bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 vaccination-infection status and immunological profile from India: a case study for prioritizing at risk population for targeted immunization
Authors: Gujjarlapudi Deepika , Mittal Ankit , Gajapathi Raju Vidyavathi Devi , Veturi Sadhana Yelamanchili , Talukdar Rupjyoti , Banerjee Rupa , Jagtap Nitin , Krishnaiah Sannapaneni , Veeraiah Namburu , Duvvur Nageshwar Reddy 
Published: February 2024

AbstractBackgroundThe COVID-19 pandemic’s global impact was mitigated through rapid vaccine development, leading to a mix of natural and vaccination-derived immunity. Immunological proﬁle in hybrid immunity remains less studies, especially in regions where non-mRNA vaccines were used. This study focuses on the immunological proﬁles and predictors of immune response in one such population.MethodsThis was a cross-sectional study to assess their humoral and cellular immune responses based on vaccination and infection history. Immunological assays were performed to measure antispike protein and neutralizing antibodies as well as interferon-γ release assay. Multivariable linear regression model was used to estimate predictors of immune response.ResultsThe study revealed signiﬁcant differences in immune response among participants based on their hybrid immunity status, vaccination, and infection history. Higher antibody titres and cellular responses were observed in individuals with hybrid immunity, especially those with dual pre-Omicron and Omicron infections (3326 BAU/ml, IQR: 770.25-5678.25 and 4.92 IU of IFN-γ/mL, IQR:3.74-16.98 respectively, p <0.001). Age and comorbidities such as diabetes and hypertension were associated with lower antibody levels and cellular response, while vaccination and hybrid immunity correlated with higher immune responses.ConclusionThe prevalence of hybrid immunity was high, yet a substantial portion of the population lacks it, indicating the necessity for targeted immunization strategies. The ﬁndings underscore the importance of prioritizing high-risk individuals, such as elderly and individuals with comorbidities, for booster vaccinations to enhance community-level protection against COVID-19.
Anti-capsule human monoclonal antibodies protect against hypervirulent and pandrug-resistantKlebsiella pneumoniae
Authors: Roscioli Emanuele , Galli Fonseca Vittoria Zucconi , Bosch Soraya Soledad , Paciello Ida , Maccari Giuseppe , Batani Giampiero , Stazzoni Samuele , Cardinali Giulia , Tiseo Giusy , Giordano Cesira , Shen Yuwei , Capoccia Laura , Ridelfi Matteo , Troisi Marco , Manganaro Noemi , Mugnaini Chiara , Cardamone Dario , Santi Concetta De , Ciabattini Annalisa , Cerofolini Linda , Fragai Marco , Licastro Danilo , Nicolau David P. , Abdelraouf Kamilia , Barnini Simona , Menichetti Francesco , Falcone Marco , Sala Claudia , Kabanova Anna , Rappuoli Rino 
Published: February 2024

SUMMARYThe silent pandemic caused by antimicrobial resistance (AMR) requires innovative therapeutic approaches. Human monoclonal antibodies (mAbs), which are among the most transformative, safe and effective drugs in oncology and autoimmunity, are rarely used for infectious diseases and not yet used for AMR. Here we applied an antigen-agnostic strategy to isolate extremely potent human mAbs againstKlebsiella pneumoniae(Kp) sequence type 147 (ST147), a hypervirulent and pandrug-resistant clonotype which is spreading globally. Isolated mAbs target the bacterial capsule and the O-antigen. Surprisingly, although both capsule- and O-antigen-specific mAbs displayed bactericidal activity in the picomolar rangein vitro, only the capsule-specific mAbs were protective against fulminant ST147 bloodstream infection. Protection correlated within vitrobacterial uptake by macrophages and enchained bacterial growth. Our study describes the only drug able to protect against pandrug-resistant Kp and provides a strategy to isolate mAbs and identify correlates of protection against AMR bacteria.
Neural Circuit Revision in Retinal Remodeling, A Pathoconnectomics Approach
Authors: Pfeiffer Rebecca L , Dahal Jeebika , Sigulinsky Crystal L , Anderson James R , Barrera Isabel A , Yang Jia-Hui , Haddadin Olivia , Houser Alexis , Garcia Jessica C , Jones Bryan W 
Published: February 2024

AbstractThe Aii glycinergic amacrine cell (Aii) plays a central role in bridging rod pathways with cone pathways, enabling an increased dynamic range of vision from scotopic to photopic ranges. The Aii integrates scotopic signals via chemical synapses from rod bipolar cells (RodBCs) onto the arboreal processes of Aii ACs, injecting signals into ON-cone bipolar cells (CBbs) via gap junctions with Aiis on the arboreal processes and the waist of the Aii ACs. The CBbs then carry this information to ON and OFF ganglion cell classes. In addition, the Aii is involved in the surround inhibition of OFF cone bipolar cells (CBas) through glycinergic chemical synapses from Aii ACs onto CBas. We have previously shown changes in RodBC connectivity as a consequence of rod photoreceptor degeneration in a pathoconnectome of early retinal degeneration: RPC1. Here, we evaluated the impact of rod photoreceptor degeneration on the connectivity of the Aii to determine the impacts of photoreceptor degeneration on the downstream network of the neural retina and its suitability for integrating therapeutic interventions as rod photoreceptors are lost. Previously, we reported that in early retinal degeneration, prior to photoreceptor cell loss, Rod BCs make pathological gap junctions with Aiis. Here, we further characterize this altered connectivity and additional shifts in both the excitatory drive and gap junctional coupling of Aiis in retinal degeneration, along with discussion of the broader impact of altered connectivity networks. New findings reported here demonstrate that Aiis make additional gap junctions with CBas increasing the number of BC classes that make pathological gap junctional connectivity with Aiis in degenerating retina. In this study, we also report that the Aii, a tertiary retinal neuron alters their synaptic contacts early in photoreceptor degeneration, indicating that rewiring occurs in more distant members of the retinal network earlier in degeneration than was previously predicted. This rewiring impacts retinal processing, presumably acuity, and ultimately its ability to support therapeutics designed to restore image-forming vision. Finally, these Aii alterations may be the cellular network level finding that explains one of the first clinical complaints from human patients with retinal degenerative disease, an inability to adapt back and forth from photopic to scotopic conditions.
Exact centriole counts are critical for B cell development but not function
Authors: Schapfl Marina A. , LoMastro Gina M. , Braun Vincent Z. , Hirai Maretoshi , Levine Michelle S. , Kiermaier Eva , Labi Verena , Holland Andrew J. , Villunger Andreas 
Published: February 2024

ABSTRACTCentrioles define centrosome structure and function. Deregulation of centriole numbers can cause developmental defects and foster malignant disease. The p53 tumor suppressor limits the growth of cells lacking or harboring additional centrioles and can be engaged by the “mitotic surveillance” or the “PIDDosome pathway”, respectively. Here, we show that early B cell progenitors frequently present extra centrioles that are rapidly lost during maturation. Increasing centriole counts beyond physiological levels by Polo-like kinase 4 (PLK4) overexpression induces apoptosis, suggesting clearance of such cells during development. Remarkably, this apoptotic response is independent of PIDD1 or p53, but can be blocked by excess BCL2. In contrast, loss of centrosomes uponPlk4deletion arrests B cell development at the pro B cell stage. This defect can be rescued by co-deletion ofUsp28, a critical component of the mitotic surveillance pathway that restores cell number and function in the absence of centrioles. In both scenarios, too many and too few centrosomes, mitochondrial apoptosis is engaged to kill B cells with abnormal centriole counts during their development with progenitor B cells being intolerant to centriole loss but permissive to centriole amplification. Unexpectedly, our findings show that centrioles are dispensable for mounting an effective humoral immune response.
Presynaptic Nrxn3 is essential for ribbon-synapse assembly in hair cells
Authors: Jukic Alma , Lei Zhengchang , Cebul Elizabeth R. , Pinter Katherine , Mosqueda Natalie , David Sandeep , Tarchini Basile , Kindt Katie 
Published: February 2024

AbstractHair cells of the inner ear rely on specialized ribbon synapses to transmit sensory information to the central nervous system. The molecules required to assemble these synapses are not fully understood. We show that Nrxn3, a presynaptic adhesion molecule, is critical for ribbon-synapse assembly in hair cells. In both mouse and zebrafish models, loss of Nrxn3 results in significantly fewer intact ribbon synapses. In zebrafish we demonstrate that a 60% loss of synapses innrxn3mutants dramatically reduces both presynaptic responses in hair cells and postsynaptic responses in afferent neurons. Despite a reduction in synapse function in this model, we find no deficits in the acoustic startle response, a behavior reliant on these synapses. Overall, this work demonstrates that Nrxn3 is a critical and conserved molecule required to assemble ribbon synapses. Understanding how ribbon synapses assemble is a key step towards generating novel therapies to treat forms of age-related and noise-induced hearing loss that occur due to loss of ribbon synapses.Summary StatementHearing and balance depend on specialized ribbon synapses that transmit sensory stimuli between hair cells and afferent neurons. We identify Nrxn3 as a key molecular player in ribbon-synapse assembly in hair cells.
Paired metagenomic and chemical evaluation of an aflatoxin contaminated dog kibble
Authors: Ottesen Andrea , Kocurek Brandon , Reed Elizabeth , Commichaux Seth , Mammel Mark , Ramachandran Padmini , McDermott Patrick , Flannery Brenna M. , Strain Errol 
Published: February 2024

AbstractIdentification of chemical toxins from complex or highly processed foods can present ‘needle in the haystack’ challenges for chemists. Metagenomic data can guide chemical toxicity evaluations with DNA-based description of the wholistic composition (bacterial, eukaryotic, protozoal, viral, and antimicrobial resistance) of any food suspected to harbor toxins, allergens, or pathogens. This approach can focus chemistry-based diagnostics, improve risk assessment, and address data gaps. There is increasing recognition that simultaneously co-occurring mycotoxins, either from single or multiple species, can impact dietary toxicity. Here we evaluate an aflatoxin contaminated kibble with known levels of specific mycotoxins and demonstrate that the abundance of DNA from putative aflatoxigenicAspergillusspp. correlated with levels of aflatoxin quantified by Liquid Chromatography Mass Spectrometry (LCMS). Metagenomic data also identified an expansive range of co-occurring fungal taxa which may produce additional mycotoxins. Metagenomic data paired with chemical data provides a novel modality to address current data gaps pertaining to mycotoxin toxicity exposures, toxigenic fungal taxonomy, and mycotoxins of emerging concern.
Maramycin, a cytotoxic isoquinolinequinone terpenoid produced through heterologous expression of a bifunctional indole prenyltransferase /tryptophan indole-lyase inS. albidoflavus
Authors: Maleckis Matiss , Wibowo Mario , Williams Sam E. , Gotfredsen Charlotte H. , Sigrist Renata , Souza Luciano D.O. , Cowled Michael S. , Charusanti Pep , Gren Tetiana , Saha Subhasish , Moreira José M. A. , Weber Tilmann , Ding Ling 
Published: February 2024

AbstractIsoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase /tryptophan indole-lyase enzyme fromStreptomyces mirabilisP8-A2 inS. albidoflavusJ1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in Nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.
Virus-free CRISPR knock-in of a chimeric antigen receptor intoKLRC1generates potent GD2-specific natural killer cells
Authors: Shankar Keerthana , Zingler-Hoslet Isabella , Shi Lei , Katta Varun , Russell Brittany E. , Tsai Shengdar Q. , Capitini Christian M. , Saha Krishanu 
Published: February 2024

AbstractNatural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt theKLRC1gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood. Genome editing with CRISPR/Cas9 ribonucleoprotein complexes yields efficient genomic disruption of theKLRC1gene with 98% knockout efficiency and specific knock-in of the GD2 CAR transgene as high as 23%, with minimal off-target activity as shown by CHANGE-Seq, in-out PCR, and next generation sequencing.KLRC1-GD2 CAR NK cells display high viability and proliferation, as well as precise cellular targeting and potency against GD2+human melanoma cells. Notably,KLRC1-GD2 CAR NK cells overcome HLA-E-based inhibition by HLA-E-expressing, GD2+melanoma cells. Using a single-step, virus-free genome editing workflow, this study demonstrates the feasibility of precisely disrupting inhibitory signaling within NK cells via CRISPR/Cas9 while expressing a CAR to generate potent allogeneic cell therapies against HLA-E+solid tumors.
Motif Interactions Affect Post-Hoc Interpretability of Genomic Convolutional Neural Networks
Authors: Lemanczyk Marta S. , Bartoszewicz Jakub M. , Renard Bernhard Y. 
Published: February 2024

ABSTRACTPost-hoc interpretability methods are commonly used to understand decisions of genomic deep learning models and reveal new biological insights. However, interactions between sequence regions (e.g. regulatory elements) impact the learning process as well as interpretability methods that are sensitive to dependencies between features. Since deep learning models learn correlations between the data and output that do not necessarily represent a causal relationship, it is difficult to say how well interacting motif sets are fully captured. Here, we investigate how genomic motif interactions influence model learning and interpretability methods by formalizing possible scenarios where interaction effects appear. This includes the choice of negative data and non-additive effects on the outcome. We generate synthetic data containing interactions for those scenarios and evaluate how they affect the performance of motif detection. We show that post-hoc interpretability methods can miss motifs if interactions are present depending on how negative data is defined. Furthermore, we observe differences in interpretability between additive and non-additive effects as well as between post-hoc interpretability methods.
Long-range chemical signallingin vivois regulated by mechanical signals
Authors: Pillai Eva K. , Mukherjee Sudipta , Gampl Niklas , McGinn Ross J. , Mooslehner Katrin A. , Becker Julia M. , Winkel Alex , Thompson Amelia J. , Franze Kristian 
Published: February 2024

AbstractBiological processes are regulated by chemical and mechanical signals, yet the interaction between these signalling modalities remains poorly understood. Using the developingXenopus laevisbrain as a model system, we identified a critical crosstalk between tissue stiffness and long-range chemical signallingin vivo. Targeted knockdown of the mechanosensitive ion channel Piezo1 in retinal ganglion cells (RGCs) led to pathfinding errorsin vivo.However, pathfinding errors were also observed in RGCs expressing Piezo1, when Piezo1 was downregulated in the surrounding brain tissue. Depleting Piezo1 in the brain parenchyma led to a decrease in the expression of the long-range chemical guidance cues Semaphorin3A (Sema3A) and Slit1, which instruct turning responses in distant cells. Furthermore, Piezo1 knockdown markedly reduced tissue stiffness. This tissue softening was independent of Sema3A depletion, and was caused by a decrease in the cell-cell adhesion proteins NCAM1 and N-Cadherin. Downregulating NCAM1 and N-Cadherin was sufficient to reduce tissue stiffness and Sema3A expression. Conversely, increasing environmental stiffnessex vivoresulted in enhanced tissue-level force generation and an increase in Slit1 and Sema3A expression. Moreover, stiffening soft brain regionsin vivoinduced ectopic Sema3A production via a Piezo1-dependent mechanism. Hence, tissue mechanics can locally modulate the availability of diffusive, long-range chemical signals, thus influencing cell function at sites distant from the mechanical cue. Such indirect regulatory mechanisms of cell function through mechanical signals are likely widespread across biological systems.
A ratiometric ER calcium sensor for quantitative comparisons across cell types and subcellular regions
Authors: Farrell Ryan J. , Bredvik Kirsten G. , Hoppa Michael B. , Hennigan S. Thomas , Brown Timothy A. , Ryan Timothy A. 
Published: February 2024

AbstractThe endoplasmic reticulum (ER) is an important regulator of Ca2+in cells and dysregulation of ER calcium homeostasis can lead to numerous pathologies. Understanding how various pharmacological and genetic perturbations of ER Ca2+homeostasis impacts cellular physiology would likely be facilitated by more quantitative measurements of ER Ca2+levels that allow easier comparisons across conditions. Here, we developed a ratiometric version of our original ER-GCaMP probe that allows for more quantitative comparisons of the concentration of Ca2+in the ER across cell types and sub-cellular compartments. Using this approach we show that the resting concentration of ER Ca2+ in primary dissociated neurons is substantially lower than that in measured in embryonic fibroblasts.
Mapping the intellectual structure and knowledge base of food literacy research: a bibliometric analysis
Authors: McManus Sarah , Pendergast Donna , Kanasa Harry 
Published: February 2024

PurposeFood literacy is a multidimensional concept that prioritises the aspects individuals require to navigate the contemporary foodscape successfully. The study aims to map the knowledge base and intellectual structure of the concept of food literacy to assess if the most cited definitions reflect these constructs.Design/methodology/approachThe inclusion criteria of full-text, peer-reviewed articles or conference papers, in English, using “food literacy” within the title, abstract, keywords or linked to the research focus produced 538 articles from the Scopus database from its inception until January 31, 2023. Articles were analysed according to exponential growth, geolocations, authors, articles, research areas and keywords using VOSviewer, CiteSpace and Excel.FindingsFood literacy research grew exponentially between 2012 and 2022 at a rate of 50% and spanned 62 research areas, with nutrition and dietetics being the most common. Vidgen and Gallegos were the most cited authors of the most cited article, and Australia was the most influential food literacy research geolocation. Research originating from developing countries within Asia, the Middle East, Africa and South America was underrepresented, and COVID-19 impacted research trends between 2020 and 2023.Practical implicationsIt is recommended to link “food literacy” to appropriate publications to increase its visibility and that food literacy be redefined and conceptualised to better reflect its intellectual structure. To complete this task, further research guided by keyword clustering can enhance conceptual understanding.Originality/valueThis study provides new insight into the knowledge base and intellectual structure of food literacy and provides scope for future research to develop the concept further.
To integrate or not? Understanding knowledge integration of target firm
Authors: Varshney Mayank 
Published: February 2024

PurposeTechnology acquisition is a common phenomenon of acquiring external knowledge, but we have a limited understanding of conditions in which the acquirer integrates the target or not. On one hand, the acquirer may have a policy to integrate the target to benefit from its prior knowledge. On the other hand, the target may face challenges in continuing its knowledge creation and the acquirer may want to provide it autonomy to not disrupt it. This paper aims to identify conditions in which targets tend to be less integrated after acquisitions, allowing them to maintain more autonomy and contribute more to knowledge creation.Design/methodology/approachWe test our arguments in the empirical setting of the global biopharmaceutical industry using a difference-in-difference approach on a longitudinal dataset of matched patents. We examine self-cites received by patents belonging to acquirers and the targets before and after the acquisitions.FindingsWe find that, on average, the targets’ prior patents do not receive more self-cites after the acquisition. We conclude that this is because their R&D activities are disrupted, suggesting a higher level of post-acquisition integration. However, more nuanced findings reveal that it may not be the case all the time. When the target has more research experience, is international or is specialized in complementary technologies, prior patents of targets continue to receive more self-cites after the acquisition. It indicates that the targets in such conditions continue knowledge creation, suggesting a lower level of post-acquisition integration.Originality/valueOur findings contribute to post-acquisition integration research. While post-acquisition integration downside is common, we present conditions in which such a downside may be less likely. We highlight that the context of an acquisition may be an important determinant of the extent of integration of the target. Moreover, we supplement the integration research (cultural, structural and human resource and leadership perspectives of integration) by adding a knowledge-based perspective to it. Such dynamics have important implications for acquirers and targets in deriving value from the acquisition.