bluuebunny/crossref_metadata_2025 huggingface dataset:
Gleissberg Cycle Dependence of Inner Zone Proton Flux
Authors: Bregou Emily J. , Hudson Mary K. , Kress Brian T. , Qin Murong , Selesnick Richard S.
Published: June 2022

Inner zone proton flux from 1980 to mid‐2021 is examined using NOAA POES satellite data, indicating a long‐term increase corresponding to a one hundred year minimum in solar activity consistent with the Centennial Gleissberg Cycle. Variation of inner belt protons is correlated with decreasing F10.7 maxima over the 40‐year period, serving as proxy for solar EUV input to Earth's atmosphere. Extending an earlier study (Qin et al., 2014; https://doi.org/10.1002/2014JA020300) of >70 MeV protons from 1980 – 2021 using the South Atlantic Anomaly (SAA) peak flux, and at fixed L = 1.3, a comparison is made between the >35, >70 and >140 MeV energy channels on POES. All three energies show an increase in proton flux over the period 1998 – 2021 using a single spacecraft. The observed flux increase is correlated with decreasing F10.7 over the longer 40‐year time interval, as with the ∼11‐year solar cycle. A phase lag during Solar Cycle 24 (January 2010 – June 2021) between the F10.7 minimum and proton flux maximum was determined to be ∼500 days, the same at all energies studied. A model calculation of the inner zone proton flux is found to generally confirm the long‐term trend examined both in absolute magnitude and phase lag. It is concluded that this long‐term trend is a manifestation of the concurrent Gleissberg cycle minimum and accompanying decrease in solar EUV. Reduced EUV at solar maximum (F10.7 proxy) reduces proton loss to the atmosphere following solar maximum, thus explaining the long‐term flux increase observed.
Chemokine receptors differentially expressed by race category and molecular subtype in the breast cancer TCGA cohort
Authors: Vazquez Elissa D. , Fang Xiangyi , Levesque Lauren A. , Huynh Mike , Venegas Citlali , Lu Nhien , Salazar Nicole
Published: June 2022

Racial disparities in mortality due to metastasis remain significant among breast cancer patients. Chemokine receptors contribute to breast tumors and metastatic outcome. We explored for significant differences in chemokine receptor expression in breast tumors from Black, Asian, and White patients in The Cancer Genome Atlas. We show that despite sharing the same molecular subtype, expression of the chemokine receptors ACKR1, CCR3, CCR6, CCRL1, CCRL2, CXCR1, CXCR2, CXCR4, CXCR6, and CXC3CR1 was significantly different depending on racial group. For patients with triple negative breast cancer, CCR3 was higher in Black versus White and CCRL2 was higher in Asian versus White. In luminal A tumors, ACKR1 was lower in Asian versus White, CCR3 was higher in Black versus White, and CCR6 and CXC3CR1 were lower in Black versus White. In luminal B tumors, CCRL2 was lower in Black versus White, CXCR1 and CXC3CR1 were lower in Asian versus White, and CXCR2 was lower in Black and Asian versus White. In HER2 enriched tumors, CCR3 was higher in Black versus White and CXCR4 lower in Asian versus White. CCR3, CCR6, and CXCR6 associated with worse patient survival. These findings can inform improved treatment strategies to decrease racial disparities in breast cancer burden.
Development of milli-second pulsed atmospheric pressure solution cathode glow discharge optical emission spectroscopy for detecting metal elements in aqueous solution
Authors: Zheng Peichao , Yang Yang , Wang Jinmei , Qazi Hafiz Imran Ahmad , Wu Meini , He Yuxin , Hu Qiang , Ding Ning
Published: June 2022

A novel atmospheric-pressure plasma source has been developed to determine metal ions in an aqueous solution by means of optical emission spectroscopy.
Numerical study of the impact of contact line with hysteresis on the Faraday instability
Authors: Li Jing , Li Xiaochen
Published: June 2022

We report a numerical study of the contact-line effect on the Faraday instability. A momentum balance model is implemented to simulate the hysteresis of the meniscus. By using this model, a stick–slip-motion of the contact line happens on the lateral wall when a vertical vibration is exerted to the container. The numerical result further supports that the contact-line hysteresis can increase the natural frequency by inference. Besides, it can largely delay the timing of the onset because of an extra dissipation provided by the capillary effect. The growth rate can also be affected by the meniscus but the impact of the hysteresis seems limited. The presence of the meniscus is the reason why Faraday instability occurs without any artificial disturbance. Finally, a linear relation between the contact-angle range and the contact-line position is observed from our computation.
Slow localized patterns in singularly perturbed two-component reaction–diffusion equations
Authors: Doelman Arjen
Published: June 2022

Localized patterns in singularly perturbed reaction–diffusion equations typically consist of slow parts, in which the associated solution follows an orbit on a slow manifold in a reduced spatial dynamical system, alternated by fast excursions, in which the solution jumps from one slow manifold to another, or back to the original slow manifold. In this paper we consider the existence and stability of stationary and travelling localized patterns that do not exhibit such jumps, i.e. that are completely embedded in a slow manifold of the singularly perturbed spatial dynamical system. These ‘slow patterns’ have rarely been considered in the literature, for two reasons: (i) in the classical Gray–Scott/Gierer–Meinhardt type models that dominate the literature, the flow on the slow manifold is typically linear and thus cannot exhibit homoclinic pulse or heteroclinic front solutions; (ii) the slow manifolds occurring in the literature are typically ‘vertical’, i.e. given by u ≡ u
0, where u is the fast variable, so that the stability problem is determined by a simple (decoupled) scalar equation. The present research concerns a general system of singularly perturbed reaction–diffusion equations and is motivated by several explicit ecosystem models that do give rise to non-vertical normally hyperbolic slow manifolds on which the flow may exhibit both homoclinic and heteroclinic orbits that correspond to either stationary or travelling localized slow patterns. The associated spectral stability problems are at leading order given by a nonlinear, but scalar, eigenvalue problem with Sturm–Liouville characteristics and we establish that homoclinic pulse patterns are typically unstable, while heteroclinic fronts can either be stable or unstable. However, we also show that homoclinic pulse patterns that are asymptotically close to a heteroclinic cycle may be stable. This result is obtained by explicitly determining the leading order approximations of four critical asymptotically small eigenvalues. By this analysis, that involves several orders of magnitude in the small parameter, we also obtain full control over the nature of the bifurcations—saddle-node, Hopf, global, etc—that determine the existence and stability of the (stationary and/or travelling) heteroclinic fronts and/or homoclinic pulses. Finally, we show that heteroclinic orbits may correspond to stable (slow) interfaces in two-dimensional space, while the homoclinic pulses must be unstable as localized stripes, even when they are stable in one space dimension.
Single-cell sequencing: expansion, integration and translation
Authors: Dai Xiaofeng , Cai Linhan , He Fule
Published: June 2022

With the rapid advancement in sequencing technologies, the concept of omics has revolutionized our understanding of cellular behaviors. Conventional omics investigation approaches measure the averaged behaviors of multiple cells, which may easily hide signals represented by a small-cell cohort, urging for the development of techniques with enhanced resolution. Single-cell RNA sequencing, investigating cell transcriptomics at the resolution of a single cell, has been rapidly expanded to investigate other omics such as genomics, proteomics and metabolomics since its invention. The requirement for comprehensive understanding of complex cellular behavior has led to the integration of multi-omics and single-cell sequencing data with other layers of information such as spatial data and the CRISPR screening technique towards gained knowledge or innovative functionalities. The development of single-cell sequencing in both dimensions has rendered it a unique field that offers us a versatile toolbox to delineate complex diseases, including cancers.
BioAutoML: automated feature engineering and metalearning to predict noncoding RNAs in bacteria
Authors: Bonidia Robson P , Santos Anderson P Avila , de Almeida Breno L S , Stadler Peter F , da Rocha Ulisses N , Sanches Danilo S , de Carvalho André C P L F
Published: June 2022

Recent technological advances have led to an exponential expansion of biological sequence data and extraction of meaningful information through Machine Learning (ML) algorithms. This knowledge has improved the understanding of mechanisms related to several fatal diseases, e.g. Cancer and coronavirus disease 2019, helping to develop innovative solutions, such as CRISPR-based gene editing, coronavirus vaccine and precision medicine. These advances benefit our society and economy, directly impacting people’s lives in various areas, such as health care, drug discovery, forensic analysis and food processing. Nevertheless, ML-based approaches to biological data require representative, quantitative and informative features. Many ML algorithms can handle only numerical data, and therefore sequences need to be translated into a numerical feature vector. This process, known as feature extraction, is a fundamental step for developing high-quality ML-based models in bioinformatics, by allowing the feature engineering stage, with design and selection of suitable features. Feature engineering, ML algorithm selection and hyperparameter tuning are often manual and time-consuming processes, requiring extensive domain knowledge. To deal with this problem, we present a new package: BioAutoML. BioAutoML automatically runs an end-to-end ML pipeline, extracting numerical and informative features from biological sequence databases, using the MathFeature package, and automating the feature selection, ML algorithm(s) recommendation and tuning of the selected algorithm(s) hyperparameters, using Automated ML (AutoML). BioAutoML has two components, divided into four modules: (1) automated feature engineering (feature extraction and selection modules) and (2) Metalearning (algorithm recommendation and hyper-parameter tuning modules). We experimentally evaluate BioAutoML in two different scenarios: (i) prediction of the three main classes of noncoding RNAs (ncRNAs) and (ii) prediction of the eight categories of ncRNAs in bacteria, including housekeeping and regulatory types. To assess BioAutoML predictive performance, it is experimentally compared with two other AutoML tools (RECIPE and TPOT). According to the experimental results, BioAutoML can accelerate new studies, reducing the cost of feature engineering processing and either keeping or improving predictive performance. BioAutoML is freely available at https://github.com/Bonidia/BioAutoML.
A comprehensive benchmarking of WGS-based deletion structural variant callers
Authors: Sarwal Varuni , Niehus Sebastian , Ayyala Ram , Kim Minyoung , Sarkar Aditya , Chang Sei , Lu Angela , Rajkumar Neha , Darfci-Maher Nicholas , Littman Russell , Chhugani Karishma , Soylev Arda , Comarova Zoia , Wesel Emily , Castellanos Jacqueline , Chikka Rahul , Distler Margaret G , Eskin Eleazar , Flint Jonathan , Mangul Serghei
Published: June 2022

Advances in whole-genome sequencing (WGS) promise to enable the accurate and comprehensive structural variant (SV) discovery. Dissecting SVs from WGS data presents a substantial number of challenges and a plethora of SV detection methods have been developed. Currently, evidence that investigators can use to select appropriate SV detection tools is lacking. In this article, we have evaluated the performance of SV detection tools on mouse and human WGS data using a comprehensive polymerase chain reaction-confirmed gold standard set of SVs and the genome-in-a-bottle variant set, respectively. In contrast to the previous benchmarking studies, our gold standard dataset included a complete set of SVs allowing us to report both precision and sensitivity rates of the SV detection methods. Our study investigates the ability of the methods to detect deletions, thus providing an optimistic estimate of SV detection performance as the SV detection methods that fail to detect deletions are likely to miss more complex SVs. We found that SV detection tools varied widely in their performance, with several methods providing a good balance between sensitivity and precision. Additionally, we have determined the SV callers best suited for low- and ultralow-pass sequencing data as well as for different deletion length categories.
Cell–cell communication inference and analysis in the tumour microenvironments from single-cell transcriptomics: data resources and computational strategies
Authors: Peng Lihong , Wang Feixiang , Wang Zhao , Tan Jingwei , Huang Li , Tian Xiongfei , Liu Guangyi , Zhou Liqian
Published: June 2022

Carcinomas are complex ecosystems composed of cancer, stromal and immune cells. Communication between these cells and their microenvironments induces cancer progression and causes therapy resistance. In order to improve the treatment of cancers, it is essential to quantify crosstalk between and within various cell types in a tumour microenvironment. Focusing on the coordinated expression patterns of ligands and cognate receptors, cell–cell communication can be inferred through ligand–receptor interactions (LRIs). In this manuscript, we carry out the following work: (i) introduce pipeline for ligand–receptor-mediated intercellular communication estimation from single-cell transcriptomics and list a few available LRI-related databases and visualization tools; (ii) demonstrate seven classical intercellular communication scoring strategies, highlight four types of representative intercellular communication inference methods, including network-based approaches, machine learning-based approaches, spatial information-based approaches and other approaches; (iii) summarize the evaluation and validation avenues for intercellular communication inference and analyze the advantages and limitations for the above four types of cell–cell communication methods; (iv) comment several major challenges while provide further research directions for intercellular communication analysis in the tumour microenvironments. We anticipate that this work helps to better understand intercellular crosstalk and to further develop powerful cell–cell communication estimation tools for tumor-targeted therapy.
A comprehensive comparison on cell-type composition inference for spatial transcriptomics data
Authors: Chen Jiawen , Liu Weifang , Luo Tianyou , Yu Zhentao , Jiang Minzhi , Wen Jia , Gupta Gaorav P , Giusti Paola , Zhu Hongtu , Yang Yuchen , Li Yun
Published: June 2022

Spatial transcriptomics (ST) technologies allow researchers to examine transcriptional profiles along with maintained positional information. Such spatially resolved transcriptional characterization of intact tissue samples provides an integrated view of gene expression in its natural spatial and functional context. However, high-throughput sequencing-based ST technologies cannot yet reach single cell resolution. Thus, similar to bulk RNA-seq data, gene expression data at ST spot-level reflect transcriptional profiles of multiple cells and entail the inference of cell-type composition within each ST spot for valid and powerful subsequent analyses. Realizing the critical importance of cell-type decomposition, multiple groups have developed ST deconvolution methods. The aim of this work is to review state-of-the-art methods for ST deconvolution, comparing their strengths and weaknesses. In particular, we construct ST spots from single-cell level ST data to assess the performance of 10 methods, with either ideal reference or non-ideal reference. Furthermore, we examine the performance of these methods on spot- and bead-level ST data by comparing estimated cell-type proportions to carefully matched single-cell ST data. In comparing the performance on various tissues and technological platforms, we concluded that RCTD and stereoscope achieve more robust and accurate inferences.
Risk stratification through allergy history: single-centre experience of specialized COVID-19 vaccine clinic
Authors: Lyons Daniel , Murray Cliodhna , Hannigan Siobhan , Sui Jacklyn , Alamin Salma , Conlon Niall , Keogan Mary , Khalib Khairin , Fitzpatrick Chris , O’B Hourihane Jonathan , Carey Michael , Edgar J David M
Published: June 2022

Anaphylaxis is a rare side-effect of COVID-19 vaccines. To (a) provide direct advice and reassurance to certain persons with a history of anaphylaxis/complex allergy, in addition to that available in national guidelines, and (b) to provide a medically supervised vaccination, a specialist regional vaccine allergy clinic was established. The main objective was to determine if risk stratification through history can lead to safe COVID-19 vaccination for maximum population coverage. A focused history was taken to establish contraindications to giving COVID-19 vaccines. People who reported a high-risk allergy history were given a vaccine not containing the excipient thought to have directly caused previous anaphylaxis. All vaccines were monitored for 30 min after administration. A total of 206 people were vaccinated between 6 July 2021 and 31 August 2021; Comirnaty (Pfizer-BioNTech) (n = 34), and Janssen (n = 172). In total, 78% were women. Ninety-two people (45%) reported a high-risk allergy history. There were no cases of anaphylaxis. Three people developed urticaria and one of these also developed transient tachycardia. One vaccinee developed a pseudoseizure. Two of 208 people (<1%) referred during this time declined vaccination based on personal preference, despite the assessment of low clinical risk. In our experience, all vaccines with high-risk allergy histories were administered Pfizer BioNTech or Janssen Covid-19 vaccines uneventfully following screening based on allergy-focussed history. Our data support that drug allergy is not associated with a higher risk of vaccine-related anaphylaxis but may act to guide the administration of alternate vaccines to people with polyethylene glycol/polysorbate 80/trometamol allergies or anaphylaxis after the first dose.
Immune cell–antibody interactions in health and disease
Authors: Karagiannis Sophia N , Arnold James N
Published: June 2022

The human immune system safeguards against pathogens through a multitude of cellular and molecular signals, involving different components of the innate and adaptive response. Contrastingly, autoimmune diseases, allergic conditions, and cancer evoke different aspects of these otherwise protective processes. Understanding the immunological hallmarks for each pathological setting is essential for improving prevention, diagnosis, prognosis, and treatment. The activatory states of immune effector cells, especially in relation to their direct or indirect interactions with antibodies, are important determinants of an efficient, protective response that results in target clearance and improved clinical outcomes. Dysregulation of effector cells and their functions alongside alternatively activated humoral immune responses may contribute to several chronic diseases including allergic inflammation, autoimmune disorders and cancer. This Review Series brings to the forefront several key activation and regulatory features of immune effector cells in different diseases including cancer, infection allergy, and autoimmunity. Specific attention is drawn on how antibodies can impact effector cell states, and their pro-inflammatory and immune protective functions. Articles in this Series discuss different effector cells and antibody isotypes in infection, inflammation, tolerance and cancer immune surveillance, covering basic and translational mechanisms, clinical and epidemiological insights into these immune responses. Understanding the critical attributes of immune cells, especially those needed to effectively engage antibodies, will undoubtedly help better exploit their potential for disease management and therapy.
Mapping frontoinsular cortex from diffusion microstructure
Authors: Cabeen Ryan P , Toga Arthur W , Allman John M
Published: June 2022

We developed a novel method for mapping the location, surface area, thickness, and volume of frontoinsular cortex (FI) using structural and diffusion magnetic resonance imaging. FI lies in the ventral part of anterior insular cortex and is characterized by its distinctive population von Economo neurons (VENs). Functional neuroimaging studies have revealed its involvement in affective processing, and histopathology has implicated VEN loss in behavioral-variant frontotemporal dementia and chronic alcoholism; however, structural neuroimaging of FI has been relatively limited. We delineated FI by jointly modeling cortical surface geometry and its coincident diffusion microstructure parameters. We found that neurite orientation dispersion in cortical gray matter can be used to map FI in specific individuals, and the derived measures reflect a range of behavioral factors in young adults from the Human Connectome Project (N=1052). FI volume was larger in the left hemisphere than the right (31%), and the percentage volume of FI was larger in women than men (15.3%). FI volume was associated with measures of decision-making (delay discounting, substance abuse), emotion (negative intrusive thinking and perception of hostility), and social behavior (theory of mind and working memory for faces). The common denominator is that larger FI size is related to greater self-control and social awareness.
Genotypic effects ofAPOE-ε4 on resting-state connectivity in cognitively intact individuals support functional brain compensation
Authors: Cacciaglia Raffaele , Operto Grégory , Falcón Carles , de Echavarri-Gómez José Maria González , Sánchez-Benavides Gonzalo , Brugulat-Serrat Anna , Milà-Alomà Marta , Blennow Kaj , Zetterberg Henrik , Molinuevo José Luis , Suárez-Calvet Marc , Gispert Juan Domingo ,   for the ALFA study, Akinci Müge , Beteta Annabella , Cañas Alba , Cumplido Irene , Deulofeu Carme , Dominguez Ruth , Emilio Maria , Fauria Karine , Fuentes Sherezade , Grau-Rivera Oriol , Hernandez Laura , Huesa Gema , Huguet Jordi , Arenaza-Urquijo Eider M , Palacios Eva M , Marne Paula , Menchón Tania , Minguillon Carolina , Palpatzis Eleni , Peña-Gómez Cleofé , Polo Albina , Pradas Sandra , Rodríguez-Fernández Blanca , Sala-Vila Aleix , Salvadó Gemma , Shekari Mahnaz , Soteras Anna , Stankeviciute Laura , Vilanova Marc , Vilor-Tejedor Natalia
Published: June 2022

The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer’s disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the ε4 allele. Yet, no study has assessed APOE-ε4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-ε4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of ε4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-ε4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the ε4-homozygotes. Our data indicate that APOE-ε4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.
Mourning in a Pandemic: The Differential Impact of COVID-19 Widowhood on Mental Health
Authors: Wang Haowei , Smith-Greenaway Emily , Bauldry Shawn , Margolis Rachel , Verdery Ashton M
Published: June 2022

Objectives

The death of a spouse is an established predictor of mental health decline that foreshadows worsening physical health and elevated mortality. The millions widowed by COVID-19 worldwide may experience even worse health outcomes than comparable pre-pandemic widows given the particularities of dying, mourning, and grieving during a pandemic defined by protracted social isolation, economic precarity, and general uncertainty. If COVID-19 pandemic bereavement is more strongly associated with mental health challenges than pre-pandemic bereavement, the large new cohort of COVID-19 widow(er)s may be at substantial risk of downstream health problems long after the pandemic abates.

Methods

We pooled population-based Survey of Health, Ageing and Retirement in Europe data from 27 countries for two distinct periods: (1) pre-pandemic (Wave 8, fielded October 2019–March 2020; N = 46,266) and (2) early pandemic (COVID Supplement, fielded June–August 2020; N = 55,796). The analysis used a difference-in-difference design to assess whether a spouse dying from COVID-19 presents unique mental health risks (self-reported depression, loneliness, and trouble sleeping), compared with pre-pandemic recent spousal deaths.

Results

We find strong associations between recent spousal death and poor mental health before and during the pandemic. However, our difference-in-difference estimates indicate those whose spouses died of COVID-19 have higher risks of self-reported depression and loneliness, but not trouble sleeping, than expected based on pre-pandemic associations.

Discussion

These results highlight that the millions of COVID-19 widow(er)s face extreme mental health risks, eclipsing those experienced by surviving spouses pre-pandemic, furthering concerns about the pandemic’s lasting impacts on health.
Flavian Literature
Authors: Dominik William J.
Published: June 2022

The Flavian age, though it lasted only twenty-seven years (69–96 ce), was of critical importance in the development of the Roman empire. The Flavian dynasty, which featured the emperors Vespasian (reigned 69–79 ce), Titus (79–81), and Domitian (81–96), followed in the path of the Julio-Claudian regime by fostering literary composition. The extant literature attests to the flourishing cultural, social, political, and economic environment of the Flavian era. Flavian literature includes not only Latin texts but also Greek. In fact, Greek writers, no less than their counterparts who wrote in Latin, are essential figures to consider when examining the full range of literary dynamics at play during the period. Some of the distinctive features and innovations of the Flavian age include the profoundly intertextual quality of its literature, which self-consciously interacts with both earlier traditions and contemporary works; Vespasian’s creation of salaried chairs of rhetoric, of which the first holder was Quintilian; Domitian’s creation of literary festivals, namely the quinquennial Capitolia at Rome and the annual Alban event, in which a poet such as Statius participated; the dispensation of patronage by the emperors and members of the senatorial and equestrian classes to Flavian writers, who in turn dedicated or addressed works to their patrons; and the fear of violence and civil war that pervades much of its literature. Scholars have published important work on how these Flavian writers communicated their ideas and related to their regimes, with much discussion occurring about the social and political stances they adopted and how they managed to navigate the sometimes murky waters of cultural and imperial politics. The result has been that modern critics are in disagreement about how to interpret passages by Flavian poets and prose writers who suggest meaning and express ideas in provocative and revealing ways both reminiscent of and different from their literary precursors. Both Latin and Greek writers of the Flavian era established themselves in a variety of genres with works that would exert a longstanding influence upon subsequent literature through the Middles Ages and Renaissance to the early modern period. Although for much of the 20th century scholars deemed the poetry and prose of the Flavian era to be secondary to the literature of the Augustan and (even) Julio-Claudian ages, partly because of Flavian writers’ adaptation and reconfiguration of literary conventions, diction, and motifs from these and earlier periods, critical appreciation and understanding of Flavian literature has increased dramatically in recent decades.
Mathilde Blind
Authors: Diedrick James
Published: June 2022

Mathilde Blind (b. 1841–d. 1896), poet and woman-of-letters, was born in Mannheim, Germany, but moved to London in 1852 after her mother and stepfather were exiled for their participation in the European revolutions of 1848. True to her family’s radicalism, her subsequent writing reflects her cosmopolitan sensibility, her freethinking, and her feminism. Blind rose to prominence in the early 1870s, both as an expert on and proponent of the poetry of Percy Bysshe Shelley and as one of the few women writers published in the Dark Blue (1871–1873), a short-lived but influential journal that published essays, tales, poems, and illustrations by Britain’s leading Pre-Raphaelites and aesthetes. By the early 1890s, Blind had published five volumes of poetry, a novel, two translations (The Old Faith and the New: A Confession by David Friedrich Strauss and The Journal of Marie Bashkirtseff), and two biographies for the Eminent Women series (George Eliot and Madame Roland). Her essays and reviews had also appeared in the Westminster Review, the Athenaeum, Fortnightly Review, National Review, Whitehall Review, New Quarterly Magazine, Examiner, and Art Weekly. A central figure in London’s literary and artistic community, Blind was close to many influential late Victorian writers and artists, including Algernon Charles Swinburne, Ford Madox Brown, Vernon Lee, Arthur Symons, Mona Caird, and Rosamund Marriott Watson. The range, subject matter, and stylistic characteristics of Blind’s poetry embody and serve to highlight both the through-line connecting mid-Victorian aestheticism and fin-de-siècle decadence and the intersections and underground alliances linking the New Woman and Decadent movements. Like many of her fellow late-century women writers, Blind was little read during much of the twentieth century, but she is now attracting renewed attention in the wake of the resurgent interest in aestheticism, cosmopolitanism, the fin de siècle, and New Woman writers.
Drug-induced adaptation along a resistance continuum in cancer cells
Authors: França Gustavo S. , Baron Maayan , Pour Maayan , King Benjamin R. , Rao Anjali , Misirlioglu Selim , Barkley Dalia , Dolgalev Igor , Ho-Tang Kwan , Avital Gal , Kuperwaser Felicia , Patel Ayushi , Levine Douglas A. , Lionnet Timothee , Yanai Itai
Published: June 2022

Advancements in rational drug design over the past decades have consistently produced new cancer therapies, but such treatments are inevitably countered through an adaptive process that fosters therapy resistance. Malignant cells achieve drug resistance through intrinsic and acquired mechanisms, rooted in genetic and non-genetic determinants. In particular, recent work has highlighted the role of intrinsic cellular heterogeneity in the emergence of transient drug-tolerant persister cells that survive drug treatment, as well as non-genetically driven cell plasticity toward stable resistance. However, these models do not account for the role of dose and treatment duration as extrinsic forces in eliciting cancer cell adaptation. Here, we show that these two components together drive the resistance of ovarian cancer cells to targeted therapy along a trajectory of cellular adaptation, that we denote the ‘resistance continuum’. We report that gradual dose exposure and prolonged treatment promote a continuous increase in fitness, and show that this process is mediated by evolving transcriptional, epigenetic and genetic changes that promote multiple cell state transitions. The resistance continuum is underpinned by the assembly of gene expression programs and epigenetically reinforced stress response regulation. Using both in vivo and in vitro models, we found that this process involves widespread reprogramming of cell survival pathways, including interferon response, lineage reprogramming, metabolic rewiring and oxidative stress regulation. Together, the resistance continuum reveals the dynamic nature of cellular adaptation, and carries implications for cancer therapies, as initial exposure to lower doses primes cells over time for increased resistance to higher doses. Beyond cancer, such continuous adaptation exposes a basic aspect of cellular plasticity, which may also be deployed in other biological systems such as development, immune response and host-pathogen interactions.
Evolutionary models predict potential mechanisms of escape from mutational meltdown
Authors: Bank Claudia , Schmitz Mark A. , Morales-Arce Ana Yansi
Published: June 2022

Mutagenic drugs are promising candidates for the treatment of various RNA virus infections. Increasing the mutation rate of the virus leads to rapid accumulation of deleterious mutation load, which is proposed to ultimately result in extinction as described by the theoretical concepts of mutational meltdown and lethal mutagenesis. However, the conditions and potential mechanisms of viral escape from the effects of mutagenic drugs have not been conceptually explored. Here we apply a computational approach to quantify the population dynamics and genetics of a population under high mutation rates and discuss the likelihood of adaptation to a mutagenic drug by means of three proposed mechanisms: (1) a proportion of “traditional” beneficial mutations that increase growth/fitness, (2) a mutation rate modifier (i.e., evolution of resistance to the mutagenic drug) that reduces the mutation rate, and (3) a modifier of the distribution of fitness effects, which either decreases or increases deleterious effects of mutations (i.e., evolution of tolerance to the mutagenic drug). We track the population dynamics and genetics of evolving populations and find that successful adaptations have to appear early to override the increasing mutational load and rescue the population from its imminent extinction. We highlight that the observed stochasticity of adaptation, especially by means of modifiers of the distribution of fitness effects, is difficult to capture in experimental trials, which may leave potential dangers of the use of mutagenic treatments unexposed.
Role of polymetallic-nodule dependent fauna on carbon cycling in the eastern Clarion-Clip-perton Fracture Zone (Pacific)
Authors: Stratmann Tanja
Published: June 2022

The abyssal seafloor in the Clarion-Clipperton Fracture Zone (CCZ) in the central Pacific is covered with large densities of polymetallic nodules, i.e., metal concretions containing iron, manganese, nickel, cobalt, and copper. These nodules are of economic interested and considered potential future resources for said metals, but they also host a variety of deep-sea fauna. In a recent study it was estimated that the removal of these nodules would lead to a loss of up to 18% of all taxa in the CCZ. Here, I assess the impact of removing these nodule-dependent taxa on carbon cycling at two sites (B4S03, B6S02) of the Belgian exploration license area in the eastern CCZ. For this purpose, I developed two highly-resolved carbon-based food web models with 72 (B6S02) to 77 (B4S03) food-web compartments consisting of different detritus pools, bacteria, metazoan meiobenthos, macrobenthic isopods, polychaetes and other macrobenthos, megabenthic cnidarians, crustaceans, poriferans, holothurians and other invertebrate megabenthos, and fish. These compartments were connected with 304 (B6S02) to 338 (B4S03) links which were reduced by 5–6% when nodule-dependent faunal compartments were removed. The models estimated the total system throughput T‥, i.e., the sum of all carbon flows in the food webs, in intact food webs as 1.24 mmol C m−2 d−1 and 1.20 mmol C m−2 d−1 at B4S03 and B6S02, respectively, whereupon 67.7% (B4S03) to 69.8% (B6S02) of T‥ flowed through the microbial loop. A removal of the nodule-dependent fauna did not affect this microbial loop, but reduced the scavenger loop by 54.6% (B6S02) to 84.1% (B4S03). Overall, nodule-dependent fauna is responsible for only a small fraction of total carbon cycling at the eastern CCZ. Therefore, when the effect of prospective deep-seabed mining on carbon cycling is investigated, its impact on benthic prokaryotes and the microbial loop should be addressed specifically.
Blocking D2/D3 dopamine receptors increases volatility of beliefs when we learn to trust others
Authors: Mikus Nace , Eisenegger Christoph , Mathys Chris , Clark Luke , Müller Ulrich , Robbins Trevor W. , Lamm Claus , Naef Michael
Published: June 2022

The ability to flexibly adjust beliefs about other people is crucial for human social functioning. Dopamine has been proposed to regulate the precision of beliefs, but direct behavioural evidence of this is lacking. We investigated how a relatively high dose of the selective D2/D3 dopamine receptor antagonist sulpiride impacts learning about other people’s prosocial attitudes in a repeated trust game. Using a Bayesian model of belief updating, we show that sulpiride increased the volatility of beliefs, which led to higher precision-weights on prediction errors. This effect was entirely driven by participants with genetically conferring higher dopamine availability (Taq1a polymorphism). Higher precision weights were reflected in higher reciprocal behaviour in the repeated trust game but not in single-round trust games. This finding suggests that antipsychotic medication might acutely reduce rigidity of pathological beliefs.
Non-redundant odorant detection in a locust
Authors: Chang Hetan , Unni Anjana , Tom Megha Treesa , Cortés Llorca Lucas , Brase Sabine , Bucks Sascha , Weniger Kerstin , Bisch-Knaden Sonja , Hansson Bill S. , Knaden Markus
Published: June 2022

Olfactory coding, from insects to humans, is canonically considered to involve considerable across-fiber coding already at the peripheral level, thereby allowing recognition of very large numbers of odor compounds. Here we show that the migratory locust, Locusta migratoria, has evolved an alternative strategy built on highly specific odorant receptors feeding into a complex primary processing center in the brain.

By collecting odors from food and different life stages of the locust, we identified 208 ecologically relevant odorants, which we used to deorphanize 48 locust olfactory receptors via ectopic expression in Drosophila. Contrary to the often broadly tuned olfactory receptors of other insects, almost all locust receptors were found to be narrowly tuned to one ligand and most of these best ligands exclusively excited only one receptor. Knocking out a single receptor using CRISPR-Cas9 resulted in an abolished physiological and behavioral response to the corresponding ligand. We conclude that the locust olfactory system, with an apparent lack of redundancy among most olfactory receptors, differs from so-far described olfactory systems.
Tilt Aftereffect Spreads Across the Visual Field
Authors: Gurbuz Busra Tugce , Boyaci Huseyin
Published: June 2022

The tilt aftereffect (TAE) is observed when adaptation to a tilted contour alters the perceived tilt of a subsequently presented contour. Thus far, the TAE has been treated as a local aftereffect observed only at the location of the adapter. Whether and how TAE spreads to other locations in the visual field has not been systematically studied. Here we sought an answer to this question by measuring TAE magnitudes at locations including but not limited to the adapter location. The adapter was a tilted grating presented at the same peripheral location throughout an experimental session. In a single trial, participants indicated the perceived tilt of a test grating presented after the adapter at one of fifteen locations in the same hemifield as the adapter. We found non-zero TAE magnitudes in all locations tested, showing that the effect spreads across the tested visual hemifield. Next, to establish a link between neuronal activity and the behavioral results, and to predict possible origins of the spread, we built a model based on known characteristics of neuronal responses in the visual cortex. Simulation results showed that the model can successfully capture the pattern of the behavioral results. Furthermore, the pattern of the optimized receptive field sizes suggests that mid-level visual areas, for example V4, could be critically involved in TAE and its spread across the visual field.
A Phylogenomic Assessment of Processes Underpinning Convergent Evolution in Open-Habitat Chats
Authors: Kakhki Niloofar Alaei , Schweizer Manuel , Lutgen Dave , Bowie Rauri C. K. , Shirihai Hadoram , Suh Alexander , Schielzeth Holger , Burri Reto
Published: June 2022

Insights into the processes underpinning convergent evolution advance our understanding of the contributions of ancestral, introgressed, and novel genetic variation to phenotypic evolution. Phylogenomic analyses characterizing genome-wide gene tree heterogeneity can provide first clues about the extent of ILS and of introgression and thereby into the potential of these processes or (in their absence) the need to invoke novel mutations to underpin convergent evolution. Here, we were interested in understanding the processes involved in convergent evolution in open-habitat chats (wheatears of the genusOenantheand their relatives). To this end, based on whole-genome resequencing data from 50 taxa of 44 species, we established the species tree, characterized gene tree heterogeneity, and investigated the footprints of ILS and introgression within the latter. The species tree corroborates the pattern of abundant convergent evolution, especially in wheatears. The high levels of gene tree heterogeneity in wheatears are explained by ILS alone only for 30% of internal branches. For multiple branches with high gene tree heterogeneity, D-statistics and phylogenetic networks identified footprints of introgression. Finally, long branches without extensive ILS between clades sporting similar phenotypes provide suggestive evidence for a role of novel mutations in the evolution of these phenotypes. Together, our results suggest that convergent evolution in open-habitat chats involved diverse processes and highlight that phenotypic diversification is often complex and best depicted as a network of interacting lineages.
Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer
Authors: Jones Ian , Dent Lucas , Higo Tomoaki , Roumeliotis Theo , Arias Garcia Mar , Shree Hansa , Choudhary Jyoti , Pedersen Malin , Bakal Chris
Published: June 2022

Almost all living cells maintain size uniformity through successive divisions. Proteins that sub- or super-scale with size act as rheostats which regulate cell progression. A comprehensive atlas of these proteins is lacking; particularly in cancer cells where both mitogen and growth signalling are dysregulated.

Utilising a multi-omic strategy, that integrates quantitative single cell imaging, phosphoproteomic and transcriptomic datasets, we leverage the inherent size heterogeneity of melanoma cells to investigate how peptides, post-translational modifications, and mRNAs scale with cell size to regulate proliferation. We find melanoma cells have different mean sizes, but all retain uniformity. Across the proteome, we identify proteins and phosphorylation events that ‘sub’ and ‘super’ scale with cell size. In particular, G2/M, biosynthetic, and cytoskeletal regulators sub- and super-scale with size. In small cells growth and proliferation processes are tightly coupled by translation which promotes CCND1 accumulation and anabolic increases in mass. Counter intuitively, anabolic growth pathways and translational process are low in large cells, which throttles the expression of factors such as CCND1 and thereby coupling proliferation from anabolic growth. Strikingly, these cells exhibit increased growth and comparable proliferation rates. Mathematical modelling suggests that decoupling growth and proliferative signalling fosters proliferation under mitogenic inhibition. As factors which promote adhesion and actin reorganization super-scale with size or are enriched in large cells, we suggest that growth/proliferation in these cells may be decoupled by cell spreading and mechanics. This study provides one of the first demonstrations of size-scaling phenomena in cancer and how morphology determines the chemistry of the cell.
Mapping molecular determinants of CaV2.2 inhibition by RGK proteins and homologs in Xenopus oocytes
Authors: Sasson Yehezkel , Subramaniam Suraj , Buki Tal , Almagor Lior , Chomsky-Hecht Orna , Katz Moshe , Puhl Henry , Ikeda Stephen R. , Dascal Nathan , Hirsch Joel A.
Published: June 2022

The CaV1 and CaV2 families of voltage-dependent calcium channels play a crucial role in neurotransmitter release, excitation-contraction and many other cellular processes. Comprised of the membrane pore-forming α1, intracellular β and extracellular α2δ subunits, these channels have been targets for pharmacological intervention for decades. Physiological functions of CaV channels are attenuated by either constitutively or transiently bounds proteins in the cellular environment. The RGK (Rad, Gem, Rem, and Rem2) G-protein family potently inhibits CaV1 and CaV2 function in heterologous expression systems. RGK proteins bind to CaVβ and inhibit channel localization and activity by forming a ternary complex with CaVα1. Here, we evaluated the influence of RGK proteins on CaV2.2 channels heterologously expressed in Xenopus oocytes. Both Gem and Rad showed no nucleotide dependency on its inhibitory function on CaV2.2. The G-domain and C-terminus could inhibit the CaV2.2 channel independently when co-expressed with channel subunits. Our results demonstrated that structural determinants in Gem, crucial for channel inhibition, lie within the 222-296 amino acid region containing both the partial G-domain and C-terminus as determined from chimeric CaVβ-Gem constructs. We expanded our mapping efforts and prepared various chimeras of Drosophila melanogaster (Dm) RGK sequences fused to CaVβ and showed that 22 residues in RGK2t and RGK3L C-terminal imparted complete CaV2.2 inhibition. Point mutations in the DmRGK C-terminus, conserved in mammalian RGK proteins, abrogated the CaV2.2 inhibition to a significant extent, pointing to a hot region in the extreme C-terminus for inhibition of CaV channels. Since RGK homologs are now recognized as physiological modulators in β-adrenergic regulation of CaV channels, the relevance of this curious G-protein family deserves close examination.