Roca Yamilee , Araujo-Castillo Roger V.
Published: October 2020

Introduction

Peru is one of the most impacted countries due to COVID-19. Given the authorized use of hydroxychloroquine (HCQ), azithromycin (AZIT), and ivermectin (IVM), we aimed to evaluate their effectiveness alone or combined to reduce mortality among COVID-19 hospitalized patients without life-threatening illness.

Methods

Retrospective cohort emulating a target trial, using nationwide data of mid- and high-level hospitals from the Peruvian Social Health Insurance 01/April/2020–19/July/2020. Patients 18 yo and above with PCR-confirmed SARS-CoV-2, and no life-threatening illness at admission were included. Five treatment groups (HCQ alone, IVM alone, AZIT alone, HCQ+AZIT, and IVM+AZIT within 48 hours of admission) were compared with standard of care alone. Primary outcome was all-cause mortality rate; secondary outcomes were all-cause death and/or ICU transfer, and all-cause death and/or oxygen prescription. Analyses were adjusted using inverse probability of treatment weighting. Propensity scores were estimated using machine learning boosting models. Weighted hazard ratios (wHR) were calculated using Cox regression.

Results

Among 5683 patients, 200 received HCT, 203 IVM, 1600 AZIT, 692 HCQ+AZIT, 358 IVM+AZIT, and 2630 standard of care. HCQ+AZIT was associated with 84% higher all-cause death hazard compared to standard care (wHR=1.84, 95%CI 1.12-3.02). Consistently, HCQ+AZIT was also associated with higher death and/or ICU transfer (wHR=1.49, 95%CI 1.01-2.19), and death and/or oxygen prescription (wHR=1.70, 95%CI 1.07-2.69). HCQ only showed higher death and/or oxygen prescription hazard. No effect was found for AZIT or IVM+AZIT.

Conclusions

Our study reported no beneficial effects of hydroxychloroquine, ivermectin, azithromycin. The HCQ+AZIT treatment seems to increase risk for all-cause death.

Funding

Instituto de Evaluación de Tecnologías en Salud e Investigación – IETSI, EsSalud
Antisense oligonucleotide-based treatment of retinitis pigmentosa caused by mutations inUSH2Aexon 13
Authors: Slijkerman Ralph , van Diepen Hester , Albert Silvia , Dona Margo , Venselaar Hanka , Zang Jingjing , Neuhauss Stephan , Peters Theo , Broekman Sanne , Pennings Ronald , Kremer Hannie , Adamson Peter , de Vrieze Erik , van Wijk Erwin
Published: October 2020

Mutations inUSH2A, encoding usherin, are the most common cause of syndromic and non-syndromic retinitis pigmentosa (RP). The two founder mutations in exon 13 (c.2299delG and c.2276G>T) collectively account for~34% ofUSH2A-associated RP cases. Skipping of exon 13 from theUSH2Atranscript during pre-mRNA splicing presents a potential treatment modality in which the resulting transcript is predicted to encode a slightly shortened usherin protein. Morpholino-induced skipping ofush2aexon 13 in larvae of the previously publishedush2aexon 13 zebrafish mutant resulted in the production of usherinΔexon13 and completely restored retinal function. RNA antisense oligonucleotides were investigated for their potential to specifically induce humanUSH2Aexon 13 skipping. Lead candidate QR-421a induced dose-dependent exon 13 skipping in iPSC-derived photoreceptor precursors from a patient homozygous for theUSH2Ac.2299delG mutation. Intravitreal delivery of QR-421a in non-human primates showed that QR-421a penetrates the retinal outer nuclear layer and induces detectable levels of exon 13 skipping until at least 3 months post injection. In conclusion, QR-421a-induced exon skipping proves to be a highly promising treatment for RP caused by mutations in exon 13 of theUSH2Agene.
A hierarchical point process model for spatial capture-recapture data
Authors: Zhang Wei , Chipperfield Joseph D. , Illian Janine B. , Dupont Pierre , Milleret Cyril , de Valpine Perry , Bischof Richard
Published: October 2020

Spatial capture-recapture (SCR) is a popular method for estimating the abundance and density of wildlife populations. A standard SCR model consists of two sub-models: one for the activity centers of individuals and the other for the detections of each individual conditional on its activity center. So far, the detection sub-model of most SCR models is designed for sampling situations where fixed trap arrays are used to detect individuals.

Non-invasive genetic sampling (NGS) is widely applied in SCR studies. Using NGS methods, one often searches the study area for potential sources of DNA such as hairs and faeces, and records the locations of these samples. To analyse such data with SCR models, investigators usually impose an artificial detector grid and project detections to the nearest detector. However, there is a trade-off between the computational efficiency (fewer detectors) and the spatial accuracy (more detectors) when using this method.

Here, we propose a point process model for the detection process of SCR studies using NGS. The model better reflects the spatially continuous detection process and allows all spatial information in the data to be used without approximation error. As in many SCR models, we also use a point process model for the activity centers of individuals. The resulting hierarchical point process model enables estimation of total population size without imputing unobserved individuals via data augmentation, which can be computationally cumbersome. We write custom distributions for those spatial point processes and fit the SCR model in a Bayesian framework using Markov chain Monte Carlo in the R package nimble.

Simulations indicate good performance of the proposed model for parameter estimation. We demonstrate the application of the model in a real-life scenario by fitting it to NGS data of female wolverines (Gulo gulo) collected in three counties of Norway during the winter of 2018/19. Our model estimates that the density of female wolverines is 9.53 (95% CI: 8–11) per 10,000km2in the study area.
Spatially resolved optical monitoring of spinal cord blood flow with a minimally invasive, multi-level epidural probe
Authors: Busch David R. , Lin Wei , Goh Chia Chieh , Gao Feng , Larson Nicholas , Wahl Joseph , Bilfinger Thomas V. , Yodh Arjun G. , Floyd Thomas F.
Published: October 2020

Spinal cord ischemia leads to iatrogenic injury in multiple surgical fields, and the ability to immediately identify onset and anatomic origin of ischemia is critical to its management. Current clinical monitoring, however, does not directly measure spinal cord blood flow, resulting in poor sensitivity/specificity, delayed alerts, and delayed intervention. We have developed an epidural device employing diffuse correlation spectroscopy (DCS) to monitor spinal cord ischemia continuously at multiple positions. We investigate the ability of this device to localize spinal cord ischemia in a porcine model and validate DCS versus Laser Doppler Flowmetry (LDF).

Specifically, we demonstrate continuous (>0.1Hz) spatially resolved (3 locations) monitoring of spinal cord blood flow in a purely ischemic model with an epidural DCS probe. Changes in blood flow measured by DCS and LDF were highly correlated (r=0.83). Spinal cord blood flow measured by DCS caudal to aortic occlusion decreased 62%, with a sensitivity of 0.87 and specificity of 0.91 for detection of a 25% decrease in flow. This technology may enable early identification and critically important localization of spinal cord ischemia.
Effects of face masks on acoustic analysis and speech perception: Implications for peri-pandemic protocols
Authors: Magee Michelle , Lewis Courtney , Noffs Gustavo , Reece Hannah , Chan Jess C. S. , Zaga Charissa J. , Paynter Camille , Birchall Olga , Azocar Sandra Rojas , Ediriweera Angela , Caverlé Marja W. , Schultz Benjamin G. , Vogel Adam P.
Published: October 2020

Wearing face masks (alongside physical distancing) provides some protection against infection from COVID-19. Face masks can also change how we communicate and subsequently affect speech signal quality. Here we investigated how three face mask types (N95, surgical and cloth) affect acoustic analysis of speech and perceived intelligibility in healthy subjects. We compared speech produced with and without the different masks on acoustic measures of timing, frequency, perturbation and power spectral density. Speech clarity was also examined using a standardized intelligibility tool by blinded raters. Mask type impacted the power distribution in frequencies above 3kHz for both the N95 and surgical masks. Measures of timing and spectral tilt also differed across mask conditions. Cepstral and harmonics to noise ratios remained flat across mask type. No differences were observed across conditions for word or sentence intelligibility measures. Our data show that face masks change the speech signal, but some specific acoustic features remain largely unaffected (e.g., measures of voice quality) irrespective of mask type. Outcomes have bearing on how future speech studies are run when personal protective equipment is worn.
JIND: Joint Integration and Discrimination for Automated Single-Cell Annotation
Authors: Goyal Mohit , Serrano Guillermo , Shomorony Ilan , Hernaez Mikel , Ochoa Idoia
Published: October 2020

Single-cell RNA-seq is a powerful tool in the study of the cellular composition of different tissues and organisms. A key step in the analysis pipeline is the annotation of cell-types based on the expression of specific marker genes. Since manual annotation is labor-intensive and does not scale to large datasets, several methods for automated cell-type annotation have been proposed based on supervised learning. However, these methods generally require feature extraction and batch alignment prior to classification, and their performance may become unreliable in the presence of cell-types with very similar transcriptomic profiles, such as differentiating cells. We propose JIND, a framework for automated cell-type identification based on neural networks that directly learns a low-dimensional representation (latent code) in which cell-types can be reliably determined. To account for batch effects, JIND performs a novel asymmetric alignment in which the transcriptomic profile of unseen cells is mapped onto the previously learned latent space, hence avoiding the need of retraining the model whenever a new dataset becomes available. JIND also learns cell-type-specific confidence thresholds to identify and reject cells that cannot be reliably classified. We show on datasets with and without batch effects that JIND classifies cells more accurately than previously proposed methods while rejecting only a small proportion of cells. Moreover, JIND batch alignment is parallelizable, being more than five or six times faster than Seurat integration. Availability:https://github.com/mohit1997/JIND.
Impulsivity and risk-seeking as Bayesian inference under dopaminergic control
Authors: Mikhael John G. , Gershman Samuel J.
Published: October 2020

Bayesian models successfully account for several of dopamine (DA)’s effects on contextual calibration in interval timing and reward estimation. In these models, tonic levels of DA control the precision of stimulus encoding, which is weighed against contextual information when making decisions. When DA levels are high, the animal relies more heavily on the (highly precise) stimulus encoding, whereas when DA levels are low, the context affects decisions more strongly. Here, we extend this idea to intertemporal choice and probability discounting tasks. In intertemporal choice tasks, agents must choose between a small reward delivered soon and a large reward delivered later, whereas in probability discounting tasks, agents must choose between a small reward that is always delivered and a large reward that may be omitted with some probability. Beginning with the principle that animals will seek to maximize their reward rates, we show that the Bayesian model predicts a number of curious empirical findings in both tasks. First, the model predicts that higher DA levels should normally promote selection of the larger/later option, which is often taken to imply that DA decreases ‘impulsivity,’ and promote selection of the large/risky option, often taken to imply that DA increases ‘risk-seeking.’ However, if the temporal precision is sufficiently decreased, higher DA levels should have the opposite effect—promoting selection of the smaller/sooner option (higher impulsivity) and the small/safe option (lower risk-seeking). Second, high enough levels of DA can result in preference reversals. Third, selectively decreasing the temporal precision, without manipulating DA, should promote selection of the larger/later and large/risky options. Fourth, when a different post-reward delay is associated with each option, animals will not learn the option-delay contingencies, but this learning can be salvaged when the post-reward delays are made more salient. Finally, the Bayesian model predicts correlations among behavioral phenotypes: Animals that are better timers will also appear less impulsive.
LEA 3: Factor models in population genetics and ecological genomics with R
Authors: Gain Cléement , François Olivier
Published: October 2020

A major objective of evolutionary biology is to understand the processes by which organisms have adapted to various environments, and to predict the response of organisms to new or future conditions. The availability of large genomic and environmental data sets provides an opportunity to address those questions, and the R package LEA has been introduced to facilitate population and ecological genomic analyses in this context. By using latent factor models, the program computes ancestry coefficients from population genetic data, and performs genotype-environment association analyses with correction for unobserved confounding variables. In this study, we present new functionalities of LEA, which include imputation of missing genotypes, fast algorithms for latent factor mixed models using multivariate predictors for genotype-environment association studies, population differentiation tests for admixed or continuous populations, and estimation of genetic offset based on climate models. The new functionalities are implemented in version 3.0 and higher releases of the package. Using simulated and real data sets, our study provides evaluations and examples of applications, outlining important practical considerations when analyzing ecological genomic data in R.
Phase-locking of resting-state brain networks with the gastric basal electrical rhythm
Authors: Choe Ann S. , Tang Bohao , Smith Kimberly R. , Honari Hamed , Lindquist Martin A. , Caffo Brian S. , Pekar James J.
Published: October 2020

A network of myenteric interstitial cells of Cajal in the corpus of the stomach serves as its “pacemaker”, continuously generating aca.0.05 Hz electrical slow wave, which is transmitted to the brain chiefly by vagal afferents. A recent study combining resting-state functional MRI (rsfMRI) with concurrent surface electrogastrography (EGG), with cutaneous electrodes placed on the epigastrium, found 12 brain regions with activity that was significantly phase-locked with this gastric basal electrical rhythm. Therefore, we asked whether fluctuations in brain resting state networks (RSNs), estimated using a spatial independent component analysis (ICA) approach, might be synchronized with the stomach. In the present study, in order to determine whether any RSNs are phase-locked with the gastric rhythm, an individual participant underwent 22 scanning sessions; in each, two 15-minute runs of concurrent EGG and rsfMRI data were acquired. EGG data from three sessions had weak gastric signals and were excluded; the other 19 sessions yielded a total of 9.5 hours of data. The rsfMRI data were analyzed using group ICA; RSN time courses were estimated using dual regression; for each run, the phase-locking value (PLV) was computed between each RSN and the gastric signal. To assess statistical significance, PLVs from all pairs of “mismatched” data (EGG and rsfMRI data acquired on different days) were used as surrogate data to generate a null distribution for each RSN. Of a total of 18 RSNs, three were found to be significantly phase-locked with the basal gastric rhythm, namely, a cerebellar network, a dorsal somatosensory-motor network, and a default mode network. Disruptions to the gut-brain axis, which sustains interoceptive feedback between the central nervous system and the viscera, are thought to be involved in various disorders; manifestation of the infra-slow rhythm of the stomach in brain rsfMRI data could be useful for studies in clinical populations.
The role of concentration on drop formation and breakup of collagen, fibrinogen, and thrombin solutions during inkjet bioprinting
Authors: Gudapati Hemanth , Ozbolat Ibrahim T.
Published: October 2020

The influence of protein concentration on drop formation and breakup of aqueous solutions of fibrous proteins collagen, fibrinogen, and globular protein thrombin in different concentration regimes is investigated during drop-on-demand (DOD) inkjet bioprinting. The capillary-driven thinning and breakup of dilute (c/c* < 1, wherecis the concentration andc* is the overlap concentration) collagen, fibrinogen, and thrombin solutions is predominantly resisted by inertial force on the initial onset of necking. The minimum diameter (Dfmin(t)) of the necked fluid up to the critical pinch-off time (tc) scales with time asDfmin(t) ∼ (tc−t)2/3, a characteristic of potential flows. Although the capillary-driven thinning and breakup of semidilute unentangled collagen (1 ≤c/c* ≤ 4) and fibrinogen (1 ≤c/c* ≤ 1.3) solutions is predominantly resisted by inertial force on the initial onset of necking, the breakup of droplets is delayed beyondtc, where the minimum diameter of the necked fluid decreases exponentially with time because of the resistance of elastic force. The resistance of viscous force to the necking of both the dilute and semidilute untangled protein solutions is negligible. Aggregates or subvisible particles (between 1 and 100 μm) constantly disrupt the formation of droplets for the semidilute unentangled protein solutions, even when their inverse Ohnesorge number (Z) is within the printability range of 4 ≤Z≤ 14. Although aggregates are present in the dilute protein solutions, they do not disrupt the formation of droplets.
Ancestry inference and grouping from principal component analysis of genetic data
Authors: Privé Florian
Published: October 2020

Here we propose a simple, robust and effective method for global ancestry inference and grouping from Principal Component Analysis (PCA) of genetic data. The proposed approach is particularly useful for methods that need to be applied in homogeneous samples. First, we show that Euclidean distances in the PCA space are proportional toFSTbetween populations. Then, we show how to use this PCA-based distance to infer ancestry in the UK Biobank and the POPRES datasets. We propose two solutions, either relying on projection of PCs to reference populations such as from the 1000 Genomes Project, or by directly using the internal data. Finally, we conclude that our method and the community would benefit from having an easy access to a reference dataset with an even better coverage of the worldwide genetic diversity than the 1000 Genomes Project.
Natural variation of the cardiac transcriptome in humans
Authors: Domitrovic Tatiana , Moreira Mariana H. , Carneiro Rodolfo L. , Ribeiro-Alves Marcelo , Palhano Fernando L.
Published: October 2020

We investigated the gene-expression variation among humans by analyzing previously published mRNA-seq and ribosome footprint profiling (RP) of heart left-ventricles from healthy donors. We ranked the genes according to their coefficient of variation values and found that the top 5% most variable genes had special features compared to the rest of the genome, such as lower mRNA levels and shorter half-lives coupled to increased translation efficiency. We observed that these genes are mostly involved with immune response and have a pleiotropic effect on disease phenotypes, indicating that asymptomatic conditions contribute to the gene expression diversity of healthy individuals.
F-Seq2: improving the feature density based peak caller with dynamic statistics
Authors: Zhao Nanxiang , Boyle Alan P.
Published: October 2020

Genomic and epigenomic features are captured at a genome-wide level by using high-throughput sequencing technologies. Peak calling is one of the first essential steps in analyzing these features by delineating regions such as open chromatin regions and transcription factor binding sites. Our original peak calling software, F-Seq, has been widely used and shown to be the most sensitive and accurate peak caller for DNase I hypersensitive sites sequencing (DNase-seq) data. However, F-Seq lacks support for user-input control dataset nor reporting test statistics, limiting its ability to capture systematic and experimental biases and accurately estimate background distributions. Here we present an improved version, F-Seq2, which combined the power of kernel density estimation and a dynamic “continuous” Poisson distribution to robustly account for local biases and solve ties when ranking candidate peaks. In F-score and motif distance analysis, we demonstrated the superior performance of F-Seq2 than other competing peak callers used by the ENCODE Consortium on simulated and real ATAC-seq and ChIP-seq datasets. The output of F-Seq2 is suitable for irreproducible discovery rate (IDR) analysis as the test statistics calculated for individual candidate summit and ties are robustly solved.
Phylogeographic analysis of shrubby beardtongues reveals range expansions during the Last Glacial Maximum and implicates the Klamath Mountains as a hotspot for hybridization
Authors: Stone Benjamin W. , Wolfe Andrea D.
Published: October 2020

Quaternary glacial cycles often altered species’ geographic distributions, which in turn altered the geographic structure of a species’ genetic diversity. In many cases, glacial expansion forced species in temperate climates to contract their ranges and reside in small pockets of suitable habitat (refugia), where they were likely to interact closely with other species, setting the stage for potential gene exchange. These introgression events, in turn, would have degraded species boundaries, making the inference of phylogenetic relationships challenging. Using high-throughput sequence data, we employ a combination of species distribution models, models of demographic history, and hybridization tests to assess the effect of glaciation on the geographic distributions, phylogenetic relationships, and patterns of gene flow of five species ofPenstemonsubgenusDasanthera, long-lived shrubby angiosperms distributed throughout the Pacific Northwest of North America. Surprisingly, we find that rather than reducing their ranges to small refugia, mostPenstemonsubgenusDasantheraspecies experienced increases in suitable habitat during the Last Glacial Maximum. We also find substantial evidence for gene exchange between species, with the bulk of introgression events occurring in or near the Klamath Mountains of southwestern Oregon and northwestern California. Subsequently, our phylogenetic inference reveals blurred taxonomic boundaries in the Klamath Mountains, where introgression is most prevalent. Our results question the classical paradigm of temperate species’ responses to glaciation, and highlight the importance of contextualizing phylogenetic inference with the demographic histories of the species of interest.
Altered Dynamics of Cortical Beta-Oscillations during Motor Learning in Cerebellar Ataxia
Authors: Klimpke Jana , Henkel Dorothea , Heinze Hans-Jochen , Stenner Max-Philipp
Published: October 2020

Cerebellar ataxia is associated with an implicit motor learning dysfunction, specifically, a miscalibration of internal models relating motor commands to state changes of the body. Explicit cognitive strategies could compensate for deficits in implicit calibration. Surprisingly, however, patients with cerebellar ataxia use insufficient strategies compared to healthy controls. We report a candidate physiological phenomenon of disrupted strategy use in cerebellar ataxia, reflected in an interaction of implicit and explicit learning effects on cortical beta oscillations. We recorded electroencephalography in patients with cerebellar ataxia (n=18), age-matched healthy controls (n=19), and young, healthy individuals (n=34) during a visuomotor rotation paradigm in which an aiming strategy was either explicitly instructed, or had to be discovered through learning. In young, healthy individuals, learning a strategy, but not implicit learning from sensory prediction error alone, decreased the post-movement beta rebound. Disrupted learning from sensory prediction error in patients, on the other hand, unmasked effects of explicit and implicit control that are normally balanced. Specifically, the post-movement beta rebound increased during strategy use when implicit learning was disrupted, i.e., in patients, but not controls. We conclude that a network disturbance due to cerebellar degeneration surfaces in imbalanced cortical beta oscillations normally involved in strategy learning.
Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia
Authors: Janssens Derek H. , Meers Michael P. , Wu Steven J. , Babaeva Ekaterina , Meshinchi Soheil , Sarthy Jay F. , Ahmad Kami , Henikoff Steven
Published: October 2020

Acute myeloid and lymphoid leukemias often harbor chromosomal translocations involving theMixed Lineage Leukemia-1gene, encoding the KMT2A lysine methyltransferase. The most common translocations produce in-frame fusions of KMT2A to other chromatin regulatory proteins. Here we develop a strategy to map the genome-wide occupancy of oncogenic KMT2A fusion proteins in primary patient samples regardless of fusion partner. By modifying the versatile CUT&Tag method for full automation we identify common and tumor-specific patterns of aberrant chromatin regulation induced by different KMT2A fusion proteins. Integration of automated and single-cell CUT&Tag uncovers epigenomic heterogeneity within patient samples and predicts sensitivity to therapeutic agents.
A pair of effectors encoded on a conditionally dispensable chromosome ofFusarium oxysporumsuppress host-specific immunity
Authors: Ayukawa Yu , Asai Shuta , Gan Pamela , Tsushima Ayako , Ichihashi Yasunori , Shibata Arisa , Komatsu Ken , Houterman Petra M. , Rep Martijn , Shirasu Ken , Arie Tsutomu
Published: October 2020

Many plant pathogenic fungi contain conditionally dispensable (CD) chromosomes that are associated with virulence, but not growthin vitro. Virulence-associated CD chromosomes carry genes encoding effectors and/or host-specific toxin biosynthesis enzymes that may contribute significantly to determining host specificity.Fusarium oxysporumcauses devastating diseases of more than 100 plant species. Among a large number of host-specific forms,F. oxysporumf. sp.conglutinans(Focn) can infect Brassicaceae plants including Arabidopsis and cabbage. Here we show thatFocnhas multiple CD chromosomes involved in virulence but also in vegetative growth, which is an atypical feature of CD chromosomes. We identified specific CD chromosomes that are required for virulence on Arabidopsis, cabbage, or both, and describe a pair of effectors encoded on one of the CD chromosomes that is required for suppression of Arabidopsis-specific phytoalexin-based immunity. The effector pair is highly conserved inF. oxysporumisolates capable of infecting Arabidopsis, but not of other plants. This study provides insight into how host specificity ofF. oxysporummay be determined by a pair of effector genes on a transmissible CD chromosome.
Western-style diet impedes colonization and clearance of gut bacterial pathogens
Authors: Gewirtz Andrew T. , Zou jun , ZHAO XU , Noriega Juan
Published: October 2020

Western-style diet (WSD), which is high in fat and low in fiber, lacks nutrients to support gut microbiota. Consequently, WSD promotes microbiota encroachment and reduces microbiota density, potentially influencing colonization resistance, immune system readiness, and, consequently host defense against pathogenic bacteria. Additionally, the low-nutrient colonic environment resulting from WSD might impact bacterial pathogens. Hence, we examined the impact of WSD on infection and colitis in response to gut bacterial pathogens. Mice fed grain-based chow (GBC), WSD, or various versions thereof, were orally infected with Citrobacter rodentium or C. difficile. Colonization and its consequences, including inflammation and death were monitored. We observed that WSD delayed Citrobacter growth, reduced its virulence gene expression and ameliorated inflammation.  However, while GBC-fed mice uniformly cleared Citrobacter and were impervious to subsequent Citrobacter challenges, most WSD-fed mice remained chronically infected with Citrobacter while those that cleared it were highly prone to re-infection. Such persistent proneness to Citrobacter infection did not reflect reduced immune responsiveness but rather reflected reduced colonization resistance likely from the low microbiota density resulting from WSD feeding. While persistent Citrobacter infection did not cause overt inflammation, it was associated with low-grade inflammation in colon and adipose tissue that was associated with insulin resistance. An analogous pattern was seen in response to C. difficile with WSD resulting in delayed colonization and mortality while enriching WSD with fiber hastened colonization but afforded clearance and survival. Thus, altering microbiota via diet can profoundly impact the course and consequence of infection following exposure to gut bacterial pathogens.