bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children
Authors: Dall’ Aglio Lorenza , Rijlaarsdam Jolien , Mulder Rosa H. , Neumann Alexander , Felix Janine F. , Kok Rianne , Bakermans-Kranenburg Marian J. , van Ijzendoorn Marinus H. , Tiemeier Henning , Cecil Charlotte A.M.
Published: December 2020

Background

Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment.

Methods

Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses.

Results

Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10−07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4.

Conclusions

These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.
Modulation of the functional connectome in major depressive disorder by ketamine therapy
Authors: Sahib Ashish K. , Loureiro Joana R. , Vasavada Megha , Anderson Cole , Kubicki Antoni , Wade Benjamin , Joshi Shantanu H. , Woods Roger P. , Congdon Eliza , Espinoza Randall , Narr Katherine L.
Published: December 2020

Background

Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.

Methods

Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.

Results

Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.

Conclusion

Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.
Making privilege palatable: Normative sustainability in chefs’ Instagram discourse
Authors: Mapes Gwynne , Ross Andrew S.
Published: December 2020

In this article we consider the discursive production of status as it relates to democratic ideals of environmental equity and community responsibility, orienting specifically to food discourse and ‘elite authenticity’ (Mapes 2018), as well as to recent work concerning normativity and class inequality (e.g. Thurlow 2016; Hall, Levon, & Milani 2019). Utilizing a dataset comprised of 150 Instagram posts, drawn from three different acclaimed chefs’ personal accounts, we examine the ways in which these celebrities emphasize local/sustainable food practices while simultaneously asserting their claims to privileged eating. Using multimodal critical discourse analysis, we document three general discursive tactics: (i) plant-based emphasis, (ii) local/community terroir, and (iii) realities of meat consumption. Ultimately, we establish how the chefs’ claims to egalitarian/environmental ideals paradoxically diminish their eliteness, while simultaneously elevating their social prestige, pointing to the often complicated and covert ways in which class inequality permeates the social landscape of contemporary eating. (Food discourse, elite authenticity, normativity, social class, locality/sustainability)*
MENDING FRAGMENTS: STONE VESSELS FROM FRANCHTHI AND OTHER GREEK NEOLITHIC SITES
Authors: Stroulia Anna
Published: December 2020

Stone vessels represent one of the rarest artifactual categories of Neolithic Greece. Only several dozen specimens (mostly fragmentary) have been recovered from 65 sites. These objects are also some of the least studied; with few exceptions, they are known only through superficial reports. Thus, their potential to shed light on social and economic aspects of Neolithic life remains unexploited. In this article, I address this problem in two ways. First, I focus on a specific stone vase assemblage: that from the well-known site of Franchthi in the north-eastern Peloponnese. This is one of the largest assemblages and is presented here in detail. Secondly, I use the Franchthi assemblage as a point of departure to attempt a synthesis of the available information on Greek Neolithic stone vases.
Human Rights and Theatre Practice in Northern Ireland: A Round-Table Discussion
Authors: FitzGerald Lisa , Urban Eva , Jenkinson Rosemary , Grant David , Maguire Tom
Published: December 2020

This round-table discussion, edited by Eva Urban and Lisa FitzGerald, took place on 5 July 2019 as part of the conference ‘New Romantics: Performing Ireland and Cosmopolitanism on the Anniversary of Human Rights’ organized by the editors at the Brian Friel Theatre, Queen’s University Belfast. Lisa FitzGerald is a theatre historian and ecocritic who completed postdoctoral fellowships at the Centre de Recherche Bretonne et Celtique (CRBC), Université Rennes 2 and the Rachel Carson Centre for Environment and Society, Ludwig Maximilian University of Munich. She is the author of Re-Place: Irish Theatre Environments (Peter Lang, 2017) and Digital Vision and the Ecological Aesthetic (forthcoming, Bloomsbury, 2020). Eva Urban is a Senior Research Fellow at the Senator George J. Mitchell Institute for Global Peace, Security, and Justice, Queen’s University Belfast, and an Associate Fellow of the Institute of Irish Studies, QUB. She is the author of Community Politics and the Peace Process in Contemporary Northern Irish Drama (Peter Lang, 2011) and La Philosophie des Lumières dans le Théâtre Breton: Tradition et Influences (Université de Rennes, 2019). Rosemary Jenkinson is a Belfast playwright and writer of five short story collections. Her plays include The Bonefire (Rough Magic), Planet Belfast (Tinderbox), White Star of the North, Here Comes the Night (Lyric), Lives in Translation (Kabosh Theatre Company), and Michelle and Arlene (Accidental Theatre). Her writing for radio includes Castlereagh to Kandahar (BBC Radio 3) and The Blackthorn Tree (BBC Radio 4). She has received a Major Individual Artist Award from the Arts Council of Northern Ireland to write a memoir. Tom Maguire is Head of the School of Arts and Humanities at Ulster University and has published widely on Irish and Scottish theatre and in the areas of Theatre for Young Audiences and Storytelling Performance. His heritage research projects include the collection Heritage after Conflict: Northern Ireland (Routledge, 2018, co-edited with Elizabeth Crooke). David Grant is a former Programme Director of the Dublin Theatre Festival and was Artistic Director of the Lyric Theatre in Belfast. He has worked extensively as a theatre director throughout Ireland and is co-investigator of an AHRC-funded research project into Arts for Reconciliation. He lectures in drama at Queen’s University Belfast.
An empirical analysis on the operational profile of liquefied natural gas carriers with steam propulsion plants
Authors: González Gutiérrez Carlos , Suárez de la Fuente Santiago , Bonello Jean-Marc , Bucknall Richard
Published: December 2020

Liquefied natural gas (LNG) offers negligible NOx and SOx emissions as well as reductions in CO2 compared with other liquid hydrocarbons. LNG is a significant player in the global energy mix, with a projection of 40% increase in demand for the next two decades. It is anticipated that the expected rise in demand will cause the fleet of LNG carriers (LNGC) to expand. This work concentrates on steam-powered LNGC, which accounted for 47% of the LNGC fleet in 2018. It performs an empirical analysis of continuous monitoring data that provide high levels of accuracy and transparency. The analysis is done on data collected from 40 LNGCs for over a year to estimate the fleet's operational profile, fuel mix and energy performance. The findings of this work are relevant for bottom-up analysis and simulation models that depend on technical assumptions, but also for emission studies such as the upcoming Fourth International Maritime Organization Greenhouse Gases study.
Large complete minors in random subgraphs
Authors: Erde Joshua , Kang Mihyun , Krivelevich Michael
Published: December 2020

Let G be a graph of minimum degree at least k and let Gp be the random subgraph of G obtained by keeping each edge independently with probability p. We are interested in the size of the largest complete minor that Gp contains when p = (1 + ε)/k with ε > 0. We show that with high probability Gp contains a complete minor of order
$\tilde{\Omega}(\sqrt{k})$
, where the ~ hides a polylogarithmic factor. Furthermore, in the case where the order of G is also bounded above by a constant multiple of k, we show that this polylogarithmic term can be removed, giving a tight bound.
Nuubo ™ improving the diagnosis of pediatric arrhythmias
Authors: Palacios Argueta Jorge R. , Punti Sala Jordi
Published: December 2020

We report an 11-year-old male with intermittent palpitations episodes, and no other pathological findings were found. With the standard Holter electrocardiogram, there is only the option of 24 to 72 hours monitoring of the patient. A Holter Nuubo ™ Vest was placed for 33 days and a supraventricular tachycardia was found.
A single-dose, comparative bioavailability study comparing amphetamine extended-release oral suspension with extended-release mixed amphetamine salts capsules
Authors: Pardo Antonio , Bouhajib Mohammed , King Thomas R. , Rafla Eman , Kando Judith C.
Published: December 2020

Background

To evaluate the relative bioavailability of a single dose of amphetamine extended-release oral suspension (AMPH EROS) compared with a single dose of extended-release mixed amphetamine salts (ER MAS) in healthy, fasted adult subjects.

Methods

The study population consisted of healthy adult volunteers. The study drug used in this study was 7.5 mL of 2.5 mg/mL AMPH EROS equivalent to 18.8 mg of amphetamine base administered after an overnight fast of at least 10 hours. AMPH EROS comprises a 3.2:1 enantiomeric ratio of d-amphetamine to l-amphetamine. The reference product was one 30 mg ER MAS capsule (equivalent to 18.8 mg of amphetamine base). Relative bioavailability between the products was determined by a statistical comparison of the area under the curve and maximum concentration (Cmax) for d-amphetamine and l-amphetamine. PK (PK) blood samples were collected prior to dosing (0-hour) and at 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48, and 60 hours after drug administration, totaling 20 samples in each period.

Results

The mean subject age was 35.0 (standard deviation ±8) years, and the overall study population comprised 19 (63.3%) males and 11 (36.7%) females. The contrasts for geometric mean ratios for all assessed PK parameters (for both l- and d-amphetamine) between the test article AMPH EROS and reference product ER MAS fell within the prescribed 80% to 125% limits.

Conclusions

The overall PK profile of single-dose AMPH EROS 7.5 mL was found to be comparable with a single dose of oral ER MAS 30 mg.
Generations of Veterans: Socioeconomic Attainment from World War II to the Contemporary Era
Authors: MacLean Alair , Kleykamp Meredith
Published: December 2020

Scholars have long examined how generations or, more technically, cohorts produce social change. According to theory, people’s lives are shaped by the years in which they were born because they experience, along with their peers, particular historical events at the same points in the life course. Despite the importance of history, however, many scholars have evaluated cohorts not defined by clear start and end dates, but rather by arbitrary cut points, such as five-year intervals. In contrast, this article uses defined changes in military service in the United States stemming from shifts between war and peace, and from draft to volunteer service to assess how cohorts have contributed to change in socioeconomic attainment. It uses the Current Population Survey from 1971 to 2017, which has not previously been used to evaluate how veteran status may have produced shifting outcomes across cohorts. It finds evidence that cohorts had different average income overall and between groups, with veterans earning more money than nonveterans who were eligible to serve during the draft era before the Vietnam War. These gaps are partially explained by racial and educational differences. The findings provide a model for analyses of changes in the relative status of other groups, as well as information about how the role of military service in social mobility changed historically.
Relationship between weedy rice (Oryza sativa) infestation level and agronomic practices in Italian rice farms
Authors: Ferrero Aldo , Fogliatto Silvia , Barberi Andrea , Vidotto Francesco
Published: December 2020

Weedy rice (Oryza sativaL.) is a troublesome rice (Oryza sativaL.) weed in Italy and in many other rice areas. The objective of this study was to correlate theO. sativainfestation level in northern Italy, the main European rice-growing area, with agricultural practices adopted by farmers by using data obtained from a farmer survey. In 2018 to 2019, a survey was carried out on 98 rice farms chosen to ensure different sizes, different cultivation practices, and variable degrees ofO. sativainfestation. The following information was acquired: farm size; area cultivated with Clearfield® varieties; the most-adopted agronomic practices (type of tillage, crop rotation, type of sowing, water management, origin of seeds, adoption of stale seedbed, use of imazamox, presence ofO. sativaresistant to imazamox); and level ofO. sativainfestation: low (≤5 plants m−2), medium (>5 to 20 plants m−2), and high (>20 plants m−2). The data were analyzed through descriptive statistics and ordinal logistic regression to determine which agronomic practices influenced the level ofO. sativainfestation. Farm clustering was also determined through two-step cluster analysis. Rice was cultivated as a monocrop and mainly sown in water, using purchased seeds, in plowed fields. More than half of the farms used the stale seedbed practice, and 63% adopted Clearfield® varieties, while about 45% of the farms reported imazamox-resistantO. sativa. The ordinal logistic regression underlined that use of a stale seedbed was correlated with the infestation level ofO. sativa, and the two-step cluster analysis showed that the farms were mainly grouped based on the use of this technique. Most of the farms that used a stale seedbed had higherO. sativainfestation than those that did not use it, meaning that this practice was mainly applied in zones whereO. sativainfestations were more serious.
Initiation and Development of a Squall Line Crossing Hangzhou Bay
Authors: Zhang Lina , Sun Juanzhen , Ying Zhuming , Xiao Xian
Published: December 2020

The purpose of this study is to examine the influences of mesoscale thermal and dynamical processes near land‐sea boundary on the formation and development of a squall line across the Hangzhou Bay (HZB) of East China Sea that resulted in strong surface winds and heavy rainfall. High‐resolution spatiotemporal analyses obtained from Variational Doppler Radar Analysis System via the assimilation of radar and surface observations are used for this study. We focus on meso‐scale factors leading to the initiation of the squall line and the development of a bow echo that caused damaging winds and heavy rainfall. It was found that a local‐scale sea breeze associated with the distinct coastline curvature of the HZB was pivotal to the formation of the squall line. The convective initiation occurred near the HZB's western coastline when the leading edge of the northeasterly sea breeze was met by a westerly outflow from a previous precipitation system to the west of HZB. After the formation of the squall line, a rear inflow jet descending from mid‐level to surface contributed to the formation of the bow echo and resulted in damaging local winds.
Toward a Better Surface Radiation Budget Analysis Over Sea Ice in the High Arctic Ocean: A Comparative Study Between Satellite, Reanalysis, and local‐scale Observations
Authors: Di Biagio C. , Pelon J. , Blanchard Y. , Loyer L. , Hudson S. R. , Walden V. P. , Raut J. ‐C. , Kato S. , Mariage V. , Granskog M. A.
Published: December 2020

Reanalysis datasets from atmospheric models and satellite products are often used for Arctic surface shortwave (SW) and longwave (LW) radiative budget analyses, but they suffer from limitations and require validation against local‐scale observations. These are rare in the high Arctic, especially for longer periods that include seasonal transitions. In this study, radiation and meteorological observations acquired during the Norwegian Young Sea Ice Cruise (N‐ICE2015) campaign over sea ice north of Svalbard (80–83°N, 5–25°E) from January–June 2015, cloud lidar observations from the Ice‐Atmosphere‐Ocean Observing System and the Cloud and Aerosol Lidar with Orthogonal Polarization are compared to daily and monthly satellite retrievals from the Clouds and the Earth's Radiant Energy System (CERES) and ERA‐Interim and ERA5 reanalysis. Results indicate that surface temperature is a significant driver for winter LW radiation biases in both satellite and reanalysis data, along with cloud optical depth in CERES. In May, the SW and LW downwelling irradiances are close to observations and cloud properties are well captured (except for ERA‐Interim), while SW upward irradiances are biased low due to surface albedo biases in all datasets. Net SW and LW radiation biases are comparable (∼20–30 Wm−2) but opposite in sign for ERA‐Interim and CERES in May, which allows for error compensation. Biases reduce to ±10 Wm−2 in ERA5. In June downward LW remains biased low (8–10 Wm−2) in all datasets suggesting unsettled cloud representation issues. Surface albedo always differs by more than 0.1 between datasets, leading to significant SW and total flux differences.
Evolution of Pseudomonas aeruginosa toward higher fitness under standard laboratory conditions
Authors: Grekov Igor , Thöming Janne Gesine , Kordes Adrian , Häussler Susanne
Published: December 2020

Identifying genetic factors that contribute to the evolution of adaptive phenotypes in pathogenic bacteria is key to understanding the establishment of infectious diseases. In this study, we performed mutation accumulation experiments to record the frequency of mutations and their effect on fitness in hypermutator strains of the environmental bacterium Pseudomonas aeruginosa in comparison to the host-niche-adapted Salmonella enterica. We demonstrate that P. aeruginosa, but not S. enterica, hypermutators evolve toward higher fitness under planktonic conditions. Adaptation to increased growth performance was accompanied by a reversible perturbing of the local genetic context of membrane and cell wall biosynthesis genes. Furthermore, we observed a fine-tuning of complex regulatory circuits involving multiple di-guanylate modulating enzymes that regulate the transition between fast growing planktonic and sessile biofilm-associated lifestyles. The redundancy and local specificity of the di-guanylate signaling pathways seem to allow a convergent shift toward increased growth performance across niche-adapted clonal P. aeruginosa lineages, which is accompanied by a pronounced heterogeneity of their motility, virulence, and biofilm phenotypes.
Time-series transcriptomics from cold, oxic subseafloor crustal fluids reveals a motile, mixotrophic microbial community
Authors: Seyler Lauren M , Trembath-Reichert Elizabeth , Tully Benjamin J , Huber Julie A
Published: December 2020

The oceanic crustal aquifer is one of the largest habitable volumes on Earth, and it harbors a reservoir of microbial life that influences global-scale biogeochemical cycles. Here, we use time series metagenomic and metatranscriptomic data from a low-temperature, ridge flank environment representative of the majority of global hydrothermal fluid circulation in the ocean to reconstruct microbial metabolic potential, transcript abundance, and community dynamics. We also present metagenome-assembled genomes from recently collected fluids that are furthest removed from drilling disturbances. Our results suggest that the microbial community in the North Pond aquifer plays an important role in the oxidation of organic carbon within the crust. This community is motile and metabolically flexible, with the ability to use both autotrophic and organotrophic pathways, as well as function under low oxygen conditions by using alternative electron acceptors such as nitrate and thiosulfate. Anaerobic processes are most abundant in subseafloor horizons deepest in the aquifer, furthest from connectivity with the deep ocean, and there was little overlap in the active microbial populations between sampling horizons. This work highlights the heterogeneity of microbial life in the subseafloor aquifer and provides new insights into biogeochemical cycling in ocean crust.
Primidone blocks RIPK1-driven cell death and inflammation
Authors: Riebeling Theresa , Jamal Kunzah , Wilson Rebecca , Kolbrink Benedikt , von Samson-Himmelstjerna Friedrich Alexander , Moerke Caroline , Ramos Garcia Laura , Dahlke Eileen , Michels Friederike , Lühder Fred , Schunk Domagoj , Doldi Philipp , Tyczynski Bartosz , Kribben Andreas , Flüh Charlotte , Theilig Franziska , Kunzendorf Ulrich , Meier Pascal , Krautwald Stefan
Published: December 2020

The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.
A novel satiety sensor detects circulating glucose and suppresses food consumption via insulin-producing cells in Drosophila
Authors: Qi Wei , Wang Gaohang , Wang Liming
Published: December 2020

Sensing satiety is a crucial survival skill for all animal species including human. Despite the discovery of numerous neuromodulators that regulate food intake in Drosophila, the mechanism of satiety sensing remains largely elusive. Here, we investigated how neuropeptidergic circuitry conveyed satiety state to influence flies’ food consumption. Drosophila tackykinin (DTK) and its receptor TAKR99D were identified in an RNAi screening as feeding suppressors. Two pairs of DTK+ neurons in the fly brain could be activated by elevated D-glucose in the hemolymph and imposed a suppressive effect on feeding. These DTK+ neurons formed a two-synapse circuitry targeting insulin-producing cells, a well-known feeding suppressor, via TAKR99D+ neurons, and this circuitry could be rapidly activated during food ingestion and cease feeding. Taken together, we identified a novel satiety sensor in the fly brain that could detect specific circulating nutrients and in turn modulate feeding, shedding light on the neural regulation of energy homeostasis.
State-level tracking of COVID-19 in the United States
Authors: Unwin H. Juliette T. , Mishra Swapnil , Bradley Valerie C. , Gandy Axel , Mellan Thomas A. , Coupland Helen , Ish-Horowicz Jonathan , Vollmer Michaela A. C. , Whittaker Charles , Filippi Sarah L. , Xi Xiaoyue , Monod Mélodie , Ratmann Oliver , Hutchinson Michael , Valka Fabian , Zhu Harrison , Hawryluk Iwona , Milton Philip , Ainslie Kylie E. C. , Baguelin Marc , Boonyasiri Adhiratha , Brazeau Nick F. , Cattarino Lorenzo , Cucunuba Zulma , Cuomo-Dannenburg Gina , Dorigatti Ilaria , Eales Oliver D. , Eaton Jeffrey W. , van Elsland Sabine L. , FitzJohn Richard G. , Gaythorpe Katy A. M. , Green William , Hinsley Wes , Jeffrey Benjamin , Knock Edward , Laydon Daniel J. , Lees John , Nedjati-Gilani Gemma , Nouvellet Pierre , Okell Lucy , Parag Kris V. , Siveroni Igor , Thompson Hayley A. , Walker Patrick , Walters Caroline E. , Watson Oliver J. , Whittles Lilith K. , Ghani Azra C. , Ferguson Neil M. , Riley Steven , Donnelly Christl A. , Bhatt Samir , Flaxman Seth
Published: December 2020

As of 1st June 2020, the US Centres for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. We estimate that Rt was only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%–4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.
Modelling genetic mosaicism of neurodevelopmental disorders in vivo by a Cre-amplifying fluorescent reporter
Authors: Trovato Francesco , Parra Riccardo , Pracucci Enrico , Landi Silvia , Cozzolino Olga , Nardi Gabriele , Cruciani Federica , Pillai Vinoshene , Mosti Laura , Cwetsch Andrzej W. , Cancedda Laura , Gritti Laura , Sala Carlo , Verpelli Chiara , Maset Andrea , Lodovichi Claudia , Ratto Gian Michele
Published: December 2020

Genetic mosaicism, a condition in which an organ includes cells with different genotypes, is frequently present in monogenic diseases of the central nervous system caused by the random inactivation of the X-chromosome, in the case of X-linked pathologies, or by somatic mutations affecting a subset of neurons. The comprehension of the mechanisms of these diseases and of the cell-autonomous effects of specific mutations requires the generation of sparse mosaic models, in which the genotype of each neuron is univocally identified by the expression of a fluorescent protein in vivo. Here, we show a dual-color reporter system that, when expressed in a floxed mouse line for a target gene, leads to the creation of mosaics with tunable degree. We demonstrate the generation of a knockout mosaic of the autism/epilepsy related gene PTEN in which the genotype of each neuron is reliably identified, and the neuronal phenotype is accurately characterized by two-photon microscopy.
TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains
Authors: Guerrero-Martínez Jose A. , Ceballos-Chávez María , Koehler Florian , Peiró Sandra , Reyes Jose C.
Published: December 2020

The Transforming Growth Factor-β (TGFβ) signaling pathway controls transcription by regulating enhancer activity. How TGFβ-regulated enhancers are selected and what chromatin changes are associated with TGFβ-dependent enhancers regulation are still unclear. Here we report that TGFβ treatment triggers fast and widespread increase in chromatin accessibility in about 80% of the enhancers of normal mouse mammary epithelial-gland cells, irrespective of whether they are activated, repressed or not regulated by TGFβ. This enhancer opening depends on both the canonical and non-canonical TGFβ pathways. Most TGFβ-regulated genes are located around enhancers regulated in the same way, often creating domains of several co-regulated genes that we term TGFβ regulatory domains (TRD). CRISPR-mediated inactivation of enhancers within TRDs impairs TGFβ-dependent regulation of all co-regulated genes, demonstrating that enhancer targeting is more promiscuous than previously anticipated. The area of TRD influence is restricted by topologically associating domains (TADs) borders, causing a bias towards co-regulation within TADs.
Excess forest mortality is consistently linked to drought across Europe
Authors: Senf Cornelius , Buras Allan , Zang Christian S. , Rammig Anja , Seidl Rupert
Published: December 2020

Pulses of tree mortality caused by drought have been reported recently in forests around the globe, but large-scale quantitative evidence is lacking for Europe. Analyzing high-resolution annual satellite-based canopy mortality maps from 1987 to 2016 we here show that excess forest mortality (i.e., canopy mortality exceeding the long-term mortality trend) is significantly related to drought across continental Europe. The relationship between water availability and mortality showed threshold behavior, with excess mortality increasing steeply when the integrated climatic water balance from March to July fell below −1.6 standard deviations of its long-term average. For −3.0 standard deviations the probability of excess canopy mortality was 91.6% (83.8–97.5%). Overall, drought caused approximately 500,000 ha of excess forest mortality between 1987 and 2016 in Europe. We here provide evidence that drought is an important driver of tree mortality at the continental scale, and suggest that a future increase in drought could trigger widespread tree mortality in Europe.
Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts
Authors: Cardozo Karina Helena Morais , Lebkuchen Adriana , Okai Guilherme Gonçalves , Schuch Rodrigo Andrade , Viana Luciana Godoy , Olive Aline Nogueira , Lazari Carolina dos Santos , Fraga Ana Maria , Granato Celso Francisco Hernandes , Pintão Maria Carolina Tostes , Carvalho Valdemir Melechco
Published: December 2020

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pressing public health systems around the world, and large population testing is a key step to control this pandemic disease. Here, we develop a high-throughput targeted proteomics assay to detect SARS-CoV-2 nucleoprotein peptides directly from nasopharyngeal and oropharyngeal swabs. A modified magnetic particle-based proteomics approach implemented on a robotic liquid handler enables fully automated preparation of 96 samples within 4 hours. A TFC-MS system allows multiplexed analysis of 4 samples within 10 min, enabling the processing of more than 500 samples per day. We validate this method qualitatively (Tier 3) and quantitatively (Tier 1) using 985 specimens previously analyzed by real-time RT-PCR, and detect up to 84% of the positive cases with up to 97% specificity. The presented strategy has high sample stability and should be considered as an option for SARS-CoV-2 testing in large populations.
DNA-PK deficiency potentiates cGAS-mediated antiviral innate immunity
Authors: Sun Xiaona , Liu Ting , Zhao Jun , Xia Hansong , Xie Jun , Guo Yu , Zhong Li , Li Mi , Yang Qing , Peng Cheng , Rouvet Isabelle , Belot Alexandre , Shu Hong-Bing , Feng Pinghui , Zhang Junjie
Published: December 2020

Upon sensing cytosolic DNA, the enzyme cGAS induces innate immune responses that underpin anti-microbial defenses and certain autoimmune diseases. Missense mutations of PRKDC encoding the DNA-dependent protein kinase (DNA-PK) catalytic subunit (DNA-PKcs) are associated with autoimmune diseases, yet how DNA-PK deficiency leads to increased immune responses remains poorly understood. In this study, we report that DNA-PK phosphorylates cGAS and suppresses its enzymatic activity. DNA-PK deficiency reduces cGAS phosphorylation and promotes antiviral innate immune responses, thereby potently restricting viral replication. Moreover, cells isolated from DNA-PKcs-deficient mice or patients carrying PRKDC missense mutations exhibit an inflammatory gene expression signature. This study provides a rational explanation for the autoimmunity of patients with missense mutations of PRKDC, and suggests that cGAS-mediated immune signaling is a potential target for therapeutic interventions.
Adaptive modulation of brain hemodynamics across stereotyped running episodes
Authors: Bergel Antoine , Tiran Elodie , Deffieux Thomas , Demené Charlie , Tanter Mickaël , Cohen Ivan
Published: December 2020

During locomotion, theta and gamma rhythms are essential to ensure timely communication between brain structures. However, their metabolic cost and contribution to neuroimaging signals remain elusive. To finely characterize neurovascular interactions during locomotion, we simultaneously recorded mesoscale brain hemodynamics using functional ultrasound (fUS) and local field potentials (LFP) in numerous brain structures of freely-running overtrained rats. Locomotion events were reliably followed by a surge in blood flow in a sequence involving the retrosplenial cortex, dorsal thalamus, dentate gyrus and CA regions successively, with delays ranging from 0.8 to 1.6 seconds after peak speed. Conversely, primary motor cortex was suppressed and subsequently recruited during reward uptake. Surprisingly, brain hemodynamics were strongly modulated across trials within the same recording session; cortical blood flow sharply decreased after 10–20 runs, while hippocampal responses strongly and linearly increased, particularly in the CA regions. This effect occurred while running speed and theta activity remained constant and was accompanied by an increase in the power of hippocampal, but not cortical, high-frequency oscillations (100–150 Hz). Our findings reveal distinct vascular subnetworks modulated across fast and slow timescales and suggest strong hemodynamic adaptation, despite the repetition of a stereotyped behavior.
NLRP3 inflammasome deficiency attenuates metabolic disturbances involving alterations in the gut microbial profile in mice exposed to high fat diet
Authors: Sokolova Marina , Yang Kuan , Hansen Simen H. , Louwe Mieke C. , Kummen Martin , Hov Johannes E. R. , Sjaastad Ivar , Berge Rolf K. , Halvorsen Bente , Aukrust Pål , Yndestad Arne , Ranheim Trine
Published: December 2020

Obesity-related diseases (e.g. type 2 diabetes mellitus and cardiovascular disorders) represent an increasing health problem worldwide. NLRP3 inflammasome activation may underlie obesity-induced inflammation and insulin resistance, and NLRP3 deficient mice exposed to high fat diet (HFD) appear to be protected from left ventricle (LV) concentric remodeling. Herein, we investigated if these beneficial effects were associated with alterations in plasma metabolites, using metabolomic and lipidomic analysis, and gut microbiota composition, using 16S rRNA sequencing of cecum content, comparing NLRP3 deficient and wild type (WT) mice on HFD and control diet. Obese NLRP3 deficient mice had lower systemic ceramide levels, potentially resulting attenuating inflammation, altered hepatic expression of fatty acids (FA) with lower mono-saturated FA and higher polyunsaturated FA levels, potentially counteracting development of liver steatosis, downregulated myocardial energy metabolism as assessed by proteomic analyses of LV heart tissue, and different levels of bile acids as compared with WT mice. These changes were accompanied by an altered composition of gut microbiota associated with decreased systemic levels of tri-methylamine-N-oxide and lipopolysaccharide, potentially inducing attenuating systemic inflammation and beneficial effects on lipid metabolism. Our findings support a role of NLRP3 inflammasome in the interface between metabolic and inflammatory stress, involving an altered gut microbiota composition.
Evaluation of spore inoculum and confirmation of pathway genetic blueprint of T13αH and DBAT from a Taxol-producing endophytic fungus
Authors: Chakravarthi Balabhadrapatruni V. S. K. , Singh Satpal , Kamalraj Subban , Gupta Vijai Kumar , Jayabaskaran Chelliah
Published: December 2020

Taxol (paclitaxel), a plant-derived anticancer drug, has been among the most successful anticancer drugs of natural origin. Endophytic fungi have been proposed as a prominent alternative source for Taxol and its intermediate Baccatin III, however the very low yields remain a hinderance to their commercial utilization. Significant research efforts towards this end are underway globally. Here, we report the results on our earlier reported Taxol-producing endophytic fungus, Fusarium solani from the standpoint of spores as seed inoculum and media selection for enhanced Taxol and baccatin III yields. Spores produced on M1D medium with 94.76% viability were used for further media optimization for Taxol and Baccatin III production in five different liquid media under static and shaker condition at different cultivation days. Taxol and Baccatin III when quantified through competitive inhibition enzyme immunoassay (CIEIA), showed maximum production at 136.3 µg L−1 and 128.3 µg L−1, respectively in the modified flask basal broth (MFBB) under shaking condition. Further, two important genes of this pathway, namely taxane 13α-hydroxylase (T13αH) and 10-deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) have been identified in this fungus. These findings are hoped to assist in further manipulation and metabolic engineering of the parent F. solani strain towards the enhanced production of Taxol and baccatin III.
Time dynamics of COVID-19
Authors: Carroll Cody , Bhattacharjee Satarupa , Chen Yaqing , Dubey Paromita , Fan Jianing , Gajardo Álvaro , Zhou Xiner , Müller Hans-Georg , Wang Jane-Ling
Published: December 2020

We apply tools from functional data analysis to model cumulative trajectories of COVID-19 cases across countries, establishing a framework for quantifying and comparing cases and deaths across countries longitudinally. It emerges that a country’s trajectory during an initial first month “priming period” largely determines how the situation unfolds subsequently. We also propose a method for forecasting case counts, which takes advantage of the common, latent information in the entire sample of curves, instead of just the history of a single country. Our framework facilitates to quantify the effects of demographic covariates and social mobility on doubling rates and case fatality rates through a time-varying regression model. Decreased workplace mobility is associated with lower doubling rates with a roughly 2 week delay, and case fatality rates exhibit a positive feedback pattern.
Exploring the effect of UV-C radiation on earthworm and understanding its genomic integrity in the context of H2AX expression
Authors: Subbiahanadar Chelladurai Karthikeyan , Selvan Christyraj Jackson Durairaj , Azhagesan Ananthaselvam , Paulraj Vennila Devi , Jothimani Muralidharan , Yesudhason Beryl Vedha , Chellathurai Vasantha Niranjan , Ganesan Mijithra , Rajagopalan Kamarajan , Venkatachalam Saravanakumar , Benedict Johnson , John Samuel Jemima Kamalapriya , Selvan Christyraj Johnson Retnaraj Samuel
Published: December 2020

Maintaining genomic stability is inevitable for organism survival and it is challenged by mutagenic agents, which include ultraviolet (UV) radiation. Whenever DNA damage occurs, it is sensed by DNA-repairing proteins and thereby performing the DNA-repair mechanism. Specifically, in response to DNA damage, H2AX is a key protein involved in initiating the DNA-repair processes. In this present study, we investigate the effect of UV-C on earthworm, Perionyx excavatus and analyzed the DNA-damage response. Briefly, we expose the worms to different doses of UV-C and find that worms are highly sensitive to UV-C. As a primary response, earthworms produce coelomic fluid followed by autotomy. However, tissue inflammation followed by death is observed when we expose worm to increased doses of UV-C. In particular, UV-C promotes damages in skin layers and on the contrary, it mediates the chloragogen and epithelial outgrowth in intestinal tissues. Furthermore, UV-C promotes DNA damages followed by upregulation of H2AX on dose-dependent manner. Our finding confirms DNA damage caused by UV-C is directly proportional to the expression of H2AX. In short, we conclude that H2AX is present in the invertebrate earthworm, which plays an evolutionarily conserved role in DNA damage event as like that in higher animals.
Insights into the chemistry of the amphibactin–metal (M3+) interaction and its role in antibiotic resistance
Authors: Kaipanchery Vidya , Sharma Anamika , Albericio Fernando , de la Torre Beatriz G.
Published: December 2020

We have studied the diversity and specificity of interactions of amphibactin produced by Vibrio genus bacterium (Vibriosp. HC0601C5) with iron and various metal ions in + 3 oxidation state in an octahedral (Oh) environment. To survive in the iron-deficient environment of their host, pathogenic bacteria have devised various efficient iron acquisition strategies. One such strategy involves the production of low molecular weight peptides called siderophores, which have a strong affinity and specificity to chelate Fe3+and can thus facilitate uptake of this metal in order to ensure iron requirements. The Fe uptake by amphibactin and the release of iron inside the cell have been studied. Comparison of the interaction of different transition metal ions (M3+) with amphibactin has been studied and it reveals that Co and Ga form stable complexes with this siderophore. The competition of Co and Ga with Fe impedes iron uptake by bacteria, thereby preventing infection.
Seroprevalence of hepatitis B virus and hepatitis C virus infection among Malaysian population
Authors: Muhamad Nor Asiah , Ab.Ghani Rimah Melati , Abdul Mutalip Mohd Hatta , Muhammad Eida Nurhadzira , Mohamad Haris Hasmah , Mohd Zain Rozainanee , Abdullah Noraidatulakma , Muhammad Azami Nor Azila , Abd Jalal Nazihah , Ismail Norliza , Mhd Yusuf Nurul Ain , Othman Raihannah , Kamalul Arifin Azwa Shawani , Abdullah Mohd Shaharom , Kamaruddin Mohd Arman , Abu Hassan Muhammad Radzi , Aris Tahir , Jamal Rahman
Published: December 2020

Malaysia is a country with an intermediate endemicity for hepatitis B. As the country moves toward hepatitis B and C elimination, population-based estimates are necessary to understand the burden of hepatitis B and C for evidence-based policy-making. Hence, this study aims to estimate the prevalence of hepatitis B and C in Malaysia. A total of 1458 participants were randomly selected from The Malaysian Cohort (TMC) aged 35 to 70 years between 2006 and 2012. All blood samples were tested for hepatitis B and C markers including hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), antibodies against hepatitis C virus (anti-HCV). Those reactive for hepatitis C were further tested for HCV RNA genotyping. The sociodemographic characteristics and comorbidities were used to evaluate their associated risk factors. Descriptive analysis and multivariable analysis were done using Stata 14. From the samples tested, 4% were positive for HBsAg (95% CI 2.7–4.7), 20% were positive for anti-HBc (95% CI 17.6–21.9) and 0.3% were positive for anti-HCV (95% CI 0.1–0.7). Two of the five participants who were reactive for anti-HCV had the HCV genotype 1a and 3a. The seroprevalence of HBV and HCV infection in Malaysia is low and intermediate, respectively. This population-based study could facilitate the planning and evaluation of the hepatitis B and C control program in Malaysia.
Exploring the genetic variability and diversity of pearl millet core collection germplasm for grain nutritional traits improvement
Authors: Govindaraj Mahalingam , Rai Kedar N. , Kanatti Anand , Upadhyaya Hari D. , Shivade Harshad , Rao Aluri S.
Published: December 2020

Improving essential nutrient content in staple food crops through biofortification breeding can overcome the micronutrient malnutrition problem. Genetic improvement depends on the availability of genetic variability in the primary gene pool. This study was aimed to ascertain the magnitude of variability in a core germplasm collection of diverse origin and predict pearl millet biofortification prospects for essential micronutrients. Germplasm accessions were evaluated in field trials at ICRISAT, India. The accessions differed significantly for all micronutrients with over two-fold variation for Fe (34–90 mg kg−1), Zn (30–74 mg kg−1), and Ca (85–249 mg kg−1). High estimates of heritability (> 0.81) were observed for Fe, Zn, Ca, P, Mo, and Mg. The lower magnitude of genotype (G) × environment (E) interaction observed for most of the traits implies strong genetic control for grain nutrients. The top-10 accessions for each nutrient and 15 accessions, from five countries for multiple nutrients were identified. For Fe and Zn, 39 accessions, including 15 with multiple nutrients, exceeded the Indian cultivars and 17 of them exceeded the biofortification breeding target for Fe (72 mg kg−1). These 39 accessions were grouped into 5 clusters. Most of these nutrients were positively and significantly associated among themselves and with days to 50% flowering and 1000-grain weight (TGW) indicating the possibility of their simultaneous improvement in superior agronomic background. The identified core collection accessions rich in specific and multiple-nutrients would be useful as the key genetic resources for developing biofortified and agronomically superior cultivars.