bluuebunny/crossref_metadata_2025 huggingface dataset:
Theatre Revivals for the Anthropocene
Authors: Lonergan Patrick
Published: August 2023

This Element argues that the climate emergency requires a new approach to the study of theatre history – a suggestion that is developed through an analysis of the practice of theatrical revival during the Anthropocene era. Staging old plays in new ways can make visible ecological or environmental features that might have previously gone unnoticed: features which, in some cases, might not have been consciously included by the original authors or makers of a work, but which will be detectable to audiences nevertheless. These links are explored through case studies from the contemporary Irish theatre – including revivals of plays by Shakespeare, Lady Gregory, and Samuel Beckett, as performed by such major Irish companies as Rough Magic, Druid Theatre, and Company SJ. The Element ultimately shows how theatre can contribute to debates about the Anthropocene, and offers new pathways for theatre practice and criticism.
Risk of bias assessment tool for systematic review and meta-analysis of the gut microbiome
Authors: Lampeter Thomas , Love Charles , Tang Trien T. , Marella Aditi S. , Lee Hayden Y. , Oganyan Armani , Moffat Devin , Kareem Anisha , Rusling Matthew , Massmann Aubrey , Orr Melanie , Bongiorno Christian , Yuan Li-Lian
Published: August 2023

Risk of bias assessment is a critical step of any meta-analysis or systematic review. Given the low sample count of many microbiome studies, especially observational or cohort studies involving human subjects, many microbiome studies have low power. This increases the importance of performing meta-analysis and systematic review for microbiome research in order to enhance the relevance and applicability of microbiome results. This work proposes a method based on the ROBINS-I tool to systematically consider sources of bias in microbiome research seeking to perform meta-analysis or systematic review for microbiome studies.
Pioneers of Precarity
Authors: Mayeri Serena
Published: August 2023

Through oral histories read in tandem with previously untapped archival sources, Margot Canaday's Queer Career unearths an entirely new body of evidence that captures the workplace experiences of a generation of gay and lesbian Americans whose stories have never been told. Canaday does so while making crucial interventions in sociolegal history, the history of gender and sexuality, and the history of capitalism, intertwining those often-siloed genres in innovative and generative ways. My aim here is to highlight just a few of Queer Career's many contributions to the legal history of sex, gender, and sexuality and to the history of social movements and antidiscrimination law.
Vine-workers of the Lord: a Reading of the Runic Sequence and Imagery of the Tollemache Orosius Flyleaf
Authors: Birkett Tom
Published: August 2023

The flyleaf to the Tollemache Orosius (London, British Library, Add. MS 47967, 1r) which includes a vine-scroll panel, symbols of the four evangelists, and several smaller notes and sketches, constitutes one of the most extensive sequences of manuscript marginalia to survive from Early Medieval England. Its iconographical complexity is compounded by the inclusion of a sequence of sixteen runes that has long puzzled runologists. This article offers a contextual interpretation of the Tollemache Orosius runic sequence informed by the wider corpus of English runica manuscripta and the particular iconographical, literary and manuscript context in which the runic note appears. Elucidating the link between the runes and the surrounding imagery helps to unravel the iconographical scheme of the flyleaf, centred on the Vineyard of the Lord. It also provides an insight into the reception of the Old English Orosius in late-tenth-century Winchester and the importance of the layered meaning of the vinea domini motif for both monastic communities and the secular church.
Mainstreaming the populist radical right? Online news exposure and voting behavior in the 2019 European Parliament election
Authors: Stier Sebastian , Froio Caterina , Ho Justin
Published: August 2023

How does media exposure relate to support for radical right populist parties (RRPPs)? We contribute to this classic debate by analyzing the web browsing histories and survey responses of six thousand study participants in France, Germany, Italy, Spain, and the UK during the 2019 European Parliament election. Linking direct measures of online news exposure to voting behavior allows us to assess the effects of the salience of issues politicized by RRPPs on their electoral support. The likelihood to vote for RRPPs was higher when the EU was more salient in individual media diets, while exposure to the less salient issue of immigration did not increase the propensity to vote for RRPPs. Alongside consistent results for other party families and interactions with pre-existing voting intentions, the findings indicate that the electoral effects of online media are contingent on the overall salience of a specific issue and voters’ predispositions.
Bottom‐Current Variability and the Relationship With Topography and Sedimentary Processes in the Drake Passage
Authors: Kreps Gastón , Lembke‐Jene Lester , Romero Silvia , Ferrari Ramiro , Lamy Frank , Miramontes Elda
Published: August 2023

Bottom‐current related sediments have been commonly used for paleoceanographic reconstructions. However, the strength and variability of bottom currents are poorly understood and thus the processes that control sedimentation in deep environments are not clear. In this study, we focus on the Drake Passage, which is connected to the Antarctic Circumpolar Current, that has a major impact on the global climate. We studied the intensity and variability of bottom currents and how they are related to sedimentary processes. For this purpose, we used 27‐years from GLORYS12 Mercator Ocean reanalysis at high resolution to evaluate the bottom current dynamics. Geophysical data and surface grain size measurements were used to identify the type of sediment deposits. Our results show that the dynamics of bottom currents is disconnected from the sea surface dynamics, and bottom circulation is strongly controlled by the rough topography of the Drake Passage. The patterns for the first modes of bottom‐current variability are related to the local topography and seem to generally control the distribution of contourites. The second and third EOF modes show patterns in the bottom currents that differ from the mean field, and they may affect the rate of erosion and deposition differently. Time series of bottom currents reveals multiple high‐speed current events, but contourite drifts seem to accumulate preferentially in zones of slow and stable bottom currents. Our study highlights the potential of using ocean reanalysis to better constrain bottom currents in zones of scarce data and to plan future campaigns of direct measurements.
Thermal Tides on Mars Before and During the 2018 Global Dust Event as Observed by TIRVIM‐ACS Onboard ExoMars Trace Gas Orbiter
Authors: Guerlet S. , Fan S. , Forget F. , Ignatiev N. , Millour E. , Kleinböhl A. , Shakun A. , Grigoriev A. , Trokhimovskiy A. , Montmessin F. , Korablev O.
Published: August 2023

Migrating tides dominate the tropical climate on Mars and are known to reach high amplitudes during global dust events (GDE). In this study, we characterize the amplitude, phase and vertical wavelength of the diurnal and semidiurnal migrating tides in Mars' lower atmosphere (up to 50 km) by exploiting temperature vertical profiles retrieved from TIRVIM, an infrared spectrometer onboard the ExoMars Trace Gas Orbiter covering multiple local times. Observations from the Mars Climate Sounder onboard the Mars Reconnaissance Orbiter are used to complement the local time coverage when needed, and to estimate a seasonal trend to subtract from TIRVIM observations. We focus on two time periods in Martian Year 34, near Ls = 150° and near Ls = 200° (during the 2018 GDE). The characteristics of the migrating tides at Ls = 150° agree very well with tidal theory: a downward propagation, amplitudes of typically 2–5 K, and a larger vertical wavelength for the semidiurnal compared to the diurnal mode. Comparisons with model predictions from the Mars Planetary Climate Model reveal an excellent agreement, except for a slightly different phase of the diurnal tide. During the GDE, the tide pattern changes spectacularly: the diurnal tide amplitude reaches 35 K at 65°S and 17 K at 50°N, being vertically trapped up to 10 Pa. The semidiurnal tide is maximum near 20–30°S with an amplitude of 8–12 K. The phase of this mode is tilted with latitude, which was not the case before the storm. This indicates a significant contribution of the asymmetric Hough modes due to hemispheric asymmetry in the dust distribution.
The oncogenic human B-cell lymphoma MYD88 L265P mutation genocopies activation by phosphorylation at the Toll/interleukin-1 receptor (TIR) domain
Authors: Minderman Marthe , Lantermans Hildo , van der Zwaan Carmen , Hoogendijk Arie J. , van den Biggelaar Maartje , Kersten Marie José , Spaargaren Marcel , Pals Steven T.
Published: August 2023

MYD88 is the key signaling adaptor-protein for Toll-like and interleukin-1 receptors. A somatic L265P mutation within the Toll/interleukin-1 receptor (TIR) domain of MYD88 is found in 90% of Waldenström macroglobulinemia cases and in a significant subset of diffuse large B-cell lymphomas. MYD88-L265P strongly promotes NF-κB pathway activation, JAK-STAT signaling and lymphoma cell survival. Previous studies have identified other residues of the TIR-domain crucially involved in NF-κB activation, including serine 257 (S257), indicating a potentially important physiological role in the regulation of MYD88 activation. Here, we demonstrate that MYD88 S257 is phosphorylated in B-cell lymphoma cells and that this phosphorylation is required for optimal TLR-induced NF-κB activation. Furthermore, we demonstrate that a phosphomimetic MYD88-S257D mutant promotes MYD88 aggregation, IRAK1 phosphorylation, NF-κB activation and cell growth to a similar extent as the oncogenic L265P mutant. Lastly, we show that expression of MYD88-S257D can rescue cell growth upon silencing of endogenous MYD88-L265P expression in lymphoma cells addicted to oncogenic MYD88 signaling. Our data suggest that the L265P mutation promotes TIR domain homodimerization and NF-κB activation by copying the effect of MY88 phosphorylation at S257, thus providing novel insights into the molecular mechanism underlying the oncogenic activity of MYD88-L265P in B-cell malignancies.
Cezanne promoted autophagy through PIK3C3 stabilization and PIK3C2A transcription in lung adenocarcinoma
Authors: Wang Yadong , Li Jiahao , Zheng Haotian , Wang Kai , Ren Xiaoyang , Wang Guanghui , Du Jiajun
Published: August 2023

Osimertinib is a promising approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treating patients with lung adenocarcinoma (LUAD) harboring EGFR-activating mutations, however, almost all patients develop resistance to Osimertinib eventually limiting the long-term efficacy. Autophagy is a vital cellular recycling process promoting Osimertinib resistance. Identifying accurate and efficient autophagy-regulatory factors is of great significance in reducing Osimertinib resistance. This study identified Cezanne, a member of the ovarian tumor protease (OTU)-deubiquitinating family, as an autophagy regulator. Cezanne was highly expressed in Osimertinib-resistant cells, and Cezanne overexpression promoted Osimertinib resistance, while chloroquine (CQ), an autophagy inhibitor, reverted this process. In the Cezanne-overexpressing cells, autophagy was activated even in the absence of autophagy inducers rapamycin and Earle’s Balanced Salt Solution (EBSS). Further study showed that Cezanne stabilized PIK3C3 by deubiquitinating K48-linked ubiquitination at Lysine 322. Surprisingly, as a compensatory mechanism of PI3P generation, PIK3C2A was shown to be upregulated by Cezanne by promoting its transcription in a POLR2A-dependent way. Based on these results, Cezanne also accelerates EGFR recycling which may explain the mechanism mediating Cezanne expression and Osimertinib resistance. In conclusion, this study establishes a new model connecting Cezanne, autophagy, and Osimertinib resistance, opening new avenues to explore the effect of Cezanne and autophagy in LUAD.
Droplet attraction and coalescence mechanism on textured oil-impregnated surfaces
Authors: Xu Haobo , Zhou Yimin , Daniel Dan , Herzog Joshua , Wang Xiaoguang , Sick Volker , Adera Solomon
Published: August 2023

Droplets residing on textured oil-impregnated surfaces form a wetting ridge due to the imbalance of interfacial forces at the contact line, leading to a wealth of phenomena not seen on traditional lotus-leaf-inspired non-wetting surfaces. Here, we show that the wetting ridge leads to long-range attraction between millimeter-sized droplets, which coalesce in three distinct stages: droplet attraction, lubricant draining, and droplet merging. Our experiments and model show that the magnitude of the velocity and acceleration at which droplets approach each other horizontally is the same as the vertical oil rise velocity and acceleration in the wetting ridge. Moreover, the droplet coalescence mechanism can be modeled using the classical mass-spring system. The insights gained from this work will inform future fundamental studies on remote droplet interaction on textured oil-impregnated surfaces for optimizing water harvesting and condensation heat transfer.
Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation
Authors: Yamanaka Satoshi , Furihata Hirotake , Yanagihara Yuta , Taya Akihito , Nagasaka Takato , Usui Mai , Nagaoka Koya , Shoya Yuki , Nishino Kohei , Yoshida Shuhei , Kosako Hidetaka , Tanokura Masaru , Miyakawa Takuya , Imai Yuuki , Shibata Norio , Sawasaki Tatsuya
Published: August 2023

Lenalidomide, an immunomodulatory drug (IMiD), is commonly used as a first-line therapy in many haematological cancers, such as multiple myeloma (MM) and 5q myelodysplastic syndromes (5q MDS), and it functions as a molecular glue for the protein degradation of neosubstrates by CRL4CRBN. Proteolysis-targeting chimeras (PROTACs) using IMiDs with a target protein binder also induce the degradation of target proteins. The targeted protein degradation (TPD) of neosubstrates is crucial for IMiD therapy. However, current IMiDs and IMiD-based PROTACs also break down neosubstrates involved in embryonic development and disease progression. Here, we show that 6-position modifications of lenalidomide are essential for controlling neosubstrate selectivity; 6-fluoro lenalidomide induced the selective degradation of IKZF1, IKZF3, and CK1α, which are involved in anti-haematological cancer activity, and showed stronger anti-proliferative effects on MM and 5q MDS cell lines than lenalidomide. PROTACs using these lenalidomide derivatives for BET proteins induce the selective degradation of BET proteins with the same neosubstrate selectivity. PROTACs also exert anti-proliferative effects in all examined cell lines. Thus, 6-position-modified lenalidomide is a key molecule for selective TPD using thalidomide derivatives and PROTACs.
A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer’s disease mouse model
Authors: Warfield Andrew E. , Gupta Pooja , Ruhmann Madison M. , Jeffs Quiana L. , Guidone Genevieve C. , Rhymes Hannah W. , Thompson McKenzi I. , Todd William D.
Published: August 2023

Alzheimer’s disease (AD) patients exhibit progressive disruption of entrained circadian rhythms and an aberrant circadian input pathway may underlie such dysfunction. Here we examine AD-related pathology and circadian dysfunction in the APPSwe-Tau (TAPP) model of AD. We show these mice exhibit phase delayed body temperature and locomotor activity with increases around the active-to-rest phase transition. Similar AD-related disruptions are associated with sundowning, characterized by late afternoon and early evening agitation and aggression, and we show TAPP mice exhibit increased aggression around this transition. We show such circadian dysfunction and aggression coincide with hyperphosphorylated Tau (pTau) development in lateral parabrachial (LPB) neurons, with these disturbances appearing earlier in females. Finally, we show LPB neurons, including those expressing dynorphin (LPBdyn), project to circadian structures and are affected by pTau, and LPBdyn ablations partially recapitulate the hyperthermia of TAPP mice. Altogether we link pTau in a brainstem circadian input pathway to AD-related disturbances relevant to sundowning.
The net electrostatic potential and hydration of ABCG2 affect substrate transport
Authors: Gose Tomoka , Aitken Heather M. , Wang Yao , Lynch John , Rampersaud Evadnie , Fukuda Yu , Wills Medb , Baril Stefanie A. , Ford Robert C. , Shelat Anang , O’Mara Megan L. , Schuetz John D.
Published: August 2023

ABCG2 is a medically important ATP-binding cassette transporter with crucial roles in the absorption and distribution of chemically-diverse toxins and drugs, reducing the cellular accumulation of chemotherapeutic drugs to facilitate multidrug resistance in cancer. ABCG2’s capacity to transport both hydrophilic and hydrophobic compounds is not well understood. Here we assess the molecular basis for substrate discrimination by the binding pocket. Substitution of a phylogenetically-conserved polar residue, N436, to alanine in the binding pocket of human ABCG2 permits only hydrophobic substrate transport, revealing the unique role of N436 as a discriminator. Molecular dynamics simulations show that this alanine substitution alters the electrostatic potential of the binding pocket favoring hydration of the transport pore. This change affects the contact with substrates and inhibitors, abrogating hydrophilic compound transport while retaining the transport of hydrophobic compounds. The N436 residue is also required for optimal transport inhibition of ABCG2, as many inhibitors are functionally impaired by this ABCG2 mutation. Overall, these findings have biomedical implications, broadly extending our understanding of substrate and inhibitor interactions.
Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling
Authors: Kim Harper S. , Parker Danitra J. , Hardiman Madison M. , Munkácsy Erin , Jiang Nisi , Rogers Aric N. , Bai Yidong , Brent Colin , Mobley James A. , Austad Steven N. , Pickering Andrew M.
Published: August 2023

Protein translation (PT) declines with age in invertebrates, rodents, and humans. It has been assumed that elevated PT at young ages is beneficial to health and PT ends up dropping as a passive byproduct of aging. In Drosophila, we show that a transient elevation in PT during early-adulthood exerts long-lasting negative impacts on aging trajectories and proteostasis in later-life. Blocking the early-life PT elevation robustly improves life-/health-span and prevents age-related protein aggregation, whereas transiently inducing an early-life PT surge in long-lived fly strains abolishes their longevity/proteostasis benefits. The early-life PT elevation triggers proteostatic dysfunction, silences stress responses, and drives age-related functional decline via juvenile hormone-lipid transfer protein axis and germline signaling. Our findings suggest that PT is adaptively suppressed after early-adulthood, alleviating later-life proteostatic burden, slowing down age-related functional decline, and improving lifespan. Our work provides a theoretical framework for understanding how lifetime PT dynamics shape future aging trajectories.
A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology
Authors: Akbari Parsa , Vuckovic Dragana , Stefanucci Luca , Jiang Tao , Kundu Kousik , Kreuzhuber Roman , Bao Erik L. , Collins Janine H. , Downes Kate , Grassi Luigi , Guerrero Jose A. , Kaptoge Stephen , Knight Julian C. , Meacham Stuart , Sambrook Jennifer , Seyres Denis , Stegle Oliver , Verboon Jeffrey M. , Walter Klaudia , Watkins Nicholas A. , Danesh John , Roberts David J. , Di Angelantonio Emanuele , Sankaran Vijay G. , Frontini Mattia , Burgess Stephen , Kuijpers Taco , Peters James E. , Butterworth Adam S. , Ouwehand Willem H. , Soranzo Nicole , Astle William J.
Published: August 2023

Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes—including cell-type specific measures of granularity, nucleic acid content and reactivity—in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types—variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.
Engineered NIR-II fluorophores with ultralong-distance molecular packing for high-contrast deep lesion identification
Authors: Feng Zhe , Li Yuanyuan , Chen Siyi , Li Jin , Wu Tianxiang , Ying Yanyun , Zheng Junyan , Zhang Yuhuang , Zhang Jianquan , Fan Xiaoxiao , Yu Xiaoming , Zhang Dan , Tang Ben Zhong , Qian Jun
Published: August 2023

The limited signal of long-wavelength near-infrared-II (NIR-II, 900–1880 nm) fluorophores and the strong background caused by the diffused photons make high-contrast fluorescence imaging in vivo with deep tissue disturbed still challenging. Here, we develop NIR-II fluorescent small molecules with aggregation-induced emission properties, high brightness, and maximal emission beyond 1200 nm by enhancing electron-donating ability and reducing the donor-acceptor (D-A) distance, to complement the scarce bright long-wavelength emissive organic dyes. The convincing single-crystal evidence of D-A-D molecular structure reveals the strong inhibition of the π-π stacking with ultralong molecular packing distance exceeding 8 Å. The delicately-designed nanofluorophores with bright fluorescent signals extending to 1900 nm match the background-suppressed imaging window, enabling the signal-to-background ratio of the tissue image to reach over 100 with the tissue thickness of ~4–6 mm. In addition, the intraluminal lesions with strong negatively stained can be identified with almost zero background. This method can provide new avenues for future long-wavelength NIR-II molecular design and biomedical imaging of deep and highly scattering tissues.
Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency
Authors: Heitmann Jonas S. , Tandler Claudia , Marconato Maddalena , Nelde Annika , Habibzada Timorshah , Rittig Susanne M. , Tegeler Christian M. , Maringer Yacine , Jaeger Simon U. , Denk Monika , Richter Marion , Oezbek Melek T. , Wiesmüller Karl-Heinz , Bauer Jens , Rieth Jonas , Wacker Marcel , Schroeder Sarah M. , Hoenisch Gravel Naomi , Scheid Jonas , Märklin Melanie , Henrich Annika , Klimovich Boris , Clar Kim L. , Lutz Martina , Holzmayer Samuel , Hörber Sebastian , Peter Andreas , Meisner Christoph , Fischer Imma , Löffler Markus W. , Peuker Caroline Anna , Habringer Stefan , Goetze Thorsten O. , Jäger Elke , Rammensee Hans-Georg , Salih Helmut R. , Walz Juliane S.
Published: August 2023

T-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose. Immunogenicity in terms of CoVac-1-induced T-cell responses and safety are the primary and secondary endpoints, respectively. No serious or grade 4 CoVac-1-related adverse events have been observed. Expected local granuloma formation has been observed in 94% of study subjects, whereas systemic reactogenicity has been mild or absent. SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469.
Momentum-independent magnetic excitation continuum in the honeycomb iridate H3LiIr2O6
Authors: de la Torre A. , Zager B. , Bahrami F. , Upton M. H. , Kim J. , Fabbris G. , Lee G.-H. , Yang W. , Haskel D. , Tafti F. , Plumb K. W.
Published: August 2023

Understanding the interplay between the inherent disorder and the correlated fluctuating-spin ground state is a key element in the search for quantum spin liquids. H3LiIr2O6 is considered to be a spin liquid that is proximate to the Kitaev-limit quantum spin liquid. Its ground state shows no magnetic order or spin freezing as expected for the spin liquid state. However, hydrogen zero-point motion and stacking faults are known to be present. The resulting bond disorder has been invoked to explain the existence of unexpected low-energy spin excitations, although data interpretation remains challenging. Here, we use resonant X-ray spectroscopies to map the collective excitations in H3LiIr2O6 and characterize its magnetic state. In the low-temperature correlated state, we reveal a broad bandwidth of magnetic excitations. The central energy and the high-energy tail of the continuum are consistent with expectations for dominant ferromagnetic Kitaev interactions between dynamically fluctuating spins. Furthermore, the absence of a momentum dependence to these excitations are consistent with disorder-induced broken translational invariance. Our low-energy data and the energy and width of the crystal field excitations support an interpretation of H3LiIr2O6 as a disordered topological spin liquid in close proximity to bond-disordered versions of the Kitaev quantum spin liquid.
Spatial patterns of vascular plant species richness in Poland - a data set
Authors: Szymura Tomasz H. , Kassa Henok , Swacha Grzegorz , Szymura Magdalena , Zając Adam , Kącki Zygmunt
Published: August 2023

Recognition of species richness spatial patterns is important for nature conservation and theoretical studies. Inventorying species richness, especially at a larger spatial extent is challenging, thus different data sources are joined and harmonized to obtain a comprehensive data set. Here we present a new data set showing vascular plant species richness in Poland based on a grid of 10 × 10 km squares. The data set was created using data from two sources: the Atlas of Distribution of Vascular Plants in Poland and the Polish Vegetation Database. Using this data set, we analysed 2,160 species with taxonomical nomenclature according to the Euro + Med PlantBase checklist in 3,283 squares covering the entire territory of Poland (ca. 312,000 km2). The species were divided into groups according to their status and frequency of distribution, and the statistics for each square were obtained. For purposes of analysis, sampling bias was assessed. The data set promotes theoretical analysis on species richness and reinforces the planning of nature conservations.
Condensed tannins, novel compounds and sources of variation determine the antiparasitic activity of Nordic conifer bark against gastrointestinal nematodes
Authors: Chylinski Caroline , Degnes Kristin Fløgstad , Aasen Inga Marie , Ptochos Sokratis , Blomstrand Berit Marie , Mahnert Karl-Christian , Enemark Heidi Larsen , Thamsborg Stig Milan , Steinshamn Håvard , Athanasiadou Spiridoula
Published: August 2023

The antiparasitic potential of plants could offer a vital solution to alleviating the costs of gastrointestinal nematode (GIN) infections in ruminant production globally. Leveraging known bioactive molecules, however, is complex, where plant species, extraction processes and seasonality impact bioavailability and efficacy. This study assessed the impact of a comprehensive set of factors on the antiparasitic activity of Norwegian conifers to identify bark compounds specific against GIN. Antiparasitic activity was determined using in vitro assays targeting morphologically distinct life stages of ovine GIN: the egg hatch assay and larval motility assay. In depth characterisation of the chemical composition of the bark extracts was carried out using chromatographic separation, UV-absorbance, and molecular mass profiles to identify compounds implicated in the activity. Three key findings emerged: (1) the activity of bark extracts varied markedly from 0 to 100% antiparasitic efficacy, owing to tree species, extraction solvent and seasonality; (2) the GIN exhibited species-and stage-specific susceptibility to the bark extracts; (3) the presence of condensed tannins, amongst other compounds, was associated with anthelmintic activity. These findings add new insights into urgently needed alternative parasite control strategies in livestock.
Solving ordinary and partial differential equations using an analog computing system based on ultrasonic metasurfaces
Authors: Uy Robert Frederik , Bui Viet Phuong
Published: August 2023

Wave-based analog computing has recently emerged as a promising computing paradigm due to its potential for high computational efficiency and minimal crosstalk. Although low-frequency acoustic analog computing systems exist, their bulky size makes it difficult to integrate them into chips that are compatible with complementary metal-oxide semiconductors (CMOS). This research paper addresses this issue by introducing a compact analog computing system (ACS) that leverages the interactions between ultrasonic waves and metasurfaces to solve ordinary and partial differential equations. The results of our wave propagation simulations, conducted using MATLAB, demonstrate the high accuracy of the ACS in solving such differential equations. Our proposed device has the potential to enhance the prospects of wave-based analog computing systems as the supercomputers of tomorrow.
Differential gut microbiome in spondyloarthritis patients associated to Blastocystis colonization
Authors: Nieto-Clavijo Carlos , Morales Liliana , Marquez-Ortiz Ricaurte Alejandro , Romero-Sánchez Consuelo , Ramos-Casallas Alejandro , Escobar-Perez Javier , Bautista-Molano Wilson , Bello-Gualtero Juan Manuel , Chaparro-Olaya Jacqueline
Published: August 2023

The role ofBlastocystisin intestinal health is an open controversy, and little is known about the potential effect of this microorganism in autoinflammatory diseases such as spondyloarthritis (SpA). Here, we analyzed the gut microbiome of 36 SpA patients and 13 control individuals and demonstrated that the richness, diversity, and taxonomic composition between these two groups are different. We also showed that colonization byBlastocystisin control individuals increases the richness and diversity of the intestinal microbiome, whereas in SpA patients, it does not seem to have any impact. This may reflect a potential role ofBlastocystisin sculpting the gut microbiome architecture in control individuals, whereas in subjects with SpA, the modulation of the microbiome may be governed by disease-dependent factors that cannot be overcome byBlastocystis. Regarding taxonomic characterization, SpA patients colonized byBlastocystisshowed significant increases in the phylumPseudomonadota, classGammaproteobacteria, familySuccinivibrionaceae, and genusSuccinivibrio. Simultaneously, there were significant increases in the classBacilli, orderLactobacillales, familiesLactobacillaceaeandClostridiaceae,and generaLactobacillusandClostridiumin non-colonized SpA patients. On the other hand, PICRUSt analysis inBlastocystis-positive SpA patients showed elevations in pathways that may enhance antioxidant capacities and alleviate intestinal inflammation, whileBlastocystis-negative SpA patients showed significant changes in pathways that promote cell division/proliferation and can lead to larger changes in the gut microbiome. Our analyses lead us to believe that these changes in the gut microbiome of SpA patients may trigger protective mechanisms as an initial response to inflammation in an attempt to restore balance in the intestinal environment.
The interleukin-11 receptor variant p.W307R results in craniosynostosis in humans
Authors: Ahmad Ilyas , Lokau Juliane , Kespohl Birte , Malik Naveed Altaf , Baig Shahid Mahmood , Hartig Roland , Behme Daniel , Schwab Roland , Altmüller Janine , Jameel Muhammad , Mucha Sören , Thiele Holger , Tariq Muhammad , Nürnberg Peter , Erdmann Jeanette , Garbers Christoph
Published: August 2023

Craniosynostosis is characterized by the premature fusion and ossification of one or more of the sutures of the calvaria, often resulting in abnormal features of the face and the skull. In cases in which growth of the brain supersedes available space within the skull, developmental delay or cognitive impairment can occur. A complex interplay of different cell types and multiple signaling pathways are required for correct craniofacial development. In this study, we report on two siblings with craniosynostosis and a homozygous missense pathogenic variant within the IL11RA gene (c.919 T > C; p.W307R). The patients present with craniosynostosis, exophthalmos, delayed tooth eruption, mild platybasia, and a basilar invagination. The p.W307R variant is located within the arginine-tryptophan-zipper within the D3 domain of the IL-11R, a structural element known to be important for the stability of the cytokine receptor. Expression of IL-11R-W307R in cells shows impaired maturation of the IL-11R, no transport to the cell surface and intracellular retention. Accordingly, cells stably expressing IL-11R-W307R do not respond when stimulated with IL-11, arguing for a loss-of-function mutation. In summary, the IL-11R-W307R variant, reported here for the first time to our knowledge, is most likely the causative variant underlying craniosynostosis in these patients.
Generative adversarial networks based skin lesion segmentation
Authors: Innani Shubham , Dutande Prasad , Baid Ujjwal , Pokuri Venu , Bakas Spyridon , Talbar Sanjay , Baheti Bhakti , Guntuku Sharath Chandra
Published: August 2023

Skin cancer is a serious condition that requires accurate diagnosis and treatment. One way to assist clinicians in this task is using computer-aided diagnosis tools that automatically segment skin lesions from dermoscopic images. We propose a novel adversarial learning-based framework called Efficient-GAN (EGAN) that uses an unsupervised generative network to generate accurate lesion masks. It consists of a generator module with a top-down squeeze excitation-based compound scaled path, an asymmetric lateral connection-based bottom-up path, and a discriminator module that distinguishes between original and synthetic masks. A morphology-based smoothing loss is also implemented to encourage the network to create smooth semantic boundaries of lesions. The framework is evaluated on the International Skin Imaging Collaboration Lesion Dataset. It outperforms the current state-of-the-art skin lesion segmentation approaches with a Dice coefficient, Jaccard similarity, and accuracy of 90.1%, 83.6%, and 94.5%, respectively. We also design a lightweight segmentation framework called Mobile-GAN (MGAN) that achieves comparable performance as EGAN but with an order of magnitude lower number of training parameters, thus resulting in faster inference times for low compute resource settings.
Modelling the impact of forest management and CO2-fertilisation on growth and demography in a Sitka spruce plantation
Authors: Argles Arthur P. K. , Robertson Eddy , Harper Anna B. , Morison James I. L. , Xenakis Georgios , Hastings Astley , Mccalmont Jon , Moore Jon R. , Bateman Ian J. , Gannon Kate , Betts Richard A. , Bathgate Stephen , Thomas Justin , Heard Matthew , Cox Peter M.
Published: August 2023

Afforestation and reforestation to meet ‘Net Zero’ emissions targets are considered a necessary policy by many countries. Their potential benefits are usually assessed through forest carbon and growth models. The implementation of vegetation demography gives scope to represent forest management and other size-dependent processes within land surface models (LSMs). In this paper, we evaluate the impact of including management within an LSM that represents demography, using both in-situ and reanalysis climate drivers at a mature, upland Sitka spruce plantation in Northumberland, UK. We compare historical simulations with fixed and variable CO2 concentrations, and with and without tree thinning implemented. Simulations are evaluated against the observed vegetation structure and carbon fluxes. Including thinning and the impact of increasing CO2 concentration (‘CO2 fertilisation’) gave more realistic estimates of stand-structure and physical characteristics. Historical CO2 fertilisation had a noticeable effect on the Gross Primary Productivity seasonal–diurnal cycle and contributed to approximately 7% higher stand biomass by 2018. The net effect of both processes resulted in a decrease of tree density and biomass, but an increase in tree height and leaf area index.
Computational modeling allows unsupervised classification of epileptic brain states across species
Authors: Dallmer-Zerbe Isa , Jajcay Nikola , Chvojka Jan , Janca Radek , Jezdik Petr , Krsek Pavel , Marusic Petr , Jiruska Premysl , Hlinka Jaroslav
Published: August 2023

Current advances in epilepsy treatment aim to personalize and responsively adjust treatment parameters to overcome patient heterogeneity in treatment efficiency. For tailoring treatment to the individual and the current brain state, tools are required that help to identify the patient- and time-point-specific parameters of epilepsy. Computational modeling has long proven its utility in gaining mechanistic insight. Recently, the technique has been introduced as a diagnostic tool to predict individual treatment outcomes. In this article, the Wendling model, an established computational model of epilepsy dynamics, is used to automatically classify epileptic brain states in intracranial EEG from patients (n = 4) and local field potential recordings from in vitro rat data (high-potassium model of epilepsy, n = 3). Five-second signal segments are classified to four types of brain state in epilepsy (interictal, preonset, onset, ictal) by comparing a vector of signal features for each data segment to four prototypical feature vectors obtained by Wendling model simulations. The classification result is validated against expert visual assessment. Model-driven brain state classification achieved a classification performance significantly above chance level (mean sensitivity 0.99 on model data, 0.77 on rat data, 0.56 on human data in a four-way classification task). Model-driven prototypes showed similarity with data-driven prototypes, which we obtained from real data for rats and humans. Our results indicate similar electrophysiological patterns of epileptic states in the human brain and the animal model that are well-reproduced by the computational model, and captured by a key set of signal features, enabling fully automated and unsupervised brain state classification in epilepsy.
Genome-wide analysis and characterization of the LRR-RLK gene family provides insights into anthracnose resistance in common bean
Authors: da Silva Dambroz Caroline Marcela , Aono Alexandre Hild , de Andrade Silva Edson Mario , Pereira Welison Andrade
Published: August 2023

Anthracnose, caused by the hemibiotrophic fungus Colletotrichum lindemuthianum, is a damaging disease of common beans that can drastically reduce crop yield. The most effective strategy to manage anthracnose is the use of resistant cultivars. There are many resistance loci that have been identified, mapped and associated with markers in common bean chromosomes. The Leucine-rich repeat kinase receptor protein (LRR-RLK) family is a diverse group of transmembrane receptors, which potentially recognizes pathogen-associated molecular patterns and activates an immune response. In this study, we performed in silico analyses to identify, classify, and characterize common bean LRR-RLKs, also evaluating their expression profile in response to the infection by C. lindemuthianum. By analyzing the entire genome of Phaseolus vulgaris, we could identify and classify 230 LRR-RLKs into 15 different subfamilies. The analyses of gene structures, conserved domains and motifs suggest that LRR-RLKs from the same subfamily are consistent in their exon/intron organization and composition. LRR-RLK genes were found along the 11 chromosomes of the species, including regions of proximity with anthracnose resistance markers. By investigating the duplication events within the LRR-RLK family, we associated the importance of such a family with an expansion resulting from a strong stabilizing selection. Promoter analysis was also performed, highlighting cis-elements associated with the plant response to biotic stress. With regard to the expression pattern of LRR-RLKs in response to the infection by C. lindemuthianum, we could point out several differentially expressed genes in this subfamily, which were associated to specific molecular patterns of LRR-RLKs. Our work provides a broad analysis of the LRR-RLK family in P. vulgaris, allowing an in-depth structural and functional characterization of genes and proteins of this family. From specific expression patterns related to anthracnose response, we could infer a direct participation of RLK-LRR genes in the mechanisms of resistance to anthracnose, highlighting important subfamilies for further investigations.
Genetic associations between alcohol phenotypes and life satisfaction: a genomic structural equation modelling approach
Authors: Bountress Kaitlin E. , Cusack Shannon E. , Hawn Sage E. , Grotzinger Andrew , Bustamante Daniel , Kirkpatrick Robert M. , Edenberg Howard J. , Amstadter Ananda B.
Published: August 2023

Alcohol use (i.e., quantity, frequency) and alcohol use disorder (AUD) are common, associated with adverse outcomes, and genetically-influenced. Genome-wide association studies (GWAS) identified genetic loci associated with both. AUD is positively genetically associated with psychopathology, while alcohol use (e.g., drinks per week) is negatively associated or NS related to psychopathology. We wanted to test if these genetic associations extended to life satisfaction, as there is an interest in understanding the associations between psychopathology-related traits and constructs that are not just the absence of psychopathology, but positive outcomes (e.g., well-being variables). Thus, we used Genomic Structural Equation Modeling (gSEM) to analyze summary-level genomic data (i.e., effects of genetic variants on constructs of interest) from large-scale GWAS of European ancestry individuals. Results suggest that the best-fitting model is a Bifactor Model, in which unique alcohol use, unique AUD, and common alcohol factors are extracted. The genetic correlation (rg) between life satisfaction-AUD specific factor was near zero, the rg with the alcohol use specific factor was positive and significant, and the rg with the common alcohol factor was negative and significant. Findings indicate that life satisfaction shares genetic etiology with typical alcohol use and life dissatisfaction shares genetic etiology with heavy alcohol use.
Genetic diversity patterns of lionfish in the Southwestern Atlantic Ocean reveal a rapidly expanding stepping-stone bioinvasion process
Authors: Maggioni Rodrigo , Rocha Rafael S. , Viana Jhonatas T. , Giarrizzo Tommaso , Rabelo Emanuelle F. , Ferreira Carlos E. L. , Sampaio Claudio L. S. , Pereira Pedro H. C. , Rocha Luiz A. , Tavares Tallita C. L. , Soares Marcelo O.
Published: August 2023

In 2020, multiple lionfish (Pterois spp.) records along the equatorial Southwestern (SW) Atlantic revealed a new expansion of these potentially damaging invasive populations, which could impact over 3500 km of Brazilian coastline over the next few years, as well as unique ecosystems and marine protected areas in its path. To assess the taxonomic status, invasion route, and correlation with other centres of distribution, we investigated the genetic diversity patterns of lionfish caught in 2022 at the Amazonia, Northeastern Brazil, and Fernando de Noronha and Rocas Atoll ecoregions, using two molecular markers, the mitochondrial COI and the nuclear S7 RP1. The data indicate that all studied lionfish belong to what is generally accepted as P. volitans, and share the same genetic signature as lionfish present in the Caribbean Sea. The shared haplotypes and alleles indicate that the SW Atlantic invasion derives from an active movement of adult individuals from the Caribbean Sea into the Brazilian coast. The Amazon mesophotic reefs likely served as a stepping-stone to overcome the biogeographical barrier represented by the Amazon-Orinoco River plume. New alleles found for S7 RP1 suggest the onset of local genetic diversification, heightening the environmental risks as this bioinvasion heads towards other South Atlantic ecoregions.