bluuebunny/crossref_metadata_2025 huggingface dataset:
Bivariate genomic prediction of phenotypes by selecting epistatic interactions across years
Authors: Vojgani Elaheh , Pook Torsten , Hölker Armin C. , Mayer Manfred , Schön Chris-Carolin , Simianer Henner
Published: November 2020

The importance of accurate genomic prediction of phenotypes in plant breeding is undeniable, as higher prediction accuracy can increase selection responses. In this study, we investigated the ability of three models to improve prediction accuracy by including phenotypic information from the last growing season. This was done by considering a single biological trait in two growing seasons (2017 and 2018) as separate traits in a multi-trait model. Thus, bivariate variants of the Genomic Best Linear Unbiased Prediction (GBLUP) as an additive model, Epistatic Random Regression BLUP (ERRBLUP) and selective Epistatic Random Regression BLUP (sERRBLUP) as epistasis models were compared with respect to their prediction accuracies for the second year. The results indicate that bivariate ERRBLUP is slightly superior to bivariate GBLUP in predication accuracy, while bivariate sERRBLUP has the highest prediction accuracy in most cases. The average relative increase in prediction accuracy from bivariate GBLUP to maximum bivariate sERRBLUP across eight phenotypic traits and studied dataset from 471/402 doubled haploid lines in the European maize landrace Kemater Landmais Gelb/Petkuser Ferdinand Rot, were 7.61 and 3.47 percent, respectively. We further investigated the genomic correlation, phenotypic correlation and trait heritability as the factors affecting the bivariate model’s predication accuracy, with genetic correlation between growing seasons being the most important one. For all three considered model architectures results were far worse when using a univariate version of the model, e.g. with an average reduction in prediction accuracy of 0.23/0.14 for Kemater/Petkuser when using univariate GBLUP.

Key Massage

Bivariate models based on selected subsets of pairwise SNP interactions can increase the prediction accuracy by utilizing phenotypic data across years under the assumption of high genomic correlation across years.
Coiled-coil and RPW8-type immune receptors function at the plasma membrane in a phospholipid dependent manner
Authors: Saile Svenja C. , Ackermann Frank M. , Sunil Sruthi , Bayless Adam , Stöbbe Eva , Bonardi Vera , Wan Li , Doumane Mehdi , Jaillais Yvon , Caillaud Marie-Cécile , Dangl Jeffery L. , Nishimura Marc T. , El Kasmi Farid
Published: November 2020

Activation of intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) results in immunity and a localized cell death response of infected cells. Cell death activity of many NLRs requires oligomerization and in some cases plasma membrane (PM) localization. However, the exact mechanisms underlying PM localization of NLRs lacking recognizable N- or C-terminal lipidation motifs or predicted transmembrane domains remains elusive. Here we show that the PM localization and stability of members of the RPW8-like coiled-coil (CCR) domain NLRs (RNLs) and a CC-type NLR (CNL) depend on the interaction with PM phospholipids. Depletion of phosphatidylinositol-4-phosphate (PI4P) from the PM led to a mislocalization of the analyzed NLRs and consequently inhibited their cell death activity. We further demonstrate activation-dependent self-association of cell death inducing RNLs. Our results provide new insights into the molecular mechanism of NLR PM localization and defines an important role of phospholipids for CNL and RNL activity during immunity.
A Proteomic Platform to Identify Off-Target Proteins Associated with Therapeutic Modalities that Induce Protein Degradation or Gene Silencing
Authors: Liu Xin , Zhang Ye , Ward Lucas D. , Yan Qinghong , Bohnuud Tanggis , Hernandez Rocio , Lao Socheata , Yuan Jing , Fan Fan
Published: November 2020

Novel modalities such as Proteolysis Targeting Chimera (PROTAC) and RNA interference (RNAi) have a mechanism of action-based potential to alter the abundance of off-target proteins. The currentin vitrosecondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluated abundance of off-target proteins. The first part of the manuscript describes the rationale and process through which the off-target proteins and cell lines were selected. The off-target proteins were selected from the entire human proteome based on genetics and pharmacology data (Deatonet al., 2018). The selection yielded 2,813 proteins, forming the nexus of a panel that we refer to as the “selected off-target proteome” (SOTP). An algorithm was then used to identify appropriate cell lines. Four human cell lines out of 932 were selected that, collectively, expressed ~ 80% of the SOTP based on transcriptome data. The second part of the manuscript describes the LC-MS/MS experimentation to quantify the intracellular and extracellular proteins of interest in the 4 selected cell lines. Among over 10,000 quantifiable proteins identified, 1,828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing rationale selection process developed and the label free LC-MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.
A scalable method for identifying recombinants from unaligned sequences
Authors: Feng Qian , Tiedje Kathryn , Ruybal-Pesántez Shazia , Tonkin-Hill Gerry , Duffy Michael , Day Karen , Shim Heejung , Chan Yao-ban
Published: November 2020

Recombination is a fundamental process in molecular evolution, and the identification of recombinant sequences is of major interest for biologists. However, current methods for detecting recombinants only work for aligned sequences, often require a reference panel, and do not scale well to large datasets. Thus they are not suitable for the analyses of highly diverse genes, such as thevargenes of the malaria parasitePlasmodium falciparum,which are known to diversify primarily through recombination.

We introduce an algorithm to detect recombinant sequences from an unaligned dataset. Our approach can effectively handle thousands of sequences without the need of an alignment or a reference panel, offering a general tool suitable for the analysis of many different types of sequences. We demonstrate the effectiveness of our algorithm through extensive numerical simulations; in particular, it maintains its accuracy in the presence of insertions and deletions.

We apply our algorithm to a dataset of 17,335 DBLαtypes invargenes from Ghana, enabling the comparison between recombinant and non-recombinant types for the first time. We observe that sequences belonging to the same ups type or DBLαsubclass recombine amongst themselves more frequently, and that non-recombinant DBLαtypes are more conserved than recombinant ones.

Author summary

Recombination is a fundamental process in molecular evolution where two genes exchange genetic material, diversifying the genes. It is important to properly model this process when reconstructing evolutionary history, and to do so we need to be able to identify recombinant genes. In this manuscript, we develop a method for this which can be applied to scenarios where current methods often fail, such as where genes are very diverse.

We specifically focus on detecting recombinants in thevargenes of the malaria parasitePlasmodium falciparum. These genes influence the length and severity of malaria infection, and therefore their study is critical to the treatment and prevention of malaria. They are also highly diverse, primarily because of recombination. Our analysis of genes from a cross-sectional study in Ghana study show fundamental relations between the patterns and prevalence of recombination in these genes and other important biological categorisations.
Motor sequence learning deficits in idiopathic Parkinson’s disease are associated with increased substantia nigra activity
Authors: Tzvi Elinor , Bey Richard , Nitschke Matthias , Brüggemann Norbert , Classen Joseph , Münte Thomas F. , Krämer Ulrike M. , Rumpf Jost-Julian
Published: November 2020

Previous studies have shown that persons with Parkinson’s disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however unsuccessfully. Finally, we found no differences between pwPD and controls in task modulation of the cortico-striato-cerebellar network. Notably, in both groups Bayesian model selection revealed cortico-cerebellar connections modulated by the task, suggesting that despite behavioral and activation differences, the same cortico-cerebellar circuitry is recruited for implementing the motor task.
Human iPSC-derived astrocytes transplanted into the mouse brain display three morphological responses to amyloid-β plaques
Authors: Preman Pranav , TCW Julia , Calafate Sara , Snellinx An , Alfonso-Triguero Maria , Corthout Nikky , Munck Sebastian , Thal Dietmar Rudolf , Goate Alison M , De Strooper Bart , Arranz Amaia M
Published: November 2020

Background

Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression.

Methods

To address these challenges, we established an approach to study human astroglia within the context of the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived glia progenitors into neonatal brains of immunodeficient mice.

Results

Xenografted (hiPSC)-derived glia progenitors differentiate into astrocytes that integrate functionally within the mouse host brain and mature in a cell-autonomous way retaining human-specific morphologies, unique features and physiological properties. In Alzheimer’s chimeric brains, transplanted hiPSC-derived astrocytes respond to the presence of amyloid plaques with various morphological changes that seem independent of theAPOEallelic background.

Conclusion

In sum, this chimeric model has great potential to analyze the role of patient-derived and genetically modified astroglia in Alzheimer’s disease.
Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota
Authors: Galindo Luis Javier , López-García Purificación , Torruella Guifré , Karpov Sergey , Moreira David
Published: November 2020

Compared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytridsAmoeboradix gromoviandSanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids’ phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.
Parasitic flatworms infecting thorny skate,Amblyraja radiata:infection by the monogeneansAcanthocotyle verrilliandRajonchocotyle emarginatain Svalbard
Authors: Hermans Raquel , Vanhove Maarten P. M. , Ditrich Oleg , Tyml Tomáš , Gelnar Milan , Artois Tom , Kmentová Nikol
Published: November 2020

Parasite diversity above the Arctic circle remains understudied even for commercially valuable host taxa. Thorny skate,Amblyraja radiata,is a common bycatch species with a growing commercial value. Its natural range covers both sides of the North Atlantic including the Arctic zone. Svalbard is a Norwegian archipelago located on the northwest corner of the Barents Shelf which sustains a spectacular species diversity. So far, several monogenean species have been reported infecting thorny skate across the Atlantic Ocean. In the present study, we intend to fill in the knowledge gap on monogenean parasites infecting thorny skate in the northern part of its range and thus indirectly assess the connectivity between the thorny skate populations off the Svalbard coast and from previously studied locations. 46 monogenean individuals were recovered from 11 specimens of thorny skate. Following morphological and molecular assessment, two species of monogeneans,Acanthocotyle verrilliandRajonchocotyle emarginata,were identified. The results serve as the northernmost record for both parasite genera and the first record of monogenean species off Svalbard. Detailed morphometric evaluation revealed a relatively high level of morphological variation inA. verrillicompared to its congeners. Phylogenetic reconstruction placedA. verrilliin a well-supported clade withA. imo.Our study also suggests high diagnostic significance of sclerotised structures in the identification ofRajonchocotyle.Even though the occurrence of two directly transmitted parasite species supports the previously suggested long-distance migration ofA. radiata, future studies employing highly variable genetic markers are needed to assess the ongoing and historical migration patterns.

Highlights

First record of monogenean species in Svalbard

Northernmost record for representatives of Acanthocotylidae and Hexabothriidae

Transatlantic occurrence of parasites supports connectivity of thorny skate populations
Ribonucleotide reductase, a novel target for gonorrhea
Authors: Narasimhan J. , Letinski S. , Jung S. , Gerasyuto A. , Wang J. , Arnold M. , Chen G. , Hedrick J. , Dumble M. , Ravichandran K. , Levitz T. S. , Chang C. , Drennan C. L. , Stubbe J. , Karp G. , Branstrom A.
Published: November 2020

Antibiotic resistantNeisseria gonorrhoeae (Ng)are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity againstNgincluding MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Activity studies and negative stain electron microscopy of theNgIa RNR suggest that these inhibitors potentiate conversion of its active α2β2state to an inactive α4β4similar to states first identified with theEscherichia coli (Ec)Ia RNR. Resistance mutations inNgmap to theN-terminal, ATP cone domain of its α subunit and disrupt the interaction with the β subunit required to form the specific quaternary inhibited state. Oral administration of PTC-672 reducesNginfection in a mouse model and may have therapeutic potential for treatment ofNgthat is resistant to current drugs.
Elucidating the neuroanatomical correlates of social connectedness, sleep quality and psychological distress in early adolescence
Authors: Jamieson Daniel , McLoughlin Larisa T , Beaudequin Denise A , Shan Zack , Boyes Amanda , Schwenn Paul , Lagopoulos Jim , Hermens Daniel F
Published: November 2020

Background

Adolescence is an important period for developing one’s sense of self. Social connectedness has been linked to a sense of self which in turn has links to resilience in mental disorders. Adolescence is also a period of increased risk of chronic sleep deprivation during a time of ongoing white matter (WM) maturation. The complex relationship between these variables and their relationship with the onset on mental disorders during adolescence remains largely unexplored.

Methods

N= 64 participants aged 12 years (M= 12.6) completed the Pittsburgh Sleep Quality Index (PSQI), Social connectedness scale (SCS) and a diffusion weighted Magnetic Resonance Imaging (MRI) scan to investigate the relationship of these variables to predict psychological distress via the Kessler psychological distress scale (K10) in early adolescents. Multiple regression analysis was used with K10 entered as the dependent variable and SCS, PSQI, and values of white matter integrity as the predictor variables.

Results

Results showed that while all four variables collectively accounted for a significant proportion of the variance in K10 (41.1%), SCS and PSQI were the only predictors that accounted for a significant proportion of variance uniquely.

Conclusions

These findings suggest interventions aimed at increasing levels of social connectedness and sleep quality during adolescence may reduce psychological distress. Future longitudinal reporting of this combination of variables is suggested.
Stress-sensitive inference of task controllability
Authors: Ligneul Romain , Mainen Zachary , Ly Verena , Cools Roshan
Published: November 2020

Estimating the controllability of the environment enables agents to better predict upcoming events and decide when to engage controlled action selection. How does the human brain estimate controllability? Trial-by-trial analysis of choices, decision times, and neural activity in an explore-and-predict task demonstrate that humans solve this problem by comparing the predictions of an “actor” model with those of a reduced “spectator” model of their environment. Neural BOLD responses within striatal and medial prefrontal areas tracked the instantaneous difference in the prediction errors generated by these two statistical learning models. BOLD activity in the posterior cingulate, temporoparietal, and prefrontal cortices covaried with changes in estimated controllability. Exposure to inescapable stressors biased controllability estimates downward and increased reliance on the spectator model in an anxiety-dependent fashion. Taken together, these findings provide a mechanistic account of controllability inference and its distortion by stress exposure.
On-site rapid molecular testing, mobile sampling teams and eHealth to support primary care physicians during the COVID-19 pandemic
Authors: Cheung N.N. , Boers S.A. , deh Kiani S. Kiani , Jansen R.W. , Mook-Kanamori D.O. , Janssens L. , Feltkamp M.C.W. , Kroes A.C.M , Mourik B.C.
Published: November 2020

Objectives

We evaluated the effects of on-site rapid molecular testing at a drive-through sampling facility, deployment of mobile sampling teams and implementation of an online eHealth platform as supportive measures for general practitioners (GPs) during the COVID-19 pandemic.

Methods

An eHealth platform was developed that allowed GPs to either refer patients to a drive-through sampling facility or to request a home visit by a sampling team. Nasopharyngeal swab samples from patients marked as urgent (n=333) were tested immediately on-site using a GeneXpert System. Non-urgent samples (n=1,460) were sent once a day to a university hospital laboratory for routine testing. Time stamps starting from referral to the moment of test report sent were recorded to calculate the turnaround time.

Results

The eHealth platform was rapidly adopted and used by a total of 517 GPs to test 1,793 patients in a period of 13 weeks. On-site rapid molecular testing reduced the median turnaround time to 03h:41m compared to 29h:15m for routine testing. Positive SARS-CoV-2 test results were identified amongst 84/1,477 (5.7%) and 33/316 (10.4%) patients sampled at the drive-through or at home, respectively. In the age category of >80 years, 80.4% of patients were tested by a mobile sampling team.

Conclusions

The combination of rapid molecular testing and eHealth reduced the time between referral and results sent back to the GP to less than four hours. In addition, mobile sampling teams helped in reaching non-mobile, elderly patient populations with a higher prevalence of COVID-19.
Breast cancer dormancy is associated with a 4NG1 state and not senescence
Authors: Prunier Chloé , Alay Ania , van Dijk Michiel , Ammerlaan Kelly L. , van Gelderen Sharon , Marvin Dieuwke L. , Teunisse Amina , Slieker Roderick C. , Szuhai Karoly , Jochemsen A.G. , Solé Xavier , Dijke Peter ten , Ritsma Laila
Published: November 2020

Reactivation of dormant cancer cells can lead to cancer relapse, metastasis and patient death. Dormancy is a non-proliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models. Here, we thoroughly characterize the dormant D2.OR and proliferative D2A1 breast cancer cell line modelsin vivoandin vitro, and assess if there is overlap between a dormant and a senescent phenotype. We show that D2.OR but not D2A1 cells become dormant in the liver of an immunocompetent model.In vitro, we show that D2.OR cells are polyploid ER+/Her2+cells, and in response to a 3D environment are growth arrested in G1, of which a subpopulation resides in a 4NG1 state. The dormancy state is reversible, and not associated with a senescence phenotype. This will aid future research on breast cancer dormancy.
Antibiotic resistance profiles and population structure of disease-associatedStaphylococcus aureusinfecting patients in Fort Portal Regional Referral Hospital, Western Uganda
Authors: Ackers-Johnson G. , Kibombo D. , Kusiima B. , Nsubuga M.L. , Kigozi E. , Kajumbula H.M. , Kateete D.P. , Walwema R. , Ackers H.L. , Goodhead I.B. , Birtles R.J. , James C.E.
Published: November 2020

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41Staphylococcus aureusisolates (2017-2019). AST revealed 73% (30/41) of isolates were resistant to one or more antibiotics and 29% (12/41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistantS. aureus(MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24% carriage ofermgenes suggests potential for rapid development of resistance. We inferred a population structure for theS. aureusisolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitiveS. aureus(MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton-Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulatingS. aureusand their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.
Inactivation of mitochondrial Complex I stimulates chloroplast ATPase in Physcomitrella (Physcomitrium patens)
Authors: Mellon Marco , Storti Mattia , Vives Antoni Mateu Vera , Kramer David M. , Alboresi Alessandro , Morosinotto Tomas
Published: November 2020

While light is the ultimate source of energy for photosynthetic organisms, mitochondrial respiration is still fundamental for supporting metabolism demand during the night or in heterotrophic tissues. Respiration is also important for the metabolism of photosynthetically active cells, acting as a sink for excess reduced molecules and source of substrates for anabolic pathways. In this work, we isolated Physcomitrella (Physcomitrium patens) plants with altered respiration by inactivating Complex I of the mitochondrial electron transport chain by independent targeting of two essential subunits. Results show that the inactivation of Complex I causes a strong growth impairment even in fully autotrophic conditions in tissues where all cells are photosynthetically active. Complex I mutants show major alterations in the stoichiometry of respiratory complexes while the composition of photosynthetic apparatus was substantially unaffected. Complex I mutants showed altered photosynthesis with higher yields of both Photosystems I and II. These are the consequence of a higher chloroplast ATPase activity that also caused a smaller ΔpH formation across thylakoid membranes as well as decreased photosynthetic control on cytochromeb6f, possibly to compensate for a deficit in ATP supply relative to demand in Complex I mutants. These results demonstrate that alteration of respiratory activity directly impacts photosynthesis inP. patensand that metabolic interaction between organelles is essential in their ability to use light energy for growth.
Lethal and sublethal effects of synthetic and bio-insecticides onTrichogramma brassicaeparasitizingTuta absoluta
Authors: Nozad-Bonab Zahra , Hejazi Mir Jalil , Iranipour Shahzad , Arzanlou Mehdi , Biondi Antonio
Published: November 2020

The invasive tomato leaf miner (TLM),Tuta absoluta(Meyrick) is an invasive pest on tomatoes worldwide. The main control measure against the pest has been chemical insecticides, but the pest developed resistance to many chemical classes. So alternative methods, such as biological control agents, alone or combined to chemical compounds must be evaluated to validate their synergistic actions. In this study, both lethal (concentration-mortality response) and sublethal effects of three synthetic insecticides, the bioinsecticide spinosad, as well as the entomopathogenic fungusMetarhizium anisopliae(Metschnikoff) Sorokin were studied onTrichogramma brassicaeBezdenko withinT. absolutaeggs. To assess the sublethal effects, the lethal concentration 25% (LC25) of chlorantraniliprole, spinosad, abamectin and indoxacarb and LC50value ofM. anisopliaewas sprayed on eggs and then offered at three time intervals to the parasitoids. Fertility and other life table parameters of the individuals emerged from treated eggs were estimated. The results showed that indoxacarb showed the highest deleterious sublethal effects onT. brassicae. On the other hand,M. anisopliaewas the safest treatment to combine toTrichogrammawith no significant effect on some parameters. The lowest LC50value forT.brassicaewas obtained for chlorantraniliprole followed by spinosad. Synergistic effect was observed whenM. anisopliaeandT. brassicaeused together. Hence, this will be a promising integration againstT. absoluta.
A novel stem cell type at the basal side of the subventricular zone maintains adult neurogenesis
Authors: Baur Katja , Abdullah Yomn , Mandl Claudia , Hölzl-Wenig Gabriele , Shi Yan , Edelkraut Udo , Khatri Priti , Hagenston Anna M. , Irmler Martin , Beckers Johannes , Ciccolini Francesca
Published: November 2020

According to the current consensus, neural stem cells (NSCs) apically contacting the lateral ventricle generate differentiated progenitors by rare asymmetric divisions or by relocating to the basal side of the ventricular-subventricular zone V-SVZ. Both processes will then ultimately lead to the generation of adult-born olfactory bulb (OB) interneurons. In contrast to this view, we here found that adult-born OB interneurons largely derive from an additional NSC type resident in the basal V-SVZ. Despite being both capable of self-renewal and long-term quiescence, apical and basal NSCs differ in Nestin expression, primary cilia extension and frequency of cell division. The expression of Notch-related genes also differed between the two NSC groups and Notch-activation was greatest in apical NSCs. Apical downregulation of Notch-effector Hes1 decreased Notch activation while increasing proliferation across the niche and neurogenesis from apical NSCs. Underscoring their different roles in neurogenesis, lactation-dependent increase in neurogenesis was paralleled by extra activation of basal but not apical NSCs. Thus, basal NSCs support OB neurogenesis whereas apical NSCs impart Notch-mediated lateral inhibition across the V-SVZ.
Grazing results in mobilization of spherulous cells and re-allocation of secondary metabolites to the surface in the spongeAplysina aerophoba
Authors: Wu Yu-Chen , García-Altares María , Pintó Berta , Ribes Marta , Hentschel Ute , Pita Lucía
Published: November 2020

On the sea floor, prey and predator commonly engage in a chemical warfare. Here, sponges thrive due to their specific and diverse chemical arsenal. Yet, some animals use these chemically-defended organisms as food and home. Most research on sponge chemical ecology has characterized crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about intraindividual chemical dynamics and responses to specialist grazers. Here, we studied the response of the spongeAplysina aerophobato grazing by the opistobranchTylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry). We characterized the distribution of two major brominated compounds inA. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalized wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidized compounds, causingT. perversadeterrence. During grazing,T. perversa’sway of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.
Arena3Dweb: Interactive 3D visualization of multilayered networks
Authors: Karatzas Evangelos , Baltoumas Fotis A. , Panayiotou Nikolaos A. , Schneider Reinhard , Pavlopoulos Georgios A.
Published: November 2020

Efficient integration and visualization of heterogeneous biomedical information in a single view is a key challenge. In this study, we present Arena3Dweb, the first, fully interactive and dependency-free, web application which allows the visualization of multilayered graphs in 3D space. With Arena3Dweb, users can integrate multiple networks in a single view along with their intra- and inter-layer connections. For clearer and more informative views, users can choose between a plethora of layout algorithms and apply them on a set of selected layers either individually or in combination. Users can align networks and highlight node topological features, whereas each layer as well as the whole scene can be translated, rotated and scaled in 3D space. User-selected edge colors can be used to highlight important paths, while node positioning, coloring and resizing can be adjusted on-the-fly. In its current version, Arena3Dwebsupports weighted and unweighted undirected graphs and is written in R, Shiny and JavaScript. We demonstrate the functionality of Arena3Dwebusing two different use-case scenarios; one regarding drug repurposing for SARS-CoV-2 and one related to GPCR signaling pathways implicated in melanoma. Arena3Dwebis available athttp://bib.fleming.gr:3838/Arena3D.
Inactivation of GalU leads the cell wall-associated polysaccharide defect to reduce the susceptibility to bacteriolytic agents inEnterococcus faecalis
Authors: Kurushima Jun , Tomita Haruyoshi
Published: November 2020

Enterococcal plasmid-encoded bacteriolysin Bac41 is a selective antimicrobial system that is considered to provide a competitive advantage toEnterococcus faecaliscells that carry the Bac41-coding plasmid. The Bac41 effector consists of the secreted proteins BacL1 and BacA, which attack the cell wall of the targetE. faecaliscell to induce bacteriolysis. Here, we demonstrated thatgalU, which encodes UTP-glucose-1-phosphate uridylyltransferase, is involved in susceptibility to the Bac41 system inE. faecalis. Spontaneous mutants that developed resistance to the antimicrobial effects of BacL1 and BacA were revealed to carry a truncation deletion of the C-terminal 288–298 a.a. region of the translated GalU protein. This truncation resulted in the depletion of UDP-glucose, leading to a failure to utilize galactose and produce the enterococcal polysaccharide antigen (EPA), which is expressed abundantly on the cell surface ofE. faecalis. This cell surface composition defect that resulted fromgalUor EPA-specific genes caused an abnormal cell morphology, with impaired polarity during cell division and alterations of the limited localization of BacL1. Interestingly, these mutants conferred reduced susceptibility to beta-lactams, despite their increased susceptibility to other bacteriostatic antimicrobial agents and chemical detergents. These data suggest that a complex mechanism of action underlies lytic killing, as exogenous bacteriolysis induced by lytic bacteriocins or beta-lactams requires an intact cell physiology inE. faecalis.

Importance

Cell wall-associated polysaccharides of bacteria are involved in various physiological characteristics. Recent studies demonstrated that the cell wall-associated polysaccharide ofEnterococcus faecalisis required for susceptibility to bactericidal antibiotic agents. Here, we demonstrated that agalUmutation resulted in resistance to the enterococcal lytic bacteriocin Bac41. ThegalUhomologue is reported to be essential for biosynthesis of species-specific cell wall-associated polysaccharides in other Firmicutes. InE. faecalis, thegalUmutant lost theE. faecalis-specific cell wall-associated polysaccharide EPA (enterococcal polysaccharide antigen). The mutant also displayed reduced susceptibility to antibacterial agents and an abnormal cell morphology. We firstly demonstrated thatgalUwas essential for EPA biosynthesis inE. faecalis, and EPA production might underlie susceptibility to lytic bacteriocin and antibiotic agents by undefined mechanism.
ATP drives efficient terpene biosynthesis in marine thraustochytrids
Authors: Zhang Aiqing , Mernitz Kaya , Wu Chao , Xiong Wei , He Yaodong , Wang Guangyi , Wang Xin
Published: November 2020

Understanding carbon flux-controlling mechanisms in a tangled metabolic network is an essential question of cell metabolism. Secondary metabolism, such as terpene biosynthesis, has evolved with low carbon flux due to inherent pathway constraints. Thraustochytrids are a group of heterotrophic marine unicellular protists, and can accumulate terpenoids under the high salt condition in their natural environment. However, the mechanism behind the terpene accumulation is not well understood. Here we show that terpene biosynthesis inThraustochytriumsp. ATCC 26185 is constrained by local thermodynamics in the mevalonate pathway. Thermodynamic analysis reveals the metabolite limitation in the nondecarboxylative Claisen condensation of acetyl-CoA to acetoacetyl-CoA step catalyzed by the acetyl-CoA acetyltransferase (ACAT). Through a sodium elicited mechanism, higher respiration leads to increased ATP investment into the mevalonate pathway, providing a strong thermodynamic driving force for enhanced terpene biosynthesis. The proteomic analysis further indicates that the increased ATP demands are fulfilled by shifting energy generation from carbohydrate to lipid metabolism. This study demonstrates a unique strategy in nature using ATP to drive a low-flux metabolic pathway, providing an alternative solution for efficient terpene metabolic engineering.

IMPORTANCE

Terpenoids are a large class of lipid molecules with important biological functions, and diverse industrial and medicinal applications. Metabolic engineering for terpene production has been hindered by the low flux distribution to its biosynthesis pathway. In practice, a high substrate load is generally required to reach high product titers. Here we show that the mevalonate-derived terpene biosynthesis is constrained by local pathway thermodynamics, which can only be partially relieved by increasing substrate levels. Through comparative proteomic and biochemical analyses, we discovered a unique mechanism for high terpene accumulation in marine protists thraustochytrids. Through a sodium induced mechanism, thraustochytrids shift their energy metabolism from carbohydrate to lipid metabolism for enhanced ATP production, providing a strong thermodynamic driving force for efficient terpene biosynthesis. This study reveals an important mechanism in eukaryotes to overcome the thermodynamic constraint in low-flux pathways by increased ATP consumption. Engineering energy metabolism thus provides an important alternative to relieve flux constraints in low-flux and energy-consuming pathways.
Combined degradome and replicated small RNA sequencing identifiesBrassica napussmall RNAs responsive to infection by a necrotrophic pathogen
Authors: Regmi Roshan , Newman Toby E. , Kamphuis Lars G. , Derbyshire Mark C.
Published: November 2020

Background

Small RNAs are short non-coding RNAs that are key gene regulators controlling various biological processes in eukaryotes. Plants may regulate discrete sets of sRNAs in response to pathogen attack.Sclerotinia sclerotiorumis an economically important pathogen affecting hundreds of plant species, including the economically important oilseedBrassica napus. However, there are limited studies on how regulation of sRNAs occurs in theS. sclerotiorumandB. napuspathosystem.

Results

We identified different classes of sRNAs fromB. napusby high throughput sequencing of replicated mock and infected samples at 24 hours post-inoculation (HPI). Overall, 3,999 sRNA loci were highly expressed, of which 730 were significantly upregulated during infection. Degradome sequencing identified numerous likely sRNA targets that were enriched for immunity-related GO terms, including those related to jasmonic acid signalling, during infection. A total of 73 conserved miRNA families were identified in our dataset. Degradome sequencing identified 434 unique cleaved mRNA products from these miRNAs, of which 50 were unique to the infected library. A novel miR1885-triggered disease resistance gene-derived secondary sRNA locus was identified and verified with degradome sequencing. We also experimentally validated silencing of a plant immunity related ethylene response factor gene by a novel sRNA using 5’-RACE.

Conclusions

The findings in this study expand the framework for understanding the molecular mechanisms of theS. sclerotiorumandB. napuspathosystem at the sRNA level.
Extracting and Interpreting the Effects of Higher Order Sequence Features on Peptide MHC Binding
Authors: Dai Zheng , Huisman Brooke D , Birnbaum Michael E , Gifford David K
Published: November 2020

Understanding the factors contributing to peptide MHC (pMHC) affinity is critical for the study of immune responses and the development of novel therapeutics. Developments in yeast display platforms have enabled the collection of pMHC binding data for vast libraries of peptides. However, methods for interpreting this data are still at an early stage. In this work we propose an approach for extracting peptide sequence features that affect pMHC binding from such datasets. In the process we develop the theoretical framework for fitting and interpreting these features. We demonstrate that these features accurately capture the kinetics underlying pMHC binding, and can be used to predict pMHC binding well enough to rival the current state of the art. We then analyze the extracted factors and show that they correlate with our current structural understanding of MHC molecules. Finally, we discuss the implication these factors have on the complexity of peptide engineering.
Using photographs and metadata to estimate house prices in South Korea
Authors: Lee Changro , Park Key-Ho
Published: November 2020

Purpose

Most prior attempts at real estate valuation have focused on the use of metadata such as size and property age, neglecting the fact that the building workmanship in the construction of a house is also a key factor for the estimation of house prices. Building workmanship, such as exterior walls and floor tiling correspond to the visual attributes of a house, and it is difficult to capture and evaluate such attributes efficiently through classical models like regression analysis. Deep learning approach is taken in the valuation process to utilize this visual information.

Design/methodology/approach

The authors propose a two-input neural network comprising a multilayer perceptron and a convolutional neural network that can utilize both metadata and the visual information from images of the front view of the house.

Findings

The authors applied the two-input neural network to Guri City in Gyeonggi Province, South Korea, as a case study and found that the accuracy of house price estimations can be improved by employing image information along with metadata.

Originality/value

Few studies considered the impact of the building workmanship in the valuation process. The authors revealed that it is useful to use both photographs and metadata for enhancing the accuracy of house price estimation.
Prediction of multiproject resource conflict risk via an artificial neural network
Authors: Bai Libiao , Wang Zhiguo , Wang Hailing , Huang Ning , Shi Huijing
Published: November 2020

Purpose

Inadequate balancing of resources often results in resource conflict in the multiproject management process. Past research has focused on how to allocate a small amount of resources optimally but has scarcely explored how to foresee multiproject resource conflict risk in advance. The purpose of this study is to address this knowledge gap by developing a model to predict multiproject resource conflict risk.

Design/methodology/approach

A fuzzy comprehensive evaluation method is used to transform subjective judgments into quantitative information, based on which an evaluation index system for multiproject resource conflict risk that focuses on the interdependence of multiple project resources is proposed. An artificial neural network (ANN) model combined with this system is proposed to predict the comprehensive risk score that can describe the severity of risk.

Findings

Accurately predicting multiproject resource conflict risks in advance can reduce the risk to the organization and increase the probability of achieving the project objectives. The ANN model developed in this paper by the authors can capture the essential components of the underlying nonlinear relevance and is capable of predicting risk appropriately.

Originality/value

The authors explored the prediction of the risks associated with multiproject resource conflicts, which is important for improving the success rate of projects but has received limited attention in the past. The authors established an evaluation index system for these risks considering the interdependence among project resources to describe the underlying factors that contribute to resource conflict risks. The authors proposed an effective model to forecast the risk of multiproject resource conflicts using an ANN. The model can effectively predict complex phenomena with complicated and highly nonlinear performance functions and solve problems with many random variables.
The effect of externally applied rotational oscillations on FIV characteristics of tandem circular cylinders for different spacing ratios
Authors: Rabiee Amir Hossein , Esmaeili Mostafa
Published: November 2020

Purpose

This study aims to explore an active control strategy for attenuation of in-line and transverse flow-induced vibration (FIV) of two tandem-arranged circular cylinders.

Design/methodology/approach

The control system is based on the rotary oscillation of cylinders around their axis, which acts according to the lift coefficient feedback signal. The fluid-solid interaction simulations are performed for two velocity ratios (V_r = 5.5 and 7.5), three spacing ratios (L/D = 3.5, 5.5 and 7.5) and three different control cases. Cases 1 and 2, respectively, deal with the effect of rotary oscillation of front and rear cylinders, while Case 3 considers the effect of applied rotary oscillation to both cylinders.

Findings

The results show that in Case 3, the FIV of both cylinders is perfectly reduced, while in Case 2, only the vibration of rear cylinder is mitigated and no change is observed in the vortex-induced vibration of front cylinder. In Case 1, by rotary oscillation of the front cylinder, depending on the reduced velocity and the spacing ratio values, the transverse oscillation amplitude of the rear cylinder suppresses, remains unchanged and even increases under certain conditions. Hence, at every spacing ratio and reduced velocity, an independent controller system for each cylinder is necessary to guarantee a perfect vibration reduction of front and rear cylinders.

Originality/value

The current manuscript seeks to deploy a type of active rotary oscillating (ARO) controller to attenuate the FIV of two tandem-arranged cylinders placed on elastic supports. Three different cases are considered so as to understand the interaction of these cylinders regarding the rotary oscillation.