bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do water and host size interactively affect the impact of a native hemiparasite on a major invasive legume?
Authors: Cirocco Robert M. , Facelli Evelina , Facelli José M. 
Published: January 2022

AbstractIt is unknown how the combined effects of host size and water availability influence parasitic plant:host associations. This is a major gap considering that parasitic plants would frequently encounter hosts of different size growing in different water conditions in nature. In a glasshouse experiment, small or largeUlex europaeus(major invasive host) were provided high or low water supply and infected or not with the Australian native shoot hemiparasitic vine,Cassytha pubescens. Infection significantly decreased host total, shoot and root biomass, in both low water and high water conditions but more severely so in the latter. Infection also significantly decreased total biomass of both large and small plants and more severely so for the latter. Infection significantly decreased host foliar nitrogen and potassium concentrations in well-watered but not in low water conditions. Infection significantly suppressed host predawn and midday quantum yield, midday electron transport rates, foliar phosphorus concentration and nodule biomass, irrespective of water conditions or host size. Parasite biomass (including g-1host total biomass) was significantly greater on hosts growing in well-watered than in low water conditions. Our results suggest that some native parasitic plants may effectively control major invasive hosts, particularly in wetter habitats and or when the host is small, leading to enhanced biodiversity protection in those settings.
Hijacking Methyl Reader Proteins for Nuclear-Specific Protein Degradation
Authors: Nalawansha Dhanusha A. , Li Ke , Hines John , Crews Craig M. 
Published: January 2022

AbstractTargeted protein degradation (TPD) by PROTACs is a promising strategy to control disease-causing protein levels within the cell. While TPD is emerging as an innovative drug discovery paradigm, there are currently only a limited number of E3 ligase: ligand pairs that are employed to induce protein degradation. Herein, we report a novel approach to induce protein degradation by hijacking a methyl reader: E3 ligase complex. L3MBTL3 is a methyl lysine reader protein that binds to the Cul4DCAF5 E3 ligase complex and targets methylated proteins for proteasomal degradation. By co-opting this natural mechanism, we report the design and biological evaluation of L3MBTL3-recruiting PROTACs and demonstrate nuclear-specific degradation of FKBP12 and BRD2. We envision this as a generalizable approach to utilize other reader protein-associated E3 ligase complexes in PROTAC design to expand the E3 ligase toolbox and explore the full potential of TPD.
Antibodies targeting conserved non-canonical antigens and endemic coronaviruses associate with favorable outcomes in severe COVID-19
Authors: Peddireddy Sai Preetham , Rahman Syed A. , Cillo Anthony R. , Vijay Godhev Manakkat , Somasundaram Ashwin , Workman Creg J. , Bain William , McVerry Bryan J. , Methe Barbara , Lee Janet S. , Ray Prabir , Ray Anuradha , Bruno Tullia C. , Vignali Dario A. A. , Kitsios Georgios D. , Morris Alison , Singh Harinder , Sarkar Aniruddh , Das Jishnu 
Published: January 2022

AbstractWhile there have been extensive analyses characterizing cellular and humoral responses across the severity spectrum in COVID-19, predictors of outcomes within severe COVID-19 remain to be comprehensively elucidated. Recently, we identified divergent monocyte states as predictors of outcomes within severe COVID-19, but corresponding humoral profiles of risk have not been delineated. Furthermore, the nature of antibodies (Abs) directed against viral antigens beyond the spike protein or endemic coronavirus antigens and their associations with disease severity and outcomes remain poorly defined. We performed deep molecular profiling of Abs directed against a wide range of antigenic specificities in severe COVID-19 patients admitted to the ICU. The profiles consisted of canonical (S, RBD, N) and non-canonical (orf3a, orf8, nsp3, nps13 and M) antigenic specificities. Notably, multivariate machine learning (ML) models, generated using profiles of Abs directed against canonical or non-canonical antigens, were equally discriminative of recovery and mortality COVID-19 outcomes. In both ML models, survivors were associated with increased virus-specific IgA and IgG3 antibodies and with higher antigen-specific antibody galactosylation. Intriguingly, pre-pandemic healthy controls had cross-reactive Abs directed against nsp13 which is a conserved protein in other alpha and beta coronaviruses. Notably, higher levels of nsp13-specific IgA antibodies were associated with recovery in severe COVID-19. In keeping with these findings, a model built on Ab profiles for endemic coronavirus antigens was also predictive of COVID-19 outcome bifurcation, with higher levels of IgA and IgG3 antibodies against OC43 S and NL63 S being associated with survival. Our results suggest the importance of Abs targeting non-canonical SARS-CoV-2 antigens as well as those directed against endemic coronaviruses in favorable outcomes of severe COVID-19.
Dopamine D1-like receptor blockade and stimulation decreases operant responding for nicotine and food in male and female rats
Authors: Chellian Ranjithkumar , Behnood-Rod Azin , Wilson Ryann , Lin Karen , King Grace Wing-Yan , Ruppert-Gomez Marcella , Teter Alexandria Nicole , Bruijnzeel Adriaan W. 
Published: January 2022

AbstractDopamine has been implicated in smoking, but there remains a need for a better understanding of the effects of dopamine D1-like receptor agonists on nicotine intake and the role of sex in the effects of dopaminergic drugs on nicotine intake. This work studied the effects of D1-like receptor stimulation and blockade on operant responding for nicotine and food and locomotor activity in male and female rats. The effects of the D1-like receptor antagonist SCH 23390 (0.003, 0.01, 0.03 mg/kg) and the D1-like receptor agonist A77636 (0.1, 0.3, 1 mg/kg) on responding for nicotine and food, and locomotor activity were investigated. The effects of SCH 23390 were investigated 15 min and 24 h after treatment, and the effects of the long-acting drug A77636 were investigated 15 min, 24 h, and 48 h later. Operant responding for nicotine and food was decreased 15 min, but not 24 h, after treatment with SCH 23390. Operant responding for nicotine was decreased 15 min, 24 h, and 48 h after treatment with A77636, and food responding was decreased 15 min and 24 h later. Locomotor activity was decreased 15 min, but not 24 h, after treatment with SCH 23390. A77636 only decreased locomotor activity 48 h after treatment. There were no sex differences in the effects of SCH 23390 or A77636. In conclusions, the D1-like receptor antagonist SCH 23390 reduces nicotine intake and causes sedation in rats. Stimulation of D1-like receptors with A77636 decreases nicotine intake at time points that the drug is not sedative.
Genomic analyses identify significant molecules and biological processes in colorectal cancer cells with DNA damage
Authors: Guo Hongmei , Zhang Mason , Gu Hanming , Liu James 
Published: January 2022

AbstractColorectal cancer is a major cause of cancer deaths in the US. DNA damage is considered to be a novel target for the treatment of colorectal cancer. However, the molecular mechanisms and functions are still unclear. In this study, we aim to identify the significant molecules and signaling by analyzing the RNA-seq data. The GSE189366 was created by the BGISEQ-500 (Homo sapiens). The KEGG and GO analyses indicated the p53 signaling pathway and Hippo signaling pathway are major affected processes in colorectal cancer by DNA damage. Furthermore, we identified ten key interactive molecules including CDK1, STAT3, MDM2, CCNB1, CCNA2, CDKN1A, PCNA, AURKA, PLK1, and CDC6. Our study may provide potential drug targets for colorectal cancer.
Seroepidemiological and genomic investigation of COVID-19 spread in North East region of India
Authors: Wahengbam Romi , Bharali Pankaj , Manna Prasenjit , Phukan Tridip , Singh Moirangthem Goutam , Gogoi Gayatri , Tapadar Yasmin Begam , Singh Anil Kumar , Konwar Rituraj , Chikkaputtaiah Channakeshavaiah , Velmurugan Natarajan , Nagamani Selvaraman , Mahanta Hridoy Jyoti , Sarma Himakshi , Sahu Ravi Kumar , Dutta Prachurjya , Wann Sawlang Borsingh , Kalita Jatin , Sastry G Narahari 
Published: January 2022

AbstractSeroepidemiology and genomics are valuable tools to investigate the transmission of COVID-19. We utilized qRT-PCR, serum antibody immunoassays, and whole genome sequencing to examine the spread of SARS-CoV-2 infections in North East (NE) region of India during the first and second pandemic waves (June 2020 to September 2021). qRT-PCR analysis was performed on a selected population from NE India during June 2020 to July 2021, and metadata were collected for the region. Seroprevalence and neutralizing antibody immunoassay were studied on selected individuals (n=2026) at three time points (August 2020, February 2021 and June 2021), as well as in a cohort (n=35) for a year (August 2020 to August 2021). SARS-CoV-2 genomes of 914 qRT-PCR positive samples (June 2020 to September 2021) were sequenced and assembled, and those obtained from the sequence databases were analyzed. Test positivity rates in first and second waves were 6.34% and 6.64% in the state of Assam, respectively, and a similar pattern was observed in other NE states. Seropositivity in August 2020, February 2021, and June 2021 were 10.63%, 40.3% and 46.33% respectively, and neutralizing antibody prevalence were 90.91%, 52.14%, and 69.30% respectively. The cohort group showed the presence of stable neutralizing antibody throughout the year. Normal variants dominated the first wave, while the variant of concerns (VOCs) B.1.617.2 and AY-sublineages dominated the second wave, and identified mostly among vaccinated individuals. All eight states of NE India reported numerous incidences of SARS-CoV-2 VOCs, especially B.1.617.2 and AY sublineages, and their prevalence co-related well with high TPR and seropositivity rate in the region. High infection and seroprevalence of COVID-19 in NE India during the second wave was associated with the emergence of VOCs. Natural infection prior to vaccination provided higher neutralizing activity than vaccination alone.
Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine
Authors: Huang Qingrui , Zeng Jiawei , Lang Qingyun , Gao Feng , Liu Dejun , Tian Siyu , Shi Rui , Luo Ling , Wang Hao , Hu Liping , Jiang Linrui , Liu Yawei , Li Kailiang , Wu Yunbo , Xu Junjie , Jiang Wenxi , Guo Ning , Chen Zhihai , Hao Xiaohua , Jin Ronghua , Yan Jinghua , Sun Yufa 
Published: January 2022

AbstractSince the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.
On the flexibility of the cellular amination network inE. coli
Authors: Schulz-Mirbach Helena , Müller Alexandra , Wu Tong , Pfister Pascal , Aslan Selçuk , von Borzyskowski Lennart Schada , Erb Tobias J. , Bar-Even Arren , Lindner Steffen N. 
Published: January 2022

AbstractAmmonium (NH4+) is essential to generate the nitrogenous building blocks of life. It gets assimilated via the canonical biosynthetic routes to glutamate and is further distributed throughout metabolism via a network of transaminases. To study the flexibility of this network, we constructed anEscherichia coliglutamate auxotrophic strain. This strain allowed us to systematically study which amino acids serve as amine source and found that several amino acids complement the auxotrophy, either by producing glutamate via transamination reactions or by their conversion to glutamate. In this network, we identified aspartate transaminase AspC as a major connector between many amino acids and glutamate. Additionally, we extended the transaminase network by the amino acids β-alanine, alanine, glycine and serine as new amine sources and identified D-amino acid dehydrogenase (DadA) as an intracellular amino acid sink removing substrates from transaminase reactions. Finally, ammonium assimilation routes producing aspartate or leucine were introduced. Our study reveals the high flexibility of the cellular amination network, both in terms of transaminase promiscuity and adaptability to new connections and ammonium entry points.
Recommendations for tissue homogenisation and extraction in DNA metabarcoding of Malaise trap samples
Authors: Zizka Vera MA , Geiger Matthias F , Hörren Thomas , Kirse Ameli , Noll Niklas W , Schäffler Livia , Scherges Alice M , Sorg Martin 
Published: January 2022

AbstractWith increased application of DNA metabarcoding in fast and high-resolution biodiversity assessment, various laboratory protocols have been optimised in recent years and their further evaluation is subject of current research. Homogenisation of bulk samples and subsequent DNA extraction from destructed tissue is one way of starting the metabarcoding process. This essential step in the protocol can either be conducted from wet sample material (e.g. bulk insect samples) soaked in fixative or from completely dried individuals. While the latter method appears to produce more consistent results, it is time consuming and more prone to cross-contamination. We tested both homogenisation approaches with regard to time efficiency and biodiversity assessment of complex arthropod bulk samples, in particular how the amount of processed tissue affects taxon recovery. Both approaches reveal similar taxa compositions and detect a similar total OTU diversity in a single extraction reaction. Increased amounts of tissue used in DNA extraction improved OTU diversity detection and recovered particularly specific low-biomass taxa, making this approach valuable for samples with high biomass and/or diversity. Due to less handling time and lower vulnerability for cross-contamination we recommend the processing of wet material when sample homogenisation is applied.
CavitySpace: A database of potential ligand binding sites in the human proteome
Authors: Wang Shiwei , Lin Haoyu , Huang Zhixian , He Yufeng , Deng Xiaobing , Xu Youjun , Pei Jianfeng , Lai Luhua 
Published: January 2022

ABSTRACTThe ligand binding sites of a protein provide useful information to uncover its functions and to direct the structure-based drug design. However, as binding site detection relies on the three-dimensional (3D) structural data of proteins, functional analysis based on protein ligand binding sites is formidable for proteins without structural information. Recent developments in protein structure prediction and the 3D structures built by AlphaFold provide an unprecedented opportunity for analyzing ligand binding sites in human proteins. We have used the reliable ligand binding site detection program CAVITY to analyse all the proteins in the human proteome and constructed the CavitySpace database, which is the first pocket library for predicted protein structures. CavitySpace can be used to predict protein function based on pocket information, to identify new druggable protein targets for drug design, and to search for new binding sites for known drugs for drug repurposing. CavitySpace is freely available at http://www.pkumdl.cn:8000/cavityspace/.
Soft topographical patterns trigger a stiffness-dependent cellular response to contact guidance
Authors: Comelles Jordi , Fernández-Majada Vanesa , Acevedo Verónica , Rebollo-Calderon Beatriz , Martínez Elena 
Published: January 2022

AbstractDirectional migration is involved in multiple physiological and pathological processes. Among other external signals, the architecture of the extracellular matrix can trigger directed cell migration through a phenomenon known as contact guidance: cells elongate, align, and migrate along the direction set by aligned extracellular matrix fibers. This process involves the orientation of focal adhesions, actin, and tubulin cytoskeleton along the direction of those fibers. Contact guidance has been extensively studied on stiff materials with topographical grooved patterns. However, how it translates to softer physiologically relevant compliances is not known. Here we show that substrate stiffness modulates the cellular response to topographical contact guidance. We found that for fibroblasts, while focal adhesions and actin responded to topography independently of the stiffness, microtubules showed a stiffness-dependent response that regulates contact guidance. On the other hand, both clusters and single breast carcinoma epithelial cells displayed stiffness-dependent contact guidance migration, leading to more directional and efficient migration when increasing substrate stiffness. These results suggest that both matrix stiffening and alignment of extracellular matrix fibers cooperate during directional cell migration, and both should be accounted when studying processes such as cancer cell invasion.TeaserChanges in the stiffness of topographical patterns modify how mesenchymal and epithelial cells perform contact guidance.
Temporal learning modulates post-interval ERPs in a categorization task with hidden reference durations
Authors: Silvestrin Mateus , Claessens Peter M. E. , Cravo André M. 
Published: January 2022

AbstractThe investigation of time-related activity in human electrophysiological activity has recently expanded from signals during the estimated interval to post-interval activity. Previous findings show timing-associated event-related potentials (ERPs) in both early (∼150ms) and late positive components (LPC; ∼300ms) post-interval signals. However, it is still unclear whether and what aspects of temporal information these different patterns of EEG activity are capturing, especially, if these signals are associated with interval duration or other task parameters. In the present work, we designed a modified temporal categorization task to investigate if participants’ adaptation to a changing decisional context led to changes in post-interval ERPs. Participants had to learn a hidden reference duration on each block to categorize the presented target intervals correctly. We found an early posterior N200 potential correlated to target durations and decisional context. A central LPC, which interacted with duration and learning of the hidden reference, predicted behavioral responses. Our findings add to the current evidence that interval duration modulates post-interval activity in timing categorization tasks and shows that late signals are associated with interval duration and decisional context.
Dexamethasone, a direct modulator of AQP2 in Menière’s disease
Authors: Mom Robin , Robert-Paganin Julien , Mom Thierry , Chabbert Christian , Réty Stéphane , Auguin Daniel 
Published: January 2022

AbstractMenière’s disease is a chronic illness characterized by intermittent episodes of vertigo associated with fluctuating sensorineural hearing loss, tinnitus and aural pressure. This pathology strongly correlates with a dilatation of the fluid compartment of the endolymph, so-called hydrops. Dexamethasone is one of the therapeutic approaches recommended when conventional antivertigo treatments have failed. Several mechanisms of actions have been hypothesized for the mode of action of dexamethasone such as anti-inflammatory effect or as a regulator of the inner ear water homeostasis. However, none of them have been experimentally confirmed so far. Aquaporins (AQPs) are transmembrane water channels and are hence central in the regulation of trans-cellular water fluxes. In the present study we investigated the hypothesis that dexamethasone could impact water fluxes in the inner ear through direct interaction with AQP2. We addressed this question through molecular dynamics simulations approaches and managed to demonstrate a direct interaction between AQP2 and dexamethasone and its significant impact on the channel water permeability. We also describe the molecular mechanisms involved in dexamethasone binding and in its regulatory action upon AQP2 function.HighlightsAQP2 water permeability is modulated by dexamethasone at physiological concentrationsThe interaction impacts water fluxes through a direct interaction with the extra-cellular surface of the aquaporinKey interactions implicate conserved residues of the ar/R constrictionNew insights on corticosteroids mode of actions in Menière’s disease treatment
The way of the light: how visual information reaches the auditory cortex in congenitally deaf adults
Authors: Giorjiani Giuliana Martinatti , Tal Zohar , Nili Hamed , Yanchao BI , Fang Fang , Almeida Jorge 
Published: January 2022

AbstractHuman and animal studies on cross-modal plasticity under congenital deafness suggest that early auditory cortex plays a significant role in the processing of visual information when congenitally deprived from its typical (auditory) input. However, the pathway by which early auditory cortex is fed with visual information is still understudied. Here we focused on addressing how visual information reaches the auditory cortex under congenital deafness. We put forth a mechanistic model that proposes that different corticocortical and subcortical connections play a central role in rerouting visual information to the early auditory cortex of congenitally deaf individuals. Specifically, we show, using Representational Connectivity Analysis (RCA) and Dynamic Causal Modeling (DCM), that connections from the right superior colliculus to the right inferior colliculus, as well as connections from right early visual cortical regions to the right early auditory cortex play a role in rerouting visual information to early auditory cortex in congenitally deaf individuals. These findings shed light on how visual information reaches the early auditory cortex of deaf individuals - specifically, they suggest that neuroplasticity reshapes subcortical connections in order to re-route visual information to the auditory stream.