bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty acid bioconversion in harpacticoid copepods in a changing environment: a transcriptomic approach
Authors: Boyen Jens , Fink Patrick , Mensens Christoph , Hablützel Pascal I. , De Troch Marleen
Published: June 2020

By 2100, global warming is predicted to significantly reduce the capacity of marine primary producers for long-chain polyunsaturated fatty acid (LC-PUFA) synthesis. Primary consumers such as harpacticoid copepods (Crustacea) might mitigate the resulting adverse effects on the food web by increased LC-PUFA bioconversion. Here, we present a high-quality de novo transcriptome assembly of the copepodPlatychelipus littoralis, exposed to changes in both temperature (+3°C) and dietary LC-PUFA availability. Using this transcriptome, we detected multiple transcripts putatively coding for LC-PUFA-bioconverting front-end fatty acid (FA) desaturases and elongases, and performed phylogenetic analyses to identify their relationship with sequences of other (crustacean) taxa. While temperature affected the absolute FA concentrations in copepods, LC-PUFA levels remained unaltered even when copepods were fed an LC-PUFA-deficient diet. While this suggests plasticity of LC-PUFA bioconversion withinP. littoralis, none of the putative front-end desaturase or elongase transcripts was differentially expressed under the applied treatments. Nevertheless, the transcriptome presented here provides a sound basis for future ecophysiological research on harpacticoid copepods.

This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids'.
Dynamics of diet-egg transfer of fatty acids in the teleost fish, red drum (
Sciaenops ocellatus
)
Authors: Hou Zhenxin , Faulk Cynthia K. , Fuiman Lee A.
Published: June 2020

Eggs of marine organisms are increasingly being recognized as important components of marine food webs. The degree to which egg fatty acid profiles reflect maternal diet fatty acid profiles, and therefore the value of fatty acids in eggs as trophic biomarkers, depends on the species' reproductive strategy and the extent of modification of ingested fatty acids. We measured the dynamics of transfer of recently ingested fatty acids to spawned eggs in a batch-spawning teleost, red drum (
Sciaenops ocellatus
). Results of 21 diet-shift experiments, from which the fatty acid profiles of the diets and eggs were compared, showed that 15 of 27 fatty acids measured (one saturated, two monounsaturated and 12 polyunsaturated fatty acids) in eggs were correlated with their levels in the recent diet, and the rate of incorporation into eggs was proportional to the magnitude of the diet shift. Large shifts in diet might occur naturally during spawning migrations or when prey communities vary over time. Results of this study indicate that fatty acids in red drum eggs can be useful for studying adult diet and exploring trophic linkages in marine systems.

This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers': evidence and significance of consumer modification of dietary fatty acids'.
Dietary fat concentrations influence fatty acid assimilation patterns in Atlantic pollock (Pollachius virens)
Authors: Budge Suzanne M. , Townsend Kathryn , Lall Santosh P. , Bromaghin Jeffrey F.
Published: June 2020

A key aspect in the use of fatty acids (FA) to estimate predator diets using quantitative FA signature analysis (QFASA) is the ability to account for FA assimilation through the use of calibration coefficients (CC). Here, we tested the assumption that CC are independent of dietary fat concentrations by feeding Atlantic pollock (Pollachius virens) three formulated diets with very similar FA proportions but different fat concentrations (5–9% of diet) for 20 weeks. CC calculated using FA profiles of diet and triacylglycerols in pollock liver were significantly different for the three diets. To test the robustness of diet estimates to these differences, we used the CC set derived from feeding the diet with the lowest fat concentration, published prey FA profiles and realistic diet estimates of pollock to construct ‘pseudo-predators'. Application of QFASA to each pseudo-predator using the three sets of CC and the same prey FA profiles resulted in diet estimate biases of twofold for major prey items and approximately fivefold for minor prey items. This work illustrates the importance of incorporating diets with fat concentrations that are similar to natural prey when conducting feeding experiments to calculate CC.

This article is part of the theme ‘The next horizons for lipids as ‘trophic biomarkers': evidence and significance of consumer modification of dietary fatty acids'.
Shifting systems: prerequisites for the application of quantitative fatty acid signature analysis in soil food webs
Authors: Kühn Jakob , Tobias Kevin , Jähngen Alexander , Ruess Liliane
Published: June 2020

Quantitative fatty acid signature analysis (QFASA) is widely used to investigate trophic interactions in marine ecosystems, as nutritionally importantω3 long-chain polyunsaturated fatty acids at the food web base allow tracing of their trophic transfer in the food chain. By contrast, the basal resources in soil food webs comprise a wider array of trophic markers, including branched-chain, cyclopropane as well as several mono- and polyunsaturated fatty acids. These diverse markers allow distinguishing between the three dominant soil carbon and energy channels, the root, bacterial and fungal pathway. QFASA has not been applied yet to soil ecosystems owing to the lack ofa prioridata to fit the model. The present work investigates the transfer of absolute and relative trophic marker fatty acids into Collembola as dominant representatives of the soil mesofauna. Three different species were fed on a variety of single diets characteristic for the green and brown food chain. Calibration coefficients were calculated and diet estimation trials for mixed diet set-ups were performed, using a library comprising 50 different resources. However, estimation of Collembola diet was only partially successful, identifying the main components, but not the correct relative proportions. Adjustments by fat content or diet group exclusion did not improve the results. Nonetheless, this work provides, to our knowledge, a first comprehensive dataset to translate the application of QFASA from marine to soil ecosystems.

This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids’.
Juvenile Dungeness crabs (Metacarcinus magister) selectively integrate and modify the fatty acids of their experimental diets
Authors: Thomas Michael D. , Schram Julie B. , Clark-Henry Zade F. , Yednock Bree K. , Shanks Alan L. , Galloway Aaron W. E.
Published: June 2020

Dungeness crabs (Metacarcinus magister) are ecologically and economically important in the coastal Northeast Pacific, yet relatively little is currently known about their feeding behaviour in the wild or their natural diet. Trophic biomarkers, such as fatty acids (FA), can be used to reveal trophic interactions. We used two feeding experiments to assess differences in FA composition of juvenile crabs fed different known foods to evaluate how they modify and integrate dietary FA into their own tissues and determine whether crab FA reflect diet changes over a six-week period. These experimental results were then compared with the FA signatures of wild caught juvenile crab with undetermined diets. We found that juvenile Dungeness crabs fed different foods assimilated dietary FA into their tissues and were distinct in their FA signatures when analysed with multivariate statistics. Experimentally fed juvenile crabs contained greater proportions of the most abundant long-chain polyunsaturated fatty acids (LCPUFA, >C20) than their foods. Crabs fed foods lacking in LCPUFA, particularly DHA (22:6ω3, docosahexaenoic acid), did not survive or grew slower than crabs fed other foods. This suggests that LCPUFA are physiologically important for this species and indicates biosynthesis of these FA does not occur or is not sufficient to meet their needs.

This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids’.
MifS, a DctB family histidine kinase, is a specific regulator of α-ketoglutarate response in Pseudomonas aeruginosa PAO1
Authors: Sarwar Zaara , Wang Michael X. , Lundgren Benjamin R. , Nomura Christopher T.
Published: June 2020

The C5-dicarboxylate α-ketoglutarate (α-KG) is a preferred nutrient source for the opportunistic pathogen

Pseudomonas aeruginosa

. However, very little is known about how

P. aeruginosa

detects and responds to α-KG in the environment. Our laboratory has previously shown that the MifS/MifR two-component signal transduction system regulates α-KG assimilation in

P. aeruginosa

PAO1. In an effort to better understand how this bacterium detects α-KG, we characterized the MifS sensor histidine kinase. In this study we show that although MifS is a homologue of the C4-dicarboxylate sensor DctB, it specifically responds to the C5-dicarboxylate α-KG. MifS activity increased >10-fold in the presence of α-KG, while the related C5-dicarboxylate glutarate caused only a 2-fold increase in activity. All other dicarboxylates tested did not show any significant effect on MifS activity. Homology modelling of the MifS sensor domain revealed a substrate binding pocket for α-KG. Using protein modelling and mutational analysis, we identified nine residues that are important for α-KG response, including one residue that determines the substrate specificity of MifS. Further, we found that MifS has a novel cytoplasmic linker domain that is required for α-KG response and is probably involved in signal transduction from the sensor domain to the cytoplasmic transmitter domain. Until this study, DctB family histidine kinases were known to only respond to C4-dicarboxylates. Our work shows that MifS is a novel member of the DctB family histidine kinase that specifically responds to α-KG.
Asip(Agouti-signaling protein) aggression gene regulate auditory processing genes in mice
Authors: Mickael Alexandra , Klimovich Pavel , Henckel Patrick , Kubick Norwin , Mickael Michel E
Published: June 2020

Covid-19 strategy of lockdown has affected the lives of millions. The strict actions to enclose the epidemic have exposed many households to inner tensions. Domestic violence has been reported to increase during the lockdown. However, the reasons for this phenomenon have not been thoroughly investigated. Melanocortin GPCRs family contribution to aggression is well documented. ASIP (nonagouti) gene plays a vital role in regulating the melanocortin GPCRs family function, and it is responsible for regulating aggression in mice. We conducted a selection analysis of ASIP. We found that it negatively purified from Shark to humans. In order to better asses the effect of this gene in mammals, we performed RNA-seq analysis of a knockout of an ASIP crisper-cas mouse model. We found that ASIP KO in mice upregulates several genes controlling auditory function, includingPhox2b,Mpk13,Fat2, Neurod2, Slc18a3, Gon4l Gbx2, Slc6a3(Dat1) Aldh1a7 Tyrp1 and Lbx1. Interestingly, we found thatSlc6a5, andLamp5as well asIL33, which are associated with startle disease, are also upregulated in response to knocking out ASIP. These findings are indicative of a direct autoimmune effect between aggression-associated genes and startle disease. Furthermore, in order to validate the link between aggression and auditory inputs processing. We conducted psychological tests of persons who experienced lockdown. We found that aggression has risen by 16 % during the lockdown. Furthermore, 3% of the subjects interviewed reported a change in their hearing abilities. Our data shed light on the importance of the auditory input in aggression and open perceptions to interpret how hearing and aggression interact at the molecular neural circuit level.
Fungal dual-domain LysM effectors undergo chitin-induced intermolecular, and not intramolecular, dimerization
Authors: Tian Hui , Fiorin Gabriel L. , Kombrink Anja , Mesters Jeroen R. , Thomma Bart P.H.J.
Published: June 2020

Chitin is a homopolymer of β-(1,4)-linkedN-acetyl-D-glucosamine (GlcNAc) and a major structural component of fungal cell walls. In plants, chitin acts as a microbe-associated molecular pattern (MAMP) that is recognized by lysin motif (LysM)-containing plant cell surface-localized pattern recognition receptors (PRRs) that activate a plethora of downstream immune responses. In order to deregulate chitin-induced plant immunity and successfully establish infection, many fungal pathogens secrete LysM domain-containing effector proteins during host colonization. It was previously shown that the LysM effector Ecp6 from the tomato leaf mould fungusCladosporium fulvumcan outcompete plant PRRs for chitin binding because two of its three LysM domains cooperate to form a composite groove with ultra-high (pM) chitin-binding affinity. However, most functionally characterized LysM effectors contain only two LysMs, includingMagnaporthe oryzaeMoSlp1,Verticillium dahliaeVd2LysM, andColletotrichum higginsianumChElp1 and ChElp2. Here, we performed modelling, structural and functional analyses to investigate whether such dual-domain LysM effectors can also form ultra-high chitin-binding affinity grooves through intramolecular LysM dimerization. However, our study suggests that intramolecular LysM dimerization does not occur. Rather, our data support the occurrence of intermolecular LysM dimerization for these effectors, associated with a significantly lower chitin binding affinity than monitored for Ecp6. Interestingly, the intermolecular LysM dimerization allows for the formation of polymeric complexes in the presence of chitin. Possibly, such polymers may precipitate at infection sites in order to eliminate chitin oligomers, and thus suppress the activation of chitin-induced plant immunity.
E-cigarette, combustible, and smokeless tobacco product use combinations among youth in the United States, 2014-2019
Authors: Tam Jamie
Published: June 2020

Introduction

Youth e-cigarette use has been rising, however U.S. prevalence data are generally reported without disaggregating by individuals’ use of other tobacco products. It is not clear how the proportion of youth e-cigarette users naïve to all combustible tobacco is changing.

Methods

Annual prevalence estimates of ever and current (defined as past 30-day use) tobacco use prevalence by school type are reported using the 2014-2019 National Youth Tobacco Surveys (NYTS) with mutually exclusive categories of e-cigarette, smokeless tobacco, and/or combustible tobacco product use. T-tests were used to compare annual estimates with the preceding year. The annual percent change (APC) for each category from 2014-2018 were analyzed using JoinPoint regression. Data for 2019 were reported separately due to the change in survey format from paper to electronic.

Results

Current use of only e-cigarettes among HS students who never used combustible tobacco increased significantly from 2014-2018 (APC = +42.4%, 95% CI: 0.7, 101.3); by 2019, prevalence peaked at 9.2% (95% CI: 8.2, 10.2) among never combustible users and 8.3% (95% CI: 7.3, 9.3) among former combustible users. This coincided with significant declines in use of only combustible tobacco (APC=-14.5%, 95% CI: −18.3, −10.5).

Conclusions

Use of only e-cigarettes among US youth with no history of combustible tobacco use has increased substantially over time, even as combustible tobacco use continues to plummet. Of the 17.5% (95% CI: 15.7, 19.0) of HS students who currently used only e-cigarettes (but not other tobacco) in 2019, more than half have no history of combustible tobacco use.
Critical Questions when Interpreting Coronavirus PCR Diagnostics
Authors: Durner Jürgen , Burggraf Siegfried , Czibere Ludwig , Fleige Tobias , Spannagel Michael , Watts David C , Becker Marc
Published: June 2020

The results of PCR measurements are regarded as unquestionable. This statement must be put into perspective. This relativization is particularly important in connection with the interpretation of SARS-CoV-2 results. Members of the critical infrastructure, such as nurses, may be quarantined although this is not necessary and are therefore missing from patient care. With our small but impressive comparison of methods and transport media for SARS-CoV-2, we not only show the different sensitivity of common routine systems and media in laboratory medicine. Further, we would like to inform clinically working physicians, who are not familiar with the technical weaknesses of the PCR investigation, about gaps and present solutions for their daily work.
Genome sequencing of the first SARS-CoV-2 reported from patients with COVID-19 in Ecuador
Authors: Márquez Sully , Prado-Vivar Belén , José Guadalupe Juan , Gutierrez Bernardo , Jibaja Manuel , Tobar Milton , Mora Francisco , Gaviria Juan , García María , Espinosa Franklin , Ligña Edison , Reyes Jorge , Barragán Verónica , Rojas-Silva Patricio , Trueba Gabriel , Grunauer Michelle , Cárdenas Paúl
Published: June 2020

SARS-CoV-2, the etiological agent of COVID-19 was first described in Wuhan in December 2019 and has now spread globally. Ecuador was the second country in South America to report confirmed cases. The first case reported in Quito, the capital city of Ecuador, was a tourist who came from the Netherlands and presented symptoms on March 10th, 2020 (index case). In this work we used the MinION platform (Oxford Nanopore Technologies) to sequence the metagenome of the bronchoalveolar lavage (BAL) from this case reported, and subsequently we sequenced the whole genome of the index case and other three patients using the ARTIC network protocols. Our data from the metagenomic approach confirmed the presence of SARS-CoV-2 coexisting with pathogenic bacteria suggesting coinfection. Relevant bacteria found in the BAL metagenome were Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus and Chlamydia spp. Lineage assignment of the four whole genomes revealed three different origins. The variant HEE-01 was imported from the Netherlands and was assigned to B lineage, HGSQ-USFQ-018, belongs to the B.1 lineage showing nine nucleotide differences with the reference strain and grouped with sequences from the United Kingdom, and HGSQ-USFQ-007 and HGSQ-USFQ-010 belong to the B lineage and grouped with sequences from Scotland. All genomes show mutations in their genomes compared to the reference strain, which could be important to understand the virulence, severity and transmissibility of the virus. Our findings also suggest that there were at least three independent introductions of SARS-CoV-2 to Ecuador.

IMPORTANCE

COVID-19, an infectious disease caused by SARS-CoV-2, has spread globally including Latin American countries including Ecuador. The first strain of SARS-CoV-2 sequenced was from Wuhan, which is considered as the reference strain. There were no data about the SARS-CoV-2 lineages in Ecuador, and the purpose of this study was to find out the origin of the different lineages circulating in the population. We also were interested in the mutations present in these genomes as they can influence virulence, transmission and infectivity.
Proteomic profiling of soft tissue sarcomas with SWATH mass spectrometry
Authors: Milighetti Martina , Krasny Lukas , Lee Alex T.J. , McCarthy Frank , Morani Gabriele , Szecsei Cornelia , Chen Yingtong , Fisher Cyril , Judson Ian , Thway Khin , Maggie C.U. Cheang , Jones Robin L. , Huang Paul H.
Published: June 2020

Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers. While large-scale genomic and epigenomic profiling of STS have been undertaken, proteomic analysis has thus far been limited. Here we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n=36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma). We quantified 2951 proteins across all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma. We further identified a subgroup of STS cases (independent of histological subtype) that have a distinct expression profile in a panel of 133 proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.
Optimal size of sample pooling for RNA pool testing: an avant-garde for scaling up SARS CoV 2 testing
Authors: Arvind Khodare , Abhishek Padhi , Ekta Gupta , Reshu Agarwal , Shantanu Dubey , Sarin SK
Published: June 2020

Introduction

Timely diagnosis is essential for the containment of the disease and breaks in the chain of transmission of SARS-CoV-2. The present situation demands countries to scale up their testing and design innovative strategies to conserve diagnostic kits and reagents. The pooling of samples saves time, manpower, and most importantly diagnostic kits and reagents. In the present study, we tried to define the pool size that could be applied with acceptable confidence for testing.

Material and methods

We used repeatedly tested positive clinical sample elutes having different levels of SARS CoV 2 RNA and negative sample elutes to prepare seven series of 11 pools each, having pool sizes ranging from 2 to 48 samples to estimate the optimal pool size. Each pool had one positive sample elute in different compositions. All the pools were tested by SARS CoV 2 RT-qPCR.

Results

Out of the 77 pools, only 53 (68.8%) were found positive. The sensitivity of pools of 2 to 48 samples was decreased from 100% (95% CL; 98.4-100) to 41.41% (95% CL; 34.9-48.1). The maximum size of the pool with acceptable sensitivity (>95%) was found to be of 6 samples. For the pool size of 6 samples, the sensitivity was 97.8% and the efficiency of pooling was 0.38.

Conclusion

The pooling of samples is a practical way for scaling up testing and ultimately containing the further spread of the COVID-19 pandemic.
When is SARS-CoV-2 in your shopping list?
Authors: Hernandez-Mejia Gustavo , Hernandez-Vargas Esteban A.
Published: June 2020

The pandemic of coronavirus disease 2019 (COVID-19) has caused, by May 24th 2020, more than 5.3 million confirmed cases worldwide. The necessity of keeping open and accessible public commercial establishments such as supermarkets or pharmacies increases during the pandemic provided that distancing rules and crowd control are satisfied.

Herein, using agent-based models, we explore the potential spread of the novel SARS-CoV-2 considering the case of a small size supermarket. For diverse distancing rules and number of simultaneous users (customers), we question flexible and limited movement policies, guiding the flow and interactions of users in place. Results indicate that a guided, limited in movement and well-organized policy combined with a distance rule of at least 1 m between users and a small number of them (15) may aid in the mitigation of potential new contagions in more than 90% compared to the usual policy of flexible movement with more users (30) which may reach up to 64% of mitigation of potential new infections under the same distancing conditions. This study may guide novel strategies for the mitigation of the current COVID-19 pandemic, at any stage, and prevention of future outbreaks of SARS-CoV-2 or related viruses.
COVID-19 Deaths: Which Explanatory Variables Matter the Most?
Authors: Riley Pete , Riley Allison , Turtle James , Ben-Nun Michal
Published: June 2020

Summary

As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads around the World, many questions about the disease are being answered; however, many more remain poorly understood. Although the situation is rapidly evolving, with datasets being continually corrected or updated, it is crucial to understand what factors may be driving transmission through different populations. While studies are beginning to highlight specific parameters that may be playing a role, few have attempted to thoroughly estimate the relative importance of these disparate variables that likely include: climate, population demographics, and imposed state interventions. In this report, we compiled a database of more than 28 potentially explanatory variables for each of the 50 U.S. states through early May 2020. Using a combination of traditional statistical and modern machine learning approaches, we identified those variables that were the most statistically significant, and, those that were the most important. These variables were chosen to be fiduciaries of a range of possible drivers for COVID-19 deaths in the USA. We found that population-weighted density (PWD), some “stay at home” metrics, monthly temperature and precipitation, race/ethnicity, and chronic low-respiratory death rate, were all statistically significant. Of these, PWD and mobility metrics dominated. This suggests that the biggest impact on COVID-19 deaths was, at least initially, a function of where you lived, and not what you did. However, clearly, increasing social distancing has the net effect of (at least temporarily) reducing the effective PWD. Our results strongly support the idea that the loosening of “lock-down” orders should be tailored to the local PWD. In contrast to these variables, while still statistically significant, race/ethnicity, health, and climate effects could only account for a few percent of the variability in deaths. Where associations were anticipated but were not found, we discuss how limitations in the parameters chosen may mask a contribution that might otherwise be present.
Structural and functional synaptic plasticity induced by convergent synapse loss requires co-innervation in the Drosophila neuromuscular circuit
Authors: Wang Yupu , Lobb-Rabe Meike , Ashley James , Carrillo Robert A.
Published: June 2020

Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other’s structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is theDrosophilalarval neuromuscular junction where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s motor neurons. We surveyed synapses on multiple muscles for this reason. Here, we identified a cell-specific promoter to ablate 1s MNs after innervation. Additionally, we genetically blocked 1s innervation. Then we measured 1b MN structural and functional responses using electrophysiology and microscopy. For all muscles, 1s MN ablation resulted in 1b MN synaptic expansion and increased basal neurotransmitter release. This demonstrates that 1b MNs can compensate for the loss of convergent inputs. However, only a subset of 1b MNs showed compensatory evoked activity, suggesting spontaneous and evoked plasticity are independently regulated. Finally, we usedDIP-αmutants that block 1s MN synaptic contacts; this eliminated robust 1b synaptic plasticity, raising the possibility that muscle co-innervation may define an activity “set point” that is referenced when subsequent synaptic perturbations occur. This model can be tested in more complex circuits to determine if co-innervation is fundamental for input-specific plasticity.

SIGNIFICANCE STATEMENT

In complex neural circuits, multiple converging inputs contribute to the output of each target cell. Thus, each input must be regulated, but whether adjacent inputs contribute to this regulation is unclear. To examine input-specific synaptic plasticity in a structurally and functionally tractable system, we turn to theDrosophilaneuromuscular circuit. Each muscle is innervated by a unique pair of motor neurons. Removal of one neuron after innervation causes the adjacent neuron to increase synaptic outgrowth and functional output. However, this is not a general feature since each MN differentially compensates. Also, robust compensation requires co-innervation by both neurons. Understanding how neurons respond to perturbations in adjacent neurons will provide insight into nervous system plasticity in both healthy and diseased states.
Allelic Variation ofMYB10is the Major Force Controlling Natural Variation of Skin and Flesh Color in Strawberry (Fragariaspp.) fruit
Authors: Castillejo Cristina , Waurich Veronika , Wagner Henning , Ramos Rubén , Oiza Nicolás , Muñoz Pilar , Triviño Juan C. , Caruana Julie , Liu Zhongchi , Cobo Nicolás , Hardigan Michael A. , Knapp Steven J. , Vallarino José G. , Osorio Sonia , Martín-Pizarro Carmen , Posé David , Toivainen Tuomas , Hytönen Timo , Oh Youngjae , Barbey Christopher R. , Whitaker Vance M. , Lee Seonghee , Olbricht Klaus , Sánchez-Sevilla José F. , Amaya Iraida
Published: June 2020

Anthocyanins are the principal color-producing compounds synthesized in developing fruits of strawberry (Fragariaspp.). Substantial natural variation in color have been observed in fruits of diploid and octoploid accessions, resulting from distinct accumulation and distribution of anthocyanins in fruits. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among whichMYB10has been shown as the main activator in strawberry fruit. Here, we show thatMYB10mutations cause most of the anthocyanin variation observed in diploid woodland strawberry(F. vesca)and octoploid cultivated strawberry (F. ×ananassa). Using a mapping-by-sequencing approach, we identified agypsy-transposon insertion inMYB10that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruitedF. vescaecotype. Two additional loss-of-functionMYB10mutations were identified among geographically diverse white-fruitedF. vescaecotypes. Genetic and transcriptomic analyses in octoploidFragaria spp.revealed thatFaMYB10-2,one of threeMYB10homoeologs identified, residing in theF. iinumae-derivedsubgenome, regulates the biosynthesis of anthocyanins in developing fruit. Furthermore, independent mutations inMYB10-2are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon(FaEnSpm-2)insertion in theMYB10-2promoter of red-fleshed accessions that was associated with enhanced expression and anthocyanin accumulation. Our findings suggest that putative cis regulatory elements provided byFaEnSpm-2are required for high and ectopicMYB10-2expression and induction of anthocyanin biosynthesis in fruit flesh. We developedMYB10-2(sub-genome) specific DNA markers for marker-assisted selection that accurately predicted anthocyanin phenotypes in octoploid segregating populations.
Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Authors: Zhou Daming , Duyvesteyn Helen ME , Chen Cheng-Pin , Huang Chung-Guei , Chen Ting-Hua , Shih Shin-Ru , Lin Yi-Chun , Cheng Chien-Yu , Cheng Shu-Hsing , Huang Yhu-Chering , Lin Tzou-Yien , Ma Che , Huo Jiandong , Carrique Loic , Malinauskas Tomas , Ruza Reinis R , Shah Pranav NM , Tan Tiong Kit , Rijal Pramila , Donat Robert F. , Godwin Kerry , Buttigieg Karen , Tree Julia , Radecke Julika , Paterson Neil G , Supasa Piyasa , Mongkolsapaya Juthathip , Screaton Gavin R , Carroll Miles W. , Jaramillo Javier G. , Knight Michael , James William , Owens Raymond J , Naismith James H. , Townsend Alain , Fry Elizabeth E , Zhao Yuguang , Ren Jingshan , Stuart David I , Huang Kuan-Ying A.
Published: June 2020

The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KDof 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.
Spike–frequency adaptation is modulated by interacting currents in an Hodgkin-Huxley-type model: Role of the Na,K–ATPase
Authors: Jolivet Renaud Blaise , Magistretti Pierre J.
Published: June 2020

Spike–frequency adaptation is a prominent feature of spiking neurons. Using a Hodgkin–Huxley–type model, we studied adaptation originating from the Na,K–ATPase electrogenic pump and its evolution in presence of a medium–duration calcium–dependent potassium channel. We found that the Na,K–ATPase induces spike–frequency adaptation with a time constant of up to a few seconds and interacts with the calcium–dependent potassium current through the output frequency, yielding a very typical pattern of instantaneous frequencies. Because channels responsible for spike–frequency adaptation can interact with each other, our results suggest that their meaningful time courses and parameters can be difficult to measure experimentally. To circumvent this problem, we developed a simple phenomenological model that captures the interaction between currents and allows the direct evaluation of the underlying biophysical parameters directly from the frequency vs. current curves. Finally, we found that for weak stimulations, the pump induces phasic spiking and linearly converts the stimulus amplitude in a finite number of spikes acting like an inhibitory spike–counter. Our results point to the importance of considering interacting currents involved in spike–frequency adaptation collectively rather than as isolated elements and underscore the importance of sodium as a messenger for long–term signal integration in neurons. Within this context, we propose that the Na,K–ATPase plays an important role and show how to recover relevant biological parameters from adapting channels using simple electrophysiological measurements.
Quantitative genetic architecture of adaptive phenology traits in the deciduous tree,Populus trichocarpa(Torr. & Gray)
Authors: Richards Thomas J , Karacic Almir , Apuli Rami-Petteri , Weih Martin , Ingvarsson Pär K. , Rönnberg-Wästljung Ann Christin
Published: June 2020

In a warming climate, the ability to accurately predict and track shifting environmental conditions will be fundamental for plant survival. Environmental cues define the transitions between growth and dormancy as plants synchronise development with favourable environmental conditions, however these cues are predicted to change under future climate projections which may have profound impacts on tree survival and growth. Here, we use a quantitative genetic approach to estimate the genetic basis of spring and autumn phenology inPopulus trichocarpato determine this species capacity for climate adaptation. We measured bud burst, leaf coloration, and leaf senescence traits across two years (2017-2018) and combine these observations with measures of lifetime growth to determine how genetic correlations between phenology and growth may facilitate or constrain adaptation. Timing of transitions differed between years, although we found strong cross year genetic correlations in all traits, suggesting that genotypes respond in consistent ways to seasonal cues. Spring and autumn phenology were correlated with lifetime growth, where genotypes that burst leaves early and shed them late had the highest lifetime growth. We also identified substantial heritable variation in the timing of all phenological transitions (h2= 0.5-0.8) and in lifetime growth (h2= 0.8). The combination of abundant additive variation and favourable genetic correlations in phenology traits suggests that cultivated varieties ofP. trichocarpahave the capability to create populations which may adapt their phenology to climatic changes without negative impacts on growth.
Enlarged Ingroup Effect: How a Shared Culture Shapes In-Group Perception
Authors: Rigo Paola , Ragunath Bindiya L. , Bornstein Marc H. , Esposito Gianluca
Published: June 2020

Increasing levels of migration and constant redefinition of a ‘sense of belonging’ characterize modern societies. Thus, social perception of people from different ethnicities as in-group or out-group members is influenced by a shared culture that might go beyond ethnicity. Using functional magnetic resonance imaging, we aim to study how sharing a common culture changes the social perceptions of in-groups and out-groups. We presented same- and different-race faces to young adults living in an integrated multicultural society. Same- and different-race faces were primed by images of environmental context that promotes identification with the participants’ ethnicity or a common shared culture.

We found that same and different-race faces recruit similar brain networks only when associated with an environmental context, which promoted identification with a common shared culture. These results support a possible emergent phenomenon in multicultural societies that we call enlarged multi-ethnic in-group effect, which may form the basis of a potential new way to categorize oneself and others in terms of membership.
Neurotransmitter Classification from Electron Microscopy Images at Synaptic Sites in Drosophila Melanogaster
Authors: Eckstein Nils , Bates Alexander Shakeel , Champion Andrew , Du Michelle , Yin Yijie , Schlegel Philipp , Lu Alicia Kun-Yang , Rymer Thomson , Finley-May Samantha , Paterson Tyler , Parekh Ruchi , Dorkenwald Sven , Matsliah Arie , Yu Szi-Chieh , McKellar Claire , Sterling Amy , Eichler Katharina , Costa Marta , Seung Sebastian , Murthy Mala , Hartenstein Volker , Jefferis Gregory S.X.E. , Funke Jan
Published: June 2020

High-resolution electron microscopy of nervous systems enables the reconstruction of connectomes. A key piece of missing information from connectomes is the synaptic sign. We show that forD. melanogaster, artificial neural networks can predict the transmitter type released at synapses from electron micrographs and thus add putative signs to connections. Our network discriminates between six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) with an average accuracy of 87%/94% for synapses/entire neurons. We developed an explainability method to reveal which features our network is using and found significant ultrastructural differences between the classical transmitters. We predict transmitters in two connectomes and characterize morphological and connection properties of tens of thousands of neurons classed by predicted transmitter expression. We find that hemilineages inD. melanogasterlargely express only one fastacting transmitter among their neurons. Furthermore, we show that neurons with different transmitters may differ in features like polarization and projection targets.
Ethylene-triggered subcellular trafficking of CTR1 enhances the response to ethylene gas
Authors: Lee Han Yong , Seo Dong Hye , Park Hye Lin , Bakshi Arkadipta , Park Chanung , Kieber Joseph J. , Binder Brad M. , Yoon Gyeong Mee
Published: June 2020

Ethylene gas controls plant growth and stress responses. Ethylene-exposed dark-grown seedlings exhibit dramatic growth reduction, yet the seedlings rapidly return to the basal growth rate when ethylene gas is removed. However, the underlying mechanism governing this reversible acclimation of dark-grown seedlings to ethylene remains enigmatic. Here, we report that ethylene triggers the translocation of the Raf-like protein kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), a negative regulator of ethylene signaling, from the endoplasmic reticulum to the nucleus. Nuclear-localized CTR1 stabilizes the ETHYLENE-INSENSITIVE3 (EIN3) transcription factor via interaction with the EIN3-BINDING F-box (EBF) proteins, thus enhancing the ethylene response and delaying growth recovery. These findings uncover a mechanism of the ethylene signaling pathway that links the spatiotemporal dynamics of cellular signaling components to organismal responses.
Temporal hierarchy of intrinsic neural timescales converges with spatial core-periphery organization
Authors: Golesorkhi Mehrshad , Gomez-Pilar Javier , Tumati Shankar , Fraser Maia , Northoff Georg
Published: June 2020

The human cortex exhibits intrinsic neural timescales that shape a temporal hierarchy. Whether this temporal hierarchy follows the spatial hierarchy of its topography namely the core-periphery organization remains an open issue. Using Magnetoencephalography data, we investigate intrinsic neural timescales during rest and task states; we measure the autocorrelation window in short (ACW-50) and, introducing a novel variant, long (ACW-0) windows. We demonstrate longer ACW-50 and ACW-0 in networks located at the core compared to those at the periphery with rest and task states showing a high ACW correlation. Calculating rest-task differences, i.e., subtracting the shared core-periphery organization, reveals task-specific ACW changes in distinct networks. Finally, employing kernel density estimation, machine learning, and simulation, we demonstrate that ACW-0 exhibits better prediction in classifying a region’s time window as core or periphery. Overall, our findings provide fundamental insight into how the human cortex’s temporal hierarchy converges with its spatial core-periphery hierarchy.
Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
Authors: Tenthorey Jeannette L. , Young Candice , Sodeinde Afeez , Emerman Michael , Malik Harmit S.
Published: June 2020

Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving “v1” loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via single adaptive substitutions. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses.
Quantifying Numerical and Spatial Reliability of Amygdala and Hippocampal Subdivisions in FreeSurfer
Authors: Kahhale Isabella , Buser Nicholas J , Madan Christopher R. , Hanson Jamie L.
Published: June 2020

On-going, large-scale neuroimaging initiatives can aid in uncovering neurobiological causes and correlates of poor mental health, disease pathology, and many other important conditions. As projects grow in scale with hundreds, even thousands, of individual participants and scans collected, quantification of brain structures by automated algorithms is becoming the onlytrulytractable approach. Here, we assessed the spatial and numerical reliability for newly deployed automated segmentation of hippocampal subfields and amygdala nuclei in FreeSurfer 7. In a sample of participants with repeated structural imaging scans (N=923), we found numerical reliability (as assessed by intraclass correlations, ICCs) was reasonable: ∼95% of hippocampal subfields have “excellent” numerical reliability (ICCs≥0.90), however, only 67% of amygdala subnuclei met this same threshold. Spatial reliability was similarly reasonable, with 58% of hippocampal subfields and 44% of amygdala subnuclei having Dice coefficients≥0.70. Notably, multiple regions had poor numerical and/or spatial reliability. We also examined correlations between spatial reliability and person-level factors (e.g., participant age; T1 image quality). Both sex and image scan quality were related to variations in spatial reliability metrics. Examined collectively, our work suggests caution should be exercised for a few hippocampal subfields and amygdala nuclei with more variable reliability.
Bacteria on steroids: the enzymatic mechanism of an NADH-dependent dehydrogenase that regulates the conversion of cortisol to androgen in the gut microbiome
Authors: Bernardi Rafael C. , Doden Heidi L. , Melo Marcelo C.R. , Devendran Saravanan , Pollet Rebecca M. , Mythen Sean M. , Bhowmik Shiva , Lesley Scott A. , Cann Isaac , Luthey-Schulten Zaida , Koropatkin Nicole M. , Ridlon Jason M.
Published: June 2020

The ability to metabolize both endogenous and exogenous compounds to a variety of metabolic products is not exclusive to our human cells. In fact, the bacterial communities that inhabit our digestive system are responsible for a network of steroid transformations that can produce hormones in the gut, which are then absorbed to act in the host. These communities have been shown to impact our health in numerous ways, affecting disease predisposition, pathogenesis, physical fitness, and dietary responsiveness. Steroid biotransformations by gut bacteria are predicted to impact the host endocrine system. A particular set of transformations facilitated by microbial enzymes has been shown to result in the formation of 11-oxy-androgens from host-derived cortisol. Since androgens have been implicated in disease and immune modulations, understanding the structure and catalytic mechanism of enzymes involved in cortisol metabolism is a key step to hasten the development of strategies that reduce the formation of disease-promoting bioactive steroids in certain individuals. Here, we combine experimental and computational techniques to describe DesC, an enzyme capable of creating 20α-dihydrocortisol and siphoning cortisol away from pathways that produce androgens. DesC diverges significantly from previously described bacterial and eukaryotic counterparts, catalyzing an NADH-dependent 20α-hydroxysteroid dehydrogenase reaction but presenting little sequence and structure similarity to them. The structural information obtained by X-ray crystallography and hybrid QM/MM simulations, validated through mutagenesis studies, show the reaction occurs through a multi-step proton relay mechanism. Free energy calculations were then used to describe the kinetics of the reaction mechanism. The mechanistic information presented here can be employed in the development of therapeutics to divert microbial pathways away from disease-promoting steroids.