bluuebunny/crossref_metadata_2025_split huggingface dataset:
ORP5 AND ORP8 ORCHESTRATE LIPID DROPLET BIOGENESIS AND MAINTENANCE AT ER-MITOCHONDRIA CONTACT SITES
Authors: Guyard Valentin , Monteiro-Cardoso Vera F. , Omrane Mohyeddine , Sauvanet Cécile , Houcine Audrey , Boulogne Claire , Mbarek Kalthoum Ben , Vitale Nicolas , Facklaris Orestis , El Khallouki Naima , Thiam Abdou Rachid , Giordano Francesca 
Published: November 2021

SUMMARYLipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the Endoplasmic Reticulum (ER). The ER-protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at Mitochondria-Associated ER Membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulate seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for the ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at membrane contact sites.HIGHLIGHTSORP5 and ORP8 localize at MAM subdomains where LDs originate.Phosphatidic acid is enriched in MAM subdomains that are the birthplace of LDs.ORP5 and ORP8 knockdown impairs LD biogenesis.ORP5 and ORP8 regulate seipin recruitment to MAM-LD contact sites.
G6PD deficiency sensitizes metastasizing melanoma cells to oxidative stress and glutaminolysis
Authors: Aurora Arin B. , Khivansara Vishal , Leach Ashley , Gill Jennifer G. , Martin-Sandoval Misty , Yang Chendong , Kasitinon Stacy Y. , Bezwada Divya , Tasdogan Alpaslan , Gu Wen , Mathews Thomas , Zhao Zhiyu , DeBerardinis Ralph J. , Morrison Sean J. 
Published: November 2021

AbstractThe pentose phosphate pathway is a major source of NADPH for oxidative stress resistance in cancer cells but there is limited insight into its role in metastasis, when some cancer cells experience high levels of oxidative stress. To test this, we mutated the substrate binding site of Glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway, in patient-derived melanomas. G6PD mutant melanomas had significantly decreased G6PD enzymatic activity and depletion of intermediates in the oxidative branch of the pentose phosphate pathway. Reduced G6PD function had little effect on the formation of primary subcutaneous tumors but when these tumors spontaneously metastasized the frequency of circulating melanoma cells in the blood and metastatic disease burden were significantly reduced. G6PD mutant melanomas exhibited increased levels of reactive oxygen species (ROS), decreased NADPH levels, and depleted glutathione as compared to control melanomas. G6PD mutant melanomas compensated for this increase in oxidative stress by increasing the production of NADPH through glutaminolysis. This generated a new metabolic vulnerability as G6PD mutant melanomas were more dependent upon glutamine as compared to control melanomas. The oxidative pentose phosphate pathway and compensatory glutaminolysis thus confer layered protection against oxidative stress during metastasis.SignificanceMelanoma metastasis is limited by oxidative stress. Cells that enter the blood experience high levels of ROS and usually die of ferroptosis. We found that melanoma cells become more dependent upon the oxidative branch of the pentose phosphate pathway to manage oxidative stress during metastasis. When pentose phosphate pathway function was disabled by G6PD mutation, the melanoma cells increased their utilization of malic enzyme, fueled by increased consumption of glutamine in the tricarboxylic acid cycle. Melanoma cells thus have redundant and layered protection against oxidative stress.
Whole transcriptome sequencing reveals drought resistance-related genes in upland cotton
Authors: Zheng Juyun , Zhang Zeliang , Liang Yajun , Gong Zhaolong , Sang Zhiwei , Li Xueyuan , Wang Jungduo 
Published: November 2021

AbstractChina, especially the Xinjiang cotton area, is facing severe agricultural water shortages, which seriously restrain the development of the cotton industry. Discovering cotton drought resistance genes and cultivating high-quality and drought-resistant cotton materials through molecular breeding methods are of great significance to the development of the cotton industry. In this study, the drought-resistant cotton material Xinluzhong NO.82 and the drought-sensitive cotton material Kexin NO.1 were used to identify a batch of drought-resistant candidate genes through whole transcriptome sequencing. The main research results obtained were as follows: the ceRNA (competing endogenous RNAs) network was constructed using full transcriptional sequencing to screen the core genes in the core pathway; two drought-related candidate genes were obtained. Gohir.A11G156000 was upregulated at 0 h vs 12 h and downregulated at 12 h vs 24 h. Gohir.A07G220600 was downregulated at 0 h vs 12 h and upregulated at 12 h vs 24 h. The results for drought-resistant materials and drought-sensitive materials were similar. Gohir.A11G156000, encoding GABA-T, which is homologous to POP2 in Arabidopsis thaliana, affects the drought resistance of plants by regulating the GABA content. Gohir.A07G220600 encodes L-aspartate oxidase, which is homologous to AO in Arabidopsis thaliana, and is involved in the early steps of NAD biosynthesis and in plant antioxidant reactions. This study confirmed that the use of gene expression regulatory networks can quickly screen reliable drought-resistance genes and can be used for subsequent gene function verification.
Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, January – September 2021
Authors: Starrfelt Jostein , Buanes Eirik Alnes , Juvet Lene Kristine , Lyngstad Trude Marie , Isaksson Rø Gunnar Øyvind , Veneti Lamprini , Meijerink Hinta 
Published: November 2021

AbstractBackgroundSARS-CoV-2 vaccines show high effectiveness against infection and (severe) disease. However, few studies estimate population level vaccine effectiveness against multiple COVID-19 outcomes, by age and including homologous and heterologous vaccine regimens.MethodsUsing Cox proportional hazard models on data from 4 293 544 individuals (99% of Norwegian adults), we estimated overall, age-, and product-specific vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, ICU admission and death in Norway, using data from national registries. Vaccine status was included as time-dependent variable and we adjusted for sex, pre-existing medical conditions, country of birth, county of residence, and crowded living conditions.FindingsAdjusted vaccine effectiveness among fully vaccinated is 72·1% (71·2–73·0) against SARS-CoV-2 infection, 92·9% (91·2–94·2) against hospitalisation, 95·5% (92·6–97·2) against ICU admission, and 88·0% (82·5–91·8) against death. Among partially vaccinated, the effectiveness is 24·3% (22·3–26·2) against infection and 82·7% (77·7–86·6) against hospitalisation. Vaccine effectiveness against infection is 84·7% (83·1-86·1) for heterologous mRNA vaccine regimens, 78·3% (76·8-79·7) for Spikevax (Moderna; mRNA-1273), 69·7% (68·6-70·8) for Comirnaty (Pfizer/BioNTech; BNT162b2), and 60·7% (57·5-63·6) for Vaxzevria (AstraZeneca; ChAdOx nCoV-19; AZD1222) with a mRNA dose among fully vaccinated.InterpretationWe demonstrate good protection against SARS-CoV-2 infection and severe disease in fully vaccinated, including heterologous vaccine regimens, which could facilitate rapid immunization. Partially vaccinated were less likely to get severe disease than unvaccinated, though protection against infection was not as high, which could be essential in making vaccine prioritisation policies especially when availability is limited.FundingNorwegian Institute of Public Health, Helse Bergen Health Trust
Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10
Authors: Ahmed Mohamed , Mackenzie Jared , Krause Robert , Truebody Barry , Tezera Liku , Garay-Baquero Diana , Vallejo Andres , Govender Katya , Adamson John , Elkington Paul , Steyn Adrie JC , Leslie Alasdair 
Published: November 2021

AbstractMycobacterium tuberculosis (Mtb) is one of the most successful human pathogens and remains a leading cause of death from infectious disease. Interferon-γ (IFN-γ) is a central regulator of the immune defense against Mtb. Several cytokines have been shown to increase virulence of other bacterial pathogens, leading us to investigate whether IFN-γ has a direct effect on Mtb. We found that both recombinant and T-cell derived IFN-γ rapidly induced a dose-dependent increase in the oxygen consumption rate (OCR) of Mtb, consistent with increased bacterial respiration. This was also observed in clinical strains, but not in the vaccine strain Bacillus Calmette–Guérin (BCG), and did not occur for other cytokines tested, including TNF-α. IFN-γ binds to the cell surface of intact Mtb, but not BCG, whilst TNF-α binds to neither. Mass spectrometry analysis identified mycobacterial membrane protein large 10 (MmpL10) as the transmembrane binding partner. Consistent with this, IFN-γ binding and the OCR response was absent in a Mtb Δmmpl10 strain and restored by complementation of the mutant strain. RNA-sequencing of IFN-γ exposed Mtb revealed a distinct transcriptional profile, including genes involved in virulence and cholesterol catabolism. Finally, exposure of Mtb cells to IFN-γ resulted in sterilization of bacilli treated with isoniazid (INH), indicating clearance of phenotypically resistant bacteria that persist in the presence of INH alone. Our data suggest a novel mechanism allowing Mtb to respond to host immune activation that may be important in the immunopathogenesis of TB and have use in novel eradication strategies.One-Sentence SummaryIFN-γ is a critical component of effective immune defense in human tuberculosis yet its causative agent, Mycobacterium tuberculosis it able to sense this cytokine and increase virulence and respiration in response.
The rice OsERF101 transcription factor regulates the NLR Xa1-mediated perception of TAL effectors and Xa1-mediated immunity
Authors: Yoshihisa Ayaka , Yoshimura Satomi , Shimizu Motoki , Sato Sayaka , Mine Akira , Yamaguchi Koji , Kawasaki Tsutomu 
Published: November 2021

SummaryPlant nucleotide-binding leucine-rich repeat receptors (NLRs) initiate immune responses and the hypersensitive response by recognizing pathogen effectors. Xa1 encodes an NLR with an N-terminal BED domain, and recognizes transcription activator-like (TAL) effectors of Xanthomonas oryzae pv. oryzae (Xoo). The molecular mechanisms controlling the recognition of TAL effectors by Xa1 and the subsequent induction of immunity remain poorly understood.Xa1 interacts in the nucleus with two TAL effectors via the BED domain. We identified the AP2/ERF-type transcription factor OsERF101/OsRAP2.6 as an interactor with Xa1, and found that it also interacts with the TAL effectors.Overexpression of OsERF101 exhibited an enhanced resistance to an incompatible Xoo strain only in the presence of Xa1, indicating that OsERF101 functions as a positive regulator of Xa1-mediated immunity. Unexpectedly, oserf101 mutants also showed enhanced Xa1-dependent resistance, but in a different manner from the overexpressing plants. This result revealed an additional Xa1-mediated immune pathway that is negatively regulated by OsERF101. Furthermore, OsERF101 directly interacted with the TAL effectors.Our results show that OsERF101 regulates the recognition of TAL effectors and the Xa1-mediated activation of the immune response. These data provide new insights into the molecular mechanism of NLR-mediated immunity in plants.
Learning induces coordinated neuronal plasticity of metabolic demands and functional brain networks
Authors: Klug Sebastian , Godbersen Godber M , Rischka Lucas , Wadsak Wolfgang , Pichler Verena , Klöbl Manfred , Hacker Marcus , Lanzenberger Rupert , Hahn Andreas 
Published: November 2021

ABSTRACTThe neurobiological basis of learning is reflected in adaptations of brain structure, network organization and energy metabolism. However, it is still unknown how different neuroplastic mechanisms act together and if cognitive advancements relate to general or task-specific changes. To address these questions, we tested how hierarchical network interactions contribute to improvements in the performance of a visuo-spatial processing task by employing simultaneous PET/MR neuroimaging before and after a 4-week learning period. We combined functional PET with metabolic connectivity mapping (MCM) to infer directional interactions across brain regions and subsequently performed simulations to disentangle the role of functional network dynamics and glucose metabolism. As a result, learning altered the top-down regulation of the salience network onto the occipital cortex, with increases in MCM at resting-state and decreases during task execution. Accordingly, a higher divergence between resting-state and task-specific effects was associated with better cognitive performance, indicating that these adaptations are complementary and both required for successful skill learning. Simulations further showed that changes at resting-state were dependent on glucose metabolism, whereas those during task performance were driven by functional connectivity between salience and visual networks. Referring to previous work, we suggest that learning establishes a metabolically expensive skill engram at rest, whose retrieval serves for efficient task execution by minimizing prediction errors between neuronal representations of brain regions on different hierarchical levels.
Framework for identification of performance metrics for research and development collaborations: Construction Innovation Centre
Authors: Fayek Aminah Robinson , Golabchi Alireza 
Published: November 2021

PurposeThe purpose of this study is to provide a framework to identify performance metrics for evaluating research and development collaborations.Design/methodology/approachThe framework is developed through a review of similar centres and academic studies, followed by surveys and interviews of researchers and industry practitioners for the case of the Construction Innovation Centre (CIC). The proposed framework consists of identification of existing industry research and development needs, development of a research roadmap representing top research priorities, and identification of the most important services to provide to industry partners, which form the context for defining performance evaluation metrics.FindingsA research roadmap is presented, outlining top research areas and methods and a list of the most in-demand services including research, practical and training and outreach services. Metrics for evaluating the performance of proposed projects, completed projects and a collaborative research centre are also identified.Originality/valueThis study presents a novel approach to defining performance metrics for the evaluation of research and development collaborations. The approach and findings of this study can be adopted by other collaborative research centres and initiatives around the world to develop effective metrics for performance measurement. The proposed framework provides a platform for defining performance metrics in the context of the research roadmap and top-priority services applicable to the research and development collaboration.
Classifying healthcare warehouses according to their performance. A Cluster Analysis-based approach
Authors: Cagliano Anna Corinna , Mangano Giulio , Rafele Carlo , Grimaldi Sabrina 
Published: November 2021

PurposeThe objective of this paper is to propose an approach to comparatively analyze the performance of drugs and consumable products warehouses belonging to different healthcare institutions.Design/methodology/approachA Cluster Analysis is completed in order to classify warehouses and identify common patterns based on similar organizational characteristics. The variables taken into account are associated with inventory levels, the number of SKUs, and incoming and outgoing flows.FindingsThe outcomes of the empirical analysis are confirmed by additional indicators reflecting the demand level and the associated logistics flows faced by the warehouses at issue. Also, the warehouses belonging to the same cluster show similar behaviors for all the indicators considered, meaning that the performed Cluster Analysis can be considered as coherent.Research limitations/implicationsThe study proposes an approach aimed at grouping healthcare warehouses based on relevant logistics aspects. Thus, it can foster the application of statistical analysis in the healthcare Supply Chain Management. The present work is associated with only one regional healthcare system.Practical implicationsThe approach might support healthcare agencies in comparing the performance of their warehouses more accurately. Consequently, it could facilitate comprehensive investigations of the managerial similarities and differences that could be a first step toward warehouse aggregation in homogeneous logistics units.Originality/valueThis analysis puts forward an approach based on a consolidated statistical tool, to assess the logistics performances in a set of warehouses and, in turn to deepen the related understanding as well as the factors determining them.
Managing projects as a mode of temporal ordering. Performative organising of time and temporality in projects
Authors: Kalff Yannick 
Published: November 2021

PurposeProject studies analyse either managing practices or the temporal nature of project management, which leaves open a research gap: the temporality of managing practice. The paper demonstrates that performativity theory with a temporal perspective helps us to understand how managing a project organises limited temporal resources by aligning activities, deadlines or milestones to reach a goal in a given time.Design/methodology/approachThe article utilises empirical data and grounded theory methodology. Ten interviews with project managers from two companies support empirically guided theory building and conceptual reasoning.FindingsThe article extends John Law's “modes of ordering” to a project-specific mode of temporal ordering. This mode of temporal ordering describes the underlying rationale of project managers who assign, order and materialise time to generate the temporal structure of the project.Research limitations/implicationsThe conceptual nature of the paper and its limited empirical data restrict the generalisation of the findings. The article's goal is to initiate further research and to offer a set of tools for such research.Originality/valueThe contribution links managing practice and temporality in a performativity approach. This link focusses the actual actions of the managers and contextualises them in the temporal flow of the project. Managing projects as a mode of temporal ordering describes how project managers enact temporal structures and how they themselves and their activities are temporally embedded.
Innovating how innovation works at Procter & Gamble
Authors: Day George S. , Shea Gregory P. 
Published: November 2021

Purpose
The authors map out a work system that was key to Procter & Gamble transforming its innovation practices from a slow-paced, cautious incrementalism toward a leaner, more entrepreneurial model able to make bigger and riskier long-term bets.

Design/methodology/approach
Starting in 2016, P&G began “innovating how they innovated”, supported by a strong leadership commitment to working differently.

Findings
The newly envisioned future included P&G exploring many smaller scale innovations within and across business units, with quick learning, conducted in close collaboration with consumers and driven by their problems and needs.

Practical/implications
Kathy Fish began this initiative by studying what innovation practices had produced “irresistible superiority” in the past.

Originality/value
Describes how P&G, a leading, long-established company instituted a systematic program of changing the system through which the work of innovation gets done. This system has eight action levers that collectively shape a supportive and productive work environment. Taking these actions in a coherent, coordinated fashion at Procter & Gamble, changed the operating environment and the company’s innovators adapted their behavior to the new system.
Beyond the “Great Man” narrative: scandals, cumulative reforms and the trajectory of anti-corruption efforts in colonial Hong Kong before MacLehose years
Authors: Yep Ray 
Published: November 2021

Purpose
This paper aims to uncover the trajectory of the anti-corruption effort of the Hong Kong colonial Government by identifying its general approach of denial in the pre-War years. It highlights the path-dependence nature, as well as the path-creation logic of the policy process of anti-corruption reform and the anxiety of the colonial administration in maintaining trust of the local population in the post-War years. These insights should enhance the general understanding of the nature of colonial governance.

Design/methodology/approach
This paper is primarily based on archival materials available at the British National Archives and Hong Kong Public Records Office.

Findings
The paper intends to go before the “Great Man narrative” in explaining the success of the anti-corruption effort in colonial Hong Kong. Whilst the colonial government was fully aware of the endemic of corruption and the substantial involvement of European officers, she was still cocooned with the misguided belief that the core of the administration was mostly “incorruptible”. The Air Raid Precaution Department scandal in 1941 was, however, a powerful wake-up that rendered the denial and self-illusion no longer defensible. The policy ideas of the 1940s did shape the Prevention of Corruption Ordinance 1948 and other related reforms, yet they were not immediately translated into fundamental changes in the institutional set-up of the anti-graft campaign. The limitations of these half-hearted measures were fully exposed in the coming decades. The cumulative effects of the piecemeal anti-graft efforts of the colonial government over the first century of rule, however, did path the way for the “revolutionary” changes in the 1970s under Murray MacLehose.

Originality/value
This is a highly original piece based on under-explored archival materials. The findings should have a major contribution to the scholarship on the nature of colonial governance and the history of anti-corruption efforts of Hong Kong.