bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses
Authors: Deng Yixiang , Tang Melbourne , Ross Ted M. , Schmidt Aaron G. , Chakraborty Arup K. , Lingwood Daniel 
Published: March 2024

AbstractThe on-going diversification of influenza virus necessicates annual vaccine updating. The vaccine antigen, the viral spike protein hemagglutinin (HA), tends to elicit strain-specific neutralizing activity, predicting that sequential immunization with the same HA strain will boost antibodies with narrow coverage. However, repeated vaccination with homologous SARS-CoV-2 vaccine eventually elicits neutralizing activity against highly unmatched variants, questioning this immunological premise. We evaluated a longitudinal influenza vaccine cohort, where each year the subjects received the same, novel H1N1 2009 pandemic vaccine strain. Repeated vaccination gradually enhanced receptor-blocking antibodies (HAI) to highly unmatched H1N1 strains within individuals with no initial memory recall against these historical viruses. Anin silicomodel of affinity maturation in germinal centers integrated with a model of differentiation and expansion of memory cells provides insight into the mechanisms underlying these results and shows how repeated exposure to the same immunogen can broaden the antibody response against diversified targets.
Genetic risk score for coronary artery calcification predicts coronary artery disease beyond traditional risk factors
Authors: Mishra Pashupati P. , Mishra Binisha H. , Lyytikäinen Leo-Pekka , Goebeler Sirkka , Martiskainen Mika , Hakamaa Emma , Kleber Marcus E. , Delgado Graciela E. , März Winfried , Kähönen Mika , Karhunen Pekka J. , Lehtimäki Terho 
Published: March 2024

AbstractAimThe modest added predictive value of the existing genetic risk scores (GRSs) for coronary artery disease (CAD) could be partly due to missing genetic components, hidden in the genetic architecture of intermediate phenotypes such as coronary artery calcification (CAC). In this study, we investigated the predictive ability of CAC GRS for CAD.Materials and methodsWe investigated the association of CAC GRSs with CAD and coronary calcification among the participants in the Ludwigshafen Risk and Cardiovascular Health study (LURIC) (n=2742), the Tampere Vascular Study (TVS) (n=133), and the Tampere Sudden Death Study (TSDS) (n=660) using summary data from the largest multi-ancestry GWAS meta-analysis of CAC to date. Added predictive value of the CAC GRS over the traditional CVD risk factors was tested with standard train–test machine learning approach using the LURIC data, which had the largest sample size.ResultsCAC GRS was significantly associated with CAD in LURIC (OR=1.41, 95% CI [1.28–1.55]), TVS (OR=1.79, 95% CI [1.05–3.21]) as well as in TSDS (OR=4.20, 95% CI [1.74–10.52]). CAC GRS showed strong association with calcification areas in left (OR=1.78, 95% CI [1.16-2.74]) and right (OR=1.71, 95% CI [1.98-2.67]) coronary arteries. In addition, there was statistically significant added predictive value of the CAC GRS for CAD over the used traditional CVD risk factors (AUC 0.734 vs 0.717, p-value = 0.02).ConclusionsThis study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors.
A novel GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE 13 is involved in the Phosphate starvation-induced lipid remodeling in rice
Authors: Dang Duong Thi Thuy , Nguyen Thi Linh , Tran Anh-Tuan , Tran Tam Thi Thanh , Tran Tuan-Anh , Vo Kieu Thi Xuan , Jeon Jong-Seong , Vu Tien Van , Kim Jae-Yean , Nguyen Phuong Nhue , Chu Hoang Ha , Do Phat Tien , To Huong Thi Mai 
Published: March 2024

AbstractPhosphorus (P) is one of the most vital macronutrient determinants in plant development and productivity. However, the bioavailability of inorganic phosphate (Pi), the only form that plants can assimilate, is limited in the soil, thus significantly affecting plant development. Plants have adopted various specialized strategies to modify their morphological, physiological, and biochemical properties for better adaptation to Pi deficiency conditions. GLYCEROPHOSPHODIESTER PHOSPHODIESTERASES (GDPDs), generally known as phospholipid remodeling proteins, have been suggested to play essential roles in maintaining phosphate homeostasis. The previous genome-wide association studies (GWAS) in a Vietnamese rice collection led to the discovery of a robust QTL namedqRST9.14associating with the phosphate adaption in rice, in whichOsGDPD13is located within this locus. Interestingly, we discovered an absence ofOsGDPD13from theIndicareference genome. A subcellular localization study showed that the GDPD13 protein localizes to the plasma membrane, cytoplasmic speckles, and plasmodesmata. Theosgdpd13knockout mutant was generated in theJaponicacv Kitaake background to characterize its function. Phenotypic analysis indicated that mutation ofOsGDPD13significantly lowered crown root number and reduced the plant height under Pi deficient condition. Moreover,osgdpd13lines reduce the capability to degrade total phospholipids compared to the wild type under Pi starvation conditions. This finding suggests the involvement of theOsGDPD13gene in rice growth and the Phosphate starvation-induced lipid remodeling under P deficiency. This work will provide valuable information for developing crop plants with higher Phosphate use efficiency.
Please Mind the Gap: Indel-Aware Parsimony for Fast and Accurate Ancestral Sequence Reconstruction and Multiple Sequence Alignment including Long Indels
Authors: Iglhaut Clara , Pečerska Jūlija , Gil Manuel , Anisimova Maria 
Published: March 2024

AbstractDespite having important biological implications, insertion and deletion (indel) events are often disregarded or mishandled during phylogenetic inference. In multiple sequence alignment, indels are represented as gaps and are estimated without considering the distinct evolutionary history of insertions and deletions. Consequently, indels are usually excluded from subsequent inference steps, such as ancestral sequence reconstruction and phylogenetic tree search.Here, we introduce indel-aware parsimony (indelMaP), a novel way to treat gaps under the parsimony criterion by considering insertions and deletions as separate evolutionary events and accounting for long indels. By identifying the precise location of an evolutionary event on the tree, we can separate overlapping indel events and use affine gap penalties for long indel modelling. Our indel-aware approach harnesses the phylogenetic signal from indels, including them into all inference stages.Validation and comparison to state-of-the-art inference tools on simulated data show that indelMaP is most suitable for densely sampled datasets with closely to moderately related sequences, where it can reach alignment quality comparable to probabilistic methods and accurately infer ancestral sequences, including indel patterns. Due to its remarkable speed, our method is well-suited for epidemiological datasets, eliminating the need for downsampling and enabling the exploitation of the additional information provided by dense taxonomic sampling. Moreover, indelMaP offers new insights into the indel patterns of biologically significant sequences and advances our understanding of genetic variability by considering gaps as crucial evolutionary signals rather than mere artefacts.
ZFAND6 is a subunit of a TRAF2-cIAP E3 ubiquitin ligase complex essential for mitophagy
Authors: Shaikh Kashif , Bowman Melissa , McCormick Sarah M. , Gao Linlin , Zhang Jiawen , Tawil John , Kapoor Arun , Arav-Boger Ravit , Choi Young Bong , Pekosz Andrew , Klein Sabra L. , Lanza Matthew , Fanburg-Smith Julie C. , García-Sastre Adolfo , Norbury Christopher C. , Chroneos Zissis C. , Harhaj Edward W. 
Published: March 2024

AbstractThe A20 ubiquitin-editing enzyme is a critical negative regulator of NF-κB signaling and inflammation. While the mechanisms by which A20 restricts inflammation have been extensively studied, the physiological functions of other A20-like proteins are largely unknown. Here, we report a previously unknown function of the A20 family member ZFAND6 as a novel regulator of mitophagy. Deletion of ZFAND6 in bone marrow-derived macrophages (BMDMs) promotes the upregulation of reactive oxygen species (ROS) and the accumulation of damaged mitochondria due to impaired mitophagy. Consequently, mitochondrial DNA (mtDNA) is released into the cytoplasm, triggering the spontaneous expression of interferon-stimulated genes (ISGs) in a cGAS-STING dependent manner, which leads to enhanced viral resistancein vitro. However, mice lacking ZFAND6 exhibit increased morbidity and mortality upon challenge with a sublethal dose of influenza A virus (IAV) due to impaired myeloid cell activation and diminished type I IFN signaling. Mechanistically, ZFAND6 bridges a TRAF2-cIAP1 interaction, which is required for the initiation of ubiquitin-dependent mitophagy. Our results suggest that ZFAND6 is a subunit of a TRAF2-cIAP E3 ligase complex that promotes the clearance of damaged mitochondria by mitophagy to maintain mitochondrial homeostasis.
Building a Collaborative DNA Barcode Library for the Diptera of Churchill, Canada: A Resource for Northern Research
Authors: Majoros S.E. , Wang J. , Levesque-Beaudin V. , Borkent C.J. , Brodo F. , Brooks S.E. , Boucher S. , Cumming J.M. , Currie D.C. , Ekrem T. , Elliott T.A. , Hebert P.D.N. , Savage J. , Schaefer P. , Sinclair B.J. , Skevington J.H. , Solecki A.M. , Stur E. , Wheeler T.A. , Woodcock T.S. , Young A. D. , Young C. , Adamowicz S.J. 
Published: March 2024

AbstractChurchill, Manitoba, Canada is a diverse Subarctic region that has been the focus of DNA barcoding efforts and research for decades. Despite this effort, there are still taxa in this region that are underrepresented in public databases, particularly hyperdiverse insect groups. We present a collaborative large-scale DNA barcode reference library for Diptera based on molecular data and expert taxonomic identification. The reference library contains 16786 specimens sampled around Churchill from 2005 to 2011. Specimens were identified by morphological means, sequenced for the animal barcode marker, and sorted into 2235 Molecular Operational Taxonomic Units (using Barcode Index Numbers: BINs) representing 68 families and 1211 named species. Eighty-four species shared a BIN with another species, 98 species were split across several BINs, and 1028 species were assigned to a unique BIN. The intraspecific and nearest neighbour distances varied across families, but most species can be easily distinguished from their nearest neighbours. By combining molecular data with taxonomic expertise, the barcode library provides species-level information for 12612 specimens, supplying future researchers with detailed taxonomic information and the opportunity to perform barcode-based specimen identifications for large-scale studies through sequence matching. Comparison of the Diptera composition of Churchill to other geographic regions reflected likely postglacial colonization northwards as well as a Beringian component. This study provides a publicly available, detailed reference library for use in future research, as well as new insights into the current diversity of Diptera present among the diverse habitats in this Subarctic region.
Formation and Retrieval of Cell Assemblies in a Biologically Realistic Spiking Neural Network Model of Area CA3 in the Mouse Hippocampus
Authors: Kopsick Jeffrey D. , Kilgore Joseph A. , Adam Gina C. , Ascoli Giorgio A. 
Published: March 2024

AbstractThe hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood. Here, we demonstrate that a data-driven SNN model quantitatively reflecting the neuron type-specific population sizes, intrinsic electrophysiology, connectivity statistics, synaptic signaling, and long-term plasticity of the mouse CA3 is capable of robust auto-association and pattern completion via cell assemblies. Our results show that a broad range of assembly sizes could successfully and systematically retrieve patterns from heavily incomplete or corrupted cues after a limited number of presentations. Furthermore, performance was robust with respect to partial overlap of assemblies through shared cells, substantially enhancing memory capacity. These novel findings provide computational evidence that the specific biological properties of the CA3 circuit produce an effective neural substrate for associative learning in the mammalian brain.
Evidence that the monoamine oxidase B (MAO-B) plays a central role in the inotropic dysfunction induced by genetic deletion of the Mas-related-G protein-coupled receptor D (MrgD) in mice
Authors: Rodrigues-Ribeiro Lucas , Rezende-Ribeiro Julia , Scalzo Sérgio , Dias Maria Luiza , Sanches Bruno de Lima , Eliezeck Marcos , de Jesus Itamar Couto , Medeiros Evaristo Joseph Albert , Sampaio Kinulpe Honorato , Peruchetti Diogo B. , Cruz Jader Santos , Nogueira Fábio César Sousa , Campagnole-Santos Maria José , Guatimosim Silvia , Santos Robson Augusto Souza , Verano-Braga Thiago 
Published: March 2024

ABSTRACTThe renin-angiotensin system (RAS) plays a critical role in the regulation of the cardiovascular system. The Mas-related G protein receptor member D (MrgD) is the receptor of alamandine, and both are components of the RAS noncanonical arm. Alamandine/MrgD induces vasodilation, anti-inflammatory, anti-fibrotic and anti-oxidative effects. In contrast,Mrgdgene deletion leads to a remarkable dilated cardiomyopathy (DCM) in mice. Here, we aimed to investigate the molecular mechanisms of DCM triggered by the deletion of MrgD in the left ventricle and isolated ventricular cardiomyocytes from 8-12 weeks old mice using phosphoproteomics. Our findings revealed an increased oxidative stress not caused by angiotensin II/AT1 hyperactivation but instead due to the up-regulation of the monoamine oxidase B (MAO-B), leading to a higher catabolism of dopamine and epinephrine in the MrgD-KO cardiac tissues. The oxidative environment induced by MAO-B hyperactivation seems to be the cause of the observed alteration in ionic dynamics - altered Ca2+transient and Na+/K+-ATPase activity - leading to altered resting membrane potential (RMP) and decreased contraction of MrgD-KO cardiomyocytes. In addition, cardiac Troponin-I phosphorylation, and Titin dephosphorylation seem to contribute to the contractile dysfunction observed in MrgD-KO. The treatment of cardiomyocytes from MrgD-KO mice with the MAO-B inhibitor Pargyline reverted the observed impaired contraction, corroborating the hypothesis that MAO-B hyperactivation is, at least partially, the cause of the failing heart observed in MrgD-KO mouse. The findings reported here provide important insights into the pathogenesis of heart failure and suggest a potential therapeutic target (MrgD activation) for managing failing hearts.
A Comprehensive Model of Blood Flow Restriction in the Post-surgical Rat
Authors: Fosam Andin , Ramos Nakandakari Susana Castelo Branco , Ohashi Yuichi , Bai Hualong , O’Connell Julie , Raines Andrew , Miranda Isabella Chavez , Dardik Alan , Allen Christina , Perry Rachel J. 
Published: March 2024

ABSTRACTBlood flow restriction (BFR) with low-load exercise (BFR-exercise) is an increasingly popular tool used to increase muscle strength and attenuate muscle atrophy, especially after injury or surgery. However, the mechanisms underlying BFR-mediated muscle growth are not well understood. Likely contributing to the mechanistic knowledge gap, rodent models of BFR-exercise have not been well described. In this methods paper, we demonstrate a comprehensive, clinically relevant protocol to establish BFR-exercise in awake rats. This protocol includes generating a muscle loss state via bilateral ACL-R, determining targeted blood flow occlusion pressures, and performing weighted hind-limb knee extension exercises with BFR. These methods can be used for further application in mechanistic and physiologic studies of BFR-exercise.
Leveraging integrative toxicogenomic approach towards development of stressor-centric adverse outcome pathway networks for plastic additives
Authors: Sahoo Ajaya Kumar , Chivukula Nikhil , Madgaonkar Shreyes Rajan , Ramesh Kundhanathan , Marigoudar Shambanagouda Rudragouda , Sharma Krishna Venkatarama , Samal Areejit 
Published: March 2024

AbstractPlastics are widespread pollutants found in atmospheric, terrestrial and aquatic ecosystems due to their extensive usage and environmental persistence. Plastic additives, that are utilized to achieve specific functionality in plastics, leach into the environment upon plastic degradation and pose considerable risk to ecological and human health. Limited knowledge concerning the presence of plastic additives throughout the plastic life cycle has hindered their effective regulation, thereby posing risks to product safety. In this study, we leveraged the adverse outcome pathway (AOP) framework to understand the mechanisms underlying plastic additives-induced toxicities. We first identified an exhaustive list of 6470 plastic additives from chemicals documented to be found in plastics. Next, we leveraged heterogenous toxicogenomics and biological endpoints data from five exposome-relevant resources, and identified associations between 1287 plastic additives and 322 complete and high quality AOPs within AOP-Wiki. Based on these plastic additive-AOP associations, we constructed a stressor-centric AOP network, wherein the stressors are categorized into 10 priority use sectors and AOPs are linked to 27 disease categories. We visualized the plastic additives-AOP network for each of the 1287 plastic additives and made them available in a dedicated website:https://cb.imsc.res.in/saopadditives/. Finally, we showed the utility of the constructed plastic additives-AOP network by identifying 28 highly relevant AOPs associated with benzo[a]pyrene, and thereafter, explored the associated toxicity pathways leading to respiratory and gastrointestinal system diseases in humans and developmental disorders in aquatic species. Overall, the constructed plastic additives-AOP network will enable regulatory risk assessment of plastic additives, thereby contributing towards a toxic-free circular economy for plastics.
Identifying the gene responsible for NPQ reversal inPhaeodactylum tricornutum
Authors: Ware Maxwell A. , Paton Andrew J. , Bai Yu , Kassaw Tessema , Lohr Martin , Peers Graham 
Published: March 2024

AbstractAlgae such as diatoms and haptophytes have distinct photosynthetic pigments from plants, including a novel set of carotenoids. This includes a primary xanthophyll cycle comprised of diadinoxanthin and its de-epoxidation product diatoxanthin that enables the switch between light harvesting and non-photochemical quenching (NPQ)-mediated dissipation of light energy. The enzyme responsible for the reversal of this cycle was previously unknown. Here, we identified zeaxanthin epoxidase 3 (ZEP3) fromPhaeodactylum tricornutumas the candidate diatoxanthin epoxidase. Knocking out the ZEP3 gene caused a loss of rapidly reversible NPQ following saturating light exposure. This correlated with the maintenance of high concentrations of diatoxanthin during recovery in low light. Xanthophyll cycling and NPQ relaxation were restored via complementation of the wild type ZEP3 gene. Thezep3knockout strains showed reduced photosynthetic rates at higher light fluxes and reduced specific growth rate in variable light regimes, likely due to the mutant strains becoming locked in a light energy dissipation state. We were able to toggle the level of NPQ capacity in a time and dose dependent manner by placing the ZEP3 gene under the control of an inducible promoter. Identification of this gene provides deeper understanding of the diversification of photosynthetic control in algae compared to plants and suggests a potential target to improve the productivity of industrial-scale cultures.
Prevalent co-release of glutamate and GABA throughout the mouse brain
Authors: Ceballos Cesar C. , Ma Lei , Qin Maozhen , Zhong Haining 
Published: March 2024

ABSTRACTSeveral neuronal populations in the brain transmit both the excitatory and inhibitory neurotransmitters, glutamate, and GABA, to downstream neurons. However, it remains largely unknown whether these opposing neurotransmitters are co-released onto the same postsynaptic neuron simultaneously or are independently transmitted at different time and locations (called co-transmission). Here, using whole-cell patch-clamp recording on acute mouse brain slices, we observed biphasic miniature postsynaptic currents, i.e., minis with time-locked excitatory and inhibitory currents, in striatal spiny projection neurons (SPNs). This observation cannot be explained by accidental coincidence of monophasic miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively), arguing for the co-release of glutamate and GABA. Interestingly, these biphasic minis could either be an mEPSC leading an mIPSC or vice versa. Although dopaminergic axons release both glutamate and GABA in the striatum, deletion of dopamine neurons did not eliminate biphasic minis, indicating that the co-release originates from another neuronal type. Importantly, we found that both types of biphasic minis were detected in other neuronal subtypes in the striatum as well as in nine out of ten additionally tested brain regions. Our results suggest that co-release of glutamate and GABA is a prevalent mode of neurotransmission in the brain.
Development and Application of Decontamination Methods for the Re-Use of Laboratory Grade Plastic Pipette Tips
Authors: Lee Sang Hyuk , Kastor William , Fu Xiao , Soni Vikas , Keidar Michael , Donohue Marc , Wood Steve , Karunasena Enusha 
Published: March 2024

AbstractDuring the SARS-CoV-2 pandemic, a need for methods to decontaminate and reuse personal protective equipment (PPE) and medical plastics became a priority. In this investigation we aimed to develop a contamination evaluation protocol for laboratory pipette tips, after decontamination. Decontamination methods tested in this study included cleaning with a common laboratory detergent (2.5% Alconox® solution followed with steam decontamination), exposure of ozone vapor at 250 and 14400 PPM * minute, and exposure to cold atmospheric plasma (CAP). All tips (control and experimental groups) were introduced to the methods described, while tips exposed to DNA extracts ofAeromonas hydrophila(ATCC-23211) were assessed for experimental groups. Decontamination was determined by turnover ratio and log reduction in detectable genomic material on the contaminated products using real-time quantitative PCR (qPCR) assay.Our results showed, cleaning tips with lab detergents along with steam decontamination removed genetic material, resulting in the highest log reduction, compared with ozone or CAP treatments. Detergent/washing methods showed the highest turnover ratio (95.9 %) and log reduction (5.943). However, the excessive residue (post-cleaning) on the plastic, within inner filters, and tip boxes suggested that washing with lab detergents was not favorable for reuse. Ozone vapor at 14400 PPM * minutes showed the second highest turnover ratio (98.4 %) and log reduction (4.511). CAP exposure with tips inverted (the tip end exposed closer to the plasma flame) for 1 minute showed a turnover ratio of (68.3 %) and log reduction (4.002). Relatively, lower turnover ratio and log reduction of CAP could be attributed to development/optimization of treatment conditions, including increases in exposure time and relative to tip positioning.