bluuebunny/crossref_metadata_2025 huggingface dataset:
The mitotic checkpoint protein MAD2 delivers monoamine transporters to endocytosis
Authors: Koban Florian , Freissmuth Michael
Published: June 2021

Monoamine transporters retrieve serotonin (SERT), dopamine (DAT) and norepinephrine (NET) from the synaptic cleft. Surface levels of transporters are also regulated by internalization. Clathrin-mediated endocytosis of cargo proteins requires adaptor protein 2 (AP2), which recruits cargo to the nascent clathrin-cage. The transporter C-terminus is required for internalization but lacks an AP2-binding site. In the present work, we show that internalization of SERT and DAT relies on MAD2, a protein of the mitotic spindle assembly checkpoint (SAC). A MAD2-interaction motif in the transporter C-terminus interacts with MAD2. This binding is contingent on the closed conformation of MAD2 and allowed for the recruitment of two additional SAC proteins, BubR1 and p31COMET as well as AP2. MAD2, BubR1 and p31COMET are present in serotoninergic neurons of the dorsal raphe, corroborating a biological role of the identified interactions. Depletion of MAD2 in HEK-293 cells stably expressing SERT and DAT decreases constitutive and triggered endocytosis, respectively. Altogether, our study describes a candidate mechanism, which connects monoamine transporters to the endocytic machinery and thus supports their internalization.
Contact guidance as a consequence of coupled morphological evolution and motility of adherent cells
Authors: Ippolito Alberto , DeSimone Antonio , Deshpande Vikram S.
Published: June 2021

Adherent cells seeded on substrates spread and evolve their morphology while simultaneously displaying motility. Phenomena such as contact guidance viz. the alignment of cells on patterned substrates, are strongly linked to the coupling of morphological evolution with motility. Here we employ a recently developed statistical thermodynamics framework for modelling the non-thermal fluctuating response of the cells to probe this coupling. This thermodynamic framework is first extended to predict temporal responses via a Langevin style model. The Langevin model is then shown to not only predict the different experimentally observed temporal scales for morphological observables such as cell area and elongation but also the interplay of morphology with motility that ultimately leads to contact guidance.

Author Summary

The evolution of cellular morphology and organization plays a crucial role in the micro-architecture of tissues and dictates their biological and mechanical functioning. Despite the importance of cellular organization in all facets of tissue biology, the fundamental question of how a cell organizes itself in an anisotropic environment is still poorly understood. We demonstrate, using a Langevin style model, that non-thermal fluctuations fuelled by nutrient exchanges between the cell and its environment are critical in allowing cells to explore their surroundings. The biochemical changes, associated with non-thermal fluctuations, drive cell motility and morphological changes and the interplay between these two emerging dynamics ultimately leads to contact guidance, a critical component for tissue morphogenesis.
Investigation of Thyroid Hormone Associated Gene-Regulatory Networks during Hepatogenesis using an Induced Pluripotent Stem Cell based Model
Authors: Ncube Audrey , Graffmann Nina , Greulich Jan , Scherer Bo , Wruck Wasco , Adjaye James
Published: June 2021

Currently, the only treatment of end-stage liver diseases is liver transplantation. The worldwide shortage of donor organs and the high number of patients suffering from end-stage liver diseases, require alternative treatment approaches. Therefore, the generation of hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells (iPSCs) is a promising treatment option. HLCs are suitable for patient-specific drug screening, disease modeling and regenerative medicine. So far, they are immature and resemble the fetal state. In this study, we employed the combined thyroid hormones triiodo-L-thyronine (T3) and L-thyroxine (T4) to drive HLCs towards maturation. HLCs expressed the maturation markers ALBUMIN (ALB), ALPHA-1 ANTITRYPSIN (A1AT), CYTOCHROME P450 3A4 (CYP3A4) and TRANSTHYRETIN (TTR). Remarkably, stimulation with T3 and T4 slightly reduced the expression of the fetal marker CYTOCHROME P450 3A7 (CYP3A7) and had an even more pronounced effect on ALPHA-FETOPROTEIN (AFP) levels. Comparative transcriptome and associated pathways in unstimulated and T3 and T4 stimulated HLCs revealed regulated expression of numerous genes within for example the peroxisome proliferator-activated receptor (PPAR), transforming growth factor beta (TGF-β), mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) signaling pathways and thyroid hormone synthesis. We propose the inclusion of combined T3 andT4 in HLC differentiation protocols to enhance maturation and therefore provide additional improvement in their applications in drug screening and disease modeling.
RCaN : a software for Chance and Necessity modelling
Authors: Drouineau Hilaire , Planque Benjamin , Mullon Christian
Published: June 2021

Uncertainty is a challenge in modelling ecological systems and has been a source of misunderstandings between modelers and non-modelers. The “Chance and Necessity” (CaN) modelling approach has been proposed to address this issue, in the case of trophic network modelling. CaN modelling focuses exploring food-web trajectories that can satisfy fundamental physical and biological laws, while being compatible with observations and domain knowledge. This type of approach can facilitate discussion among actors as it promotes sharing of information and does not presuppose any knowledge of modelling practices. It is therefore suitable for participatory modelling, i.e. a modelling approach in which different actors can confront their knowledge and understanding of the marine system and of the associated uncertainties.

One important ingredient to achieve participatory modelling is the availability of a modelling platform that is efficient, fast and transparent, so that all actors can understand and follow the modelling steps and choices, and can rapidly visualize and discuss the results. But, until now, there existed no software to easily perform CaN modelling. Here, we present RCaN and RCaNconstructor. Combined, these provide the first tool to build CaN models in an intuitive way that is 1) suitable within participatory frameworks, 2) transparent, 4) computationally efficient, 5) fully documented through the provision of meta-information and 6) supportive of exploratory analyses through predefined graphical functions.
Polypeptides IGF-1C and P24 synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro through the p38 and JNK signaling pathways
Authors: Ran Gaoying , Fang Wei , Zhang Lifang , Peng Yuting , Li Jiatong , Ding Xianglong , Zeng Shuguang , He Yan
Published: June 2021

Objectives

Insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein 2 (BMP-2) both promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs). IGF-1C, the C domain peptide of IGF-1, and P24, a BMP-2-derived peptide, both have similar biological activities as their parent growth factors. This study aimed to investigate the effects and their mechanisms of polypeptides IGF-1C and P24 on the osteogenic differentiation of BMSCs.

Methods

The optimum concentrations of IGF-IC and P24 were explored. The effects of the two polypeptides on the proliferation and osteogenic differentiation of BMSCs were examined using the Cell Counting Kit-8(CCK-8), Alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qPCR, and western blotting. In addition, specific pathway inhibitors were utilized to explore whether p38 and JNK pathways were involved in this process.

Results

The optimal concentrations of action were both 50 μg/ml. IGF-1C and P24 synergistically promoted the proliferation of BMSCs, increased ALP activity and the formation of calcified nodules and upregulated the mRNA and protein levels of osterix (Osx), runt-related transcription factor 2 (Runx2), and osteocalcin (Ocn), phosphorylation level of p38 and JNK proteins also improved. Inhibition of the pathways significantly reduced the activation of p38 and JNK, blocked the expression of Runx2 while inhibiting ALP activity and the formation of calcified nodules.

Conclusions

These findings suggest IGF-1C and P24 synergistically promote the osteogenesis of BMSCs through activation of p38 and JNK signal pathways.
Multiscale computer model of the spinal dorsal horn reveals changes in network processing associated with chronic pain
Authors: Medlock Laura , Sekiguchi Kazutaka , Hong Sungho , Dura-Bernal Salvador , Lytton William W , Prescott Steven A.
Published: June 2021

Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made in identifying the types of excitatory and inhibitory neurons that comprise the SDH, and there is some information about how neuron types are connected, but it remains unclear how the overall circuit processes sensory input or how that processing is disrupted under chronic pain conditions. To explore SDH function, we developed a computational model of the circuit that is tightly constrained by experimental data. Our model comprises conductance-based neuron models that reproduce the characteristic firing patterns of spinal neurons. Excitatory and inhibitory neuron populations, defined by their expression of genetic markers, spiking pattern, or morphology, were synaptically connected according to available qualitative data. Using a genetic algorithm, synaptic weights were tuned to reproduce projection neuron firing rates (model output) based on primary afferent firing rates (model input) across a range of mechanical stimulus intensities. Disparate synaptic weight combinations could produce equivalent circuit function, revealing degeneracy that may underlie heterogeneous responses of different circuits to perturbations or pathological insults. To validate our model, we verified that it responded to reduction of inhibition (i.e. disinhibition) and ablation of specific neuron types in a manner consistent with experiments. Thus validated, our model offers a valuable resource for interpreting experimental results and testing hypotheses in silico to plan experiments for examining normal and pathological SDH circuit function.

Significance Statement

We developed a multiscale computer model of the posterior part of spinal cord gray matter (spinal dorsal horn), involved in perception of touch and pain. The model reproduces several experimental observations and makes predictions about how specific types of spinal neurons and synapses influence projection neurons that send information to the brain. Misfiring of these projection neurons can produce anomalous sensations associated with chronic pain. Our computer model will not only assist in planning future experiments, but will also be useful for developing new pharmacotherapy for chronic pain disorders, connecting the effect of drugs acting at the molecular scale with emergent properties of neurons and circuits that shape the pain experience.
Underwater CAM photosynthesis elucidated by Isoetes genome
Authors: Wickell David , Kuo Li-Yaung , Yang Hsiao-Pei , Ashok Amra Dhabalia , Irisarri Iker , Dadras Armin , de Vries Sophie , de Vries Jan , Huang Yao-Moan , Li Zheng , Barker Michael S. , Hartwick Nolan T. , Michael Todd P. , Li Fay-Wei
Published: June 2021

To conserve water in arid environments, numerous plant lineages have independently evolved Crassulacean Acid Metabolism (CAM). Interestingly, Isoetes, an aquatic lycophyte, can also perform CAM as an adaptation to low CO2 availability underwater. However, little is known about the evolution of CAM in aquatic plants and the lack of genomic data has hindered comparison between aquatic and terrestrial CAM. Here, we investigated the underwater CAM in Isoetes taiwanensis by generating a high-quality genome assembly and RNA-seq time course. Despite broad similarities between CAM in Isoetes and terrestrial angiosperms, we identified several key differences. Notably, for carboxylation of PEP, Isoetes recruited the lesser-known “bacterial-type” PEPC, along with the “plant-type” exclusively used in other terrestrial CAM and C4 plants. Furthermore, we found that circadian control of key CAM pathway genes has diverged considerably in Isoetes relative to flowering plants. This suggests the existence of more evolutionary paths to CAM than previously recognized.
Toward a More Accurate 3D Atlas ofC. elegansNeurons
Authors: Skuhersky Michael , Wu Tailin , Yemini Eviatar , Boyden Edward , Tegmark Max
Published: June 2021

Determining cell identity in volumetric images of tagged neuronal nuclei is an ongoing challenge in contemporary neuroscience. Frequently, cell identity is determined by aligning and matching tags to an “atlas” of labeled neuronal positions and other identifying characteristics. Previous analyses of suchC. elegansdatasets have been hampered by the limited accuracy of such atlases, especially for neurons present in the ventral nerve cord, and also by time-consuming manual elements of the alignment process. We present a novel automated alignment method for sparse and incomplete point clouds of the sort resulting from typicalC. elegansfluorescence microscopy datasets. This method involves a tunable learning parameter and a kernel that enforces biologically realistic deformation. We also present a pipeline for creating alignment atlases from datasets of the recently developed NeuroPAL transgene. In combination, these advances allow us to label neurons in volumetric images with confidence much higher than previous methods. We release, to the best of our knowledge, the most completeC. elegans3D positional neuron atlas, encapsulating positional variability derived from 7 animals, for the purposes of cell-type identity prediction for myriad applications (e.g., imaging neuronal activity, gene expression, and cell-fate).
The calcifying interface in a stony coral’s primary polyp: An interplay between seawater and an extracellular calcifying space
Authors: Khalifa Gal Mor , Levy Shani , Mass Tali
Published: June 2021

Stony coral exoskeletons build the foundation to the most biologically diverse yet fragile marine ecosystems on earth, coral reefs. Understanding corals biomineralization mechanisms is therefore crucial for coral reef management and for using coral skeletons in geochemical studies. In this study, we combine in-vivo and cryo-electron microscopy with single-cell RNA-seq data to gain novel insights into the calcifying micro-environment that facilitates biomineralization in primary polyps of the stony coralStylophora pistillata. We show an intimate involvement of seawater in this micro-environment. We further document increased tissue permeability and a highly dispersed cell packing in the tissue secreting the coral skeleton (i.e. calicoblastic). We also observe an extensive filopodial network containing carbon-rich vesicles extruding from some of the calicoblastic cells. Single-cell RNA-Seq data interrogation shows that calicoblastic cells express genes involved in filopodia and vesicle structure and function. These observations provide a new conceptual framework for resolving stony corals biomineralization processes.
Impact of AI-based Real Time Image Quality Feedback for Chest Radiographs in the Clinical Routine
Authors: Poggenborg Joerg , Yaroshenko Andre , Wieberneit Nataly , Harder Tim , Gossmann Axel
Published: June 2021

Purpose

To implement a tool for real time image quality feedback for chest radiographs into the clinical routine and to evaluate the effect of the system on the image quality of the acquired radiographs.

Materials and Methods

A real time Artificial Intelligence (AI) image quality feedback tool is developed that analyzes chest PA x-rays right after the completion of the examination at the x-ray system and provides visual feedback to the system operator with respect to adherence to desired standards of collimation, patient rotation and inspiration. In order to track image quality changes over time, results were compared to image quality assessment for images, acquired prior to system implementation.

Results

Compared to the image quality prior to the installation of the real time image quality feedback solution, it is shown that a relative increase of images with optimal image quality with respect to collimation, patient rotation and inspiration is achieved by 30% (p<0.01). A relative improvement of 28% (p<0.01) is observed for the increase of images with optimal collimation, followed by a relative increase of 4% (p<0.01) of images with optimal inspiration. Finally, a detailed analysis is presented that shows that the average unnecessarily exposed area is reduced by 34% (p<0.01).

Discussion

This study shows that it is possible to significantly improve image quality using a real time AI-based image quality feedback tool. The developed tool not only provides objective and impartial criticism and helps x-ray operators identify areas for improvement, but also gives positive feedback.

Key Findings

A substantial amount of images acquired in the clinical routine does not suffice the international guidelines

Continuous AI-based image quality feedback to the x-ray system operator in the clinical routine leads to a significant image quality improvement over time

Using the developed tool, the overall fraction of images with optimal patient positioning could be improved by 30%, followed by a 34% decrease of unnecessarily exposed area.
Salvage of Ribose from Uridine or RNA Supports Glycolysis when Glucose is Limiting
Authors: Jourdain Alexis A. , Skinner Owen S. , Kawakami Akinori , Goodman Russel P. , Shen Hongying , Kemény Lajos V. , Joesch-Cohen Lena , Rees Matthew G. , Roth Jennifer A. , Fisher David E. , Mootha Vamsi K.
Published: June 2021

Summary paragraph

Glucose is vital for life, serving both as a source of energy and as a carbon building block for growth. When glucose availability is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized, genome-wide genetic screening and growth assays of 482 pooled PRISM cancer cell lines. We report that catabolism of uridine enables the growth of cells in the complete absence of glucose. While previous studies have shown that the uracil base of uridine can be salvaged to support growth in the setting of mitochondrial electron transport chain deficiency (1), our work shows that the ribose moiety of uridine can be salvaged via a pathway we call “uridinolysis” defined as: [1] the phosphorylytic cleavage of uridine by UPP1/2 into uracil and ribose-1-phosphate (R1P), [2] the conversion of R1P into fructose-6-P and glyceraldehyde-3-P by PGM2 and the non-oxidative branch of the pentose phosphate pathway (non-oxPPP), and [3] their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Intriguingly, we report that uridine nucleosides derived from RNA are also a substrate for uridinolysis and that RNA can support growth in glucose-limited conditions. Our results underscore the malleability of central carbon metabolism and raise the provocative hypothesis that RNA can also serve as a potential storage for energy.
Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: An immuno-histochemical proof
Authors: Gupta T. , Kaur M. , Sahni D.
Published: June 2021

Introduction

The atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation.

Materials and Methods

The study was conducted on longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric non-diseased hearts. Tissue was studied histologically using H&E and Gömöri trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies.

Results

The AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining.

Conclusion

Pulmonary veins nodes are similar to the specialized cardiac conductive tissue in, histological arrangement of compact and transitional zones, cellular characteristics, and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge these nodes are being described for the first time in human.
Parkin drives pS65-Ub turnover independently of canonical autophagy in Drosophila
Authors: Usher Joanne L. , Lee Juliette J. , Sanchez-Martinez Alvaro , Whitworth Alexander J.
Published: June 2021

Parkinson’s disease-related proteins, PINK1 and Parkin, act in a common pathway to maintain mitochondrial quality control. While the PINK1-Parkin pathway can promote autophagic mitochondrial turnover (mitophagy) in cell culture, recent studies have questioned whether they contribute to mitophagy in vivo, and alternative PINK1- and Parkin-dependent mitochondrial quality control pathways have been proposed. To determine the mechanisms by which the Pink1-Parkin pathway operates in vivo, we developed methods to detect Ser65-phosphorylated ubiquitin (pS65-Ub) in Drosophila. Exposure to the oxidant paraquat led to robust, Pink1-dependent pS65-Ub production. Surprisingly, parkin-null flies displayed strikingly elevated basal levels of pS65-Ub, suggestive of disrupted flux through the Pink1-parkin pathway. Depletion of the core autophagy proteins Atg1, Atg5 and Atg8a did not cause pS65-Ub accumulation to the same extent as loss of parkin, and overexpression of parkin was able to reduce both basal and paraquat-induced pS65-Ub levels in an Atg5-null background. Taken together, these results suggest that the Pink1-parkin pathway is able to promote mitochondrial turnover independently of canonical autophagy in vivo.
A chemical strategy toward novel brain-penetrant EZH2 inhibitors
Authors: Liang Rui , Tomita Daisuke , Sasaki Yusuke , Ginn John , Michino Mayako , Huggins David J. , Baxt Leigh , Kargman Stacia , Shahid Maaz , Aso Kazuyoshi , Duggan Mark , Stamford Andrew W. , DeStanchina Elisa , Liverton Nigel , Meinke Peter T. , Foley Michael A. , Phillips Richard E.
Published: June 2021

Aberrant gene-silencing through dysregulation of polycomb protein activity has emerged as an important oncogenic mechanism in cancer, implicating polycomb proteins as important therapeutic targets. Recently, an inhibitor targeting EZH2, the methyltransferase component of PRC2, received FDA approval following promising clinical responses in cancer patients. However, the current array of EZH2 inhibitors have poor brain-penetrance limiting their use in patients with CNS malignancies, a number of which have been shown to be sensitive to EZH2 inhibition. To address this need, we have identified a chemical strategy, based on computational modeling of pyridone-containing EZH2 inhibitor scaffolds, to minimize P-glycoprotein activity and here we report the first brain-penetrant EZH2 inhibitor, TDI-6118 (compound 5). Additionally, in the course of our attempts to optimize this compound we discovered TDI-11904 (compound 21); a novel, highly-potent, and peripherally active EZH2 inhibitor based on a 7 member ring structure.
Novel and highly distributed classes of hindbrain neuronal activity contribute to sensory processing and motor control in the Xenopus laevis tadpole
Authors: Messa Giulia , Koutsikou Stella
Published: June 2021

An animal’s survival depends heavily on the selection and execution of timely and well-coordinated motor responses. The brainstem controls the activity of spinal neural circuits to produce and modify movements. However, important questions remain unanswered about the origin of this descending control and how brainstem neuronal activity integrates sensory inputs and determines motor functions. Here, we record hindbrain extracellular activity in response to trunk skin stimulation, which in turn leads to fictive swimming in the hatchling Xenopus laevis tadpole. We identify four distinct classes of single unit activity, distributed along the hindbrain rostro-caudal axis, whose firing patterns correlate to distinct motor states. We observe different firing patterns in response to stimulation that leads to fictive swimming versus the application of a weak stimulus which does not evoke movement. We identify differences in the temporal activation of the four classes of hindbrain activity in relation to the initiation of fictive swimming. We propose a simple network encompassing the novel neuronal populations embedded within the currently known sensory pathway and central pattern generators of the tadpole brainstem. By identifying the contribution of the individual supraspinal neuronal populations we build a better understanding of how the brain controls and modulates movement.
Dynamic urine proteome changes in a rat model of simvastatin-induced skeletal muscle injury
Authors: Wei Jing , Huan Yuhang , Heng Ziqi , Zhao Chenyang , Gao Youhe
Published: June 2021

Background

Statin-associated muscle symptoms (SAMS) are the main side effects of statins. Currently, there are no effective biomarkers for accurate clinical diagnosis. Urine is not subject to homeostatic control and therefore accumulates early changes, making it an ideal biomarker source. We therefore examined urine proteome changes associated with SAMS in an animal model.

Methods

Here, we established a SAMS rat model by intragastric intubation with simvastatin (80 mg/kg). Biochemical analyses and hematoxylin and eosin (H&E) staining were used to evaluate the degree of muscle injury. The urine proteome on days 3, 6, 9 and 14 was profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) with the data-independent acquisition (DIA) method.

Results

Differential proteins on day 14 of SAMS were mainly associated with glycolysis/gluconeogenesis, pyruvate metabolism, metabolism of reactive oxygen species and apoptosis, all of which were reported to be associated with the pathological mechanism of SAMS. Among the 14 differentially expressed proteins on day 3, FIBG, OSTP and CRP were associated with muscle damage, while EHD1, CUBN and FINC were associated with the pathogenic mechanisms of SAMS. MYG and PRVA increased dramatically compared with CK elevation in serum on day 14 of SAMS.

Conclusions

Our preliminary results indicated that the urine proteome can reflect early changes in the SAMS rat model, providing the potential for monitoring drug side effects in future clinical research.
Notch pathway is required for protection against heat-stress in spermatogonial stem cells
Authors: Moreno Acosta Omar D. , Boan Agustín F. , Hattori Ricardo S. , Fernandino Juan I.
Published: June 2021

Environmentally favorable conditions the sustainability of spermatogenesis is brought about by a balance between two types of division, the self-renewal division for the maintenance of the stem cell pool and the differentiation division for continuous production of spermatozoa. The production of gametes under unfavorable, stressful conditions can decrease or even be interrupted, compromising fertility parameters. Thus, the survival of spermatogonial stem cells (SSCs) is crucial for the recovery of spermatogenesis after stressful situations (e.g. high temperature). Here, we show that the Notch pathway protects the spermatogonial stem cells against thermal stress, ensuring reproductive success after normal conditions are restored. First, presenilin enhancer-2 (pen-2), the catalytic subunit of γ-secretase complex, was localized in SSCs of the medaka testis. The exposure of adult males to thermal stress condition induced apoptosis in all spermatogenics cells, with the exception of SSCs. Concomitantly, the Notch pathways was up-regulated, including the pen-2, its ligands (dll4, jag1-2) and its receptors (notch1a-3); pen-2 expression was restricted to the SSCs during thermal stress. The importance of this pathway was further supported by an ex vivo approach, in which the inhibition of Notch activity induced a loss of SSCs. Overall, this study demonstrates that the Notch pathways activity is necessary for the protection of SSCs under chronic thermal stress.
Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis
Authors: Wilmerding Axelle , Bouteille Lauranne , Caruso Nathalie , Bidaut Ghislain , Etchevers Heather , Graba Yacine , Delfini Marie-Claire
Published: June 2021

Most human cancers demonstrate activated MAPK/ERK pathway signaling as a key tumor initiation step, but the immediate steps of further oncogenic progression are poorly understood due to a lack of appropriate models. Spinal cord differentiation follows caudal elongation in vertebrate embryos; both processes are regulated by a FGF8 gradient highest in neuromesodermal progenitors (NMP), where kinase effectors ERK1/2 maintain an undifferentiated state. FGF8/ERK signal attenuation is necessary for NMPs to progress to differentiation. We show that sustained ERK1/2 activity, using a constitutively active form of the kinase MEK1 (MEK1ca) in the chicken embryo, reproducibly provokes neopasia in the developing spinal cord. Transcriptomic data show that neoplasia not only relies on the maintenance of NMP gene expression, and the inhibition of genes expressed in the differentiating spinal cord, but also on a profound change in the transcriptional signature of the spinal cord cells leading to a complete loss of cell-type identity. MEK1ca expression in the developing spinal cord of the chicken embryo is therefore a tractable in vivo model to identify the critical factors fostering malignancy in ERK-induced tumorigenesis.
Readiness Potential Prevalence During a Deliberate Decision-Making Task
Authors: Blignaut J. , van den Heever D.J.
Published: June 2021

This study investigated the hypothesis that neural markers associated with arbitrary decision-making are present in higher order, deliberate decisions. Furthermore, the study aimed to investigate the effect of higher order decision content on neurophysiological markers such as the readiness potential and the P300 potential. An experiment was designed to measure, evaluate, and compare these electroencephalographic potentials under both arbitrary and deliberate choice conditions. Participants were presented with legal cases and had to convict and acquit criminal offenders. Distinct readiness potentials and P300 potentials were observed for both arbitrary and deliberate decisions across all participants. These findings support the hypothesis that the readiness potential and the P300 potential are present in the neurophysiological data for higher order deliberate decisions. The study also showed initial findings of how the readiness potential may inherently relate to decision content. Increased readiness potential amplitudes were observed for participants with previous exposure to violent crime when they had to acquit or convict criminals accused of violent crimes.
Hybridization potential between Amaranthus tuberculatus and Amaranthus albus
Authors: Murphy Brent P , Chatham Laura A , McCormick Danielle M , Tranel Patrick J
Published: June 2021

The genus Amaranthus is composed of numerous annual herbs, several of which are primary driver weeds within annual production agricultural systems. In particular, Amaranthus tuberculatus, a dioecious species, is noteworthy for rapid growth rates, high fecundity, and an expanding geographic distribution. Interspecific hybridization within and between the subgenera Amaranthus and Acnidia is reported both in controlled environment and field studies, however a gap in knowledge exists with the subgenus Albersia. Interspecific hybridization may contribute to genetic diversity, and may contribute to the current range expansion of A. tuberculatus. Recently, a herbicide resistance survey of A. tuberculatus across five Midwestern states reported alleles of PPX2 similar to sequences of Amaranthus albus, a monoecious species. Here, we seek to generate empirical data for the hybridization potential of A. albus and A. tuberculatus through replicated, controlled crosses in a greenhouse. Of 65,000 progeny screened from A. albus grown with A. tuberculatus males, three were confirmed as hybrids. Hybrids were dioecious, possessed phenotypic traits of both species, and had limited to no fertility. DNA content analysis of backcross progeny suggested a polyploid state may be required for hybrid formation. Screening of 120 progeny of A. tuberculatus females grown with A. albus identified no hybrids, though a skew to female progeny was observed. The female skew may be due to apomixis or auto-pollination, the spontaneous generation of male flowers on otherwise female plants. Our results indicate that introgression between A. albus and A. tuberculatus will occur less frequently than what has often been reported from hybridization studies with different pairs of Amaranthus species.
Charge density studies of multicentre two-electron bonding of an anion radical at non-ambient temperature and pressure
Authors: Milašinović Valentina , Molčanov Krešimir , Krawczuk Anna , Bogdanov Nikita E. , Zakharov Boris A. , Boldyreva Elena V. , Jelsch Christian , Kojić-Prodić Biserka
Published: June 2021

The variation of charge density of two-electron multicentre bonding (pancake bonding) between semiquinone radicals with pressure and temperature was studied on a salt of 5,6-dichloro-2,3-dicyanosemiquinone radical anion (DDQ) with 4-cyano-N-methylpyridinium cation (4-CN) using the Transferable Aspheric Atom Model (TAAM) refinement. The pancake-bonded radical dimers are stacked by non-bonding π-interactions. With rising pressure, the covalent character of interactions between radicals increases, and above 2.55 GPa, the electron density indicates multicentric covalent interactions throughout the stack. The experimental charge densities were verified and corroborated by periodic DFT computations. The TAAM approach has been tested and validated for atomic resolution data measured at ambient pressure; this work shows this approach can also be applied to diffraction data obtained at pressures up to several gigapascals.
Hexanuclear copper(II) complex of 2-hydroxy-N,N′-bis[1-(2-hydroxyphenyl)ethylidene]propane-1,3-diamine incorporating an open-cubane core
Authors: Kébé Momath , Thiam Ibrahima Elhadji , Sow Mouhamadou Moustapha , Diouf Ousmane , Barry Aliou Hamady , Sall Abdou Salam , Retailleau Pascal , Gaye Mohamed
Published: June 2021

The title molecular structure, namely, diaquatris(μ3-1,3-bis{[1-(2-oxidophenyl)ethylidene]amino}propan-2-olato)-μ3-hydroxido-dinitratohexacopper(II) ethanol trisolvate, [Cu6(C19H19N2O3)3(NO3)2(OH)(H2O)2]·3C2H5OH, corresponds to a non-symmetric hexanuclear copper complex. The complex exhibits one core in which three CuII metal centres are mutually interconnected, two by two, via three phenolato oxygen anions acting in a μ2-mode. These three copper cations are interconnected in a μ3-mode by one hydroxyl group. An open-cube structure is generated in which each of the CuII cations of the three CuO4N units is connected by two μ2-O anions from phenolate groups and one μ3-O atom from a hydroxy anion. Each of the three pentacoordinated CuII cations situated in the open-cube unit has a distorted NO4 square-pyramidal environment. Each of these three CuII centres is interconnected with another CuII cation via one enolate O atom in μ2-mode, yielding one CuNO4 unit and two CuNO3 units. The pentacoordinated CuII atom has a distorted square-pyramidal environment while the two tetracoordinated copper(II) cations are situated in a square-planar environment. A series of intramolecular O—H...O hydrogen bonds are observed. In the crystal, the units are connected two by two by intermolecular C—H...O and O—H...O hydrogen bonds, thus forming sheets parallel to the ac plane.
Knowledge-enabled digital twin for smart designing of aircraft assembly line
Authors: Chang Xiao , Jia Xiaoliang , Liu Kuo , Hu Hao
Published: June 2021

Purpose

The purpose of this paper is to provide a knowledge-enabled digital twin for smart design (KDT-SD) of aircraft assembly line (AAL) to enhance the AAL efficiency, performance and visibility. Modern AALs usually need to have capabilities such as digital-physical interaction and self-evaluation that brings significant challenges to traditional design method for AAL. The digital twin (DT) combining with reusable knowledge, as the key technologies in this framework, is introduced to promote the design process by configuring, understanding and evaluating design scheme.

Design/methodology/approach

The proposed KDT-SD framework is designed with the introduction of DT and knowledge. First, dynamic design knowledge library (DDK-Lib) is established which could support the various activities of DT in the entire design process. Then, the knowledge-driven digital AAL modeling method is proposed. At last, knowledge-based smart evaluation is used to understand and identify the design flaws, which could further improvement of the design scheme.

Findings

By means of the KDT-SD framework proposed, it is possible to apply DT to reduce the complexity and discover design flaws in AAL design. Moreover, the knowledge equips DT with the capacities of rapid modeling and smart evaluation that improve design efficiency and quality.

Originality/value

The proposed KDT-SD framework can provide efficient design of AAL and evaluate the design performance in advance so that the feasibility of design scheme can be improved as much as possible.
IDMPF: intelligent diabetes mellitus prediction framework using machine learning
Authors: Ismail Leila , Materwala Huned
Published: June 2021

Purpose

Machine Learning is an intelligent methodology used for prediction and has shown promising results in predictive classifications. One of the critical areas in which machine learning can save lives is diabetes prediction. Diabetes is a chronic disease and one of the 10 causes of death worldwide. It is expected that the total number of diabetes will be 700 million in 2045; a 51.18% increase compared to 2019. These are alarming figures, and therefore, it becomes an emergency to provide an accurate diabetes prediction.

Design/methodology/approach

Health professionals and stakeholders are striving for classification models to support prognosis of diabetes and formulate strategies for prevention. The authors conduct literature review of machine models and propose an intelligent framework for diabetes prediction.

Findings

The authors provide critical analysis of machine learning models, propose and evaluate an intelligent machine learning-based architecture for diabetes prediction. The authors implement and evaluate the decision tree (DT)-based random forest (RF) and support vector machine (SVM) learning models for diabetes prediction as the mostly used approaches in the literature using our framework.

Originality/value

This paper provides novel intelligent diabetes mellitus prediction framework (IDMPF) using machine learning. The framework is the result of a critical examination of prediction models in the literature and their application to diabetes. The authors identify the training methodologies, models evaluation strategies, the challenges in diabetes prediction and propose solutions within the framework. The research results can be used by health professionals, stakeholders, students and researchers working in the diabetes prediction area.
Independent board, gender diversity and bank performance in Nigeria: a system-GMM approach
Authors: Okoyeuzu Chinwe , Ujunwa Augustine , Ujunwa Angela Ifeanyi , Onah Emmanuel Onyebuchi
Published: June 2021

Purpose

This study aims to examine the effects of board independence and gender diversity on bank performance in Nigeria.

Design/methodology/approach

The two-step system-generalized method moment was used to estimate the effect of board independence and gender diversity on bank performance in Nigeria using annual data of 15 deposit money banks from 2006 to 2018.

Findings

The results revealed that gender diversity is a significant positive predictor of bank performance, whereas board independence is a negative predictor of bank performance in Nigeria.

Practical implications

Despite the significant positive relationship between gender diversity and bank performance, this paper does not recommend mandatory quota-based initiates of female representation on corporate boards because of the increasing number of female representations on corporate boards of banks in Nigeria.

Originality/value

The study contributes to corporate governance literature from developing country perspective and policy, particularly, on the relevance or otherwise of market-based measures in assessing bank performance in developing counties. This paper finds that market-based variables are not good measures of firm performance in economies with underdeveloped markets.
The development of self-efficacy and self-leadership within USA accredited sales programs: an exploratory study on sales career preparedness
Authors: Knight Peter , Peesker Karen , Mich Claudia C.
Published: June 2021

Purpose

The purpose of this exploratory study is to investigate the impact of sales education on recent graduates' career preparedness and understand how sales programs might prepare students better for successful sales careers. We investigate the known competencies leading to sales success that were, or were not, adequately developed by their university sales programs.

Design/methodology/approach

The authors collected and analyzed qualitative data from in-depth interviews with a sample of 20 recent university sales graduates working in a sales career. Over 23 h of interviews were transcribed and analyzed via NVivo. Braun and Clarke’s (2006) framework was applied in this study to code the data.

Findings

The study identifies that while respondents are positive about their overall sales education and feel confident about their knowledge of the sales process, they are not always confident in their ability to deal with ambiguity and the unknown. This study revealed that constructs of self-leadership and career choice self-efficacy deserve further consideration as components of the university sales program curriculum.

Research limitations/implications

As with all exploratory research, there are limits to generalizability; however, this study revealed that the constructs of goal setting, self-leadership and self-knowledge hold promise for further study as a means to increase sales-related self-efficacy and career readiness.

Practical implications

Respondents were positive about their overall sales education experience but identified a need for more effective sales education in cold calling, prospecting and the inherent level of rejection to be prepared for inside sales positions in which sales graduates increasingly start their careers.

Social implications

Lower turnover and better educational preparedness of sales program graduates clearly will accrue socioeconomic benefits.

Originality/value

This is the first study to examine the impact of sales education on recent graduates’ career preparedness and the first study for this journal to focus on sales as an area of professional competency and related sales pedagogy. Further, the qualitative methodology, which is relatively unique in sales research, provides rich data that is particularly useful for exploratory research to help provide a structure for universities to strengthen their sales programs through targeted training to help students enhance self-leadership and career preparedness.
Internet of services-based business model: a case study in the livestock industry
Authors: Reis Jacqueline Zonichenn , Goncalves Rodrigo Franco , Lage Epaminondas de Souza , Nääs Irenilza de Alencar
Published: June 2021

Purpose

Considering the relevance of innovative business models in the digitally transformed market and the lack of clarity on the internet of services (IoS) contribution for a business model deployment in current literature, this study aims to fill this gap by evaluating a business model that converges to an IoS adoption in a direct sale of free-range eggs from farmers to consumers.

Design/methodology/approach

From the bibliographical research regarding the IoS and business model, the authors developed an IoS-based model framework. The framework has been evaluated in a real business scenario by using a single case study through an interview with the entrepreneur and documental analysis.

Findings

As the main result, a framework with the attributes can be considered a tool for an IoS-based business model deployment. The case study concluded that the business is aligned with the IoS adoption, and the framework presents adherence to it.

Research limitations/implications

The case study was limited to only one company owing to the IoS’s novelty and the lack of correlated business models. Although the case study limits to the agriculture field, the proposed framework may be broadly applied.

Originality/value

Considering that the lack of a comprehensive business model causes new businesses to face challenges, it is relevant bringing up the present case study of the IoS-based business model, which correlates these two subjects, still poorly explored in the scientific literature: IoS and business models.
The effects of leader expectation and coworker pressure on research engagement in higher education: the moderating role of achievement value
Authors: Nguyen Ngoc Lan
Published: June 2021

Purpose

While being largely studied in organizational research, job engagement has rarely been empirically investigated in the context of higher education. In this study, this paper aim to examine the effects of leader performance expectation and coworker pressure on research engagement of lecturers and the moderation of achievement value.

Design/methodology/approach

The authors based the survey on the data collected from public higher educational institutions in Vietnam.

Findings

The findings contribute to the literature of job engagement in higher education from an organizational behavior perspective by explaining the mid-level impacts of departmental factors affecting research engagement.

Originality/value

The authors develop an organizational behavior perspective related to middle-level factors to understand factors influencing one specific research job of lecturers in higher education in a non-Western developing nation.