bluuebunny/crossref_metadata_2025 huggingface dataset:
Coevolution of larval signalling and worker response can trigger developmental caste determination in social insects
Authors: Lagos-Oviedo Juan J. , Pen Ido , Kreider Jan J.
Published: September 2023

Eusocial insects belong to distinct queen and worker castes, which, in turn, can be divided into several morphologically specialised castes of workers. Caste determination typically occurs by differential nutrition of developing larvae. We present a model for the coevolution of larval signalling and worker task allocation – both modelled by flexible smooth reaction norms – to investigate the evolution of caste determination mechanisms and worker polymorphism. In our model, larvae evolve to signal their nutritional state to workers. The workers evolve to allocate time to foraging for resources versus feeding the brood, conditional on the larval signals and their body size. Worker polymorphism evolves under accelerating foraging returns of increasing body size, which causes selection to favour large foraging and small nursing workers. Worker castes emerge because larvae evolve to amplify their signals after obtaining some food, which causes them to receive more food, while the other larvae remain unfed. This leads to symmetry-breaking among the larvae who either are well-nourished or malnourished; thus, emerging as small or large workers. Our model demonstrates the evolution of nutrition-dependent caste determination and worker polymorphism by a self-reinforcement mechanism that evolves from the interplay of larval signalling and worker response to the signals.
Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration
Authors: Liu Jian , Copland David A. , Clare Alison J. , Gorski Mathias , Richards Burt T. , Scott Louis , Theodoropoulou Sofia , Greferath Ursula , Cox Katherine , Bell Oliver H. , Ou Kepeng , Le Brun Powell Jenna , Wu Jiahui , Robles Luis Martinez , Li Yingxin , Nicholson Lindsay B. , Coffey Peter J. , Fletcher Erica L. , Guymer Robyn , Radeke Monte J. , Heid Iris M. , Hageman Gregory S. , Chan Ying Kai , Dick Andrew D.
Published: September 2023

Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression in RPE declined with age or oxidative stress and was further reduced in AMD. IRAK-M-deficient mice exhibited increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M disrupted RPE cell homeostasis, including compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of AAV-expressing IRAK-M rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in IRAK-M- deficient mice. Our data support that replenishment of IRAK-M expression may redress dysregulated pro-inflammatory processes in AMD, thereby treating degeneration.

One Sentence Summary

IRAK-M is a protective molecule and promising therapeutic target for macular degeneration
Phylogenomics reveals an island as a genetic reservoir of a continental population
Authors: Aoki Daisuke , Senzaki Masayuki , Ando Haruko , Odaya Yoshiya , Heim Wieland , Kitazawa Munehiro , Tom Wulf , Trense Daronja , Bastardot Mark , Fukuda Atsunori , Takahashi Masao , Kondo Natsuko
Published: September 2023

Islands as biodiversity sinks due to their small population size and low genetic variation are recently challenged by a phenomenon where a continental lineage originates from islands. This raises an important question about through what demographic processes insular genetic variation is introduced to the continent and its evolutionary consequences on the continent. We address this question by focusing on an Asian rail species, the Swinhoe’s RailCoturnicops exquisitus, where frequent trans-oceanic dispersal in a continent-island system is expected. We reconstructed a spatiotemporally explicit demographic history of this species in the continent-island system, using integrative phylogenomics. Multiple lines of evidence supported asymmetric gene flow from an island population to the continental population that once diverged around the Middle Pleistocene. This has possibly impacted the continental genetic variation because ancient genetic variation may have been preserved in the large island population. Re-establishment of the island by the continental population was also detected, suggesting that the insular genetic variation has been maintained also by receiving a part of continental genetic variation. These results indicated that the maintenance of insular genetic variation through dynamic continent-island metapopulation may have allowed the island to act as a genetic reservoir for continental genetic variation.

Teaser text

What process allows island populations that are small and at the “evolutionary dead-end” to become the source of continental colonization? Using a cutting-edge integrative phylogenomics approach, we disentangled the demographic history of the little-studied Swinhoe’s Rail in East Asia, where it has survived by maintaining a dynamic metapopulation across a continent-island system. Particularly, gene flow from the island impacted the contemporary genetic variation of the continental population, possibly facilitating its demographic expansion. We suggested that maintenance of metapopulation and asymmetric gene flow from islands are key for islands to introduce their genetic variation to the continent.
Pan-tissue scaling of stiffness versus fibrillar collagen reflects contractility-driven strain that inhibits fibril degradation
Authors: Saini K. , Cho S. , Tewari M. , Jalil AA.R. , Wang M. , Kasznel A.J. , Yamamoto K. , Chenoweth D.M. , Discher D.E.
Published: September 2023

Polymer network properties such as stiffness often exhibit characteristic power laws in polymer density and other parameters. However, it remains unclear whether diverse animal tissues, composed of many distinct polymers, exhibit such scaling. Here, we examined many diverse tissues from adult mouse and embryonic chick to determine if stiffness (Etissue) follows a power law in relation to the most abundant animal protein, Collagen-I, even with molecular perturbations. We quantified fibrillar collagen in intact tissue by second harmonic generation (SHG) imaging and from tissue extracts by mass spectrometry (MS), and collagenase-mediated decreases were also tracked. Pan-tissue power laws for tissue stiffness versus Collagen-I levels measured by SHG or MS exhibit sub-linear scaling that aligns with results from cellularized gels of Collagen-I but not acellular gels. Inhibition of cellular myosin-II based contraction fits the scaling, and combination with inhibitors of matrix metalloproteinases (MMPs) show collagenase activity is strain - not stress- suppressed in tissues, consistent with past studies of gels and fibrils. Beating embryonic hearts and tendons, which differ in both collagen levels and stiffness by >1000-fold, similarly suppressed collagenases at physiological strains of ∼5%, with fiber-orientation regulating degradation. Scaling ofEtissuebased on ‘use-it-or-lose-it’ kinetics provides insight into scaling of organ size, microgravity effects, and regeneration processes while suggesting contractility-driven therapeutics.
Clonal fitness decline in somatic differentiation hierarchies
Authors: Ahmed Iftikhar , Dingli David , Huang Weini , Werner Benjamin
Published: September 2023

The concept of clonal fitness is fundamental to describe the evolutionary dynamics in somatic tissues. It is now well established that otherwise healthy somatic tissues become increasingly populated by expanding clones with age. However, the dynamic properties and respective fitnesses of these clones are less well understood. Here we show, that in somatic tissues organised as a differentiation hierarchy, theory predicts a natural decline of effective clonal fitness over time in the absence of additional driver events. This decline is intrinsic to the tissue organisation and can be captured quantitatively by a simple heuristic equation that is proportional to 1/time. We also show that the expected fitness decline is directly observable in human haematopoiesis. The predicted short and long term dynamics agree within vivoobservations using data of Neutrophil recovery after bone marrow transplants and naturally progressing Chronic Lymphocyte Leukemia (CLL). We further show that theory predicts the existence of a long term equilibrium fitness. All CLL patients transition into a stable equilibrium fitness eventually. We find significant inter-patient variation of long term fitness and a strong correlation with disease aggressiveness. Interestingly, CLL long term fitness can be forecast based on the early stages of disease progression, suggesting a Big Bang like model for CLL evolution.
Immune modulation of innate and adaptive responses restores immune surveillance and establishes anti-tumor immunological memory
Authors: Alvero Ayesha B. , Fox Alexandra , Madina Bhaskara , Krady Marie , Gogoi Radhika , Chehade Hussein , Nakaar Valerian , Almassian Bijan , Yarovinsky Timur , Rutherford Thomas , Mor Gil
Published: September 2023

Current immunotherapies have proven effective in strengthening anti-tumor immune responses but constant opposing signals from tumor cells and surrounding microenvironment eventually lead to immune escape. We hypothesize that in situ release of antigens and regulation of both the innate and adaptive arms of the immune system will provide a robust and long-term anti-tumor effect by creating immunological memory against the tumor. To achieve this, we developed CARG-2020, a virus-like-vesicle (VLV). It is a genetically modified and self-amplifying RNA with oncolytic capacity and encodes immune regulatory genes. CARG-2020 carries three transgenes: 1) the pleiotropic antitumor cytokine IL-12 in which the subunits (p35 and p40) are tethered together; 2) the extracellular domain (ECD) of the pro-tumor IL-17RA, which can serve as a dominant negative antagonist; and 3) shRNA for PD-L1. Using a mouse model of ovarian cancer, we demonstrate the oncolytic effect and immune modulatory capacities of CARG-2020. By enhancing IL-12 and blocking IL-17 and PD-L1, CARG-2020 successfully reactivates immune surveillance by promoting M1 instead of M2 macrophage differentiation, inhibiting MDSC expansion, and establishing a potent CD8+ T cell mediated anti-tumoral response. Furthermore, we demonstrate that this therapeutic approach provides tumor-specific and long-term protection preventing the establishment of new tumors. Our results provide rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients to enhance the anti-tumor response and to prevent recurrence.
Individual variation in male pheromone production inXylocopa sonorinacorrelates with size and gland color
Authors: Goffinet Andrew J. , Darragh Kathy , Saleh Nicholas , Ostwald Madeleine M. , Buchmann Stephen L. , Ramirez Santiago R.
Published: September 2023

Sex pheromones are species-specific chemical signals that facilitate the location, identification, and selection of mating partners. These pheromones can vary between individuals, and act as signals of mate quality. Here, we investigate the variation of male pheromones in the mesosomal glands of the large carpenter beeXylocopa sonorina, within a Northern California population. We tested the hypothesis that morphological traits are correlated with the observed variation in chemical blend composition of these bees. We also conducted behavioral assays to test whether these male pheromones act as long-range attractants to conspecifics. We found that larger males with darker mesosomal glands have a higher pheromone amount in their glands. Our analysis also shows initial evidence that this pheromone blend serves as a long-range attractant to both males and females. We show that both male body size and sexual maturation are important factors influencing pheromone abundance, and that this pheromone blend acts as a long-range attractant. We hypothesize that this recorded variation in male pheromone could be important for female choice.
Predictive Deep Learning Model for Neural Vessel Occlusion
Authors: Karlsberg Aaron , Kim Sandy , Zaghari Nima , Li Lu
Published: September 2023

Recent advances in medical applications for clot removal have enabled physicians to unblock blood vessel occlusions that occur in extremely narrow regions of the brain along the Horizontal (M1) segment of the middle cerebral artery. FDA approved, clinical trials have proven the significant cerebral recovery that can be achieved for victims of ischemic stroke when they undergo swift surgical intervention for clot removal. That said, carrying out such a delicate operation simultaneously requires extreme surgical expertise, and the ability to quickly identify the site of occlusion from 2D x-ray images of the brain. Fortunately, recent efforts in object detection and classification within the fields of deep learning and computer vision have dramatically improved the predictive power of the computer. Accordingly, the goal of this research project is to develop a deep learning model capable of accurately predicting the site of occlusion from frontal view cerebral angiograms in real time. Our current model utilizes YOLOv3 architecture and identifies the site of occlusion in 94.4% of all cases given a minimum 25% confidence threshold. Furthermore, in 83.97% of cases, the occlusion region is detected with at least 50% average intersection over union between the predicted region and the ground truth region. Finally, distributed over the entire validation set, the average intersection over union between the predicted region and the ground truth region was 74.29%.
mTORC1/S6K1 signaling promotes sustained oncogenic translation through modulating CRL3IBTK-mediated non-degradative ubiquitination of eIF4A1
Authors: Jiao Dongyue , Sun Huiru , Zhao Xiaying , Chen Yingji , Lv Zeheng , Shi Qing , Li Yao , Wang Chenji , Gao Kun
Published: September 2023

Enhanced protein synthesis is a crucial molecular mechanism that allows cancer cells to survive, proliferate, metastasize, and develop resistance to anti-cancer treatments, and often arises as a consequence of increased signaling flux channeled to mRNA-bearing eukaryotic initiation factor 4F (eIF4F). However, the post-translational regulation of eIF4A1, an ATP-dependent RNA helicase and subunit of the eIF4F complex, is still poorly understood. Here, we demonstrate that IBTK, a substrate-binding adaptor of Cullin 3-RING ubiquitin ligase (CRL3) complex, interacts with eIF4A1. The non-degradative ubiquitination of eIF4A1 catalyzed by CRL3IBTKcomplex promotes cap-dependent translational initiation, nascent protein synthesis, oncogene expression, and tumor cell growth bothin vivoandin vitro. Moreover, we show that mTORC1 and S6K1, two key regulators of protein synthesis, directly phosphorylate IBTK to augment eIF4A1 ubiquitination and sustained oncogenic translation. This link between the CRL3IBTKcomplex and the mTORC1/S6K1 signaling pathway, which is frequently dysregulated in cancer, represents a promising target for anti-cancer therapies.

Statement of Significance:Overexpression of IBTK contributes to the process of tumorigenesis by amplifying translation, and represents a promising target for anti-cancer therapies.
Molecular analysis for ovarian cancer detection in patient-friendly samples
Authors: Wever Birgit M.M. , Schaafsma Mirte , Bleeker Maaike C.G. , van den Burgt Yara , van den Helder Rianne , Lok Christianne A.R. , Dijk Frederike , van der Pol Ymke , Mouliere Florent , Moldovan Norbert , van Trommel Nienke E. , Steenbergen Renske D.M.
Published: September 2023

Background

High ovarian cancer mortality rates motivate the development of effective and patient-friendly diagnostics. Here, we explored the potential of molecular testing in patient-friendly samples for ovarian cancer detection.

Patients and methods

Home-collected urine, cervicovaginal self-samples, and clinician-taken cervical scrapes were prospectively collected from 54 patients diagnosed with a highly suspicious ovarian mass (benign n=25, malignant n=29). All samples were tested for nine methylation markers, using quantitative methylation-specific PCRs that were verified on ovarian tissue samples, and compared to unpaired patient-friendly samples of 110 healthy controls. Copy number analysis was performed on a subset of urine samples of ovarian cancer patients by shallow whole-genome sequencing.

Results

Three methylation markers were significantly elevated in full void urine of ovarian cancer patients as compared to healthy controls (C2CD4D,p=0.008;CDO1,p=0.022;MAL,p=0.008), of which two were also discriminatory in cervical scrapes (C2CD4D,p=0.001;CDO1,p=0.004). When comparing benign and malignant ovarian masses,GHSRshowed significantly elevated methylation levels in the urine sediment of ovarian cancer patients (p=0.024). Other methylation markers demonstrated comparably high methylation levels in benign and malignant ovarian masses. Cervicovaginal self-samples showed no elevated methylation levels in patients with ovarian masses as compared to healthy controls. Copy number changes were identified in 4 out of 23 urine samples of ovarian cancer patients.

Conclusion

Our study revealed increased methylation levels of ovarian cancer-associated genes and copy number aberrations in the urine of ovarian cancer patients. Our findings support continued research into urine biomarkers for ovarian cancer detection and highlight the importance of including benign ovarian masses in future studies to develop a clinically useful test.

HIGHLIGHTS

Ovarian cancer is often diagnosed at an advanced stage with a poor prognosis

We studied the potential of molecular testing in different types of patient-friendly material for ovarian cancer detection

Elevated methylation of ovarian cancer-associated genes can be measured in cervical scrapes and urine

Copy number aberrations are detectable in urine of ovarian cancer patients

DNA-based testing in cervical scrapes and urine could aid ovarian cancer diagnosis upon further development

GRAPHICAL ABSTRACT

Created withBioRender.com.
Generative Artificial Intelligence for Clinical Communication: Implications for Non-Pharmacological Interventions in Health Care
Authors: Hanai Akiko , Ishikawa Tetsuo , Kawauchi Shoichiro , Iida Yuta , Kawakami Eiryo
Published: September 2023

Objectives

The objective of this study was to evaluate the potential of Generative Artificial Intelligence (AI) in facilitating clinical communication, particularly in addressing sexual health concerns, which are often challenging for patients to discuss.

Methods

We employed the Generative Pre-trained Transformer-3.5 (GPT) as the generative AI platform and utilized DocsBot for citation retrieval (June 2023). A structured prompt was devised to generate 100 questions from the AI, based on epidemiological survey data regarding sexual difficulties among cancer survivors. These questions were submitted to Bot1 (standard GPT) and Bot2 (sourced from two clinical guidelines). The responses from both bots were compared to assess consistency and adherence to clinical guidelines.

Results

Our analysis revealed no censorship of sexual expressions or medical terms. The most common themes among the generated questions were cancer treatment, sexual health, and advice. The similarity rate between responses from Bot1 and Bot2 averaged 92.5% (range 77.0% to 98.4%), with notably lower similarity for items not covered in the guidelines. Despite the lack of reflection on guideline recommendations, counseling and other non-pharmacological interventions were significantly more prevalent in both bots’ responses compared to drug interventions, with odds ratios of 4.8 (p=0.04) in Bot1 and 14.9 (p<0.001) in Bot2.

Discussion

Generative AI can serve for providing health information on sensitive topics such as sexual health, despite the potential for policy-restricted content. There was a significant skew towards non-pharmacological interventions in responses, possibly due to the prohibitive nature of medical topics. This shift warrants attention as it could potentially trigger patients’ expectations for non-pharmacological interventions.
Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity
Authors: Smith Kirk , Deutsch Aaron J. , McGrail Carolyn , Kim Hyunkyung , Hsu Sarah , Mandla Ravi , Schroeder Philip H. , Westerman Kenneth E. , Szczerbinski Lukasz , Majarian Timothy D. , Kaur Varinderpal , Williamson Alice , Claussnitzer Melina , Florez Jose C. , Manning Alisa K. , Mercader Josep M. , Gaulton Kyle J. , Udler Miriam S.
Published: September 2023

We identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions. Polygenic scores derived from the clusters differed in distribution between ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a BMI of 30 kg/m2in the European subpopulation and 24.2 (22.9- 25.5) kg/m2in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg/m2in the East Asian group, explaining about 75% of the difference in BMI thresholds. Thus, these multi-ancestry T2D genetic subtypes encompass a broader range of biological mechanisms and help explain ancestry-associated differences in T2D risk profiles.
Predictors of vaccination card retention in Tamale Metropolis, Ghana
Authors: Konlan Matthew Y. , Mahama Fuseini , Abubakari Braimah B. , Konka Paul , Appiah Benedict O. , Yeboah Maxwell O. , Kwarteng Peter G. , Apea Porbilla O. , Adjei Michael R. , Adokiya Martin N. , Boadum Oheneba , Abiwu Hilarius A. K.
Published: September 2023

Background

The home-based vaccination card (HBR) is an important health record for determining vaccination status of children during surveys, particularly in low- and middle-income countries (LMICs). However, there are limited evidence on the factors that influence its retention in Ghana. We assessed the predictors of vaccination card retention in Tamale Metropolis, Ghana

Methods

We conducted a cross-sectional study from 21stDecember 2022 to 10thJanuary 2023 among children aged 0-59 months in the Tamale Metropolis. Multi-stage sampling was used to select caregivers of children aged 0-59 months for enrolment in the study. Data were collected using validated questionnaire through face-to-face interviews of caregivers. A vaccination card was retained if it was presented for physical inspection by research assistants. The factors that influence vaccination card retention were determined in a multivariate logistic regression analysis at p<0.05.

Results

A total of 1,566 eligible children were enrolled in this study. Vaccination card retention was 89.5%. Negative predictors of card retention included: being resident in the Nyohini (AOR=0.26; 95% CI=0.15-0.47) and Tamale Central (AOR= 0.52; 95% CI=0.30-0.92) sub-Metro areas, and children belonging to age group 24-59 months (AOR=0.40; 95% CI=0.23-0.67). On the other hand, paying for the vaccination card (AOR=5.20; 95% CI=2.98-9.04) was a positive predictor of vaccination card retention.

Conclusion

In this study, vaccination card retention among children aged 0-59 months was higher than national estimates. Vaccination card retention was mainly influenced by place of residence, age of child and mode of acquisition of the card such as out-of-pocket payment. There is need to design and deliver tailored messages including the importance of vaccination card retention to caregivers of children based on geographic context. Additionally, the vaccination cards should be supplied to health facilities and made readily accessible to caregivers to prevent out-of-pocket payment.
Verbenone and L-arginine fromDaucus carotaSeeds Attenuate Oxidative Stress in Streptozotocin-Nicotinamide (STZ-NAD)-Induced Diabetic Mice: Evidence fromIn vitroandIn vivoStudies
Authors: Tijjani Habibu , Ibrahim Umar , Tijani Sadiq , Alka Sadiya , Olatunde Ahmed , Kura Aminu Umar , Gagman Haladu Ali , Saliu Oluremi A. , Idowu Oluwafemi A. , Ebhodaghe Frank Eromosele
Published: September 2023

Free radicals are produced in diabetes mellitus (DM), due to protein glycosylation and glucose autooxidation. However, compounds from plants were proven to be effective in the management of DM and related conditions. This study evaluated the antioxidant effect of verbenone, L-arginine, and their ratio combinations in diabetic mice. DM was induced in mice by intraperitoneal (IP) injection of streptozotocin and nicotinamide adenine dinucleotide (NAD) and the diabetic mice were treated with verbenone, L-arginine, and their ratios for 28 days. In thein vitrostudy, L-arginine expressed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, while verbenone and L-arginine expressed higher nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging activities, especially at higher concentrations when compared with vitamin C. At the end of the treatment period, the levels of blood glucose, total protein, and malondialdehyde were significantly increased while the levels of reduced glutathione, nitrite, and activities of glutathione peroxidase, glutathione transferase, catalase, superoxide dismutase were significantly decreased in the diabetic untreated mice. However, these diabetes-induced alterations were reversed to normal levels after the administration of verbenone, L-arginine, and their ratio combinations at 100 and 200 mg/kg body weight. Furthermore,in silicostudies revealed the antioxidant potential of both verbenone and L-arginine by their interaction with antioxidant proteins, expressing their potential antioxidant properties. The results of the study indicated that verbenone, L-arginine, and their ratio combination possess antioxidant property and attenuate oxidative stress in diabetic mice.

Highlights

Verbenone and L-arginine are natural compounds found inDaucus carotaseeds and other plants.

Verbenone and L-arginine possessin vitroandin vivoantioxidant activities.

Verbenone, L-arginine and their ratio combination (1:1) enhance the activities of antioxidant enzymes in streptozotocin-nicotinamide (NAD-STZ) induced diabetic mice.

Furthermore, the two compounds interacted with antioxidant proteins, expressing their potential antioxidant property in anin silicomodel.
Marmosets mutually compensate for differences in rhythms when coordinating vigilance
Authors: Phaniraj Nikhil , Brügger Rahel K. , Burkart Judith M.
Published: September 2023

Synchronisation is widespread in animals, and studies have often emphasised how this seemingly complex phenomenon can emerge from very simple rules. However, the amount of flexibility and control that animals might have over synchronisation properties, such as the strength of coupling, remains underexplored. Here, we studied how pairs of marmoset monkeys coordinated vigilance while feeding. By modelling them as coupled oscillators, we noted that (1) individual marmosets do not show perfect periodicity in vigilance behaviours, (2) even then, pairs of marmosets developed a tendency to take turns being vigilant, a case of anti-phase synchrony, (3) marmosets could couple flexibly; the coupling strength varied with every new joint feeding bout, and (4) marmosets could control the coupling strength; dyads showed increased coupling if they began in a more desynchronised state. Such flexibility and control over synchronisation require more than simple interaction rules. Minimally, animals must estimate the current degree of asynchrony and adjust their behaviour accordingly. Moreover, the fact that each marmoset is inherently non-periodic adds to the cognitive demand. Overall, our study taps into the cognitive aspects of synchronisation and provides a mathematical framework to investigate the phenomenon more widely, where individuals may not display perfectly rhythmic behaviours.
Advancement in Cellular Topographic and Nanoparticle Capture Imaging by High Resolution Microscopy Incorporating a Freeze-Drying and Gaseous Nitrogen-based Approach
Authors: Uryu Kunihiro , Soplop Nadine , Sheahan Timothy P. , Catanese Maria-Teresa , Huynh Chuong , Pena John , Boudreau Nancy , Matei Irina , Kenific Candia , Hashimoto Ayako , Hoshino Ayuko , Rice Charles M. , Lyden David
Published: September 2023

Scanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO4) and ethanol-based tissue preparation. However, conventional SEM methods limit optimal resolution due to ethanol and lipid interactions and interfere with visualization of fluorescent reporter proteins. Therefore, SEM correlative light and electron microscopy (CLEM) has been hindered by the adverse effects of ethanol and OsO4on retention of fluorescence signals. To overcome this technological gap in achieving high-resolution SEM and retain fluorescent reporter signals, we developed a freeze-drying method with gaseous nitrogen (FDGN). We demonstrate that FDGN preserves cyto-architecture to allow visualization of detailed membrane topography while retaining fluorescent signals and that FDGN processing can be used in conjunction with a variety of high-resolution imaging systems to enable collection and validation of unique, high-quality data from these approaches. In particular, we show that FDGN coupled with high resolution microscopy provided detailed insight into viral or tumor-derived extracellular vesicle (TEV)-host cell interactions and may aid in designing new approaches to intervene during viral infection or to harness TEVs as therapeutic agents.
SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants
Authors: Hassan Sk. Sarif , Bhattacharya Tanishta , Nawn Debaleena , Jha Ishana , Basu Pallab , Redwan Elrashdy M. , Lundstrom Kenneth , Barh Debmalya , Andrade Bruno Silva , Tambuwala Murtaza M. , Aljabali Alaa A. , Hromić-Jahjefendić Altijana , Baetas-da-Cruz Wagner , Uversky Vladimir N.
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional NSP14 enzyme, possessing exonuclease and mRNA capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscores the dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer
Authors: Zhao Na , Kabotyanski Elena B. , Saltzman Alexander B. , Malovannaya Anna , Yuan Xueying , Reineke Lucas C. , Lieu Nadia , Gao Yang , Pedroza Diego A , Calderon Sebastian J , Smith Alex J , Hamor Clark , Safari Kazem , Savage Sara , Zhang Bing , Zhou Jianling , Solis Luisa M. , Hilsenbeck Susan G. , Fan Cheng , Perou Charles M. , Rosen Jeffrey M.
Published: September 2023

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A by Zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages towards an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade.

Mechanistic studies revealed that Zotatifin reprograms the tumor translational landscape, inhibits the translation ofSox4 andFgfr1, and induces an interferon response uniformly across models. The induction of an interferon response is partially due to the inhibition ofSox4translation by Zotatifin. A similar induction of interferon-stimulated genes was observed in breast cancer patient biopsies following Zotatifin treatment. Surprisingly, Zotatifin significantly synergizes with carboplatin to trigger DNA damage and an even heightened interferon response resulting in T cell-dependent tumor suppression. These studies identified a vulnerability of eIF4A in TNBC, potential pharmacodynamic biomarkers for Zotatifin, and provide a rationale for new combination regimens comprising Zotatifin and chemotherapy or immunotherapy as treatments for TNBC.

One Sentence Summary

Targeting EIF4A sensitizes TNBC to immune therapy and chemotherapy by suppressing Sox4, inducing an interferon response, and reprograming the tumor immune microenvironment.
Simulation-based Benchmarking of Ancient Haplotype Inference for Detecting Population Structure
Authors: Tretmanis Jazeps Medina , Jay Flora , Ávila-Arcos María C. , Huerta-Sanchez Emilia
Published: September 2023

Paleogenomic data has informed us about the movements, growth, and relationships of ancient populations. It has also given us context for medically relevant adaptations that appear in present-day humans due to introgression from other hominids, and it continues to help us characterize the evolutionary history of humans. However, ancient DNA (aDNA) presents several practical challenges as various factors such as deamination, high fragmentation, environmental contamination of aDNA, and low amounts of recoverable endogenous DNA, make aDNA recovery and analysis more difficult than modern DNA. Most studies with aDNA leverage only SNP data, and only a few studies have made inferences on human demographic history based on haplotype data, possibly because haplotype estimation (or phasing) has not yet been systematically evaluated in the context of aDNA. Here, we evaluate how the unique challenges of aDNA can impact phasing quality. We also develop a software tool that simulates aDNA taking into account the features of aDNA as well as the evolutionary history of the population. We measured phasing error as a function of aDNA quality and demographic history, and found that low phasing error is achievable even for very ancient individuals (∼ 400 generations in the past) as long as contamination and read depth are adequate. Our results show that population splits or bottleneck events occurring between the reference and phased populations affect phasing quality, with bottlenecks resulting in the highest average error rates. Finally, we found that using estimated haplotypes, even if not completely accurate, is superior to using the simulated genotype data when reconstructing changes in population structure after population splits between present-day and ancient populations.

Availability

All software used for simulation and analysis is available at github.com/Jazpy/Paleogenomic-Datasim
Pigmentation level of human iPSC-derived retinal pigment epithelium cell does not indicate a specific gene expression profile
Authors: Nakai-Futatsugi Yoko , Jin Jianshi , Ogawa Taisaku , Sakai Noriko , Maeda Akiko , Hironaka Ken-ichi , Fukuda Masakazu , Danno Hiroki , Tanaka Yuji , Hori Seiji , Shiroguchi Katsuyuki , Takahashi Masayo
Published: September 2023

Retinal pigment epithelium (RPE) cells show heterogeneous level of pigmentation when culturedin vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized in 4 clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.
Emotional showdown on social media: analyzing user reactions to the 2016 US presidential campaign
Authors: Bagić Babac Marina
Published: September 2023

Purpose

Social media platforms are highly visible platforms, so politicians try to maximize their benefits from their use, especially during election campaigns. On the other side, people express their views and sentiments toward politicians and political issues on social media, thus enabling them to observe their online political behavior. Therefore, this study aims to investigate user reactions on social media during the 2016 US presidential campaign to decide which candidate invoked stronger emotions on social media.

Design/methodology/approach

For testing the proposed hypotheses regarding emotional reactions to social media content during the 2016 presidential campaign, regression analysis was used to analyze a data set that consists of Trump’s 996 posts and Clinton’s 1,253 posts on Facebook. The proposed regression models are based on viral (likes, shares, comments) and emotional Facebook reactions (Angry, Haha, Sad, Surprise, Wow) as well as Russell’s valence, arousal, dominance (VAD) circumplex model for valence, arousal and dominance.

Findings

The results of regression analysis indicate how Facebook users felt about both presidential candidates. For Clinton’s page, both positive and negative content are equally liked, while Trump’s followers prefer funny and positive emotions. For both candidates, positive and negative content influences the number of comments. Trump’s followers mostly share positive content and the content that makes them angry, while Clinton’s followers share any content that does not make them angry. Based on VAD analysis, less dominant content, with high arousal and more positive emotions, is more liked on Trump’s page, where valence is a significant predictor for commenting and sharing. More positive content is more liked on Clinton’s page, where both positive and negative emotions with low arousal are correlated to commenting and sharing of posts.

Originality/value

Building on an empirical data set from Facebook, this study shows how differently the presidential candidates communicated on social media during the 2016 election campaign. According to the findings, Trump used a hard campaign strategy, while Clinton used a soft strategy.
Resolving organizational peer conflict via integrative behaviors: the role of trust and informational support
Authors: Sims Randi L. , Barreto Tais S. , Sell Katelynn M. , Lawrence Eleanor T. , Seymour Paul
Published: September 2023

Purpose

The purpose of this study is to investigate the role of trust, informational support and integrative behaviors in the effective outcomes of peer conflict in the workplace.

Design/methodology/approach

Deidentified secondary data were provided by a human resource management company that offers conflict resolution training. The authors studied a sample of 815 supervisors and middle-level managers (51% female; average age = 40) who reported their primary work experience was in the USA. Each respondent described a workplace conflict with a peer. A regression-based bootstrapping technique was used to test the hypothesized relationships between the constructs of trust, informational support, integrative behaviors and effective outcomes in peer conflict.

Findings

The relationship between trust and the use of integrative behaviors during peer conflict is conditional on the availability of informational support, such that those who solicit a third party’s views are more likely to exhibit integrative behaviors during the conflict under study, even at relatively lower levels of trust in the conflict relationship.

Originality/value

In this study, the authors add to social interdependence theory and the role of integrative behaviors by proposing the importance of interpersonal trust and informational support, which may reduce uncertainty during peer conflict. The authors also extend existing literature on cooperation, cooperative approaches to managing conflict and integrative behaviors in the workplace by examining peer-to-peer organizational conflict.
Audit partner attributes and key audit matters readability
Authors: Mwintome Gordon , Agana Joseph Akadeagre , Zamore Stephen
Published: September 2023

Purpose

The authors examine the association between two important audit partner characteristics and the readability of key audit matters (KAMs) disclosed in the audit reports. Specifically, the authors examine how the readability of KAMs is associated with audit partner tenure and workload.

Design/methodology/approach

The authors conduct the study in the audit context of Norway and applied the Flesch reading ease scale to measure the readability levels of reported KAMs in the audit reports of companies listed on the Oslo Stock Exchange. Panel data estimation techniques are applied in estimating how partner tenure and workload are associated with the readability of KAMs. In addition, several robustness tests including different measures of KAMs readability and subsample analyses are performed.

Findings

The authors find that audit partner tenure and workload have significant associations with the level of KAMs readability. Specifically, the results show that the reported KAMs become more readable as the audit partner tenure increases but are less readable for partners with more workload. These results appear stronger in subsamples of KAMs typically noted to be more complex and associated with higher risks.

Research limitations/implications

As KAMs represent the most significant issues in financial statements audit, these results provide important insights to stakeholders on the potential impact of audit partner tenure and workload on KAMs readability. Less readable KAMs could derail stakeholders' desire to bridge the information gap between auditors and users of the audit report. The uniqueness of this study lies in its focus on audit partner characteristics as opposed to the audit firm.

Practical implications

Excessive audit partner workload impairs KAMs readability.

Originality/value

As KAMs represent the most significant issues in financial statements audit, these results provide important insights to stakeholders on the potential impact of audit partner tenure and workload on KAMs readability. Less readable KAMs could derail stakeholders' desire to bridge the information gap between auditors and users of the audit report. The uniqueness of this study lies in its focus on audit partner characteristics as opposed to the audit firm.
Value relevance of compliance with IFRS 7: evidence from Canada
Authors: Mnif Yosra , Znazen Oumaima
Published: September 2023

Purpose

This paper aims to test whether the extent of compliance with International Financial Reporting Standards (IFRS) 7 requirements is value relevant and whether it influences the value relevance of the firm's accounting information (book value of shareholders' equity and net income).

Design/methodology/approach

The sample for this paper consists of 288 financial institutions listed on the Toronto Stock Exchange (TSX) from 2016 to 2019. Panel regressions have been used in this study.

Findings

The findings reveal that compliance with IFRS 7 is positively associated with the firm's market value. After making a classification between high-compliance and low-compliance companies, the authors' results indicate that the compliance level is positively associated with the value relevance of net income. Surprisingly, when examining the value relevance of financial instruments disclosures (FID) supplied after the adoption of IFRS 9, the authors find that book values of shareholders' equity and earnings are not more value relevant in the post-IFRS 9 period.

Research limitations/implications

Given that the authors' analysis has been restricted to the Canadian setting, the regression results might not be generalized for other countries with different capital markets features.

Practical implications

The authors' findings point out that FID can affect investors' decisions as well as their confidence in the companies in which they invest. Hence, the regulatory bodies should gear more efforts to ensure high-compliance levels.

Originality/value

To the best of the authors' knowledge, this research is among the first attempts to investigate whether the new FID (after the adoption of IFRS 9) improves the firm disclosure quality and enhances the value relevance of accounting information.
Influencing factors and prediction of overcapacity of new energy enterprises in China
Authors: Lou Wen-Qian , Wu Bin , Zhu Bo-Wen
Published: September 2023

Purpose

This study aims to clarify influencing factors of overcapacity of new energy enterprises in China and accurately predict whether these enterprises have overcapacity.

Design/methodology/approach

Based on relevant data including the experience and evidence from the capital market in China, the research establishes a generic univariate selection-comparative machine learning model to study relevant factors that affect overcapacity of new energy enterprises from five dimensions. These include the governmental intervention, market demand, corporate finance, corporate governance and corporate decision. Moreover, the bridging approach is used to strengthen findings from quantitative studies via the results from qualitative studies.

Findings

The authors' results show that the overcapacity of new energy enterprises in China is brought out by the combined effect of governmental intervention corporate governance and corporate decision. Governmental interventions increase the overcapacity risk of new energy enterprises mainly by distorting investment behaviors of enterprises. Corporate decision and corporate governance factors affect the overcapacity mainly by regulating the degree of overconfidence of the management team and the agency cost. Among the eight comparable integrated models, generic univariate selection-bagging exhibits the optimal comprehensive generalization performance and its area under the receiver operating characteristic curve Area under curve (AUC) accuracy precision and recall are 0.719, 0.960, 0.975 and 0.983, respectively.

Originality/value

The proposed integrated model analyzes causes and predicts presence of overcapacity of new energy enterprises to help governments to formulate appropriate strategies to deal with overcapacity and new energy enterprises to optimize resource allocation. Ten main features which affect the overcapacity of new energy enterprises in China are identified through generic univariate selection model. Through the bridging approach, the impact of the main features on the overcapacity of new energy enterprises and the mechanism of the influence are analyzed.