bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shigella O-specific polysaccharide functional IgA responses mediate protection against shigella infection in an endemic high-burden setting
Authors: Bernshtein Biana , Kelly Meagan , Cizmeci Deniz , Zhiteneva Julia A. , Macvicar Ryan , Kamruzzaman Mohammad , Bhuiyan Taufiqur R. , Chowdhury Fahima , Khan Ashraful Islam , Qadri Firdausi , Charles Richelle C. , Xu Peng , Kováč Pavol , Kaminski Robert W. , Alter Galit , Ryan Edward T. 
Published: May 2023

AbstractShigella is the second leading cause of diarrheal disease-related death in young children in low and middle income countries. The mechanism of protection against shigella infection and disease in endemic areas is uncertain. While historically LPS-specific IgG titers have been associated with protection in endemic settings, emerging deeper immune approaches have recently elucidated a protective role for IpaB-specific antibody responses in a controlled human challenge model in North American volunteers. To deeply interrogate potential correlates of immunity in areas endemic for shigellosis, here we applied a systems approach to analyze the serological response to shigella across endemic and non-endemic populations. Additionally, we analyzed shigella-specific antibody responses over time in the context of endemic resistance or breakthrough infections in a high shigella burden location. Individuals with endemic exposure to shigella possessed broad and functional antibody responses across both glycolipid and protein antigens compared to individuals from non-endemic regions. In high shigella burden settings, elevated levels of OSP-specific FcαR binding antibodies were associated with resistance to shigellosis. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation and reactive oxygen species production. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody mediated activation of neutrophils and monocytes. Overall, our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against shigella infection in high-burden settings. These findings will assist in the development and evaluation of shigella vaccines.
An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique
Authors: Pandya Medha , shukla Dhruvam , Shah Sejal , Das Kajari , Dave Sushma , Das Jayashankar 
Published: May 2023

AbstractA novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.
Brain cell type specific proteomics approach to discover pathological mechanisms in the childhood CNS disorder mucolipidosis type IV
Authors: Sangster Madison , Shahriar Sanjid , Niziolek Zachary , Carisi Maria Carla , Lewandowski Michael , Budnik Bogdan , Grishchuk Yulia 
Published: May 2023

Abstract1 Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations inMCOLN1, the gene encoding the lysosomal cation channel TRPML1. The disease primarily affects the central nervous system (CNS) and manifests in the first year with cognitive and motor developmental delay, followed by a gradual decline in neurological function across the second decade of life, blindness, and premature death in third or fourth decades. Brain pathology manifestations in MLIV are consistent with hypomyelinating leukodystrophy with brain iron accumulation. Presently, there are no approved or investigational therapies for MLIV, and pathogenic mechanisms remain largely unknown. The MLIV mouse model,Mcoln1-/-mice, recapitulates all major manifestations of the human disease. Here, to better understand the pathological mechanisms in the MLIV brain, we performed cell type specific LC-MS/MS proteomics analysis in the MLIV mouse model and reconstituted molecular signatures of the disease in either freshly isolated populations of neurons, astrocytes, oligodendrocytes, and neural stem cells, or whole tissue cortical homogenates from young adult symptomaticMcoln1-/-mice. Our analysis confirmed on the molecular level major histopathological hallmarks of MLIV universally present inMcoln1-/-tissue and brain cells, such as hypomyelination, lysosomal dysregulation, and impaired metabolism of lipids and polysaccharides. Importantly, pathway analysis in brain cells revealed mitochondria-related alterations in allMcoln1-/-brain cells, except oligodendrocytes, that was not possible to resolve in whole tissue. We also report unique proteome signatures and dysregulated pathways for each brain cell population used in this study. These data shed new light on cell-intrinsic mechanisms of MLIV and provide new insights for biomarker discovery and validation to advance translational studies for this disease.
Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain
Authors: Gayden Jenesis , Puig Stephanie , Srinivasan Chaitanya , Phan BaDoi N. , Abdelhady Ghada , Buck Silas A. , Gamble Mackenzie C. , Tejeda Hugo A. , Dong Yan , Pfenning Andreas R. , Logan Ryan W. , Freyberg Zachary 
Published: May 2023

SummaryStriatal projection neurons (SPNs) are traditionally segregated into two subpopulations expressing dopamine (DA) D1-like or D2-like receptors. However, this dichotomy is challenged by recent evidence. Functional and expression studies raise important questions: do SPNs co-express different DA receptors, and do these differences reflect unique striatal spatial distributions and expression profiles? Using RNAscope in mouse striatum, we report heterogenous SPN subpopulations distributed across dorsal-ventral and rostral-caudal axes. SPN subpopulations co-express multiple DA receptors, including D1and D2(D1/2R) and D1and D3. Our integrative approach using single-nuclei multi-omics analyses provides a simple consensus to describe SPNs across diverse datasets, connecting it to complementary spatial mapping. Combining RNAscope and multi-omics shows D1/2R SPNs further separate into distinct subtypes according to spatial organization and conserved marker genes. Each SPN cell type contributes uniquely to genetic risk for neuropsychiatric diseases. Our results bridge anatomy and transcriptomics to offer new understandings of striatal neuron heterogeneity.
Prophage rates in the human microbiome vary by body site and host health
Authors: Inglis Laura K. , Roach Michael J. , Edwards Robert A. 
Published: May 2023

AbstractPhages integrated into a bacterial genome–called prophages–continuously monitor the health of the host bacteria to determine when to escape the genome, protect their host from other phage infections, and may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies focus on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. We compared the prophages identified in 11,513 bacterial genomes isolated from human body sites to characterise prophage DNA in the human microbiome. Here, we show that prophage DNA comprised an average of 1-5% of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human, and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.
Exploiting long read sequencing to detect azole fungicide resistance mutations inPyrenophora teresusing unique molecular identifiers
Authors: Zulak Katherine G. , Farfan-Caceres Lina , Knight Noel L. , Lopez-Ruiz Francisco J. 
Published: May 2023

AbstractResistance to fungicides is a global challenge as target proteins under selection can evolve rapidly, reducing fungicide efficacy. To manage resistance, detection technologies must be fast and flexible enough to cope with a rapidly increasing number of mutations. The most important agricultural fungicides are azoles that target the ergosterol biosynthetic enzyme sterol 14α-demethylase (CYP51). Mutations associated with azole resistance in theCyp51promoter and coding sequence can co-occur in the same allele at different positions and codons, increasing the complexity of resistance detection. Resistance mutations arise rapidly and cannot be detected using traditional amplification-based methods if they are not known. To capture the complexity of azole resistance in two net blotch pathogens of barley we used the Oxford Nanopore MinION to sequence the promoter and coding sequence ofCyp51A. This approach detected all currently known mutations from biologically complex samples increasing the simplicity of resistance detection as multiple alleles can be profiled in a single assay. With the mobility and decreasing cost of long read sequencing, we demonstrate this approach is broadly applicable for characterizing resistance within known agrochemical target sites.
Dopamine D2 receptors in mossy cells reduce excitatory transmission and are essential for hippocampal function
Authors: Gulfo Michelle C. , Lebowitz Joseph J. , Ramos Czarina , Hwang Dong-Woo , Nasrallah Kaoutsar , Castillo Pablo E. 
Published: May 2023

ABSTRACTHilar mossy cells (MCs) are principal excitatory neurons of the dentate gyrus (DG) that play critical roles in hippocampal function and have been implicated in brain disorders such as anxiety and epilepsy. However, the mechanisms by which MCs contribute to DG function and disease are poorly understood. Expression from the dopamine D2 receptor (D2R) gene (Drd2) promoter is a defining feature of MCs, and previous work indicates a key role for dopaminergic signaling in the DG. Additionally, the involvement of D2R signaling in cognition and neuropsychiatric conditions is well-known. Surprisingly, though, the function of MC D2Rs remain largely unexplored. In this study, we show that selective and conditional removal ofDrd2from MCs of adult mice impaired spatial memory, promoted anxiety-like behavior and was proconvulsant. To determine the subcellular expression of D2Rs in MCs, we used a D2R knockin mouse which revealed that D2Rs are enriched in the inner molecular layer of the DG, where MCs establish synaptic contacts with granule cells. D2R activation by exogenous and endogenous dopamine reduced MC to dentate granule cells (GC) synaptic transmission, most likely by a presynaptic mechanism. In contrast, removingDrd2from MCs had no significant impact on MC excitatory inputs and passive and active properties. Our findings support that MC D2Rs are essential for proper DG function by reducing MC excitatory drive onto GCs. Lastly, impairment of MC D2R signaling could promote anxiety and epilepsy, therefore highlighting a potential therapeutic target.SIGNIFICANCEGrowing evidence indicates that hilar mossy cells (MCs) of the dentate gyrus play critical but incompletely understood roles in memory and brain disorders, including anxiety and epilepsy. Dopamine D2 receptors (D2Rs), implicated in cognition and several psychiatric and neurological disorders, are considered to be characteristically expressed by MCs. Still, the subcellular localization and function of MC D2Rs are largely unknown. We report that removing theDrd2gene specifically from MCs of adult mice impaired spatial memory and was anxiogenic and proconvulsant. We also found that D2Rs are enriched where MCs synaptically contact dentate granule cells (GC) and reduce MC-GC transmission. This work uncovered the functional significance of MC D2Rs, thus highlighting their therapeutic potential in D2R- and MC-associated pathologies.
Quantifying the relationship between within-host dynamics and transmission for viral diseases of livestock
Authors: Gubbins Simon 
Published: May 2023

AbstractUnderstanding the population dynamics of an infectious disease requires linking within-host dynamics and between-host transmission in a quantitative manner, but this is seldom done in practice. Here a simple phenomenological model for viral dynamics within a host is linked to between-host transmission by assuming that the probability of transmission is related to log viral titre. Data from transmission experiments for two viral diseases of livestock, foot-and- mouth disease virus in cattle and swine influenza virus in pigs, are used to parameterise the model and, importantly, test the underlying assumptions. The model allows the relationship between within-host parameters and transmission to be determined explicitly through their influence on the individual reproduction number and generation time. Furthermore, these critical within-host parameters (time and level of peak titre, viral growth and clearance rates) can be computed from more complex within-host models, raising the possibility of assessing the impact of within-host processes on between-host transmission in a more detailed quantitative manner.Author summaryFor a pathogen to be able to transmit between hosts it must replicate to a sufficiently high level within an infected host. Because of this linking the dynamics of a pathogen within a host to transmission between hosts is important for understanding an infectious disease and its control. In this study I develop a simple mathematical model for the within-host dynamics and combine it with a model relating the probability of transmission to the level of the pathogen. I use the model derive explicit relationships between parameters related to the within-host dynamics, such as viral growth and clearance rates, and summary transmission measures, such as the reproduction number and generation time. I test the assumptions in the underlying model and estimate parameters using data from transmission experiments for two important viral diseases, foot-and-mouth disease virus in cattle and swine influenza virus in pigs. Identifying the critical within host parameters that influence transmission allows the impact of within-host processes on between-host transmission to be investigated in a more detailed quantitative manner.
Genetic inactivation of essentialHSF1reveals an isolated transcriptional stress response selectively induced by protein misfolding
Authors: Ciccarelli Michela , Masser Anna E. , Kaimal Jayasankar Mohanakrishnan , Planells Jordi , Andréasson Claes 
Published: May 2023

ABSTRACTHeat Shock Factor 1 (Hsf1) in yeast drives the basal transcription of key proteostasis factors and its activity is induced as part of the core heat shock response. Exploring Hsf1 specific functions has been challenging due to the essential nature of theHSF1gene and the extensive overlap of target promoters with environmental stress response (ESR) transcription factors Msn2 and Msn4 (Msn2/4). In this study, we constructed a viablehsf1Δ strain by replacing theHSF1open reading frame with genes that constitutively express Hsp40, Hsp70 and Hsp90 from Hsf1-independent promoters. Phenotypic analysis showed that thehsf1Δ strain grow slowly, is sensitive to heat as well as protein misfolding and accumulates protein aggregates. Transcriptome analysis revealed that the transcriptional response to protein misfolding induced by azetidine-2-carboxylic acid is fully dependent of Hsf1. In contrast, thehsf1Δ strain responded to heat shock through the ESR. Following HS, Hsf1 and Msn2/4 showed functional compensatory induction with stronger activation of the remaining stress pathway when the other branch was inactivated. Thus, we provide a long overdue genetic test of the function of Hsf1 in yeast using the novelhsf1Δ construct. Our data highlight that the accumulation of misfolded proteins is uniquely sensed by Hsf1-Hsp70 chaperone titration inducing a highly selective transcriptional stress response.
Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply inKRASmutant colorectal cancer
Authors: Lu Lingeng , Zhang Qian , Shen Xinyi , Zhen Pinyi , Marin Audrey , Milian Rolando Garcia- , Roper Jatin , Khan Sajid A. , Johnson Caroline H. 
Published: May 2023

AbstractThe nutrient status of the tumor microenvironment has major impacts on cell growth. Under nutrient depletion, asparagine synthetase (ASNS)-mediated asparagine production increases to sustain cell survival. G protein-coupled estrogen receptor-1 (GPER1) signaling converges via cAMP/PI3K/AKT with KRAS signaling to regulateASNSexpression. However, the role of GPER1 in CRC progression is still debated, and the effect of nutrient supply on bothASNSandGPER1relative toKRASgenotype is not well understood. Here, we modeled a restricted nutrient supply by eliminating glutamine from growing cancer cells in a 3D spheroid model of human female SW48KRASwild-type (WT) andKRASG12A mutant (MT) CRC cells, to examine effects onASNSandGPER1expression. Glutamine depletion significantly inhibited cell growth in bothKRASMT and WT cells; however,ASNSandGPER1were upregulated inKRASMT compared to WT cells. When nutrient supply was adequate,ASNSandGPER1were not altered between cell lines. The impact of estradiol, a ligand for GPER1, was examined for any additional effects on cell growth. Under glutamine deplete conditions, estradiol decreased the growth ofKRASWT cells but had no effect onKRASMT cells; estradiol had no additive or diminutive effect on the upregulation ofASNSorGPER1between the cell lines. We further examined the association ofGPER1andASNSlevels with overall survival in a clinical colon cancer cohort of The Cancer Genome Atlas. Both highGPER1andASNSexpression associated with poorer overall survival for females only in advanced stage tumors. These findings suggest thatKRASMT cells have mechanisms in place that respond to decreased nutrient supply, typically observed in advanced tumors, by increasing the expression ofASNSandGPER1to drive cell growth. Furthermore,KRASMT cells are resistant to the protective effects of estradiol under nutrient deplete conditions. ASNS and GPER1 may therefore be potential therapeutic targets that can be exploited to manage and controlKRASMT CRC.
Why millennials of smart city are willing to pay premium for toxic-free food products: social media perspective
Authors: Trivedi Mridul , Bulsara Hemantkumar P. , Shukla Yupal 
Published: May 2023

PurposeThis study aims to investigate the smart city millennials’ willingness to pay a premium (WTP) toward toxic-free food products (TFPs). Specifically, it explores the role of social media and environmental concern (EC), using the theory of planned behavior.Design/methodology/approachThe authors used a self-administered questionnaire to gather data from 337 millennials living in an Indian smart city, and analyzed them using PLS-SEM.FindingsThe authors found that both EC and social media influence millennials' attitude and purchase intention (PI). The PI so formed, in turn, has both a significant and positive influence on the WTP for TFPs.Originality/valueTo the best of the authors' knowledge, the study is possibly pioneering, especially in the Indian context, as it considers the theory of planned behavior (TPB)'s perspective on millennials of a smart city with respect to TFP. Besides, data on the willingness to pay premium vis-à-vis the social media influence have also shed light on the contexts' uniqueness.
Determinants of Polish young adults' attitudes toward food safety
Authors: Czernyszewicz Eugenia 
Published: May 2023

PurposeDetermine the elements of young adult consumers' attitudes toward food safety using a food safety attitude (FSA) questionnaire and identify the factors influencing them.Design/methodology/approachThis study adopts a descriptive and explanatory perspective to the research problem. Determination of students' attitudes was carried out by direct survey using a questionnaire. The ABC model of attitude was used to construct the statements in the questionnaire. The respondents' answers were analyzed using statistical methods.FindingsThe proposed questionnaire has proven to be a useful tool for assessing food safety attitudes and has identified important new elements in consumers' attitudes. Students' attitudes toward food safety are shaped by sociodemographic and psychosocial factors such as customer type, attitude toward risk, and how they make food purchasing decisions.Research limitations/implicationsInformation about students' attitudes was obtained only from surveys. The survey results provide valuable insights for business practice.Practical implicationsFindings can be used to increase the effectiveness of efforts by various organizations aimed at changing consumer attitudes and behavior and to help understand why consumers implement some food safety behaviors and not others.Social implicationsThe research results will help more effectively target efforts to change consumer attitudes, which could translate into a reduction in cases of illness caused by eating unsafe food or following proper practices when shopping and at the home preparation stage.Originality/valueDevelopment of a reliable tool for the study of attitudes. Identify the new elements of young adult consumers' attitudes and the factors that shape them.
Embedding Canva into the marketing classroom: a dialogic and social learning approach to classroom innovation
Authors: Hinchcliff Mercedez , Mehmet Michael 
Published: May 2023

PurposeThe purpose of this paper is to introduce a conceptual framework as a six-stage guided implementation for educators to embed Canva (an online design tool) into their marketing subjects to encourage super-skills of the 21st century including stronger collaboration, creativity, critical thinking and communication which in turn increases a student's work readiness.Design/methodology/approachThe framework is designed from sociocultural and experiential approaches of learning and teaching. It is based on dialogic and social learning theories and guided by the 21st century skills, experience, student interactions and reflections.FindingsBased on the initial staff and student reflections and the author's extensive teaching experience, the implementation of Canva into marketing subjects suggests students are increasing their creativity, design, collaborative and critical thinking skills due to the unique features of the tool. This is suggestive that the implementation process developed through the conceptual framework of embedding Canva supported not only the students’ learning experience but allowed for a more immersive experience for teaching staff as well.Originality/valueThis paper provides a pedagogical and theoretically supported rationalisation for a staged approach to embed Canva into a classroom to assist educators in fostering students’ critical thinking skills, communication, collaboration whilst encouraging higher quality and creativity of assessments. This paper may have a continued flow on effect to student's work readiness by equipping them with a needed marketing tool in their career pursuits.