bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-charging your fats: Charmm36 parameters for neutral lipids triacylglycerol and diacylglycerol
Authors: Campomanes Pablo , Prabhu Janak , Zoni Valeria , Vanni Stefano
Published: October 2021

Neutral lipids (NLs) are an abundant class of cellular lipids. They are characterized by the total lack of charged chemical groups in their structure, and, as a consequence, they play a major role in intracellular lipid storage. NLs that carry a glycerol backbone, such as triacylglycerols (TGs) and diacylglycerols (DGs), are also involved in the biosynthetic pathway of cellular phospholipids, and they have recently been the subject of numerous structural investigations by means of atomistic molecular dynamics (MD) simulations. However, conflicting results on the physicochemical behavior of NLs were observed depending on the nature of the atomistic force field used. Here, we show that current phospholipid-derived CHARMM36 parameters for DGs and TGs cannot reproduce adequately interfacial properties of these NLs, due to excessive hydrophilicity at the glycerol-ester region. By following a CHARMM36-consistent parameterization strategy, we develop new parameters for both TGs and DGs that are compatible with both cutoffbased and Particle Mesh Ewald (PME) schemes for the treatment of Lennard Jones interactions. We show that our new parameters can reproduce interfacial properties of NLs and their behavior in more complex lipid assemblies. We discuss the implications of our findings in the context of intracellular lipid storage and NLs cellular activity.
Loss of Nrf1 rather than Nrf2 leads to inflammatory accumulation of lipids and reactive oxygen species (ROS) in human hepatoma cells, which is alleviated by 2-bromopalmitate
Authors: Deng Rongzhen , Zheng Ze , Hu Shaofan , Wang Meng , Feng Jing , Mattjus Peter , Zhang Zhengwen , Zhang Yiguo
Published: October 2021

Since Nrf1 and Nrf2 are essential for regulating the lipid metabolism pathways, their dysregulation has thus been shown to be critically involved in the non-controllable inflammatory transformation into cancer. Herein, we have explored the molecular mechanisms underlying their distinct regulation of lipid metabolism, by comparatively analyzing the changes in those lipid metabolism-related genes inNrf1α–/–and/orNrf2–/–cell lines relative to wild-type controls. The results revealed that loss of Nrf1α leads to lipid metabolism disorders. That is, its lipid synthesis pathway was up-regulated by the JNK-Nrf2-AP1 signaling, while its lipid decomposition pathway was down-regulated by the nuclear receptor PPAR-PGC1 signaling, thereby resulting in severe accumulation of lipids as deposited in lipid droplets. By contrast, knockout of Nrf2 gave rise to decreases in lipid synthesis and uptake capacity. These demonstrate that Nrf1 and Nrf2 contribute to significant differences in the cellular lipid metabolism profiles and relevant pathological responses. Further experimental evidence unraveled that lipid deposition inNrf1α–/–cells resulted from CD36 up-regulation by activating the PI3K-AKT-mTOR pathway, leading to abnormal activation of the inflammatory response. This was also accompanied by a series of adverse consequences, e.g., accumulation of reactive oxygen species (ROS) inNrf1α–/–cells. Interestingly, treatment ofNrf1α–/–cells with 2-bromopalmitate (2BP) enabled the yield of lipid droplets to be strikingly alleviated, as accompanied by substantial abolishment of CD36 and critical inflammatory cytokines. SuchNrf1α–/–led inflammatory accumulation of lipids, as well as ROS, was significantly ameliorated by 2BP. Overall, this study provides a potential strategy for cancer prevention and treatment by precision targeting of Nrf1, Nrf2 alone or both.
A phylogenetic and transcriptomic study of the β-1,3-glucanase family in tomato identifies candidate targets for fruit improvement
Authors: Paniagua Candelas , Perry Louisa , Benitez-Alfonso Yoselin
Published: October 2021

Tomato, Solanum lycopersicum, is one of the most cultivated fruits. However, between one-quarter and half of their production is lost during transport and storage. Modifications in cell walls, and specifically pectin composition, delay fruit softening but, so far, the impact of callose metabolism in this process has not been investigated. Callose accumulates in cell walls around plasmodesmata to modify symplasmic transport. It also plays a role in reinforcing cell walls in response to bruising or pathogen invasion. The aim of this work is to identify cell wall β-1,3-glucanases expressed in tomato fruit that can be used as targets to modify callose accumulation during ripening. A phylogenetic analysis identified fifty candidate β -1,3-glucanases in tomato distributed in three clusters (α, β and γ) with evolutionary relations previously characterised in the model Arabidopsis thaliana. Analysis of tomato microarray data indicates different regulatory patterns: the expression of a subset of enzymes in cluster α decreased during ripening, while enzymes in cluster β and γ displayed higher expression in white-red stages. qRT-PCR experiments confirm the differential regulation of enzymes in different clusters suggesting evolutionary divergences that correlate with differences in their predicted localization and function. The potential to exploit this information in the selection of targets to modify cell walls and fruit development is discussed.
CoCoRV: a rare variant analysis framework using publicly available genotype summary counts to prioritize germline disease-predisposition genes
Authors: Chen Wenan , Wang Shuoguo , Tithi Saima Sultana , Ellison David , Wu Gang
Published: October 2021

Sequencing cases without matched healthy controls hinders prioritization of germline disease-predisposition genes. To circumvent this problem, genotype summary counts from public data sets can serve as controls. However, systematic inflation and false positives can arise if confounding factors are not addressed. We propose a new framework,consistent summarycounts basedrarevariant burden test (CoCoRV), to address these challenges. CoCoRV has consistent variant quality control and filtering, ethnicity-stratified rare variant association test, accurate estimation of inflation factors, powerful FDR control, and can detect rare variants in high linkage disequilibrium. When we applied CoCoRV to pediatric cancer cohorts, the top genes identified were cancer-predisposition genes. We also applied CoCoRV to identify disease-predisposition genes in adult brain tumors and amyotrophic lateral sclerosis. Given that potential confounding factors were well controlled after applying the framework, CoCoRV provides a cost-effective solution to prioritizing disease-risk genes enriched with rare pathogenic variants.
Augmented Transcutaneous Stimulation Using an Injectable Electrode
Authors: Verma Nishant , Graham Robert D , Mudge Jonah , Trevathan James K , Franke Manfred , Shoffstall Andrew J , Williams Justin , Dalrymple Ashley N , Fisher Lee E , Weber Doug J , Lempka Scott F , Ludwig Kip A
Published: October 2021

Minimally invasive neuromodulation technologies seek to marry the neural selectivity of implantable devices with the low-cost and non-invasive nature of transcutaneous electrical stimulation (TES). The Injectrode® is a needle-delivered electrode that is injected onto neural structures under image guidance. Power is then transcutaneously delivered to the Injectrode using surface electrodes. The Injectrode serves as a low-impedance conduit to guide current to the deep on-target nerve, reducing activation thresholds by an order of magnitude compared to using only surface stimulation electrodes. To minimize off-target recruitment of cutaneous fibers, the energy transfer efficiency from the surface electrodes to the Injectrode must be optimized.

TES energy is transferred to the Injectrode through both capacitive and resistive mechanisms. Electrostatic finite element models generally used in TES research consider only the resistive means of energy transfer by defining tissue conductivities. Here, we present an electroquasistatic model, taking into consideration both the conductivity and permittivity of tissue, to understand transcutaneous power delivery to the Injectrode. The model was validated with measurements taken from (n=4) swine cadavers. We used the validated model to investigate system and anatomic parameters that influence the coupling efficiency of the Injectrode energy delivery system. Our work suggests the relevance of electroquasistatic models to account for capacitive charge transfer mechanisms when studying TES, particularly when high-frequency voltage components are present, such as those used for voltage-controlled pulses and sinusoidal nerve blocks.
Pan-cancer analysis of patient tumor single-cell transcriptomes identifies promising selective and safe CAR targets in head and neck cancer
Authors: Madan Sanna , Sinha Sanju , Gutkind Silvio J. , Cohen Ezra E. W. , Schäffer Alejandro A. , Ruppin Eytan
Published: October 2021

BACKGROUND:Chimeric antigen receptor (CAR) T cell therapies have yielded transformative clinical success for patients with blood tumors, but their full potential remains to be unleashed against solid tumors. One challenge is finding selective targets: cell surface proteins that are expressed widely by cancer cells and minimally by healthy cells in the tumor microenvironment and other normal tissues.

METHODS:Analyzing pan-cancer patient tumor single cell transcriptomics data, we first define and quantify selectivity and safety scores of existing CAR targets for indications in which they are in clinical trials or approved. Selectivity scores are computed by the ability of a given surfaceome gene to classify tumor from nontumor cells in the tumor microenvironment. Safety scores are computed by mining healthy tissue transcriptomics and proteomics atlas data. Second, we identify new candidate cell surface CAR targets that have better selectivity and safety scores than the leading targets among those currently being tested, in an indication-specific manner.

RESULTS:Remarkably, in almost all cancer types, we cannot find such better targets, testifying to the overall near optimality of the current target space. However, in HPV-negative head and neck squamous cell carcinoma (HNSC), for which there is currently a dearth of existing CAR targets, we find five new targets that have both superior selectivity and safety scores. Among the HNSC new targets, we find a few that additionally are strongly essentiality in HNSC cell lines.
DnaK response to expression of protein mutants is dependent on translation rate and stability
Authors: Christensen Signe , Rämisch Sebastian , André Ingemar
Published: October 2021

Chaperones play a central part in the quality control system in cells by clearing misfolded and aggregated proteins. The chaperone DnaK acts as a sensor for molecular stress by recognising short hydrophobic stretches of misfolded proteins. As the level of unfolded protein is a function of protein stability, we hypothesised that the level of DnaK response upon overexpression of recombinant proteins would be correlated to stability. Using a set of mutants of the λ-repressor with varying thermal stabilities and a fluorescent reporter system, the effect of stability on DnaK response and protein abundance was investigated. Our results demonstrate that the initial DnaK response is largely dependent on protein synthesis rate but as the recombinantly expressed protein accumulates and homeostasis is approached the response correlates strongly with stability. Furthermore, we observe a large degree of cell-cell variation in protein abundance and DnaK response in more stable proteins.
Molecular characterization ofMycobacterium ulceransDNA gyrase and identification of mutations reduced susceptibility against quinolonesin vitro
Authors: Kim Hyun , Mori Shigtarou , Kenri Tsuyoshi , Suzuki Yasuhiko
Published: October 2021

Buruli ulcer disease is a neglected necrotizing and disabling cutaneous tropical illness caused byMycobacterium ulcerans(Mul). Fluoroquinolone (FQ), used in the treatment of this disease, has been known to act by inhibiting the enzymatic activities of DNA gyrase; however, the detailed molecular basis of these characteristics and the FQ resistance mechanisms inMulremains unknown. This study investigated the detailed molecular mechanism ofMulDNA gyrase and the contribution of FQ resistancein vitrousing recombinant proteins from theMulsubsp. shinshuense and Agy99 strains with reduced sensitivity to FQs. The IC50of FQs against Ala91Vla and Asp95Gly mutants ofMulshinshuense and Agy99 GyrA subunits were 3.7- to 42.0-fold higher than those against wild-type enzyme. Similarly, the CC25was 10- to 210-fold higher than those for the WT enzyme. Furthermore, the interaction between the amino acid residues of WT/mutantMulDNA gyrase and FQ side chains was assessed via molecular docking studies. This is the first detailed study showing the contribution ofMulDNA GyrA subunit mutations to reduce the susceptibility against FQs.
Why can we detect lianas from space?
Authors: Visser Marco D. , Detto Matteo , Meunier Félicien , Wu Jin , Foster Jane R. , Marvin David C. , van Bodegom Peter M. , Bongalov Boris , Nunes Matheus Henrique , Coomes David , Verbeeck Hans , Guzmán Q J. Antonio , Sanchez-Azofeifa Arturo , Chandler Chris J. , van der Heijden Geertje M.F , Boyd Doreen S. , Foody Giles M. , Cutler Mark E.J. , Broadbent Eben N. , Serbin Shawn P. , Schnitzer Stefan , Rodríguez-Ronderos M. Elizabeth , Sterck Frank , Medina-Vega José A. , Pacala Steve
Published: October 2021

Lianas, woody vines acting as structural parasites of trees, have profound effects on the composition and structure of tropical forests, impacting tree growth, mortality, and forest succession. Remote sensing offers a powerful tool for quantifying the scale of liana infestation, provided the availability of robust detection methods. We analyze the consistency and global specificity of spectral signals from liana-infested tree crowns and forest stands, examining the underlying mechanisms. We compiled a database, including leaf reflectance spectra from 5424 leaves, fine-scale airborne reflectance data from 999 liana-infested canopies, and coarse-scale satellite reflectance data covering hectares of liana-infested forest stands. To unravel the mechanisms of the liana spectral signal, we applied mechanistic radiative transfer models across scales, corroborated by field data on liana leaf chemistry and canopy structure. We find a consistent liana spectral signature at canopy and stand scales across sites. This signature mainly arises at the canopy level due to direct effects of leaf angles, resulting in a larger apparent leaf area, and indirect effects from increased light scattering in the NIR and SWIR regions, linked to lianas’ less costly leaf construction compared to trees. The existence of a consistent global spectral signal for lianas suggests that large-scale quantification of liana infestation is feasible. However, because the traits identified are not exclusive to lianas, accurate large-scale detection requires rigorously validated remote sensing methods. Our models highlight challenges in automated detection, such as potential misidentification due to leaf phenology, tree life-history, topography, and climate, especially where the scale of liana infestation is less than a single remote sensing pixel. The observed cross-site patterns also prompt ecological questions about lianas’ adaptive similarities across environments, indicating possible convergent evolution due to shared constraints on leaf biochemical and structural traits.

Open data statement

Of the 17 datasets used, 10 are published and publicly accessible, with links provided in this submission (Appendix S1: Section S1). Upon acceptance, remaining seven datasets will be provided via Smithsonian’s Dspace. The open-source model code is available as R-package ccrtm (https://cran.r-project.org/web/packages/ccrtm/index.html) and on github (https://github.com/MarcoDVisser/ccrtm). Code will be archived in Zenodo should the manuscript be accepted for publication
S. pombe wtf genes use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive
Authors: Nuckolls Nicole L. , Srinivasa Ananya Nidamangala , Mok Anthony C. , Bravo Núñez María Angélica , Lange Jeffrey J. , Gallagher Todd J. , Seidel Chris W. , Zanders Sarah E.
Published: October 2021

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This dual transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.

Author Summary

Killer meiotic drivers are one type of selfish DNA sequence. When only one copy of a killer meiotic driver is found in a genome, the driver is expected to be transmitted to only half of the gametes (e.g. eggs or sperm). Killer meiotic drivers, however, kill developing gametes that do not inherit them, giving the driver a transmission advantage into the next generation. The molecular mechanisms used by these killers are not well understood. In this work, we analyzed how one killer meiotic driver, wtf4 from fission yeast, ensures targeted gamete (spore) killing. Previous work showed that wtf meiotic drivers encode a poison protein that is transmitted to all spores and an antidote protein that rescues only spores that inherit the locus. Here, we show that different timing of the expression of the two proteins, combined with differential inclusion of the proteins in developing spores, both contribute to targeted spore killing. We also demonstrate that wtf4 exploits an essential gene expression pathway, making it difficult for the genome to prevent this locus from being expressed and killing. This extends our knowledge both of how these genetic parasites act and how they are equipped to evade host suppression mechanisms.
Strain and rupture of HIV-1 capsids during uncoating
Authors: Yu Alvin , Lee Elizabeth M.Y. , Briggs John A.G. , Ganser-Pornillos Barbie K. , Pornillos Owen , Voth Gregory A.
Published: October 2021

Viral replication in HIV-1 relies on a fullerene-shaped capsid to transport genetic material deep into the nucleus of an infected cell. Capsid stability is linked to the presence of cofactors, including inositol hexakisphosphate (IP6) that bind to pores found in the capsid. Using extensive all-atom molecular dynamics simulations of HIV-1 cores imaged from cryo-electron tomography (cryo-ET) in intact virions, which contain IP6 and a ribonucleoprotein complex, we find markedly striated patterns of strain on capsid lattices. The presence of these cofactors also increases rigidity of the capsid. Conformational analysis of capsid (CA) proteins show CA accommodates strain by locally flexing away from structures resolved using x-ray crystallography and cryo-electron microscopy. Then, cryo-ET of HIV-1 cores undergoing endogenous reverse transcription demonstrate that lattice strain increases in the capsid prior to mechanical failure and that the capsid ruptures by crack propagation along regions of high strain. These results uncover HIV-1 capsid properties involved in their critical disassembly process.

Significance statement

The mature capsids of HIV-1 are transiently stable complexes that self-assemble around the viral genome during maturation, and uncoat to release preintegration complexes that archive a double-stranded DNA copy of the virus in the host cell genome. However, a detailed view of how HIV cores rupture remains lacking. Here, we elucidate the physical properties involved in capsid rupture using a combination of large-scale all-atom molecular dynamics simulations and cryo-electron tomography. We find that intrinsic strain on the capsid forms highly correlated patterns along the capsid surface, along which cracks propagate. Capsid rigidity also increases with high strain. Our findings provide fundamental insight into viral capsid uncoating.
Anisotropy of plasmalemmal sterols and cell mating require StARkin domain proteins Ysp2 and Lam4
Authors: Chauhan Neha , Fairn Gregory D.
Published: October 2021

In the budding yeast S. cerevisiae Cdc42 is required for polarized growth and the formation of mating projections (shmoos). Negatively charged lipids including phosphatidylserine and phosphatidylinositol 4,5-bisphosphate support a positive feedback loop that recruits Cdc42 effectors and MAP kinase scaffolds, many of which contain polybasic patches that directly interact with the membrane. Here, using genetically encoded sterol sensor ALOD4 we find that ergosterol is accumulated in the cytosolic leaflet of buds and shmoos. The accumulation of ergosterol in the plasma membrane requires both Osh and Lam proteins however cells lacking Ysp2/Lam2 and Lam4 displayed a reversal in the polarity of ergosterol. The redistribution of ergosterol impairs the polarization of phosphatidylserine and phosphatidylinositol 4,5-bisphophate which further impacts shmoo formation, MAPK signaling and mating efficiency. Our observations demonstrate that the ability of Lam proteins to deliver ergosterol from the plasma membrane to the ER helps maintain a gradient of ergosterol which in turn supports robust cell polarity.

The sterol sensor ALOD4 is enriched at sites of polarized growth. Elimination of the Osh proteins solubilized the ALOD4 whereas elimination of Ysp2 and Lam4 reversed ALOD4 polarization. Cells lacking Ysp2 and Lam4 have defects in mating and MAP kinase signaling.
A Role for Cell Polarity in Lifespan and Mitochondrial Quality Control in the Budding Yeast Saccharomyces cerevisiae
Authors: Yang Emily J. , Pernice Wolfgang M , Pon Liza A.
Published: October 2021

Babies are born young, largely independent of the age of their mothers. Mother-daughter age asymmetry in yeast is achieved, in part, by inheritance of higher-functioning mitochondria by daughter cells and retention of some high-functioning mitochondria in mother cells. The mitochondrial F-box protein, Mfb1p, tethers mitochondria at both poles in a cell cycle-regulated manner: it localizes to and anchors mitochondria to the mother cell tip throughout the cell cycle, and to the bud tip prior to cytokinesis. Here, we report that cell polarity and polarized localization of Mfb1p decline with age in S. cerevisiae. Moreover, deletion of BUD1/RSR1, a Ras protein required for cytoskeletal polarization during asymmetric yeast cell division, results in depolarized Mfb1p localization, defects in mitochondrial distribution and quality control, and reduced replicative lifespan. Our results demonstrate a role for the polarity machinery in lifespan through modulating Mfb1 function in asymmetric inheritance of mitochondria during yeast cell division.
Cost-effective, high-throughput phenotyping system for 3D reconstruction of fruit form
Authors: Feldmann Mitchell J. , Tabb Amy
Published: October 2021

Reliable phenotyping methods that are simple to operate and inexpensive to deploy are critical for studying quantitative traits in plants. Traditional fruit shape phenotyping relies on human raters or 2D analyses to assess form, e.g., size and shape. Systems for 3D imaging using multi-view stereo have been implemented, but frequently rely on commercial software and/or specialized hardware, which can lead to limitations in accessibility and scalability. We present a complete system constructed of consumer-grade components for capturing, calibrating, and reconstructing the 3D form of small-to-moderate sized fruits and tubers. Data acquisition and image capture sessions are 9 seconds to capture 60 images. The initial prototype cost was $1600 USD. We measured accuracy by comparing reconstructed models of 3D printed ground truth objects to the original digital files of those same ground truth objects. TheR2between length of the primary, secondary, and tertiary axes, volume, and surface area of the ground-truth object and the reconstructed models was>0.97 and root-mean square error (RMSE) was<3mm for objects without locally concave regions. Measurements from 1mm and 2mm resolution reconstructions were consistent (R2>0.99). Qualitative assessments were performed on 48 fruit and tubers, including 18 strawberries, 12 potatoes, 5 grapes, 7 peppers, and 4 Bosc and 2 red Anjou pears. Our proposed phenotyping system is fast, relatively low cost, and has demonstrated accuracy for certain shape classes, and could be used for the 3D analysis of fruit form.
Competitive evolution of H1N1 and H3N2 influenza viruses in the United States: A mathematical modeling study
Authors: Wilasang Chaiwat , Suttirat Pikkanet , Chadsuthi Sudarat , Wiratsudakul Anuwat , Modchang Charin
Published: October 2021

Seasonal influenza causes vast public health and economic impact globally. The prevention and control of the annual epidemics remain a challenge due to the antigenic evolution of the viruses. Here, we presented a novel modeling framework based on changes in amino acid sequences and relevant epidemiological data to retrospectively investigate the competitive evolution and transmission of H1N1 and H3N2 influenza viruses in the United States during October 2002 and April 2019. To do so, we estimated the time-varying disease transmission rate from the reported influenza cases and the time-varying antigenic change rate of the viruses from the changes in amino acid sequences. By incorporating the time-varying antigenic change rate into the transmission models, we found that the models could capture the evolutionary transmission dynamics of influenza viruses in the United States. Our modeling results also showed that the antigenic change of the virus plays an essential role in seasonal influenza dynamics.
Regulation of the Evolutionarily Conserved Muscle Myofibrillar Matrix by Cell Type Dependent and Independent Mechanisms
Authors: Ajayi Peter T. , Katti Prasanna , Willingham T. Bradley , Sun Ye , Bleck Christopher K.E. , Glancy Brian
Published: October 2021

Skeletal muscles play a central role in human movement through forces transmitted by contraction of the sarcomere. We recently showed that mammalian sarcomeres are connected through frequent branches forming a singular, mesh-like myofibrillar matrix. However, the extent to which myofibrillar connectivity is evolutionarily conserved as well as mechanisms which regulate the specific architecture of sarcomere branching remain unclear. Here, we demonstrate the presence of a myofibrillar matrix in the tubular, but not indirect flight (IF) muscles within Drosophila melanogaster. Moreover, we find that loss of transcription factor H15 increases sarcomere branching frequency in the tubular jump muscles, and we show that sarcomere branching can be turned on in IF muscles by salm-mediated conversion to tubular muscles. Finally, we demonstrate that neurochondrin knockdown results in myofibrillar connectivity in IF muscles without conversion to tubular muscles. These data indicate an evolutionarily conserved myofibrillar matrix regulated by both cell-type dependent and independent mechanisms.
Cancer cell states and emergent properties of the dynamic tumor system
Authors: Barkley Dalia , Rao Anjali , Pour Maayan , França Gustavo S. , Yanai Itai
Published: October 2021

Phenotypic heterogeneity within malignant cells of a tumor is emerging as a key property of tumorigenesis. Recent work using single-cell transcriptomics has led to the identification of distinct cancer cell states across a range of cancer types, but their functional relevance and the advantage that they provide to the tumor as a system remain elusive. We present here a definition of cancer cell states in terms of coherently and differentially expressed gene modules and review the origins, dynamics, and impact of states on the tumor system as a whole. The spectrum of cell states taken on by a malignant population may depend on cellular lineage, epigenetic history, genetic mutations, or environmental cues, which has implications for the relative stability or plasticity of individual states. Finally, evidence has emerged that malignant cells in different states may cooperate or compete within a tumor niche, thereby providing an evolutionary advantage to the tumor through increased immune evasion, drug resistance, or invasiveness. Uncovering the mechanisms that govern the origin and dynamics of cancer cell states in tumorigenesis may shed light on how heterogeneity contributes to tumor fitness and highlight vulnerabilities that can be exploited for therapy.
Inducing, Collecting, and Storing Ascites
Authors: Greenfield Edward A.
Published: October 2021

Ascitic fluid (also called ascites) is an intraperitoneal fluid extracted from mice that have developed a peritoneal tumor. For antibody production, the tumor is induced by injecting hybridoma cells into the peritoneum, which serves as a growth chamber for the cells. The hybridoma cells grow to high densities and continue to secrete the antibody of interest, thus creating a high-titered solution of antibodies for collection. A single mouse may yield as much as 10 mL of ascitic fluid or as little as 1 mL per batch. Antibody concentrations will typically be between 1 and 10 mg/mL. The most common problem encountered in storing ascites is contamination of these solutions with bacteria or fungi. This can be prevented by the addition of sodium azide.
Open and strong-scaling tools for atom-probe crystallography: high-throughput methods for indexing crystal structure and orientation
Authors: Kühbach Markus , Kasemer Matthew , Gault Baptiste , Breen Andrew
Published: October 2021

Volumetric crystal structure indexing and orientation mapping are key data processing steps for virtually any quantitative study of spatial correlations between the local chemical composition features and the microstructure of a material. For electron and X-ray diffraction methods it is possible to develop indexing tools which compare measured and analytically computed patterns to decode the structure and relative orientation within local regions of interest. Consequently, a number of numerically efficient and automated software tools exist to solve the above characterization tasks. For atom-probe tomography (APT) experiments, however, the strategy of making comparisons between measured and analytically computed patterns is less robust because many APT data sets contain substantial noise. Given that sufficiently general predictive models for such noise remain elusive, crystallography tools for APT face several limitations: their robustness to noise is limited, and therefore so too is their capability to identify and distinguish different crystal structures and orientations. In addition, the tools are sequential and demand substantial manual interaction. In combination, this makes robust uncertainty quantification with automated high-throughput studies of the latent crystallographic information a difficult task with APT data. To improve the situation, the existing methods are reviewed and how they link to the methods currently used by the electron and X-ray diffraction communities is discussed. As a result of this, some of the APT methods are modified to yield more robust descriptors of the atomic arrangement. Also reported is how this enables the development of an open-source software tool for strong scaling and automated identification of a crystal structure, and the mapping of crystal orientation in nanocrystalline APT data sets with multiple phases.
Analysis of the interaction between safety measures and workers' safety awareness from the construction workers' perspective
Authors: Yılmaz Fatih
Published: October 2021

Purpose

The research was carried out to statistically evaluate the relationship between the safety measures at the construction sites and the actual and perceived knowledge levels of the employees about these measures.

Design/methodology/approach

Face-to-face surveys were conducted with the workers. The survey included some perception-based questions about preventive measures at the construction site, as well as determining the level of awareness of employees on occupational health and safety (OHS) practices. The data were analyzed with descriptive statistical methods and bivariate correlation analysis.

Findings

The actual knowledge levels of workers on OHS measures in the workplace is significantly lower than their perceived knowledge levels. However, there is a positive, linear and strong relationship between the actual knowledge levels of the employees about some OHS rules applied in the workplace and the general level of knowledge they perceive about themselves. Some protective measures such as occupational safety expert, OHS board, employee representatives, training and information activities at construction sites positively affect the safety awareness of employees. However, low-frequency and documentation-intensive activities such as risk assessment, emergency activities and periodic controls have no or weak correlations.

Originality/value

Perception-based opinions of construction site workers on occupational safety issues are transformed into numerical data and analyzed with a quantitative method.
OCTO SCM: assessment of determinants of seaport logistics for the export supply chain of agricultural products
Authors: Amonkar Raj V. , Sengupta Tuhin , Patnaik Debasis
Published: October 2021

Learning outcomes

The learning outcomes of this paper are as follows: to understand the context of seaport logistics and supply chain design structure, to apply Monte Carlo simulation in the interface of the supply chain and to analyze the Monte Carlo simulation algorithm and statistical techniques for identifying the key seaport logistics factors.

Case overview/synopsis

It was 9:00 p.m. on November 10, 2020, and Nishadh Amonkar, the CEO of OCTO supply chain management (SCM) was glued to the television watching the final cricket match of the Indian Premier League, 2020. Amonkar’s mobile phone rang and it was a call from Vinod Nair, a member Logistics Panel of Ranji Industries Federation. Nair informed Amonkar that it was related to the rejection of several export consignments of agricultural products from Ranji (in the western part of India). The rejection was due to the deterioration in the quality of the exported agricultural products during transit from Ranji to various locations in Europe.

Complexity academic level

This course is suitable at the MBA level for the following courses: Operations research (Focus/Session: Applications on Monte Carlo Simulation). SCM (Focus/Session: Global SCM, Logistics Planning, Distribution Network). Logistics management (Focus/Session: Transportation Planning). Business statistics (Focus/Session: Application of Hypothesis Testing).

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 9: Operations and logistics.
Can gamification and interface design aesthetics lead to MOOCs' success?
Authors: Cheng Yung-Ming
Published: October 2021

Purpose

The purpose of this study is to propose an integrated post-adoption model based on expectation-confirmation model (ECM) and flow theory to examine whether gamification and interface design aesthetics as antecedents to students' beliefs can affect their continuance intention of massive open online courses (MOOCs) and perceived impact on learning.

Design/methodology/approach

Sample data for this study were collected from students enrolled in a comprehensive university in Taiwan. A total of 600 questionnaires were distributed in the campus, and 318 (53.0%) useable questionnaires were analyzed using structural equation modeling in this study.

Findings

This study's results verified that students' perceived gamification and interface design aesthetics of MOOCs positively affected their perceived usefulness, confirmation and flow experience elicited by MOOCs, and these in turn directly or indirectly led to their satisfaction, continuance intention of MOOCs and perceived impact on learning. Essentially, the results strongly support the research model with all hypothesized links being significant.

Originality/value

It should be particularly noticed that this study contributes to the application of capturing both ECM and flow experience (i.e. an intrinsic motivator) for completely explaining students' perceived gamification and interface design aesthetics as external variables to their continuance intention of MOOCs and perceived impact on learning, and this study's empirical evidence can further shed light on the possible formulation of MOOCs success.
“Ubuntu” I am because we are: COVID-19 and the legal framework for addressing communicable disease in the South African prison system
Authors: Van Hout Marie Claire , Wessels Jakkie
Published: October 2021

Purpose

The purpose of the paper was to conduct a legal-realist assessment of the South African prison system response to COVID-19. Severely congested and ill-resourced prison systems in Africa face unprecedented challenges amplified by COVID-19. South Africa has recorded the highest COVID-19 positivity rate in Africa and, on March 15th 2020, declared a national state of disaster. The first prison system case was notified on April 6th 2020.

Design/methodology/approach

A legal-realist assessment of the South African prison system response to COVID-19 in the 12 months following initial case notification focused on the minimum State obligations to comply with human rights norms, and the extent to which human, health and occupational health rights of prisoners and staff were upheld during disaster measures.

Findings

A legal-realist account was developed, which revealed the indeterminate nature of application of South African COVID-19 government directives, ill-resourced COVID-19 mitigation measures, alarming occupational health and prison conditions and inadequate standards of health care in prisons when evaluated against the rule of law during State declaration of disaster.

Originality/value

This legal-realist assessment is original by virtue of its unique evaluation of the South African prison system approach to tackling COVID-19. It acknowledged State efforts, policymaking processes and outcomes and how these operated within the prison system itself. By moving beyond the deleterious impacts of the COVID-19 pandemic on the already precarious South African prison system, the authors argue for rights assurance for those who live and work in its prisons, improved infrastructure and greater substantive equality of all deprived of their liberty in South Africa.
Comparative analysis of ranking the lean supply chain enablers: An AHP, BWM and fuzzy SWARA based approach
Authors: Sharma Hemant , Sohani Nagendra , Yadav Ashish
Published: October 2021

Purpose

In the recent scenario, there has been an increasing trend toward lean practices and implementation in production systems for the improvement of an organization’s performance as its basic nature is to eliminate the wastes. The increasing interest of customers in customized products and the fulfillment of customers’ demand with good productivity and efficiency within time are the challenges for the manufacturing organization; that is why adopting lean manufacturing concept is very crucial in the current scenario.

Design/methodology/approach

In this paper, the authors considered three different methodologies for fulfilling the objective of our research. The analytical hierarchy process, best–worst method and fuzzy step-wise weight assessment ratio analysis are the three methods employed for weighting all the enablers and finding the priority among them and their final rankings.

Findings

Further, the best results among these methodologies could be used to analyze their interrelationships for successful lean supply chain management implementation in an organization. In this paper, 35 key enablers were identified after the rigorous analysis of literature review and the opinion of a group of experts consisting of academicians, practitioners and consultants. Thereafter, the brainstorming sessions were conducted to finalize 28 lean supply chain enablers (LSCEs).

Practical implications

For lean manufacturing practitioners, the result of this study can be beneficial where the manufacturer is required to increase efficiency and reduce cost and wastage of resources in the lean manufacturing process.

Originality/value

This paper is the first of the research papers that considered deep literature review of identified LSCEs as the initial step, followed by finding the best priority weightage and developing the ranking of various lean enablers of supply chain with the help of various methodologies.
Staying positive among negativities: strategies employed by teachers in Sri Lankan state universities to manage their wellbeing
Authors: Fernandez-Chung Rozilini Mary , De Zoysa Sudakshi Medhani
Published: October 2021

Purpose

Teacher wellbeing is critical given its impact on students’ experience and achievement. This qualitative study provides insights into teacher wellbeing in Sri Lankan state universities. The study occurs during the coronavirus disease (COVID-19) pandemic, where institutions are stretched for resources and teachers sought better work–life balance while working from home.

Design/methodology/approach

The study uses semi-structured interviews of teachers from four state universities in Sri Lanka to discover their strategies for managing teacher wellbeing and staying positive among negativities.

Findings

It concludes that the strategies can be expounded to existing research and categorized under four overarching themes: Versatility and Devotion, Pillars of Support, Conformity over Individualism, and Avoidance and Detachment. Sri Lankan university teachers, like many of their global counterparts, believe in staying positive.

Research limitations/implications

Like most qualitative research studies, if not all, this research studies the specific phenomenon of teacher wellbeing among university teachers in Sri Lanka. The findings, though supported, has its limitation to only public universities teachers thus cannot be generalized and may not apply to teacher wellbeing in private universities in Sri Lanka. Nevertheless, the application of the themes developed forms a valuable framework to support any future study of teacher wellbeing. The conceptual robustness of the findings will make this framework particularly useful for Sri Lanka and other South Asian countries.

Practical implications

The findings will inform future studies on teacher wellbeing, particularly in other South Asian countries. This study may also be the impetus for starting a discourse on related policies in Sri Lanka.

Social implications

Teacher wellbeing positively impacts teacher relations with peers and leadership, which has direct implications on student wellbeing. Happy teachers make happy students.

Originality/value

The findings revealed eight strategies employed by Sri Lankan state university teachers. These strategies were framed under four overarching themes: Versatility and Devotion, Pillars of Support, Conformity over Individualism, and Avoidance and Detachment.
Federal sex offender registration and notification act (SORNA) offenders: sexual versatility, criminal careers and supervision outcomes
Authors: Drury Alan J. , DeLisi Matt , Elbert Michael
Published: October 2021

Purpose

Sex offender registration and notification act (SORNA) offenders are a source of scholarly study across the social, behavioral, forensic and legal sciences with the bulk of literature focusing on the legal standing and deterrent value of sexual offender registries. Less research focuses on the offending careers of current SORNA offenders relative to other types of sexual offenders whose current offense is not SORNA. The purpose of the current study is to examine this issue empirically.

Design/methodology/approach

Using cross-sectional data from a census of male federal offenders who ever perpetrated a sexual offense from the central USA between 2016 and 2020, the current study used t-tests, logistic regression and negative binomial regression to compare current SORNA offenders to other federal correctional clients in terms of their lifetime offending history, sexual violence and compliance on federal supervision.

Findings

Current SORNA offenders are significantly more severe and versatile in their sexual offending, have more extensive criminal careers and criminal justice system involvement, and exhibit significantly increased odds of revocation on supervised release despite controls for age, race and ethnicity. However, sensitivity models that specified the federal Post-Conviction Risk Assessment reduced the effects of SORNA status to non-significance in all models.

Originality/value

SORNA offenders are potentially a significant offender group with evidence of both and given their versatile and specialized lifetime offending and noncompliance on federal supervision. However, current SORNA status is rendered spurious once a risk assessment is controlled suggesting more research is needed to evaluate whether sex offender registries posit greater crime control benefit.
Islamic apparel brand personality model
Authors: Zaki Rana M. , Kheir El Din Amr , Elseidi Reham I.
Published: October 2021

Purpose

The Islamic modest fashion industry is growing rapidly and becoming more competitive within an increasing number of brands available in the market. Based on this reason, both marketers and designers need to create differentiation in their brands. One of the ways to create such differentiation is by establishing a brand personality. Thus, the purpose of this study is to develop a reliable measure of Islamic apparel personality that incorporates the relevant dimensions/traits Muslim females attribute to their apparel.

Design/methodology/approach

Islamic apparel brand personality model was developed based on the Qur’an verses, hadith (sayings of Prophet Muhammad), traits in Aaker’s and other Islamic brand personality models. Focus groups were used to generate a list of traits. Following this, a survey research method was used to gather data. Then, exploratory and confirmatory factor analyses were conducted on a sample of 190 Egyptian Muslim females.

Findings

This study introduces five dimensions of the Islamic apparel brand personality model, namely, simplicity, feminine, modesty, Islamic and righteousness.

Practical implications

This study contributes to the branding as well as Islamic apparel marketing literature as it is the first Islamic apparel brand personality framework. With the Islamic apparel brand personality model, Islamic apparel designers, producers and marketers can create a strong brand image, use advertising strategies effectively and ultimately attract more potential consumers.

Originality/value

The Islamic apparel brand personality model being the first of its kind is significant for the Islamic apparel industry. It reflects dimensions that are supported by the Quran and hadith and therefore suits the Muslim customer market.