bluuebunny/crossref_metadata_2025 huggingface dataset:
Do I Have HIV or Not? Lack of RNA Detection and the Case for Sensitive DNA Testing
Authors: Springer Sandra A , Masciotra Silvina , Johnson Jeffrey A , Campbell Sheldon
Published: October 2020

We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management.
Efficacy and Safety of Carbapenems vs New Antibiotics for Treatment of Adult Patients With Complicated Urinary Tract Infections: A Systematic Review and Meta-analysis
Authors: Ezure Yukiko , Rico Veronica , Paterson David L , Hall Lisa , Harris Patrick N A , Soriano Alex , Roberts Jason A , Bassetti Matteo , Roberts Matthew J , Righi Elda , Wright Hugh
Published: October 2020

This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems for the treatment of complicated urinary tract infections (cUTIs), with the comparators being new antibiotics evaluated for this indication. We searched 13 electronic databases for published randomized controlled trials (RCTs) and completed and/or ongoing trials. The search terms were developed using the Population, Intervention, Comparison, Outcomes, and Study framework. Pooled efficacy estimates of composite cure (clinical success and microbiological eradication) favored the new antibiotic groups, although this was not statistically significant (risk ratio [RR], 0.91; 95% CI, 0.79–1.04). A pooled estimate examining clinical response alone showed no difference between treatment arms (RR, 1.00; 95% CI, 0.96–1.05), however, new antibiotic treatments were superior to carbapenems for microbiological response (RR, 0.85; 95% CI, 0.79–0.91). New antibiotic treatments demonstrated a superior microbiological response compared with carbapenems in clinical trials of cUTI, despite an absence of carbapenem resistance. However, it is noteworthy that the clinical response and safety profile of new antibiotics were not different from those of carbapenems.
Policing in Dispute: Academia versus Activism
Authors: Kilgallon Ashley
Published: October 2020

This paper offers a short commentary on Professor Stott’s paper, Patterns of ‘disorder’ during the 2019 protests in Hong Kong: policing, social identity, intergroup dynamics and radicalisation. The commentary seeks to explore the paper from the perspective of how it can contribute to the public-order policing field, as opposed to a commentary on the policing of protest in Hong Kong.
Dendritic cell integrin expression patterns regulate inflammation in the rheumatoid arthritis joint
Authors: Schittenhelm Leonie , Robertson Jamie , Pratt Arthur G , Hilkens Catharien M , Morrison Vicky L
Published: October 2020

Objectives

Immune dysregulation contributes to the development of RA. Altered surface expression patterns of integrin adhesion receptors by immune cells is one mechanism by which this may occur. We investigated the role of β2 integrin subunits CD11a and CD11b in dendritic cell (DC) subsets of RA patients.

Methods

Total β2 integrin subunit expression and its conformation (‘active’ vs ‘inactive’ state) were quantified in DC subsets from peripheral blood (PB) and SF of RA patients as well as PB from healthy controls. Ex vivo stimulation of PB DC subsets and in vitro-generated mature and tolerogenic monocyte-derived DCs (moDCs) were utilized to model the clinical findings. Integrin subunit contribution to DC function was tested by analysing clustering and adhesion, and in co-cultures to assess T cell activation.

Results

A significant reduction in total and active CD11a expression in DCs in RA SF compared with PB and, conversely, a significant increase in CD11b expression was found. These findings were modelled in vitro using moDCs: tolerogenic moDCs showed higher expression of active CD11a and reduced levels of active CD11b compared with mature moDCs. Finally, blockade of CD11b impaired T cell activation in DC–T cell co-cultures.

Conclusion

For the first time in RA, we show opposing expression of CD11a and CD11b in DCs in environments of inflammation (CD11alow/CD11bhigh) and steady state/tolerance (CD11ahigh/CD11blow), as well as a T cell stimulatory role for CD11b. These findings highlight DC integrins as potential novel targets for intervention in RA.
Reliability and Replicability of Implicit and Explicit Reinforcement Learning Paradigms in People With Psychotic Disorders
Authors: Pratt Danielle N , Barch Deanna M , Carter Cameron S , Gold James M , Ragland John D , Silverstein Steven M , MacDonald Angus W
Published: October 2020

Background

Motivational deficits in people with psychosis may be a result of impairments in reinforcement learning (RL). Therefore, behavioral paradigms that can accurately measure these impairments and their change over time are essential.

Methods

We examined the reliability and replicability of 2 RL paradigms (1 implicit and 1 explicit, each with positive and negative reinforcement components) given at 2 time points to healthy controls (n = 75), and people with bipolar disorder (n = 62), schizoaffective disorder (n = 60), and schizophrenia (n = 68).

Results

Internal consistency was acceptable (mean α = 0.78 ± 0.15), but test-retest reliability was fair to low (mean intraclass correlation = 0.33 ± 0.25) for both implicit and explicit RL. There were no clear effects of practice for these tasks. Largely, performance on these tasks shows intact implicit and impaired explicit RL in psychosis. Symptom presentation did not relate to performance in any robust way.

Conclusions

Our findings replicate previous literature showing spared implicit RL and impaired explicit reinforcement in psychosis. This suggests typical basal ganglia dopamine release, but atypical recruitment of the orbitofrontal and dorsolateral prefrontal cortices. However, we found that these tasks have only fair to low test-retest reliability and thus may not be useful for assessing change over time in clinical trials.
Lag Analysis of Fast fMRI Reveals Delayed Information Flow Between the Default Mode and Other Networks in Narcolepsy
Authors: Järvelä M , Raatikainen V , Kotila A , Kananen J , Korhonen V , Uddin L Q , Ansakorpi H , Kiviniemi V
Published: October 2020

Narcolepsy is a chronic neurological disease characterized by dysfunction of the hypocretin system in brain causing disruption in the wake-promoting system. In addition to sleep attacks and cataplexy, patients with narcolepsy commonly report cognitive symptoms while objective deficits in sustained attention and executive function have been observed. Prior resting-state functional magnetic resonance imaging (fMRI) studies in narcolepsy have reported decreased inter/intranetwork connectivity regarding the default mode network (DMN). Recently developed fast fMRI data acquisition allows more precise detection of brain signal propagation with a novel dynamic lag analysis. In this study, we used fast fMRI data to analyze dynamics of inter resting-state network (RSN) information signaling between narcolepsy type 1 patients (NT1, n = 23) and age- and sex-matched healthy controls (HC, n = 23). We investigated dynamic connectivity properties between positive and negative peaks and, furthermore, their anticorrelative (pos-neg) counterparts. The lag distributions were significantly (P < 0.005, familywise error rate corrected) altered in 24 RSN pairs in NT1. The DMN was involved in 83% of the altered RSN pairs. We conclude that narcolepsy type 1 is characterized with delayed and monotonic inter-RSN information flow especially involving anticorrelations, which are known to be characteristic behavior of the DMN regarding neurocognition.
Gender Differences in Retirement Behavior: How Family, Work, and Pension Regime Explain Retirement in Chile
Authors: Canales Andrea , Salinas Viviana , Biehl Andrés
Published: October 2020

While there is vast research on the Chilean pension system, its financial sustainability, and overall effects on the economy, the literature is scanter about gender differences in retirement and its determinants in the context of a high-income developing country with low rates of female labor market participation and less generous welfare provisions. This study seeks to address these gaps. Employing data from the Longitudinal Social Protection Survey (LSPS), we conduct survival analyses to (a) estimate differences in the risk of retirement between men and women, and to (b) investigate how the decision of retirement is influenced by family, work/socioeconomic factors, and pension regimes. Our analyses focused on the age of the first pension receipt. We carry out supplemental analyses on whether pension receipt leads to permanent exit from the labor market. Our results showed that women have a higher risk of receiving their first pension and retire earlier than men. We found that different work experiences prompt women to leave the labor market earlier than men. These results differ from prior research in developed countries that indicated that in countries with low female labor participation rates, women retire later than men.
The ‘twins’ and the ‘bachelor’, new potential synapomorphies inside the Cholevinae (Coleoptera: Leiodidae)
Authors: Gnaspini Pedro , Gomyde Eduardo C , Antunes-Carvalho Caio
Published: October 2020

The fine morphology of the tarsus has recently been shown to provide phylogenetic signal at several supraspecific levels in leiodid beetles, as well as in other insects. We here include another system, namely, the spines at the apical margin of the tarsomeres and associated structures. The tribe Ptomaphagini, with a Holarctic-Neotropical-Oriental distribution, has been characterized by having a comb of equal, flat spines around the apex of the tibiae of all legs, with a row of spines extending along the outer edge of the protibia in some genera (which has also been reported in the Eucatopini). We here recognize (as a new synapomorphy for the tribe) that special, strong spines, forming a loose comb, also appear at the apex of the first three or four tarsomeres of the Ptomaphagini. Special features appear on the apical margin of the mesotarsomeres: a long and thin seta, here called the ‘bachelor’, appears between two spines at the external-lateral-ventral face of the first tarsomeres, whereas a group of two (three in some cases) special spines (with the apex bent, facing opposite to each other), here called the ‘twins’, appears on the opposite, internal-lateral-ventral face of the first three (or sometimes two) tarsomeres. We found the ‘twins’ were also present in the Anemadini: Eunemadina and Nemadina, and the Eucatopini; the ‘bachelor seta’ seems to also occur in the Anemadini: Nemadina.
Obscure by name: solving the enigma ofChelytherium obscurum, the first described Triassic turtle
Authors: Szczygielski Tomasz
Published: October 2020

The material historically referred to Chelytherium obscurum is exceptional for a number of reasons. It is the first described Triassic turtle, the oldest testudinate among the British palaeontological collections, and it is one of the oldest testudinates in the world. Nevertheless, after its establishment in 1863, the taxon remained in a taxonomic limbo and was eventually almost forgotten. However, the recent reconsideration of proterochersid turtles, with improved understanding of their anatomy, allows reassessment of Chelytherium obscurum as a member of the Proterochersidae, subjectively synonymous with Proterochersis robusta. Despite nomenclatural priority, in accordance with the suggestions of previous authors, the name Proterochersis robusta is endorsed to be upheld.
Exercise does not enhance short-term deprivation-induced ocular dominance plasticity: evidence from dichoptic surround suppression
Authors: Baldwin Alex S , Green Hayden M , Finn Abigail E , Gant Nicholas , Hess Robert F
Published: October 2020

Abstract

The input from the two eyes is combined in the brain. In this combination, the relative strength of the input from each eye is determined by the ocular dominance. Recent work has shown that this dominance can be temporarily shifted. Covering one eye with an eye patch for a few hours makes its contribution stronger. It has been proposed that this shift can be enhanced by exercise. Here, we test this hypothesis using a dichoptic surround suppression task, and with exercise performed according to American College of Sport Medicine guidelines. We measured detection thresholds for patches of sinusoidal grating shown to one eye. When an annular mask grating was shown simultaneously to the other eye, thresholds were elevated. The difference in the elevation found in each eye is our measure of relative eye dominance. We made these measurements before and after 120 minutes of monocular deprivation (with an eye patch). In the control condition, subjects rested during this time. For the exercise condition, 30 minutes of exercise were performed at the beginning of the patching period. This was followed by 90 minutes of rest. We find that patching results in a shift in ocular dominance that can be measured using dichoptic surround suppression. However, we find no effect of exercise on the magnitude of this shift. We further performed a meta-analysis on the four studies that have examined the effects of exercise on the dominance shift. Looking across these studies, we find no evidence for such an effect.
Disentangling age-dependent DNA methylation: deterministic, stochastic, and nonlinear
Authors: Vershinina O. , Bacalini M.G. , Zaikin A. , Franceschi C. , Ivanchenko M.
Published: October 2020

DNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of “deterministic” CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of “stochastic” CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.
Cortical beta oscillatory activity evoked during reactive balance recovery scales with perturbation difficulty and individual balance ability
Authors: Ghosn Nina J. , Palmer Jacqueline A. , Borich Michael R. , Ting Lena H. , Payne Aiden M.
Published: October 2020

I.

Cortical beta oscillations (13-30 Hz) reflect sensorimotor cortical activity, but have not been fully investigated in balance recovery behavior. We hypothesized that more challenging balance conditions would lead to greater recruitment of cortical sensorimotor brain regions for balance recovery. We predicted that beta power would be enhanced when balance recovery is more challenging, either due to more difficult perturbations or due to lower intrinsic balance ability. In 19 young adults, we measured beta power evoked over motor cortical areas (Cz electrode) during 3 magnitudes of backward support-surface translational perturbations using electroencephalography. Peak beta power was measured during early (50-150 ms), late (150-250 ms), and overall (0-400 ms) time bins, and wavelet-based analyses quantified the time course of evoked beta power and agonist and antagonist ankle muscle activity. We further assessed the relationship between individual balance ability measured in a challenging beam walking task and perturbation-evoked beta power within each time bin. In balance perturbations, cortical beta power increased ∼50 ms after perturbation onset, demonstrating greater increases with increasing perturbation magnitude. Balance ability was negatively associated with peak beta power in only the late (150-250 ms) time bin, with higher beta power in individuals who performed worse in the beam walking task. Additionally, the time course of cortical beta power followed a similar waveform as the evoked muscle activity, suggesting these evoked responses may be initially evoked by shared underlying mechanisms. These findings support the active role of sensorimotor cortex in balance recovery behavior, with greater recruitment of cortical resources under more challenging balance conditions. Cortical beta power may therefore provide a biomarker for engagement of sensorimotor cortical resources during reactive balance recovery and reflect the individual level of balance challenge.
Neural network dynamics underlying gamma synchronization deficits in schizophrenia
Authors: Koshiyama Daisuke , Miyakoshi Makoto , Joshi Yash B. , Molina Juan L. , Tanaka-Koshiyama Kumiko , Sprock Joyce , Braff David L. , Swerdlow Neal R. , Light Gregory A.
Published: October 2020

Gamma band (40-Hz) activity is associated with many sensory and cognitive functions, and is critical for cortico-cortical transmission and the integration of information across neural networks. The capacity to support gamma band activity can be indexed by the auditory steady-state response (ASSR); schizophrenia patients have selectively reduced synchrony to 40-Hz stimulation. While 40-Hz ASSR is a translatable electroencephalographic biomarker with emerging utility for therapeutic development for neuropsychiatric disorders, the spatiotemporal dynamics underlying the ASSR have not yet been characterized. In this study, a novel Granger causality analysis was applied to assess the propagation of gamma oscillations in response to 40-Hz steady-state stimulation across cortical sources in schizophrenia patients (n=426) and healthy comparison subjects (n=293). Results revealed distinct, hierarchically sequenced temporal and spatial response dynamics underlying gamma synchronization deficits in patients. During the response onset interval, patients exhibited abnormal connectivity of superior temporal and frontal gyri, followed by decreased information flow from superior temporal to middle cingulate gyrus. In the later (300–500 ms) interval of the ASSR response, patients showed significantly increased connectivity from superior temporal to middle frontal gyrus followed by broad failures to engage multiple prefrontal brain regions. In conclusion, these findings reveal the rapid disorganization of neural circuit functioning in response to simple gamma-frequency stimulation in schizophrenia patients. Deficits in the generation and maintenance of gamma-band oscillations in schizophrenia reflect a fundamental connectivity abnormality across a distributed network of temporo-frontal networks.
Oxygen-generating cryogels restore T cell-mediated cytotoxicity in hypoxic tumors
Authors: Colombani Thibault , Eggermont Loek J. , Hatfield Stephen M. , Rezaeeyazdi Mahboobeh , Memic Adnan , Sitkovsky Michail V. , Bencherif Sidi A.
Published: October 2020

Solid tumors are protected from antitumor immune responses due to their hypoxic microenvironments. Weakening hypoxia-driven immunosuppression by hyperoxic breathing of 60% oxygen has shown to be effective in unleashing antitumor immune cells against solid tumors. However, efficacy of systemic oxygenation is limited against solid tumors outside of lungs. Therefore, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to cancer immunotherapies. Herein, we report on injectable oxygen-generating cryogels (O2-cryogels) to reverse tumor-induced hypoxia. These macroporous biomaterials were designed to locally deliver oxygen, inhibit the expression of hypoxia-inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. O2-cryogels enhance T cell-mediated secretion of cytotoxic proteins, restoring the killing ability of tumor-specific CTLs, both in vitro and in vivo. In summary, O2-cryogels provide a unique and safe platform to supply oxygen as a co-adjuvant in hypoxic tumors and improve cancer immunotherapies.
The role of animal faces in the animate-inanimate distinction in the ventral temporal cortex
Authors: Proklova D. , Goodale M.A.
Published: October 2020

Animate and inanimate objects elicit distinct response patterns in the human ventral temporal cortex (VTC), but the exact features driving this distinction are still poorly understood. One prominent feature that distinguishes typical animals from inanimate objects and that could potentially explain the animate-inanimate distinction in the VTC is the presence of a face. In the current fMRI study, we investigated this possibility by creating a stimulus set that included animals with faces, faceless animals, and inanimate objects, carefully matched in order to minimize other visual differences. We used both searchlight-based and ROI-based representational similarity analysis (RSA) to test whether the presence of a face explains the animate-inanimate distinction in the VTC. The searchlight analysis revealed that when animals with faces were removed from the analysis, the animate-inanimate distinction almost disappeared. The ROI-based RSA revealed a similar pattern of results, but also showed that, even in the absence of faces, information about agency (a combination of animal’s ability to move and think) is present in parts of the VTC that are sensitive to animacy. Together, these analyses showed that animals with faces do elicit a stronger animate/inanimate response in the VTC, but that this effect is driven not by faces per se, or the visual features of faces, but by other factors that correlate with face presence, such as the capacity for self-movement and thought. In short, the VTC appears to treat the face as a proxy for agency, a ubiquitous feature of familiar animals.

Significance Statement

Many studies have shown that images of animals are processed differently from inanimate objects in the human brain, particularly in the ventral temporal cortex (VTC). However, what features drive this distinction remains unclear. One important feature that distinguishes many animals from inanimate objects is a face. Here, we used fMRI to test whether the animate/inanimate distinction is driven by the presence of faces. We found that the presence of faces did indeed boost activity related to animacy in the VTC. A more detailed analysis, however, revealed that it was the association between faces and other attributes such as the capacity for self-movement and thinking, not the facesper se, that was driving the activity we observed.
Leaf pigments and photosystems stoichiometry underpin photosynthetic efficiency of related C3, C3-C4and C4grasses under shade
Authors: Sagun JV , Chow WS , Ghannoum O
Published: October 2020

The quantum yield of CO2assimilation (QY) is generally lower in C3relative to C4plants at warm temperatures, and differs among the C4subtypes. Here, we investigated whether variations in QY are linked to light absorption or conversion efficiency. We grew six representative grasses with C3, C3-C4and C4photosynthesis under full (control) or 20% (shade) sunlight, and measured thein vivoactivity and stoichiometry of PSI and PSII, leaf spectral properties and pigment contents, and photosynthetic enzyme activities. Overall, shade reduced leaf photosynthesis, absorptance, especially in the green region, as well as carotenoids/chlorophylls and chlorophyll a/b ratios in C4more than non-C4species. Amongst C4, NADP-ME species had the highest QY and cyclic electron flow (CEF), and the NAD-ME species underwent the greatest reduction in leaf absorptance and pigments and PSII contents under shade, whist CEF and PSII/PSI were unaffected. These results demonstrate that the greater efficiency of the CO2concentrating mechanism in NADP-ME grasses at low light depends on light absorption and harvesting properties in addition to coordination between the C3and C4cycles. This is important for maximising light energy absorption and providing the right ATP/NADPH ratio while minimising photoinhibition under variable light conditions.

SUMMARY STATEMENT

Changes in leaf absorptance, pigment contents and photosystems stoichiometry underpin photosynthetic efficiency and responses of closely related C3, C3-C4and C4grasses under shade
Epileptic Spike Detection Using Neural Networks with Linear-Phase Convolutions
Authors: Fukumori Kosuke , Yoshida Noboru , Sugano Hidenori , Nakajima Madoka , Tanaka Toshihisa
Published: October 2020

To cope with the lack of highly skilled professionals, machine learning with proper signal processing is key for establishing automated diagnostic-aid technologies with which to conduct epileptic electroencephalogram (EEG) testing. In particular, frequency filtering with the appropriate passbands is essential for enhancing the biomarkers—such as epileptic spike waves—that are noted in the EEG. This paper introduces a novel class of neural networks (NNs) that have a bank of linear-phase finite impulse response filters at the first layer as a preprocessor that can behave as bandpass filters that extract biomarkers without destroying waveforms because of a linear-phase condition. Besides, the parameters of the filters are also data-driven. The proposed NNs were trained with a large amount of clinical EEG data, including 15,833 epileptic spike waveforms recorded from 50 patients, and their labels were annotated by specialists. In the experiments, we compared three scenarios for the first layer: no preprocessing, discrete wavelet transform, and the proposed data-driven filters. The experimental results show that the trained data-driven filter bank with supervised learning behaves like multiple bandpass filters. In particular, the trained filter passed a frequency band of approximately 10–30 Hz. Moreover, the proposed method detected epileptic spikes, with the area under the receiver operating characteristic curve of 0.967 in the mean of 50 intersubject validations.
Identity and provenance of neighbors, genotype-specific traits and abiotic stress affect intraspecific interactions in the annual legumeMedicago truncatula
Authors: Tomiolo Sara , Damgaard Christian F. , Zhang Sha , Kelly Simon , Tao Ke , Ronfort Joëlle , Gay Lauréne , Prosperi Jean-Marie , Radutoiu Simona , Ehlers Bodil K.
Published: October 2020

Accounting for intraspecific variation may improve our understanding of species coexistence. However, our knowledge of what factors maintain intraspecific variation is limited. We predicted that 1) a plant grows larger when with non-kin (i.e. different genotypes) than kin (i.e. same genotype) neighbors, 2) abiotic stress alters the outcome of kin vs. non-kin interactions, 3) genetic identity of plants affects composition of soil microbiome.

We set up mini-communities ofMedicago truncatula, where focal genotypes were grown together with two kin or two non-kin neighbors from different origins. We analyzed how origin, identity of interacting genotypes and abiotic stress affected growth and fruit production. We also analyzed the composition of soil microbial communities.

Focal plants grew larger in non-kin than in kin mini-communities. This pattern was stronger in low level of abiotic stress and when interacting genotypes were from similar origins. However, genotypic variation in growth and response to competition had a stronger effect on growth than mini-community type. Plant genotype identity did not affect soil microbiome.

We find that intraspecific variation is affected by genotype-specific traits and abiotic stress. Geographic, rather than genetic, distance among interacting genotypes affects the outcome of intraspecific interactions.
Mapping QTL for spike fertility related traits in two double haploid wheat (Triticum aestivum L.) populations
Authors: Pretini Nicole , Vanzetti Leonardo S. , Terrile Ignacio I. , Donaire Guillermo , González Fernanda G.
Published: October 2020

In breeding programs, the selection of cultivars with the highest yield potential consisted in the selection of the yieldper se, which resulted in cultivars with a higher grain number per spike (GN) and occasionally higher grain weight (GW) (main numerical components of the yield). This task could be facilitated with the use of molecular markers such us single nucleotide polymorphism (SNP). In this study, quantitative trait loci (QTL) for GW, GN and spike fertility traits related to GN determination were mapped using two double haploid (DH) populations (Baguette Premium 11 x BioINTA 2002 and Baguette 19 x BioINTA 2002, BP11xB2002 and B19xB2002). Both populations were genotyped with the iSelect 90K SNP array and evaluated in four (BP11xB19) or five (B19xB2002) environments. We identify a total of 305 QTL for 14 traits, however 28 QTL for 12 traits were considered significant with an R2> 10% and stable for being present at least in three environments. There were detected eight hotspot regions on chromosomes 1A, 2B, 3A, 5A, 5B, 7A and 7B were at least two major QTL sheared confident intervals. QTL on two of these regions have previously been described, but the other six regions were never observed, suggesting that these regions would be novel. The R5A1 (QSL.perg-5A, QCN.perg-5A,QGN.perg-5A)and R5A.2 (QFFTS.perg-5A, QGW.perg-5A)regions together with theQGW.perg-6B resulted in a final higher yield suggesting them to have high relevance as candidates to be used in MAS to improve yield.

Author contribution statement

Key message

28 stable and major QTL for 12 traits associated to spike fertility, GN and GW were detected. Two regions on 5A Ch., andQGW.perg-6B showed direct pleiotropic effects on yield.
Determining and Predicting Soil Chemistry with a Point-of-Use Sensor Toolkit and Machine Learning Model
Authors: Grell Max , Barandun Giandrin , Asfour Tarek , Kasimatis Michael , Collins Alex , Wang Jieni , Güder Firat
Published: October 2020

Overfertilization with nitrogen fertilizers has damaged the environment and health of soil; yields are declining, while the population continues to rise. Soil is a complex, living organism which is constantly evolving, physically, chemically and biologically. Standard laboratory testing of soil to determine the levels of nitrogen (mainly NH4+and NO3−) is infrequent as it is expensive and slow and levels of nitrogen vary on short timescales. Current testing practices, therefore, are not useful to guide fertilization. We demonstrate that Point-of-Use (PoU) measurements of NH4+, when combined with soil conductivity, pH, easily accessible weather (in this study, we simulated weather in the laboratory) and timing data (i.e. days passed since fertilization), allow instantaneous prediction of levels of NO3−in soil with of R2=0.70 using a machine learning (ML) model (the use of higher-precision laboratory measurements instead of PoU measurements increase R2to 0.87 for the same model). We also show that a long short-term memory recurrent neural network model can be used to predict levels of NH4+and NO3−up to 12 days into the future from a single measurement at day one, with R2NH4+= 0.64 and R2NO3-= 0.70, for unseen weather conditions. To measure NH4+in soil at the PoU easily and inexpensively, we also developed a new sensor that uses chemically functionalized near ‘zero-cost’ paper-based electrical gas sensors. This new technology can detect the concentration of NH4+in soil down to 3±1ppm (R2=0.85). Gas-phase sensing provides a robust method of sensing NH4+due to the reduced complexity of the gas-phase sample. Our machine learning-based approach eliminates the need of using dedicated, expensive sensing instruments to determine the levels of NO3−in soil which is difficult to measure reliably with inexpensive technologies; furthermore, crucial nitrogenous soil nutrients can be determined and predicted with enough accuracy to forecast the impact of climate on fertilization planning, and tune timing for crop requirements, reducing overfertilization while improving crop yields.
The interaction between endogenous GABA, functional connectivity and behavioral flexibility is critically altered with advanced age
Authors: Heise Kirstin-Friederike , Rueda-Delgado Laura , Chalavi Sima , King Bradley R. , Monteiro Thiago Santos , Edden Richard A. E. , Mantini Dante , Swinnen Stephan P.
Published: October 2020

The flexible adjustment of ongoing behavior challenges the nervous system’s dynamic control mechanisms and has shown to be specifically susceptible to age-related decline. Previous work links endogenous gamma-aminobutyric acid (GABA) with behavioral efficiency across perceptual and cognitive domains, with potentially the strongest impact on those behaviors that require a high level of dynamic control. Based on the integrated analyses of behavior and modulation of interhemispheric phase-based connectivity during dynamic motor state transitions and endogenous GABA concentration, we provide converging evidence for age-related differences in the behaviorally more beneficial state of endogenous GABA concentration. We suggest that the increased interhemispheric connectivity seen in the older adults represents a compensatory mechanism caused by rhythmic entrainment of neural populations in homotopic motor cortices. This mechanism appears to be most relevant in the presence of a less optimal tuning of the inhibitory tone to uphold the required flexibility of behavioral action.
Individual differences in the engagement of habitual control over alcohol seeking predicts the development of compulsive alcohol seeking and drinking
Authors: Giuliano Chiara , Puaud Mickaël , Cardinal Rudolf N. , Belin David , Everitt Barry J.
Published: October 2020

Excessive drinking is an important behavioural characteristic of alcohol addiction, but not the only one. Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences, and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to anterior dorsolateral striatum, dopamine-dependent mechanisms implicated in habit learning and individuals in whom alcohol-seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment. Here, we tested the hypothesis that the development of habitual alcohol-seeking predicts the development of compulsive seeking and that, once developed, it is associated with compulsive alcohol drinking. Male alcohol-preferring rats were pre-exposed intermittently to a two-bottle choice procedure, and trained on a seeking–taking chained schedule of alcohol reinforcement until some individuals developed punishment-resistant seeking behaviour. The associative basis of their seeking responses was probed with an outcome-devaluation procedure, early or late in training. After seeking behaviour was well established, subjects that had developed greater resistance to outcome-devaluation (were more habitual) were more likely to show punishment-resistant (compulsive) alcohol seeking. These individuals also drank more alcohol, despite quinine adulteration, even though having similar alcohol preference and intake before and during instrumental training. They were also less sensitive to changes in the contingency between seeking responses and alcohol outcome, providing further evidence of recruitment of the habit system. We therefore provide direct behavioural evidence that compulsive alcohol seeking emerges alongside compulsive drinking in individuals that have preferentially engaged the habit system.
The marine gastropodCrepidula fornicataremains resilient to ocean acidification across two life history stages
Authors: Reyes Christopher L , Benson Brooke E , Levy Morgan , Chen Xuqing , Pires Anthony , Pechenik Jan A , Davies Sarah W
Published: October 2020

Rising atmospheric CO2reduces seawater pH causing ocean acidification (OA). Understanding how resilient marine organisms respond to OA may help predict how community dynamics will shift as CO2continues rising. The common slipper shell snailCrepidula fornicatais a resilient marine gastropod native to eastern North America, which has been a successful invader along the western European coastline and elsewhere. To examine its potential resilience to OA, we conducted two controlled laboratory experiments. First, we examined several phenotypes and genome-wide gene expression ofC. fornicatain response to pH treatments (7.5, 7.6, 8.0) throughout the larval stage and then tested how conditions experienced as larvae influenced juvenile stages (i.e. carryover effects). Second, we examined genome-wide gene expression patterns ofC. fornicatalarvae in response to acute (4, 10, 24 and 48 hours) pH treatment (7.5, 8.0). BothC. fornicatalarvae and juveniles exhibited resilience to OA and gene expression responses highlight the role of transcriptome plasticity in OA resilience. Larvae did not exhibit reduced growth under OA until they were at least 4 days old. These phenotypic effects were preceded by broad transcriptomic changes, which likely serve as an acclimation mechanism for combating reduced pH conditions frequently experienced in littoral zones. Delayed metamorphosis was observed for larvae reared at reduced pH. Although juvenile size reflected larval rearing pH conditions, no carryover effects in juvenile growth rates were observed. Transcriptomic analyses suggest increased metabolism under OA, which may indicate compensation in reduced pH environments. Time course transcriptomic analyses suggest energetic burdens experienced under OA eventually dissipate, allowingC. fornicatato reduce metabolic demands and acclimate to reduced pH. This study highlights the importance of assessing the effects of OA across life history stages and demonstrates how transcriptomic plasticity can allow highly resilient organisms, likeC. fornicata, acclimate to reduced pH environments.
Time-dependent dual effect of NLRP3 inflammasome in brain ischemia
Authors: Palomino-Antolin Alejandra , Narros-Fernández Paloma , Farré-Alins Víctor , Sevilla-Montero Javier , Decouty-Pérez Celine , Lopez-Rodriguez Ana Belen , Fernández Nuria , Monge Luis , Casas Ana I. , Calzada María José , Egea Javier
Published: October 2020

Background and purpose

Post-ischemic inflammation contributes to worsening of ischemic brain injury and in this process, the inflammasomes play a key role. Inflammasomes are cytosolic multiprotein complexes which upon assembly activate the maturation and secretion of the inflammatory cytokines IL-1β and IL-18. However, participation of the NLRP3 inflammasome in ischemic stroke remains controversial. Our aims were to determine the role of NLRP3 in ischemia and to explore the mechanism involved in the potential protective effect of the neurovascular unit.

Methods

WT and NLRP3 knock-out mice were subjected to ischemia by middle cerebral artery occlusion (60 minutes) with or without treatment with MCC950 at different time points post-stroke. Brain injury was measured histologically with 2,3,5-triphenyltetrazolium chloride (TTC) staining.

Results

We identified a time-dependent dual effect of NLRP3. While neither the pre-treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post-reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose-dependent manner. Importantly, MCC950 improved the neuro-motor function and reduced the expression of different pro-inflammatory cytokines (IL-1β, TNF-α), NLRP3 inflammasome components (NLRP3, pro-caspase-1), protease expression (MMP9) and endothelial adhesion molecules (ICAM, VCAM). We observed a marked protection of the blood-brain barrier (BBB), which was also reflected in the recovery of the tight junctions proteins (ZO-1, Claudin-5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration.

Conclusions

These findings suggest that post-reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood-brain barrier in cerebral ischemia with potential clinical translation.
Single-cell transcriptomes of developing and adult olfactory receptor neurons inDrosophila
Authors: McLaughlin Colleen N. , Brbić Maria , Xie Qijing , Li Tongchao , Horns Felix , Kolluru Sai Saroja , Kebschull Justus M. , Vacek David , Xie Anthony , Li Jiefu , Jones Robert C. , Leskovec Jure , Quake Steven R. , Luo Liqun , Li Hongjie
Published: October 2020

Recognition of environmental cues is essential for the survival of all organisms. Precise transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes ofDrosophilaolfactory receptor neurons (ORNs), thermosensory and hygrosensory neurons from the third antennal segment at an early developmental and adult stage. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using these receptors and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuronal types across multiple developmental stages. Cell-type-specific transcriptomes, in part, reflected axon trajectory choices in early development and sensory modality in adults. Our analysis also uncovered type-specific and broadly expressed genes that could modulate adult sensory responses. Collectively, our data reveal important transcriptomic features of sensory neuron biology and provides a resource for future studies of their development and physiology.
Rainbow smelt population responses to species invasions and change in environmental condition
Authors: Bruel Rosalie , Marsden J. Ellen , Pientka Bernie , Staats Nick , Mihuc Timothy , Stockwell Jason D.
Published: October 2020

Invasive species can have major disruptions on native food webs, yet the impact of species introductions and whether they will become invasive appears to be context-dependent. Rainbow smelt and alewife co-exist as invasive species in the Laurentian Great Lakes and as native species on the Atlantic coast of North America, but in Lake Champlain rainbow smelt is the dominant native forage fish and alewife are invasive. Alewife became abundant by 2007, providing an opportunity to explore the dynamics of these two species in a system where only one is invasive. We used data from a 31-year forage fish survey to compare demographics of rainbow smelt populations in three basins of Lake Champlain with different pelagic volumes, nutrient levels, and predator abundances. Rainbow smelt catch-per-unit-effort (CPUE) remained constant in the large, deep Main Lake before and after alewife invaded, but decreased in the two smaller basins. Declines were primarily a result of increased age-0 and age-1 mortality. Predation by top piscivores, system productivity, and resource competition alone could not explain the patterns in CPUE across the basins. The mechanisms that allow alewife and rainbow smelt to co-exist could be related to system volume and oxythermal habitat availability, and may explain why the two species do not negatively affect each other in other systems. Summer hypoxia in the smaller basins could force individuals into smaller habitat volumes with higher densities of competitors and cannibalistic adult smelt. Our findings suggest that habitat size mediates the impact of invasive alewife on native rainbow smelt.
Exactp-values for global network alignments via combinatorial analysis of shared GO terms
Authors: Hayes Wayne B.
Published: October 2020

Network alignment aims to uncover topologically similar regions in the protein-protein interaction (PPI) networks of two or more species under the assumption that topologically similar regions perform similar functions. Although there exist a plethora of both network alignment algorithms and measures of topological similarity, currently no “gold standard” exists for evaluating how well either is able to uncover functionally similar regions. Here we propose a formal, mathematically and statistically rigorous method for evaluating the statistical significance of shared GO terms in a global, 1-to-1 alignment between two PPI networks. We use combinatorics to precisely count the number of possible network alignments in whichkproteins share a particular GO term. When divided by the number of all possible network alignments, this provides an explicit, exactp-value for a network alignment with respect to a particular GO term.
Genome engineering ofNannochloropsiswith large deletions for constructing microalgal minigenomes
Authors: Wang Qintao , Gong Yanhai , He Yuehui , Xin Yi , Lv Nana , Du Xuefeng , Li Yun , Jeong Byeong-ryool , Xu Jian
Published: October 2020

Industrial microalgae are promising photosynthetic cell factories, yet tools for targeted genome engineering are limited. Here for the model industrial oleaginous microalgaNannochloropsis oceanicawe established a method to precisely and serially delete large genome fragments of ~100 kb from its 30.01-Mb nuclear genome. We started by identifying the “non-essential” chromosomal regions (i.e., low-expression region or LER) based on minimal gene expression under N-replete and N-depleted conditions. The largest such LER (LER1) is ~98 kb in size, located near the telomere of the 502.09 kb-long Chromosome 30 (Chr 30). We deleted 81 kb and further distal and proximal deletions of up to 110 kb (21.9% of Chr 30) in LER1 by dual targeting the boundaries with the episome-based CRISPR/Cas9 system. The telomere-deletion mutants showed normal telomeres consisting of CCCTAA repeats, revealing telomere regeneration capability after losing distal part of Chr 30. Interestingly, the deletions caused no significant alteration in growth, lipid production or photosynthesis (transcript-abundance change for < 3% genes under N depletion). We also performed double-deletion of both LER1 and LER2 (from Chr 9) that totals ~214 kb, and phenotypes are essentially normal. Therefore, loss of the large yet “non-essential” regions does not necessarily sacrifice important traits. Such serial targeted deletions of large genomic regions have not been reported in plants or microalgae, and will accelerate crafting minimal genomes as chassis for photosynthetic production.