bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism is a major driver of hydrogen isotope fractionation recorded in tree-ring glucose of Pinus nigra
Authors: Wieloch Thomas , Grabner Michael , Augusti Angela , Serk Henrik , Ehlers Ina , Yu Jun , Schleucher Jürgen 
Published: July 2021

Summary–Stable isotope abundances convey valuable information about plant physiological processes and underlying environmental controls. Central gaps in our mechanistic understanding of hydrogen isotope abundances impede their widespread application within the plant and biogeosciences.–To address these gaps, we analysed intramolecular deuterium abundances in glucose of Pinus nigra extracted from an annually resolved tree-ring series (1961 to 1995).–We found fractionation signals (i.e., temporal variability in deuterium abundance) at glucose H1 and H2 introduced by closely related metabolic processes. Regression analysis indicates that these signals (and thus metabolism) respond to drought and atmospheric CO2 concentration beyond a response change point. They explain ≈60% of the whole-molecule deuterium variability. Altered metabolism is associated with below-average yet not exceptionally low growth.–We propose the signals are introduced at the leaf-level by changes in sucrose-to-starch carbon partitioning and anaplerotic carbon flux into the Calvin-Benson cycle. In conclusion, metabolism can be the main driver of hydrogen isotope variation in plant glucose.
A burst of regulatory and protein innovation at the origin of placental mammals drove the emergence of placenta and underpins divergent early pregnancy strategies in modern mammals
Authors: Taylor Alysha S. , Tinning Haidee , Ovchinnikov Vladimir , Smith William , Pullinger Anna L. , Sutton Ruth A. , Constantinides Bede , Wang Dapeng , Forde Niamh , O’Connell Mary J 
Published: July 2021

Summary paragraphThe origin of live birth in mammals ∼148 million years ago was a dramatic shift in reproductive strategy, yet the molecular changes that established mammal viviparity are largely unknown. Although progesterone receptor signalling predates the origin of mammals andis highly conserved in, and critical for, successful mammal pregnancy, it alone cannot explain the origin and subsequent diversity of implantation strategies throughout the placental mammal radiation. MiRNAs are known to be flexible and dynamic regulators with a well established role in the pathophysiology of mammal placenta. We propose that a dynamic core microRNA (miRNA) network originated early in placental mammal evolution, responds to conserved mammal pregnancy cues (e.g. progesterone), and facilitates species-specific responses. Here we identify 13 miRNAs that arose at the origin of placental mammals and were subsequently retained in all descendent lineages. The expression of these 13 miRNAs in response to early pregnancy molecules is regulated in a species-specific manner in endometrial epithelia of species with extremes of implantation strategies. Furthermore, these 13 miRNAs preferentially target 84 proteins under positive selective pressure on ancestral eutherian. Discovery of this core “live-birth” toolkit and specifically adapted proteins helps explain the origin and evolution of the placenta in mammals.
How clustered protocadherin binding specificity is tuned for neuronal self/non-self-recognition
Authors: Goodman Kerry M. , Katsamba Phinikoula S. , Rubinstein Rotem , Ahlsén Göran , Bahna Fabiana , Mannepalli Seetha , Dan Hanbin , Sampogna Rosemary , Shapiro Lawrence , Honig Barry 
Published: July 2021

AbstractThe stochastic expression of fewer than 60 clustered protocadherin (cPcdh) isoforms provides diverse identities to individual vertebrate neurons and a molecular basis for self/non-self- discrimination. cPcdhs form chains mediated by alternating cis and trans interactions between apposed membranes, which has been suggested to signal self-recognition. Such a mechanism requires that cPcdh cis dimers form promiscuously to generate diverse recognition units, and that trans interactions have precise specificity so that isoform mismatches terminate chain growth. However, the extent to which cPcdh interactions fulfill these requirements has not been definitively demonstrated. Here we report biophysical experiments showing that cPcdh cis interactions are promiscuous, but with preferences favoring formation of heterologous cis dimers. Trans-homophilic interactions are remarkably precise, with no evidence for heterophilic interactions between different isoforms. A new C-type cPcdh crystal structure and mutagenesis data help to explain these observations. Overall, the interaction characteristics we report for cPcdhs help explain their function in neuronal self/non-self-discrimination.
Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct
Authors: de Guglielmo Giordano , Carrette Lieselot LG , Kallupi Marsida , Brennan Molly , Boomhower Brent , Maturin Lisa , Conlisk Dana , Sedighim Sharona , Tieu Lani , Fannon McKenzie J , Martinez Angelica R. , Velarde Nathan , Othman Dyar , Sichel Ben , Ramborger Jarryd , Lau Justin , Kononoff Jenni , Kimbrough Adam , Simpson Sierra , Smith Lauren C , Shankar Kokila , Bonnet-Zahedi Selene , Sneddon Elizabeth A. , Avelar Alicia , Plasil Sonja L. , Mosquera Joseph , Crook Caitlin , Chun Lucas , Vang Ashley , Milan Kristel K. , Schweitzer Paul , Lin Bonnie , Peng Beverly , Chitre Apurva , Polleskaya Oksana , Solberg Woods Leah C , Palmer Abraham A. , George Olivier 
Published: July 2021

AbstractAddiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences. However, the factors contributing to the transition from moderate drug use to these problematic patterns remain unclear, particularly regarding the role of sex. Many preclinical studies have been limited by small sample sizes, low genetic diversity, and restricted drug access, making it challenging to model significant levels of intoxication or dependence and translate findings to humans. To address these limitations, we characterized addiction-like behaviors in a large sample of >500 outbred heterogeneous stock (HS) rats using an extended cocaine self-administration paradigm (6 h/daily). We analyzed individual differences in escalation of intake, progressive-ratio (PR) responding, continued use despite adverse consequences (contingent foot shocks), and irritability-like behavior during withdrawal. Principal component analysis showed that escalation of intake, progressive ratio responding, and continued use despite adverse consequences loaded onto a single factor that was distinct from irritability-like behaviors. Categorizing rats into resilient, mild, moderate, and severe addiction-like phenotypes showed that females exhibited higher addiction-like behaviors, with a lower proportion of resilient individuals compared to males. These findings suggest that, in genetically diverse rats with extended drug access, escalation of intake, continued use despite adverse consequences, and PR responding are highly correlated measures of a shared underlying construct. Furthermore, our results highlight sex differences in resilience to addiction-like behaviors.
THESEUS1 modulates cell wall stiffness and abscisic acid production in Arabidopsis thaliana
Authors: Bacete Laura , Schulz Julia , Engelsdorf Timo , Bartosova Zdenka , Vaahtera Lauri , Yan Guqi , Gerhold Joachim , Tichá Tereza , Øvstebø Camilla , Gigli-Bisceglia Nora , Johannessen-Starheim Svanhild , Margueritat Jeremie , Kollist Hannes , Dehoux Thomas , McAdam Scott A.M. , Hamann Thorsten 
Published: July 2021

AbstractPlant cells can be distinguished from animal cells by their cell walls and high turgor pressure. Although changes in turgor and stiffness of cell walls seem coordinated, we know little about the mechanism responsible for coordination. Evidence has accumulated that plants, like yeast, have a dedicated cell wall integrity maintenance mechanism. This mechanism monitors the functional integrity of the wall and maintains it through adaptive responses when cell wall damage occurs during growth, development, and interactions with the environment. The adaptive responses include osmo-sensitive-induction of phytohormone production, defence responses as well as changes in cell wall composition and structure. Here, we investigate how the cell wall integrity maintenance mechanism coordinates changes in cell wall stiffness and turgor in Arabidopsis thaliana. We show that the production of abscisic acid (ABA), the phytohormone modulating turgor pressure and responses to drought, depends on the presence of a functional cell wall. We find that the cell wall integrity sensor THESEUS1 modulates mechanical properties of walls, turgor loss point and ABA biosynthesis. We identify RECEPTOR-LIKE PROTEIN 12 as a new component of cell wall integrity maintenance controlling cell wall damage-induced jasmonic acid production. Based on the results we propose that THE1 is responsible for coordinating changes in turgor pressure and cell wall stiffness.Significance statementPlants need to constantly adapt to a changing environment. This includes responses to biotic and abiotic stress. Key elements influencing the response to abiotic stress are the plant cell walls surrounding all cells and the phytohormone abscisic acid, which influences turgor pressure in plants. Turgor pressure in plant cells is much higher than in animal cells and a key driver of plant growth and development. Here we investigate the mechanism regulating cell wall stiffness and coordinating changes in stiffness and turgor. We characterize key elements of the mechanism and dissect its mode of action. This knowledge will enable us to pursue novel approaches to improve plant resistance to drought stress, which is crucial in a rapidly changing environment.
Polymer-Conjugated Carbon Nanotubes for Biomolecule Loading
Authors: Jackson Christopher T. , Wang Jeffrey W. , González-Grandío Eduardo , Goh Natalie S. , Mun Jaewan , Krishnan Sejal , Landry Markita P. 
Published: July 2021

AbstractNanomaterials have emerged as an invaluable tool for the delivery of biomolecules such as DNA and RNA, with various applications in genetic engineering and post-transcriptional genetic manipulation. Alongside this development, there has been an increasing use of polymer-based techniques, such as polyethyleneimine (PEI), to electrostatically load polynucleotide cargoes onto nanomaterial carriers. However, there remains a need to assess nanomaterial properties, conjugation conditions, and biocompatibility of these nanomaterial-polymer constructs, particularly for use in plant systems. In this work, we develop mechanisms to optimize DNA loading on single-walled carbon nanotubes (SWNTs) with a library of polymer-SWNT constructs and assess DNA loading ability, polydispersity, and both chemical and colloidal stability. Counterintuitively, we demonstrate that polymer hydrolysis from nanomaterial surfaces can occur depending on polymer properties and attachment chemistries, and describe mitigation strategies against construct degradation. Given the growing interest in delivery applications in plant systems, we also assess the toxicity of polymer-based nanomaterials in plants and provide recommendations for future design of nanomaterial-based polynucleotide delivery strategies.
Leptin protects against the development and expression of cocaine addiction-like behavior in heterogenous stock rats
Authors: Carrette L.L.G. , Coral C. , Crook C. , Boomhower B. , Brennan M. , Ortez C. , Shankar K. , Simpson S. , Maturin L. , de Guglielmo G. , Woods L. Solberg , Palmer A. A. , George O. 
Published: July 2021

AbstractIn addition to its pleasurable effects, weight control is a significant contributor to initiation, maintenance and relapse of cocaine use. This suggests that individual differences in bodyweight control and feeding hormones, such as leptin may contribute to the vulnerability to cocaine use disorder. While pre-clinical studies have shown a mutually inhibitory relationship between leptin and cocaine, they have used small sample sizes and did not investigate individual differences in a large heterogeneous population. Here, we tested if individual differences in bodyweight and blood leptin level is associated with high or low vulnerability to addiction-like behaviors using data from 500 heterogenous stock rats and 160 blood samples from the Cocaine Biobank, using a model of extended access to intravenous self-administration of cocaine. Finally, we tested a separate cohort to evaluate the causal effect of exogenous leptin administration on cocaine seeking. Bodyweight, while changing due to cocaine self-administration in males, was not related to the vulnerability to addiction-like behavior. Blood leptin levels after ~6 weeks of cocaine self-administration did not correlate with addiction-like behaviors, however, baseline blood leptin levels before any access to cocaine negatively predicted addiction-like behavior. Finally, administration of leptin reduced cocaine intake after acute withdrawal and cocaine seeking after 6 weeks of protracted abstinence. These results demonstrate that high blood leptin level before access to cocaine may be a protective factor against the development of cocaine addiction-like behavior, that exogenous leptin reduces the motivation to take and seek cocaine, but that blood leptin level and bodyweight changes in current users are not good biomarkers for addiction-like behaviors.
Exome first approach to reduce diagnostic costs and time – retrospective analysis of 111 individuals with rare neurodevelopmental disorders
Authors: Klau Julia , Jamra Rami Abou , Radtke Maximilian , Oppermann Henry , Lemke Johannes R. , Beblo Skadi , Popp Bernt 
Published: July 2021

ABSTRACTThis single center study aims to determine the time, diagnostic procedure and cost saving potential of early exome sequencing in a cohort of 111 individuals with genetically confirmed neurodevelopmental disorders.We retrospectively collected data regarding diagnostic time points and procedures from the individuals’ medical histories and developed criteria for classifying diagnostic procedures in terms of requirement, followed by a cost allocation. The genetic variants of all individuals were reevaluated according to ACMG recommendations and considering the individuals’ phenotype.Individuals who developed first symptoms of their underlying genetic disorder when Next Generation Sequencing (NGS) diagnostics were already available received a diagnosis significantly faster than individuals with first symptoms before this cutoff. The largest amount of potentially dispensable diagnostics was found in genetic, metabolic, and cranial magnetic resonance imaging examinations. Out of 407 performed genetic examinations, 296 (72.7%) were classified as potentially dispensable. The same applied to 36 (27.9%) of 129 cranial magnetic resonance imaging and 111 (31.8%) of 349 metabolic examinations. Dispensable genetic examinations accounted 302,947.07€ (90.2%) of the total 335,837.49€ in potentially savable costs in this cohort. The remaining 32,890.42€ (9.8%) are related to non-required metabolic and cranial magnetic resonance imaging diagnostics. On average, the total potentially savable costs in our study amount to €3,025.56 per individual.Cost savings by first tier exome sequencing lie primarily in genetic, metabolic, and cMRI testing in this German cohort, underscoring the utility of performing exome sequencing at the beginning of the diagnostic pathway and the potential for saving diagnostic costs and time.
Controlled human malaria infection with PvW1 – a new clone of Plasmodium vivax with high quality genome assembly
Authors: Minassian Angela M. , Themistocleous Yrene , Silk Sarah E. , Barrett Jordan R. , Kemp Alison , Quinkert Doris , Nielsen Carolyn M. , Edwards Nick J. , Rawlinson Thomas A. , Lopez Fernando Ramos , Roobsoong Wanlapa , Ellis Katherine J. , Cho Jee-Sun , Aunin Eerik , Otto Thomas D. , Reid Adam J. , Bach Florian , Labbé Geneviève M. , Poulton Ian D. , Marini Arianna , Zaric Marija , Mulatier Margaux , Ramon Raquel Lopez , Baker Megan , Mitton Celia H. , Sousa Jason C. , Rachaphaew Nattawan , Kumpitak Chalermpon , Maneechai Nongnuj , Suansomjit Chayanut , Piteekan Tianrat , Hou Mimi M. , Khozoee Baktash , Roberts David J. , Lawrie Alison M. , Blagborough Andrew M. , Nugent Fay L. , Taylor Iona J. , Johnson Kimberly J. , Spence Philip J. , Sattabongkot Jetsumon , Biswas Sumi , Rayner Julian C. , Draper Simon J. 
Published: July 2021

AbstractControlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs and vaccines. However, unlike Plasmodium falciparum, well-characterized P. vivax parasites that are safe and suitable for use in modern CHMI models are limited. Here, two healthy malaria-naïve UK adults with universal donor blood group were safely infected with a clone of P. vivax from Thailand by mosquito-bite CHMI. Parasitemia developed in both volunteers and, prior to treatment, each volunteer donated blood to produce a cryopreserved stabilate of infected red blood cells. Following stringent safety screening, the parasite stabilate from one of these donors (“PvW1”) was thawed and used to inoculate six healthy malaria-naïve UK adults by blood-stage CHMI, at three different dilutions. Parasitemia developed in all volunteers, who were then successfully drug treated. PvW1 parasite DNA was isolated and sequenced to produce a high quality genome assembly by using a hybrid assembly method. We analysed leading vaccine candidate antigens and multigene families, including the Vivax interspersed repeat (VIR) genes of which we identified 1145 in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.
Understanding the role of memory re-activation and cross-reactivity in the defense against SARS-CoV-2
Authors: Denninger Viola , Xu Catherine K. , Meisl Georg , Morgunov Alexey S. , Fiedler Sebastian , Ilsley Alison , Emmenegger Marc , Malik Anisa Y. , Piziorska Monika A. , Schneider Matthias M. , Devenish Sean R. A. , Kosmoliaptsis Vasilis , Aguzzi Adriano , Fiegler Heike , Knowles Tuomas P. J. 
Published: July 2021

AbstractRecent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potential beneficial as well as detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be re-activated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Understanding the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be deconvoluted by surface-based assays like enzyme-linked immunosorbent assays (ELISAs) which are routinely used to assess cross-reactivity.Here, we have used microfluidic antibody-affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory re-activation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2.
Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice
Authors: Lopez-Tello Jorge , Schofield Zoe , Kiu Raymond , Dalby Matthew J. , van Sinderen Douwe , Le Gall Gwénaëlle , Sferruzzi-Perri Amanda N , Hall Lindsay J 
Published: July 2021

AbstractThe gut microbiota plays a central role in regulating host metabolism. While substantial progress has been made in discerning how the microbiota influences host functions post birth and beyond, little is known about how key members of the maternal gut microbiota can influence feto-placental growth. Notably, in pregnant women, Bifidobacterium represents a key beneficial microbiota genus, with levels observed to increase across pregnancy. Here, using germ-free and specific-pathogen-free mice, we demonstrate that the bacterium Bifidobacterium breve UCC2003 modulates maternal body adaptations, placental structure and nutrient transporter capacity, with implications for fetal metabolism and growth. Maternal and placental metabolome were affected by maternal gut microbiota (i.e. acetate, formate and carnitine). Histological analysis of the placenta confirmed that Bifidobacterium modifies placental structure via changes in Igf2P0, Dlk1, Mapk1 and Mapk14 expression. Additionally, B. breve UCC2003, acting through Slc2a1 and Fatp1-4 transporters, was shown to restore fetal glycaemia and fetal growth in association with changes in the fetal hepatic transcriptome. Our work emphasizes the importance of the maternal gut microbiota on feto-placental development and sets a foundation for future research towards the use of probiotics during pregnancy.
PDZ-containing proteins targeted by the ACE2 receptor
Authors: Caillet-Saguy Célia , Wolff Nicolas 
Published: July 2021

AbstractAngiotensin converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residues segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein interacting domains called PSD-95/Dlg/ZO-1 (PDZ).Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role on ACE2 internalization and recycling that could benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in neurological symptoms of COVID-19.