bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bruno 1 regulates cytoskeleton dynamics and a temporal splicing transition to promote myofibril assembly, growth and maturation inDrosophilaflight muscle
Authors: Nikonova Elena , Canela Grimau Marc , Barz Christiane , Esser Alexandra , Bouterwek Jessica , Roy Akanksha , Gensler Heidemarie , Heß Martin , Straub Tobias , Forne Ignasi , Spletter Maria L. 
Published: June 2023

AbstractMuscles undergo developmental transitions in gene expression and alternative splicing that are necessary to refine sarcomere structure and contractility. CUG-BP and ETR-3-like (CELF) family RNA binding proteins are important regulators of RNA processing during myogenesis that are misregulated in diseases such as myotonic dystrophy (DM1). Here we report a conserved function for Bruno 1 (Bru1, Arrest), a CELF1/2 family homolog inDrosophila, during early muscle myogenesis. Loss of Bru1 in flight muscles results in disorganization of the actin cytoskeleton leading to aberrant myofiber compaction and defects in pre-myofibril formation. Temporally-restricted rescue and RNAi knockdown demonstrate that early cytoskeletal defects interfere with subsequent steps in sarcomere growth and maturation. Early defects are distinct from a later requirement forbru1to regulate sarcomere assembly dynamics during myofiber maturation. We identify an imbalance in growth in sarcomere length and width during later stages of development as the mechanism driving abnormal radial growth, myofibril fusion and the formation of hollow myofibrils inbru1mutant muscle. Molecularly, we characterize a genome-wide transition from immature to mature sarcomere gene isoform expression in flight muscle development that is blocked inbru1mutants. We further demonstrate that temporally restricted Bru1 rescue can partially alleviate hypercontraction in late pupal and adult stages, but it cannot restore myofiber function or correct structural deficits. Our results reveal the conserved nature of CELF function in regulating cytoskeletal dynamics in muscle development, and demonstrate that defective RNA processing due to misexpression of CELF proteins causes wide-reaching structural defects and progressive malfunction of affected muscles that cannot be rescued by late-stage gene replacement.
Metabolic engineering ofCorynebacterium glutamicumfor the production of anthranilate from glucose and xylose
Authors: Mutz Mario , Brüning Vincent , Brüsseler Christian , Müller Moritz-Fabian , Noack Stephan , Marienhagen Jan 
Published: June 2023

AbstractAnthranilate and its derivative aniline are important basic chemicals for the synthesis of polyurethanes as well as various dyes and food additives. Today, aniline is mainly chemically produced from petroleum-derived benzene, but it could be also obtained more sustainably by decarboxylation of the microbially produced shikimate pathway intermediate anthranilate. In this study,Corynebacterium glutamicumwas engineered for the microbial production of anthranilate from a carbon source mixture of glucose and xylose. First, a feedback-resistant 3-deoxy- arabinoheptulosonate-7-phosphate synthase fromE. coli, catalyzing the first step of the shikimate pathway, was functionally introduced intoC. glutamicumto enable anthranilate production. Modulation of the translation efficiency of the genes for the shikimate kinase (aroK) and the anthranilate phosphoribosyltransferase (trpD) improved product formation. Deletion of two genes, one for a putative phosphatase (nagD) and one for a quinate/shikimate dehydrogenase (qsuD), abolished by-product formation of glycerol and quinate. However, the introduction of an engineered anthranilate synthase (TrpEG) unresponsive to feedback inhibition by tryptophan had the most pronounced effect on anthranilate production. Component I of this enzyme (TrpE) was engineered using a biosensor-basedin vivoscreening strategy for identifying variants with increased feedback-resistance in a semi-rational library of TrpE muteins. The final strain accumulated up to 5.9 g/L (43 mM) anthranilate in defined CGXII medium from a mixture of glucose and xylose in bioreactor cultivations. We believe that the constructedC. glutamicumvariants are not only limited to anthranilate production, but could also be suitable for the synthesis of other biotechnologically interesting shikimate pathway intermediates, or any other aromatic compound derived thereof.
A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle
Authors: Hernandez-Hernandez Gonzalo , O’Dwyer Samantha C. , Matsumoto Collin , Tieu Mindy , Fong Zhihui , Yang Pei-Chi , Lewis Timothy J. , Santana L. Fernando , Clancy Colleen E. 
Published: June 2023

AbstractThe function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe anin-silicomodel, which we call the “Hernandez-Hernandez model”, of electrical and Ca2+signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca2+signaling during the development of myogenic tone in arterial blood vessels. Although experimental data suggest that KV1.5 channel currents have similar amplitudes, kinetics, and voltage dependencies in male and female myocytes, simulations suggest that the KV1.5 current is the dominant current regulating membrane potential in male myocytes. In female cells, which have larger KV2.1 channel expression and longer time constants for activation than male myocytes, predictions from simulated female myocytes suggest that KV2.1 plays a primary role in the control of membrane potential. Over the physiological range of membrane potentials, the gating of a small number of voltage-gated K+channels and L-type Ca2+channels are predicted to drive sex-specific differences in intracellular Ca2+and excitability. We also show that in an idealized computational model of a vessel, female arterial smooth muscle exhibits heightened sensitivity to commonly used Ca2+channel blockers compared to male. In summary, we present a new model framework to investigate the potential sex-specific impact of anti-hypertensive drugs.
Differences in Hepatocellular Iron Metabolism Underlie Sexual Dimorphism in Hepatocyte Ferroptosis
Authors: Tao Hui , Dar Hamid Y , Tian Cheng , Banerjee Somesh , Glazer Evan S , Srinivasan Shanthi , Zhu Liqin , Pacifici Roberto , He Peijian 
Published: June 2023

AbstractMales show higher incidence and severity than females in hepatic injury and many liver diseases, but the mechanisms are not well understood. Ferroptosis, an iron-mediated lipid peroxidation-dependent death, plays an important role in the pathogenesis of liver diseases. We determined whether hepatocyte ferroptosis displays gender difference, accounting for sexual dimorphism in liver diseases. Compared to female hepatocytes, male hepatocytes were much more vulnerable to ferroptosis by iron and pharmacological inducers including RSL3 and iFSP1. Male but not female hepatocytes exhibited significant increases in mitochondrial Fe2+and mitochondrial ROS (mtROS) contents. Female hepatocytes showed a lower expression of iron importer transferrin receptor 1 (TfR1) and mitochondrial iron importer mitoferrin 1 (Mfrn1), but a higher expression of iron storage protein ferritin heavy chain 1 (FTH1). It is well known that TfR1 expression is positively correlated with ferroptosis. Herein, we showed that silencing FTH1 enhanced while knockdown of Mfrn1 decreased ferroptosis in HepG2 cells. Removing female hormones by ovariectomy (OVX) did not dampen but rather enhanced hepatocyte resistance to ferroptosis. Mechanistically, OVX potentiated the decrease in TfR1 and increase in FTH1 expression. OVX also increased FSP1 expression in ERK-dependent manner. Elevation in FSP1 suppressed mitochondrial Fe2+accumulation and mtROS production, constituting a novel mechanism of FSP1-mediated inhibition of ferroptosis. In conclusion, differences in hepatocellular iron handling between male and female account, at least in part, for sexual dimorphism in induced ferroptosis of the hepatocytes.
Thanks to repetition, dustbathing detection can be automated combining accelerometry and wavelet analysis
Authors: Fonseca R.G. , Flesia A.G. , Spanevello F.C. , de la Fuente M.V. , Bosch M.C. , Marin R.H. , Barberis L. , Kembro J.M. 
Published: June 2023

AbstractDustbathing is performed by many groups of birds, including Galliformes. It consists of a well-defined orderly sequence of movements. Repetitive changes in body position during dustbathing can be automatically detected through data processing of body mounted accelerometer recordings, specifically the complex Morlet continuous wavelet transform. The approach was tested in 13 adult male Japanese quail(Coturnix japonica) fitted with a backpack containing a triaxial accelerometer and video-recorded during at least 6h. Rhythmicity (period 25-60s) in the y-axis acceleration vector is reflected as large power values, and is associated almost exclusively to dustbathing events. Thus, by implementing a threshold value we detected events automatically with an accuracy of 80% (range 66-100%). We show potential uses for characterizing temporal dynamics (e.g. daily rhythms) of dustbathing and for the assessment of intra- and inter-individual variability over long-term studies, even within large complex environments (e.g. natural environments or breeding facilities).Summary statementWe propose a method for automatically detecting dustbathing (i.e a behavior performed by many groups of birds, including Galliformes) from triaxial accerometer recoding using a wavelet technique.
TOMM40 and TOMM22 of the Translocase Outer Mitochondrial Membrane Complex rescue statin-impaired mitochondrial dynamics, morphology, and mitophagy in skeletal myotubes
Authors: Yang Neil V. , Rogers Sean , Guerra Rachel , Pagliarini David J. , Theusch Elizabeth , Krauss Ronald M. 
Published: June 2023

ABSTRACTBackgroundStatins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated as a cause of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates transcription ofTOMM40andTOMM22, genes that encode major subunits of the translocase of outer mitochondrial membrane (TOM) complex which is responsible for importing nuclear-encoded proteins and maintaining mitochondrial function. We therefore investigated the role ofTOMM40andTOMM22in mediating statin effects on mitochondrial function, dynamics, and mitophagy.MethodsCellular and biochemical assays and transmission electron microscopy were used to investigate effects of simvastatin andTOMM40andTOMM22expression on measures of mitochondrial function and dynamics in C2C12 and primary human skeletal cell myotubes.ResultsKnockdown ofTOMM40andTOMM22in skeletal cell myotubes impaired mitochondrial oxidative function, increased production of mitochondrial superoxide, reduced mitochondrial cholesterol and CoQ levels, disrupted mitochondrial dynamics and morphology, and increased mitophagy, with similar effects resulting from simvastatin treatment. Overexpression ofTOMM40andTOMM22in simvastatin-treated muscle cells rescued statin effects on mitochondrial dynamics, but not on mitochondrial function or cholesterol and CoQ levels. Moreover, overexpression of these genes resulted in an increase in number and density of cellular mitochondria.ConclusionThese results confirm that TOMM40 and TOMM22 are central in regulating mitochondrial homeostasis and demonstrate that downregulation of these genes by statin treatment mediates disruption of mitochondrial dynamics, morphology, and mitophagy, effects that may contribute to statin-induced myopathy.GRAPHICAL ABSTRACT
TheVEGFG-quadruplex forming promoter is repaired via long-patch BER
Authors: Hussen Adil , Kravitz Haley L. , Freudenthal Bret D. , Whitaker Amy M. 
Published: June 2023

AbstractIn response to oxidative damage, base excision repair (BER) enzymes perturb the structural equilibrium of theVEGFpromoter between B-form and G4 DNA conformations, resulting in epigenetic-like modifications of gene expression. However, the mechanistic details remain enigmatic, including the activity and coordination of BER enzymes on the damaged G4 promoter. To address this, we investigated the ability of each BER factor to conduct its repair activity onVEGFpromoter G4 DNA substrates by employing pre-steady-state kinetics assays andin vitrocoupled BER assays. OGG1 was able to initiate BER on double-strandedVEGFpromoter G4 DNA substrates. Moreover, pre-steady-state kinetics revealed that compared to B-form DNA, APE1 repair activity on the G4 was decreased ∼2-fold and is the result of slower product release as opposed to inefficient strand cleavage. Interestingly, Pol β performs multiple insertions on G4 substates via strand displacement DNA synthesis in contrast to a single insertion on B-form DNA. The multiple insertions inhibit ligation of the Pol β products, and hence BER is not completed on theVEGFG4 promoter substrates through canonical short-patch BER. Instead, repair requires the long-patch BER flap-endonuclease activity of FEN1 in response to the multiple insertions by Pol β prior to ligation. Because the BER proteins and their repair activities are a key part of theVEGFtranscriptional enhancement in response to oxidative DNA damage of the G4VEGFpromoter, the new insights reported here on BER activity in the context of this promoter are relevant toward understanding the mechanism of transcriptional regulation.
Wound-Induced Syncytia Outpace Mononucleate Neighbors duringDrosophilaWound Repair
Authors: White James S. , Su Jasmine J. , Ruark Elizabeth M. , Hua Junmin , Shane Hutson M. , Page-McCaw Andrea 
Published: June 2023

ABSTRACTAll organisms have evolved to respond to injury. Cell behaviors like proliferation, migration, and invasion replace missing cells and close wounds. However, the role of other wound-induced cell behaviors is not understood, including the formation of syncytia (multinucleated cells). Wound-induced epithelial syncytia were first reported around puncture wounds in post-mitoticDrosophilaepidermal tissues, but have more recently been reported in mitotically competent tissues such as theDrosophilapupal epidermis and zebrafish epicardium. The presence of wound-induced syncytia in mitotically active tissues suggests that syncytia offer adaptive benefits, but it is unknown what those benefits are. Here, we usein vivolive imaging to analyze wound-induced syncytia in mitotically competentDrosophilapupae. We find that almost half the epithelial cells near a wound fuse to form large syncytia. These syncytia use several routes to speed wound repair: they outpace diploid cells to complete wound closure; they reduce cell intercalation during wound closure; and they pool the resources of their component cells to concentrate them toward the wound. In addition to wound healing, these properties of syncytia are likely to contribute to their roles in development and pathology.
Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in pancreatic beta cells
Authors: Bracey Kai M. , Noguchi Pi’illani , Edwards Courtney , Cario Alisa , Gu Guoqiang , Kaverina Irina 
Published: June 2023

AbstractIn pancreatic islet beta cells, molecular motors use cytoskeletal polymers microtubules as tracks for intracellular transport of insulin secretory granules. Beta-cell microtubule network has a complex architecture and is non-directional, which provide insulin granules at the cell periphery for rapid secretion response, yet to avoid over-secretion and subsequent hypoglycemia. We have previously characterized a peripheral sub-membrane microtubule array, which is critical for withdrawal of excessive insulin granules from the secretion sites. Microtubules in beta cells originate at the Golgi in the cell interior, and how the peripheral array is formed is unknown. Using real-time imaging and photo-kinetics approaches in clonal mouse pancreatic beta cells MIN6, we now demonstrate that kinesin KIF5B, a motor protein with a capacity to transport microtubules as cargos, slides existing microtubules to the cell periphery and aligns them to each other along the plasma membrane. Moreover, like many physiological beta-cell features, microtubule sliding is facilitated by a high glucose stimulus. These new data, together with our previous report that in high glucose sub-membrane MT array is destabilized to allow for robust secretion, indicate that MT sliding is another integral part of glucose-triggered microtubule remodeling, likely replacing destabilized peripheral microtubules to prevent their loss over time and beta-cell malfunction.
Revealing future trajectories in sustainable food production: convergence and openness in the innovation ecosystem
Authors: Panetti Eva , Leone Daniele , Caporuscio Andrea , Pietronudo Maria Cristina 
Published: June 2023

PurposeThis paper aims to explore the evolutionary dynamics of innovation ecosystems in the food industry by adopting both open innovation and convergence approaches to derive practical policy implications to develop impactful innovation ecosystems to promote food production sustainably.Design/methodology/approachStarting from the cutting-edge case of Foodvalley in the Netherlands, the study adopts a backcasting approach to reach a future vision of food ecosystems from a sustainable food production perspective. The authors set the backcasting analysis in four steps: (1) description of the present and trends analysis, (2) selection of trustworthy criteria and goals, (3) development of future images and (4) analysis of how to reach the images.FindingsThe trends analysis has identified three existing innovation fields – protein shift, circular agrifood and food and health – and two strategic directions – convergence and localness decrease. The study reports how a long-term commitment may lead the valley toward a best future scenario.Practical implicationsThe study suggests that policymakers and stakeholders can promote innovation strategies in sustainable food production ecosystems by encouraging collaboration between different sectors, reducing regulatory barriers, attracting innovative actors, and investing in education and training programs. To achieve measurable environmental and social impact outcomes, policies should promote entrepreneurship and create an enabling environment that encourages innovation and risk-taking.Originality/valueThe originality of this paper concerns the backcasting perspective applied to the analysis of the food ecosystem. This approach facilitates the identification of a path direction for successfully managing open innovation and industry convergence toward a desirable future of sustainable food production.
Awareness and adoption of wearable technologies for health and safety management in the Nigerian construction industry
Authors: Ibrahim Kabir , Simpeh Fredrick , Adebowale Oluseyi Julius 
Published: June 2023

PurposeTechnologies have had a positive impact on the construction industry. Technologies such as BIM, automation, augmented and virtual reality, Internet of Things and robotics have been adopted by construction firms to enhance productivity. However, not much research has been done on the awareness and adoption of wearable technologies for health and safety (H&S) management. This paper investigates the level of awareness and adoption of wearable technologies for H&S management in the Nigerian construction industry.Design/methodology/approachA quantitative research method was adopted for the study. An electronic questionnaire format was used as an instrument to collect the data. Both descriptive (mean score) and inferential statistics (Kruskal–Wallis test) were used to analyse the data.FindingsThe results indicate that organisations rarely use H&S wearable devices for H&S management although professionals within the construction industry are somewhat aware of the common H&S wearable devices. The findings further indicate that all 11 variables were perceived as “rarely adopted”, whereas 2 variables were perceived as “aware”, 3 variables as “slightly aware” and the remaining 6 variables as “somewhat aware”.Research limitations/implicationsData were collected from only construction professionals working in government agencies, consultancy firms and grade D contracting firms in Lagos and Abuja. For a broader perspective, a study that expands the number of states and categories of construction firms is recommended.Practical implicationsThe construction industry in Nigeria can use the recommendations to improve H&S management on site. Moreover, the recommendations can contribute to the development of policies to promote the adoption of wearable technologies in construction sites.Originality/valueResearch on wearable technologies, particularly in the Nigerian construction industry, is at the developing stage. With this article, the authors contribute to the body of knowledge in this area of research.
A student’s satisfaction model for an executive education blended learning approach, considering aspects for marketing applications
Authors: Negm Eiman Medhat 
Published: June 2023

Purpose This study investigates the main factors that lead to students’ satisfaction toward executive education blended learning.Design/methodology/approach Merging five theories (consumer satisfaction theory, self-determination theory, investment model, happy-productive student theory and service quality model), the author used quantitative research to develop a model, explaining executive education satisfaction taught in a blended learning approach. Administrated questionnaires were physically distributed in various business universities that offer education to mid-career executives in Egypt. Two hundred and seventy questionnaires were examined through structural equation modeling path coefficient analysis.Findings Results show that satisfaction with executive education in traditional classroom boundaries are due to three internal factors (personal/psychological): self-regulated learning, perceived future financial rewards and perceived ease of course; and two external factors: quality of instructor and course design. When courses are given online, satisfaction is developed due to two internal factors (personal/psychological): self-regulated learning and perceived future financial reward; and one external factor, course design.Practical implications Marketization signifies students as consumers of universities; student’s satisfaction is increasingly important for educational entities to attract and retain students. Thus, this study develops a coherent student’s satisfaction model to better manage and market executive education, leading to students’ contentment in theory and practice.Originality/value Student’s satisfaction has multiple facets that are stochastic as education evolves and develops. The contribution stems from the incorporation of various theories to explain student’s satisfaction of executive education taught in a blended approach: traditional classroom boundaries and digital platforms that offer access to online education. The research extracts significant set of reasons, showing executive education satisfaction is not entirely similar to other education programs; and satisfaction toward blended learning in executive education is not entirely similar to education offered solely online or physically.