bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome- and Transcriptome-wide Splicing Associations with Problematic Alcohol Use and Alcohol Use Disorder
Authors: Huggett Spencer B. , Ikeda Ami S. , Yuan Qingyue , Benca-Bachman Chelsie E. , Palmer Rohan H.C. 
Published: April 2021

ABSTRACTGenetic mechanisms of alternative mRNA splicing have been shown in the brain for a variety of neuropsychiatric traits, but not substance use disorders. Our study used RNA-sequencing data on alcohol use disorder (AUD) in the brain’s reward circuitry (n=56; ages 40-73; 100% ‘Caucasian’; four brain regions) and genome-wide association data on problematic alcohol use (n=435,563, ages 22-90; 100% European-American) to investigate potential genetic links with alcohol-related alternative mRNA splicing. Polygenic scores of problematic alcohol use predicted alternative mRNA brain splicing associated with AUD, which depended on brain region. Across brain regions, we found 714 differentially spliced genes in various putative addiction genes and other novel gene targets. We found 6,463 splicing quantitative trait loci (sQTLs) that were associated with the AUD differentially spliced genes. sQTLs were enriched in loose chromatin genomic regions and downstream gene targets. Additionally, the heritability of problematic alcohol use was significantly enriched for DNA variants in and around differentially spliced genes associated with AUD. Our study also performed splicing transcriptome-wide association studies (TWASs) of problematic alcohol use and other drug use traits that unveiled individual genes for follow-up and robust splicing correlations across SUDs. Finally, we show that differentially spliced genes associated showed significant overlap in primate models of chronic alcohol consumption at the gene-level in similar brain regions. Altogether, our study illuminates substantial genetic contributions of alternative mRNA splicing in relation to problematic alcohol use and AUD.
Automatic Multi-functional Integration Program (AMFIP) towards All-optical Mechanobiology Interrogation
Authors: Luo Qin , Zhang Justin , Lin Gaoming , Huang Miao , Tanaka Mai , Lepler Sharon , Guan Juan , Siemann Dietmar , Tang Xin 
Published: April 2021

AbstractAutomatic operations of multi-functional and time-lapse live-cell imaging are necessary for biomedical studies of active, multi-faceted, and long-term biological phenomena. To achieve automatic control, most existing solutions often require the purchase of extra software programs and hardware that rely on the manufacturers’ own specifications. However, these software programs are usually non-user-programmable and unaffordable for many laboratories. μManager is a widely used open-source software platform for controlling many optoelectronic instruments. Due to limited development since its introduction, μManager lacks compatibility with some of the latest microscopy equipment. To address this unmet need, we have developed a novel software-based automation program, titled Automatic Multi-functional Integration Program (AMFIP), as a new Java-based and hardware-independent plugin for μManager. Without extra hardware, AMFIP enables the functional synchronization of μManager, the Nikon NIS-Elements platform, and other 3rdparty software to achieve automatic operations of most commercially available microscopy systems, including but not limited to Nikon. AMFIP provides a user-friendly and programmable graphical user interface (GUI), opening the door to expanding the customizability for many hardware and software. Users can customize AMFIP according to their own specific experimental requirements and hardware environments. To verify AMFIP’s performance, we applied it to elucidate the relationship between cell spreading and spatial-temporal cellular expression of Yes-associated protein (YAP), a mechanosensitive protein that shuttles between cytoplasm and nucleus upon mechanical stimulation, in an epithelial cell line. We found that the ratio of YAP expression in nucleus and cytoplasm decreases as the spreading area of cells increases, suggesting that the accumulation of YAP in the nucleus decreases throughout the cell spreading processes. In summary, AMFIP provides a new open-source and charge-free solution to integrate multiple hardware and software to satisfy the need of automatic imaging operations in the scientific community.
Piecemeal regulation of convergent neuronal lineages by bHLH transcription factors inC. elegans
Authors: Masoudi Neda , Yemini Eviatar , Schnabel Ralf , Hobert Oliver 
Published: April 2021

ABSTRACTClassic cell lineage studies in the nematodeCaenorhabditis elegansas well as recent lineage tracing in vertebrates have shown that cells of the same type can be generated by distinct cellular lineages that originate in different parts of the developing embryo (“lineage convergence”). SeveralC. elegansneuron classes composed of left/right or radially symmetric class members display such lineage convergence, in that individual neurons of the same class derive from distinct, non-bilaterally symmetric lineages. We show here that theC. elegansAtonal homologlin-32/Ato, a bHLH transcription factor, is differentially expressed in neuronal lineages that give rise to left/right or radially symmetric class members. Loss oflin-32/Atoresults in the selective loss of the expression of panneuronal markers and terminal selector-type transcription factors that confer neuron class-specific features. We discovered that another bHLH transcription factor, the Achaete Scute-homologhlh-14is expressed in mirror image pattern tolin-32/Atoin a subset of the left/right symmetric neuron pairs and is required to induce neuronal identity and terminal selector expression on the contralateral side of the animal. These findings demonstrate that distinct lineage histories converge via distinct bHLH factors on the level of induction of terminal selector identity determinants, which thus serve as integrators of distinct lineage histories. We also describe neuron-to-neuron identity transformations inlin-32/Atomutants, which we propose to also be the result of misregulation of terminal selector gene expression.
Short-interval reburns in the boreal forest alter soil bacterial communities, reflecting increased pH and poor conifer seedling establishment
Authors: Woolet Jamie , Whitman Ellen , Parisien Marc-André , Thompson Dan K. , Flannigan Mike D. , Whitman Thea 
Published: April 2021

AbstractIncreasing burn rates (percentage area burned annually) in some biomes are leading to fires burning in close succession, triggering rapid vegetation change as well as altering soil properties. Despite the importance of soil microbes for nutrient cycling and as plant symbionts, the effects of increased fire frequency on belowground microbial communities remain largely unknown. We present a study of the effects of short interval reburns (defined here as <20 years between fires) on soil bacterial communities in the boreal forest of northwestern Canada, using a paired site design that spans wetlands and uplands, with 50 sites total. We asked whether short interval reburns significantly alter soil bacterial community composition and richness, and which bacterial taxa are associated with greater or lower fire frequency. We found that, while short interval reburns had no significant effect on bacterial richness, there were significant changes in overall community composition. We did not find correlations between understory vegetation community dissimilarities and bacterial community dissimilarities, suggesting the primary drivers of changes induced by short interval reburns may differ between plants and microbes. We identified an abundantBlastococcus sp. that was consistently enriched in short interval reburns, in both wetlands and uplands, indicating its role as a strongly “pyrophilous” bacterium. We also identified an abundantCallaberonia sordidicolataxon as being consistently depleted in short interval reburns. This endophytic diazotrophic organism is a robust colonizer of pine and spruce seedlings and has the ability to increase seedling growth, due in part to large contributions of fixed nitrogen. Its depletion in short-interval reburn sites raises questions about whether this is contributing to – or merely reflects – poor conifer seedling recolonization post-fire at short-interval reburns.
To knot or not to knot: Multiple conformations of the SARS-CoV-2 frameshifting RNA element
Authors: Schlick Tamar , Zhu Qiyao , Dey Abhishek , Jain Swati , Yan Shuting , Laederach Alain 
Published: April 2021

AbstractThe SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, “RAG” (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure has a viable alternative, an HL-type 3-stem pseudoknot (3_3) for longer constructs. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribo-some during translation. For full-length genomes, a stem-loop motif (2_2) may compete with these forms. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.
Decreased adaptation at human disease genes as a possible consequence of interference between advantageous and deleterious variants
Authors: Di Chenlu , Tortosa Diego Salazar , Lauterbur M. Elise , Enard David 
Published: April 2021

AbstractAdvances in genome sequencing have dramatically improved our understanding of the genetic basis of human diseases, and thousands of human genes have been associated with different diseases. Despite our expanding knowledge of gene-disease associations, and despite the medical importance of disease genes, their evolution has not been thoroughly studied across diverse human populations. In particular, recent genomic adaptation at disease genes has not been well characterized, even though multiple evolutionary processes are expected to connect disease and adaptation at the gene level. Understanding the relationship between disease and adaptation at the gene level in the human genome is severely hampered by the fact that we don’t even know whether disease genes have experienced more, less, or as much adaptation as non-disease genes during recent human evolution. Here, we compare the rate of strong recent adaptation in the form of selective sweeps between disease genes and non-disease genes across 26 distinct human populations from the 1,000 Genomes Project. We find that disease genes have experienced far less selective sweeps compared to non-disease genes during recent human evolution. This sweep deficit at disease genes is particularly visible in Africa, and less visible in East Asia or Europe, likely due to more intense genetic drift in the latter populations creating more spurious selective sweeps signals. Investigating further the possible causes of the sweep deficit at disease genes, we find that this deficit is very strong at disease genes with both low recombination rates and with high numbers of associated disease variants, but is inexistant at disease genes with higher recombination rates or lower numbers of associated disease variants. Because recessive deleterious variants have the ability to interfere with adaptive ones, these observations strongly suggest that adaptation has been slowed down by the presence of interfering recessive deleterious variants at disease genes. These results clarify the evolutionary relationship between disease genes and recent genomic adaptation, and suggest that disease genes suffer not only from a higher load of segregating deleterious mutations, but also an inability to adapt as much, and/or as fast as the rest of the genome.
Two timescales control the creation of large protein aggregates in
cells
Authors: Miangolarra A. Movilla , Duperray-Susini A. , Coppey M. , Castellana M. 
Published: April 2021

ABSTRACT
Protein aggregation is of particular interest due to its connection with
many diseases and disorders. Many factors can alter the dynamics and result of
this process, one of them being the diffusivity of the monomers and aggregates
in the system. Here, we study experimentally and theoretically an aggregation
process in cells, and we identify two distinct physical timescales that set the
number and size of aggregates. The first timescale involves fast aggregation of
small clusters freely diffusing in the cytoplasm, while, in the second one, the
aggregates are larger than the pore size of the cytoplasm and thus barely
diffuse, and the aggregation process is slowed down. However, the process is not
entirely halted, potentially reflecting a myriad of active but random forces
forces that stir the aggregates. Such slow timescale is essential to account for
the experimental results of the aggregation process. These results could also
have implications in other processes of spatial organization in cell biology,
such as phase-separated droplets.

SIGNIFICANCE
Protein aggregation is a physico-chemical process that underlies
many diseases and disorders, such as Alzheimer’s or Huntington’s
disease. Here, we study experimental and theoretically the effect of
a sharp decrease of diffusivity in the aggregation dynamics, such as
the one that could happen in the cell due to the presence of
obstacles. We find that two different timescales are important in
setting the size of large aggregates and we give an estimate of the
size of the aggregate at which this dramatic change in behaviour
occurs, which could not be exclusive of protein aggregation but
affect many other intracellular processes.
Patients' perceptions of quality in Swedish primary care – a study of differences between private and public ownership
Authors: Andersson Thomas , Eriksson Nomie , Müllern Tomas 
Published: April 2021

PurposeThe purpose of the paper is to describe and analyze differences in patients' quality perceptions of private and public primary care centers in Sweden.Design/methodology/approachThe article explores the differences in quality perceptions between patients of public and private primary care centers based on data from a large patient survey in Sweden. The survey covers seven dimensions, and in this paper the measure Overall impression was used for the comparison. With more than 80,000 valid responses, the survey covers all primary care centers in Sweden which allowed for a detailed analysis of differences in quality perceptions among patients from the different categories of owners.FindingsThe article contributes with a detailed description of different types of private owners: not-for-profit and for profit, as well as corporate groups and independent care centers. The results show a higher quality perception for independent centers compared to both public and corporate groups.Research limitations/implicationsThe small number of not-for-profit centers (21 out of 1,117 centers) does not allow for clear conclusions for this group. The results, however, indicate an even higher patient quality perception for not-for-profit centers. The study focus on describing differences in quality perceptions between the owner categories. Future research can contribute with explanations to why independent care centers receive higher patient satisfaction.Social implicationsThe results from the study have policy implications both in a Swedish as well as international perspective. The differentiation between different types of private owners made in this paper opens up for interesting discussions on privatization of healthcare and how it affects patient satisfaction.Originality/valueThe main contribution of the paper is the detailed comparison of different categories of private owners and the public owners.
Fine‐scale environmental heterogeneity and conservation management: Beach‐cast wrack creates microhabitats for thermoregulation in shorebirds
Authors: Davis Timothy John , Keppel Gunnar 
Published: April 2021

Abstract

Conservation management to protect coastal ecosystems sometimes overlooks site‐specific fine‐scale heterogeneity. For example, while habitat loss is a known key driver of population declines in many shorebirds, these birds are also dependent on high‐quality habitats to maximize energy stores. Here we describe the microhabitats provided by beach‐cast wrack (washed up macroalgae and seagrasses), a resource threatened by harvesting and beach cleaning, and how shorebirds utilize these.

We measured the temperature and absolute humidity at 10 cm above three substrates (fresh wrack, aged wrack and sand) and then related bird behaviour (roosting vs. foraging) to climatic and environmental data.

Freshly beach‐cast wrack mostly provided cooler and less humid habitats, but warmer temperatures than aged wrack or sand in the early mornings. Microtopography created by shelter from prevailing winds and wrack depth modified these general trends.

Generally, temperature predicted where shorebirds overall and the two most common species, the double‐banded plover Charadrius bicinctus and red‐necked stint Calidris ruficollis, were observed. During most of the day, foraging and roosting were more likely to occur on the warmer aged wrack. In the early morning, when fresh wrack provided the warmer temperatures, birds tended to roost and forage on fresh wrack.

Synthesis and Applications. Beach‐cast wrack creates a complex mosaic of unique microclimates varying in space and time, which allows shorebirds to minimize energy expenditure by selecting the thermally most favourable habitats for roosting and foraging. Removal of beach‐cast wrack for commercial and aesthetic reasons thus reduces habitat quality and increases energy expenditure in shorebirds. Associated declines in energy stores may be contributing to declines in shorebird populations. Management of coastal ecosystems and shorebirds therefore needs to consider and maintain fine‐scale environmental heterogeneity at local scales.
Large predators can mitigate nutrient losses associated with off‐site removal of animals from a wildlife reserve
Authors: Abraham Andrew J. , Webster Andrea B. , Prys‐Jones Tomos O. , le Roux Elizabeth , Smith Dylan , McFayden Duncan , de Jager Pieter C. , Clauss Marcus , Doughty Christopher E. 
Published: April 2021

Abstract

Animals concentrate key nutrients in their bodies. In fenced wildlife reserves where nutrient input and/or retention is low, the off‐site removal of animals may constitute a significant loss of nutrients for the ecosystem.

Here we add wildlife capture and removal into the phosphorus (P) and calcium (Ca) budget for a 121,700 ha fenced game reserve located in the southern Kalahari. We then use faecal P concentrations from 11 mammal herbivores >10 kg as an indicator of potential nutrient stress in this system to investigate whether the implications of nutrient loss via off‐site wildlife removal may be cause for concern. Finally, we assess the role of natural predation as a mechanism to minimise the need for wildlife removal and concomitant nutrient loss.

During the period 2009–2018, mean loss of P and Ca via wildlife removal was 2.9 and 6.2 kg km−2 year−1, respectively. This compares to 1.0 and 2.1 kg km−2 year−1 of P and Ca added via the provision of mineral licks. If it is assumed that natural fluxes of these elements are in steady state, then anthropogenic activities have resulted in a net deficit of 18.5 kg/km2 of P and 40.6 kg/km2 of Ca over the decade.

We found that dry season herbivore faecal P concentrations are close to or below a widely cited minimum threshold of 2,000 mg/kg, below which most vertebrates begin suffering growth and reproductive issues. Large animals were more likely to be under this threshold. Prolonged continuation of off‐site wildlife removal may result in nutrient losses that can lead to long‐term ecological degradation. Natural predation levels were, however, found sufficient to mitigate the need for wildlife removal and present a management strategy whereby herbivore populations can be regulated without a loss of nutrients.

Synthesis and applications. We find that the capture and permanent removal of large‐bodied animals from wildlife reserves can be a significant cause of nutrient loss. Over time, in sites where nutrient input and/or retention is low, this may contribute to nutritional stress for remaining resident animals. Where possible, holistic management strategies that promote the retention of animals and carcasses within the reserve—such as the reintroduction of large carnivores—should be preferred.
A meta‐analysis of the influence of anthropogenic noise on terrestrial wildlife communication strategies
Authors: Duquette Cameron Albert , Loss Scott R. , Hovick Torre J. 
Published: April 2021

Abstract

Human‐caused noise pollution dominates the soundscape of modern ecosystems, from urban centres to national parks. Although wildlife can generally alter their communication to accommodate many types of natural noise (e.g. wind, wave action, heterospecific communication), noise pollution from anthropogenic sources pushes the limits of wildlife communication flexibility by causing loud, low‐pitched and near‐continuous interference. Because responses to noise pollution are variable and taxa specific, multi‐species risk assessments and mitigation are not currently possible.

We conducted a meta‐analysis to synthesize noise pollution effects on terrestrial wildlife communication. Specifically, we assessed: (a) the impacts of noise pollution on modulation of call rate, duration, amplitude and frequency (including peak, minimum and maximum frequency); and (b) the literature on anthropogenic noise pollution by region, taxa, study design and disturbance type.

Terrestrial wildlife (results driven by avian studies) generally respond to noise pollution by calling with higher minimum frequencies, while they generally do not alter the amplitude, maximum frequency, peak frequency, duration and rate of calling.

The literature on noise pollution research is biased towards birds, population‐level studies, urban noise sources and study systems in North America.

Synthesis and applications. Our study reveals the ways in which wildlife can alter their signals to contend with anthropogenic noise, and discusses the potential fitness and management consequences of these signal alterations. This information, combined with an identification of current research needs, will allow researchers and managers to better develop noise pollution risk assessment protocols and prioritize mitigation efforts to reduce anthropogenic noise.