bluuebunny/crossref_metadata_2025 huggingface dataset:
Single amino acid exchange in ACTIN2 confers increased tolerance to oxidative stress in Arabidopsis der1-3 mutant
Authors: Kubenova Lenka , Takac Tomas , Samaj Jozef , Ovecka Miroslav
Published: December 2020

Single-point mutation in the ACTIN2 gene of der1-3 mutant revealed that ACTIN2 is an essential actin isovariant required for root hair tip growth, and leads to shorter, thinner and more randomly oriented actin filaments in comparison to wild-type C24 genotype. Actin cytoskeleton has been linked to plant defence against oxidative stress, but it is not clear how altered structural organization and dynamics of actin filaments may help plants to cope with oxidative stress. In this study, we characterized seed germination, root growth, plant biomass, actin organization and antioxidant activity of der1-3 mutant under oxidative stress induced by paraquat and H2O2. Under these conditions, plant growth was better in der1-3 mutant, while actin cytoskeleton in der1-3 carrying pro35S::GFP:FABD2 construct showed lower bundling rate and higher dynamicity. Biochemical analyses documented lower degree of lipid peroxidation, elevated capacity to decompose superoxide and hydrogen peroxide. These results support the view that der1-3 mutant is more resistant to oxidative stress. Single amino acid exchange in mutated ACTIN2 protein (Cys to Arg at the position 97) is topologically exposed to the protein surface and we propose that this might alter protein post-translational modifications and/or protein-protein interactions, leading to enhanced tolerance of der1-3 mutant against oxidative stress.
Do honey bee species differ in the odometer used for the waggle dance?
Authors: George Ebi Antony , Thulasi Neethu , Kohl Patrick L. , Suresh Sachin , Rutschmann Benjamin , Brockmann Axel
Published: December 2020

Honey bees estimate distances to food sources using image motion experienced on the flight path and they use this measure to tune the waggle phase duration in their dance communication. Most studies on the relationship between experienced optic flow and the dance-related odometer are based on experiments withApis melliferaforagers trained into a small tunnel with black and white patterns which allowed quantifiable changes in the optic flow. In this study we determined the calibration curves for foragers of the two Asian honey bee species,A. floreaandA. cerana, in two different natural environments with clear differences in the vegetation conditions and hence visual contrast. We found that the dense vegetation condition (with higher contrast) elicited a more rapid increase in the waggle phase duration with distance than the sparse vegetation inA. floreabut not inA. cerana. Visual contrast did not affect the perception of the food reward, measured as the number of dance circuits produced per distance, in both species. Our findings suggest that contrast sensitivity of the waggle dance odometer, or other aspects of flight behaviour, might vary among honey bee species.
Genome architecture shapes evolutionary adaptation to DNA replication stress
Authors: Fumasoni Marco , Murray Andrew W.
Published: December 2020

In haploid budding yeast, evolutionary adaptation to constitutive DNA replication stress alters three genome maintenance modules: DNA replication, the DNA damage checkpoint, and sister chromatid cohesion. We asked how these trajectories depend on a population’s genome architecture by comparing the adaptation of haploids to that diploids and recombination deficient haploids. In all three genome architectures, adaptation happens within 1000 generations at rates that are linearly correlated with the initial fitness defect of the ancestors. Mutations in individual genes are selected at different frequencies in different architectures, but the benefits these mutations confer are similar in all three architectures, and combinations of these mutations reproduce the fitness gains of evolved populations. Despite the differences in the selected mutations, the evolutionary trajectories target the same three functional modules in all architectures revealing a common evolutionary response to DNA replication stress.
Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications
Authors: Morotti Stefano , Liu Caroline , Hegyi Bence , Ni Haibo , Iseppe Alex Fogli , Wang Lianguo , Ripplinger Crystal M. , Bers Donald M. , Edwards Andrew G. , Grandi Eleonora
Published: December 2020

Animal experimentation is key in the evaluation of cardiac efficacy and safety of novel therapeutic compounds. However, inter-species differences in the mechanisms regulating excitation-contraction coupling can limit the translation of experimental findings from animal models to human physiology, and undermine the assessment of drugs’ efficacy and safety. Here, we built a suite of translators for quantitatively mapping electrophysiological responses in ventricular myocytes across species. We trained these statistical operators using a broad dataset obtained by simulating populations of our biophysically detailed computational models of action potential and Ca2+transient in mouse, rabbit, and human. We then tested our translators against experimental data describing the response to stimuli, such as ion channel block, change in beating rate, and β-adrenergic challenge. We demonstrate that this approach is well suited to predicting the effects of perturbations across different species or experimental conditions, and suggest its integration into mechanistic studies and drug development pipelines.
Catalytic Promiscuity of Rice 2-Oxoglutarate/Fe(II)-Dependent Dioxygenases Supports Xenobiotic Metabolism
Authors: Takamura Natsuki , Yamazaki Akihiko , Sakuma Nozomi , Hirose Sakiko , Takani Yukie , Sakai Motonari , Oshima Masahiro , Kuroki Makoto , Tozawa Yuzuru
Published: December 2020

The rice 2-oxoglutarate/Fe(II)–dependent dioxygenase HIS1 mediates the catalytic inactivation of five distinct β-triketone herbicides (bTHs). During a search for potential inhibitors of HIS1, we found that it mediates the hydroxylation of trinexapac-ethyl (TE) in the presence of Fe2+and 2-oxoglutarate. TE is a plant growth regulator that blocks gibberellin biosynthesis, and we observed that its addition to culture medium induced growth retardation of rice seedlings in a concentration-dependent manner. Similar treatment with hydroxylated TE revealed that hydroxylation greatly attenuated the inhibitory effect of TE on plant growth. Forced expression ofHIS1in a ricehis1mutant also reduced its sensitivity to TE compared with that of the nontransformant. These results indicated that HIS1 metabolizes TE and thereby markedly reduces its ability to slow plant growth. Furthermore, testing of five HIS1-related proteins (HSLs) of rice revealed that OsHSL2 and OsHSL4 also metabolize TE in vitro. HSLs from wheat and barley also showed such activity. In contrast, OsHSL1, which shares the highest amino acid sequence identity with HIS1 and metabolizes the bTH tefuryltrione, did not manifest TE-metabolizing activity. Site-directed mutagenesis of OsHSL1 informed by structural models showed that substitution of three amino acids with the corresponding residues of HIS1 conferred TE-metabolizing activity similar to that of HIS1. Our results thus reveal a catalytic promiscuity of HIS1 and its related enzymes that supports xenobiotic metabolism in plants.

One-sentence summary

The rice 2-oxoglutarate/Fe(II)-dependent dioxygenase HIS1 and related enzymes show broad substrate specificity and mediate metabolism of the growth regulator trinexapac-ethyl as well as of herbicides.
Real time, field-deployable whole genome sequencing of malaria parasites using nanopore technology
Authors: Razook Zahra , Mehra Somya , Gilchrist Brittany , Utama Digjaya , Lautu-Gumal Dulcie , Fola Abebe , Menard Didier , Kazura James , Laman Moses , Mueller Ivo , Robinson Leanne J. , Bahlo Melanie , Barry Alyssa E.
Published: December 2020

Malaria parasite genomes have been generated predominantly using short read sequencing technology which can be slow, requires advanced laboratory training and does not adequately interrogate complex genomic regions that harbour important malaria virulence determinants. The portable Oxford Nanopore Technologies MinION platform generates long reads in real time and may overcome these limitations. We present compelling evidence that Nanopore sequencing delivers valuable additional information for malaria parasites with comparable data fidelity for single nucleotide variant (SNV) calls, compared to standard Illumina whole genome sequencing. We demonstrate this through sequencing of purePlasmodium falciparumDNA, mock infections and natural isolates. Nanopore has low error rates for haploid SNV genotyping and identifies structural variants (SVs) not detected with short reads. Nanopore genomes are directly comparable to publically available genomes and produce high quality end to end chromosome assemblies. Nanopore sequencing will expedite genomic surveillance of malaria and provide new insights into parasite genome biology.
Altered functional brain dynamics in chromosome 22q11.2 deletion syndrome during facial affect processing
Authors: Cornblath Eli J. , Mahadevan Arun , He Xiaosong , Ruparel Kosha , Lydon-Staley David M. , Moore Tyler M. , Gur Ruben C. , Zackai Elaine H. , Emanuel Beverly , McDonald-McGinn Donna M. , Wolf Daniel H. , Satterthwaite Theodore D. , Roalf David R. , Gur Raquel E. , Bassett Danielle S.
Published: December 2020

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder associated with multiple congenital anomalies, variable medical features, and neurodevelopmental differences resulting in diverse psychiatric phenotypes, including marked deficits in facial memory and social cognition. Neuroimaging in individuals with 22q11.2DS has revealed differences relative to matched controls in BOLD fMRI activation during facial affect processing tasks, but time-varying interactions between brain areas during facial affect processing have not yet been studied in 22q11.2DS. We applied constrained principal component analysis to identify temporally overlapping brain activation patterns from BOLD fMRI data acquired during an emotion identification task from 58 individuals with 22q11.2DS and 58 age-, race-, and sex-matched healthy controls. Delayed frontal-motor feedback signals were diminished in individuals with 22q11.2DS, as were delayed emotional memory signals engaging amygdala, hippocampus, and entorhinal cortex. Early task-related engagement of motor and visual cortices and salience-related insular activation were relatively preserved in 22q11.2DS. Insular activation was associated with task performance within the 22q11.2DS sample. Differences in cortical surface area, but not cortical thickness, showed spatial alignment with an activation pattern associated with face processing. These findings suggest that relative to matched controls, primary visual processing and insular function are relatively intact in individuals with 22q11.22DS, while motor feedback, face processing, and emotional memory processes are more affected. Such insights may help inform potential interventional targets and enhance the specificity of neuroimaging indices of cognitive dysfunction in 22q11.2DS.
The dynamic landscape of parasitaemia dependent intestinal microbiota shifting at species level and the correlated gut transcriptome during Plasmodiumyoeliiinfection
Authors: Yawen Zong , Lei Cheng , Xiangyun Cheng , Binyou Liao , Xingchen Ye , Taiping Liu , Jiyao Li , Xuedong Zhou , Wenyue Xu , Biao Ren
Published: December 2020

Background

Malaria, caused byPlasmodium, is a global life-threatening infection disease especially during the COVID-19 pandemic. However, it is still unclear about the dynamic change and the interactions between intestinal microbiota and host immunity. Here, we investigated the change of intestinal microbiome and transcriptome during the wholePlasmodiuminfection process in mice to analyze the dynamic landscape of parasitaemia dependent intestinal microbiota shifting and related to host immunity.

Results

There were significant parasitaemia dependent changes of intestinal microbiota and transcriptome, and the microbiota was significantly correlated to the intestinal immunity. We found that (i) the diversity and composition of the intestinal microbiota represented a significant correlation along with thePlasmodiuminfection in family, genus and species level; (ii) the up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways along with the malaria development, particularly, naive CD4+ T cells differentiation; (iii) the abundance of the parasitaemia phase-specific microbiota represented a high correlation with the phase-specific immune cells development, particularly, Th1 cell with familyBacteroidalesBS11 gut group, generaPrevotella9,RuminococcaceaeUCG 008,Moryellaand specieSutterella*, Th2 cell with specieSutterella*, Th17 cell with familyPeptococcaceae, genusLachnospiraceaeFCS020 group and spicesRuminococcus1*,RuminococcusUGG 014* andEubacterium plexicaudatumASF492, Tfh and B cell with generaMoryellaand speciesErysipelotrichaceae bacterium canine oral taxon255.

Conclusion

There was a remarkable dynamic landscape of the parasitaemia dependent shifting of intestinal microbiota and immunity, and a notable correlation between the abundance of intestinal microbiota.
Temporal kinetics of RNAemia and associated systemic cytokines in hospitalized COVID-19 patients
Authors: van Riel Debby , Embregts Carmen W.E. , Sips Gregorius J. , van den Akker Johannes P.C. , Endeman Henrik , van Nood Els , van Kampen Jeroen , Molenkamp Richard , Koopmans Marion , van de Vijver David , GeurtsvanKessel Corine H.
Published: December 2020

COVID-19 is associated to a wide range of extra-respiratory complications, of which the pathogenesis is currently not fully understood. In this study we report the temporal kinetics of viral RNA and inflammatory cytokines and chemokines in serum during the course of COVID-19. We show that a RNAemia occurs more frequently and lasts longer in patients that develop critical disease compared to patients that develop moderate or severe disease. Furthermore we show that concentrations of IL-10 and MCP-1—but not IL-6—are associated with viral load in serum. However, higher levels of IL-6 were associated with the development of critical disease. The direct association of inflammatory cytokines with viral load or disease severity highlights the complexity of systemic inflammatory response and the role of systemic viral spread.
Epidemiology of developmental dyslexia: A comparison of DSM-5 and ICD-11 criteria
Authors: Di Folco Cécile , Guez Ava , Peyre Hugo , Ramus Franck
Published: December 2020

The two major medical classifications (ICD-11 and DSM-5), define diagnostic criteria for developmental dyslexia that partly differ and that are open to multiple interpretations, inducing different prevalence estimates and discordant cases. The present study evaluates the prevalence of developmental dyslexia for the first time in France in an extensive population representative of French sixth-graders (N=25,000), investigating the consequences of using one classification or the other, and of the different ways of implementing each criterion. Moreover, students diagnosed with dyslexia were compared with the reference population in the other available characteristics. Overall, prevalence estimates ranged from 1.3% to 17.2% depending on the criteria and thresholds used. A reasonable set of criteria and thresholds (−1.5 SD below mean for reading score, -0.5 SD for achievement) yielded a prevalence of dyslexia in France of 6.6% according to DSM-5 and 3.5% according to ICD-11. Factors that had the greatest influence on prevalence estimates were the criteria relative to 1) IQ, and 2) impact on academic achievement. DSM-5, being more liberal than ICD-11 on the IQ criterion, included more cases with relatively low IQ and thus yielded higher prevalence estimates. Compared with the reference population, children with dyslexia were more likely to be boys, to be schooled in a disadvantaged area, and to have lower SES, IQ, and math results. Our results emphasize that the choice of classification and the operationalization of specific criteria have a large impact on who is diagnosed with dyslexia.
EBV deletions as biomarkers of response to treatment of Chronic Active Epstein Barr Virus
Authors: Venturini Cristina , Houldcroft Charlotte J , Lazareva Arina , Wegner Fanny , Morfopoulou Sofia , Amrolia Persis J. , Golwala Zainab , Rao Anupama , Marks Stephen D. , Simmonds Jacob , Yoshikawa Tetsushi , Farrell Paul J. , Cohen Jeffrey I. , Worth Austen J. , Breuer Judith
Published: December 2020

Chronic active Epstein Barr Virus (CAEBV) is a rare condition occurring in previously healthy individuals associated with persistent EBV viraemia, fever, lymphadenopathy and hepatosplenomegaly. Viral deletions have been found in CAEBV and other lymphomas. However, it is unclear how stable these deletions are, whether they are present in different sites and how they evolve overtime. We sequenced fourteen longitudinal blood samples from three European CAEBV patients and compared with CAEBV saliva samples and other sequences from EBV-related conditions. We observed large EBV deletions in blood, but not saliva from CAEBV patients. Deletions were stable over time but were lost following successful treatment. Our results are consistent with the likelihood that certain deletions in the virus from CAEBV patients are associated with the evolution and persistence of haematological clones. We propose that the loss of deletions following successful treatment should be investigated as a potential biomarker to aid CAEBV management.
Coinfection with Respiratory Pathogens in COVID-19 in Korea
Authors: Roh Kyoung Ho , Kim Yu Kyung , Kim Shin-Woo , Kang Eun-Rim , Yang Yong-Jin , Jung Sun-Kyung , Lee Sun-Hwa , Sung Nackmoon
Published: December 2020

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in upper and lower respiratory specimens and coinfection with other respiratory pathogens in patients with coronavirus disease 2019 (COVID-19) were investigated. From the study subjects (N = 258) retrospectively enrolled when confirmed as SARS-CoV-2 positive, nasopharyngeal (NPS), oropharyngeal swabs (OPS), and sputum specimens were restored for retesting SARS-CoV-2 and detecting respiratory pathogens. Majority of the study subjects (95.7%, N = 247) were confirmed as SARS-CoV-2 positive using NPS/OPS specimens, suggesting that the upper respiratory specimen is most valuable in detecting SARS-CoV-2. Coinfection rates in COVID-19 patients (N = 258) with respiratory pathogens were 9.7% (N = 25); 8.5% (N = 22) respiratory viruses and 1.2% (N = 3) Mycoplasma pneumoniae, an atypical bacterium. Of the respiratory virus coinfection cases (N = 22), 20 (90.9%) were co-infected with a single respiratory virus and 2 (0.8%) (metapneumovirus/adenovirus and rhinovirus/bocavirus 1/2/3/4) with two viruses. Respiratory viruses in single viral coinfection cases with SARS-CoV-2 were as follows: non-SARS-CoV-2 coronaviruses (229E, NL63, and OC43, N = 5, 1.9%), rhinovirus (N = 4, 1.6%), metapneumovirus (N = 3, 1.2%), influenza A (N = 3, 1.2%), respiratory syncytial virus A and B (N = 3, 1.2%), and adenovirus (N = 2, 0.8%). No mixed coinfections with respiratory viruses and M. pneumoniae were found. In conclusion, the diagnostic value of utilizing NPS/OPS specimen is excellent, and, as the first report in Korea, coinfection with respiratory pathogens were detected at a rate of 9.7% in patients with COVID-19.
Are college campuses superspreaders? A data-driven modeling study
Authors: Lu Hannah , Weintz Cortney , Pace Joseph , Indana Dhiraj , Linka Kevin , Kuhl Ellen
Published: December 2020

The COVID-19 pandemic continues to present enormous challenges for colleges and universities and strategies for save reopening remain a topic of ongoing debate. Many institutions that reopened cautiously in the fall experienced a massive wave of infections and colleges were soon declared as the new hotspots of the pandemic. However, the precise effects of college outbreaks on their immediate neighborhood remain largely unknown. Here we show that the first two weeks of instruction present a high-risk period for campus outbreaks and that these outbreaks tend to spread into the neighboring communities. By integrating a classical mathematical epidemiology model and Bayesian learning, we learned the dynamic reproduction number for 30 colleges from their daily case reports. Of these 30 institutions, 14 displayed a spike of infections within the first two weeks of class, with peak seven-day incidences well above 1,000 per 100,000, an order of magnitude larger than the nation-wide peaks of 70 and 150 during the first and second waves of the pandemic. While most colleges were able to rapidly reduce the number of new infections, many failed to control the spread of the virus beyond their own campus: Within only two weeks, 17 campus outbreaks translated directly into peaks of infection within their home counties. These findings suggests that college campuses are at risk to develop an extreme incidence of COVID-19 and become superspreaders for neighboring communities. We anticipate that tight test-trace-quarantine strategies, flexible transition to online instruction, and–most importantly–compliance with local regulations will be critical to ensure a safe campus reopening after the winter break.
Assessment of effective mitigation and prediction of the spread of SARS-CoV-2 in Germany using demographic information and spatial resolution
Authors: Kühn Martin J. , Abele Daniel , Mitra Tanmay , Koslow Wadim , Abedi Majid , Rack Kathrin , Siggel Martin , Khailaie Sahamoddin , Klitz Margrit , Binder Sebastian , Spataro Luca , Gilg Jonas , Kleinert Jan , Häberle Matthias , Plötzke Lena , Spinner Christoph D. , Stecher Melanie , Zhu Xiao Xiang , Basermann Achim , Meyer-Hermann Michael
Published: December 2020

Non-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coron-avirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic pre-pandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.

Mathematics Subject Classification (2010) 00A72 · 65L05 · 68U20
Real Bodies Not Required? Placebo Analgesia and Pain Perception in Immersive Virtual and Augmented Reality
Authors: Ho Jasmine T. , Krummenacher Peter , Lesur Marte Roel , Lenggenhager Bigna
Published: December 2020

Pain represents an embodied process, wherein inferences are not only drawn from sensory inputs, but also from bodily states. Previous research has demonstrated that a placebo administered to an embodied rubber hand can effectively induce analgesia, providing first evidence that placebos can work even when applied to temporarily embodied, artificial body parts. Using a heat pain paradigm, the present study investigates placebo analgesia and pain perception during virtual embodiment. We examined whether a virtual placebo (a sham heat protective glove) can successfully induce analgesia, even when administered to a virtual body. The analgesic efficacy of the virtual placebo to the real hand (augmented reality setting) or virtual hand (virtual reality setting) was compared to a physical placebo administered to the own, physical body (physical reality setting). Furthermore, pain perception and subjective embodiment were compared between settings. Healthy participants (n=48) were assigned to either an analgesia-expectation or control-expectation group, where subjective and objective pain was measured at pre- and post-intervention time points. Results evinced that pre-intervention pain intensity was lower in the virtual reality setting, and that participants in the analgesia-expectation condition, after the intervention, exhibited significantly higher pain thresholds, and lower pain intensity and unpleasantness ratings than control-expectation participants, independent of the setting. Our findings evince that a virtual placebo can elicit placebo analgesia comparable to that of a physical placebo, and that administration of a placebo does not necessitate physical bodily interaction to produce analgesic responses, which might pave the way for effective new non-pharmacological approach for pain management.
Evolution and insights into the structure and function of the DedA superfamily containing TMEM41B and VMP1
Authors: Okawa Fumiya , Hama Yutaro , Zhang Sidi , Morishita Hideaki , Yamamoto Hayashi , Levine Tim P. , Mizushima Noboru
Published: December 2020

TMEM41B and VMP1 are endoplasmic reticulum (ER)-localizing multi-spanning membrane proteins required for ER-related cellular processes such as autophagosome formation, lipid droplet homeostasis, and lipoprotein secretion in eukaryotes. Both proteins have a VTT domain, which is similar to the DedA domain found in bacterial DedA family proteins. However, the molecular function and structure of the DedA and VTT domains (collectively referred to as DedA domains) and the evolutionary relationships among the DedA domain-containing proteins are largely unknown. Here, we conduct remote homology search and identify a new clade consisting mainly of bacterial PF06695 proteins of unknown function. Phylogenetic analysis reveals that the TMEM41, VMP1, DedA, and PF06695 families form a superfamily with a common origin, which we term the DedA superfamily. Coevolution-based structural prediction suggests that the DedA domain contains two reentrant loops that face each other in the membrane. This topology is biochemically verified by the substituted cysteine accessibility method. The predicted structure is topologically similar to that of the substrate-binding region of Na+-coupled glutamate transporter solute carrier 1. A potential ion-coupled transport function of the DedA superfamily proteins is discussed.
HPF1 and nucleosomes mediate a dramatic switch in activity of PARP1 from polymerase to hydrolase
Authors: Rudolph Johannes , Roberts Genevieve , Muthurajan Uma M. , Luger Karolin
Published: December 2020

Poly(ADP-ribose) polymerase 1 (PARP1) is an important player in the response to DNA damage. Recently, histone PARylation factor (HPF1) was shown to be a critical modulator of the activity of PARP1 by facilitating PARylation of histones and redirecting the target amino acid specificity from acidic to serine residues. Here we investigate the mechanism and specific consequences of HPF1-mediated PARylation using nucleosomes as both activators and substrates for PARP1. HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. Surprisingly, HPF1 partitions most of the reaction product to free ADPR, resulting in much shorter PAR chains compared to reactions in the absence of HPF1. This HPF1-mediated switch from polymerase to hydrolase has important implications for the PARP1-mediated response to DNA damage and raises interesting new questions about the role of intracellular ADPR and depletion of NAD+.
The evolution of anisogamy does not always lead to male competition
Authors: Siljestam Mattias , Martinossi-Allibert Ivain
Published: December 2020

Anisogamy has evolved in a large proportion of sexually reproducing multicellular organisms allowing the definition of the female and male sexes, producing large and small gametes, respectively. Anisogamy is the initial sexual dimorphism: it has lead the sexes to experience selection differently, which makes it a good starting point to understand the evolution of further sexual dimorphisms. For instance, it is generally accepted that anisogamy sets the stage for more intense intrasexual competition in the male sex than in the female sex. However, we argue that this idea may rely on assumptions on the conditions under which anisogamy has evolved in the first place. We consider here two widely accepted scenarios for the evolution of anisogamy:gamete competitionorgamete limitation. We present a mechanistic mathematical model in which both gamete size and an intrasexual competition trait for fertilisation can coevolve in a population starting without dimorphism between its two mating types. Two different intrasexual competition traits are investigated, gamete motility and the ability of gametes to capture gametes of the opposite mating type. We show thatgamete competitionandgamete limitationcan lead to greatly different outcomes in terms of which sex competes most for fertilisation. Our results suggest thatgamete competitionis most likely to lead to stronger competition in males. On the other hand, undergamete limitation, competition in form of motility can evolve in either sex while gamete capture mainly evolves in females. This study suggests that anisogamy does notper selead to more intense male competition. The conditions under which anisogamy evolves matter, as well as the competition trait considered.
Predicting placenta transcriptional regulatory interactions based on immunohistochemistry images data and convolutional neural network
Authors: Liu Yajun , Guo Yilin , Gao Ya , Hu Guiming , Ma Ju , Cui Jinquan
Published: December 2020

Aims: The dysfunction of placenta development is correlated to the defects of pregnancy and fetal growth. The detailed molecular mechanism of placenta development is not identified in human due to the lack of material in vivo. Image-based reconstructions of GRN are still very underdeveloped. Methods and Results: In this study, immunohistochemistry images of different TFs in chorionic villus were obtained by a high-resolution scanner. Next, we used a convolutional neural network and machine learning method to infer gene interaction networks of human placenta from these images based on the transfer learning technique. The experimental results show that deep learning models reveals regulatory roles that have not yet been fully recognized. The spatial expression data reveal new regulatory relationships that traditional experiments have failed to recognize, and has allowed the development of gene regulation networks based on the spatial distribution of gene expression. Conclusions: We demonstrate the effectiveness of this approach in building networks using high-resolution images of the human placenta. Our analysis is of certain significance for further exploration of the development of the placenta and the occurrence of pregnancy-related diseases in the future. The datasets and analysis provide a useful source for the researchers in the field of the maternal-fetal interface and the establishment of pregnancy.
Cannabidiol effects on cocaine-seeking behaviour and incubation of craving in mice
Authors: Alegre-Zurano Laia , Luján Miguel Á. , Cantacorps Lídia , Martín-Sánchez Ana , García-Baos Alba , Valverde Olga
Published: December 2020

Background and Purpose

To remain abstinent represents one of the major challenges for the treatment of cocaine use disorder. Cocaine seeking elicited by drug-associated cues progressively intensifies during abstinence in a process termed incubation of craving, representing an aggravating factor for relapse. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-seeking behaviour, although its effects on cocaine-craving incubation have never been elucidated.

Experimental Approach

We developed a mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving. Changes in the protein expression of AMPAR subunits and ERK1/2phosphorylation were analysed. We also assessed the effects of cannabidiol (20 mg·kg-1) administered either during acquisition of cocaine self-administration or abstinence.

Key Results

Mice efficiently performed the demand task and incubation of cocaine craving. Besides, changes in GluA1 and GluA2 protein levels were found along the abstinence in prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK1/2phosphorylation in ventral striatum. Cannabidiol reduced ongoing cocaine intake when administered during the acquisition phase of the self-administration, but failed to alter the subsequent demand task performance and incubation of cocaine craving. No effects were found when cannabidiol was administered during the abstinence period.

Conclusion and Implications

We provide here a novel model of behavioural economic analysis of demand curves and cue-induced incubation of cocaine-seeking behaviour for mice. Moreover, we show that cannabidiol exerts differential effects on the current model depending on the self-administration phase in which it was administered.

What is already known

Behavioural economics and incubation of cocaine craving are well-stablished paradigms to evaluate cocaine seeking in rats.

CBD reduces cocaine-seeking and cocaine-taking behaviours.

What this study adds

A mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving.

CBD reduces cocaine self-administration and has no effect over demand task and cocaine-craving incubation.

Clinical significance

A new behavioural model for studying cocaine addiction in mice.

CBD exerts differential effects depending on when it was administered in the addictive process.

Tables ofLinks
The bacterial virulence factors rhamnolipids and their (R)-3-hydroxyalkanoate precursors activateArabidopsisinnate immunity through two independent mechanisms
Authors: Schellenberger Romain , Crouzet Jérôme , Nickzad Arvin , Kutschera Alexander , Gerster Tim , Borie Nicolas , Dawid Corinna , Cloutier Maude , Villaume Sandra , Dhondt-Cordelier Sandrine , Hubert Jane , Cordelier Sylvain , Mazeyrat-Gourbeyre Florence , Schmid Christian , Ongena Marc , Renault Jean-Hugues , Haudrechy Arnaud , Hofmann Thomas , Baillieul Fabienne , Clément Christophe , Zipfel Cyril , Gauthier Charles , Déziel Eric , Ranf Stefanie , Dorey Stéphan
Published: December 2020

Plant innate immunity is activated upon perception of invasion pattern molecules by plant cell-surface immune receptors. Several bacteria of the generaPseudomonasandBurkholderiaproduce rhamnolipids (RLs) from L- rhamnose and (R)-3-hydroxyalkanoate precursors (HAAs). RL and HAA secretion is required to modulate bacterial surface motility, biofilm development, and thus successful colonization of hosts. Here, we show that the lipidic secretome from the opportunistic pathogenPseudomonas aeruginosamostly comprising RLs and HAAs stimulatesArabidopsisimmunity. We demonstrate that HAAs are sensed by the bulb-type lectin receptor kinase LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION/S-DOMAIN-1-29 (LORE/SD1-29) that also mediates medium-chain 3-hydroxy fatty acid (mc-3-OH-FA) perception in the plantArabidopsis thaliana. HAA sensing induces canonical immune signaling and local resistance to plant pathogenicPseudomonasinfection. By contrast, RLs trigger an atypical immune response and resistance toPseudomonasinfection independent of LORE. Thus, the glycosyl moieties of RLs, albeit abolishing sensing by LORE, do not impair their ability to trigger plant defense. In addition, our results show that RL-triggered immune response is affected by the sphingolipid composition of the plasma membrane. In conclusion, RLs and their precursors released by bacteria can both be perceived by plants but through distinct mechanisms.

Significance

Activation of plant innate immunity relies on the perception of microorganisms through self and nonself elicitors. Rhamnolipids and their precursor HAAs are exoproducts produced by beneficial and pathogenic bacteria. They are involved in bacterial surface dissemination and biofilm development. As these compounds are released in the extracellular milieu, they have the potential to be perceived by the plant immune system. Our work shows that both compounds independently activate plant immunity. We demonstrate that HAAs are perceived by the receptor protein kinase LORE. By contrast, rhamnolipids are not senses by LORE but activate a non-canonical immune response affected by the sphingolipid composition of the plant plasma membrane. Thus, plants are able to sense bacterial molecules as well as their direct precursors to trigger a distinct immune response.
Interactive regulation between aliphatic hydroxylation and aromatic hydroxylation of thaxtomin D in TxtC: a theoretical investigation
Authors: Yuan Chang , Ouyang Qingwen , Wang Xixi , Li Xichen , Tan Hongwei , Chen Guangju
Published: December 2020

TxtC is an unusual bifunctional cytochrome P450 that is able to perform sequential aliphatic and aromatic hydroxylation of the diketopiperazine substrate thaxtomin D in two remote sites to produce thaxtomin A. Though the X-ray structure of TxtC complexed with thaxtomin D revealed a binding mode for its aromatic hydroxylation, the preferential hydroxylation site is aliphatic C14. It is thus intriguing to unravel how TxtC accomplishes such two-step catalytic hydroxylation on distinct aliphatic and aromatic carbons and why the aliphatic site is preferred in the hydroxylation step. In this work, by employing molecular docking and molecular dynamics (MD) simulation, we revealed that thaxtomin D could adopt two different conformations in the TxtC active site, which were equal in energy with either the aromatic C-H or aliphatic C14-H laying towards the active Cpd I oxyferryl moiety. Further ONIOM calculations indicated that the energy barrier for the rate-limiting hydroxylation step on the aliphatic C14site was 8.9 kcal/mol more favorable than that on the aromatic C20site. The hydroxyl group on the monohydroxylated intermediate thaxtomin B C14site formed hydrogen bonds with Ser280 and Thr385, which induced theL-Phe moiety to rotate around the Cβ−Cγbond of the 4-nitrotryptophan moiety. Thus, it adopted an energy favorable conformation with aromatic C20adjacent to the oxyferryl moiety. In addition, the hydroxyl group induced solvent water molecules to enter the active site, which propelled thaxtomin B towards the heme plane and resulted in heme distortion. Based on this geometrical layout, the rate-limiting aromatic hydroxylation energy barrier decreased to 15.4 kcal/mol, which was comparable to that of the thaxtomin D aliphatic hydroxylation process. Our calculations indicated that heme distortion lowered the energy level of the lowest Cpd I α-vacant orbital, which promoted electron transfer in the rate-limiting thaxtomin B aromatic hydroxylation step in TxtC.
Rotavirus Replication Factories Are Complex Ribonucleoprotein Condensates
Authors: Geiger Florian , Papa Guido , Arter William E. , Acker Julia , Saar Kadi L. , Erkamp Nadia , Qi Runzhang , Bravo Jack , Strauss Sebastian , Krainer Georg , Burrone Oscar R. , Jungmann Ralf , Knowles Tuomas P.J. , Engelke Hanna , Borodavka Alexander
Published: December 2020

RNA viruses induce formation of subcellular organelles that provide microenvironments conducive to their replication. Here we show that replication factories of rotaviruses represent protein-RNA condensates that are formed via liquid-liquid phase separation. We demonstrate that rotavirus proteins NSP5 and NSP2 undergo phase separationin vitroand form RNA-rich condensatesin vivothat can be reversibly dissolved by aliphatic diols. During infection, these RNA-protein condensates became less dynamic and impervious to aliphatic diols, indicating a transition from a liquid to solid state. Some aspects of assembly of rotavirus replication factories mirror the formation of cytoplasmic ribonucleoprotein granules, while the selective enrichment of viral transcripts appears to be a unique feature of these condensates. Such complex RNA-protein condensates that underlie replication of RNA viruses represent an attractive target for developing novel therapeutic approaches.
SNPnexus COVID: Facilitating the analysis of COVID-19 host genetics
Authors: Oscanoa Jorge , Sivapalan Lavanya , Abdollahyan Maryam , Gadaleta Emanuela , Chelala Claude
Published: December 2020

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented a crisis for global healthcare systems. Human SARS-CoV-2 infection can result in coronavirus disease 2019 (COVID-19), which has been characterised as an acute respiratory illness, with most patients displaying flu-like symptoms, such as a fever, cough and dyspnoea. However, the range and severity of individual symptoms experienced by patients can vary significantly, indicating a role for host genetics in impacting the susceptibility and severity of COVID-19 disease. Whilst most symptomatic infections are known to manifest in mild to moderate respiratory symptoms, severe pneumonia and complications including cytokine release syndrome, which can lead to multi-organ dysfunction, have also been observed in cases worldwide. Global initiatives to sequence the genomes of patients with COVID-19 have driven an expanding new field of host genomics research, to characterise the genetic determinants of COVID-19 disease. The functional annotation and analysis of incoming genomic data, within a clinically relevant turnaround time, is therefore imperative given the importance and urgency of research efforts to understand the biology of SARS-CoV-2 infection and disease. To address these requirements, we developed SNPnexus COVID. This is a web-based variant annotation tool, powered by the SNPnexus software.
Arabidopsis root responses to salinity depend on pectin modification and cell wall sensing
Authors: Gigli-Bisceglia Nora , van Zelm Eva , Huo Wenying , Lamers Jasper , Testerink Christa
Published: December 2020

Soil salinity is an increasing worldwide problem for agriculture, affecting plant growth and yield. To understand the molecular mechanisms activated in response to salt in plants, we investigated theCatharanthus roseusReceptor like Kinase 1 Like (CrRLK1L) family, which contains well described sensors previously shown to be involved in maintaining and sensing the structural integrity of the cell walls. We found thatherk1the1-4double mutants, lacking the function of theArabidopsis thalianaReceptor like Kinase HERKULES1 combined with a gain-of-function allele of THESEUS1, phenocopied the phenotypes previously reported in plants lacking FERONIA (FER) function. We report that bothfer-4andherk1the1-4mutants respond strongly to salt application, resulting in a more intense activation of early and late stress responses. We also show that salt triggers de-methyl esterification of loosely bound pectins, responsible for the activation of several salt response signaling pathways. Addition of calcium chloride or chemically inhibiting pectin methyl esterase (PME) activity reduced activation of the early signaling protein Mitogen Activated Protein Kinase 6 (MPK6) as well as amplitude of salt-induced marker gene induction. MPK6 is required for the full induction of the salt-induced gene expression markers we tested. The sodium specific root halotropism response on the other hand, appears independent of MPK6 or calcium application, and is only mildly influenced by the cell wall sensors FER/HERK1/THE1-4 or alteration of PME activity. We hypothesize a model where salt-triggered modification of pectin requires the functionality of FER alone or the HERK1/THE1 combination to attenuate salt responses. Collectively, our results show the complexity of salt stress responses and salt sensing mechanisms and their connection to cell wall modifications, responsible for several salt response pathways and ultimately plant resilience to salinity.
Artificial light at night leads to circadian disruption in a songbird: integrated evidence from behavioural, genomic and metabolomic data
Authors: Dominoni Davide M. , de Jong Maaike , van Oers Kees , O’Shaughnessy Peter , Blackburn Gavin , Atema Els , Mateman Christa A. , D’Amelio Pietro B. , Trost Lisa , Bellingham Michelle , Clark Jessica , Visser Marcel E. , Helm Barbara
Published: December 2020

Globally increasing levels of artificial light at night (ALAN) are associated with shifts in circadian rhythms of behaviour in many wild species. However, it is still unclear whether changes in behavioural timing are underlined by parallel shifts in the molecular clock, and whether such internal shifts may differ between different tissues and physiological pathways, which could highlight circadian disruption. We tackled these questions in a comprehensive study that integrated behavioural, gene expression and metabolomic analyses. We exposed captive male great tits (Parus major) to three ALAN intensities or to dark nights, recorded their activity rhythms and obtained mid-day and midnight samples of brain, liver, spleen and blood. ALAN advanced wake-up time, and this shift was paralleled by an advance in the expression of the clock geneBMAL1in all tissues, suggesting close links of brain and peripheral clock gene expression with activity rhythms. However, several metabolic and immune genes were desynchronised the shiftedBMAL1expression, suggesting circadian disruption of behaviour and physiology. This result was reinforced by untargeted metabolomic profiling, which showed that only 9.7% of the 755 analysed metabolites followed the behavioural shift. We suggest circadian as a key mediator of the health impacts of ALAN on wild animals.
Where are they now? Tracking the Mediterranean Lionfish Invasion via Local Dive Centers
Authors: Phillips Elizabeth W , Kotrschal Alexander
Published: December 2020

Invasive species are globally on the rise due to human-induced environmental change and are often a source of harm to their new ecosystems. Tracking the spread of invaders is crucial to better management of invasive species, and citizen science is often used to collect sighting data. However, this can be unreliable due to the general public’s limited expertise for accurate identification and a lack of clear absence data. Here, we introduce a refined method of citizen science by tracking the spread of the invasive lionfish (Pterois miles) in the Mediterranean Sea using dive centers’ expertise on local marine wildlife. We contacted 1131 dive centers on the Mediterranean coast via email and received 216 responses reporting whether or not lionfish were present in their area and, if present, the year they were first sighted. Currently, lionfish sightings are observed in the eastern half of the Mediterranean, though the front is continuing to move west with the furthest sighting as far as Corfu, Greece (19.939423°E, 39.428017°N). In 2020, lionfish also expanded their invasive range north on the Turkish Aegean coast to Karaburun (26.520657°E, 38.637033°N), showing that the invasion is ongoing. We found that the invasive range is now exceeding previous invasion models, highlighting the need for additional research on lionfish biology to inform management efforts. Continuous monitoring of invasive fronts based on dive center reports and a better understanding of what makes lionfish so invasive is crucial to mitigating their negative impact on native ecosystems.