bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-di-AMP hydrolysis by a novel type of phosphodiesterase promotes differentiation of multicellular bacteria
Authors: Latoscha Andreas , Drexler David Jan , Al-Bassam Mahmoud M. , Kaever Volkhard , Findlay Kim C. , Witte Gregor , Tschowri Natalia 
Published: October 2019

ABSTRACTAntibiotic-producing Streptomyces use the diadenylate cyclase DisA to synthesize the nucleotide second messenger c-di-AMP but the mechanism for terminating c-di-AMP signaling and the proteins that bind the molecule to effect signal transduction are unknown. Here, we identify the AtaC protein as a new type of c-di-AMP-specific phosphodiesterase that is also conserved in pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis. AtaC is monomeric in solution and binds Mn2+ to specifically hydrolyze c-di-AMP to AMP via the intermediate 5’-pApA. As an effector of c-di-AMP signaling, we characterize the RCK-domain protein CpeA as the first c-di-AMP-binding protein to be identified in Streptomyces. CpeA interacts with the predicted cation / proton antiporter, CpeB, linking c-di-AMP signaling to ion homeostasis in actinobacteria. Hydrolysis of c-di-AMP is critical for normal growth and differentiation in Streptomyces, connecting osmotic stress to development. Thus, we present the discovery of two novel components of c-di-AMP signaling in bacteria and show that precise control of this second messenger is essential for osmoregulation and coordinated development in Streptomyces.
Tiled STED Imaging of Extended Sample Regions
Authors: Alvelid Jonatan , Testa Ilaria 
Published: October 2019

AbstractStimulated Emission Depletion (STED) nanoscopy has become one of the most used nanoscopy techniques over the last decade. However, most recordings are done in specimen regions no larger than 10–30 × 10–30 µm2 due to aberrations, instability and manual mechanical stages. Here, we demonstrate automated STED nanoscopy of extended sample regions up to 0.5 × 0.5 mm2 by using a back-aperture-stationary beam scanning system. The setup allows up to 80–100 x 80–100 µm2 field of view (FOV) with uniform spatial resolution, a mechanical stage allowing sequential tiling to record larger sample areas, and a feedback system keeping the sample in focus at all times. Taken together, this allows automated recording of theoretically unlimited-sized sample areas and volumes, without compromising the achievable spatial resolution and image quality.
Self-controlled practice and nudging during structural learning of a novel control interface
Authors: Lee Mei-Hua , Jayasinghe Shanie A.L. 
Published: October 2019

AbstractSelf-controlled practice schedules have been shown to enhance motor learning in several contexts, but their effectiveness in structural learning tasks, where the goal is to eventually learn an underlying structure or rule, is not well known. Here we examined the use of self-controlled practice in a novel control interface requiring structural learning. In addition, we examined the effect of ‘nudging’ – i.e., whether altering task difficulty could influence self-selected strategies, and hence facilitate learning. Participants wore four inertial measurement units (IMUs) on their upper body and the goal was to use motions of the upper body to move a screen cursor to different targets presented on the screen. The structure in this task that had to be learned was based on the fact that the signals from the IMUs were linearly mapped to the x- and y-position of the cursor. Participants (N = 62) were split into 3 groups (random, self-selected, nudge) based on whether they had control over the sequence in which they could practice the targets. To test whether participants learned the underlying structure, participants were tested both on the trained targets, as well as novel targets that were not practiced during training. Results showed that during training, the self-selected group showed shorter movement times relative to the random group, and both self-selected and nudge groups adopted a strategy of tending to repeat targets. However, in the test phase, we found no significant differences in task performance between groups, indicating that structural learning was not reliably affected by the type of practice. In addition, nudging participants by adjusting task difficulty did not show any significant benefits to overall learning. These results suggest that although self-controlled practice influenced practice structure and facilitated learning, it did not provide any additional benefits relative to practicing on a random schedule in this task.
Expanding functional protein sequence space using generative adversarial networks
Authors: Repecka Donatas , Jauniskis Vykintas , Karpus Laurynas , Rembeza Elzbieta , Zrimec Jan , Poviloniene Simona , Rokaitis Irmantas , Laurynenas Audrius , Abuajwa Wissam , Savolainen Otto , Meskys Rolandas , Engqvist Martin K. M. , Zelezniak Aleksej 
Published: October 2019

ABSTRACTDe novoprotein design for catalysis of any desired chemical reaction is a long standing goal in protein engineering, due to the broad spectrum of technological, scientific and medical applications. Currently, mapping protein sequence to protein function is, however, neither computationionally nor experimentally tangible1,2. Here we developed ProteinGAN, a specialised variant of the generative adversarial network3that is able to ‘learn’ natural protein sequence diversity and enables the generation of functional protein sequences. ProteinGAN learns the evolutionary relationships of protein sequences directly from the complex multidimensional amino acid sequence space and creates new, highly diverse sequence variants with natural-like physical properties. Using malate dehydrogenase as a template enzyme, we show that 24% of the ProteinGAN-generated and experimentally tested sequences are soluble and display wild-type level catalytic activity in the tested conditionsin vitro, even in highly mutated (>100 mutations) sequences. ProteinGAN therefore demonstrates the potential of artificial intelligence to rapidly generate highly diverse novel functional proteins within the allowed biological constraints of the sequence space.
Topological analysis of TMEM180, a newly identified membrane protein that is highly expressed in colorectal cancer cells
Authors: Anzai Takahiro , Matsumura Yasuhiro 
Published: October 2019

AbstractNew target molecules for diagnosis of and drug development for colorectal cancer (CRC) are always in great demand. Previously, we identified a new colorectal cancer–specific protein, TMEM180, and successfully developed an anti-TMEM180 monoclonal antibody (mAb) for the diagnosis and treatment of CRC. Although TMEM180 is categorized as a member of the cation symporter family and multi-pass membrane protein, little is known about its function. In this study, we examined topology of this membrane protein and analyzed its function. Using a homology model of human TMEM180, we experimentally determined that the protein has 12 transmembrane domains, and that its N-terminal and C-termini are exposed extracellularly. Moreover, we found that the putative cation-binding site of TMEM180 is conserved among orthologs, and that its position is similar to that of melibiose transporter MelB. These results suggest that TMEM180 acts as a cation symporter. Our topological analysis based on the homology model provides insight into functional and structural roles of TMEM180 that may help to elucidate the pathology of CRC.HighlightsA homology model of human TMEM180 was generated by secondary structure prediction.Putative cation-binding residues are conserved in TMEM180 orthologs.Both the N-terminus and C-terminus of TMEM180 are extracellularly exposed.TMEM180 is a 12-transmembrane protein.TMEM180 could act as a cation symporter.
Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response against the AH1 tumor rejection antigen
Authors: Probst Philipp , Stringhini Marco , Neri Dario 
Published: October 2019

AbstractThe possibility to cure immunocompetent mice bearing murine CT26 colorectal tumors using cytokine-based therapeutics allows to study the tumor rejection process at a molecular level. Following treatment with L19-mIL12 or F8-mTNF, two antibody fusion proteins which preferentially concentrate a murine cytokine payload at the tumor site, CT26 tumors could be cured in a process that crucially relies on CD8+ T cells. In both settings, the AH1 peptide (derived from the gp70 envelop protein of murine leukemia virus) acted as the main tumor rejection antigen and ~50% of CD8+ T cells in the tumor mass are AH1-specific after therapy. In order to characterize the clonality of the T cell response after successful antibody-cytokine immunotherapy, we isolated CD8+ T cells from tumors and submitted them to T cell receptor (TCR) sequencing. As expected, different TCR sequences were found in different mice, as these molecules originate from a stochastic rearrangement process. CD8+ T cells featuring the ten most abundant TCR sequences represented more than 60% of total CD8+ T cell clones in the tumor mass, but less than 10% in the spleen. Looking at sorted CD8+ T cells from individual animals, AH1-specific TCRs were consistently found among the most abundant sequences. Collectively, these data suggest that the antitumor response driven by two different antibody-cytokine fusions proceeds through an oligoclonal expansion and activation of tumor-infiltrating CD8+ T cells.
Testing the myth of humid versus dry cold: birds do not care
Authors: O’Connor Ryan S. , Vézina François 
Published: October 2019

ABSTRACTAt high air temperatures (Ta) atmospheric water vapor can markedly influence an animal’s heat dissipation by reducing evaporative cooling capacities. At low Tahowever, the impact of increased water vapor on heat exchange has sparsely been investigated, despite human populations at northern latitudes insisting on feeling colder on days with higher humidity (i.e., humid-cold). Here, we aimed to investigate the humid-cold perception by determining whether Black-capped Chickadees (Poecile atricapillus) exhibited greater energy expenditure through increased heat loss under humid-cold conditions relative to dry-cold. We measured resting metabolic rates (RMR) of captive chickadees (n=10) during exposure to two Tatreatments, below freezing (Ta≈ −7°C) and above freezing (Ta≈ 10°C), with either dry or saturated air. We found that Tasubstantially impacted RMR, with RMR ≈1.5-fold greater at −7°C compared with 10°C. Conversely, humidity did not have a statistically significant impact on RMR at either Ta. Our data thus suggest that humidity does not significantly influence an individual’s heat exchange with the environment at cold Ta. This presumably reflects the fact that cold air can hold minimal amounts of water vapor and any possible influence on heat loss is negligible. Instead, we suggest that a greater contributor to the humid-cold myth is the frequency of overcast days during which direct solar radiation is blocked.Summary statementBlack-capped chickadees significantly increased their resting metabolic rates at air temperatures below freezing relative to air temperatures above freezing, whereas humidity level did not significantly affect resting metabolic rates.
Large body size variation is linked to low communication success in tandem running ants
Authors: Thomas Wagner , Lena Bachenberg , Simone Glaser , Avgousta Oikonomou , Melissa Linn , Christoph Grüter 
Published: October 2019

AbstractDiversity in animal groups is often assumed to increase group performance. In insect colonies, genetic, behavioral and morphological variation among workers can improve colony functioning and resilience. However, it has been hypothesized that during communication processes, differences between workers, e.g. in body size, could also have negative effects. Tandem running is a common recruitment strategy in ants and allows a leader to guide a nestmate follower to resources. A substantial proportion of tandem runs fail because leader and follower loose contact. Using the antTemnothorax nylanderias a model system, we tested the hypothesis that tandem running success is impaired if leader and follower differ in size. Indeed, we found that the success rate of tandem pairs drops considerably as size variation increases: only ~7% of tandem runs were successful when the leader-follower size difference exceeded 10%, whereas 80% of tandem runs were successful when ants differed less than 5% in body length. One possible explanation is that ant size is linked to the preferred walking speed. Ants did not choose partners of similar size, but extranidal workers were larger than intranidal workers, which could reduce recruitment mistakes because it reduced the chance that very large and very small ants perform tandem runs together. Our results suggest that phenotypic differences between interacting workers can have negative effects on the efficiency of communication processes. Whether phenotypic variation has positive or negative effects is likely to depend on the task and the phenotypic trait that shows variation.
Resource conservation manifests in the genetic code
Authors: Shenhav Liat , Zeevi David 
Published: October 2019

AbstractNutrient limitation is a strong selective force, driving competition for resources. However, much is unknown about how selective pressures resulting from nutrient limitation shape microbial coding sequences. Here, we study this ‘resource-driven’ selection using metagenomic and single-cell data of marine microbes, alongside environmental measurements. We show that a significant portion of the selection exerted on microbes is explained by the environment and is strongly associated with nitrogen availability. We further demonstrate that this resource conservation optimization is encoded in the structure of the standard genetic code, providing robustness against mutations that increase carbon and nitrogen incorporation into protein sequences. Overall, we demonstrate that nutrient conservation exerts a significant selective pressure on coding sequences and may have even contributed to the evolution of the genetic code.
Enhancing autophagy by redox regulation extends lifespan inDrosophila
Authors: Lennicke Claudia , Bjedov Ivana , Grönke Sebastian , Menger Katja E. , James Andrew M. , Castillo-Quan Jorge Iván , van Leeuwen Lucie A. G. , Foley Andrea , Buricova Marcela , Adcott Jennifer , Montoya Alex , Kramer Holger B. , Shliaha Pavel V. , Logan Angela , Cabreiro Filipe , Murphy Michael P. , Partridge Linda , Cochemé Helena M. 
Published: October 2019

AbstractDysregulation of redox homeostasis has been implicated in the ageing process and the pathology of age-related diseases. To study redox signalling by H2O2in vivo, we established a redox-shifted model by manipulating levels of the H2O2-degrading enzyme catalase inDrosophila. Here we report that ubiquitous over-expression of catalase robustly extends lifespan in flies. As anticipated, these flies were strongly resistant to a range of oxidative stress challenges, but interestingly were sensitive to starvation, which could not be explained by differences in levels of energy reserves. This led us to explore the contribution of autophagy, which is an important mechanism for organismal survival in response to starvation. We show that autophagy is essential for the increased lifespan upon catalase up-regulation, as the survival benefits were completely abolished upon global autophagy knock-down. Furthermore, using a specific redox-inactive knock-in mutant, we highlight thein vivorole of a key regulatory cysteine residue in Atg4a, which is required for the lifespan extension in our catalase model. Altogether, these findings confirm the redox regulation of autophagyin vivoas an important modulator of longevity.
High-fidelity continuum modeling predicts avian voiced sound production
Authors: Jiang W. , Rasmussen J.H. , Xue Q. , Ding M. , Zheng X. , Elemans C.P.H. 
Published: October 2019

AbstractVoiced sound production is the primary form of acoustic communication in terrestrial vertebrates, particularly birds and mammals, including humans. Developing a causal physics-based model that links descending vocal motor control to tissue vibration and sound requires embodied approaches that include realistic representations of voice physiology. Here we first implement and then experimentally test a high-fidelity three-dimensional continuum model for voiced sound production in birds. Driven by individual-based physiologically quantifiable inputs, combined with non-invasive inverse methods for tissue material parameterization, our model accurately predicts observed key vibratory and acoustic performance traits. These results demonstrate that realistic models lead to accurate predictions and support the continuum model approach as a critical tool towards a causal model of motor control of voiced sound production.
Diabetic conditions induce intolerance to accumulation of pathogenic mitochondrial DNAs
Authors: Ogasawara Emi , Katada Shun , Mito Takayuki , Hayashi Jun-Ichi , Nakada Kazuto 
Published: October 2019

AbstractMarked accumulation of mitochondrial DNA (mtDNA) with a particular pathogenic mutation is necessary for the mutant mtDNA to express its pathogenicity as mitochondrial respiration defects. However, the nuclear genome background, or the physiological status, or both, might also be important for the pathogenic regulation of mutant mtDNAs, because most mitochondrial function is controlled by polypeptides encoded in the nuclear genome. To test this, we generated diabetic mice carrying pathogenic mtDNA with a large-scale deletion (ΔmtDNA) that loses six tRNA genes and seven structural genes essential for mitochondrial respiration. Compared with non-diabetic mice carrying ΔmtDNA, diabetic mice carrying ΔmtDNA showed a decrease in mitochondrial biogenesis regulated by nuclear-encoded genes, and mitochondrial respiration defects and the resultant mitochondrial disease phenotypes were induced even in the case of low loads of ΔmtDNA. In addition, diabetic culture conditions intensified the pathogenicity of human mtDNA with an A3243G point mutation in the tRNALue (UUR) gene. Our results indicated that the diabetic conditions are a modifier that exacerbates mitochondrial respiration defects due to mutant mtDNAs. The finding suggests the possibility that recovery from diabetic conditions might be an effective treatment strategy for some disorders involving both mutant mtDNAs and diabetic signs.Author SummaryIt has been reported that accumulation of pathogenic mutant mitochondrial DNA (mtDNA) and the resultant mitochondrial metabolic dysfunction are associated with a wide variety of disorders, such as mitochondrial diseases, diabetes, neuo-degenerative disorders, and cancers. Considering that most mitochondrial function is regulated by nuclear-genome-encoded polypeptides, it is very important to focus on cooperation between mutant mtDNA, nuclear genetic background, and vital conditions for understanding precise pathogeneses of mtDNA-mediated disorders. By using model cells and mice carrying pathogenic mtDNAs, we report here that diabetic conditions are a modifier for the pathogenic regulation of mutant mtDNAs. Because the onset and progression of diabetes are often associated with aging, our finding suggests that some age-associated disorders with mutant mtDNAs and diabetic complications might be induced partly by enhancement of the pathogenicity of mutant mtDNAs by diabetic conditions.
Brain, music and emotion: An EEG proof-of-concept study on musically continuous, non-personalized emotional responses
Authors: Papatzikis Efthymios , Herbst Anri 
Published: October 2019

AbstractIt has been repeatedly reported that motivation for listening to music is majorly driven by the latter’s emotional effect. There is a relative opposition to this approach, however, suggesting that music does not elicit true emotions. Counteracting this notion, contemporary research studies indicate that listeners do respond affectively to music providing a scientific basis in differentially approaching and registering affective responses to music as of their behavioral or biological states. Nevertheless, no studies exist that combine the behavioral and neuroscientific research domains, offering a cross-referenced neuropsychological outcome, based on a non-personalized approach specifically using a continuous response methodology with ecologically valid musical stimuli for both research domains. Our study, trying to fill this void for the first time, discusses a relevant proof-of-concept protocol, and presents the technical outline on how to multimodally measure elicited responses on evoked emotional responses when listening to music. Specifically, we showcase how we measure the structural music elements as they vary from the beginning to the end within two different compositions, suggesting how and why to analyze and compare standardized, non-personalized behavioral to electroencephalographic data. Reporting our preliminary findings based on this protocol, we focus on the electroencephalographic data collected from n=13 participants in two separate studies (i.e., different equipment and sample background), cross-referencing and cross-validating the biological side of the protocol’s structure. Our findings suggest (a) that all participants – irrespectively of the study – reacted consistently in terms of hemispheric lateralization for each stimulus (i.e., uniform intra-subjective emotional reaction; non-statistically significant differentiation in individual variability) and (b) that diverse patterns of biological representations emerge for each stimulus between the subjects in the two studies (variable inter-subjective emotional reaction; statistically significant differentiation in group variability) pointing towards exogenous to the measurements process factors. We conclude discussing further steps and implications of our protocol approach.
Isolation and characterisation of watermelon (Citrullus lanatus) extracellular vesicles and their cargo
Authors: Timms Kate , Holder Beth , Day Anil , McLaughlin John , Westwood Melissa , Forbes Karen 
Published: October 2019

AbstractExtracellular vesicles (EVs) facilitate cell-cell communication in animals and are integral to many physiological and pathological processes. Evidence for the presence and function of EVs in plants is limited. Here, we report that EVs derived from watermelon fruit mesocarp are of similar size and morphology to the animal EV subtype known as exosomes. Analysis of EV constituents revealed that watermelon EVs are negative for endoplasmic reticulum markers, and that the miRNA and protein profiles differ from that of watermelon mesocarp cells, suggesting that these EVs are actively synthesised and are not merely cellular debris. Furthermore, we report a panel of proteins found in in watermelon EVs as well as the published proteomes of grape, grapefruit, lemon andArabidopsis thalianaEVs that are novel potential plant EV markers. Bioinformatic analyses suggest that plastids and multivesicular bodies are likely sites of biogenesis for EVs from watermelon and other plants. Predicted functional roles of watermelon EVs include development and metabolism, with several of their cargo molecules likely to be key in regulation of fruit development and ripening. Further understanding of how EVs may contribute to these processes would improve understanding of plant cell-cell communication and could aid in the harnessing of plant EVs for greater temporal control of crop development/ripening for the agricultural and retail industries.