bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ongoing shuffling of protein fragments diversifies core viral functions linked to interactions with bacterial hosts
Authors: Smug Bogna J. , Szczepaniak Krzysztof , Rocha Eduardo P.C. , Dunin-Horkawicz Stanislaw , Mostowy Rafał J. 
Published: December 2022

AbstractBiological modularity enhances evolutionary adaptability by allowing rearrangement of functional components. One striking example are bacterial viruses (phages). They exhibit extensive genomic modularity by being built of independent functional modules that evolve separately and combine in various ways, making them astoundingly diverse. While multiple studies have investigated genomic modularity in phages, less attention has been given to protein modularity—proteins having distinct building blocks or domains that can evolve and recombine, enhancing functional and genetic diversity. To better understand the impact of protein modularity on viral evolution, we quantified it by detecting instances of domain mosaicism, defined as a homologous fragment sharing between two otherwise unrelated proteins. We used highly sensitive homology detection to quantify domain mosaicism between pairs of 133,574 representative phage proteins and to understand its relationship with functional diversity in phage genomes. We found that diverse functional classes often shared homologous domains. This phenomenon was often linked to protein modularity, particularly in receptor-binding proteins, endolysins and DNA polymerases. We also identified multiple instances of recent diversification via exchange and gain/loss of domains in receptor-binding proteins, neck passage structures, endolysins and some members of the core replication machinery. Diversification via protein fragment exchange often transcended distant taxonomic and ecological borders. We argue that the ongoing diversification via shuffling of protein domains associated with those functions is reflective of co-evolutionary arms race and the resulting diversifying selection to overcome multiple mechanisms of bacterial resistance against phages.
Metagenomics reveals that Dung Beetles (Coleoptera: Scarabaeinae) broadly feed on Reptile dung and could feed on that of Dinosaurs
Authors: Lopes Fernando , Rossini Michele , Losacco Federica , Montanaro Giulio , Gunter Nicole , Tarasov Sergei 
Published: December 2022

ABSTRACTAccording to traditional views, the evolution of dung beetles (Coleoptera: Scarabaeinae) and their feeding habits are largely attributed to mammal dung. In this paper, we challenge this view and provide evidence that many dung beetle communities are actually associated with the dung of reptiles and birds (= Sauropsida). In turn, this indicates that sauropsid dung may have played a crucial evolutionary role that was previously underestimated. We argue that it is physiologically realistic to consider that coprophagy in dung beetles could have evolved during the Cretaceous in response to the massive amount of dung produced by dinosaurs. Furthermore, we demonstrate that sauropsid dung may be one of the major factors driving the emergence of insular dung beetle communities across the globe. We support our findings with amplicon-metagenomic analyses, trapping experiments, and meta-analysis of the published literature.
Precise Traits From Sloppy Components: Perception and the Origin of Phenotypic Response
Authors: Frank Steven A. 
Published: December 2022

AbstractOrganisms perceive their environment and respond. The origin of perception-response traits presents a puzzle. Perception provides no value without response. Response requires perception. Recent advances in machine learning may provide a solution. A randomly connected network creates a reservoir of perceptive information about the recent history of environmental states. In each time step, a relatively small number of inputs drives the dynamics of the relatively large network. Over time, the internal network states retain memory of past inputs. To achieve a functional response to past states or to predict future states, a system must learn only how to match states of the reservoir to the target response. In the same way, a random biochemical or neural network of an organism can provide an initial perceptive basis. With a solution for one side of the two-step perception-response challenge, evolving an adaptive response may not be so difficult. Two broader themes emerge. First, organisms may often achieve precise traits from sloppy components. Second, evolutionary puzzles often follow the same outlines as the challenges of machine learning. In each case, the basic problem is how to learn, either by artificial computational methods or by natural selection.
Effect ofAscosphaera apisinfestation on the activities of four antioxidant enzymes in Asian honey bee larval guts
Authors: Zhang Kaiyao , Fu Zhongmin , Fan Xiaoxue , Wang Zixin , Wang Siyi , Guo Sijia , Gao Xuze , Zhao Haodong , Jing Xin , Zou Peiyuan , Li Qiming , Chen Mengjun , Chen Dafu , Guo Rui 
Published: December 2022

AbstractAscosphaera apisexclusively infects bee larvae and causes chalkbrood, a lethal fungal disease that results in the sharp reduction in adult bees and colony productivity. However, little is known about the effect ofA. apisinfestation on the activities of antioxidant enzymes in bee larvae. Here,A. apisspores were purified and used to inoculate Asian honey bee (Apis cerana) larvae, followed by detection of the host survival rate and evaluation of the activities of four major antioxidant enzymes. At 6 days post inoculation (dpi) withA. apisspores, white mycelia penetrated the posterior end of the larva, extended to the anterior end, and eventually covered the entire larval body surface, presenting an obvious symptom of chalkbrood disease similar to that occurs inApis melliferalarvae. Additionally, PCR identification showed that the expected fragment was amplified from theA. apis-inoculated larval guts and theA. apisspores, verifying theA. apisinfection ofA. ceranalarvae. The survival rate of larvae inoculated withA. apiswas high at 1–2 dpi, sharply decreased to 4.16% at 4 dpi, and reached 0% at 5 dpi; whereas that of un-inoculated larvae was always high at 1~8 dpi, with an average survival rate of 95.37%, indicating the negative impact ofA. apisinfection on larval survival. Furthermore, in comparison with those in the corresponding un-inoculated groups, the superoxide dismutase (SOD) and catalase (CAT) activities in the 4-day-old larval gut in theA. apis-inoculated groups were reduced (p> 0.05), while those in the 5- and 6-day-old larval guts were significantly decreased (p< 0.05); the glutathione S-transferase (GST) activity in the 4- and 5-day-old larval guts was significantly increased (p< 0.05), while that in the 6-day-old larval gut was reduced (p> 0.05); the polyphenol oxidase (PPO) activity in 4-day-old larval gut was increased (p> 0.05) and that in the 5-day-old larval gut was significantly increased (p< 0.05), whereas that in the 6-day-old larval gut was significantly reduced (p< 0.01). These results together suggested that the activities of SOD and CAT in the larval guts were suppressed during the process ofA. apisinfestation, while the GST activity was induced to activation, and the PPO activity was first enhanced and then inhibited. Our findings not only unravel the response ofA. ceranalarvae toA. apisinfestation from a biochemical perspective, but also offer a valuable insight into the interaction between Asian honey bee larvae andA. apis.
Structural damping renders the insect exoskeleton mechanically insensitive to non-sinusoidal deformations
Authors: Wold Ethan S. , Lynch James , Gravish Nick , Sponberg Simon 
Published: December 2022

AbstractMuscles act through elastic and dissipative elements to mediate movement, but these elements can introduce dissipation and filtering which are important for energetics and control. The high power requirements of flapping flight can be reduced by the insect’s exoskeleton, which acts as a structurally damped spring under purely sinusoidal deformation. However, this purely sinusoidal dynamic regime does not encompass the asymmetric wing strokes of many insects or non-periodic deformations induced by external perturbations. As such, it remains unknown whether a structural damping model applies broadly and what implications it has for control. We used a vibration testing system to measure the mechanical properties of isolatedManduca sextathoraces under symmetric, asymmetric, and band-limited white noise deformations. We measured a thoracic stiffness of 2980Nm−1at 25 Hz and physiological peak-to-peak amplitude of 0.92 mm. Power savings and dissipation were indistinguishable between symmetric and asymmetric conditions, demonstrating that no additional energy is required to deform the thorax non-sinusoidally. Under white noise conditions, stiffness and damping were invariant with frequency, which is consistent with a structural damping model and suggests the thorax has no frequency-dependent filtering properties. A simple flat frequency response function fits our measured frequency response. This work demonstrates the potential of structurally damped materials to simplify motor control by eliminating any velocity-dependent filtering that viscoelastic elements usually impose between muscle and appendage.
Improved genetically encoded fluorescent biosensors for monitoring of intra- and extracellular L-lactate
Authors: Nasu Yusuke , Aggarwal Abhi , Le Giang N. T. , Kamijo Yuki , Boisvert Marc , Paquet Marie-Eve , Drobizhev Mikhail , Podgorski Kaspar , Campbell Robert E. 
Published: December 2022

Abstractl-Lactate is increasingly appreciated as a key metabolite and signaling molecule in mammals. To enable investigations of both the inter- and intra-cellular dynamics ofl-Lactate, we develop a second-generation green fluorescent extracellularl-Lactate biosensor, designated eLACCO2.1, and a red fluorescent intracellularl-Lactate biosensor, designated R-iLACCO1. Compared to the first-generation eLACCO1.1 (ΔF/F= 1.5 in cultured neurons), eLACCO2.1 exhibits better membrane localization and fluorescence response (ΔF/F= 8.1 in cultured neurons) with faster response kinetics to extracellularl-Lactate on the surface of live mammalian cells. R-iLACCO1 and its affinity variants exhibit large fluorescence responses to changes inl-Lactate concentrationin vitro(ΔF/F= 15 to 22) and in live mammalian cells (ΔF/F= 5.5 to 11). We demonstrate that these biosensors enable cellular-resolution imaging of extracellular and intracellularl-Lactate in cultured mammalian cells.
Effects of canagliflozin and irbesartan on renal fibrosis in Dahl salt-sensitive rats
Authors: Zhai Jianlong , Wang Zhongli , Zhang Tingting , He Lili , Ma Sai , Zuo Qingjuan , Zhang Guorui , Wang Xinyu , Guo Yifang 
Published: December 2022

AbstractHypertension is one of the major contributors to cardiovascular and chronic kidney disease (CKD). Sodium-glucose cotransporter 2 (SGLT2) inhibitors and angiotensin receptor blockers (ARBs) have become the preferred treatment for patients with CKD. However, the renoprotective effects of the combined therapy of the two drugs on hypertensive renal fibrosis are still largely understood. The aim of this study was to compare the antifibrotic effects of canagliflozin, with or without irbesartan, in the kidneys of Dahl salt-sensitive (Dahl SS) rats on a high salt (HS) diet. After the preconditioning stage, Dahl SS rats (n = 47) were divided into 5 experimental groups as follows: low salt control (n=7), HS control (n=10), high salt with canagliflozin (n=10), high salt with irbesartan (n=10), and high salt with canagliflozin plus irbesartan (n=10). Mean food and water intake, body weight (BW), and systolic blood pressure (SBP) were measured during the whole experimental period. After 12 weeks, the rats were euthanized, and the kidneys were excised for histomorphometric evaluation and immunohistochemical evaluation. An HS diet increased SBP, renal fibrosis, expression of fibrotic protein factors, and TGF-β/Smad2/3 pathway compared to the LS group. We found that irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced BW and renal fibrosis and downregulated the TGF-β/Smad2/3 pathway. The combined therapy showed better renoprotection in all outcome parameters. In conclusion, these results indicate that canagliflozin and irbesartan exert different benefits on nephroprotection in salt-sensitive hypertensive rats.
Muscle function during locomotion on skis at varying speed and incline conditions
Authors: Werkhausen Amelie , Lundervold Anders , Gløersen Øyvind 
Published: December 2022

AbstractThe human musculoskeletal system is well adapted to use energy efficient muscle-tendon mechanics during walking and running but muscle behaviour during on-snow locomotion is unknown. Therefore, we examined muscle and muscle-tendon unit behaviour during diagonal style roller skiing at three speed and incline conditions.We assessed lower leg muscle and muscle-tendon unit mechanics and muscle activity in thirteen high-level skiers during treadmill roller skiing using synchronised ultrasound, motion capture, electromyography and ski-binding force measurements. Participants skied using diagonal style at 2.5 and 3.5 m·s−1at 5°, and at 2.5 m·s−1at 10°.We found an uncoupling of muscle and joint behaviour during most parts of the propulsive kick phase in all conditions (P<0.01). Gastrocnemius muscle fascicles actively shortened ~9 mm during the kick phase, while the muscle-tendon unit went through a stretch-shortening cycle. Peak muscle-tendon unit shortening velocity was five times higher than fascicle velocity (375 vs 74 mm·s−1,P<0.01). Increased incline was met by greater muscle activity (24%,P=0.04) and slower fascicle shortening velocities (34 vs. 45 mm·s−1,P<0.01). Increased speed was met by greater peak muscle activity (23%,P<0.01) and no change in fascicle shortening velocity.Our data show that muscle behaviour was uncoupled from the joint movement, which enables beneficial contractile conditions and energy utilisation during diagonal style at different slopes and speeds. Active preloading in the end of the glide phase may benefit the mechanisms.Summary statementWe examined muscle function during diagonal style cross country skiing in competitive cross-country skiers. Our data show an uncoupling of muscle and joint behaviour in the lower leg during skiing.
ISG15-modification of the Arp2/3 complex restricts pathogen spread
Authors: Zhang Yifeng , Ripley Brittany , Ouyang Wei , Sturtz Miranda , Upton Ellen , Luhmann Emma , Vessely Madeleine , Coloma Rocio , Schwery Nathan , Anthony Scott M. , Goeken Adam , Moninger Thomas O. , Harty John T. , Klingelhutz Aloysius , Lundberg Emma , Meyerholz David K. , Manicassamy Balaji , Stipp Christopher , Guerra Susana , Radoshevich Lilliana 
Published: December 2022

SummaryThe ubiquitin-like protein, ISG15, can act as a cytokine or can covalently modify host and pathogen-derived proteins. The consequences of ISG15 modification on substrate fate remain unknown. Here we reveal that ISGylation of the Arp2/3 complex slows actin filament formation and stabilizes Arp2/3 dependent structures including cortical actin and lamella. When properly controlled, this serves as an antibacterial and antiviral host defense strategy to directly restrict actin-mediated pathogen spread. However,Listeria monocytogenestakes advantage in models of dysregulated ISGylation, leading to increased mortality due to augmented spread. The underlying molecular mechanism responsible for the ISG15-dependent impact on actin-based motility is due to failed bacterial separation after division. This promotes spread by enabling the formation of multi-headed bacterial “bazookas” with stabilized comet tails that can disseminate deeper into tissues. A bacterial mutant that cannot recruit Arp2/3 or a non-ISGylatable mutant of Arp3 is sufficient to rescue slowed comet tail speed and restrict spread. Importantly, ISG15-deficient neonatal mice have aberrant epidermal epithelia characterized by keratinocytes with diffuse cortical actin, which could underlie observed defects in wound healing in human patients who lack ISG15. Ultimately, our discovery links host innate immune responses to cytoskeletal dynamics with therapeutic implications for viral infection and metastasis.
Viral and host small RNA transcriptome analysis of SARS-CoV-1 and SARS-CoV-2-infected human cells reveals novel viral short RNAs
Authors: Driedonks Tom , Nyberg Lyle H. , Conte Abigail , Ma Zexu , Pekosz Andrew , Duban Eduard , Sültmann Holger , Turchinovich Andrey , Witwer Kenneth 
Published: December 2022

ABSTRACTRNA viruses have been shown to express various short RNAs, some of which have regulatory roles during replication, transcription, and translation of viral genomes. However, short viral RNAs (svRNAs) generated by SARS-CoV-1 and SARS-CoV-2 remained largely unexplored, mainly due limitations of the widely used library preparation methods for small RNA deep sequencing and corresponding data processing. By analyzing publicly available small RNA-seq datasets, we observed that human cells infected by SARS-CoV-1 or SARS-CoV-2 produce multiple short viral RNAs (svRNAs), ranging in size from 15 to 26 nt and deriving predominantly from (+) RNA strands. In addition, we verified the presence of the five most abundant SARS-CoV-2 svRNAs in SARS-CoV-2-infected human lung adenocarcinoma cells by qPCR. Interestingly, the copy number of the observed SARS-CoV-2 svRNAs dramatically exceeded the expression of previously reported viral miRNAs in the same cells. We hypothesize that the reported SARS-CoV-2 svRNAs could serve as biomarkers for early infection stages due to their high abundance. Finally, we found that both SARS-CoV-1 and SARS-CoV-2 infection induced up- and down-regulation of multiple endogenous human short RNAs that align predominantly to protein-coding and lncRNA transcripts. Interestingly, a significant proportion of short RNAs derived from full-length viral genomes also aligned to various hg38 sequences, suggesting opportunities to investigate regulatory roles of svRNAs during infection. Further characterization of the small RNA landscape of both viral and host genomes is clearly warranted to improve our understanding of molecular events related to infection and to design more efficient strategies for therapeutic interventions as well as early diagnosis.
Biocontainment strategies forin vivoapplications ofSaccharomyces boulardii
Authors: Hedin Karl Alex , Kruse Vibeke , Vazquez-Uribe Ruben , Sommer Morten Otto Alexander 
Published: December 2022

AbstractThe human gastrointestinal tract is a complex and dynamic environment, playing a crucial role in human health. Microorganisms engineered to express a therapeutic activity have emerged as a novel modality to manage numerous diseases. Such advanced microbiome therapeutics (AMTs) must be contained within the treated individual. Hence safe and robust biocontainment strategies are required to prevent the proliferation of microbes outside the treated individual. Here we present the first biocontainment strategy for a probiotic yeast, demonstrating a multilayered strategy combining an auxotrophic and environmental-sensitive strategy. We knocked out the genesTHI6andBTS1, causing thiamine auxotrophy and increased sensitivity to cold, respectively. The biocontainedSaccharomyces boulardiiwas unable to grow in the absence of thiamine above 1 ng/mL and exhibited a severe growth defect at temperatures below 20°C. The biocontained strain was well tolerated and viable in mice and demonstrated equal efficiency in peptide production as the ancestral non-biocontained strain. In combination, the data support thatthi6Δ andbts1Δ enable biocontainment ofS. boulardii, which could be a relevant chassis for future yeast-based AMTs.
Validation of the EEG signal of the URGOnight neurofeedback device, associated with a new SMR detection method
Authors: Saulnier Rudy , Spiluttini Béatrice , Touré-Cuq Emma , Benchenane Karim 
Published: December 2022

AbstractSensorimotor (SMR) neurofeedback is a promising therapy for several health disorders but is still not widely used due to the high cost of the equipment. URGOnight offers a low-cost solution to democratize these therapies by providing an at-home EEG headband with dry electrodes connected to a mobile application. The first aim of this study is both to validate the URGOnight EEG signal and to compare it to Enobio-20, a medical grade EEG device. The second aim of the study is to propose a new method to detect SMR rhythm based on its oscillatory properties and discriminate it from alpha oscillations.In our study, we compared the URGOnight headband EEG signal (C3/C4) to Enobio-20 (CP3/CP4), placed on subjects simultaneously equipped with the two headbands. All subjects (n=33) performed a dual blocking task inspired by Kulhman (1978) based on the blocking effect of movement and eyes opening on SMR and alpha respectively. This task was followed by SSVEP stimulations to evaluate the frequency response of the two EEG devices. The performance of the EEG headbands was statistically identical for most of the characteristics of the EEG signal, including the frequency response to SSVEP (from 4Hz to 20Hz). The main difference was a larger amplitude in the 8-15Hz due to the location of the reference in URGOnight that did not impair the detection of both alpha and SMR.In addition, we show that our new method allows to discriminate alpha and SMR rhythms based on their oscillatory properties with a single recording site (C3/C4). The method is fast enough to be used in real time. We show that the detected SMR rhythm is modulated by movement as opposed to the 12-15Hz frequency band often used as indicator of SMR in most neurofeedback studies.Altogether, our results validate the quality of the EEG recordings obtained with URGOnight since it gives similar results as the one obtained with Enobio-20, a validated EEG medical grade system. In addition, we provide a new method allowing the identification and the separation of the alpha and SMR with a single recording site C3/C4. This method opens up a new research lead to improve SMR neurofeedback efficiency and thus of its clinical possibilities by focusing on the reinforcement of the SMR oscillation strictly speaking.Highlights-Validation of the URGOnight EEG device suitable for neurofeedback at home-New method for the detection and the discrimination of alpha rhythm and SMR rhythm with a small number of recording sites-The oscillatory activity related to the SMR displays different properties compared to the 12-15Hz frequency band.-Description of a full validation procedure for wireless EEG devices usable at home for neurofeedback-Comparison of the signal of URGOnight (dry electrodes) with a wet electrode EEG device
Social defeat induces REM sleep fragmentation through the PFC-VLPO pathway
Authors: Chouvaeff M. , Bagur S. , Mace L. , Gallopin T. , Benchenane K. 
Published: December 2022

ABSTRACTThe brainstem and hypothalamic structures implementing the daily cycles of wake, REM and NREM sleep have now been identified in remarkable detail. However, sleep structure dynamically adapts to environmental stressors, likely requiring top-down cortical feedback that is as yet unidentified. Here, we investigate the role of projections from prefrontal cortex (PFC), a key hub in stress regulation, to the ventro-lateral preoptic areas (VLPO), a master regulator of sleep states. Usingex vivooptogenetics, we demonstrate that activation of PFC terminals induces monosynaptic excitatory glutamatergic currents in VLPO NREM-promoting neurons.In vivo, activation of PFC-VLPO projections interrupts ongoing REM in favour of NREM, leading to fragmented REM bouts. Remarkably, chemogenetic inhibition of PFC-VLPO projections has no effect in baseline conditions but it blocks the REM fragmentation induced by Social Defeat Stress. Therefore, the PFC-VLPO pathway provides a top-down regulation specifically recruited in stressful conditions to induce short, fragmented REM bouts and favor NREM sleep.