bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction
Authors: Richter Klaus
Published: June 2020

The introduction sets out the central objective of the book: to retrace the consequences of territorial fragmentation and responses to it from the First World War to the end of the 1920s. Never before had Europe’s map been so thoroughly transformed as after 1918. New borders, reinforced by military means and soaring tariffs, intersected centuries-old commercial, social, and cultural networks. East Central Europe, as the site of imperial collapse and of the emergence of a range of new ‘small’ states, such as Poland and the Baltic states, was particularly affected by fragmentation. To gauge the consequences of fragmentation for politics and state-building, this breaking apart has to be understood as a gradual process rather than as a sudden rupture. Because fragmentation is both an international phenomenon and has an internationalizing effect, its history must be written as an international history.
A Future Not as Gloomy as It Seems
Authors: Richter Klaus
Published: June 2020

The chapter traces the emergence of Poland, Lithuania, Latvia, and Estonia as independent states from the First World War. It starts out by looking at the change of German war aims against the background of the rapid advance into the multi-ethnic western parts of the Russian Empire and traces how German politicians, academics, and military staff conceived of plans to integrate newly created states in the region deeply into a German-dominated Central Europe—firstly in alliance with Poland, then in the form of an openly anti-Polish system. Subsequently, the chapter investigates how politicians of these new states struggled to secure independence after German defeat. It finishes by showing that in domestic politics these politicians had to accept post-war territorial fragmentation as irreversible. At the international level, on the other hand, they had to fit the new states into the post-war international order by conceptualizing them as strictly anti-Bolshevik and anti-German.
The Science of Starving in Victorian Literature, Medicine, and Political Economy
Authors: Mangham Andrew
Published: June 2020

What actually happens to our bodies when we starve? How does the sensation of hunger come about, and how exactly does going without food lead to death? Do we die from hunger, or do we die from the secondary conditions it causes? And how is the physiology of something so familiar to us, experienced by each of us every day, so little known? This book is the first study to suggest that these questions were first explored in detail in the nineteenth century. The Science of Starving in Victorian Literature, Medicine, and Political Economy is a reassessment of the languages and methodologies used, throughout the nineteenth century, for discussing extreme hunger. Set against the providentialism of conservative political economy, this study uncovers an emerging, dynamic way of describing literal starvation in the period’s medicine and physiology. No longer seen as a divine punishment for individual failings, starvation became, in the human sciences, a pathology whose horrific symptoms registered failings of state and statute. Providing new and historically rich readings of the works of Charles Kingsley, Elizabeth Gaskell, and Charles Dickens, this work suggests that the realism we have come to associate with Victorian social-problem fiction learned a vast amount from the empirical, materialist objectives of the medical sciences, and that, within the work of these intersections, we find important re-examinations of how we might think about this ongoing humanitarian issue.
Charles Dickens
Authors: Mangham Andrew
Published: June 2020

This chapter illustrates how Charles Dickens found the materiality of starvation a powerful method for addressing the social injustices that angered him. Less balanced than Gaskell and less conflicted than Kingsley, he pulled no punches when it came to the ‘Parrots of Society’—those subscribers to hypocritical, dogmatic interpretations of political economy whose efforts to deal with social problems became, he believed, abortive subscriptions to a malicious laissez faire. The chapter argues that we need to understand these red-hot polemics as a response to, and an appropriation of, the scientific registers of men like Thomas Southwood Smith. What Dickens found in science was a materialism that allowed his challenges to the shallow cant of reformers and politicians to morph into an attack on their perceived stupidity: Dickens was able to use the science of starving as a means of grounding a radical position within a thoughtful materialist one.
Adrian Zuckerman’s New Evidence Scholarship
Authors: Roberts Paul
Published: June 2020

Civil procedure has been the primary focus of Adrian Zuckerman’s evidentiary scholarship in recent decades. In contributing to a celebration of his profound and lasting influence on the procedural law and scholarship of England and Wales, this essay concentrates on Zuckerman’s earlier work primarily addressing criminal evidence and procedure. It identifies and elaborates on three particularly significant conceptual innovations in Zuckerman’s evidentiary writings concerning the (1) disciplinary domain; (2) institutional context(s); and (3) normative sources of evidence law. These conceptual advances are expounded in terms of three correlative dynamic disciplinary and institutional transitions: (1) from ‘Law of Evidence’ to ‘Evidence and Proof’; (2) from transubstantivity to procedural differentiation; and (3) from evidentiary rules to principled discretion. In his ground-breaking work on the principles of criminal evidence, I argue, Zuckerman challenged us to rethink the disciplinary contours, normative foundations and jurisprudential methodologies of common law evidence. Against the prevailing common law orthodoxy of a Thayerite model of generic exclusionary rules, Zuckerman insisted that criminal evidence should be reconceptualized as the practical wisdom of principled discretion rooted in the normative values and objectives of penal justice.
The Bright but Modest Potential of Algorithms in the Courtroom
Authors: Higgins Andrew , Levy Inbar , Lienart Thibaut
Published: June 2020

This chapter investigates the potential of algorithms and machine learning (ML) to improve decision-making. It considers the best roles for algorithms while maintaining important elements of human judgment. There are essential human skills in judging, but algorithms could help systematize the judicial function and thus reduce the risk of human error, inconsistency, and individual bias. Algorithmic decision-making and ML could in principle mitigate these problems since algorithms are more consistent and rely on and can synthesize more data than a human. Yet, recent proposals to use algorithms in the civil justice system are still underdeveloped and face scepticism. This chapter evaluates the risks and benefits of using algorithms in adjudication by pointing out specific elements of legal skill and expertise and identifying tasks better suited for an algorithm. While there are significant reliability and fairness limitations in using AI to make legal decisions, it is important to recognize that many of these weaknesses already exist to varying degrees in human judicial decision-making.
Business in times of crisis
Authors: Johnstone-Louis Mary , Kustin Bridget , Mayer Colin , Stroehle Judith , Wang Boya
Published: June 2020

Government bailouts of corporate sectors in the COVID-19 crisis are part of a tripartite arrangement between government, business and institutional investors. Business should respond to the changing preferences of customers, employees and societies by identifying value propositions that justify the provision of risk capital by institutional investors. Critical to this is the determination and implementation of corporate purposes by owners and board directors that focus on inter-generational horizons. Family owners are particularly well placed to do this, but institutional investors need to make it part of their stewardship function as well. Measurement is key and significant reforms are required in the areas of accounting, valuation and reporting. Consistent with these observations, companies that had strong environmental, social and governance records performed better during the initial stages of the crisis, as did family owned firms and those that avoided high levels of leverage prior to the crisis.
The impact of the COVID-19 pandemic on the mental health of healthcare professionals
Authors: Braquehais M D , Vargas-Cáceres S , Gómez-Durán E , Nieva G , Valero S , Casas M , Bruguera E
Published: June 2020

Introduction

Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the novel coronavirus disease (COVID-19) pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years.

Aim

To analyze the impact of the COVID-19 pandemic on the mental health of HPs.

Method

We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020.

Results

Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: (i) COVID-19 exposure; (ii) epidemiological issues; (iii) material resources; (iv) human resources; and (v) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs’ distress.

Conclusion

A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.
Dorsal horn disinhibition and movement-induced behaviour in a rat model of inflammatory arthritis
Authors: Locke Samantha , Yousefpour Noosha , Ribeiro-da-Silva Alfredo
Published: June 2020

Objectives

Alterations beyond joint inflammation such as changes in dorsal horn (DH) excitability contribute to pain in inflammatory arthritis (IA). More complete understanding of specific underlying mechanisms will be important to define novel targets for the treatment of IA pain. Pre-clinical models are useful, but relevant pain assays are vital for successful clinical translation. For this purpose, a method is presented to assess movement-induced pain-related behaviour changes that was subsequently used to investigate DH disinhibition in IA.

Methods

IA was induced by intra-articular injection of complete Freund’s adjuvant (CFA) in male rats, and weight distribution was assessed before and after walking on a treadmill. To confirm increased activity in nociception-related pathways, fos expression was assessed in the superficial DH, including in nociceptive neurons, identified by neurokinin 1 (NK1) immunoreactivity, and interneurons. Inhibitory terminal density onto NK1+ neurons was assessed and lastly, a cohort of animals was treated for 3 days with gabapentin.

Results

At 4 weeks post-CFA, walking reduced weight distribution to the affected joint and increased DH fos expression, including in NK1+ neurons. Neuronal activity in inhibitory cells and inhibitory terminal density on NK1+ neurons were decreased in CFA-treated animals compared with controls. Treatment with gabapentin led to recovered behaviour and DH neuronal activity pattern in CFA-treated animals.

Conclusion

We describe an assay to assess movement-induced pain-related behaviour changes in a rodent IA model. Furthermore, our results suggest that disinhibition may contribute to pain related to movement in IA.
Discretionary powers in the Austrian Private Foundation Law
Authors: Olbrich Daniela
Published: June 2020

The fact that only an objective qualification of the foundation board is decisive with regard to its liability is sufficiently ruled by the Austrian Supreme Court. However, in the end the board member is left alone with the question of what is required in concrete terms. A recent decision of the Austrian Supreme Court granting the foundation’s executive board an extremely wide scope for decision-making where the foundation statute does not provide detailed guidelines came as a surprise. This article deals with the issues faced by foundation board members in avoiding liability when exercising their powers and the need to limit the wide discretionary powers of such board members by creating an adequate statutory framework.
Development and Application of a Transcriptomic Signature of Bioactivation in an Advanced In Vitro Liver Model to Reduce Drug-induced Liver Injury Risk Early in the Pharmaceutical Pipeline
Authors: Kang Wen , Podtelezhnikov Alexei A , Tanis Keith Q , Pacchione Stephen , Su Ming , Bleicher Kimberly B , Wang Zhibin , Laws George M , Griffiths Thomas G , Kuhls Matthew C , Chen Qing , Knemeyer Ian , Marsh Donald J , Mitra Kaushik , Lebron Jose , Sistare Frank D
Published: June 2020

Early risk assessment of drug-induced liver injury (DILI) potential for drug candidates remains a major challenge for pharmaceutical development. We have previously developed a set of rat liver transcriptional biomarkers in short-term toxicity studies to inform the potential of drug candidates to generate a high burden of chemically reactive metabolites that presents higher risk for human DILI. Here, we describe translation of those NRF1-/NRF2-mediated liver tissue biomarkers to an in vitro assay using an advanced micropatterned coculture system (HEPATOPAC) with primary hepatocytes from male Wistar Han rats. A 9-day, resource-sparing and higher throughput approach designed to identify new chemical entities with lower reactive metabolite-forming potential was qualified for internal decision making using 93 DILI-positive and -negative drugs. This assay provides 81% sensitivity and 90% specificity in detecting hepatotoxicants when a positive test outcome is defined as the bioactivation signature score of a test drug exceeding the threshold value at an in vitro test concentration that falls within 3-fold of the estimated maximum drug concentration at the human liver inlet following highest recommended clinical dose administrations. Using paired examples of compounds from distinct chemical series and close structural analogs, we demonstrate that this assay can differentiate drugs with lower DILI risk. The utility of this in vitro transcriptomic approach was also examined using human HEPATOPAC from a single donor, yielding 68% sensitivity and 86% specificity when the aforementioned criteria are applied to the same 93-drug test set. Routine use of the rat model has been adopted with deployment of the human model as warranted on a case-by-case basis. This in vitro transcriptomic signature-based strategy can be used early in drug discovery to derisk DILI potential from chemically reactive metabolites by guiding structure-activity relationship hypotheses and candidate selection.
The function annotations of ST3GAL4 in human LAMP1 and Lassa virus GP-C interaction from the perspective of systems virology
Authors: Chukwudozie Onyeka S.
Published: June 2020

Lassa virus (LASV) is a single-stranded RNA virus that has plagued the Sub-Saharan part of Africa, precisely Nigeria where various pathogenic strains with varied genomic isoforms have been identified. The human lysosomal-associated membrane protein 1 (LAMP1) is alternately required for the micropinocytosis of LASV. Therefore, it is of interest to understand the mechanism of action of the host LAMP1 with LASV protein during infection. The role of ST3 beta-galactoside alpha-2, 3-sialyltransferase 4 (ST3GAL4) in the interaction between LASV (glycoprotein) GP-C and the human LAMP1 is relevant in this context. Deposited curated protein sequences of both LAMP1 and LASV GP-C were retrieved for the study. The ST3GAL4 associated data was constructed and analysed from weighted network analysis to infer the function annotations and molecular mediators that characterize the LASV infection. The gene network shows that glycoprotein sialylation, sialyltransferase enzymatic activities and glycosphingolipid biosynthesis are linked with the ST3GAL4 function. However, the physical interaction of FAM 213A, CD8B molecule and proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N) with ST3GAL4 is intriguing in this perspective. There are 11 glycosylated asparagine sequons of the human LAMP1 but only nine were assigned a sialylated glycan cap to mediate the LASV GP-C and LAMP1 interaction having exceeded a recommended glycosylation threshold of 0.5. Therefore, the sialylated glycans of the human LAMP1 are a total of nine and these sialylated glycans mediate the molecular recognition between LASV and LAMP1. This study therefore, predicts that there is a cellular interchange between N-linked glycosylation properties of the human LAMP1 and LASV glycoprotein, and sialylation functions of ST3GAL4 in LASV infectivity. Further studies and the clinical trial of this predictive model on the sialylated glycans of LAMP1 will facilitate the understanding of the LASV micropinocytosis process in host cells.
Improving Landsat predictions of rangeland fractional cover with multitask learning and uncertainty
Authors: Allred Brady W. , Bestelmeyer Brandon T. , Boyd Chad S. , Brown Christopher , Davies Kirk W. , Ellsworth Lisa M. , Erickson Tyler A. , Fuhlendorf Samuel D. , Griffiths Timothy V. , Jansen Vincent , Jones Matthew O. , Karl Jason , Maestas Jeremy D. , Maynard Jonathan J. , McCord Sarah E. , Naugle David E. , Starns Heath D. , Twidwell Dirac , Uden Daniel R.
Published: June 2020

Operational satellite remote sensing products are transforming rangeland management and science. Advancements in computation, data storage, and processing have removed barriers that previously blocked or hindered the development and use of remote sensing products. When combined with local data and knowledge, remote sensing products can inform decision making at multiple scales.

We used temporal convolutional networks to produce a fractional cover product that spans western United States rangelands. We trained the model with 52,012 on-the-ground vegetation plots to simultaneously predict fractional cover for annual forbs and grasses, perennial forbs and grasses, shrubs, trees, litter, and bare ground. To assist interpretation and to provide a measure of prediction confidence, we also produced spatiotemporal-explicit, pixel-level estimates of uncertainty. We evaluated the model with 5,780 on-the-ground vegetation plots removed from the training data.

Model evaluation averaged 6.3% mean absolute error and 9.6% root mean squared error. Evaluation with additional datasets that were not part of the training dataset, and that varied in geographic range, method of collection, scope, and size, revealed similar metrics. Model performance increased across all functional groups compared to the previously produced fractional product.

The advancements achieved with the new rangeland fractional cover product expand the management toolbox with improved predictions of fractional cover and pixel-level uncertainty. The new product is available on the Rangeland Analysis Platform (https://rangelands.app/), an interactive web application that tracks rangeland vegetation through time. This product is intended to be used alongside local on-the-ground data, expert knowledge, land use history, scientific literature, and other sources of information when making interpretations. When being used to inform decision-making, remotely sensed products should be evaluated and utilized according to the context of the decision and not be used in isolation.
Contribution of odorant binding proteins to olfactory detection of (Z)-11-hexadecenal inHelicoverpa armigera
Authors: Guo Hao , Guo Ping-Ping , Sun Ya-Lan , Huang Ling-Qiao , Wang Chen-Zhu
Published: June 2020

Helicoverpa armigerautilizes (Z)-11-hexadecenal (Z11-16:Ald) as its major sex pheromone component. Three pheromone binding proteins (PBPs) and two general odorant binding proteins (GOBPs) are abundantly expressed in male antennae ofH. armigera. However, their precise roles in the olfactory detection of Z11-16:Ald remain enigmatic. To answer this question, we first synthesized the antibody against HarmOR13, a pheromone receptor (PR) primarily responding to Z11-16:Ald and mapped the local associations between PBPs / GOBPs and HarmOR13. Immunostaining showed that HarmPBPs and HarmGOBPs were localized in the supporting cells of sensilla trichodea and sensilla basiconica respectively. In particular, HarmPBP1 and HarmPBP2 were colocalized in the cells surrounding the olfactory receptor neurons (ORNs) expressing HarmOR13. Next, using two noninterfering binary expression tools, we heterologously expressed HarmPBP1, HarmPBP2 and HarmOR13 inDrosophilaT1 sensilla to validate the functional interplay between PBPs and HarmOR13. We found that the addition of HarmPBP1 or HarmPBP2 significantly increased the sensitivity of HarmOR13 to Z11-16:Ald. However, the presence of either HarmPBP1 or HarmPBP2 was ineffective to change the tuning breadth of HarmOR13. Taken together, our results support the idea that PBPs are contributors to the peripheral olfactory sensitivity but do not affect the selectivity. Lastly, we discovered that HarmOR13 and theDrosophilaOR67d employed a similar coding mechanism to detect pheromones, suggesting that pheromone detection across different insect orders appears to co-opt a conserved molecular principle to recognize pheromone ligands.
Identification of a lymphocyte minor histocompatibility antigen in Mauritian cynomolgus macaques
Authors: Weinfurter Jason T. , Graham Michael E. , Ericsen Adam J. , Matschke Lea M. , Llewellyn-Lacey Sian , Price David A. , Wiseman Roger W. , Reynolds Matthew R.
Published: June 2020

Allogeneic hematopoietic stem cell transplantation can lead to dramatic reductions in human immunodeficiency virus (HIV) reservoirs. This effect is mediated in part by donor T cells that recognize lymphocyte-expressed minor histocompatibility antigens (mHAgs). The potential to mark malignant and latently infected cells for destruction makes mHAgs attractive targets for cellular immunotherapies. However, testing such HIV reservoir reduction strategies will likely require preclinical studies in nonhuman primates (NHPs). In this study, we used a combination of alloimmunization, whole exome sequencing, and bioinformatics to identify a mHAg in Mauritian cynomolgus macaques (MCMs). We mapped the minimal optimal epitope to a 10-mer peptide (SW10) in apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3) and determined the major histocompatibility complex class I restriction element as Mafa-A1*063, which is expressed in almost 90% of MCMs. APOBEC3C SW10-specific CD8+ T cells recognized immortalized B cells but not fibroblasts from a mHAg positive MCM. These results collectively provide a framework for identifying mHAgs in a nontransplant setting and suggest that APOBEC3C SW10 could be used as a lymphocyte-restricted model antigen in NHPs to test various mHAg-targeted immunotherapies.

Importance

Cellular immunotherapies developed to treat blood cancers may also be effective against latent HIV. Preclinical studies of such immunotherapies are hindered by a lack of known target antigens. We used a combination of alloimmunization, basic immune assays, whole exome sequencing, and bioinformatics to identify a lymphocyte-restricted minor histocompatibility antigen in a genetically related population of nonhuman primates. This minor histocompatibility antigen provides an actionable target for piloting cellular immunotherapies designed to reduce or eliminate latent reservoirs of HIV.
Preserved efficacy and reduced toxicity with intermittent linezolid dosing in combination with bedaquiline and pretomanid in a murine TB model
Authors: Bigelow Kristina M. , Tasneen Rokeya , Chang Yong S. , Dooley Kelly E. , Nuermberger Eric L.
Published: June 2020

The novel regimen of bedaquiline, pretomanid, and linezolid (BPaL) is highly effective against drug resistant tuberculosis, but linezolid toxicities are frequent. We hypothesized that, for a similar total weekly cumulative dose, thrice-weekly administration of linezolid would preserve efficacy while reducing toxicity compared to daily dosing, in the context of the BPaL regimen.

Using C3HeB/FeJ and BALB/c mouse models of tuberculosis disease, thrice-weekly linezolid dosing was compared to daily dosing, with intermittent dosing introduced (a) from treatment initiation or (b) following an initial period of daily dosing. In all animals, BPa was dosed daily throughout treatment. Blood counts were used to assess hematologic toxicity. Following unexpected findings of apparent antagonism, we conducted additional experiments to investigate strain-to-strain differences in the contribution of linezolid to regimen efficacy comparing each 1- and 2-drug component to the BPaL regimen in BALB/c mice infected withMycobacterium tuberculosisH37Rv or HN878.

Giving linezolid daily for 1-2 months achieved the greatest efficacy, but following that, results were similar if the drug was stopped, dosed thrice-weekly, or continued daily. Erythrocyte counts were lower with daily than thrice-weekly dosing. Linezolid had additive effects with BPa againstM. tuberculosisH37Rv but antagonistic effects with BPa againstM. tuberculosisHN878. However, overall efficacy of BPaL was high and similar against both strains.

Dosing linezolid daily for the first two months, then less frequently thereafter, may optimize its therapeutic margin. Linezolid’s contribution to BPaL regimens may depend onM. tuberculosisstrain.
Over-accessible chromatin links myeloma initiating genetic events to oncogenic transcriptomes and aberrant transcription factor regulatory networks
Authors: Alvarez-Benayas Jaime , Katsarou Alexia , Trasanidis Nikolaos , Chaidos Aristeidis , May Philippa C , Ponnusamy Kanagaraju , Xiao Xiaolin , Bua Marco , Atta Maria , Roberts Irene AG , Auner Holger W , Hatjiharissi Evdoxia , Papaioannou M Maria , Caputo Valentina S , Sudbery IM Ian M , Karadimitris Anastasios
Published: June 2020

Multiple myeloma is a genetically heterogeneous cancer of the bone marrow plasma cells (PC). Myeloma initiating genetic events define subgroups (MIE) and drive distinct oncogenic transcriptomes that converge into a mutually exclusive overexpression ofCCND1andCCND2oncogenes. Here, with reference to normal PC, we dissect how MIE impact the chromatin regulatory landscape of MM. We find that chromatin accessibility combined with transcriptome profiling classifies myeloma genetic subgroups, while in a topologically constrained manner, distal rather than proximal regulatory elements influence myeloma transcriptomes. Across and within MIE-defined subgroups, genes and pathways critical for myeloma biology can be linked to developmentally activated orde novoformed enhancers. We show that existing transcription factors, co-opted to organise highly ordered, aberrant regulatory networks, generate known and novel myeloma cell dependencies and help identify prognostic markers. Finally, we discover and functionally validate the critical enhancer that regulates ectopic expression ofCCND2in MM.
Evolutionary heritage shapes tree distributions along an Amazon-to-Andes elevation gradient
Authors: Griffiths Andy R. , Silman Miles R. , Rios William Farfán , Feeley Kenneth J. , Cabrera Karina García , Meir Patrick , Salinas Norma , Dexter Kyle G.
Published: June 2020

Understanding how evolutionary constraints shape the elevational distributions of tree lineages provides valuable insight into the future of tropical montane forests under global change. With narrow elevational ranges, high taxonomic turnover, frequent habitat specialisation, and exceptional levels of endemism, tropical montane forests and trees are predicted to be highly sensitive to environmental change. Using plot census data from a gradient traversing >3000 m in elevation on the Amazonian flank of the Peruvian Andes, we employ phylogenetic approaches to assess the influence of evolutionary heritage on distribution trends of trees at the genus level. We find that closely related lineages tend to occur at similar mean elevations, with sister genera pairs occurring a mean 254 m in elevation closer to each other than the mean elevational difference for all genera pairs. We also demonstrate phylogenetic clustering both above and below 1750 m a.s.l, corresponding roughly to the cloud-base ecotone. Belying these general trends, some lineages occur across many different elevations. However, these highly plastic lineages are not phylogenetically clustered. Overall, our findings suggest that tropical montane forests are home to unique tree lineage diversity, constrained by their evolutionary heritage and vulnerable to substantial losses under environmental changes, such as rising temperatures or an upward shift of the cloud base.
Rapid ageing and species identification of natural mosquitoes for malaria surveillance
Authors: Siria Doreen J. , Sanou Roger , Mitton Joshua , Mwanga Emmanuel P. , Niang Abdoulaye , Sare Issiaka , Johnson Paul C.D. , Foster Geraldine , Belem Adrien M.G. , Wynne Klaas , Murray-Smith Roderick , Ferguson Heather M. , González-Jiménez Mario , Babayan Simon A. , Diabaté Abdoulaye , Okumu Fredros O. , Baldini Francesco
Published: June 2020

The malaria parasite, which is transmitted by severalAnophelesmosquito species, requires more time to reach its human-transmissible stage than the average lifespan of a mosquito. Monitoring the species-specific age structure of mosquito populations is critical to evaluating the impact of vector control interventions on malaria risk. We developed a rapid, cost-effective surveillance method based on deep learning of mid-infrared spectra of mosquitoes’ cuticle that simultaneously identifies the species and the age of three main malaria vectors, in natural populations. Using over 40,000 ecologically and genetically diverse females, we could speciate and age gradeAn. gambiae, An. arabiensis, andAn. coluzziiwith up to 95% accuracy. Further, our model learned the age of new populations with minimal sampling effort and detected the impact of control interventions on simulated mosquito populations, measured as a shift in their age structures. We anticipate our method to be applied to other arthropod vector-borne diseases.
Extracellular histones trigger disseminated intravascular coagulation by lytic cell death
Authors: Wu Congqing , Zhang Yan , Li Lan , Pandeya Ankit , Zhang Guoying , Cui Jian , Kirchhofer Daniel , Wood Jeremy P. , Smyth Susan S. , Wei Yinan , Li Zhenyu
Published: June 2020

Histones are cationic nuclear proteins that are essential for the structure and functions of eukaryotic chromatin. However, extracellular histones trigger inflammatory responses and contribute to death in sepsis by unknown mechanisms. We recently reported that inflammasome activation and pyroptosis trigger coagulation activation through a tissue factor (TF)-dependent mechanism. Here, we show that histones trigger coagulation activationin vivoas evidenced by coagulation parameters and fibrin deposition in tissues. However, histone-induced coagulopathy was neither dependent on caspase 1/11 and gasdermin D (GSDMD), nor on TLR2 and TLR4, as deficiency of these genes in mice did not protect against histone-induced coagulopathy. Incubation of histones with macrophages induced lytic cell death and phosphatidylserine (PS) exposure, which is required for TF activity, a key initiator of coagulation. Neutralization of TF diminished histone-induced coagulation. Our findings reveal lytic cell death as a novel mechanism of histone-induce coagulation activation and thrombosis.

Key Points

Histones trigger DIC in a tissue factor dependent mechanism

Histones induce tissue factor activation through lytic cell death
Increasing glucose uptake into neurons antagonizes brain aging and promotes health and life span under dietary restriction inDrosophila
Authors: Oka Mikiko , Suzuki Emiko , Asada Akiko , Saito Taro , Iijima Koichi M. , Ando Kanae
Published: June 2020

Brain neurons play a central role in organismal aging, but there is conflicting evidence about the roles of neuronal glucose availability, glucose uptake and metabolism in aging and extended lifespan. Here, we analyzed metabolic changes in the brain neurons ofDrosophiladuring aging. Using a genetically-encoded fluorescent ATP biosensor, we found decreased ATP concentration in the neuronal somata of aged flies, which was correlated with decreased glucose content, expression of glucose transporter and glycolytic enzymes and mitochondrial quality. The age-associated reduction in ATP concentration did not occur in brain neurons with suppressed glycolysis or enhanced glucose uptake, suggesting these pathways contribute to reductions in ATP. Despite age-associated mitochondrial damage, increasing glucose uptake maintained ATP levels, suppressed age-dependent locomotor deficits and extended the life span. Increasing neuronal glucose uptake during dietary restriction resulted in the longest lifespans, suggesting an additive effect of enhancing glucose availability during a bioenergetic challenge on aging.
Factors influencing riverine utilization patterns in two sympatric macaques
Authors: Otani Yosuke , Bernard Henry , Wong Anna , Tangah Joseph , Tuuga Augustine , Hanya Goro , Matsuda Ikki
Published: June 2020

Many species of terrestrial animals, including primates, live in varied association with the aquatic (e.g., riverine or coastal) environment. However, the benefits that each species receive from the aquatic environment are thought to vary depending on their social and ecological characteristics, and thus, elucidating those benefits to each species is important for understanding the principles of wild animal behaviour. In the present study, to gain a more complete picture of aquatic environment use, including social and ecological factors in primates, factors affecting riverine habitat utilization of two macaque species(Macaca nemestrinaandM. fascicularis)were identified and qualitative comparisons were made with sympatric proboscis monkeys(Nasalis larvatus), which have different social and ecological characteristics. Temporal variation in sighting frequency of macaques at the riverbanks was positively related to the fruit availability of a dominant riparian plant species and negatively related to the river water level which affects the extent of predation pressure. Riverine utilization of macaques was greatly influenced by distribution and abundance of food (especially fruit) resources, possibly in association with predation pressure. Additionally, qualitative ecological comparisons with sympatric proboscis monkeys suggest that the drivers of riverine utilization depend on the feeding niches of the species, and different anti-predator strategies resulting from their differing social structures.
Opponent intracerebral signals for reward and punishment prediction errors in humans
Authors: Gueguen Maëlle CM , Billeke Pablo , Lachaux Jean-Philippe , Rheims Sylvain , Kahane Philippe , Minotti Lorella , David Olivier , Pessiglione Mathias , Bastin Julien
Published: June 2020

Whether maximizing rewards and minimizing punishments rely on distinct brain systems remains debated, inconsistent results coming from human neuroimaging and animal electrophysiology studies. Bridging the gap across species and techniques, we recorded intracerebral activity from twenty patients with epilepsy while they performed an instrumental learning task. We found that both reward and punishment prediction errors (PE), estimated from computational modeling of choice behavior, correlated positively with broadband gamma activity (BGA) in several brain regions. In all cases, BGA increased with both outcome (reward or punishment versus nothing) and surprise (how unexpected the outcome is). However, some regions (such as the ventromedial prefrontal and lateral orbitofrontal cortex) were more sensitive to reward PE, whereas others (such as the anterior insula and dorsolateral prefrontal cortex) were more sensitive to punishment PE. Thus, opponent systems in the human brain might mediate the repetition of rewarded choices and the avoidance of punished choices.
Ancient DNA Insights into Aboriginal Australian Mortuary Practices
Authors: Wasef Sally , Wright Joanne L , Adams Shaun , Westaway Michael C , Flinders Clarence , Willerslev Eske , Lambert David
Published: June 2020

Paleogenetics is a relatively new and promising field that has the potential to provide new information about past Indigenous social systems, including insights into the complexity of burial practices. We present results of the first ancient DNA (aDNA) investigation into traditional mortuary practices among Australian Aboriginal people with a focus on North-East Australia. We recovered mitochondrial and Y chromosome sequences from five ancestral Aboriginal Australian remains that were excavated from the Flinders Island group in Cape York, Queensland. Two of these individuals were sampled from disturbed beach burials, while the other three were from bundle burials located in rock shelters. Genomic analyses showed that individuals from all three rock shelter burials and one of the two beach burials had a close genealogical relationship to contemporary individuals from communities from Cape York. In contrast the remaining male individual, found buried on the beach, had a mitochondrial DNA sequence that suggested that he was not from this location but that he was closely related to people from central Queensland or New South Wales. In addition, this individual was associated with a distinctive burial practice to the other four people. It has been suggested that traditionally non-locals or lower status individuals were buried on beaches. Our findings suggest that theories put forward about beach burials being non-local, or less esteemed members of the community, can potentially be resolved through analyses of uniparental genomic data. Generally, these results support the suggestion often derived from ethnohistoric accounts that inequality in Indigenous Australian mortuary practices might be based on the status, sex, and/or age of individuals and may instead relate to place of geographic origin. There is, however, some departure from the traditional ethnohistoric account in that complex mortuary internments were also offered to female individuals of the community, with genomic analyses helping to confirm that the gender of one of the rockshelter internments was that of a young female.
Herkogamy but not reciprocity is a better predictor of legitimate pollen transfer and fruit set inJasminum malabaricum, a self-compatible species with stigma-height dimorphism
Authors: Ganguly Shatarupa , Barua Deepak
Published: June 2020

Premise

Reciprocity and herkogamy, morphological traits that define style length polymorphisms, are thought to be critical in determining legitimate inter-morph pollen transfer in plants with style length polymorphism. However, the consequences of individual-level variation in these traits for pollen transfer and reproductive success have rarely been examined, and the relationship between these two fundamental traits remains unexplored.

Methods

We quantified individual-level estimates of herkogamy and reciprocity and tested the assumption that higher herkogamy and reciprocity result in higher legitimate pollen transfer and reproductive success in natural populations ofJasminum malabaricum, a species that exhibits stigma-height dimorphism. Additionally, we examined the relationship between herkogamy and reciprocity to understand potential consequences for avoiding self-pollination and encouraging legitimate pollen deposition.

Results

Surprisingly, reciprocity was not related to pollen load, legitimate pollen fraction or reproductive success. In contrast, herkogamy was positively associated with legitimate pollen fraction and fruit set in the long-styled morph. Interestingly, we observed a negative relationship between herkogamy and reciprocity in the long-styled morph.

Conclusions

Herkogamy was more important than reciprocity in increasing legitimate pollen transfer and reproductive success inJ. malabaricum. Herkogamy might be particularly important in stabilising species with stigma-height dimorphism and other such polymorphic intermediates with low reciprocity, and this may allow the evolution of reciprocal arrangement of sex organs at a later stage in the pathway towards distyly. The negative relationship between herkogamy and reciprocity suggests a trade-off between avoidance of self-pollen deposition and promotion of legitimate pollen deposition.
Automated conservation assessment of the orchid family using deep learning
Authors: Zizka Alexander , Silvestro Daniele , Vitt Pati , Knight Tiffany M.
Published: June 2020

IUCN Red List assessments are essential for prioritizing conservation needs but are resource-intensive and therefore only available for a fraction of global species richness. Tropical plant species are particularly under-represented on the IUCN Red List. Automated conservation assessments based on digitally available geographic occurrence records can be a rapid alternative, but it is unclear how reliable these assessments are. Here, we present automated conservation assessments for 13,910 species of the diverse and globally distributed Orchid family (Orchidaceae), based on a novel method using a deep neural network (IUC-NN), most of which (13,049) were previously unassessed by the IUCN Red List. We identified 4,342 (31.2 % of the evaluated orchid species) asPossibly Threatenedwith extinction (equivalent to the IUCN categories CR, EN, or VU) and point to Madagascar, East Africa, south-east Asia, and several oceanic islands as priority areas for orchid conservation. Furthermore, the Orchid family provides a model, to test the sensitivity of automated assessment methods to issues with data availability, data quality and geographic sampling bias. IUC-NN identified threat-ened species with an accuracy of 84.3%, with significantly lower geographic evaluation bias compared to the IUCN Red List, and was robust against low data availability and geographic errors in the input data. Overall, our results demonstrate that automated assessments have an important role to play in achieving goals of identifying the species that are at greatest risk of extinction.
Pseudo-Location: A novel predictor for predicting pseudo-temporal gene expression patterns using spatial functional regression
Authors: Ahn Kyungmin , Fujiwara Hironobu
Published: June 2020

Statement of withdrawal

The authors have withdrawn version 1 of this manuscript because a draft manuscript, which was still in the early stages of preparation and required major revisions including the replacement of the source RNA-seq datasets, was erroneously submitted. The authors do not wish this version to be cited as reference for this study. We will post a revised manuscript in the future. If you have any questions, please contact the corresponding author.
Prediction of complex phenotypes using theDrosophilametabolome
Authors: Rohde Palle Duun , Kristensen Torsten Nygaard , Sarup Pernille , Muñoz Joaquin , Malmendal Anders
Published: June 2020

Understanding the genotype – phenotype map and how variation at different levels of biological organization are associated are central topics in modern biology. Fast developments in sequencing technologies and other molecular omic tools enable researchers to obtain detailed information on variation at DNA level and on intermediate endophenotypes; such as RNA, proteins and metabolites. This can facilitate our understanding of the link between genotypes and molecular and functional organismal phenotypes. Here, we use theDrosophilaGenetic Reference Panel and nuclear magnetic resonance (NMR) metabolomics to investigate the ability of the metabolome to predict organismal phenotypes. We performed NMR metabolomics on four replicate pools of male flies from each of 170 different isogenic lines. Our results show that metabolite profiles are variable among the investigated lines and that this variation is highly heritable. Secondly, we identify genes associated with metabolome variation. Thirdly, using the metabolome gave better prediction accuracies than genomic information for four of five quantitative traits analysed. Our comprehensive characterization of population-scale diversity of metabolomes and its genetic basis illustrates that metabolites have large potential as predictors of organismal phenotypes. This finding is of great importance e.g. in human medicine and animal and plant breeding.
Insertion of an endogenous Jaagsiekte Sheep Retrovirus element into theBCO2 -gene abolishes its function and leads to yellow discoloration of adipose tissue in Norwegian Spælsau (Ovis aries)
Authors: Kent Matthew , Moser Michel , Boman Inger Anne , Lindtveit Kristine , Árnyasi Mariann , Sundsaasen Kristil Kindem , Våge Dag Inge
Published: June 2020

Background

The accumulation of carotenoids in adipose tissue leading to yellow fat is, in sheep, a heritable recessive trait that can be attributed to a nonsense mutation in thebeta-carotene oxygenase 2 (BCO2)gene. However, not all sheep breeds suffering from yellow fat have this nonsense mutation, meaning that other functional mechanisms must exist. We investigated one such breed, the Norwegian spælsau.

Results

In spælsau we detected an aberration inBCO2mRNA. Nanopore sequencing of genomic DNA revealed the insertion of a 7.9 kb endogenous Jaagsiekte Sheep Retrovirus (enJSRV) sequence in the first intron of theBCO2gene. Close examination of its cDNA revealed that theBCO2genes first exon was spliced together with enJSRV-sequence immediately downstream of a potential - AG splice acceptor site at enJSRV position 415. The hybrid protein product consists of 29 amino acids coded by theBCO2exon 1, followed by 29 amino acids arbitrary coded for by the enJSRV-sequence, before a translation stop codon is reached.

Conclusions

Considering that the functional BCO2 protein consists of 575 amino acids, it is unlikely that the 58 amino acid BCO2/enJSRV hybrid protein can display any enzymatic function. The existence of this novelBCO2allele represents an alternative functional mechanism accounting forBCO2inactivation and is a perfect example of the potential benefits for searching for structural variants using long-read sequencing data.
Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells
Authors: Wong Candida , Darby Jocelyn M. , Murphy Peter R. , Pinfold Terry L. , Lennard Patrick R. , Woods Gregory M , Lyons A. Bruce , Flies Andrew S.
Published: June 2020

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumours. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.

Highlights

Key immune checkpoint receptor-ligand interactions are conserved in marsupials.

Live cell-based assays show Tasmanian devil CD28 and CTLA4 can capture CD80 and CD86in transfrom adjacent cells.

Mutation of the conserved CTLA4MYPPPYligand binding motif to CTLA4MYPPPAreduces binding to CD80 and intercellular protein transfer.

Removal of conserved CTLA4YVKMprotein recycling binding motif in CTLA4 results in bidirectional intercellular protein transfer between CTLA4 and CD80.

Highly successful human immune checkpoint immunotherapies have the potential to be translated for veterinary and conservation medicine.