bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionized emission and absorption in a large sample of ultraluminous X-ray sources
Authors: Kosec P , Pinto C , Reynolds C S , Guainazzi M , Kara E , Walton D J , Fabian A C , Parker M L , Valtchanov I
Published: September 2021

Most ultraluminous X-ray sources (ULXs) are thought to be powered by super-Eddington accretion on to stellar-mass compact objects. Accretors in this extreme regime are naturally expected to ionize copious amounts of plasma in their vicinity and launch powerful radiation-driven outflows from their discs. High spectral resolution X-ray observations [with reflection grating spectrometer (RGS) gratings onboard XMM–Newton] of a few ULXs with the best data sets indeed found complex line spectra and confirmed such extreme (0.1–0.3c) winds. However, a search for plasma signatures in a large ULX sample with a rigorous technique has never been performed, thereby preventing us from understanding their statistical properties such as the rate of occurrence, to constrain the outflow geometry, and its duty cycle. We developed a fast method for automated line detection in X-ray spectra and applied it to the full RGS ULX archive, rigorously quantifying the statistical significance of any candidate lines. Collecting the 135 most significant features detected in 89 observations of 19 objects, we created the first catalogue of spectral lines detected in soft X-ray ULX spectra. We found that the detected emission lines are concentrated around known rest-frame elemental transitions and thus originate from low-velocity material. The absorption lines instead avoid these transitions, suggesting they were imprinted by blueshifted outflows. Such winds therefore appear common among the ULX population. Additionally, we found that spectrally hard ULXs show fewer line detections than soft ULXs, indicating some difference in their accretion geometry and orientation, possibly causing overionization of plasma by the harder spectral energy distributions of harder ULXs.
Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs
Authors: Schlegel Mark K , Matsuda Shigeo , Brown Christopher R , Harp Joel M , Barry Joseph D , Berman Daniel , Castoreno Adam , Schofield Sally , Szeto John , Manoharan Muthiah , Charissé Klaus , Egli Martin , Maier Martin A
Published: September 2021

We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc–siRNA conjugates in rodents, and that these findings could be mitigated by seed-pairing destabilization using a single GNA nucleotide placed within the seed region of the guide strand. Here, we report further investigation of the unique and poorly understood GNA/RNA cross-pairing behavior to better inform GNA-containing siRNA design. A reexamination of published GNA homoduplex crystal structures, along with a novel structure containing a single (S)-GNA-A residue in duplex RNA, indicated that GNA nucleotides universally adopt a rotated nucleobase orientation within all duplex contexts. Such an orientation strongly affects GNA-C and GNA-G but not GNA-A or GNA-T pairing in GNA/RNA heteroduplexes. Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, respectively. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile, and maintained in vivo activity and guide strand liver levels more consistent with the parent siRNAs than those modified with isomeric GNA-C or -G, thereby expanding our toolbox for the design of siRNAs with minimized off-target activity.
NCATS Inxight Drugs: a comprehensive and curated portal for translational research
Authors: Siramshetty Vishal B , Grishagin Ivan , Nguyễn Ðắc-Trung , Peryea Tyler , Skovpen Yulia , Stroganov Oleg , Katzel Daniel , Sheils Timothy , Jadhav Ajit , Mathé Ewy A , Southall Noel T
Published: September 2021

The United States has a complex regulatory scheme for marketing drugs. Understanding drug regulatory status is a daunting task that requires integrating data from many sources from the United States Food and Drug Administration (FDA), US government publications, and other processes related to drug development. At NCATS, we created Inxight Drugs (https://drugs.ncats.io), a web resource that attempts to address this challenge in a systematic manner. NCATS Inxight Drugs incorporates and unifies a wealth of data, including those supplied by the FDA and from independent public sources. The database offers a substantial amount of manually curated literature data unavailable from other sources. Currently, the database contains 125 036 product ingredients, including 2566 US approved drugs, 6242 marketed drugs, and 9684 investigational drugs. All substances are rigorously defined according to the ISO 11238 standard to comply with existing regulatory standards for unique drug substance identification. A special emphasis was placed on capturing manually curated and referenced data on treatment modalities and semantic relationships between substances. A supplementary resource ‘Novel FDA Drug Approvals’ features regulatory details of newly approved FDA drugs. The database is regularly updated using NCATS Stitcher data integration tool that automates data aggregation and supports full data access through a RESTful API.
MetazExp: a database for gene expression and alternative splicing profiles and their analyses based on 53 615 public RNA-seq samples in 72 metazoan species
Authors: Liu Jinding , Yin Fei , Lang Kun , Jie Wencai , Tan Suxu , Duan Rongjing , Huang Shuiqing , Huang Wen
Published: September 2021

RNA-seq has been widely used in experimental studies and produced a massive amount of data deposited in public databases. New biological insights can be obtained by retrospective analyses of previously published data. However, the barrier to efficiently utilize these data remains high, especially for those who lack bioinformatics skills and computational resources. We present MetazExp (https://bioinfo.njau.edu.cn/metazExp), a database for gene expression and alternative splicing profiles based on 53 615 uniformly processed publicly available RNA-seq samples from 72 metazoan species. The gene expression and alternative splicing profiles can be conveniently queried by gene IDs, symbols, functional terms and sequence similarity. Users can flexibly customize experimental groups to perform differential and specific expression and alternative splicing analyses. A suite of data visualization tools and comprehensive links with external databases allow users to efficiently explore the results and gain insights. In conclusion, MetazExp is a valuable resource for the research community to efficiently utilize the vast public RNA-seq datasets.
“I Smoked That Cigarette, and It Calmed Me Down”: A Qualitative Analysis of Intrapersonal, Social, and Environmental Factors Influencing Decisions to Smoke Among Youth Experiencing Homelessness
Authors: Patterson Joanne G , Glasser Allison M , Macisco Joseph M , Hinton Alice , Wermert Amy , Nemeth Julianna M
Published: September 2021

Introduction

Approximately 70% of youth experiencing homelessness smoke cigarettes; many try to quit and are interested in formal smoking cessation programs. The purpose of this study was to describe the intrapersonal, social, and environmental contexts associated with the most recent smoking experience among youth experiencing homelessness and (2) identify differences in contextual factors by age and willingness to quit.

Methods

Thirty-six youth experiencing homelessness aged 14–24 years and who reported current smoking were recruited from a drop-in center in a Midwestern city. Semi-structured in-person interviews were analyzed to understand smoking behaviors.

Results

Two-thirds of participants reported stress and nicotine dependence as primary reasons for smoking, and older youth (aged 18–24 years) reported smoking to de-escalate negative emotions associated with stressful events. For 25% of participants, and especially older youth, smoking was described as part of a routine. Over 80% of participants smoked outside at the homeless drop-in center or the places they lived. Social prompts from drop-in center peers regularly preempted smoking. Younger youth (aged 14–17 years) reported smoking socially while older youth were more likely to smoke alone.

Conclusions

For youth experiencing homelessness, smoking is integrated into daily life and is often used to manage stress associated with homelessness and engage socially with homeless peers. Multicomponent interventions to reduce structural stressors specific to homelessness, change social smoking norms (environmental and social context), and address stress management and nicotine dependence (intrapersonal context) are needed to support smoking cessation among youth experiencing homelessness.

Implications

Youth experiencing homelessness overwhelmingly described how daily stressors associated with homelessness and nicotine dependence preceded recent smoking. Older youth (aged 18–24 years) also reported smoking as “routine”, which likely underscores nicotine dependence in this group. Younger youth (aged 14–17 years) described social smoking. Researchers must develop optimized multilevel interventions to support youth experiencing homelessness who want to quit smoking. Interventions directly targeting social determinants of stress (e.g., poverty, housing instability, food insecurity) and linkages to supportive services are needed. Complementary strategies to address stress coping and nicotine dependence (intrapersonal context) and social smoking norms (social and environmental context) are also necessitated.
Birthright Citizenship
Authors: Honohan Iseult
Published: September 2021

Birthright citizenship refers to the legal status of citizenship when acquired through birth to a citizen parent (ius sanguinis) or birth in the territory of a state (ius soli). This is how most people acquire citizenship, often unconditionally and automatically at birth. A minority across the globe acquire citizenship through naturalization. Historically ius soli predominated from the Early Modern period, when those born in the sovereign’s territory automatically became their subjects. Ius sanguinis arose following the French Revolution, reflecting the free citizen father’s right to pass citizenship on to his child. Both forms spread globally through imitation and colonization. All states now award citizenship by birth; most have a combination of the two forms. But the strength of provisions varies. All states have substantial ius sanguinis provision; fewer have strong ius soli. In both, acquisition may depend on certain restrictive conditions related to parental birthplace or residence, marital status, gender, religion, ethnicity, or race. Until recently citizenship has been studied more by lawyers than political scientists, and birthright citizenship has received less attention than naturalization. Studies have tended to focus on the citizenship laws and policies of a limited number of states, mainly in the Global North. Only recently have studies covering a greater number and diversity of countries begun to emerge. Comparative scholars have sought to identify and explain different patterns of birthright citizenship provision related to the strength of ius soli and ius sanguinis. These have been interpreted variously as alternative models reflecting different national conceptions of citizenship, as determined by civil or common law traditions, or as dependent on histories of emigration, immigration, and colonization. Contemporary changes have been understood as a function of domestic electoral politics, developments in international law, norm diffusion among states, or a range of contingent contextual factors. Scholars dispute whether diversity of citizenship regimes has been succeeded by convergence. More complex typologies and indices, including birthright citizenship, have emerged, along with increasing availability of data on citizenship around the world. The justification of birthright citizenship has been much debated. Birthright citizenship has been seen as an appropriate way of allocating democratic membership, providing intergenerational continuity of citizenry, reducing the incidence of statelessness, and integrating immigrants. But ius sanguinis has often been criticized as exclusive and illiberal. It is debated whether ius soli is better justified, or if all forms of birthright citizenship should be seen as conveying arbitrary privilege and contributing to global inequality.
Gene regulatory networks for compatible versus incompatible grafts identify a role for SlWOX4 during junction formation
Authors: Thomas Hannah , Van den Broeck Lisa , Spurney Ryan , Sozzani Rosangela , Frank Margaret
Published: September 2021

Grafting has been adopted for a wide range of crops to enhance productivity and resilience; for example, grafting of Solanaceous crops couples disease-resistant rootstocks with scions that produce high-quality fruit. However, incompatibility severely limits the application of grafting and graft incompatibility remains poorly understood. In grafts, immediate incompatibility results in rapid death, but delayed incompatibility can take months or even years to manifest, creating a significant economic burden for perennial crop production. To gain insight into the genetic mechanisms underlying this phenomenon, we developed a model system using heterografting of tomato (Solanum lycopersicum) and pepper (Capsicum annuum). These grafted plants express signs of anatomical junction failure within the first week of grafting. By generating a detailed timeline for junction formation, we were able to pinpoint the cellular basis for this delayed incompatibility. Furthermore, we inferred gene regulatory networks for compatible self-grafts and incompatible heterografts based on these key anatomical events, which predict core regulators for grafting. Finally, we examined the role of vascular development in graft formation and uncovered SlWOX4 as a potential regulator of graft compatibility. Following this predicted regulator up with functional analysis, we show that Slwox4 homografts fail to form xylem bridges across the junction, demonstrating that indeed, SlWOX4 is essential for vascular reconnection during grafting, and may function as an early indicator of graft failure.
Development of a Novel Brief Quantitative Sensory Testing Protocol That Integrates Static and Dynamic Pain Assessments: Test-Retest Performance in Healthy Adults
Authors: De Vita Martin J , Buckheit Katherine , Gilmour Christina E , Moskal Dezarie , Maisto Stephen A
Published: September 2021

Objective

Quantitative sensory testing is an expanding pain research domain with numerous clinical and research applications. There is a recognized need for brief reliable quantitative sensory testing protocols that enhance assessment feasibility. This study aimed to integrate static (pain threshold, tolerance, suprathreshold) and dynamic (conditioned pain modulation, offset analgesia, temporal summation) pain reactivity measures into a brief 20-minute protocol that uses a single portable device. The test-retest performance of this optimized protocol was evaluated.

Design

Using a test-retest design, the brief quantitative sensory testing assessment was administered to participants on two occasions separated by exactly 7 days.

Setting

A clinical psychology research laboratory at Syracuse University.

Subjects

Participants were 33 healthy adults recruited from Syracuse University’s online research participation pool.

Methods

A portable computerized quantitative sensory testing device delivered contact-heat pain to assess static and dynamic pain measures in participants. Dynamic responses were continuously recorded using a computerized visual analog scale.

Results

Pain threshold, tolerance, and suprathreshold exhibited excellent reliability (intraclass correlations ranged from 0.80 to 0.83). Conditioned pain modulation, offset analgesia, temporal summation yielded reliability in the good to excellent range (intraclass correlations ranged from 0.66 to 0.71).

Conclusions

Findings suggested that this brief integrated QST protocol may reliably monitor human pain reactivity over brief periods. This protocol may enhance quantitative sensory testing feasibility in clinical and research settings.
Cross-Sectional Skewness
Authors: Oh Sangmin S , Wachter Jessica A
Published: September 2021

What distribution best characterizes the time series and cross-section of individual stock returns? To answer this question, we estimate the degree of cross-sectional return skewness relative to a benchmark that nests many models considered in the literature. We find that cross-sectional skewness in monthly returns far exceeds what this benchmark model predicts. However, cross-sectional skewness in long-run returns in the data is substantially below what the model predicts. We show that fat-tailed idiosyncratic events appear to be necessary to explain skewness in the data. (JEL, G10, G11, G12, G13, G14).
Firm Characteristics and Global Stock Returns: A Conditional Asset Pricing Model
Authors: Windmüller Steffen
Published: September 2021

This paper studies the relation between 36 firm-level characteristics and stock returns in 48 countries using instrumented principal components analysis. A non-U.S. country-neutral conditional factor model performs well in describing risk and returns and generates small and statistically insignificant anomaly intercepts when allowing for three or more latent factors. The non-U.S. model performs better in emerging than in developed markets, while showing substantial differences across countries. On average, only 10 characteristics significantly contribute to the models’ performance. Market beta, momentum, and firm size characteristics instrument for systemic exposure in U.S. and non-U.S. models, while investment and book-to-market do not. (JEL G11, G12, G14, G15)

Received January 28, 2021; editorial decision July 30, 2021
Measuring societal impact of research—Developing and validating an impact instrument for occupational health and safety
Authors: Sørensen Ole Henning , Bjørner Jakob , Holtermann Andreas , Dyreborg Johnny , Sørli Jorid Birkelund , Kristiansen Jesper , Nielsen Steffen Bohni
Published: September 2021

Research funders and policymakers increasingly focus on societal benefits of their investments in research. Research institutions thus face increasing pressure to demonstrate their societal impact to prove their legitimacy and worth. To this end, research institutions need reliable, quantitative methods to measure societal impact. This article describes the development and test of an instrument to quantitatively measure societal impact of applied research at research institution and program levels. It demonstrates the successful validation of the instrument in the multi-disciplinary field of occupational health and safety. The instrument, the Societal Impact Instrument: Occupational Health and Safety Research (SII:OHSR), produces an aggregate measure of societal impact for the research institution as a whole and subscales for each research program. The SII:OHSR instrument is built on a process model of knowledge translation and exchange. It has been developed in the context of multi-disciplinary occupational health and safety research. The instrument is constructed as a generalized and context-independent tool that can be relocated to other research domains and languages. To the best of our knowledge, it is the first singular instrument that quantitatively measures societal impact. It is therefore highly pertinent for the research evaluation field.
The Life Cycle Effects of Corporate Takeover Defenses
Authors: Johnson William C , Karpoff Jonathan M , Yi Sangho
Published: September 2021

We document that the relation between firm value and the use of takeover defenses is positive for young firms but becomes negative as firms age. This value reversal pattern reflects specific changes in the costs and benefits of takeover defenses as firms age and arises because defenses are sticky and rarely removed. Firms can attenuate the value reversal by removing defenses, but do so only when the defenses become very costly and adjustment costs are low. The value reversal explains previous mixed evidence about takeover defenses and implies that firm age proxies for takeover defenses’ heterogeneous impacts on firm value.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
“Littered with Logos!”: An Investigation into the Relationship between Water Provision, Humanitarian Branding, Donor Accountability, and Self-Reliance in Ugandan Refugee Settlements
Authors: Martin Diana , Brown Julia
Published: September 2021

The branding of humanitarian assets and programme signage (often in English) is common practice in displacement contexts. Such visibility is a reminder of the special status of refugee spaces and a requirement imposed by donors. However, such branding, which forms part of the humanitarian organisations’ accountability to donors, raises profound issues in relation to the Comprehensive Refugee Response Framework (CRRF) and the agenda of refugee self-reliance. Drawing on our work on water access in Ugandan refugee settlements for humanitarian NGOs, we present a case study that explores the humanitarian response and its implications on the sustainability of water provision through the lens of branding and accountability. As donors and taxpayers become the (distant) audiences of visibility strategies, we argue that the branding of water structures, coupled with the lack of accountability to affected populations (AAPs) potentially undermines refugees’ sense of ownership necessary for the future upkeep and maintenance of water sources. The sector may thus compromise the sustainability of programming as advanced by the CRRF. As accountability to donors is prioritised over AAP, we argue that the impact of branding on sustainability of water provision can be better understood by investigating its psychological effects on programme beneficiaries.
The role of Universities in Transformative Innovation Policy
Authors: Parker Rachel , Lundgren Petra
Published: September 2021

The entrepreneurial and innovative activities that universities perform in addition to teaching and research have been aligned to an Innovation Systems Policy framework, which has been the dominant paradigm of innovation policy for several decades. However, Innovation Policy is being reframed in response to the growing recognition that inequality, poverty, climate change, and environmental challenges persist and are deepening despite substantial public investment in science and technology and the growth of university outreach activities associated with the entrepreneurial Third Mission vision. This paper outlines an alternative Transformative Innovation Policy agenda that unpacks the role of Universities in social change. This conceptual framework is operationalised through a description of the research practices that would underpin a Transformative Innovation Policy mission for Universities in addressing major social changes associated with obesity, decarbonisation of transport, ocean plastics, and pandemics.
Treating, Preventing, Feigning, Concealing: Sickness, Agency and the Medical Culture of the British Naval Seaman at the End of the Long Eighteenth Century
Authors: Caputo Sara
Published: September 2021

Seen as a crucial historical step in the development of ‘modern’ institutional healthcare, eighteenth-century British naval medicine has traditionally been studied from the point of view of the state and of physicians and surgeons: naval sailors’ attitudes towards health, medicine and their own bodies remain virtually unexplored. Using official and personal sources, this article sketches a ‘patient’s history’ of late-eighteenth- and early-nineteenth-century British ratings. Aiming to counterbalance Foucauldian interpretations, it highlights some of the ways in which individuals, even when apparently most powerless, confined in ships far from home, and controlled by rigidly disciplined institutions, could take responsibility for their health, successfully or otherwise, within, against or alongside the system. If the unprecedented administrative requirements of the French Wars strengthened and standardised top-down medical authority, they also brought opportunities for evasion and negotiation. This complicates established narratives of the relationship between modern medicine, the armed forces and power.
“My Favorite One Is the One Who Is There Right Now”: Socioeconomic Differences in Support Exchanges within Stepfamilies
Authors: Amorim Mariana
Published: September 2021

Family scholars have raised concerns that the reshaping of American families over the last decades might have changed kin support networks and resource sharing within families. Much of this concern stems from documented socioeconomic inequalities in exposure to divorce and separation, formation of new marital or cohabiting unions, and multiple-partner fertility. There is a dearth of research, however, on whether and how the experience of different family structures is shaped by socioeconomic status. This study draws on in-depth interviews with 47 older stepparents in order to investigate exchanges of support with biological and stepchildren in different socioeconomic contexts. Results suggest that scarcity of resources among socioeconomically disadvantaged stepparents and the instability of their (and their children’s) social and economic environments promote a specific type of supportive tie—contingent ties. This study shows that ambiguity and contingency in the establishment of supportive relationships with children may represent an adaptive, healthy, and reasonable strategy among older stepparents with scarce resources.
How to Render Species Comparable Taxonomic Units Through Deep Time: A Case Study on Intraspecific Osteological Variability in Extant and Extinct Lacertid Lizards
Authors: Tschopp Emanuel , Napoli James G , Wencker Lukardis C M , Delfino Massimo , Upchurch Paul
Published: September 2021

Generally, the species is considered to be the only naturally occurring taxon. However, species recognized and defined using different species delimitation criteria cannot readily be compared, impacting studies of biodiversity through Deep Time. This comparability issue is particularly marked when comparing extant with extinct species because the only available data for species delimitation in fossils are derived from their preserved morphology, which is generally restricted to osteology in vertebrates. Here, we quantify intraspecific, intrageneric, and intergeneric osteological variability in extant species of lacertid lizards using pairwise dissimilarity scores based on a data set of 253 discrete osteological characters for 99 specimens referred to 24 species. Variability is always significantly lower intraspecifically than between individuals belonging to distinct species of a single genus, which is in turn significantly lower than intergeneric variability. Average values of intraspecific variability and associated standard deviations are consistent (with few exceptions), with an overall average within a species of 0.208 changes per character scored. Application of the same methods to six extinct lacertid species (represented by 40 fossil specimens) revealed that intraspecific osteological variability is inconsistent, which can at least in part be attributed to different researchers having unequal expectations of the skeletal dissimilarity within species units. Such a divergent interpretation of intraspecific and interspecific variability among extant and extinct species reinforces the incomparability of the species unit. Lacertidae is an example where extant species recognized and defined based on a number of delimitation criteria show comparable and consistent intraspecific osteological variability. Here, as well as in equivalent cases, application of those skeletal dissimilarity values to paleontological species delimitation potentially provides a way to ameliorate inconsistencies created by the use of morphology to define species. [Intraspecific variation; Lacertidae; morphological disparity; osteology; species delimitation; taxonomic bias.]
Maximum Parsimony Inference of Phylogenetic Networks in the Presence of Polyploid Complexes
Authors: Yan Zhi , Cao Zhen , Liu Yushu , Ogilvie Huw A , Nakhleh Luay
Published: September 2021

Phylogenetic networks provide a powerful framework for modeling and analyzing reticulate evolutionary histories. While polyploidy has been shown to be prevalent not only in plants but also in other groups of eukaryotic species, most work done thus far on phylogenetic network inference assumes diploid hybridization. These inference methods have been applied, with varying degrees of success, to data sets with polyploid species, even though polyploidy violates the mathematical assumptions underlying these methods. Statistical methods were developed recently for handling specific types of polyploids and so were parsimony methods that could handle polyploidy more generally yet while excluding processes such as incomplete lineage sorting. In this article, we introduce a new method for inferring most parsimonious phylogenetic networks on data that include polyploid species. Taking gene tree topologies as input, the method seeks a phylogenetic network that minimizes deep coalescences while accounting for polyploidy. We demonstrate the performance of the method on both simulated and biological data. The inference method as well as a method for evaluating evolutionary hypotheses in the form of phylogenetic networks are implemented and publicly available in the PhyloNet software package. [Incomplete lineage sorting; minimizing deep coalescences; multilabeled trees; multispecies network coalescent; phylogenetic networks; polyploidy.]
Air Pollution as a Determinant of Undernutrition Prevalence among Under-Five Children in India: An Exploratory Study
Authors: Bora Kaustubh
Published: September 2021

Aim

The association of air pollution with prevalence of undernutrition indices (namely, anaemia, stunting, wasting and underweight) among under-five children in India was investigated.

Methods

Estimates of population weighted annual average gridded PM2.5 concentrations and proportion of households using solid cooking fuel (HSCF usage percent) during 2017 in India, reflecting the magnitude of ambient and household air pollution respectively, were extracted in a state-wise manner from India State Level Disease Burden Initiative (ISLDBI) reports. Their relationships with the corresponding prevalence of anaemia, underweight, wasting and stunting in under-five children were analysed.

Results

The state-level PM2.5 concentrations (mean: 65.5 µg/m3; median: 49.2 µg/m3; range: 17.3–209.0 µg/m3) correlated significantly (P < 0.01) with anaemia (r = 0.65), stunting (r = 0.58) and underweight (r = 0.50) prevalence; while HSCF usage (mean: 49.3%; median: 46.0%; range: 1.9–81.5%) correlated significantly (P < 0.01) with stunting (r = 0.69) and underweight (r = 0.58) prevalence. When examined across median cut-offs and after adjusting for socio-demographic index, the association of anaemia prevalence with PM2.5 concentrations persisted. This association was maintained even after controlling for the coverage of anaemia-specific interventions (namely, iron supplements and deworming medications). The mean difference in PM2.5 concentrations between the high and low PM2.5 states was 58.6 µg/m3, which accounted for 11.8% higher anaemia prevalence in the former as compared to the latter.

Conclusion

The burden of childhood undernutrition, particularly anaemia, in India may be linked to PM2.5 levels. To mitigate this burden, it may be necessary to complement the ongoing nutritional interventions with air pollution control measures.
The Potential Biocontrol Agent Paenibacillus polymyxa TP3 Produces Fusaricidin-Type Compounds Involved in the Antagonism Against Gray Mold Pathogen Botrytis cinerea
Authors: Tsai Shuen-Huang , Chen Yu-Ting , Yang Yu-Liang , Lee Bo-Yi , Huang Chien-Jui , Chen Chao-Ying
Published: September 2021

Paenibacillus polymyxa is a beneficial bacterium for plant health. P. polymyxa TP3 exhibits antagonistic activity toward Botrytis cinerea and alleviates gray mold symptoms on the leaves of strawberry plants. Moreover, suppression of gray mold on the flowers and fruits of strawberry plants in field trials, including vegetative cells and endospores, was demonstrated, indicating the potential of strain TP3 as a biological control agent. To examine the anti-B. cinerea compounds produced by P. polymyxa TP3, we performed matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, and fusaricidin-corresponding mass spectra were detected. Moreover, fusaricidin-related signals appeared in imaging mass spectrometry of TP3 when confronted with B. cinerea. By using liquid chromatography mass spectrometry-based molecular networking approach, we identified several fusaricidins including a new variant of mass/charge ratio 917.5455 with serine in the first position of the hexapeptide. Via advanced mass spectrometry and network analysis, fusaricidin-type compounds produced by P. polymyxa TP3 were efficiently disclosed and were presumed to play roles in the antagonism against gray mold pathogen B. cinerea.
Normalizing Service Learning in Medical Education to Sustain Medical Student-Led Initiatives
Authors: Nguemeni Tiako Max Jordan , Johnson Shawn F. , Nkinsi Naomi Tweyo , Landry Adaira
Published: September 2021

Medical students demonstrate their passion for participating in and improving health care both within and outside the classroom. As the COVID-19 pandemic swept across the world, medical students in the United States engaged in student-led service-learning initiatives to contribute to medicine and their local communities, including collecting and distributing personal protective equipment, creating and translating pandemic-related educational materials, and providing childcare for frontline workers. Their impact was recognized and appreciated.

Service learning is an education method that incorporates community outreach with didactic coursework and student reflection. In this commentary, the authors argue for including service learning as a required component in the medical school curriculum to provide students with the tools and support to be advocates and leaders within society, as no such curriculum currently exists. The authors also discuss the history of medical student-led service-learning efforts through to the present day, barriers to implementing and sustaining student-led service-learning initiatives, and solutions to prepare students for service-learning initiatives.
Prevalence of Mycoplasma genitalium fluoroquinolone-resistance markers, and dual-class-resistance markers, in asymptomatic men who have sex with men
Authors: Chua Teck-Phui , Bodiyabadu Kaveesha , Machalek Dorothy A. , Garland Suzanne M. , Bradshaw Catriona S. , Plummer Erica L. , Danielewski Jennifer , Vodstrcil Lenka A. , Doyle Michelle L. , Murray Gerald L.
Published: September 2021

Introduction. Failure of fluoroquinolones, the principal treatment option for macrolide-resistant

Mycoplasma genitalium

infections, has recently emerged. This is of particular concern for men who have sex with men (MSM), who have high proportions of macrolide-resistant

M. genitalium

infections. Treatment failure with moxifloxacin is likely the result of single nucleotide polymorphisms (SNPs) in parC, whilst concurrent gyrA mutations may play a role.

Gap Statement. The levels of fluoroquinolone resistance and dual-class (i.e. macrolide and fluoroquinolone) resistance in

M. genitalium

among asymptomatic MSM is unknown.

Aim. To (i) determine the proportion of fluoroquinolone resistance and dual-class resistance in

M. genitalium

infections among asymptomatic MSM, (ii) explore any clinical and behavioural associations with fluoroquinolone resistance, and (iii) determine the distribution of antibiotic resistance among M. genitalium mgpB sequence types (STs).

Methodology.

M. genitalium

positive samples (N=94) were obtained from 1001 asymptomatic MSM enrolled in a study at Melbourne Sexual Health Centre (Carlton, Australia) between August 2016 and September 2017. Sanger sequencing was performed to determine the proportion of

M. genitalium

infections with SNPs in parC that have previously been associated with failure of moxifloxacin (corresponding to amino changes S83I, D83R, D87Y and D87N) and in gyrA (corresponding to amino acid changes M95I, D99N, D99Y and D99G). Associations between clinical/behavioural factors and parC SNPs were examined. Strain typing was performed by sequencing a portion of the mgpB gene.

Results. The proportion of MSM with infections harbouring parC and gyrA SNPs was 13.0 % [95 % confidence interval (CI): 6.8–23.2 %] and 4.7 % (95 % CI: 1.1–13.4 %), respectively; dual-class resistance was 13.0 %. No significant clinical/behavioural associations were found. Antibiotic resistance was not restricted to specific mgpB STs.

Conclusion. One in eight (13 %) of asymptomatic MSM with

M. genitalium

had an infection with dual-class-resistance mutations. Typing by mgpB sequence suggested fluoroquinolone resistance is arising from independent mutation events. This study illustrates that asymptomatic MSM may act as a reservoir for antibiotic-resistant

M. genitalium

.
Arbuscular mycorrhizal fungi influence host infection during epidemics in a wild plant pathosystem
Authors: Eck Jenalle L. , Kytöviita Minna-Maarit , Laine Anna-Liisa
Published: September 2021

While pathogenic and mutualistic microbes are ubiquitous across ecosystems and often co-occur within hosts, how they interact to determine patterns of disease in genetically diverse wild populations is unknown.

To test whether microbial mutualists provide protection against pathogens, and whether this varies among host genotypes, we conducted a field experiment in three naturally-occurring epidemics of a fungal pathogen,Podosphaera plantaginis, infecting a host plant,Plantago lanceolata, in the Åland Islands, Finland. In each population, we collected epidemiological data on experimental plants from six allopatric populations that had been inoculated with a mixture of mutualistic arbuscular mycorrhizal fungi or a non-mycorrhizal control.

Inoculation with arbuscular mycorrhizal fungi increased growth in plants from every population, but also increased host infection rate. Mycorrhizal effects on disease severity varied among host genotypes and strengthened over time during the epidemic. Host genotypes that were more susceptible to the pathogen received stronger protective effects from inoculation.

Our results show that arbuscular mycorrhizal fungi introduce both benefits and risks to host plants, and shift patterns of infection in host populations under pathogen attack. Understanding how mutualists alter host susceptibility to disease will be important for predicting infection outcomes in ecological communities and in agriculture.

Plain Language Summary

Beneficial, ‘mycorrhizal’ fungi in roots help plants grow and may protect them from diseases caused by pathogenic microbes. This study shows that arbuscular mycorrhizal fungi can influence patterns of plant disease during pathogen outbreaks in a natural landscape.
Identification of novel chemical scaffolds that inhibit the growth of Mycobacterium tuberculosis in macrophages
Authors: Ahmed Sara , Manning Alyssa , Flint Lindsay , Awasthi Divya , Parish Tanya
Published: September 2021

Mycobacterium tuberculosis is an important global pathogen for which new drugs are urgently required. The ability of the organism to survive and multiply within macrophages may contribute to the lengthy treatment regimen with multiple drugs that are required to cure the infection. We screened the MyriaScreen II diversity library of 10,000 compounds to identify novel inhibitors of M. tuberculosis growth within macrophage-like cells using high content analysis. Hits were selected which inhibited the intramacrophage growth of M. tuberculosis without significant cytotoxicity to infected macrophages. We selected and prioritized compound series based on their biological and physicochemical properties and the novelty of the chemotypes. We identified five chemical classes of interest and conducted limited catalog structure-activity relationship studies to determine their tractability. We tested activity against intracellular and extracellular M. tuberculosis, as well as cytoxicity against murine RAW264.7 and human HepG2 cells. Benzene amide ethers, thiophene carboxamides and thienopyridines were only active against intracellular bacteria, whereas the phenylthiourea series was also active against extracellular bacteria. One member of a phenyl pyrazole series was moderately active against extracellular bacteria. We identified the benzene amide ethers as an interesting series for further work. These new compound classes serve as starting points for the development of novel drugs to target intracellular M. tuberculosis.
Assessing the role of fungal diversity in decomposition: A meta-analysis
Authors: Drost Sytske M. , van der Wal Annemieke , de Boer Wietse , Bodelier Paul. L.E.
Published: September 2021

Fungi play an important role in carbon - and nutrient cycling. It is, however, unclear if diversity of fungi is essential to fulfill this role. With this meta-analysis, we aim to understand the relationship between fungal diversity and decomposition of plant materials (leaf litter and wood) in terrestrial and aquatic environments. The selection criteria for papers were the presence of a fungal diversity gradient and quantification of decomposition as mass loss. In total 40 papers met the selection criteria. We hypothesized that increase of fungal species will result in stronger decomposition, especially in species poor communities. Both artificial inoculated and naturally assembled fungal communities were included in the analysis in order to assess whether manipulated experiments are representative for field situations. We found a significant positive effect of increased fungal diversity on decomposition. However, in manipulated experiments this relationship was only positive when a control treatment of one fungus was compared with multispecies communities. This relationship became negative when comparisons of higher initial richness (at least two fungal species as “control”) were included. In contrast, under natural field conditions increased fungal diversity coincided with increased decomposition. This suggests that manipulated experiments are not representative for field situations. Possible reasons for this are discussed. Yet, both in manipulated and field experiments, environmental factors can influence diversity – decomposition relationships as indicated by a negative relationship of increasing C:N ratio on the effect of fungal diversity on decomposition. Overall, our results show that fungal diversity can have an important role in decomposition, but that design of experiments (manipulated or field) and quality of the plant material should be taken into account for interpretation of this diversity-functioning relationship.
Infectivity of three Mayaro Virus (Genus Alphavirus, Family Togaviridae) geographic isolates in human cell lines
Authors: Patel Aum R. , Dulcey Melissa , Abid Nabil , Cash Melanie N. , Dailey Jordan , Salemi Marco , Mavian Carla , Vittor Amy Y.
Published: September 2021

Mayaro virus (MAYV) is an emergent arthropod-borne virus that causes an acute febrile illness accompanied by arthralgia, similar to chikungunya virus. Increasing urbanization of MAYV outbreaks in the Americas has led to concerns that this virus could further expand its geographic range. Given the potential importance of this pathogen, we sought to fill some critical gaps in knowledge regarding MAYV infectivity and geographic variation. This study describes the cytopathogenicity of MAYV in human dermal fibroblasts, human skeletal muscle satellite cells, human embryonic kidney cells (HEK), peripherally derived human macrophages, and Vero cells. MAYV strain isolated from Bolivia (MAYV-U) infected cells more rapidly compared to MAYV strains isolated in Peru and Brazil (MAYV-P; MAYV-B), with high titers (1×108 pfu/ml) peaking at 37 hours post infection. MAYV-U also caused the most cytopathic effect in a time dependent manner. Furthermore, differently from the other two prototypic strains, MAYV-U harbors unique mutations in the E2 protein, D60G and S205F, likely to interact with the host cell receptor, which may explain the observed differences in infectivity. We further demonstrate that pre-treatment of cells with interferon-β inhibited viral replication in a dose-dependent manner. Together, these findings advance our understanding of MAYV infection of human target cells and provide initial data regarding MAYV phenotypic variation according to geography.

Author Summary

Arthropod-borne viruses are of great public health concern, causing epidemics worldwide due to climate change, changes in land use, rapid urbanization, and the expanding geographic ranges of suitable vectors. Among these viruses, Mayaro is an emerging virus for which little is currently known. This study aims to answer fundamental questions of Mayaro virus biology using three geographically distinct viral strains to examine variability in infection kinetics and infectivity in susceptible cell types. We found one geographic isolate to have accelerated infection kinetics and increased cell damage because of infection. To better understand what was unique about this isolate, we compared their envelope protein, which is critical for entry into a cell. We found that the isolate with increased replication kinetics possessed mutations at sites that may promote viral entry, which could explain these findings. Together, these findings further our understanding of Mayaro virus biology and provide insight into factors that contribute to Mayaro transmission and infectivity.
Nucleolar translocation of human DNA topoisomerase II by ATP depletion and its disruption by the RNA polymerase I inhibitor BMH-21
Authors: Morotomi-Yano Keiko , Yano Ken-ichi
Published: September 2021

DNA topoisomerase II (Top2) is a nuclear protein that resolves DNA topological problems and plays critical roles in multiple nuclear processes. Human cells have two Top2 proteins, Top2A and Top2B, that are localized in both the nucleoplasm and nucleolus. Previously, ATP depletion was shown to augment the nucleolar localization of Top2B, but the molecular details of subnuclear distributions, particularly of Top2A, remained to be fully elucidated in relation to the status of cellular ATP. Here, we analyzed the nuclear dynamics of human Top2A and Top2B in ATP-depleted cells. Both proteins rapidly translocated from the nucleoplasm to the nucleolus in response to ATP depletion. FRAP analysis demonstrated that they were highly mobile in the nucleoplasm and nucleolus. The nucleolar retention of both proteins was sensitive to the RNA polymerase I inhibitor BMH-21, and the Top2 proteins in the nucleolus were immediately dispersed into the nucleoplasm by BMH-21. Under ATP-depleted conditions, the Top2 poison etoposide was less effective, indicating the therapeutic relevance of Top2 subnuclear distributions. These results give novel insights into the subnuclear dynamics of Top2 in relation to cellular ATP levels and also provide discussions about its possible mechanisms and biological significance.