bluuebunny/crossref_metadata_2025 huggingface dataset:
The EMU and the European Social Dimension
Authors: Costamagna Francesco
Published: March 2021

The Economic Monetary Union (EMU) has been famously portrayed as a ‘metaphor for the European Union’, involving high stakes for the integration process as a whole. Since its origins, the creation of the EMU was an eminently political project, with a direct bearing on the prospects of the European Union (EU) as a polity, its social model, and its constitutional identity. Yet, the main political aspects of the project were mostly discarded in the process that led to the establishment of the EMU’s institutional structure and its substantive rules. The creation of the common currency was not accompanied by the establishment of supranational institutions with a strong political mandate to accommodate conflicting interests, while the exercise of political autonomy at national level has been increasingly seen as a potential danger for the stability of the whole edifice. The crisis and the ensuing reform of the European economic governance consolidated the technocratic character of the EMU architecture and hardened its grip on national political processes.
The European Central Bank
Authors: Ioannidis Michael
Published: March 2021

The European Central Bank (ECB) is the only central bank governed by supranational constitutional law. As such, it is not only the most important institution of the Economic and Monetary Union (EMU), but it also marks a new stage in the history of central banking in general. Historically, the tasks and functions of the ECB have reflected the different stages of development of the EMU. The basic principles governing its function were set out in Maastricht, reflecting the interests and ideas about Europe’s economic constitution prevailing at that time. The sovereign debt crisis that hit Europe in 2010 was the second defining moment for the ECB after Maastricht. It posited the ECB–like the rest of the EMU–to challenges that some of the drafters of the Maastricht Treaty had not fully anticipated. These new challenges led to the adoption of novel instruments and the further clarification of fundamental rules and principles. Most important of these developments was the entrustment of the ECB with a new task, banking supervision, and the adoption of unconventional measures, which proved necessary to fulfil its monetary-policy mandate. Ultimately, not only did the ECB withstand the crisis but it emerged as a protagonist in securing the unity and integrity of the EMU.
European Monetary Union and the Courts
Authors: Sarmiento Daniel , Hartmann Moritz
Published: March 2021

European Monetary Union (EMU) is one of the cornerstones of the post-Maastricht European project. Inasmuch as the Maastricht Treaty adopted a binding horizon for the creation of a unitary currency comprising the vast majority of the Member States, the Treaty provided for the blueprint, as of 1992, to initiate, in the area of monetary policy, the still lasting process of the European project’s political integration. As a result, the first pillars of a European economic policy followed, creating an edifice under the name of EMU that is still in the making, but has nevertheless developed, at this point, into a crucial pillar of the European Union’s (EU) constitutional charter.
Prudential supervisory tasks (Article 127(6) TFEU, monetary policy vs prudential supervision): ‘Kissing awake the Sleeping Beauty provision’
Authors: Lastra Rosa M , Psaroudakis Georgios
Published: March 2021

This chapter attempts to describe the interplay between Economic Monetary Union (EMU) and Banking Union and the central function of the European Central Bank (ECB) in both areas. It offers a historical background to the development of European Union (EU) level prudential supervision on the basis of the Treaty on the Functioning of the European Union (TFEU) and examines issues at the intersection between monetary policy and banking supervision. Relatedly, financial stability is discussed as a public good that informs both areas of ECB activity. The chapter further examines difficult organizational choices, arising from the development of a Banking Union not foreseen in the Maastricht Treaty (which only included an ‘enabling clause’): Should the same institution (ie, the ECB) have both monetary and prudential competence? If so, what governance arrangements are necessary for this institution, also given that final authority over all matters rests with the Governing Council according to the Treaty itself?
Article 35 Data protection impact assessment
Authors: Kosta Eleni
Published: March 2021

Article 24 (Responsibility of controller); Article 25 (Data protection by design and by default); Article 32 (Security of processing); Article 36 (Prior consultation) (see too recitals 94–95); Article 39 (Tasks of data protection officer); Article 40 (Codes of conduct); Article 63 (Consistency mechanism); Article 64 (Opinions of EDPB).
Article 92 Exercise of the delegation
Authors: Tosoni Luca
Published: March 2021

Article 12(7)–(8) (Standardised icons) (see too recitals 60 and 166); Article 42(1) (Certification); Article 43(8) (Certification bodies) (see too recitals 100 and 166); Article 70(1)(q)–(r) (Tasks of the Board); Article 93 (Committee procedure).
Direct Effects and Indirect Effects of Union Law
Authors: Schütze Robert
Published: March 2021

Classic international law holds that each state can choose the relationship between its ‘domestic’ law and ‘international’ law. Two—constitutional—theories thereby exist: monism and dualism. Monist states make international law part of their domestic legal order. International law will here directly apply as if it was domestic law. By contrast, dualist states consider international law separate from domestic law: international law is viewed as the law between states; national law is the law within a state. International law needs to be ‘transposed’ or ‘incorporated’ into domestic law; and it can therefore only have indirect effects through the medium of national law. For dualist states, all European law would need to be ‘incorporated’ into national law before it could have domestic effects. Individuals would here never come into direct contact with European law; and where a Member State violated European law, individuals could not invoke ‘their’ European rights in the national courts.
Network Structure in Small Groups and Survival in Disasters
Authors: Cornwell Benjamin , Ho Jing-Mao
Published: March 2021

People in disaster and emergency situations (e.g., building fires) tend to adhere to the social obligations and expectations that are embedded in their preexisting roles and relationships. Accordingly, people survive or perish in groups—specifically, alongside those to whom they were connected before the situation emerged. This article uses social network analysis to expand on this collective behavior account. Specifically, we consider structural heterogeneity with respect to the internal configurations of social ties that compose small groups facing these situations together. Some groups are composed of cohesive subsets of members who can split off from each other during evacuation without violating their group’s internal role-based expectations. We argue that groups that possess this “breakaway” structure can respond to emergencies more flexibly. We explore this using data from the Beverly Hills Supper Club fire of 1977, which killed 165 people. Our data include 303 groups (“parties”) that consisted of 746 people who were present in the dining room where most of the fatalities occurred. Fatality rates were significantly lower in groups that were internally structured such that they could split up in different ways during the escape while still maintaining their strongest social bonds.
Fluoroscopic Evaluation of the Bile Ducts: Anatomic Variants, Benign and Malignant Pathologies and Bile Leaks: Part I
Authors: Sridhar Shravan , Keshav Nandan , Shiehmorteza Masoud , Thompson William M.
Published: March 2021

Direct cholangiography (DC) includes endoscopic retrograde cholangiopancreatography (ERCP), intraoperative cholangiography (IOC), T-tube cholangiography (TTC), and percutaneous transhepatic cholangiography (PTC). Radiologists need to understand how each technique is performed and how to interpret each study. In many institutions, radiologists do not interpret ERCPs. Currently, common duct explorations are rarely performed; therefore, radiologists are not interpreting TTCs as frequently as they did in the past. In addition, many institutions are using alternative techniques to replace IOC. Therefore, our radiology residents are not being trained to perform and interpret DC. This presentation describes the important aspects of the performance and interpretation of DC.
Cardiovascular and metabolic consequences in patients with asymptomatic adrenal adenomas
Authors: Hamidi Oksana
Published: March 2021

Purpose of review

The incidence of adrenal tumors has increased over the past 20 years, most of which are incidentally discovered nonfunctioning adenomas (NFA) and tumors with mild autonomous cortisol secretion (MACS). This review aimed to summarize recent progress in understanding cardiometabolic risk in patients with NFA and MACS and to provide updates on the effect of treatment on improving outcomes in this population.

Recent findings

NFA and MACS are associated with adverse cardiovascular risk factors and metabolic derangements, which are likely mediated by excessive glucocorticoid secretion. Recent studies showed significantly higher prevalence of hypertension, impaired glucose metabolism, obesity, and dyslipidemia in patients with NFA and MACS. Adrenalectomy may improve comorbidities in selected patients.

Asymptomatic adrenal adenomas are common and are associated with adverse cardiometabolic changes. In selected patients, adrenalectomy may reduce cardiometabolic risk and improve clinical outcomes.
Genetics of pheochromocytoma and paraganglioma
Authors: Wachtel Heather , Fishbein Lauren
Published: March 2021

Purpose of review

This review summarizes our current understanding of germline and somatic genetics and genomics of pheochromocytomas and paragangliomas (PCC/PGL), describes existing knowledge gaps, and discusses future research directions.

Recent findings

Germline pathogenic variants (PVs) are found in up to 40% of those with PCC/PGL. Tumors with germline PVs are broadly categorized as Cluster 1 (pseudohypoxia), including those with SDH, VHL, FH, and EPAS1 PVs, or Cluster 2 (kinase signaling) including those with NF1, RET, TMEM127, and MAX PVs. Somatic driver mutations exist in some of the same genes (RET, VHL, NF1, EPAS1) as well as in additional genes including HRAS, CSDE1 and genes involved in cell immortalization (ATRX and TERT). Other somatic driver events include recurrent fusion genes involving MAML3.

PCC/PGL have the highest association with germline PVs of all human solid tumors. Expanding our understanding of the molecular pathogenesis of PCC/PGL is essential to advancements in diagnosis and surveillance and the development of novel therapies for these unique tumors.
Excess Mortality Associated With the COVID-19 Pandemic—Los Angeles County, March-September 2020
Authors: Traub Elizabeth , Amoon Aryana T. , Rollin-Alamillo Louise , Haddix Meredith , Poortinga Kathleen , Ibrahim Mireille , Feregrino Gustavo , Foo Chelsea , Itano Alison , Lee Rebecca , Fisher Rebecca , Jarashow Claire , Balter Sharon , Gounder Prabhu
Published: March 2021

Objective:

To more comprehensively estimate COVID-19–related mortality in Los Angeles County by determining excess all-cause mortality and pneumonia, influenza, or COVID (PIC) mortality.

Design:

We reviewed vital statistics data to identify deaths registered in Los Angeles County between March 15, 2020, and August 15, 2020. Deaths with an ICD-10 (International Classification of Diseases, Tenth Revision) code for pneumonia, influenza, or COVID-19 listed as an immediate or underlying cause of death were classified as PIC deaths. Expected deaths were calculated using negative binomial regression. Excess mortality was determined by subtracting the expected from the observed number of weekly deaths. The Department of Public Health conducts surveillance for COVID-19–associated deaths: persons who died of nontraumatic/nonaccidental causes within 60 days of a positive COVID-19 test result were classified as confirmed COVID-19 deaths. Deaths without a reported positive SARS-Cov-2 polymerase chain reaction result were classified as probable COVID-19 deaths if COVID-19 was listed on their death certificate or the death occurred 60 to 90 days of a positive test. We compared excess PIC deaths with the number of confirmed and probable COVID-19 deaths ascertained by surveillance.

Setting:

Los Angeles County.

Participants:

Residents of Los Angeles County who died.

Main Outcome Measure:

Excess mortality.

Results:

There were 7208 excess all-cause and 5128 excess PIC deaths during the study period. The Department of Public Health also reported 5160 confirmed and 323 probable COVID-19–associated deaths.

Conclusions:

The number of excess PIC deaths estimated by our model was approximately equal to the number of confirmed and probable COVID-19 deaths identified by surveillance. This suggests our surveillance definition for confirmed and probable COVID-19 deaths might be sufficiently sensitive for capturing the true burden of deaths caused directly or indirectly by COVID-19.
COVID-19 Sources of Information, Knowledge, and Preventive Behaviors Among the US Adult Population
Authors: Shafiq Mehr , Elharake Jad A. , Malik Amyn A. , McFadden SarahAnn M. , Aguolu Obianuju Genevieve , Omer Saad B.
Published: March 2021

Context:

The COVID-19 pandemic has resulted in more than 20 million cases and 350 000 deaths in the United States. With the ongoing media coverage and spread of misinformation, public health authorities need to identify effective strategies and create culturally appropriate and evidence-based messaging that best encourage preventive health behaviors to control the spread of COVID-19.

Objective:

The purpose of this study was to understand the relationship between COVID-19 sources of information and knowledge, and how US adults' knowledge may be associated with preventive health behaviors to help mitigate COVID-19 cases and deaths.

Design and Setting:

For this cross-sectional study, survey data pertaining to COVID-19 were collected via online platform, Qualtrics, in February and May 2020.

Participants:

Data responses included 718 US adults from the February survey and 672 US adults from the May survey—both representative of the US adult population.

Main Outcome Measures:

Sociodemographic characteristics, COVID-19 knowledge score, COVID-19 reliable sources of information, and adherence to COVID-19 preventive health behaviors.

Results and Conclusions:

The main findings showed that disseminating COVID-19 information across various sources, particularly television, health care providers, and health officials, to increase people's COVID-19 knowledge contributes to greater adherence to infection prevention behaviors. Across February and May 2020 survey data, participants 55 years and older and those with higher educational background reported a higher average COVID-19 knowledge score. In addition, among the racial and ethnic categories, Black/African American and Native American/Alaska Native participants reported a lower average COVID-19 knowledge score than white participants—signaling the need to establish COVID-19 communication that is culturally-tailored and community-based. Overall, health care authorities must deliver clear and concise messaging about the importance of adhering to preventive health behaviors, even as COVID-19 vaccines become widely available to the general public. Health officials must also focus on increasing COVID-19 knowledge and dispelling misinformation.
Rapid, widespread, and preferential increase of SARS-CoV-2 B.1.1.7 variant in Houston, TX, revealed by 8,857 genome sequences
Authors: Musser James M. , Olsen Randall J. , Christensen Paul A. , Long S. Wesley , Subedi Sishir , Davis James J. , Gollihar Jimmy
Published: March 2021

Genetic variants of the SARS-CoV-2 virus have become of great interest worldwide because they have the potential to detrimentally alter the course of the SARS-CoV-2 pandemic, and disease in individual patients. We recently sequenced 20,453 SARS- CoV-2 genomes from patients with COVID-19 disease in metropolitan Houston (population 7 million), dating from March 2020 to early February 2021. We discovered that all major variants of concern or interest are circulating in the region. To follow up on this discovery, we analyzed 8,857 genome sequences from patients in eight Houston Methodist hospitals dispersed throughout the metroplex diagnosed from January 1, 2021 to March 7, 2021. This sample represents 94% of Houston Methodist cases and 4.8% of all reported cases in metropolitan Houston during this period. We discovered rapid, widespread, and preferential increase of the SARS-CoV-2 UK B.1.1.7 throughout the region. The estimated case doubling time in the Houston area is 6.9 days. None of the 648 UK B.1.1.7 samples identified had the E484K change in spike protein that can cause decreased recognition by antibodies.
The relationship between relative aerobic load, energy cost, and speed of walking in individuals post-stroke
Authors: Blokland Ilse , Gravesteijn Arianne , Busse Mathijs , Groot Floor , van Bennekom Coen , van Dieen Jaap , de Koning Jos , Houdijk Han
Published: March 2021

Background

Individuals post-stroke walk slower than their able-bodied peers, which limits participation. This might be attributed to neurological impairments, but could also be caused by a mismatch between aerobic capacity and aerobic load of walking.

Research question

What is the potential impact of aerobic capacity and aerobic load of walking on walking ability post-stroke?

Methods

In a cross-sectional study, forty individuals post-stroke (more impaired N=21; preferred walking speed (PWS)<0.8m/s, less impaired N=19), and 15 able-bodied individuals performed five, 5-minute treadmill walking trials at 70%, 85%, 100%, 115% and 130% of PWS. Energy expenditure (mlO2/kg/min) and energy cost (mlO2/kg/m) were derived from oxygen uptake. Relative load was defined as energy expenditure divided by peak aerobic capacityand byat ventilatory threshold. Relative load and energy cost at PWS were compared between groups with one-way ANOVA’s. The effect of speed on these parameters was modeled with GEE.

Results

Both more and less impaired individuals post-stroke showed lower PWS than able-bodied controls (0.44[0.19-0.76] and 1.04[0.81-1.43] vs 1.36[0.89-1.53] m/s) and higher relative load at PWS (50.2±14.4 and 51.7±16.8 vspeak and 101.9±20.5 and 97.0±27.3 vs). No differences in relative load were found between stroke groups. Energy cost at PWS of more impaired (0.30[.19-1.03] mlO2/kg/m) was higher than less-impaired (0.19[0.10-0.24] mlO2/kg/m) and able-bodied (0.15[0.13-0.18] mlO2/kg/m). For post-stroke individuals, increasing walking speed above PWS decreased energy cost, but resulted in a relative load above endurance threshold.

Significance

Individuals post-stroke seem to reduce walking speed to prevent unsustainably high relative aerobic loads at the expense of reduced economy. When aiming to improve walking ability in individuals post-stroke, it is important to consider training aerobic capacity.
Miniaturizing wet scrubbers for aerosolized droplet capture
Authors: Lee Ulri N. , van Neel Tammi L. , Lim Fang Yun , Khor Jian Wei , He Jiayang , Vaddi Ravi S. , Ong Angelo Q.W. , Tang Anthony , Berthier Jean , Meschke John S. , Novosselov Igor V. , Theberge Ashleigh B. , Berthier Erwin
Published: March 2021

Aerosols dispersed and transmitted through the air (e.g., particulate matter pollution, bioaerosols) are ubiquitous and one of the leading causes of adverse health effects and disease transmission. A variety of sampling methods (e.g., filters, cyclones, impactors) have been developed to assess personal exposures. However, a gap still remains in the accessibility and ease-of-use of these technologies for people without experience or training in collecting airborne samples. Additionally, wet scrubbers (large non-portable industrial systems) utilize liquid sprays to remove aerosols from the air; the goal is to “scrub” (i.e., clean) the exhaust of industrial smokestacks, not collect the aerosols for analysis. Inspired by wet scrubbers, we developed a device fundamentally different from existing portable air samplers by using aerosolized microdroplets to capture aerosols in personal spaces (e.g., homes, offices, schools). Our aerosol-sampling device is the size of a small teapot, can be operated without specialized training, and features a winding flow path in a supersaturated relative humidity environment enabling droplet growth. The integrated open mesofluidic channels shuttle coalesced droplets to a collection chamber for subsequent sample analysis. Here, we present the experimental demonstration of aerosol capture into water droplets. Iterative study optimized the non-linear flow manipulating baffles and enabled an 83% retention of the aerosolized microdroplets in the confined volume of our device. As a proof-of-concept for aerosol capture into a liquid medium, 0.5-3 µm model particles were used to evaluate aerosol capture efficiency. Finally, we demonstrate the device can capture and keep a bioaerosol (bacteriophage MS2) viable for downstream analysis.
Epidemiological dynamics of viral infection in a marine picoeukaryote
Authors: Listmann Luisa , Heath Sarah , Vale Pedro F. , Schaum C. Elisa , Collins Sinead
Published: March 2021

Ostreococcus tauri is a ubiquitous marine pico-eukaryote that is susceptible to lysis upon infection by its species specific Ostreococcus tauri viruses (OtVs). In natural populations of O. tauri, costs of resistance are usually invoked to explain the persistence or reappearance of susceptible individuals in resistant populations. Given the low costs of resistance measured in laboratory experiments with the O. tauri/OtV system to date, the question remains of why susceptible individuals persist in the wild at all. Epidemiological models of host and pathogen population dynamics are one useful approach to understand the conditions that can allow the coexistence of susceptible and resistant hosts. We used a SIR (Susceptible-Infected-Resistant) model to investigate epidemiological dynamics under different laboratory culturing regimes that are commonly used in the O.tauri/OtV system. When taking into account serial transfer (i.e. batchcycle lengths) and dilution rates as well as different resistance costs, our model predicts that no susceptible cells should be detected under any of the simulated conditions – this is consistent with laboratory findings. We thus considered an alternative model that is not used in laboratory experiments, but which incorporates one key process in natural populations: host populations are periodically re-seeded with new infective viruses. In this model, susceptible individuals re-occurred in the population, despite low costs of resistance. This suggests that periodic attack by new viruses, rather than (or in addition to) costs of resistance, may explain the high proportion of susceptible hosts in natural populations, and underlie the discrepancy between laboratory studies and observations of fresh isolates.

Importance

In natural samples of Ostreococcus sp. and its associated viruses, susceptible hosts are common. However, in laboratory experiments, fully resistant host populations readily and irreversibly evolve. Laboratory experiments are powerful methods for studying process because they offer a stripped-down simplification of a complex system, but this simplification may be an oversimplification for some questions. For example, laboratory and field systems of marine microbes and their viruses differ in population sizes and dynamics, mixing or migration rates, and species diversity, all of which can dramatically alter process outcomes. We demonstrate the utility of using epidemiological models to explore experimental design and to understand mechanisms underlying host-virus population dynamics. We highlight that such models can be used to form strong, testable hypotheses about which key elements of natural systems need to be included in laboratory systems to make them simplified, rather than oversimplified, versions of the processes we use them to study.
Correction of multiple-blinking artefacts in photoactivated localisation microscopy
Authors: Jensen Louis G , Hoh Tjun Yee , Williamson David J , Griffié Juliette , Sage Daniel , Rubin-Delanchy Patrick , Owen Dylan M
Published: March 2021

Photoactivated localisation microscopy (PALM) produces an array of localisation coordinates by means of photoactivatable fluorescent proteins. However, observations are subject to fluorophore multiple-blinking and each protein is included in the dataset an unknown number of times at different positions, due to localisation error. This causes artificial clustering to be observed in the data. We present a workflow using calibration-free estimation of blinking dynamics and model-based clustering, to produce a corrected set of localisation coordinates now representing the true underlying fluorophore locations with enhanced localisation precision. These can be reliably tested for spatial randomness or analysed by other clustering approaches, and previously inestimable descriptors such as the absolute number of fluorophores per cluster are now quantifiable, which we validate with simulated data. Using experimental data, we confirm that the adaptor protein, LAT, is clustered at the T cell immunological synapse, with its nanoscale clustering properties depending on location and intracellular phosphorylatable tyrosine residues.
Investigations on regulation of miRNAs in rice reveal [Ca2+]cytsignal transduction regulated miRNAs
Authors: Kansal Shivani , Panwar Vaishali , Mutum Roseeta Devi , Raghuvanshi Saurabh
Published: March 2021

MicroRNAs are critical components of the multi-dimensional regulatory networks in eukaryotic systems. They regulate a spectrum of developmental and metabolic processes in both plants and animals. Thus, it is quite apparent that the transcription, processing as well as activity of the miRNAs themselves is very dynamically regulated. One of the most important and universally implicated signalling molecule is [Ca2+]cyt. It is known to regulate a plethora of developmental and metabolic processes in both plants and animals, however their impact on the regulation of miRNA expression is relatively less explored. The current study employed a combination of internal and external calcium channel inhibitors, to establish that [Ca2+]cytsignatures actively regulate miRNA expression in rice. Involvement of [Ca2+]cytin regulation of miRNA expression was further confirmed by treatment with calcimycin, the calcium ionophore. Modulation of the cytosolic calcium levels was also found to regulate the drought responsive expression as well as ABA mediated response of miRNA genes in rice seedlings. The study further establishes the role of calmodulins and Calmodulin-binding Transcription Activators (CAMTAs) as important components of the signal transduction schema that regulates miRNA expression. Yeast-one-hybrid assay established that OsCAMTA4 & 6 are involved in the transcriptional regulation of miR156a and miR167h. Thus, the study was able to clearly establish that [Ca2+]cytis actively involved in regulating expression of miRNA genes both under control and stress conditions.
Taking full advantage of modelling to better assess environmental risk due to xenobiotics
Authors: Charles Sandrine , Ratier Aude , Baudrot Virgile , Multari Gauthier , Siberchicot Aurélie , Wu Dan , Lopes Christelle
Published: March 2021

In the European Union, more than 100,000 man-made chemical substances are awaiting an environmental risk assessment (ERA). Simultaneously, ERA of chemicals has now entered a new era. Indeed, recent recommendations from regulatory bodies underline a crucial need for the use of mechanistic effect models, allowing assessments that are not only ecologically relevant, but also more integrative, consistent and efficient. At the individual level, toxicokinetic-toxicodynamic (TKTD) models are particularly encouraged for the regulatory assessment of pesticide-related risks on aquatic organisms. In this paper, we first propose a brief review of classical dose-response models to put into light the on-line MOSAIC tool offering all necessary services in a turnkey web platform whatever the type of data to analyze. Then, we focus on the necessity to account for the time-dimension of the exposure by illustrating how MOSAIC can support a robust calculation of bioaccumulation factors. At last, we show how MOSAIC can be of valuable help to fully complete the EFSA workflow regarding the use of TKTD models, especially with GUTS models, providing a user-friendly interface for calibrating, validating and predicting survival over time under any time-variable exposure scenario of interest. Our conclusion proposes a few lines of thought for an even easier use of modelling in ERA.

Graphical art
Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates
Authors: Joyce Michael G. , King Hannah A. D. , Naouar Ines Elakhal , Ahmed Aslaa , Peachman Kristina K. , Cincotta Camila Macedo , Subra Caroline , Chen Rita E. , Thomas Paul V. , Chen Wei-Hung , Sankhala Rajeshwer S. , Hajduczki Agnes , Martinez Elizabeth J. , Peterson Caroline E. , Chang William C. , Choe Misook , Smith Clayton , Lee Parker J. , Headley Jarrett A. , Taddese Mekdi G. , Elyard Hanne A. , Cook Anthony , Anderson Alexander , McGuckin-Wuertz Kathryn , Dong Ming , Swafford Isabella , Case James B. , Currier Jeffrey R. , Lal Kerri G. , O’Connell Robert J. , Molnar Sebastian , Nair Manoj S. , Dussupt Vincent , Daye Sharon P. , Zeng Xiankun , Barkei Erica K. , Staples Hilary M. , Alfson Kendra , Carrion Ricardo , Krebs Shelly J. , Paquin-Proulx Dominic , Karasavva Nicos , Polonis Victoria R. , Jagodzinski Linda L. , Amare Mihret F. , Vasan Sandhya , Scott Paul T. , Huang Yaoxing , Ho David D. , de Val Natalia , Diamond Michael S. , Lewis Mark G. , Rao Mangala , Matyas Gary R. , Gromowski Gregory D. , Peel Sheila A. , Michael Nelson L. , Bolton Diane L. , Modjarrad Kayvon
Published: March 2021

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50µg) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.

One-Sentence Summary

A SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.
Genetic differentiation ofXylella fastidiosafollowing the introduction into Taiwan
Authors: Castillo Andreina I. , Tsai Chi-Wei , Su Chiou-Chu , Weng Ling-Wei , Lin Yu-Chen , Cho Shu-Ting , Almeida Rodrigo P. P. , Kuo Chih-Horng
Published: March 2021

The economically important plant pathogenXylella fastidiosahas been reported in multiple regions of the globe during the last two decades, threatening a growing list of crops and industries.Xylella fastidiosasubspeciesfastidiosacauses disease in grapevines (Pierce’s disease of grapevines, PD), a current problem in the United States (US), Spain, and Taiwan. We studied PD-causing subsp.fastidiosapopulations and compared the genome sequences of 33 isolates found in Central Taiwan with 171 isolates from the US and two from Spain.

Phylogenetic relationships, haplotype network, and genetic diversity analyses confirm that subsp.fastidiosawas recently introduced into Taiwan from the Southeast US (i.e., the PD-I lineage in Georgia based on available data). Recent core genome recombination events were detected among introduced subsp.fastidiosaisolates in Taiwan and contributed to the development of genetic diversity, particularly in the Houli District of Taichung City in Central Taiwan. Unexpectedly, despite comprehensive sampling of all regions with high PD incidences in Taiwan, the genetic diversity observed include contributions through recombination from unknown donors, suggesting that higher diversity exists in the region. Nevertheless, no recombination event was detected betweenX. fastidiosasubsp.fastidiosaand the endemic sister speciesXylella taiwanensis. In summary, this study improved our understanding of the genetic diversity of PD-causing subsp.fastidiosaafter invasion to a new region.
ADAR2-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair
Authors: Jimeno Sonia , Prados-Carvajal Rosario , Fernández-Ávila María Jesús , Silva Sonia , Silvestris Domenico Alessandro , Endara-Coll Martín , Domingo-Prim Judit , Mejías-Navarro Fernando , Rodríguez-Real Guillermo , Romero-Franco Amador , Jimeno-González Silvia , Barroso Sonia , Cesarini Valeriana , Aguilera Andrés , Gallo Angela , Visa Neus , Huertas Pablo
Published: March 2021

The maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call theRNAEditingDAmageResponse (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution.

One sentence summary:

DNA recombination requires RNA editing of DNA:RNA hybrids to ease their melting and facilitate DNA end resection
Modelling nonlinear dendritic processing of facilitation in a dragonfly target-tracking neuron
Authors: Bekkouche Bo M. B. , Shoemaker Patrick A. , Fabian Joseph M. , Rigosi Elisa , Wiederman Steven D. , O’Carroll David C.
Published: March 2021

Dragonflies are highly skilled and successful aerial predators that are even capable of selectively attending to one target within a swarm. Detection and tracking prey is likely to be driven by small target motion detector (STMD) neurons identified from several insect groups. Prior work has shown that dragonfly STMD responses are facilitated by targets moving on a continuous path, enhancing the response gain at the present and predicted future location of targets. In this study, we combined detailed morphological data with computational modelling to test whether a combination of dendritic morphology combined with the nonlinear properties of NMDA receptors could explain these observations. We developed a hybrid neuronal model of neurons within the dragonfly optic lobe, which integrates numerical and morphological components. The model was able to generate potent facilitation for targets moving on continuous trajectories, including a localized spotlight of maximal sensitivity close to the last seen target location, as also measured duringin vivorecordings. The model did not, however, include a mechanism capable of producing a traveling or spreading wave of facilitation. Our data support a strong role for the high dendritic density seen in the dragonfly neuron in enhancing non-linear facilitation. An alternative model based on morphology of an unrelated type of motion processing neuron from a dipteran fly required more than 3 times higher synaptic gain in order to elicit similar levels of facilitation, despite having only 20% fewer synapses. Our data supports a potential role for NMDA receptors in target tracking and also demonstrates the feasibility of combining biologically plausible dendritic computations with more abstract computational models for basic processing as used in earlier studies.
A year in the life of the Eastern Mediterranean: Monthly dynamics of phytoplankton and bacterioplankton in an ultra-oligotrophic sea
Authors: Reich Tom , Ben-Ezra Tal , Belkin Natalya , Tsemel Anat , Aharonovich Dikla , Roth-Rosenberg Dalit , Givati Shira , Bialik Or , Herut Barak , Berman-Frank Ilana , Frada Miguel , Krom Michael D. , Lehahn Yoav , Rahav Eyal , Sher Daniel
Published: March 2021

The Eastern Mediterranean Sea (EMS) is a poorly studied ultra-oligotrophic marine environment, dominated by small-size phyto- and bacterioplankton. Here, we describe the dynamics of a single annual cycle (2018-19) of phyto- and bacterioplankton (abundances, pigments and productivity) in relation to the physical and chemical conditions in the photic water column at an offshore EMS site (Station THEMO-2, ∼1,500m depth, 50km offshore). We show that phytoplankton biomass (as chlorophyll a), primary and bacterial productivity differed between the mixed winter (January-April) and the thermally stratified (May-December) periods.ProchlorococcusandSynechococcusnumerically dominated the picophytoplankton populations, with each clade revealing different temporal and depth changes indicative to them, while pico-eukaryotes (primarily haptophytes) were less abundant, yet likely contributed significant biomass. Estimated primary productivity (∼32 gC m-2y-1) was lower compared with other well-studied oligotrophic locations, including the north Atlantic and Pacific (BATS and HOT observatories), the western Mediterranean (DYFAMED observatory) and the Red Sea, and was on-par with the ultra-oligotrophic South Pacific Gyre. In contrast, integrated bacterial production (∼11 gC m-2y-1) was similar to other oligotrophic locations. Phytoplankton seasonal dynamics were similar to those at BATS and the Red Sea, suggesting an observable effect of winter mixing in this ultra-oligotrophic location. These results highlight the ultra-oligotrophic conditions in the EMS and provide, for the first time in this region, a full-year baseline and context to ocean observatories in the region.

Highlights

Bacterioplankton dynamics were assessed monthly in the Eastern Mediterranean Sea

Small-sized picophytoplankton numerically dominated the phytoplankton community

Seasonal phytoplankton dynamics are similar to BATS and Red Sea, but not to HOT

Annual primary productivity is among the lowest in the world’s oceans

Bacterial to primary production ratio is higher than most oligotrophic seas
Searching match for single-cell open-chromatin profiles in large pools of single-cell transcriptomes and epigenomes for reference supported analysis
Authors: Mishra Shreya , Pandey Neetesh , Chawla Smriti , SenGupta Debarka , Natrajan Kedar Nath , Kumar Vibhor
Published: March 2021

The true benefits of large datasets of the single-cell transcriptome and epigenome profiles can be availed only with their inclusion and search for annotating individual cells. Matching a single cell epigenome profile to a large pool of reference cells remains a major challenge. We developed a method (scEpiSearch) to resolve the challenges of searching and comparing single-cell open-chromatin profiles against large pools of single-cell expression and open chromatin datasets. scEpiSearch is more accurate than other methods when comparing single cell open-chromatin profiles to single-cell transcriptomes and epigenomes. scEpiSearch also provides a robust method for reference-supported co-embedding of single-cell open chromatin profiles. In performance benchmarks, scEpiSearch outperformed multiple methods for the low dimensional co-embedding of single-cell open-chromatin profiles irrespective of platforms and species. scEpiSearch works with both reference single-cell expression and epigenome profiles, enabling classification of single-cell open-chromatin profiles. Here we demonstrate the unconventional utilities of scEpiSearch by applying it on single-cell epigenome profiles of K562 cells and samples from patients with acute leukaemia to reveal different aspects of their heterogeneity, multipotent behaviour and de-differentiated states. Applying scEpiSearch on our single-cell open-chromatin profiles from embryonic stem cells(ESCs), we identified ESC subpopulations with more activity and poising for endoplasmic reticulum stress and unfolded protein response. Thus, scEpiSearch solves the non-trivial problem of amalgamating information from a large pool of single-cells to identify and study the regulatory states of cells using their single-cell epigenomes.The true benefits of large datasets of the single-cell transcriptome and epigenome profiles can be availed only with their inclusion and search for annotating individual cells.
Profiling DNA break sites and transcriptional changes in response to contextual fear learning
Authors: Stott Ryan T. , Kritsky Oleg , Tsai Li-Huei
Published: March 2021

Neuronal activity generates DNA double-strand breaks (DSBs) at specific lociin vitroand this facilitates the rapid transcriptional induction of early response genes (ERGs). Physiological neuronal activity, including exposure of mice to learning behaviors, also cause the formation of DSBs, yet the distribution of these breaks and their relation to brain function remains unclear. Here, following contextual fear conditioning (CFC) in mice, we profiled the locations of DSBs genome-wide in the medial prefrontal cortex and hippocampus using γH2AX ChIP-Seq. Remarkably, we found that DSB formation is widespread in the brain compared to cultured primary neurons and they are predominately involved in synaptic processes. We observed increased DNA breaks at genes induced by CFC in neuronal and non-neuronal nuclei. Activity-regulated and proteostasis-related transcription factors appear to govern some of these gene expression changes across cell types. Finally, we find that glia but not neurons have a robust transcriptional response to glucocorticoids, and many of these genes are sites of DSBs. Our results indicate that learning behaviors cause widespread DSB formation in the brain that are associated with experience-driven transcriptional changes across both neuronal and glial cells.
The species-specificity of energy landscapes for soaring birds, and its consequences for transferring suitability models across species
Authors: Scacco Martina , Arrondo Eneko , Donázar J. Antonio , Flack Andrea , Sánchez-Zapata J. Antonio , Duriez Olivier , Wikelski Martin , Safi Kamran
Published: March 2021

Soaring birds use the energy available in the environment in the form of atmospheric uplifts, to subsidize their flight. Their dependence on soaring opportunities makes them extremely sensitive to anthropogenic wind energy development. Predictive modelling is now considered instrumental to forecast the impact of wind farms on single species of concern. However, as multiple species often coexist in the same area, there is clear need to overcome the limitations of single species approaches.

We looked for converging patterns in the way two obligate soaring species use the energy available in the landscape to soar, using movement data from 57 white storks,Ciconia ciconia, and 27 griffon vultures,Gyps fulvus. We first compared the soaring efficiency of the two species. We then tested the accuracy of topographic features, important correlates of collision risk in soaring birds, in predicting their soaring behaviour. We finally tested the transferability of soaring suitability models across species.

Topography alone can predict and map the soaring opportunities available to storks across Europe, but not as efficiently in vultures. Only 20.5% of the study area was suitable to both species to soar, suggesting the existence of species-specific requirements in the use of the landscape for soaring. Storks relied on uplift occurrence while vultures on uplift quality, needing stronger uplifts to support their higher body mass and wing loading.

Synthesis and applications:Our results indicate that the flight of highly specialized soaring species is more dependent on atmospheric conditions than on static features, and that more knowledge is required to accurately predict their behaviour. Despite the superficially similar soaring behaviour, the two species have different environmental requirements, suggesting that energy landscapes are species-specific. Our models provide a base to explore the effects that changes in the landscape have on the flight behaviour of different soaring species and suggest that there is no reliable and responsible way to shortcut risk assessment in areas where multiple species might be at risk by anthropogenic structures.
Transcriptional and cellular signatures of cortical morphometric similarity remodelling in chronic pain
Authors: Martins Daniel , Dipasquale Ottavia , Veronese Mattia , Turkheimer Federico , Loggia Marco L. , McMahon Stephen , Howard Matthew A , Williams Steven CR
Published: March 2021

Chronic pain is a highly debilitating and poorly understood condition. Here, we attempt to advance our understanding of the brain mechanisms driving chronic pain by investigating alterations in morphometric similarity (MS) and corresponding transcriptomic and cellular signatures, in three cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain and fibromyalgia). We uncover a novel pattern of cortical MS remodelling involving mostly MS increases in the insula and limbic cortex, which cuts across the boundaries of specific pain syndromes. We show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes involved in the glial immune response and neuronal plasticity. Cortical remodelling in chronic pain might involve a disruption of multiple elements of the cellular architecture of the brain. Therefore, multi-target therapeutic approaches tackling both glial activation and neuronal hyperexcitability might better encompass the full neurobiology of chronic pain.
Class I Histone Deacetylases (HDAC1–3) are Histone Lysine Delactylases
Authors: Moreno-Yruela Carlos , Zhang Di , Wei Wei , Bæk Michael , Gao Jinjun , Nielsen Alexander L. , Bolding Julie E. , Yang Lu , Jameson Samuel T. , Wong Jiemin , Olsen Christian A. , Zhao Yingming
Published: March 2021

Lysinel-lactylation [K(l-la)] is a newly discovered histone mark that can be stimulated under conditions of high glycolysis, such as the Warburg effect. K(l-la) is associated with functions that are different from the widely studied histone acetylation. While K(l-la) can be introduced by the acetyltransferase p300, histone delactylase enzymes remain unknown. Here, we report the systematic evaluation of zinc- and NAD+-dependent HDACs for their ability to cleave ε-N-l-lactyllysine marks. Our screens identified HDACs 1–3 and SIRT1–3 as delactylases in vitro. HDACs 1–3 show robust activity toward not only K(l-la) but also K(d-la) and diverse short-chain acyl modifications. We further confirmed the de-l-lactylase activity of HDACs 1 and 3 in cells. Identification of p300 and HDAC3 as regulatory enzymes suggests that histone lactylation is installed and removed by enzymes as opposed to spontaneous chemical reactivity. Our results therefore represent an important step toward full characterization of this pathway’s regulatory elements.