bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proportional intracranial volume correction differentially biases behavioral predictions across neuroanatomical features and populations
Authors: Dhamala Elvisha , Rong Ooi Leon Qi , Chen Jianzhong , Kong Ru , Anderson Kevin M. , Chin Rowena , Yeo B.T. Thomas , Holmes Avram J. 
Published: March 2022

AbstractIndividual differences in brain anatomy can be used to predict variability in cognitive function. Most studies to date have focused on broad population-level trends, but the extent to which the observed predictive features are shared across sexes and age groups remains to be established. While it is standard practice to account for intracranial volume (ICV) using proportion correction in both regional and whole-brain morphometric analyses, in the context of brain-behavior predictions the possible differential impact of ICV correction on anatomical features and subgroups within the population has yet to be systematically investigated. In this work, we evaluate the effect of proportional ICV correction on sex-independent and sex-specific predictive models of individual cognitive abilities across multiple anatomical properties (surface area, gray matter volume, and cortical thickness) in healthy young adults (Human Connectome Project; n=1013, 548 females) and typically developing children (Adolescent Brain Cognitive Development study; n=1823, 979 females). We demonstrate that ICV correction generally reduces predictive accuracies derived from surface area and gray matter volume, while increasing predictive accuracies based on cortical thickness in both adults and children. Furthermore, the extent to which predictive models generalize across sexes and age groups depends on ICV correction: models based on surface area and gray matter volume are more generalizable without ICV correction, while models based on cortical thickness are more generalizable with ICV correction. Finally, the observed neuroanatomical features predictive of cognitive abilities are unique across age groups regardless of ICV correction, but whether they are shared or unique across sexes (within age groups) depends on ICV correction. These findings highlight the importance of considering individual differences in ICV, and show that proportional ICV correction does not remove the effects of cranium volumes from anatomical measurements and can introduce ICV bias where previously there was none. ICV correction choices affect not just the strength of the relationships captured, but also the conclusions drawn regarding the neuroanatomical features that underlie those relationships.
SLC15A4 favors inflammasome function via mTORC1 signaling and autophagy restraint in dendritic cells
Authors: López-Haber Cynthia , Hutchins Zachary , Ma Xianghui , Hamilton Kathryn E. , Mantegazza Adriana R. 
Published: March 2022

AbstractPhagocytosis is the first step in the assessment of foreign microbes or particles and enables activation of innate immune pathways such as the inflammasome. However, missing links between phagosomes and inflammasomes remain to be discovered. We show that in murine dendritic cells (DCs) the lysosomal histidine/peptide solute carrier transporter SLC15A4, associated with human inflammatory disorders, is recruited to phagosomes and is required for optimal inflammasome activity after infectious or sterile stimuli. Dextran sodium sulphate-treated SLC15A4-deficient mice exhibit decreased colon inflammation, reduced IL-1β production by intestinal DCs and increased autophagy. Similarly, SLC15A4-deficient DCs infected withSalmonellatyphimurium show reduced caspase-1 cleavage and IL-1β production. This correlates with peripheral NLRC4 inflammasome assembly and increased autophagy. Overexpression of constitutively active mTORC1 rescues decreased IL-1β levels and caspase-1 cleavage, and restores perinuclear inflammasome positioning. Our findings suggest that SLC15A4 is a novel link that couples phagocytosis with inflammasome perinuclear assembly and inhibition of autophagy through phagosomal content sensing. Our data also reveal the previously unappreciated importance of mTORC1 signaling pathways to promote and sustain inflammasome activity.
Optogenetic stimulation of medial septal glutamatergic neurons modulates theta-gamma coupling in the hippocampus
Authors: Dmitrieva Elena , Malkov Anton 
Published: March 2022

AbstractThe oscillatory activity of the hippocampus and parahippocampal structures encodes information during cognition. Multiple researchers emphasize hippocampal cross-frequency theta-gamma coupling (TGC) as a basic mechanism for information processing, retrieval, and consolidation of long-term and working memory. While the role of entorhinal afferents in the modulation of hippocampal TGC is widely accepted, the influence of other main input to the hippocampus, from the medial septal area (MSA, the pacemaker of the hippocampal theta rhythm) is poorly understood. This area innervates multiple targets in the hippocampus, so information about the participation of MSA in cross-frequency interactions might be critical for an understanding of neural coding.Optogenetics allows us to explore how different neuronal populations of septohippocampal circuits control neuronal oscillations in vivo. It was shown that optogenetic activation of glutamatergic projections to the hippocampus with theta-frequency stimuli paces the hippocampal theta rhythm. Here we investigated the influence of phasic activation of MSA glutamatergic neurons expressing channelrhodopsin II on theta-gamma coupling in the hippocampus. Transgenic mice B6.Cg-Tg (Thy1-COP4/EYFP)18Gfng/J were used in this experiment. Expression of ChRII in MSA was verified immunohistochemically and the optic fibers just above MSA and the recording electrodes in the CA1 hippocampal field were implanted. During the experiment, local field potentials of MSA and hippocampus of freely behaving mice were modulated by 470nm light flashes with theta frequency (2-10) Hz.It was shown that both the power and the strength of modulation of gamma rhythm nested on hippocampal theta waves depend on the frequency of stimulation. The modulation of the amplitude of slow gamma rhythm (30-50 Hz) prevailed over modulation of fast gamma (55-100 Hz) during flash trains and the observed effects were specific for theta stimulation of MSA. We discuss the possibility that phasic depolarization of septal glutamatergic neurons controls theta-gamma coupling in the hippocampus and plays a role in memory retrieval and consolidation.
Targeted deletion of uterine glandular Foxa2 induces embryonic diapause in mice
Authors: Matsuo Mitsunori , Yuan Jia , Kim Yeon Sun , Dewar Amanda , Fujita Hidetoshi , Dey Sudhansu K. , Sun Xiaofei 
Published: March 2022

AbstractEmbryonic diapause is a reproductive strategy in which embryo development and growth is temporarily arrested within the uterus to ensure the survival of neonates and mothers during unfavorable conditions. Pregnancy is reinitiated when conditions become favorable for neonatal survival. The mechanism of how the uterus enters diapause remains unclear. Mice with uterine deletion of Foxa2, a transcription factor, are infertile. In this study, we show that dormant blastocysts are recovered from these mice on day 8 of pregnancy with persistent uterine Msx1 expression, a gene critical to maintaining the uterine quiescent state, suggesting that these mice enter embryonic diapause. Leukemia inhibitory factor (LIF) can resume implantation in these mice. Although estrogen is critical for implantation in progesterone (P4)-primed uterus, our current model reveals that FOXA2-independent estrogenic effects are detrimental to sustaining uterine quiescence. Interestingly, P4 and anti-estrogen can prolong uterine quiescence in the absence of FOXA2. While we find that Msx1 expression persists in the uterus deficient in Foxa2, the complex relationship of FOXA2 with Msx genes and estrogen receptors remains to be explored.
Developmental phenomics suggests that H3K4 monomethylation catalyzed by Trr functions as a phenotypic capacitor
Authors: Gandara Lautaro , Tsai Albert , Ekelöf Mans , Galupa Rafael , Noon Ella Preger-Ben , Alexandrov Theodore , Crocker Justin 
Published: March 2022

AbstractHow epigenetic modulators of gene regulation affect the development and evolution of animals has been difficult to ascertain. Despite the widespread presence of histone 3 lysine 4 monomethylation (H3K4me1) on enhancers, hypomethylation appears to have minor effects on animal development and viability. In this study, we performed quantitative, unbiased and multi-dimensional explorations of key phenotypes on Drosophila melanogaster with genetically induced hypomethylation. Hypomethylation reduced transcription factor enrichment in nuclear microenvironments, leading to reduced gene expression, and phenotypes outside of standard laboratory conditions. Our developmental phenomics survey further showed that H3K4me1 hypomethylation led to context-dependent changes in morphology, metabolism, and behavior. Therefore, H3K4me1 may contribute to phenotypic evolution as a phenotypic capacitor by buffering the effects of chance, genotypes and environmental conditions on transcriptional enhancers.Quote“Developmental biologists are often not so much opposed to a role for ecology as they simply ignore it” –Doug Erwin1
A conserved immune trajectory of recovery in hospitalized COVID-19 patients
Authors: Burnett Cassandra E. , Hauge Okholm Trine Line , Tenvooren Iliana , Marquez Diana M. , Tamaki Stanley , Sandoval Priscila Munoz ,   The UCSF COMET Consortium, Calfee Carolyn S. , Hendrickson Carolyn M. , Kangelaris Kirsten N. , Langelier Charles R. , Krummel Matthew F. , Woodruff Prescott G. , Erle David J. , Ansel K. Mark , Spitzer Matthew H. 
Published: March 2022

AbstractMany studies have provided insights into the immune response to COVID-19; however, little is known about the immunological changes and immune signaling occurring during COVID-19 resolution. Individual heterogeneity and variable disease resolution timelines obscure unifying immune characteristics. Here, we collected and profiled >200 longitudinal peripheral blood samples from patients hospitalized with COVID-19, with other respiratory infections, and healthy individuals, using mass cytometry to measure immune cells and signaling states at single cell resolution. COVID-19 patients showed a unique immune composition and an early, coordinated and elevated immune cell signaling profile, which correlated with early hospital discharge. Intra-patient time course analysis tied to clinically relevant events of recovery revealed a conserved set of immunological processes that accompany, and are unique to, disease resolution and discharge. This immunological process, together with additional changes in CD4 regulatory T cells and basophils, accompanies recovery from respiratory failure and is associated with better clinical outcomes at the time of admission. Our work elucidates the biological timeline of immune recovery from COVID-19 and provides insights into the fundamental processes of COVID-19 resolution in hospitalized patients.
Increases in vein length compensate for leaf area lost to lobing in grapevine
Authors: Migicovsky Zoë , Swift Joel F. , Helget Zachary , Klein Laura L. , Ly Anh , Maimaitiyiming Matthew , Woodhouse Karoline , Fennell Anne , Kwasniewski Misha , Miller Allison J. , Cousins Peter , Chitwood Daniel H. 
Published: March 2022

AbstractPremiseThere is considerable variation in leaf lobing and leaf size, including among grapevines, some of the most well-studied leaves. We examined the relationship between leaf lobing and leaf size across grapevine populations which varied in extent of leaf lobing.MethodsWe used homologous landmarking techniques to measure 2,632 leaves across two years in 476 unique, genetically distinct grapevines from 5 biparental crosses which vary primarily in the extent of lobing. We determined to what extent leaf area could explain variation in lobing, vein length, and vein to blade ratio.ResultsAlthough lobing was the primary source of variation in shape across the leaves we measured, leaf area varied only slightly as a function of lobing. Rather, leaf area increases as a function of total major vein length, total branching vein length, and decreases as a function of vein to blade ratio. These relationships are stronger for more highly lobed leaves, with the residuals for each model differing as a function of distal lobing.ConclusionsFor a given leaf area, more highly lobed leaves have longer veins and higher vein to blade ratios, allowing them to maintain similar leaf areas despite increased lobing. These findings show how more highly lobed leaves may compensate for what would otherwise result in a reduced leaf area, allowing for increased photosynthetic capacity through similar leaf size.
MiXcan: a Framework for Cell-Type-Specific Transcriptome-Wide Association Studies with an Application to Breast Cancer
Authors: Song Xiaoyu , Ji Jiayi , Rothstein Joseph H. , Alexeeff Stacey E. , Sakoda Lori C. , Sistig Adriana , Achacoso Ninah , Jorgenson Eric , Whittemore Alice S. , Klein Robert J. , Habel Laurel A. , Wang Pei , Sieh Weiva 
Published: March 2022

AbstractHuman bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study (TWAS) approaches predict gene expression at the tissue level from genotype data, without considering cell-type heterogeneity, and test associations of the predicted tissue-level gene expression with disease. Here we develop MiXcan, a new TWAS approach that predicts cell-type-specific gene expression levels, identifies disease-associated genes via combination of cell-type-specific association signals for multiple cell types, and provides insight into the disease-critical cell type. We conducted the first cell-type-specific TWAS of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared with only eight genes using conventional approaches. Importantly, MiXcan identified genes with distinct associations in mammary epithelial versus stromal cells, including three new breast cancer susceptibility genes. These findings demonstrate that cell-type-specific TWAS can reveal new insights into the genetic and cellular etiology of breast cancer and other diseases.
Is virulence phenotype evolution driven exclusively by Lr gene deployment in French Puccinia triticina populations?
Authors: Fontyn Cécilia , Zippert Anne-Catherine , Delestre Ghislain , Marcel Thierry C , Suffert Frédéric , Goyeau Henriette 
Published: March 2022

AbstractPuccinia triticina is a highly damaging wheat pathogen. The efficacy of leaf rust control by genetic resistance is mitigated by the adaptive capacity of the pathogen, expressed as changes in its virulence combinations (pathotypes). An extensive P. triticina population survey has been carried out in France over the last 30 years, describing the evolution dynamics of this pathogen in response to cultivar deployment. We analyzed the dataset for the 2006-2016 period to determine the relationship between the Lr genes in the cultivars and virulence in the pathotypes. Rust populations were dominated by a small number of pathotypes, with variations in most of the virulence frequencies related to the corresponding Lr gene frequencies in the cultivated landscape. Furthermore, the emergence and spread of a new virulence matched the introduction and use of the corresponding Lr gene (Lr28), confirming that the deployment of qualitative resistance genes is an essential driver of evolution in P. triticina populations. However, PCA revealed that certain pathotype-cultivar associations cannot be explained solely by the distribution of Lr genes in the landscape. This conclusion is supported by the predominance of a few pathotypes on some cultivars, with the persistence of several other compatible pathotypes at low frequencies. Specific interactions are not, therefore, sufficient to explain the distribution of virulence in rust populations. Our findings suggest that aggressiveness is a driver of changes in pathotype frequencies. Accordingly, the hypothesis of “dual selection”, based on both qualitative and quantitative interactions between P. triticina populations and bread wheat cultivars, is favored.
Genetic interaction analysis reveals that Cryptococcus neoformans utilizes multiple acetyl-CoA-generating pathways during infection
Authors: Alden Katy M. , Jezewski Andrew J. , Beattie Sarah R. , Fox David , Krysan Damian J. 
Published: March 2022

AbstractCryptococcus neoformans is an important human fungal pathogen for which the external environment is its primary niche. To cause infection and disease, C. neoformans must adapt to a plethora of conditions and stresses inherent to the host environment. Of these stresses, the role of central carbon metabolism has been of interest not only at the level of fundamental pathobiology but also as a potential target for new antifungal drug therapy. Previous work has shown that two non-essential acetyl-CoA metabolism enzymes, ATP-citrate lyase (ACL1) and acetyl-CoA synthetase (ACS1), play important roles in C. neoformans infection. Here, we took a genetic interaction approach to studying the interplay between these two enzymes along with an enzyme initially called ACS2 but which we have found is an acetoacetyl-CoA synthetase; we have renamed the gene 2-ketobutyryl CoA synthetase 1 (KBC1) based on its biochemical activity and the systematic name of its substrate. ACL1 and ACS1 represent a synthetic lethal pair of genes based on our genetic interaction studies. Double mutants of KBC1 with either ACS1 or ACL1 do not have significant synthetic phenotypes in vitro, although we find that deletion of any one of these enzymes reduces fitness within macrophages. Importantly, the acs1Δ kbc1Δ double mutant has significantly reduced fitness in the CNS relative to either single mutant as well as WT (~2 log10 CFU reduction in fungal burden), indicating the important role these enzymes play during infection. The expression of both ACS1 and KBC1 is increased in vivo relative to in vitro conditions. The acs1Δ mutant is hypersusceptible to fluconazole in vivo despite its minimal in vitro phenotypes. These data not only provide insights into the in vivo mechanism of action for a new class of antifungal Acs inhibitors but also into metabolic adaptations of C. neoformans to the host environment.Author SummaryThe adaptation of environmental fungal pathogens to the mammalian host is critical to pathogenesis. Of these adaptations, the remodeling of carbon metabolism is particularly important. Here, we generated a focused set of double mutants of non-essential genes (ACL1, ACS1, KBC1) involved in acetyl-CoA metabolism and examined their fitness in vitro and during CNS infection. From these studies, we found that all three enzymes play important roles during infection but that the role of ACS1/KBC1 was minimal in vitro. Consistent with these observations, the expression of ACS1 and KBC1 was increased in vivo relative to standard in vitro conditions. Furthermore, strains lacking both ACL1 and ACS1 were not viable. These data clearly show that C. neoformans employs multiple carbon metabolism pathways to adapt to the host environment. They also provide insights into the potential mechanism of action for anti-cryptococcal Acs inhibitors.
PeroxiHUB: a modular cell-free biosensing platform using H2O2 as signal integrator
Authors: Soudier Paul , Duigou Thomas , Voyvodic Peter L. , Zúñiga Ana , Bazi-Kabbaj Kenza , Kushwaha Manish , Bonnet Jerome , Faulon Jean-Loup 
Published: March 2022

ABSTRACTCell-free systems have great potential for delivering robust, cheap, and field-deployable biosensors. Many cell-free biosensors rely on transcription factors responding to small molecules, but their discovery and implementation still remain challenging. Here we report the engineering of PeroxiHUB, an optimized H2O2-centered sensing platform supporting cell-free detection of different metabolites. H2O2 is a central metabolite and a by-product of numerous enzymatic reactions. PeroxiHUB uses enzymatic transducers to convert metabolites of interest into H2O2, enabling rapid reprogramming of sensor specificity using alternative transducers. We first screen several transcription factors and optimize OxyR for the transcriptional response to H2O2 in cell-free, highlighting the need for pre-incubation steps to obtain suitable signal-to-noise ratios. We then demonstrate modular detection of metabolites of clinical interest – lactate, sarcosine, and choline – using different transducers mined via a custom retro-synthesis workflow publicly available on the SynBioCAD Galaxy portal. We find that expressing the transducer during the pre-incubation step is crucial for optimal sensor operation. Finally, we show that different reporters can be connected to PeroxiHUB, providing high adaptability for various applications. Given the wide range of enzymatic reactions producing H2O2, the PeroxiHUB platform will support cell-free detection of a large number of metabolites in a modular and scalable fashion.
Robots at your service: value facilitation and value co-creation in restaurants
Authors: Zhang Xiya , Balaji M.S. , Jiang Yangyang 
Published: March 2022

Purpose
This paper aims to understand the process of guest-robot value co-creation in the restaurant context. It empirically examines the guest perception of value facilitation by service robots and its impact on guest value co-creation and advocacy intentions. It also investigates the moderating role of interaction comfort in the relationship between service robot value facilitation and guest value co-creation.

Design/methodology/approach
A mixed-methods approach was adopted. Ten customers who had dined at a service robot restaurant in China were interviewed in the qualitative study, followed by a quantitative study with 252 restaurant patrons to test the relationships between service robot value facilitation, guest value co-creation, interaction comfort and advocacy intentions.

Findings
Guest perceptions of six robot attributes, including role significance, competence, social presence, warmth, autonomy and adaptability, determine service robot value facilitation. Interaction comfort moderates the influence of service robot value facilitation on guest value co-creation. Additionally, guest value co-creation mediates the effect of service robot value facilitation on advocacy intentions.

Research limitations/implications
This study offers an understanding of six robot attributes that can improve service robot value facilitation. Nevertheless, the authors collected data from guests who had experience at service robot restaurants. The authors encourage future research to use random sampling methods to ensure study representativeness.

Practical implications
This study offers strategic guidance for managers to deploy service robots in frontline roles in restaurants and provides important implications for service robot design to improve their facilitating role in the guest value co-creation process.

Originality/value
This study responds to a recent call for research on the role of service robots in the guest value co-creation experience. Unlike prior studies that focused on the adoption or acceptance of service robots, it examines the role of service robots in the value co-creation process (post-adoption stage). Furthermore, it is one of the early studies to identify and empirically examine the service robot attributes that enable value facilitation and foster value co-creation in guest-robot service encounters.