bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenacity, Perseverance, and Imagination in the ‘Private International Prosecution’ of Hissène Habré
Authors: Brody Reed
Published: June 2020

This chapter focuses on Human Rights Watch’s strategy, challenges, the role played by civil society, and the strokes of fate that accompanied the twenty-year effort to convict Hissène Habré. The Habré trial was the fruit of what has been called ‘one of the world's most patient and tenacious campaigns for justice’. This campaign was waged over two decades by Habré's victims and their supporters, who improbably succeeded in creating the political conditions to bring a former African president to justice in Africa, with the support of the African Union. The victims' coalition ‘essentially served the case to the EAC on a silver platter’, determining the contours of the prosecution and dictating the nature of the trial itself, thereby contributing to its emancipatory impact. Ultimately, the Habré case shows how a ‘private international prosecution’ can allow victims to achieve criminal justice on their own terms.
In His Own Words
Authors: Gazette La
Published: June 2020

This chapter presents Hissène Habré's own thoughts on his regime and his threatened extradition, excerpted from his 2011 interview with Senegalese reporters from La Gazette. Habré moved to Dakar, Senegal following his expulsion from Chad in 1990, where he lived as a private citizen in an upscale residential neighbourhood. Although he left public politics, he participated in local Muslim political life in Senegal, and was protected by Senegal's President Abdoulaye Wade. However, waves of international attention put pressure on Senegal to extradite or prosecute Habré. On 25 July 2011, a film crew and reporters from La Gazette interviewed Habré in his home in Almadies. It was rumoured that President Wade was preparing to extradite Habré to Chad, where he had already been sentenced to death, in absentia, under Idriss Déby's regime. In response, Habré broke his typical media silence and agreed to an interview. In this interview, Habré did not deny that ‘there were deviations or blemishes’ under his regime, but he insisted that he is not responsible for these.
Reflections on the Habré Appeals Decision
Authors: Wafi Judge Ouagadeye
Published: June 2020

This chapter offers reflections of EAC Appeals Judge Ouagadeye Wafi, who discusses producing the highly anticipated appeals decision. Specifically, he comments on the challenge of ruling on multiple procedural challenges raised by the defence, as well as the reasoning behind maintaining the conviction in its entirety save for acquitting Hissène Habré of personally raping Khadidja Hassan Zidane. In hindsight, the main challenge presented by the appeal was to satisfactorily deal with the recognition of the civil parties and the question of compensation with only twenty-eight working weeks to do so. Although Judge Wafi did not observe any political influence or pressure, he feels that the time limit, albeit understandable and intrinsically linked to the budget, served to hinder the work of justice, which in itself should not be so strictly regulated. As a result, the Appeals Court was forced to encumber the Trust Fund for Victims with tasks that it could have undertaken itself had it had the necessary human, financial, and time resources. Particularly in terms of eligibility, this would have allowed the victims to definitely be in the know at the time of the verdict was announced, and which would also have prevented new actors from the need to delve into such a sprawling file, saving precious time.
Expertise in the Bench? The Dis-embeddedness of International Criminal Justice
Authors: Seroussi Julien
Published: June 2020

This chapter discusses how contextualizing facts can alter judicial outcomes, arguing for the necessity of developing a sociological theory about the facts of a case in order to ascribe responsibility in a court. Judges in international courts have very sparse access to information when they have to judge foreign situations from abroad. Thus, judges elaborate what can be called ‘folk sociological theories’ (FST), which are sociological narratives that can provide them with a grasp of the situation and a guide for the selection of facts that can demonstrate responsibility or guilt in the accomplishment of crimes. The chapter applies FSTs to the Germain Katanga and Mathieu Ngudjolo cases, suggesting that they raise important conceptual implications for understanding the epistemological limitations of international criminal proceedings. It also considers the production of FSTs through a pragmatic approach, showing when FSTs successfully produce the irrelevance of facts in fact-finding processes, and when they fail the reality tests of legal procedure.
The ICJ’s Senegal v Belgium Judgment and the Obligation to Prosecute or Extradite Alleged Torturers
Authors: Ventura Manuel J , Băieşu Victor
Published: June 2020

This chapter addresses the wider jurisprudential frameworks established by the International Court of Justice (ICJ) in its decision regarding the extradition of Hissène Habré. The judgment in the Questions Relating to the Obligation to Prosecute or Extradite (Belgium v Senegal) case was the first judgment in which the ICJ's judges authoritatively articulated the material scope and the measures necessary for the implementation of an obligation to prosecute or extradite. In this case, this obligation arose under the Convention Against Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment (Torture Convention) (1984). The ICJ's judges also decisively held that the prohibition of torture had attained the status of jus cogens and that the existence of a common interest of State Parties to the Torture Convention (1984) in the compliance with erga omnes obligations alone suffices for any State Party to have standing to invoke the responsibility of any other State Party for breaching such obligations. These were broad-reaching, novel, and significant findings with potential reverberations beyond the Habré case. The chapter then analyses the impact of these ICJ pronouncements in the context of the ICC's arrest warrants against Sudan's Omar Al Bashir who, since being deposed in April of 2019, now only enjoys functional immunity ratione materiae.
Hissène Habré, the Little Bird on the Branch, and the Challenges of International Criminal Justice
Authors: Hazan Pierre
Published: June 2020

This chapter discusses the geopolitical and temporal context of the Hissène Habré trial. The trial, held in Dakar in 2016, and concluding with a sentence of imprisonment for life for ‘crimes against humanity, war crimes, and crimes of torture’ for the ex-dictator, was a historic one on many levels. It set important precedents in the struggle against impunity in Africa and testifies to the slow construction of a system of global justice. It also gives a foretaste of even greater challenges that criminal justice in Africa must meet. The chapter then demonstrates that the Chadian ex-dictator's trial was only held thanks to a singular conjunction of judicial and political factors. More precisely, the case against Habré was solid, but the creation of the Extraordinary African Chambers (EAC) was, essentially, the product of a power struggle created and won by Habré's victims and international human rights organizations. This, in and of itself, questions the respective places of law and politics in the processes of transitional justice.
The ICC and Africa
Authors: Goldstone Richard
Published: June 2020

This chapter assesses Africa’s relationship to international justice via its fraught contestation of the International Criminal Court (ICC). The relationship between Africa and the ICC is a complex and complicated one. There is a tension between the strong desire of most African states and their people to bring justice to the victims of war crimes and the perceived bias against Africa arising from the fact that all but one of the eleven situations before the ICC relate to African states. The problem is exacerbated by the failure of the Security Council to refer to the ICC egregious cases of war crimes committed on other continents and particularly in Sri Lanka and Syria. The chapter then looks at the politics of the relationship between the ICC and Africa and how the optics have changed during the first fifteen years of the active life of the ICC. It also considers the future of the ICC in Africa and highlights the importance of positive complementarity.
Directionality and Virtuous Ends
Authors: Ripstein Arthur , Tenenbaum Sergio
Published: June 2020

This chapter examines the question of the moral status of animals in Kantian moral theory. Kant’s view that all our duties regarding non-human animals are duties to ourselves is widely thought to capture neither the content of these duties nor their ground. The chapter, therefore, focuses on the supposed problem of the directionality of our moral obligations. It seeks to articulate and defend an account of Kant’s understanding of the directionality of duty, and to deploy it to explain and defend his notorious claim that our duties regarding animals are duties to ourselves. More generally, we seek to explain the relation between the content of a duty and its directionality. The chapter identifies three possible sources of the directionality problem: the issues of it involving the wrong content, or a kind of instrumentality, or a kind of contingency. It argues that the contingency worry is the key one and suggests a response to it.
Introduction
Authors: del Guayo Íñigo , Godden Lee , Zillman Donald N. , Montoya Milton F. , Juan González José
Published: June 2020

Energy Justice has emerged as a pressing concern in many parts of the world, driven by factors as diverse as global inequality and poverty, climate change and environmental degradation, and the need to ensure effective economic transitions in the eneegy sector. In this chapter, the editors assess the current trends in energy law and energy justice in terms of fairness, sustainability, and universal access. In this assessment, they take into account the Sustainable Development Goals (SDGs) and the realities of different energy markets. The Introduction canvasses the variety of approaches to determining energy justice which are covered in the subsequent chapters. The approaches to justice are premised on four themes: distributive; procedural; restorative and recognition justice that are explored in theoretically informed chapters and in the case studies grounded in national and regional experience.
Energy Justice
Authors: McHarg Aileen
Published: June 2020

The explosion of interest in energy justice as a guiding principle for energy law and policy is a highly significant development with potentially radical implications. This ‘ethical turn’ is associated with increased attention to energy matters by social scientists, driven by disillusionment with neo-liberal energy policies and the challenges of the energy transition. Energy justice scholars seek a more holistic, human-centred approach to energy decision-making, which understands the fundamental importance of energy and energy systems to human flourishing, and the complexity of energy decision-making as a socially-embedded phenomenon involving more than merely technical and economic considerations. However, review of the literature reveals a range of different conceptual and theoretical understandings of energy justice in play, which are not always fully developed or mutually consistent. More attention is also required to questions of implementation, particularly what implications energy justice might have for legal and regulatory systems, as well as judicial decision-making.
Energy Justice Along the ‘New Silk Road’
Authors: Boute Anatole
Published: June 2020

Central Asia holds massive energy reserves, but its energy systems are generally unreliable and inefficient. Although the region’s energy prices are amongst the lowest in the world, increasing prices to improve utilities’ financial situations and ensuring the urgently needed investments are made are issues of high social and political sensitivity. Popular discontent with tariff increases has already helped to trigger regime change in Kyrgyzstan in 2010. Given the sensitivity of energy price increases and tight budgetary constraints in the region, what legal options are available to restore utilities’ financial viability without jeopardizing the affordability of energy supply? Focusing on procedural justice, this chapter argues that domestic courts have an important role to play in balancing utilities’ right to cost-recovery tariffs and consumers’ rights to affordable energy supply.
Energy Justice and Energy Transition in Australia
Authors: Godden Lee
Published: June 2020

Australia is in energy transition despite a national policy supportive of fossil fuels. Regional and remote areas, however, remain dependent on fossil fuels, including diesel. Renewable energy is becoming accessible for some regional communities, due to renewable energy incentives. This chapter considers the energy transition in Australia through the energy justice lens. It analyses the distribution of benefits and burdens of energy activities upon remote Indigenous communities, and examines energy price impacts and consumer protection reforms in liberalized electricity markets in the south. The analysis examines how social justice needs to inform the energy transition, also recognising that energy injustice cannot be separated from other social ills, such as poverty and discrimination based on factors including class, race, gender, or indigeneity. It concludes that there are significant protections emerging for energy consumers in the national electricity market, but an inequitable distribution of energy benefits and burdens in remote Aboriginal communities.
Reflection on China’s Energy Justice During a Transitional Period
Authors: Mingyuan Wang , Xue Yang
Published: June 2020

China’s economic model is transforming from a traditional planned economy to a modern market economy, in which context great changes have also taken place in the field of energy. From law, policy, and reform perspectives, this chapter aims to systematically describe the new trend of China’s energy development, including marketization, humanization, and ecologicalization. Based on the theory of energy justice, in particular, distributive justice and intergenerational justice, this chapter will also analyse the coincidence between the new trend of China’s energy development and energy justice, and find out the gap between them. In the transitional period, the Chinese government has made remarkable achievements in energy justice, but there is still a long way to go.
Legal Dimensions of Access to Modern Energy Services in Africa
Authors: Omorogbe Yinka
Published: June 2020

This chapter examines strategies to achieve access to electricity, premised against the necessity for legal solutions and structures that will stimulate or encourage effective implementation of necessary objectives. It primarily focuses on three sub-Saharan African countries, Nigeria, Ghana, and Rwanda, while drawing examples as necessary from other countries in Africa. It opines that electricity access has to be pro-poor. Also that the success or failure of governments to increase energy access is tied to their realization of the criticality of electricity as a catalyst for development, and to the presence of effective policies. Synergy between critical actors is also an essential component.
‘Temporarily’ Abroad: Partisan Organisation and Mobilisation outside Australia
Authors: Gauja Anika
Published: June 2020

This article explores the relationship between partisan organisation outside a country of origin and the voting rights and migration patterns of its citizens. Using Australian political parties operating overseas as case studies, it examines the extent to which the electoral context of expatriate voting influences why and how parties establish organisational structures abroad. Electoral law in Australia allows citizens to vote while living overseas only for a limited period—as long as they intend to return to Australia within six years. Because of this relatively limited opportunity, we might expect party organisations abroad to exist primarily to mobilise support at election times in areas where there are high concentrations of Australian expatriate voters, rather than create lasting communities of partisan supporters. The article finds, in line with this expectation, that ‘parties abroad’ are relatively modest, geographically rooted in cities with large expatriate populations and facilitated by online and social media technologies.
Getting Cold Feet in the First World War: Leaky Boots, Trench Foot and Vernacular Medicine Among British Soldiers
Authors: McWhinney Georgia
Published: June 2020

During the First World War, trench warfare spurred the onset of various medical conditions. Yet, when soldiers fell ill, it was not immediately recognised that some maladies stemmed from contamination—soiling, infestation and poisons—in their uniforms. With a new focus on preventive medicine, doctors and medical scientists investigated numerous medical conditions that spread through contaminated uniforms. It is well known that these medical professionals developed a body of knowledge on the prevention of uniform contamination. It is far less known that soldiers also developed a set of medical ideas. Different ‘systems of medical ideas’ developed simultaneously during the Great War, and this is demonstrated through the study of trench foot. This article employs soldiers’ voices not only to highlight their reliance on vernacular medicine in the trenches but also to reformulate the boundaries of medical practice and ask who can be considered a medical practitioner.
Transcriptome Profiling Data ofBotrytis cinereaInfection on Whole PlantSolanum lycopersicum
Authors: Srivastava Dhruv Aditya , Arya Gulab Chand , Pandaranayaka Eswari PJ , Manasherova Ekaterina , Prusky Dov B. , Elad Yigal , Frenkel Omer , Harel Arye
Published: June 2020

Botrytis cinerea is a foliar necrotrophic fungal-pathogen capable of infecting >580 genera of plants, is often used as model organism for studying fungal-host interactions. We used RNAseq to study transcriptome of B. cinerea infection on a major (worldwide) vegetable crop, tomato (Solanum lycopersicum). Most previous works explored only few infection stages, using RNA extracted from entire leaf-organ diluting the expression of studied infected region. Many studied B. cinerea infection, on detached organs assuming that similar defense/physiological reactions occurs in the intact plant. We analyzed transcriptome of the pathogen and host in 5 infection stages of whole-plant leaves at the infection site. We supply high quality, pathogen-enriched gene count that facilitates future research of the molecular processes regulating the infection process.
Childbearing Decisions in Residency: A Multicenter Survey of Female Residents
Authors: Stack Shobha W. , Jagsi Reshma , Biermann J. Sybil , Lundberg Gina P. , Law Karen L. , Milne Caroline K. , Williams Sigrid G. , Burton Tracy C. , Larison Cindy L. , Best Jennifer A.
Published: June 2020

Purpose

To characterize how female residents make decisions about childbearing, factors associated with the decision to delay childbearing, and satisfaction with these decisions.

Method

In 2017, the authors sent a voluntary, anonymous survey to 1,537 female residents enrolled across 78 graduate medical education programs, consisting of 25 unique specialties, at 6 U.S. academic medical centers. Survey items included personal, partner, and institutional characteristics, whether the respondent was delaying childbearing during residency, and the respondent’s satisfaction with this decision.

Results

The survey response rate was 52% (n = 804). Among the 447 (56%) respondents who were married or partnered, 274 (61%) were delaying childbearing. Residents delaying childbearing were significantly more likely to be younger (P < .001), not currently a parent (P < .001), in a specialty with an uncontrollable lifestyle (P = .001), or in a large program (P = .004). Among self-reported reasons for delaying childbearing, which were not mutually exclusive, the majority cited a busy work schedule (n = 255; 93%) and desire not to extend residency training (n = 145; 53%). Many cited lack of access to childcare (n = 126; 46%), financial concerns (n = 116; 42%), fear of burdening colleagues (n = 96; 35%), and concern for pregnancy complications (n = 74; 27%). Only 38% (n = 103) of respondents delaying childbearing were satisfied with this decision, with satisfaction decreasing with increasing age.

Conclusions

Decisions to delay childbearing are more common in certain specialties, and many residents who delay childbearing are not satisfied with that decision. These findings suggest that greater attention is needed overall, and particularly in certain specialties, to promote policies and cultures that both anticipate and normalize parenthood in residency, thus minimizing the conflict between biological and professional choices for female residents.
Risk Factors for Developing Severe Acute Kidney Injury in Adult Patients With Refractory Postcardiotomy Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation
Authors: Lepère Victoria , Duceau Baptiste , Lebreton Guillaume , Bombled Camille , Dujardin Olivier , Boccara Lucile , Charfeddine Ahmed , Amour Julien , Hajage David , Bouglé Adrien
Published: June 2020

Objectives:

Postcardiotomy cardiogenic shock occurs in 2–6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients.

Design:

Retrospective observational cohort study between January 2013 and December 2016.

Setting:

An 18-bed surgical ICU in a university hospital.

Patients:

A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients.

Interventions:

None.

Measurements and Main Results:

The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3–16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31–6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01–1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02–1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001–1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006–1.018]; p < 0.001) on the day of implantation.

Conclusions:

Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.
Physical, Mental, and Cognitive Health Status of ICU Survivors Before ICU Admission: A Cohort Study
Authors: Geense Wytske W. , van den Boogaard Mark , Peters Marco A. A. , Simons Koen S. , Ewalds Esther , Vermeulen Hester , van der Hoeven Johannes G. , Zegers Marieke
Published: June 2020

Objectives:

Although patient’s health status before ICU admission is the most important predictor for long-term outcomes, it is often not taken into account, potentially overestimating the attributable effects of critical illness. Studies that did assess the pre-ICU health status often included specific patient groups or assessed one specific health domain. Our aim was to explore patient’s physical, mental, and cognitive functioning, as well as their quality of life before ICU admission.

Design:

Baseline data were used from the longitudinal prospective MONITOR-IC cohort study.

Setting:

ICUs of four Dutch hospitals.

Patients:

Adult ICU survivors (n = 2,467) admitted between July 2016 and December 2018.

Interventions:

None.

Measurements and Main Results:

Patients, or their proxy, rated their level of frailty (Clinical Frailty Scale), fatigue (Checklist Individual Strength-8), anxiety and depression (Hospital Anxiety and Depression Scale), cognitive functioning (Cognitive Failure Questionnaire-14), and quality of life (Short Form-36) before ICU admission. Unplanned patients rated their pre-ICU health status retrospectively after ICU admission. Before ICU admission, 13% of all patients was frail, 65% suffered from fatigue, 28% and 26% from symptoms of anxiety and depression, respectively, and 6% from cognitive problems. Unplanned patients were significantly more frail and depressed. Patients with a poor pre-ICU health status were more often likely to be female, older, lower educated, divorced or widowed, living in a healthcare facility, and suffering from a chronic condition.

Conclusions:

In an era with increasing attention for health problems after ICU admission, the results of this study indicate that a part of the ICU survivors already experience serious impairments in their physical, mental, and cognitive functioning before ICU admission. Substantial differences were seen between patient subgroups. These findings underline the importance of accounting for pre-ICU health status when studying long-term outcomes.
Dynamic linkage of COVID-19 test results between Public Health England’s Second Generation Surveillance System and UK Biobank
Authors: Armstrong Jacob , Rudkin Justine K. , Allen Naomi , Crook Derrick W. , Wilson Daniel J. , Wyllie David H. , O’Connell Anne Marie
Published: June 2020

UK Biobank (UKB) is an international health resource enabling research into the genetic and lifestyle determinants of common diseases of middle and older age. It comprises 500 000 participants. Public Health England’s Second Generation Surveillance System is a centralized microbiology database covering English clinical diagnostics laboratories that provides national surveillance of legally notifiable infections, bacterial isolations and antimicrobial resistance. We previously developed secure, pseudonymized, individual-level linkage of these systems. In this study, we implemented rapid dynamic linkage, which allows us to provide a regular feed of new COVID-19 (SARS-CoV-2) test results to UKB to facilitate rapid and urgent research into the epidemiological and human genetic risk factors for severe infection in the cohort. Here, we have characterized the first 1352 cases of COVID-19 in UKB participants, of whom 895 met our working definition of severe COVID-19 as inpatients hospitalized on or after 16 March 2020. We found that the incidence of severe COVID-19 among UKB cases was 27.4 % lower than the general population in England, although this difference varied significantly by age and sex. The total number of UKB cases could be estimated as 0.6 % of the publicly announced number of cases in England. We considered how increasing case numbers will affect the power of genome-wide association studies. This new dynamic linkage system has further potential to facilitate the investigation of other infections and the prospective collection of microbiological cultures to create a microbiological biobank (bugbank) for studying the interaction of environment, human and microbial genetics on infection in the UKB cohort.
Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress
Authors: Rajgarhia Ayan , Ayyasola Kameshwar , Zaghloul Nahla , Da Re Jorge M. Lopez , Miller Edmund J. , Ahmed Mohamed
Published: June 2020

Background

Chronic hypoxic stress induces epigenetic modifications in cardiac fibroblasts, such as inactivation of tumor suppressor genes (RASSF1A), and activation of kinases (ERK1/2). The effects of the antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), on these epigenetic changes has not been fully explored.

Objectives

To define the effect of EC-SOD overexpression on cardiac fibrosis induced by chronic hypoxia.

Methods

Wild type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG) were housed in hypoxia (10% O2) for 21 days. Right ventricular tissue was studied for cardiac fibrosis markers using RT-PCR and Western Blot analyses. Downstream effects were studied, for both RASSF-1 expression and methylation and its relation to ERK1/2, usingin-vivo&in-vitromodels

Results

There were significant increases in markers of cardiac fibrosis : Collagen 1, Alpha Smooth Muscle Actin (ASMA) and SNAIL, in the WT hypoxic animals as compared to the TG hypoxic group (p< 0.05). Expression of DNA methylation enzymes (DNMT 1,2) was significantly increased in the WT hypoxic mice as compared to the hypoxic TG mice (p<0.001). RASSF1A expression was significantly lower and ERK1/2 was significantly higher in hypoxia WT compared to the hypoxic TG group (p<0.05). Use of SiRNA to block RASSF1A gene expression in murine cardiac fibroblast tissue culture led to increased fibroblast proliferation (p<0.05). Methylation of RASSF1A promoter region showed a significant reduction in the TG hypoxic group compared to the WT hypoxic group (0.59 vs 0.75 respectively).

Conclusions

EC-SOD significantly attenuates RASSF1A gene methylation, and plays a pivotal role cardiac fibrosis induced by hypoxia.
Controlling protein nanocage assembly with hydrostatic pressure
Authors: Vay Kristian Le , Carter Ben M. , Watkins Daniel W. , Tang T-Y. Dora , Ting Valeska P. , Cölfen Helmut , Rambo Robert P. , Smith Andrew J. , Anderson J. L. Ross , Perriman Adam W.
Published: June 2020

Controlling the assembly and disassembly of nanoscale protein cages for the capture and internalisation of protein or non-proteinaceous components is fundamentally important to a diverse range of bionanotechnological applications. Here, we study the reversible, pressure-induced dissociation of a natural protein nanocage,E. colibacterioferritin (Bfr), using synchrotron radiation small angle X-ray scattering (SAXS) and circular dichroism (CD). We demonstrate that hydrostatic pressures of 450 MPa are sufficient to completely dissociate the Bfr icositetramer into protein dimers, and the reversibility and kinetics of the reassembly process can be controlled by selecting appropriate buffer conditions. We also demonstrate that the heme B prosthetic group present at the subunit dimer interface influences the stability and pressure lability of the cage, despite its location being discrete from the inter-dimer interface that is key to cage assembly. This indicates a major cage-stabilising role for heme within this family of ferritins.
ENHANCEMENT OF PARVALBUMIN INTERNEURON-MEDIATED NEUROTRANSMISSION IN THE RETROSPLENIAL CORTEX OF ADOLESCENT MICE FOLLOWING THIRD TRIMESTER-EQUIVALENT ETHANOL EXPOSURE
Authors: Bird Clark W. , Chavez Glenna J. , Barber Megan J. , Valenzuela C. Fernando
Published: June 2020

Prenatal ethanol exposure causes a variety of cognitive deficits that have a persistent impact on quality of life, some of which may be explained by ethanol-induced alterations in interneuron function. Studies from several laboratories, including our own, have demonstrated that a single binge-like ethanol exposure during the equivalent to the third trimester of human pregnancy leads to acute apoptosis and long-term loss of interneurons in the rodent retrosplenial cortex (RSC). The RSC is interconnected with the hippocampus, thalamus, and other neocortical regions and plays distinct roles in visuospatial processing and storage, as well as retrieval of hippocampal-dependent episodic memories. Here we used slice electrophysiology to characterize the acute effects of ethanol on GABAergic neurotransmission in the RSC of neonatal mice, as well as the long-term effects of neonatal ethanol exposure on parvalbumin-interneuron mediated neurotransmission in adolescent mice. Mice were exposed to ethanol using vapor inhalation chambers. In postnatal day (P) 7 mouse pups, ethanol unexpectedly failed to potentiate GABAAreceptor-mediated synaptic transmission. Binge-like ethanol exposure of P7 mice expressing channel rhodopsin in parvalbumin-positive interneurons enhanced the peak amplitudes, asynchronous activity and total charge, while decreasing the rise-times of optically-evoked GABAAreceptor-mediated inhibitory postsynaptic currents in adolescent animals. These effects could partially explain the learning and memory deficits that have been documented in adolescent and young adult mice exposed to ethanol during the third trimester-equivalent developmental period.
High-Accuracy Multiplexed SARS-CoV-2 Antibody Assay with Avidity and Saliva Capability on a Nano-Plasmonic Platform
Authors: Liu Tiancheng , Hsiung Jessica , Zhao Su , Kost Jessica , Sreedhar Deepika , Olson Kjerstie , Keare Douglas , Roche John , Hanson Carl V. , Press Cynthia , Boggs John , Rodriguez-Soto Jorge P. , Montoya Jose G. , Tang Meijie , Dai Hongjie
Published: June 2020

The outbreak and rapid spread of SARS-CoV-2 virus has led to a dire global pandemic with millions of people infected and ~ 400,000 deaths thus far. Highly accurate detection of antibodies for COVID-19 is an indispensable part of the effort to combat the pandemic1,2. Here we developed two-plex antibody detection against SARS-CoV-2 spike proteins3(the S1 subunit and receptor binding domain RBD) in human serum and saliva on a near-infrared nano-plasmonic gold (pGOLD) platform4–8. By testing nearly 600 serum samples, pGOLD COVID-19 assay achieved ~ 99.78 % specificity for detecting both IgG and IgM with 100 % sensitivity in sera collected > 14 days post disease symptom onset, with zero cross-reactivity to other diseases. Two-plex correlation analysis revealed higher binding of serum IgM to RBD than to S1. IgG antibody avidity toward multiple antigens were measured, shedding light on antibody maturation in COVID-19 patients and affording a powerful tool for differentiating recent from remote infections and identifying re-infection by SARS-CoV-2. Just as important, due to high analytical sensitivity, the pGOLD COVID-19 assay detected minute amounts of antibodies in human saliva, offering the first non-invasive detection of SARS-CoV-2 antibodies.
Crystal structure of SARS-CoV-2 main protease in complex with a Chinese herb inhibitor shikonin
Authors: Li Jian , Zhou Xuelan , Zhang Yan , Zhong Fanglin , Lin Cheng , McCormick Peter J. , Jiang Feng , Zhou Huan , Wang Qisheng , Duan Jingjing , Zhang Jin
Published: June 2020

Main protease (Mpro, also known as 3CLpro) has a major role in the replication of coronavirus life cycle and is one of the most important drug targets for anticoronavirus agents. Here we report the crystal structure of main protease of SARS-CoV-2 bound to a previously identified Chinese herb inhibitor shikonin at 2.45 angstrom resolution. Although the structure revealed here shares similar overall structure with other published structures, there are several key differences which highlight potential features that could be exploited. The catalytic dyad His41-Cys145 undergoes dramatic conformational changes, and the structure reveals an unusual arrangement of oxyanion loop stabilized by the substrate. Binding to shikonin and binding of covalent inhibitors show different binding modes, suggesting a diversity in inhibitor binding. As we learn more about different binding modes and their structure-function relationships, it is probable that we can design more effective and specific drugs with high potency that can serve as effect SARS-CoV-2 anti-viral agents.
Chloroplast acquisition without the gene transfer in kleptoplastic sea slugs,Plakobranchus ocellatus
Authors: Maeda Taro , Takahashi Shunichi , Yoshida Takao , Shimamura Shigeru , Takaki Yoshihiro , Nagai Yukiko , Toyoda Atsushi , Suzuki Yutaka , Arimoto Asuka , Ishii Hisaki , Satoh Noriyuki , Nishiyama Tomoaki , Hasebe Mitsuyasu , Maruyama Tadashi , Minagawa Jun , Obokata Junichi , Shigenobu Shuji
Published: June 2020

Some sea slugs sequester chloroplasts from algal food in their intestinal cells and photosynthesize for months. This phenomenon, kleptoplasty, poses a question of how the chloroplast retains its activity without the algal nucleus. There have been debates on the horizontal transfer of algal genes to the animal nucleus. To settle the arguments, this study reported the genome of a kleptoplastic sea slugPlakobranchus ocellatusand found no evidence of photosynthetic genes encoded on the nucleus. Nevertheless, it was confirmed that light illumination prolongs the life of mollusk under starvation. These data presented a paradigm that a complex adaptive trait, as typified by photosynthesis, can be transferred between eukaryotic kingdoms by a unique organelle transmission without nuclear gene transfer. Our phylogenomic analysis showed that genes for proteolysis and immunity undergo gene expansion and are up-regulated in chloroplast-enriched tissue, suggesting that these molluskan genes are involved in the DNA-independent phenotype acquisition.
Detection of SARS-CoV-2 RNA by multiplex RT-qPCR
Authors: Kudo Eriko , Israelow Benjamin , Vogels Chantal B.F. , Lu Peiwen , Wyllie Anne L. , Tokuyama Maria , Venkataraman Arvind , Brackney Doug E , Ott Isabel M. , Petrone Mary E. , Earnest Rebecca , Lapidus Sarah , Muenker M. Catherine , Moore Adam J. , Casanovas-Massana Arnau ,   Yale IMPACT Research Team, Omer Saad B. , Cruz Charles S. Dela , Farhadian Shelli F. , Ko Albert I. , Grubaugh Nathan D. , Iwasaki Akiko
Published: June 2020

The current RT-qPCR assay recommended for SARS-CoV-2 testing in the United States requires analysis of three genomic targets per sample: two viral and one host. To simplify testing and reduce the volume of required reagents, we developed a multiplex RT-qPCR assay to detect SARS-CoV-2 in a single reaction. We used existing N1, N2, and RP primer and probe sets by the CDC, but substituted fluorophores to allow multiplexing of the assay. The cycle threshold (Ct) values of our multiplex RT-qPCR were comparable to those obtained by the singleplex assay adapted for research purposes. Low copies (>500 copies / reaction) of SARS-CoV-2 RNA were consistently detected by the multiplex RT-qPCR. Our novel multiplex RT-qPCR improves upon current singleplex diagnostics by saving reagents, costs, time and labor.
Single cell transcriptomic profiling identifies molecular phenotypes of newborn human lung cells
Authors: Bhattacharya Soumyaroop , Myers Jacquelyn L. , Baker Cameron , Guo Minzhe , Danopoulos Soula , Myers Jason R. , Bandyopadhyay Gautam , Romas Stephen , Huyck Heidie L. , Misra Ravi S. , Dutra Jennifer , Holden-Wiltse Jeanne , McDavid Andrew , Ashton John M. , Alam Denise Al , Potter S. Steven , Whitsett Jeffrey A. , Xu Yan , Pryhuber Gloria S. , Mariani Thomas J.
Published: June 2020

Rationale

While animal model studies have extensively defined mechanisms controlling cell diversity in the developing mammalian lung, the limited data available from late stage human lung development represents a significant knowledge gap. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung.

Methods

Single cell RNA sequencing generated transcriptional profiles of 5500 cells obtained from two one-day old human lungs (born at gestational ages of 39 and 31 weeks) from the LungMAP Human Tissue Core Biorepository at the University of Rochester. Frozen single cell isolates were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Single cell sequence data from 32000 postnatal day 1, 3, 7 and 10 mouse lung (n = 2 at each time point) cells generated by the LungMAP Research Center at Cincinnati Children’s Hospital and Medical Center, using Dropseq platform, was integrated with the human data. In situ hybridization was used to confirm the spatial location of cellular phenotypes.

Results

Transcriptional interrogation of donor newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, and immune cells and signature genes for each of these populations were identified. Computational integration of newborn human and postnatal mouse lung development cellular transcriptomes facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the human and mouse cellular transcriptomes also demonstrated cell type-specific differences in developmental states of the newborn human lung cells. In particular, matrix fibroblasts could be separated into those representative of younger cells (n=393), or older cells (n=158).

This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of development. Our results indicate that integrated single cell RNA profiling of human and mouse lung will help identify common and species-specific mechanisms of lung development and respiratory disease.
Longitudinal Saliva Omics Responses to Immune Perturbation: A Case Study
Authors: Mias George I. , Singh Vikas Vikram , Rogers Lavida R.K. , Xue Shuyue , Zheng Minzhang , Domanskyi Sergii , Kanada Masamitsu , Piermarocchi Carlo , He Jin
Published: June 2020

Saliva omics, a rapidly developing field for non-invasive diagnostics, may be utilized for monitoring very young or elderly populations, as well as individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over 100 timepoints, over three periods involving: (i) hourly sampling over 24 hours without intervention, (ii) hourly sampling over 24 hours including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (iii) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome were profiled, and salivary extracellular vesicles were derived, from which small-RNA sequencing was used to determine RNA, miRNA, piRNA and bacterial RNA components. The two 24-hour periods were used in a paired analysis to reveal vaccination responses. Temporal trends were classified and collective behavior revealed broad immune-responses captured in saliva, both at the innate as well as the adaptive response time frames.
Time Course of COVID-19 epidemic in Algeria: Retrospective estimate of the actual burden
Authors: Hamidouche Mohamed , Belmessabih Nassira
Published: June 2020

Since December 2019, the five continents have been incrementally invaded by SARS-CoV-2. Africa is the last and least affected to date. However, Algeria is among the first countries affected since February 25, 2020. In order to benefit from its experience in the least affected countries, this study aims to describe the epidemic’s current situation and then retrospectively estimate its real burden.

As a first part of the study, we described the epidemic’s indicators as; the cumulative and daily reported cases and deaths, and we computed the R0 evolution. Secondly, we used the New York City cases-fatality rate standardized by Algerian age structure, to retrospectively estimate the actual burden.

We found that reported cases are in a clear diminution, but, the epidemic epicentre is moving from Blida to other cities. We noted a clear peak in daily cases-fatality from March 30, to April 17, 2020, Fig. 3, due to underestimating the actual infections of the first 25 days. Since May 8, 2020, the daily R0 is around one, Fig. 4. Moreover, we noticed 31% reduction of its mean value from 1,41 to 0,97 between the last two months. The Algerian Age-Standardized Infection Fatality Rate we found is 0,88%. Based on that, we demonstrated that only 1,5% of actual infections were detected and reported before March 30, and 20% after March 31, Fig. 5. Therefore, the actual infections burden is currently five times higher than reported. At the end, we found that at least 0,2 % of the population have been infected until May 27. Consequently, the acquired herd immunity to date is therefore not sufficient to avoid a second wave.

We believe that, the under estimation of the epidemic’s actual burden is probably due to the lack of testing capacities, however, all the indicators show that the situation is currently controlled. This requires more vigilance for the next weeks during the gradual easing of the preventive measures.
Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts
Authors: Kwong Alex S. F. , Pearson Rebecca M. , Adams Mark J. , Northstone Kate , Tilling Kate , Smith Daniel , Fawns-Ritchie Chloe , Bould Helen , Warne Naomi , Zammit Stan , Gunnell David , Moran Paul , Micali Nadia , Reichenberg Abraham , Hickman Matthew , Rai Dheeraj , Haworth Simon , Campbell Archie , Altschul Drew , Flaig Robin , McIntosh Andrew M. , Lawlor Deborah A. , Porteous David , Timpson Nicholas J.
Published: June 2020

Background

The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic?

Methods

We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parent’s generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19.

Findings

In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers.

Interpretation

These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services.

Funding

The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.