bluuebunny/crossref_metadata_2025 huggingface dataset:
Facilitative priority effects drive parasite assembly under coinfection
Authors: Halliday Fletcher W. , Penczykowski Rachel M. , Barrès Benoit , Eck Jenalle L. , Numminen Elina , Laine Anna-Liisa
Published: April 2020

Host individuals are often coinfected with diverse parasite assemblages, resulting in complex interactions among parasites within hosts. Within hosts, priority effects occur when the infection sequence alters the outcome of interactions among parasites. Yet, the role of host immunity in this process remains poorly understood. We hypothesized that the host response to first infection could generate priority effects among parasites, altering the assembly of later arriving strains during epidemics. We tested this by infecting sentinel host genotypes ofPlantago lanceolatawith strains of the fungal parasite,Podosphaera plantaginis, and measuring susceptibility to subsequent infection during experimental and natural epidemics. In these experiments, prior infection by one strain often increased susceptibility to other strains, and these facilitative priority effects altered the structure of parasite assemblages, but this effect depended on host genotype, host population, and parasite genotype. Thus, host genotype, spatial structure, and priority effects among strains all independently altered parasite assembly. Then, using a fine-scale survey and sampling of infections on wild hosts in several populations, we identified a signal of facilitative priority effects, which altered parasite assembly during natural epidemics. Together, these results provide evidence that within host priority effects by early arriving strains can drive parasite assembly, with implications for how strain diversity is spatially and temporally distributed during epidemics.
Predicting candidate genes from phenotypes, functions, and anatomical site of expression
Authors: Chen Jun , Althagafi Azza , Hoehndorf Robert
Published: April 2020

Motivation

Over the past years, many computational methods have been developed to incorporate information about phenotypes for disease gene prioritization task. These methods generally compute the similarity between a patient’s phenotypes and a database of gene-phenotype to find the most phenotypically similar match. The main limitation in these methods is their reliance on knowledge about phenotypes associated with particular genes, which is not complete in humans as well as in many model organisms such as the mouse and fish. Information about functions of gene products and anatomical site of gene expression is available for more genes and can also be related to phenotypes through ontologies and machine learning models.

Results

We developed a novel graph-based machine learning method for biomedical ontologies which is able to exploit axioms in ontologies and other graph-structured data. Using our machine learning method, we embed genes based on their associated phenotypes, functions of the gene products, and anatomical location of gene expression. We then develop a machine learning model to predict gene–disease associations based on the associations between genes and multiple biomedical ontologies, and this model significantly improves over state of the art methods. Furthermore, we extend phenotype-based gene prioritization methods significantly to all genes which are associated with phenotypes, functions, or site of expression.

Availability

Software and data are available athttps://github.com/bio-ontology-research-group/DL2Vec.

Contact

robert.hoehndorf@kaust.edu.sa
PremalignantNf1, Trp53-null Oligodendrocyte Precursor Cells Become Stalled in a Heterogeneous State of Replication Stress Before Gliomagenesis
Authors: Sutcliffe Matthew D. , Galvao Rui P. , Wang Lixin , Kim Jungeun , Rosenfeld Lauren K. , Singh Shambhavi , Zong Hui , Janes Kevin A.
Published: April 2020

Cancer evolves from premalignant clones that accumulate mutations and adopt unusual cell states to achieve transformation. Previously, we pinpointed the oligodendrocyte precursor cell (OPC) as a cell-of-origin for glioma, but the early changes of mutant OPCs during premalignancy remained unknown. Using mice engineered for inducibleNf1–Trp53loss in OPCs, we acutely isolated labeled mutant OPCs by laser-capture microdissection and determined gene-expression changes by bulk RNA sequencing and a fluctuation analysis, called stochastic profiling, which uses RNA-sequencing measurements from random pools of 10 mutant cells. At 12 days afterNf1–Trp53deletion, while bulk differences were mostly limited to mitotic hallmarks and genes for ribosome biosynthesis, stochastic profiling revealed a spectrum of stem-progenitor (Axl, Aldh1a1), proneural, and mesenchymal states as potential starting points for gliomagenesis. At 90 days, bulk sequencing detected very few differentially expressed transcripts, whereas stochastic profiling revealed cell states for neurons and mural cells that do not give rise to glial tumors, suggesting cellular dead-ends for gliomagenesis. Importantly, we identified mutant OPCs that strongly expressed key effectors of nonsense-mediated decay (Upf3b) and homology-dependent DNA repair (Rad51c, Slx1b, Ercc4) along with DNA-damage markers suggesting transcription-associated replication stress. Analysis of 10-cell transcriptomes at 90 days identified a locus of elevated gene expression containing an additional repair endonuclease (Mus81) andRin1,a Ras–Raf antagonist and possible counterbalance toNf1loss. At 150 days,Rin1was microdeleted in some gliomas and downregulated in all others. Replication stress may pose a considerable bottleneck that must be resolved for gliomas to initiate.

Statement of significance

In situ stochastic profiling of heterogeneous cell states in a mouse model of glioma uncovers regulatory confusion in a glioma cell-of-origin and defines a state of replication stress that precedes tumor initiation.
Using spatial genetics to quantify mosquito dispersal for control programs
Authors: Filipović I , Hapuarachchi HC , Tien WP , Muhammed ABAR , Lee C , Tan CH , Devine GJ , Rašić G
Published: April 2020

Background

Hundreds of millions of people get a mosquito-borne disease every year, of which nearly one million die. Mosquito-borne diseases are primarily controlled and mitigated through the control of mosquito vectors. Accurately quantified mosquito dispersal in a given landscape is critical for the design and optimization of the control programs, yet the field experiments that measure dispersal of mosquitoes recaptured at certain distances from the release point (mark-release-recapture MRR studies) are challenging for such small insects and often unrepresentative of the insect’s true field behavior. Using Singapore as a study site, we show how mosquito dispersal patterns can be characterized from the spatial analyses of genetic relatedness among individuals sampled over a short time span without interruption of their natural behaviors.

Methods and Findings

We captured ovipositing females ofAedes aegypti, a major arboviral disease vector, across floors of high-rise apartment blocks and genotyped them using thousands of genome-wide SNP markers. We developed a methodology that produces a dispersal kernel for distance that results from one generation of successful breeding (effective dispersal), using the distances separating full siblings, 2ndand 3rddegree relatives (close kin). In Singapore, the estimated dispersal distance kernel was exponential (Laplacian), giving the mean effective dispersal distance (and dispersal kernel spread σ) of 45.2 m (95%CI: 39.7-51.3 m), and 10% probability of dispersal >100 m (95%CI: 92-117 m). Our genetic-based estimates matched the parametrized dispersal kernels from the previously reported MRR experiments. If few close-kin are captured, a conventional genetic isolation-by-distance analysis can be used, and we show that it can produce σ estimates congruent with the close-kin method, conditioned on the accurate estimation of effective population density. We also show that genetic patch size, estimated with the spatial autocorrelation analysis, reflects the spatial extent of the dispersal kernel ‘tail’ that influences e.g. predictions of critical radii of release zones andWolbachiawave speed in mosquito replacement programs.

Conclusions

We demonstrate that spatial genetics (the newly developed close-kin analysis, and conventional IBD and spatial autocorrelation analyses) can provide a detailed and robust characterization of mosquito dispersal that can guide operational vector control decisions. With the decreasing cost of next generation sequencing, acquisition of spatial genetic data will become increasingly accessible, and given the complexities and criticisms of conventional MRR methods, but the central role of dispersal measures in vector control programs, we recommend genetic-based dispersal characterization as the more desirable means of parameterization.
Assessment of prevalence and risk factors for intestinal parasitosis, malnutrition and anemia among school children in Ghindae area, Eritrea
Authors: Kesete Yafet , Tesfahiwet Huruy , Fessehaye Ghimja , Kidane Yohana , Tekle Yafet , Yacob Asmerom , Seltene Biemnet
Published: April 2020

Background

Intestinal parasitic infections, anemia, and malnutrition are very endemic in resource-limited regions. School-aged children are at greater risk for the disease than any other age group as they are more susceptible to parasitosis, associated undergrowth and anemia. This study is aimed at evaluating the risk factors of intestinal parasitosis, malnutrition and anemia amongst elementary and junior school students in Ghindae area, Eritrea.

Methods

A cross sectional study was conducted in 6 schools around Ghindae from February to April 2018. 450 children were randomly selected for analysis and consent was taken from guardians. The pertinent sociodemographic data was collected and anthropometric measurements were carried out to determine the proportion of students with malnutrition, stunting and thinness. Fecal samples were examined by formal concentration technique and blood specimen was collected for the assessment of hemoglobin using hemocue analyzer.

Results

The overall prevalence of intestinal parasitosis was 45.3%. Protozoa infections (38.2%) were more prevalent than soil-transmitted helminthes infections (10.4%). The presence of different intestinal parasitic infections has statistically significant association with the residence area, washing habits, source of water, types of schools and type of latrine used with (p < 0.05). The prevalence of malnutrition was 37.1% with 18.5% stunting and 21.2% thinness. Malnutrition was in higher prevalence in semi-urban areas outside Ghindae. Students from Embatkala and Dongolo had 4.77 and 2.86 times higher odds of having low BMI for age than their counterpart respectively. The current prevalence of anemia was 12.4%, out of which, 7.6 % had mild while 4.4% of them had moderate anemia and 0.4% were severely anemic.

Conclusion

The prevalence of intestinal parasitic infections, especially, protozoan infection was very high in the school children. Stunting was increased rate in rural areas around Ghindae. The prevalence of anemia was regarded as mild health burden. The high prevalence of parasitic infections in these children indicates that the protozoa and helminthes concerned are very common in the environment of these area and results of the risk factors analysis suggest that the transmission is from several routes. Access to clean water and latrines, with some hygiene and sanitation communication activities, in addition to introduction of micronutrient programs could improve health of children in that area.
Early behavior of Madrid Covid-19 disease outbreak: A mathematical model
Authors: García-Iglesias Daniel , de Cos Juez Francisco Javier
Published: April 2020

Introduction

Madrid Covid-19 disease outbreak started on 28 February 2020 and since then it became the main Covid-19 disease cluster in Spain. On 26 March 2020, a total of 17166 cases were already reported, with 2090 deaths. Globally a R0 index of 2-3 has been reported. We aimed to build an experimental mathematical model that help to analyze the early characteristics of Madrid Covid-19 disese outbreak and to explore the actual R0 index on Madrid Covid-19 outbreak.

Material and Methods

A simulated mathematical model was built, based on a SIR epidemiological model and the reported characteristics of Wuhan Covid-19 disease outbreak. Monte Carlo simulations were further done to estimate the R0 value over time in the Madrid Covid-19 disease outbreak.

Results

Mean estimated R0 value along the early period is of 2.22 (+/-1.21 SD). A significant increase of 0.093 (+/-0.037, p=0.025) in R0 value each day of outbreak is found.

Conclussions

Our proposed Mathematical Simulation model may be useful to evaluate early characteristics of this outbreak. The present work is the first reported estimation of R0 value in the Spanish Madrid Covid-19 outbreak, with similar results to the previous reported in the Wuhan outbreak, although it may suggest a slightly increase on R0 along time.
Autonomous Magnetic Resonance Imaging
Authors: Ravi Keerthi Sravan , Geethanath Sairam
Published: April 2020

Access to Magnetic Resonance Imaging (MRI) across developing countries from being prohibitive to scarcely available. For example, eleven countries in Africa have no scanners. One critical limitation is the absence of skilled manpower required for MRI usage. Some of these challenges can be mitigated using autonomous MRI (AMRI) operation. In this work, we demonstrate AMRI to simplify MRI workflow by separating the required intelligence and user interaction from the acquisition hardware. AMRI consists of three components: user node, cloud and scanner. The user node voice interacts with the user and presents the image reconstructions at the end of the AMRI exam. The cloud generates pulse sequences and performs image reconstructions while the scanner acquires the raw data. An AMRI exam is a custom brain screen protocol comprising of one T1-, T2- and T2*-weighted exams. A neural network is trained to incorporate Intelligent Slice Planning (ISP) at the start of the AMRI exam. A Look Up Table was designed to perform intelligent protocolling by optimising for contrast value while satisfying signal to noise ratio and acquisition time constraints. Data were acquired from four healthy volunteers for three experiments with different acquisition time constraints to demonstrate standard and self-administered AMRI. The source code is available online. AMRI achieved an average SNR of 22.86 ± 0.89 dB across all experiments with similar contrast. Experiment #3 (33.66% shorter table time than experiment #1) yielded a SNR of 21.84 ± 6.36 dB compared to 23.48 ± 7.95 dB for experiment #1. AMRI can potentially enable multiple scenarios to facilitate rapid prototyping and research and streamline radiological workflow. We believe we have demonstrated the first Autonomous MRI of the brain.
Double trouble? When a pandemic and seasonal virus collide
Authors: Zipfel Casey , Colizza Vittoria , Bansal Shweta
Published: April 2020

As healthcare capacities in the US and Europe reach their limits due to a surge in the COVID-19 pandemic, both regions enter the 2020-2021 influenza season. Southern hemisphere countries that had suppressed influenza seasons provide a hopeful example, but the lack of reduction in influenza in the 2019-2020 influenza season and heterogeneity in nonpharmaceutical and pharmaceutical interventions show that we cannot assume the same effect will occur globally. The US and Europe must promote the implementation and continuation of these measures in order to prevent additional burden to healthcare systems due to influenza.
RNF213variation, a broader role in neurovascular disease in Caucasian and Japanese populations
Authors: Lorenzo-Betancor Oswaldo , Blackburn Patrick R. , Farrugia Luca , Soto-Beasley Alexandra I. , Walton Ronald L. , Edwards Emily , Tawk Rabih G. , Klee Eric W. , Freeman William D. , Miller David , Meschia James , Ross Owen A.
Published: April 2020

Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease that predominantly affects East Asian populations. The major genetic mutation associated with MMD in Asian populations is the p.R4810K substitution in Ring Finger Protein 213 (RNF213). Interestingly, variants in theRNF213gene have also been implicated in intracranial aneurysms (IA) in French-Canadian population, suggesting that variation in this gene may play a broader role in cerebrovascular phenotypes. In a recent genome-wide association study (GWAS) in a Caucasian population, variants rs6565653 and rs12601526 in theSolute Carrier Family 26 Member 11(SLC26A11) gene, which is less than 10kb away fromRNF213, showed a suggestive association with young onset ischemic stroke. We propose that the signal could be tagging an association with common variation in theRNF213gene. We analyzed the linkage disequilibrium (LD) pattern in theSLC26A11-RNF213gene region and we observed a high LD between variants in this region based on D’ values. We show thatSLC26A11rs6565653 variant tagsRNF213rs12944088, a missense variant that is more common among subjects with IA than in healthy individuals. Given the fact that rs6565653 tags severalRNF213variants, it is highly likely that some of these tagged variants modify the risk of suffering stroke. The LD analyses suggest that theSLC26A11signal from the young onset ischemic stroke GWAS performed in a Caucasian population is also tagging variation at theRNF213loci, supporting the hypothesis thatRNF213variation may result in a variety of neurovascular disorders including an increased risk and/or worse prognosis following ischemic stroke in Caucasian population.
The Crohn’s disease-related AIEC strain LF82 assembles a biofilm-like matrix to protect intracellular microcolonies from phagolysosomal attack
Authors: Prudent Victoria , Demarre Gaëlle , Vazeille Emilie , Wery Maxime , Ravet Antinéa , Quenech’Du Nicole , Girault Julie Dauverd , Bringer Marie-Agnès , Descrimes Marc , Barnich Nicolas , Rimsky Sylvie , Morillon Antonin , Espéli Olivier
Published: April 2020

Patients with Crohn’s disease exhibit abnormal colonization of the intestine by proteobacteria, and among these bacteria, the adherent invasiveE. coli(AIEC) family. They are predominant in the mucus, adhere to epithelial cells, colonize them and survive inside macrophages. We recently demonstrated that the acclimation of the AIEC strain LF82 to phagolysosomal stress requires stringent and SOS responses. Such adaptation involves a long lag phase in which many LF82 cells become antibiotic tolerant. Later during infection, they proliferate in vacuoles and form colonies harboring dozens of LF82 bacteria. In the present work, we investigated the mechanism sustaining this phase of growth. We found that intracellular LF82 produced an extrabacterial matrix composed of exopolysaccharides and amyloid fibers that surrounded each individual LF82 cell. This matrix acts as a biofilm and controls the formation of LF82 intracellular bacterial communities (IBCs) inside phagolysosomes for several days post infection. Using genomics assays, we characterized the gene set involved in IBCs formation and revealed the crucial role played by a pathogenicity island presents in the genome of most AIEC strains in this process. Iron capture, by the yersiniabactin system encoded by this pathogenicity island, is essential to form IBC and LF82 survival within macrophages. These results demonstrate that AIEC have developed a sophisticated strategy to establish their replicative niche within macrophages, which might have implications for envisioning future antibacterial strategies for Crohn’s disease.
Culture conditions antagonize lineage-promoting signaling in the mouse blastocyst
Authors: Frum Tristan , Ralston Amy
Published: April 2020

The mouse preimplantation embryo is a paradigm for discovery of the molecular principles governing formation of specific cell types during development. We show that conditions commonly used forex vivoculture of preimplantation development are themselves antagonistic to a pathway that is critical for blastocyst lineage commitment.
Speed modulation of hippocampal theta frequency and power predicts water maze learning
Authors: Young Calvin K. , Ruan Ming , McNaughton Neil
Published: April 2020

Theta oscillations in the hippocampus have many behavioural correlates, with the magnitude and vigour of ongoing movement being the most salient. Many consider correlates of locomotion with hippocampal theta to be a confound in delineating theta contributions to cognitive processes. But, theory and empirical experiments suggest theta-movement relationships are important if spatial navigation is to support higher cognitive processes. In the current study, we tested if variations in speed modulation of hippocampal theta can predict spatial learning rates in the water maze. Using multi-step regression, we find the magnitude and robustness of hippocampal theta frequency versus speed scaling can predict water maze learning rates. Using generalised linear models, we also demonstrate that speed and water maze learning are the best predictors of hippocampal theta frequency and power. Theta oscillations recorded from the supramammillary area showed much weaker, or non-existent, relationships, which supports the idea that hippocampal theta has specific roles in speed representation and spatial learning. Our findings suggest movement-speed correlations with hippocampal theta frequency may be actively used in spatial learning.
Oxygen-glucose deprivation and reoxygenation on human cerebral organoids alters expression related to lipid metabolism
Authors: Iwasa Naoki , Matsui Takeshi K. , Morikawa Naritaka , Sakaguchi Yoshihiko M. , Shiota Tomo , Iguchi Naohiko , Nishimura Yuhei , Mori Eiichiro , Sugie Kazuma
Published: April 2020

Ischemic stroke is one of the most common neurological disease. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown; due to a lack of ischemic human brain samples. In this study, we used cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). We identified 15 differentially expressed genes (DEGs); and found that all the DEGs were downregulated. Pathway analysis showed the relationship of vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor signaling pathway, and complement and coagulation cascades. These findings indicate the mechanisms underlying ischemic injury in human cerebral tissue.
CPPred-sORF: Coding Potential Prediction of sORF based on non-AUG
Authors: Tong Xiaoxue , Hong Xu , Xie Juan , Liu Shiyong
Published: April 2020

In recent years, researchers have discovered thousands of sORFs that can encode micropeptides, and more and more discoveries that non-AUG codons can be used as translation initiation sites for these micropeptides. On the basis of our previous tool CPPred, we develop CPPred-sORF by adding two features and using non-AUG as the starting codon, which makes a comprehensive evaluation of sORF. The database of CPPred-sORF are constructed by small coding RNA and lncRNA as positive and negative data, respectively. Compared to the small coding RNAs and small ncRNAs, lncRNAs and small coding RNAs are less distinguishable. This is because the longer the sequences, the easier to include open reading frames. We find that the sensitivity, specificity and MCC value of CPPred-sORF on the independent testing set can reach 88.22%, 88.84% and 0.768, respectively, which shows much better prediction performance than the other methods.
Learning-related population dynamics in the auditory thalamus
Authors: Gilad Ariel , Maor Ido , Mizrahi Adi
Published: April 2020

Learning to associate sensory stimuli with a chosen action has been classically attributed to the cortex. Whether the thalamus, considered mainly as an upstream area relative to cortex, encodes learning-related information is still largely unknown. We studied learning-related activity in the dorsal and medial regions of the medial geniculate body (MGB), part of the non-lemniscal auditory pathway. Using fiber photometry, we continuously imaged population calcium dynamics as mice learned a go/no-go auditory discrimination task. The MGB was tuned to frequency shortly after stimulus onset and responded to cognitive features like the choice of the mouse several hundred milliseconds later. Encoding of choice in the MGB increased with learning, and was highly correlated with the learning curves of the mice. MGB also encoded motor parameters of the mouse during the task. These results provide evidence that the MGB encodes task- motor- and learning-related information.
Chromatin 3D interaction analysis of theSTARD10locus unveilsFCHSD2as a new regulator of insulin secretion
Authors: Hu Ming , Cebola Inês , Carrat Gaelle , Jiang Shuying , Nawaz Sameena , Khamis Amna , Canouil Mickael , Froguel Philippe , Schulte Anke , Solimena Michele , Ibberson Mark , Marchetti Piero , Cardenas-Diaz Fabian L. , Gadue Paul J. , Hastoy Benoit , Alemeida-Souza Leonardo , McMahon Harvey , Rutter Guy A.
Published: April 2020

Genome-wide association studies have identified thousands of genetic variants associated with type 2 diabetes (T2D) risk. Using chromatin conformation capture we show that an enhancer cluster in theSTARD10T2D locus forms a defined 3D chromatin domain. A 4.1 Kb region within this region, carrying five disease-associated variants, physically interacts with CTCF-binding regions and with an enhancer possessing strong transcriptional activity. Analysis of human islet 3D chromatin interaction maps identifiesFCHSD2gene as an additional target of the enhancer cluster. CRISPR-Cas9-mediated deletion of the variant region, or of an associated enhancer, in human pancreatic beta cells impaired glucose-stimulated insulin secretion. Expression of bothSTARD10andFCHSD2, but notARAP1, was reduced in cells harboring CRISPR deletions, and expression ofSTARD10andFCHSD2was associated with the possession of variant alleles in human islets. Finally, CRISPR-Cas9-mediated loss ofSTARD10orFCHSD2impaired regulated insulin secretion. Thus, multiple genes at theSTARD10locus influence β cell function.
Can genetic polymorphisms predict response variability to anodal transcranial direct current stimulation of the primary motor cortex?
Authors: Pellegrini Michael , Zoghi Maryam , Jaberzadeh Shapour
Published: April 2020

Genetic mediation of cortical plasticity and the role genetic variants play in previously observed response variability to transcranial direct current stimulation (tDCS) have become important issues in the tDCS literature in recent years. This study investigated whether inter-individual variability to tDCS was in-part genetically mediated. In sixty-one healthy males, anodal-tDCS (a-tDCS) and sham-tDCS were administered to the primary motor cortex at 1mA for 10-minutes via 6×4cm active and 7×5cm return electrodes. Twenty-five single-pulse transcranial magnetic stimulation (TMS) motor evoked potentials (MEP) were recorded to represent corticospinal excitability (CSE).

Twenty-five paired-pulse MEPs were recorded with 3ms inter-stimulus interval (ISI) to assess intracortical inhibition (ICI) via short-interval intracranial inhibition (SICI) and 10ms ISI for intracortical facilitation (ICF). Saliva samples tested for specific genetic polymorphisms in genes encoding for excitatory and inhibitory neuroreceptors. Individuals were sub-grouped based on a pre-determined threshold and via statistical cluster analysis. Two distinct subgroups were identified, increases in CSE following a-tDCS (i.e. Responders) and no increase or even reductions in CSE (i.e. Non-responders). No changes in ICI or ICF were reported. No relationships were reported between genetic polymorphisms in excitatory receptor genes and a-tDCS responders. An association was reported between a-tDCS responders and GABRA3 gene polymorphisms encoding for GABA-A receptors suggesting potential relationships between GABA-A receptor variations and capacity to undergo tDCS-induced cortical plasticity. In the largest tDCS study of its kind, this study presents an important step forward in determining the contribution genetic factors play in previously observed inter-individual variability to tDCS.
Eco-evolutionary interaction in competing phytoplankton: genotype sorting likely explains dominance shift and species responses to CO2
Authors: Listmann Luisa , Hattich Giannina S. I. , Matthiessen Birte , Reusch Thorsten B.H.
Published: April 2020

How ecological and evolutionary processes interact and together determine species and community responses to climate change is poorly understood. We studied long-term dynamics (over approximately 200 asexual generations) in two phytoplankton species, a coccolithophore (Emiliania huxleyi) and a diatom (Chaetoceros affinis), to increased CO2growing alone or competing with one another in co-occurrence. To allow for rapid evolutionary responses, the experiment started with a standing genetic variation of nine genotypes in each of the species. Under co-occurrence of both species, we observed a dominance shift fromC. affinistoE. huxleyiafter about 120 generations in both CO2treatments, but more pronounced under high CO2. Associated with this shift, we only found weak adaptation to high CO2in the diatom and none in the coccolithophore in terms of species’ growth rates. In addition, no adaptation to interspecific competition could be observed by comparing the single to the two-species treatments in reciprocal assays, regardless of the CO2treatment. Nevertheless, highly reproducible genotype sorting left only one genotype remaining for each of the species among all treatments. This strong evolutionary selection coincided with the dominance shift fromC. affinistoE. huxleyi. Since all other conditions were kept constant over time, the most parsimonious explanation for the dominance shift is that the strong evolutionary selection potentially altered competitive ability of the two species. Thus, here observed changes in the simplest possible two-species phytoplankton “community” demonstrated that eco-evolutionary interactions can be critical for predicting community responses to climate change in rapidly dividing organisms such as phytoplankton.
Substrate sensing institutes sequential and asymmetric electron transfer in the nitrogenase-like DPOR complex
Authors: Corless Elliot I. , Bennett Brian , Antony Edwin
Published: April 2020

Dark-operative protochlorophyllide oxidoreductase (DPOR) catalyzes the reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide), a key penultimate step in the biosynthesis of bacteriochlorophyll. DPOR shares structural homology with nitrogenase and is made of electron donor (BchL) and electron acceptor (BchNB) component proteins. ATP driven assembly of the BchL and BchNB proteins drives electron transfer and Pchlide reduction. BchNB is composed of two subunits each of BchN and BchB arranged as an α2ß2 heterotetramer. Here, we describe extensive allosteric communication between the two identical active sites in BchNB that drives sequential and asymmetric electron transfer. Pchlide binding and electron transfer activities in one half of the BchNB tetramer allosterically regulates activities in the other half. Pchlide binding is sensed and recognizedin transby an Asp274 from the opposing half and is positioned in the active site to likely serve as the initial proton donor. An Asp274 to Ala substituted DPOR binds to two Pchlide molecules in the BchNB complex but is unable to conformationally poise one Pchlide molecule. Thus, stalling Pchlide reduction in both active sites. The [4Fe-4S] cluster of the BchNB protein is pre-reduced and donates the first electron to Pchlide, a mechanism similar to the deficit-spending model observed in nitrogenase. In half-reactive DPOR complexes, incapacitating proton donation in one half generates a stalled intermediate and Pchlide reduction in both halves is abolished. The results showcase long-range allosteric communication and sequential ET in the two symmetric halves. The findings shed light on the functional advantages imparted by the oligomeric architecture found in many electron transfer enzymes.
Genome and time-of-day transcriptome ofWolffia australianalink morphological extreme minimization with un-gated plant growth
Authors: Michael Todd P. , Ernst Evan , Hartwick Nolan , Chu Philomena , Bryant Douglas , Gilbert Sarah , Ortleb Stefan , Baggs Erin L. , Sree K. Sowjanya , Appenroth Klaus J. , Fuchs Joerg , Jupe Florian , Sandoval Justin P. , Krasileva Ksenia V. , Borisjuk Ljudmylla , Mockler Todd C. , Ecker Joseph R. , Martienssen Robert A. , Lam Eric
Published: April 2020

Wolffia is the fastest growing plant genus on Earth with a recorded doubling time of less than a day. Wolffia has a dramatically reduced body plan, primarily growing through a continuous, budding-type asexual reproduction with no obvious phase transition. Most plants are bound by the 24-hour light-dark cycle with the majority of processes such as gene expression partitioned or phased to a specific time-of-day (TOD). However, the role that TOD information and the circadian clock plays in facilitating the growth of a fast-growing plant is unknown. Here we generated draft reference genomes forWolffia australiana(Benth.) Hartog & Plas to monitor gene expression over a two-day time course under light-dark cycles.Wolffia australianahas the smallest genome size in the genus at 357 Mb and has a dramatically reduced gene set at 15,312 with a specific loss of root (WOX5), vascular (CASP), circadian (TOC1), and light-signaling (NPH3) genes. Remarkably, it has also lost all but one of the NLR genes that are known to be involved in innate immunity. In addition, only 13% of its genes cycle, which is far less than in other plants, with an overrepresentation of genes associated with carbon processing and chloroplast-related functions. Despite having a focused set of cycling genes, TOD cis-elements are conserved inW. australiana, consistent with the overall conservation of transcriptional networks. In contrast to the model plantsArabidopsis thalianaandOryza sativa, the reduction in cycling genes correlates with fewer pathways under TOD control in Wolffia, which could reflect a release of functional gating. Since TOD networks and the circadian clock work to gate activities to specific times of day, this minimization of regulation may enable Wolffia to grow continuously with optimal economy. Wolffia is an ideal model to study the transcriptional control of growth and the findings presented here could serve as a template for plant improvement.
Emotional responsiveness task in emotional distress: correlated of functional neuroimaging in anorexia and bulimia
Authors: D’Agata Federico , Caroppo Paola , Spalatro Angela , Lavagnino Luca , Daga Giovanni Abbate , Boghi Andrea , Bergui Mauro , Cicerale Alessandro , Vitiello Benedetto , Fassino Secondo , Derntl Birgit , Amianto Federico
Published: April 2020

Aim

The present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms.

Methods

The current study applied a neuroimaging paradigm eliciting affective responses to 44 female participants with newly diagnosed AN or BN and 20 matched controls. The measurements also included an extensive assessment comprised of clinical scales, neuropsychological tests, measures of emotion processing and empathy.

Results

AN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, scores of eating disorder and psychopathological clinical scores, as well alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala.

Conclusions

Our data are against the hypothesis that participants with AN or BN display a reduced emotional responsiveness. This supports the hypothesis that relational difficulties, as well as therapeutic resistance, are not secondary to simple difficulty in feeling and identifying basic negative emotions in AN and BN participants.
Detecting tropical selective logging with SAR data requires a time series approach
Authors: Hethcoat MG , Carreiras JMB , Edwards DP , Bryant RG , Quegan S
Published: April 2020

Selective logging is the primary driver of forest degradation in the tropics and reduces the capacity of forests to harbour biodiversity, maintain key ecosystem processes, sequester carbon, and support human livelihoods. While the preceding decade has seen a tremendous improvement in the ability to monitor forest disturbances from space, advances in forest monitoring have almost universally relied on optical satellite data from the Landsat program, whose effectiveness is limited in tropical regions with frequent cloud cover. Synthetic aperture radar (SAR) data can penetrate clouds and have been utilized in forest mapping applications since the early 1990s, but no study has exclusively used SAR data to map tropical selective logging. A detailed selective logging dataset from three lowland tropical forest regions in the Brazilian Amazon was used to assess the effectiveness of SAR data from Sentinel-1, RADARSAT-2 and PALSAR-2 for monitoring tropical selective logging. We built Random Forest models in an effort to classify pixel-based differences in logged and unlogged areas. In addition, we used the BFAST algorithm to assess if a dense time series of Sentinel-1 imagery displayed recognizable shifts in pixel values after selective logging. Random Forest classification with SAR data (Sentinel-1, RADARSAT-2, and ALOS-2 PALSAR-2) performed poorly, having high commission and omission errors for logged observations. This suggests little to no difference in pixel-based metrics between logged and unlogged areas for these sensors. In contrast, the Sentinel-1 time series analyses indicated that areas under higher intensity selective logging (> 20 m3ha−1) show a distinct spike in the number of pixels that included a breakpoint during the logging season. BFAST detected breakpoints in 50% of logged pixels and exhibited a false alarm rate of approximately 10% in unlogged forest. Overall our results suggest that SAR data can be used in time series analyses to detect tropical selective logging at high intensity logging locations within the Amazon (> 20 m3ha−1). These results have important implications for current and future abilities to detect selective logging with freely available SAR data from SAOCOM 1A, the planned continuation missions of Sentinel-1 (C and D), ALOS PALSAR-1 archives (expected to be opened for free access in 2020), and the upcoming launch of NISAR.
Regulation of light harvesting in Chlamydomonas: two protein phosphatases are involved in state transitions
Authors: Cariti Federica , Chazaux Marie , Lefebvre-Legendre Linnka , Longoni Paolo , Ghysels Bart , Johnson Xenie , Goldschmidt-Clermont Michel
Published: April 2020

Protein phosphorylation plays important roles in short-term regulation of photosynthetic electron transfer. In a mechanism known as state transitions, the kinase STATE TRANSITION 7 (STT7) ofChlamydomonas reinhardtiiphosphorylates components of light-harvesting antenna complex II (LHCII). This reversible phosphorylation governs the dynamic allocation of a part of LHCII to photosystem I or photosystem II, depending on light conditions and metabolic demands. Little is however known in the green alga on the counteracting phosphatase(s). In Arabidopsis, the homologous kinase STN7 is specifically antagonized by PROTEIN PHOSPHATASE 1/THYLAKOID-ASSOCIATED PHOSPHATASE 38 (PPH1/TAP38). Furthermore, the paralogous kinase STN8 and the countering phosphatase PHOTOSYSTEM II PHOSPHATASE (PBCP), which count subunits of PSII amongst their major targets, influence thylakoid architecture and high-light tolerance. Here we analyze state transitions inC. reinhardtiimutants of the two homologous phosphatases, CrPPH1 and CrPBCP. The transition from state 2 to state 1 is retarded inpph1, and surprisingly also inpbcp. However both mutants can eventually return to state 1. In contrast, the double mutantpph1;pbcpappears strongly locked in state 2. The complex phosphorylation patterns of the LHCII trimers and of the monomeric subunits are affected in the phosphatase mutants. Their analysis indicates that the two phosphatases have different yet overlapping sets of protein targets. The dual control of thylakoid protein de-phosphorylation and the more complex antenna phosphorylation patterns in Chlamydomonas compared to Arabidopsis are discussed in the context of the stronger amplitude of state transitions and the more diverse LHCII isoforms in the alga.
The Na+/K+ATPase Regulates Glycolysis and Modifies Immune Metabolism in Tumors
Authors: Sanderson Sydney M. , Xiao Zhengtao , Wisdom Amy J. , Bose Shree , Liberti Maria V. , Reid Michael A. , Hocke Emily , Gregory Simon G. , Kirsch David G. , Locasale Jason W.
Published: April 2020

Cancer therapies targeting metabolism have been limited due to a lack of understanding of the controlling properties of vulnerable pathways. The Na+/K+ATPase is responsible for a large portion of cellular energy demands but how these demands influence metabolism and create metabolic liabilities are not known. Using metabolomic approaches, we first show that digoxin, a cardiac glycoside widely used in humans, acts through disruption to central carbon metabolism via on target inhibition of the Na+/K+ATPase that was fully recovered by expression of an allele resistant to digoxin. We further show in vivo that administration of digoxin inhibits glycolysis in both malignant and healthy cells, particularly within clinically relevant cardiac tissue, while exhibiting tumor-specific cytotoxic activity in an allografted soft tissue sarcoma. Single-cell expression analysis of over 31,000 cells within the sarcoma shows that acute Na+/K+ATPase inhibition shifts the immune composition of the tumor microenvironment, leading to selective alterations to metabolic programs in specific immune cells thus acting both through tumor cell and microenvironmental (e.g. macrophage) cells. These results provide evidence that altering energy demands can be used to regulate glycolysis with cell-type specific consequences in a multicellular environment of biomedical interest.
Chandelier cell anatomy and function reveal a variably distributed but common signal
Authors: Schneider-Mizell Casey M. , Bodor Agnes L. , Collman Forrest , Brittain Derrick , Bleckert Adam A. , Dorkenwald Sven , Turner Nicholas L. , Macrina Thomas , Lee Kisuk , Lu Ran , Wu Jingpeng , Zhuang Jun , Nandi Anirban , Hu Brian , Buchanan JoAnn , Takeno Marc M. , Torres Russel , Mahalingam Gayathri , Bumbarger Daniel J. , Li Yang , Chartrand Tom , Kemnitz Nico , Silversmith William M. , Ih Dodam , Zung Jonathan , Zlateski Aleksandar , Tartavull Ignacio , Popovych Sergiy , Wong William , Castro Manuel , Jordan Chris S. , Froudarakis Emmanouil , Becker Lynne , Suckow Shelby , Reimer Jacob , Tolias Andreas S. , Anastassiou Costas , Seung H. Sebastian , Reid R. Clay , Maçarico da Costa Nuno
Published: April 2020

The activity and connectivity of inhibitory cells has a profound impact on the operation of neuronal networks. While the average connectivity of many inhibitory cell types has been characterized, we still lack an understanding of how individual interneurons distribute their synapses onto their targets and how heterogeneous the inhibition is onto different individual excitatory neurons. Here, we use large-scale volumetric electron microscopy (EM) and functional imaging to address this question for chandelier cells in layer 2/3 of mouse visual cortex. Using dense morphological reconstructions from EM, we mapped the complete chandelier input onto 153 pyramidal neurons. We find that the number of input synapses is highly variable across the population, but the variability is correlated with structural features of the target neuron: soma depth, soma size, and the number of perisomatic synapses received. Functionally, we found that chandelier cell activityin vivowas highly correlated and tracks pupil diameter, a proxy for arousal state. We propose that chandelier cells provide a global signal whose strength is individually adjusted for each target neuron. This approach, combining comprehensive structural analysis with functional recordings of identified cell types, will be a powerful tool to uncover the wiring rules across the diversity of cortical cell types.
Early-life hypoxia alters adult physiology and reduces stress resistance and lifespan inDrosophila
Authors: Polan Danielle M , Alansari Mohammad , Lee Byoungchun , Grewal Savraj
Published: April 2020

In many animals, short-term fluctuations in environmental conditions in early life often exert long-term effects on adult physiology. In Drosophila, one ecologically relevant environmental variable is hypoxia.Drosophilalarvae live on rotting, fermenting food rich in microorganisms – an environment characterized by low ambient oxygen. They have therefore evolved to tolerate hypoxia. While the acute effects of hypoxia in larvae have been well studied, whether early-life hypoxia affects adult physiology and fitness is less clear. Here we show that Drosophila exposed to hypoxia during their larval period subsequently show reduced starvation stress resistance and shorter lifespan as adults, with these effects being stronger in males. We find that these effects are associated with reduced whole-body insulin signaling but elevated TOR kinase activity, a manipulation known to reduce lifespan. We also identify a sexually dimorphic effect of larval hypoxia on adult nutrient storage and mobilization. Thus, we find that males, but not females, showing elevated levels of lipids and glycogen. Moreover, we see that both males and females exposed to hypoxia as larvae show defective lipid mobilization upon starvation stress as adults. These data show how early-life hypoxia can exert persistent, sexually dimorphic, long-term effects on Drosophila adult physiology and lifespan.
DriveWays: A Method for Identifying Possibly Overlapping Driver Pathways in Cancer
Authors: Baali Ilyes , Erten Cesim , Kazan Hilal
Published: April 2020

Abstract

Motivation

The majority of the previous methods for identifying cancer driver modules output non-overlapping modules. This assumption is biologically inaccurate as genes can participate in multiple molecular pathways. This is particularly true for cancer-associated genes as many of them are network hubs connecting functionally distinct set of genes. It is important to provide combinatorial optimization problem definitions modeling this biological phenomenon and to suggest efficient algorithms for its solution.

Results

We provide a formal definition of the Overlapping Driver Module Identification in Cancer (ODMIC) problem. We show that the problem is NP-hard. We propose a seed-and-extend based heuristic named DriveWays that identifies overlapping cancer driver modules from the graph built from the IntAct PPI network. DriveWays incorporates mutual exclusivity, coverage, and the network connectivity information of the genes.

We show that DriveWays outperforms the state-of-the-art methods in recovering well-known cancer driver genes performed on TCGA pan-cancer data. Additionally, DriveWays’s output modules show a stronger enrichment for the reference pathways in almost all cases. Overall, we show that enabling modules to overlap improves the recovery of functional pathways filtered with known cancer drivers, which essentially constitute the reference set of cancer-related pathways.

Availability

The data, the source code, and useful scripts are available at:https://github.com/abu-compbio/DriveWays

Supplementary information

Supplementary data are available atBiorxiv.