bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency and bioavailability of new synthetic strigolactone mimics with potential for sustainable agronomical applications
Authors: Borghi Lorenzo , Screpanti Claudio , Lumbroso Alexandre , Lachia Mathilde , Gübeli Christian , De Mesmaeker Alain
Published: May 2021

Purpose

Arbuscular mycorrhizal fungi (AMF) play important roles in agriculture because of their ability to improve plant resilience against abiotic and biotic stresses. AMF as a technology to promote a more sustainable agriculture holds great potential, yet many factors affect the efficiency of this plant-microbe symbiosis leading to inconsistency in performance. The beneficial symbiosis between plants and AM fungi, also-known-as the mycorrhiza is promoted by strigolactones (SLs), carotenoid derivatives active as phytohormones and rhizosphere signals. Natural SLs are effective at extremely low concentrations, however their bioavailability in soil is scarce because their biosynthesis and exudation are plant-regulated, their degradation is fast and their mobility in soil is limited.

Methods

Through a broad synthetic chemistry approach, we explored how structurally diverse SL derivatives could improve hyphal branching ofGigaspora sppAMF under laboratory conditions and thus possibly boost mycorrhization into soil.

Results

We tested twenty-six different derivatives and we could highlight structural enhancements to promote hyphal branching of in vitro germinated AMF spores at equal, and in some cases higher levels compared to natural SLs. A subset of these derivatives was tested for bioavailability, but no clear correlation was found with their activity on hyphal branching.

Conclusion

This study suggests that we could use a targeted, chemical-design approach to synthetize new SL derivatives to enable enhanced promotion of mycorrhization and potentially enhanced bioavailability compared to natural SLs. Due to the roles of AMF in crop production systems, these results highlight new innovative approaches to promote sustainable agriculture.
Endowment effects in the risky investment game?
Authors: Holden Stein T. , Tilahun Mesfin
Published: May 2021

The risky investment game of Gneezy and Potters (Q J Econ 112(2):631–645, 1997) has been proposed as a simple tool to measure risk aversion in applied settings, especially attractive in settings where participants may have limited education. However, this game can produce a significant endowment effect (attached to the initial position), so that analysis of the behavior in this game should not be done in the Expected Utility Theory (EUT) framework. The paper illustrates this point, by showing that risk tolerance can be much higher when the initial endowment concerns a risky lottery.
Decrease in Skin Prion-Seeding Activity of Prion-Infected Mice Treated with a Compound Against Human and Animal Prions: a First Possible Biomarker for Prion Therapeutics
Authors: Ding Mingxuan , Teruya Kenta , Zhang Weiguanliu , Lee Hae Weon , Yuan Jue , Oguma Ayumi , Foutz Aaron , Camacho Manuel V. , Mitchell Marcus , Greenlee Justin J. , Kong Qingzhong , Doh-ura Katsumi , Cui Li , Zou Wen-Quan
Published: May 2021

Previous studies have revealed that the infectious scrapie isoform of prion protein (PrPSc) harbored in the skin tissue of patients or animals with prion diseases can be amplified and detected through the serial protein misfolding cyclic amplification (sPMCA) or real-time quaking-induced conversion (RT-QuIC) assays. These findings suggest that skin PrPSc-seeding activity may serve as a biomarker for the diagnosis of prion diseases; however, its utility as a biomarker for prion therapeutics remains largely unknown. Cellulose ethers (CEs, such as TC-5RW), widely used as food and pharmaceutical additives, have recently been shown to prolong the lifespan of prion-infected mice and hamsters. Here we report that in transgenic (Tg) mice expressing hamster cellular prion protein (PrPC) infected with the 263K prion, the prion-seeding activity becomes undetectable in the skin tissues of TC-5RW-treated Tg mice by both sPMCA and RT-QuIC assays, whereas such prion-seeding activity is readily detectable in the skin of untreated mice. Notably, TC-5RW exhibits an inhibitory effect on the in vitro amplification of PrPSc in both skin and brain tissues by sPMCA and RT-QuIC. Moreover, we reveal that TC-5RW is able to directly decrease protease-resistant PrPSc and inhibit the seeding activity of PrPSc from chronic wasting disease and various human prion diseases. Our results suggest that the level of prion-seeding activity in the skin may serve as a useful biomarker for assessing the therapeutic efficacy of compounds in a clinical trial of prion diseases and that TC-5RW may have the potential for the prevention/treatment of human prion diseases.
The Life History of Learning Subsistence Skills among Hadza and BaYaka Foragers from Tanzania and the Republic of Congo
Authors: Lew-Levy Sheina , Ringen Erik J. , Crittenden Alyssa N. , Mabulla Ibrahim A. , Broesch Tanya , Kline Michelle A.
Published: May 2021

Aspects of human life history and cognition, such as our long childhoods and extensive use of teaching, theoretically evolved to facilitate the acquisition of complex tasks. The present paper empirically examines the relationship between subsistence task difficulty and age of acquisition, rates of teaching, and rates of oblique transmission among Hadza and BaYaka foragers from Tanzania and the Republic of Congo. We further examine cross-cultural variation in how and from whom learning occurred. Learning patterns and community perceptions of task difficulty were assessed through interviews. We found no relationship between task difficulty, age of acquisition, and oblique transmission, and a weak but positive relationship between task difficulty and rates of teaching. While same-sex transmission was normative in both societies, tasks ranked as more difficult were more likely to be transmitted by men among the BaYaka, but not among the Hadza, potentially reflecting cross-cultural differences in the sexual division of subsistence and teaching labor. Further, the BaYaka were more likely to report learning via teaching, and less likely to report learning via observation, than the Hadza, possibly owing to differences in socialization practices.
The policy consequences of defining rewilding
Authors: Schulte to Bühne Henrike , Pettorelli Nathalie , Hoffmann Michael
Published: May 2021

More than 30 years after it was first proposed as a biodiversity conservation strategy, rewilding remains a controversial concept. There is currently little agreement about what the goals of rewilding are, and how these are best achieved, limiting the utility of rewilding in mainstream conservation. Achieving consensus about rewilding requires agreeing about what “wild” means, but many different definitions exist, reflecting the diversity of values in conservation. There are three key debates that must be addressed to find a consensual definition of “wild”: (1) to which extent can people and “wild” nature co-exist?; (2) how much space does “wild” nature need? and (3) what kinds of “wild” nature do we value? Depending on the kinds of “wild” nature rewilding aims to create, rewilding policy will be faced with managing different opportunities and risks for biodiversity and people.
Microplastic pollution in African countries’ water systems: a review on findings, applied methods, characteristics, impacts, and managements
Authors: Aragaw Tadele Assefa
Published: May 2021

Owed to their simplicity, flexibility, lightweight, and low cost, plastics have become highly demanded in Africa as well as worldwide. However, the management of plastic wastes, particularly in African countries, is inadequate and most of the plastic debris is gatewayed into the water bodies. Nowadays, environmentalists, organizations, and governments are aware of microplastic pollution in the marine and terrestrial environment. Thus, addressing a compressive literature review in one referenced paper, as they draw up the articles, is essential to propose new research directions, to synthesize the existing theories among the existing studies. The abundance of microplastics is variable depending on the sampling and identification techniques. In this review, the available publications on microplastic pollution in African countries’ water systems were retrieved. Investigations found that microplastic pollution levels in the studied water bodies were reported in high concentrations. It was observed that different sampling and analytical methods were applied for the detection of microplastics, and suggestions were raised at it may affect the reliability of the results. Most of the detected and quantified microplastics were confirmed as they are from secondary sources. Most of the microplastic pollution research was conducted dominantly in South Africa, and secondly Nigeria, although other countries should also start conducting in their water systems. Surface water and sediment samples were dominantly carried out, but are limited with biota samples; hence, the risk assessment of microplastics is not yet determined. Some of the African countries have regulations on the prevention of macroplastic wastes, but the implementations are unsuccessful and most have not yet been established resulting in a threat of microplastics pollution. Thus, the research priorities on microplastic detection should be identified, and the African countries’ governments should be more proactive in eradicating macroplastic, which ends up as microplastics, pollutions in the water environments.

Graphic abstract

Article Highlights

Researches on microplastic pollution in African countries water system is limited .

A high microplastics abundance is found in African countries water system.

Sampling methods and used analytical techniques for microplastic detection were included.

Harmonized standard methods for microplastic pollution research should be established.

Combined analytical tools at once should be adopted to detect reliable microplastics.
Quantum Field Theory
Authors: Kleiss Ronald
Published: May 2021

Quantum field theory (QFT), the language of particle physics, is crucial to a physicist's graduate education. Based on lecture notes for courses taught for many years at Radboud University in the Netherlands, this book presents an alternative approach to teaching QFT using Feynman diagrams. A diagrammatic approach to understanding QFT exposes young physicists to an orthogonal introduction to the theory, bringing new ways to understand challenges in the field. Diagrammatic techniques using Feynman diagrams are used didactically, starting from simple discussions in lower dimensions to more complex topics in the Standard Model. Worked-out examples and exercises help the reader develop a deep understanding and intuition that enhances their problem-solving skills and understanding of QFT. Classroom-tested, this accessible textbook is valuable for physics graduates and for researchers.
Money and the Rule of Law
Authors: Boettke Peter J. , Salter Alexander William , Smith Daniel J.
Published: May 2021

Contemporary monetary institutions are flawed at a foundational level. The reigning paradigm in monetary policy holds up constrained discretion as the preferred operating framework for central banks. But no matter how smart or well-intentioned are central bankers, discretionary policy contains information and incentive problems that make macroeconomic stability systematically unlikely. Furthermore, central bank discretion implicitly violates the basic jurisprudential norms of liberal democracy. Drawing on a wide body of scholarship, this volume presents a novel argument in favor of embedding monetary institutions into a rule of law framework. The authors argue for general, predictable rules to provide a sturdier foundation for economic growth and prosperity. A rule of law approach to monetary policy would remedy the flaws that resulted in misguided monetary responses to the 2007-8 financial crisis and the COVID-19 pandemic. Understanding the case for true monetary rules is the first step toward creating more stable monetary institutions.
The Nature of Desert Claims
Authors: Kinghorn Kevin
Published: May 2021

Our everyday conversations reveal the widespread assumption that positive and negative treatment of others can be justified on the grounds that 'they deserve it'. But what is it exactly to deserve something? In this book, Kevin Kinghorn explores how we came to have this concept and offers an explanation of why people feel so strongly that redress is needed when outcomes are undeserved. Kinghorn probes for that core concern which is common to the range of everyday desert claims people make, ultimately proposing an alternative model of desert which represents a fundamental challenge to the received wisdom on the structure of desert claims. In the end, he argues, our plea for deserved treatment ends up being linked to the universal human concern for a shared narrative, as we seek healthy relationships within a community.
Collegiate Principal Structures in Implementing a School Behaviour Support Program: The Role of the Local Management Group Model
Authors: Foggett Judith , Conway Robert , Dally Kerry
Published: May 2021

Student problem behaviour in schools is an issue for teachers, schools, and education jurisdictions. Problem behaviour also has an effect on families, the individual student, and the community. It is one of the principal issues of discussion for teachers, preservice teachers, principals, and policymakers. The purpose of this study was to examine a model that supports schools in managing available resources to promote positive behaviour and address problem behaviour. Interviews were conducted with 12 primary and high school principals to investigate their experiences of working together in 6 local management groups (LMGs) for the management of student behaviour. The findings revealed that the LMG model supported effective collaborative leadership practices between the high school and primary school principals and encouraged collegial networks among primary and high school teachers through joint professional learning opportunities. The benefits of the LMG model highlighted some positive outcomes for principals, teachers, and students with problem behaviour within their local schools.
Governance Quality, Fairness Perceptions, and Satisfaction with Democracy in Latin America
Authors: Saxton Gregory W.
Published: May 2021

How do individuals’ fairness judgments aﬀect their political evaluations? This article argues that when citizens perceive high levels of distributive unfairness in society, they will be less satisfied with the way democracy functions. Yet good governance—that is, impartiality in the exercise of political authority—should mitigate the negative inﬂuence of perceived distributive unfairness on satisfaction. Using a cross-national analysis of 18 Latin American countries from 2011 to 2015, this study demonstrates that individuals are significantly less satisfied with democracy when they perceive their country’s income distribution as unfair. Yet good governance significantly oﬀsets this negative relationship, even in a region with the highest level of inequality in the world. These findings imply that policymakers can bolster democratic satisfaction, even in places where citizens perceive the income distribution as fundamentally unfair, by committing to good governance and fair democratic procedures.
Introduction: Refugees, Returnees and Internally Displaced Persons in Africa
Authors: Adeola Romola , Oette Lutz , Lwabukuna Olivia , Viljoen Frans
Published: May 2021

On 10 September 2019, the Organisation of African Unity (OAU) Convention Governing the Specific Aspects of Refugee Problems in Africa (OAU Refugee Convention) turned 50, while on 23 October 2019 the African Union (AU) Convention for the Protection and Assistance of Internally Displaced Persons in Africa (Kampala Convention) turned 10. It is against this backdrop that the designation by the AU Assembly of Heads of State and Government of 2019 as the Year of Refugees, Returnees and Internally Displaced Persons (IDPs) in Africa, is significant.
Global extinction risk for seahorses, pipefishes and their near relatives (Syngnathiformes)
Authors: Pollom Riley A. , Ralph Gina M. , Pollock Caroline M. , Vincent Amanda C.J.
Published: May 2021

Few marine taxa have been comprehensively assessed for their conservation status, despite heavy pressures from fishing, habitat degradation and climate change. Here we report on the first global assessment of extinction risk for 300 species of syngnathiform fishes known as of 2017, using the IUCN Red List criteria. This order of bony teleosts is dominated by seahorses, pipefishes and seadragons (family Syngnathidae). It also includes trumpetfishes (Aulostomidae), shrimpfishes (Centriscidae), cornetfishes (Fistulariidae) and ghost pipefishes (Solenostomidae). At least 6% are threatened, but data suggest a mid-point estimate of 7.9% and an upper bound of 38%. Most of the threatened species are seahorses (Hippocampus spp.: 14/42 species, with an additional 17 that are Data Deficient) or freshwater pipefishes of the genus Microphis (2/18 species, with seven additional that are Data Deficient). Two species are Near Threatened. Nearly one-third of syngnathiformes (97 species) are Data Deficient and could potentially be threatened, requiring further field research and evaluation. Most species (61%) were, however, evaluated as Least Concern. Primary threats to syngnathids are (1) overexploitation, primarily by non-selective fisheries, for which most assessments were determined by criterion A (Hippocampus) and/or (2) habitat loss and degradation, for which assessments were determined by criterion B (Microphis and some Hippocampus). Threatened species occurred in most regions but more are found in East and South-east Asia and in South African estuaries. Vital conservation action for syngnathids, including constraining fisheries, particularly non-selective extraction, and habitat protection and rehabilitation, will benefit many other aquatic species.
Circulating microRNAs 34a, 122, and 192 are linked to obesity-associated inflammation and metabolic disease in pediatric patients
Authors: Lischka Julia , Schanzer Andrea , Hojreh Azadeh , Ba-Ssalamah Ahmed , de Gier Charlotte , Valent Isabella , Item Chike Bellarmine , Greber-Platzer Susanne , Zeyda Maximilian
Published: May 2021

Background

Obesity-associated chronic low-grade inflammation leads to dysregulation of central lipid and glucose metabolism pathways leading to metabolic disorders. MicroRNAs (miRNAs) are known to control regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with inflammatory modulators and metabolic disorders in pediatric obesity.

Methods

From a pediatric cohort with severe obesity (n = 109), clinically thoroughly characterized including diverse routine blood parameters, oral glucose tolerance test, and liver MRI, a panel of 16 circulating miRNAs was quantified using qRT-PCR. Additionally, markers of inflammation TNFα, IL1 receptor antagonist, procalcitonin, CRP, and IL-6 were measured.

Results

Markers of obesity-associated inflammation, TNFα, IL-1Ra, and procalcitonin, all significantly correlated with concentrations of miRNAs 122 and 192. Concentrations of these miRNAs negatively correlated with serum adiponectin and were among those strongly linked to parameters of dyslipidemia and liver function. Moreover, miRNA122 concentrations correlated with HOMA-IR. Several miRNA levels including miRNAs 34a, 93, 122, and 192 were statistically significantly differing between individuals with prediabetes, impaired glucose tolerance, metabolic syndrome, or nonalcoholic fatty liver disease compared to the respective controls. Additionally, miRNA 192 was significantly elevated in metabolically unhealthy obesity.

Conclusions

A miRNA pattern associated with obesity-associated inflammation and comorbidities may be used to distinguish metabolically healthy from unhealthy pediatric patients with obesity. Moreover, these changes in epigenetic regulation could potentially be involved in the etiology of obesity-linked metabolic disease in children and adolescents.
Association between perinatal factors, genetic susceptibility to obesity and age at adiposity rebound in children of the EDEN mother–child cohort
Authors: Cissé Aminata Hallimat , Lioret Sandrine , de Lauzon-Guillain Blandine , Forhan Anne , Ong Ken K. , Charles Marie Aline , Heude Barbara
Published: May 2021

Background

Early adiposity rebound (AR) has been associated with increased risk of overweight or obesity in adulthood. However, little is known about early predictors of age at AR. We aimed to study the role of perinatal factors and genetic susceptibility to obesity in the kinetics of AR.

Methods

Body mass index (BMI) curves were modelled by using mixed-effects cubic models, and age at AR was estimated for 1415 children of the EDEN mother–child cohort study. A combined obesity risk-allele score was calculated from genotypes for 27 variants identified by genome-wide association studies of adult BMI. Perinatal factors of interest were maternal age at delivery, parental education, parental BMI, gestational weight gain, maternal smoking during pregnancy, and newborn characteristics (sex, prematurity, and birth weight). We used a hierarchical level approach with multivariable linear regression model to investigate the association between these factors, obesity risk-allele score, and age at AR.

Results

A higher genetic susceptibility to obesity score was associated with an earlier age at AR. At the most distal level of the hierarchical model, maternal and paternal educational levels were positively associated with age at AR. Children born to parents with higher BMI were more likely to exhibit earlier age at AR. In addition, higher gestational weight gain was related to earlier age at AR. For children born small for gestational age, the average age at AR was 88 [±39] days lower than for children born appropriate for gestational age and 91 [±56] days lower than for children born large for gestational age.

Conclusion

The timing of AR seems to be an early childhood manifestation of the genetic susceptibility to adult obesity. We further identified low birth weight and gestational weight gain as novel predictors of early AR, highlighting the role of the intrauterine environment in the kinetics of adiposity.
Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer
Authors: Naso Francesco Davide , Boi Dalila , Ascanelli Camilla , Pamfil Georgiana , Lindon Catherine , Paiardini Alessandro , Guarguaglini Giulia
Published: May 2021

The Aurora-A kinase regulates cell division, by controlling centrosome biology and spindle assembly. Cancer cells often display elevated levels of the kinase, due to amplification of the gene locus, increased transcription or post-translational modifications. Several inhibitors of Aurora-A activity have been developed as anti-cancer agents and are under evaluation in clinical trials. Although the well-known mitotic roles of Aurora-A point at chromosomal instability, a hallmark of cancer, as a major link between Aurora-A overexpression and disease, recent evidence highlights the existence of non-mitotic functions of potential relevance. Here we focus on a nuclear-localised fraction of Aurora-A with oncogenic roles. Interestingly, this pool would identify not only non-mitotic, but also kinase-independent functions of the kinase. We review existing data in the literature and databases, examining potential links between Aurora-A stabilisation and localisation, and discuss them in the perspective of a more effective targeting of Aurora-A in cancer therapy.
Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19
Authors: Ma Shengli , Zhang Fan , Zhou Fengxia , Li Hui , Ge Wenyu , Gan Rui , Nie Huan , Li Biao , Wang Yindong , Wu Meng , Li Duo , Wang Dongmei , Wang Zheng , You Yuhong , Huang Zhiwei
Published: May 2021

COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil–lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.
Hyperbaric oxygen promotes not only glioblastoma proliferation but also chemosensitization by inhibiting HIF1α/HIF2α-Sox2
Authors: Wang Pan , Gong Sheng , Pan Jinyu , Wang Junwei , Zou Dewei , Xiong Shuanglong , Zhao Lu , Yan Qian , Deng Yangming , Wu Nan , Liao Bin
Published: May 2021

There exists a consensus that combining hyperbaric oxygen (HBO) and chemotherapy promotes chemotherapy sensitivity in GBM cells. However, few studies have explored the mechanism involved. HIF1α and HIF2α are the two main molecules that contribute to GBM malignant progression by inhibiting apoptosis or maintaining stemness under hypoxic conditions. Moreover, Sox2, a marker of stemness, also contributes to GBM malignant progression through stemness maintenance or cell cycle arrest. Briefly, HIF1α, HIF2α and Sox2 are highly expressed under hypoxia and contribute to GBM growth and chemoresistance. However, after exposure to HBO for GBM, whether the expression of the above factors is decreased, resulting in chemosensitization, remains unknown. Therefore, we performed a series of studies and determined that the expression of HIF1α, HIF2α and Sox2 was decreased after HBO and that HBO promoted GBM cell proliferation through cell cycle progression, albeit with a decrease in stemness, thus contributing to chemosensitization via the inhibition of HIF1α/HIF2α-Sox2.
Minor changes in fibre intake in the UK population between 2008/2009 and 2016/2017
Authors: Gressier Mathilde , Frost Gary
Published: May 2021

The benefits of increasing populations’ and individuals’ fibre intake on non-communicable disease risk have been known and promoted for decades in the UK and in the world. Public health campaigns, including dietary recommendations, called populations to increase their consumption of whole grains, fruits and vegetables, while manufacturers increased the fibre content of their products. In particular, the SACN report in 2015 highlighted the importance of fibres for the UK population. We analysed trends in fibre consumption for the whole population, by age group and gender using the UK National Diet and Nutrition Survey from 2008/09 to 2016/17. We investigated changes in total fibre intake and calculated the contribution to fibre intake and time trends from each food group. We compared the fibre content of food groups between 2008/09 and 2016/17. We found that fibre intake remained fairly stable. While the fibre content of some cereal-based products increased, it decreased for potato-based products. All age groups derived increasing fibre from pasta and other cereal-based products, and decreasing fibre from potato products. Adults, but not children or adolescents derived more fibre from vegetables. This resulted in an increase in fibre intake in adults, but not in children or adolescents.
The landscape and driver potential of site-specific hotspots across cancer genomes
Authors: Juul Randi Istrup , Nielsen Morten Muhlig , Juul Malene , Feuerbach Lars , Pedersen Jakob Skou
Published: May 2021

Large sets of whole cancer genomes make it possible to study mutation hotspots genome-wide. Here we detect, categorize, and characterize site-specific hotspots using 2279 whole cancer genomes from the Pan-Cancer Analysis of Whole Genomes project and provide a resource of annotated hotspots genome-wide. We investigate the excess of hotspots in both protein-coding and gene regulatory regions and develop measures of positive selection and functional impact for individual hotspots. Using cancer allele fractions, expression aberrations, mutational signatures, and a variety of genomic features, such as potential gain or loss of transcription factor binding sites, we annotate and prioritize all highly mutated hotspots. Genome-wide we find more high-frequency SNV and indel hotspots than expected given mutational background models. Protein-coding regions are generally enriched for SNV hotspots compared to other regions. Gene regulatory hotspots show enrichment of potential same-patient second-hit missense mutations, consistent with enrichment of hotspot driver mutations compared to singletons. For protein-coding regions, splice-sites, promoters, and enhancers, we see an excess of hotspots associated with cancer genes. Interestingly, missense hotspot mutations in tumor suppressors are associated with elevated expression, suggesting localized amino-acid changes with functional impact. For individual non-coding hotspots, only a small number show clear signs of positive selection, including known sites in theTERTpromoter and the 5’ UTR ofTP53. Most of the new candidates have few mutations and limited driver evidence. However, a hotspot in an enhancer of the oncogenePOU2AF1, which may create a transcription factor binding site, presents multiple lines of driver-consistent evidence.
Nano-imaging of strain-tuned stripe textures in a Mott crystal
Authors: McLeod A. S. , Wieteska A. , Chiriaco G. , Foutty B. , Wang Y. , Yuan Y. , Xue F. , Gopalan V. , Chen L. Q. , Mao Z. Q. , Millis A. J. , Pasupathy A. N. , Basov D. N.
Published: May 2021

The 4d transition metal perovskites Can+1RunO3n+1 have attracted interest for their strongly interacting electronic phases showing pronounced sensitivity to controllable stimuli like strain, temperature, and even electrical current. Through multi-messenger low-temperature nano-imaging, we reveal a spontaneous striped texture of coexisting insulating and metallic domains in single crystals of the bilayer ruthenate Ca3(TixRu1-x)2O7 across its first-order Mott transition at $$T \approx 95$$

T
≈
95

K. We image on-demand anisotropic nucleation and growth of these domains under in situ applied uniaxial strain rationalized through control of a spontaneous Jahn-Teller distortion. Our scanning nano-susceptibility imaging resolves the detailed susceptibility of coexisting phases to strain and temperature at the transition threshold. Comparing these nano-imaging results to bulk-sensitive elastoresistance measurements, we uncover an emergent “domain susceptibility” sensitive to both the volumetric phase fractions and elasticity of the self-organized domain lattice. Our combined susceptibility probes afford nano-scale insights into strain-mediated control over the insulator-metal transition in 4d transition metal oxides.
Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
Authors: Stone Addison E. , Scheuermann Sarah E. , Haile Colin N. , Cuny Gregory D. , Velasquez Marcela Lopez , Linhuber Joshua P. , Duddupudi Anantha L. , Vigliaturo Jennifer R. , Pravetoni Marco , Kosten Therese A. , Kosten Thomas R. , Norton Elizabeth B.
Published: May 2021

Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based haptens. We tested adjuvants derived from the heat-labile toxin of E. coli including dmLT and LTA1 by intramuscular, sublingual or intranasal delivery. Our results show anti-fentanyl serum antibodies and antibody secreting cells in the bone-marrow after vaccination with highest levels observed with an adjuvant (alum, dmLT, or LTA1). Vaccine adjuvanted with LTA1 or dmLT elicited the highest levels of anti-fentanyl antibodies, whereas alum achieved highest levels against the carrier protein. Vaccination with sublingual dmLT or intranasal LTA1 provided the most robust blockade of fentanyl-induced analgesia and CNS penetration correlating strongly to anti-FEN IgA. In conclusion, this study demonstrates dmLT or LTA1 adjuvant as well as mucosal delivery may be attractive strategies for improving the efficacy of vaccines against SUD.
Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
Authors: Meyers Lauren M. , Gutiérrez Andres H. , Boyle Christine M. , Terry Frances , McGonnigal Bethany G. , Salazar Andres , Princiotta Michael F. , Martin Wiliam D. , De Groot Anne S. , Moise Leonard
Published: May 2021

Natural and vaccine-induced SARS-CoV-2 immunity in humans has been described but correlates of protection are not yet defined. T cells support the SARS-CoV-2 antibody response, clear virus-infected cells, and may be required to block transmission. In this study, we identified peptide epitopes associated with SARS-CoV-2 T-cell immunity. Using immunoinformatic methods, T-cell epitopes from spike, membrane, and envelope were selected for maximal HLA-binding potential, coverage of HLA diversity, coverage of circulating virus, and minimal potential cross-reactivity with self. Direct restimulation of PBMCs collected from SARS-CoV-2 convalescents confirmed 66% of predicted epitopes, whereas only 9% were confirmed in naive individuals. However, following a brief period of epitope-specific T-cell expansion, both cohorts demonstrated robust T-cell responses to 97% of epitopes. HLA-DR3 transgenic mouse immunization with peptides co-formulated with poly-ICLC generated a potent Th1-skewed, epitope-specific memory response, alleviating safety concerns of enhanced respiratory disease associated with Th2 induction. Taken together, these epitopes may be used to improve our understanding of natural and vaccine-induced immunity, and to facilitate the development of T-cell-targeted vaccines that harness pre-existing SARS-CoV-2 immunity.
Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
Authors: Khakhum Nittaya , Bharaj Preeti , Walker David H. , Torres Alfredo G. , Endsley Janice J.
Published: May 2021

Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-specific IgM and IgG (IgG2b/c > IgG1 > IgG3) antibodies in sera and lungs, and lung IgA antibodies. Sera confers complement-independent bactericidal activity and macrophages opsonophagocytic uptake but is insufficient in passive transfer experiments to provide significant protection. Both vaccines elicit memory Th1 and Th17 CD4+ T-cell responses in lung and spleen after Bpm antigen-specific recall. The PBK001 vaccine is superior in generating respiratory IgA post-boost, anamnestic IgG at challenge, T-cell recall to specific antigen, and development of diverse polyfunctional memory T-cell pools. Analysis of lung histology suggests that potent polyfunctional T-cell memory and/or IL-17 signatures generated with PBK001 vaccination may be associated with moderate lung inflammation post vaccination.
Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2
Authors: McDonald Ian , Murray Sam M. , Reynolds Catherine J. , Altmann Daniel M. , Boyton Rosemary J.
Published: May 2021

As SARS-CoV-2 vaccines are deployed worldwide, a comparative evaluation is important to underpin decision-making. We here report a systematic literature review and meta-analysis of Phase I/II/III human trials and non-human primates (NHP) studies, comparing reactogenicity, immunogenicity and efficacy across different vaccine platforms for comparative evaluation (updated to March 22, 2021). Twenty-three NHP and 32 human studies are included. Vaccines result in mostly mild, self-limiting adverse events. Highest spike neutralizing antibody (nAb) responses are identified for the mRNA-1273-SARS-CoV and adjuvanted NVX-CoV2373-SARS-CoV-2 vaccines. ChAdOx-SARS-CoV-2 produces the highest T cell ELISpot responses. Pre-existing nAb against vaccine viral vector are identified following AdH-5-SARS-CoV-2 vaccination, halving immunogenicity. The mRNA vaccines depend on boosting to achieve optimal immunogenicity especially in the elderly. BNT162b2, and mRNA-1273 achieve >94%, rAd26/5 > 91% and ChAdOx-SARS-CoV-2 > 66.7% efficacy. Across different vaccine platforms there are trade-offs between antibody binding, functional nAb titers, T cell frequency, reactogenicity and efficacy. Emergence of variants makes rapid mass rollout of high efficacy vaccines essential to reduce any selective advantage.
Global carbon budget of reservoirs is overturned by the quantification of drawdown areas
Authors: Keller Philipp S. , Marcé Rafael , Obrador Biel , Koschorreck Matthias
Published: May 2021

Reservoir drawdown areas—where sediment is exposed to the atmosphere due to water-level fluctuations—are hotspots for carbon dioxide (CO2) emissions. However, the global extent of drawdown areas is unknown, precluding an accurate assessment of the carbon budget of reservoirs. Here we show, on the basis of satellite observations of 6,794 reservoirs between 1985 and 2015, that 15% of the global reservoir area was dry. Exposure of drawdown areas was most pronounced in reservoirs close to the tropics and shows a complex dependence on climatic (precipitation, temperature) and anthropogenic (water use) drivers. We re-assessed the global carbon emissions from reservoirs by apportioning CO2and methane emissions to water surfaces and drawdown areas using published areal emission rates. The new estimate assigns 26.2 (15–40) (95% confidence interval) TgCO2-C yr−1to drawdown areas, and increases current global CO2emissions from reservoirs by 53% (60.3 (43.2–79.5) TgCO2-C yr−1). Taking into account drawdown areas, the ratio between carbon emissions and carbon burial in sediments is 2.02 (1.04–4.26). This suggests that reservoirs emit more carbon than they bury, challenging the current understanding that reservoirs are net carbon sinks. Thus, consideration of drawdown areas overturns our conception of the role of reservoirs in the carbon cycle.
Exact statistical solution for the hopping transport of trapped charge via finite Markov jump processes
Authors: Pil’nik Andrey A. , Chernov Andrey A. , Islamov Damir R.
Published: May 2021

In this study, we developed a discrete theory of the charge transport in thin dielectric films by trapped electrons or holes, that is applicable both for the case of countable and a large number of traps. It was shown that Shockley–Read–Hall-like transport equations, which describe the 1D transport through dielectric layers, might incorrectly describe the charge flow through ultra-thin layers with a countable number of traps, taking into account the injection from and extraction to electrodes (contacts). A comparison with other theoretical models shows a good agreement. The developed model can be applied to one-, two- and three-dimensional systems. The model, formulated in a system of linear algebraic equations, can be implemented in the computational code using different optimized libraries. We demonstrated that analytical solutions can be found for stationary cases for any trap distribution and for the dynamics of system evolution for special cases. These solutions can be used to test the code and for studying the charge transport properties of thin dielectric films.
Surge of severe acute respiratory syndrome coronavirus 2 infections linked to single introduction of a virus strain in Myanmar, 2020
Authors: Nyunt Myat Htut , Soe Hnin Ohnmar , Aye Kay Thi , Aung Wah Wah , Kyaw Yi Yi , Kyaw Aung Kyaw , Myat Theingi Win , Latt Aung Zaw , Win Min Min , Win Aye Aye , Htun Yin Min , Zaw Khaing Mar , Ei Phyu Win , Hein Kyaw Thu , San Lai Lai , Oo Nan Aye Thida , Lin Htin , Mon Nan Cho Nwe , Yee Khin Than , Htun Khin Lapyae , Aye Lynn Pa Pa , Ko Yamin Ko , Htoo Thitsar Htet Htet , Aung Kham Mo , Azili Hnin , Han Soe Soe , Zaw Ni Ni , Win Su Mon , Thwe Wai Myat , Aye Thin Thin , Hlaing Myat Su , Minn Wai Yan , Thu Pyae Phyo , Thu Hlaing Myat , Htun Zaw Than
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major health concern globally. Genomic epidemiology is an important tool to assess the pandemic of coronavirus disease 2019 (COVID-19). Several mutations have been reported by genome analysis of the SARS-CoV-2. In the present study, we investigated the mutational and phylogenetic analysis of 30 whole-genome sequences for the virus's genomic characteristics in the specimens collected in the early phase of the pandemic (March–June, 2020) and the sudden surge of local transmission (August–September, 2020). The four samples in the early phase of infection were B.6 lineage and located within a clade of the samples collected at the same time in Singapore and Malaysia, while five returnees by rescue flights showed the lineage B. 1.36.1 (three from India), B.1.1 (one from India) and B.1.80 (one from China). However, there was no evidence of local spread from these returnees. Further, all 19 whole-genome sequences collected in the sudden surge of local transmission showed lineage B.1.36. The surge of the second wave on SARS-CoV-2 infection was linked to the single-introduction of a variant (B.1.36) that may result from the strict restriction of international travel and containment efforts. These genomic data provides the useful information to disease control and prevention strategy.
Persistence of topological phases in non-Hermitian quantum walks
Authors: Mittal Vikash , Raj Aswathy , Dey Sanjib , Goyal Sandeep K.
Published: May 2021

Discrete-time quantum walks are known to exhibit exotic topological states and phases. Physical realization of quantum walks in a lossy environment may destroy these phases. We investigate the behaviour of topological states in quantum walks in the presence of a lossy environment. The environmental effects in the quantum walk dynamics are addressed using the non-Hermitian Hamiltonian approach. We show that the topological phases of the quantum walks are robust against moderate losses. The topological order in one-dimensional split-step quantum walk persists as long as the Hamiltonian respects exact $${{\mathcal {P}}}{{\mathcal {T}}}$$

P
T

-symmetry. Although the topological nature persists in two-dimensional quantum walks as well, the $${{\mathcal {P}}}{{\mathcal {T}}}$$

P
T

-symmetry has no role to play there. Furthermore, we observe topological phase transition in two-dimensional quantum walks that is induced by losses in the system.
Daily variation of macronutrient concentrations in mature human milk over 3 weeks
Authors: Leghi Gabriela E. , Lai Ching T. , Narayanan Ardra , Netting Merryn J. , Dymock Michael , Rea Alethea , Wlodek Mary E. , Geddes Donna T. , Muhlhausler Beverly S.
Published: May 2021

Human milk (HM) composition is known to be highly variable, both between individuals and across the duration of lactation. It is less clear, however, to what extent fat, lactose and protein concentrations in HM change daily over shorter time periods in mature HM, and no studies have evaluated this to date. The aim of this study was to systematically assess and compare HM macronutrient concentrations in samples collected at different times of day, from left and right breasts and daily across a 3-week period in the same woman. Fifteen lactating women (1.6–4.9 months postpartum) collected daily pre-feed HM samples from both breasts each morning for 21 consecutive days and completed intensive sampling once a week (morning, afternoon and evening samples) during this period. Concentrations of fat, protein and lactose in HM did not differ according to time of day, day of week or breast used for collection. The results of this study suggest that pre-feed samples collected at any point across a 3-week period and from either the left or right breast provide comparable measures of fat, protein and lactose concentrations in mature HM, in pragmatic studies where women are collecting their own HM samples.

Clinical trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12619000606189).
On the flexible needle insertion into the human liver
Authors: Chiroiu Veturia , Nedelcu Nicoleta , Pisla Doina , Munteanu Ligia , Rugină Cristian
Published: May 2021

In the present research, the navigation of a flexible needle into the human liver in the context of the robotic-assisted intraoperative treatment of the liver tumors, is reported. Cosserat (micropolar) elasticity is applied to describe the interaction between the needle and the human liver. The theory incorporates the local rotation of points and the couple stress (a torque per unit area) as well as the force stress (force per unit area) representing the chiral features of the human liver. To predict the deformation of the needle and the liver, the elastic properties of the human liver have been evaluated. Outcomes reveal that considering smaller deformations of the needle and the liver results in better needle navigation mechanism. The needle geometry can enhance the penetration.
Spinal pain increases the risk of becoming overweight in Danish schoolchildren
Authors: Hestbaek Lise , Aartun Ellen , Côté Pierre , Hartvigsen Jan
Published: May 2021

Spinal pain is common in adolescence, and overweight in children and adolescence is an increasing public health problem globally. Since musculoskeletal pain is a known barrier for physical activity which potentially can lead to overweight, the primary objective of this study was to determine if self-reported lifetime spinal pain in 2010 was associated with being overweight or obese in 2012 in a cohort of 1080 normal-weighted Danish children, aged 11–13 years at baseline. Overweight was based on body mass index measured by trained staff. Spinal pain was self-reported by questionnaires during school hours. Estimates were adjusted for relevant covariates. The 2-year incidence rate of overweight was 5.3% (95% CI 3.98–7.58) for children with spinal pain at baseline versus 1.6% (95% CI 0.19–5.45) for children without. There was stepwise and statistically significant increased risk of overweight with increasing frequency of pain and for having pain in more than one part of the spine. Despite the short follow-up time where only 40 children developed overweight, these results indicate that spinal pain might increase the risk of subsequent overweight.