bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Image Statistics for Mouse Vision
Authors: Abballe Luca , Asari Hiroki 
Published: April 2021

AbstractThe mouse has dichromatic color vision based on two different types of opsins: short (S)- and middle (M)-wavelength-sensitive opsins with peak sensitivity to ultraviolet (UV; 360 nm) and green light (508 nm), respectively. In the mouse retina, cone photoreceptors that predominantly express the S-opsin are more sensitive to contrasts and denser towards the ventral retina, preferentially sampling the upper part of the visual field. In contrast, the expression of the M-opsin gradually increases towards the dorsal retina that encodes the lower visual field. Such a distinctive retinal organization is assumed to arise from a selective pressure in evolution to efficiently encode the natural scenes. However, natural image statistics of UV light remain largely unexplored. Here we developed a multi-spectral camera to acquire high-quality UV and green images of the same natural scenes, and examined the optimality of the mouse retina to the image statistics. We found that the local contrast and the spatial correlation were both higher in UV than in green for images above the horizon, but lower in UV than in green for those below the horizon. This suggests that the dorsoventral functional division of the mouse retina is not optimal for maximizing the bandwidth of information transmission. Factors besides the coding efficiency, such as visual behavioral requirements, will thus need to be considered to fully explain the characteristic organization of the mouse retina.
Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq
Authors: Fustero-Torre Coral , Jiménez-Santos María José , García-Martín Santiago , Carretero-Puche Carlos , García-Jimeno Luis , Di Domenico Tomás , Gómez-López Gonzalo , Al-Shahrour Fátima 
Published: April 2021

AbstractWe present Beyondcell (https://gitlab.com/bu_cnio/beyondcell/), a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score in a collection of drug signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines therapeutic differences among cell populations, and generates a prioritised ranking of the differential sensitivity drugs between chosen conditions to guide drug selection. We performed Beyondcell analysis in four single-cell datasets to validate our score and to demonstrate that TCs can be exploited to target malignant cells both in cancer cell lines and tumour patients.
Naïve individuals promote collective exploration in homing pigeons
Authors: Valentini Gabriele , Pavlic Theodore P. , Walker Sara Imari , Pratt Stephen C. , Biro Dora , Sasaki Takao 
Published: April 2021

AbstractGroup-living animals that rely on stable foraging or migratory routes can develop behavioural traditions to pass route information down to inexperienced individuals. Striking a balance between exploitation of social information and exploration for better alternatives is essential to prevent the spread of maladaptive traditions. We investigated this balance during cumulative route development in the homing pigeonColumba livia. We quantified information transfer within pairs of birds in a transmission-chain experiment and determined how birds with different levels of experience contributed to the exploration– exploitation trade-off. Newly introduced naïve individuals were initially more likely to initiate exploration than experienced birds, but the pair soon settled into a pattern of alternating leadership with both birds contributing equally. Experimental pairs showed an oscillating pattern of exploration over generations that might facilitate the discovery of more efficient routes. Our results introduce a new perspective on the roles of leadership and information pooling in the context of collective learning.
Radiation exposure of the base of the heart accelerates coronary atherosclerosis
Authors: Nepali Prerna R. , Mathieu Mickael , Kitz Sarah , Nakauchi Chiharuko , Gabriels Karen , Russell James , Monette Sebastien , te Poele Johannes A. , Heeneman Sylvia , Rimner Andreas , Qiu Yunping , Kurland Irwin J. , Stewart Fiona A. , Jaimes Edgar A. , Haimovitz-Friedman Adriana 
Published: April 2021

AbstractClinical studies have identified cardiac exposure as an independent predictor for cardiovascular mortality in patients treated with radiation therapy (RT) for thoracic malignancies. Although the mechanisms are not completely understood, the available evidence indicate that direct injury to the coronary arteries endothelium is implicated. In these studies we tested the hypothesis that different areas of the heart are more sensitive to the effects of RT on the formation of atherosclerotic plaque in apolipoprotein E deficient (ApoE-/-) mice, a well validated model of atherosclerosis.MethodsApoE-/-mice on a high fat diet (HFD) received 16Gy cardiac irradiation targeted to the whole or partial (apical or basal) region of the heart at 9 weeks or 16 weeks of age. Atherosclerotic lesions and inflammatory changes in the hearts as compared to control unirradiated mice were assessed eight weeks following radiation.ResultsAfter either basal or whole heart RT at 9 weeks of age the number of subendocardial atherosclerotic lesions at the heart base was higher as compared to unirradiated mice. Irradiation of the apex did not increase the number of subendocardial atherosclerotic lesions in any region. After basal RT at 16 weeks of age the number of coronary and subendocardial atherosclerotic lesions was higher as compared to controls. Neither apical or whole heart RT had an impact on the development or acceleration of lesions in the basal region of the hearts of 16 week old mice, thus demonstrating the adverse impact of basal irradiation. Infiltration of inflammatory cells (CD45+and CD3+) and enhanced expression of endothelial adhesion molecules (CD31), were differentially and locally regulated based upon the site of irradiation. In support of a role of eicosanoid mediators for base or whole heart atherogenic irradiation effects, apex irradiation eicosanoid mediators are not clearly atherogenic, in contrast to eicosanoid mediators detected in serum after base heart irradiation. These results indicate that the base of the heart is significantly more prone to the development of atherosclerotic lesions in the coronary arteries post-RT.ConclusionOur results indicate that the base of the heart is more susuceptible to development of RT-induced atherosclerotic lesions and therefore avoidance from RT direct exposure to this area may reduce the risk for atherosclerotic disease in patients undergoing RT.
A genomic portrait of zebrafish transposable elements and their spatiotemporal embryonic expression
Authors: Chang Ni-Chen , Rovira Quirze , Wells Jonathan N. , Feschotte Cédric , Vaquerizas Juan M. 
Published: April 2021

AbstractThere is considerable interest in understanding the effect of transposable elements (TEs) on embryonic development. Studies in humans and mice are limited by the difficulty of working with mammalian embryos, and by the relative scarcity of active TEs in these organisms. Zebrafish is an outstanding model for the study of vertebrate development and over half of its genome consists of diverse TEs. However, zebrafish TEs remain poorly characterized. Here we describe the demography and genomic distribution of zebrafish TEs and their expression throughout embryogenesis using bulk and single-cell RNA sequencing data. These results reveal a highly dynamic genomic ecosystem comprising nearly 2,000 distinct TE families, which vary in copy number by four orders of magnitude and span a wide range of ages. Longer retroelements tend to be retained in intergenic regions, whilst short interspersed nuclear elements (SINEs) and DNA transposons are more frequently found nearby or within genes. Locus-specific mapping of TE expression reveals extensive TE transcription during development. While two thirds of TE transcripts are likely driven by nearby gene promoters, we still observe stage and tissue-specific expression patterns in self-regulated TEs. Long terminal repeat (LTR) retroelements are most transcriptionally active immediately following zygotic genome activation, whereas DNA transposons are enriched amongst transcripts expressed in later stages of development. Single-cell analysis reveals several endogenous retroviruses expressed in specific somatic cell lineages. Overall, our study provides an important resource for using zebrafish as a model to study the impact of TEs on vertebrate development.
Emergent myxobacterial behaviors arise from reversal suppression induced by kin contacts
Authors: Balagam Rajesh , Cao Pengbo , Sah Govind P. , Zhang Zhaoyang , Subedi Kalpana , Wall Daniel , Igoshin Oleg A. 
Published: April 2021

AbstractA wide range of biological systems – from microbial swarms to bird flocks, display emergent behaviors driven by coordinated movement of individuals. To this end, individual organisms interact by recognizing their kin and adjusting their motility based on others around them. However, even in the best-studied systems, the mechanistic basis of the interplay between kin recognition and motility coordination is not understood. Here, using a combination of experiments and mathematical modeling, we uncover the mechanism of an emergent social behavior inMyxococcus xanthus. By overexpressing cell surface adhesins, TraA and TraB, involved in kin recognition, large numbers of cells adhere to one another and form organized macroscopic circular aggregates that spin clockwise or counterclockwise. Mechanistically, TraAB adhesion results in sustained cell-cell contacts that trigger cells to suppress cell reversals, and circular aggregates form as the result of cells’ ability to follow their own cellular slime trails. Furthermore, ourin-silicosimulations demonstrate a remarkable ability to predict self-organization patterns when phenotypically distinct strains are mixed. For example, defying naïve expectations, both models and experiments found that strains engineered to overexpress different and incompatibletraABallelles nevertheless form mixed circular aggregates. Therefore, this work provides key mechanistic insights intoM. xanthussocial interactions and demonstrates how local cell contacts induce emergent collective behaviors by millions of cells.ImportanceIn many species, large populations exhibit emergent behaviors whereby all related individuals move in unison. For example, fish in schools can all dart in one direction simultaneously to avoid a predator. Currently, it is impossible to explain how such animals recognize kin through brain cognition and elicit such behaviors at a molecular level. However, microbes also recognize kin and exhibit emergent collective behaviors that are experimentally tractable. Here, using a model social bacterium, we engineer dispersed individuals to organize into synchronized collectives that create emergent patterns. With experimental and mathematical approaches we explain how this occurs at both molecular and population levels. The results demonstrate how the combination of local physical interactions triggers intracellular signaling, which in turn leads to emergent behavior on a population scale.
A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2
Authors: Tsegay Kaleb B. , Adeyemi Christiana M. , Gniffke Edward P. , Sather D. Noah , Walker John K. , Smith Stephen E. P. 
Published: April 2021

AbstractRepurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding by <90%, measured the EC50of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.
Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy
Authors: Koh Eun-Ik , Oluoch Peter O. , Ruecker Nadine , Proulx Megan K. , Soni Vijay , Murphy Kenan C. , Papavinasasundaram Kadamba G. , Reames Charlotte J. , Trujillo Carolina , Zaveri Anisha , Zimmerman Matthew D. , Aslebagh Roshanak , Baker Richard E. , Shaffer Scott A. , Guinn Kristine M. , Fitzgerald Michael , Dartois Véronique A. , Ehrt Sabine , Hung Deborah T. , Ioerger Thomas R. , Rubin Eric , Rhee Kyu Y. , Schnappinger Dirk , Sassetti Christopher M. 
Published: April 2021

AbstractCurrent chemotherapy againstMycobacterium tuberculosis(Mtb), an important human pathogen, requires a multidrug regimen lasting several months. While efforts have been made to optimize therapy by exploiting drug-drug synergies, testing new drug combinations in relevant host environments remains arduous. In particular, host environments profoundly affect the bacterial metabolic state and drug efficacy, limiting the accuracy of predictions based onin vitroassays alone. In this study, we utilize conditionalMtbknockdown mutants of essential genes as an experimentally-tractable surrogate for drug treatment, and probe the relationship betweenMtbcarbon metabolism and chemical-genetic interactions (CGI). We examined the anti-tubercular drugs isoniazid, rifampicin and moxifloxacin, and found that CGI are differentially responsive to the metabolic state, defining both environment-independent and –dependent interactions. Specifically, growth on thein vivo-relevant carbon source, cholesterol, reduced rifampicin efficacy by altering mycobacterial cell surface lipid composition. We report that a variety of perturbations in cell wall synthesis pathways restore rifampicin efficacy during growth on cholesterol, and that both environment-independent and cholesterol-dependentin vitroCGI could be leveraged to enhance bacterial clearance in the mouse infection model. Our findings present an atlas of novel chemical-genetic-environmental interactions that can be used to optimize drug-drug interactions as well as provide a framework for understandingin vitrocorrelates ofin vivoefficacy.SignificanceEfforts to improve tuberculosis therapy include optimizing multi-drug regimens to take advantage of drug-drug synergies. However, the complex host environment has a profound effect on bacterial metabolic state and drug activity, making predictions of optimal drug combinations difficult. In this study, we leverage a newly developed library of conditional knockdownMycobacterium tuberculosismutants in which genetic depletion of essential genes mimics the effect of drug therapy. This tractable system allowed us to assess the effect of growth condition on predicted drug-drug interactions. We found that these interactions can be differentially sensitive to the metabolic state and selectin vitro-defined interactions can be leveraged to accelerate bacterial killing during infection. These findings suggest new strategies for optimizing tuberculosis therapy.
Honeybee Queen mandibular pheromone induces starvation in Drosophila
melanogaster, implying a role for nutrition signalling in the evolution
of eusociality
Authors: Lovegrove Mackenzie R. , Duncan Elizabeth J. , Dearden Peter K. 
Published: April 2021

Abstract
Eusocial insect societies are defined by the reproductive division of
labour, a social structure that is generally enforced by the reproductive
dominant or ‘queen’. Reproductive dominance is maintained through behavioural
dominance in some species as well as production of queen pheromones in others,
or a mixture of both. Queen mandibular pheromone (QMP) is produced by honeybee
(Apis mellifera) queens and has been
characterised chemically. How QMP acts to repress worker reproduction, and how
it has evolved this activity, remains less well understood. Surprisingly, QMP is
capable of repressing reproduction in non-target arthropods which have not
co-evolved with QMP, are never exposed to QMP in nature, and are up to 530
million years diverged from the honeybee.
Here we show that, in Drosophila melanogaster,
QMP treatment mimics nutrient limiting conditions, leading to disrupted
reproduction. Exposure to QMP induces an increase in food consumption,
consistent with that observed in D. melanogaster in
response to starvation conditions. This response induces the activation of two
checkpoints within the ovary that inhibit oogenesis. The first is the 2a/b
ovarian checkpoint in the germarium, which reduces the flow of presumptive
oocytes. A stage 9 ovarian checkpoint is also activated, causing degradation of
oocytes. The magnitude of activation of both checkpoints is indistinguishable
between QMP treated and starved individuals.
As QMP seems to trigger a starvation response in an insect highly diverged
from honeybees, we propose that QMP originally evolved by co-opting nutrition
signalling pathways to regulate reproduction, a key step in the evolution of
eusociality.
No observable guide-RNA-independent off-target mutation induced by prime editor
Authors: Gao Runze , Fu Zhi-Can , Li Xiangyang , Wang Ying , Wei Jia , Li Guangye , Wang Lijie , Wu Jing , Xue Wei , Huang Xingxu , Yang Li , Chen Jia 
Published: April 2021

ABSTRACTPrime editor (PE) has been recently developed to induce efficient and precise ontarget editing, whereas its guide RNA (gRNA)-independent off-target effects remain unknown. Here, we used whole-genome and whole-transcriptome sequencing to determine gRNA-independent off-target mutations in cells expanded from single colonies, in which PE generated precise editing at on-target sites. We found that PE triggered no observable gRNA-independent off-target mutation genome-wide or transcriptome-wide in transfected human cells, highlighting its high specificity.
An investigation on the existence of warped product irrotational screen-real lightlike submanifolds of metallic semi-Riemannian manifolds
Authors: Shanker Gauree , Yadav Ankit 
Published: April 2021

PurposeThe purpose of this paper is to study the geometry of screen real lightlike submanifolds of metallic semi-Riemannian manifolds. Also, the authors investigate whether these submanifolds are warped product lightlike submanifolds or not.Design/methodology/approachThe paper is design as follows: In Section 3, the authors introduce screen-real lightlike submanifold of metallic semi Riemannian manifold. In Section 4, the sufficient conditions for the radical and screen distribution of screen-real lightlike submanifolds, to be integrable and to be have totally geodesic foliation, have been established. Furthermore, the authors investigate whether these submanifolds can be written in the form of warped product lightlike submanifolds or not.FindingsThe geometry of the screen-real lightlike submanifolds has been studied. Also various results have been established. It has been proved that there does not exist any class of irrotational screen-real r-lightlike submanifold such that it can be written in the form of warped product lightlike submanifolds.Originality/valueAll results are novel and contribute to further study on lightlike submanifolds of metallic semi-Riemannian manifolds.
Social media and the spread of COVID-19 infodemic
Authors: Adekoya Clement Ola , Fasae Joseph Kehinde 
Published: April 2021

Purpose
The purpose of this paper is to investigate the social media application and the spread of COVID-19 infodemic in Nigeria.

Design/methodology/approach
A descriptive survey research design was used for this study. A total of 1,200 social media users, regardless of their professions, were randomly selected for the study betweenmid-June and July 2020. Stratified and purposive sampling techniques were used for this study. The questionnaire was designed using Google form and administered using WhatsApp and Telegram to social media users above 18 years old in Nigeria. The data generated was analyzed using descriptive (frequency count) and inferential (mean) statistics, and was presented in tables.

Findings
It was found that people make use of social media during COVID-19 pandemic for diverse reasons such as listening to announcement to be informed, knowing the necessary measures to take by those infected and spreading up-to-date information on the pandemic. Social media tools were highly used during the COVID-19 pandemic, especially WhatsApp and Zoom. Findings reflected that misinformation was spread on social media. This study also showed that the infodemic associated with COVID-19 is managed by confirming the source of the information before sharing it and trusting information from reliable sources.

Research limitations/implications
The result of this research will contribute to the body of knowledge on social media application, fake news and the spread of COVID-19 infodemic in Nigeria and beyond.

Practical implications
Infodemic is a disaster in the health sector. The spread of infodemic is capable of misleading people, losing trust in government, health providers and health regulatory authorities. This study will help social media users to know how to properly manage social media infodemic during a pandemic or any health-related situations.

Originality/value
This study is novel as it approaches fake news from a COVID-19 perspective. Very few articles emanate from the developing countries in this area. This was because most of the narrative around fake news previously centered around the Western occurrences such as the Iraqi invasion by the USA, the US presidential elections and BREXIT. COVID-19 has demonstrated that the developing world is not immune from fake news as well. This study, therefore, assessed the management of infodemic associated with COVID-19 in Nigeria.
Outpatient regulation system in health management: economic benefits of technological innovations
Authors: Camargo Jr Alceu Salles 
Published: April 2021

Purpose
The purpose of this paper is to evaluate the economic benefits of managing an outpatient appointments system with technological innovations.

Design/methodology/approach
This study uses a quantitative methodological procedures aiming to evaluate the cost-benefit relation and also the payback of the management and operation of an outpatient appointments system with technological innovations.

Findings
This study found a great benefit-cost relation of 30.6 showing the great economic value and social impact of managing an outpatient appointments regulation system with technological innovations.

Research limitations/implications
This study presents contribution to the literature discussion about the economic evaluation of the benefits of managing and operating more effective outpatient appointments systems because of important technological innovations.

Practical implications
This paper presents and discusses the most important and commonly used strategies and technological innovations to deal with and to manage an outpatient appointment regulation system aiming to reduce the patient no-show rates.

Social implications
The findings of this study show a great benefit-cost relation of about 30.6 which is being reverted to the society.

Originality/value
There not exist many similar studies in the pertinent literature, mostly with the Brazilian contexts.