bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entanglement of AGE-RAGE axis in cardiac pathosis
Authors: Wasim Rufaida , Mahmood Tarique , Siddiqui Mohammed Haris , Wani Tanveer A. , Zargar Seema , Singh Aditya , Mohammed Saad , Ahsan Farogh , Wahajuddin Muhammad 
Published: July 2023

AbstractCardiovascular diseases are the major cause of death globally. Acute coronary syndrome is one of numerous cardiovascular illnesses, including advanced glycation end products (AGEs), which play an instrumental part in their development and progression. A substance with multiple pleiotropic characteristics is rosuvastatin. This study examined the cardioprotective effects of rosuvastatin in isoproterenol-induced myocardial injury, as well as the alterations in advanced glycation end products and their roles in cardiac damage. Rosuvastatin (10 mg/kg, orally) was given to male rats daily for 4 weeks, and on the 29th and 30th days, isoproterenol (85 mg/kg, subcutaneously) was administered to cause cardiac damage. Rats were euthanised on the 31st day, and various samples were collected for examination. Administration of isoproterenol increased cardiac mass, levels of cardiac damage markers, lipid oxidation, and collagen content in the heart. Additionally, it reduced the activities of SOD, CAT, GST, GR, and all other antioxidants. Additionally, isoproterenol raises levels of inflammatory markers including TNF-α and IL-6. It has been observed that advanced glycation end products rise along with heart injury. The AGE-RAGE cascade also messes with the injured heart’s echocardiogram. Additionally, histopathological alterations were noticed. According to the study, rosuvastatin has cardioprotective effects on the experimental model, which were supported by an array of physical, biochemical, and histological characteristics.SummaryThis study examined the cardioprotective effects of rosuvastatin in isoproterenol-induced myocardial injury, as well as the alterations in advanced glycation end products and their roles in cardiac damage. According to the study, rosuvastatin has cardioprotective effects on the experimental model, which were supported by a number of physiological, biochemical, and histological characteristics. By showing how the functional AGE/RAGE axis is inhibited following rosuvastatin medication, this work provides an etiologic theory involving rosuvastatin therapy in heart injury. These findings may also have practical significance since they highlight the intriguing possibility that rosuvastatin-induced modulation of AGE-RAGE signalling may represent a unique therapeutic approach for the prevention and treatment of other cardiovascular diseases.
Neural mechanism underlying preview effects and masked priming effects in visual word processing
Authors: Huang Xin , Wong Brian W. L. , Ng Hezul Tin-Yan , Sommer Werner , Dimigen Olaf , Maurer Urs 
Published: July 2023

AbstractTwo classic experimental paradigms – masked repetition priming and the boundary paradigm – have played a pivotal role in understanding the process of visual word recognition. Traditionally, these paradigms have often been employed by different communities of researchers, with their own long-standing research traditions. Nevertheless, a review of the literature suggests that the brain-electric correlates of word processing established with both paradigms may show interesting similarities, in particular with regard to the location, timing, and direction of N1 and N250 effects. However, as of yet, no direct comparison has been undertaken between both paradigms. In the current study, we used combined eye-tracking/EEG to perform such a within-subject comparison using the same materials (single Chinese characters) as stimuli. Our results show the typical early repetition effects of N1 and N250 for both paradigms. However, repetition effects in N250 (i.e., a reduced negativity following identical-word primes/previews as compared to different-word primes/previews) were larger in the boundary paradigm than with masked priming. For N1 effects, repetition effects were similar across the two paradigms showing a larger N1 after repetitions as compared to alternations. Therefore, the results indicate that at the neural level, a briefly presented and masked foveal prime produces qualitatively similar facilitatory effects on visual word recognition as a parafoveal preview before a saccade, although such effects appear to be stronger in the latter case.
An integrative proteomics approach identifies tyrosine kinase KIT as a novel therapeutic target for SPINK1-positive prostate cancer
Authors: Manzar Nishat , Khan Umar Khalid , Goel Ayush , Carskadon Shannon , Gupta Nilesh , Palanisamy Nallasivam , Ateeq Bushra 
Published: July 2023

AbstractElevated Serine Peptidase Inhibitor, Kazal type 1 (SPINK1) levels in ∼10-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis in PCa, and identified tyrosine kinase KIT as a highly enriched kinase. Furthermore, high to moderate levels of KIT expression was detected in ∼85% of SPINK1-positive PCa specimens. KIT signaling regulates SPINK1-associated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and distant metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/β-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling restores AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide new treatment modalities for advanced-stage SPINK1-positive subtype.
The evolution of competitive effectiveness and tolerance in populations ofDrosophila melanogasteradapted to chronic larval crowding at varying combinations of egg number and food volume
Authors: Venkitachalam Srikant , Temura Chinmay , Kokile Ramesh , Joshi Amitabh 
Published: July 2023

AbstractThe theory of density-dependent selection posits that genotypic fitness can vary depending on the population density. Several long-term selection experiments on outbred populations ofDrosophilaadapted to chronically high larval densities have shown that the most common evolutionary response of such rearing is an increase in larval competitive ability. Some authors have proposed that a better understanding of the evolution of competitive ability can be achieved by its partitioning into effectiveness and tolerance components. Effectiveness is the amount of competitive inhibition imposed by a competitor on another, whereas tolerance is the degree to which a competitor can withstand inhibition. In this study, we have explored the evolution of effectiveness and tolerance components of competitive ability using three sets of outbred populations ofD.melanogasteradapted to chronic larval crowding at different respective combinations of egg number, food volume and container dimensions. Effectiveness and tolerance were found to be dependent on the particular selection regime, the starting food amount and the trait used as the outcome of competition. Eclosion, dry biomass and dry weight per fly distributions over time indicated that competitive ability can also express itself in a time-dependent manner. The results suggest that larval competition and the evolution of competitive ability inDrosophilaare extremely nuanced.
Coordinated interplay between palmitoylation, phosphorylation and SUMOylation regulates kainate receptor surface expression
Authors: Yucel Busra P. , Al Momany Enaam M. , Evans Ashley J. , Seager Richard , Wilkinson Kevin A. , Henley Jeremy M. 
Published: July 2023

AbstractKainate receptors (KARs) are key regulators of neuronal excitability and synaptic transmission. KAR surface expression is tightly controlled in part by post-translational modifications (PTMs) of the GluK2 subunit. We have shown previously that agonist activation of GluK2-containing KARs leads to phosphorylation of GluK2 at S868, which promotes subsequent SUMOylation at K886 and receptor endocytosis. Furthermore, GluK2 has been shown to be palmitoylated. However, how the interplay between palmitoylation, phosphorylation and SUMOylation orchestrate KAR trafficking remains unclear. Here, we used a library of site-specific GluK2 mutants to investigate the interrelationship between GluK2 PTMs, and their impact on KAR surface expression. We show that GluK2 is basally palmitoylated and that this is decreased by kainate stimulation. Moreover, a non-palmitoylatable GluK2 mutant (C858/C871A) shows enhanced S868 phosphorylation and K886 SUMOylation under basal conditions and is insensitive to KA-induced internalisation. These results indicate that GluK2 palmitoylation contributes to stabilising KAR surface expression and that dynamic depalmitoylation promotes downstream phosphorylation and SUMOylation to mediate activity-dependent KAR endocytosis.Significance StatementPost-translational modifications (PTMs) are biochemical switches that control substrate protein properties and interactions. In consequence, PTMs are critical regulators of essentially all cellular pathways and are vital for eukaryotic cell survival. In the brain, among other roles, PTMs influence neuronal growth, differentiation, synaptic activity and plasticity. Kainate receptors (KARs) play core roles in all these processes and previous work has shown that the GluK2 subunit of KARs is subject to multiple PTMs. Here, using GluK2 as an exemplar protein, we delineate the sequence, coordination, and consequences of the PTMs palmitoylation, phosphorylation and SUMOylation on KAR surface expression. Our data show how the complex interplay between PTMs dynamically regulates synaptic proteins and neuronal function.
Inflammation plays a critical role in damage to the bronchiolar epithelium induced byTrueperella pyogenes in vitroandin vivo
Authors: Qin Lei , Meng Fandan , He Haijuan , Li Siqi , Zhang Hongliang , Sun Yuan , Zhang Wenlong , An Tongqing , Cai Xuehui , Wang Shujie 
Published: July 2023

AbstractTrueperella pyogenescan cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined.T. pyogenes-induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS) and respiratory epithelium of mice remains unknown. In this study, we usedT. pyogenes20121 to infect PBECs in air-liquid interface conditions and porcine PCLS.T. pyogenescould adhere to, colonize and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in infected mice lungs. Furthermore, western blot showed the NOD-like receptor (NLR)/ C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B (NF-κB) pathway were involved in inflammation in PCLS and lungs of mice, which also confirms PCLS provide a platform to analyze pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase (JNK), p-extracellular signal-regulated kinase (ERK) and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase (MAPK) and Akt pathways were also involved of inflammation inT. pyogenes-infected mice. In addition, we usedT. pyogenes20121 to infect tumour necrosis factor alpha (TNF-α)-/-mice, the results indicated apoptosis and injury in respiratory epithelium of infected TNF-α-/-mice were alleviated. Thus, pro-inflammatory cytokine TNF-α played a role in apoptosis and respiratory epithelium injury of mice lungs. Collectively, our study provides an insight into the inflammatory injury induced byT. pyogenes, and suggests that blocking NLR or TNF-α may be a potential therapeutic strategy againstT. pyogenesinfection.
Changes in dorsomedial striatum activity mediate expression of goal-directed vs. habit-like cue-induced cocaine seeking
Authors: Bender Brooke N. , Stringfield Sierra J. , Torregrossa Mary M. 
Published: July 2023

AbstractA preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking when drug seeking is goal-directed but not habitual. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habitual cue-induced cocaine seeking and how it is impacted by cue extinction. Rats trained to self-administer cocaine paired with an audiovisual cue on schedules of reinforcement that promote goal-directed or habitual cocaine seeking had different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium and dopamine responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habitual behavior and the DLS are unaffected.
The effect of intercellular medium salinity on the dielectric constant of cell membranes and the excitation thresholds of the action potential
Authors: Shneider M. N. , Pekker M. 
Published: July 2023

AbstractA mechanism for axon swelling and subsequent compression in the area of action potential passage is considered. It is shown that the dynamics of changes in the radius of the axon during the passage of the action potential can be explained by changes in osmotic pressure. Axon swelling occurs at the leading edge of the action potential when Na+ions flow from the extracellular electrolyte into the intracellular space, and subsequent compression occurs at the trailing edge during the ejection of K+ions. The change in dielectric constant of the axon membrane is also discussed, and a possible explanation for the decrease in the excitation threshold of the action potential with an increase in salinity of the external electrolyte is proposed.
Mechano-dependent sorbitol accumulation supports biomolecular condensate
Authors: Torrino Stephanie , Oldham William M , Tejedor Andrés R , Burgos Ignacio S. , Rachedi Nesrine , Fraissard Kéren , Chauvet Caroline , Sbai Chaima , O’Hara Brendan P. , Abélanet Sophie , Brau Frederic , Clavel Stephan , Collepardo-Guevara Rosana , Espinosa Jorge R. , Ben-Sahra Issam , Bertero Thomas 
Published: July 2023

AbstractBiomolecular condensates regulate a wide range of cellular functions from signaling to RNA metabolism1, 2, yet, the physiologic conditions regulating their formation remain largely unexplored. Biomolecular condensate assembly is tightly regulated by the intracellular environment. Changes in the chemical or physical conditions inside cells can stimulate or inhibit condensate formation3–5. However, whether and how the external environment of cells can also regulate biomolecular condensation remain poorly understood. Increasing our understanding of these mechanisms is paramount as failure to control condensate formation and dynamics can lead to many diseases6, 7. Here, we provide evidence that matrix stiffening promotes biomolecular condensationin vivo. We demonstrate that the extracellular matrix links mechanical cues with the control of glucose metabolism to sorbitol. In turn, sorbitol acts as a natural crowding agent to promote biomolecular condensation. Usingin silicosimulations andin vitroassays, we establish that variations in the physiological range of sorbitol, but not glucose, concentrations, are sufficient to regulate biomolecular condensates. Accordingly, pharmacologic and genetic manipulation of intracellular sorbitol concentration modulates biomolecular condensates in breast cancer – a mechano-dependent disease. We propose that sorbitol is a mechanosensitive metabolite enabling protein condensation to control mechano-regulated cellular functions. Altogether, we uncover molecular driving forces underlying protein phase transition and provide critical insights to understand the biological function and dysfunction of protein phase separation.
Dynamics of Collagen Oxidation and Cross Linking in Regenerating and Irreversibly Infarcted Myocardium
Authors: Akam Eman A. , Bergemann David , Ridley Sterling J. , To Samantha , Andrea Brittany , Moon Brianna , Ma Hua , Zhou Yirong , Aguirre Aaron , Caravan Peter , Gonzalez-Rosa Juan Manuel , Sosnovik David E. 
Published: July 2023

AbstractIn mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.
pHusion: A robust and versatile toolset for automated detection and analysis of exocytosis
Authors: O’Shaughnessy Ellen C. , Lam Mable , Ryken Samantha E. , Wiesner Theresa , Lukasik Kimberly , Zuchero Bradley J , Leterrier Christophe , Adalsteinsson David , Gupton Stephanie L. 
Published: July 2023

AbstractExocytosis is a fundamental process used by eukaryotic cells to regulate the composition of the plasma membrane and facilitate cell-cell communication. To investigate the role exocytosis plays in neuronal morphogenesis, previously we developed computational tools with a graphical user interface (GUI) to enable the automatic detection and analysis of exocytic events (ADAE GUI) from fluorescence timelapse images. Though these tools have proven useful, we found that the code was brittle and not easily adapted to different experimental conditions. Here, we have developed and validated a robust and versatile toolkit, named pHusion, for the analysis of exocytosis written in ImageTank, a graphical programming language that combines image visualization and numerical methods. We tested this method using a variety of imaging modalities and pH-sensitive fluorophores, diverse cell types, and various exocytic markers to generate a flexible and intuitive package. Using pHusion, we show that VAMP3-mediated exocytosis occurs 30-times more frequently in melanoma cells compared with primary oligodendrocytes, that VAMP2-mediated fusion events in mature rat hippocampal neurons are longer lasting than those in immature murine cortical neurons, and that exocytic events are clustered in space yet random in time in developing cortical neurons.Summary StatementExocytosis is an essential process by which cells change shape, alter membrane composition, and communicate with other cells. Though all eukaryotic cells carry out exocytosis, the regulation of vesicle fusion, the cargo of vesicles, and the role exocytosis plays in cell fate differ greatly across cell types. Here, we developed a flexible and robust set of tools to enable automatic identification and analysis of exocytic events across a wide range of cell types, vesicle types, and imaging conditions.
Urban resilience for sustainable homeownership: the role of self-help in the ancient city of Benin, Nigeria
Authors: Ebekozien Andrew , Aigbavboa Clinton , Samsurijan Mohamad Shaharudin , Salman Ahmad , Amadi Godspower C. 
Published: July 2023

PurposeThe organised self-help approach successfully enhances urban low-income earners' (LIE) homeownership in some developing countries. The technique can enhance urban resilience for sustainable LIE homeownership. There is a paucity of studies concerning sustainable homeownership for Nigeria's urban LIE through a self-help approach. The study investigated the housing needs of the urban LIE via organised self-help mechanisms and how the same can enhance urban resilience for sustainable homeownership in the Ancient City of Benin, Nigeria.Design/methodology/approachGiven the unexplored nature of the issue, 20 face-to-face interviews were conducted with experts and analysed through a thematic approach.FindingsFindings identified eleven main barriers faced by the urban LIE. This includes the absence of government housing policy, funding frameworks, urban land scarcity, high property development costs, naira devaluation, high-interest rates, inflation, bribery and corruption, lax mortgage sub-sector, high cost of infrastructure, and government bureaucracy.Originality/valueThis study will contribute to pioneering the role of organised self-help mechanisms in urban resilience for sustainable LIE homeownership in developing cities via a qualitative approach. Also, findings would significantly contribute to developing countries' sustainable housing and urban resilience literature.
Generations and the Future of Work: case study exploration of Business Stakeholder perspectives on Zillennials in the Northern Irish workplace
Authors: Moffett Stephanie Gabrielle , Bradley Laura , Hampton Alison , McGowan Pauric 
Published: July 2023

PurposeThis research aims to better understand the Zillennial Generation within the workplace, specifically using the perspectives of Business Stakeholders within the context of Northern Ireland. Understanding the perceptions of Zillennials in the workplace is important due to their growing numbers and subsequent impact on the future of work.Design/Methodology/ApproachA case study approach is used to gain a deeper understanding of stakeholder opinions and experiences of Zillennials. The authors draw on extant research and use semi-structured interviews to explore the experiences and views of stakeholders within three case firms employing Zillennials.FindingsThe study concludes that discrepancies can be seen between Zillennial performance and behaviour, compared with Business Stakeholder workplace expectations. Findings suggest that according to Business Stakeholders observations, Zillennials display some, but not all, attributes of Generation Z and Millennials. Business Stakeholders observations also reveal that Zillennials demonstrate some, but not all, entrepreneurial behaviours and competencies.Originality/ValueWhile many studies focus on both Generation Z and Millennials, research focused on unique cusp generations is limited. No research has been conducted that investigates the perception of Zillennials within the context of Northern Ireland.