bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular understanding ofEubacterium limosumchemostat methanol metabolism
Authors: Wood Jamin C. , Gonzalez-Garcia R. Axayacatl , Daygon Dara , Talbo Gert , Plan Manuel R. , Marcellin Esteban , Virdis Bernardino 
Published: November 2022

AbstractMethanol is a promising renewable energy carrier that can be used as a favourable substrate for biotechnology, due to its high energy efficiency conversion and ease of integration within existing infrastructure. Some acetogenic bacteria have the native ability to utilise methanol, along with other C1substrates such as CO2and formate, to produce valuable chemicals. Continuous cultures favour economically viable bioprocesses, however, the performance of acetogens has not been investigated at the molecular level when grown on methanol. Here we present steady-state chemostat quantification of the metabolism ofEubacterium limosum, finding maximum methanol uptake rates up to 640±22 mmol/gDCW/d, with significant fluxes to butyrate. To better understand metabolism of acetogens under methanol growth conditions, we sampled chemostats for proteomics and metabolomics. Changes in protein expression and intracellular metabolomics highlighted key aspects of methanol metabolism, and highlighted bottleneck conditions preventing formation of the more valuable product, butanol. Interestingly, a small amount of formate in methylotrophic metabolism triggered a cellular state known in other acetogens to correlate with solventogenesis. Unfortunately, this was prevented by post-translation effects including an oxidised NAD pool. There remains uncertainty around ferredoxin balance at the methylene-tetrahydrofolate reductase (MTHFR) and at the Rnf level.
Spatial regulation of the glycocalyx component Podocalyxin is a switch for pro-metastatic function
Authors: Román-Fernández Alvaro , Mansour Mohammed A. , Kugeratski Fernanda G. , Anand Jayanthi , Sandilands Emma , Galbraith Laura , Rakovic Kai , Freckmann Eva C. , Cumming Erin M. , Park Ji , Nikolatou Konstantina , Lilla Sergio , Shaw Robin , Strachan David , Mason Susan , Patel Rachana , McGarry Lynn , Katoch Archana , Campbell Kirsteen J. , Nixon Colin , Miller Crispin J. , Leung Hing Y. , Le Quesne John , Norman James C. , Zanivan Sara , Blyth Karen , Bryant David M. 
Published: November 2022

AbstractThe glycocalyx component and sialomucin Podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumour types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for Galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL highversuslow surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipulated cells or those with different surface levels of PODXL define that this axis controls metastasisin vivo. Clinically, interplay between PODXL-GAL3 stratifies prostate cancer patients with poor outcome. Our studies define the molecular mechanisms and context in which PODXL promotes invasion and metastasis.
Can recent evolutionary history promote resilience to environmental change?
Authors: Bladon Eleanor Kate , Pascoal Sonia , Kilner Rebecca Mary 
Published: November 2022

AbstractPrinciples of social evolution have long been used retrospectively to interpret social interactions, but have less commonly been applied predictively to inform conservation and animal husbandry strategies. We investigate whether differences in developmental environment, facilitated by divergent social conditions, can predict resilience to environmental change. Upon exposure to harsh novel environments, populations that previously experienced more benign social environments are predicted either to suffer fitness losses (the “mutation load hypothesis” and “selection filter hypothesis”) or maintain fitness (the “beneficial mutation hypothesis”). We tested these contrasting predictions using populations of burying beetlesNicrophorus vespilloideswe had evolved experimentally for 45 generations under contrasting social environments by manipulating the supply of post-hatching parental care. We exposed sexually immature adults from each population to varying heat stress and measured the effect on survival and reproduction. The greater the level of parental care previously experienced by a population, the better its survival under heat stress during sexual maturation. Although this is consistent with the “beneficial mutation hypothesis”, it is also possible that populations that had evolved without post-hatching care were simply more prone to dying during maturation, regardless of their thermal environment. Overall, we suggest that stochastic genetic variation, probably due to founder effects, had a stronger influence on resilience. We discuss the implications for translocation and captive breeding programmes.Lay summaryCan we use knowledge of a population’s evolutionary history to predict how individuals might cope with environmental change? We investigated whether burying beetles that had evolved for 45 generations with or without post-hatching parental care differed in their resilience to extreme temperatures as they developed to sexual maturity. We found limited evidence that experimental evolution under different regimes of parental care contributed to thermal resilience, which instead was better explained by chance historical events.
A new take on model-based and model-free influences on mental effort and striatal prediction errors
Authors: da Silva Carolina Feher , Lombardi Gaia , Edelson Micah , Hare Todd A. 
Published: November 2022

AbstractA standard assumption in neuroscience is that low-effort model-free learning is automatic and continuously employed, while more complex model-based strategies are only used when the rewards they generate are worth the additional effort. We present evidence refuting this assumption. First, we demonstrate flaws in previous reports of combined model-free and model-based reward prediction errors in the ventral striatum that likely led to spurious results. More appropriate analyses yield no evidence of a model-free prediction errors in this region. Second, we find that task instructions generating more correct model-based behaviour reduce rather than increase mental effort. This is inconsistent with cost-benefit arbitration between model-based and model-free strategies. Together, our data suggest that model-free learning may not be automatic. Instead, humans can reduce mental effort by using a model-based strategy alone rather than arbitrating between multiple strategies. Our results call for re-evaluation of the assumptions in influential theories of learning and decision-making.
Prediction of elimination of intrahepatic cccDNA in hepatitis B virus-infected patients by a combination of noninvasive viral markers
Authors: Kim Kwang Su , Iwamoto Masashi , Kitagawa Kosaku , Hayashi Sanae , Tsukuda Senko , Matsui Takeshi , Atsukawa Masanori , Chuaypen Natthaya , Tangkijvanich Pisit , Allweiss Lena , Nishiyama Takara , Nakamura Naotoshi , Fujita Yasuhisa , Kawakami Eiryo , Nakaoka Shinji , Muramatsu Masamichi , Aihara Kazuyuki , Wakita Takaji , Perelson Alan S. , Dandri Maura , Watashi Koichi , Iwami Shingo , Tanaka Yasuhito 
Published: November 2022

AbstractEvaluation of intrahepatic covalently closed circular DNA (cccDNA) is a key for searching an elimination of hepatitis B virus (HBV) infection. HBV RNA and HBV core-related antigen have been proposed as surrogate markers for evaluating cccDNA activity, although they do not necessarily estimate the amount of cccDNA. Here, we developed a novel multiscale mathematical model describing intra- and inter-cellular viral propagation, based on the experimental quantification data in both HBV-infected cell culture and humanized mouse models. We applied it to HBV-infected patients under treatment and developed a model which can predict intracellular HBV dynamics only by use of noninvasive extracellular surrogate biomarkers. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well-correlated with the liver biopsy data. Thus, our noninvasive method enables to predict the amount of cccDNA in patients and contributes to determining the treatment endpoint required for elimination of intrahepatic cccDNA.
PRMT5 links lipid metabolism to contractile function of skeletal muscles
Authors: Kim Kun Ho , Jia Zhihao , Snyder Madigan M. , Chen Jingjuan , Qiu Jiamin , Oprescu Stephanie N. , Chen Xiyue , Syed Sabriya A , Yue Feng , Roseguini Bruno T. , Imbalzano Anthony N. , Hu Changdeng , Kuang Shihuan 
Published: November 2022

AbstractThe skeletal muscle plays a key role in systemic energy homeostasis besides its canonical contractile function, but what couples these functions is poorly defined. Protein Arginine MethylTransferase 5 (PRMT5) is a well-known oncoprotein but also expressed in healthy tissues with unclear physiological functions. As adult muscles express high levels ofPrmt5, we generated myocyte-specificPrmt5knockout (Prmt5MKO) mice. We observed reduced muscle mass, oxidative capacity, force production and exercise performance inPrmt5MKOmice. The motor deficiency is associated with scarce lipid droplets in myofibers due to defects in lipid biosynthesis and degradation. First,Prmt5MKOreduced demethylation and stability of Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a), a master regulator ofde novolipogenesis. Second,Prmt5MKOimpaired the repressive H4R3Me2s (histone H4 arginine-3 symmetric demethylation) at thePnpla2gene, elevating the level of its encoded protein ATGL, the rate-limiting enzyme catalyzing lipolysis. Accordingly, myocyte-specific double knockout ofPnpla2andPrmt5normalized muscle mass and function. Together, our findings delineate a physiological function of PRMT5 in linking lipid metabolism to contractile function of myofibers.
HIV-1 Vpr induces ciTRAN to prevent transcriptional silencing of the provirus
Authors: Bhardwaj Vipin , Singh Aman , Dalavi Rishikesh , Ralte Lalchhanhima , Chawngthu Richard L. , Kumar Nachimuthu Senthil , Vijay Nagarjun , Chande Ajit 
Published: November 2022

AbstractThe functional relevance of circular RNA (circRNA) expression in HIV-1 infection remains unclear. By developing a customized protocol involving direct RNA nanopore sequencing here, we captured circRNAs in their native state from HIV-1 infected T cells and identified ciTRAN, acircRNA modulator of HIV-1Transcription. We show that HIV-1 infection of monocytic, T cell lines and primary CD4+ T cells induces ciTRAN expression in a Vpr-dependent manner. ciTRAN protein interactome analysis by proximity biotinylation and mass spectrometry identified SRSF-1 as a prominent interactor of the circular RNA. SRSF-1 is known to negatively regulate HIV-1 transcription, which the virus overcomes by a yet unknown mechanism. We demonstrate that HIV-1 Vpr induced ciTRAN sequesters SRSF1 away from the viral transcriptional complex to promote efficient viral transcription. Accordingly, ciTRAN depletion by CRISPR-Cas phenocopied the effects of SRSF1 overexpression and improved SRSF1 association with HIV-1 transcriptional complex. Finally, we show that an SRSF-1-inspired competing peptide can inhibit HIV-1 transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a new facet of primate lentiviruses in overcoming transmission bottlenecks.
Bold but not innovative in an urban exploiter, the red fox (Vulpes vulpes)
Authors: Morton F. Blake , Gartner Marieke , Norrie Ellie-Mae , Haddou Yacob , Soulsbury Carl D. , Adaway Kristy A. 
Published: November 2022

AbstractUrbanisation is the fastest form of landscape transformation on the planet, but researchers’ understanding of the relationships between urbanisation and animal adaptability is still in its infancy. In terms of foraging, bold and innovative behaviours are proposed to help urban animals access, utilise, and exploit novel anthropogenic food sources. Red foxes (Vulpes vulpes) are one of the best known and widespread urban-dwelling species. However, despite frequent stories, images, and videos portraying them as “pests” due to their exploitation of food-related objects (e.g., raiding the contents of outdoor bins), it is unknown whether they are bolder and more innovative in terms of their likelihood of exploiting these resources compared to rural populations. In the current study, we gave novel food-related objects to foxes from 104 locations (one object per location) across a large urban-rural gradient. To access the food, foxes had to use behaviours necessary for exploiting many food-related objects in the real world (e.g., biting, pushing, pulling, or lifting human-made materials). Despite all foxes acknowledging the objects, foxes from 31 locations touched them, while foxes from 12 locations gained access to the food inside. A principal component analysis of urban and other landscape variables (e.g., road, greenspace, and human population density) revealed that urbanisation was significantly and positively related to the likelihood of foxes touching, but not exploiting, the objects. Thus, while urban foxes may be bolder than rural populations in terms of their willingness to physically touch novel food-related objects, our findings are inconsistent with the notion that they are more innovative and pose a general nuisance to people by exploiting these anthropogenic resources.HighlightsThe impact of urbanisation on animal adaptability remains unclearBold and innovative behaviour may help some urban species thriveWe studied wild red foxes’ responses to novel food-related objectsUrban foxes were bolder, but not more innovative, than rural foxesUrbanisation may favour bolder, not more innovative, fox behaviour
Optogenetic control of YAP can enhance the rate of wound healing
Authors: Toh Pearlyn Jia Ying , Sudol Marius , Saunders Timothy Edward 
Published: November 2022

AbstractBackgroundTissues need to regenerate to restore function after injury. Yet, this regenerative capacity varies significantly between organs and between species. For example, in the heart, some species retain full regenerative capacity throughout their lifespan but human cardiac cells display limited ability to repair injury. After a myocardial infarction, the function of cardiomyocytes is impaired and reduces the ability of the heart to pump, causing heart failure. Therefore, there is a need to restore the function of an injured heart post myocardial infarction. We investigate in cell culture the role of the YAP, a transcriptional co-regulator with a pivotal role in growth, in driving repair after injury.MethodsWe express optogenetic YAP (optoYAP) in three different cell lines. We characterised the behaviour and function of optoYAP using fluorescence imaging and quantitative real-time PCR of downstream YAP target genes. Mutant constructs were generated using site-directed mutagenesis. Nuclear localised optoYAP was functionally tested using wound healing assay and anchorage-independent colony formation assay.ResultsUtilising optoYAP, which enables precise control of pathway activation, we show that YAP induces the expression of downstream genes involved in proliferation and migration. optoYAP can increase the speed of wound healing in H9c2 cardiomyoblasts. Interestingly, this is not driven by an increase in proliferation, but by collective cell migration. We subsequently dissect specific phosphorylation sites in YAP to identify the molecular driver of accelerated healing.ConclusionsThis study shows that optogenetic YAP is functional in H9c2 cardiomyoblasts and its controlled activation can potentially enhance wound healing in a range of conditions.
Distinct feedforward and feedback pathways for cell-type specific attention effects
Authors: Spyropoulos Georgios , Schneider Marius , van Kempen Jochem , Gieselmann Marc Alwin , Thiele Alexander , Vinck Martin 
Published: November 2022

AbstractSpatial attention selectively enhances neural responses to visual stimuli. There are two long-standing hypotheses about how top-down feedback enhances sensory responses in areas like V4: First, by amplifying V1-to-V4 feedforward communication via 30-80Hz gamma-coherence. Second, via top-down feedback to V4 supra- and infra-granular layers. To test these hypotheses, we recorded distinct cell-types across macaque V1 and V4 layers. Attention increased both V1-V4 gamma-coherence and V4 spike-rates, yet with distinct laminar and cell-type profiles. Surprisingly, V1 gamma did not engage V4 excitatory neurons, but only Layer-4 fast-spiking interneurons. Similar observations were made in mouse visual-cortex, where feedforward gamma-influences preferentially recruit optogenetically-tagged PV+ and narrowwaveform SSt+ interneurons. By contrast, attention enhanced V4 spike-rates in both excitatory neurons and fast-spiking interneurons, with the strongest and earliest modulation in Layer-2/3, consistent with a feedback influence. These findings reveal distinct feedforward and feedback pathways for the attentional modulation of inter-areal coherence and spike rates, respectively.
Selective degradation of ARF monomers controls auxin response in Marchantia
Authors: Das Shubhajit , de Roij Martijn , Bellows Simon , Kohlen Wouter , Farcot Etienne , Weijers Dolf , Borst Jan Willem 
Published: November 2022

AbstractThe plant signaling molecule auxin controls a variety of growth and developmental processes in land plants. Auxin regulates gene expression through a nuclear auxin signaling pathway (NAP) consisting of a ubiquitin ligase auxin receptor TIR1/AFB, its Aux/IAA degradation substrate, and the DNA-binding ARF transcription factors. While extensive qualitative understanding of the pathway and its interactions has been obtained by studying the flowering plantArabidopsis thaliana, it is so far unknown how these translate to quantitative system behaviourin vivo, a problem that is confounded by large NAP gene families in this species. Here we used the minimal NAP of the liverwortMarchantia polymorphato quantitatively map NAP protein accumulation and dynamicsin vivothrough the use of knock-in fluorescent fusion proteins. Beyond revealing the native accumulation profile of the entire NAP protein network, we discovered that the two central ARFs MpARF1 and MpARF2 are proteasomally degraded. This degradation serves two functions: it tunes the stoichiometry of auxin-responsive, positively acting MpARF1 and auxin-independent, negatively acting MpARF2, thereby permitting auxin response. Secondly, through mapping a minimal degradation motif, we found that degradation is likely selective for MpARF2 monomers and favours accumulation of dimers. Interfering with MpARF1:MpARF2 stoichiometry or preventing degradation of MpARF2 monomers caused strong growth defects associated with auxin response defects. Thus, quantitative analysis of the entire Marchantia NAP, allowed to identify a novel regulatory mechanism in auxin response, built on regulated ARF degradation.
Arbuscular mycorrhizal fungusRhizophagus irregularisexpresses an outwardly Shaker-like channel involved in rice potassium nutrition
Authors: Corratgé-Faillie Claire , Matic Louise , Chmaiss Layla , Zhour Houssein , Lolivier Jean-Pierre , Audebert Pierre-Alexandre , Bui Xuan Thai , Seck Maguette , Chinachanta Kawiporn , Fizames Cécile , Wipf Daniel , Sentenac Hervé , Very Anne-Aliénor , Courty Pierre-Emmanuel , Luu Doan Trung 
Published: November 2022

AbstractPotassium (K+) plays crucial roles in many physiological, molecular and cellular processes in plants. Direct uptake of this nutrient by root cells has been extensively investigated, however, indirect uptake of K+mediated by the interactions of the roots with fungi in the frame of a mutualistic symbiosis, also called mycorrhizal nutrient uptake pathway, is much less known. We identified an ion channel in the arbuscular mycorrhizal (AM) fungusRhizophagus irregularis. This channel exhibits the canonical features of Shaker-like channel shared in other living kingdoms and is named RiSKC3. Transcriptionally expressed in hyphae and in arbuscules of colonized rice roots, RiSKC3 has been shown to be located in the plasma membrane. Voltage-clamp functional characterization inXenopusoocytes revealed that RiSKC3 is endowed with outwardly-rectifying voltage-gated activity with a high selectivity for potassium over sodium ions. RiSKC3 may have a role in the AM K+pathway for rice nutrition in normal and salt stress conditions. The current working model proposes that K+ions taken up by peripheral hyphae ofR. irregularisare secreted towards the host root into periarbuscular space by RiSKC3.Significance StatementArbuscular mycorhizal fungusRhizophagus irregularisexpresses a Shaker-like channel, located in the plasma membrane, endowed with a strictly outwardly-rectifying voltage-gated activity with a high selectivity for potassium over sodium ions. The current working model proposes that K+ions taken up by peripheral hyphae ofR. irregularisare secreted towards the host root into periarbuscular space by this Shaker-like channel.
Measuring the 3D wake of swimming dice snakes using volumetric velocimetry
Authors: Stin Vincent , Godoy-Diana Ramiro , Bonnet Xavier , Herrel Anthony 
Published: November 2022

ABSTRACTExperimental observations of the 3-dimensional wake of swimmers are scarce. This study provides the first experimental measurements of the three-dimensional vortical structures of an anguilliform swimmer. A volumetric velocimetry (DDPTV) setup was used to quantify the wake of freely swimming dice snakes (Natrix tessellata) in a tank. Multiple swimming trials were recorded with three snakes swimming at a forward swimming speed ranging from 0.2 to 0.8L.s−1. The volumetric measurements show that during swimming,Natrix tessellatasheds vortex tubes from different parts of its body with oscillating lateral undulations. The vortex tubes are then linked to form a hairpin-like structure as predicted by computational fluid dynamic analyses. Quantitative measurements show that the vortex size gradually increases over time. The vortex circulation decreases after attaining a maximum. These results provide an experimental demonstration that the 3D wake structure of an anguilliform swimmer takes well organized dynamic shapes as predicted and provide baseline data for future studies comparing the wake structure of snakes with different locomotor ecologies.