bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light-sensitive phosphorylation regulates enzyme activity and filament assembly of human IMPDH1 retinal splice variants
Authors: Calise S. John , O’Neill Audrey G. , Burrell Anika L. , Dickinson Miles S. , Molfino Josephine , Clarke Charlie , Quispe Joel , Sokolov David , Buey Rubén M. , Kollman Justin M. 
Published: September 2023

ABSTRACTInosine monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme inde novoguanosine triphosphate (GTP) synthesis and is controlled by feedback inhibition and allosteric regulation. IMPDH assembles into micron-scale filaments in cells, which desensitizes the enzyme to feedback inhibition by GTP and boosts nucleotide production. The vertebrate retina expresses two tissue-specific splice variants IMPDH1(546) and IMPDH1(595). IMPDH1(546) filaments adopt high and low activity conformations, while IMPDH1(595) filaments maintain high activity. In bovine retinas, residue S477 is preferentially phosphorylated in the dark, but the effects on IMPDH1 activity and regulation are unclear. Here, we generated phosphomimetic mutants to investigate structural and functional consequences of phosphorylation in IMPDH1 variants. The S477D mutation re-sensitized both variants to GTP inhibition, but only blocked assembly of IMPDH1(595) filaments and not IMPDH1(546) filaments. Cryo-EM structures of both variants showed that S477D specifically blocks assembly of the high activity assembly interface, still allowing assembly of low activity IMPDH1(546) filaments. Finally, we discovered that S477D exerts a dominant-negative effect in cells, preventing endogenous IMPDH filament assembly. By modulating the structure and higher-order assembly of IMPDH, phosphorylation at S477 acts as a mechanism for downregulating retinal GTP synthesis in the dark, when nucleotide turnover is decreased. Like IMPDH1, many other metabolic enzymes dynamically assemble filamentous polymers that allosterically regulate activity. Our work suggests that posttranslational modifications may be yet another layer of regulatory control to finely tune activity by modulating filament assembly in response to changing metabolic demands.SIGNIFICANCE STATEMENTOver 20 different metabolic enzymes form micron-scale filaments in cells, suggesting that filament assembly is a conserved mechanism for regulating diverse metabolic pathways. Filament assembly regulates catalytic activity of many of these enzymes, including inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme inde novoGTP biosynthesis. The vertebrate retina expresses two IMPDH1 splice variants that are critical for maintaining nucleotide levels required for phototransduction. Here, we show that filament assembly by these variants is itself controlled by phosphorylation at a single residue, adding further complexity to the tight regulation of nucleotide metabolism in the retina. Phosphorylation and other posttranslational modifications are likely to be a general regulatory mechanism controlling filament assembly by enzymes in many different metabolic pathways.
Methionine Alkylation as an Approach to Quantify Methionine Oxidation Using Mass Spectrometry
Authors: Hoare Margaret , Tan Ruiyue , Welle Kevin A. , Swovick Kyle , Hryhorenko Jennifer R. , Ghaemmaghami Sina 
Published: September 2023

AbstractPost-translational oxidation of methionine residues can destabilize proteins or modify their functions. Although levels of methionine oxidation can provide important information regarding the structural integrity and regulation of proteins, their quantitation is often challenging as analytical procedures in and of themselves can artifactually oxidize methionines. Here, we develop a mass spectrometry-based method called Methionine Oxidation by Blocking with Alkylation (MObBa) that quantifies methionine oxidation by selectively alkylating and blocking unoxidized methionines. Thus, alkylated methionines can be used as a stable proxy for unoxidized methionines. Using proof of concept experiments, we demonstrate that MObBa can be used to measure methionine oxidation levels within individual synthetic peptides and on proteome-wide scales. MObBa may provide a straightforward experimental strategy for mass spectrometric quantitation of methionine oxidation.Significance StatementOver time, cellular proteins can become oxidatively damaged by reactive oxygen species (ROS). A residue that is particularly prone to oxidative damage is methionine. Here, we develop and validate a methodology for detecting and quantifying levels of methionine oxidation by mass spectrometry. This approach has a number of practical advantages over methods currently available for analysis of methionine oxidation. The ability to accurately quantify methionine oxidation will provide important insights into factors that influence protein homeostasis within a cell.
The Inflammasome Pathway is Activated by Dengue Virus Non-structural Protein 1 and is Protective During Dengue Virus Infection
Authors: Wong Marcus P. , Juan Evan Y.W. , Chelluri Sai S. , Wang Phoebe , Pahmeier Felix , Castillo-Rojas Bryan , Blanc Sophie F. , Biering Scott B. , Vance Russell E. , Harris Eva 
Published: September 2023

SummaryDengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.
PAI-1 Deficiency Drives Pulmonary Vascular Smooth Muscle Remodeling and Pulmonary Hypertension
Authors: Kudryashova Tatiana V. , Zaitsev Sergei , Jiang Lifeng , Buckley Benjamin J , McGuckin Joshua P. , Goncharov Dmitry , Zhyvylo Iryna , Lin Derek , Newcomb Geoffrey , Piper Bryce , Bogamuwa Srimathi , Saiyed Aisha , Teos Leyla , Ranson Marie , Wolters Paul J. , Kelso Michael J. , Poncz Mortimer , DeLisser Horace M. , Cines Douglas B. , Goncharova Elena A. , Farkas Laszlo , Stepanova Victoria 
Published: September 2023

ABSTRACTPulmonary arterial hypertension (PAH) is a progressive and potentially a rapidly fatal disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PA) leading to increased pulmonary vascular resistance and right heart failure. Central to the remodeling process is a switch of the smooth muscle cells in small PAs (PASMC) to a proliferative, apoptosis-resistant phenotype.There is reason to suspect that the plasminogen activator system may play an important role in the remodeling program in PAH based on its roles in vascular post-injury restenosis, fibrosis, angiogenesis and tumorigenesis. Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of the plasminogen activators - urokinase-type and tissue-type (uPA and tPA, respectively). Immunohisto- chemical and immunoblot analyses revealed that PAI-1 was deficient in smooth muscle areas of small remodeled PAs and early-passage PASMC from subjects with PAH compared to non-PAH controls.PAI1-/-male and female mice developed spontaneous pulmonary vascular remodeling and pulmonary hypertension (PH) as evidenced by significant increase in PA medial thickness, systolic right ventricular pressure, and right ventricular hypertrophy. Lastly, the uPA inhibitors upamostat (WX-671) and amiloride analog BB2-30F down-regulated mTORC1 and SMAD3, restored PAI-1 levels, reduced proliferation, and induced apoptosis in human PAH PASMC. We examined the effect of inhibition of uPA catalytic activity by BB2-30F on the development of SU5416/Hypoxia (SuHx)-induced PH in mice. Vehicletreated SuHx-exposed mice had up-regulated mTORC1 in small PAs, developed pulmonary vascular remodeling and PH, as evidenced by significant increase of PA MT, sRVP, RV hypertrophy, and a significant decrease in the pulmonary artery acceleration time/pulmonary ejection time (PAAT/PET) ratio compared to age- and sex-matched normoxia controls, whereas BB2-30F-treated group was protected from all these pathological changes. Taken together, our data strongly suggest that PAI-1 down- regulation in PASMC from human PAH lungs promotes PASMC hyper-proliferation, remodeling, and spontaneous PH due to unopposed uPA activation. Further studies are needed to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate the progression and/or reverse pulmonary vascular remodeling and PH.
MarrowDLD: a microfluidic method for label-free retrieval of fragile bone marrow cells
Authors: Porro Gloria , Sarkis Rita , Obergozo Clara , Godot Lucie , Amato Francesco , Humbert Magali , Naveiras Olaia , Guiducci Carlotta 
Published: September 2023

AbstractFunctional bone marrow studies have focused primarily on hematopoietic progenitors, leaving limited knowledge about other fragile populations, such as bone marrow adipocytes (BMAds) and megakaryocytes. The isolation of these cells is challenging due to rupture susceptibility and large size. We introduce here a label-free cytometry microsystem, MarrowDLD, based on deterministic lateral displacement. MarrowDLD enables the isolation of fragile cells based on intrinsic size properties while preserving their viability and functionality. Bone marrow adipocytes, obtained from mouse and human stromal line differentiation, as well as megakaryocytes, from primary human CD34+ hematopoietic stem and progenitor cells, were used for validation. Precise micrometer-range separation cutoffs were adapted for each cell type. Cells were sorted directly in culture media, without pre-labeling steps, and with real-time imaging for quality control. At least 106cells were retrieved intact per sorting round. Our method outperformed two FACS instruments in purity and yield, particularly for large cell size fractions. MarrowDLD represents a non-destructive sorting tool for fragile cells, facilitating the separation of phenotypically pure populations of BMAds and megakaryocytes to further investigate their physiological and pathological roles.
Spine apparatus modulates Ca2+in spines through spatial localization of sources and sinks
Authors: Mesa M. Herńandez , Garcia G. C. , Hoerndli F. J. , McCabe K. J. , Rangamani P. 
Published: September 2023

AbstractDendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca2+dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca2+transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca2+in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca2+presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca2+dynamics differently from spines without ER through a combination of geometry and receptor localization.1HighlightsRyR opening in dendritic spine ER is location dependent and spine geometry dependent.Ca2+buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated.RyRs located towards the ER neck allow for more Ca2+to reach the dendrites.RyRs located towards the spine head are favorable for increased Ca2+in spines.Figure 1:Graphical abstract.Factors governing the dynamics of Ca2+in dendritic spines include plasma membrane geometry, RyR distribution and ER laminarity.
Sensitivity of the timing ofDrosophilapupal wing morphogenesis to external perturbations
Authors: Piscitello-Gómez Romina , Mahmoud Ali , Dye Natalie A , Eaton Suzanne 
Published: September 2023

AbstractThe morphogenesis of the pupal wing ofDrosophila melanogasteris a powerful model for understanding the physical mechanisms of tissue morphogenesis. During this process, the wing undergoes a dramatic reshaping where the hinge region contracts and pulls on the blade region, triggering a dynamic pattern of cell elongation changes, cell divisions, and cell neighborhood changes Etournay et al. (2015). Over our several year study of this process, we noticed that sometime after the year 2016, the onset of morphogenesis became consistently delayed by ∼6 h compared to previous years. Thus, the peak of cell elongation was now observed at 28 hours after puparium formation (hAPF) rather than at 20-22 hAPF. We show here that this delay is independent of genetic background and that the speed of the overall process is relatively unchanged, implying that an environmental factor causes a shift in the onset of the process relative to the start of pupariation. We then investigated how various environmental factors influence the timing of pupal wing morphogenesis, using the dynamics of cell elongation as a proxy. We find that imaging conditions, temperature, diet,Wolbachiainfection, and the light/dark cycle have relatively little effect. Preliminary data show that the spectra of light used to rear the flies affects cell elongation dynamics, although the delay was not completely reverted and more experiments are needed to know precisely how this variable affects morphogenesis. In sum, our work suggests the presence of a gate controlling the onset of pupal wing morphogenesis that is influenced by a specific, yet unclear, environmental factor. Once the gate is released, pupal wing morphogenesis occurs at a fairly constant rate, remarkably robust to many environmental variables.
Banking in the metaverse: a new frontier for financial institutions
Authors: Ooi Keng-Boon , Tan Garry Wei-Han , Aw Eugene Cheng-Xi , Cham Tat-Huei , Dwivedi Yogesh K. , Dwivedi Rohita , Hughes Laurie , Kar Arpan Kumar , Loh Xiu-Ming , Mogaji Emmanuel , Phau Ian , Sharma Anshuman 
Published: September 2023

PurposeTechnological advancements have catalyzed disruption in the banking sector. The impact of the metaverse on the banking sector is no exception. In view of this, the current paper aims to provide valuable insights into four key areas (i.e. corporate banking, retail banking, banking employees and public policy) that the metaverse could significantly disrupt.Design/methodology/approachInsights into four key areas of the banking sector that the metaverse could significantly impact were gathered from various invited contributors.FindingsThe invited contributors first introduce the association between their respective key areas with the metaverse. Subsequently, the opportunities and challenges relevant to the key areas were identified. Finally, future research agendas were proposed for the attention of all relevant stakeholders.Originality/valueThe metaverse's impact on key areas of the banking sector is discussed in this paper. Following the metaverse's potentially wide application in the banking sector, insights from the invited contributions offer great value to the relevant stakeholders.
Privacy governance not included: analysis of third parties in learning management systems
Authors: Sanfilippo Madelyn Rose , Apthorpe Noah , Brehm Karoline , Shvartzshnaider Yan 
Published: September 2023

Purpose
This paper aims to address research gaps around third party data flows in education by investigating governance practices in higher education with respect to learning management system (LMS) ecosystems. The authors answer the following research questions: how are LMS and plugins/learning tools interoperability (LTI) governed at higher education institutions? Who is responsible for data governance activities around LMS? What is the current state of governance over LMS? What is the current state of governance over LMS plugins, LTI, etc.? What governance issues are unresolved in this domain? How are issues of privacy and governance regarding LMS and plugins/LTIs documented or communicated to the public and/or community members?

Design/methodology/approach
This study involved three components: (1) An online questionnaire about LMS, plugin and LTI governance practices from information technology professionals at seven universities in the USA (n = 4) and Canada (n = 3). The responses from these individuals helped us frame and design the interview schedule. (2) A review of public data from 112 universities about LMS plugin and LTI governance. Eighteen of these universities provide additional documentation, which we analyze in further depth. (3) A series of extensive interviews with 25 university data governance officers with responsibilities for LMS, plugin and/or LTI governance, representing 14 different universities.

Findings
The results indicate a portrait of fragmented and unobtrusive, unnoticed student information flows to third parties. From coordination problems on individual college campuses to disparate distributions of authority across campuses, as well as from significant data collection via individual LTIs to a shared problem of scope across many LTIs, the authors see that increased and intentional governance is needed to improve the state of student privacy and provide transparency in the complex environment around LMSs. Yet, the authors also see that there are logical paths forward based on successful governance and leveraging existing collaborative networks among data governance professionals in higher education.

Originality/value
Substantial prior work has examined issues of privacy in the education context, although little research has directly examined higher education institutions’ governance practices of LMS, plugin and LTI ecosystems. The tight integration of first and third-party tools in this ecosystem raises concerns that student data may be accessed and shared without sufficient transparency or oversight and in violation of established education privacy norms. However, these technologies and the university governance practices that could check inappropriate data handling remain under-scrutinized. This paper addresses this gap by investigating the governance practices of higher education institutions with respect to LMS ecosystems.
Intensive and extensive margins of India's agricultural trade: implications for export diversification and development
Authors: Elumalai Kanan , Kumar Anjani 
Published: September 2023

PurposeThis paper aims to analyze relative contribution of intensive margin (IM) and extensive margin (EM) to growth in India's agricultural exports for the period 2001 to 2020. It also analyses the determinants of IM and EMs through a standard gravity model.Design/methodology/approachThe study uses export data from United Nations Comtrade, which is accessed through World Integrated Trade Solution (WITS) software. Data for the period 2001 to 2020 were compiled for analysis using the Harmonized System (HS) of commodity classification system at the six-digit level. This study decomposed the contribution of IM and EM in the growth of Indian agricultural trade by using Hummels and Klenow's approach. After performing the export decomposition analysis, the authors analyze the factors influencing IM and EM by using the Tobit regression model and Poisson pseudo-maximum-likelihood (PPML) method of estimation.FindingsThe EM grew at 1.24% per annum, while the intensive margin (IM) increased by 0.23%. The contribution of growth at the EM increased from 58.8% in 2001 to 70.2% in 2020. Export growth along the IM was relatively high for animal products and agricultural raw materials, while growth at the EM was an important contributor to the export growth of horticultural and processed agricultural products. There was a positive and significant effect of the free trade agreement (FTA) on export margins.Research limitations/implicationsMore disaggregated commodity-specific studies on value chain analysis would provide valuable insights into the issues hindering exports and realizing the untapped export potential.Originality/valueThere is a scarcity of holistic and recent studies illustrating the role of IM and EMs in agricultural trade growth, covering a large number of commodities and geographies associated with Indian agricultural trade. The study would be helpful to the stakeholders in facilitating informed policy decisions.
An arts-based process to build Workforce agility
Authors: M Janani , V Vijayalakshmi 
Published: September 2023

PurposeThe world of work is constantly evolving such that the Workforce in the previous era was driven by the need for stability and is now driven by the desire for creative disruption. While firms must respond to the challenges and dynamics continuously, employees must be ready for any upcoming change to progress despite the turbulence and attain a competitive position. This paper's focal theme is Workforce agility – the ability of employees to respond to and make the most out of changes. Studies on the personal factors affected by changes, in turn, influencing Workforce agility have been scarce. The authors propose a conceptual model with propositions to address this gap. Additionally, the authors propose an employee-centric experiential training practice to foster agility.Design/methodology/approachThe authors have employed conceptual description methodology to build propositions about the personal factors influencing Workforce agility and an arts-based intervention to enhance it.FindingsIntermodal arts-based intervention (IABI) can influence employees' epistemic curiosity, which aids with managing ruminative thoughts, thus enhancing Workforce agility, while dispositional joy moderates this relationship.Practical implicationsThe proposed “Intermodal Arts-Based Intervention (IABI)” can help firms move from a traditional training-based approach to an experiential one to foster their Workforce's agile capacities. Considerations for its implementation are explained.Originality/valueThis study is one of the first attempts to integrate multiple art forms as a change management practice. The conceptualized model also brings out the adaptive and maladaptive aspects of epistemic curiosity and rumination and the role of joy in promoting agile behaviors.