bluuebunny/crossref_metadata_2025 huggingface dataset:
Distance sampling with vehicle-mounted cameras for the estimation of farmland bird abundance over a wide area
Authors: Kumada Nao , Fukasawa Keita , Yoshioka Akira , Tsuda Naoe , Ouchi Hirofumi
Published: June 2023

Agricultural birds are declining due to farmland abandonment and agricultural intensification, and monitoring approaches, including efficient survey methods, are crucial for the development of effective conservation strategies. Roadside surveys (RS), especially those using vehicle-mounted video cameras, can be used to efficiently search for targets; however, they are limited by the unknown detection range. Distance sampling (DS), in which animal density or abundance is estimated from the distance between the observer and the detected individual, can provide a complimentary approach to address this limitation of RS.

We developed a DS model robust to location uncertainty based on video-based RS. We integrated location errors determined by an independent field test using RS and unmanned aerial vehicles (UAVs) into a stochastic DS model. We estimated the abundance of herons and egrets in farmlands in and around the evacuation zone of the Fukushima Daiichi nuclear power plant accident by combining RS and DS.

The video-based RS covered 7,031 km of roads and 24.41 km2of farmlands. All herons and egrets were observed around the evacuation zone and none were detected in the zone. The predicted abundance of herons and egrets differed substantially between areas inside (0.0158 ± 0.0174/km2) and outside of the zone (4.62 ± 5.41/km2).

Integrating location uncertainty into the DS model did not affect predicted heron and egret population densities (4.62 ± 5.41 vs. 4.66 ± 5.45/km2, with or without integrating location uncertainty, respectively). Accordingly, our survey method combining RS and DS is robust to location uncertainty. The study system (i.e., herons and egrets in farmlands) and the inability of location error to exceed the size of one farmland separated by levees may contribute to the accuracy of RS in this study.

Synthesis and Applications:Combining RS with vehicle-mounted cameras and DS considering location uncertainty is widely applicable to open land species and can improve the efficiency of monitoring. When large location errors are expected by conventional approaches, DS models incorporating location uncertainty determined by RS and UAVs could be effective for abundance estimation over wide areas.
Generating human neural diversity with a multiplexed morphogen screen in organoids
Authors: Amin Neal D. , Kelley Kevin W. , Hao Jin , Miura Yuki , Narazaki Genta , Li Tommy , McQueen Patrick , Kulkarni Shravanti , Pavlov Sergey , Paşca Sergiu P.
Published: June 2023

Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells toward particular neural cell fatesin vitrooften relies upon combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and knowledge of the general principles of regional specification remain in-complete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Leveraging advances in multiplexed RNA sequencing technology and annotated single cell references of the human fetal brain we discovered that this screening approach generated considerable regional and cell type diversity across the neural axis. By deconvoluting morphogen-cell type relationships, we extracted design principles of brain region specification, including critical morphogen timing windows and combinatorics yielding an array of neurons with distinct neuro-transmitter identities. Tuning GABAergic neural subtype diversity unexpectedly led to the derivation of primate-specific interneurons. Taken together, this serves as a platform towards anin vitromorphogen atlas of human neural cell differentiation that will bring insights into human development, evolution, and disease.
Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based onPseudomonasexotoxin A
Authors: Grossman Brian D. , Sanford Jack D. , Zhu Yuyi , Zeller Cynthia B. , Weldon John E.
Published: June 2023

Furin is a mammalian serine protease with important roles in cellular homeostasis and disease. It cleaves and activates numerous endogenous and exogenous substrates, including the SARS-CoV-2 viral spike protein and protein toxins such as diphtheria toxin andPseudomonasexotoxin A (PE). Recombinant immunotoxins (RITs) are toxin conjugates used as cancer therapeutics that connect tumor-directed antibodies with toxins for targeted cell killing. RITs based on PE have shown success in treating a variety of cancers, but often suffer from safety and efficacy concerns when used clinically. We have explored furin as a potential limiting factor in the intoxication pathway of PE-based RITs. Although the furin has widely recognized importance in RIT intoxication, its role is incompletely understood. Circumstantial evidence suggests that furin may act as a transporter for RITs in addition to its role of activation by cleavage. Here, we describe the creation of a CRISPR-engineered furin-deficient HEK293 cell line, ΔFur293. Using ΔFur293 and derivatives that express mutant forms of furin, we confirm the importance of furin in the PE RIT intoxication pathway and show that furin trafficking has a significant impact on RIT efficacy. Our data support the hypothesis that furin acts as a transporter during RIT intoxication, and suggest furin as a target to improve the effectiveness of RITs.
In vivo evolution of a Klebsiella pneumoniae capsule defect promotes complement-mediated opsono-phagocytosis and persistence during recurrent infection
Authors: Bain William , Ahn Brian , Penaloza Hernan , McElheny Christi , Tolman Nathanial , van der Geest Rick , Gonzalez-Ferrer Shekina , Chen Nathalie , An Xiaojing , Hosuru Ria , Tabary Mohammadreza , Papke Erin , Kohli Naina , Farooq Nauman , Bachman William , Olonisakin Tolani , Xiong Zeyu , Griffith Marissa P , Sullivan Mara , Franks Jonathan , Mustapha Mustapha , Iovleva Alina , Suber Tomeka , Shanks Robert MQ , Ferreira Viviana , Stolz Donna B , Van Tyne Daria , Doi Yohei , Lee Janet
Published: June 2023

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) bloodstream infections rarely overwhelm the host but are associated with high mortality. The complement system is a key host defense against bloodstream infection. However, there are varying reports of serum resistance among KPC-Kp isolates. We assessed growth of 59 KPC-Kp clinical isolates in human serum and found increased resistance in 16/59 (27%). We identified five genetically-related bloodstream isolates with varying serum resistance profiles collected from a single patient during an extended hospitalization marked by recurrent KPC-Kp bloodstream infections. We noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ, that emerged during infection was associated with decreased polysaccharide capsule content, and resistance to complement-mediated killing. Surprisingly, disruption of wcaJ increased deposition of complement proteins on the microbial surface compared to the wild-type strain and led to increased complement-mediated opsono-phagocytosis in human whole blood. Disabling opsono-phagocytosis in the airspaces of mice impaired in vivo control of the wcaJ loss-of-function mutant in an acute lung infection model. These findings describe the rise of a capsular mutation that promotes KPC-Kp persistence within the host by enabling co-existence of increased bloodstream fitness and reduced tissue virulence.
ACTIVATION OF CYCLIN-DEPENDENT KINASE 5 BROADENS ACTION POTENTIALS IN HUMAN SENSORY NEURONS
Authors: Tiwari Manindra Nath , Hall Bradford E. , Terse Anita , Amin Niranjana , Chung Man-Kyo , Kulkarni Ashok B.
Published: June 2023

Chronic pain is one of the most devastating and unpleasant conditions, associated with many pathological conditions. Tissue or nerve injuries induce comprehensive neurobiological plasticity in nociceptive neurons, which leads to chronic pain. Recent studies suggest that cyclin-dependent kinase 5 (CDK5) in primary afferents is a key neuronal kinase that modulates nociception through phosphorylation-dependent manner under pathological conditions. However, the impact of the CDK5 on nociceptor activity especially in human sensory neurons are not known. To determine the CDK5-mediated regulation of human dorsal root ganglia (hDRG) neuronal properties, we have performed the whole-cell patch clamp recordings in neurons dissociated from hDRG. CDK5 activation induced by overexpression of p35 depolarized the resting membrane potential and reduced the rheobase currents as compared to the uninfected neurons. CDK5 activation evidently changed the shape of the action potential (AP) by increasing AP rise time, AP fall time, and AP half width. The application of a prostaglandin E2 (PG) and bradykinin (BK) cocktail in uninfected hDRG neurons induced the depolarization of RMP and the reduction of rheobase currents along with increased AP rise time. However, PG and BK applications failed to induce any further significant changes in addition to the aforementioned changes of the membrane properties and AP parameters in the p35-overexpressing group. We conclude that CDK5 activation through the overexpression of p35 in dissociated hDRG neurons broadens AP in hDRG neurons and that CDK5 may play important roles in the modulation of AP properties in human primary afferents under pathological conditions, contributing to chronic pain.
Universal features of Nsp1-mediated translational shutdown by coronaviruses
Authors: Schubert Katharina , Karousis Evangelos D. , Ban Ivo , Lapointe Christopher P. , Leibundgut Marc , Bäumlin Emilie , Kummerant Eric , Scaiola Alain , Schönhut Tanja , Ziegelmüller Jana , Puglisi Joseph D. , Mühlemann Oliver , Ban Nenad
Published: June 2023

Nonstructural protein 1 (Nsp1) produced by coronaviruses shuts down host protein synthesis in infected cells. The C-terminal domain of SARS-CoV-2 Nsp1 was shown to bind to the small ribosomal subunit to inhibit translation, but it is not clear whether this mechanism is broadly used by coronaviruses, whether the N-terminal domain of Nsp1 binds the ribosome, or how Nsp1 specifically permits translation of viral mRNAs. Here, we investigated Nsp1 from three representativeBetacoronaviruses– SARS-CoV-2, MERS-CoV, and Bat-Hp-CoV – using structural, biophysical, and biochemical assays. We revealed a conserved mechanism of host translational shutdown across the three coronaviruses. We further demonstrated that the N-terminal domain of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit, where it would prevent mRNA and eIF1A binding. Structure-based biochemical experiments identified a conserved role of these inhibitory interactions in all three coronaviruses and showed that the same regions of Nsp1 are responsible for the preferential translation of viral mRNAs. Our results provide a mechanistic framework to understand howBetacoronavirusesovercome translational inhibition to produce viral proteins.
KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing
Authors: Dillingham Caleb M. , Cormaty Harshini , Morgan Ellen C. , Tak Andrew I. , Esgdaille Dakarai E. , Boutz Paul L. , Sridharan Rupa
Published: June 2023

Histone modifying enzymes play a central role in maintaining cell identity by establishing a conducive chromatin environment for lineage specific transcription factor activity. Pluripotent embryonic stem cell (ESC) identity is characterized by a lower abundance of gene repression associated histone modifications that enables rapid response to differentiation cues. The KDM3 family of histone demethylases removes the repressive histone H3 lysine 9 dimethylation (H3K9me2). Here we uncover a surprising role for the KDM3 proteins in the maintenance of the pluripotent state through post-transcriptional regulation. We find that KDM3A and KDM3B interact with RNA processing factors such as EFTUD2 and PRMT5. Acute selective degradation of the endogenous KDM3A and KDM3B proteins resulted in altered splicing independent of H3K9me2 status or catalytic activity. These splicing changes partially resemble the splicing pattern of the more blastocyst-like ground state of pluripotency and occurred in important chromatin and transcription factors such asDnmt3b, Tbx3andTcf12. Our findings reveal non-canonical roles of histone demethylating enzymes in splicing to regulate cell identity.
MCAK Inhibitors Induce Aneuploidy in Triple Negative Breast Cancer Models
Authors: Smith John C. , Husted Stefan , Pilrose Jay , Ems-McClung Stephanie C. , Stout Jane R. , Carpenter Richard L. , Walczak Claire E.
Published: June 2023

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

Simple Summary

Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype with few treatment options available. Standard of care for TNBC involves the use of taxanes, which are initially effective, but dose limiting toxicities are common, and patients often relapse with resistant tumors. Specific drugs that produce taxane-like effects may be able to improve patient quality of life and prognosis. In this study we identify three novel inhibitors of the Kinesin-13 MCAK. MCAK inhibition induces aneuploidy; similar to cells treated with taxanes. We demonstrate that MCAK is upregulated in TNBC and is associated with poorer prognoses. These MCAK inhibitors reduce the clonogenic survival of TNBC cells, and the most potent of the three inhibitors, C4, sensitizes TNBC cells to taxanes, similar to the effects of MCAK knockdown. This work will expand the field of precision medicine to include aneuploidy-inducing drugs that have the potential to improve patient outcomes.
CD4+T-cell immunity of SARS-CoV-2 patients determine pneumonia development
Authors: Naito Erika , Uchida Takahiro , Yamasaki Satoshi , Hashimoto Kosuke , Miura Yu , Shiono Ayako , Kawamura Takayuki , Mouri Atsuto , Yamaguchi Ou , Imai Hisao , Kaira Kyoichi , Nemoto Manabu , Mitsutake Kotaro , Nagata Makoto , Kagamu Hiroshi
Published: June 2023

Most humans infected with SARS-CoV-2 will recover without developing pneumonia. A few SARS-CoV-2 infected patients, however, develop pneumonia, and occasionally develop cytokine storms. In such cases, it is assumed that there is an inadequate immune response to eliminate viral infected cells and an excessive inappropriate immune response causing organ damage, but little is known about this mechanism. In this study, we used single cell RNA sequencing and mass cytometry to analyze peripheral blood T cells from patients hospitalized with proven COVID-19 infection in order to clarify the differences in host immune status among COVID-19 pneumonia cases, non-pneumonia cases, and healthy controls. The results showed that a specific CD4+T cell cluster with chemokine receptor expression patterns, CXCR3+CCR4-CCR6+(Th1/17), was less abundant in COVID-19 pneumonia patients. Interestingly, these CD4+T-cell clusters were identical to those we have reported to correlate with antitumor immunity and predict programmed cell death (PD)-1 blockade treatment response in lung cancer. The Th1/17 cell percentages had biomarker performance in diagnosing pneumonia cases. In addition, CTLA-4 expression of type17 helper T cells (Th17) and regulatory T cells (Treg) was found to be significantly lower. This indicates that functional suppression of Th17 was less effective and Treg function was impaired in pneumonia cases. These results suggest that imbalance of CD4+T-cell immunity generates excessive immunity that does not lead to viral eradication. This might be a potential therapeutic target mechanism to prevent severe viral infections.

Importance

In this observational study, 49 consecutive patients with SARS-CoV-2 infection confirmed by PCR testing and admitted to Saitama Medical University Hospital and Saitama Medical University International Medical Centre between December 4, 2020 and January 17, 2022 were included. Of these 49 patients, 29 were diagnosed with COVID-19 pneumonia by computed tomography (CT) scan (Table 1). The unique CD4+T-cell immunity with less abundant Th1/17 CD4+T-cell cluster and low expression of CTLA-4 in Th17 and Treg was consistently found in SARS-CoV-2 pneumonia patients on admission and 1-week of admission. The imbalance of CD4+T-cell immunity may contribute to develop pneumonia in SARS-CoV-2 virus infected patients by delaying viral clearance and resulting in an excessive immune response.
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

Cell 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

Pseudomonas 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.

IMPORTANCE

Cyanide 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

Klebsiella 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

PTEN, 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

Diacylglycerol 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.
Genetics and Gene Editing Methods inXenopus laevisandXenopus tropicalis
Authors: Guille Matthew , Grainger Robert
Published: June 2023

Our understanding of biological systems has for many years been heavily influenced by experimental approaches that exploit genetic methods. These include gain-of-function experiments that overexpress transgenes or ectopically express injected RNA and loss-of-function experiments that knock out genes or knock down RNAs. Here, we review how these methods have been applied inXenopusfrogs and introduce a variety of protocols for genetic manipulation ofXenopus laevisandXenopus tropicalis.
Determination of Mosquito Probing and Feeding Time to Evaluate Mosquito Blood Feeding
Authors: Martin-Martin Ines , Williams Adeline E. , Calvo Eric
Published: June 2023

Hematophagous arthropods are animals that feed on vertebrate blood for egg production. Mosquitoes must pierce the host skin, locate blood vessels, and extract blood without being noticed. Mosquito stylets lacerate host tissues, triggering the activation of the three branches of hemostasis, or stopping of blood flow: vasoconstriction, platelet aggregation, and coagulation. Mosquitoes inject saliva into the host skin during their intradermal search for blood (also called probing), and salivary proteins counteract hemostasis. Blood feeding dynamics have been traditionally described by observational studies, in which researchers using magnifying glasses watched mosquitoes in the act of blood feeding. These studies provided the foundation for protocols to evaluate mosquito blood feeding in a more quantitative manner. Here, we introduce mosquito blood feeding biology with a focus on the feeding steps, which include penetration, probing, and feeding. Understanding blood feeding dynamics is crucial for evaluating probing time and other relevant parameters derived from blood feeding, such as blood meal size, fecundity, and fertility. Other considerations, including the relationship between probing and pathogen transmission and novel technologies to address blood feeding, are also discussed.
Quantitative alignment parameter estimation for analyzing X-ray photoelectron spectra
Authors: Ozon Matthew , Tumashevich Konstantin , Prisle Nønne L.
Published: June 2023

The interpretation of X-ray photoelectron spectroscopy (XPS) data relies on measurement models that depend on several parameters, including the photoelectron attenuation length and X-ray photon flux. However, some of these parameters are not known, because they are not or cannot be measured. The unknown geometrical parameters can be lumped together in a multiplicative factor, the alignment parameter. This parameter characterizes the ability of the exciting light to interact with the sample. Unfortunately, the absolute value of the alignment parameter cannot be measured directly, in part because it depends on the measurement model. Instead, a proxy for the experimental alignment is often estimated, which is closely related to the alignment parameter. Here, a method for estimating the absolute value of the alignment parameter based on the raw XPS spectra (i.e. non-processed photoelectron counts), the geometry of the sample and the photoelectron attenuation length is presented. The proposed parameter estimation method enables the quantitative analysis of XPS spectra using a simplified measurement model. All computations can be executed within the open and free Julia language framework PROPHESY. To demonstrate feasibility, the alignment parameter estimation method is first tested on simulated data with known acquisition parameters. The method is then applied to experimental XPS data and a strong correlation between the estimated alignment parameter and the typically used alignment proxy is shown.
Double-slit X-ray dynamical diffraction in curved crystals
Authors: Balyan Minas K.
Published: June 2023

The theoretical investigation of double-slit X-ray dynamical diffraction in curved crystals shows that Young's interference fringes are formed. An expression for the period of the fringes has been established which is polarization sensitive. The position of the fringes in the cross section of the beam depends on the deviation from the Bragg exact orientation for a perfect crystal, on the curvature radius and on the thickness of the crystal. This type of diffraction can be used for determination of the curvature radius by measuring the shift of the fringes from the centre of the beam.
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

Purpose

This 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/approach

The 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.

Findings

The 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/implications

The 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 implications

The 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 implications

This 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/value

The 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

Purpose

Building 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/approach

This study uses survey and regression estimation.

Findings

The 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 implications

Improving 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/value

Despite 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.
Homestay Accommodation in Brunei Darussalam
Authors: Adli Amalena , Chin Wei Lee
Published: June 2023

Homestay is an alternative product to mass tourism where tourists are accommodated with local family allowing the tourist to learn local culture and lifestyle. The changing tourists' preferences influence the phenomenon of this accommodation trend for unique experiences, increasing competition in the market, and the rapid development in communication technology. This paper aims to observe the current state of the homestay situation in Brunei. This research utilized qualitative in-depth semi-structured interviews with a total sample of 23 respondents consisting of homestay operators, local community and tourism officers. The findings are that homestay in Brunei experienced issues with licensing and standards due to unending bureaucracy and unclear instructions, an elusive search of successors for long-term sustainability, and issues on participatory management within the community. This paper contributes valuable insights to developing strategies for the sustainability of homestay tourism, particularly for the stakeholders involved, such as homestay operators, policymakers and tourism practitioners.
Knowledge of E-Waste Recycling Among Communities in Selangor, Malaysia
Authors: Yahya Amirah Sariyati Mohd , Hamzah Tengku Adeline Adura Tengku , Shafie Aziz
Published: June 2023

The environment and human health can be jeopardized if E-waste is not properly managed. Global E-waste production continued to rise as a result of rapid technological advancement and increased purchasing power among the global population. One of the possible sustainable methods for managing E-waste is to recycle E-waste. This study aims to find out which demographic factor has the most influence on local residents' understanding of E-waste recycling in Selangor. Selangor is one of Peninsular Malaysia's wealthiest states, with a wide range of ethnic and racial backgrounds among its residents. In 2019, 779 people took part in a survey to learn more about local residents' understanding of E-waste recycling and the social and demographic factors influencing that understanding. Three characteristics of a person's background stand out: their educational attainment, the nature of their job, and the amount of money they make. The p-value for each of these variables was less than.05. Respondents with the following social backgrounds have the best understanding of E-waste recycling: higher education, employment in the private sector, and a monthly income between RM1,501 and RM3,000. The government and other stakeholders, such as non-profits and the private sector, should take more comprehensive and coordinated actions to ensure that the public is informed about E-waste recycling.
Organic Solidarity in the National Response to COVID-19 in Brunei Darussalam
Authors: Ho Hannah Ming Yit
Published: June 2023

This paper examines the national solidarity in Brunei Darussalam during the COVID-19 pandemic and its consequential impact on younger generations. Utilising Emile Durkheim's solidarity theories, I examine how young people's social media use builds on state discourse in the pandemic. I contend that a shift towards an organic society is visible through a social cohesion that is based on differentiated roles. I argue that the citizenry plays a vital role in the forward momentum toward Industrial Revolution (IR) 4.0, which illustrates that solidarity cannot be forged as a top-down directive. By prompting economic and creative divisions of labour, the local use of social media in a public health crisis has shown the government a new way to foster solidarity. Significant implications for youth as future leaders of the nation are discussed.
Digitalization in the Land Service Delivery: Comparison between Bangladesh and Indonesia
Authors: Akter Marufa
Published: June 2023

The administration of a country's land system has a major impact on its economy and society. Digital land management has the potential to improve the land administration of developing countries and make it more efficient. The governments of Bangladesh and Indonesia have implemented a digital land management framework in the land system to ensure optimal land development, in particular, to deliver land services efficiently. The land offices of both countries have a variety of obstacles when it comes to delivering digital services. Because of this, it is important to recognize the current use of digitalization and identify the variables influencing digitalization in land service delivery by land offices in order to make informed decisions about their future. Content analysis was applied to gather data for the study, which used a qualitative approach. The correct deployment of digitization in land administration in both nations is being slowed down by a lack of institutional and operational capability and personnel misconduct in service delivery.
The Impact of COVID-19 on Palliative Care Services in a Tertiary Hospital in Brunei Darussalam
Authors: Shaharudin Muhammad Yusuf , Mohamad Zulkhairi , Husaini Asmah
Published: June 2023

The wake of the novel coronavirus (COVID-19) pandemic had caused substantial disruptions to the usual delivery of healthcare services. This is because of restrictive orders that were put in place to curb the spread of the infection. Palliative care services in Brunei also face challenges to deliver effective services during this period. However, the impact of advanced illnesses on patients' health and end-of-life care are issues that cannot be planned, postponed or cancelled. Hence, the palliative care team needs to continue to deliver effective palliative care services. As Brunei faced its second pandemic wave in August 2021, crucial adaptations were made to ensure palliative care service was not disrupted. This reflective case study aims to discuss the adaptations made in providing palliative care during this era of disruptions.
Misinformation in Media during COVID-19 in Bangladesh Socio-Legal Analysis of the Infodemic in Comparison with Vietnam & Singapore
Authors: Kabir Tamanna Tabassum , Tanvir Sakin
Published: June 2023

This article examines the misinformation on the COVID-19 pandemic in social media and electronic media, as well as whether the existing legal administration and laws in Bangladesh, Singapore, and Vietnam are adequate to combat the infodemic. People who believe misinformation and fake news about Coronavirus, prevention, and treatment may put their lives in danger. False information about Coronavirus has spread throughout the world, not just in South and Southeast Asian countries, causing widespread concern in the global healthcare community. We employed a qualitative approach as well as the case study analysis method. Case studies were conducted using news reports and news channels. We examined the legal provisions of the People's Republic of Bangladesh's Constitution, as well as factual analyses of Singapore and Vietnam. We discovered the impact of misinformation dissemination through social and electronic media, which is prevalent not only among rural Bangladeshis but also in almost all classes in Singapore and Vietnam, and how such influence can be detrimental to the interests of Bangladesh, Vietnam, and Singapore.
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

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.