bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterospecific song quality as social information for settlement decisions: an experimental approach in a wild bird
Authors: Morinay Jennifer , Forsman Jukka T. , Doligez Blandine
Published: August 2019

Assessing local habitat quality via social cues provided by con- or heterospecific individuals sharing the same needs is a widespread strategy of social information use for breeding habitat selection. However, gathering information about putative competitors may involve agonistic costs. The use of social cues reflecting local habitat quality acquired from a distance, such as acoustic cues, could therefore be favoured. Bird songs are conspicuous signals commonly assumed to reliably reflect producer quality, and thereby local site quality. Birds of different species have been shown to be attracted to breeding sites by heterospecific songs, but whether they can use fine heterospecific song features as information on producer (and by extension habitat) quality remains unknown. We used a playback experiment in a wild population of collared flycatchers (Ficedula albicollis), a species known to eavesdrop on dominant great tits’ (Parus major) presence and performance, to test whether flycatchers preferred to settle near broadcasts of a high quality great tit song (i.e. song with large repertoire size, long strophes, high song rate), a low quality great tit song or a chaffinch song (control). Among old females, aggressive ones preferred to settle near broadcasts of high quality tit song and avoided broadcasts of low quality tit song, while less aggressive females preferred to settle near broadcasts of low quality tit song. Male personality or age did not influence settlement decisions. Our results show that collared flycatcher females use great tit song quality features as information for settlement decisions, though differently depending on their own competitive ability and/or previous experience with great tit songs. Our study therefore further illustrates the complex condition-dependent use of heterospecific social information for breeding habitat selection.
Genetic variation in parental effects contribute to the evolutionary potential of prey responses to predation risk
Authors: Tigreros Natasha , Agrawal Anurag A. , Thaler Jennifer S.
Published: August 2019

Despite the ubiquity of parental effects and their potential impact on evolutionary dynamics, their contribution to the evolution of ecologically relevant adaptations remains poorly understood. Using quantitative genetics, here we demonstrate that parental effects contribute substantially to the evolutionary potential of larval antipredator responses in a leaf beetle (Leptinotarsa decemlineata). Previous research showed that largerL. decemlineatalarvae elicit stronger antipredator responses, and mothers perceiving predators improved offspring responses by increasing intraclutch cannibalism –an extreme form of offspring provisioning. We now report substantial additive genetic variation underlying maternal ability to induce intraclutch cannibalism, indicating the potential of this adaptive maternal effect to evolve by natural selection. We also show that paternal size, a heritable trait, impacted larval responses to predation risk, but that larval responses themselves had little additive genetic variation. Together, these results demonstrate how larval responses to predation risk can evolve via two types of parental effects, both of which provide indirect sources of genetic variation for offspring traits.
Nanopore sequencing of the glucocerebrosidase (GBA) gene in a New Zealand Parkinson’s disease cohort
Authors: Graham O.E.E. , Pitcher T.L. , Liau Y. , Miller A.L. , Dalrymple-Alford J.C. , Anderson T.J. , Kennedy M.A.
Published: August 2019

Introduction

Bi-allelic mutations in the gene for glucocerebrosidase (GBA) cause Gaucher disease, an autosomal recessive lysosomal storage disorder. Gaucher disease causing GBA mutations in the heterozygous state are also high risk factors for Parkinson’s disease (PD). GBA analysis is challenging due to a related pseudogene and structural variations (SVs) that can occur at this locus. We have applied and refined a recently developed nanopore DNA sequencing method to analyze GBA variants in a clinically assessed New Zealand longitudinal cohort of PD.

Method

We examined amplicons encompassing the coding region of GBA (8.9kb) from 229 PD cases and 50 healthy controls using the GridION nanopore sequencing platform, and Sanger validation.

Results

We detected 23 variants in 21 PD cases (9.2% of patients). We detected modest PD risk variant p.N409S (rs76763715) in one case, p.E365K (rs2230288) in 12 cases, and p.T408M (rs75548401) in seven cases, one of whom also had p.E365K. We additionally detected the possible risk variants p.R78C (rs146774384) in one case, p.D179H (rs147138516) in one case which occurred on the same haplotype as p.E365K, and one novel variant c.335C>T or p.(L335=), that potentially impacts splicing of GBA transcripts. Additionally, we found a higher prevalence of dementia among patients with GBA variants.

Conclusion

This work confirmed the utility of nanopore sequencing as a high-throughput method to identify known and novel GBA variants, and to assign precise haplotypes. Our observations may contribute to improved understanding of the effects of variants on disease pathogenesis, and to the development of more targeted treatments.
LaeA controls citric acid production through regulation of a citrate exporter encodingcexAinAspergillus luchuensismut.kawachii
Authors: Kadooka Chihiro , Nakamura Eri , Mori Kazuki , Okutsu Kayu , Yoshizaki Yumiko , Takamine Kazunori , Goto Masatoshi , Tamaki Hisanori , Futagami Taiki
Published: August 2019

The putative methyltransferase LaeA is a global regulator of metabolic and development processes in filamentous fungi. We characterized the homologouslaeAgenes of the white koji fungusAspergillus luchuensismut.kawachii(A. kawachii) to determine their role in the hyperproduction of citric acid. The ΔlaeAstrain exhibited a significant reduction in citric acid productivity. Cap-analysis gene expression (CAGE) revealed thatlaeAis required for the gene expression of a putative citrate exporter encodingcexA, which is critical for citric acid production. The deficit in the productivity of citric acid by the ΔlaeAstrain was rescued by the overexpression ofcexAto a level comparable with that of thecexA-overexpressing ΔcexAstrain. In addition, chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) analysis indicated that LaeA regulates the expression ofcexAvia methylation levels of the histones H3K4 and H3K9. These results indicate that LaeA is involved in citric acid production through epigenetic regulation ofcexAinA. kawachii.

IMPORTANCE

A. kawachiihas been traditionally used for production of the distilled spirit shochu in Japan. Citric acid produced byA. kawachiiplays an important role in preventing microbial contamination during the shochu fermentation process. This study characterized homologouslaeAgenes; using CAGE, complementation test, and ChIP-qPCR, it was found thatlaeAis required for citric acid production though regulation ofcexAinA. kawachii. The epigenetic regulation of citrate production elucidated in this study will be useful for controlling the fermentation processes of shochu.
Colonization and extinction dynamics and their link to the distribution of European trees at continental scale
Authors: Guyennon Arnaud , Reineking Björn , Dahlgren Jonas , Lehtonen Aleksi , Ratcliffe Sophia , Ruiz-Benito Paloma , Zavala Miguel A. , Kunstler Georges
Published: August 2019

Aim

Processes driving current tree species distribution are still largely debated. Attempts to relate species distribution and population demography metrics have shown mixed results. In this context, we would like to test the hypotheses that the metapopulation processes of colonization and extinction are linked to species distribution models.

Location

Europe: Spain, France, Germany, Finland, and Sweden.

Taxon

Angiosperms and Gymnosperms.

Methods

For the 17 tree species analyzed we fitted species distribution model (SDM) relating environmental variables to presence absence data across Europe. Then using independent data from national forest inventories across Europe we tested whether colonization and extinction probabilities are related to occurrence probability estimated by the SDMs. Finally, we tested how colonization and extinction respectively drive probability of presence at the metapopulation equilibrium.

Results

We found that for most species at least one process (colonization/extinction) is related to the occurrence probability, but rarely both.

Main conclusions

Our study supports the view that metapopulation dynamics are partly related to SDM occurrence probability through one of the metapopulation probabilities. However these links are relatively weak and the metapopulation models tend to overestimate the occurrence probability. Our results call for caution in model extrapolating SDM models to metapopulation dynamics.
SeqBreed: a python tool to evaluate genomic prediction in complex scenarios
Authors: Pérez-Enciso M. , Ramírez-Ayala L. C. , Zingaretti L.M.
Published: August 2019

Background

Genomic Prediction (GP) is the procedure whereby molecular information is used to predict complex phenotypes. Although GP can significantly enhance predictive accuracy, it can be expensive and difficult to implement. To help in designing optimum experiments, including genome wide association studies and genomic selection experiments, we have developed SeqBreed, a generic and flexible python3 forward simulator.

Results

SeqBreed accommodates sex and mitochondrion chromosomes as well as autopolyploidy. It can simulate any number of complex phenotypes determined by any number of causal loci. SeqBreed implements several GP methods, including single step GBLUP. We demonstrate its functionality with Drosophila Genome Reference Panel (DGRP) sequence data and with tetraploid potato genotypes.

Conclusions

SeqBreed is a flexible and easy to use tool appropriate for optimizing GP or genome wide association studies. It incorporates some of the most popular GP methods and includes several visualization tools. Code is open and can be freely modified. Software, documentation and examples are available at https://github.com/miguelperezenciso/SeqBreed.
A novel methodology for defining stromal expression of atypical chemokine receptors in vivo
Authors: Hansell Christopher A.H. , Love Samantha , Pingen Marieke , Wilson Gillian J , MacLeod Megan , Graham Gerard J.
Published: August 2019

Analysis of chemokine receptor, and atypical chemokine receptor, expression is frequently hampered by the lack of availability of high-quality antibodies and the species-specificity of those that are available. We have previously described methodology utilising Alexa-Fluor labelled chemokine ligands as versatile reagents to detect receptor expression. Previously this has been limited to haematopoietic cells and methodology for assessing expression of receptors on stromal cells has been lacking. Amongst chemokine receptors the ones most frequently expressed on stromal cells belong to the atypical chemokine receptor subfamily. These receptors do not signal in the classic sense in response to ligand but scavenge their ligands and degrade them and thus sculpt in vivo chemokine gradients. Here we demonstrate the ability to use either intratracheal, or intravenous, Alexa-Fluor labelled chemokine administration to detect stromal cell populations expressing the atypical chemokine receptor ACKR2. Using this methodology we demonstrate, for the first time, expression of ACKR2 on blood endothelial cells. This observation sets the lung aside from other tissues in which ACKR2 is exclusively expressed on lymphatic endothelial cells. In summary therefore we described a novel method for the in situ labelling of atypical chemokine receptor expressing cells appropriate for subsequent flow cytometric analysis. We propose that this methodology will work in a range of species and for a range of receptors and therefore will have significant versatility
Maintenance of High Inbreeding Depression in Selfing Populations: Effects of Coupling of Early- and Late-Acting Mutations
Authors: Sakai Satoki
Published: August 2019

High estimates of inbreeding depression have been obtained in many plant populations with high selfing rates. However, deleterious mutations might be purged from such populations as a result of selfing. I developed a simulation model assuming the presence of mutations at two sets of loci, namely, early- and late-acting loci, and the selective abortion of embryos coupled with ovule overproduction. In the model, early-acting loci are expressed during embryo initiation, and less vigorous embryos are aborted. Late-acting loci are expressed after selective abortion ends; the surviving embryos (seeds) compete, and some of them form the next generation. If mutations are allowed to occur in both early- and late-acting loci, they increase in frequency in populations with high selfing rates in both sets of loci. However, this phenomenon does not occur if mutations occur in only the early- or late-acting loci. Consistent results are observed even if the total number of loci in which mutations are allowed to occur is the same among simulations with both early- and late-acting loci or only early- or late-acting loci, indicating that the presence of both sets of loci is the causal factor. Thus, the coupling effects of early- and late-acting mutations promote the maintenance of these mutations in populations with high selfing rates.
The Alzheimer’s disease associated bacterial protease RgpB from P. gingivalis activates the alternative β-secretase meprin β thereby increasing Aβ generation
Authors: Armbrust Fred , Colmorgen Cynthia , Pietrzik Claus U. , Becker-Pauly Christoph
Published: August 2019

Alzheimer’s disease (AD) is the most common type of dementia and characterized by tau hyperphosphorylation, oxidative stress, reactive microglia and amyloid-β (Aβ) deposits. A recent study revealed that Porphyromonas gingivalis infection is associated with amyloid β generation in Alzheimer’s disease. Increased Aβ levels, tau degradation and neuronal toxicity were observed as a consequence of ginigipain R (RgpB) activity, a cysteine protease constitutively secreted by P. gingivalis. Of note, we previously identified RgpB as a potent activator of the metalloproteinase meprin β. Interestingly, meprin β is an alternative β-secretase of the amyloid precursor protein (APP), which together with the γ-secretase leads to the generation of aggregation-prone N-terminally truncated Aβ2-x peptides. Importantly, identification of a risk gene variant of meprin β (rs173032) for Alzheimer’s disease using whole-exome sequencing of the BDR cohort further supports the impact of this alternative β-secretase. Thus, we wondered if increased Aβ levels as a consequence of P. gingivalis colonization into the brain might be due to meprin β activation by RgpB. Here, we demonstrate that i) upon incubation with RgpB the proteolytic activity of meprin β at the cell surface of transfected HEK cells or of endogenously expressed enzyme in SH-SY5Y neuroblastoma cells was significantly increased, and that ii) RgpB-mediated increase in meprin β activity leads to massive generation of Aβ-peptides. In conclusion, our findings would further explain the pathogenesis of P. gingivalis in AD brain.
The global phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunistStenotrophomonas maltophilia
Authors: Gröschel Matthias I , Meehan Conor J , Barilar Ivan , Diricks Margo , Gonzaga Aitor , Steglich Matthias , Conchillo-Solé Oscar , Scherer Isabell-Christin , Mamat Uwe , Luz Christian F. , De Bruyne Katrien , Utpatel Christian , Yero Daniel , Gibert Isidre , Daura Xavier , Kampmeier Stefanie , Rahman Nurdyana Abdul , Kresken Michael , van der Werf Tjip S , Alio Ifey , Streit Wolfgang R. , Zhou Kai , Schwartz Thomas , Rossen John W A , Farhat Maha R , Schaible Ulrich E , Nübel Ulrich , Rupp Jan , Steinmann Joerg , Niemann Stefan , Kohl Thomas A
Published: August 2019

Recent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analysed an international collection of the emerging, multidrug-resistant, opportunistic pathogenStenotrophomonas maltophiliafrom 22 countries to infer population structure and clonality at a global level. We show that theS. maltophiliacomplex is divided into 23 monophyletic lineages, most of which harboured strains of all degrees of human virulence. Lineage Sm6 comprised the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identified potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.

One Sentence Summary

TheS. maltophiliacomplex comprises genetically diverse, globally distributed lineages with evidence for intra-hospital transmission.
Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice
Authors: Daharsh Lance , Ramer-Tait Amanda E. , Li Qingsheng
Published: August 2019

Background

Humanized mice featuring a functional human immune system are an important pre-clinical model for examining immune responses to human-specific pathogens. This model has been widely utilized to study human diseases that are otherwise impossible or difficult to investigate in humans or with other animal models. However, one limitation of using humanized mice is their native murine gut microbiome, which significantly differs from the one found in humans. These differences may be even greater for mice housed and bred in specific pathogen free conditions. Given the importance of the gut microbiome to human health and disease, these differences may profoundly impact the ability to translate the results from humanized mice studies to human disease. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We therefore created double humanized mice with both a functional human immune system and stable human-like gut microbiome.

Results

Surgery was performed on NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice to create bone-marrow, liver, thymus (BLT) humanized mice. After immune reconstitution, mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and then transplanted with fecal material from healthy human donors. Characterization of 173 fecal samples obtained from 45 humanized mice revealed that double humanized mice had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors compared to humanized mice.

Conclusions

Here, we describe successful engraftment of a stable human microbiome in BLT humanized mice to further improve this preclinical humanized mouse model. These double humanized mice represent a unique and tractable new model to study the complex relationships between the human gut microbiome, human immune system, and human disease in vivo.
Variant calling for cpn60 barcode sequence-based microbiome profiling
Authors: Vancuren Sarah J. , Santos Scott J. Dos , Hill Janet E. ,   the Maternal Microbiome Legacy Project Team
Published: August 2019

Amplification and sequencing of conserved genetic barcodes such as the cpn60 gene is a common approach to determining the taxonomic composition of microbiomes. Exact sequence variant calling has been proposed as an alternative to previously established methods for aggregation of sequence reads into operational taxonomic units (OTU). We investigated the utility of variant calling for cpn60 barcode sequences and determined the minimum sequence length required to provide species-level resolution. Sequence data from the 5’ region of the cpn60 barcode amplified from the human vaginal microbiome (n=45), and a mock community were used to compare variant calling to de novo assembly of reads, and mapping to a reference sequence database in terms of number of OTU formed, and overall community composition. Variant calling resulted in microbiome profiles that were consistent in apparent composition to those generated with the other methods but with significant logistical advantages. Variant calling is rapid, achieves high resolution of taxa, and does not require reference sequence data. Our results further demonstrate that 150 bp from the 5’ end of the cpn60 barcode sequence is sufficient to provide species-level resolution of microbiota.
Combinatory therapy targeting mitochondrial oxidative phosphorylation improves efficacy of IDH mutant inhibitors in acute myeloid leukemia
Authors: Stuani Lucille , Sabatier Marie , Wang Feng , Poupin Nathalie , Bosc Claudie , Saland Estelle , Castelli Florence , Gales Lara , Montersino Camille , Boet Emeline , Turtoi Evgenia , Kaoma Tony , Farge Thomas , Broin Nicolas , Larrue Clément , Baran Natalia , Conti Marc , Loric Sylvain , Mouchel Pierre-Luc , Gotanègre Mathilde , Cassan Cédric , Fernando Laurent , Cognet Guillaume , Zavoriti Aliki , Hosseini Mohsen , Boutzen Héléna , Morita Kiyomi , Futreal Andrew , Chu-Van Emeline , Cam Laurent Le , Carroll Martin , Selak Mary A. , Vey Norbert , Calmettes Claire , Pigneux Arnaud , Bidet Audrey , Castellano Rémy , Fenaille Francois , Turtoi Andrei , Cazals Guillaume , Bories Pierre , Gibon Yves , Nicolay Brandon , Ronseaux Sébastien , Marszalek Joe , DiNardo Courtney D. , Konopleva Marina , Collette Yves , Linares Laetitia K. , Bellvert Floriant , Jourdan Fabien , Takahashi Koichi , Récher Christian , Portais Jean-Charles , Sarry Jean-Emmanuel
Published: August 2019

Isocitrate dehydrogenases (IDH) are involved in redox control and central metabolism. Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, BCL-2 dependence and susceptibility to mitochondrial inhibitors in cancer cells. Here we show that high sensitivity to mitochondrial oxidative phosphorylation (OxPHOS) inhibitors is due to an enhanced mitochondrial oxidative metabolism in cell lines, PDX and patients with acute myeloid leukemia (AML) harboring IDH mutation. Along with an increase in TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurs through the increase in methylation-driven CEBPα- and CPT1a-induced fatty acid oxidation, electron transport chain complex I activity and mitochondrial respiration in IDH1 mutant AML. Furthermore, an IDH mutant inhibitor that significantly and systematically reduces 2-HG oncometabolite transiently reverses mitochondrial FAO and OxPHOS gene signature and activities in patients who responded to the treatment and achieved the remission. However, at relapse or in patients who did not respond, IDH mutant inhibitor failed to block these mitochondrial properties. Accordingly, OxPHOS inhibitors such as IACS-010759 improve anti-AML efficacy of IDH mutant inhibitors alone and in combination with chemotherapyin vivo. This work provides a scientific rationale for combinatory mitochondrial-targeted therapies to treat IDH mutant-positive AML patients, especially those unresponsive to or relapsing from IDH mutant-specific inhibitors.
Genome-wide discovery of hidden genes mediating known drug-disease association using KDDANet
Authors: Yu Hua , Lu Lu , Chen Ming , Li Chen , Zhang Jin
Published: August 2019

Many of genes mediating Known Drug-Disease Association (KDDA) are escaped from experimental detection. Identifying of these genes (hidden genes) is of great significance for understanding disease pathogenesis and guiding drug repurposing. Here, we presented a novel computational tool, called KDDANet, for systematic and accurate uncovering the hidden genes mediating KDDA from the perspective of genome-wide functional gene interaction network. KDDANet demonstrated the competitive performances in both sensitivity and specificity of identifying genes in mediating KDDA in comparison to the existing state-of-the-art methods. Case studies on Alzheimer’s disease (AD) and obesity uncovered the mechanistic relevance of KDDANet predictions. Furthermore, when applied with multiple types of cancer-omics datasets, KDDANet not only recapitulated known genes mediating KDDAs related to cancer, but also revealed novel candidates that offer new biological insights. Importantly, KDDANet can be used to discover the shared genes mediating multiple KDDAs. KDDANet can be accessed at http://www.kddanet.cn and the code can be freely downloaded at https://github.com/huayu1111/KDDANet.
The Ficus erecta genome to identify the Ceratocystis canker resistance gene for breeding programs in common fig (F. carica)
Authors: Shirasawa Kenta , Yakushiji Hiroshi , Nishimura Ryotaro , Morita Takeshige , Jikumaru Shota , Ikegami Hidetoshi , Toyoda Atsushi , Hirakawa Hideki , Isobe Sachiko
Published: August 2019

Ficus erecta, a wild relative of common fig (F. carica), is a donor of Ceratocystis canker resistance in fig breeding programs. Interspecific hybridization followed by recurrent backcrossing is an effective method to transfer the resistance trait from wild to cultivated fig; however, this is time consuming and labor-intensive for trees, especially for gynodioecious plants such as fig. In this study, genome resources were developed for F. erecta to facilitate fig breeding programs. The genome sequence of F. erecta was determined using single-molecule real-time sequencing technology. The resultant assembly spanned 331.6 Mb with 538 contigs and an N50 length of 1.9 Mb, from which 51,806 high-confidence genes were predicted. Pseudomolecule sequences corresponding to the chromosomes of F. erecta were established with a genetic map based on single nucleotide polymorphisms from double-digest restriction-site associated DNA sequencing. Subsequent linkage analysis and whole genome resequencing identified a candidate gene for the Ceratocystis canker resistance trait. Genome-wide genotyping analysis enabled selection of female lines that possessed resistance and effective elimination of donor genome from progeny. The genome resources provided in this study will accelerate and enhance disease resistance breeding programs in fig.
Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats
Authors: Cruz Ana M. , Malekizadeh Yasaman , Vlachaki Walker Julia M. , Weightman Potter Paul G. , Pye Katherine , Shaw Simon J. , Ellacott Kate L.J. , Beall Craig
Published: August 2019

AMP-activated protein kinase (AMPK) is a critical cellular and whole body energy sensor activated by energy stress, including hypoglycemia, which is frequently experienced by people with diabetes. Previous studies using direct delivery of an AMPK activator to the ventromedial hypothalamus (VMH) in rodents increased hepatic glucose production. Moreover, recurrent glucoprivation in the hypothalamus leads to blunted AMPK activation and defective hormonal responses to subsequent hypoglycemia. These data suggest that amplifying AMPK activation may prevent or reduce frequency hypoglycemia in diabetes. We used a novel brain-permeable AMPK activator, R481, which potently increased AMPK phosphorylation in vitro. R481 significantly increased peak glucose levels during glucose tolerance tests in rats, which were attenuated by treatment with AMPK inhibitor SBI-0206965 and completely abolished by blockade of the autonomic nervous system. This occurred without altering insulin sensitivity measured by hyperinsulinemic-euglycemic clamps. Endogenous insulin secretion was not altered by R481 treatment. During hyperinsulinemic-hypoglycemic clamp studies, R481 treatment reduced exogenous glucose requirements and amplified peak glucagon levels during hypoglycemia. These data demonstrate that peripheral administration of the brain permeable AMPK activator R481 amplifies the counterregulatory response to hypoglycemia in rats, which could have clinical relevance for prevention of hypoglycemia.
Adaptation and correlated fitness responses over two time scales in Drosophila suzukii populations evolving in different environments
Authors: Olazcuaga Laure , Foucaud Julien , Gautier Mathieu , Deschamps Candice , Loiseau Anne , Leménager Nicolas , Facon Benoit , Ravigné Virginie , Hufbauer Ruth A. , Estoup Arnaud , Rode Nicolas O.
Published: August 2019

The process of local adaptation involves differential changes in fitness over time across different environments. While experimental evolution studies have extensively tested for patterns of local adaptation at a single time point, there is relatively little research that examines fitness more than once during the time course of adaptation. We allowed replicate populations of the fruit pest Drosophila suzukii to evolve in one of eight different fruit media. After five generations, populations with the highest initial levels of maladaptation had mostly gone extinct, whereas experimental populations evolving on cherry, strawberry and cranberry media had survived. We measured the fitness of each surviving population in each of the three fruit media after five and after 26 generations of evolution. After five generations, adaptation to each medium was associated with increased fitness in the two other media. This was also true after 26 generations, except when populations that evolved on cranberry medium developed on cherry medium. These results suggest that, in the theoretical framework of a fitness landscape, the fitness optima of cherry and cranberry media are the furthest apart. Our results show that studying how fitness changes across several environments and across multiple generations provides insights into the dynamics of local adaptation that would not be evident if fitness were analyzed at a single point in time. By allowing a qualitative mapping of an experimental fitness landscape, our approach will improve our understanding of the ecological factors that drive the evolution of local adaptation in D. suzukii.
BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty
Authors: Tiberi Simone , Robinson Mark D
Published: August 2019

Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript-level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly model the variability between samples, and treats the transcript allocation of reads as latent variables. We perform an extensive benchmark across both simulated and experimental RNA-seq datasets, where BANDITS has extremely favorable performance with respect to the competitors considered.
Clathrin’s adaptor interaction sites are repurposed to stabilize microtubules during mitosis
Authors: Rondelet Arnaud , Lin Yu-Chih , Singh Divya , Porfetye Arthur T. , Thakur Harish C. , Hecker Andreas , Brinkert Pia , Schmidt Nadine , Bendre Shweta , Müller Franziska , Widlund Per O. , Bange Tanja , Hiller Michael , Vetter Ingrid R. , Bird Alexander W.
Published: August 2019

Clathrin plays an important role to ensure mitotic spindle stability and efficient chromosome alignment, independently of its well-characterized functions in vesicle trafficking. While clathrin clearly localizes to the mitotic spindle and kinetochore-fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules have remained elusive. Here we show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the mitotic spindle. Structural analyses reveal that multiple clathrin-box motifs on GTSE1 interact directly with different clathrin adaptor interaction sites on CHC, in a manner structurally analogous to that which occurs between adaptor proteins and CHC near membranes. Specific disruption of this interaction in cells releases GTSE1 from spindles and causes defects in chromosome alignment. Surprisingly, this disruption causes destabilization of astral microtubules, but not kinetochore-microtubule attachments, and the resulting chromosome alignment defect is due to a failure of chromosome congression independent of kinetochore-microtubule attachment stability. Finally, we show that GTSE1 recruited to the spindle by clathrin stabilizes microtubules and promotes chromosome congression by inhibiting the activity of the microtubule depolymerase MCAK. This work thus uncovers a novel role of clathrin to stabilize non-kinetochore-fiber microtubules to support chromosome congression. This role is carried out via clathrin adaptor-type interactions of CHC with GTSE1, defining for the first time an important repurposing of this endocytic interaction mechanism during mitosis.
Prognostic value of Red Blood Cell Distribution Width in Acute Kidney Injury Patients: A Systematic Review and Meta-analysis
Authors: Liu Zhengsheng , Wang Shanshan , Yao Xiongbo , Xing Jinchun
Published: August 2019

Background

The conflicting result with regard to Red Cell Distribution Width (RDW) with Acute Kidney Injury (AKI) has been reported. This systematic review and meta-analysis were aimed to investigate RDW and prognostic value in AKI patients.

Methods/Main Results

This meta-analysis included 1251 cases and 1663 controls with a total of 7 enrolled published papers. The results of RDW levels were significantly associated with patients of AKI (WMD=1.127, 95% CI=0.426-1.827; P=0.002), with statistically significant heterogeneity (I2 =95.80%, Pheterogeneity =0.000, random-effects model).

Conclusions

In conclusion, the results of this present meta-analysis suggest that the RDW value is a positive prognostic indicator in patients with AKI. However, these results were obtained on the basis of RCS or small sample sizes studies. Further functional studies with additional data would be needed to validate our findings.
ORAL HEALTH BEHAVIOUR PERCEPTION SCALE APPLIED AMONG A SAMPLE OF PORTUGUESE ADOLESCENTS
Authors: Veiga Nélio Jorge , Amaral Odete , Correia Maria José , Coelho Inês
Published: August 2019

Introduction

The application of a scale can be particularly useful for the epidemiological studies comparing different populations and for analysis of the influence of distinct aspects of oral health on the development of certain health conditions. The aim of this study consists in the creation of a scale to classify the level of perception of the oral health behaviors applicable to the sample of Portuguese adolescents.

Materials and methods

An observational cross-sectional study was designed with a total of 649 adolescents between the ages of 12 and 18 years old from five public schools in the Viseu and Guarda districts, in Portugal. Data was collected by the application of a self-administered questionnaire and, after analysis of data collection, the newly Universidade Católica Portuguesa (UCP) oral health perception scale was created.

Results

Analyzing the sample included in the present study, we verified, by the UCP oral health perception scale created, that 67.9% of the sample presented a poor perception of their oral health behaviors, 23.9% intermediate/sufficient and only 8.2% presented what is considered in the scale as having a good classification in terms of oral health behaviors perception respecting the assumptions defined for the elaboration of the present scale.

Conclusions

For this purpose, through the scale to classify the level of oral health behaviors applicable to the sample of portuguese adolescents, it is possible to compare the data of several samples and understand what are the most frequent oral or eating habits among adolescents.
Incorporating evaporative water loss into bioenergetic models of hibernation to test for relative influence of host and pathogen traits on white-nose syndrome
Authors: Haase Catherine G. , Fuller Nathan W. , Hranac C. Reed , Hayman David T. S. , McGuire Liam P. , Norquay Kaleigh J. O. , Silas Kirk A. , Willis Craig K. R. , Plowright Raina K. , Olson Sarah H.
Published: August 2019

Hibernation consists of extended durations of torpor interrupted by periodic arousals. The ‘dehydration hypothesis’ proposes that hibernating mammals arouse to replenish water lost through evaporation during torpor. Arousals are energetically expensive, and increased arousal frequency can alter survival throughout hibernation. Yet we lack a means to assess the effect of evaporative water loss (EWL), determined by animal physiology and hibernation microclimate, on torpor bout duration and subsequent survival. White-nose syndrome (WNS), a devastating disease impacting hibernating bats, causes increased frequency of arousals during hibernation and EWL has been hypothesized to contribute to this increased arousal frequency. WNS is caused by a fungus, which grows well in humid hibernaculum environments and damages wing tissue important for water conservation. Here, we integrated the effect of EWL on torpor expression in a hibernation energetics model, including the effects of fungal infection, to determine the link between EWL and survival. We collected field data forMyotis lucifugus, a species that experiences high mortality from WNS, to gather parameters for the model. In saturating conditions we predicted healthy bats experience minimal mortality. Infected bats, however, suffer high fungal growth in highly saturated environments, leading to exhaustion of fat stores before spring. Our results suggest that host adaptation to humid environments leads to increased arousal frequency from infection, which drives mortality across hibernaculum conditions. Our modified hibernation model provides a tool to assess the interplay between host physiology, hibernaculum microclimate, and diseases such as WNS on winter survival.
ROP INTERACTIVE PARTNER b interacts with RACB and supports fungal penetration into barley epidermal cells
Authors: McCollum Christopher , Engelhardt Stefan , Weiss Lukas , Hückelhoven Ralph
Published: August 2019

RHO of Plants (ROP) G-proteins are key components of cell polarization processes in plant development. The barley (Hordeum vulgare) ROP protein RACB, is a susceptibility factor in the interaction of barley with the barley powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh). RACB also drives polar cell development, and this function might be coopted during formation of fungal haustoria in barley epidermal cells. In order to understand RACB signaling during the interaction of barley with Bgh, we searched for potential downstream interactors of RACB. Here, we show that ROP INTERACTIVE PARTNER b (RIPb, synonym: INTERACTOR OF CONSTITUTIVE ACTIVE ROP b; ICRb) directly interacts with RACB in yeast and in planta. Over-expression of RIPb supports susceptibility of barley to Bgh. RIPb further interacts with itself at microtubules. However, the interaction with activated RACB takes place at the plasma membrane. Both, RIPb and RACB are recruited to the site of fungal attack around the neck of developing haustoria suggesting locally enhanced ROP activity. We further assigned different functions to different domains of the RIPb protein. The N-terminal coiled-coil CC1 domain is required for microtubule localization, while the C-terminal coiled-coil CC2 domain is sufficient to interact with RACB and to fulfill a function in susceptibility at the plasma membrane. Hence, RIPb appears to be localized at microtubules and is then recruited by activated RACB for a function at the plasma membrane during formation of the haustorial complex.

One Sentence summary

RIPb acts downstream of the powdery mildew susceptibility factor RACB of barley and influences susceptibility
Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion
Authors: Lekszas Caroline , Foresti Ombretta , Raote Ishier , Liedtke Daniel , König Eva-Maria , Nanda Indrajit , Vona Barbara , De Coster Peter , Cauwels Rita , Malhotra Vivek , Haaf Thomas
Published: August 2019

The transport and Golgi organization 1 (TANGO1) family proteins have been shown to play pivotal roles in the secretory pathway. Full length TANGO1 is a transmembrane protein localised at endoplasmic reticulum exit sites (ERES), where it binds bulky cargo within the ER lumen and recruits membranes from the ER Golgi intermediate compartment (ERGIC) to create an exit route for their export. Tango1 knockout mice display a global collagen secretion defect and perinatal lethality. Here we report the first TANGO1-associated syndrome in humans, which mainly manifests in a collagenopathy. A synonymous substitution that results in exon 8 skipping in most mRNA molecules, ultimately leading to a truncated TANGO1 protein was identified as the disease-causing mutation. The four homozygously affected sons of a consanguineous family display severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the corresponding truncated TANGO1 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1 impairs cellular collagen I secretion.
scHLAcount: Allele-specific HLA expression from single-cell gene expression data
Authors: Darby Charlotte A. , Stubbington Michael J. T. , Marks Patrick J. , Barrio Álvaro Martínez , Fiddes Ian T.
Published: August 2019

Studies in bulk RNA sequencing data suggest cell-type and allele-specific expression of the human leukocyte antigen (HLA) genes. These loci are extremely diverse and they function as part of the major histocompatibility complex (MHC) which is responsible for antigen presentation. Mutation and or misregulation of expression of HLA genes has implications in diseases, especially cancer. Immune responses to tumor cells can be evaded through HLA loss of function. However, bulk RNA-seq does not fully disentangle cell type specificity and allelic expression. Here we present scHLAcount, a workflow for computing allele-specific molecule counts of the HLA genes in single cells an individualized reference. We demonstrate that scHLAcount can be used to find cell-type specific allelic expression of HLA genes in blood cells, and detect different allelic expression patterns between tumor and normal cells in patient biopsies. scHLAcount is available at https://github.com/10XGenomics/scHLAcount.
Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of “quasi-ordered” states
Authors: Clouser Amanda F. , Baughman Hannah E.R. , Basanta Benjamin , Guttman Miklos , Nath Abhinav , Klevit Rachel E.
Published: August 2019

Small heat shock proteins (sHPSs) are nature’s “first responders” to cellular stress, interacting with affected proteins to prevent their aggregation. Little is known about sHSP structure beyond its structured α-crystallin domain (ACD), which is flanked by disordered regions. In the human sHSP HSPB1, the disordered N-terminal region (NTR) represents nearly 50% of the sequence. Here, we present a hybrid approach involving NMR, hydrogen-deuterium exchange mass spectrometry, and modeling to provide the first residue-level characterization of the NTR. The results support a model in which multiple grooves on the ACD interact with specific NTR regions, creating an ensemble of “quasi-ordered” NTR states that can give rise to the known heterogeneity and plasticity of HSPB1. Phosphorylation-dependent interactions inform a mechanism by which HSPB1 is activated under stress conditions. Additionally, we examine the effects of disease-associated NTR mutations on HSPB1 structure and dynamics, leveraging our emerging structural insights.
Antibiotic Resistance Increases Evolvability and Maximizes Opportunities Across Fitness Landscapes
Authors: Spagnolo Fabrizio , Dykhuizen Daniel E.
Published: August 2019

Antibiotic resistance continues to grow as a public health problem. One of the reasons for this continued growth is that resistance to antibiotics is strongly selected for in the presence of antibiotics and weakly selected against after their removal. This is frequently thought to be due to the effects of compensatory mutations. However, compensatory mutations are often not found in clinically relevant strains of antibiotic resistant pathogens. Here, we conduct experimentsin vitrothat highlight the role that fine scale differences in environment play in the maintenance of populations after selection for resistance. We show that differences in the mode of growth, dictated by environmental factors, are capable of reliably changing the force and direction of selection. Our results show that antibiotic resistance can increase evolvability in environments if conditions for selection exist, selecting differentially for newly arising variation and moving populations to previously unavailable adaptive peaks.

Significance

Antibiotic resistant bacteria are a large and growing problem for public health. A major question has been why antibiotic resistant strains do not disappear when they must compete with higher fitness drug sensitive strains. Here we show that selection for antibiotic resistant strains is particularly sensitive to differences in environmental conditions and that these differences help to define the fitness landscapes upon which these populations adapt. The result is an increase in evolvability, with many adaptive peaks that drug resistant populations can explore through natural selection, making predictions of evolution difficult and selection against resistant strains improbable.
Functional characterization of fatty acyl desaturase Fads2 and Elovl5 elongase in the Boddart’s goggle-eyed goby,Boleophthalmus boddarti(Gobiidae) suggest an incapacity for long-chain polyunsaturated fatty acid biosynthesis
Authors: Soo Han-Jie , Chong Joey , Sean Lau Nyok , Ting Seng Yeat , Kei Sam Ka , Kuah Meng-Kiat , Kwang Sim Yee , Janaranjani M. , Shu-Chien Alexander Chong
Published: August 2019

Long-chain polyunsaturated fatty acid biosynthesis, a process to convert C18 polyunsaturated fatty acids to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or arachidonic acid (ARA) requires the concerted activities of two enzymes, the fatty acyl desaturase (Fads) and elongase (Elovl). This study highlights the cloning, functional characterisation and tissue expression pattern of a Fads and Elovl from the Boddart’s goggle-eyed goby (Boleophthalmus boddarti), a mudskipper species widely distributed in the Indo-Pacific region. Phylogenetic analysis revealed that the cloned Fads and Elovl are clustered with other teleost Fads2 and Elovl5 orthologs, respectively. Interrogation of the genome of several mudskipper species, namelyB. pectinirostris, Periophthalmus schlosseriandP. magnuspinnatusrevealed a single Fads2 for each respective species while two elongases, Elovl5 and Elovl4 were detected. Using a heterologous yeast assay, theB. boddartiFads2 was shown to possess low desaturation activity on C18 PUFA. In addition, there was no desaturation of C20 and C22 substrates. In comparison, the Elovl5 showed a wide range of substrate specificity, with capacity to elongate C18, C20 and C22 PUFA substrates. We identified an amino acid residue in theB. boddartiElovl5 that affect the capacity to bind C22 PUFA substrate. Both genes are highly expressed in brain tissue. Among all tissues, DHA is highly concentrated in neuron-rich tissues while EPA is highly deposited in gills. Taken together, the results showed that due to disability of desaturation steps,B. boddartiis unable to biosynthesis LC-PUFA, relying on dietary intake to acquire these nutrients.