bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration of ergovaline exposure influences serotonin-mediated vasoactivity of bovine mesenteric vasculature
Authors: Trotta Ronald J , Harmon David L , Ji Huihua , Klotz James L 
Published: April 2023

Abstract
Ergovaline (ERV), produced in toxic endophyte-infected tall fescue, causes potent vasoconstriction of bovine peripheral and visceral vasculature. Ergovaline acts as both an agonist and an antagonist in bovine gut blood vessels through serotonin (5-HT) receptors and it appears that the type of action could be influenced by the extent of ERV exposure. Because it was unclear how the duration of ERV exposure influences 5-HT-mediated vasoactivity, experiments were designed to evaluate how simultaneous or prior ERV exposure influenced 5-HT-mediated vasoactivity of mesenteric artery (MA) and vein (MV) segments from Holstein steers (N = 10). Vessels were incubated in Krebs–Henseleit buffer containing 0, 0.01, or 0.1 μM ERV for 24 h prior to the 5-HT dose-response or exposed to fixed concentrations of 0, 0.01, or 0.1 μM ERV simultaneously during the 5-HT dose-response. Vessels were suspended in chambers of a multimyograph containing Krebs–Henseleit buffer and equilibrated to 1 g tension for 90 min. Vessels were exposed to increasing concentrations of 5-HT (5 × 10−8 M to 1 × 10−4 M) every 15 min and contractile responses were normalized as a percentage of the maximum contractile response induced by 120 mM KCl reference addition. Two-way analysis of variance was used to separately analyze data for each vessel type and duration of exposure using the MIXED procedure of SAS. When 5-HT concentration increased from 5 × 10−8 to 1 × 10−6 M, simultaneous addition of 0.1 μM ERV increased (P &lt; 0.01) the contractile response of MV compared with additions of 0 and 0.01 μM ERV. At 1 × 10−4 M 5-HT, the simultaneous presence of 0.01 and 0.1 μM ERV decreased (P &lt; 0.01) the contractile response of both MA and MV compared with 0 μM ERV addition. As 5-HT concentrations increased, the contractile response increased (P &lt; 0.01) in both MA and MV with no previous ERV exposure, but decreased in MA and MV with 24 h prior exposure to 0.01 and 0.1 μM ERV. These data demonstrate that the duration of ERV exposure influences 5-HT-mediated vasoconstriction and likely vasorelaxation in bovine mesenteric vasculature. If ERV and 5-HT exposure occur simultaneously, ERV can act as a partial agonist of 5-HT-mediated vasoconstriction. If 5-HT exposure occurs after blood vessels have had prior ERV exposure, it appears that 5-HT may induce vasorelaxation of blood vessels. More research is needed to identify cellular and molecular mechanisms involved with 5-HT-mediated vasoactivity.
Predation and parasitism of naturally occurring and sentinel stink bug egg masses ofHalyomorpha halys(Stål) andNezara viridula(L.) (Hemiptera: Pentatomidae) in various southeastern habitats
Authors: Tillman P Glynn , Grabarczyk Erin E , Balusu Rammohan , Kesheimer Katelyn , Blaauw Brett , Sial Ashfaq , Vinson Edgar , Cottrell Ted E 
Published: April 2023

AbstractStink bugs, including Halyomorpha halys (Stål) and Nezara viridula (L.), are agricultural pests that feed on fruit in a variety of crops. Monitoring predation and parasitism of stink bug egg masses furthers our understanding of potential biological control tactics. However, best practices for laboratory and field assessments of parasitism and predation of egg masses require further attention. We carried out a series of laboratory and field experiments to test whether parasitism and predation for three types of sentinel H. halys egg masses, fresh, frozen, and refrigerated, varied in agricultural commodities. In addition, we asked if predation and parasitism differed between sentinel and naturally occurring H. halys and N. viridula egg masses in soybean. In the laboratory, more H. halys eggs were parasitized by Trissolcus euschisti (Ashmead) (Hymenoptera: Scelionidae) if they were frozen or refrigerated compared to fresh eggs. Similarly, in the field, parasitism was higher for frozen egg masses than fresh. In 2018 and 2019, H. halys natural egg masses had higher parasitism and lower predation compared to sentinel egg masses in soybean. In a paired field test during 2020 and 2021, there was no difference in parasitism between H. halys natural and sentinel eggs, but much higher incidence of parasitism was detected in natural N. viridula egg masses than sentinel eggs. Collecting natural egg masses is the best methodology for field assessment of parasitism of stink bug egg masses; however, if natural egg masses are not easily available, deploying refrigerated sentinel egg masses is a good alternative.
Early C-reactive protein kinetics predicts immunotherapy response in non-small cell lung cancer in the phase III OAK trial
Authors: Saal Jonas , Bald Tobias , Eckstein Markus , Ritter Manuel , Brossart Peter , Ellinger Jörg , Hölzel Michael , Klümper Niklas 
Published: April 2023

Abstract
Static biomarkers like programmed death-ligand 1 (PD-L1) are insufficient to accurately predict response to immune checkpoint inhibition. Therefore, on-treatment biomarkers, which measure immediate therapy-associated changes, are currently shifting into the focus of immuno-oncology. A prime example of a simple predictive on-treatment biomarker is the early C-reactive protein (CRP) kinetics with its predictive CRP flare-response phenomenon. Here, we were able to confirm the predictive value of CRP flare-response kinetics in the pivotal phase III OAK trial (NCT02008227), which compared atezolizumab with docetaxel in patients with non-small cell lung cancer. Of note, CRP flare-response predicted favorable outcomes only in the immune checkpoint inhibition–treated subgroup, which suggests that it is an immunotherapy-specific phenomenon. In conclusion, we have for the first time validated the high predictive value of early CRP kinetics in a pivotal phase III trial, justifying the broad use of this cost-effective and easy-to-implement on-treatment biomarker to optimize therapy monitoring for patients with non-small cell lung cancer.
Management of low colorectal anastomotic leakage using negative pressure therapy with Transanal Minimally Invasive Surgery (TAMIS): description of a case and review of the literature
Authors: Pende Vito , Fiori Giulia , Lucandri Giorgio , Genualdo Flaminia , Lucchese Sara , Falbo Francesco , Biancucci Andrea , Mazzocchi Paolo , Farina Massimo , Santoro Emanuele 
Published: April 2023

AbstractAnastomotic leakage (AL) represents a major post-operative complication after low anterior resection (LAR) for rectal cancer. It is associated with increased morbidity, mortality, length of hospital stay and risk of permanent stoma. Herein we report the case of a 75-year-old male patient submitted to a minimally invasive LAR who developed an AL on the fifth post-operative day. This complication has been successfully managed by placing a Vacuum-Assisted Therapy device (Endo-SPONGE®) with an unusual Transanal Minimally Invasive Surgery (TAMIS) approach; the size of the abscess cavity was measured and the Endo-SPONGE® was cut according to the size of the fistulous defect. This procedure has been performed at regular intervals, achieving quick reduction of anastomotic defect. After the discharge from our department, the patient was addressed to adjuvant treatment. TAMIS may represent an alternative to the endoscopic approach to position an Endo-SPONGE® whenever a conservative management of an AL is required.
Ethanol root extract and fractions of Sphenocentrum jollyanum abrogate hyperglycaemia and low body weight in streptozotocin-induced diabetic Wistar albino rats
Authors: Ugwu Okechukwu Paul-Chima , Alum Esther Ugo , Okon Michael Ben , Aja Patrick M , Obeagu Emmanuel Ifeanyi , Onyeneke E C 
Published: April 2023

Abstract

Objectives
Effects of ethanol root extract and fractions of Sphenocentrum jollyanum on fasting blood glucose and body weight of streptozotocin-induced diabetic albino rats were carried.

Methods
Forty-eight rats were randomly assigned into eight groups. Groups 1 and 2 were diabetic rats treated with 0.5 ml of normal saline and 0.5 mg/kg b.w of glibenclamide, respectively while group 3 were non-diabetic rats treated with 0.5 ml of normal saline. Groups 4, 5 and 6 rats were diabetic rats treated with 250, 500 and 1 000 mg/kg b.w of extract, respectively, while rats in groups 7 and 8 were diabetic rats treated with 250 mg/kg b.w of methanol and ethylacetate fractions of S. jollyanum, respectively. Diabetes was induced by intraperitoneal injection of a single dose of 70 mg/kg b.w of streptozotocin. Fasting blood glucose levels were determined with glucometer.

Key findings
Treatment of diabetic rats with the extract and fractions of S. jollyanum at varied doses significantly (P &lt; 0.05) decreased glucose level in a dose- and time-dependent manner. There was an increase in body weights of rats during treatment.

Conclusion
The extract and fractions lowered glucose levels and raised body weights of diabetic rats. This suggests that S. jollyanum possess antidiabetic property and could be useful in the management of diabetes.
Stochastic modeling of a gene regulatory network driving B cell development in germinal centers
Authors: Koshkin Alexey , Herbach Ulysse , Martínez María Rodríguez , Gandrillon Olivier , Crauste Fabien 
Published: April 2023

AbstractGerminal centers (GCs) are the key histological structures of the adaptive immune system, responsible for the development and selection of B cells producing high-affinity antibodies against antigens. Due to their level of complexity, unexpected malfunctioning may lead to a range of pathologies, including various malignant formations. One promising way to improve the understanding of malignant transformation is to study the underlying gene regulatory networks (GRNs) associated with cell development and differentiation. Evaluation and inference of the GRN structure from gene expression data is a challenging task in systems biology: recent achievements in single-cell (SC) transcriptomics allow the generation of SC gene expression data, which can be used to sharpen the knowledge on GRN structure. In order to understand whether a particular network of three key gene regulators (BCL6, IRF4, BLIMP1), influenced by two external stimuli signals (surface receptors BCR and CD40), is able to describe GC B cell differentiation, we used a stochastic model to fit SC transcriptomic data from a human lymphoid organ dataset. The model is defined mathematically as a piecewise-deterministic Markov process. We showed that after parameter tuning, the model qualitatively recapitulates mRNA distributions corresponding to GC and plasmablast stages of B cell differentiation. Thus, the model can assist in validating the GRN structure and, in the future, could lead to better understanding of the different types of dysfunction of the regulatory mechanisms.
Multiple repeat regions within mouse DUX recruit chromatin regulators to facilitate an embryonic gene expression program
Authors: Smith Christina M. , Grow Edward J. , Shadle Sean C. , Cairns Bradley R. 
Published: April 2023

AbstractThe embryonic transcription factor DUX regulates chromatin opening and gene expression in totipotent cleavage-stage mouse embryos, and its expression in embryonic stem cells promotes their conversion to 2-cell embryo-like cells (2CLCs) with extraembryonic potential. However, little is known regarding which domains within mouse DUX interact with particular chromatin and transcription regulators. Here, we reveal that the C-terminus of mouse DUX contains five uncharacterized ∼100 amino acid (aa) repeats followed by an acidic 14 amino acid tail. Unexpectedly, structure-function approaches classify two repeats as ‘active’ and three as ‘inactive’ in cleavage/2CLC transcription program enhancement, with differences narrowed to a key 6 amino acid section. Our proximity dependent biotin ligation (BioID) approach identified factors selectively associated with active DUX repeat derivatives (including the 14aa ‘tail’), including transcription and chromatin factors such as SWI/SNF (BAF) complex, as well as nucleolar factors that have been previously implicated in regulating the Dux locus. Finally, our mechanistic studies reveal cooperativity between DUX active repeats and the acidic tail in cofactor recruitment, DUX target opening, and transcription. Taken together, we provide several new insights into DUX structure-function, and mechanisms of chromatin and gene regulation.
Does social antagonism facilitate supergene expansion? A novel region of suppressed recombination in a 4-haplotype supergene system
Authors: Scarparo Giulia , Palanchon Marie , Brelsford Alan , Purcell Jessica 
Published: April 2023

AbstractModels of both sex chromosome evolution and the genetic basis of local adaptation suggest that selection acts to lock beneficial combinations of alleles together in regions of reduced or suppressed recombination. Drawing inspiration from such models, we apply similar logic to investigate whether an autosomal supergene underlying colony social organization in ants expanded to include “socially antagonistic” alleles. We tested this premise in aFormicaant species wherein we identified four supergene haplotypes on chromosome 3 underlying colony social organization and sex ratio. Remarkably, we discovered a novel rearranged supergene variant (9r) on chromosome 9 underlying queen miniaturization. The 9r is tightly linked to one of the haplotypes (P2) on chromosome 3, found predominantly in multi-queen (polygyne) colonies. We suggest that queen miniaturization is strongly disfavored in the single queen (monogyne) background, and thus socially antagonistic. As such, divergent selection experienced by ants living in alternative social ‘environments’ (monogyne and polygyne) may have contributed to the emergence of a genetic polymorphism on chromosome 9 and associated queen size dimorphism. Consequently, an ancestral polygyne-associated haplotype may have expanded to include the polymorphism on chromosome 9, resulting in a larger region of suppressed recombination spanning two chromosomes. This process is analogous to the formation of neo-sex chromosomes and consistent with models of expanding regions of suppressed recombination. We also propose that miniaturized queens, 16-20% smaller than queens without 9r, could be incipient intraspecific social parasites.Significance statementWhen sets of gene variants work well together, selection may lead to a reduction in recombination between them. Here, we discover a novel supergene region on chromosome 9 that controls a previously undescribed queen size polymorphism inFormica cinereaants. The haplotype that is found in small queens, 9r, is tightly linked to a supergene haplotype on chromosome 3 that is found in multi-queen colonies. We propose that the region of suppressed recombination expanded to include both chromosome 3 and chromosome 9 because small queens could be successful in the multi-queen but not in the single-queen environment.
Similar deamination activity but different phenotypic outcomes induced by APOBEC3 enzymes in breast epithelial cells
Authors: Rodríguez Milaid Granadillo , Wong Lai , Chelico Linda 
Published: April 2023

AbstractAPOBEC3 (A3) enzymes deaminate cytosine to uracil in viral single-stranded DNA as a mutagenic barrier for some viruses. A3-induced deaminations can also occur in human genomes resulting in an endogenous source of somatic mutations in multiple cancers. However, the roles of each A3 are unclear since few studies have assessed these enzymes in parallel. Thus, we developed stable cell lines expressing A3A, A3B, or A3H Hap I using non-tumorigenic MCF10A and tumorigenic MCF7 breast epithelial cells, to assess their mutagenic potential and cancer phenotypes in breast cells. The activity of these enzymes was characterized by γH2AX foci formation andin vitrodeamination. Cell migration, and soft agar colony formation assays assessed cellular transformation potential. We found that all three A3 enzymes had similar γH2AX foci formation, despite different deamination activityin vitro. Notably, in nuclear lysates thein vitrodeaminase activity of A3A, A3B, and A3H did not require digestion of cellular RNA, in contrast to A3B and A3H in whole cell lysates. Their similar activities in cells nonetheless resulted in distinct phenotypes where A3A decreased colony formation in soft agar, A3B decreased colony formation in soft agar after hydroxyurea treatment, and A3H Hap I promoted cell migration. Overall, we show thatin vitrodeamination data does not always reflect in cell deamination, all three A3s induce somatic mutagenesis, and the impact of each is different.
Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities
Authors: Müller-Dott Sophia , Tsirvouli Eirini , Vázquez Miguel , Ramirez Flores Ricardo O. , Badia-i-Mompel Pau , Fallegger Robin , Lægreid Astrid , Saez-Rodriguez Julio 
Published: April 2023

ABSTRACTGene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, and their target genes, the so called TF regulons, can be coupled with computational algorithms to estimate the activity of TFs. However, to interpret these findings accurately, regulons of high reliability and coverage are needed. In this study, we present and evaluate a collection of regulons created using the CollecTRI meta-resource containing signed TF-gene interactions for 1,183 TFs. In this context, we introduce a workflow to integrate information from multiple resources and assign the sign of regulation to TF-gene interactions that could be applied to other comprehensive knowledge bases. We find that the signed CollecTRI-derived regulons outperform other public collections of regulatory interactions in accurately inferring changes in TF activities in perturbation experiments. Furthermore, we showcase the value of the regulons by investigating hallmarks of TF activity profiles inferred from the transcriptomes of three different cancer types. Overall, the CollecTRI-derived TF regulons enable the accurate and comprehensive estimation of TF activities and thereby help to interpret transcriptomics data.GRAPHICAL ABSTRACT
Connectivity-based Meta-Bands: A new approach for automatic frequency band identification in connectivity analyses
Authors: Rodríguez-González Víctor , Núñez Pablo , Gómez Carlos , Shigihara Yoshihito , Hoshi Hideyuki , Miguel Ángel Tola-Arribas , Cano Mónica , Ángel Guerrero , García-Azorín David , Hornero Roberto , Poza Jesús 
Published: April 2023

AbstractThe majority of electroencephalographic (EEG) and magnetoencephalographic (MEG) studies filter and analyse neural signals in specific frequency ranges, known as “canonical” frequency bands. However, this segmentation, is not exempt from limitations, mainly due to the lack of adaptation to the neural idiosyncrasies of each individual. In this study, we introduce a new data-driven method to automatically identify frequency ranges based on the topological similarity of the frequency-dependent functional neural network. The resting-state neural activity of 195 cognitively healthy subjects from three different databases (MEG: 123 subjects; EEG1: 27 subjects; EEG2: 45 subjects) was analysed. In a first step, MEG and EEG signals were filtered with a narrow-band filter bank (1 Hz bandwidth) from 1 to 70 Hz with a 0.5 Hz step. Next, the connectivity in each of these filtered signals was estimated using the orthogonalized version of the amplitude envelope correlation to obtain the frequency-dependent functional neural network. Finally, a community detection algorithm was used to identify communities in the frequency domain showing a similar network topology. We have called this approach the “Connectivity-based Meta-Bands” (CMB) algorithm. Additionally, two types of synthetic signals were used to configure the hyper-parameters of the CMB algorithm. We observed that the classical approaches to band segmentation reflect the underlying network topologies at group level for the MEG signals, but they fail to adapt to the individual differentiating patterns revealed by our methodology. On the other hand, the sensitivity of EEG signals to reflect this underlying frequency-dependent network structure is limited. To the best of our knowledge, this is the first study that proposes an unsupervised band segmentation method based on the topological similarity of functional neural network across frequencies. This methodology fully accounts for subject-specific patterns, providing more robust and personalized analyses, and paving the way for new studies focused on exploring the frequency-dependent structure of brain connectivity.
Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation
Authors: Lu Jiansen , Zhang Jiahuan , Jiang Huaji , Hu Zhiqiang , Zhang Yufen , He Lian , Yang Jianwu , Xie Yingchao , Wu Dan , Li Hongyu , Zeng Ke , Tan Peng , Xiao Qingyue , Song Zijing , Pan Chenglong , Bai Xiaochun , Yu Xiao 
Published: April 2023

AbstractVan Gogh-like 2 (Vangl2), a core planar cell polarity (PCP) component, plays an important role in polarized cellular and tissue morphology induction, growth development and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of NF-κB signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2 deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of pro-inflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.
Characterization of regeneration initiating cells duringXenopus laevistail regeneration
Authors: Radek Sindelka , Pavel Abaffy , Daniel Zucha , Ravindra Naraine , Daniel Kraus , Jiri Netusil , Karel Smetana , Lacina Lukas , Beduya Endaya Berwini , Jiri Neuzil , Martin Psenicka , Mikael Kubista 
Published: April 2023

AbstractEmbryos are regeneration and wound healing masters. They not only rapidly close their wounds, remodel injured tissue without a scar, but also regenerate body parts. Many animal models with variable regenerative capabilities have already been studied. Additionally, with the introduction of high throughput techniques, novel regeneration mechanisms including genes and signaling pathways, and specialized cell types required for regeneration control in spatial and temporal aspects have been identified. Until now our knowledge has been limited to primarily the late phases of regeneration (> 1 day post injury). In this paper, we reveal the critical steps for regeneration initiation. We have discovered Regeneration Initiating Cells (RICs) using single cell and spatial transcriptomic analyses during tail regeneration inXenopus laevis. RICs are formed transiently from the basal epidermal cells and are critical for the modification of the surrounding extracellular matrix to allow for migration of other cell types such as regeneration organizing cells that further promote regeneration. Absence or deregulation of RICs leads to excessive extracellular matrix deposition and regeneration defects.