bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythritol Ingestion Causes Concentration-Dependent Mortality in Eastern Subterranean Termites (Blattodea: Rhinotermitidae)
Authors: Caponera Virginia , Barrett Meghan , Marenda Daniel R , O’donnell Sean
Published: August 2019

Damage from termite infestations is economically significant and control can be costly when requiring the widespread use of conventional insecticides. Erythritol, a polyalcohol sweetener that is safe for human consumption, causes increased mortality when ingested by some insects, indicating potential as a safe alternative insecticide. Here, we investigated the applicability of erythritol as a novel toxicant method of termite control. Eastern subterranean termites, Reticulitermes flavipes Kollar (Blattodea: Rhinotermitidae), were fed paper foods treated with increasing concentrations of erythritol and were assessed for mortality and bait consumption. Termite survival to 8 d (the duration of the experiment) significantly decreased as erythritol treatment concentration increased, indicating that the lethal effects of erythritol were concentration-dependent. Termites consumed erythritol-treated paper at all concentrations and did not display avoidance in choice assays, suggesting that erythritol may be practical for use as an ingestible bait. These results provide a basis for further development of erythritol as a safe alternative method of termite control.
Enhanced-Efficacy Iranian Diatomaceous Earth for Controlling Two Stored-Product Insect Pests
Authors: Delgarm Najmeh , Ziaee Masumeh , McLaughlin Alan
Published: August 2019

The present study was conducted to evaluate the insecticidal activity of three diatomaceous earth (DE) products, SilicoSec (Biofa GmbH, Munsingen, Germany), Protect-It (Hedley Technologies Inc., Canada), and Mamaghan. The silica aerogel was mixed to enhance the efficacy of Mamaghan DE with 10, 15, and 20% rates. The DE products were applied at treatment rates of 100, 200, and 400 ppm against adults of Tribolium confusum Jacquelin du Val. (Coleoptera: Tenebrionidae) and Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae). In the second experiment, 0.1 and 0.5% deltamethrin was added to Mamaghan DE–10% silica aerogel to enhance the activity of the DE. Adult mortality was recorded 2, 5, 7, 10, and 14 d after exposure. Parental adults were removed after 14-d exposure time and progeny developed was evaluated after 65 d. Mamaghan–15 and 20% silica aerogel caused the highest mortality (>97%) against T. confusum after 10 d of exposure at the highest dose of 400 ppm which exceeded to 100% mortality after 14 d. However, the toxicity of Mamaghan DE against R. dominica was lower than that of the two commercial formulations at all dose rates. The presence of 0.1% deltamethrin increased the insecticidal activity of Mamaghan DE and significantly suppressed progeny production of both species. Even at the lowest dose of Mamaghan–10% + 0.1% deltamethrin, progeny production of both species was very low (four or less individuals per vial). However, no progeny was recorded in Mamaghan–10% + 0.5% deltamethrin. Thus, adding low rates of silica aerogel and deltamethrin considerably enhanced the efficacy of Mamaghan DE in controlling T. confusum and R. dominica.
Anterior knee schwannoma
Authors: Ilagan Charmaine , Poliakin Lauren , Asarian Armand , Xiao Philip , Sirsi Sandeep
Published: August 2019

Peripheral nerve tumors are relatively uncommon with schwannomas being the most common type. Schwannomas are usually benign encapsulated tumors composed of neoplastic Schwann cells that generally do not transform to malignancy. Many are discovered incidentally as solitary tumors. The cause is unknown. Most occur spontaneously, while some develop in association with genetic disorders such as neurofibromatosis type 2 or schwannomatosis. Schwannomas can occur anywhere in the body. They affect all ages, with peaking incidence between ages 20 and 50 years, without predilection to sex or race. Many are asymptomatic; however, presenting signs and symptoms, such as paresthesia and pain, are due to mass effect and direct nerve invasion. Diagnosing includes combinations of thorough physical examination, imaging modalities such as magnetic resonance imaging and surgical biopsy. Treatment depends on factors such as location of the tumor and severity of symptoms. Asymptomatic patients are treated conservatively while symptomatic patients undergo surgical resection with favorable prognosis.
Revisiting Debussy’s Relationships with Otherness: Difference, Vibrations, and the Occult
Authors: Pasler Jann
Published: August 2019

To commemorate the centenary of Debussy’s death, this article proposes a new perspective on the composer’s relationship to Otherness. While many have argued for the influence of japonisme and Javanese music on his oeuvre, here I look at experiences, influences, and ideas that shaped these and similar encounters, together with their implications. I argue that symbolism was not alone in motivating Debussy’s resistance to overt mimesis and ambivalence about assimilation; Japan’s evolving political identity between 1868 and 1904 may also have played a role. I examine what Debussy may have learned from, or at least shared with, Edmond Bailly, Robert Godet, Victor Segalen, and Louis Laloy. These connections draw particular attention to contemporary conceptions of sound, as promoted in esoteric philosophy, and especially nature’s relationship to the arts through ‘vibrations’—ideas later implicit in Vladimir Jankélévitch’s philosophical approach, here re-evaluated after the 2012 colloquy in the Journal of the American Musicological Society. They offer intriguing historical foundations for today’s ‘sound studies’ research.
Potential softening and eccentricity dynamics in razor-thin, nearly Keplerian discs
Authors: Sefilian Antranik A , Rafikov Roman R
Published: August 2019

In many astrophysical problems involving discs (gaseous or particulate) orbiting a dominant central mass, gravitational potential of the disc plays an important dynamical role. Its impact on the motion of external objects, as well as on the dynamics of the disc itself, can usually be studied using secular approximation. This is often done using softened gravity to avoid singularities arising in calculation of the orbit-averaged potential – disturbing function – of a razor-thin disc using classical Laplace–Lagrange theory. We explore the performance of several softening formalisms proposed in the literature in reproducing the correct eccentricity dynamics in the disc potential. We identify softening models that, in the limit of zero softening, give results converging to the expected behaviour exactly, approximately or not converging at all. We also develop a general framework for computing secular disturbing function given an arbitrary softening prescription for a rather general form of the interaction potential. Our results demonstrate that numerical treatments of the secular disc dynamics, representing the disc as a collection of N gravitationally interacting annuli, are rather demanding: for a given value of the (dimensionless) softening parameter, ς ≪ 1, accurate representation of eccentricity dynamics requires N ∼ Cς−χ ≫ 1, with C ∼ O(10), 1.5 ≲ χ ≲ 2. In discs with sharp edges a very small value of the softening parameter ς (≲ 10−3) is required to correctly reproduce eccentricity dynamics near the disc boundaries; this finding is relevant for modelling planetary rings.
Large polar caps for twisted magnetosphere of magnetars
Authors: Tong H
Published: August 2019

The magnetic field of magnetars may be twisted compared with that of normal pulsars. Previous works mainly discussed magnetic energy release in the closed field line regions of magnetars. For a twisted magnetic field, the field lines will inflate in the radial direction. Similar to normal pulsars, the idea of light cylinder radius is introduced. More field lines will cross the light cylinder and become open for a twisted magnetic field. Therefore, magnetars may have a large polar cap, which may correspond to the hot spot during outburst. Particle flow in the open field line regions will result in the untwisting of the magnetic field. Magnetic energy release in the open field line regions can be calculated. The model calculations can catch the general trend of magnetar outburst: decreasing X-ray luminosity, shrinking hot spot etc. For magnetic energy release in the open field line regions, the geometry will be the same for different outburst in one magnetar.
Origin of the PN molecule in star-forming regions: the enlarged sample
Authors: Fontani F , Rivilla V M , van der Tak F F S , Mininni C , Beltrán M T , Caselli P
Published: August 2019

Phosphorus nitride (PN) is the P-bearing species with the highest number of detections in star-forming regions. Multiline studies of the molecule have shown that the excitation temperature of PN is usually lower than the gas kinetic temperature, suggesting that PN is likely in conditions of sub-thermal excitation. We present an analysis of PN that takes the possible sub-thermal excitation conditions into account in a sample of 24 massive star-forming regions. We observed PN (2–1), (3–2), (4–3), and (6–5) with the IRAM-30m and APEX telescopes and detected PN lines in 15 of them. Together with 9 similar sources detected in PN in previous works, we have analysed the largest sample of star-forming regions to date, made of 33 sources with 24 detections in total (among which 13 are new detections). Hence, we have increased the number of star-forming regions detected in PN by more than a factor 2. Our analysis indicates that the PN lines are indeed sub-thermally excited, but well described by a single excitation temperature. We have compared line profiles and fractional abundances of PN and SiO, a typical shock tracer, and found that almost all objects detected in PN have high-velocity SiO wings. Moreover, the SiO and PN abundances with respect to H2 are correlated over several orders of magnitude, and uncorrelated with gas temperature. This clearly shows that the production of PN is strongly linked to the presence of shocked gas, and rules out alternative scenarios based on thermal evaporation from iced grain mantles.
G-quadruplex located in the 5′UTR of the BAG-1 mRNA affects both its cap-dependent and cap-independent translation through global secondary structure maintenance
Authors: Jodoin Rachel , Carrier Julie C , Rivard Nathalie , Bisaillon Martin , Perreault Jean-Pierre
Published: August 2019

The anti-apoptotic BAG-1 protein isoforms are known to be overexpressed in colorectal tumors and are considered to be potential therapeutic targets. The isoforms are derived from alternative translation initiations occuring at four in-frame start codons of a single mRNA transcript. Its 5′UTR also contains an internal ribosome entry site (IRES) regulating the cap-independent translation of the transcript. An RNA G-quadruplex (rG4) is located at the 5′end of the BAG-1 5′UTR, upstream of the known cis-regulatory elements. Herein, we observed that the expression of BAG-1 isoforms is post-transcriptionally regulated in colorectal cancer cells and tumors, and that stabilisation of the rG4 by small molecules ligands reduces the expression of endogenous BAG-1 isoforms. We demonstrated a critical role for the rG4 in the control of both cap-dependent and independent translation of the BAG-1 mRNA in colorectal cancer cells. Additionally, we found an upstream ORF that also represses BAG-1 mRNA translation. The structural probing of the complete 5′UTR showed that the rG4 acts as a steric block which controls the initiation of translation at each start codon of the transcript and also maintains the global 5′UTR secondary structure required for IRES-dependent translation.
Withdrawal Symptoms From E-Cigarette Abstinence Among Adult Never-Smokers: A Pilot Experimental Study
Authors: Hughes John R , Peters Erica N , Callas Peter W , Peasley-Miklus Catherine , Oga Emmanuel , Etter Jean-Francois , Morley Nicholas
Published: August 2019

Introduction

Use of e-cigarettes among never-smokers has substantially increased; yet there are few descriptions of the consequences of such use. We assessed whether adult never-smokers can have withdrawal from cessation of e-cigarettes.

Methods

In an un-blinded pre-post clinical trial, 30 never-smoker daily e-cigarette users used their own nicotine-containing e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence. Participants monitored symptoms of nicotine withdrawal nightly via an Interactive Voice Response system. They attended three lab visits/week to provide expired carbon monoxide and urine samples to determine compliance.

Findings

Abstinence increased all the DSM5 symptoms of tobacco withdrawal and this occurred in the majority of participants. The increase in severity of withdrawal was small and rarely impaired functioning.

Conclusions

Our finding suggests that withdrawal symptoms can occur in never-smokers who stop e-cigarettes abruptly. However, the severity of withdrawal appears to be small and may not be of clinical or regulatory significance. Although our sample size was small and thus replication tests of our results are indicated, it may be prudent to warn never-smokers that withdrawal symptoms may occur.

Implications

This study indicates that withdrawal symptoms can occur in never-smokers who are daily e-cigarette users. However, the severity of withdrawal from e-cigarette abstinence in never-smokers appears to be small and may not be of clinical or regulatory significance. Given our small sample size, replication of our results is warranted. Nevertheless, it might be prudent to warn never-smokers of addiction to e-cigarettes.

Clinical Trial Registration = NCT02825459
Nasal polyp epithelial atypia and exposure to nickel and copper
Authors: Perić A , Vukomanović Đurđević B
Published: August 2019

Background

Possible factors for cell atypia in nasal mucosa include noxious chemicals: ammonia, formaldehyde and heavy metals.

Aims

Case presentation of a nasal polyp with epithelial dysplasia in a worker exposed to nickel and copper salt dust.

Case report

A 27-year-old man complained of impaired nasal breathing and mild right-sided epistaxis. He was exposed to copper and nickel salt dust for 6 years. Clinical examination showed a polypoid lesion arising from the right middle turbinate. Histopathological examination of the excised lesion showed high-grade epithelial dysplasia. Duration of exposure and concentration of heavy metals in serum suggest the biological plausibility of exposure to these factors and development of epithelial dysplasia in the nasal mucosa.

Conclusion

Epithelial dysplasia may occasionally be noted in inflammatory nasal polyps, especially in workers exposed to heavy metals.
The composition of the perinatal intestinal microbiota in horse
Authors: Husso A , Jalanka J , Alipour MJ , Huhti P , Kareskoski M , Pessa-Morikawa T , Iivanainen A , Niku M
Published: August 2019

The establishment of the intestinal microbiota is critical for the digestive and immune systems. We studied the early development of the microbiota in horse, a hindgut fermenter, from birth until 7 days of age, by qPCR and 16S rRNA gene amplicon sequencing. To evaluate initial sources of foal microbiota, we characterized dam fecal, vaginal and oral microbiotas. We utilised an amplicon sequence variant (ASV) based pipeline to maximize resolution and reproducibility. Stringent ASV filtering based on prevalence and abundance in samples and controls purged reagent contaminants while preserving intestinal taxa. The newborn rectum contained small amounts of diverse bacterial DNA, with a profile closer to mare feces and vagina than mouth. 24 hours after birth, the intestine was colonized by Firmicutes and Proteobacteria, some foals dominated by a single genus. At day 7, the phylum-level composition resembled adult feces but genera were different. The mare vaginal microbiota contributed to 24 h and 7 day microbiotas. It contained few lactobacilli, withCorynebacterium,Porphyromonas,CampylobacterandHelcococcusas the most abundant genera. In the oral mucosa,Gemellawas extremely abundant. Our observations suggest that bacteria or bacterial components translocate to the equine fetus, but the intestinal microbiota changes rapidly after birth.
Migrant semipalmated sandpipers (Calidris pusilla) have over four decades steadily shifted towards safer stopover locations
Authors: Hope David D. , Lank David B. , Smith Paul A. , Paquet Julie , Ydenberg Ronald C.
Published: August 2019

Peregrine falcons (Falco peregrinus) have undergone a steady hemisphere-wide recovery since the ban on DDT in 1973, resulting in an ongoing increase in the level of danger posed for migrant birds, such as Arctic-breeding sandpipers. We anticipate that in response migrant semipalmated sandpipers (Calidris pusilla) have adjusted migratory behaviour, including a shift in stopover site usage towards locations offering greater safety from falcon predation.

We assessed semipalmated sandpiper stopover usage within the Atlantic Canada Shorebird Survey dataset. Based on 3,030 surveys (totalling ∼32M birds) made during southward migration, 1974 - 2017, at 198 stopover locations, we assessed the spatial distribution of site usage in each year (with a ‘priority matching distribution’ index, PMD) in relation to the size (intertidal area) and safety (proportion of a site’s intertidal area further than 150m of the shoreline) of each location. The PMD index value is > 1 when usage is concentrated at dangerous locations, 1.0 when usage matches location size, and < 1 when usage is concentrated at safer locations.

A large majority of migrants were found at the safest sites in all years, however our analysis of the PMD demonstrated that the fraction using safer sites increased over time. In 1974, 80% of birds were found at the safest 20% of the sites, while in 2017, this had increased to 97%. A sensitivity analysis shows that the shift was made specifically towards safer (and not just larger) sites. The shift as measured by a PMD index decline cannot be accounted for by possible biases inherent in the data set. We conclude that the data support the prediction that increasing predator danger has induced a shift by southbound migrant semipalmated sandpipers to safer sites.
Genomic history and ecology of the geographic spread of rice
Authors: Gutaker Rafal M. , Groen Simon C. , Bellis Emily S. , Choi Jae Y. , Pires Inês S. , Bocinsky R. Kyle , Slayton Emma R. , Wilkins Olivia , Castillo Cristina C. , Negrão Sónia , Oliveira M. Margarida , Fuller Dorian Q. , d’Alpoim Guedes Jade A. , Lasky Jesse R. , Purugganan Michael D.
Published: August 2019

Rice (Oryza sativa) is one of the world’s most important food crops. We reconstruct the history of rice dispersal in Asia using whole-genome sequences of >1,400 landraces, coupled with geographic, environmental, archaeobotanical and paleoclimate data. We also identify extrinsic factors that impact genome diversity, with temperature a leading abiotic factor. Originating ∼9,000 years ago in the Yangtze Valley, rice diversified into temperate and tropical japonica during a global cooling event ∼4,200 years ago. Soon after, tropical rice reached Southeast Asia, where it rapidly diversified starting ∼2,500 yBP. The history of indica rice dispersal appears more complicated, moving into China ∼2,000 yBP. Reconstructing the dispersal history of rice and its climatic correlates may help identify genetic adaptation associated with the spread of a key domesticated species.

One sentence summary

We reconstructed the ancient dispersal of rice in Asia and identified extrinsic factors that impact its genomic diversity.
In uteroestrogenic endocrine disruption alters the stroma to increase extracellular matrix density and mammary gland stiffness
Authors: Wormsbaecher Clarissa , Hindman Andrea R. , Avendano Alex , Cortes Marcos , Bushman Andrew , Onua Lotanna , Kovalchin Claire E. , Murphy Alina R. , Helber Hannah L. , Shapiro Ali , Voytovitch Kyle , Kuang Xingyan , Song Jonathan W. , Burd Craig J.
Published: August 2019

In uteroendocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Several lines of evidence indicate the stroma mediates endocrine disruption following early-life (orin utero)exposure. Herein, we utilized BPA as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Using RNA-seq transcriptional profiling of adult primary fibroblasts isolated from female mice exposed to BPAin utero, we identified deregulated genes associated with the extracellular matrix. Specifically, multiple collagen genes had increased expression in exposed mice. In line with the transcriptional data, collagen deposition is increased in adult BPA-exposed mice. We further demonstratein vitrothat fibroblasts exposed to BPAin uteroremodel a collagen matrix, thereby decreasing permeability of the collagen matrix. These alterations to the mammary gland resulted in increased gland stiffness in the adult mice. Our data connects early life endocrine disruption to breast density. Interestingly, increased collagen deposition and gland stiffness were not observed in the developing glands of younger mice, suggesting risk factors for breast cancer continue to develop throughout life following these exposures. Finally, we assessed whetherin uteroexposure to two other endocrine disruptors, BPS and DES, also increase breast stiffness in adult mice. While DES increased breast stiffness, BPS did not, suggesting this BPA alternative may in fact pose less breast cancer risk than its predecessor. As breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically link endocrine disruptor exposures and molecular alterations to increased disease susceptibility in the gland.
A template-matching algorithm for laminar identification of cortical recording sites from evoked response potentials
Authors: Matteucci Giulio , Riggi Margherita , Zoccolan Davide
Published: August 2019

In recent years, the advent of the so-called silicon probes has made it possible to homogeneously sample spikes and local field potentials (LFPs) from a regular grid of cortical recording sites. In principle, this allows inferring the laminar location of the sites based on the spatiotemporal pattern of LFPs recorded along the probe, as in the well-known current source-density (CSD) analysis. This approach, however, has several limitations, since it relies on visual identification of landmark features (i.e., current sinks and sources) by human operators – features that can be absent from the CSD pattern if the probe does not span the whole cortical thickness, thus making manual labelling harder. Furthermore, as any manual annotation procedure, the typical CSD-based workflow for laminar identification of recording sites is affected by subjective judgment undermining the consistency and reproducibility of results. To overcome these limitations, we developed an alternative approach, based on finding the optimal match between the LFPs recorded along a probe in a given experiment and a template LFP profile that was computed using 18 recording sessions, in which the depth of the recording sites had been recovered through histology. We show that this method can achieve an accuracy of 79 µm in recovering the cortical depth of recording sites and a 76% accuracy in inferring their laminar location. As such, our approach provides an alternative to CSD that, being fully automated, is less prone to the idiosyncrasies of subjective judgment and works reliably also for recordings spanning a limited cortical stretch.

New and noteworthy

Knowing the depth and laminar location of the microelectrodes used to record neuronal activity from the cerebral cortex is crucial to properly interpret the recorded patterns of neuronal responses. Here we present an innovative approach that allows inferring such properties with high accuracy and in an automated way (i.e., without the need of visual inspection and manual annotation) from the evoked response potentials (ERPs) elicited by sensory (e.g., visual) stimuli.
Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms
Authors: Tretina Kyle , Pelle Roger , Orvis Joshua , Gotia Hanzel T. , Ifeonu Olukemi O. , Kumari Priti , Palmateer Nicholas C. , Iqbal Shaikh B.A. , Fry Lindsay , Nene Vishvanath M. , Daubenberger Claudia , Bishop Richard P. , Silva Joana C.
Published: August 2019

Background

The apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals are at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome.

Results

The re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized.

Conclusions

The process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translation modification in apicomplexan parasites.
Defective cell death of distinct microglial subsets contributes to ADHD-like behavior in mice
Authors: Chuang Hsiu-Chun , Nichols Eva K. , Rauch Isabella , Chang Wei-Cheng , Misra Rhea , Lin Patrick M. , Kitaoka Maiko , Vance Russell E. , Saijo Kaoru
Published: August 2019

Microglia are resident immune cells in the central nervous system that play essential roles to maintain homeostasis and neuronal function. Microglia are heterogeneous cells but the mechanisms by which they contribute to normal brain development remain unclear. Here,we show that microglia in the developing striatum and thalamus undergo pyroptosis,a type of lytic cell death that occurs as a result of Caspase-1 (CASP1) activation downstream of inflammasomes. We observe that pyroptosis occurs in a spatiotemporally regulated and Casp1-dependent manner during fetal brain development. Mice lacking Casp1 or the inflammasome regulating molecules, NLRP3, IL-1R, and Gasdermin D exhibit behavior changes characterized by hyperactivity, inattention, and impulsivity that are similar to attention-deficit/hyperactivity disorder (ADHD). Furthermore, re-expression of Casp1 in Cx3cr1+ cells including microglia restores normal behavior and cell death. We demonstrate that injection of an NLRP3 inhibitor into pregnant wild-type mice is sufficient to induce ADHD-like behaviors in offspring. These data suggest that microglial inflammasome activation and pyroptosis are essential for normal brain development and that genetic and pharmacological disruptions in this pathway may represent new ADHD risk factors.
Multigenerational exposure to elevated temperatures leads to a reduction in standard metabolic rate in the wild
Authors: Pilakouta Natalie , Killen Shaun S. , Kristjánsson Bjarni K. , Skúlason Skúli , Lindström Jan , Metcalfe Neil B. , Parsons Kevin J.
Published: August 2019

In light of global climate change, there is a pressing need to understand and predict the capacity of populations to respond to rising temperatures. Metabolic rate is a key trait that is likely to influence the ability to cope with climate change. Yet, empirical and theoretical work on metabolic rate responses to temperature changes has so far produced mixed results and conflicting predictions.

Our study addresses this issue using a novel approach of comparing fish populations in geothermally warmed lakes and adjacent ambient-temperature lakes in Iceland. This unique ‘natural experiment’ provides repeated and independent examples of populations experiencing contrasting thermal environments for many generations over a small geographic scale, thereby avoiding the confounding factors associated with latitudinal or elevational comparisons. Using Icelandic sticklebacks from three warm and three cold habitats, we measured individual metabolic rates across a range of acclimation temperatures to obtain reaction norms for each population.

We found a general pattern for a lower standard metabolic rate in sticklebacks from warm habitats when measured at a common temperature, as predicted by Krogh’s rule. Metabolic rate differences between warm- and cold-habitat sticklebacks were more pronounced at more extreme acclimation temperatures, suggesting the release of cryptic genetic variation upon exposure to novel conditions, which can reveal hidden evolutionary potential. We also found a stronger divergence in metabolic rate between thermal habitats in allopatry than sympatry, indicating that gene flow may constrain physiological adaptation when dispersal between warm and cold habitats is possible.

In sum, our study suggests that fish may diverge toward a lower standard metabolic rate in a warming world, but this might depend on connectivity and gene flow between different thermal habitats.
BRAin INteractive Sequencing Analysis Tool (BRAIN-SAT); facilitating interactive transcriptome analyses (http://brainsat.eu/)
Authors: Dubbelaar M.L. , Brummer M.L. , Meijer M. , Eggen B.J.L. , Boddeke H.W.G.M.
Published: August 2019

Over the last decade, a large number of glia transcriptome studies has been published. New technologies and platforms have been developed to allow access and interrogation of the published data. The increase in large transcriptomic data sets allows for innovative in silico analyses to address biological questions. Here we present BRAIN-SAT, the follow-up of our previous database GOAD, with several new features available on an interactive platform that enables access to recent, high quality bulk and single cell RNA-Seq data. The combination of several functions including gene searches, differential and quantitative expression analysis and a single cell expression analysis feature enables the exploration of published data sets at different levels. These different functionalities can be used for researchers and research companies in the neuroscience field to evaluate and visualize gene expression levels in a set of relevant publications. Here, we present a new platform with easy access to published gene expression studies for data exploration and gene of interest searches.
Multiple separate cases of pseudogenized meiosis genes Msh4 and Msh5 in Eurotiomycete fungi: associations with Zip3 sequence evolution and homothallism, but not Pch2 losses
Authors: Savelkoul Elizabeth , Toll Cynthia , Benassi Nathan , Logsdon John M.
Published: August 2019

The overall process of meiosis is conserved in many species, including some lineages that have lost various ancestrally present meiosis genes. The extent to which individual meiosis gene losses are independent from or dependent on one another is largely unknown. Various Eurotiomycete fungi were investigated as a case system of recent meiosis gene losses after BLAST and synteny comparisons found Msh4, Msh5, Pch2, and Zip3 to be either pseudogenized or undetected inAspergillus nidulansyet intact in congeners such asA. fumigatus. Flanking gene-targeted degenerate PCR primers applied to 9 additionalAspergillusspecies found (i) Msh4, Msh5, and Zip3 pseudogenized inA. rugulosus(sister taxon toA. nidulans) but intact in all other amplified sequences; and (ii) Pch2 not present at the syntenic locus in most of the 9 species. Topology tests suggested two independent Pch2 losses in genusAspergillus, neither directly coinciding with pseudogenization of the other three genes. TheA. nidulans-A. conjunctusclade Pch2 loss was not associated with significant Ka/Kschanges for Msh4, Msh5, or Zip3; this suggests against prior Pch2 loss directly altering sequence evolution constraints on these three genes. By contrast, Zip3 Ka/Kstended to be elevated in several other Eurotiomycete fungi with independently pseudogenized Msh4 and Msh5 (Talaromyces stipitatus,Eurotium herbariorum). The coinciding Ka/Kselevation and/or clear pseudogenization of Zip3 in taxa with pseudogenized Msh4 and Msh5 is consistent with some degree of molecular coevolution. Possible molecular, environmental, and life history variables (e.g., homothallism) that may be associated with these numerous independent meiosis gene losses (Msh4: 3, Msh5: 3, Zip3: ≥ 1, Pch2: 4) are discussed.
The meninges enhance leukemia survival in cerebral spinal fluid
Authors: Basile Patrick , Jonart Leslie M. , Ebadi Maryam , Johnson Kimberly , Kerfeld Morgan , Gordon Peter M.
Published: August 2019

Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) despite current CNS-directed therapies that are also associated with significant short and long-term toxicities. Herein, we showed that leukemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS), and increased cell death in CSF both in vitro and in vivo. However, interactions between leukemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukemia and suggests novel therapeutic approaches for more effectively targeting leukemia cells in the CNS.
Single-cell RNA Profiling Identifies Diverse Cellular Responses to EWSR1-FLI1 Down-regulation in Ewing Sarcoma
Authors: Khoogar Roxane , Lawlor Elizabeth R. , Chen Yidong , Ignatius Myron , Kitagawa Katsumi , Huang Tim H.-M. , Houghton Peter J.
Published: August 2019

Single-cell analyses provide insight into time dependent behaviors in response to dynamic changes of oncogene expression. We developed an unbiased approach to study gene expression variation using a model of cellular dormancy induced via EWSR1-FLI1 down-regulation in Ewing sarcoma (EWS) cells. We propose that variation in the expression of EWSR1-FLI1 over time determines cellular responses. Cell state and functions were assigned using random forest feature selection in combination with machine learning. Notably, three distinct expression profiles were uncovered contributing to Ewing sarcoma cell heterogeneity. Our predictive model identified ∼1% cells in a dormant-like state and ∼2-4% with higher stem-like and neural stem-like features in an exponentially proliferating EWS cell line and EWS xenografts. Following oncogene knockdown, cells re-entering the proliferative cycle have greater stem-like properties, whereas for those remaining quiescent, FAM134B-dependent dormancy provides a survival mechanism. We also show cell cycle heterogeneity related to EWSR1-FLI1 expression as an independent feature driving cancer heterogeneity, and drug resistance.

SIGNIFICANCE

We show that time-dependent changes induced by suppression of oncogenic EWSR1-FLI1 induces dormancy, with different subpopulation dynamics, including stem-like characteristics and prolonged dormancy. Cells with these characteristics are identified in exponentially growing cell populations and confer drug resistance, and could potentially contribute to metastasis or late recurrence in patients.
Genome-wide misexpression associated with hybrid sterility inMimulus(monkeyflower)
Authors: Kerwin Rachel E. , Sweigart Andrea L.
Published: August 2019

Divergence in gene expression regulation is common between closely related species and may give rise to incompatibilities in their hybrid progeny. In this study, we investigated the relationship between regulatory evolution within species and reproductive isolation between species. We focused on a well-studied case of hybrid sterility betweenMimulus guttatusandM. nasutus, two closely related yellow monkeyflower species, that is caused by two epistatic loci,hybrid male sterility 1(hms1) andhybrid male sterility 2(hms2). We quantified and compared global transcript abundance across male and female reproductive tissues (i.e.stamens and carpels) ofM. guttatusandM. nasutus, as well as sterile and fertile progeny from an advancedM. nasutus-M. guttatusintrogression line that carries thehms1-hms2incompatibility. We observed substantial variation in transcript abundance betweenM. guttatusandM. nasutus, including distinct but overlapping patterns of tissue-biased expression, providing evidence for regulatory divergence between these species. Furthermore, we found pervasive genome-wide misexpression exclusively associated with hybrid sterility – only observed in the affected tissues (i.e.stamens) of sterile introgression hybrids. Examining patterns of allele-specific expression in sterile and fertile hybrids, we found evidence ofcis-andtrans-regulatory divergence, as well ascis-transcompensatory evolution (likely to be driven by stabilizing selection). However, regulatory divergence does not appear to cause misexpression in sterile hybrids, which instead likely manifests as a downstream consequence of sterility itself.
TRIM21 and PHLDA3 Negatively Regulate the Cross-Talk between the PI3K/AKT Pathway and PPP Metabolism
Authors: Cheng Jie , Huang Yan , Zhang Xiaohui , Yu Yue , Zhang Wanru , Wu Shumin , Jiao Jing , Wang Mei , Tran Linh , Zhang Liuzhen , Wang Mengyao , Yan Wenyu , Wu Yilin , Chi Fangtao , Jiang Peng , Zhang Xinxiang , Wu Hong
Published: August 2019

PI3K/AKT signaling is known to regulate cancer metabolism but whether metabolic pathway feedbacks and regulates the PI3K/AKT pathway is unclear. Here, we demonstrate the important reciprocal cross-talks between the PI3K/AKT signal and PPP branching metabolic pathways. PI3K/AKT activation stabilizes G6PD, the rate-limiting enzyme of PPP, by inhibiting a newly identified E3 ligase TIRM21, and promotes PPP. PPP metabolites, in turn, reinforce AKT activation and further promote cancer metabolic reprogramming by blocking the expression of an AKT inhibitor PHLDA3. Knockout TRIM21 or PHLDA3 promotes the cross-talks and cell proliferation. Importantly, PTEN null human cancer cells and in vivo murine models are sensitive to anti-PPP treatments, suggesting the importance of PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. Our study suggests that blockade of these reciprocal cross-talks may have a therapeutic benefit for cancers with PTEN loss or PI3K/AKT activation.
Analysis of promoter-associated chromatin interactions reveals biologically relevant candidate target genes at endometrial cancer risk loci
Authors: O’Mara Tracy A. ,   Endometrial Cancer Association Consortium, Spurdle Amanda B. , Glubb Dylan M.
Published: August 2019

The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer-promoter interactions, a mechanism through which GWAS variation may target genes, we captured loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11,SRP14,HOXB2andBCL11A) was associated with risk variation, providing further evidence for their regulation. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes.
Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism
Authors: Handley Ava , Wu Qiuli , Sherry Tessa , Pocock Roger
Published: August 2019

To maintain metabolic homeostasis, the nervous system must adapt and respond to an ever-changing environment. Transcription factors are key drivers of this adaptation, eliciting gene expression changes that can alter neuronal activity. Here we show inCaenorhabditis elegansthat the terminal selector transcription factor ETS-5 not only establishes the identity of the BAG sensory neurons, but is re-purposed to shape the functional output of the BAG neurons post-mitotically. We find that ETS-5 directly regulates the expression of INS-1, an insulin-like peptide, in the BAG sensory neurons. INS-1 expression in the BAG neurons, and not in other INS-1-expressing neurons, decreases intestinal lipid levels and promotes foraging behaviour. Usingin vivoanalysis, we show that elevated intestinal lipid stores, driven by a high glucose diet, downregulates ETS-5-driven expression of INS-1. Together, our data reveal an inter-tissue regulatory loop by which a single neuron can control systemic metabolism, and that the activity of this neuron is modulated by the metabolic state of the organism.
About a tetraploid ivy in Sicily: from autochthonous Hedera to horticultural-invasive-hybrid package?
Authors: Fridlender Alain , Pech N.
Published: August 2019

In Sicily, H. helix is the unique known native species whereas H. helix susbsp. poetarum is putatively naturalized in some forests and H. canariensis cultivated in various urban’s garden. Trichome morphology and genome size of some ivies from various west Mediterranean forests were compared to Sicilian ones. Ivies from southern Italy, continental France, Corsica and Mallorca belong to typical European diploid stellate trichomes Hedera helix. Hexaploid ivies from southern Spain have been identified as native H. iberica. Contrariwise, Sicilian ivies studied are related to western European H. hibernica (tetraploids with stellate trichomes). Is H. helix the most widespread and indigenous ivy in Sicily? Therefore, it would be the first time that tetraploid would be reported in Sicily where it could possibly correspond to an unnoticed autochthonous taxon. However, our results let us think it rather represents an invasive which impact on this island rich in endemic species could be considerable.
Priors for Genotyping Polyploids
Authors: Gerard David , Ferrão Luís Felipe Ventorim
Published: August 2019

Motivation

Empirical Bayes techniques to genotype polyploid organisms usually either (i) assume technical artifacts are knowna priorior (ii) estimate technical artifacts simultaneously with the prior genotype distribution. Case (i) is unappealing as it places the onus on the researcher to estimate these artifacts, or to ensure that there are no systematic biases in the data. However, as we demonstrate with a few empirical examples, case (ii) makes choosing the class of prior genotype distributions extremely important. Choosing a class that is either too flexible or too restrictive results in poor genotyping performance.

Results

We propose two classes of prior genotype distributions that are of intermediate levels of flexibility: the class of proportional normal distributions and the class of unimodal distributions. We provide a complete characterization of and optimization details for the class of unimodal distributions. We demonstrate, using both simulated and real data, that using these classes results in superior genotyping performance.

Availability and Implementation

Genotyping methods that use these priors are implemented in the updog R package available on the Comprehensive R Archive Network:https://cran.r-project.org/package=updog. All code needed to reproduce the results of this paper is available on GitHub:https://github.com/dcgerard/reproduce_prior_sims.

Contact

dgerard@american.edu
Analysis of Independent Differences (AID) detects complex thermal proteome profiles independent of shape and identifies candidate panobinostat targets
Authors: Panov Alexandra , Gygi Steven P.
Published: August 2019

Identifying global cellular targets of small molecules is a challenge for drug discovery. Thermal proteome profiling (TPP) is a recent technique that uses quantitative proteomics to identify all small molecule protein targets in a single experiment. One current TPP analysis method relies on two major assumptions: sigmoidal melting curve behavior and that intra-condition dependencies preclude an independent and identically distributed model. Herein, we use a previously published panobinostat TPP dataset to show that these assumptions do not hold true and present a novel, shape-independent method, named Analysis of Independent Differences (AID). For each temperature, AID models the differences between conditions of fractions of non-denatured protein as an independent Normal distribution, resulting in a Multivariate Normal observation for each protein. The log of a Multivariate Normal p-value ranks the proteins from most to least likely shifted, and individual Normal p-values within each protein allow for qualitative inspection. Applying AID to the panobinostat dataset revealed known targets in the top 3% of most shifted proteins, as well as candidate targets involved in myeloid leukocyte activation. AID detects complex melting profiles and can be extended to any number of temperature channels, ligand-protein or protein-protein interactions, or general curve data for deeper biological insight.
Intra-genus metabolic diversity facilitates co-occurrence of multiple Ferrovum species at an acid mine drainage site
Authors: Grettenberger Christen L. , Havig Jeff R. , Hamilton Trinity L.
Published: August 2019

Background

Ferrovum spp. are abundant in acid mine drainage sites globally where they play an important role in biogeochemical cycling. All known taxa in this genus are Fe(II) oxidizers. Thus, co-occurring members of the genus could be competitors within the same environment. However, we found multiple, co-occurring Ferrovum spp. in Cabin Branch, an acid mine drainage site in the Daniel Boone National Forest, KY.

Results

Here we describe the distribution of Ferrovum spp. within the Cabin Branch communities and metagenome assembled genomes (MAGs) of two new Ferrovum spp.. In contrast to previous studies, we recovered multiple 16S rRNA gene sequence variants suggesting the commonly used 97% cutoff may not be appropriate to differentiate Ferrovum spp. We also retrieved two nearly-complete Ferrovum spp. genomes from metagenomic data. The genomes of these taxa differ in several key ways relating to nutrient cycling, motility, and chemotaxis.

Conclusions

Previously reported Ferrovum genomes are also diverse with respect to these categories suggesting that the genus Ferrovum contains substantial metabolic diversity. This diversity likely explains how the members of this genus successfully co-occur in Cabin Branch and why Ferrovum spp. are abundant across geochemical gradients.