bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine desynchronizes the retinal clock through a melanopsin-dependent regulation of acetylcholine retinal waves during development
Authors: Kinane Chaimaa , Calligaro Hugo , Jandot Antonin , Coutanson Christine , Haddjeri Nasser , Bennis Mohamed , Dkhissi-Benyahya Ouria 
Published: April 2021

AbstractDopamine (DA) plays a critical role in retinal physiology, including resetting of the retinal circadian clock that in turn regulates DA release. DA acts on major classes of retinal cells by reconfiguring electrical and chemical synapses. Although a bidirectional regulation between intrinsically photosensitive melanopsin ganglion cells (ipRGCs) and dopaminergic cells has been demonstrated during development and adulthood, DA involvement in the ontogeny of the retinal clock is still unknown.Using wild-typePer2Lucand melanopsin knockout (Opn4-/-::Per2Luc) mice at different postnatal stages, we found that the retina can generate self-sustained circadian rhythms from postnatal day 5 that emerge in the absence of external time cues in both genotypes. Intriguingly, DA lengthens the endogenous period only in wild-type retinas, suggesting that this desynchronizing effect requires melanopsin. Furthermore, blockade of cholinergic retinal waves in wild-type retinas induces a shortening of the period, similarly toOpn4-/-::Per2Lucexplants. Altogether, these data suggest that DA desynchronizes the retinal clock through a melanopsin-dependent regulation of acetylcholine retinal waves, thus offering a new role of melanopsin in setting the period of the retinal clock during development.
Versioning Biological Cells for Trustworthy Cell Engineering
Authors: Tellechea-Luzardo Jonathan , Hobbs Leanne , Velázquez Elena , Pelechova Lenka , Woods Simon , de Lorenzo Victor , Krasnogor Natalio 
Published: April 2021

Abstract“Full-stack”biotechnology platforms for cell line (re)programming are on the horizon, due mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration with informatics, the internet of things and automation. These emerging platforms will accelerate the production and consumption of biological products. Hence, transparency, traceability and -ultimately-trustworthiness is required -from cradle to grave- for engineered cell lines and their engineering processes. We report here the first version control system for cell engineering that integrates a new cloud-based version control software for cell lines’ digital footprint with molecular barcoding of living samples. We argue that version control for cell engineering marks a significant step towards more open, reproducible, easier to trace and share, and more trustworthy engineering biology.One Sentence SummaryWe demonstrate a transparent and open way of engineering and sharing cell lines.
GFAT2 and AMDHD2 act in tandem to control the hexosamine biosynthetic pathway
Authors: Kroef Virginia , Ruegenberg Sabine , Horn Moritz , Allmeroth Kira , Ebert Lena , Bozkus Seyma , Miethe Stephan , Schermer Bernhard , Baumann Ulrich , Denzel Martin S. 
Published: April 2021

AbstractThe hexosamine biosynthetic pathway (HBP) produces the essential metabolite UDP-GlcNAc and plays a key role in metabolism, cancer, and aging. The HBP is controlled by its rate-limiting enzyme glutamine fructose-6-phosphate amidotransferase (GFAT) that is directly inhibited by UDP-GlcNAc in a feedback loop. HBP regulation by GFAT is well studied but other HBP regulators have remained obscure. Elevated UDP-GlcNAc levels counteract the glycosylation toxin tunicamycin (TM) and thus we screened for TM resistance in haploid mouse embryonic stem cells (mESCs) using random chemical mutagenesis to pinpoint new HBP regulators. We identified the N-acetylglucosamine deacetylase AMDHD2 that catalyzes a reverse reaction in the HBP and its loss strongly elevated UDP-GlcNAc. To better understand AMDHD2, we solved the crystal structure and found that loss-of-function is caused by protein destabilization or interference with its catalytic activity. Finally, we show that mESCs express AMDHD2 together with GFAT2 instead of the more common paralog GFAT1. Compared with GFAT1, GFAT2 had a much lower sensitivity to UDP-GlcNAc inhibition, explaining how AMDHD2 loss-of-function resulted in HBP activation. This HBP configuration in which AMDHD2 serves to balance GFAT2 activity was also observed in other mESCs and, consistently, the GFAT2/GFAT1 ratio decreased with differentiation of mouse and human embryonic stem cells. Together, our data reveal a critical function of AMDHD2 in limiting UDP-GlcNAc production in cells that use GFAT2 for metabolite entry into the HBP.
Social foraging in vampire bats is predicted by long-term cooperative relationships
Authors: Ripperger Simon P. , Carter Gerald G. 
Published: April 2021

AbstractStable social bonds in group-living animals can provide greater access to food. A striking example is that female vampire bats often regurgitate blood to socially bonded kin and nonkin that failed in their nightly hunt. Food-sharing relationships form via preferred associations and social grooming within roosts. However, it remains unclear whether these cooperative relationships extend beyond the roost. To evaluate if long-term cooperative relationships in vampire bats play a role in foraging, we tested if foraging encounters measured by proximity sensors could be explained by wild roosting proximity, kinship, or rates of co-feeding, social grooming, and food sharing during 22 months in captivity. We assessed evidence for six hypothetical scenarios of social foraging, ranging from individual to collective hunting. We found that female vampire bats departed their roost individually, but often re-united far outside the roost. Nonrandomly repeating foraging encounters were predicted by within-roost association and histories of cooperation in captivity, even when controlling for kinship. Foraging bats demonstrated both affiliative and competitive interactions and a previously undescribed call type. We suggest that social foraging could have implications for social evolution if ‘local’ cooperation within the roost and ‘global’ competition outside the roost enhances fitness interdependence between frequent roostmates.
Restriction ofWolbachiabacteria in early embryogenesis of neotropicalDrosophilaspecies via ER-mediated autophagy
Authors: Strunov Anton , Schmidt Katy , Kapun Martin , Miller Wolfgang J. 
Published: April 2021

AbstractWolbachiabacteria are maternally transmitted intracellular microbes that are not only restricted to the reproductive organs but also found in various somatic tissues of their native hosts. The abundance of the endosymbiont in somatic tissues, usually a dead end for vertically transmitted bacteria, causes a multitude of effects on life history traits of their hosts, which are still not well understood. Thus, deciphering the host-symbiont interactions on a cellular level throughout a host’s lifecycle is of great importance to understand their homeostatic nature, persistence and spreading success. Using fluorescent and transmission electron microscopy, we conducted a comprehensive analysis ofWolbachiatropism in somatic and reproductive tissues of sixDrosophilaspecies at the intracellular level during host development. Our data uncovered diagnostic patterns of infections to embryonic primordial germ cells and to particular cells of somatic tissues in three different neotropicalDrosophilaspecies of the willistoni and saltans groups that have apparently evolved in both independently. We further found that restricted patterns ofWolbachiatropism are already determined in early fly embryogenesis. This is achieved via selective autophagy, and the restriction of infection is preserved through larval hatching and metamorphosis. We further uncovered tight interactions ofWolbachiawith membranes of the endoplasmic reticulum, which might play a scaffolding role for autophagosome formation and subsequent elimination of the endosymbiont. Finally, by analyzingD. simulanslines transinfected with non-nativeWolbachia, we uncovered that the host genetic background regulates tissue tropism of infection. Our data demonstrate a peculiar and novel mechanism to limit and spatially restrict bacterial infection in somatic tissues during a very early stage of host development.
A key role of astrocytic calcium dynamics to link neuronal activity with the BOLD signal
Authors: Tesler Federico , Linne Marja-Leena , Destexhe Alain 
Published: April 2021

ABSTRACTFunctional magnetic resonance imaging (fMRI) relies on the coupling between neuronal and vascular activity, but the mechanisms behind this coupling are still under discussion. Recent experimental evidence suggests that calcium signaling may play a significant role in neurovascular coupling. However, it is still controversial where this calcium signal is located (in neurons or elsewhere), how it operates and how relevant is its role. In this paper we introduce a biologically plausible model of the neurovascular coupling and we show that calcium signaling in astrocytes can explain the main aspects of the dynamics of the coupling. We find that calcium signaling can explain so-far unrelated features such as the linear and non-linear regimes, the negative vascular response (undershoot) and the emergence of a (calcium-driven) Hemodynamic Response Function. These features are reproduced here for the first time by a single model of the detailed neuronal-astrocyte-vascular pathway. Furthermore, we analyze how information is coded and transmitted from the neuronal to the vascular system and we find that frequency modulation of astrocytic calcium dynamics plays a key role in this process. Finally, our work provides a framework to link neuronal activity to the BOLD signal, and vice-versa, where neuronal activity can be inferred from the BOLD signal. This opens new ways to link known alterations of astrocytic calcium signaling in neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s diseases) with detectable changes in neurovascular coupling.
Large-scale analysis of SARS-CoV-2 synonymous mutations reveals the adaptation to the human codon usage during the virus evolution
Authors: Ramazzotti Daniele , Angaroni Fabrizio , Maspero Davide , Mauri Mario , D’Aliberti Deborah , Fontana Diletta , Antoniotti Marco , Elli Elena Maria , Graudenzi Alex , Piazza Rocco 
Published: April 2021

AbstractMany large national and transnational studies have been dedicated to the analysis of SARS-CoV-2 genome, most of which focused on missense and nonsense mutations. However, approximately 30% of the SARS-CoV-2 variants are synonymous, therefore changing the target codon without affecting the corresponding protein sequence.By performing a large-scale analysis of sequencing data generated from almost 400,000 SARS-CoV-2 samples, we show that silent mutations increasing the similarity of viral codons to the human ones tend to fixate in the viral genome over-time. This indicates that SARS-CoV-2 codon usage is adapting to the human host, likely improving its effectiveness in using the human aminoacyl-tRNA set through the accumulation of deceitfully neutral silent mutations.One-Sentence SummarySynonymous SARS-CoV-2 mutations related to the activity of different mutational processes may positively impact viral evolution by increasing its adaptation to human codon usage.
Spatiotemporal cytokinin signaling imaging reveals IPT3 function in nodule development inMedicago truncatula
Authors: Triozzi Paolo M. , Irving Thomas B. , Schmidt Henry W. , Keyser Zachary P. , Chakraborty Sanhita , Balmant Kelly M. , Pereira Wendell J. , Dervinis Christopher , Mysore Kirankumar S. , Wen Jiangqi , Ané Jean-Michel , Kirst Matias , Conde Daniel 
Published: April 2021

ABSTRACTMost legumes can establish a symbiotic association with soil rhizobia that triggers the development of root nodules. These nodules host the rhizobia and allow them to fix nitrogen efficiently. The perception of bacterial lipo-chitooligosaccharide (LCO) signal in the epidermis initiates a signaling cascade that allows rhizobial intracellular infection in the root and de-differentiation and activation of cell division that gives rise to the nodule. Nodule organogenesis and rhizobial infection need to be coupled in space and time for successful nodulation. The plant hormone cytokinin (CK) acts as an essential positive regulator of nodule organogenesis, and specific CK receptors are required for nodule formation. Temporal regulation of tissue-specific CK signaling and biosynthesis in response to LCOs orSinorhizobium melilotiinoculation inMedicago truncatularemains poorly understood. In the present study, using a fluorescence-based CK sensor (TCSn::nls:tGFP), we performed a high-resolution tissue-specific temporal characterization of the CK response’s sequential activation during root infection and nodule development inM. truncatulaafter inoculation withS. meliloti. Loss-of-function mutants of the CK-biosynthetic geneISOPENTENYL TRANSFERASE 3(IPT3) showed impairment of nodulation, suggesting that IPT3 is required for nodule development inM. truncatula. Simultaneous live imaging ofpIPT3::tdTOMATOand the CK sensor showed thatIPT3induction in the root stele at the base of nodule primordium contributes to CK biosynthesis, which in turn promotes expression of positive regulators of nodule organogenesis inM. truncatula.One-sentence summaryHigh-resolution spatiotemporal imaging of cytokinin signaling reveals IPT3 function during indeterminate nodule development inMedicago truncatula
TheBrachypodium distachyoncold-acclimated plasma membrane proteome is primed for stress resistance
Authors: Juurakko Collin L. , Bredow Melissa , Nakayama Takato , Imai Hiroyuki , Kawamura Yukio , diCenzo George C. , Uemura Matsuo , Walker Virginia K. 
Published: April 2021

ABSTRACTIn order to survive sub-zero temperatures, some plants undergo cold acclimation where low, non-freezing temperatures and/or shortened day lengths allow cold hardening and survival during subsequent freeze events. Central to this response is the plasma membrane, where low-temperature is perceived and cellular homeostasis must be preserved by maintaining membrane integrity. Here, we present the first plasma membrane proteome of cold-acclimatedBrachypodium distachyon, a model species for the study of monocot crops. A time course experiment investigated cold acclimation-induced changes in the proteome following two-phase partitioning plasma membrane enrichment and label-free quantification by nano-liquid chromatography mass spectrophotometry. Two days of cold acclimation were sufficient for membrane protection as well as an initial increase in sugar levels, and coincided with a significant change in the abundance of 154 proteins. Prolonged cold acclimation resulted in further increases in soluble sugars and abundance changes in more than 680 proteins, suggesting both a necessary early response to low-temperature treatment, as well as a sustained cold acclimation response elicited over several days. A meta-analysis revealed that the identified plasma membrane proteins have known roles in low-temperature tolerance, metabolism, transport, and pathogen defense as well as drought, osmotic stress and salt resistance suggesting crosstalk between stress responses, such that cold acclimation may prime plants for other abiotic and biotic stresses. The plasma membrane proteins identified here present keys to an understanding of cold tolerance in monocot crops and the hope of addressing economic losses associated with modern climate-mediated increases in frost events.
In vivo Analysis Reveals that ATP-hydrolysis Couples Remodeling to SWI/SNF Release from Chromatin
Authors: Tilly Ben C. , Chalkley Gillian E. , van der Knaap Jan A. , Moshkin Yuri M. , Kan Tsung Wai , Dekkers Dick H. W. , Demmers Jeroen A. A. , Verrijzer C. Peter 
Published: April 2021

AbstractATP-dependent chromatin remodelers control the accessibility of genomic DNA through nucleosome mobilization. However, the dynamics of genome exploration by remodelers, and the role of ATP hydrolysis in this process remain unclear. We used live-cell imaging ofDrosophilapolytene nuclei to monitor Brahma (BRM) remodeler interactions with its chromosomal targets. In parallel, we measured local chromatin condensation and its effect on BRM association. Surprisingly, only a small portion of BRM is bound to chromatin at any given time. BRM binds decondensed chromatin but is excluded from condensed chromatin, limiting its genomic search space. BRM-chromatin interactions are highly dynamic, whereas histone-exchange is limited and much slower. Intriguingly, loss of ATP hydrolysis enhanced chromatin retention and clustering of BRM, which was associated with reduced histone turnover. Thus, ATP hydrolysis couples nucleosome remodeling to remodeler release, driving a continuous transient probing of the genome.
Investigating genetic drivers of juvenile dermatomyositis pathogenesis using bioinformatics methods
Authors: Wang Kai , Zhang Zhongyuan , Meng Deqian , Li Ju 
Published: April 2021

AbstractJuvenile dermatomyositis (JDM) is a chronic autoimmune disease. The pathogenic mechanisms remain ill‐defined. The purpose of this study was to identify key genes related to JDM. Microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEG) were identified. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein–protein interaction (PPI) network were carried out. In addition, the hub genes were selected by cytoHubba. The expression profile and diagnostic capacity (receiver–operator curve [ROC]) of interested hub genes were verified. Gene set enrichment analysis (GSEA) was also carried out. Moreover, the signature of hub genes was then used as a search query to explore the Connectivity Map (CMAP). A total of 128 DEG were identified. The enriched functions and pathways of the DEG include response to virus, negative regulation of cell migration, cadmium ion transmembrane transport, defense response to Gram‐negative bacterium, positive regulation of megakaryocyte differentiation, and negative regulation of angiogenesis. Twenty‐one hub genes were identified. The expression levels of the interested genes were also confirmed. ROC analysis confirmed that the expression of these genes can distinguish JDM from controls. GSEA showed that these genes are mainly related to “inflammatory response”, “complement”, “interferon‐α response”, “IL6/JAK/STAT3 signaling”, “TGF‐β signaling”, “IL2/STAT5 signaling” and “TNF‐α signaling via NF‐κB”. The CMAP research found some compounds with the potential to counteract the effects of the dysregulated molecular signature in JDM. In this study, bioinformatics methods were used to identify DEG, which helps us understand the molecular mechanisms of JDM and provide candidate targets for diagnosis and treatment of JDM.
Atorvastatin reverses high cholesterol‐induced cardiac remodelling and regulates mitochondrial quality‐control in a cholesterol‐independent manner: An experimental study
Authors: Zheng Peng , Ding Yanzi , Lu Feiyan , Liu Nannan , Wu Hengfang , Bian Zhiping , Chen Xiangjian , Yang Di 
Published: April 2021

AbstractMitochondria are key regulators of cell fate, maintaining self‐stability by a fine‐tuned quality‐control network including mitophagy, biogenesis, fission and fusion processes. Myocardial mitochondria can be impaired by hypercholesterolemia. Statins, such as atorvastatin, are considered the cornerstone in the management of hypercholesterolaemia primarily due to their marked cholesterol‐lowering ability. The direct effect of atorvastatin on myocardial mitochondria remains unclear. We aimed to explore whether atorvastatin could attenuate myocardial mitochondrial defects induced by high cholesterol, and whether cycloastragenol, a potent telomerase activator, could be used as a potential complementary bioactive compound for obesity and hypercholesterolaemia treatment. We found that atorvastatin at a low dose (3 mg/kg) did not reduce elevated serum cholesterol, but reversed cardiac remodelling and dysfunction in C57BL/6J mice fed with high‐fat diet (HFD). Atorvastatin reversed the upregulated mitophagy, mitochondrial fission and fusion, accompanied by mitochondrial biogenesis activation in HFD‐fed mice hearts. Mitochondrial structural impairments were attenuated by atorvastatin in HFD‐fed mice and oxidized low‐density lipoprotein (ox‐LDL) exposed HL‐1 cardiomyocytes. The depolarized mitochondrial membrane potential and increased mitochondrial oxygen consumption rates in ox‐LDL exposed HL‐1 cells were recovered by atorvastatin. Furthermore, atorvastatin co‐treated with cycloastragenol had better effects on reducing body weight, improving cardiac remodelling and dysfunction, and protecting mitochondria in high cholesterol. Conclusively, low‐dose atorvastatin exhibited a cholesterol‐independent cardioprotective effect through improving the mitochondrial quality‐control network and repairing mitochondrial ultrastructure in high cholesterol. Atorvastatin plus cycloastragenol supplement therapy has a better effect on treating obesity and hypercholesterolaemia.
Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi‐institutional patterns of practice review
Authors: Liu Howard Yu‐hao , Lee Yoo‐young Dominique , Sridharan Swetha , Choong Ee Siang , Le Hien , Wang Wei , Khor Richard , Chu Julie , Oar Andrew , Mott Rebekah , Smart Joanne , Jenkins Trish , Anderson Nigel , Cross Shamira , Loo Kee Fong , Wigg Alan , Stuart Katherine , Pryor David 
Published: April 2021

AbstractIntroductionStereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.MethodsThis was a multi‐institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated.ResultsThree hundred and seventeen patients were evaluated with a median age of 67 years (range, 32–90). Liver cirrhosis was present in 88.6%, baseline Child‐Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10–280). 63.1% had early‐stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced‐stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED10) delivered was 85.5 Gy for early‐stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100–120 Gy BED10 (32.8%).ConclusionSBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT.