bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interdependent regulation of alternative splicing by SR and hnRNP proteins
Authors: Holmes Megan E. , Hertel Klemens J. 
Published: August 2024

AbstractAlternative pre-mRNA splicing is a combinatorial process involving SR and hnRNP splicing factors. These proteins can silence or enhance splicing based on their expression levels and binding positions. To better understand their combinatorial and interdependent regulation, computational analyses were performed using HepG2 and K562 cell knockdown and binding datasets from the ENCODE Project. Analyses of diMerential splicing for 6 SR proteins and 13 hnRNP knockdowns revealed statistically significant exon overlap among most RBP combinations, albeit at diMerent levels. Neither SR proteins nor hnRNPs showed strong preferences for collaborating with specific RBP classes in mediating exon inclusion. While SRSF1, hnRNPK, and hnRNPC stand out as major influencers of alternative splicing, they do so predominantly independent of other RBPs. Meanwhile, minor influencers of alternative splicing such as hnRNPAB and hnRNPA0 predominantly regulate exon inclusion in concert with other RBPs, indicating that inclusion can be mediated by both single and multiple RBPs. Interestingly, the higher the number of RBPs that regulate the inclusion of an exon, the more variable exon inclusion preferences become. Interdependently regulated exons are more modular and have diMerent physical characteristics such as reduced exon length compared to their independent counterparts. A comparison of RBP interdependence between HepG2 and K562 cells provides the framework that explains cell-type-specific alternative splicing. Our study highlights the importance of the interdependent regulation of alternative exons and identifies characteristics of interdependently regulated exons that diMer from independently regulated exons.
Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing
Authors: Shvedova Maria , Thanapaul Rex Jeya Rajkumar Samdavid , Ha Joy , Dhillon Jannat , Shin Grace H , Crouch Jack , Gower Adam C , Gritli Sami , Roh Daniel S 
Published: August 2024

AbstractSenescent cells (SnC) accumulate in aging tissues, impairing their ability to undergo repair and regeneration following injury. Previous research has demonstrated that targeting tissue senescence with senolytics can enhance tissue regeneration and repair by selectively eliminating SnCs in specific aged tissues. In this study, we focused on eliminating SnC skin cells in aged mice to assess the effects on subsequent wound healing. We applied ABT-263 directly to the skin of 24-month-old mice over a 5-day period. Following topical ABT-263, aged skin demonstrated decreased gene expression of senescent markers p16 and p21, accompanied by reductions in SA-β-gal and p21-positive cells compared to DMSO controls. However, ABT-263 also triggered a temporary inflammatory response and macrophage infiltration in the skin. Bulk RNA sequencing of ABT-263-treated skin revealed prompt upregulation of genes associated with wound healing pathways, including hemostasis, inflammation, cell proliferation, angiogenesis, collagen synthesis, and extracellular matrix organization. Aged mice skin pre-treated with topical ABT-263 exhibited accelerated wound closure. In conclusion, topical ABT-263 effectively reduced several senescence markers in aged skin, thereby priming the skin for improved subsequent wound healing. This enhancement may be attributed to ABT-263-induced senolysis which in turn stimulates the expression of genes involved in extracellular matrix remodeling and wound repair pathways.
Functional Regrowth of Norepinephrine Axons in the Adult Mouse Brain Following Injury
Authors: Cooke Patrick , Linden David J. 
Published: August 2024

AbstractIt is widely believed that axons in the central nervous system of adult mammals do not regrow following injury. This failure is thought, at least in part, to underlie the limited recovery of function following injury to the brain or spinal cord. Some studies of fixed tissue have suggested that, counter to dogma, norepinephrine (NE) axons regrow following brain injury. Here, we have used in vivo two-photon microscopy in layer 1 of the primary somatosensory cortex in transgenic mice harboring a fluorophore selectively expressed in NE neurons. This protocol allowed us to explore the dynamic nature of NE axons following injury with the selective NE axon toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Following DSP4 treatment, NE axons were massively depleted and then slowly and partially recovered their density over a period of weeks. This regrowth was dominated by new axons entering the imaged volume. There was almost no contribution from local sprouting from spared NE axons. Regrown axons did not appear to use either the paths of previously lesioned NE axons nor NE axons that were spared and survived DSP4 treatment as a guide. To measure NE release, GCaMP8s was selectively expressed in neocortical astrocytes and startle-evoked, NE receptor-mediated Ca2+transients were measured. These Ca2+transients were abolished soon after DSP4 lesion but returned to pre-lesion values after 3-5 weeks, roughly coincident with NE axon regrowth, suggesting that the regrown NE axons are competent to release NE in response to a physiological stimulus in the awake mouse.Significance StatementIt is widely believed that axons in the central nervous system (CNS) of adult mammals are incapable of regrowth following injury. Counter to this notion, we describe the structural and functional regrowth of norepinephrine axons following brain injury in the adult mouse. These results extend previous studies describing the regenerative capacity of serotonin axons in the CNS by demonstrating axon regrowth of another neuronal subtype and the capacity of these regrown axons to respond normally to an external physiological stimulus. Taken together, these findings suggest that monoaminergic neurons share a common program for axon regrowth. Elucidation of this molecular and genetic program could inform therapies to promote axon regrowth and functional recovery following injury to the CNS.
High-throughput affinity measurements of direct interactions between activation domains and co-activators
Authors: DelRosso Nicole , Suzuki Peter H. , Griffith Daniel , Lotthammer Jeffrey M. , Novak Borna , Kocalar Selin , Sheth Maya U. , Holehouse Alex S. , Bintu Lacramioara , Fordyce Polly 
Published: August 2024

AbstractSequence-specific activation by transcription factors is essential for gene regulation1,2. Key to this are activation domains, which often fall within disordered regions of transcription factors3,4and recruit co-activators to initiate transcription5. These interactions are difficult to characterize via most experimental techniques because they are typically weak and transient6,7. Consequently, we know very little about whether these interactions are promiscuous or specific, the mechanisms of binding, and how these interactions tune the strength of gene activation. To address these questions, we developed a microfluidic platform for expression and purification of hundreds of activation domains in parallel followed by direct measurement of co-activator binding affinities (STAMMPPING, for Simultaneous Trapping of Affinity Measurements via a Microfluidic Protein-Protein INteraction Generator). By applying STAMMPPING to quantify direct interactions between eight co-activators and 204 human activation domains (>1,500Kds), we provide the first quantitative map of these interactions and reveal 334 novel binding pairs. We find that the metazoan-specific co-activator P300 directly binds >100 activation domains, potentially explaining its widespread recruitment across the genome to influence transcriptional activation. Despite sharing similar molecular properties (e.g.enrichment of negative and hydrophobic residues), activation domains utilize distinct biophysical properties to recruit certain co-activator domains. Co-activator domain affinity and occupancy are well-predicted by analytical models that account for multivalency, andin vitroaffinities quantitatively predict activation in cells with an ultrasensitive response. Not only do our results demonstrate the ability to measure affinities between even weak protein-protein interactions in high throughput, but they also provide a necessary resource of over 1,500 activation domain/co-activator affinities which lays the foundation for understanding the molecular basis of transcriptional activation.
DIAMOND2GO: A rapid Gene Ontology assignment and enrichment tool for functional genomics
Authors: Golden Christopher , Studholme David J. , Farrer Rhys A. 
Published: August 2024

AbstractDIAMOND2GO (D2GO) is a new toolset to rapidly assign Gene Ontology (GO) terms to genes or proteins based on sequence similarity searches. D2GO uses DIAMOND for alignment, which is 100 - 20,000 X faster than BLAST. D2GO leverages GO- terms already assigned to sequences in the NCBI non-redundant database to achieve rapid GO-term assignment on large sets of query sequences. In one test, 98% of the 130,184 predicted human proteins and splice variants were assigned GO-terms (>2 million in total) in < 13 minutes on a laptop computer. D2GO also features the ability to perform enrichment analysis between subsets of data, thereby allowing rapid assignment and detection of over-represented GO-terms in novel sets of sequences. D2GO is freely available under the MIT licence fromhttps://github.com/rhysf/DIAMOND2GO
A criterion characterizing accumulated neurotoxicity of Aβ oligomers in Alzheimer’s disease
Authors: Kuznetsov Andrey V. 
Published: August 2024

AbstractThe paper develops a criterion to quantify the accumulated neurotoxicity of Aβ oligomers in Alzheimer’s disease (AD). Accumulated neurotoxicity is determined by integrating the concentration of Aβ oligomers within the control volume over time. In the scenario of a low rate of free Aβ oligomer deposition into senile plaques and dysfunctional degradation machinery, resulting in an infinitely long half-life of Aβ monomers and aggregates, the obtained analytical solution reveals a quadratic relationship between accumulated neurotoxicity and time. This suggests that initially, neurotoxicity increases slowly but accelerates as time progresses. This could help to understand the prolonged delay in the onset of AD symptoms. Furthermore, as the model indicates that accumulated neurotoxicity increases with the duration of the aggregation process, it implies that if the protein degradation system is compromised, the onset of AD becomes unavoidable. Eventually, neuronal death is only a question of time. The only way to prevent this outcome is to ensure that the degradation machinery for Aβ peptides and their aggregates remains functional. A threshold value of accumulated neurotoxicity is suggested. The developed theory suggests that if this value is exceeded, nearby neurons will die. The progression of accumulated neurotoxicity over time is analyzed. An S-shaped growth pattern as the half-deposition time of Aβ aggregates into senile plaques increases is revealed. Additionally, the sensitivity of accumulated neurotoxicity to different parameter values is examined.
Temperature fluctuations influence predictions of landscape-scale patterns of spruce budworm defoliation
Authors: Black Emily N. , Pureswaran Deepa S. , Marshall Katie E. 
Published: August 2024

AbstractThe geographic range of insects is heavily influenced by their tolerance for stressful abiotic conditions, including temperature. While many studies on insect thermal tolerance consider temperature exposure, the frequency of temperature exposures is emerging as an important and generally overlooked driver of insect fitness. The (eastern) spruce budworm (Choristoneura fumiferana) is a lepidopteran defoliating pest of coniferous forests across Canada whose outbreaks lead to large-scale tree mortality. Studies have shown the frequency of temperature fluctuations affects spruce budworm overwintering survival rates in the laboratory; however, the influence of temperature fluctuations on spruce budworm defoliation at the landscape level has not been investigated. We used a species distribution model approach to evaluate the influence of temperature fluctuations on the distribution and severity of spruce budworm defoliation. We combined publicly available maps of spruce budworm outbreaks between 2006-2016 in Quebec with climate, temperature fluctuation, and forest composition predictors to train a species distribution model. Our model evaluated how predictors influence spruce budworm defoliation, and compared these results to a model trained without temperature fluctuations. Additionally, we predicted future spruce budworm defoliation under 2041-2070 climate change conditions using the models trained with and without temperature fluctuation predictors and compared the results to determine the effect of temperature fluctuations on future defoliation predictions. We found that model performance improved with the inclusion of temperature fluctuation predictors, and these predictors ranked highly, relative to predictors in other categories. The model trained with temperature fluctuation predictors also predicted vastly different defoliation distribution and severity across Quebec and Ontario than the model trained without them under climate change conditions. These results reveal the previously overlooked importance of temperature fluctuations on landscape-scale spruce budworm defoliation and support their inclusion in insect species distribution models.
Unveiling success factors for implementing and sustaining circular economy practices in small and medium-sized firms: multi-level perspective
Authors: Ahmadov Tarlan , Durst Susanne , Gerstlberger Wolfgang 
Published: August 2024

Purpose
This study aims to identify and understand critical success factors for implementing and sustaining circular economy (CE) practices in manufacturing small and medium-sized enterprises (SMEs). More precisely, this study examines the complex interplay between micro-, meso- and macro-level success factors that are deemed critical for implementing and sustaining CE practices.

Design/methodology/approach
The study is based on a two-stage methodology that combines a comprehensive literature review and an interview study with 12 Swedish manufacturing SMEs that implement CE practices.

Findings
The study identifies and categorizes success factors for implementing and sustaining CE practices in manufacturing SMEs. Based on the findings, a holistic framework is proposed that takes into account multiple perspectives, i.e. at the micro, meso and macro levels. This framework enables a deeper understanding and thus a more nuanced discussion of the complexity inherent in the transition to a CE from the perspective of manufacturing SMEs.

Originality/value
This study contributes to the growing body of research on CE transition. By focusing on SMEs in particular, the paper adds the needed diversity to the study of CE practices and influencing factors at different levels.
A systematic review of information and communication technologies (ICTs) on student motivation: researchers’ reflections on a selected higher education institution (HEIs)
Authors: Nhleko Nhlanhla Mzameleni , Aroba Oluwasegun Julius , Chisita Collence Takaingenhamo 
Published: August 2024

Purpose
Through the review of several journal articles on the adoption of information and communication technologies (ICTs) and how it impacts students’ motivation to continue with their studies or to drop out of their academic program, this study aims to review the literature on the impact of ICTs on student motivation at a university.

Design/methodology/approach
This paper is based on a systematic literature review steered by the PRISMA guidelines. This paper uses both Durban University of Technology subscription-based and publicly available papers. The research articles examined were published between 2018 and 2023 in Scopus, Web of Science and ScienceDirect.

Findings
Reviewed literature bespeaks that ICTs can increase student motivation by enhancing interactive, engaging and individualized learning. Digital technologies that engage students and offer a more engaging learning environment include instructional apps, online simulations and multimedia content. Using ICTs may be useful in lowering university dropout rates.

Originality/value
The systematic review yielded valuable insights for both academic research and real-world applications in education regarding the Durban University of Technology. The study offers a comprehensive analysis of the nexus between ICTs and student motivation.
A conceptual soft skills competency framework for enhancing graduate intern employability
Authors: Bisschoff Zelda S. , Massyn Liezel 
Published: August 2024

PurposeThe paper aims to close a literature gap by proposing a comprehensive conceptual soft skills competency framework for enhancing graduate intern employability through the cultivation of employability capital.Design/methodology/approachThe study employed a theoretical inquiry and delved into the existing literature on employability, soft skills competencies and employability capital to establish a comprehensive foundation to formulate the conceptual framework. A content analysis of existing empirical studies was conducted to derive a generic list of employers’ required soft skills. A Delphi technique was employed to harness expert consensus and insights into the derived framework.FindingsEmployability capital can be cultivated in the setting of work-integrated learning programmes and synergised through emotional and social intelligence interventions to enhance soft skills competency and graduate employability.Research limitations/implicationsThe soft skills identified may overlook other important skills required by employers. Increasing participation in the Delphi study could yield additional valuable insights. Validation of the framework is needed in practical settings to understand its effectiveness and applicability to real-world organisational needs.Practical implicationsThis study significantly enhances understanding of the role of employability capital in soft skills competency development and graduate employability through work-integrated learning programs and self-development. In addition, the framework has the potential to positively impact the employer-employee relationship.Originality/valueThe key theoretical contribution is a soft skill development framework that offers employers and graduates a means to identify and address deficiencies through WIL and self-development.
Learning designs that empower: navigating sandbox data science at the intersection of computing, big data and social media
Authors: Barany Amanda , Scarola Andi Danielle , Acquah Alex , Reza Sayed Mohsin , Johnson Michael A. , Walker Justice 
Published: August 2024

Purpose
There is a need for precollege learning designs that empower youth to be epistemic agents in contexts that intersect burgeoning areas of computing, big data and social media. The purpose of this study is to explore how “sandbox” or open-inquiry data science with social media supports learning.

Design/methodology/approach
This paper offers vignettes from an illustrative youth study case that highlights the pedagogical prospects and obstacles tied to designing for open-ended inquiry with computational data science to access or “scrape” Twitter/X. The youth case showcases how social media can be taken up productively and in ways that facilitate epistemological agency, an approach where individuals actively shape understanding and knowledge-creation processes, highlighting the potentially transformative impact this approach might have in empowering learners to engage productively.

Findings
The authors identify three key affordances for learning that emerged from the illustrative case: (1) flexible opportunities for content-specific domain mastery, (2) situated inquiry that embodies next-generation science practices and (3) embedded computational skill development. The authors discuss these findings in relation to contemporary education needs to broaden participation in data science and computing.

Originality/value
To address challenges in current data science education associated with supporting sustained and productive engagement in computing-based data science, the authors leverage a “sandbox” approach – an original pedagogical framework to support open inquiry with precollege groups. The authors demonstrate how “big data” drawn from social media with high school-aged youth supports learning designs and outcomes by emphasizing learner interests and authentic practice.
Low-SAPS additives for lubrication in next-generation vehicles
Authors: He Xin , Chretien Christelle , Weathers Thomas , Burel Celine , Gody Guillaume , Back Olivier 
Published: August 2024

Purpose
The purpose of this study is to create sustainable additives for future vehicles, characterized by low levels of sulfated ash, sulfur and phosphorus (SAPS) or even SAPS-free alternatives. These newly developed additives must not only match or outperform the current commercial benchmarks in terms of tribological performance, but also align with the emerging sustainability trends. It is anticipated that this innovative technology will yield promising outcomes in the realm of hybrid and electric vehicles.

Design/methodology/approach
This research primarily focused on chemical synthesis, performance evaluation and characterizations. These aspects were studied through collaboration between Syensqo, Southwest Research Institute (the USA) and the Lab of the Future in France. The data was generated and analyzed by a team of research scientists, internship students and technical specialists.

Findings
Two types of additives have been specifically designed and synthesized in accordance with sustainable requirements. Both technologies have exhibited exceptional frictional and wear-resistant properties. Moreover, the leading candidates exhibit a lower rate of copper corrosion, stable electric conductivity and outstanding thermal stability when compared to commercial benchmarks. This study is expected to open a new research avenue for developing next-generation additives for lubricants, with wide potential applications including hybrid electric vehicle and electric vehicle markets.

Originality/value
In the current lubricant market, there is a lack of effective low-SAPS or SAPS-free additives. This research aims to address this gap by designing sustainable additives for next-generation vehicles that not only meet specific requirements but also maintain optimal lubrication performance.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-01-2024-0033/