bluuebunny/crossref_metadata_2025_split huggingface dataset:
TANGO-Light - optogenetic control of transcriptional modulators
Authors: Przybyszewska-Podstawka Alicja , Kałafut Joanna , Czapiński Jakub , Ngo Thu Ha , Czerwonka Arkadiusz , Rivero-Müller Adolfo 
Published: June 2023

ABSTRACTCell signalling pathways, in particular downstream receptor activation, frequently converge in the activation of transcriptional modulators. Yet, cells are able to differentiate the stimulation of each receptor. It has become clear that transcriptional modulators, such as transcription factors, do not work in on or off states but rather in patterns of active/inactivate conformations. Thus, it is the intensity and duration of such fluctuating activity that result in differential cellular and genes expression changes, and this is challenging to replicate using traditional methods such as inhibitors or genetic constructs. Optogenetics, which is based on the use of light-responsive proteins, offers precise control over biological processes, in a spatio-temporal manner, allowing targeted fine-tuned modulation of specific proteins or signalling pathways. Here, we engineered an optogenetic system to control transcriptional modulators, by fusing a photoactivatable receptor and the TANGO system. By this mean we show that we are able to control a plethora of transcriptional modulators by light. And by doing so, changing cells fate - inducing cells to acquire a more mesenchymal or epithelial phenotype. This optogenetic system was also adapted to mimic signalling pathways such as Notch and Wnt in a light-dose dependent manner. Finally, we show that this light-responsive system can be induced by natural light sources upon cell-cell contact/proximity.
Cyanide-dependent control of terminal oxidase hybridization byPseudomonas aeruginosaMpaR
Authors: Smiley Marina K. , Sekaran Doran C. , Price-Whelan Alexa , Dietrich Lars E.P. 
Published: June 2023

ABSTRACTPseudomonas aeruginosais a common, biofilm-forming pathogen that exhibits complex pathways of redox metabolism. It produces four different types of terminal oxidases for aerobic respiration, and for one of these–thecbb3-type terminal oxidases–it has the capacity to produce at least 16 isoforms encoded by partially redundant operons. It also produces small-molecule virulence factors that interact with the respiratory chain, including the poison cyanide. Previous studies had indicated a role for cyanide in activating expression of an “orphan” terminal oxidase subunit gene calledccoN4and that the product contributes toP. aeruginosacyanide resistance, fitness in biofilms, and virulence–but the mechanisms underlying this process had not been elucidated. Here, we show that the regulatory protein MpaR, which is predicted to be a pyridoxal phosphate-binding transcription factor and is encoded just upstream ofccoN4, controlsccoN4expression in response to endogenous cyanide. Paradoxically, we find that cyanide production is required to support CcoN4’s contribution to respiration in biofilms. We identify a palindromic motif required for cyanide- and MpaR-dependent expression ofccoN4and co-expressed, adjacent loci. We also characterize the regulatory logic of this region of the chromosome. Finally, we identify residues in the putative cofactor-binding pocket of MpaR that are required forccoN4expression. Together, our findings illustrate a novel scenario in which the respiratory toxin cyanide acts as a signal to control gene expression in a bacterium that produces the compound endogenously.IMPORTANCECyanide is an inhibitor of heme-copper oxidases, which are required for aerobic respiration in all eukaryotes and many prokaryotes. This fast-acting poison can arise from diverse sources, but mechanisms by which bacteria sense it are poorly understood. We investigated the regulatory response to cyanide in the pathogenic bacteriumPseudomonas aeruginosa, which produces cyanide as a virulence factor. AlthoughP. aeruginosahas the capacity to produce a cyanide-resistant oxidase, it relies primarily on heme-copper oxidases and even makes additional heme-copper oxidase proteins specifically under cyanide-producing conditions. We found that the protein MpaR controls expression of cyanide-inducible genes inP. aeruginosaand elucidated the molecular details of this regulation. MpaR contains a DNA-binding domain and a domain predicted to bind pyridoxal phosphate (vitamin B6), a compound that is known to react spontaneously with cyanide. These observations provide insight into the understudied phenomenon of cyanide-dependent regulation of gene expression in bacteria.
Transposon mutagenesis screen inKlebsiella pneumoniaeidentifies genetic determinants required for growth in human urine and serum
Authors: Gray Jessica , Torres Von Vergel L , Goodall Emily CA , McKeand Samantha A , Scales Danielle , Collins Christy , Wetherall Laura , Lian Zheng Jie , Bryant Jack A , Milner Matthew T , Dunne Karl A , Icke Chris , Rooke Jessica L , Schneiders Thamarai , Lund Peter A , Cunningham Adam F , Cole Jeffrey A , Henderson Ian R 
Published: June 2023

AbstractKlebsiella pneumoniaeis a global public health concern due to the rising myriad of hypervirulent and multi-drug resistant clones both alarmingly associated with high mortality. The molecular microbial genetics underpinning these recalcitrantK. pneumoniaeinfections is unclear, coupled with the emergence of lineages resistant to nearly all present day clinically important antimicrobials. In this study, we performed a genome-wide screen inK. pneumoniaeECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani medium), human urine and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options forK. pneumoniaeinfections.
The lipid phosphatase activity of PTEN dampens FRA1 expression via AKT/mTOR signaling to suppress melanoma
Authors: Xu Xiaonan , Bok Ilah , Jasani Neel , Wang Kaizhen , Chadourne Manon , Deng Ou , Welsh Eric A. , Kinose Fumi , Rix Uwe , Karreth Florian A. 
Published: June 2023

ABSTRACTPTEN, a phosphatase frequently inactivated in melanoma, opposes PI3K/AKT/mTOR pathway activation. However, AKT- and mTOR-targeted therapies have so far yielded insufficient results in preclinical models and clinical trials of melanoma. We therefore examined whether PTEN suppresses melanoma through lipid phosphatase-independent functions or by opposing lipid phosphatase-dependent, AKT-independent pathways. Restoring different PTEN functions in PTEN-deficient cells or mouse models revealed that PTEN lipid phosphatase activity predominantly suppresses melanoma with minimal contribution from its protein phosphatase and scaffold functions. A drug screen highlighted the dependence of PTEN-deficient melanoma cells on the AKT/mTOR pathway. Moreover, activation of AKT was sufficient to overcome several aspects of PTEN-mediated melanoma suppression. Phosphoproteomics analysis of the PTEN lipid phosphatase activity identified the AP-1 transcription factor FRA1 as a downstream effector. PTEN regulates FRA1 translation via AKT/mTOR and FRA1 overexpression overcomes PTEN-mediated melanoma suppression. Our study affirms AKT as the key mediator of PTEN inactivation in melanoma and identifies an AKT/mTOR/FRA1 axis as a driver of melanomagenesis.
Diacylglycerol kinase-ε isS-palmitoylated on cysteine in the cytoplasmic end of its N-terminal transmembrane fragment
Authors: Traczyk Gabriela , Hromada-Judycka Aneta , Świątkowska Anna , Wiśniewska Julia , Ciesielska Anna , Kwiatkowska Katarzyna 
Published: June 2023

AbstractDiacylglycerol kinase-ε (DGKε) catalyzes phosphorylation of diacylglycerol to phosphatidic acid with a unique specificity toward 1-stearoyl-2-arachidonoyl-sn-glycerol which is a backbone of phosphatidylinositol (PI). Owing to this specificity, DGKε is involved in the PI cycle maintaining the cellular level of phosphorylated PI derivatives of signaling activity, and was also found crucial for lipid metabolism. DGKε dysfunction is linked with the development of atypical hemolytic uremic syndrome and possibly other human diseases. Despite the DGKε significance, data on its regulation by co/posttranslational modifications are scarce. Here we report that DGKε isS-palmitoylated at Cys38/40 (mouse/human DGKε) located in the cytoplasmic end of its N-terminal putative transmembrane fragment. TheS-palmitoylation of DGKε was revealed by metabolic labeling of cells with a palmitic acid analogue followed by click chemistry, and with acyl-biotin and acyl-PEG exchange assays. TheS-acyltransferases zDHHC7 and zDHHC17, and the zDHHC6/16 tandem were found to catalyze DGKεS-palmitoylation which also increased the DGKε abundance. Mouse DGKε-Myc ectopically expressed in HEK293 cells localized to the endoplasmic reticulum where zDHHC6/16 reside and in small amounts also to the Golgi apparatus where zDHHC7 and zDHHC17 are present. The Cys38Ala substitution upregulated while hyperpalmitoylation of wild type DGKε reduced the kinase activity, indicating an inhibitory effect of the Cys38S-palmitoylation. Additionally, the substitution of neighboring Pro31 with Ala also diminished the activity of DGKε. Taken together, our data indicate thatS-palmitoylation can fine-tune DGKε activity in distinct cellular compartments, possibly by affecting the distance between the kinase and its substrate in a membrane.
The impacts of reforming agricultural policy support on cereal prices: a CGE modeling approach
Authors: Valera Harold Glenn A. , Gopalakrishnan Badri Narayanan , Chakravarthy Sumathi , Bharathi Sindhu , Balié Jean , Pede Valerien Olivier 
Published: June 2023

PurposeThis paper investigates the effects of the total abolition of all forms of agricultural subsidies to producers and border tariffs on the prices of staple cereals.Design/methodology/approachThe authors use the GTAP global economy-wide model and focus on 27 countries and 8 regions. The GTAP database that is used contains information on budgetary transfers to producers and market price support such as domestic price support, tariffs, export subsidies, quotas on exports or imports and other border measures.FindingsThe removal of subsidies is estimated to significantly increase the prices of wheat and other cereal grains in Japan, paddy rice in Malaysia and Indonesia, processed rice in Malaysia and Indonesia and wheat in Brazil and India. When border tariffs are removed, cereal prices are projected to fall in several countries, but the decline is more pronounced for wheat in Kenya and Japan, other cereal grains in South Korea and all staples in Nepal.Research limitations/implicationsThe alternative scenarios on the removal of agricultural subsidies in all agricultural sectors and the elimination of border tariffs are purely speculative as the analysis ignores important political economy considerations of agricultural and food policy reforms.Practical implicationsThe findings from this study point to the importance of implementing additional policy measures to mitigate the possible negative effect of repurposing the support to agriculture and ensure the food security and welfare of those categories of buyers who heavily depend on the price of staple food for their livelihoods.Social implicationsThis study’s findings confirm that the elimination of agricultural subsidies would impact global food security directly by making staple food less affordable to the poorest and indirectly by decreasing the available household budget for other presumably more nutritious food groups. Consequently, it is expected that these price increases could make segments of the world population poorer, particularly the net-food buyers due to a decline in their real income.Originality/valueThe authors assess the impact of removing the subsidies on the economy in a comprehensive way, particularly given the recent policy focus on net zero emissions and Sustainable Development Goals that include healthy foods. The authors also consider the counter effects of tariff reduction on this, which is price-reducing.
Can top managers' impostor feelings affect performance?
Authors: Guedes Maria João 
Published: June 2023

PurposeBuilding on the premise that top managers' characteristics affect firm outcomes, the study aims to examine whether the impostor feelings of top managers are associated with firm performance.Design/methodology/approachThis study uses survey and regression estimation.FindingsThe results show that there is no strong association between the impostor phenomenon and firm performance, when considering the overall sample. However, in the case of women who experience strong impostor feelings, performance is negatively affected. There is no evidence that being a CEO or workload are mechanisms that explain this result.Practical implicationsImproving the understanding of whether top manager impostor feelings sabotage or improve firm performance can encourage managers to engage in preventive actions to overcome or explore its effects adequately so that positive firm outcomes are fostered.Originality/valueDespite the economic importance of how top managers' judgment affects their decisions, little is known about how the cognitive frames of their top managers affect firm outcomes. In particular, there is no clear understanding of how top managers' feelings of inadequacy, intellectual phoniness and deceitfulness (the impostor phenomenon) affect firm profitability.
Enhancing bank stability from diversification and digitalization perspective in ASEAN
Authors: Lestari Diyan , Ma Shiguang , Jun Aelee 
Published: June 2023

Purpose
The financial sector's resilience is associated with greater prosperity and a better average income. Banks have evolved their business model and diversified their sources of income, and bank digitalization has become one of the prominent strategies. The purpose of this study is to examine how bank service expansion represented by revenue diversification activities and digital strategy will enhance bank stability in ASEAN countries from 2010 to 2021.

Design/methodology/approach
This study uses information from the Datastream database and banks’ annual reports to measure bank stability, diversification and market power, which also provide information for bank digital strategy. This study uses the two-step system generalized method of moments to investigate the effect of diversification and digitalization on bank stability in ASEAN.

Findings
The results of this study show that bank revenue diversification has no effect on bank stability, and the presence of the chief digital officer and digital disclosure improves banks’ stability. However, alliance strategy with financial technology companies does not significantly impact bank stability and might increase bank risk.

Practical implications
The findings of this study provide relevant policy implications: the regulation should support bank business to diversify the source of income; regulators and policymakers should regulate and enhance the Information and Communication Technology infrastructure; and banks should design their strategy comprehensively.

Originality/value
This study provides new evidence of the essential role of digital strategy in enhancing bank stability in ASEAN. In addition, this study also shows how banks diversify their business in a competitive environment.
An epidemiological framework for chronic wasting disease in multihost communities
Authors: Mysterud Atle 
Published: June 2023

Abstract

Many pathogens can infect several host species, which complicates the management of wildlife diseases. Even for generalist pathogens, hosts are not equally competent, and variable niche overlap between hosts leads to different exposure levels within hosts when compared with that between hosts. Hence, the processes determining spillover risk and the subsequent transmission dynamics within and between species differ.

Chronic wasting disease (CWD) is a contagious prion disease of the cervids detected across expanded geographic ranges over the last few decades. Multihost management has become topical with CWD detection among reindeer Rangifer tarandus in Europe, with an immediate spillover risk to sympatric species. Here, I argue for the use of a community epidemiological framework that distinguishes between‐ and within‐host dynamics arising from host competence and exposure processes.

In CWD, host competence is mainly determined by how variants of the prion protein gene (PRNP) affect susceptibility. The exposure level is not only linked to the density of infected and susceptible hosts both within and between species but also to the spatiotemporal niche overlap between species and social organization within species.

Mule deer Odocoileus hemionus and white‐tailed deer Odocoileus virginianus are highly susceptible and expected to show true multihost dynamics; however, mule deer have a higher CWD prevalence in sympatric areas, indicating only partially linked dynamics. Moose Alces alces are highly susceptible, but cases of CWD‐infected moose are few and appear to be spillover events with subsequent epidemic die outs. Elk Cervus canadensis have less susceptible PRNP variants and low levels of prion shedding in lymphoid tissues, indicating lower contagiousness. CWD prevalence in elk is lower and appears to result from spillover and subsequent within‐species emergence, which is partially independent of sympatric deer.

Synthesis and applications. Stronger awareness of the different expected CWD dynamics within and between species may facilitate effective surveillance and management. Surveillance should consider the potential lack of linked dynamics between species when designing sampling. Multihost management can target niche overlap at different scales to limit spillover risk: (1) geographic distribution ranges, (2) density reductions in overlap zones and (3) co‐use of transmission hot spots.
Using the Theoretical Domain Framework to understand what helps and hinders the use of different sensory approaches in Australian psychiatric units: A survey of mental health clinicians
Authors: Wright Lisa , Bennett Sally , Meredith Pamela 
Published: June 2023

AbstractBackground/AimAlthough sensory approaches are recommended to relieve distress and agitation and reduce the use of seclusion and restraint, many Australian psychiatric units have struggled to sustain their practice. The aim of this study was to investigate the barriers and enablers influencing the use of different sensory approaches across one health region in Australia and to obtain recommendations for strategies to improve their use.MethodThis cross‐sectional survey was informed by the Theoretical Domain Framework. Likert scale questions considered barriers and enablers to the use of non‐weighted sensory interventions, weighted modalities, sensory rooms, and sensory assessments/plans. Open‐ended questions explored participant concerns and recommendations to improve the use of sensory approaches.ResultsParticipants (n = 211) were from nursing, allied health, medical, and peer support staff across inpatient psychiatric units. Factors most frequently identified as enablers for using sensory approaches were beliefs of positive benefits to consumers (e.g. decreasing distress and agitation); belief it was within the staff's role; and knowledge of the approaches. Limited time was the most common identified barrier. Factors statistically associated with more frequent use were knowledge, skills, confidence, availability, and easy access to sensory tools/equipment. Only 30% of participants were concerned about potential risks of sensory approaches, with this risk mitigated through adequate supervision and thorough risk assessment. Recommendations to improve practice included improved access to, and maintenance of, equipment, more training, and increased staffing.ConclusionThis study revealed how barriers and enablers vary for different sensory approaches and how these factors impact their frequency of use in psychiatric units. It provides insights into staff recommendations to improve the use of sensory approaches in one health region in Australia. This knowledge will lead to the development of implementation strategies to address identified barriers and improve the use of sensory approaches in psychiatric units.
Childhood social capital and drug use disorder in adulthood: A retrospective study on antecedent determinants of the type of drug use
Authors: Sørensen Jens Fyhn Lykke , Hansen Jens Bæk 
Published: June 2023

AbstractBased on a sample of Danish adults who were enroled in treatment for drug use disorders as a prerequisite for qualifying for receiving unemployment benefits, we analyse the relationship between low social capital in childhood (LSCC) and the type of drug use in adulthood. The type of drug use is measured by distinguishing between those who were treated for using hard drugs (e.g., heroin and cocaine) and those who were treated for using soft drugs (cannabis). Extracting data from the initial treatment registration report, social capital is operationalised into seven different LSCC categories, and the total number of LSCC (the LSCC score) is recorded. Based on logistic regressions, the LSCC score shows a strong graded dose‐response relationship with hard drug use. With each additional LSCC, the probability of being treated for hard drug use increases with 9%. Parental child abuse is the most important single predictor of being treated for hard drug use. Having been parentally abused as a child raises the probability by 32%. The results hold after controlling for age, initiation age, and number of years of drug use, all of which show a significant reversed U‐shaped relationship with hard drug use.
Postpartum haemorrhage in high‐resource settings: Variations in clinical management and future research directions based on a comparative study of national guidelines
Authors: de Vries Pauline L. M. , Deneux‐Tharaux Catherine , Baud David , Chen Kenneth K. , Donati Serena , Goffinet Francois , Knight Marian , D’Souzah Rohan , Sueters Marieke , van den Akker Thomas 
Published: June 2023

AbstractObjectiveTo compare guidelines from eight high‐income countries on prevention and management of postpartum haemorrhage (PPH), with a particular focus on severe PPH.DesignComparative study.SettingHigh‐resource countries.PopulationWomen with PPH.MethodsSystematic comparison of guidance on PPH from eight high‐income countries.Main outcome measuresDefinition of PPH, prophylactic management, measurement of blood loss, initial PPH‐management, second‐line uterotonics, non‐pharmacological management, resuscitation/transfusion management, organisation of care, quality/methodological rigour.ConclusionsOur study highlights areas where strong evidence is lacking. There is need for a universal definition of (severe) PPH. Consensus is required on how and when to quantify blood loss to identify PPH promptly. Future research may focus on timing and sequence of second‐line uterotonics and non‐pharmacological interventions and how these impact maternal outcome. Until more data are available, different transfusion strategies will be applied. The use of clear transfusion‐protocols are nonetheless recommended to reduce delays in initiation. There is a need for a collaborative effort to develop standardised, evidence‐based PPH guidelines.ResultsDefinitions of (severe) PPH varied as to the applied cut‐off of blood loss and incorporation of clinical parameters. Dose and mode of administration of prophylactic uterotonics and methods of blood loss measurement were heterogeneous. Recommendations on second‐line uterotonics differed as to type and dose. Obstetric management diverged particularly regarding procedures for uterine atony. Recommendations on transfusion approaches varied with different thresholds for blood transfusion and supplementation of haemostatic agents. Quality of guidelines varied considerably.