bluuebunny/crossref_metadata_2025 huggingface dataset:
Volatiles and Intraplate Magmatism: a Variable Role for Carbonated and Altered Oceanic Lithosphere in Ocean Island Basalt Formation
Authors: Kirstein Linda A , Walowski Kristina J , Jones Rosemary E , Burgess Ray , Fitton J Godfrey , De Hoog Jan C M , Savov Ivan P , Kalnins Lara M ,   E I M F
Published: April 2023

Recycling of material at subduction zones has fundamental implications for melt composition and mantle rheology. Ocean island basalts (OIBs) sample parts of the mantle from variable depths that have been diversely affected by subduction zone processes and materials, including the subducted slab, metasomatising melts and fluids. Resultant geochemical differences are preserved at a variety of scales from melt inclusions to whole rocks, from individual islands to chains of islands. Here we examine a global dataset of ocean island basalt compositions with a view to understanding the connection between silica-saturation, olivine compositions, and halogens in glass and olivine-hosted melt inclusions to reveal information regarding the mantle sources of intraplate magmatism. We find that minor elements incorporated into olivine, although informative, cannot unambiguously discriminate between different source contributions, but indicate that none of the OIB analysed here are derived solely from dry peridotite melting. Nor can differences in lithospheric thickness explain trace element variability in olivine between different ocean islands. We present new halogen (F, Cl, Br/Cl, I/Cl) data along with incompatible trace element data for the global array and encourage measurement of fluorine along with heavier halogens to obtain better insight into halogen cycling. We suggest that Ti-rich silica-undersaturated melts require a contribution from carbonated lithosphere, either peridotite or eclogite and are an important component sampled by ocean island basalts, together with altered oceanic crust. These results provide new insights into our understanding of mantle-scale geochemical cycles, and also lead to the potential for the mantle transition zone as an underestimated source for observed volatile and trace-element enrichment in ocean island basalts.
The production of within-family inequality: Insights and implications of integrating genetic data
Authors: Fletcher Jason M , Wu Yuchang , Zhao Zijie , Lu Qiongshi
Published: April 2023

The integration of genetic data within large-scale social and health surveys provides new opportunities to test long-standing theories of parental investments in children and within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments of young children's abilities that are uncontaminated by parental investments, and family-based samples allow indirect tests of whether children's abilities are reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank to test whether the relative ranking of siblings’ polygenic scores for educational attainment is consequential for actual attainments. We find evidence consistent with compensatory processes, on average, where the association between genotype and phenotype of educational attainment is reduced by over 20% for the higher-ranked sibling compared to the lower-ranked sibling. These effects are most pronounced in high socioeconomic status areas. We find no evidence that similar processes hold in the case of height or for relatives who are not full biological siblings (e.g. cousins). Our results provide a new use of polygenic scores to understand processes that generate within-family inequalities and also suggest important caveats to causal interpretations the effects of polygenic scores using sibling difference designs. Future work should seek to replicate these findings in other data and contexts.
Targeting thiol isomerase activity with zafirlukast to treat ovarian cancer from the bench to clinic
Authors: Gelzinis Justine A. , Szahaj Melanie K. , Bekendam Roelof H. , Wurl Sienna E. , Pantos Megan M. , Verbetsky Christina A. , Dufresne Alexandre , Shea Meghan , Howard Kaitlind C. , Tsodikov Oleg V. , Garneau‐Tsodikova Sylvie , Zwicker Jeffrey I. , Kennedy Daniel R.
Published: April 2023

Thiol isomerases, including PDI, ERp57, ERp5, and ERp72, play important and distinct roles in cancer progression, cancer cell signaling, and metastasis. We recently discovered that zafirlukast, an FDA‐approved medication for asthma, is a pan‐thiol isomerase inhibitor. Zafirlukast inhibited the growth of multiple cancer cell lines with an IC50 in the low micromolar range, while also inhibiting cellular thiol isomerase activity, EGFR activation, and downstream phosphorylation of Gab1. Zafirlukast also blocked the procoagulant activity of OVCAR8 cells by inhibiting tissue factor‐dependent Factor Xa generation. In an ovarian cancer xenograft model, statistically significant differences in tumor size between control vs treated groups were observed by Day 18. Zafirlukast also significantly reduced the number and size of metastatic tumors found within the lungs of the mock‐treated controls. When added to a chemotherapeutic regimen, zafirlukast significantly reduced growth, by 38% compared with the mice receiving only the chemotherapeutic treatment, and by 83% over untreated controls. Finally, we conducted a pilot clinical trial in women with tumor marker‐only (CA‐125) relapsed ovarian cancer, where the rate of rise of CA‐125 was significantly reduced following treatment with zafirlukast, while no severe adverse events were reported. Thiol isomerase inhibition with zafirlukast represents a novel, well‐tolerated therapeutic in the treatment of ovarian cancer.
Revisiting Moral Courage as an Educational Objective
Authors: Caldicott Catherine V.
Published: April 2023

In a 2005 paper about the variety of ethical conflicts third-year medical students observed, and their responses to those conflicts, a reluctance to speak up for fear of reprisal emerged as a salient finding. Based on that finding, the authors proposed that moral courage falls within the realm of professional expectations for medical students and that its cultivation is an appropriate formal objective for medical education. Since then, one of those authors has engaged in remediating trainees and practicing clinicians who have committed professional misdeeds, including failures in professionalism, ethics, and maintaining professional boundaries. The perspective gained from working with these individuals and hearing their stories, as well as concepts from behavioral science, have broadened that author’s understanding of how poor professional judgments are made and misdeeds committed and expanded her appreciation for the role of moral courage. Most individuals arrive at their remedial course knowing on some level that what they did was wrong, but are incredulous at how they became capable of acting so improperly. They must learn that every student and practitioner, without exception, is at risk for committing a professional misdeed. Moral courage is required to participate in the kind of reflection and self-assessment necessary to examine one’s own professional wrongdoing and practice safely and competently at all times, just as it is required to speak truth to power and risk negative consequences. The author concludes that medical educators can and should assist trainees to mitigate their risks through regularly—and courageously—assessing themselves and their circumstances with honesty and clarity to develop a mature professional identity, safeguard patients, and ultimately cherish the privilege of licensure.
Elevated basal AMP-activated protein kinase activity sensitizes colorectal cancer cells to growth inhibition by metformin
Authors: Morrison Kaitlin R. , Wang Tingting , Chan Kuan Yoow , Trotter Eleanor W. , Gillespie Ari , Michael Michael Z. , Oakhill Jonathan S. , Hagan Iain M. , Petersen Janni
Published: April 2023

Expression and activity of the AMP-activated protein kinase (AMPK)
α
1 catalytic subunit of the heterotrimeric kinase significantly correlates with poor outcome for colorectal cancer patients. Hence there is considerable interest in uncovering signalling vulnerabilities arising from this oncogenic elevation of AMPK
α
1 signalling. We have therefore attenuated mammalian target of rapamycin (mTOR) control of AMPK
α
1 to generate a mutant colorectal cancer in which AMPK
α
1 signalling is elevated because AMPK
α
1 serine 347 cannot be phosphorylated by mTORC1. The elevated AMPK
α
1 signalling in this HCT116
α
1.S347A cell line confers hypersensitivity to growth inhibition by metformin. Complementary chemical approaches confirmed this relationship in both HCT116 and the genetically distinct HT29 colorectal cells, as AMPK activators imposed vulnerability to growth inhibition by metformin in both lines. Growth inhibition by metformin was abolished when AMPK
α
1 kinase was deleted. We conclude that elevated AMPK
α
1 activity modifies the signalling architecture in such a way that metformin treatment compromises cell proliferation. Not only does this mutant HCT116
AMPKα1-S347A
line offer an invaluable resource for future studies, but our findings suggest that a robust biomarker for chronic AMPK
α
1 activation for patient stratification could herald a place for the well-tolerated drug metformin in colorectal cancer therapy.
Quantifying allo-grooming in wild chacma baboons (Papio ursinus) using tri-axial acceleration data and machine learning
Authors: Christensen Charlotte , Bracken Anna M. , O'Riain M. Justin , Fehlmann Gaëlle , Holton Mark , Hopkins Phillip , King Andrew J. , Fürtbauer Ines
Published: April 2023

Quantification of activity budgets is pivotal for understanding how animals respond to changes in their environment. Social grooming is a key activity that underpins various social processes with consequences for health and fitness. Traditional methods use direct (focal) observations to calculate grooming rates, providing systematic but sparse data. Accelerometers, in contrast, can quantify activity budgets continuously but have not been used to quantify social grooming. We test whether grooming can be accurately identified using machine learning (random forest model) trained on labelled acceleration data from wild chacma baboons (Papio ursinus). We successfully identified giving and receiving grooming with high precision (81% and 91%) and recall (87% and 79%). Giving grooming was associated with a distinct rhythmical signal along the surge axis. Receiving grooming had similar acceleration signals to resting, and thus was more difficult to assign. We applied our machine learning model ton= 680 collar data days fromn= 12 baboons and found that grooming rates obtained from accelerometers were significantly and positively correlated with direct observation rates for giving but not receiving grooming. The ability to collect continuous grooming data in wild populations will allow researchers to re-examine and expand upon long-standing questions regarding the formation and function of grooming bonds.
Observing a trained demonstrator influences associative appetitive learning in rats
Authors: Agee Laura A. , Ortega Miriam E. , Lee Hongjoo J. , Monfils Marie-H.
Published: April 2023

The ability to acquire information about the environment through social observation or instruction is an essential form of learning in humans and other animals. Here, we assessed the ability of rats to acquire an association between a light stimulus and the presentation of a reward that is either hidden (sucrose solution) or visible (food pellet) via observation of a trained demonstrator. Subsequent training of observers on the light-reward association indicated that while observation alone was not sufficient for observers to acquire the association, contact with the reward location was higher in observers that were paired with a demonstrator. However, this was only true when the light cue predicted a sucrose reward. Additionally, we found that in the visible reward condition, levels of demonstrator orienting and food cup contact during the observation period tended to be positively correlated with the corresponding behaviour of their observer. This relationship was only seen during later sessions of observer training. Together, these results suggest that while our models were not sufficient to induce associative learning through observation alone, demonstrator behaviour during observation did influence how their paired observer's behavioural response to the cue evolved over the course of direct individual training.
Uncovering the cytotoxic effects of air pollution with multi-modal imaging of
in vitro
respiratory models
Authors: Al-Rekabi Zeinab , Dondi Camilla , Faruqui Nilofar , Siddiqui Nazia S. , Elowsson Linda , Rissler Jenny , Kåredal Monica , Mudway Ian , Larsson-Callerfelt Anna-Karin , Shaw Michael
Published: April 2023

Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive,
in vitro
respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of
in vitro
imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art
in vitro
respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell–pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.
A Kermack–McKendrick model with age of infection starting from a single or multiple cohorts of infected patients
Authors: Demongeot Jacques , Griette Quentin , Maday Yvon , Magal Pierre
Published: April 2023

The infectiousness of infected individuals is known to depend on the time since the individual was infected, called the age of infection. Here, we study the parameter identifiability of the Kermack–McKendrick model with age of infection which takes into account this dependency. By considering a single cohort of individuals, we show that the daily reproduction number can be obtained by solving a Volterra integral equation that depends on the flow of newly infected individuals. We test the consistency of the method by generating data from deterministic and stochastic numerical simulations. Finally, we apply our method to a dataset from SARS-CoV-1 with detailed information on a single cluster of patients. We stress the necessity of taking into account the initial data in the analysis to ensure the identifiability of the problem.
Development of an immunochromatographic lateral flow assay to rapidly detect OXA-23-, OXA-40-, OXA-58- and NDM-mediated carbapenem resistance determinants in Acinetobacter baumannii
Authors: Mertins Sonja , Higgins Paul G. , Thunissen Caroline , Magein Henri , Gilleman Quentin , Mertens Pascal , Rodríguez María González , Maus Liza Marie , Seifert Harald , Krönke Martin , Klimka Alexander
Published: April 2023

Introduction.

Acinetobacter baumannii

infections can be extremely challenging to treat owing to the worldwide prevalence of multidrug-resistant isolates, especially against carbapenems. Colonization with carbapenem-resistant

A. baumannii

(CRAb) requires rapid action from an infection control perspective because the organism is known for its propensity for epidemic spread.

Hypothesis/Gap Statement. There is an unmet medical need to rapidly identify CRAb to enable appropriate antimicrobial treatment and to prevent transmission.

Aim. Our aim was to expand the OXA-detection abilities of the rapid immunochromatographic test (ICT) OXA-23 K-SeT (Coris BioConcept) to include OXA-40- and OXA-58-like carbapenemases, which together confer carbapenem resistance to more than 94 % of CRAb isolates worldwide.

Methodology. We used hybridoma technology to generate mAbs against OXA-40 and OXA-58 and selected them for productivity and specificity against recombinant and endogenous OXA-40 and OXA-58. Combinations of the resulting mAbs were analysed in ICT format for their ability to detect recombinant rOXA-40His6 or rOXA-58His6, respectively. Subsequently, selected antibody pairs were implemented into single-OXA-40 or single-OXA-58 prototypes and the final OXA-23/40/58/NDM ICT and were evaluated on clinical

Acinetobacter

spp. isolates with well-defined carbapenem resistance mechanisms.

Results. Five anti-OXA-40 and anti-OXA-58 mAbs were selected. Competition ELISA with combinations of these antibodies revealed that the anti-OXA-40 antibodies bind to one of two binding clusters on OXA-40, while anti-OXA-58 antibodies bind to one of four binding clusters on OXA-58. Direct binding to the corresponding antigen in an ICT format has left only three antibodies against rOXA-40His6 and rOXA-58His6, respectively for the subsequent sandwich ICT selection procedure, which revealed that the anti-OXA-40 (#5) and anti-OXA-58 (#A8) mAbs in combination with the cross-reactive mAb #C8 performed best. They were implemented into single-OXA-40 and single-OXA-58 ICT prototypes and evaluated. These single ICT prototypes demonstrated 100 % specificity and sensitivity. Based on these results, an OXA-23/40/58/NDM-ICT was developed, complemented with OXA-23 and NDM-specific detection. An evaluation with selected carbapenem-resistant

Acinetobacter

spp. isolates (n=34) showed 100 % specificity.

Conclusion. With this easy-to-use detection assay, one can save 12–48 h in diagnostics, which helps to treat patients earlier with appropriate antibiotics and allows immediate intervention to control transmission of CRAb.
RoMIA: A Framework for Creating Robust Medical Imaging AI
Authors: Anand Aditi , Krithivasan Sarada , Roy Kaushik
Published: April 2023

Artificial Intelligence (AI) methods, particularly Artificial Neural Networks (ANNs) have shown great promise in a range of medical imaging tasks. Despite their promise, the susceptibility of ANNs to produce erroneous outputs under the presence of input noise, variations, or adversarial attacks is of great concern and one of the largest challenges to adoption in medical settings. Towards addressing this challenge, we explore the robustness of ANNs trained for chest radiograph classification under a range of perturbations reflective of clinical settings. We propose RoMIA, a framework for the creation ofRobustMedical ImagingANNs. RoMIA adds three key steps to the model training and deployment flow: (i) Noise-added training, wherein a part of the training data is synthetically transformed to represent common noise sources, (ii) Fine-tuning with input mixing, in which the model is refined with inputs formed by mixing data from the original training set with a small number of images from a different source, and (iii) DCT-based denoising, which removes a fraction of high-frequency components of each image before applying the model to classify it. We applied RoMIA to create six different robust ANNs for classifying chest radiographs using the CheXpert dataset. We evaluated the models on the CheXphoto dataset, consisting of naturally and synthetically perturbed images intended to evaluate robustness. Models produced by RoMIA show 3-5% improvement in robust accuracy, suggesting that the proposed methods can be a useful step towards enabling the adoption of ANNs in medical imaging applications.
Reducing the Mitochondrial Oxidative Burden Alleviates Lipid-Induced Muscle Insulin Resistance in Humans
Authors: Fiorenza Matteo , Onslev Johan , Henríquez-Olguín Carlos , Persson Kaspar W. , Hesselager Sofie A. , Jensen Thomas E. , Wojtaszewski Jørgen F.P. , Hostrup Morten , Bangsbo Jens
Published: April 2023

Pre-clinical models suggest a causative nexus between mitochondrial oxidative stress and insulin resistance. However, the translational and pathophysiological significance of this mechanism in humans remains unclear. Herein, we employed an invasivein vivomechanistic approach in humans to manipulate mitochondrial redox state while assessing insulin action. To this end, we combined intravenous infusion of a lipid overload with intake of a mitochondria-targeted antioxidant (mtAO) in conjunction with insulin clamp studies. During lipid overload, insulin-stimulated muscle glucose uptake, as determined by the femoral arteriovenous balance technique, was increased by mtAO. At the muscle molecular level, mtAO did not affect canonical insulin signaling but augmented insulin-stimulated GLUT4 translocation while decreasing the mitochondrial oxidative burden under lipid oversupply.Ex vivostudies revealed that mtAO ameliorated features of mitochondrial bioenergetics, including diminished mitochondrial H2O2emission, in muscle fibers exposed to high intracellular lipid levels. These findings provide translational and mechanistic evidence implicating mitochondrial oxidants in the development of lipid-induced muscle insulin resistance in humans.

GRAPHICAL ABSTRACT
ATP synthase evolution on a cross-braced dated tree of life
Authors: Mahendrarajah Tara A. , Moody Edmund R. R. , Schrempf Dominik , Szánthó Lénárd L. , Dombrowski Nina , Davín Adrián A. , Pisani Davide , Donoghue Philip C. J. , Szöllősi Gergely J. , Williams Tom A. , Spang Anja
Published: April 2023

The timing of early cellular evolution from the divergence of Archaea and Bacteria to the origin of eukaryotes remains poorly constrained. The ATP synthase complex is thought to have originated prior to the Last Universal Common Ancestor (LUCA) and analyses of ATP synthase genes, together with ribosomes, have played a key role in inferring and rooting the tree of life. Here we reconstruct the evolutionary history of ATP synthases using an expanded sampling of Archaea, Bacteria, and eukaryotes. We developed a phylogenetic cross-bracing approach making use of endosymbioses and ancient gene duplications of the major ATP synthase subunits to infer a highly resolved, dated species tree and establish an absolute timeline for ATP synthase evolution. Our analyses show that the divergence of the ATP synthase into F- and A/V-type lineages, was a very early event in cellular evolution dating back to more than 4Ga potentially predating the diversification of Archaea and Bacteria. Our cross-braced, dated tree of life also provides insight into more recent evolutionary transitions including eukaryogenesis, showing that the eukaryotic nuclear and mitochondrial lineages diverged from their closest archaeal (2.67-2.19Ga) and bacterial (2.58-2.12Ga) relatives at roughly the same time, with the nuclear stem being moderately longer.
Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection
Authors: Norris Geoffrey T. , Ames Joshua M. , Ziegler Steven F. , Oberst Andrew
Published: April 2023

In order to recover from infection, organisms must balance robust immune responses to pathogens with the tolerance of immune-mediated pathology. This balance is particularly critical within the central nervous system, whose complex architecture, essential function, and limited capacity for self-renewal render it susceptible to both pathogen-and immune-mediated pathology. Here, we identify the alarmin IL-33 and its receptor ST2 as critical for host survival to neuroinvasive flavivirus infection. We identify oligodendrocytes as the critical source of IL-33, and microglia as the key cellular responders. Notably, we find that the IL-33/ST2 axis does not impact viral control or adaptive immune responses; rather, it is required to promote the activation and survival of microglia. In the absence of intact IL-33/ST2 signaling in the brain, neuroinvasive flavivirus infection triggered aberrant recruitment of monocyte-derived peripheral immune cells, increased neuronal stress, and neuronal cell death, effects that compromised organismal survival. These findings identify IL-33 as a critical mediator of CNS tolerance to pathogen-initiated immunity and inflammation.

Author Summary

The central nervous system (CNS) is an extraordinarily complex organ system with limited capacity for repair and renewal. When infectious pathogens invade the CNS, resulting immune responses must clear the pathogen while limiting immune-mediated tissue pathology. IL-33 is an “alarmin” cytokine, whose release from dying cells can promote a variety of immune responses. IL-33 is expressed at high levels in the brain, and previous work has implicated signaling by IL-33 in CNS development as well as in the response to parasitic infection of the CNS. Here, we identify IL-33 as a key mediator of disease tolerance in the context of neuroinvasive infection with the flaviviruses West Nile virus and Zika virus. Notably, we find that IL-33 signaling is not involved in the clearance of virus from the brain; rather, IL-33 is required to promote the survival and reprogramming brain-resident immune cells (microglia). When IL-33 signaling is disrupted in mice, flavivirus infection results in defective microglial activation, increased death of both microglia and neurons, increased invasion of the brain by peripheral immune cells, and increased host death. This work suggests that IL-33 is a key mediator of host tolerance upon neuroinvasive flavivirus infection.
Resting State Brain Connectivity analysis from EEG and FNIRS signals
Authors: Blanco Rosmary , Koba Cemal , Crimi Alessandro
Published: April 2023

Contemporary neuroscience is highly focused on the synergistic use of machine learning and network analysis. Indeed, network neuroscience analysis intensively capitalizes on clustering metrics and statistical tools. In this context, the integrated analysis of functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) provides complementary information about the electrical and hemodynamic activity of the brain. Evidence supports the mechanism of the neurovascular coupling mediates brain processing. However, it is not well understood how the specific patterns of neuronal activity are represented by these techniques. Here we have investigated the topological properties of functional networks of the resting-state brain between synchronous EEG and fNIRS connectomes, across frequency bands, using source space analysis, and through graph theoretical approaches. We observed that at global-level analysis small-world topology network features for both modalities. The edge-wise analysis pointed out increased inter-hemispheric connectivity for oxy-hemoglobin compared to EEG, with no differences across the frequency bands. Our results show that graph features extracted from fNIRS can reflect both shortand longrange organization of neural activity, and that is able to characterize the large-scale network in the resting state. Further development of integrated analyses of the two modalities is required to fully benefit from the added value of each modality. However, the present study highlights that multimodal source space analysis approaches can be adopted to study brain functioning in healthy resting states, thus serving as a foundation for future work during tasks and in pathology, with the possibility of obtaining novel comprehensive biomarkers for neurological diseases.
Temporal origin of nestedness in interaction networks
Authors: Staniczenko Phillip P. A. , Panja Debabrata
Published: April 2023

Nestedness is a common property of communication, finance, trade, and ecological networks. In networks with high levels of nestedness, the link positions of low-degree nodes (those with few links) form nested subsets of the link positions of high-degree nodes (those with many links), leading to matrix representations with characteristic upper-triangular or staircase patterns. Recent theoretical work has connected nestedness to the functionality of complex systems and has suggested it is a structural by-product of the skewed degree distributions often seen in empirical data. However, mechanisms for generating nestedness remain poorly understood, limiting the connections that can be made between system processes and observed network structures. Here, we show that a simple probabilistic model based on phenology — the timing of co-presences among interaction partners — can produce nested structures and correctly predict around two-thirds of interactions in two fish market networks and around one-third of interactions in 22 plant-pollinator networks. Notably, the links most readily explained by frequent actor co-presences appear to form a backbone of nested interactions, with the remaining interactions attributable to opportunistic interactions or preferences for particular interaction partners that are not routinely available.

Significance statement

Networks describe the relationships among actors in complex systems. In nested networks, actors involved in few interactions are connected to actors involved in many interactions, with those highly-connected actors also interacting with other highly-connected actors. This pattern is seen in a variety of empirical systems and influences the response to external perturbations, but little is known about the processes that give rise to nestedness. We show that phenology, the day-to-day timing of interaction partner availability, is a general mechanism that generates nested structures. We present a simple probabilistic model which accounts for actor overlap through time but assumes actors have no preference for specific interaction partners, thereby providing an instructive baseline for investigating higher-level selection processes in interaction networks.
Quantification of Rho-terminationin vivousing qRT-PCR: a comprehensive analysis
Authors: Abishek N Monford Paul , Jeon Heung Jin , Wang Xun , Lim Heon M.
Published: April 2023

In prokaryotes, the Rho protein mediates Rho-dependent termination (RDT) by identifying a non-specific cytosine-rich Rho utilization site on the newly synthesized RNA. As a result of RDT, downstream RNA transcription is reduced. Due to the bias in reverse transcription and PCR amplification, we were unable to identify the RDT site by directly measuring the amount of mRNA upstream and downstream of RDT sites. To overcome this difficulty, we employed a 77 bp reporter geneargX, coding transfer RNA that binds L-arginine, tRNAargfromBrevibacterium albidum, and transcriptionally fused it to the sequences to be assayed. We constructed a series of plasmids by combining a segment of the galactose (gal) operon sequences, both with and without the RDT regions at the ends of cistrons (galE,galT,andgalM) upstream ofargX. The RNA polymerase will transcribe thegaloperon sequence andargXunless it encounters the RDT encoded by the inserted sequence. We observed similar tRNAarghalf-lives expressed in these transcriptional fusion plasmids. Therefore, the amount of tRNAargdirectly represents the number of transcripts transcribed. Using this approach, we were able to effectively assay the RDTs in thegaloperon by quantifying the relative amount of tRNAargusing quantitative real-time PCR (qRT-PCR) analyses. The resultant RDT% forgalET, galTK, and at the end ofgalMwere 36, 26, and 63, individually. Our findings demonstrate that combining tRNAarg, with qRT-PCR can directly measure RDT efficienciesin vivo, making it a useful tool for gene expression research.
LOCC: a novel visualization and scoring of cutoffs for continuous variables
Authors: Luo George , Letterio John J.
Published: April 2023

Objective

There is a need for new methods to select and analyze cutoffs employed to define genes that are most prognostic significant and impactful. We designed LOCC (Luo’s Optimization Categorization Curve), a novel tool to visualize and score continuous variables for a dichotomous outcome.

Methods

To demonstrate LOCC with real world data, we analyzed TCGA hepatocellular carcinoma gene expression and patient data using LOCC. We compared LOCC visualization to receiver operating characteristic (ROC) curve for prognostic modeling to showcase its utility in understanding predictors in various TCGA datasets.

Results

Analysis ofE2F1expression in hepatocellular carcinoma using LOCC demonstrated appropriate cutoff selection and validation. In addition, we compared LOCC visualization and scoring to ROC curves and c-statistics, demonstrating that LOCC better described predictors. Analysis of a previously published gene signature showed large differences in LOCC scoring, and removing the lowest scoring genes did not affect prognostic modeling of the gene signature demonstrating LOCC scoring could distinguish which predictors were most critical.

Conclusion

Overall, LOCC is a novel visualization tool for understanding and selecting cutoffs, particularly for gene expression analysis in cancer. The LOCC score can be used to rank genes for prognostic potential and is more suitable than ROC curves for prognostic modeling.

Graphical Abstract
TEAD1 regulates ITGA1 and ITGA2 to control prostate cancer progression
Authors: Sara Cruz Pereira , Qin Zhang , Raman Devarajan , Paia Christos , Binjie Luo , Kai Zhang , Jihan Xia , Anne Ahtikoski , Markku Vaarala , Tomasz Wenta , Gong-Hong Wei , Aki Manninen
Published: April 2023

The extracellular matrix (ECM) undergoes significant changes during prostate cancer (PCa) progression and actively regulates PCa growth and invasion. Here, we performed a meta-analysis of PCa cohorts and found that downregulation or loss ofITGA1andITGA2integrin genes was associated with tumor progression to metastasis and poor prognosis in PCa patients. Genomic deletion of both α1- and α2-integrins activated epithelial-to-mesenchymal transition (EMT) in benign prostate epithelial cells, thereby enhancing their invasive potentialin vitroand converting them into tumorigenic cellsin vivo. Mechanistically, EMT was induced by enhanced secretion and subsequent activation of autocrine TGFβ1 and nuclear targeting of YAP1. Our unbiased genome-wide co-expression analysis of large PCa cohort datasets identified the transcription factor TEAD1 as a key regulator ofITGA1andITGA2expression in PCa cells while TEAD1 loss phenocopied the dual loss of α2- and α2-integrins in vitro and in vivo. Notably, clinical data analysis revealed thatTEAD1downregulation or loss was associated with aggressive PCa and could synergize withITGA1andITGA2expression to impact PCa prognosis and progression. Altogether, our results demonstrate that loss of α1- and α2-integrins, either via deletion/inactivation of theITGA1/ITGA2locus or via loss ofTEAD1, contributes to PCa progression by inducing TGFβ1-driven EMT.
POWTEX visits POWGEN
Authors: Houben Andreas , Meinerzhagen Yannick , Nachtigall Noah , Jacobs Philipp , Dronskowski Richard
Published: April 2023

The high-intensity time-of-flight (TOF) neutron diffractometer POWTEX for powder and texture analysis is currently being built prior to operation in the eastern guide hall of the research reactor FRM II at Garching close to Munich, Germany. Because of the world-wide 3He crisis in 2009, the authors promptly initiated the development of 3He-free detector alternatives that are tailor-made for the requirements of large-area diffractometers. Herein is reported the 2017 enterprise to operate one mounting unit of the final POWTEX detector on the neutron powder diffractometer POWGEN at the Spallation Neutron Source located at Oak Ridge National Laboratory, USA. As a result, presented here are the first angular- and wavelength-dependent data from the POWTEX detector, unfortunately damaged by a 50g shock but still operating, as well as the efforts made both to characterize the transport damage and to successfully recalibrate the voxel positions in order to yield nonetheless reliable measurements. Also described is the current data reduction process using the PowderReduceP2D algorithm implemented in Mantid [Arnold et al. (2014). Nucl. Instrum. Methods Phys. Res. A, 764, 156–166]. The final part of the data treatment chain, namely a novel multi-dimensional refinement using a modified version of the GSAS-II software suite [Toby & Von Dreele (2013). J. Appl. Cryst.
46, 544–549], is compared with a standard data treatment of the same event data conventionally reduced as TOF diffraction patterns and refined with the unmodified version of GSAS-II. This involves both determining the instrumental resolution parameters using POWGEN's powdered diamond standard sample and the refinement of a friendly-user sample, BaZn(NCN)2. Although each structural parameter on its own looks similar upon comparing the conventional (1D) and multi-dimensional (2D) treatments, also in terms of precision, a closer view shows small but possibly significant differences. For example, the somewhat suspicious proximity of the a and b lattice parameters of BaZn(NCN)2 crystallizing in Pbca as resulting from the 1D refinement (0.008 Å) is five times less pronounced in the 2D refinement (0.038 Å). Similar features are found when comparing bond lengths and bond angles, e.g. the two N—C—N units are less differently bent in the 1D results (173 and 175°) than in the 2D results (167 and 173°). The results are of importance not only for POWTEX but also for other neutron TOF diffractometers with large-area detectors, like POWGEN at the SNS or the future DREAM beamline at the European Spallation Source.
SDU – software for high-throughput automated data collection at the Swiss Light Source
Authors: Smith Kate Mary Louise , Panepucci Ezequiel , Kaminski Jakub Wojciech , Aumonier Sylvain , Huang Chia-Yiang , Eris Deniz , Buntschu Dominik , Meier Nathalie , Glettig Wayne , McAuley Katherine Evelyn , Wang Meitian , Sharpe May Elizabeth , Wojdyla Justyna Aleksandra
Published: April 2023

Recent advances in automation have fostered the development of unattended data collection services at a handful of synchrotron facilities worldwide. At the Swiss Light Source, the installation of new high-throughput sample changers at all three macromolecular crystallography beamlines and the commissioning of the Fast Fragment and Compound Screening pipeline created a unique opportunity to automate data acquisition. Here, the DA+ microservice software stack upgrades, implementation of an automatic loop-centering service and deployment of the Smart Digital User (SDU) software for unattended data collection are reported. The SDU software is the decision-making software responsible for communications between services, sample and device safety, sample centering, sample alignment with grid based X-ray diffraction and, finally, data collection.
Statistical analyses of the oxidized P-clusters in MoFe proteins using the bond-valence method: towards their electron transfer in nitrogenases
Authors: Xie Zhen-Lang , Yuan Chang , Zhou Zhao-Hui
Published: April 2023

26 well selected oxidized P-clusters (P2+) from the crystallographic data deposited in the Protein Data Bank have been analysed statistically by the bond-valence sum method with weighting schemes for MoFe proteins at different resolutions. Interestingly, the oxidation states of P2+ clusters correspond to Fe2
3+Fe6
2+ with high electron delocalization, showing the same oxidation states as the resting states of P-clusters (PN) in nitrogenases. The previously uncertain reduction of P2+ to PN clusters by two electrons was assigned as a double protonation of P2+, in which decoordination of the serine residue and the peptide chain of cysteine take place, in MoFe proteins. This is further supported by the obviously shorter α-alkoxy C—O bond (average of 1.398 Å) in P2+ clusters and longer α-hydroxy C—O bond (average of 1.422 Å) in PN clusters, while no change is observed in the electronic structures of Fe8S7 Fe atoms in P-clusters. Spatially, the calculations show that Fe3 and Fe6, the most oxidized and most reduced Fe atoms, have the shortest distances of 9.329 Å from the homocitrate in the FeMo cofactor and 14.947 Å from the [Fe4S4] cluster, respectively, and may well function as important electron-transport sites.
Determinants of COVID-19 masking among artisanal fisherfolks in Ghana: the role of time discounting
Authors: Akpalu Wisdom , Adanu Kwami
Published: April 2023

Purpose

Daily COVID-19-related morbidity and mortality rates are still high globally, and masking is considered a reliable method of preventing its infections. Yet, the rate of voluntary compliance with masking remains very low in most parts of the world, especially in developing countries. The authors hypothesize that the decision to wear a mask entails some benefit-cost analysis that involves time discounting. In addition, the authors surmise that feel-good benefits from pro-social behavior and from wearing fashionable masks are substantial.

Design/methodology/approach

The study is based on a survey of 900 fishermen and fish traders in Ghana. A simple experiment was designed to elicit individual rates of time preference. In addition, the fishers were asked questions about their political affiliation and knowledge of the COVID-19 pandemic, among others. A logit model is used to investigate the determinants of the decision to wear a mask.

Findings

The authors found that masking compliance increases in time discounting for fishmongers, suggesting that private benefits from pro-social behavior or feel-good benefits from wearing a mask are very strong. In addition, those who belonged to the ruling political party were more likely to wear a mask. Other factors increasing the likelihood of masking include affiliation with the ruling political party, knowledge of COVID-19 and knowledge of someone who lost his/her job due to COVID-19.

Originality/value

To the best of the authors’ knowledge, this is the first study to investigate the effect of time discounting on the voluntary compliance of a health safety measure, which could provide a direct utility. In addition, the study explores the effect of political affiliation on voluntary masking behavior.
Utilisation of drones in achieving various applications in smart warehouse management
Authors: Ali Sadia Samar , Khan Shahbaz , Fatma Nosheen , Ozel Cenap , Hussain Aftab
Published: April 2023

Purpose

Organisations and industries are often looking for technologies that can accomplish multiple tasks, providing economic benefits and an edge over their competitors. In this context, drones have the potential to change many industries by making operations more efficient, safer and more economic. Therefore, this study investigates the use of drones as the next step in smart/digital warehouse management to determine their socio-economic benefits.

Design/methodology/approach

The study identifies various enablers impacting drone applications to improve inventory management, intra-logistics, inspections and surveillance in smart warehouses through a literature review, a test of concordance and the fuzzy Delphi method. Further, the graph theory matrix approach (GTMA) method was applied to ranking the enablers of drone application in smart/digital warehouses. In the subsequent phase, researchers investigated the relation between the drone application's performance and the enablers of drone adoption using logistic regression analysis under the TOE framework.

Findings

This study identifies inventory man agement, intra-logistics, inspections and surveillance are three major applications of drones in the smart warehousing. Further, nine enablers are identified for the adoption of drone in warehouse management. The findings suggest that operational effectiveness, compatibility of drone integration and quality/value offered are the most impactful enablers of drone adoption in warehouses. The logistic regression findings are useful for warehouse managers who are planning to adopt drones in a warehouse for efficient operations.

Research limitations/implications

This study identifies the enablers of drone adoption in the smart and digital warehouse through the literature review and fuzzy Delphi. Therefore, some enablers may be overlooked during the identification process. In addition to this, the analysis is based on the opinion of the expert which might be influenced by their field of expertise.

Practical implications

By considering technology-organisation-environment (TOE) framework warehousing companies identify the opportunities and challenges associated with using drones in a smart warehouse and develop strategies to integrate drones into their operations effectively.

Originality/value

This study proposes a TOE-based framework for the adoption of drones in warehouse management to improve the three prominent warehouse functions inventory management, intra-logistics, inspections and surveillance using the mixed-method.
Emergence, evolution, challenges and future prospect in LIS education and its impact on job opportunity of LIS education in Pakistan
Authors: Shah Suhaib Hussain , Pei Lei , Chen Tianyu
Published: April 2023

Purpose

This study aims to investigate the status of library and information science (LIS) education in Pakistan, as well as LIS progress, level of employment and issues, infrastructure and facilities, challenges faced by LIS institutions and future prospects of the profession.

Design/methodology/approach

A total of 115 permanent/regular and visiting academic members from different Pakistani institutions/universities participated in the research. A mixed-method was used, and data was collected through questionnaires and interviews. The data was analyzed quantitatively and qualitatively.

Findings

This study’s results showed that assistant, associate and associate professors have been very involved in producing high-quality research articles and producing quality graduates. This study also found that there are several problems with LIS education in Pakistan, such as a lack of qualified teachers, resources and facilities. This study provides all the answers to these problems. They are useful for LIS teachers and students in Pakistan because LIS education has been around for a long time, but there are still some problems that need to be fixed. The results could have an immediate effect on the direction, ability to survive and future of LIS education in Pakistan.

Originality/value

Previously, different studies have been conducted on evolution and challenges to the LIS profession, but to the best of the authors’ knowledge, no study has been reported based on the professional experiences in other Universities of Pakistan. According to the research, the findings are crucial for LIS professors and students in Pakistan. In addition, the research investigates the challenges faced by LIS teachers in Pakistan. It concludes with suggestions on how to address some of these problems. It is also said that Pakistan must develop universal standards for LIS to close the gap between what users want and what library workers can do.