bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high soluble-fibre allele in wheat encodes a defective cell wall peroxidase responsible for dimerization of ferulate moieties on arabinoxylan
Authors: Mitchell Rowan A.C. , Oszvald Maria , Pellny Till K. , Freeman Jackie , Halsey Kirstie , Sparks Caroline A. , Huttly Alison , Specel Sebastien , Leverington-Waite Michelle , Griffiths Simon , Shewry Peter R. , Lovegrove Alison 
Published: March 2023

AbstractIncreasing dietary fibre (DF) intake is an important target to improve health and an attractive strategy for this is to increase the fibre content of staple foods, particularly white bread which is the staple food in many countries. DF in wheat white flour is derived principally from the endosperm cell wall polysaccharide arabinoxylan (AX) and the water-extractable form of this (WE-AX) accounts for the majority of soluble dietary fibre (SDF), which is believed to confer particular health benefits. We previously identified QTLs for soluble dietary fibre (SDF) on 1B and 6B chromosomes in wheat in biparental populations. Here we show that the 6B high SDF allele encodes a peroxidase protein (PER1-v) with a single missense compared to the more common low SDF form (PER1). Wheat lines with the natural PER1-v allele and with an induced knock-out mutation in PER1 showed similar characteristics of reduced dimerization of ferulate associated with water-extractable WE-AX. Decreased ferulate dimerization is associated with decreased cross-linking of the WE-AX chains and increased solubility of AX. Transiently expressed PER1_RFP fusion driven by native promoter in wheat endosperm was shown to localise to cell walls whereas PER1-v_RFP did not; we therefore propose that PER1-v lacks capacity to dimerise AX ferulatein vivodue to mis-localisation. PER1 is the first peroxidase reported to be responsible for oxidative coupling of ferulate on AX, a key process in all grass cell walls. Understanding its role and the effect of variants on AX properties offers a route to control the properties of wheat DF in the human diet.
Abnormal enteric nervous system and motor activity in the ganglionic proximal bowel of Hirschsprung’s disease
Authors: Edwards Brian S. , Stiglitz Emma S. , Davis Brian M. , Smith-Edwards Kristen M. 
Published: March 2023

ABSTRACTHirschsprung’s disease (HSCR) is a congenital defect in which the enteric nervous system (ENS) does not develop in the distal bowel, requiring surgical removal of the portions of bowel without ENS ganglia (‘aganglionic’) and reattachment of the ‘normal’ proximal bowel with ENS ganglia. Unfortunately, many HSCR patients have persistent dysmotility (e.g., constipation, incontinence) and enterocolitis after surgery, suggesting that the remaining bowel is not normal despite having ENS ganglia. Anatomical and neurochemical alterations have been observed in the ENS-innervated proximal bowel from HSCR patients and mice, but no studies have recorded ENS activity to define the circuit mechanisms underlying post-surgical HSCR dysfunction. Here, we generated a HSCR mouse model with a genetically-encoded calcium indicator to map the ENS connectome in the proximal colon. We identified abnormal spontaneous and synaptic ENS activity in proximal colons from GCaMP-Ednrb-/-mice with HSCR that corresponded to motor dysfunction. Many HSCR-associated defects were also observed in GCaMP-Ednrb+/-mice, despite complete ENS innervation. Results suggest that functional abnormalities in the ENS-innervated bowel contribute to post-surgical bowel complications in HSCR patients, and HSCR-related mutations that do not cause aganglionosis may cause chronic colon dysfunction in patients without a HSCR diagnosis.
Predatory fireflies and their toxic firefly prey have evolved distinct toxin resistance strategies
Authors: Yang Lu , Borne Flora , Betz Anja , Aardema Matthew L. , Zhen Ying , Peng Julie , Visconti Regina , Wu Mariana , Roland Bartholomew P. , Talsma Aaron D. , Palladino Mike J. , Petschenka Georg , Andolfatto Peter 
Published: March 2023

SummaryToxic cardiotonic steroids (CTS) act as a defense mechanism in many firefly species (Lampyridae) by inhibiting a crucial enzyme called Na+,K+-ATPase (NKA). While most fireflies produce these toxins internally, species of the genusPhoturisacquire them from a surprising source: predation on other fireflies. The contrasting physiology of toxin exposure and sequestration betweenPhoturisand other firefly genera suggests that distinct strategies may be required to prevent self-intoxication. Our study demonstrates that bothPhoturisand their firefly prey have evolved highly-resistant NKAs. Using an evolutionary analysis of the specific target of CTS (ATPα) in fireflies, and gene-editing inDrosophila, we find that the initial steps towards resistance were shared amongPhoturisand other firefly lineages. However, thePhoturislineage subsequently underwent multiple rounds of gene duplication and neofunctionalization, resulting in the development of ATPα paralogs that are differentially expressed and exhibit increasing resistance to CTS. In contrast, other firefly species have maintained a single copy. Our results implicate gene duplication as a facilitator in the transition ofPhoturisto its distinct ecological role as predator of toxic firefly prey.One-Sentence SummaryGene duplication and neofunctionalization distinguish firefly predators from their toxic firefly prey.
Enthesis Maturation in Engineered Ligaments is Differentially Driven by Loads that Mimic Slow Growth Elongation and Rapid Cyclic Muscle Movement
Authors: Brown M. Ethan , Puetzer Jennifer L. 
Published: March 2023

AbstractEntheses are complex attachments that translate load between elastic-ligaments and stiff-bone via organizational and compositional gradients. Neither natural healing, repair, nor engineered replacements restore these gradients, contributing to high re-tear rates. Previously, we developed a novel culture system which guides ligament fibroblasts in high-density collagen gels to develop early postnatal-like entheses, however further maturation is needed. Mechanical cues, including slow growth elongation and cyclic muscle activity, are critical to enthesis developmentin vivobut these cues have not been widely explored in engineered entheses and their individual contribution to maturation is largely unknown. Our objective here was to investigate how slow stretch, mimicking ACL growth rates, and intermittent cyclic loading, mimicking muscle activity, individually drive enthesis maturation in our system so to shed light on the cues governing enthesis development, while further developing our engineered replacements. Interestingly, we found these loads differentially drive organizational maturation, with slow stretch driving improvements in the interface/enthesis region, and cyclic load improving the ligament region. However, despite differentially affecting organization, both loads produced improvements to interface mechanics and zonal composition. This study provides new insight into how mechanical cues differentially affect enthesis development, while producing some of the most organized engineered enthesis to date.
Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys
Authors: Lovich Stephanie N , King Cynthia D , Murphy David L.K. , Abbasi Hossein , Bruns Patrick , Shera Christopher A , Groh Jennifer 
Published: March 2023

AbstractAuditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioral tasks, subjects, and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for.
Differential universal ortholog composition ofCoffea arabicaL. sub-genomes and its contribution to regulatory networks governing essential biological processes
Authors: Ribeiro Thales Henrique Cherubino , Oliveira Raphael Ricon de , Antonio Chalfun-Junior 
Published: March 2023

AbstractThe polyploidy ofCoffea arabicais an important trait affecting the evolution of this species. Genetic variability is scarce due to its recent origin as an interspecific hybrid from a single successful crossing event betweenCoffea canephoraandCoffea eugenioidesrelatives. To further investigate the genomic composition of an allotetraploid we coupled high-throughput methodologies of co-expression analysis and full-length protein coding genes inference. Many of the expected orthologs were found to be missing from one of the two homoeologous chromosomes. The gene expression machinery is mainly represented by single-copy essential orthologs located in theCoffea eugenioidessub-genome. This result suggests a preference of the transcriptional and RNA processing machinery to be regulated by one parental sub-genome. To understand the operational modules of the sub-genomes transcription, we performed co-expression analysis that revealed 23 co-regulated modules. This system-wide approach clarified how biological processes (i.e., photosynthesis, cell wall biogenesis, translation, transcription, catabolism and biosynthesis) are running in synchrony and reinforces that there is an ongoing selective pressure inC. arabicathat constrains the number of copies of some universal orthologues. Thus, this work contributes to our understanding of genome evolution in recent polyploids and supports crop breeding programs.
Sex- and Age-dependent Skin Mechanics – A Detailed Look in Mice
Authors: Lin Chien-Yu , Sugerman Gabriella P. , Kakaletsis Sotirios , Meador William D. , Buganza Adrian T. , Rausch Manuel K. 
Published: March 2023

ABSTRACTSkin aging is of immense societal and, thus, scientific interest. Because mechanics play a critical role in skin’s function, a plethora of studies have investigated age-induced changes in skin mechanics. Nonetheless, much remains to be learned about the mechanics of aging skin. This is especially true when considering sex as a biological variable. In our work, we set out to answer some of these questions using mice as a model system. Specifically, we combined mechanical testing, histology, collagen assays, and two-photon microscopy to identify age- and sex-dependent changes in skin mechanics and to relate them to structural, microstructural, and compositional factors. Our work revealed that skin stiffness, thickness, and collagen content all decreased with age and were sex dependent. Interestingly, sex differences in stiffness were age induced. We hope our findings not only further our fundamental understanding of skin aging but also highlight both age and sex as important variables when conducting studies on skin mechanics.
phytools 2.0: An updated R ecosystem for phylogenetic comparative methods (and other things)
Authors: Revell Liam J. 
Published: March 2023

ABSTRACTPhylogenetic comparative methods comprise the general endeavor of using an estimated phylogenetic tree (or set of trees) to make secondary inferences: about trait evolution, diversification dynamics, biogeography, community ecology, and a wide range of other phenomena or processes. Over the past ten years or so, thephytoolsR package (Revell 2012) has grown to become an important research tools for phylogenetic comparative analysis.phytoolsis a diverse contributed R library now consisting of hundreds of different functions covering a variety of methods and purposes in phylogenetic biology. As of the time of writing,phytoolsincluded functionality for fitting models of trait evolution, for reconstructing ancestral states, for studying diversification on trees, and for visualizing phylogenies, comparative data, and fitted models, as well numerous other tasks related to phylogenetic biology. Here, I describe some significant features of and recent updates tophytools, while also illustrating several popular workflows of thephytoolscomputational software.
Modification of social cheating facilitates the stabilization and chronic infection of polymorphicPseudomonas aeruginosapopulation
Authors: Zhao Kelei , Yang Xiting , Zeng Qianglin , Zhang Yige , Li Heyue , Li Jing Shirley , Liu Huan , Du Liangming , Wu Yi , Huang Gui , Huang Ting , Zhang Yamei , Zhou Hui , Wang Xinrong , Chu Yiwen , Zhou Xikun 
Published: March 2023

AbstractChronic infection of the common bacterial pathogenPseudomonas aeruginosafrequently leads to the coexistence of heterogeneous individuals to engage in several group behaviors. However, further evolution of the polymorphicP. aeruginosapopulation, including the dynamic change of social cooperation and its impact on host immune system, still remain elusive. We show that the evolution ofP. aeruginosain the patients with chronic obstructive pulmonary disease frequently selects the isolates deficient in producing the costly and sharable extracellular products for nutrient acquisition. The evolution of polymorphicP. aeruginosapopulation is mainly concentrated on modifying the adaptability oflasRmutants, which are typical cheaters in the competition of quorum-sensing-controlled extracellular proteases. Importantly,lasRmutants with varying degrees of evolution interact with wild-typeP. aeruginosain a framework termed cascaded public goods game to compete for extracellular proteases and siderophores, and thus perpetuate social cooperation under different conditions. Finally, we find that a polymorphic population comprised oflasR-intactP. aeruginosaand evolvedlasR-mutant can minimize the host immune fluctuation for persistent colonization. This study demonstrates the multistage evolution and complex interaction ofP. aeruginosain adaptation to host lungs, and provides an explanation for the success of cooperation in public goods game.
Characterizing the extracellular matrix transcriptome of endometriosis
Authors: Cook Carson J. , Fogg Kaitlin C. 
Published: March 2023

AbstractIn recent years, the matrisome, a set of proteins that make up the extracellular matrix (ECM) or are closely involved in ECM behavior, has been shown to have great importance for characterizing and understanding disease pathogenesis and progression. The matrisome is especially critical for examining diseases characterized by extensive tissue remodeling. Endometriosis is characterized by the extrauterine growth of endometrial tissue, making it an ideal condition to study through the lens of matrisome gene expression. While large gene expression datasets have become more available, and gene dysregulation in endometriosis has been the target of several studies, the gene expression profile of the matrisome specifically in endometriosis has not been well characterized. In our study, we explored three Gene Expression Omnibus (GEO) DNA microarray datasets containing endometriosis and healthy samples of eutopic endometrium. We established that matrisome gene expression alone can stratify healthy and endometriosis samples and identified the matrisome genes and gene networks that hold inferential significance for the onset and progression of endometriosis. Furthermore, we found that menstrual cycle phase accounted for over a third of the variance of matrisome gene expression within the samples. Taken together, these findings may aid in developing futurein vitromodels of disease and identifying novel treatment strategies for this underserved patient population.
Inhibition of muscarinic receptor signaling protects human enteric inhibitory neurons against platin chemotherapy toxicity
Authors: Richter Mikayla N , Farahvashi Sina , Samuel Ryan M , Majd Homa , Chemel Angeline K , Ramirez Jonathan T , Majd Alireza , Scantlen Megan D , Elder Nicholas , Cesiulis Andrius , Garcia Kristle , Joshi Tanvi , Keefe Matthew G , Samiakalantari Bardia , Turkalj Elena M , Yu Johnny , Arab Abolfazl , Yin Keyi , Culbertson Bruce , Vora Bianca , Xiong Chenling , Kattah Michael G , Irannejad Roshanak , Kroetz Deanna L , Nowakowski Tomasz J , Goodarzi Hani , Fattahi Faranak 
Published: March 2023

AbstractGI toxicity is a common dose-limiting adverse effect of platin chemotherapy treatment. Up to 50% of cancer survivors continue to experience symptoms of chronic constipation or diarrhea induced by their chemotherapy for many years after their treatment. This drug toxicity is largely attributed to damage to enteric neurons that innervate the GI tract and control GI motility. The mechanisms responsible for platin-induced enteric neurotoxicity and potential preventative strategies have remained unknown. Here, we use human pluripotent stem cell derived enteric neurons to establish a new model system capable of uncovering the mechanism of platin-induced enteric neuropathy. Utilizing this scalable system, we performed a high throughput screen and identified drug candidates and pathways involved in the disease. Our analyses revealed that excitotoxicity through muscarinic cholinergic signaling is a key driver of platin-induced enteric neuropathy. Using single nuclei transcriptomics and functional assays, we discovered that this disease mechanism leads to increased susceptibility of specific neuronal subtypes, including inhibitory nitrergic neurons, to platins. Histological assessment of the enteric nervous system in platin-treated patients confirmed the selective loss of nitrergic neurons. Finally, we demonstrated that pharmacological and genetic inhibition of muscarinic cholinergic signaling is sufficient to rescue enteric neurons from platin excitotoxicityin vitroand can prevent platin-induced constipation and degeneration of nitrergic neurons in mice. These studies define the mechanisms of platin-induced enteric neuropathy and serve as a framework for uncovering cell type-specific manifestations of cellular stress underlying numerous intractable peripheral neuropathies.
LRRC8A anion channels modulate vasodilation via association with Myosin Phosphatase Rho Interacting Protein (MPRIP)
Authors: Choi Hyehun , Miller Michael R. , Nguyen Hong-Ngan , Rohrbough Jeffrey C. , Koch Stephen R. , Boatwright Naoko , Yarboro Michael T. , Sah Rajan , McDonald W. Hayes , Reese J. Jeffrey , Stark Ryan J. , Lamb Fred S. 
Published: March 2023

AbstractBackgroundIn vascular smooth muscle cells (VSMCs), LRRC8A volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A physically associates with NADPH oxidase 1 (Nox1) and supports its production of extracellular superoxide (O2-•).Methods and ResultsMice lacking LRRC8A exclusively in VSMCs (Sm22α-Cre, KO) were used to assess the role of VRACs in TNFα signaling and vasomotor function. KO mesenteric vessels contracted normally to KCl and phenylephrine, but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). 48 hours ofex vivoexposure to TNFα (10ng/ml) markedly impaired dilation to ACh and SNP in WT but not KO vessels. VRAC blockade (carbenoxolone, CBX, 100 μM, 20 min) enhanced dilation of control rings and restored impaired dilation following TNFα exposure. Myogenic tone was absent in KO rings. LRRC8A immunoprecipitation followed by mass spectroscopy identified 35 proteins that interacted with LRRC8A. Pathway analysis revealed actin cytoskeletal regulation as the most closely associated function of these proteins. Among these proteins, the Myosin Phosphatase Rho-Interacting protein (MPRIP) links RhoA, MYPT1 and actin. LRRC8A-MPRIP co-localization was confirmed by confocal imaging of tagged proteins, Proximity Ligation Assays, and IP/western blots which revealed LRRC8A binding at the second Pleckstrin Homology domain of MPRIP. siLRRC8A or CBX treatment decreased RhoA activity in cultured VSMCs, and MYPT1 phosphorylation at T853 was reduced in KO mesenteries suggesting that reduced ROCK activity contributes to enhanced relaxation. MPRIP was a target of redox modification, becoming oxidized (sulfenylated) after TNFα exposure.ConclusionsInteraction of Nox1/LRRC8A with MPRIP/RhoA/MYPT1/actin may allow redox regulation of the cytoskeleton and link Nox1 activation to both inflammation and vascular contractility.
Administration of the glutamate-modulating drug riluzole after stress reverses its delayed effects on the amygdala
Authors: Datta Siddhartha , Rashid Zubin , Naskar Saptarnab , Chattarji Sumantra 
Published: March 2023

AbstractExtracellular glutamate levels are elevated across brain regions immediately after stress. Despite sharing common features in their genesis, the patterns of stress-induced plasticity that eventually take shape are strikingly different between these brain areas. While stress impairs structure and function in the hippocampus, it has the opposite effect on the amygdala. Riluzole, an FDA-approved drug known to modulate glutamate release and facilitate glutamate clearance, prevents stress-induced deficits in the hippocampus. But, whether the same drug is also effective in countering the opposite effects of stress in the amygdala remains unexplored. We addressed this question by using a rat model wherein even a single 2-hour acute immobilization stress causes a delayed build-up, 10 days later, in anxiety-like behavior, alongside stronger excitatory synaptic connectivity in the basolateral amygdala (BLA). This temporal profile – several days separating the acute stressor and its delayed impact – allowed us to test if these effects can be reversed by administering riluzole in the drinking waterafteracute stress. Post-stress riluzole not only prevented the delayed increase in anxiety-like behavior on the elevated plus-maze, but also reversed the increase in spine-density on BLA neurons 10 days later. Further, stress-induced increase in the frequency of miniature excitatory postsynaptic currents recorded in BLA slices, 10 days later, was reversed by the same post-stress riluzole administration. Together, these findings underscore the importance of therapeutic strategies, aimed at glutamate uptake and modulation, in correcting the delayed behavioral, physiological, and morphological effects of stress on the amygdala.Significance statementStress disorders are characterized by impaired cognitive function alongside enhanced emotionality. Consistent with this, the same stress elicits contrasting effects in the rodent hippocampus versus amygdala. This poses a therapeutic challenge – the same pharmacological intervention against stress has to counter these opposite effects. Yet, the immediate consequence of stress – enhanced extracellular glutamate – is similar across these two areas. To target this common feature, we treated rats with riluzole, a drug that prevents stress-induced glutamate surge. Although the drug was administered after the end of stress, it reversed its delayed impact on amygdalar structure and function. Since riluzole also enhances glutamate-uptake through glial-transporters and is approved for human use, these results highlight the importance of therapeutic strategies focused on neuron-astrocyte interactions.