bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Differentially expressed genes and Molecular pathways in Peanut Allergy Induced Dynamic Changes involved in Peanut-Specific Immune Responses: A Systematic and Bioinformatics Approach
Authors: Parmar Glory Simon , Gulati Manisha , Rabby Md Khoshnade , Merugu Ramchander , Mohanty Satabdi , Kulsum Umme , Pujari Dhanshree Gajanan , More Swapnja Rohit , Prakash Om , Bhore Priyanka Shrikant , Satish Deepshikha 
Published: May 2024

ABSTRACTPeanut allergy poses a significant global health concern, triggering hypersensitivity reactions upon exposure to peanuts. Understanding the molecular mechanisms governing peanut-specific immune responses is imperative for developing effective therapeutic approaches. This study aimed to investigate differentially expressed genes (DEGs) and associated molecular pathways implicated in peanut allergy-induced immune responses. Employing a systematic and bioinformatics-driven approach, we analyzed gene expression profiles from peanut-allergic individuals and healthy controls using RNAseq Next-Generation Sequencing (NGS) data. Enrichment analysis of DEGs revealed their involvement in various inflammatory conditions, including autoinflammatory, allergic, and respiratory disorders. Additionally, pathway enrichment analysis highlighted perturbed molecular pathways such as Asthma, IL-17 signaling pathway, and Inflammatory bowel diseases, underscoring their role in modulating peanut-specific immune responses. Protein-protein interaction network analysis identified central regulatory hubs, elucidating the intricate molecular interplay underlying the immune response to peanut allergens. Overall, our findings offer comprehensive insights into the molecular landscape of peanut allergy, delineating key DEGs and pathways associated with peanut-specific immune responses. This systematic and bioinformatics-driven approach enhances our understanding of allergic reactions to peanuts, providing potential targets for the development of novel therapeutic interventions and diagnostic biomarkers for peanut allergy management.
Lipoprotein(a) metabolomic and proteomic features and atherosclerotic cardiovascular disease in young, healthy adults
Authors: Goonewardena Sascha N. , Jurga Tomasz , Lloyd-Jones Donald , Damodaran Dilna , Thyagarajan Bharat , Jacobs David R. , Shore Supriya , Brandt Eric J. , Clish Clary , Tanriverdi Kahraman , Freedman Jane E. , Emmer Brian T. , Wilkins John T. , Do Ron , Bittner Vera A. , Rosenson Robert S. , Shah Ravi V. , Murthy Venkatesh L. 
Published: May 2024

ABSTRACTBackgroundElevated lipoprotein (a) [Lp(a)] is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) events. Although Lp(a) is a genetically determined risk factor, the metabolomic and proteomic features that may mediate or be associated with this risk are unknown.MethodsIn young, healthy Coronary Artery Risk Development in Young Adults (CARDIA) participants, we defined the relationships between year 7 (Y7) Lp(a) and metabolomic (n=563)/proteomic (n=184) features, derived quantitative Lp(a)-omic scores from these features, and related these quantitative scores to ASCVD phenotypes.ResultsCARDIA participants had a mean age of 32 years at Y7 in this study and a median follow-up of 27.1 years. In the overall cohort (n=3920), Y7 Lp(a) levels were associated prospectively with ASCVD phenotypes at year 25 (Y25), including hs-CRP, coronary artery calcification (CAC), and incident CHD. In the subcohort (n=2290) that had measurements of Lp(a), proteomics, and metabolomics, Y7 Lp(a) levels were associated with distinct proteomic and metabolomic features indicative of immune responses, lipoprotein metabolism, atherogenesis, and arginine/steroid biosynthesis. Using machine learning approaches, Lp(a) metabolomic, proteomic, and transomic quantitative scores were derived. The Y7 Lp(a) transomic score was more strongly associated with Y25 incident CAC (standardized β = 0.29, p=0.04), hs-CRP (standardized β = 0.18, p =0.0008), and incident any CHD (standardized β = 0.51, p = 0.05), than the Y7 Lp(a) concentration itself (no significant associations).ConclusionsTo our knowledge, this is the first study to identify relationships between Lp(a) and associated metabolomic/proteomic features in young, healthy adults and joint associations with ASCVD phenotypes. The multi-omics approaches employed here provide insight into the pathobiology of Lp(a)-driven ASCVD and enable more nuanced mechanistic risk assessment compared with Lp(a) concentrations alone.
Genetically recoding respiratory syncytial virus to visualize nucleoprotein dynamics and virion assembly
Authors: Mitrovich Margaret D. , Vahey Michael D. 
Published: May 2024

AbstractRNA viruses possess small genomes encoding a limited repertoire of essential and often multifunctional proteins. Although genetically tagging viral proteins provides a powerful tool for dissecting mechanisms of viral replication and infection, it remains a challenge. Here, we leverage genetic code expansion to develop a recoded strain of respiratory syncytial virus (RSV) in which the multifunctional nucleoprotein is site-specifically modified with an unnatural amino acid. The resulting virus replicates exclusively in cells capable of amber stop codon suppression and is amenable to labeling with tetrazine-modified fluorophores, achieving high signal-to-background. We use this tool to visualize the transfer of nucleoprotein complexes from cytoplasmic condensates directly to budding viral filaments at the cell surface and to cytoplasmic compartments containing viral surface proteins, suggesting multiple pathways for viral assembly.
Bile acids activate the antibacterial T6SS1 in the gut pathogenVibrio parahaemolyticus
Authors: Schiffmann Sarah , Mass Shir , Salomon Dor 
Published: May 2024

AbstractThe marine bacteriumVibrio parahaemolyticusis a major cause of seafood-borne gastroenteritis in humans and of acute hepatopancreatic necrosis disease in shrimp. Bile acids, produced by the host and modified into secondary bile acids by commensal bacteria in the gastrointestinal tract, induce the virulence factors leading to disease in humans and shrimp. Here, we show that secondary bile acids also activate this pathogen’s type VI secretion system 1 (T6SS1), a toxin-delivery apparatus mediating interbacterial competition. This finding implies thatVibrio parahaemolyticusexploits secondary bile acids to activate its virulence factors and identify the presence of commensal bacteria that it needs to outcompete in order to colonize the host.ImportanceBacterial pathogens often manipulate their host and cause disease by secreting toxic proteins. However, to successfully colonize a host, they must also remove commensal bacteria that reside in it and may compete with them over resources. Here, we find that the same host-derived molecules that activate the secreted virulence toxins in a gut bacterial pathogen,Vibrio parahaemolyticus, also activate an antibacterial toxin delivery system that targets such commensal bacteria. These findings suggest that a pathogen can use one cue to launch a coordinated, trans-kingdom attack that enables it to colonize a host.
Coumarin as a general switching auxiliary to prepare photochromic and spontaneously blinking fluorophores
Authors: Jradi Fadi M. , English Brian P. , Brown Timothy A. , Aaron Jesse , Khuon Satya , Galbraith James A. , Galbraith Catherine G. , Lavis Luke D. 
Published: May 2024

ABSTRACTSingle-molecule localization microscopy (SMLM) uses activatable or switchable fluorophores to create non-diffraction limited maps of molecular location in biological samples. Despite the utility of this imaging technique, the portfolio of appropriate labels for SMLM remains limited. Here, we describe a general strategy for the construction of “glitter bomb” labels by simply combining rhodamine and coumarin dyes though an amide bond. Condensation of theortho-carboxyl group on the pendant phenyl ring of rhodamine dyes with a 7-aminocoumarin yields photochromic or spontaneously blinking fluorophores depending on the parent rhodamine structure. We apply this strategy to prepare labels useful super-resolution experiments in fixed cells using different attachment techniques. This general glitter bomb strategy should lead to improved labels for SMLM, ultimately enabling the creation of detailed molecular maps in biological samples.
An N-terminal domain specifies developmental control by the SMAX1-LIKE family of transcriptional co-repressors inArabidopsis thaliana
Authors: Chang Sun Hyun , George Wesley J. , Nelson David C. 
Published: May 2024

ABSTRACTSMAX1-LIKE (SMXL) proteins are transcriptional co-repressors that regulate many aspects of plant growth and development. Proteins from the SMAX1- and SMXL78-clades of this family are targeted for degradation after karrikin or strigolactone perception, triggering downstream responses. We investigated how SMXL proteins control development.SMXL7can partially replicateSMAX1function in seeds and seedlings, butSMAX1cannot replaceSMXL7in shoot branching control. Therefore, the distinct roles of these genes arise from differences in protein activity more than expression. Analysis of chimeras and domain deletions of SMAX1 and SMXL7 proteins revealed that an N-terminal domain is necessary and sufficient to specify developmental functions. We screened 158 transcription factors for interactions with SMAX1. The N-terminal domain is necessary and/or sufficient for the majority of candidate interactions. These discoveries enable cross-wiring of karrikin and strigolactone control of plant development and lay a foundation for understanding how SMXL proteins evolved functional differences.
A novel motif in calcimembrin/C16orf74 dictates multimeric dephosphorylation by calcineurin
Authors: Bradburn Devin A. , Reis Joana C. , Qayyum Shariq , Viennet Thibault , Arthanari Haribabu , Cyert Martha S. 
Published: May 2024

AbstractCalcineurin, the Ca2+/calmodulin-activated protein phosphatase, recognizes substrates and regulators via short linear motifs, PxIxIT and LxVP, which dock to distinct sites on calcineurin and determine calcineurin distribution and catalysis, respectively. Calcimembrin/C16orf74 (CLMB), an intrinsically disordered microprotein whose expression correlates with poor cancer outcomes, targets calcineurin to membranes where it may promote oncogenesis by shaping calcineurin signaling. We show that CLMB associates with membranes via lipidation, i.e. N-myristoylation and reversible S-acylation. Furthermore, CLMB contains an unusual composite ‘LxVPxIxIT’ motif, that binds the PxIxIT-docking site on calcineurin with extraordinarily high affinity when phosphorylated,33LxVPxIxITxx(p)T44. Calcineurin dephosphorylates CLMB to decrease this affinity, but Thr44 is protected from dephosphorylation when PxIxIT-bound. We propose that CLMB is dephosphorylated in multimeric complexes, where one PxIxIT-bound CLMB recruits calcineurin to membranes, allowing a second CLMB to engage via its LxVP motif to be dephosphorylated.In vivoandin vitrodata, including nuclear magnetic resonance (NMR) analyses of CLMB-calcineurin complexes, supports this model. Thus, the CLMB composite motif imposes unique properties to calcineurin signaling at membranes including sensitivity to CLMB:calcineurin ratios, CLMB phosphorylation and dynamic S-acylation.
Patterns of morbidity and mortality among neonates admitted in Mirwais regional hospital, Kandahar, Afghanistan
Authors: Tareen Zarghoon , Tareen Ahmad Tameem , Amirzada Mohammad Essa , Zafare Nik Mohammad 
Published: May 2024

ABSTRUCTBackgroundNeonatal health is a critical global concern that reflects the national and global progress and challenges of health systems. Neonatal morbidity and mortality are major global public health problems.MethodsWe conducted a hospital-based cross-sectional descriptive study of all neonates admitted to the NICU of the pediatric ward of Mirwais Regional Hospital between March 2023 and February 2024.The objective of this study was to determine the pattern of neonatal morbidity and mortality as well as to compute case fatality rates in Mirwais Regional Hospital in Kandahar City, Afghanistan.ResultsIn our study, there were 3387 newborns admitted to the neonatal ward of Mirwais Regional Hospital over a one-year period (from March 2023 to February 2024). Prematurity was the most common reason for admission to the neonatal ward (1048/3387, 30.9 %). Other common conditions included neonatal sepsis (909/3387, 26.8%), birth asphyxia (785/3387, 23.1%), jaundice (466/3387, 13.7%), and tetanus (9/3387, 0.3%). Surgical causes contributed to (170/3387, 5.0%) morbidities.The overall mortality rate was 13.0% (442/ 3387). The major causes of mortality were premature birth (39.8%, 176/442), birth asphyxia (25.6%, 113/442), and neonatal sepsis (22.1%, 98/442). Other causes of mortality were neonatal jaundice (7.9%, 35/442), neonatal tetanus (0.9%, 4/442), and surgical disease (3.6%, 16/442). Neonatal tetanus had the highest mortality rate (44.4%).ConclusionPrematurity was the most common reason for admission, followed by birth asphyxia, neonatal sepsis, and jaundice. The overall mortality rate was 13%. Prematurity is a leading cause of neonatal mortality. Neonatal tetanus has a high mortality rate.Author summaryNeonates were defined as those the in first 28 days of life. In humans, they are more vulnerable to diseases than any other age group. Neonatal morbidity and mortality are major public health problems with approximately 3.1 million babies worldwide dying each year in the first month of life. The main goal of this study was to estimate the types of neonatal morbidity and mortality in Merwais Regional Hospital, located in Kandahar City, Afghanistan. This study found that premature birth (birth before 37 weeks of gestation) was the most common reason for admission to the neonatal ward. Other common conditions include neonatal sepsis, birth asphyxia, neonatal jaundice, and neonatal tetanus. The overall mortality rate was high in the present study. The main cause of mortality was prematurity, followed by birth asphyxia and neonatal sepsis. Interventions should be planned and implemented at different levels in the community to prevent and reduce the incidence of neonatal diseases and deaths.
Immune signaling induced by plant Toll/interleukin-1 receptor (TIR) domains is thermostable
Authors: Demont Héloïse , Remblière Céline , Deslandes Laurent , Bernoux Maud 
Published: May 2024

SummaryPlant disease is a major threat in agriculture and climate change is predicted to intensify it. Above the optimal plant’s growth range, plant immunity and in particular immune responses induced by nucleotide-binding leucine rich repeat receptors (NLRs) are dampened, but the underlying molecular mechanisms remains elusive. NLRs usually contain an N-terminal signaling domain, such as Toll/interleukin-1 receptor (TIR) domain, which is self-sufficient to trigger immune signaling. By using inducible Arabidopsis transgenic lines expressing TIR-containing NLRs (TNLs) or corresponding isolated TIR domains from Arabidopsis RPS4 and flax L6 NLRs, we showed that immune signaling induced downstream of TNL activation is not affected by an elevation of temperature. Conditional activation of TNL- and isolated TIR-mediated immune responses follow the same signaling route at permissive temperature (EDS1/RNLs requirement and activation of the salicylic acid sector). Yet, this signaling pathway is maintained under elevated temperature (30°C) when induced by isolated TIRs, but not full-length TNLs. This work underlines the need to further study how NLRs are impacted by an increase of temperature, which is particularly important to improve the resilience of plant disease resistance in a warming climate.
Mining the biosynthetic landscape of lactic acid bacteria unearths a new family of RiPPs assembled by a novel type of ThiF-like adenylyltransferases
Authors: Wang Mengjiao , Wu Mengyue , Han Meng , Niu Xiaogang , Fan Aili , Zhu Shaozhou , Tong Yigang 
Published: May 2024

AbstractRibosomally synthesized and post-translationally modified peptides (RiPPs) are chemically diverse natural products of ribosomal origin. These peptides, which frequently act as signals or antimicrobials, are biosynthesized by conserved enzymatic machineries, making genome mining a powerful strategy for unearthing previously uncharacterized members of their class. Herein, we investigate the untapped biosynthetic potential of Lactobacillales (i.e. lactic acid bacteria) – an order of Gram-positive bacteria closely associated with human life, including pathogenic species and industrially-relevent fermenters of dairy products. Through genome mining methods, we systematically explored the distribution and diversity of ThiF-like adenylyltransferases-utilizing RiPP systems in lactic acid bacteria and identified a number of unprecedented biosynthetic gene clusters. In one of these clusters, we found a previously undescribed group of macrocyclic imide biosynthetic pathways containing multiple transporters and may be involved in potential quorum sensing (QS) system. Through in vitro assays, we determined that one such adenylyltranferase specifically catalyzes the intracyclization of its precursor peptide through macrocyclic imide formation. Incubating the enzyme with various primary amines revealed it could effectively amidate the C-terminus of the precursor peptide. This new transformation adds to the growing list of Nature’s peptide macrocyclization strategies and expands the impressive catalytic repertoire of the adenylyltransferase family. The diverse RiPP systems identified herein represent a vast, unexploited landscape for discovery of novel class of natural products and potential QS systems.Abstract Figure(For Table of Contents use only)
Hypocotyl Development in Arabidopsis and other Brassicaceae Displays Evidence of Photoperiodic Memory
Authors: Ronald James , Lock Sarah C.L , Claydon Will , Zhu Zihao , McCarthy Kayla , Pendlington Elizabeth , Redmond Ethan J. , Vong Gina Y.W. , Stanislas Sanoj P. , Davis Seth J. , Quint Marcel , Ezer Daphne 
Published: May 2024

AbstractSensing and responding to photoperiod changes is essential for plants to adapt to seasonal progression. Most of our understanding of how plants sense photoperiodic changes is through studies on flowering time. However, other aspects of plant development are regulated by the photoperiod, including hypocotyl elongation. Unlike flowering, hypocotyl elongation displays a greater plasticity to changes in the photoperiod with increases in daylength causing greater inhibition of growth until a threshold is met. Previous studies have only looked at hypocotyl development in the context of a stationary photoperiod. It is unknown if changes in the photoperiod during development influence hypocotyl elongation. Here, we developed a physiological assay to investigate this question. We have discovered that hypocotyl elongation is influenced by a memory of past photoperiod exposure in Arabidopsis and Brassicaceae cultivars used for microgreen agriculture. Photoperiodic memory persisted for multiple days, although it weakened over time, and the strength of the memory was dependent on the genetic background. We identified that phyB and ELF3, key regulators of hypocotyl development, were required for photoperiodic memory. Finally, we identified that the circadian clock is unlikely to function as a repository for photoperiodic memory as circadian rhythms quickly re-aligned with the new photoperiod. In summary, our work highlights for the first-time evidence of a photoperiodic memory that can control plant development.
Detecting boosted dark photons with gaseous detectors
Authors: Graesser Michael L. , Gustafson R. Andrew , Hildebrandt Kate , Mathur Varun , Shoemaker Ian M. 
Published: May 2024

We search for indirect signals of O(keV) dark matter annihilating or decaying into O(eV) dark photons. These dark photons will be highly boosted, predominantly transversely polarized, have decay lengths larger than the Milky Way, and can be absorbed by neutrino or dark matter experiments at a rate dependent on the photon-dark photon kinetic mixing parameter and the optical properties of the experiment. We show that current experiments cannot probe new parameter space, but future large-scale gaseous detectors with low backgrounds (i.e., CYGNUS, NEXT, PANDAX-III) may be sensitive to this signal when the annihilation cross section is especially large.

Published by the American Physical Society
2024
Quantum state engineering by steering in the presence of errors
Authors: Medina-Guerra E. , Kumar Parveen , Gornyi I. V. , Gefen Yuval 
Published: May 2024

Quantum state engineering plays a vital role in various applications in the field of quantum information. Different strategies, including drive-and-dissipation, adiabatic cooling, and measurement-based steering, have been proposed for state generation and manipulation, each with its upsides and downsides. Here, we address a class of measurement-based state engineering protocols where a sequence of generalized measurements is employed to steer a quantum system toward a desired (pure or mixed) target state. Previously studied measurement-based protocols relied on idealized procedures and avoided exploration of the effects of various errors stemming from imperfections of experimental realizations and external noise. We employ the quantum trajectory formalism to provide a detailed analysis of the robustness of these steering protocols against multiple classes of errors. We study a set of realistic errors that can be classified as dynamic or static, depending on whether they remain unchanged while running the protocol. More specifically, we investigate the impact of the erroneous choice of detector-system coupling, erroneous re-initialization of the detector state following a measurement step, fluctuating steering directions, and environmentally induced errors in the detector-system interaction. We show that the protocol remains fully robust against the erroneous choice of detector-system coupling parameters and presents reasonable robustness against other types of errors. Our analysis employs various quantifiers such as fidelity, trace distance, and linear entropy to characterize the protocol's robustness and provide analytical results for these quantifiers against various errors. We introduce averaging hierarchies of stochastic equations describing individual quantum trajectories associated with detector readouts. Subsequently, we demonstrate the commutation between the classical expectation value and the time-ordering operator of the exponential of a Hamiltonian with multiplicative white noise, as well as the commutation of the expectation value and the partial trace with respect to detector outcomes. Our ideas are implemented and demonstrated for a specific class of steering platforms, addressing a single qubit.

Published by the American Physical Society
2024