bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep modifications of the microbiome of rice roots infected by the parasitic nematode Meloidogyne graminicola in highly infested fields in Vietnam
Authors: Masson Anne-Sophie , Ho Bich Hai , Simonin Marie , Nguyen Thi Hue , Czernic Pierre , Moulin Lionel , Bellafiore Stéphane
Published: May 2020

Meloidogyne graminicola, also known as the rice root-knot nematode, is one of the most damaging plant-parasitic nematode, especially on rice. This obligate soilborne parasite induces the formation of galls that disturb the root morphology and physiology. Its impact on the root microbiome is still not well described. Here, we conducted a survey in Northern Vietnam where we collected infected (with galls) and non-infected root tips from the same plants in three naturally infested fields. Using a metabarcoding approach, we discovered that M. graminicola infection caused modifications of the root bacterial community composition and network structure. Interestingly, we observed in infected roots a higher diversity and species richness (+24% observed ESVs) as well as a denser and more complex co-occurrence network (+44% nodes and +136% links). We identified enriched taxa that include several hubs, which could serve as potential indicators or biocontrol agents of the nematode infection. Moreover, the community of infected roots is more specific suggesting changes in the functional capabilities to survive in the gall environment. We thus describe the signature of the gall microbiome (the ‘gallobiome’) with shifting abundances and enrichments that lead to a strong restructuration of the root microbiome.
The interplay between iron limitation, light and carbon in the proteorhodopsin-containing Photobacterium angustum S14
Authors: Koedooder Coco , Van Geersdaële Rémy , Guéneuguès Audrey , Bouget François-Yves , Obernosterer Ingrid , Blain Stéphane
Published: May 2020

Iron (Fe) limitation is known to affect heterotrophic bacteria within the respiratory electron transport chain, therefore strongly impacting the overall intracellular energy production. We investigated whether the gene expression pattern of the light-sensitive proton pump, proteorhodopsin (PR), is influenced by varying light, carbon and Fe concentrations in the marine bacterium Photobacterium angustum S14 and whether PR can alleviate the physiological processes associated with Fe starvation. Our results show that the gene expression of PR increases as cells enter the stationary phase, irrespective of Fe-replete or Fe-limiting conditions. This upregulation is coupled to a reduction in cell size, indicating that PR gene regulation is associated with a specific starvation-stress response. We provide experimental evidence that PR gene expression does not result in an increased growth rate, cell abundance, enhanced survival or ATP concentration within the cell in either Fe-replete or Fe-limiting conditions. However, independent of PR gene expression, the presence of light did influence bacterial growth rates and maximum cell abundances under varying Fe regimes. Our observations support previous results indicating that PR phototrophy seems to play an important role within the stationary phase for several members of the Vibrionaceae family, but that the exact role of PR in Fe limitation remains to be further explored.
Disparities in Objective Sleep Quality as Assessed Through Wrist Actigraphy in Minority Patients With Inflammatory Bowel Disease
Authors: Qazi Taha , Smith Alexander , Alexander Megan , Hammer David , Wu Ting , Auerbach Sanford , Noronha Ansu , Wasan Sharmeel , Jones Eric , Weinberg Janice , Farraye Francis A
Published: May 2020

Background

Inflammatory bowel disease (IBD) is associated with a reduced quality of life. Minority patients with IBD specifically report more impairing symptoms compared with nonminority patients. Sleep quality, a key component of quality of life, is significantly compromised in minority patients compared with nonminority patients. Nevertheless, subjective and objective sleep assessments in minority patients with IBD have not explicitly been assessed. The purpose of this prospective cohort study is to assess and compare objective sleep parameters utilizing wrist actigraphy between minority and nonminority IBD patients.

Methods

In this institutional review board approved study, 74 patients with IBD were recruited and stratified into 2 cohorts by self-identification: white nonminority patients and minority patients. Patients in the minority cohort included black and Hispanic individuals (black and nonblack). Exclusion criteria included significant comorbidity, a history of an underlying sleep disorder, or patients who did not self-identify into categorized cohorts. Sleep was measured not only through wrist-based actigraphy but also with sleep surveys. Sleep parameters were compared between minority and nonminority cohorts. Regression analyses were performed to assess for factors independently associated with parameters of poor sleep quality.

Results

Sixty-four patients (86.4%) were included in the final analysis. Thirty-one individuals (48.4%) were categorized into the nonminority cohort, and 33 (51.6%) patients were in the minority cohort. A significantly higher number of minority patients had poorer sleep efficiency and fragmented sleep compared with nonminority patients (90.9% vs 67.7%; P = 0.03 and 87.8% vs 61.3%; P = 0.02). In the adjusted analysis, minority status was independently associated with poor sleep efficiency (odds ratio = 6.41; 95% confidence interval, 1.48-28.17; P = 0.0139) and fragmented sleep (odds ratio = 4.98; 95% confidence interval, 1.09-22.89; P = 0.0389).

Conclusions

Minority patients with IBD were shown to have poorer objective measures of sleep as assessed through wrist actigraphy compared to nonminority patients. Cultural competency in the care of minority patients with IBD, specifically focusing on the management of psychosocial issues, is needed to address these disparities in sleep. The inclusion of minority patients with IBD in studies investigating sleep and other psychosocial issues are warranted not only to assess potential disparities in disease course but also to determine the etiologies of poor sleep in minority patients with IBD.
Industry-collected target strength of high seas orange roughy in the Indian Ocean
Authors: Scoulding Ben , Kloser Rudy
Published: May 2020

Visually verified in situ target strengths (TS) are the state of the science for determining the conversion from acoustic echo-integration surveys to biomass. Here, we show how these measurements can be made by high seas fisheries during normal operations using a net-attached acoustic optical system (AOS) without specialized personnel on board. In situ TS were collected from ∼45 cm standard length (SL) orange roughy (Hoplostethus atlanticus) in the southern Indian Ocean at 38 and 120 kHz. We use a multiple lines of evidence approach to demonstrate that the previous TS–SL equation developed for ∼10 cm smaller fish in Australia and New Zealand is not suitable for the larger orange roughy and instead propose new TS–SL equations. Our findings show that biomass estimates at 38 kHz will be reduced by ∼58% when using this new TS–SL compared to the existing TS–SL for smaller fish. This highlights the error of extrapolating TS–SL equations outside the measurement range. For this high sea region, the net-attached AOS represented a practical cost-effective method to obtain measurements and provide a result that could be used to inform the management of the stocks. We suggest that this method would be useful in all deep-water fisheries to monitor the TS of the fish for a range of environmental and ontogenetic conditions.
Virtue Ethics and Laboratory Animal Research
Authors: Walker Rebecca L
Published: May 2020

This article appeals to virtue ethics to help guide laboratory animal research by considering the role of character and flourishing in these practices. Philosophical approaches to animal research ethics have typically focused on animal rights or on the promotion of welfare for all affected, while animal research itself has been guided in its practice by the 3Rs (reduction, refinement, replacement). These different approaches have sometimes led to an impasse in debates over animal research where the philosophical approaches are focused on whether or when animal studies are justifiable, while the 3Rs assume a general justification for animal work but aim to reduce harm to sentient animals and increase their welfare in laboratory spaces. Missing in this exchange is a moral framework that neither assumes nor rejects the justifiability of animal research and focuses instead on the habits and structures of that work. I shall propose a place for virtue ethics in laboratory animal research by considering examples of relevant character traits, the moral significance of human-animal bonds, mentorship in the laboratory, and the importance of animals flourishing beyond mere welfare.
Psychometric properties of the Bulgarian version of Hospital Survey on Patient Safety Culture
Authors: Keskinova Donka , Dimova Rositsa , Stoyanova Rumyana
Published: May 2020

Objective

To explore the psychometrics of the Bulgarian version of the Hospital Survey on Patient Safety Culture (B-HSOPSC) and its suitability for use in Bulgaria.

Design

A national web-based cross-sectional survey of the safety patient culture.

Setting

The hospitals’ staffs from 28 administrative areas in the country.

Interventions

Web-based self-administered questionnaire.

Participants

Physicians and non-physicians such as nurses, midwifes, etc., working at hospitals.

Main Outcome Measures

Confirmatory factor analysis (CFA) was performed to assess the psychometric properties of the original US structure. Assessment of construct validity included convergent validity, discriminant validity, and nomological validity of constructs.

Results

A total of 525 valid cases were included in the analysis. The results of CFA revealed acceptable values for absolute indices and lower for the incremental index, comparative fit index. Due to the very low convergence validity, the dimension ‘staffing’ was removed from the model. Additionally, one item was removed from another dimension. The B-HSOPSC included 11 dimensions and 37 items.

Conclusions

The B-HSOPSC had acceptable levels of global and local fits. Its safety culture dimensions were sufficiently distinguishable and correlated with outcome variables.
The influence and added value of a Standardized Assessment and Reporting System for functioning outcomes upon national rehabilitation quality reports
Authors: Maritz Roxanne , Ehrmann Cristina , Prodinger Birgit , Tennant Alan , Stucki Gerold
Published: May 2020

Objective

To demonstrate the influence and added value of a Standardized Assessment and Reporting System (StARS) upon the reporting of functioning outcomes for national rehabilitation quality reports. A StARS builds upon an ICF-based (International Classification of Functioning, Disability and Health) and interval-scaled common metric.

Design

Comparison of current ordinal-scaled Swiss national rehabilitation outcome reports including an expert-consensus-based transformation scale with StARS-based reports through descriptive statistical methods and content exploration of further development areas of the reports with relevant ICF Core Sets.

Setting

Swiss national public rehabilitation outcome quality reports on the clinic level.

Participants

A total of 29 Swiss rehabilitation clinics provided their quality report datasets including 18 047 patients.

Interventions

Neurological or musculoskeletal rehabilitation.

Main outcome measures

Functional Independence Measure™ or Extended Barthel Index.

Results

Outcomes reported with a StARS tended to be smaller but more precise than in the current ordinal-scaled reports, indicating an overestimation of achieved outcomes in the latter. The comparison of the common metric’s content with ICF Core Sets suggests to include ‘energy and drive functions’ or ‘maintaining a basic body position’ to enhance the content of functioning as an indicator.

Conclusions

A StARS supports the comparison of outcomes assessed with different measures on the same interval-scaled ICF-based common metric. Careful consideration is needed whether an ordinal-scaled or interval-scaled reporting system is applied as the magnitude and precision of reported outcomes is influenced. The StARS’ ICF basis brings an added value by informing further development of functioning as a relevant indicator for national outcome quality reports in rehabilitation.
Mapping scientific landscapes in UMLS research: a scientometric review
Authors: Kim Meen Chul , Nam Seojin , Wang Fei , Zhu Yongjun
Published: May 2020

Objective

The Unified Medical Language System (UMLS) is 1 of the most successful, collaborative efforts of terminology resource development in biomedicine. The present study aims to 1) survey historical footprints, emerging technologies, and the existing challenges in the use of UMLS resources and tools, and 2) present potential future directions.

Materials and Methods

We collected 10 469 bibliographic records published between 1986 and 2019, using a Web of Science database. graph analysis, data visualization, and text mining to analyze domain-level citations, subject categories, keyword co-occurrence and bursts, document co-citation networks, and landmark papers.

Results

The findings show that the development of UMLS resources and tools have been led by interdisciplinary collaboration among medicine, biology, and computer science. Efforts encompassing multiple disciplines, such as medical informatics, biochemical sciences, and genetics, were the driving forces behind the domain’s growth. The following topics were found to be the dominant research themes from the early phases to mid-phases: 1) development and extension of ontologies and 2) enhancing the integrity and accessibility of these resources. Knowledge discovery using machine learning and natural language processing and applications in broader contexts such as drug safety surveillance have recently been receiving increasing attention.

Discussion

Our analysis confirms that while reaching its scientific maturity, UMLS research aims to boundary-span to more variety in the biomedical context. We also made some recommendations for editorship and authorship in the domain.

Conclusion

The present study provides a systematic approach to map the intellectual growth of science, as well as a self-explanatory bibliometric profile of the published UMLS literature. It also suggests potential future directions. Using the findings of this study, the scientific community can better align the studies within the emerging agenda and current challenges.
Constraints on the circumburst environments of short gamma-ray bursts
Authors: O’Connor Brendan , Beniamini Paz , Kouveliotou Chryssa
Published: May 2020

Observational follow up of well localized short gamma-ray bursts (SGRBs) has left $20\!-\!30{{\ \rm per\ cent}}$ of the population without a coincident host galaxy association to deep optical and NIR limits (≳26 mag). These SGRBs have been classified as observationally hostless due to their lack of strong host associations. It has been argued that these hostless SGRBs could be an indication of the large distances traversed by the binary neutron star system (due to natal kicks) between its formation and its merger (leading to an SGRB). The distances of GRBs from their host galaxies can be indirectly probed by the surrounding circumburst densities. We show that a lower limit on those densities can be obtained from early afterglow light curves. We find that ${\lesssim}16{{\ \rm per\ cent}}$ of short GRBs in our sample took place at densities ≲10−4 cm−3. These densities represent the expected range of values at distances greater than the host galaxy’s virial radii. We find that out of the five SGRBs in our sample that have been found to be observationally hostless, none are consistent with having occurred beyond the virial radius of their birth galaxies. This implies one of two scenarios. Either these observationally hostless SGRBs occurred outside of the half-light radius of their host galaxy, but well within the galactic halo, or in host galaxies at moderate to high redshifts (z ≳ 2) that were missed by follow-up observations.
Stellar migrations and metal flows – Chemical evolution of the thin disc of a simulated Milky Way analogous galaxy
Authors: Vincenzo Fiorenzo , Kobayashi Chiaki
Published: May 2020

In order to understand the roles of metal flows in galaxy formation and evolution, we analyse our self-consistent cosmological chemodynamical simulation of a Milky Way like galaxy during its thin-disc phase. Our simulated galaxy disc qualitatively reproduces the variation of the dichotomy in [α/Fe]–[Fe/H] at different Galactocentric distances as derived by APOGEE-DR16, as well as the stellar age distribution in [α/Fe]–[Fe/H] from APOKASC-2. The disc grows from the inside out, with a radial gradient in the star-formation rate during the entire phase. Despite the radial dependence, the outflow-to-infall ratio of metals in our simulated halo shows a time-independent profile scaling with the disc growth. The simulated disc undergoes two modes of gas inflow: (i) an infall of metal-poor and relatively low-[α/Fe] gas, and (ii) a radial flow where already chemically enriched gas moves inwards with an average velocity of ∼0.7 km s−1. Moreover, we find that stellar migrations mostly happen outwards, on typical time-scales of ∼5 Gyr. Our predicted radial metallicity gradients agree with the observations from APOGEE-DR16, and the main effect of stellar migrations is to flatten the radial metallicity profiles by 0.05 dex/kpc in the slopes. We also show that the effect of migrations can appear more important in [α/Fe] than in the [Fe/H]–age relation of thin-disc stars.
Two Cases of Vancomycin-Resistant Enterococcus faecium Bacteremia With Development of Daptomycin-Resistant Phenotype and its Detection Using Oxford Nanopore Sequencing
Authors: Udaondo Zulema , Jenjaroenpun Piroon , Wongsurawat Thidathip , Meyers Erik , Anderson Courtney , Lopez James , Mohan Meera , Tytarenko Ruslana , Walker Brian , Ussery David , Kothari Atul , Jun Se-Ran
Published: May 2020

In this work, we report 2 cases of vancomycin-resistant Enterococcus faecium bacteremia with development of daptomycin resistance in 2 patients with acute myeloid leukemia and myelodysplastic syndrome. Mutations related to daptomycin-nonsusceptible phenotype in liaSR genes were found in all strains of the study, including those with a minimum inhibitory concentration <1 µg/mL collected before daptomycin therapy. Epidemiological investigation using core genome single nucleotide polymorphism and core genome multilocus sequence typing revealed clonality of all the isolates. In this study, we conclude that real-time genome sequencing of clinical isolates can provide rapid access to timely information on daptomycin-resistant genotypes that would help clinicians speed up and optimize the selection of the antibiotic for treatment.
Impacts of remdesivir on dynamics and efficacy stratified by the severity of COVID- 19: a simulated two-arm controlled study
Authors: Lin Ting-Yu , Chang Wei-Jung , Hsu Chen-Yang , Lai Chao-Chih , Yen Amy Ming-Fang , Chen Sam Li-Sheng , Chen Hsiu-Hsi
Published: May 2020

Background: The impact of remdesivir on length of stay of hospitalization, high-risk state, and death stratified by the severity of COVID-19 at enrollment is controversial.
Methods: We applied a simulated two-arm controlled study design to the data on compassionate use of remdesivir as a secondary analysis. Dynamics of risk states and death from COVID-19 patients defined by the six-point disease severity recommended by the WHO R&D and the time to discharge from hospital were used to evaluate the efficacy of remdesivir treatment compared with standard care.
Results: Stratified by the risk state at enrollment, low-risk patients exhibited the highest efficacy of remdesivir in reducing subsequent progression to high-risk state by 67% (relative risk (RR)=0.33,95% CI: 0.30-0.35) and further to death by 55% (RR=0.45, 95%CI: 0.39-0.50). For the medium-risk patients, less but still statistically significant efficacy results were noted in reducing progression to high-risk state by 52% (RR=0.48, 95% CI: 0.45-0.51) and further to death by 40% (RR=0.60, 95% CI:0.54-0.66). High-risk state patients treated with remdesivir led to a 25% statistically significant reduction in death (RR=0.75, 95% CI: 0.69-0.82). Regarding the outcome of discharge, remdesivir treatment was most effective for medium-risk patients at enrollment (RR: 1.41, 95% CI: 1.35-1.47) followed by high- (RR=1.34, 95% CI: 1.27-1.42) and low-risk patients (RR=1.28, 95% CI: 1.25-1.31).
Conclusion: Our results with a simulated two-arm controlled study have provided a new insight into the precision treatment of remdesivir for COVID-19 patients based on risk-stratified efficacy.
Chidamide combined with doxorubicin leads to synergistic anti-cancer effect and induces autophagy through inhibiting the PI3K/Akt/mTOR pathway in anaplastic thyroid carcinoma
Authors: He Yishan , Qiu Xinguang
Published: May 2020

Anaplastic thyroid carcinoma (ATC) is a fatal malignant tumor, which belongs to the thyroid cancer with an overwhelmingly poor prognosis and eagerly demands effective systemic treatment strategies. We aimed to investigate the antitumor characteristics of Chidamide (CS055) in combination with doxorubicin (Dox) on ATC, and explore the underlying molecular mechanism. Herein, we found that CS055 and Dox inhibited proliferation, invasion and migration and promoted apoptosis of ATC cells. CS055 and Dox induced autophagic cell death (ADC) of ATC cell lines. And the expression of autophagy markers, BECN1, Atg5 and LC3-II was significantly enhanced in ATC cell lines treated with CS055 and Dox. Similarly, thein vivostudy showed that CS055 and Dox administration significantly reduced tumor growth and induced tumor cell autophagy. Interestingly, the synergistic anti-cancer effect of CS055 in combination with doxorubicin was observedin vitroandin vivo. In addition, CS055 and Dox suppressed the proteins expression of p-P13K, p-AKT and mTORin vitroandin vivoand combination of CS055 and Dox exhibited greatest inhibitory effect. Taken together, our findings concluded that CS055 in combination with Dox exerted antitumor activities and triggered autophogy in thyroid carcinoma probably through inhibiting the P13K/AKT/m/TOR signaling pathway.
SARS-CoV-2 RNA concentrations in primary municipal sewage sludge as a leading indicator of COVID-19 outbreak dynamics
Authors: Peccia Jordan , Zulli Alessandro , Brackney Doug E. , Grubaugh Nathan D. , Kaplan Edward H. , Casanovas-Massana Arnau , Ko Albert I. , Malik Amyn A. , Wang Dennis , Wang Mike , Warren Joshua L. , Weinberger Daniel M. , Omer Saad B.
Published: May 2020

We report a time course of SARS-CoV-2 RNA concentrations in primary sewage sludge during the Spring COVID-19 outbreak in a northeastern U.S. metropolitan area. SARS-CoV-2 RNA was detected in all environmental samples, and when adjusted for the time lag, the virus RNA concentrations tracked the COVID-19 epidemiological curve. SARS-CoV-2 RNA concentrations were a leading indicator of community infection ahead of compiled COVID-19 testing data and local hospital admissions. Decisions to implement or relax public health measures and restrictions require timely information on outbreak dynamics in a community.
Evaluation and Optimization of Motion Correction in Spinal Cord fMRI Preprocessing
Authors: Dehghani Hamed , Weber Kenneth A , Batouli Seyed Amir Hossein , Oghabian Mohammad Ali , Khatibi Ali
Published: May 2020

Motion correction is an essential step in the preprocessing of functional magnetic resonance imaging (fMRI) data, improving the temporal signal to noise ratio (tSNR) and removing unwanted variance. Because of the characteristics of the spinal cord (non-rigidity, surrounded by moving organs), motion correction becomes especially challenging. We compared the efficiency of different motion correction protocols and suggest a preferred method for spinal cord fMRI data. Here we acquired gradient-echo echo-planar-imaging axial lumbar spinal cord fMRI data during painful mechanical stimulation of the left lower extremity of 15 healthy volunteers on a 3T scanner. We compared multiple motion correction techniques: 2D and 3D FLIRT realignment with and without slice-wise regulation, SliceCorr (implemented in the Spinal Cord Toolbox) and proposed a method 3D FLIRT in addition to Slice Regulation (SLiceReg) along the spinal cord. TSNR, image entropy, DVARS, image Sum of Absolute Differences and number of activated voxels in the spinal cord from GLM analysis to evaluate the performance of multiple motion correction procedures. The tSNR and DVARS 3D FLIRT + SLiceReg were significantly improved over other realignment methods (p<0.001). In comparison, tSNR=14.20±0.02 and DVARS=165.77±1.54 were higher than other methods. Additionally, the number of activated voxels of the statistical map in our suggested method was higher than the other realignment methods (p<0.05). Our results illustrated the proposed motion correction algorithm that integrated 3D motion correction and 2D slicewise regularization along spinal cord curvature could improve subject-level processing outputs by reducing the effects of motions. Our proposed protocols can improve subject-level analysis, especially in lumbar region that suffers from involuntary motions and signal loss due to susceptibility effect more than other spinal cord regions.
Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking
Authors: Ojima Kento , Shiraiwa Kazuki , Doura Tomohiro , Takato Mikiko , Komatsu Kazuhiro , Yuzaki Michisuke , Hamachi Itaru , Kiyonaka Shigeki
Published: May 2020

The regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for AMPA-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Here, we develop a new method for the rapid and selective labeling of chemical probes to AMPARs by combining affinity-based protein labeling and bioorthogonal click chemistry under physiological conditions. This method allowed us to quantify AMPAR distribution and trafficking, which revealed some unique features of AMPARs, such as a long lifetime and a rapid recycling in neurons. This method was also successfully expanded to selectively label NMDA-type glutamate receptors. Thus, bioorthogonal two-step labeling may be a versatile tool for investigating the physiological and pathophysiological roles of glutamate receptors in neurons.
Development of thalamus mediates paternal age effect on offspring reading: A preliminary investigation
Authors: Xia Zhichao , Wang Cheng , Hancock Roeland , Vandermosten Maaike , Hoeft Fumiko
Published: May 2020

The importance of (inherited) genetic impact in reading development is well-established.De novomutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor forde novomutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offspring’s reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was associated significantly with worse reading, explaining an additional 9.5% of the variations after controlling for a number of confounds—including familial factors and cognitive-linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE-related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offspring’s diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research.

Highlights

Paternal age at childbirth (PatAGE) is negatively correlated with offspring’s reading abilities.

PatAGE is related to volumetric maturation of the left posterior thalamus.

Thalamic development mediates the PatAGE effect on reading.

The PatAGE-related thalamic area is more likely to connect with the dorsal attention network.
Neural attentional-filter mechanisms of listening success in middle-aged and older individuals
Authors: Tune Sarah , Alavash Mohsen , Fiedler Lorenz , Obleser Jonas
Published: May 2020

Successful listening crucially depends on intact attentional filters that separate relevant from irrelevant information. Research into their neurobiological implementation has focused on two potential auditory filter strategies: the lateralization of alpha power and selective neural speech tracking. However, the functional interplay of the two neural filter strategies and their potency to index listening success in an ageing population remains unclear. Using electroencephalography and a dual-talker task in a representative sample of listeners (N=155; age=39–80 years), we here demonstrate an often-missed link from single-trial behavioural outcomes back to trial-by-trial changes in neural attentional filtering. First, we observe preserved attentional–cue-driven modulation of both neural filters across chronological age and hearing levels. Second, neural filter states vary independently of one another, demonstrating complementary neurobiological solutions of spatial selective attention. Stronger neural speech tracking but not alpha lateralization boosts trial-to-trial behavioural performance. Our results highlight the translational potential of neural speech tracking as an individualized neural marker of adaptive listening behaviour.
Derivation of ringed seal (Phoca hispida) induced multipotent stem cells
Authors: Beklemisheva Violetta R. , Belokopytova Polina S. , Fishman Veniamin S. , Menzorov Aleksei G.
Published: May 2020

Induced pluripotent stem (iPS) cells have been produced just for a few species among order Carnivora: snow leopard, Bengal tiger, serval, jaguar, cat, dog, ferret, and American mink. We applied the iPS cell derivation protocol to the ringed seal (Phoca hispida) fibroblasts. The resulting cell line had the expression of pluripotency marker geneRex1. Differentiation in embryoid body-like structures allowed us to register expression ofAFP, endoderm marker, andCdx2, trophectoderm marker, but not neuronal (ectoderm) markers. The cells readily differentiated into adipocytes and osteocytes, mesoderm cell types of origin. Transcriptome analysis allowed us to conclude that the cell line does not resemble human pluripotent cells, and, therefore, most probably are not pluripotent. Thus, we produced ringed seal multipotent stem cell line capable of differentiation into adipo- and osteocytes.
Contextual and spatial associations between objects interactively modulate visual processing
Authors: Quek Genevieve L. , Peelen Marius V.
Published: May 2020

Much of what we know about object recognition arises from the study of isolated objects. In the real world, however, we commonly encounter groups of contextually-associated objects (e.g., teacup, saucer), often in stereotypical spatial configurations (e.g., teacupabovesaucer). Here we used EEG to test whether identity-based associations between objects (e.g., teacup-saucervs. teacup-stapler) are encoded jointly with their typical relative positioning (e.g., teacupabovesaucervs. belowsaucer). Observers viewed a 2.5Hz image stream of contextually-associated object pairs intermixed with non-associated pairs as every fourth image. The differential response to non-associated pairs (measurable at 0.625Hz in 28/37 participants), served as an index of contextual integration, reflecting the association of object identities in each pair. Over right occipitotemporal sites, this signal was larger for typically-positioned object streams, indicating that spatial configuration facilitated the extraction of the objects’ contextual association. This high-level influence of spatial configuration on object identity integration arose ∼320ms post stimulus onset, with lower-level perceptual grouping (shared with inverted displays) present at ∼130ms. These results demonstrate that contextual and spatial associations between objects interactively influence object processing. We interpret these findings as reflecting the high-level perceptual grouping of objects that frequently co-occur in highly stereotyped relative positions.
Pharmacokinetics trumps pharmacodynamics during cocaine choice: a reconciliation with the dopamine hypothesis of addiction
Authors: Canchy Ludivine , Girardeau Paul , Durand Audrey , Vouillac-Mendoza Caroline , Ahmed Serge H.
Published: May 2020

Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this difference would explain, at least in part, why the latter are eventually given up in favor of continued cocaine use during the transition to addiction. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative, sometimes to the exclusion of continued drug use. Here we report converging evidence that reconciles this finding with the dopamine hypothesis of addiction. Briefly, our data suggest that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics. Finally, this study also reveals important gaps in our understanding of drug reward delays that need to be filled by future experimental and theoretical work.
Vein-to-blade ratio is an allometric indicator of climate-induced changes in grapevine leaf size and shape
Authors: Chitwood Daniel H. , Mullins Joey , Migicovsky Zoë , Frank Margaret , VanBuren Robert , Londo Jason P.
Published: May 2020

Premise

As a leaf expands, its shape dynamically changes. Previously, we documented an allometric relationship between vein and blade area in grapevine leaves. Larger leaves have a smaller ratio of primary and secondary vein area relative to blade area compared to smaller leaves. We sought to use allometry as an indicator of leaf size to measure the environmental effects of climate on grapevine leaf morphology.

Methods

We measure the ratio of vein-to-blade area in 8,412 leaves from the same 208 vines across four growing seasons (2013, 2015, 2016, and 2017) using 21 homologous landmarks. Matching leaves by vine and node, we correlate size and shape of grapevine leaves with climate variables.

Key results

Vein-to-blade ratio varies strongly between years in ways that blade or vein area do not. Maximum daily temperature and to a lesser degree precipitation are the most strongly correlated climate variables with vein-to-blade ratio, indicating that smaller leaves are associated with heat waves and drought. Leaf count and overall leaf area of shoots and the vineyard population studied also diminish with heat and drought. Grapevine leaf primordia initiate in buds the year prior to when they emerge, and we find that climate during the previous growing season exerts the largest statistical effects over these relationships.

Conclusions

Our results demonstrate the profound effects of heat and drought on the vegetative morphology of grapevines and show that vein-to-blade ratio is a strong allometric indicator of the effects of climate on grapevine leaf morphology.
A systematic investigation of human DNA preservation in medieval skeletons
Authors: Parker Cody , Rohrlach Adam B. , Friederich Susanne , Nagel Sarah , Meyer Matthias , Krause Johannes , Bos Kirsten I. , Haak Wolfgang
Published: May 2020

Ancient DNA (aDNA) analyses necessitate the destructive sampling of archaeological material. Currently the dense inner portion of the petrous pyramid, the location of the skull that houses the inner ear, is the most sought after skeletal element for molecular analyses of ancient humans as it has been shown to yield high amounts of endogenous DNA. Destructive sampling of the petrous pyramid, assuming its recovery, is often not recommended for highly valued specimens. To investigate alternatives, we present a survey of human aDNA preservation for each of ten skeletal elements in a skeletal collection from Medieval Germany. Through comparison of human DNA content and quality we confirm best performance of the petrous pyramid and identify seven additional sampling locations across four skeletal elements that yield adequate aDNA for most applications in human palaeogenetics. Our study provides a better perspective on DNA preservation across the human skeleton and takes a further step toward the more responsible use of ancient materials in human aDNA studies.
The human SKI complex prevents DNA-RNA hybrid-associated telomere instability
Authors: Herrera-Moyano Emilia , Porreca Rosa Maria , Ranjha Lepakshi , Skourti Eleni , Gonzalez-Franco Roser , Sun Ying , Stylianakis Emmanouil , Montoya Alex , Kramer Holger , Vannier Jean-Baptiste
Published: May 2020

Super killer (SKI) complex is a well-known cytoplasmic 3′ to 5′ mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs. Recently, SKIV2L, the 3′ to 5′ RNA helicase of the human SKI (hSKI) complex has been implicated in the degradation of nuclear non-coding RNAs escaping to the cytoplasm. Here, we show that hSKI is present in the nucleus, on chromatin and in particular at telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomeric loss, and DNA damage response activation, and its absence leads to DNA-RNA hybrid-mediated telomere fragility. Moreover, we demonstrate that purified hSKI complex preferentially unwinds telomeric DNA-RNA hybridsin vitro. Taken together, our results provide a nuclear function of the hSKI complex in overcoming replication stress caused by aberrant processing of telomeric DNA-RNA hybrids and thus maintaining telomere stability.
MARK4 with an Alzheimer’s disease-related mutation promotes tau hyperphosphorylation directly and indirectly and exacerbates neurodegeneration
Authors: Oba Toshiya , Saito Taro , Asada Akiko , Shimizu Sawako , Iijima Koichi M. , Ando Kanae
Published: May 2020

Accumulation of the microtubule-associated protein tau is associated with Alzheimer’s disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser262 and Ser356 play critical roles in tau accumulation and toxicity. Microtubule-affinity regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a doublede novomutation in the linker region of MARK4, ΔG316E317InsD, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317Dincreases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser262/356-dependent and -independent mechanisms. Using transgenicDrosophilaexpressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that co-expression of MARK4wtand MARK4ΔG316E317Dincreased total tau levels and enhanced tau-induced neurodegeneration, and that MARK4ΔG316E317Dhad more potent effects than MARK4wt. Interestingly, thein vitrokinase activities of MARK4wtand MARK4ΔG316E317Dwere similar. Blocking tau phosphorylation at Ser262 and Ser356 by alanine substitutions protected tau from the effects of MARK4wt, but not from MARK4ΔG316E317D. While both MARK4wtand MARK4ΔG316E317Dincreased the levels of oligomeric forms of tau, MARK4ΔG316E317Dfurther boosted the levels of tau phosphorylated at several sites other than Ser262/356 and increased the detergent insolubility of tauin vivo. Together, these findings suggest that MARK4ΔG316E317Dincreases tau levels and exacerbates tau toxicity via an additional gain-of-function mechanism, and that modification in this region of MARK4 may impact disease pathogenesis.
Networks of Splice Factor Regulation by Unproductive Splicing Coupled With Nonsense Mediated mRNA Decay
Authors: Desai Anna , Hu Zhiqiang , French Courtney E. , Lloyd James P. B. , Brenner Steven E.
Published: May 2020

Background

Nonsense mediated mRNA decay (NMD) is an RNA surveillance pathway that degrades aberrant transcripts harboring premature termination codons. This pathway, in conjunction with alternative splicing, regulates gene expression post-transcriptionally. Nearly all serine and arginine-rich (SR) proteins and many heterogeneous nuclear ribonucleoproteins (hnRNPs) produce isoforms that can be degraded by the NMD pathway. Many splicing factors have been reported to be regulated via alternative splicing coupled to NMD. However, it is still uncharacterized that to what extent NMD contributes to the regulation of splicing factors.

Results

Here, we characterized a regulatory network of splicing factors through alternative splicing coupled to NMD. Based upon an extensive literature search, we first assembled a network that encompasses the current knowledge of splice factors repressing or activating the expression of other splicing factors through alternative splicing coupled to NMD. This regulatory network is limited, including just a handful of well-studied splicing factors. To gain a more global and less biased overview, we examined the splicing factor-mRNA interactions from public crosslinking-immunoprecipitation (CLIP)-seq data, which provides information about protein–RNA interactions. A network view of these interactions reveals extensive binding among splicing regulators. We also found that splicing factors bind more frequently to transcripts of other splicing factors than to other genes. In addition, many splicing factors are targets of NMD, and might be regulated via alternative splicing coupled to NMD, which is demonstrated by the significant overlap between the experimental network and eCLIP-network. We found that hierarchy of the splicing-factor interaction network differs from the hierarchy observed for transcription factors.

Conclusion

The extensive interaction between splicing factors and transcripts of other splicing factors suggests that the potential regulation via alternative splicing coupled with NMD is widespread. The splicing factor regulation is fundamentally different from that of transcription factors.
Convalescent plasma treatment of severe COVID-19: A matched control study
Authors: Liu Sean T. H. , Lin Hung-Mo , Baine Ian , Wajnberg Ania , Gumprecht Jeffrey P. , Rahman Farah , Rodriguez Denise , Tandon Pranai , Bassily-Marcus Adel , Bander Jeffrey , Sanky Charles , Dupper Amy , Zheng Allen , Altman Deena R. , Chen Benjamin K. , Krammer Florian , Mendu Damodara Rao , Firpo-Betancourt Adolfo , Levin Matthew A. , Bagiella Emilia , Casadevall Arturo , Cordon-Cardo Carlos , Jhang Jeffrey S. , Arinsburg Suzanne A. , Reich David L. , Aberg Judith A. , Bouvier Nicole M.
Published: May 2020

Background
Since December 2019, Coronavirus Disease 2019 (COVID-19) has become a global pandemic, causing mass morbidity and mortality. Prior studies in other respiratory infections suggest that convalescent plasma transfusion may offer benefit to some patients. Here, the outcomes of thirty-nine hospitalized patients with severe to life-threatening COVID-19 who received convalescent plasma transfusion were compared against a cohort of retrospectively matched controls.
Methods
Plasma recipients were selected based on supplemental oxygen needs at the time of enrollment and the time elapsed since the onset of symptoms. Recipients were transfused with convalescent plasma from donors with a SARS-CoV-2 (severe acute respiratory disease coronavirus 2) anti-spike antibody titer of ≥1:320 dilution. Matched control patients were retrospectively identified within the electronic health record database. Supplemental oxygen requirements and survival were compared between plasma recipients and controls.
Results
Convalescent plasma recipients were more likely than control patients to remain the same or have improvements in their supplemental oxygen requirements by post-transfusion day 14, with an odds ratio of 0.86 (95% CI: 0.75~0.98; p=0.028). Plasma recipients also demonstrated improved survival, compared to control patients (log-rank test: p=0.039). In a covariates-adjusted Cox model, convalescent plasma transfusion improved survival for non-intubated patients (hazard ratio 0.19 (95% CI: 0.05 ~0.72); p=0.015), but not for intubated patients (1.24 (0.33~4.67); p=0.752).
Conclusions
Convalescent plasma transfusion is a potentially efficacious treatment option for patients hospitalized with COVID-19; however, these data suggest that non-intubated patients may benefit more than those requiring mechanical ventilation.
Quantifying Effects, Forecasting Releases, and Herd Immunity of the Covid-19 Epidemic in S. Paulo – Brazil
Authors: Celaschi S.
Published: May 2020

A simple and well known epidemiological deterministic model was selected to estimate the main results for the basic dynamics of the Covid-19 epidemic breakout in the city of São Paulo – Brazil. The methodology employed the SEIR Model to characterize the epidemics outbreak and future outcomes. A time-dependent incidence weight on the SEIR reproductive basic number accounts for local Mitigation Policies (MP). The insights gained from analysis of these successful interventions were used to quantify shifts and reductions on active cases, casualties, and estimatives on required medical facilities (ITU). This knowledge can be applied to other Brazilian areas. The analysis was applied to forecast the consequences of releasing the MP over specific periods of time. Herd Immunity (HI) analysis allowed estimating how far we are from reaching the HI threshold value, and the price to be paid.
Altered Capicua expression drives regional Purkinje neuron vulnerability through ion channel gene dysregulation in Spinocerebellar ataxia type 1
Authors: Chopra Ravi , Bushart David D , Cooper John P , Yellajoshyula Dhananjay , Morrison Logan M , Huang Haoran , Scoles Daniel R , Pulst Stefan M , Orr Harry T , Shakkottai Vikram G
Published: May 2020

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 corepressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, lentiviral overexpression of Cic in the nodular zone accelerated both aberrant Purkinje neuron spiking and neurodegeneration. These findings reinforce the central role for Cic in SCA1 cerebellar pathophysiology and suggest that only modest reductions in Cic are needed to have profound therapeutic impact in SCA1.