bluuebunny/crossref_metadata_2025 huggingface dataset:
Fever-like temperature impacts onStaphylococcus aureusandPseudomonas aeruginosainteraction, physiology, and virulence bothin vitroandin vivo
Authors: Solar Venero EC , Galeano MB , Luqman A , Ricardi MM , Serral F , Fernandez Do Porto D , Robaldi SA , Ashari BAZ , Munif TH , Egoburo DE , Nemirovsky S , Escalante J , Nishimura B , Ramirez MS , Götz F , Tribelli PM
Published: March 2023

Background

Staphylococcus aureusandPseudomonas aeruginosacause a wide variety of bacterial infections and coinfections, showing a complex interaction that involves the production of different metabolites and metabolic changes. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could be exposed to an increment in temperature during fever development. We analyzed the previously unexplored effect of fever-like temperatures (39°C) onS. aureusUSA300 andP. aeruginosaPAO1 microaerobic mono- and co-cultures compared with 37°C, by using RNAseq and physiological assays includingin-vivoexperiments.

Results

In general terms both temperature and co-culturing had a strong impact on both PA and SA with the exception of the temperature response of monocultured PA. We studied metabolic and virulence changes on both species. Altered metabolic features at 39°C included arginine biosynthesis and the periplasmic glucose oxidation inS. aureusandP. aeruginosamonocultures respectively. When PA co-cultures were exposed at 39°C they upregulated ethanol oxidation related genes along with an increment in organic acid accumulation. Regarding virulence factors, monocultured SA showed an increase in the mRNA expression of theagroperon andhld, pmsαandpmsβgenes at 39°C. Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis, staphylxantin production and a decrease in biofilm formation at 39°C. On the side of PA monocultures, we observed increase in extracellular lipase and protease and biofilm formation at 39°C along with a decrease in motility in correlation with changes observed at mRNA abundance. Additionally, we assessed host-pathogen interaction bothin-vitroandin-vivo.S. aureusmonocultured at 39°C showed a decrease in cellular invasion and an increase in IL-8 -but not in IL-6- production by A549 cell line. PA also decreased its cellular invasion when monocultured at 39°C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when co-cultured at 37°C and 39°C. Finally, we observed increased lethality in mice intranasally inoculated withS. aureusmonocultures pre-incubated at 39°C and even higher levels when inoculated with co-cultures. The bacterial burden forP. aeruginosawas higher in liver when the mice were infected with co-cultures previously incubated at 39°C comparing with 37°C.

Conclusion

Our results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposed to fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host-pathogen interactions and coevolution.
An epigenetic molluscicide
Authors: Luviano Nelia , Halby Ludovic , Jallet Corinne , Arimondo Paola B. , Cosseau Celine , Grunau Christoph
Published: March 2023

Biomphalaria glabratais a fresh-water mollusk that serves as obligatory intermediate host toSchistosoma mansoni, agent of the neglected tropical disease schistosomiasis that affects roughly 250 Mio people. One of the ways to control the pathogenic agent is to interrupt the life cycle by eliminating the intermediate snail host though foal treatment of water bodies with molluscicides. Currently recommended molluscicides were developed in the 1950ths and lack sufficient specificity, e.g., they are toxic to fish. To provide new lead compounds for the development of a new type of molluscicides we used a rational approach based on the hypotheses that interfering with an important epigenetic mark, DNA methylation, would impede development of the snail host. We present here the compound 29, analogues-based compound that mimic substrates of DNA methyltransferases. We show that compound 29 has (i) low cytotoxicity for human cells, (ii) it inhibits DNA methylation, and (iii) it decreases fecundity inB.glabrata. It is therefore conceivable to produce compounds that act as specific epigenetic molluscicides.
Endocytic myosin-1 is a force-insensitive, power-generating motor
Authors: Pedersen Ross TA , Snoberger Aaron , Pyrpassopoulos Serapion , Safer Daniel , Drubin David G , Ostap E Michael
Published: March 2023

Myosins are required for clathrin-mediated endocytosis, but their precise molecular roles in this process are not known. This is, in part, because the biophysical properties of the relevant motors have not been investigated. Myosins have diverse mechanochemical activities, ranging from powerful contractility against mechanical loads to force-sensitive anchoring. To better understand the essential molecular contribution of myosin to endocytosis, we studied the in vitro force-dependent kinetics of theSaccharomyces cerevisiaeendocytic type I myosin called Myo5, a motor whose role in clathrin-mediated endocytosis has been meticulously studied in vivo. We report that Myo5 is a low-duty-ratio motor that is activated ∼10-fold by phosphorylation, and that its working stroke and actin-detachment kinetics are relatively force-insensitive. Strikingly, the in vitro mechanochemistry of Myo5 is more like that of cardiac myosin than like that of slow anchoring myosin-1s found on endosomal membranes. We therefore propose that Myo5 generates power to augment actin assembly-based forces during endocytosis in cells.

Pedersen, Snoberger et al. measure the force-sensitivity of the yeast endocytic the myosin-1 called Myo5 and find that it is more likely to generate power than to serve as a force-sensitive anchor in cells. Implications for Myo5’s role in clathrin-mediated endocytosis are discussed.
Structures of LIG1 active site mutants reveal the importance of DNA end rigidity for mismatch discrimination
Authors: Gulkis Mitchell , Tang Qun , Petrides Matthew , Çağlayan Melike
Published: March 2023

ATP-dependent DNA ligases catalyze phosphodiester bond formation in the conserved three-step chemical reaction of nick sealing. Human DNA ligase I (LIG1) finalizes almost all DNA repair pathways following DNA polymerase-mediated nucleotide insertion. We previously reported that LIG1 discriminates mismatches depending on the architecture of the 3’-terminus at a nick, however the contribution of conserved active site residues to faithful ligation remains unknown. Here, we comprehensively dissect the nick DNA substrate specificity of LIG1 active site mutants carrying Ala(A) and Leu(L) substitutions at Phe(F)635 and Phe(F)F872 residues and show completely abolished ligation of nick DNA substrates with all 12 non-canonical mismatches. LIG1EE/AAstructures of F635A and F872A mutants in complex with nick DNA containing A:C and G:T mismatches demonstrate the importance of DNA end rigidity, as well as uncover a shift in a flexible loop near 5’-end of the nick, which causes an increased barrier to adenylate transfer from LIG1 to the 5’-end of the nick. Furthermore, LIG1EE/AA/8oxoG:A structures of both mutants demonstrated that F635 and F872 play critical roles during steps 1 or 2 of the ligation reaction depending on the position of the active site residue near the DNA ends. Overall, our study contributes towards a better understanding of the substrate discrimination mechanism of LIG1 against mutagenic repair intermediates with mismatched or damaged ends and reveals the importance of conserved ligase active site residues to maintain ligation fidelity.
Effectiveness of using reward strategies combined with transcranial direct current stimulation (RstDCS) on motivation in chronic stroke patients with upper limb disorders: study protocol for a randomized controlled trial
Authors: Zhou Ping , Li Wenxi , Zhao Jingwang , Chen Siyun , Chen Yufeng , Shen Xia , Xu Dongsheng
Published: March 2023

Introduction

Stroke survivors tend to have low motivation for rehabilitation, which prevent them from completing the rehabilitation training task effectively and participating in daily activities. Reward strategies can stimulate patients’ motivation for rehabilitation, but the duration of their effect is unknown. tDCS is a technique capable of promoting plastic changes and functional reorganization of cortical functional areas. When it acts on dlPFC, it can improve the functional connectivity of brain areas associated with goal-directed behavior. Reward strategies combined with tDCS (RstDCS) have been shown to make normal individuals work harder at performing tasks. However, there are no studies on whether this combined strategy improves motivation in stroke patients and whether it has a long-lasting effect on motivation maintenance.

Methods and analysis

87 stroke survivors who have low motivation and upper extremity dysfunction will be randomized to receive conventional, Rs, or RstDCS treatment. Patients in each group will undertake 15 sessions of tDCS real or sham stimulation of the left dlPFC for 3 weeks in conjunction with conventional rehabilitation or reward strategy training. Following this, the RS treatment group and RstDCS treatment group will be given a 3-week outpatient self-monitoring training program, while the conventional group will be given home rehabilitation instruction prior to discharge.

Rehabilitation motivation is the primary outcome measure and will be assessed using RMS. RMS,FMA, FIM and ICF activity and social engagement scale will be compared at baseline, 3 weeks, 6 weeks, and 3 months after enrollment.

Ethics and dissemination

The study has been approved by the Ethics Committee of Yueyang Hospital of Integrated Chinese and Western Medicine Affiliated to SHUTCM (2021-122). All participating patients will provide written informed consent. The results will be disseminated through (open access) peer-reviewed publications, networks of scientists, professionals, and the public.

Trial registration number:ChiCTR2300069068
Cardiovascular events and venous thromboembolism after primary malignant and non-malignant brain tumour diagnosis: a population matched cohort study in Wales (United Kingdom)
Authors: Poon Michael TC , Brennan Paul M , Jin Kai , Sudlow Cathie LM , Figueroa Jonine D
Published: March 2023

Background

Elevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the distribution of risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities.

Methods

Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥18 years in the primary care database with first diagnosis of malignant and non-malignant brain tumour identified in the cancer registry in 2000-2014, and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any tumour diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour and follow-up period.

Results

There were 2,869 and 3,931 people diagnosed with malignant and non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). Risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) remained to be higher than controls for those surviving one year. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls.

Conclusions

The elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.
Whole blood DNA methylation changes are associated with anti-TNF drug concentration in patients with Crohn’s disease
Authors: Lin Simeng , Hannon Eilis , Reppell Mark , Waring Jeffrey F. , Smaoui Nizar , Pivorunas Valerie , Guay Heath , Chanchlani Neil , Bewshea Claire , Bai Benjamin Y H , Kennedy Nicholas A , Goodhand James R , Mill Jonathan , Ahmad Tariq ,   PANTS Consortium
Published: March 2023

Background and Aims

Anti-TNF treatment failure in patients with inflammatory bowel disease (IBD) is common and frequently related to low drug concentrations.

In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14.

Methods

DNA methylation from 1,104 whole blood samples from the Personalised Anti-TNF Therapy in Crohn’s disease (PANTS) study were assessed using the Illumina EPIC Beadchip at baseline, weeks 14, 30 and 54. We compared DNA methylation profiles in anti-TNF-treated patients who experienced primary non-response at week 14 and were not in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 94) with patients who responded at week 14 and were in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 93).

Results

Overall, between baseline and week 14, we observed 4,999 differentially methylated probes (DMPs) annotated to 2376 genes following anti-TNF treatment. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses.

Epigenome-wide association (EWAS) analysis identified 323 DMPs annotated to 210 genes at baseline associated with higher anti-TNF drug concentrations at week 14. Of these, 125 DMPs demonstrated shared associations with other common traits (proportion of shared CpGs compared to DMPs) including body mass index (23.2%), followed by CRP (11.5%), smoking (7.4%), alcohol consumption per day (7.1%) and IBD type (6.8%). EWAS of primary non-response to anti-TNF identified 20 DMPs that were associated with both anti-TNF drug concentration and primary non-response to anti-TNF with a strong correlation of the coefficients (Spearman’s rho = −0.94, p < 0.001).

Conclusion

Baseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14 to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy.
Time trends and modifiable factors of contact tracing coverage in Geneva, Switzerland, June 2020 to February 2022
Authors: Mongin Denis , Bürgisser Nils ,   the Covid-SMC Study Group, Courvoisier Delphine Sophie
Published: March 2023

Background

Contact tracing has been one of the central non-pharmaceutical interventions implemented worldwide to try to control the spread of Sars-CoV-2, but its effectiveness strongly depends on its ability to detect contacts.

Methods

We analysed 166’892 concomitant infections occurring at the same address from June 2020 until February 2022 using an extensive operational database of SARS-CoV-2 tests in Geneva and used permutations statistics to compare the total number of secondary infections occurring at the address with those reported through contact tracing.

Results

Manual contact tracing captured on average 41% of the secondary infections, with variation in time from 23% during epidemic peaks to 60% during low epidemic activity. People living in wealthy neighbourhoods were less likely to report contacts (adjusted odds ratio (aOR): 1.6). People living in buildings, compared to people living in single house, were also less likely to report contacts than those living in houses, with an aOR of 1.1 to 3.1 depending on the variant, the size of the building and the presence of shops. This under-reporting of contacts in buildings decreased during periods of mandatory face masking and restriction of private gathering.

Conclusions

Contact tracing alone does not detect enough secondary infections to efficiently reduce the propagation of Sars-CoV-2. Public messages and outreach campaigns targeting specific populations, such as those in affluent areas, could enhance coverage. Additionally, measures like wearing face masks, improving ventilation, and implementing gathering restrictions should also be considered to reduce the number of infections occurring during interactions that may not be perceived as high risk.
Structure and Function of the Dot/Icm T4SS
Authors: Dutka Przemysław , Liu Yuxi , Maggi Stefano , Ghosal Debnath , Wang Jue , Carter Stephen D. , Zhao Wei , Vijayrajratnam Sukhithasri , Vogel Joseph P. , Jensen Grant J.
Published: March 2023

TheLegionella pneumophilaDot/Icm type IV secretion system (T4SS) delivers effector proteins into host cells during infection. Despite its significance as a potential drug target, our current understanding of its atomic structure is limited to isolated subcomplexes. In this study, we used subtomogram averaging and integrative modeling to construct a nearly-complete model of the Dot/Icm T4SS accounting for seventeen protein components. We locate and provide insights into the structure and function of six new components including DotI, DotJ, DotU, IcmF, IcmT, and IcmX. We find that the cytosolic N-terminal domain of IcmF, a key protein forming a central hollow cylinder, interacts with DotU, providing insight into previously uncharacterized density. Furthermore, our model, in combination with analyses of compositional heterogeneity, explains how the cytoplasmic ATPase DotO is connected to the periplasmic complex via interactions with membrane-bound DotI/DotJ proteins. Coupled within situinfection data, our model offers new insights into the T4SS-mediated secretion mechanism.
Temporal genome-wide fitness analysis ofMycobacterium marinumduring infection reveals genetic requirement for virulence and survival in amoebae and microglial cells
Authors: Lefrançois Louise H. , Nitschke Jahn , Panis Gaël , Prados Julien , Butler Rachel E. , Mendum Tom A. , Hanna Nabil , Stewart Graham R. , Soldati Thierry
Published: March 2023

Tuberculosis remains the most pervasive infectious disease and the recent emergence of multiple or even fully drug-resistant strains increases the risk and emphasizes the need for more efficient and better drug treatments. A key feature of mycobacteria pathogenesis is the metabolic switch during infection and expression of virulence genes is often adapted to specific infection conditions. This study aims to identify genes that are involved in the establishment and maintenance of the infection. To answer these questions, we have applied Transposon Sequencing (Tn-Seq) inM. marinum, an unbiased genome-wide strategy that combines saturation insertional mutagenesis and high throughput sequencing. This approach allowed us to precisely identify the localization and relative abundance of insertions in pools of Tn mutants. The essentiality and fitness cost, in terms of growth advantage and disadvantage of over 105mutants were quantitatively compared betweenin vitroand different stages of infection in two evolutionary distinct hosts,D. discoideumand BV2 microglial cells. We found that 57% of TA sites in theM. marinumgenome were disrupted and that 568 genes (10.2%) are essential forM. marinum, which is comparable to previous Tn-Seq studies onM. tuberculosis. The major pathways involved in the survival ofM. marinumduring infection ofD. discoideumwere related to vitamin metabolism, theesx-1operon, as well as the mce1 operon.
Experimental validation of the mechanism of stomatal development diversification
Authors: Doll Yuki , Koga Hiroyuki , Tsukaya Hirokazu
Published: March 2023

Stomata are the structures responsible for gas exchange in plants. The established framework for stomatal development is based on the model plant Arabidopsis, but diverse patterns of stomatal development have been observed in other plant lineages and species. The molecular mechanisms behind these diversified patterns are still poorly understood. We recently proposed a model for the molecular mechanisms of the diversification of stomatal development based on the genusCallitriche(Plantaginaceae), according to which a temporal shift in the expression of key stomatal transcription factors SPEECHLESS and MUTE leads to changes in the behavior of meristemoids (stomatal precursor cells). In the present study, we have tried to validate this model through genetic manipulation experiments on Arabidopsis. By altering the timing of MUTE expression, we successfully generated Arabidopsis plants with early differentiation or prolonged divisions of meristemoids, as predicted by the model. The epidermal morphology of the generated lines resembled that of species with prolonged or no meristemoid divisions. Thus, the evolutionary process was reproduced via shifting MUTE expression. We also observed unexpected phenotypes, which indicated the participation of additional factors in the evolution of the patterns observed in nature. This study provides novel experimental insights into the diversification of meristemoid behaviors.

Highlight

Genetic manipulation in Arabidopsis uncovered how changes in temporal gene expression patterns lead to the diversification of stomatal patterns, providing new experimental insights into the evolution of stomatal development.
Interspecies interactions determine growth dynamics of biopolymer degrading populations in microbial communities
Authors: D’Souza Glen , Schwartzman Julia , Keegstra Johannes , Schreier Jeremy E , Daniels Michael , Cordero Otto , Stocker Roman , Ackermann Martin
Published: March 2023

Microbial communities perform essential ecosystem functions such as the remineralization of organic carbon that exists as biopolymers. The first step in mineralization is performed by biopolymer degraders, which harbor enzymes that can break down polymers into constituent oligo- or monomeric forms. The released nutrients not only allow degraders to grow, but also promote growth of cells that either consume the breakdown products, i.e., exploiters, or consume metabolites released by the degraders, i.e., scavengers. It is currently not clear how such remineralizing communities assemble at the microscale – how interactions between the different guilds influence their growth and spatial distribution, and hence the development and dynamics of the community. Here we address this knowledge gap by studying marine microbial communities that grow on the abundant marine biopolymer alginate. We used batch growth assays and microfluidics coupled to time-lapse microscopy to quantitatively investigate growth and spatial distribution of single cells. We found that the presence of exploiters or scavengers alters the spatial distribution of degrader cells. In general, exploiters and scavengers – which we collectively refer to as consumer cells – slowed down the growth of degrader cells. In addition, coexistence with consumers altered the production of the extracellular enzymes that breakdown polymers by degrader cells. Our findings reveal that ecological interactions by non-degrading community members have a profound impact on the functions of microbial communities that remineralize carbon biopolymers in nature.

Importance

Biopolymers are the most abundant source of carbon on the planet and their breakdown by microbial degraders releases metabolic products that allow cross-feeding cells to grow and fuel the assembly of microbial communities. While it is known that the growth of degraders can facilitate growth of downstream cross-feeders in microbial communities, it has remained generally unclear if and how cross-feeders influence growth of degraders. Bridging this knowledge gap is important because degraders primarily drive the remineralization of carbon, a central process in the carbon cycle. We found that the presence cross-feeders can influence the growth of degraders by altering their spatial distribution as well as extracellular breakdown enzyme activity. Our study sheds light on the role of microbial interactions in shaping the rate of carbon remineralization in nature.
Multicellular PD Control in Microbial Consortia
Authors: Martinelli Vittoria , Salzano Davide , Fiore Davide , di Bernardo Mario
Published: March 2023

We propose a multicellular implementation of a biomolecular PD feedback controller to regulate gene expression in a microbial consortium. The implementation involves distributing the proportional and derivative control actions between two different cellular populations that can communicate with each other and regulate the output of a third target cellular population. We derive analytical conditions on biological parameters and control gains to adjust the system’s static and dynamical properties. We then validate the strategy’s performance and robustness through extensivein silicoexperiments.
Thermogenetic control of Ca2+levels in cells and tissues
Authors: Ermakova Yulia G. , Waadt Rainer , Ozturk Mehmet S. , Roshchin Matvey , Lanin Aleksandr A. , Chebotarev Artem , Pochechuev Matvey , Pak Valeriy , Kelmanson Ilya , Smolyarova Daria , Keutler Kaya , Matyushenko Alexander M. , Tischer Christian , Balaban Pavel M. , Nikitin Evgeniy S. , Schumacher Karin , Zheltikov Aleksei M. , Prevedel Robert , Schultz Carsten , Belousov Vsevolod V.
Published: March 2023

Virtually all major processes in cells and tissues are regulated by calcium ions (Ca2+). Understanding the influence of Ca2+on cell function requires technologies that allow for non-invasive manipulation of intracellular calcium levels including the formation of calcium patterns, ideally in a way that is expandable to intact organisms. The currently existing tools for optical and optogenetic Ca2+manipulation are limited with respect to response time, and tissue penetration depth. Here we presentGeneticallyEncodedCalciumController (GECCO), a system for thermogenetic Ca2+manipulation based on snake TRP channels optically controlled by infrared illumination. GECCO is functional in animal and plant cells and allows studying how cells decode different profiles of Ca2+signals. GECCO enabled the shaping of insulin release from β-cells, the identification of drugs that potentiate Ca2+-induced insulin release, and the generation of synthetic Ca2+signatures in plants.
Assessing vaccine-mediated protection in an ultra-low doseMycobacterium tuberculosismurine model
Authors: Plumlee C.R. , Barrett H.W. , Shao D.E. , Lien K.A. , Cross L.M. , Cohen S.B. , Edlefsen P.T , Urdahl K.B.
Published: March 2023

Despite widespread immunization with Bacille-Calmette-Guerin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack of a robust animal model to assess vaccine efficacy has hindered our ability to prioritize candidates for human clinical trials. Here we use a murine ultra-low dose (ULD)Mycobacterium tuberculosis(Mtb) challenge model to assess protection conferred by BCG vaccination.We show that BCG confers a reduction in lung bacterial burdens that is more durable than that observed after conventional dose challenge, curbs Mtb dissemination to the contralateral lung, and, in a small percentage of mice, prevents detectable infection.These findings are consistent with the ability of human BCG vaccination to mediate protection, particularly against disseminated disease, in specific human populations and clinical settings. Overall, our findings demonstrate that the ultra-low dose Mtb infection model can measure distinct parameters of immune protection that cannot be assessed in conventional dose murine infection models and could provide an improved platform for TB vaccine testing.
Artificial selection footprints in domestic chicken genomes
Authors: Wu Siwen , Dou Tengfei , Wang Kun , Yuan Sisi , Yan Shixiong , Xu Zhiqiang , Liu Yong , Jian Zonghui , Zhao Jingying , Zhao Rouhan , Wu Hao , Gu Dahai , Liu Lixian , Li Qihua , Wu Dong-Dong , Su Zhengchang , Ge Changrong , Jia Junjing
Published: March 2023

Accurate and low-cost next generation sequencing technologies make re-sequencing of large populations of a species possible. Although many studies related to artificial selection signatures of commercial and indigenous chickens have been carried out, quite a small number of genes have been found to be under selection. In this study, we re-sequenced 85 individuals of five indigenous chicken breeds with distinct traits from Yunnan, a southwest province of China. By analyzing these indigenous chickens together with 116 individuals of commercial chickens (broilers and layers) and 35 individuals of red jungle fowl, we find a substantially large number of selective sweeps and affected genes for each chicken breed using a rigorous statistic model than previously reported. We confirm most of previously identified selective sweeps and affected genes. Meanwhile the vast majority (∼98.3%) of our identified selective sweeps overlap known chicken quantitative trait loci. Thus, our predictions are highly reliable. For each breed, we also identify candidate genes and selective sweeps that might be related to the unique traits of the chickens.
PARP inhibition and pharmacological ascorbate demonstrate synergy in castration-resistant prostate cancer
Authors: Gordon Nicolas , Gallagher Peter T. , Neupane Neermala Poudel , Mandigo Amy C. , McCann Jennifer K. , Dylgjeri Emanuela , Vasilevskaya Irina , McNair Christopher , Paller Channing J. , Kelly Wm. Kevin , Knudsen Karen E. , Shafi Ayesha A. , Schiewer Matthew J.
Published: March 2023

Prostate cancer (PCa) is the second leading cause of cancer death for men in the United States. While organ-confined disease has reasonable expectation of cure, metastatic PCa is universally fatal upon recurrence during hormone therapy, a stage termed castration-resistant prostate cancer (CRPC). Until such time as molecularly defined subtypes can be identified and targeted using precision medicine, it is necessary to investigate new therapies that may apply to the CRPC population as a whole.

The administration of ascorbate, more commonly known as ascorbic acid or Vitamin C, has proved lethal to and highly selective for a variety of cancer cell types. There are several mechanisms currently under investigation to explain how ascorbate exerts anti-cancer effects. A simplified model depicts ascorbate as a pro-drug for reactive oxygen species (ROS), which accumulate intracellularly and generate DNA damage. It was therefore hypothesized that poly(ADP-ribose) polymerase (PARP) inhibitors, by inhibiting DNA damage repair, would augment the toxicity of ascorbate.

Results

Two distinct CRPC models were found to be sensitive to physiologically relevant doses of ascorbate. Moreover, additional studies indicate that ascorbate inhibits CRPC growthin vitrovia multiple mechanisms including disruption of cellular energy dynamics and accumulation of DNA damage. Combination studies were performed in CRPC models with ascorbate in conjunction with escalating doses of three different PARP inhibitors (niraparib, olaparib, and talazoparib). The addition of ascorbate augmented the toxicity of all three PARP inhibitors and proved synergistic with olaparib in both CRPC models. Finally, the combination of olaparib and ascorbate was testedin vivoin both castrated and non-castrated models. In both cohorts, the combination treatment significantly delayed tumor growth compared to monotherapy or untreated control.

Conclusions

These data indicate that pharmacological ascorbate is an effective monotherapy at physiological concentrations and kills CRPC cells. Ascorbate-induced tumor cell death was associated with disruption of cellular energy dynamics and accumulation of DNA damage. The addition of PARP inhibition increased the extent of DNA damage and proved effective at slowing CRPC growth bothin vitroandin vivo. These findings nominate ascorbate and PARPi as a novel therapeutic regimen that has the potential to improve CRPC patient outcomes.
Tn5 tagments and transposes oligos to single-stranded DNA for strand-specific RNA sequencing
Authors: Zhang Yanjun , Tang Yin , Sun Zhongxing , Jia Junqi , Fang Yuan , Wan Xinyi , Fang Dong
Published: March 2023

Tn5 transposon tagments double-stranded DNA and RNA/DNA hybrids to generate nucleic acids that are ready to be amplified for high-throughput sequencing. The nucleic acid substrates for the Tn5 transposon must be explored to increase the applications of Tn5. Here, we found that the Tn5 transposon can transpose oligos into the 5′ end of single-stranded DNA longer than 140 nucleotides. Based on this property of Tn5, we developed a tagmentation-based and ligation-enabled single-stranded DNA sequencing method called TABLE-seq. Through a series of reaction temperature, time, and enzyme concentration tests, we applied TABLE-seq to strand-specific RNA sequencing, starting with as little as 30 pg of total RNA. Moreover, compared with traditional dUTP-based strand-specific RNA sequencing, this method detects more genes, has a higher strand specificity, and shows more evenly distributed reads across genes. Together, our results provide insights into the properties of Tn5 transposons and expand the applications of Tn5 in cutting-edge sequencing techniques.
Novel setup for rapid phase contrast CT imaging of heavy and bulky specimens
Authors: Dullin Christian , D'Amico Lorenzo , Saccomano Giulia , Longo Elena , Wagner Willi L. , Reiser Johanna , Svetlove Angelika , Albers Jonas , Contillo Adriano , Abrami Alessandro , Sturari Luca , Tromba Giuliana , Sodini Nicola , Dreossi Diego
Published: March 2023

This work introduces a novel setup for computed tomography of heavy and bulky specimens at the SYRMEP beamline of the Italian synchrotron Elettra. All the key features of the setup are described and the first application to off-center computed tomography scanning of a human chest phantom (approximately 45 kg) as well as the first results for vertical helical acquisitions are discussed.
Systematic process for crop insurance development: area-yield rice insurance with machine learning technology implementation in Thailand
Authors: Sethanand Krish , Chaiyawat Thitivadee , Gowanit Chupun
Published: March 2023

Purpose

This paper presents the systematic process framework to develop the suitable crop insurance for each agriculture farming region which has individual differences of associated crop, climate condition, including applicable technology to be implemented in crop insurance practice. This paper also studies the adoption of new insurance scheme to assess the willingness to join crop insurance program.

Design/methodology/approach

Crop insurance development has been performed through IDDI conceptual framework to illustrate the specific crop insurance diagram. Area-yield insurance as a type of index-based insurance advantages on reducing basis risk, adverse selection and moral hazard. This paper therefore aims to develop area-yield crop insurance, at a provincial level, focusing on rice insurance scheme for the protection of flood. The diagram demonstrates the structure of area-yield rice insurance associates with selected machine learning algorithm to evaluate indemnity payment and premium assessment applicable for Jasmine 105 rice farming in Ubon Ratchathani province. Technology acceptance model (TAM) is used for new insurance adoption testing.

Findings

The framework produces the visibly informative structure of crop insurance. Random Forest is the algorithm that gives high accuracy for specific collected data for rice farming in Ubon Ratchathani province to evaluate the rice production to calculate an indemnity payment. TAM shows that the level of adoption is high.

Originality/value

This paper originates the framework to generate the viable crop insurance that suitable to individual farming and contributes the idea of technology implementation in the new service of crop insurance scheme.
Brand awareness and relationship intention: the moderating role of perceived corporate social responsibility dimensions
Authors: Hasudungan Albert , Saragih Harriman Samuel
Published: March 2023

Purpose

Using a hierarchical component model conceptualization, this study aims to investigate the moderating role of perceived corporate social responsibility (CSR) dimensions (i.e., economic, environmental and social) on the impact of brand awareness towards consumer relationship intention.

Design/methodology/approach

This study used a two-stage disjoint approach of partial least squares structural equation modeling using data from 325 respondents based in a Southeast Asian region. The case of ecolabel brands was chosen as the context of the investigation.

Findings

The results suggest that brand awareness and perceived CSR dimensions positively impact consumer relationship intention. It was also observed that perceived CSR dimensions moderate the relationship between brand awareness and relationship intention. Consumers with more favorable sentiments of economic, environmental and social dimensions as reflected by the firms' CSR programs exhibit a higher degree of relationship intention.

Research limitations/implications

Using the stakeholder theory as well as the brand value chain framework, this study adds to the literature regarding the significance of perceived CSR dimensions to better build and maintain relationships with the targeted customers of an environmentally friendly product. CSR strategies should be emphasized for relevant companies in terms of the economic, environmental and social aspects. According to this research, customer views about the three CSR initiative characteristics may act as a moderator in the interactions between consumer awareness and relationship intention.

Practical implications

CSR may be utilized in addition to traditional marketing communication to represent the firm's unique value proposition in the market. It is vital to create a CSR program that combines economic, environmental and social factors. Firms may collaborate with various stakeholders to ensure that their CSR initiatives include three elements.

Originality/value

This study adds to the literature on the moderating role of perceived CSR dimensions on the relationship of consumer brand awareness and relationship intention using the theoretical lens of the stakeholder theory and the brand value chain.
Tackling organizational wicked problems: a heuristics study based on a qualitative comparative analysis approach
Authors: Wang Xuan , Xiao Mimi , Jia Liangding
Published: March 2023

Purpose

Organizational wicked problems are ill-defined phenomena arising in complex environments with intertwined and evolving interests. This paper aims to use a nonlinear epistemological approach to explore how multiple management decision tools work together to form configurational paths to deal with organizational wicked problems and to propose some heuristic toolkits for tackling them.

Design/methodology/approach

Based on interviews with 53 senior executives dealing with 62 organizational wicked problems, this paper uses grounded theory to construct an antecedent theoretical framework and then uses qualitative comparative analysis (QCA) to conduct configuration analysis on the strategy portfolios that can tackle organizational wicked problems.

Findings

This paper used grounded theory to identify six theoretical dimensions as management decision tools for dealing with organizational wicked problems: change adaptation, goal performing, administration, mechanical integration, organic integration and entrepreneuring. In addition, this paper used QCA to explore and propose three heuristic toolkits – synergy oriented, institution oriented and innovation oriented – as multiple equivalent paths to help deal with organizational wicked problems.

Originality/value

This paper uses configuration analysis instead of the net effect analysis of the traditional econometric method and captures multiple antecedent conditions for decision-makers to deal with organizational wicked problems from a holistic perspective. This paper constructs three heuristic toolkits and matches each of them with the most suitable type of organizational wicked problem, constructing a complete research chain of “identifying–tackling” the organizational wicked problem and providing a reference for organizations facing similar situations in future practice.
Marketing or methodology? Exposing the fallacies of PLS with simple demonstrations
Authors: Rönkkö Mikko , Lee Nick , Evermann Joerg , McIntosh Cameron , Antonakis John
Published: March 2023

Purpose

Over the past 20 years, partial least squares (PLS) has become a popular method in marketing research. At the same time, several methodological studies have demonstrated problems with the technique but have had little impact on its use in marketing research practice. This study aims to present some of these criticisms in a reader-friendly way for non-methodologists.

Design/methodology/approach

Key critiques of PLS are summarized and demonstrated using existing data sets in easily replicated ways. Recommendations are made for assessing whether PLS is a useful method for a given research problem.

Findings

PLS is fundamentally just a way of constructing scale scores for regression. PLS provides no clear benefits for marketing researchers and has disadvantages that are features of the original design and cannot be solved within the PLS framework itself. Unweighted sums of item scores provide a more robust way of creating scale scores.

Research limitations/implications

The findings strongly suggest that researchers abandon the use of PLS in typical marketing studies.

Practical implications

This paper provides concrete examples and techniques to practicing marketing and social science researchers regarding how to incorporate composites into their work, and how to make decisions regarding such.

Originality/value

This work presents a novel perspective on PLS critiques by showing how researchers can use their own data to assess whether PLS (or another composite method) can provide any advantage over simple sum scores. A composite equivalence index is introduced for this purpose.
Gifts to whom? Towards a network view of gift receivers
Authors: Branco-Illodo Ines , Heath Teresa , Tynan Caroline
Published: March 2023

Purpose

This research paper aims to understand how givers characterise and manage their gift giving networks by drawing on attachment theory (AT). This responds to the need to illuminate the givers–receivers’ networks beyond traditional role-based taxonomies and explore their changing dynamics.

Design/methodology/approach

A multi-method, qualitative approach was used involving 158 gift experiences captured in online diaries and 27 follow-up interviews.

Findings

Results show that givers organise receivers into gifting networks that are grounded in a contextual understanding of their relationships. The identification of direct, surrogate and mediated bonds reflects three different dimensions that inform gift-giving networks of support, care or belongingness rooted in AT. The relative position of gift receivers in this network influences the nature of support, the type of social influences and relationship stability in the network.

Research limitations/implications

This study illustrates the complexity of relationships based on the data collected over two specific periods of time; thus, there might be further types of receivers within a giver’s network that the data did not capture. This limitation was minimised by asking about other possible receivers in interviews.

Practical implications

The findings set a foundation for gift retailers to assist gift givers in finding gifts that match their perceived relations to the receivers by adapting communication messages and offering advice aligned with specific relationship contexts.

Originality/value

This study illuminates gift-giving networks by proposing a taxonomy of gifting networks underpinned by AT that can be applied to study different relationship contexts from the perspective of the giver. This conceptualisation captures different levels of emotional support, social influences and relationship stability, which have an impact on the receivers’ roles within the giver’s network. Importantly, results reveal that the gift receiver is not always the target of gift-giving. The target can be someone whom the giver wants to please or an acquaintance they share with the receiver with whom they wish to reinforce bonds.
Research and evidence-based standards paving the way for a digital and sustainable transformation of the built environment
Authors: Klungseth Nora Johanne , Nielsen Susanne Balslev , Alves da Graça Moacyr Eduardo , Lavy Sarel
Published: March 2023

Purpose

Researchers and standardisation bodies are key to accelerating societal transition and contributing to society’s demands for sustainability, resilience and digitalisation. Standards are the agreed-upon best practices published by national or international bodies and are key enablers of transformation. Scholars have not yet identified a relationship between standards and facilities management (FM) research. The purpose of this paper is to investigate the role of formal standards in FM research.

Design/methodology/approach

A literature review was conducted to identify journal articles addressing standards and FM. A total of 198 journal articles published from 2010 to 2021 were identified. After screening these articles, 27 journal articles were considered the most relevant for data analysis.

Findings

The findings show that the role of standards in research can be analysed thematically, categorically, textually, methodologically and directionally. Standards are relevant to research by defining terms, creating backgrounds, guiding research, supporting the development of new standards and encouraging more collaboration between research and standardisation. Some studies have shown how standards influence research, but only a few have explored how research influences standards.

Research limitations/implications

This research provides examples that inspire stronger collaboration between people and processes in research and standardisation.

Originality/value

The articles collected and analysed in this study comprise original research. A limited preliminary study of ten core articles was presented at the International Council for Research and Innovation in Building and Construction World Congress 2022. This presentation of this work provides an expanded framework for analysing the roles of standards in research. This framework includes (1) categorical analysis of research and standardisation streams; (2) thematic analysis of the topic of interest; (3) textual analysis of the use of the term “standard”; (4) methodological analysis of the influence of standards on the research method; and (5) directional analysis of the intended audience.