bluuebunny/crossref_metadata_2025 huggingface dataset:
Worldwide analysis of reef surveys sorts coral taxa by associations with recent and past heat stress
Authors: Selmoni Oliver , Lecellier Gaël , Berteaux-Lecellier Véronique , Joost Stéphane
Published: November 2021

Coral reefs around the world are under threat from anomalous heat waves that are causing the widespread decline of hard corals. Different coral taxa are known to have different sensitivities to heat, although variation in susceptibilities have also been observed within the same species living in different environments. Characterizing such taxa-specific variations is key to enforcing efficient reef conservation strategies.

Here, we combine worldwide-reef-survey data with remote sensed environmental variables to evaluate how local differences in taxa-specific coral cover are associated with past trends of thermal anomalies, as well as of non-heat related conditions. While the association with non-heat related environmental variation was seldom significant, we found that heat stress trends matched local differences in coral cover. Coral taxa were sorted based on the different patterns of associations with heat stress.

For branching, tabular and corymbose Acroporidae, reefs exposed to recent heat stress (measured the year before the survey) had lower coral cover than locally expected; and among these reefs, those previously exposed to frequent past heat stress (measured since 1985) displayed relatively higher coral cover, compared to those less frequently exposed. For massive and encrusting Poritidae, and for meandroid Favidae and Mussidae, we observed a negative association of coral cover with recent heat stress; however, unlike with Acroporidae, these associations were weaker and did not vary with past heat exposure. For Pocilloporidae, we found a positive association between coral cover and recent heat stress for reefs frequently exposed to past heat, while we found a negative association at reefs less frequently exposed to past heat. A similar pattern was observed for the branching Poritidae, although the associations were weaker and not statistically significant.

Overall, these results show taxa-specific heat association patterns that might correspond to taxa-specific responses to past heat exposure, such as shifts in the assembly of coral communities, evolutionary adaptation or physiological acclimation.
Comprehensive analysis of behavioral dynamics in the protochordateCiona intestinalis
Authors: Athira Athira , Dondorp Daniel , Rudolf Jerneja , Peytral Olivia , Chatzigeorgiou Marios
Published: November 2021

Vertebrate nervous systems can generate a remarkable diversity of behaviors. However, our understanding of how behaviors may have evolved in the chordate lineage is limited by the lack of neuroethological studies leveraging our closest invertebrate relatives.

Here we combine high-throughput video acquisition with pharmacological perturbations of bioamine signaling to systematically reveal the global structure of the motor behavioral repertoire in theCiona intestinalislarvae. Most ofCiona’spostural variance can be captured by six basic shapes, which we term “Eigencionas”. Motif analysis of postural time series further demonstrated that bioamines influence numerous stereotyped behavioral maneuvers including “startle-like” and “beat-and-glide”. Employing computational modeling of swimming dynamics and spatio-temporal embedding of postural features revealed that subtle behavioural differences are generated at the levels of motor modules and the transitions between, both modulated by bioamines. Finally, we show that flexible motor module usage gives rise to diverse behaviors in response to different light stimuli.
mTOR-neuropeptide Y signaling sensitizes nociceptors to drive neuropathic pain
Authors: Chen Lunhao , Hu Yaling , Wang Siyuan , Cao Kelei , Mai Weihao , Sha Weilin , Ma Huan , Gao Yong-Jing , Duan Shumin , Wang Yue , Gao Zhihua
Published: November 2021

Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found that mTOR is preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. We show that injury- induced mTOR activation promoted transcriptional induction of NPY likely via signal transducer and activator of transcription 3 (STAT3) phosphorylation. NPY further acted primarily on Y2 receptors (Y2R) to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented pain restoration. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
IMPACT OF ADOLESCENT INTERMITTENT ETHANOL EXPOSURE IN MALE AND FEMALE RATS ON SOCIAL DRINKING AND NEUROPEPTIDE GENE EXPRESSION
Authors: Towner Trevor T. , Papastrat Kimberly M. , Spear Linda P. , Varlinskaya Elena I. , Werner David F.
Published: November 2021

Background

Alcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol (AIE) exposure. These consequences of AIE may influence adult social drinking in a sex-specific manner.

Methods

To test effects of AIE on social drinking, male and female Sprague-Dawley rats exposed to water or ethanol [0 or 4 g/kg, intragastrically, every other day, between postnatal day (P) 25 and 45] were tested as adults (P72-83) in a social drinking paradigm (30-minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same-sex littermates across two 4-day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, with further assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP) and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum.

Results

Males exposed to AIE consumed more ethanol than water-exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE-exposed females consumed less ethanol and more supersac than water-exposed controls. Water-exposed females drinking ethanol showed more social investigation as well as significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac.

Conclusions

Collectively, these findings provide new evidence regarding sex-specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex- and adolescent exposure-dependent manner.
Analyzing and Reconciling Colocalization and Transcriptome-wide Association Studies from the Perspective of Inferential Reproducibility
Authors: Hukku Abhay , Sampson Matthew G. , Luca Francesca , Pique-Regi Roger , Wen Xiaoquan
Published: November 2021

Transcriptome-wide association studies and colocalization analysis are popular computational approaches for integrating genetic association data from molecular and complex traits. They show the unique ability to go beyond variant-level genetic association evidence and implicate critical functional units, e.g., genes, in disease etiology. However, in practice, when the two approaches are applied to the same molecular and complex trait data, the inference results can be markedly different. This paper systematically investigates the inferential reproducibility between the two approaches through theoretical derivation, numerical experiments, and analyses of 4 complex trait GWAS and GTEx eQTL data. We identify two classes of inconsistent inference results. We find that the first class of inconsistent results may suggest an interesting biological phenomenon, i.e., horizontal pleiotropy; thus, the two approaches are truly complementary. The inconsistency in the second class can be understood and effectively reconciled. To this end, we propose a novel approach for locus-level colocalization analysis. We demonstrate that the joint TWAS and locus-level colocalization analysis improves specificity and sensitivity for implicating biological-relevant genes.
Identification and tracking of alloreactive T cell clones in Rhesus Macaques through the RM-scTCR-Seq platform
Authors: Gerdemann Ulrike , Fleming Ryan A. , Kaminski James , McGuckin Connor , Rui Xianliang , Lane Jennifer F. , Keskula Paula , Cagnin Lorenzo , Shalek Alex K. , Tkachev Victor , Kean Leslie S.
Published: November 2021

T cell receptor clonotype tracking is a powerful tool for interrogating T cell mediated immune processes. New methods to pair a single cell’s transcriptional program with its T cell receptor (TCR) identity allow monitoring of T cell clonotype-specific transcriptional dynamics. While these technologies have been available for human and mouse T cells studies, they have not been developed for Rhesus Macaques, a critical translational organism for autoimmune diseases, vaccine development and transplantation. We describe a new pipeline, ‘RM-scTCR-Seq’, which, for the first time, enables RM specific single cell TCR amplification, reconstitution and pairing of RM TCR’s with their transcriptional profiles. We apply this method to a RM model of GVHD, and identify and track in vitro detected alloreactive clonotypes in GVHD target organs and explore their GVHD driven cytotoxic T cell signature. This novel, state-of-the-art platform fundamentally advances the utility of RM to study protective and pathogenic T cell responses.
Evolutionary history limits species’ ability to match color sensitivity to available habitat light
Authors: Murphy Matthew J. , Westerman Erica L.
Published: November 2021

The spectrum of light that an animal sees – from ultraviolet to far red light – is governed by the number and wavelength sensitivity of a family of retinal proteins called opsins. It has been hypothesized that the spectrum of light available in an environment influences the range of colors that a species has evolved to see. However, invertebrates and vertebrates use phylogenetically distinct opsins in their retinae, and it remains unclear whether these distinct opsins influence what animals see, or how they adapt to their light environments. Systematically utilizing published visual sensitivity data from across animal phyla, we found that terrestrial animals are more sensitive to shorter and longer wavelengths of light than aquatic animals, and that invertebrates are more sensitive to shorter wavelengths of light than vertebrates. Controlling for phylogeny removes the effects of habitat and lineage on visual sensitivity. Closed and open habitat terrestrial species have similar spectral sensitivities when comparing across the Metazoa, and deep water animals are more sensitive to shorter wavelengths of light than shallow water animals. Our results suggest that animals do adapt to their light environment, however the invertebrate-vertebrate evolutionary divergence has limited the degree to which animals can perform visual tuning.
Solvation dynamics-powered structure and function of multi-molecular cellular systems exemplified by non-equilibrium cereblon-degrader-CK1α ternary complex formation
Authors: Wan Hongbin , Aravamuthan Vibhas , Williams Sarah , Wartchow Charles , Duca José S. , Pearlstein Robert A.
Published: November 2021

Cellular functions are executed via a form of analog computing that is based on the switchable covalent and non-covalent states of multi-molecular fluxes (i.e., time-dependent species/state concentrations) operating in the non-linear dynamics regime. We and others have proposed that the non-covalent states and state transitions of aqueous fluxes are powered principally by the storage and release of potential energy to/from the anisotropic H-bond network of solvating water (which we refer to as the “solvation field”), which is a key tenet of a first principles theory on cellular structure and function (called Biodynamics) that we outlined previously. This energy is reflected in water occupancy as a function of solute surface position, which can be probed computationally using WATMD software. In our previous work, we used this approach to deduce the structural dynamics of the COVID main protease, including substrate binding-induced enzyme activation and dimerization, and product release-induced dimer dissociation. Here, we examine:

1)

The general relationships between surface composition/topology and solvation field properties for both high and low molecular weight (HMW and LMW) solutes.

2)

The general means by which structural dynamics are powered by solvation free energy, which we exemplify via binding between the E3 ligase CUL4A/RBX1/DDB1/CRBN, LMW degraders, and substrates. We propose that degraders organize the substrate binding surface of cereblon toward complementarity with native and neo substrates, thereby speeding the association rate constant and incrementally slowing the dissociation rate constant.

3)

Structure-activity relationships (SAR) based on complementarity between the solvation fields of cognate protein-ligand partners exemplified via LMW degraders.
Epigenomic and transcriptomic prioritization of candidate obesity-risk regulatory GWAS SNPs
Authors: Zhang Xiao , Li Tianying , Xiao Hong-Mei , Ehrlich Kenneth C. , Shen Hui , Deng Hong-Wen , Ehrlich Melanie
Published: November 2021

Concern about rising rates of obesity has prompted searches for its genetic risk determinants in genome-wide association studies (GWAS). Most genetic variants that contribute to the increased risk of a given trait are probably regulatory single nucleotide polymorphisms (SNPs). However, identifying plausible regulatory SNPs is difficult because of their varied locations relative to their target gene and linkage disequilibrium, which makes most GWAS-derived SNPs only proxies for many fewer functional SNPs. We developed a systematic approach to prioritizing GWAS-derived obesity SNPs using detailed epigenomic and transcriptomic analysis in adipose tissue vs. heterologous tissues. From 50 obesity-related GWAS and 121,064 expanded SNPs, we prioritized 47 potential causal regulatory SNPs (Tier-1 SNPs) for 14 gene loci. A detailed examination of seven of these genes revealed that four (CABLES1, PC, PEMT,andFAM13A) had Tier-1 SNPs that might regulate alternative use of transcription start sites resulting in different polypeptides being generated or different amounts of an intronic microRNA gene being expressed.HOXA11and long noncoding RNA geneRP11-392O17.1had Tier-1 SNPs in their 3’ or promoter region, respectively, and strong preferences for expression in subcutaneous vs. visceral adipose tissue.ZBED3-AS1had two intragenic Tier-1 SNPs, each of which might contribute to mediating obesity risk through modulating long-distance chromatin interactions. We conclude that prioritization of regulatory SNP candidates should focus on their surrounding epigenetic features in a trait-relevant tissue. Our approach not only revealed especially credible novel regulatory SNPs, but also helped evaluate previously highlighted obesity GWAS SNPs that were candidates for transcription regulation.
Decoding grasp and speech signals from the cortical grasp circuit in a tetraplegic human
Authors: Wandelt S. K. , Kellis S. , Bjånes D. A. , Pejsa K. , Lee B. , Liu C. , Andersen R. A.
Published: November 2021

Tetraplegia from spinal cord injury leaves many patients paralyzed below the neck, leaving them unable to perform most activities of daily living. Brain-machine interfaces (BMIs) could give tetraplegic patients more independence by directly utilizing brain signals to control external devices such as robotic arms or hands. The cortical grasp network has been of particular interest because of its potential to facilitate the restoration of dexterous object manipulation. However, a network that involves such high-level cortical areas may also provide additional information, such as the encoding of speech. Towards understanding the role of different brain areas in the human cortical grasp network, neural activity related to motor intentions for grasping and performing speech was recorded in a tetraplegic patient in the supramarginal gyrus (SMG), the ventral premotor cortex (PMv), and the somatosensory cortex (S1). We found that in high-level brain areas SMG and PMv, grasps were well represented by firing rates of neuronal populations already at visual cue presentation. During motor imagery, grasps could be significantly decoded from all brain areas. At identical neuronal population sizes, SMG and PMv achieved similar highly-significant decoding abilities, demonstrating their potential for grasp BMIs. During speech, SMG encoded both spoken grasps and colors, in contrast to PMv and S1, which were not able to significantly decode speech.These findings suggest that grasp signals can robustly be decoded at a single unit level from the cortical grasping circuit in human. Data from PMv suggests a specialized role in grasping, while SMG’s role is broader and extends to speech. Together, these results indicate that brain signals from high-level areas of the human cortex can be exploited for a variety of different BMI applications.
Suppression of a dsRNA-induced plant immunity pathway by viral movement protein
Authors: Huang Caiping , Sede Ana Rocio , Mutterer Jerome , Boutant Emmanuel , Heinlein Manfred
Published: November 2021

The virome of plants is dominated by RNA viruses1and several of these cause devastating diseases in cultivated plants leading to global crop losses2. To infect plants, RNA viruses engage in complex interactions with compatible plant hosts. In cells at the spreading infection front, RNA viruses replicate their genome through double-stranded RNA (dsRNA) intermediates and interact with cellular transport processes to achieve cell-to-cell movement of replicated genome copies through cell wall channels called plasmodesmata (PD)3. In order to propagate, viruses also must overcome host defense responses. In addition to triggering the antiviral RNA silencing response, RNA virus infection also elicits pattern-triggered immunity (PTI)4whereby dsRNA, a hallmark of virus replication, acts as an important elicitor5. This innate antiviral immune response is also triggered when dsRNA is applied externally and does not require sequence homology to the virus5. However, the mechanism by which PTI restricts virus infection is not known. Here, we show that dsRNA inhibits the progression of virus infection by triggering callose deposition at plasmodesmata and the inhibition of transport through these cell-to-cell communication channels. The dsRNA-induced signaling pathway leading to callose deposition is independent of ROS production and thus distinguished from pathways triggered by bacterial and fungal elicitors. The dsRNA-induced host response at plasmodesmata is suppressed by theTobacco mosaic virusmovement protein (MP). Thus, the virus uses MP to inhibit innate dsRNA-induced immunity at plasmodesmata, which could be a general strategy of phytoviruses to overcome plant defenses and spread infection.
Autologous mitochondria transport via transzonal filopodia rejuvenates aged oocytes by UC-MSCs derived granulosa cells-oocyte aggregation
Authors: Tang Shuang , Yang Nannan , Yu Mingxi , Wang Shuo , Hu Xiangdong , Ni Heliang , Cai Wenyang
Published: November 2021

Mitochondria transfer can rescue oocyte aging-related infertility. However, heterologous techniques are suspended due to heteroplasmy. Regarding autologous approaches, the donor source and manipulating procedures require further optimization. Here we propose a strategy using umbilical cord mesenchymal stem cells (UC-MSCs) as mitochondria donor cells and employing intercellular mitochondria transport as the transfer method. We cryopreserved UC-MSCs of the female pup. When the female aged, its UC-MSCs were induced into granulosa cells (iGCs). The zona-weakened GV oocytes were aggregated with autologous iGCs into iGC-oocyte complexes. After cultivation in GDF9-containing media, mitochondria migrated from iGCs into the GV oocyte via transzonal filopodia. The maturation rate, quality, and developmental potential of these oocytes were substantially increased. Furthermore, the birth rate after embryo transfer has been improved. This approach utilized noninvasive procedures to collect mitochondria donor cells and optimized mitochondria transfer manipulations, so may represent a promising advance towards the improvement of aging-related infertility.
Underlying factors that influence the acceptance of COVID-19 vaccine in a country with a high vaccination rate
Authors: Toro-Ascuy Daniela , Cifuentes-Muñoz Nicolás , Avaria Andrea , Pereira-Montecinos Camila , Cruzat Gilena , Zorondo-Rodriguez Francisco , Fuenzalida Loreto F
Published: November 2021

Control of the COVID-19 pandemic largely depends on the effectiveness of the vaccination. Several factors including vaccine hesitancy can affect the vaccination process. Understanding the factors that underlie the willingness to accept vaccination brings pivotal information to control the pandemic. We analyzed the association between the willingness level to accept the COVID-19 vaccine, and vaccine determinants amidst the Chilean vaccination process. Individual-level survey data was collected from nationally representative samples of 744 respondents, and multivariate regression models used to estimate the association between outcome and explanatory variables. We found that trust in the COVID-19 vaccine, scientists, and medical professionals increased the willingness to: accept the vaccine, a booster dose, annual vaccination, and children vaccination. Our results are critical to understand the acceptance of COVID-19 vaccines in the context of a country with one of the world’s highest vaccination rates. We provide information for decision-making, policy design and communication of vaccination programs.
Cross-border transmissions of delta substrain AY.29 during Olympic and Paralympic Games
Authors: Koyama Takahiko , Tokumasu Reitaro , Katayama Kotoe , Saito Ayumu , Kudo Michiharu , Imoto Seiya
Published: November 2021

Tokyo Olympic and Paralympic Games, postponed for COVID-19 pandemic, were finally held in summer of 2021. Just before the games, alpha variant was being replaced with more contagious delta variant (B.1.617.2). AY.4 substrain AY.29, which harbors two additional characteristic mutations of 5239C>T (NSP3 Y840Y) and 5514T>C (NSP3 V932A), emerged in Japan and became the dominant strain in Tokyo by the time of the Olympic Games. As of October 18, 98 AY.29 samples are identified in 16 countries outside of Japan. Phylogenetic analysis and ancestral searches identified 46 distinct introductions of AY.29 strains into those 16 countries. United States has 44 samples with 10 distinct introductions, and United Kingdom has 13 distinct AY.29 strains introduced in 16 samples. Other countries or regions with multiple introductions of AY.29 are Canada, Germany, South Korea, and Hong Kong while Italy, France, Spain, Sweden, Belgium, Peru, Australia, New Zealand, and Indonesia have only one distinct strain introduced. There exists no unambiguous evidence that Olympic and Paralympic Games induced cross-border transmission of the delta substrain AY.29. Since most of unvaccinated countries are also under sampled for genome analysis with longer lead time for data sharing, it will take longer to capture the whole picture of cross-border transmissions of AY.29.
Association between maternal depression and the nutritional status of children under five-years-old in Peru: An analysis of the Demographic and Health Survey 2014-2017
Authors: Villagaray-Pacheco Nicole , Villacorta-Landeo Pamela , Mejía-Guerrero Leslie , Virú-Loza Manuel A. , Soto-Becerra Percy
Published: November 2021

Objective

To evaluate the association between maternal depression and nutritional status of children under 5 years old in Peru.

Design

Cross-sectional study of the Demographic and Health Survey 2014-2017. Outcomes were mild (height Z-score for age <-2 SD) and moderate/severe (<-3DE) childhood chronic undernutrition and also mild (hemoglobin <11 g/dL) and moderate/severe (hemoglobin <10 g/dL) childhood anemia. Maternal depression was assessed by the questionnaire PHQ-9. Odds ratios and their confidence intervals (CIs) were estimated by multinomial logistic regression models, considering the complex sample design.

Setting

Peru

Participants

Peruvian women of childbearing age from 15 to 49 years who live with children from 6 to 59 months.

Results

Maternal depression was significantly associated with a higher odds of moderate/severe chronic undernutrition in children aged 6-59 months (OR = 2.67; 95% CI 1.16-6.16).

Conclusions

There was evidence that maternal depression was associated with an increased risk of moderate/severe chronic undernutrition
A blood-based miRNA signature with prognostic value for overall survival in advanced stage non-small cell lung cancer treated with immunotherapy
Authors: Rajakumar Timothy , Horos Rastislav , Jehn Julia , Schenz Judith , Muley Thomas , Pelea Oana , Hofmann Sarah , Kittner Paul , Kahraman Mustafa , Heuvelman Marco , Sikosek Tobias , Feufel Jennifer , Skottke Jasmin , Nötzel Dennis , Hinkfoth Franziska , Tikk Kaja , Daniel-Moreno Alberto , Ceiler Jessika , Mercaldo Nathaniel , Uhle Florian , Uhle Sandra , Weigand Markus A , Elshiaty Mariam , Lusky Fabienne , Schindler Hannah , Ferry Quentin , Sauka-Spengler Tatjana , Wu Qianxin , Rabe Klaus F , Reck Martin , Thomas Michael , Christopoulos Petros , Steinkraus Bruno R
Published: November 2021

Immunotherapies have recently gained traction as highly effective therapies in a subset of late-stage cancers. Unfortunately, only a minority of patients experience the remarkable benefits of immunotherapies, whilst others fail to respond or even come to harm through immune related adverse events. For immunotherapies within the PD-1/PD-L1 inhibitor class, patient stratification is currently performed using tumor (tissue-based) PD-L1 expression. However, PD-L1 is an accurate predictor of response in only ∼30% of cases. There is pressing need for more accurate biomarkers for immunotherapy response prediction.

We sought to identify peripheral blood biomarkers, predictive of response to immunotherapies against lung cancer, based on whole blood microRNA profiling. Using three well characterized cohorts consisting of a total of 334 stage IV NSCLC patients, we have defined a 5 microRNA risk score (miRisk) that is predictive of overall survival following immunotherapy in training and independent validation (HR 2.40, 95% CI 1.37-4.19; P < 0.01) cohorts. We have traced the signature to a myeloid origin and performed miRNA target prediction to make a direct mechanistic link to the PD-L1 signalling pathway and PD-L1 itself. The miRisk score offers a potential blood-based companion diagnostic for immunotherapy that outperforms tissue-based PD-L1 staining.
Pan-cancer mapping of single T cell profiles reveals a TCF1:CXCR6-CXCL16 regulatory axis essential for effective anti-tumor immunity
Authors: Jerby-Arnon Livnat , Tooley Katherine , Escobar Giulia , Dandekar Gitanjali , Madi Asaf , Goldschmidt Ella , Lambden Conner , Rozenblatt-Rosen Orit , Anderson Ana C. , Regev Aviv
Published: November 2021

Unleashing cytotoxic CD8+ T cells for effective cancer treatment requires understanding T cell states across different tumor microenvironments. Here, we developed an algorithm to recover both shared and tumor type specific programs and used it to analyze a scRNA-seq compendium of 38,852 CD8+ T cells from 141 patients spanning nine different human cancers. We uncovered a pan-cancer T cell dysfunction program that was predictive of clinical responses to immunotherapy and highlighted CXCR6 as a pan-cancer marker of dysfunctional T cells. In mouse models, CXCR6 increased following checkpoint blockade and was repressed by TCF1. Its ligand, CXCL16, was expressed primarily by myeloid cells, and was co-regulated with antigen presentation genes. CXCR6 deletion decreased Tox, CX3CR1, and Bcl2 expression, predisposing dysfunctional PD-1+Tim3+CD8+ T cells to apoptosis, and compromising tumor growth control. Our approach discovered a TCF1:CXCR6-CXCL16 regulatory axis essential for effective anti-tumor immunity, revealing a new perspective on T cell dysfunction and new opportunities for modulating this cell state.
Hybridoma Screening by Antibody Capture: Dot Blot
Authors: Greenfield Edward A.
Published: November 2021

A dot blot is an appropriate hybridoma screening procedure when the antigen is a protein that is available in purified form. The antigen is bound directly to a nitrocellulose sheet and incubated with hybridoma tissue culture supernatant. A dot blot is widely used to determine the productivity of a given hybridoma, and this is described here. This assay can also be used to screen a fusion or subclone plate for productive hybridoma clones.
Electrophysiological Approaches to Studying Normal and Abnormal Retinotectal Circuit Development in the Xenopus Tadpole
Authors: Pratt Kara G.
Published: November 2021

The Xenopus tadpole retinotectal projection is the main component of the amphibian visual system. It comprises the retinal ganglion cells (RGCs) in the eye, which project an axon to synapse onto tectal neurons in the optic tectum. There are many attributes of this relatively simple projection that render it uniquely well-suited for studying the functional development of neural circuits. One major experimental advantage of this circuit is that it can be genetically or pharmacologically altered and then assessed at high resolution via whole-cell electrophysiological recordings using an ex vivo isolated brain preparation. This protocol provides instructions for performing such electrophysiological investigations using the ex-vivo-isolated brain preparation. It allows one to measure many different aspects of synaptic transmission between the RGC axons and individual postsynaptic tectal neurons, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to NMDA (N-methyl-d-aspartate) ratios, strength of individual RGC axons, paired pulse facilitation, and strength of individual synapses.
Examining the impact of external reference prices on seller price image dimensions and purchase intentions in pay what you want (PWYW)
Authors: Rai Shivam , Narwal Preeti
Published: November 2021

Purpose

Pay what you want (PWYW) is a participative pricing mechanism that permits customers complete freedom to choose prices. PWYW literature reports the influence of external reference price (ERP) on customers' price decisions and payments. The current research examines the influence of ERP presence, salience and understanding at the seller level by analysing customers' perceptions of seller price image dimensions and purchase intentions.

Design/methodology/approach

Study 1 tests the impact of ERP presence and salience in controlled lab settings while Study 2 takes this investigation further by including the moderating effect of ERP understanding on seller price image dimensions and purchase intentions in online settings.

Findings

Results illustrate the positive impact of ERP presence on all seller price image dimensions excluding the perceived price level. Perceived price fairness mediates the impact of ERP presence on perceived value. ERP salience positively impacts price processability. ERP presence and salience attached to it positively impact customers' purchase intentions through seller price image dimensions.

Originality/value

This is possibly the first paper to investigate the ERP effect on seller price image dimensions in a PWYW context that lacks fixed posted prices.
SCAFFOLDing all abilities into makerspaces: a design framework for universal, accessible and intersectionally inclusive making and learning
Authors: Seo JooYoung , Richard Gabriela T.
Published: November 2021

Purpose

In response to the underexplored need for holistically inclusive makerspaces for learning, we put propose the “SCAFFOLD” framework, which considers equity, inclusion and accessibility in the design of spaces and activities for socioculturally diverse learners.

Design/methodology/approach

This paper proposes a universal design (UD) framework that is intersectionally inclusive for learners with diverse needs in makerspaces and maker activities. This paper provides conjecture mapping to put forth theoretical and empirical arguments for the design of holistically inclusive makerspaces that consider gender equity and cultural inclusivity, as well as accessibility for diverse learners with divergent and unique abilities and dis/abilities.

Findings

Combining related literature and three existing UD frameworks (i.e. UD, web accessibility and UD for learning) and prior research on equity and inclusivity in making, this paper proposes the integration of eight principles, which leverage individuals’ diverse abilities to become agentic makers: simplicity, collaboration, accessibility, flexibility, fail-safe, object-oriented, linkability and diversity.

Research limitations/implications

Researchers who have implemented conjecture maps (Leeet al., 2018) have found them to be useful for developing theory and learning designs grounded in research and practice. However, it should be noted that design research is iterative and contextual, and conjecture maps are effective in providing visibility and rigor, but are meant to be flexible and responsive to changes in context (Leeet al., 2018; Sandoval, 2014).

Originality/value

This paper provides practical guidelines and principles for researchers, educators, instructional designers and product developers to assess and redesign makerspaces and activities that are intersectionally and universally inclusive, equitable and accessible.
Molecular dynamics study on the mechanical and tribological properties of polyimide reinforced by lanthana
Authors: Cai Peng , Xu Chengpeng , Zheng Fei , Song Jingfu , Zhao Gai
Published: November 2021

Purpose

The purpose of this paper is to investigate the effect of lanthana (La2O3) on the mechanical and tribological properties of polyimide (PI).

Design/methodology/approach

The mechanical and tribological properties of PI nanocomposites filled with La2O3 were studied by molecular dynamic simulations to explore the deep mechanisms from an atomic or molecular view.

Findings

The results showed that the hardness of the PI matrix increased after La2O3 modification with a decrease of 72.4% nanoindentation depth. Besides, the friction coefficient of PI decreased by 72.2% after filling La2O3, and the shear deformation was largely reduced under the same conditions. The adsorption effect of La2O3 on the PI molecular, which reduced the atomic relative concentration, velocity, interaction with counterpart Fe layer and the temperature rise in the frictional interface, contributed to the improvement of the mechanical and tribological performance.

Originality/value

This study reveals the friction and wear mechanism of PI composites filled with rare earth oxide at the nanoscale.
Analyzing the Internet financial market risk management using data mining and deep learning methods
Authors: Feng Ran , Qu Xiaoe
Published: November 2021

Purpose

To identify and analyze the occurrence of Internet financial market risk, data mining technology is combined with deep learning to process and analyze. The market risk management of the Internet is to improve the management level of Internet financial risk, improve the policy of Internet financial supervision and promote the healthy development of Internet finance.

Design/methodology/approach

In this exploration, data mining technology is combined with deep learning to mine the Internet financial data, warn the potential risks in the market and provide targeted risk management measures. Therefore, in this article, to improve the application ability of data mining in dealing with Internet financial risk management, the radial basis function (RBF) neural network algorithm optimized by ant colony optimization (ACO) is proposed.

Findings

The results show that the actual error of the ACO optimized RBF neural network is 0.249, which is 0.149 different from the target error, indicating that the optimized algorithm can make the calculation results more accurate. The fitting results of the RBF neural network and ACO optimized RBF neural network for nonlinear function are compared. Compared with the performance of other algorithms, the error of ACO optimized RBF neural network is 0.249, the running time is 2.212 s, and the number of iterations is 36, which is far less than the actual results of the other two algorithms.

Originality/value

The optimized algorithm has a better spatial mapping and generalization ability and can get higher accuracy in short-term training. Therefore, the ACO optimized RBF neural network algorithm designed in this exploration has a high accuracy for the prediction of Internet financial market risk.
Differential impacts of the US–China trade war and the outbreak of COVID-19 on Chinese air quality
Authors: Shahbaz Muhammad , Sinha Avik , Shah Muhammad Ibrahim
Published: November 2021

Purpose

Over the last couple of years, the Chinese manufacturing sector was affected by the onset of the US–China trade war and the outbreak of coronavirus disease 2019 (COVID-19). In such a scenario air quality in China has encountered a shock, and the impacts of these two incidents are unknown. In this study, the authors analyze the convergence of air quality in China in the presence of multiple structural breaks and how the impacts of these two events are different from each other.

Design/methodology/approach

In order to assess the nature of shocks in the presence of multiple structural breaks, unit root tests with multiple structural breaks are employed.

Findings

The results reveal that air quality in China is showing the sign of convergence, and it is consistent across 18 provinces which are worst hit by the outbreak of COVID-19. In the presence of transitory shocks, the impact of COVID-19 outbreak is found to be higher, whereas the impact of the US–China trade war is found to be more persistent. Lastly, the outbreak of COVID-19 has been found to have more impact on pollutants with higher severity of health hazard.

Originality/value

To the best of the authors’ knowledge, this is the first study that contributes to the empirical literature in terms of investigating the convergence of overall air pollution and individual air pollutants taking COVID-19 and the trade war into account.
Tree mortality response to drought‐density interactions suggests opportunities to enhance drought resistance
Authors: Bradford John. B. , Shriver Robert K. , Robles Marcos D. , McCauley Lisa A. , Woolley Travis J. , Andrews Caitlin A. , Crimmins Michael , Bell David M.
Published: November 2021

The future of dry forests around the world is uncertain given predictions that rising temperatures and enhanced aridity will increase drought‐induced tree mortality. Using forest management and ecological restoration to reduce density and competition for water offers one of the few pathways that forests managers can potentially minimize drought‐induced tree mortality. Competition for water during drought leads to elevated tree mortality in dense stands, although the influence of density on heat‐induced stress and the durations of hot or dry conditions that most impact mortality remain unclear.

Understanding how competition interacts with hot‐drought stress is essential to recognize how, where and how much reducing density can help sustain dry forests in a rapidly changing world. Here, we integrated repeat measurements of 28,881 ponderosa pine trees across the western US (2000–2017) with soil moisture estimates from a water balance model to examine how annual mortality responds to competition, temperature and soil moisture conditions.

Tree mortality responded most strongly to basal area, and was elevated in places with high mean temperatures, unusually hot 7‐year high temperature anomalies, and unusually dry 8‐year low soil moisture anomalies. Mortality was also lower in places that experienced unusually wet 3‐year soil moisture anomalies between measurements. Importantly, we found that basal area interacts with temperature and soil moisture, exacerbating mortality during times of stress imposed by high temperature or low moisture.

Synthesis and applications. Our results imply that a 50% reduction in forest basal area could reduce drought‐driven tree mortality by 20%–80%. The largest impacts of density reduction are seen in areas with high current basal area and places that experience high temperatures and/or severe multiyear droughts. These interactions between competition and drought are critical to understand past and future patterns of tree mortality in the context of climate change, and provide information for resource managers seeking to enhance dry forest drought resistance.
Molecular identification and phylogenetic analysis of Papaver based on ITS2 barcoding
Authors: Cheng Liu , Lin Ziqing , Xin Cairui , Sun Haolin , Li Xinyu
Published: November 2021

In forensic cases suspected to involvePapaver somniferum, species identification is key to the investigation. To accurately detect and identifyP. somniferumas well as common adulterants of the same genus, 19 internal transcribed spacer 2 (ITS2) sequences ofP. somniferum(256 bp),Papaver canescens(254 bp),Papaver nudicaule(254 bp),Papaver pavoninum(250 bp),Papaver radicatum(254 bp), andPapaver rhoeas(256 bp) were obtained. Based on the ITS2 sequence, similarity analysis via BLAST, the nearest Kimura‐2‐parameter (K2P) genetic distances were calculated, and a phylogenetic tree was constructed using MEGA X software for the identification of six species ofPapaver. Finally, differences in the ITS2 secondary structure between species were analyzed. The best matches of theP. somniferumITS2 sequence were of otherP. somniferumfrom different sources. The nearest K2P genetic distances betweenP. somniferumand its counterparts from other sources were zero, which was the smallest pairwise genetic distance among distances from the other five Papaver species. Various sources ofP. somniferumclustered into an independent branch in the phylogenetic tree. The secondary structures ofP. somniferumandP. rhoeaswere significantly different from those of the other four species of Papaver. In summary,P. somniferumcan be effectively distinguished from five closely related plants of the same genus by using ITS2 as a DNA barcode.
Bidirectional association between executive and physical functions among older adults: A systematic review
Authors: Heaw Yu Chi , Singh Devinder Kaur Ajit , Tan Maw Pin , Kumar Saravana
Published: November 2021

Objective

We aimed to examine the bidirectional associations between specific executive function (EF) and physical function (PF) subdomains among older adults.

Methods

A systematic literature search (MEDLINE, EMBASE, PsycINFO, EBSCOHOST, Scopus and EmCare) was undertaken from February 2018 to May 2020. Observational studies measuring associations between EF and PF subdomains among older adults were included.

Results

Twenty‐nine studies met the inclusion criteria. Twenty‐seven studies reported associations between EF and PF. There were bidirectional associations between slower processing speed and slower gait speed; slower processing speed and lower muscle strength; and lower verbal fluency and slower gait speed. Lower muscle strength was unilaterally associated with lower working memory.

Conclusions

We found consistent bidirectional associations between processing speed with gait speed and muscle strength, and verbal fluency and gait speed. There was a unidirectional association between muscle strength and working memory. Common causal mechanisms for EF and PF require further studies.
Management and outcomes of patients for non‐functioning pancreatic neuroendocrine tumours: a multi‐institutional analysis
Authors: Du Bingqing , Wang Xing , Zhang Wangfa , Tan Qingquan , Wei Yisheng , Shao Zili
Published: November 2021

Background

To analysed the short‐ and long‐term outcomes of patients who underwent surgical resection for non‐functioning pancreatic neuroendocrine tumours (NF‐PNETs) to gain insights into treatment approaches for this rare and heterogeneous entity.

Methods

All patients who underwent surgical resection for NF‐PNETs at The Second Affiliated Hospital of Guangzhou Medical University, and West China Hospital, Sichuan University, from 2009 to 2019 were retrospectively reviewed. The data of patients was including perioperative management, pathologic analysis and follow‐up.

Results

A total of 119 cases with histologically or cytologically confirmed NF‐PNETs, The mean age of the patients was 52, and 56.3% were female. Twenty‐three patients received post‐operative adjuvant therapy, and five of nine (55.6%) patients with distant metastasis showed recurrence 14(60.9%) G2/G3 patients without distant metastasis received post‐operative therapy with octreotide. Of these 14 patients, 3 (21.4%) revealed recurrence. Univariate analysis indicated that symptoms (P = 0.03), tumour size >4 cm (P = 0.029), ENETS stages III–IV (P < 0.001), positive lymph nodes (P < 0.001), vascular/perineural invasion (P < 0.001), and pathology grade G2 were associated with significantly higher risks of recurrence; age, gender, surgery type, and tumour location were not. Multivariate analysis revealed that positive lymph nodes (P < 0.001), vascular/peripheral invasion (P < 0.001), and pathology grade G3 (P = 0.03) are significant prognostic factors of tumour recurrence.

Conclusion

Positive lymph nodes, vascular/peripheral invasion and pathology grade G3 were related to recurrence of NF‐PNETs. Lymph node resection is recommend when FNA biopsy indicates pathology grade G3 for patients with NF‐PNETs.