bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive intron gain in the most intron-rich eukaryotes is driven by introner-like transposable elements of unprecedented diversity and flexibility
Authors: Roy Scott William , Gozashti Landen , Bowser Bradley A. , Weinstein Brooke N. , Larue Graham E.
Published: October 2020

Spliceosomal introns, which interrupt nuclear genes and are removed from RNA transcripts by machinery termed spliceosomes, are ubiquitous features of eukaryotic nuclear genes [1]. Patterns of spliceosomal intron evolution are complex, with some lineages exhibiting virtually no intron creation while others experience thousands of intron gains [2–5]. One possibility is that this punctate phylogenetic distribution is explained by intron creation by Introner-Like Elements (ILEs), transposable elements capable of creating introns, with only those lineages harboring ILEs undergoing massive intron gain [6–10]. However, ILEs have been reported in only four lineages. Here we study intron evolution in dinoflagellates. The remarkable fragmentation of nuclear genes by spliceosomal introns reaches its apex in dinoflagellates, which have some twenty introns per gene [11,12]. Despite this, almost nothing is known about the molecular and evolutionary mechanisms governing dinoflagellate intron evolution. We reconstructed intron evolution in five dinoflagellate genomes, revealing a dynamic history of intron loss and gain. ILEs are found in 4/5 studied species. In one species,Polarella glacialis, we find an unprecedented diversity of ILEs, with ILE insertion leading to creation of some 12,253 introns, and with 15 separate families of ILEs accounting for at least 100 introns each. These ILE families range in mobilization mechanism, mechanism of intron creation, and flexibility of mechanism of intron creation. Comparison within and between ILE families provides evidence that biases in so-called intron phase, the distribution of introns relative to codon periodicity, are driven by ILE insertion site requirements [9,13,14]. Finally, we find evidence for multiple additional transformations of the spliceosomal system in dinoflagellates, including widespread loss of ancestral introns, and alterations in required, tolerated and favored splice motifs. These results reveal unappreciated intron creating elements diversity and spliceosomal evolutionary capacity, and suggest complex evolutionary dependencies shaping genome structures.
Hand-selective visual regions represent how to grasp 3D tools: brain decoding during real actions
Authors: Knights Ethan , Mansfield Courtney , Tonin Diana , Saada Janak , Smith Fraser W. , Rossit Stéphanie
Published: October 2020

Most neuroimaging experiments that investigate how tools and their actions are represented in the brain use visual paradigms where tools or hands are displayed as 2D images and no real movements are performed. These studies discovered selective visual responses in occipito-temporal and parietal cortices for viewing pictures of hands or tools, which are assumed to reflect action processing, but this has rarely been directly investigated. Here, we examined the responses of independently visually defined category-selective brain areas when participants grasped 3D tools. Using real action fMRI and multi-voxel pattern analysis, we found that grasp typicality representations (i.e., whether a tool is being grasped appropriately for use) were decodable from hand-selective areas in occipito-temporal and parietal cortices, but not from tool-, object-, or body-selective areas, even if partially overlapping. Importantly, these effects were exclusive for actions with tools, but not for biomechanically matched actions with control nontools. In addition, decoding of grasp typicality was significantly higher in hand than tool-selective parietal regions. Notably, grasp typicality representations were automatically evoked even when there was no requirement for tool use and participants were naïve to object category (tool vs non-tools). Finding a specificity for typical tool grasping in hand-, rather than tool-, selective regions challenges the long-standing assumption that brain activation for viewing tool images reflects sensorimotor processing linked to tool manipulation. Instead our results show that typicality representations for tool grasping are automatically evoked in visual regions specialised for representing the human hand, the brain’s primarytoolfor interacting with the world.

Significance Statement

The unique ability of humans to manufacture and use tools is unsurpassed across the animal kingdom, with tool use considered a defining feature of our species. Most neuroscientific studies that investigate the brain mechanisms that support tool use, record brain activity while people simply view images of tools or hands and not when people perform actual hand movements with tools. Here we show that specific areas of the human visual system that preferentially process hands automatically encode how to appropriately grasp 3D tools, even when no actual tool use is required. These findings suggest that visual areas optimized for processing hands represent fundamental aspects of tool grasping in humans, such as which side they should be grasped for correct manipulation.
Ensemble epistasis: thermodynamic origins of non-additivity between mutations
Authors: Morrison Anneliese J. , Wonderlick Daria R. , Harms Michael J.
Published: October 2020

Non-additivity between mutations—epistasis—profoundly shapes evolution. It can be difficult to understand its mechanistic origins. Here we show that “ensemble epistasis” is likely a universal feature of macromolecules. Using a simple analytical model, we found that epistasis arises when two conditions are met: 1) a macro-molecule populates at least three structures and 2) mutations have differential effects on a least two of the inactive structures. To explore the relative magnitude of ensemble epistasis, we performed a virtual deep-mutational scan of the allostericCa2+signaling protein S100A4. We found that 27% of mutation pairs gave ensemble epistasis with a magnitude on the order of thermal fluctuations, 1 kT. We observed many forms of epistasis: magnitude, sign, and reciprocal sign epistasis. Depending on the effector concentration, the same mutation pair could even exhibit different forms of epistasis. The ubiquity of ensembles in biology and its pervasiveness in our dataset suggests that ensemble epistasis may be a universal mechanism of epistasis.

Significance statement

Addressing the mechanistic origins of evolutionary unpredictability is critical to understanding how mutations combine to determine phenotype. Here we lay the theoretical foundations and investigate the plausibility of a potentially universal mechanism of unpredictability in macromolecules. Macromolecules often adopt a set of interchanging structures, called a thermodynamic ensemble. Mutations can change the relative population of each structure, introducing unpredictability in the mapping between genotype and phenotype. The conditions under which we expect this to arise are common in macromolecules, suggesting that this form of unpredictability may be pervasive in evolution. We conclude that the thermodynamic ensemble bakes unpredictability into biology and that future attempts to address it might incorporate this mechanistic insight.
COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding
Authors: Abitogun Folagbade , Srivastava R. , Sharma S. , Komarysta V. , Akurut E. , Munir N. , Macalalad L. , Olawale O. , Owolabi O. , Abayomi G. , Debnath S.
Published: October 2020

The COVID19 pandemic has resulted in 1,092,342 deaths as of 14thOctober 2020, indicating the urgent need for a vaccine. This study highlights novel protein sequences generated by shot gun sequencing protocols that could serve as potential antigens in the development of novel subunit vaccines and through a stringent inclusion criterion, we characterized these protein sequences and predicted their 3D structures. We found distinctly antigenic sequences from the SARS-CoV-2 that have led to identification of 4 proteins that demonstrate an advantageous binding with Human leukocyte antigen-1 molecules. Results show how previously unexplored proteins may serve as better candidates for subunit vaccine development due to their high stability and immunogenicity, reinforce by their HLA-1 binding propensities and low global binding energies. This study thus takes a unique approach towards furthering the development of vaccines by employing multiple consensus strategies involved in immuno-informatics technique.
Selective connectivity limits functional binocularity in the retinogeniculate pathway of the mouse
Authors: Bauer Joel , Weiler Simon , Fernholz Martin , Laubender David , Scheuss Volker , Hübener Mark , Bonhoeffer Tobias , Rose Tobias
Published: October 2020

Eye-specific segregation of retinal ganglion cell (RGC) axons in the dorsal lateral geniculate nucleus (dLGN) is considered a hallmark of visual system development. However, a recent anatomical study showed that nearly half of the neurons in dLGN of adult mice still receive input from both retinae, but functional data about binocularity in mature dLGN is conflicting. Here, we found that a variable but small fraction of thalamocortical neurons is binocularin vivo. Using dual-channel optogeneticsin vitrowe correspondingly found that dLGN neurons are dominated by retinogeniculate input from one eye only, although most neurons also received small but detectable input from the non-dominant eye. Anatomical overlap between RGC axons and dLGN neuron dendrites did not explain this strong bias towards monocularity. Our data rather suggest that functional input selection and refinement, leaving the remaining non-dominant eye inputs in a juvenile-like state, underlies the prevalent monocularity of neurons in dLGN.
Vaginal Isolates ofCandida glabrataare Uniquely Susceptible to Ionophoric Killer Toxins Produced bySaccharomyces cerevisiae
Authors: Fredericks Lance R. , Lee Mark D. , Eckert Hannah R. , Li Shunji , Shipley Mason A. , Roslund Cooper R. , Boikov Dina A. , Kizer Emily A. , Sobel Jack D. , Rowley Paul A.
Published: October 2020

Compared to other species ofCandidayeasts, the growth ofCandida glabratawas inhibited by many different strains ofSaccharomyceskiller yeasts. The ionophoric K1 and K2 killer toxins were broadly inhibitory to all clinical isolates ofC. glabratafrom patients with recurrent vulvovaginal candidiasis, despite high levels of resistance to clinically relevant antifungal therapeutics.
Temporal stability of human sperm mosaic mutations results in life-long threat of transmission to offspring
Authors: Yang Xiaoxu , Breuss Martin W. , Xu Xin , Antaki Danny , James Kiely N. , Stanley Valentina , Ball Laurel L. , George Renee D. , Wirth Sara A. , Cao Beibei , Nguyen An , McEvoy-Venneri Jennifer , Chai Guoliang , Nahas Shareef , Van Der Kraan Lucitia , Ding Yan , Sebat Jonathan , Gleeson Joseph G.
Published: October 2020

Every newborn harbors scores of new single nucleotide variants (SNVs) that may impact health and disease1–4; the majority of these are contributed by the paternal germ cells5. In some cases, these mutations are identifiable in a subset of the parents’ cells—a phenomenon called mosaicism, which is capable of producing disease recurrence6–8. Here, we provide a comprehensive analysis of male gonadal mosaic mutations, employing 300× whole genome sequencing (WGS) of blood and sperm in 17 healthy individuals, including assessment across multiple samples and age groups. Approximately 1 in 15 healthy males is predicted to harbor a transmissible, likely pathogenic exonic variant that is mosaic in his sperm. In general, only a third of sperm mosaic mutations were detectable in blood cells, all were remarkably stable over the course of months to years, and 23% were present in 5% or more of sperm cells. There was no evidence of age-dependent clonal expansion or collapse, as seen in hematopoiesis. Thus, despite the observed increase of mutations in offspring of men with advanced paternal age, detectable sperm mosaicism remains stable, represents a life-long transmission risk to offspring, and suggests a testis stem cell niche that prevents widespread clonality.
Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies
Authors: Murin Charles D. , Gilchuk Pavlo , Ilinykh Philipp A. , Huang Kai , Kuzmina Natalia , Shen Xiaoli , Bruhn Jessica F. , Bryan Aubrey L. , Davidson Edgar , Doranz Benjamin J. , Williamson Lauren E. , Copps Jeffrey , Alkutkar Tanwee , Flyak Andrew I. , Bukreyev Alexander , Crowe James E. , Ward Andrew B.
Published: October 2020

Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use ofIGHV1-69andIGHJ6germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies.
Reinvestigation of grain weight genesTaTGW6andOsTGW6casts doubt on their role in auxin regulation in developing grains
Authors: Kabir Muhammed Rezwan , Nonhebel Heather M.
Published: October 2020

TheTHOUSAND-GRAIN WEIGHT 6genes (TaTGW6andOsTGW6) are reported to result in larger grains of wheat and rice by reducing production of indole-3-acetic acid (IAA) in developing grains. However, a critical comparison of data onTaTGW6andOsTGW6with other reports on IAA synthesis in cereal grains requires that this hypothesis be reinvestigated. Here, we show thatTaTGW6andOsTGW6are members of a large gene family that has undergone major, lineage-specific gene expansion. Wheat has nine genes, and rice three genes encoding proteins with more than 80% amino acid identity with TGW6 making it difficult to envisage how a single inactive allele could have a major effect on IAA levels. TGW6 is proposed to affect auxin levels by catalysing the hydrolysis of IAA-glucose (IAA-Glc). However, we show that developing wheat grains contain undetectable levels of ester IAA in comparison to free IAA and do not express an IAA-glucose synthase. Previous work onTGW6, reported maximal expression at 20 days after anthesis (DAA) in wheat and 2 DAA in rice. However, we show that neither gene is expressed in developing grains. Instead,TaTGW6, OsTGW6and their close homologues are exclusively expressed in pre-emergence inflorescences;TaTGW6is expressed particularly in microspores prior to mitosis. This combined with evidence for high levels of IAA production from tryptophan in developing grains demonstratesTaTGW6andOsTGW6cannot regulate grain size via the hydrolysis of IAA-Glc. Instead, their similarity to rice strictosidine synthase-like (OsSTRL2) suggests they play a key role in pollen development.
Use of convalescent serum reduces severity of COVID-19 in nonhuman primates
Authors: Cross Robert W. , Prasad Abhishek N. , Borisevich Viktoriya , Woolsey Courtney , Agans Krystle N. , Deer Daniel J. , Dobias Natalie S. , Geisbert Joan B. , Fenton Karla A. , Geisbert Thomas W.
Published: October 2020

Passive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against SARS-CoV-2 is currently being used to treat COVID-19 patients. However, most patients have been treated outside of randomized clinical trials making it difficult to determine the efficacy of this approach. Here, we assessed the efficacy of convalescent sera in a newly developed African green monkey model of COVID-19. Groups of SARS-CoV-2-infected animals were treated with pooled convalescent sera containing either high or low to moderate anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and disease pathology were minimal between monkeys that received the lower titer convalescent sera and untreated controls. However, and importantly, lower levels of SARS-CoV-2 in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several parameters associated with coagulation and inflammatory processes were observed in monkeys that received convalescent sera versus untreated controls. Our data support human studies suggesting that convalescent plasma therapy is an effective strategy if donors with high level of antibodies against SARS-CoV-2 are employed and if recipients are at an early stage of disease.
Experimental phasing with vanadium and application to nucleotide-binding membrane proteins
Authors: El Omari Kamel , Mohamad Nada , Bountra Kiran , Duman Ramona , Romano Maria , Schlegel Katja , Kwong Hok-Sau , Mykhaylyk Vitaliy , Olesen Claus , Moller Jesper Vuust , Bublitz Maike , Beis Konstantinos , Wagner Armin
Published: October 2020

The structure determination of soluble and membrane proteins can be hindered by the crystallographic phase problem, especially in the absence of a suitable homologous structure. Experimental phasing is the method of choice for novel structures; however, it often requires heavy-atom derivatization, which can be difficult and time-consuming. Here, a novel and rapid method to obtain experimental phases for protein structure determination by vanadium phasing is reported. Vanadate is a transition-state mimic of phosphoryl-transfer reactions and it has the advantage of binding specifically to the active site of numerous enzymes catalyzing this reaction. The applicability of vanadium phasing has been validated by determining the structures of three different protein–vanadium complexes, two of which are integral membrane proteins: the rabbit sarcoplasmic reticulum Ca2+-ATPase, the antibacterial peptide ATP-binding cassette transporter McjD from Escherichia coli and the soluble enzyme RNAse A from Bos taurus. Vanadium phasing was successful even at low resolution and despite severe anisotropy in the data. This method is principally applicable to a large number of proteins, representing six of the seven Enzyme Commission classes. It relies exclusively on the specific chemistry of the protein and it does not require any modifications, making it a very powerful addition to the phasing toolkit. In addition to the phasing power of this technique, the protein–vanadium complexes also provide detailed insights into the reaction mechanisms of the studied proteins.
Harnessing the power of an X-ray laser for serial crystallography of membrane proteins crystallized in lipidic cubic phase
Authors: Lee Ming-Yue , Geiger James , Ishchenko Andrii , Han Gye Won , Barty Anton , White Thomas A. , Gati Cornelius , Batyuk Alexander , Hunter Mark S. , Aquila Andrew , Boutet Sébastien , Weierstall Uwe , Cherezov Vadim , Liu Wei
Published: October 2020

Serial femtosecond crystallography (SFX) with X-ray free-electron lasers (XFELs) has proven highly successful for structure determination of challenging membrane proteins crystallized in lipidic cubic phase; however, like most techniques, it has limitations. Here we attempt to address some of these limitations related to the use of a vacuum chamber and the need for attenuation of the XFEL beam, in order to further improve the efficiency of this method. Using an optimized SFX experimental setup in a helium atmosphere, the room-temperature structure of the adenosine A2A receptor (A2AAR) at 2.0 Å resolution is determined and compared with previous A2AAR structures determined in vacuum and/or at cryogenic temperatures. Specifically, the capability of utilizing high XFEL beam transmissions is demonstrated, in conjunction with a high dynamic range detector, to collect high-resolution SFX data while reducing crystalline material consumption and shortening the collection time required for a complete dataset. The experimental setup presented herein can be applied to future SFX applications for protein nanocrystal samples to aid in structure-based discovery efforts of therapeutic targets that are difficult to crystallize.
A moderated mediation model for the relationship between inclusive leadership and job embeddedness
Authors: Elsaied Mervat Mohamed
Published: October 2020

Purpose

This study aimed to examine the effect of inclusive leadership (IL) on job embeddedness (JE) by developing a moderated mediation model. The model focuses on the mediating role of the organizational identification (OID) that underpins the relationship between IL and JE, as well as the moderating influence of person–supervisor fit (P–S fit) on the mediation.

Design/methodology/approach

Data were collected from 364 employees working in 25 five-star hotels in Hurghada, Egypt. Statistical methods such as hierarchical regression, correlation analysis and a bootstrapping test were used to analyze the data.

Findings

The results indicated that OID fully mediated the positive relationship between IL and JE. It also found that P–S fit moderated the mediated relationship between IL and JE via OID. This resulted in the mediated relationship becoming stronger for employees who perceive higher P–S fit rather than who perceive lower P–S fit with their leaders.

Originality/value

This study is the first to consider the effect of OID (a mediator) on the relationship between IL and JE. It also extends our understanding of the mechanism linking IL and JE by testing the mediating influence of OID and the moderating influence of P–S fit.
The influence of showrooming on Millennial generational cohorts online shopping behaviour
Authors: Johnson Olivia , Ramirez Stefanie Ann
Published: October 2020

Purpose

Omnichannel retailing has changed the behaviour of consumers by empowering activities like showrooming which is the process of collecting product information in store then making the purchase online. Since individuals, particularly Millennials, interact with multiple touchpoints throughout their shopping journey, retailers must consider how these experiences influence purchasing behaviour. Literature regarding showrooming has focussed primarily on antecedents to the phenomenon and the negative effects to brick and mortar retailers, however limited studies have investigated the quantitative influence of showrooming from the consumers' perspective. While data show that interest in online shopping is spiking, a vast majority of retail sales are made in-store suggesting barriers to online shopping still exist. Thus, the purpose of this research is to identify the role of showrooming in decreasing risk in an online shopping context. Additionally, Millennial generational cohorts (MGCs) were proposed as moderators in exploring the differences between the dimensions of perceived risk and online shopping intention.

Design/methodology/approach

To explore the relationship between showrooming and MGCs online shopping behaviour an online survey was administered. Data were collected from 480 Millennial consumers at a large southwestern university. Multiple linear regression was used to determine the direction, magnitude and significance of relationships within the models.

Findings

Results from the analysis revealed showrooming and MGCs influence online shopping behaviour as it relates to dimensions of risk. Moreover, showrooming increased online shopping intention specifically in relation to product and financial risk.

Originality/value

This paper contributes to the relevant literature by proposing a relationship between showrooming and online shopping behaviour. This research provides evidence that Millennials are not a monolithic generation and consume differently.
Does institutional quality affect tourism demand? Evidence from India
Authors: Mushtaq Reffat , Thoker Aijaz Abdullah , Bhat Aaqib Ahmad
Published: October 2020

Purpose

The purpose of this paper is to empirically examine the impact of institutional quality on the international tourism demand of India. To carry out the analysis, the study first analyses the impact of composite institutional quality index and then proceeds to examine the impact of each of the individual components of institutional quality on the international tourism demand of India. The impact of income of the tourist originating countries, tourism price, trade openness and Human Development Index (HDI) on tourism demand has also been examined.

Design/methodology/approach

The study employed panel autoregressive distributed lag (ARDL) model, with data from top 30 tourist originating countries for India for the period of 1995–2016.

Findings

The results indicated that an increase in the income of the tourist originating countries has spillover effects on the development of tourism sector of India. The impact of cost of travel proxied by relative prices between the destination and origin country is found to be negative, however, statistically insignificant. The impact of trade openness and development level of the host country (proxied by HDI) is found to have positive association with the tourism demand. Institutional quality is found to have positive association with international tourism demand of India. Among the individual components of institutional quality, rule of law, regulatory quality, control of corruption and voice and accountability are found to promote the tourism sector development in the economy. Contrarily, the impact of government effectiveness is found to be negative. In the short run, most of the variables were found to support their counterpart results in long run.

Practical implications

This study has practical implication not only in formulating tourism sector policies of the host countries but also for issuing tourist advisories in tourist originating countries. The study holds that policymakers should work for improving institutional environment of the country such as bureaucracy, legislature, regulatory quality, rule of law and for reducing corruption at all levels so as to ensure a sustained rise in tourist inflows to India.

Originality/value

This study validates the link between institutional quality of a country and international demand for its tourism. To the best of the authors' knowledge, the study is the first attempt that has comprehensively analysed the impact of institutional quality on tourism demand in Indian context which has been generally ignored in the tourism literature.
Coping strategies and perceived productivity in open-plan offices with noise problems
Authors: Appel-Meulenbroek Rianne , Steps Sven , Wenmaekers Remy , Arentze Theo
Published: October 2020

Purpose

To study effects of different sources of noise in office environments on perceived productivity, how different types of employees cope with different noise sources, and the perceived effect of different coping strategies on individual productivity.

Design/methodology/approach

Data on coping behavior and noise perception was collected through a survey among 150 employees of 3 organizations with an office in the Netherlands. These were analyzed withX2-tests and the lift-ratio.

Findings

When coping with noise, people are most inclined to either “Make even a greater effort” or “Discuss the noise problem with colleagues,” despite the expectation that this does not have a major positive effect on their productivity. Overall, approach coping strategies were chosen less often than the avoidance coping strategies. There are clear preferences for specific coping strategies when exposed to specific noise sources. Personal differences did not appear to relate to the perception of noise sources but did show differences in coping behavior as well.

Originality/value

This study adds insights about preferred coping strategies for specific noise sources, differences in these preferences related to specific personal characteristics, and how successful these strategies are perceived to be with regard to support of individual productivity.
Targeted policy proposals for managing spontaneous forest expansion in the Mediterranean
Authors: Varela Elsa , Pulido Fernando , Moreno Gerardo , Zavala Miguel Á.
Published: October 2020

Recent forest expansion in Euro‐Mediterranean countries predominantly results from secondary succession in abandoned farmland, rather than from artificial afforestation. This major forest transition involves the delivery of both ecosystem services and disservices, which must be balanced through new land‐use planning and policy approaches.

Ecosystem services arising from this expansion of forests include increased carbon sequestration, water infiltration, provision of forest products, soil retention and forest coalescence. Nevertheless, ecosystem disservices such as reductions in water yield, landscape homogenisation, increased wildfire risk and/or the loss of high nature value managed habitats caution against generalisation of the benefits of such expansion.

Most EU funds related to forests are being allocated to conservation, restoration, or fire prevention and extinction efforts, whereas sustainable forest management and the maintenance of multifunctional agro‐silvo‐pastoral mosaics are hampered by the lack of financial incentives and by environmental regulations.

Policy implications. We advocate for more‐targeted policies based on landscape planning that favours multifunctionality while reducing environmental and economic uncertainties and maximising the ecosystem service/disservice ratio. The following recommendations follow from this approach: (a) a climate‐smart policy favouring fire‐resistant landscapes and enhancing value chains that stimulate active forest management; (b) the adoption of a territorial perspective, beyond forest and farm‐based measures and payments, that relies on management actions and minimises socio‐ecological tensions; (c) refocusing CAP Pillar II grants from afforestation and forest protection measures to sustainable forest management; (d) transforming the CAP direct payments to support multifunctional farming systems (e.g. agroforestry); (e) a more balanced inclusion of different land uses in the Natura 2000 network and intensification of the support for High Nature Value farming in less‐favoured areas.
The contribution of the edaphic factor as a driver of recent plant diversification in a Mediterranean biodiversity hotspot
Authors: Buira Antoni , Fernández‐Mazuecos Mario , Aedo Carlos , Molina‐Venegas Rafael
Published: October 2020

The high diversification rates of plant lineages in the Mediterranean Basin hotspot have been linked to a complex interaction of climatic stressors, geographic isolation and soil type, but the question remains as to which of these factors has been the most significant environmental driver of recent speciation.

Here, we draw on distributional data for the entire endemic flora of the Iberian Peninsula, together with DNA‐based phylogenies and spatial phylogenetic methods, to explore the patterns of relative phylogenetic endemism at different spatial resolutions and phylogenetic scales (superclades) and assess how environmental factors contribute to explain these patterns.

We found that recent diversification of angiosperms as a whole, and particularly of eudicots, has been boosted by environmental stressors including high values of soil pH and dry‐seasonal climatic conditions, while diversification of monocots has not been associated with soil conditions but with high elevation and less seasonal climate.

Synthesis. These results provide robust insights into the environmental factors driving recent plant diversification in the Mediterranean Basin, including a role of soil properties that had not been quantified before. The contrasting environmental drivers of diversification in eudicots and monocots highlight the importance of analysing spatial phylogenetic patterns at multiple phylogenetic scales to get a better understanding of the processes that shape biodiversity.
The economic and social benefit of coal mining: the case of regional Queensland
Authors: Williams Galina , Nikijuluw Ruth
Published: October 2020

This paper examines economic impacts of coal mining across local government areas (LGAs) in Australia. Three main distinguishing features of this research are a) the analysis through the mining boom and bust cycle, b) a focus on small regional areas within one state in Australia and c) the use of socio‐economic indicators in addition to the standard income and employment indicators. An analysis of socio‐economic changes in the LGAs during the business cycle provides insights as to how coal mining affects sustainable development of regions in the long run. Focus on one state reduces endogeneity in statistical analyses. The use of various socio‐economic indicators helps understanding of the reported negative impacts of mining on local economies. The results show that the coal mining sector creates a spillover effect resulting in an increase in non‐mining employment. The income indicators suggest that the coal mining sector creates positive impacts as indicated by the decreased share of low‐income families in the area. However, some potential risks to housing are found since an increase in coal mining employment leads to increased financial stress due to increased rental costs for low‐income households.
Impact of literacy across content on middle school students' reading comprehension in a rural context
Authors: Gutierrez de Blume Antonio P. , Katz Anne , Bass Jenna
Published: October 2020

Background

Reading comprehension is an essential skill not only during learning but also to successfully navigate everyday life. However, reading comprehension is a task that is challenging even among some adept readers. Thus, in the present investigation, we explored how to improve reading comprehension skills among a sample of middle school students (N = 124) in rural southeast Georgia, United States.

Methods

Employing a quasi‐experimental pre‐test/post‐test design, we randomly assigned six classrooms to serve as either intervention (three classrooms with n = 66 students) or control (three classrooms with n = 58 students). The treatment involved implementing evidence‐based literacy instruction across content areas by the three content‐area teachers whose classrooms formed part of the intervention group. Data on students' reading comprehension skill as measured by the Reading Inventory (RI) and Georgia Milestones Assessment System (GMAS) Lexile were collected at baseline (2018) and post‐test (2019).

Results

Results revealed that students exposed to literacy instruction across content significantly outperformed students in the control group on both post‐test RI and GMAS scores, after controlling for prior knowledge pre‐test scores, albeit the effect was three times larger for GMAS Lexile than RI scores.

Conclusion

Implementing literacy instruction across content areas is an effective method for enhancing reading comprehension. We discuss implications for research and practice considering these findings.
ASAP: assemble species by automatic partitioning
Authors: Puillandre Nicolas , Brouillet Sophie , Achaz Guillaume
Published: October 2020

Here, we describe Assemble Species by Automatic Partitioning (ASAP), a new method to build species partitions from single locus sequence alignments (i.e., barcode data sets). ASAP is efficient enough to split data sets as large 104 sequences into putative species in several minutes. Although grounded in evolutionary theory, ASAP is the implementation of a hierarchical clustering algorithm that only uses pairwise genetic distances, avoiding the computational burden of phylogenetic reconstruction. Importantly, ASAP proposes species partitions ranked by a new scoring system that uses no biological prior insight of intraspecific diversity. ASAP is a stand‐alone program that can be used either through a graphical web‐interface or that can be downloaded and compiled for local usage. We have assessed its power along with three others programs (ABGD, PTP and GMYC) on 10 real COI barcode data sets representing various degrees of challenge (from small and easy cases to large and complicated data sets). We also used Monte‐Carlo simulations of a multispecies coalescent framework to assess the strengths and weaknesses of ASAP and the other programs. Through these analyses, we demonstrate that ASAP has the potential to become a major tool for taxonomists as it proposes rapidly in a full graphical exploratory interface relevant species hypothesis as a first step of the integrative taxonomy process.
Paper Cuts: How Reporting Resources Affect Political News Coverage
Authors: Peterson Erik
Published: October 2020

Media outlets provide crucial inputs into the democratic process, yet they face increasingly severe economic challenges. I study how a newly salient manifestation of this pressure, reduced reporting capacity, influences political coverage. Focusing on newspapers in the United States, where industry‐wide employment fell over 40% between 2007 and 2015, I use panel data to assess the relationship between reporting capacity and political coverage. Staff cuts substantially decrease the amount of political coverage newspapers provide. Across different samples and measurement approaches, a typical cutback to a newspaper's reporting staff reduces its annual political coverage by between 300 and 500 stories. These political news declines happen against the backdrop of similar reductions in nonpolitical coverage, meaning the share of newspaper articles focused on politics remains stable over this period. This demonstrates that economic pressure affects the political information environment by shaping the media's capacity to cover politics.
Who really cares about the environment? CEOs’ military service experience and firms’ investment in environmental protection
Authors: Gao Yongqiang , Wang Yingli , Zhang Miaohan
Published: October 2020

Prior literature suggests that the chief executive officer (CEO) plays a significant role in a firm's environmental performance or voluntary pro‐environmental behaviors; we extend this line of research to examine the effect of CEOs’ military service experience on firms’ investment in environmental protection. Drawing upon the insights of imprinting theory, we argue that military service experience may instill in CEOs pro‐environmental values such as duty, self‐discipline, self‐sacrifice, and sense of community, which motivate them to adopt pro‐environmental behaviors such as investing more resources in environmental protection. However, we argue that the effects of pro‐environmental values imprinted on CEOs through military service are likely to vary across regions. In regions where the market is more developed and the local value system has experienced greater exposure to the impact of foreign values, and in regions where firms are more concerned about profit, this effect is likely to be attenuated. An analysis of three waves of a nationwide survey of private firms in China using the Tobit regression model supports these predictions. This study makes a unique contribution to the existing literature by linking a firm's pro‐environmental behaviors (i.e., environmental protection investment) to its CEO’s experiences in early life (i.e., military service experience).
Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study
Authors: Marchesini Gessica , Nadali Gianpaolo , Facchinelli Davide , Candoni Anna , Cattaneo Chiara , Laurenti Luca , Fanci Rosa , Farina Francesca , Lessi Federica , Visentin Andrea , Marchesi Francesco , Prezioso Lucia , Spolzino Angelica , Tisi Maria Chiara , Trastulli Fabio , Picardi Marika , Verga Luisa , Dargenio Michelina , Busca Alessandro , Pagano Livio ,   for Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM)
Published: October 2020

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib.
How we use molecular minimal residual disease (MRD) testing in acute myeloid leukaemia (AML)
Authors: Dillon Richard , Potter Nicola , Freeman Sylvie , Russell Nigel
Published: October 2020

In recent years there have been major advances in the use of molecular diagnostic and monitoring techniques for patients with acute myeloid leukaemia (AML). Coupled with the simultaneous explosion of new therapeutic agents, this has sown the seeds for significant improvements to treatment algorithms. Here we show, using a selection of real‐life examples, how molecular monitoring can be used to refine clinical decision‐making and to personalise treatment in patients with AML with nucleophosmin (NPM1) mutations, core binding factor translocations and other fusion genes. For each case we review the established evidence base and provide practical recommendations where evidence is lacking or conflicting. Finally, we review important technical considerations that clinicians should be aware of in order to safely exploit these technologies as they undergo widespread implementation.
Debate: Remote learning during COVID‐19 for children with high functioning autism spectrum disorder
Authors: Reicher Debra
Published: October 2020

The COVID‐19 pandemic has illuminated preference of children with autism spectrum disorder of near average to above average intelligence (high functioning autism – HFA) for remote learning. While many children with HFA excel at the academic curriculum, the majority struggle with the so‐called hidden curriculum, which includes such things as social rules and societal norms. Explicit teaching of the hidden curriculum is often lacking in mainstream education classes and can be a tremendous stumbling block for children with HFA. The result is often anxiety and depression which can be exacerbated or sometimes even caused by the intense demands for sociability and flexibility required in most mainstream educational settings. Remote learning, while not a legitimate option until now, has provided these children with an opportunity to flourish at home and improve not only their grades but also their mental health. While remote learning or hybrid models may continue to be appropriate for some children, understanding of the hidden curriculum is necessary beyond the school years. Both mental health and academic proficiency will flourish to the degree we are able to make the hidden curriculum more explicit to children with HFA.
TMLRpred: A machine learning classification model to distinguish reversible EGFR double mutant inhibitors
Authors: Saini Ravi , Fatima Shehnaz , Agarwal Subhash Mohan
Published: October 2020

The EGFR is a clinically important therapeutic drug target in lung cancer. The first‐generation tyrosine kinase inhibitors used in clinics are effective against L858R‐mutated EGFR. However, relapse of the disease due to the presence of resistant mutation (T790M) makes these inhibitors ineffective. This has necessitated the need to identify new potent EGFR inhibitors against the resistant double mutants. Therefore, various machine learning techniques ((instance‐based learner (IBK), naïve Bayesian (NB), sequential minimal optimization (SMO), and random forest (RF)) were employed to develop twelve classification models on three different datasets (high, moderate, and weakly active inhibitors). The models were validated using fivefold cross‐validation and independent validation datasets. It was observed that the random forest‐based models showed best performance. Also, functional groups, PubChem fingerprints, and substructure of highly active inhibitors were compared to inactive to identify structural features which are important for activity. To promote open‐source drug discovery, a tool has been developed, which incorporates the best performing models and allows users to predict the potential of chemical molecules as anti‐TMLR inhibitor. It is expected that the machine learning classification models developed in this study will pave way for identifying novel inhibitors against the resistant EGFR double mutants.
A natural language processing approach based on embedding deep learning from heterogeneous compounds for quantitative structure–activity relationship modeling
Authors: Bouhedjar Khalid , Boukelia Abdelbasset , Khorief Nacereddine Abdelmalek , Boucheham Anouar , Belaidi Amine , Djerourou Abdelhafid
Published: October 2020

Over the past decade, rapid development in biological and chemical technologies such as high‐throughput screening, parallel synthesis, has been significantly increased the amount of data, which requires the creation and the integration of new analytical methods, especially deep learning models. Recently, there is an increasing interest in deep learning utilization in computer‐aided drug discovery due to its exceptional successful application in many fields. The present work proposed a natural language processing approach, based on embedding deep neural networks. Our method aims to transform the Simplified Molecular Input Line Entry System format into word embedding vectors to represent the semantics of compounds. These vectors are fed into supervised machine learning algorithms such as convolutional long short‐term memory neural network, support vector machine, and random forest to build up quantitative structure–activity relationship models on toxicity data sets. The obtained results on toxicity data to the ciliate Tetrahymena pyriformis (IGC50), and acute toxicity rat data expressed as median lethal dose of treated rats (LD50) show that our approach can eventually be used to predict the activities of chemical compounds efficiently. All material used in this study is available online through the GitHub portal (https://github.com/BoukeliaAbdelbasset/NLPDeepQSAR.git).