bluuebunny/crossref_metadata_2025 huggingface dataset:
A test of the Baldwin Effect: Differences in both constitutive expression and inducible responses to parasites underlie variation in host response to a parasite
Authors: Fuess Lauren , Weber Jesse N. , den Haan Stijn , Steinel Natalie C. , Shim Kum Chuan , Bolnick Daniel I.
Published: July 2020

Despite the significant effect of host-parasite interactions on both ecological systems and organism health, there is still limited understanding of the mechanisms driving evolution of host resistance to parasites. One model of rapid evolution, the Baldwin Effect, describes the role of plasticity in adaptation to novel conditions, and subsequent canalization of associated traits. While mostly applied in the context of environmental conditions, this theory may be relevant to the evolution of host resistance to novel parasites. Here we test the applicability of the Baldwin Effect to the evolution of resistance in a natural system using threespine stickleback fish (Gasterosteus aculeatus) and their cestode parasiteSchistochephalus solidus. We leverage a large transcriptomic data set to describe the response toS. solidusinfection by three different genetic crosses of stickleback, from a resistant and a tolerant population. Hosts mount a multigenic response to the parasite that is similar among host genotypes. In addition, we document extensive constitutive variation in gene expression among host genotypes. However, although many genes are both infection-induced and differentially expressed between genotypes, this overlap is not more extensive than expected by chance. We also see little evidence of canalization of infection-induced gene expression in the derived resistant population. These patterns do not support the Baldwin Effect, though they illustrate the importance of variation in both constitutive expression and induced responses to parasites. Finally, our results improve understanding of the cellular mechanisms underlying a putative resistance phenotype (fibrosis). Combined, our results highlight the importance of both constitutive and inducible variation in the evolution of resistance to parasites, and identify new target genes contributing to fibrosis. These findings advance understanding of host-parasite interactions and co-evolutionary relationships in natural systems.
FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis
Authors: de Sousa Herdson Renney , de Oliveira Getúlio Pereira , de Oliveira Frazão Stefânia , de Melo Gorgonha Kaio Cesar , Rosa Camila Pereira , Melgaço Garcez Emãnuella , Lucas Joaquim , Correia Amabel Fernandes , de Freitas Waleriano Ferreira , Borges Higor Matos , Paes Hugo Costa , Trilles Luciana , Lazera Marcia dos Santos , Pinto Vitor Laerte , Felipe Maria Sueli Soares , Casadevall Arturo , Silva-Pereira Ildinete , Albuquerque Patrícia , Nicola André Moraes
Published: July 2020

Cryptococcusspp. are important human pathogens responsible for about 180,000 deaths per year. Studying their virulence attributes can lead to better cryptococcosis prevention and treatment. In this work, we systematically investigated virulence attributes ofCryptococcusspp. clinical isolates and correlated them with patient data. We collected 66C. neoformansand 19C. gattiiisolates from Brazilian patients and analyzed multiple phenotypes related with their capsule, production of laccase, melanin and extracellular vesicles. We also tested their virulence inGalleria mellonellaand ability to evade macrophage LC3-associated phagocytosis (LAP). All phenotypes analyzed varied widely among the isolates, butC. neoformansisolates tended to melanize faster and more intensely and produce thinner capsules in comparison withC. gattii. We also observed correlations that match previous studies, such as that between secreted laccase – but not total melanin production – and disease outcome in patients. The most striking results, though, came from our measurements ofCryptococcuscolony melanization kinetics, which followed a sigmoidal curve for most isolates. Faster melanization correlated positively with LAP evasion, virulence inG. mellonellaand worse prognosis in humans. These results suggest that the speed of melanization, more than the total amount of melaninCryptococcusspp. produces, is crucial for virulence.

Graphical abstract
Biallelic mutation ofCLRN2causes non-syndromic hearing loss in humans
Authors: Vona Barbara , Mazaheri Neda , Lin Sheng-Jia , Dunbar Lucy A , Maroofian Reza , Azaiez Hela , Booth Kevin T. , Vitry Sandrine , Rad Aboulfazl , Varshney Pratishtha , Fowler Ben , Beetz Christian , Alagramam Kumar N. , Murphy David , Shariati Gholamreza , Sedaghat Alireza , Houlden Henry , VijayKumar Shruthi , Smith Richard J. H. , Haaf Thomas , El-Amraoui Aziz , Bowl Michael R. , Varshney Gaurav K. , Galehdari Hamid
Published: July 2020

Deafness, the most frequent sensory deficit in humans, is extremely heterogenous with hundreds of genes probably involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identifyCLRN2, encoding a tetraspan protein as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 15.2 Mb locus on chromosome 4p15.32p15.1 containing a missense pathogenic variant inCLRN2(c.494C>A, NM_001079827.2) segregating with the disease. Usingin vitroRNA splicing analysis, we show that theCLRN2c.494C>A mutation leads to two events: 1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and 2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identifyCLRN2as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.
Preferential activation of the posterior Default-Mode Network with sequentially predictable task switches
Authors: Araña-Oiarbide Garazi , Daws Richard E. , Lorenz Romy , Violante Ines R. , Hampshire Adam
Published: July 2020

The default-mode network (DMN) has been primarily associated with internally-directed and self-relevant cognition. This perspective is expanding to recognise its importance in executive behaviours like switching. We investigated the effect different task-switching manipulations have on DMN activation in two studies with novel fMRI paradigms. In the first study, the paradigm manipulated visual discriminability, visuo-perceptual distance and sequential predictability during switching. Increased posterior cingulate/precuneus (PCC/PrCC) activity was evident during switching; critically, this was strongest when the occurrence of the switch was predictable. In the second study, we sought to replicate and further investigate this switch-related effect with a fully factorial design manipulating sequential, spatial and visual-feature predictability. Whole-brain analysis again identified a PCC/PrCC-centred cluster that was more active for sequentially predictable versus unpredictable switches, but not for the other predictability dimensions. We propose PCC/PrCC DMN subregions may play a prominent executive role in mapping the sequential structure of complex tasks.
APOBEC2 is a Transcriptional Repressor required for proper Myoblast Differentiation
Authors: Lorenzo Jose Paulo , Molla Linda , Ibarra Ignacio L. , Ruf Sandra , Ridani Jana , Subramani Poorani Ganesh , Boulais Jonathan , Harjanto Dewi , Vonica Alin , Di Noia Javier M. , Dieterich Christoph , Zaugg Judith B. , Papavasiliou F. Nina
Published: July 2020

The activation induced cytidine deaminase/apolipoprotein B editing complex (AID/APOBEC) family comprises several nucleic acid editors with roles ranging from antibody diversification to mRNA editing. APOBEC2, an evolutionarily conserved member of this family, has neither an established substrate nor a mechanism of action, however genetic evidence suggests functional relevance in tissues such as muscle. Here, we demonstrate that in muscle, APOBEC2 does not have any of the attributed molecular functions of the AID/APOBEC family, such as RNA editing, DNA demethylation, or DNA mutation. Instead, we show that APOBEC2 occupies chromatin at promoter regions of certain genes, whose expression is repressed during muscle cell differentiation. We further demonstrate that APOBEC2 on one hand binds promoter region DNA directly and in a sequence specific fashion, while on the other it interacts with HDAC transcriptional corepressor complexes. Therefore, APOBEC2, by actively repressing the expression of non-myogenesis pathway genes, plays a key role in enforcing the proper establishment of muscle cell fate.
Unfolding of the chromatin fiber driven by overexpression of bridging factors
Authors: Malhotra Isha , Oyarzún Bernardo , Mognetti Bortolo Matteo
Published: July 2020

Nuclear molecules control the functional properties of the chromatin fiber by shaping its morphological properties. The biophysical mechanisms controlling how bridging molecules compactify the chromatin are a matter of debate. On the one side, bridging molecules could cross-link faraway sites and fold the fiber through the formation of loops. Interacting bridging molecules could also mediate long-range attractions by first tagging different locations of the fiber and then undergoing microphase separation. Using a coarse-grained model and Monte Carlo simulations, we study the conditions leading to compact configurations both for interacting and non-interacting bridging molecules. In the second case, we report on an unfolding transition at high densities of the bridging molecules. We clarify how this transition, which disappears for interacting bridging molecules, is universal and controlled by entropic terms. In general, chains are more compact in the case of interacting bridging molecules since, in this case, interactions are not valence-limited. However, this result is conditional on the ability of our simulation methodology to relax the system towards its ground state. In particular, we clarify how, unless using reaction dynamics that change the length of a loop in a single step, the system is prone to remain trapped in metastable, compact configurations featuring long loops.
A polycomb-independent role of EZH2 in TGFβ1-damaged epithelium triggers a fibrotic cascade with mesenchymal cells
Authors: Le Huy Quang , Hill Matthew Alexander , Kollak Ines , Skronska-Wasek Wioletta , Schroeder Victoria , Wirth Johannes , Schruf Eva , Quast Karsten , Herrmann Franziska Elena , Thomas Matthew James , Garnett James Peter
Published: July 2020

To restore organ homeostasis, a myriad of cell types need to activate rapid and transient programs to adjust cell fate decisions and elicit a collective behaviour. Characterisation of such programs are imperative to elucidate an organ’s regenerative capacity and its aberrant repair in disease. By modelling epithelial-mesenchymal crosstalk, we provide direct evidence for transforming growth factor β1 (TGFβ1)-damaged epithelium initiating a bi-directional fibrotic cascade with the mesenchyme. Strikingly, TGFβ1-damaged epithelia facilitates the release of Enhancer of Zester Homolog 2 (EZH2) from Polycomb Repressive Complex 2 (PRC2) to establish a novel fibrotic transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin. Perturbing this complex by disrupting epithelial EZH2 or actomyosin remodelling abrogates the fibrotic crosstalk. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve global H3K27me3 occupancy. Our results reveal an important non-canonical function of EZH2, paving the way for therapeutic interventions in fibrotic disease.
PLEKHA4 Promotes Wnt/β-catenin Signaling-Mediated G1/S Transition and Proliferation in Melanoma
Authors: Shah Adnan Shami , Cao Xiaofu , White Andrew C. , Baskin Jeremy M.
Published: July 2020

Melanoma patients incur substantial mortality, despite promising recent advances in targeted therapies and immunotherapies. In particular, inhibitors targeting BRAF-mutant melanoma can lead to resistance, and no targeted therapies exist for NRAS-mutant melanoma, motivating the search for additional therapeutic targets and vulnerable pathways. Here, we identify a regulator of Wnt/β-catenin signaling, PLEKHA4, as a factor required for melanoma proliferation and survival. PLEKHA4 knockdown in vitro leads to lower Dishevelled levels, attenuated Wnt/β-catenin signaling, and a block of progression through the G1/S cell cycle transition. In mouse xenograft models, inducible PLEKHA4 knockdown attenuated tumor growth in BRAF- and NRAS-mutant melanomas and synergized with the clinically used inhibitor encorafenib in a BRAF-mutant model. As an E3 ubiquitin ligase regulator with both lipid and protein binding partners, PLEKHA4 presents several opportunities for targeting with small molecules. Our work identifies PLEKHA4 as a promising drug target for melanoma and clarifies a controversial role for Wnt/β-catenin signaling in the control of melanoma proliferation.
Vascular calcification has a role in acute non-renal phosphate clearance
Authors: Turner Mandy E , Lansing Austin P , Jeronimo Paul S , Lee Lok Hang , Svajger Bruno A , Zelt Jason GE , Forster Corey M , Petkovich Martin P , Holden Rachel M , Adams Michael A
Published: July 2020

Rationale

Non-renal extravasation of phosphate from the circulation and transient accumulation into tissues and extracellular fluid is a regulated process of acute phosphate homeostasis that is not well understood. Following oral consumption of phosphate, circulating levels normalize long before urinary excretion has been completed. This process is especially relevant in the setting of chronic kidney disease (CKD), where phosphate exposure is prolonged due to inefficient kidney excretion. Furthermore, CKD-associated dysregulation of mineral metabolism exacerbates pathological accumulation of phosphate causing vascular calcification (VC).

Objective

Determine whether the systemic response to acute phosphate challenges is altered by the development and progression of VC.

Methods/Results

Acute circulating and tissue deposition of an acute phosphate challenge was assessed in two rat models of VC using radio-labelled phosphate tracer. In an adenine-induced model of CKD with VC, animals with VC had a blunted elevation of circulating33PO4following oral phosphate administration and the discordant deposition could be traced to the calcifying vasculature. In a non-CKD model of VC, VC was induced with 0.5ug/kg calcitriol and then withdrawn. The radio-labelled phosphate challenge was given to assess for vascular preference for phosphate uptake with and without the presence of an active calcification stimulus. The new transport to the calcifying vasculature correlates to the pre-existing burden of calcification, and can be substantially attenuated by removing the stimulus for calcification. The accrual is stimulated by a phosphate challenge, and not present in the same degree during passive disposition of circulating phosphate.

Conclusions

Our data indicate that calcifying arteries alter the systemic disposition of a phosphate challenge and acutely deposit substantial phosphate. This study supports the importance of diet as it relates to acute fluctuations of circulating phosphate and the importance of bioavailability and meal-to-meal management in CKD patients as a mediator of cardiovascular risk.
Time-resolved proteomic profiling of the ciliary Hedgehog response reveals that GPR161 and PKA undergo regulated co-exit from cilia
Authors: May Elena A. , Kalocsay Marian , D’Auriac Inès Galtier , Gygi Steven P. , Nachury Maxence V. , Mick David U.
Published: July 2020

The primary cilium is a signaling compartment that interprets Hedgehog signals through changes of its protein, lipid and second messenger compositions. Here, we combine proximity labeling of cilia with quantitative mass spectrometry to unbiasedly profile the time-dependent alterations of the ciliary proteome in response to Hedgehog. This approach correctly identifies the three factors known to undergo Hedgehog-regulated ciliary redistribution and reveals two such additional proteins. First, we find that a regulatory subunit of the cAMP-dependent protein kinase (PKA) rapidly exits cilia together with the G protein-coupled receptor GPR161 in response to Hedgehog; and we propose that the GPR161/PKA module senses and amplifies cAMP signals to modulate ciliary PKA activity. Second, we identify the putative phosphatase Paladin as a cell type-specific regulator of Hedgehog signaling that enters primary cilia upon pathway activation. The broad applicability of quantitative ciliary proteome profiling promises a rapid characterization of ciliopathies and their underlying signaling malfunctions.
Laying Hens Affected By Newcastle Virus And Laryngotracheitis Virus Show Rapid Recovery After Treatment With Ivermectin
Authors: Fernandez-Díaz Manolo , Guevara Luis , Icochea Eliana , Montalván Angela , Villanueva-Pérez Doris , Fernandez-Sánchez Manolo , Ticona Julio , Zimic Mirko ,   COVID-19 Working Group in Perú
Published: July 2020

This is an anecdotal observation of an intervention study involving laying hens from a commercial farm in the city of Chincha, Peru, who suffered an outbreak caused by Newcastle disease virus (NDV) and infectious laryngotracheitis virus (ILTV), confirmed by clinical observations, serological and molecular tests (PCR).

In addition to receiving standard treatment appropriate to the state of health at the time of the operation, a group of birds were treated with a single dose of ivermectin administered subcutaneously (0.2 mL of a 1% solution equivalent to 200 µg/kg body weight), with a group of control birds not receiving the treatment being reserved.

The results showed a remarkable recovery of symptoms after 24 hours of treatment among the birds that received ivermectin. At 4 days after treatment, the birds that received ivermectin showed visibly greater mobility and vivacity, as well as a recovery in egg production. PCR tests after 4 days of treatment with ivermectin were negative for NDV and ILTV.

These results are interesting and suggest a possible effect of ivermectin against NDV and ILTV in birds. More controlled studies are needed to confirm this hypothesis.
Defending as a unit: sex- and context-specific territorial defence in a duetting bird
Authors: Mentesana Lucia , Moiron Maria , Guedes Ernesto , Cavalli Enzo , Tassino Bettina , Adreani Nicolas M.
Published: July 2020

Behaviours such as territorial defence represent functionally integrated traits that underlie multiple behavioural variables such as physical and acoustic responses. Characterizing the multivariate structure of such traits is fundamental to understand their evolution. In bird species that form stable pair bonds and are territorial year-round, both sexes are expected to defend their territory; however, the role that each sex plays in defending their shared territory remains largely unknown. Evidence for the sex-roles during territorial defence is mixed and sex- and context-specific characterizations of territorial defence embracing the multivariate nature of the trait are currently lacking. Here we investigated sex- and context-specific variation in a hypothesised latent variable called “territorial defence” and tested whether duets were part of territorial defence in a wild population of rufous hornero (Furnarius rufus). To do so, we combined a simulated territorial intrusion approach during nest building and provisioning contexts with a structural equation modelling approach. Our results showed that, in males and females, the six measured behavioural variables were linked by a single latent trait, territorial defence, in both contexts. Flights over the decoy and duet songs were equally good proxies of territorial defence. Although males were defending more the territory than females, pair members showed a positive correlation in their behaviour. The structural equation modelling framework enabled us to capture a complex correlation pattern among behavioural variables, expanding upon a classic body of research on territorial defence. Thus, the combination of classical behavioural approaches with sophisticated statistical analyses brings new exciting possibilities to the field of behavioural ecology.

Significance statement

Territorial defence is a key behaviour in territorial species as it plays a major role in an individual’s reproductive success and survival. Additionally, territorial defence has been proposed as one possible evolutionary driver of duetting behaviour, one of the most fascinating vocal behaviours in birds. As behaviours are evolutionary characters, they must be studied in a multivariate framework. In this study we focused on characterizing territorial defence during a simulated territorial intrusion in an integrative manner using a classical territorial intrusion framework. We did so in male and female rufous horneros (Aves:Furnaridae) across two breeding contexts, while simultaneously testing theoretical predictions about the role of duetting behaviour as key part of territorial defence. Overall, our study provides for the first time a sex- and context-comparison of the multivariate, latent variable “territorial defence” in duetting birds, while highlighting the potential of combining field behavioural approaches with structural equation modelling.
Metabolic effects of aripiprazole and olanzapine multiple-dose treatment in healthy volunteers. Association with pharmacogenetics
Authors: Koller Dora , Almenara Susana , Mejía Gina , Saiz-Rodríguez Miriam , Zubiaur Pablo , Román Manuel , Ochoa Dolores , Navares-Gómez Marcos , Santos-Molina Elena , Pintos-Sánchez Elena , Abad-Santos Francisco
Published: July 2020

Background

Aripiprazole and olanzapine are atypical antipsychotics. Both drugs can induce metabolic changes, however, the metabolic side effects produced by aripiprazole are more benign.

Objectives

To evaluate if aripiprazole and olanzapine alter prolactin levels, lipid and glucose metabolism and hepatic, hematological, thyroid and renal function.

Methods

Twenty-four healthy volunteers received 5 daily oral doses of 10 mg aripiprazole and 5 mg olanzapine in a crossover randomized clinical trial and were genotyped for 51 polymorphisms in 17 genes by qPCR. Drug plasma concentrations were measured by LC-MS. The biochemical and hematological analyses were performed by enzymatic methods.

Results

Olanzapine induced hyperprolactinemia but not aripiprazole.DRD3Ser/Gly andABCB1rs10280101, rs12720067 and rs11983225 polymorphisms and CYP3A phenotype had an impact on plasma prolactin levels. C-peptide concentrations were higher after aripiprazole administration and were influenced byCOMTrs4680 and rs13306278 polymorphisms. Olanzapine and theUGT1A1rs887829 polymorphism were associated with elevated glucose levels. CYP3A poor metabolizers had increased insulin levels. Triglyceride concentrations were decreased due to olanzapine and aripiprazole treatment and were variable based on CYP3A phenotypes and theAPOC3rs4520 genotype. Cholesterol levels were also decreased and depended onHTR2Ars6314 polymorphism. All hepatic enzymes, platelet and albumin levels and prothrombin time were altered during both treatments. Additionally, olanzapine reduced the leucocyte count, aripiprazole increased free T4 and both decreased uric acid concentrations.

Conclusions

Short term treatment with aripiprazole and olanzapine had a significant influence on the metabolic parameters. However, it seems that aripiprazole provokes less severe metabolic changes.
Impact Analysis of SARS-CoV2 on Signaling Pathways during COVID19 Pathogenesis using Codon Usage Assisted Host-Viral Protein Interactions
Authors: Das Jayanta Kumar , Chakraborty Subhadip , Roy Swarup
Published: July 2020

Understanding the molecular mechanism of COVID19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The pathogen may target cell signaling pathways to disrupt the pathway genes’ regular activities, resulting in disease. Understanding the interaction mechanism of viral and host proteins involved in different signaling pathways may help decipher the attacking mechanism on the signal transmission during diseases, followed by discovering appropriate therapeutic solutions.

The expression of any viral gene depends mostly on the host translational machinery. Recent studies report the great significance of codon usage biases in establishing host-viral protein-protein interactions (PPI). Exploiting the codon usage patterns between a pair of co-evolved host and viral proteins may present novel insight into the host-viral protein interactomes during disease pathogenesis. Leveraging the codon usage pattern similarity (and dissimilarity), we propose a computational scheme to recreate the hostviral protein interaction network (HVPPI). We use seventeen (17) essential signaling pathways for our current work and study the possible targeting mechanism of SARS-CoV2 viral proteins on such pathway proteins. We infer both negatively and positively interacting edges in the network. We can find a relationship where one host protein may target by more than one viral protein.

Extensive analysis performed to understand the network topologically and the attacking behavior of the viral proteins. Our study reveals that viral proteins, mostly utilize codons, rare in the targeted host proteins (negatively correlated interaction). Among non-structural proteins, NSP3 and structural protein, Spike (S) protein, are the most influential proteins in interacting multiple host proteins. In ranking the most affected pathways, MAPK pathways observe to be worst affected during the COVID-19 disease. A good number of targeted proteins are highly central in host protein interaction networks. Proteins participating in multiple pathways are also highly connected in their own PPI and mostly targeted by multiple viral proteins.
Transcription inhibitors with XRE DNA-binding and cupin signal-sensing domains drive metabolic diversification in Pseudomonas
Authors: Trouillon Julian , Ragno Michel , Simon Victor , Attrée Ina , Elsen Sylvie
Published: July 2020

Transcription factors (TFs) are instrumental in the bacterial response to new environmental conditions. They can act as direct signal sensors and subsequently induce changes in gene expression leading to physiological adaptation. Here, by combining RNA-seq and DAP-seq, we studied a family of eight TFs in Pseudomonas aeruginosa. This family, encompassing TFs with XRE-like DNA-binding and cupin signal-sensing domains, includes the metabolic regulators ErfA, PsdR and PauR and five so far unstudied TFs. The genome-wide delineation of their regulons identified 39 regulatory interactions with genes mostly involved in metabolism. We found that the XRE-cupin TFs are inhibitors of their neighboring genes, forming local, functional units encoding proteins with functions in condition-specific metabolic pathways. The phylogenetic analysis of this family of regulators across the Pseudomonas genus revealed a wide diversity of such metabolic regulatory modules and identified species with potentially higher metabolic versatility. Numerous uncharacterized XRE-cupin TFs were found near metabolism-related genes, illustrating the need of further systematic characterization of transcriptional regulatory networks in order to better understand the mechanisms of bacterial adaptation to new environments.

IMPORTANCE

Bacteria of the Pseudomonas genus, including the major human pathogen P. aeruginosa, are known for their complex regulatory networks and high number of transcription factors, which contribute to their impressive adaptive ability. However, even in the most studied species, most of the regulators are still uncharacterized. With the recent advances in high-throughput sequencing methods, it is now possible to fill this knowledge gap and help understanding how bacteria adapt and thrive in new environments. By leveraging these methods, we provide an example of a comprehensive analysis of an entire family of transcription factors and bring new insights into metabolic and regulatory adaptation in the Pseudomonas genus.
Visual field reconstruction using fMRI-based techniques
Authors: Carvalho Joana , Invernizzi Azzurra , Martins Joana , Jansonius Nomdo M. , Renken Remco J. , Cornelissen Frans W.
Published: July 2020

Purpose

To evaluate the accuracy and reliability of functional magnetic resonance imaging (fMRI)-based techniques to assess the integrity of the visual field (VF).

Methods

We combined fMRI and neurocomputational models, i.e conventional population receptive field (pRF) mapping and a new advanced pRF framework “micro-probing” (MP), to reconstruct the visual field representations of different cortical areas. To demonstrate their scope, both approaches were applied in healthy participants with simulated scotomas (SS) and participants with glaucoma. For the latter group we compared the VFs obtained with standard automated perimetry (SAP) and via fMRI.

Results

Using SS, we found that the fMRI-based techniques can detect absolute defects in VFs that are larger than 3 deg, in single participants, and based on 12 minutes of fMRI scan time. Moreover, we found that MP results in a less biased estimation of the preserved VF. In participants with glaucoma, we found that fMRI-based VF reconstruction detected VF defects with a correspondence to SAP that was decent, reflected by the positive correlation between fMRI-based sampling density and SAP-based contrast sensitivity loss (SAP) r2=0.44, p=0.0002.This correlation was higher for our new approach (MP) compared to that for the conventional pRF analysis.

Conclusions

fMRI-based reconstruction of the VF enables the evaluation of vision loss and provides useful details on the properties of the visual cortex.

Translational Relevance

fMRI-based VF reconstruction provides an objective alternative to detect VF defects. It may either complement SAP, or could provide VF information in patients unable to perform SAP.
Neuroligin affects metastatic performance of CD66+ cells: Theoretical analysis of Multi-tissue RNA expressions through System modeling based Network mapping underin-vitroconstraints
Authors: Prakash Om
Published: July 2020

Present study deals with theoretical analysis of multi-tissue RNA expressions through system model based network mapping under the constraints ofin-vitroexperiments. Here, effect of Neuroligin was evaluated on the performance of metastatic behavior of CD66+ cells of human female reproductive cell lines. Total 10 genes and 14 cell lines were considered in the study. Clustering of cell lines was done on the basis of network mapping under the same homeostatic constraints. Neuroligin was found to affect metastatic performance of CD66+ cells. Two CD66+ cell lines hTERT-HME1 and SK-BR-3 were found to most effective, in similar manner as brain cell lines as U-138MG & U-87MG.
Optimized gene expression from bacterial chromosome by high-throughput integration and screening
Authors: Saleski Tatyana E. , Chung Meng Ting , Carruthers David N. , Khasbaatar Azzaya , Kurabayashi Katsuo , Lin Xiaoxia Nina
Published: July 2020

Chromosomal integration of recombinant genes is desirable compared to expression from plasmids due to increased stability, reduced cell-to-cell variability, and the elimination of antibiotics for plasmid maintenance. Here, we present a new approach for tuning pathway gene expression levels via random integrations and high-throughput screening. We demonstrate multiplexed gene integration and expression-level optimization for isobutanol production inEscherichia coli. The integrated strains could, with significantly lower expression levels than plasmid-based expression, produce high titers (10.0 ± 0.9 g/L isobutanol in 48 h) and yields (69 % of the theoretical maximum). Close examination of pathway expression in the top-performing, as well as other isolates, reveals the complexity of cellular metabolism and regulation, underscoring the need for precise optimization while integrating pathway genes into the chromosome. This new method for multiplexed pathway gene integration and expression optimization could be readily extended to a wide range of pathways and chassis to create robust and efficient production strains.
Single molecule dynamics at a bacterial replication fork after nutritional downshift
Authors: Hernández-Tamayo Rogelio , Schmitz Hannah , Graumann Peter L.
Published: July 2020

Replication forks must respond to changes in nutrient conditions, especially in bacterial cells. By investigating the single molecule dynamics of replicative helicase DnaC, DNA primase DnaG, and of lagging strand polymerase DnaE in the model bacteriumBacillus subtilisin response to transient replication blocks due to DNA damage, to inhibition of the replicative polymerase, or to downshift of serine availability, we show that proteins react differentially to the stress conditions. DnaG appears to be recruited to the forks by a diffusion and capture mechanism, becomes more statically associated after arrest of polymerase PolC, but binds much less often after fork blocks due to DNA damage or to nutritional downshift. These results indicate that binding of the alarmone ppGpp due to the stringent response prevents DnaG from binding to forks rather than blocking bound primase. Dissimilar behaviour of DnaG and of DnaE suggest that both proteins are recruited independently to the forks, rather than jointly. Turnover of all three proteins was increased during replication block after nutritional downshift, different from the situation due to DNA damage or polymerase inhibition, showing high plasticity of forks in response to different stress conditions. Forks persisted during all stress conditions, apparently ensuring rapid return to replication extension.
Pulsations and flows in tissues: two collective dynamics with simple cellular rules
Authors: Thiagarajan Raghavan , Bhat Alka , Salbreux Guillaume , Inamdar Mandar M. , Riveline Daniel
Published: July 2020

Collective motions of epithelial cellsin vivoare essential for morphogenesis in developmental biology. Tissues elongate, contract, flow, and oscillate, thus sculpting embryos. These tissue level dynamics are known, but the physical mechanisms at the cellular level are unclear, with various behaviors depending on the tissues and species. Moreover, investigations onin vitrotissue behavior usually focus on only one type of cell dynamics and use diverse theoretical approaches, making systematic comparisons between studies challenging. Here, we show that a single epithelial monolayer of Madin Darby Canine Kidney (MDCK) cells can exhibit two types of local tissue kinematics, pulsations and long range coherent flows. We analyzed these distinct motions by using quantitative live imaging. We also report that these motions can be controlled with internal and external cues such as specific inhibitors, and friction modulation of the substrate by microcontact printing method. We further demonstrate with a unified vertex model that both behaviors depend on the competition between velocity alignment and random diffusion of cell polarization. When alignment and diffusion are comparable, a pulsatile flow emerges, whereas the tissue undergoes long-range flows when velocity alignment dominates. We propose that environmental friction, acto-myosin distributions, and cell polarization kinetics are important in regulating the dynamics of tissue morphogenesis.
On the presence of elusive sea slugs and snails in the western Mediterranean (Mollusca: Gastropoda): new records
Authors: Salvador Xavier , Fernández-Vilert Robert , Moles Juan
Published: July 2020

Citizen science provides us with much information about charismatic taxa such as the opisthobranchs, thus contributing enormously to enlarging the geographic distribution of species. This study collects new records of elusive sea slugs and snails in the Western Mediterranean coast (especially in the Catalan coast and the French Mediterranean coast) and contributes to new ecological information regarding phenology, diet, and behaviour. Out of the 36 species reported here, 20 correspond to new records in the Catalan coast (NE Spain), three are new records of pelagic pteropods for the Spanish coast, and 10 other species are new records for the French Mediterranean coast. All records have been registered at the online database of the NGO named Catalan Opisthobranch Research Group (GROC). This study highlights the importance of sampling at night and, especially, in shallow, often-understudied waters, which usually gather high species diversity. We believe the high-quality pictures and related species’ information will serve future researchers and divers find and recognize these species in the Mediterranean basin.
Decoding the covert shift of spatial attention from electroencephalographic signals permits reliable control of a brain-computer interface
Authors: Reichert Christoph , Dürschmid Stefan , Bartsch Mandy V. , Hopf Jens-Max , Heinze Hans-Jochen , Hinrichs Hermann
Published: July 2020

Objective

One of the main goals of brain-computer interfaces (BCI) is to restore communication abilities in patients. BCIs often use event-related potentials (ERPs) like the P300 which signals the presence of a target in a stream of stimuli. The P300 and related approaches, however, are inherently limited, as they require many stimulus presentations to obtain a usable control signal. Many approaches depend on gaze-direction to focus the target, which is also not a viable approach in many cases, because eye movements might be impaired in potential users. Here we report on a BCI that avoids both shortcomings by decoding spatial target information, independent of gaze shifts.

Approach

We present a new method to decode from the electroencephalogram (EEG) covert shifts of attention to one out of four targets simultaneously presented in the left and right visual field. The task is designed to evoke the N2pc component – a hemisphere lateralized response, elicited over the occipital scalp contralateral to the attended target. The decoding approach involves decoding of the N2pc based on data-driven estimation of spatial filters and a correlation measure.

Main results

Despite variability of decoding performance across subjects, 22 out of 24 subjects performed well above chance level. Six subjects even exceeded 80% (cross-validated: 89%) correct predictions in a four-class discrimination task. Hence, the single-trial N2pc proves to be a component that allows for reliable BCI control. An offline analysis of the EEG data with respect to their dependence on stimulation time and number of classes demonstrates that the present method is also a workable approach for two-class tasks.

Significance

Our method extends the range of strategies for gaze-independent BCI control. The proposed decoding approach has the potential to be efficient in similar applications intended to decode ERPs.
Loss of Kinesin-8 improves the robustness of the acentrosomal spindle
Authors: Pineda-Santaella Alberto , Fernández-Castillo Nazaret , Sánchez-Gómez Ángela , Fernández-Álvarez Alfonso
Published: July 2020

Chromosome segregation in female meiosis is inherently error-prone, among other reasons, because the acentrosomal spindle assembles and segregates chromosomes without the major microtubule-organizing centres in eukaryotes, the centrosomes, which causes high rate of aneuploidy. The molecular basis underlying formation of acentrosomal spindles is not as well-understood as that of centrosomal spindles and, consequently, strategies to improve spindle robustness are difficult to address. Recently, we noticed during fission yeast meiosis the formation of unexpected microtubules arrays, independent of the spindle pole bodies (yeast centrosome equivalent), with ability to segregate chromosomes. Here, we establish such microtubules formation as bonafide self-assembled spindles that depend on the canonical microtubule crosslinker Ase1/PRC1, share similar structural polarity and harbour the microtubule polymerase Alp14/XMAP215, while being independent of conventional γ-tubulin-mediated nucleation mechanisms. Remarkably, acentrosomal spindle robustness was reinforced by deletion of the Klp6/Kinesin-8, which, consequently, led to a reduced meiotic aneuploidy rate. Our results enlighten the molecular basis of acentrosomal meiosis, a crucial event in understanding gametogenesis.
The influence of autotoxicity on the dynamics of vegetation spots
Authors: Iuorio Annalisa , Veerman Frits
Published: July 2020

Plant autotoxicity has proved to play an essential role in the behaviour of local vegetation. We analyse a reaction-diffusion-ODE model describing the interactions between vegetation, water, and autotoxicity. The presence of autotoxicity is seen to induce movement and deformation of spot patterns in some parameter regimes, a phe-nomenon which does not occur in classical biomass-water models. We aim to analytically quantify this novel feature, by studying travelling wave solutions in one spatial dimension. We use geometric singular perturbation theory to prove the existence of symmetric, stationary and non-symmetric, travelling pulse solutions, by constructing appropriate homoclinic orbits in the associated 5-dimensional dynamical system. In the singularly perturbed context, we perform an extensive scaling analysis of the dynamical system, identifying multiple asymptotic scaling regimes where (travelling) pulses may or may not be constructed. We show that, while the analytically constructed stationary pulse corresponds to its numerical counterpart, there is a discrepancy between the numerically observed travelling pulse and its analytical counterpart. Our findings indicate how the inclusion of an additional ODE may significantly influence the properties of classical biomass-water models of Klausmeier/Gray–Scott type.
A collection ofSerratia marcescensdiffering in their insect pathogenicity towardsManduca sextalarvae
Authors: Jensen Ellen C. , Katz Amburn Diana Sue , Schlegel Aimee Hultine , Nickerson Kenneth W.
Published: July 2020

We investigated the ability ofSerratia marcescensto killManduca sexta(tobacco/tomato hornworm) larvae following injection of ca. 5 × 105bacteria into the insect hemolymph. Fifteen bacterial strains were examined, including 12 non-pigmented clinical isolates from humans. They fell into 6 groups depending on the timing and rate at which they caused larval death. Relative insect toxicity was not correlated with pigmentation, colony morphology, biotype, motility, capsule formation, iron availability, surfactant production, swarming ability, antibiotic resistance, bacteriophage susceptibility, salt tolerance, nitrogen utilitization patterns, or the production of 4 exoenzymes: proteases, DNase, lipase, or phospholipase. There were marked differences in chitinase production, the types of homoserine lactone (HSL) quorum sensing molecules produced, and the blood agar hemolysis patterns observed. However, none of these differences correlated with the six insect larval virulence groups. Thus, the actual offensive or defensive virulence factors possessed by these strains remain unidentified. The availability of this set ofS. marcescensstrains, covering the full range from highly virulent to non-virulent, should permit future genomic comparisons to identify the precise mechanisms of larval toxicity.
Livestock grazing is associated with seasonal reduction in pollinator biodiversity and functional dispersion but cheatgrass invasion is not: variation in bee assemblages in a multi-use shortgrass prairie
Authors: Thapa-Magar Khum Bahadur , Davis Thomas Seth , Kondratieff Boris C.
Published: July 2020

Livestock grazing and non-native plant species affect rangeland habitats globally. These factors may have important effects on ecosystem services including pollination, yet, interactions between pollinators, grazing, and invasive plants are poorly understood. To address this, we tested the hypothesis that cattle grazing and site colonization by cheatgrass (Bromus tectorum) impact bee foraging and nesting habitats, and the biodiversity of wild bee communities, in a shortgrass prairie system. Bee nesting habitats (litter and wood cover) were marginally improved in non-grazed sites, though foraging habitat (floral cover and richness) did not differ among grazed, non-grazed, or cheatgrass colonized sites. However, floral cover was a good predictor of bee abundance and functional dispersion. Mean bee abundance, richness, diversity and functional diversity were significantly lower in cattle-grazed habitats than in cheatgrass-colonized or non-grazed habitats. Differences in bee diversity among habitats were pronounced early in the growing season (May) but by late-season (August) these differences eroded. Fourth-corner analysis revealed that sites with high floral cover tended to support large, social, polylectic bees; sites with high grass cover tended to support oligolectic solitary bees. Both cattle-grazed and cheatgrass-colonized sites were associated with lower abundances of above-ground nesting bees but higher abundance of below-ground nesters. We conclude that cheatgrass-invaded sites are not associated with reduced bee biodiversity or abundance, but cattle grazing was negatively associated with bee abundances and altered species composition. Although floral cover is an important predictor of bee assemblages, this was not impacted by grazing and our suggests that cattle likely impact bee communities through effects other than those mediated by forbs, including soil disturbance or nest destruction. Efforts aimed at pollinator conservation in prairie habitats should focus on managing cattle impacts early in the growing season to benefit sensitive bee species.
Enhanced BCR signalling inflicts early plasmablast and germinal centre B cell death
Authors: Yam-Puc JC , Zhang L , Maqueda-Alfaro RA , Garcia-Ibanez L , Zhang Y , Davies J , Senis YA , Snaith M , Toellner KM
Published: July 2020

It is still not clear how B-cell receptor (BCR) signalling intensity affects plasma cell and germinal centre (GC) B cell differentiation. We generated Cγ1Cre/+Ptpn6fl/flmice where SHP-1, a negative regulator of BCR signalling, is deleted rapidly after B cell activation. Although immunisation with T-dependent antigens increased BCR signalling, it led to plasma cells reduction and increased apoptosis. Dependent on the antigen, the early GC B cell response was equally reduced and apoptosis increased. At the same time, a higher proportion of GC B cells expressed cMYC, indicating increased GC B cell – Tfh cell interactions. While GC B cell numbers returned to normal at later stages, affinity maturation was suppressed in the long term. This confirms that BCR signalling not only directs affinity dependent B cell selection but also, without adequate Tfh cell help, can inflict cell death, which may be important for the maintenance of B cell tolerance.