bluuebunny/crossref_metadata_2025_split huggingface dataset:
5,6-dimethylxanthenone-4-acetic acid (DMXAA), a Partial STING Agonist, Competes for Human STING Activation
Authors: Temizoz Burcu , Shibahara Takayuki , Hioki Kou , Hayashi Tomoya , Kobiyama Kouji , Jann Lee Michelle Sue , Surucu Naz , Sag Erdal , Kumanogoh Atsushi , Yamamoto Masahiro , Gursel Mayda , Ozen Seza , Kuroda Etsushi , Coban Cevayir , Ishii Ken J. 
Published: December 2023

Abstract5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a mouse-selective stimulator of interferon gene (STING) agonist exerting STING-dependent anti-tumor activity. Although DMXAA can not fully activate human STING, DMXAA reached phase III in lung cancer clinical trials. How DMXAA is effective against human lung cancer is completely unknown. Here, we show that DMXAA is a partial STING agonist interfering with agonistic STING activation, which may explain its partial anti-tumor effect observed in humans, as STING was reported to be pro-tumorigenic for lung cancer cells with low antigenicity. Furthermore, we developed a DMXAA derivative—3-hydroxy-5-(4-hydroxybenzyl)-4-methyl-9H-xhanthen-9one (HHMX)—that can potently antagonize STING-mediated immune responses both in humans and mice. Notably, HHMX suppressed aberrant responses induced bySTINGgain-of-function mutations causing STING-associated vasculopathy with onset in infancy (SAVI) inin vitroexperiments. Furthermore, HHMX treatment suppressed aberrant STING pathway activity in peripheral blood mononuclear cells from SAVI patients. Lastly, HHMX showed a potent therapeutic effect in SAVI mouse model by mitigating disease progression. Thus, HHMX offers therapeutic potential for STING-associated autoinflammatory diseases.
Influence of plant defense signaling and innate insect metabolic differences to the overall performance of fall armyworm (Spodoptera frugiperda) corn and rice strains on maize as a host
Authors: Israni Bhawana , Raguschke Bettina , Reichelt Michael , Gershenzon Jonathan , Vassão Daniel Giddings 
Published: December 2023

AbstractThe fall armyworm (FAW,Spodoptera frugiperda) is a well-known crop pest that feeds mainly on grasses. Separate strains are known to infest maize (corn) and rice that show varying degrees of developmental and metabolic differences, as well as reproductive isolation. Here we show that the greater performance of the corn compared to the rice strain on maize leaves may be explained by several factors. Maize plants respond to herbivory by the rice strain with greater levels of defense hormone signaling and greater accumulation of defensive benzoxazinoids. Moreover, measurements of the activity of a glucosyltransferase involved in benzoxazinoid metabolism and the transcript levels of the encoding gene revealed that the corn strain had higher benzoxazinoid detoxification potential than the rice strain. The two strains also exhibit constitutive differences in the expression of an alternate variant, with potential consequences for differential regulation of the glucosylation activity. These factors may account for the better performance of corn strain larvae on maize leaves, perhaps in combination with the other differences we found in maize defense metabolites after FAW herbivory by untargeted metabolomics.
A bovine pulmosphere model and multiomics analyses identify a signature of early host response toMycobacterium tuberculosisinfection
Authors: Bhaskar Vinay , Kumar Rishi , Praharaj Manas Ranjan , Gandham Sripratyusha , Maity Hemanta Kumar , Sarkar Uttam , Dey Bappaditya 
Published: December 2023

AbstractInteractions between the tubercle bacilli and lung cells during the early stages of tuberculosis (TB) are crucial for disease outcomes. Conventional 2D cell culture inadequately replicates the multicellular complexity of lungs. We introduce a 3D pulmosphere model forMycobacterium tuberculosisinfection in bovine systems, demonstrating through comprehensive transcriptome and proteome analyses that these 3D structures closely replicate the diverse cell populations and abundant extracellular matrix proteins, emphasizing their similarity to thein vivopulmonary environment. While both avirulent BCG and virulentM. tuberculosis-infected pulmospheres exhibit commonalities in the upregulation of several host signaling pathways, distinct features such as upregulation of ECM receptors, neutrophil chemotaxis, interferon signaling, and RIG-1 signaling pathways characterize the unique early response to virulentM. tuberculosis. Moreover, a signature of seven genes/proteins, including IRF1, CCL5, CXCL8, CXCL10, ICAM1, COL17A1, and CFB, emerges as indicative of the early host response toM. tuberculosisinfection. Overall, this study presents a superiorex vivomulticellular bovine pulmosphere TB model, with implications for discovering disease biomarkers, enabling high-throughput drug screening, and improving TB control strategies.
CtBP2 triggers CCN1-induced metastatic dissemination of osteosarcoma cells in a non-hypoxic microenvironment
Authors: Patria Laura Di , Habel Nadia , Olaso Robert , Stefanovska Bojana , Fromigue Olivia 
Published: December 2023

AbstractOsteosarcoma is the most prevalent pediatric solid bone tumor. These tumors are highly metastatic and frequently develop resistance to chemotherapy, leading to poor survival rate for patients. We found that C-terminal Binding Protein 2 (CtBP2) and Cysteine-rich protein 61 (CYR61/CCN1) expression level correlated positively in a panel of cell lines.In silicoanalysis of protein-protein interaction network revealed a link with stemness markers. We confirmed that CtBP2 influences stemness markers expression, cell clonogenicity, cell migration, matrix metalloproteinase activity and cell invasion. Surprisingly, using syngeneic tumor cells graft models, while induction of CtBP2 expression correlated with the metastatic dissemination process, it occurred only at the invasive front. Hypoxic conditions in central tumor region interfered with CtBP2 induction. Globally, we identify for the first time that CtBP2 is a required inducing factor in the CYR61-related metastatic progression of osteosarcoma. Moreover, we demonstrate that while CtBP2 is a downstream transcriptional target of CYR61 signaling cascade, it occurs only under non-hypoxic conditions. The present study suggests that CtBP2 may represent a potential pivotal target for therapeutic management of metastases spreading in osteosarcoma.
The interacting effects of climate and land-use/land-cover changes on ecological communities
Authors: Thompson Kimberly L. , Chase Jonathan M. , Remelgado Ruben , Meyer Carsten 
Published: December 2023

AbstractHuman activities continue to create land-use/land-cover (LULC) change across the Earth’s surface, and together with climate change, are major drivers of changes in biodiversity through time. However, the impacts of these spatiotemporally variable drivers on biodiversity change can be complex. We examined the effects of interactions between climate and LULC change on bird communities across the continental United States over nearly three decades. We analyzed temperature and precipitation data alongside data on tree-canopy, cropland, urban, and surface-water cover to understand how climate/LULC-change interactions influence species richness and abundance. Our results revealed stable or increasing trends in species richness, but a decline in overall abundance primarily from common species and a consequent increase in aspects of evenness of communities. We found that areas experiencing warming and drying climates exhibited increased species richness and slower declines in abundance. However, impacts of LULC change had contrasting effects on richness and abundance. Areas that experienced increasing tree-canopy cover over time had increasing trends in species richness, but exacerbated declines in abundance. On the other hand, areas with increasing cropland had moderated abundance declines, but more declining trends in richness. Finally, we found that the effects of climate/LULC-change interactions varied across the range of each pressure. While some interactions support a dominant role of climate change in structuring communities, others indicate that LULC change can mitigate or exacerbate the impact of climate change on biodiversity. Overall, our results highlight the importance of considering the direction and magnitude of each driver when assessing how climate and LULC interactions shape ecological communities.
Heterogeneous lineage-specific arginine deiminase expression within dental microbiome species
Authors: Mann Allison E. , Chakraborty Brinta , O’Connell Lauren M. , Nascimento Marcelle M. , Burne Robert A. , Richards Vincent P. 
Published: December 2023

ABSTRACTArginine catabolism by the bacterial arginine deiminase system (ADS) has anticariogenic properties through the production of ammonia, which modulates the pH of the oral environment. Given the potential protective capacity of the ADS pathway, the exploitation of ADS competent oral microbes through pre- or probiotic applications is a promising therapeutic target to prevent tooth decay. To date, most investigations of the ADS in the oral cavity and its relation to caries have focused on indirect measures of activity, or on specific bacterial groups, yet the pervasiveness and rate of expression of the ADS operon in diverse mixed microbial communities in oral health and disease remains an open question. Here we use a multivariate approach, combining ultra-deep metatranscriptomic sequencing with paired metataxonomic andin vitrocitrulline quantification to characterize the microbial community and ADS operon expression in healthy and late-stage cavitated teeth. While ADS activity is higher in healthy teeth, we identify multiple bacterial lineages with upregulated ADS activity on cavitated teeth that are distinct from those found on healthy teeth using both reference-based mapping anddenovoassembly methods. Our dual metataxonomic and metatranscriptomic approach demonstrates the importance of species abundance for gene expression data interpretation and that patterns of differential expression can be skewed by low abundance groups. Finally, we identify several potential candidate probiotic bacterial lineages within species that may be useful therapeutic targets for the prevention of tooth decay and propose that the development of a strain-specific, mixed-microbial probiotic may be a beneficial approach given the heterogeneity of taxa identified here across health groups.IMPORTANCETooth decay is the most common preventable chronic disease, globally affecting more than two billion people. The development of caries on teeth is primarily a consequence of acid production by cariogenic bacteria that inhabit the plaque microbiome. Other bacterial strains in the oral cavity may suppress or prevent tooth decay by producing ammonia as a byproduct of the arginine deiminase metabolic pathway, increasing the pH of the plaque biofilm. While the benefits of arginine metabolism on oral health have been extensively documented in specific bacterial groups, the prevalence and consistency of ADS activity among oral bacteria in a community context remains an open question. In the current study, we use a multi-omics approach to document the pervasiveness of expression of the ADS operon in both health and disease to better understand the conditions in which ADS activity may prevent tooth decay.
Neurophysiological correlates of short-term recognition of sounds: Insights from magnetoencephalography
Authors: Serra E. , Lumaca M. , Brattico E. , Vuust P. , Kringelbach M. L. , Bonetti L. 
Published: December 2023

AbstractUnderstanding the brain’s dynamic retrieval and updating of encoded information is a key focus in memory research. This study employed a same versus different auditory paradigm to investigate short-term auditory recognition within a predictive coding (PC) framework, concerning the perceptual interplay between experience-informed predictions and incoming sensory information. Using magnetoencephalography (MEG), we captured the neurophysiological correlates associated with a single-sound, short-term memory task. Twenty-six healthy participants were tasked with recognizing whether presented sounds were same or different compared to strings of standard stimuli. To prompt conscious memory retention, a white noise interlude separated these sounds from the standards. MEG sensor-level results revealed that recognition of same sounds elicited two significantly stronger negative components of the event-related field compared to different sounds. The first one was the N1, peaking 100ms post-sound onset, while the second one corresponded to a slower negative component arising between 300 and 600ms after sound onset. This effect was observed in several significant clusters of MEG sensors, especially temporal and parietal regions of the scalp. Conversely, different sounds produced scattered and smaller clusters of stronger activity than same sounds, peaking later than 600ms after sound onset. Source reconstruction using beamforming algorithms revealed the involvement of auditory cortices, hippocampus, and cingulate gyrus in both conditions. Overall, the results are coherent with PC principles and previous results on the brain mechanisms underlying auditory recognition, highlighting the relevance of early and later negative brain responses for successful prediction of previously listened sounds in the context of conscious short-term memory.
Paternally-induced environmental programming of placenta development, offspring birth weight and health phenotypes in a mouse model
Authors: Chen Elaine , da Cruz Raquel Santana , Nascimento Aallya , Joshi Meghali , Pereira Duane Gischewski , Dominguez Odalys , Fernandes Gabriela , Smith Megan , Paiva Sara P.C. , de Assis Sonia 
Published: December 2023

AbstractMounting evidence suggests that environmentally induced epigenetic inheritance occurs in mammals and that traits in the progeny can be shaped by parental environmental experiences. Epidemiological studies link parental exposure to environmental toxicants, such as the pesticide DDT, to health phenotypes in the progeny, including low birth and increased risk of chronic diseases later in life. Here, we show that the progeny of male mice exposed to DDT in the pre-conception period are born smaller and exhibit sexual dimorphism in metabolic function, with male offspring developing both glucose intolerance and insulin resistance compared to controls. These phenotypes in DDT offspring were linked to reduced fetal growth and placenta size as well as placenta-specific reduction of glycogen levels and the nutrient sensor and epigenetic regulator OGT, with more pronounced phenotypes observed in male placentas. However, placenta-specific genetic reduction of OGT only partially replicates the metabolic phenotype observed in offspring of DDT-exposed males. Our findings reveal a role for paternal pre-conception environmental experiences in shaping placenta development and in fetal growth restriction. While many questions remain, our data raise the tantalizing possibility that placenta programming could be a mediator of environmentally induced intergenerational epigenetic inheritance of phenotypes and needs to be further evaluated.
Large Quantities of Bacterial DNA and Protein in Common Dietary Protein Source Used in Microbiome Studies
Authors: Bartlett Alexandria , Blakeley-Ruiz J. Alfredo , Richie Tanner , Theriot Casey M. , Kleiner Manuel 
Published: December 2023

AbstractDiet has been shown to greatly impact the intestinal microbiota. To understand the role of individual dietary components, defined diets with purified components are frequently used in diet-microbiota studies. Many of the frequently used defined diets use purified casein as the protein source. Previous work indicated that this casein contains microbial DNA potentially impacting results of microbiome studies. Other diet-based microbially derived molecules that may impact microbiome measurements, such as proteins detected by metaproteomics, have not been determined for casein. Additionally, other protein sources used in microbiome studies have not been characterized for their microbial content. We used metagenomics and metaproteomics to identify and quantify microbial DNA and protein in a casein-based defined diet to better understand potential impacts on metagenomic and metaproteomic microbiome studies. We further tested six additional defined diets with purified protein sources with an integrated metagenomic-metaproteomic approach and show that contaminating microbial protein is unique to casein within the tested set as microbial protein was not identified in diets with other protein sources. We also illustrate the contribution of diet-derived microbial protein in diet-microbiota studies by metaproteomic analysis of stool samples from germ-free mice (GF) and mice with a conventional microbiota (CV) following consumption of diets with casein and non-casein protein. This study highlights a potentially confounding factor in diet-microbiota studies that must be considered through evaluation of the diet itself within a given study.ImportanceMany diets used in diet-microbiota studies use casein as the source of dietary protein. We found large quantities of microbial DNA and protein in casein-based diets. This microbial DNA and protein are resilient to digestion as it is present in fecal samples of mice consuming casein-based diets. This contribution of diet-derived microbial DNA and protein to microbiota measurements may influence results and conclusions and must therefore be considered in diet-microbiota studies. We tested additional dietary protein sources and did not detect microbial DNA or protein. Our findings highlight the necessity of evaluating diet samples in diet-microbiota studies to ensure that potential microbial content of the diet can be accounted for in microbiome measurements.
Physical constraints during Snowball Earth drive the evolution of multicellularity
Authors: Crockett William W. , Shaw Jack O. , Simpson Carl , Kempes Christopher P. 
Published: December 2023

AbstractMolecular and fossil evidence suggest that complex eukaryotic multicellularity evolved during the late Neoproterozoic era, coincident with Snowball Earth glaciations, where ice sheets covered most of the globe. During this period, environmental conditions—such as sea water temperature and the availability of photosynthetically active light in the oceans—likely changed dramatically. Such changes would have had significant effects on both resource availability and optimal phenotypes. Here, we construct and apply mechanistic models to explore (i) how environmental changes during Snowball Earth and biophysical constraints generated selective pressures and (ii) how these pressures may have had differential effects on organisms with different forms of biological organization. By testing a series of alternate—and commonly debated—hypotheses, we demonstrate how multicellularity was likely acquired differently in eukaryotes and prokaryotes due to selective differences in the biophysical and metabolic regimes they experience: decreasing temperatures and resource-availability instigated by the onset of glaciations generated selective pressures towards smaller sizes in organisms in a diffusive regime and towards larger sizes in motile heterotrophs. These results suggest that changing environmental conditions during Snowball Earth glaciations gave multicellular eukaryotes an evolutionary advantage, paving the way for the complex multicellular lineages that followed.
A chloroplast sulfate transporter modulates glutathione-mediated redox cycling to regulate cell division
Authors: Huang Pin-jui , Chen Chun-Han , Lin Yen-Ling , Lin Hsiang-Yin , Fang Su-Chiung 
Published: December 2023

AbstractGlutathione redox cycling is important for cell cycle regulation. However, the underlying mechanisms remain unclear. We previously identified a cell-size mutant,suppressor of mat3 15-1(smt15-1), that has elevated cellular glutathione, increased number of cell divisions, and small daughter cells. Here, we demonstrated that SMT15 is a chloroplast-associated membrane protein that is capable of transporting sulfate. Reducing expression ofγ-GLUTAMYLCYSTEINE SYNTHETASE, which encodes the rate-limiting enzyme required for glutathione biosynthesis, corrected the size defect ofsmt15-1cells. Moreover, overexpressingGLUTATHIONE SYNTHETASErecapitulated the small-size phenotype ofsmt15-1mutant, confirming the role of glutathione in modulation of the cell division. Hence, SMT15 may regulate chloroplast sulfate concentration to modulate cellular glutathione levels. Interestingly, glutathione was found to accumulate in the cytosol at the G1 phase and its level decreased substantially as cells entered the S/M phase in wild-type cells. Even though cytosolic glutathione of the small-sized mutants,smt15-1andGSH2overexpressors, followed the pattern of wild-type cells being accumulated at G1 and declined at the S/M phase, the basal body-specific accumulation of glutathione was associated with only the small-sized mutants. Therefore, we propose that glutathione-mediated redox in the basal bodies may regulate mitotic division number inChlamydomonas reinhardtii. Our results support the link between glutathione-mediated redox regulation and mitotic cell division and suggest a new mechanism through which glutathione regulates the cell cycle.One sentence summaryGlutathione-mediated redox regulation in basal bodies is important for cell division control
Revisitingbicoidfunction: complete inactivation reveals an additional fundamental role inDrosophilaegg geometry specification
Authors: Baumgartner Stefan 
Published: December 2023

AbstractIntroductionThebicoid(bcd) gene inDrosophilahas served as a paradigm for a morphogen in textbooks for decades. Discovered in 1986 as a mutation affecting anterior development in the embryo, its expression pattern as a protein gradient later confirmed the prediction from transplantation experiments. These experiments suggested that the protein fulfills the criteria of a true morphogen, with the existence of a homeodomain crucial for activation of genes along the anterior-posterior axis, based on the concentration of the morphogen. Thebcdgene undergoes alternative splicing, resulting in, among other isoforms, a small and often neglected isoform with low abundance, which lacks the homeodomain, termedsmall bicoid(smbcd). Most importantly, all known classical strongbcdalleles used in the past to determinebcdfunction apparently do not affect the function of this isoform.ResultsTo overcome the uncertainty regarding which isoform regulates what, I removed thebcdlocus entirely using CRISPR technology.bcdCRISPReggs exhibited a short and round appearance. The phenotype could be ascribed tosmbcdbecause allbcdalleles affecting the function of the major transcript, termedlarge bicoid(lgbcd) showed normally sized eggs. Several patterning genes for the embryo showed expression in the oocyte, and their expression patterns were altered inbcdCRISPRoocytes. InbcdCRISPRembryos, all downstream segmentation genes showed altered expression patterns, consistent with the expression patterns in “classical” alleles; however, due to the altered egg geometry resulting in fewer blastoderm nuclei, additional constraints came into play, further affecting their expression patterns.ConclusionsThis study unveils a novel and fundamental role ofbcdin shaping the egg’s geometry. This discovery demands a comprehensive revision of our understanding of this important patterning gene and prompts a reevaluation of past experiments conducted under the assumption thatbcdmutants werebcdnull-mutants.