bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational analysis of human host binding partners of chikungunya and dengue viruses during coinfection
Authors: Ghildiyal Ritu , Gabrani Reema 
Published: September 2021

ABSTRACTMosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are transmitted by the same vector. Thus, the probability of their coinfection gets increased with more severe clinical complications in the patients. The present study was undertaken to elucidate the common human interacting partners of CHIKV and DENV proteins during coinfection. The viral–host protein–protein interactome was constructed using Cytoscape. Subsequently, significant host interactors were identified during coinfection. The network analysis elucidated 57 human proteins interacting with both CHIKV and DENV, represented as hub-bottlenecks. The functional and biological analyses of the 40 hub-bottlenecks revealed that they are associated with phosphoinositide 3-kinases (PI3K)/AKT, p53 signaling pathways, regulation of cell cycle and apoptosis during coinfection. Moreover, the molecular docking analysis uncovered the tight and robust binding of selected hub-bottlenecks with CHIKV/DENV proteins. Additionally, 23 hub-bottlenecks were predicted as druggable candidates that could be targeted to eradicate the host–viral interactions. The elucidated common host binding partners during DENV and CHIKV coinfection as well as indicated approved drugs can support the therapeutics development.
Identifying Site-Specific Superoxide and Hydrogen Peroxide Production Rates From the Mitochondrial Electron Transport System Using a Computational Strategy
Authors: Duong Quynh V , Levitsky Yan , Dessinger Maria J , Strubbe-Rivera Jasiel O , Bazil Jason N 
Published: September 2021

Abstract
Mitochondrial reactive oxygen species (ROS) play important roles in cellular signaling; however, certain pathological conditions such as ischemia/reperfusion (I/R) injury disrupt ROS homeostasis and contribute to cell death. A major impediment to developing therapeutic measures against oxidative stress-induced cellular damage is the lack of a quantitative framework to identify the specific sources and regulatory mechanisms of mitochondrial ROS production. We developed a thermodynamically consistent, mass-and-charge balanced, kinetic model of mitochondrial ROS homeostasis focused on redox sites of electron transport chain complexes I, II, and III. The model was calibrated and corroborated using comprehensive data sets relevant to ROS homeostasis. The model predicts that complex I ROS production dominates other sources under conditions favoring a high membrane potential with elevated nicotinamide adenine dinucleotide (NADH) and ubiquinol (QH2) levels. In general, complex I contributes to significant levels of ROS production under pathological conditions, while complexes II and III are responsible for basal levels of ROS production, especially when QH2 levels are elevated. The model also reveals that hydrogen peroxide production by complex I underlies the non-linear relationship between ROS emission and O2 at low O2 concentrations. Lastly, the model highlights the need to quantify scavenging system activity under different conditions to establish a complete picture of mitochondrial ROS homeostasis. In summary, we describe the individual contributions of the electron transport system complex redox sites to total ROS emission in mitochondria respiring under various combinations of NADH- and Q-linked respiratory fuels under varying workloads.
The Association Between Epigenetic Clocks and Physical Functioning in Older Women: A 3-Year Follow-up
Authors: Föhr Tiina , Törmäkangas Timo , Lankila Hannamari , Viljanen Anne , Rantanen Taina , Ollikainen Miina , Kaprio Jaakko , Sillanpää Elina 
Published: September 2021

AbstractBackgroundEpigenetic clocks are composite markers developed to predict chronological age or mortality risk from DNA methylation (DNAm) data. The present study investigated the associations between 4 epigenetic clocks (Horvath’s and Hannum’s DNAmAge and DNAm GrimAge and PhenoAge) and physical functioning during a 3-year follow-up.MethodWe studied 63- to 76-year-old women (N = 413) from the Finnish Twin Study on Aging. DNAm was measured from blood samples at baseline. Age acceleration (AgeAccel), that is, discrepancy between chronological age and DNAm age, was determined as residuals from linear model. Physical functioning was assessed under standardized laboratory conditions at baseline and at follow-up. A cross-sectional analysis was performed with path models, and a longitudinal analysis was conducted with repeated measures linear models. A nonrandom missing data analysis was performed.ResultsIn comparison to the other clocks, GrimAgeAccel was more strongly associated with physical functioning. At baseline, GrimAgeAccel was associated with lower performance in the Timed Up and Go (TUG) test and the 6-minute walk test. At follow-up, significant associations were observed between GrimAgeAccel and lowered performance in the TUG, 6-minute and 10-m walk tests, and knee extension and ankle plantar flexion strength tests.ConclusionsThe DNAm GrimAge, a novel estimate of biological aging, associated with decline in physical functioning over the 3-year follow-up in older women. However, associations between chronological age and physical function phenotypes followed similar pattern. Current epigenetic clocks do not provide strong benefits in predicting the decline of physical functioning at least during a rather short follow-up period and restricted age range.
A National Study of Racial–Ethnic Differences in COVID-19 Concerns Among Older Americans: Evidence From the Health and Retirement Study
Authors: Lin Zhiyong , Liu Hui 
Published: September 2021

Abstract

Objectives
Concerns about coronavirus disease 2019 (COVID-19) are an important emotional reaction to the pandemic and represent a key pandemic-related mental health outcome. We provide the first population-based evidence of racial–ethnic differences in COVID-19 concerns among older Americans during the COVID-19 outbreak.

Methods
We analyzed data from the 2020 Health and Retirement Study COVID-19 project. The sample included 2,879 respondents (aged 50 and older) who were interviewed from June to September 2020 and had completed measures on COVID-19 concerns and other key covariates. Ordinary least squares regression models were estimated to assess racial–ethnic differences in COVID-19 concerns. Formal mediation analysis was conducted to test potential mediating roles of exposures to COVID-19 risks, preexisting health status, and socioeconomic resources in accounting for racial–ethnic differences in COVID-19 concerns.

Results
Non-Hispanic Black and Hispanic Americans showed significantly greater concerns about the COVID-19 pandemic than non-Hispanic White Americans. Racial–ethnic minority older adults also had higher proportions of knowing someone who had contracted or died from COVID-19 than White older adults. Unequal exposures to COVID-19 risks by race–ethnicity and, to a lesser degree, preexisting health inequalities accounted for only part of the racial–ethnic differences in COVID-19 concerns.

Discussion
Our findings call for more research and policy interventions to lessen the disproportionate burden of COVID-19 experienced by older adults of racial–ethnic minority groups.
Enhanced glycolysis and GSK3 inactivation promote brain metabolic adaptations following neuronal mitochondrial stress
Authors: Garcia Sofia , Saldana-Caboverde Amy , Anwar Mir , Raval Ami Pravinkant , Nissanka Nadee , Pinto Milena , Moraes Carlos Torres , Diaz Francisca 
Published: September 2021

Abstract
We analyzed early brain metabolic adaptations in response to mitochondrial dysfunction in a mouse model of mitochondrial encephalopathy with complex IV deficiency [neuron-specific COX10 knockout (KO)]. In this mouse model, the onset of the mitochondrial defect did not coincide with immediate cell death, suggesting early adaptive metabolic responses to compensate for the energetic deficit. Metabolomic analysis in the KO mice revealed increased levels of glycolytic and pentose phosphate pathway intermediates, amino acids and lysolipids. Glycolysis was modulated by enhanced activity of glycolytic enzymes, and not by their overexpression, suggesting the importance of post-translational modifications in the adaptive response. Glycogen synthase kinase 3 inactivation was the most upstream regulation identified, implying that it is a key event in this adaptive mechanism. Because neurons are thought not to rely on glycolysis for adenosine triphosphate production in normal conditions, our results indicate that neurons still maintain their ability to upregulate this pathway when under mitochondrial respiration stress.
Impending disaster: rise of the epsilon variant in Pakistan and the way forward
Authors: Moin Alina , Usmani Shajie Ur Rehman , Khan Hashim 
Published: September 2021

Abstract
The constantly mutating severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) does not appear to be slowing down any time soon. All countries, particularly developing countries, must adapt and strategically plan their way of life around the pandemic, while doing everything possible to keep the mortality rate and spread of the newly emerging variants as low as possible, in order to avoid a further blow to the economy and way of life. Pakistan is one such developing country that is currently battling the dangerous delta strain of SARS-COV-2 with limited resources and has recently seen the emergence of an equally transmissible and highly infectious epsilon strain. This is a concerning situation considering that Pakistan's already overburdened health system and faltering economy cannot withstand another dangerous SARS-COV-2 variant attack. This article highlights some strategies for the country to fortify its defences to prevent the epsilon variant from spreading before it is too late, and emphasises that while identifying potential immune evasion mechanisms in SARS-COV-2 variants is critical in the fight against COVID-19, it is also critical to develop methods of efficient and cost-effective detection to identify an early outbreak and then vigilantly and systematically plan area lockdowns before any hope of conquering this pandemic is lost.
Taxonomic Diversity of the Quill Mites of the Family Syringophilidae (Acariformes: Prostigmata) Associated With Old World Parrots (Psittaciformes: Psittaculidae)
Authors: Marciniak–Musial Natalia , Hromada Martin , Sikora Bozena 
Published: September 2021

Abstract
The quill mite fauna of the family Syringophilidae Lavoipierre, 1953 (Acariformes: Prostigmata) associated with parrots (Aves: Psittaciformes) are reviewed. Seven new species are described: Pipicobia cyclopsitta Marciniak-Musial, Hromada & Sikora sp. nov. from the Double-Eyed Fig-Parrot Cyclopsitta diophthalma in Papua New Guinea; P. fuscata Marciniak-Musial, Hromada & Sikora sp. nov. from the Dusky Lory Pseudeos fuscata in Papua New Guinea; P. tahitiana Marciniak-Musial, Hromada & Sikora sp. nov. from the Blue Lorikeet Vini peruviana in Tahiti (French Polynesia); P. malherbi Marciniak-Musial, Hromada & Sikora sp. nov. from the Malherbe’s Parakeet Cyanoramphus malherbi in New Zealand; Lawrencipicobia eclectus Marciniak-Musial, Hromada & Sikora sp. nov. from the Eclectus Parrot Eclectus roratus in Papua New Guinea; Neoaulobia pseudeos Marciniak-Musial, Hromada & Sikora sp. nov. from the Dusky Lory Pseudeos fuscata in Papua New Guinea; and N. Skorackii Marciniak-Musial, Hromada & Sikora sp. nov. from the Eastern Rosella Platycercus eximius in Australia.
Aspects of the Ventive-Energic in Official Aramaic
Authors: Sjörs Ambjörn 
Published: September 2021

Abstract
The use of a linking element -n- between the verb stem of the imper- fective and an object pronoun suffix is a well-known feature of Western Aramaic languages and dialects. This linking element is traditionally thought to be formally related to the so-called energic suffixes in West Semitic, which in turn are assumed to be cognate with the ven- tive morpheme in Akkadian. It is argued that the formal identification of the energic with the ventive can explain the morphophonological distribution of the linking element -n- in Biblical Aramaic and that the functional identification of the energic with the ventive can explain the use of -n without an object pronoun suffix in the A$$hiqar proverbs as a reflexive-benefactive marker.1
Treatise on International Criminal Law
Authors: Ambos Kai 
Published: September 2021

Abstract
This second edition of Volume I of the three-volume Treatise on International Criminal Law addresses the foundations of international criminal law and the emerging general principles. It examines the history of the discipline and the concepts behind it. Starting with the development of international criminal justice, the book proceeds as follows: it attends to the sources of international criminal law, then moves to investigate the general structure of crime in international criminal law, and addresses in detail the concept and forms of individual criminal responsibility; it then turns to the subjective requirements of criminal responsibility, and defences that exclude such responsibility. International criminal justice is a flourishing field, with the birth of new international criminal tribunals and both accountability and investigative mechanisms. Case law increases rapidly, so does the ensuing substantive scholarship. This is also true for international criminal law’s foundations and general principles, treated in this volume. Thus, the previous edition has been completely revised, updated, and rewritten in some parts. The author strived to include both relevant case law and scholarly work up to March 2021.
International Criminal Justice Institutions: From the First Ad Hoc Tribunals and Their Precedents to the ICC and Beyond
Authors: Ambos Kai 
Published: September 2021

Abstract
This chapter is both an institutional and historical analysis of International Criminal Justice. Even though the International Military Tribunals in Nuremberg and Tokyo are widely perceived as the birth of International Criminal Justice, the chapter starts with historical precedents of these tribunals: for instance, the Versailles Peace Treaty (VPT) as the first international instrument providing for the prosecution of war criminals. The international Nuremberg and Tokyo tribunals are then examined in detail and from several perspectives – except the procedural perspective that is dealt with by Volume III. These tribunals laid the groundwork for subsequent Tribunals and mechanisms. Thus, the chapter proceeds with the establishment of the UN Ad Hoc Tribunals, the International Criminal Court and the more recent mixed or hybrid Tribunals. The focus of the analysis lies on the development of those tribunals, their institutional setting, and main aspects of both their legal regime and developed case law. The practice of the ICC is especially evaluated against the background of criticism regarding its alleged African focus or even bias. The last section on hybrid tribunals also takes a broader look at other investigative and accountability mechanisms.
Omission, in Particular Command Responsibility
Authors: Ambos Kai 
Published: September 2021

Abstract
This chapter continues the effort of this Volume to combine both comparative legal concepts with unique features of International Criminal Law. It is thus a direct result of the foundational work in Chapter II: International Criminal Law’s focus on individual criminal responsibility leads to an expressive purpose of punishments that again requires a criminalization of remote behavior by commanders and State leaders. This criminalization is based on the centuries old debate revolving around liability for omission. The chapter thus starts with a general explanation of the concept of omission vis-á-vis action. The author answers the question of whether a general omission liability exists in International Criminal Law affirmatively, recognizing a general principle of law, albeit with strict requirements. Drawing on the results from Chapter II, the author argues in favor of a criminalization of omission based on the prevention of harm and the protection of important legal goods/interests. The basis for this criminalization/liability is the respective person’s duty to act.
The
Principle of Non-refoulement—Part 2
Authors: Goodwin-Gill Guy S , McAdam Jane , Dunlop Emma 
Published: September 2021

Abstract
This chapter details how, under general principles of international law, State responsibility may arise directly from the acts and omissions of government officials and agents, or indirectly where domestic legal and administrative systems fail to implement the observance of international standards. The fact that the harm caused by State action may be inflicted outside the territory of the actor, or in an area identified by municipal law as an international zone, in no way diminishes the responsibility of the State. While the principle of non-refoulement does not entail a right for refugees to be granted asylum in a particular State, it does require States to ensure that whatever course of action they adopt, refugees are not sent—either directly or indirectly—to a place where their lives or freedom would be in danger on account of one of the five Convention grounds, or contrary to the principle of non-refoulement under human rights law. In order to give effect to those obligations consistently with the general rule, ‘States will be required to grant individuals seeking international protection access to the territory and to fair and efficient asylum procedures’. The chapter then looks at the relationship between the principle of non-refoulement and flight by sea.
International Cooperation, Protection, and
Solutions
Authors: Goodwin-Gill Guy S , McAdam Jane , Dunlop Emma 
Published: September 2021

Abstract
This chapter addresses international cooperation, protection, and solutions. ‘Protection’ is useful shorthand to describe the complex of obligations derived from general international law and from international refugee and human rights law. ‘Protection’ is often an end in itself, but it also has a goal beyond that moment, which is a durable solution in which refugees can live in safety and with dignity, not subject to arbitrary expulsion, discrimination, or alienation. ‘Solutions’, in turn, is the overarching objective of the international refugee regime itself, premised upon international cooperation to solve humanitarian problems, which is among the purposes and guiding principles of the United Nations. The chapter considers the rights background which undergirds the situation of the displaced, and then examines the three traditional durable solutions of voluntary repatriation, local integration, and resettlement, as well as labour mobility and other complementary pathways that may secure refugees admission to, and inclusion in, a State.
Treaty Standards and their Implementation in National
Law
Authors: Goodwin-Gill Guy S , McAdam Jane , Dunlop Emma 
Published: September 2021

Abstract
This chapter describes how the main treaties governing the status and treatment of refugees have attracted wide, if not universal acceptance, although they do not in fact either comprehend every refugee known to the world, or, in many cases, offer any but the most basic guarantees. Indeed, both the 1951 Convention and the 1967 Protocol are widely accepted. For those found to qualify, the benefits for which they call are often improved upon in actual practice, and supplemented substantially or filled out by the provisions of regional and related instruments. The Convention and the Protocol represent a point of departure in considering the appropriate standard of treatment of refugees, often exceeded, but still at base proclaiming the fundamental principles of protection, without which no refugee can hope to attain a satisfactory and lasting solution to his or her plight. The chapter examines the provisions of these and related agreements, with a view to determining the appropriate convention standards of treatment applicable to refugees and asylum seekers, whether lawfully or unlawfully in the territory of contracting States.
Displacement related to the Impacts of Disasters and
Climate Change
Authors: Goodwin-Gill Guy S , McAdam Jane , Dunlop Emma 
Published: September 2021

Abstract
This chapter explores the nature of movement occasioned by the impacts of disasters and climate change. There is scientific consensus that the effects of climate change are aggravating and amplifying many ‘natural’ environmental hazards. This, in turn, may threaten a range of human rights including the right to life, health, housing, culture, means of subsistence, and the right to be free from inhuman or degrading treatment. Moreover, disasters linked to sudden-onset natural hazards continue to trigger the largest number of new internal displacements annually. The chapter then considers the law as it pertains to internally displaced persons (IDPs), as well as the limits and capacity of the international and regional legal frameworks that may apply to those who were displaced across an international border (refugee law, human rights law, and the law on statelessness). While a number of international instruments now include language on climate change, disasters, and displacement, including the 2018 Global Compact for Safe, Orderly and Regular Migration, more is required to give full effect to these undertakings, both with regard to the capacity to anticipate displacement, and to determine what kind of ‘protection’ is called for, by whom, and where.
Nationality, Statelessness, and Protection
Authors: Goodwin-Gill Guy S , McAdam Jane , Dunlop Emma 
Published: September 2021

Abstract
This chapter studies nationality, statelessness, and protection. Domestic law determines the content of nationality, and historically only those elements of nationality bearing on the relations between States were considered of relevance to international law. Questions of nationality, therefore, are in principle within the reserved domain of domestic jurisdiction, even if that leaves many questions open. At one time, it was easier to envisage that the realm of the domestic might not be co-extensive with the realm of the international—that a State’s nationals for the purposes of international law, might yet be divided ‘back home’ into those who did, and those who did not, enjoy the full benefits of civil status. In a post-modern age sensible of human rights, such distinctions, though not unknown, are difficult to justify. If the domestic conception of citizenship did not encompass a sense of protection by the State, including admission or re-admission, then it failed as an instance of nationality in the sense of international law. The chapter then reflects on statelessness in international law and practice. It looks at the elimination and prevention of statelessness and the protection of stateless refugees.