bluuebunny/crossref_metadata_2025 huggingface dataset:
Potent neutralization antibodies induced by a recombinant trimeric Spike protein vaccine candidate containing PIKA adjuvant for COVID-19
Authors: Tong Jiao , Zhu Chenxi , Lai Hanyu , Feng Chunchao , Zhou Dapeng
Published: February 2021

Neutralizing antibodies are critical to prevent corona virus infection. The structures of immunogens to elicit most potent neutralization antibodies are still under investigation. Here we tested the immunogenicity of the trimeric, full length Spike protein with 2 proline mutations to preserve its prefusion conformation. Recombinant trimeric Spike protein expressed by CHO cells was used with polyI:C (PIKA) adjuvant to immunize mice by 0-7-14 day schedule. The results showed that Spike-specific antibody was induced at day 21 with titer of more than 50,000 in average as measured by direct binding to Spike protein. The titer of neutralization reached more than 1000 in average when tested by a pseudo-virus system, using monoclonal antibodies (40592-MM57 and 40591-MM43) with neutralizing IC50 at 1 μg/ml as standards. Protein/peptide array showed that the antibodies induced by trimeric S protein vaccine bind similarly to natural infection with the receptor binding domain (RBD) as major immunodominant region. No linear epitopes were found in RBD, although several linear epitopes were found in C-terminal domain right after RBD, and heptad repeat regions. Our study supports the efficacy of recombinant trimeric Spike protein vaccine candidate for COVID-19, with excellent safety and readiness for storage and distribution in developing countries.
The Need for Sustainable Leadership in Academia – a German Case Study
Authors: Haage Verena , Voss Linn , Nguyen Daniela , Eggert Friderike
Published: February 2021

Academic leaders are selected based on their publication record, citation index and acquisition of third party funding. However, heading a successful research team, also requires leadership skills. Despite the clear need, leadership development has been systematically neglected in the present academic system. At the same time, growing evidence suggests that leadership styles of academic supervisors can dramatically affect the mental health of academic employees as well as drive highly skilled researchers out of academia. Here, we assessed the current state of academic leadership in the German academic system by surveying 368 participants currently employed in academia in Germany. We report that 64% of current academic leaders did not feel prepared for their current position while 86% of participants expressed their interest in leadership development programs offered by their research institutions. Our results highlight the demand for leadership development programs in German academic institutions to ensure a more efficient academic system.
Broadly reactive human monoclonal antibodies targeting the pneumococcal histidine triad protein protect against fatal pneumococcal infection
Authors: Huang Jiachen , Gingerich Aaron D. , Royer Fredejah , Paschall Amy V. , Pena-Briseno Alma , Avci Fikri Y. , Mousa Jarrod J.
Published: February 2021

Streptococcus pneumoniaeremains a leading cause of bacterial pneumonia despite the widespread use of vaccines. While vaccines are effective at reducing the incidence of most vaccine-included serotypes, a rise in infection due to non-vaccine serotypes, and moderate efficacy against some vaccine included serotypes have contributed to high disease incidence. Additionally, numerous isolates ofS. pneumoniaeare antibiotic or multi-drug resistant. Several conserved pneumococcal proteins prevalent in the majority of serotypes have been examined as vaccines in preclinical and clinical trials. An additional, yet unexplored tool for disease prevention and treatment is the use of human monoclonal antibodies (mAbs) targeting conserved pneumococcal proteins. Here, we isolate the first human mAbs (PhtD3, PhtD6, PhtD7, PhtD8, PspA16) against the pneumococcal histidine triad protein (PhtD), and the pneumococcal surface protein A (PspA), two conserved and protective antigens. mAbs to PhtD target diverse epitopes on PhtD, and mAb PspA16 targets the N-terminal segment of PspA. The PhtD-specific mAbs bind to multiple serotypes, while mAb PspA16 serotype breadth is limited. mAbs PhtD3 and PhtD8 prolong the survival of mice infected with pneumococcal serotype 3. Furthermore, mAb PhtD3 prolongs the survival of mice in intranasal and intravenous infection models with pneumococcal serotype 4, and in mice infected with pneumococcal serotype 3 when administered 24 hours after pneumococcal infection. All PhtD and PspA mAbs demonstrate opsonophagocytic activity, suggesting a potential mechanism of protection. Our results provide new human mAbs for pneumococcal disease prevention and treatment, and identify epitopes on PhtD and PspA recognized by human B cells.
How the replication and transcription complex functions in jumping transcription of SARS-CoV-2
Authors: Liang Jianguang , Shi Jinsong , Chen Shunmei , Duan Guangyou , Yang Fan , Cheng Zhi , Li Xin , Ruan Jishou , Mi Dong , Gao Shan
Published: February 2021

Background

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC) and 16 non-structural proteins, named NSP1-16.

Results

In the present study, we proposed a two-route model to answer how the RTC functions in the jumping transcription of CoVs. The key step leading to this model was that the motif AAACH for METTL3 recognition flanking the transcription regulatory sequence (TRS) motif was discovered to determine the m6A methylation of SARS-CoV-2 RNAs, by reanalyzing public Nanopore RNA-seq data. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. In addition, we reported canonical TRS motifs of all CoVs to prove the importance of our findings.

Conclusions

The main conclusions are: (1) TRS hairpins can be used to identify recombination regions in CoV genomes; (2) RNA methylation of CoVs participates in the determination of the RNA secondary structures by affecting the formation of base pairing; and (3) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.
The role of genus and life span in predicting seed and vegetative trait variation and correlation inLathyrus,Phaseolus, andVicia(Fabaceae)
Authors: Herron Sterling A. , Rubin Matthew J. , Albrecht Matthew A. , Long Quinn G. , Sandoval Marissa C. , Miller Allison J.
Published: February 2021

PREMISE OF THE STUDY

Annual and perennial life history transitions are abundant among angiosperms, and understanding the phenotypic variation underlying life span shifts is a key endeavor of plant evolutionary biology. Comparative analyses of trait variation and correlation networks among annual and perennial plants is increasingly important as new perennial crops are being developed in a predominately annual-based agricultural setting. However, it remains unclear how seed to vegetative growth trait relationships may correlate with life span.

METHODS

We measured 29 annual and perennial congeneric species of three herbaceous legume genera (Lathyrus,Phaseolus, andVicia) for seed size and shape, germination proportion, and early vegetative height and leaf growth over three months in order to assess relative roles of genus and life span in predicting phenotypic variation and correlation.

KEY RESULTS

Genus was the greatest predictor of seed size and shape variation, while life span consistently predicted static vegetative growth traits. Correlation networks revealed that annual species had significant associations between seed traits and vegetative traits, while perennials had no significant seed-vegetative associations. Each genus also differed in the extent of integration between seed and vegetative traits, as well as within-vegetative trait correlation patterns.

CONCLUSIONS

Genus and life span were important for predicting aspects of early life stage phenotypic variation and trait relationships. Differences in phenotypic correlation may indicate selection on seed size traits will impact vegetative growth differently depending on life span, which has important implications for nascent perennial breeding programs.
Eliciting a potent antitumor immune response by expressing tumor antigens in a skin commensal
Authors: Chen Y. Erin , Atabakhsh Katayoon , Dimas Alex , Nagashima Kazuki , Fischbach Michael A.
Published: February 2021

Immune modulation has become central to treating cancer. However, global immune stimulation is only effective in a subset of patients and can lead to serious complications, including colitis and type I diabetes. Newer modalities like engineered T cells and tumor vaccines are more specific, but they have shown limited efficacy in solid tumors and are difficult to scale. Bacterial strains from the human microbiome can induce antigen-specific T cells to help maintain barrier function. Here, we redirect CD8+ and CD4+ T cells elicited by the skin commensalStaphylococcus epidermidisto recognize tumor cells by expressing tumor-derived antigens in the bacterial cell.S. epidermidisexpressing the model antigen ovalbumin (S. epidermidis-OVA) stimulates antigen-specific CD8+ and CD4+ T cells in vitro. The subcellular localization of the antigen skews the response: cell wall-attached OVA preferentially stimulates CD8+ T cells whereas secreted OVA predominantly induces CD4+ T cells. In a syngeneic tumor model (OVA-expressing B16 melanoma), mice colonized topically withS. epidermidis-OVA exhibit a marked reduction in subcutaneous tumor volume compared to mice colonized withS. epidermidisexpressing mCherry; this effect is dependent on live bacteria and a combination of CD8+ and CD4+ T cells.S. epidermidis-OVA also reduces tumor burden when tumor cells are injected intravenously (a model of metastasis), demonstrating that the antitumor effect operates in tissues distant from the site of bacterial colonization.S. epidermidisstrains expressing neoantigen peptides from the B16 tumor cell line exhibit potent antitumor efficacy without inducing an autoimmune response against melanocytes in healthy tissue. Antigen-expressing colonists are a simple but powerful strategy to elicit a targeted T cell response in the context of cancer and other diseases.
Shared functional connections within and between cortical networks predict cognitive abilities in adult males and females
Authors: Dhamala Elvisha , Jamison Keith W. , Jaywant Abhishek , Kuceyeski Amy
Published: February 2021

A thorough understanding of sex-independent and sex-specific neurobiological features that underlie cognitive abilities in healthy individuals is essential for the study of neurological illnesses in which males and females differentially experience and exhibit cognitive impairment. Here, we evaluate sex-independent and sex-specific relationships between functional connectivity and individual cognitive abilities in 392 healthy young adults (196 males) from the Human Connectome Project. First, we establish that sex-independent models comparably predict crystallised abilities in males and females, but more accurately predict fluid abilities in males. Second, we demonstrate sex-specific models comparably predict crystallised abilities within and between sexes, and generally fail to predict fluid abilities in either sex. Third, we reveal that largely overlapping connections between visual, dorsal attention, ventral attention, and temporal parietal networks are associated with better performance on crystallised and fluid cognitive tests in males and females, while connections within visual, somatomotor, and temporal parietal networks are associated with poorer performance. Together, our findings suggest that shared neurobiological features of the functional connectome underlie crystallised and fluid abilities across the sexes.
A draft genome ofAlliaria petiolata(garlic mustard) as a model system for invasion genetics
Authors: Alabi Nikolay , Wu Yihan , Bossdorf Oliver , Rieseberg Loren H. , Colautti Robert I.
Published: February 2021

The emerging field of invasion genetics examines the genetic causes and consequences of biological invasions, but few study systems are available that integrate deep ecological knowledge with genomic tools. Here we report on thede novoassembly and annotation of a genome for the biennial herbAlliaria petiolata(M. Bieb.) Cavara & Grande (Brassicaceae), which is widespread in Eurasia and invasive across much of temperate North America. Our goal was to sequence and annotate a genome to complement resources available from hundreds of published ecological studies, a global field survey, and hundreds of genetic lines maintained in Germany and Canada. We sequenced a genotype (EFCC-3-20) collected from the native range near Venice, Italy and sequenced paired-end and mate pair libraries at ~70 × coverage. Ade novoassembly resulted in a highly continuous draft genome (N50= 121 Mb; L50= 2) with 99.7 % of the 1.1 Gb genome mapping to scaffolds of at least 50 Kb in length. A total of 64,770 predicted genes in the annotated genome include 99 % of plant BUSCO genes and 98 % of transcriptome reads. Consistent with previous reports of (auto)hexaploidy in western Europe, we found that almost one third of BUSCO genes (390/1440) mapped to two or more scaffolds despite < 2 % genome-wide average heterozygosity. The continuity and gene space quality of our draft assembly will enable molecular and functional genomic studies ofA. petiolatato address questions relevant to invasion genetics and conservation strategies.
Remyelination restores myelin content on distinct neuronal subtypes in the cerebral cortex
Authors: Call Cody L. , Bergles Dwight E.
Published: February 2021

Axons in the cerebral cortex exhibit diverse patterns of myelination, with some axons devoid of myelin, some exhibiting discontinuous patches of myelin, and others continuous myelin that is interrupted only by nodes of Ranvier. Oligodendrocytes establish this pattern by sorting through a high density of potential targets to select a small cohort of axons for myelination; however, the myelination patterns established on distinct excitatory and inhibitory neurons within the cortex remain to be fully defined and little is known about the extent to which these patterns are restored after oligodendrocyte regeneration. Here we show that axons in layer I of the somatosensory cortex, a key region for integration of input from local and distant sources, exhibit an extraordinarily diverse range of myelination patterns, even among distinct neuronal subtypes. Although larger axons were more often selected for myelination, neuronal identity profoundly influenced the probability of myelination. The relative differences in myelination among neuron subtypes were preserved between cortical areas with widely varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis, rather than selective reduction of myelin on distinct neuron subtypes. By following the loss and regeneration of myelin sheaths along defined neuronsin vivowe show that even though the distribution of myelin on individual PV and VM neuron axons was altered following remyelination, the overall myelin content on these neurons was restored. The findings suggest that local changes in myelin can be tolerated, allowing opportunistic selection of available targets by newly formed oligodendrocytes to restore relative differences in myelin content between functionally distinct neurons.
Twitches emerge postnatally during quiet sleep in human infants and are synchronized with sleep spindles
Authors: Sokoloff Greta , Dooley James C. , Glanz Ryan M. , Wen Rebecca Y. , Hickerson Meredith M. , Evans Laura G. , Laughlin Haley M. , Apfelbaum Keith S. , Blumberg Mark S.
Published: February 2021

Summary

In humans and other mammals, the stillness of sleep is punctuated by bursts of rapid eye movements (REMs) and myoclonic twitches of the limbs [1]. Contrary to the notion that twitches are mere by-products of dreams, sensory feedback arising from twitching limbs provides a rich and unique source of activation to the developing sensorimotor system [2]. In fact, it is partly because of the behavioral activation of REM sleep that this state is also called active sleep (AS), in contrast with the behavioral quiescence that gives quiet sleep (QS)—the second major stage of sleep—its name. In human infants, for which AS occupies eight or more hours of each day [3], limb twitching is one among several components that help to identify the state [4-7]; nonetheless, we know relatively little about the structure and functions of twitching across development. Recently, in sleeping infants over the first seven postnatal months [8], we documented a pronounced shift in the temporal expression of twitching beginning around three months of age that suggested a qualitative shift in how twitches are produced. Here, we combine behavioral assessments of twitching with high-density electroencephalography (EEG) and demonstrate that this shift reflects the developmental emergence of limb twitches during QS. Twitches during QS are not only unaccompanied by REMs, but they also occur synchronously with sleep spindles, a hallmark of QS. As QS-related twitching increases with age, sleep spindle rate also increases along the sensorimotor strip. The emerging synchrony between subcortically generated twitches and cortical oscillations suggests the development of functional connectivity among distant sensorimotor structures, with potential implications for detecting and explaining atypical developmental trajectories.
FRAGMENTED BIODIVERSITY: FERNS AND LYCOPHYTES FROM FOREST FRAGMENTS IN JUIZ DE FORA, MINAS GERAIS, BRAZIL
Authors: Lima Lucas Vieira , de Oliveira Dittrich Vinícius Antonio , de Souza Filipe Soares , da Fonseca Cassiano Ribeiro , Salino Alexandre
Published: February 2021

The Atlantic Forest is one of the most threatened formations in the world. In this context, the urbanization process stands out as one of the major factors causing environmental degradation, mainly due to the loss of native vegetation and habitat destruction. In order to fill this gap, we carried out the inventory of ferns and lycophytes in the forest remnants of the municipality of Juiz de Fora. We analyzed more than 1,353 samplings recorded throughout approximately 150 years, as result we recorded a total of 174 species distributed in 73 genera and 26 families. The most representative families were Pteridaceae with 32 species, followed by Polypodiaceae with 26 and Thelypteridaceae with 20. In addition, we present the historical data on the sampling of ferns and lycophytes, as well as the history of the fragmentation process of the Atlantic Forest remnants in the municipality. Juiz de Fora becomes an interesting model for broader floristic studies, generating subsequent subsidies for conservation actions and preservation of the natural patrimony.
Process-explicit models reveal pathway to extinction for woolly mammoth using pattern-oriented validation
Authors: Fordham Damien A. , Brown Stuart C. , Reşit Akçakaya H. , Brook Barry W. , Haythorne Sean , Manica Andrea , Shoemaker Kevin T. , Austin Jeremy J. , Blonder Benjamin , Pilowsky Julia , Rahbek Carsten , Nogues-Bravo David
Published: February 2021

Pathways to extinction start long before the death of the last individual. However, causes of early-stage population declines and the susceptibility of small residual populations to extirpation are typically studied in isolation. Using validated process-explicit models, we disentangle the ecological mechanisms and threats that were integral in the initial decline and later extinction of the woolly mammoth. We show that reconciling ancient DNA data on woolly mammoth population decline with fossil evidence of location and timing of extinction requires process-explicit models with specific demographic and niche constraints, and a constrained synergy of climatic change and human impacts. Validated models needed humans to hasten climate-driven population declines by many millennia, and to allow woolly mammoths to persist in mainland Arctic refugia until the mid-Holocene. Our results show that the role of humans in the extinction dynamics of woolly mammoth began well before the Holocene, exerting lasting effects on the spatial pattern and timing of its range-wide extinction.
Kinesin-6 Klp9 orchestrates spindle elongation by regulating microtubule sliding and growth
Authors: Krüger Lara K. , Gélin Matthieu , Ji Liang , Kikuti Carlos , Houdusse Anne , Théry Manuel , Blanchoin Laurent , Tran Phong T.
Published: February 2021

Mitotic spindle function depends on the precise regulation of microtubule dynamics and microtubule sliding. Throughout mitosis, both processes have to be orchestrated to establish and maintain spindle stability. We show that during anaphase B spindle elongation inS. pombe, the sliding motor Klp9 (kinesin-6) also promotes microtubule growthin vivo. In vitro, Klp9 can enhance and dampen microtubule growth, depending on the tubulin concentration. This indicates that the motor is able to promote and block tubulin subunit incorporation into the microtubule lattice in order to set a well-defined microtubule growth velocity. Moreover, Klp9 recruitment to spindle microtubules is dependent on its dephosphorylation mediated by XMAP215/Dis1, a microtubule polymerase, to link the regulation of spindle length and spindle elongation velocity. Collectively, we unravel the mechanism of anaphase B, from Klp9 recruitment to the motors dual-function in regulating microtubule sliding and microtubule growth, allowing an inherent coordination of both processes.
Spatial modulation of individual behaviors enables collective decision-making during bacterial group migration
Authors: Bai Yang , He Caiyun , Long Junjiajia , Li Xuefei , Fu Xiongfei
Published: February 2021

Coordination of individuals with diversity often requires sophisticated communications and high-order computational abilities. Microbial populations can exhibit diverse individualistic behaviors and yet can engage in collective migratory patterns with a spatially sorted arrangement of phenotypes following a self-generated attractant gradient. However, it’s unclear how individual bacteria without complex computational abilities can achieve the consistent group performance and determine their positions in the group while facing spatiotemporally dynamic stimuli. Here, we investigate the statistics of bacterial run-and-tumble trajectories during group migration. We discover that, despite of the constant migrating speed as a group, the individual drift velocity exhibits a spatially dependent structure that decreases from the back to the front of the group. The spatial modulation of individual stochastic behaviors constrains cells in the group, ensuring the coherent population movement with ordered patterns of phenotypes. These results reveal a simple computational principle for emergent collective behaviors from heterogeneous individuals.
Intrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells
Authors: Cuevas-Velazquez Cesar L , Vellosillo Tamara , Guadalupe Karina , Schmidt H Broder , Yu Feng , Moses David , Brophy Jennifer AN , Cosio-Acosta Dante , Das Alakananda , Wang Lingxin , Jones Alexander M , Covarrubias Alejandra A , Sukenik Shahar , Dinneny José R
Published: February 2021

Cell homeostasis is perturbed when dramatic shifts in the external environment cause the physical-chemical properties inside the cell to change. Methods that dynamically monitor these intracellular effects are currently lacking. Here, we leveraged the environmental sensitivity and structural plasticity of intrinsically disordered regions (IDRs) to develop a FRET biosensor capable of monitoring rapid intracellular changes caused by osmotic stress. The biosensor, named SED1, utilizes the Arabidopsis intrinsically disordered AtLEA4-5 protein expressed in plants under water deficit. Computational modeling andin vitrostudies reveal that SED1 is highly sensitive to macromolecular crowding. SED1 exhibits large and near-linear osmolarity-dependent changes in FRET inside living bacteria, yeast, plant, and human cells, demonstrating the broad utility of this tool for studying water-associated stress. This study demonstrates the remarkable ability of IDRs to sense the cellular environment across the tree of life and provides a blueprint for their use in environmentally-responsive molecular tools.
Compression for population genetic data through finite-state entropy
Authors: Chen Winfield , Elliott Lloyd T.
Published: February 2021

We improve the efficiency of population genetic file formats and GWAS computation by leveraging the distribution of sample ordering in population-level genetic data. We identify conditional exchangeability of these data, recommending finite state entropy algorithms as an arithmetic code naturally suited to population genetic data. We show between 10% and 40% speed and size improvements over dictionary compression methods for population genetic data such asZstdandZlibin computation and and decompression tasks. We provide a prototype for genome-wide association study with finite state entropy compression demonstrating significant space saving and speed comparable to the state-of-the-art.
Phospholipid membrane formation templated by coacervate droplets
Authors: Cakmak Fatma Pir , Marianelli Allyson M. , Keating Christine D.
Published: February 2021

We report formation of coacervate-supported phospholipid membranes by hydrating a dried lipid film in the presence of coacervate droplets. In contrast to traditional giant lipid vesicles formed by gentle hydration in the absence of coacervates, the coacervate-templated membrane vesicles are more uniform in size, shape, and apparent lamellarity. Due to their fully-coacervate model cytoplasm, these simple artificial cells are macromolecularly crowded and can be easily pre-loaded with high concentrations of proteins or nucleic acids. Coacervate-supported membranes were characterized by fluorescence imaging, polarization, fluorescence recovery after photobleaching of labeled lipids, lipid quenching experiments, and solute uptake experiments. Our findings are consistent with the presence of lipid membranes around the coacervates, with many droplets fully coated with what appear to be continuous lipid bilayers. Within the same population, other coacervate droplets are coated with membranes having defects or pores that permit solute entry, and still others are coated with multilayered membranes. These membranes surrounding protein-based coacervate droplets provided protection from a protease added to the external solution. The simplicity of producing artificial cells having a coacervate model cytoplasm surrounded by a model membrane is at the same time interesting as a potential mechanism for prebiotic protocell formation and appealing for biotechnology. We anticipate that such structures could serve as a new type of model system for understanding interactions between intracellular phases and cell- or organelle membranes, which are implicated in a growing number of processes ranging from neurotransmission to signaling.
Third Backcross Generation Indonesian Indigenous ChickenKampongBroiler-Type (Kambro)SOX5Gene Polymorphism
Authors: Ardo T , Perdamaian A. B. I. , Mahardhika I. W. S. , Daryono B S
Published: February 2021

The comb is an accessory organ on the head of chicken which is influenced by testosterone hormone and can be used as an indicator of chicken’s fertility. Comb shape is related to climate adaptation and associated with a dominant mutation in chicken chromosome 1. Therefore this research was aimed to study the association betweenPea-combshape andSOX5gene polymorphism in the population of progenies (BC-IIIKambro) derived from a crossbreed between femalesPelungand males second backcross generationKampongBroiler-Type (BC-IIKambro). Chicken(Gallus gallus) SOX5gene was acquired from NCBI GenBank with the Ref. Seq.418195. Primers used to amplify theSOX5gene are(F):5’-AGGTAGCCATGGTGACAAGC-3’,(R):5’-GATCTGTGAGGCAGCCAGTT-3’. Progenies showed 100%Pea-combshape, while parental generation composed ofPea-combshape andSingle-combshape. PCR-RFLP and endonuclease restriction enzymeHindIIIwere unable to determine the genotype of the female parent withPea-comb. The result ofSOX5gene polymorphism showed the comb shape uniformity between progenies and parental ofKambrobackcross generation. This study concluded that the genotype ofPea-combshape femalePelungwas undetermined and there was no polymorphism of theSOX5gene between pea and single comb. PCR-RFLP using endonuclease restriction enzymeHindIIIproduced both target products and non-target/artifact products. The sequencing procedure was required to provide nucleotide sequences.
Biological and Transcriptomic Characterization of Pre-haustorial Resistance to Sunflower Broomrape (Orobanche cumanaW.)
Authors: Sisou Dana , Tadmor Yaakov , Plakhine Dina , Hübner Sariel , Eizenberg Hanan
Published: February 2021

Infestations with sunflower broomrape (Orobanche cumanaWallr.), an obligatory root parasite, constitute a major limitation to sunflower production in many regions around the world. Breeding for resistance is the most effective approach to reduce sunflower broomrape infestation, yet resistance mechanisms are often overcome by new races of the pathogen. Elucidating the mechanisms controlling the resistance to broomrape at the molecular level is thus the most desirable pathway to obtaining long-lasting resistance and reducing yield loss in sunflower. In this study, we investigated broomrape resistance in a confectionery sunflower hybrid with a robust and long-lasting resistance to sunflower broomrape. Visual screening and histological examination of sunflower roots revealed that penetration of the intrusive broomrape cells into the host root endodermis is blocked at the host cortex, indicating a pre-haustorial mechanism of resistance. A comparative RNA-Seq experiment conducted between roots obtained from the resistant cultivar, a bulk of five broomrape resistant lines and a bulk of five broomrape susceptible lines allowed the identification of genes that were significantly differentially expressed upon broomrape infestation. Among these differentially expressed genes, β-1,3-endoglucanase, β-glucanase and ethylene-responsive transcription factor4 (ERF4) genes were identified. These genes were previously reported to be pathogenesis-related genes in other plant species. This genetics investigation together with the histological examinations led us to conclude that the resistance mechanism involves the identification of the broomrape and the consequent formation of a physical barrier that prevents the penetration of the broomrape into the sunflower roots.
Frequent intergenotypic recombination between the non-structural and structural genes is a major driver of epidemiological fitness in caliciviruses
Authors: Mahar Jackie E , Jenckel Maria , Huang Nina , Smertina Elena , Holmes Edward C , Strive Tanja , Hall Robyn N
Published: February 2021

The diversity of lagoviruses (Caliciviridae) in Australia has increased considerably. By the end of 2017, five variants from three viral genotypes were present in populations of Australian rabbits, while prior to 2014 only two variants were known. To understand the interactions between these lagovirus variants we monitored their geographical distribution and relative incidence over time through a landscape-scale competition study, and from this, revealed potential drivers of epidemiological fitness. Within three years of the arrival of GI.1bP-GI.2 (RHDV2) into Australia, we observed the emergence of two novel recombinant lagovirus variants, GI.4eP-GI.2 (4e-recombinant) in New South Wales and GI.4cP-GI.2 (4c-recombinant) in Victoria. Although both novel recombinants contain the non-structural genes from benign, rabbit-specific, enterotropic viruses, these variants were recovered from the livers of both rabbits and hares that had died acutely. This suggests that determinants of host and tissue tropism for lagoviruses are associated with the structural genes, and that tropism is intricately connected with pathogenicity. Phylogenetic analyses demonstrated that the 4c-recombinant emerged independently on multiple occasions, with five distinct lineages observed. Both new recombinant variants replaced the previous dominant parental RHDV2 in their respective geographical areas, despite sharing an identical or near-identical (i.e., single amino acid change) major capsid protein with the parental virus. This suggests that epidemiological fitness of these recombinants was not driven by antigenic variation in the capsid, implicating the non-structural genes as key drivers of epidemiological fitness. Molecular clock estimates place the GI4.e recombination event in early to mid-2015, while the five GI.4c recombination events occurred from late 2015 through to early 2017. The emergence of at least six viable recombinant variants within a two-year period highlights an unprecedented frequency of these events, detectable only due to intensive surveillance, and demonstrates the importance of recombination in lagovirus evolution.
A D-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR
Authors: Xiao Dan , Zhang Wen , Guo Xiaoting , Liu Yidong , Hu Chunxia , Guo Shiting , Kang Zhaoqi , Xu Xianzhi , Ma Cuiqing , Gao Chao , Xu Ping
Published: February 2021

D-2-Hydroxyglutarate (D-2-HG) is a metabolite in many physiological metabolic processes. When D-2-HG is aberrantly accumulated due to mutations in isocitrate dehydrogenases or D-2-HG dehydrogenase, it functions in a pro-oncogenic manner and is thus considered a therapeutic target and biomarker in many cancers. In this study, DhdR fromAchromobacter denitrificansNBRC 15125 was identified as an allosteric transcription factor that negatively regulates D-2-HG dehydrogenase expression and responds to presence of D-2-HG. It is the first known transcription regulator specifically responding to D-2-HG across all domains of life. Based on the allosteric effect of DhdR, a D-2-HG biosensor was developed by combining DhdR with amplified luminescent proximity homogeneous assay technology. The biosensor was able to detect D-2-HG in serum, urine, and cell culture with high specificity and sensitivity. Additionally, this biosensor was also successfully used to identify the role of D-2-HG metabolism in lipopolysaccharide biosynthesis ofPseudomonas aeruginosa, demonstrating its broad usages.
Collective detection based on visual information in animal groups
Authors: Davidson Jacob D. , Sosna Matthew M. G. , Twomey Colin R. , Sridhar Vivek H. , Leblanc Simon P. , Couzin Iain D.
Published: February 2021

The spatio-temporal distribution of individuals within a group (i.e its internal structure) plays a defining role in how individuals interact with their environment, make decisions, and transmit information via social interactions. Group-living organisms across taxa, including many species of fish, birds, ungulates, and insects, use vision as the predominant modality to coordinate their collective behavior. Despite this importance, there have been few quantitative studies examining visual detection capabilities of individuals within groups. We investigate key principles underlying individual, and collective, visual detection of stimuli (which could include cryptic predators, potential food items, etc.) and how this relates to the internal structure of groups. While the individual and collective detection principles are generally applicable, we employ a model experimental system of schooling golden shiner fish (Notemigonus crysoleucas) to relate theory directly to empirical data, using computational reconstruction of the visual fields of all individuals to do so. Our integrative approach allows us to reveal how the external visual information available to each group member depends on the number of individuals in the group, the position within the group, and the location of the external visually-detectable stimulus. We find that in small groups, individuals have detection capability in nearly all directions, while in large groups, occlusion by neighbors causes detection capability to vary with position within the group. We then formulate a simple, and generally applicable, model that captures how visual detection properties emerge due to geometric scaling of the space occupied by the group and occlusion caused by neighbors. We employ these insights to discuss principles that extend beyond our specific system, such as how collective detection depends on individual body shape, and the size and structure of the group.
On the sensitivity analysis of porous finite element models for cerebral perfusion estimation
Authors: Józsa T. I. , Padmos R. M. , El-Bouri W. K. , Hoekstra A. G. , Payne S. J.
Published: February 2021

Computational physiological models are promising tools to enhance the design of clinical trials and to assist in decision making. Organ-scale haemodynamic models are gaining popularity to evaluate perfusion in a virtual environment both in healthy and diseased patients. Recently, the principles of verification, validation, and uncertainty quantification of such physiological models have been laid down to ensure safe applications of engineering software in the medical device industry. The present study sets out to establish guidelines for the usage of a three-dimensional steady state porous cerebral perfusion model of the human brain following principles detailed in the verification and validation (V&V 40) standard of the American Society of Mechanical Engineers. The model relies on the finite element method and has been developed specifically to estimate how brain perfusion is altered in ischaemic stroke patients before, during, and after treatments. Simulations are compared with exact analytical solutions and a thorough sensitivity analysis is presented covering every numerical and physiological model parameter.

The results suggest that such porous models can approximate blood pressure and perfusion distributions reliably even on a coarse grid with first order elements. On the other hand, higher order elements are essential to mitigate errors in volumetric blood flow rate estimation through cortical surface regions. Matching the volumetric flow rate corresponding to major cerebral arteries is identified as a validation milestone. It is found that inlet velocity boundary conditions are hard to obtain and that constant pressure inlet boundary conditions are feasible alternatives. A one-dimensional model is presented which can serve as a computationally inexpensive replacement of the three-dimensional brain model to ease parameter optimisation, sensitivity analyses and uncertainty quantification.

The findings of the present study can be generalised to organ-scale porous perfusion models. The results increase the applicability of computational tools regarding treatment development for stroke and other cerebrovascular conditions.
Functional MRI of native and non-native speech production in sequential German-English bilinguals
Authors: Treutler Miriam , Sörös Peter
Published: February 2021

Bilingualism and multilingualism are highly prevalent. Non-invasive brain imaging has been used to study the neural correlates of native (L1) and non-native (L2) speech and language production, mainly on the lexical and syntactic level. Here, we acquired continuous fast event-related FMRI during visually cued overt production of exclusively German and English vowels and syllables. We analyzed data from 13 university students, native speakers of German and sequential English bilinguals. The production of non-native English sounds was associated with increased activity of the left primary sensori-motor cortex, bilateral cerebellar hemispheres (lobule VI), left inferior frontal gyrus, and left anterior insula compared to native German sounds. The contrast German > English sounds was not statistically significant. Our results emphasize that the production of non-native speech requires additional neural resources already on a basic phonological level in sequential bilinguals.
Recovering sedimentary ancient DNA of harmful dinoflagellates off Eastern Tasmania, Australia, over the last 9 000 years
Authors: Armbrecht Linda , Paine Bradley , Bolch Christopher J.S. , Cooper Alan , McMinn Andrew , Woodward Craig , Hallegraeff Gustaaf
Published: February 2021

Harmful algal blooms (HABs) have significantly impacted the seafood industry along the Tasmanian east coast over the past four decades. To investigate the history of regional HABs, we applied sedimentary ancient DNA analyses (sedaDNA) to coastal sediments up to ∼9 000 years old collected inshore and offshore Maria Island, Tasmania. We used metagenomic shotgun sequencing combined with a hybridisation capture array (‘HABbaits1’) to target harmful dinoflagellates of the generaAlexandrium, Gymnodinium,andNoctiluca scintillans. Bioinformatic analyses were used to verifysedaDNA sequences and their presence in older layers, especially for microreticulate cyst forming species includingGymnodinium catenatumdue to its important role in shellfish toxicity. Our results show that theAlexandriumgenus (up to 854 and 20 reads per sample inshore and offshore, respectively, based on capture-data) has been present off eastern Tasmania within the last ∼8 307 years. ForG. catenatumwe detected a total of only 9 unambiguously verified reads sporadically between ∼7 638 years ago and the present in the offshore core. We recovered verifiedsedaDNA of the fragile, non-fossilising speciesN. scintillans, along with evidence of increased relative abundance from 2010, consistent with plankton surveys. This study identifies challenges regardingsedaDNA sequence validation of some species (in particular, forG. catenatum), and provides guidance for the development of tools to monitor past and present HAB species and events, and to improve future HAB event predictions.

Highlights

MetagenomicsedaDNA and hybridisation capture enabled analyses of harmful dinoflagellates off Tasmania

Sequence validation was used to confirm the presence ofAlexandriumspp.,Gymnodiniumspp. andNoctiluca scintillans

AlexandriumandGymnodiniumhave been present in Tasmanian waters during the past ∼9 000 years

Noctiluca scintillans sedaDNA derived relative abundance correlates with its recorded increase since 2010
Contribution of interneuron subtype-specific GABAergic signalling to emergent sensory processing in somatosensory whisker barrel cortex in mouse
Authors: Baruchin Liad J. , Kohl Michael M. , Butt Simon J.B
Published: February 2021

Mammalian neocortex is important for conscious processing of sensory information. Fundamental to this function is balanced glutamatergic and GABAergic signalling. Yet little is known about how this interaction arises in the developing forebrain despite increasing insight into early GABAergic interneuron (IN) circuits. To further study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex. Specifically we explored the role of INs in speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity, and showed refinement over the period leading to active whisking onset. We then conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked activity in an age and layer-dependent manner. Silencing SST+ INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP+ IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results reveal how these IN subtypes differentially contribute to early sensory processing over the first few postnatal weeks.
Integration of differential gene expression with weighted gene correlation network analysis identifies genes whose expression is remodeled throughout physiological aging in mouse tissues
Authors: Ferreira Margarida , Francisco Stephany , Soares Ana R. , Nobre Ana , Pinheiro Miguel , Reis Andreia , Neto Sonya , Rodrigues Ana João , Sousa Nuno , Moura Gabriela , Santos Manuel A. S.
Published: February 2021

Gene expression alterations occur in all mouse tissues during aging, but recent works highlight minor rather than major dysregulation amplitude for most genes, questioning whether differentially expressed genes on their own provide deep insight into aging biology. To clarify this issue, we have combined differential gene expression with weighted gene correlation network analysis (WGCNA) to identify expression signatures accounting for the pairwise relations between gene expression profiles and the cumulative effect of genes with small fold- changes during aging in the brain, heart, liver, skeletal muscle, and pancreas of C57BL/6 mice. Functional enrichment analysis of the overlap of genes identified in both approaches showed that immunity-related responses, mitochondrial energy metabolism, tissue regeneration and detoxification are prominently altered in the brain, heart, muscle, and liver, respectively, reflecting an age-related global loss of tissue function. While data showed little overlap among the age-dysregulated genes between tissues, aging triggered common biological processes in distinct tissues, particularly proteostasis-related pathways, which we highlight as important features of murine tissue physiological aging.
MEG, myself, and I: individual identification from neurophysiological brain activity
Authors: Da Silva Castanheira Jason , Orozco Hector D , Misic Bratislav , Baillet Sylvain
Published: February 2021

Large, openly available datasets and current analytic tools promise the emergence of population neuroscience. The considerable diversity in personality traits and behaviour between individuals is reflected in the statistical variability of neural data collected in such repositories. This amount of variability challenges the sensitivity and specificity of analysis methods to capture the personal characteristics of a putative neural portrait. Recent studies with functional magnetic resonance imaging (fMRI) have concluded that patterns of resting-state functional connectivity can both successfully identify individuals within a cohort and predict some individual traits, yielding the notion of aneural fingerprint. Here, we aimed to clarify the neurophysiological foundations of individual differentiation from features of the rich and complex dynamics of resting-state brain activity using magnetoencephalography (MEG) in 158 participants. Akin to fMRI approaches, neurophysiological functional connectomes enabled the identification of individuals, with identifiability rates similar to fMRI’s. We also show that individual identification was equally successful from simpler measures of the spatial distribution of neurophysiological spectral signal power. Our data further indicate that identifiability can be achieved from brain recordings as short as 30 seconds, and that it is robust over time: individuals remain identifiable from recordings performed weeks after their baseline reference data was collected. Based on these results, we can anticipate a vast range of further research and practical applications of individual differentiation from neural electrophysiology in personalized, clinical, and basic neuroscience.