bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of Limch1 alternative splicing in skeletal muscle function
Authors: Penna Matthew S. , Rodney George G. , Hu Rong-Chi , Cooper Thomas A. 
Published: October 2022

AbstractPostnatal skeletal muscle development is a highly dynamic period associated with extensive transcriptome remodeling. A significant aspect of postnatal development is widespread alternative splicing changes, required for the adaptation of tissues to adult function. These splicing events have significant implications since the reversion of adult mRNA isoforms to fetal isoforms is observed in forms of muscular dystrophy. LIM and Calponin Homology Domains 1 (LIMCH1) is a stress fiber associated protein that is alternative spliced to generate uLIMCH1, a ubiquitously expressed isoform, and mLIMCH1, a skeletal muscle-specific isoform. mLIMCH1 contains 454 in-frame amino acids which are encoded by six contiguous exons simultaneously included after birth in mouse. The developmental regulation and tissue specificity of this splicing transition is conserved in mice and humans. To determine the physiologically relevant functions of mLIMCH1 and uLIMCH1, CRISPR-Cas9 was used to delete the genomic segment containing the six alternatively spliced exons of LIMCH1 in mice, thereby forcing the constitutive expression of the predominantly fetal isoform, uLIMCH1 in adult skeletal muscle. mLIMCH1 knockout mice had significant grip strength weakness in vivo and maximum force generated was decreased ex vivo. Calcium handling deficits were observed during myofiber stimulation that could explain the mechanism by which mLIMCH1 knockout leads to muscle weakness. Additionally, LIMCH1 is mis-spliced in myotonic dystrophy type 1 with the muscle blind-like (MBNL) family of proteins acting as the likely major regulator of Limch1 alternative splicing in skeletal muscle.
A novel antiviral formulation inhibits SARS-CoV-2 infection of human bronchial epithelium
Authors: Purves Kevin , Haverty Ruth , O’Neill Tiina , Folan David , O’Reilly Sophie , Baird Alan W. , Scholz Dimitri , Mallon Patrick W , Gautier Virginie , Folan Michael , Fletcher Nicola F 
Published: October 2022

AbstractA novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air-liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of in vitro cellular toxicity was detected in ViruSAL treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together these findings highlight the potential for ViruSAL as a novel and potent antiviral for use within clinical and prophylactic settings.
Revealing Pentose Catabolism in Pseudomonas putida
Authors: Park Mee-Rye , Gauttam Rahul , Fong Bonnie , Chen Yan , Lim Hyun Gyu , Feist Adam M. , Mukhopadhay Aindrila , Petzold Christopher J. , Simmons Blake A. , Singer Steven W. 
Published: October 2022

ABSTRACTThe Pseudomonas putida group in the Gammaproteobacteria has been intensively studied for bioremediation and plant growth promotion. Members of this group have recently emerged as promising hosts to convert intermediates derived from plant biomass to biofuels and biochemicals. However, most strains of P. putida cannot metabolize pentose sugars derived from hemicellulose. Here we describe three isolates that provide a broader view of the pentose sugar catabolism in the P. putida group. One of these isolates clusters with the well-characterized P. alloputida KT2440 (strain BP6); the second isolate clustered with plant growth-promoting strain P. putida W619 (strain M2), while the third isolate represents a new species in the group (strain BP8). Each of these isolates possessed homologous genes for oxidative xylose catabolism (xylDXA) and a potential xylonate transporter. Strain M2 grew on arabinose and had genes for oxidative arabinose catabolism (araDXA). A CRISPRi system was developed for strain M2 and identified conditionally essential genes for xylose growth. A glucose dehydrogenase was found to be responsible for initial oxidation of xylose and arabinose in strain M2. These isolates have illuminated inherent diversity in pentose catabolism in the P. putida group and may provide alternative hosts for biomass conversion.Originality-Significance StatementMembers of the Pseudomonas putida group are intensively studied for their role in plant growth promotion and biomass conversion. Despite this interest, the scope of pentose oxidation, key sugars in plant biomass, in this group is not known. Here, we report targeted isolation of members of the P. putida group that grow by xylose and arabinose oxidation. Using a combined genomic and proteomic approach, we identify gene products involved in pentose oxidation and identify conditionally essential genes for xylose oxidation using a CRISPRi gene repression approach. This work describes a targeted isolation and analysis strategy that may applied for many microbial groups of industrial and agricultural interest.
Differential Boric Acid and Water Transport in Type I and Type II Pores of Arabidopsis Nodulin 26-Intrinsic Proteins
Authors: Beamer Zachary G. , Routray Pratyush , Agrawal Rupesh , Li Tian , Gibson Katey M. , Ostrouchov Katherine E. , Smith Jeremy C. , Roberts Daniel M. 
Published: October 2022

AbstractNodulin-26 intrinsic proteins (NIPs) are plant-specific multifunctional aquaporin-like channels that are phylogenetically and structurally segregated into three subfamilies: NIP I, II, and III. Each subfamily has a characteristic selectivity filter sequence (the “aromatic-arginine” region, or ar/R) that controls substrate transport specificity based on steric constraints, hydrophobicity, and the spatial orientation of hydrogen bonding moieties. All three NIP subfamilies transport metalloid hydroxides, both beneficial as well as toxic, but with different selectivities. Here we investigated the B, As, and water selectivity of representative Arabidopsis thaliana NIP I and II proteins as well as their ar/R mutants in transport assays as well as through B complementation analysis in the B sensitive nip5;1 mutant background. All NIP proteins, and their ar/R mutants, showed equal permeability to arsenite, but showed differences in boric acid and aquaporin activities that was linked to the amino acid at the helix 2 (H2) position of the ar/R filter (Ala for NIP II and Trp for NIP I). The presence of an alanine at this position in NIP II proteins enhances boric acid permeability and drastically reduces the aquaporin/water permeability of the channel. A NIP II structural model generated from the AlphaFold2 resource and evaluated by MD simulation shows that the alanine results in a wider ar/R pore that accommodates the trigonal boric acid molecule and may allow gating of the pore in a manner that affects water permeability. In contrast, NIP I proteins adopt a more classical aquaporin/glyceroporin arrangement in the ar/R that allows metalloid permeability, although with greater selectivity, as well as permeation by water.
Foxg1 regulates translation of neocortical neuronal genes, including the main NMDA receptor subunit gene,Grin1
Authors: Artimagnella Osvaldo , Esposito Mauro , Maftei Elena Sabina , Sanges Remo , Mallamaci Antonello 
Published: October 2022

ABSTRACTMainly known as a transcription factor patterning the rostral brain and governing its histogenesis, Foxg1 has been also detected outside the nucleus, however biological meaning of that has been only partially clarified. Here, moving from Foxg1 expression in cytoplasm of neocortical neurons, we investigated its implication in translational control. We documented an impact of Foxg1 on ribosomal recruitment ofGrin1-mRNA, encoding for the main subunit of NMDA receptor. Next, we showed that Foxg1 increases Grin1 protein level by enhancing translation of its mRNA, while not increasing its stability. Such enhancement was associated to augmented translational initiation and, possibly, polypeptide elongation. Molecular mechanisms at the basis of this activity included Foxg1 interaction with Eif4e and Eef1d as well as withGrin1-mRNA. Besides, we found that, within murine neocortical cultures, Grin1de novosynthesis undergoes a prominent and reversible, homeostatic regulation and Foxg1 is instrumental to that. Finally, through TRAP-seq, we discovered that Foxg1 is implicated in the translation of hundreds of neuronal genes at the level of ribosome engagement and progression. All that points to Foxg1 as a key effector, crucial to multi-scale temporal tuning of neocortical pyramid activity, an issue with profound physiological and neuropathological implications.
Dynamic subcellular localization of sodium-bicarbonate cotransporter NBCn1/SLC4A7 to plasma membrane, centrosomes, spindle, and primary cilia
Authors: Severin Marc , Pedersen Emma Lind , Borre Magnus Thane , Axholm Ida , Christiansen Frederik Bendix , Ponniah Muthulakshmi , Czaplinska Dominika , Larsen Tanja , Pardo Luis Angel , Pedersen Stine Falsig 
Published: October 2022

ABSTRACTFinely tuned regulation of transport protein localization is vital for epithelial function. Sodium-bicarbonate co-transporter NBCn1 (SLC4A7) is a key contributor to epithelial pH homeostasis, yet the regulation of its subcellular localization is not understood. Here, we show that a predicted N-terminal β-sheet and short C-terminal α-helical motif are essential for NBCn1 plasma membrane localization in epithelial cells. This localization was abolished by cell-cell contact disruption, and co-immunoprecipitation (co-IP) and proximity ligation (PLA) revealed NBCn1 interaction with E-cadherin and DLG1, linking the transporter to adherens junctions and the Scribble complex. NBCn1 also interacted with RhoA and localized to lamellipodia and filopodia in migrating cells. Finally, analysis of localization of native and GFP-tagged NBCn1, subcellular fractionation, co-IP of NBCn1 with Arl13B and CEP164, and PLA of NBCn1 and tubulin in mitotic spindles led to the surprising conclusion that NBCn1 additionally localizes to the centrosome and primary cilium in non-dividing, polarized epithelial cells, and to spindle, centrosome and midbodies during mitosis. We propose that NBCn1 traffics between lateral junctions, leading edge, and cell division machinery in Rab11 endosomes, adding new insight to the role of NBCn1 in cell cycle progression.Summary statementWe unravel molecular determinants of plasma membrane localization of the Na+,HCO3− cotransporter NBCn1 and discover that NBCn1 also localizes to centrosomes, spindle, midbody and primary cilia, likely cycling between these compartments.
Discovery and biosynthesis of imidazolium antibiotics from a probiotic Bacillus licheniformis
Authors: Ham Song Lim , Lee Tae Hyun , Kim Kyung Jun , Kim Jung Ha , Hwang Su Jung , Lee Sun Ho , Lee Wonsik , Lee Hyo Jong , Kim Chung Sub 
Published: October 2022

AbstractAntibiotic resistance is one of the world’s most urgent public health problems and therefore novel antibiotics to kill drug-resistant bacteria are desperately needed. So far, natural product-derived small molecules have been the major sources for new antibiotics. Here we describe a family of antibacterial metabolites isolated from a probiotic bacterium Bacillus licheniformis. Cross-streaking assay followed by activity-guided isolation yielded a novel antibacterial metabolite bacillimidazole G, which possesses a rare imidazolium ring in the structure, showing MIC values of 0.7–2.6 μg/mL against human pathogenic Gram-positive and Gram-negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and a lipopolysaccharide(LPS)-lacking Acinetobacter baumannii ΔlpxC. Bacillimidazole G also lowered MICs of colistin, a Gram-negative antibiotic, up to 8-fold against wild-type E. coli MG1655 and Acinetobacter baumannii. We propose biosynthetic pathway of the characterized metabolites based on the precursor-feeding studies, chemical biological approach, biomimetic total synthesis, and biosynthetic genes knockout method.TOC/Abstract Graphic
Chromatin architecture and cis-regulatory landscape of the DACT2-SMOC2 locus in the developing synovial joint
Authors: Nowosad Karol , Hordyjewska-Kowalczyk Ewa , Malesa Aneta , Odrzywolski Adrian , Brouwer Rutger W. W. , Kolovos Petros , Boltsis Ilias , Birkhoff Judith C. , van IJcken Wilfred F. J. , Grosveld Frank G. , Conidi Andrea , Huylebroeck Danny , Tylzanowski Przemko 
Published: October 2022

AbstractBackgroundSynovial joints form in several steps, starting with the formation of an interzone, a condensation of mesenchymal cells at the sites of prospective joints. Despite the identification of multiple factors essential for formation of interzone, little is known about the regulation of their spatio-temporal gene expression during that process in limb development. Here, we investigated the cis- regulatory landscape of the Wnt-modulator encoding genes DACT2 and SMOC2, both expressed in the forming joint interzone.ResultsMechanically collected interzone and phalange samples, respectively, from chick embryos were found to express acknowledged marker genes (GDF5 and MATN1), as well as DACT2 and SMOC2. Using Targeted Chromatin Capture (T2C) we characterized the 3D chromatin structure of a ~3.45 Mb-long region encompassing DACT2 and SMOC2, which revealed differences at sub-TAD level between interzones and phalange. We identified candidate enhancers (CEs) based on H3-histone marks (H3K427ac and H3K4me1) located in close proximity to the promoters of DACT2 and SMOC2, and further documented these CEs in a zebrafish enhancer assay.ConclusionsOur approach yields new insight into the regulation, in dynamic chromatin context, of two Wnt-signaling modulatory genes during synovial joint induction.
Inventive redesign for automatic assembly in the household appliances industry
Authors: Bianchini Augusto , Ceruti Alessandro , D’Anniballe Andrea , Rossi Jessica , Zompi Giorgio 
Published: October 2022

Purpose
In the redesign process of assembly components that need adaptation to robotic assembly, designers can find support from structured methodologies for innovation, such as the theory of inventive problem solving (TRIZ). This paper aims to illustrate the authors’ methodology for redesigning gas hobs components for adaptation to robotic assembly.

Design/methodology/approach
A designer approaching a redesign task of an assembly component of any kind for adaptation to robotic assembly must consider, first of all, the features and limitations of existing robotic assembly systems; the generation of new design ideas that best fit the requirements may result to be a very challenging task. Here, the TRIZ methodology has proven useful for generating design ideas and finding the best solution.

Findings
The authors’ methodology approaches the challenges of redesign tasks for robotic assembly adaptation, which exploits knowledge of automatic and robotic assembly systems and the TRIZ method for innovation; it has proven useful in the redesign, checks and prototyping of gas hobs components.

Originality/value
This paper shows how the TRIZ methodology can be integrated into the redesign process and its impact on an industrial environment. The work’s main value is to provide a set of steps to help the designers change their design components approach that is necessary but not still implemented to optimize the use of the automation.
A knowledge-based real-time scheduling system for steam turbine assembly under CPS environment
Authors: Wang Teng , Hu Xiaofeng , Zhang Yahui 
Published: October 2022

Purpose
Steam turbine final assembly is a dynamic process, in which various interference events occur frequently. Currently, data transmission relies on oral presentation, while scheduling depends on the manual experience of managers. This mode has low information transmission efficiency and is difficult to timely respond to emergencies. Besides, it is difficult to consider various factors when manually adjusting the plan, which reduces assembly efficiency. The purpose of this paper is to propose a knowledge-based real-time scheduling system under cyber-physical system (CPS) environment which can improve the assembly efficiency of steam turbines.

Design/methodology/approach
First, an Internet of Things based CPS framework is proposed to achieve real-time monitoring of turbine assembly and improve the efficiency of information transmission. Second, a knowledge-based real-time scheduling system consisting of three modules is designed to replace manual experience for steam turbine assembly scheduling.

Findings
Experiments show that the scheduling results of the knowledge-based scheduling system outperform heuristic algorithms based on priority rules. Compared with manual scheduling, the delay time is reduced by 43.9%.

Originality/value
A knowledge-based real-time scheduling system under CPS environment is proposed to improve the assembly efficiency of steam turbines. This paper provides a reference paradigm for the application of the knowledge-based system and CPS in the assembly control of labor-intensive engineering-to-order products.
Foreign direct investment and stock market development in Nepal
Authors: Khatri Chettri Keshab , Bhattarai Jeevan Kumar , Gautam Ramji 
Published: October 2022

PurposeThe purpose of this paper is to investigate the impact of foreign direct investment (FDI) on the stock market development in Nepal.Design/methodology/approachThe study used Johansen cointegration approach to determine long-run relationship and VEC Granger causality test to check the causal relations between the variables. The sample covered annual time-series data for the period 1996–2020.FindingsThe results suggest that FDI plays significant positive role in the stock market development in the long-run but inversely affect in the short-run. Unidirectional causality running from FDI to stock market development is observed in the long-run and bidirectional in the short-run. There is an insignificant positive relationship between exchange rate and FDI in the short-run. Banking sector development complements stock market development in the short-run but act as a substitute in the long-run. The statistically negative coefficient of exchange rate imply that the appreciation of the home currency encourage the development of the stock market in the long-run.Originality/valueThe positive and statistical coefficients of cointegration results indicate that FDI complements the development of stock market in Nepal in the long-run. Furthermore, the depreciation of the domestic currency may potentially contribute to the foreign direct investments in Nepal.
Education skills for digital age toward sustainable development – analysis and future directions
Authors: AlDhaen Esra 
Published: October 2022

Purpose
This study provides an insight on education skills for digital age that could be considered by higher education institutions (HEIs) toward sustainable development. This study summarizes academic literature and provides a proposal for integrating a set of educational skills toward United Nations Sustainable Development Goals that are aligned with competencies mapped with international practices delivered by qualification frameworks. This paper will act as guiding tool for academics while revising or developing academic curricular for Business Education Sector.

Design/methodology/approach
This paper uses a combination of academic literature, published practices of HEIs and policy/regulatory standards as well as academic frameworks used as drivers for implementing educational skills for sustainable development.

Findings
HEIs need to rethink its curricular design and revisit the graduate attributes in sync with set of evaluation mechanisms to assess key educational skills for digital age and sustainable development to create a societal impact particularly in Business Education Sector with the focus on interdisciplinary for digital age including technology and management skills.

Research limitations/implications
The method used is exploratory. Future research could be developed with a structured approach to validate the findings.

Practical implications
HEIs could use the proposed set of educational skills for digital age to be inculcated within the curricular of business education sector, at policymaking level HEIs may revisit their current strategies and include different policies and procedures to assess the impact of integrating key educational skills for digital age skills toward sustainable development.

Social implications
Student, parents, employers will have better understanding of expected education skills for digital age toward sustainable development which will support learning progression and career pathways.

Originality/value
Little research has been conducted on the impact of education skills for digital age toward sustainable development in line with competencies related to national framework, the outcome of this study provides original contribution to support HEIs adaptation.
Leveraging coaching as an instrument for training transfer: a case of learners in a Fintech Firm
Authors: Dixit Ramnath , Sinha Vinita 
Published: October 2022

Purpose
The purpose of this case study is to emphasize the effectiveness of coaching as an instrument to drive transfer of training of behavioral skills disseminated during training programs back at the workplace.

Design/methodology/approach
Insights were collected through qualitative semi-structured in-depth interviews with learners, followed by a thematic analysis of the interview transcripts.

Findings
The findings of this study revealed promising results with the use of coaching as a medium to facilitate workplace training transfer for learners. The learners also informed a positive experience on account of “personalized touch” experienced during the course of coaching sessions for posttraining application of skills and knowledge.

Practical implications
This study offers incisive information in the domain of training transfer through the effective use of workplace coaching in a posttraining environment.

Social implications
Coaching as a training transfer tool has the ability to provide the necessary impetus to application of behavioral trainings across organizations and institutions, thus encouraging learners to implement what they learn during trainings.

Originality/value
This study is novel on account of its applicability in ensuring successful learning transfer through coaching. The insights from this study have replicability in diverse industries and have the potential to deliver superior results in organizational training transfer.