bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and strong amplifiers of natural selection
Authors: Tkadlec Josef , Pavlogiannis Andreas , Chatterjee Krishnendu , Nowak Martin A. 
Published: June 2021

AbstractSelection and random drift determine the probability that novel mutations fixate in a population. Population structure is known to affect the dynamics of the evolutionary process. Amplifiers of selection are population structures that increase the fixation probability of beneficial mutants compared to well-mixed populations. Over the past 15 years, extensive research has produced remarkable structures called strong amplifiers which guarantee that every beneficial mutation fixates with high probability. But strong amplification has come at the cost of considerably delaying the fixation event, which can slow down the overall rate of evolution. However, the precise relationship between fixation probability and time has remained elusive. Here we characterize the slowdown effect of strong amplification. First, we prove that all strong amplifiers must delay the fixation event at least to some extent. Second, we construct strong amplifiers that delay the fixation event only marginally as compared to the well-mixed populations. Our results thus establish a tight relationship between fixation probability and time: Strong amplification always comes at a cost of a slowdown, but more than a marginal slowdown is not needed.
Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1
Authors: Lu Yue , Ng Alphonsus H. C. , Chow Frances E. , Everson Richard G. , Helmink Beth A. , Tetzlaff Michael T. , Thakur Rohit , Wargo Jennifer A. , Cloughesy Timothy F. , Prins Robert M. , Heath James R. 
Published: June 2021

AbstractThe response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues collected from patients with recurrent glioblastoma and high-risk melanoma, both treated with neoadjuvant checkpoint blockade. We develop a framework that uses multiplex spatial protein profiling, machine learning-based image analysis, and data-driven computational models to investigate the pathophysiological and molecular factors within the tumor microenvironment that influence treatment response. Using melanoma to guide the interpretation of glioblastoma analyses, we interrogate the protein expression in microscopic compartments of tumors, and determine the correlates of cytotoxic CD8+ T cells, tumor growth, treatment response, and immune cell-cell interaction. This work reveals similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade.
Ferroelectric-tuned van der Waals heterojunction with band alignment evolution
Authors: Chen Yan , Wang Xudong , Huang Le , Wang Xiaoting , Jiang Wei , Wang Zhen , Wang Peng , Wu Binmin , Lin Tie , Shen Hong , Wei Zhongming , Hu Weida , Meng Xiangjian , Chu Junhao , Wang Jianlu 
Published: June 2021

AbstractVan der Waals integration with abundant two-dimensional materials provides a broad basis for assembling functional devices. In a specific van der Waals heterojunction, the band alignment engineering is crucial and feasible to realize high performance and multifunctionality. Here, we design a ferroelectric-tuned van der Waals heterojunction device structure by integrating a GeSe/MoS2 VHJ and poly (vinylidene fluoride-trifluoroethylene)-based ferroelectric polymer. An ultrahigh electric field derived from the ferroelectric polarization can effectively modulate the band alignment of the GeSe/MoS2 heterojunction. Band alignment transition of the heterojunction from type II to type I is demonstrated. The combination of anisotropic GeSe with MoS2 realizes a high-performance polarization-sensitive photodetector exhibiting low dark current of approximately 1.5 pA, quick response of 14 μs, and high detectivity of 4.7 × 1012 Jones. Dichroism ratios are also enhanced by ferroelectric polarization in a broad spectrum from visible to near-infrared. The ferroelectric-tuned GeSe/MoS2 van der Waals heterojunction has great potential for multifunctional detection applications in sophisticated light information sensing. More profoundly, the ferroelectric-tuned van der Waals heterojunction structure provides a valid band-engineering approach to creating versatile devices.
Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase
Authors: Rechkoblit Olga , Johnson Robert E. , Gupta Yogesh K. , Prakash Louise , Prakash Satya , Aggarwal Aneel K. 
Published: June 2021

AbstractPrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3′−terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)•A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3′-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.
Design of carbon supports for metal-catalyzed acetylene hydrochlorination
Authors: Kaiser Selina K. , Surin Ivan , Amorós-Pérez Ana , Büchele Simon , Krumeich Frank , Clark Adam H. , Román-Martínez Maria C. , Lillo-Ródenas Maria A. , Pérez-Ramírez Javier 
Published: June 2021

AbstractFor decades, carbons have been the support of choice in acetylene hydrochlorination, a key industrial process for polyvinyl chloride manufacture. However, no unequivocal design criteria could be established to date, due to the complex interplay between the carbon host and the metal nanostructure. Herein, we disentangle the roles of carbon in determining activity and stability of platinum-, ruthenium-, and gold-based hydrochlorination catalysts and derive descriptors for optimal host design, by systematically varying the porous properties and surface functionalization of carbon, while preserving the active metal sites. The acetylene adsorption capacity is identified as central activity descriptor, while the density of acidic oxygen sites determines the coking tendency and thus catalyst stability. With this understanding, a platinum single-atom catalyst is developed with stable catalytic performance under two-fold accelerated deactivation conditions compared to the state-of-the-art system, marking a step ahead towards sustainable PVC production.
Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy
Authors: Fisher Allison L. , Sangkhae Veena , Balušíková Kamila , Palaskas Nicolaos J. , Ganz Tomas , Nemeth Elizabeta 
Published: June 2021

AbstractIron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy.
Ubiquitous organic molecule-based free-standing nanowires with ultra-high aspect ratios
Authors: Kamiya Koshi , Kayama Kazuto , Nobuoka Masaki , Sakaguchi Shugo , Sakurai Tsuneaki , Kawata Minori , Tsutsui Yusuke , Suda Masayuki , Idesaki Akira , Koshikawa Hiroshi , Sugimoto Masaki , Lakshmi G. B. V. S. , Avasthi D. K. , Seki Shu 
Published: June 2021

AbstractThe critical dimension of semiconductor devices is approaching the single-nm regime, and a variety of practical devices of this scale are targeted for production. Planar structures of nano-devices are still the center of fabrication techniques, which limit further integration of devices into a chip. Extension into 3D space is a promising strategy for future; however, the surface interaction in 3D nanospace make it hard to integrate nanostructures with ultrahigh aspect ratios. Here we report a unique technique using high-energy charged particles to produce free-standing 1D organic nanostructures with high aspect ratios over 100 and controlled number density. Along the straight trajectory of particles penetrating the films of various sublimable organic molecules, 1D nanowires were formed with approximately 10~15 nm thickness and controlled length. An all-dry process was developed to isolate the nanowires, and planar or coaxial heterojunction structures were built into the nanowires. Electrical and structural functions of the developed standing nanowire arrays were investigated, demonstrating the potential of the present ultrathin organic nanowire systems.
The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis
Authors: Deruelle Vincent , Bouillot Stéphanie , Job Viviana , Taillebourg Emmanuel , Fauvarque Marie-Odile , Attrée Ina , Huber Philippe 
Published: June 2021

AbstractPseudomonas aeruginosa can cause nosocomial infections, especially in ventilated or cystic fibrosis patients. Highly pathogenic isolates express the phospholipase ExoU, an effector of the type III secretion system that acts on plasma membrane lipids, causing membrane rupture and host cell necrosis. Here, we use a genome-wide screen to discover that ExoU requires DNAJC5, a host chaperone, for its necrotic activity. DNAJC5 is known to participate in an unconventional secretory pathway for misfolded proteins involving anterograde vesicular trafficking. We show that DNAJC5-deficient human cells, or Drosophila flies knocked-down for the DNAJC5 orthologue, are largely resistant to ExoU-dependent virulence. ExoU colocalizes with DNAJC5-positive vesicles in the host cytoplasm. DNAJC5 mutations preventing vesicle trafficking (previously identified in adult neuronal ceroid lipofuscinosis, a human congenital disease) inhibit ExoU-dependent cell lysis. Our results suggest that, once injected into the host cytoplasm, ExoU docks to DNAJC5-positive secretory vesicles to reach the plasma membrane, where it can exert its phospholipase activity
Cnidarian-bilaterian comparison reveals the ancestral regulatory logic of the β-catenin dependent axial patterning
Authors: Lebedeva Tatiana , Aman Andrew J. , Graf Thomas , Niedermoser Isabell , Zimmermann Bob , Kraus Yulia , Schatka Magdalena , Demilly Adrien , Technau Ulrich , Genikhovich Grigory 
Published: June 2021

AbstractIn animals, body axis patterning is based on the concentration-dependent interpretation of graded morphogen signals, which enables correct positioning of the anatomical structures. The most ancient axis patterning system acting across animal phyla relies on β-catenin signaling, which directs gastrulation, and patterns the main body axis. However, within Bilateria, the patterning logic varies significantly between protostomes and deuterostomes. To deduce the ancestral principles of β-catenin-dependent axial patterning, we investigate the oral–aboral axis patterning in the sea anemone Nematostella—a member of the bilaterian sister group Cnidaria. Here we elucidate the regulatory logic by which more orally expressed β-catenin targets repress more aborally expressed β-catenin targets, and progressively restrict the initially global, maternally provided aboral identity. Similar regulatory logic of β-catenin-dependent patterning in Nematostella and deuterostomes suggests a common evolutionary origin of these processes and the equivalence of the cnidarian oral–aboral and the bilaterian posterior–anterior body axes.
Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD
Authors: Sangermano Riccardo , Deitch Iris , Peter Virginie G. , Ba-Abbad Rola , Place Emily M. , Zampaglione Erin , Wagner Naomi E. , Fulton Anne B. , Coutinho-Santos Luisa , Rosin Boris , Dunet Vincent , AlTalbishi Ala’a , Banin Eyal , Sousa Ana Berta , Neves Mariana , Larson Anna , Quinodoz Mathieu , Michaelides Michel , Ben-Yosef Tamar , Pierce Eric A. , Rivolta Carlo , Webster Andrew R. , Arno Gavin , Sharon Dror , Huckfeldt Rachel M. , Bujakowska Kinga M. 
Published: June 2021

AbstractPathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E. Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare INPP5E variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all INPP5E variants for deleteriousness and phenotypic correlation. We observe that the combined impact of INPP5E variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype–phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of INPP5E disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD.
Biomedical potential of Anabaena variabilis NCCU-441 based Selenium nanoparticles and their comparison with commercial nanoparticles
Authors: Afzal Bushra , Yasin Durdana , Naaz Haleema , Sami Neha , Zaki Almaz , Rizvi Moshahid Alam , Kumar Raj , Srivastava Pooja , Fatma Tasneem 
Published: June 2021

AbstractSelenium nanoparticles (SeNPs) are gaining importance in the field of medicines due to their high surface area and unique properties than their other forms of selenium. In this study, biogenic selenium nanoparticles (B-SeNPs) were synthesized using cyanobacteria and their bioactivities (antioxidant, antimicrobial, anticancer and biocompatibility) were determined for comparison with commercially available chemically synthesized selenium nanoparticles (C-SeNPs). Color change of reaction mixture from sky blue to orange-red indicated the synthesis of biogenic SeNPs (B-SeNPs). UV–Vis spectra of the reaction mixture exhibited peak at 266 nm. During optimization, 30 °C of temperature, 24 h of time and 1:2 concentration ratio of sodium selenite and cell extract represented the best condition for SeNPs synthesis. Various functional groups and biochemical compounds present in the aqueous extract of Anabaena variabilis NCCU-441, which may have possibly influenced the reduction process of SeNPs were identified by FT-IR spectrum and GC–MS. The synthesized cyanobacterial SeNPs were orange red in color, spherical in shape, 10.8 nm in size and amorphous in nature. The B-SeNPs showed better anti-oxidant (DPPH, FRAP, SOR and ABTS assays), anti-microbial (antibacterial and antifungal) and anti-cancer activitities along with its biocompatibility in comparison to C-SeNPs suggesting higher probability of their biomedical application.
Delayed subsidence of the Dead Sea shore due to hydro-meteorological changes
Authors: Vey Sibylle , Al-Halbouni D. , Haghighi M. Haghshenas , Alshawaf F. , Vüllers J. , Güntner A. , Dick G. , Ramatschi M. , Teatini P. , Wickert J. , Weber M. 
Published: June 2021

AbstractMany studies show the sensitivity of our environment to manmade changes, especially the anthropogenic impact on atmospheric and hydrological processes. The effect on Solid Earth processes such as subsidence is less straightforward. Subsidence is usually slow and relates to the interplay of complex hydro-mechanical processes, thus making relations to atmospheric changes difficult to observe. In the Dead Sea (DS) region, however, climatic forcing is strong and over-use of fresh water is massive. An observation period of 3 years was thus sufficient to link the high evaporation (97 cm/year) and the subsequent drop of the Dead Sea lake level (− 110 cm/year), with high subsidence rates of the Earth’s surface (− 15 cm/year). Applying innovative Global Navigation Satellite System (GNSS) techniques, we are able to resolve this subsidence of the “Solid Earth” even on a monthly basis and show that it behaves synchronous to atmospheric and hydrological changes with a time lag of two months. We show that the amplitude and fluctuation period of ground deformation is related to poro-elastic hydro-mechanical soil response to lake level changes. This provides, to our knowledge, a first direct link between shore subsidence, lake-level drop and evaporation.
Risk of esophageal and gastric adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer
Authors: Shore Richard , Yu Jingru , Ye Weimin , Lagergren Jesper , Rutegård Martin , Akre Olof , Stattin Pär , Lindblad Mats 
Published: June 2021

AbstractThe aim of this study was to explore the male predominance in esophageal and gastric adenocarcinoma by evaluating the preventive potential of androgen deprivation therapy (ADT). This matched cohort study was based on a national Swedish database of prostate cancer patients in 2006–2013. Prostate cancer patients receiving ADT were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for confounders. There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.
Reporter cell assay for human CD33 validated by specific antibodies and human iPSC-derived microglia
Authors: Wißfeld Jannis , Mathews Mona , Mossad Omar , Picardi Paola , Cinti Alessandro , Redaelli Loredana , Pradier Laurent , Brüstle Oliver , Neumann Harald 
Published: June 2021

AbstractCD33/Sialic acid-binding Ig-like lectin 3 (SIGLEC3) is an innate immune receptor expressed on myeloid cells and mediates inhibitory signaling via tyrosine phosphatases. Variants of CD33 are associated with Alzheimer’s disease (AD) suggesting that modulation of CD33 signaling might be beneficial in AD. Hence, there is an urgent need for reliable cellular CD33 reporter systems. Therefore, we generated a CD33 reporter cell line expressing a fusion protein consisting of the extracellular domain of either human full-length CD33 (CD33M) or the AD-protective variant CD33ΔE2 (D2-CD33/CD33m) linked to TYRO protein tyrosine kinase binding protein (TYROBP/DAP12) to investigate possible ligands and antibodies for modulation of CD33 signaling. Application of the CD33-specific antibodies P67.6 and 1c7/1 to the CD33M-DAP12 reporter cells resulted in increased phosphorylation of the kinase SYK, which is downstream of DAP12. CD33M-DAP12 but not CD33ΔE2-DAP12 expressing reporter cells showed increased intracellular calcium levels upon treatment with CD33 antibody P67.6 and partially for 1c7/1. Furthermore, stimulation of human induced pluripotent stem cell-derived microglia with the CD33 antibodies P67.6 or 1c7/1 directly counteracted the triggering receptor expressed on myeloid cells 2 (TREM2)-induced phosphorylation of SYK and decreased the phagocytic uptake of bacterial particles. Thus, the developed reporter system confirmed CD33 pathway activation by CD33 antibody clones P67.6 and 1c7/1. In addition, data showed that phosphorylation of SYK by TREM2 activation and phagocytosis of bacterial particles can be directly antagonized by CD33 signaling.
Cell wall integrity is compromised under temperature stress in Schizosaccharomyces pombe expressing a valproic acid-sensitive vas4 mutant
Authors: Qiao Sen , Luo Xiaofang , Wang Hui , Fang Yue , Zhang Lili 
Published: June 2021

AbstractValproic acid (VPA) is widely used as a eutherapeutic and safe anticonvulsant drug, but the mechanism is not well elucidated. Histone deacetylases (HDACs) were first identified as direct targets of VPA. Many loss-of function mutants in S. pombe have been shown to be VPA sensitive but not sensitive to other HDAC inhibitors, such as sodium butyrate or trichostatin A (TSA). This difference suggests that there are multiple VPA target genes. In the current study, we isolated a VPA-sensitive (vas) mutant, vas4-1, and cloned the VPA target gene vas4+/vrg4+ by performing complementation experiments. The vas4+/vrg4+ gene encodes a putative Golgi GDP-mannose transporter, Vrg4, which is highly homologous with ScVrg4p. Physiological experiments indicated that SpVrg4p is involved in maintaining cell wall integrity (CWI) under high- or low-temperature stress. The results of a coimmunoprecipitation assay suggested that SpVrg4p may be transferred from the ER to the Golgi through SpGot1p loaded COPII vesicles, and both single and double mutations (S263C and A271V) in SpVrg4p compromised this transfer. Our results suggested that CWI in S. pombe is compromised under temperature stress by the VPA-sensitive vas4 mutant.