bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique features of a recombinant haemagglutinin influenza vaccine that influence vaccine performance
Authors: Arunachalam Arun B. , Post Penny , Rudin Deborah 
Published: December 2021

AbstractThe influenza vaccine field has been constantly evolving to improve the speed, scalability, and flexibility of manufacturing, and to improve the breadth and longevity of the protective immune response across age groups, giving rise to an array of next generation vaccines in development. Among these, the recombinant influenza vaccine tetravalent (RIV4), using a baculovirus expression vector system to express recombinant haemagglutinin (rHA) in insect cells, is the only one to have reached the market and has been studied extensively. We describe how the unique structural features of rHA in RIV4 improve protective immune responses compared to conventional influenza vaccines made from propagated influenza virus. In addition to the sequence integrity, characteristic of recombinant proteins, unique post-translational processing of the rHA in insect cells instills favourable tertiary and quaternary structural features. The absence of protease-driven cleavage and addition of simple N-linked glycans help to preserve and expose certain conserved epitopes on HA molecules, which are likely responsible for the high levels of broadly cross-reactive and protective antibodies with rare specificities observed with RIV4. Furthermore, the presence of uniform compact HA oligomers and absence of egg proteins, viral RNA or process impurities, typically found in conventional vaccines, are expected to eliminate potential adverse reactions to these components in susceptible individuals with the use of RIV4. These distinct structural features and purity of the recombinant HA vaccine thus provide a number of benefits in vaccine performance which can be extended to other viral targets, such as for COVID-19.
Human blastoids model blastocyst development and implantation
Authors: Kagawa Harunobu , Javali Alok , Khoei Heidar Heidari , Sommer Theresa Maria , Sestini Giovanni , Novatchkova Maria , Scholte op Reimer Yvonne , Castel Gaël , Bruneau Alexandre , Maenhoudt Nina , Lammers Jenna , Loubersac Sophie , Freour Thomas , Vankelecom Hugo , David Laurent , Rivron Nicolas 
Published: December 2021

AbstractOne week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.
A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
Authors: Roy Susree , Ghosh Suchandrima , Banerjee Mallica , Laha Sayantan , Bhattacharjee Dipanjan , Sarkar Rajib , Ray Sujay , Banerjee Arko , Ghosh Ranajoy , Halder Aniket , Ghosh Alakendu , Chatterjee Raghunath , Datta Simanti , Dhali Gopal Krishna , Banerjee Soma 
Published: December 2021

AbstractDifferentiation of Crohn’s disease (CD) from intestinal tuberculosis (ITB) is a big challenge to gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish ITB/CD patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Among the three differentially expressed miRNAs obtained from small RNA transcriptomic profiling of ileocaecal/terminal ileal tissue of ITB/CD patients (n = 3), only two down-regulated miRNAs, miR-31-5p, and miR-215-5p showed comparable data in qRT-PCR. Out of which, only miR-215-5p was detectable in the patient’s plasma, but there was no significant difference in expression between ITB/CD. On the other hand, miR-375-3p, the pulmonary TB specific marker was found in higher amount in the plasma of ITB patients than CD while reverse expression was observed in the ileocaecal/terminal ileal tissues of the same patients. Next, using Bioplex pro-human cytokine 48-plex screening panel, only three chemokines, Eotaxin-1/CCL11, SDF-1α/CXCL12, and G-CSF have noted significantly different levels in the serum of ITB/CD patients. ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p + Eotaxin-1/CCL11 + SDF-1α /CXCL12 + G-CSF showed a better AUC of 0.83, 95% CI (0.69–0.96) with 100% specificity and positive predictive value while sensitivity, negative predictive value, and accuracy were 56%, 69%, and 78% respectively in distinguishing ITB from CD. This study suggests that a combination of plasma markers shows better potential in differentiating ITB from CD than a single marker and this panel of markers may be used for clinical management of ITB/CD patients.
The optics of the human eye at 8.6 µm resolution
Authors: Bonaque-González Sergio , Trujillo-Sevilla Juan M. , Velasco-Ocaña Miriam , Casanova-González Óscar , Sicilia-Cabrera Miguel , Roqué-Velasco Alex , Ceruso Sabato , Oliva-García Ricardo , Martín-Hernández Javier , Gomez-Cardenes Oscar , Marichal-Hernández José G. , Gatinel Damien , Holladay Jack T. , Rodríguez-Ramos José M. 
Published: December 2021

AbstractOcular optics is normally estimated based on up to 2,600 measurement points within the pupil of the eye, which implies a lateral resolution of approximately 175 µm for a 9 mm pupil diameter. This is because information below this resolution is not thought to be relevant or even possible to obtain with current measurement systems. In this work, we characterize the in vivo ocular optics of the human eye with a lateral resolution of 8.6 µm, which implies roughly 1 million measurement points for a pupil diameter of 9 mm. The results suggest that the normal human eye presents a series of hitherto unknown optical patterns with amplitudes between 200 and 300 nm and is made up of a series of in-phase peaks and valleys. If the results are analysed at only high lateral frequencies, the human eye is also found to contain a whole range of new information. This discovery could have a great impact on the way we understand some fundamental mechanisms of human vision and could be of outstanding utility in certain fields of ophthalmology.
Young honeybees show learned preferences after experiencing adulterated pollen
Authors: Lajad Rocío , Moreno Emilia , Arenas Andrés 
Published: December 2021

AbstractPollen selection affects honeybee colony development and productivity. Considering that pollen is consumed by young in-hive bees, and not by foragers, we hypothesized that young bees learn pollen cues and adjust their preferences to the most suitable pollens. To assess whether young bees show preferences based on learning for highly or poorly suitable pollens, we measured consumption preferences for two pure monofloral pollens after the bees had experienced one of them adulterated with a deterrent (amygdalin or quinine) or a phagostimulant (linoleic acid). Preferences were obtained from nurse-aged bees confined in cages and from nurse bees in open colonies. Furthermore, we tested the bees’ orientation in a Y-maze using a neutral odour (Linalool or Nonanal) that had been previously associated with an amygdalin-adulterated pollen. Consumption preferences of bees, both in cages and in colonies, were reduced for pollens that had been adulterated with deterrents and increased for pollens that had been supplemented with linoleic acid. In the Y-maze, individuals consistently avoided the odours that they had previously experienced paired with the deterrent-adulterated pollen. Results show that nurse-aged bees associate pollen-based or pollen-related cues with either a distasteful/malaise experience or a tasty/nutritious event, leading to memories that bias their pollen-mediated response.
TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia
Authors: Dratwa Marta , Wysoczańska Barbara , Butrym Aleksandra , Łacina Piotr , Mazur Grzegorz , Bogunia-Kubik Katarzyna 
Published: December 2021

AbstractAcute myeloid leukaemia (AML) is a neoplasm of immature myeloid cells characterized by various cytogenetic alterations. The present study showed that in addition to the FLT3-ITD and NPM1 mutation status, telomere length (TL) and telomerase reverse transcriptase (TERT) gene polymorphisms may affect risk and overall survival (OS) in AML. TL was longer in healthy controls than in AML patients and positively correlated with age in the patients, but not in healthy subjects. TL was found to be independently affected by the presence of the FLT3-ITD mutation. As for the TERT gene polymorphism, AML patients with the TERT rs2853669 CC genotype were characterized by significantly shorter OS than patients carrying the T allele. Another observation in our study is the difference in TL and OS in patients belonging to various risk stratification groups related to the FLT3-ITD and NPM1 mutation status. Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.
Comparing deuterium excess to large-scale precipitation recycling models in the tropics
Authors: Cropper Stephen , Solander Kurt , Newman Brent D. , Tuinenburg Obbe A. , Staal Arie , Theeuwen Jolanda J. E. , Xu Chonggang 
Published: December 2021

AbstractPrecipitation recycling is essential to sustaining regional ecosystems and water supplies, and it is impacted by land development and climate change. This is especially true in the tropics, where dense vegetation greatly influences recycling. Unfortunately, large-scale models of recycling often exhibit high uncertainty, complicating efforts to estimate recycling. Here, we examine how deuterium excess (d-excess), a stable-isotope quantity sensitive to recycling effects, acts as an observational proxy for recycling. While past studies have connected variability in d-excess to precipitation origins at local or regional scales, our study leverages >3000 precipitation isotope samples to quantitatively compare d-excess against three contemporary recycling models across the global tropics. Using rank-correlation, we find statistically significant agreement ($$\bar \tau = 0.52$$

τ

¯

=
0.52

to $$0.70$$
0.70
) between tropical d-excess and recycling that is strongly mediated by seasonal precipitation, vegetation density, and scale mismatch. Our results detail the complex relationship between d-excess and precipitation recycling, suggesting avenues for further investigation.
Growing environmental footprint of plastics driven by coal combustion
Authors: Cabernard Livia , Pfister Stephan , Oberschelp Christopher , Hellweg Stefanie 
Published: December 2021

AbstractResearch on the environmental impacts from the global value chain of plastics has typically focused on the disposal phase, considered most harmful to the environment and human health. However, the production of plastics is also responsible for substantial environmental, health and socioeconomic impacts. We show that the carbon and particulate-matter-related health footprint of plastics has doubled since 1995, due mainly to growth in plastics production in coal-based economies. Coal-based emissions have quadrupled since 1995, causing almost half of the plastics-related carbon and particulate-matter-related health footprint in 2015. Plastics-related carbon footprints of China’s transportation, Indonesia’s electronics industry and India’s construction sector have increased more than 50-fold since 1995. In 2015, plastics caused 4.5% of global greenhouse gas emissions. Moreover, 6% of global coal electricity is used for plastics production. The European Union and the United States have increasingly consumed plastics produced in coal-based economies. In 2015, 85% of the workforce required for plastics consumed by the European Union and the United States was employed abroad, but 80% of the related value added was generated domestically. As high-income regions have outsourced the energy-intensive steps of plastics production to coal-based economies, renewable energy investments throughout the plastics value chain are critical for sustainable production and consumption of plastics.
NEIL1 and NEIL2 DNA glycosylases modulate anxiety and learning in a cooperative manner in mice
Authors: Hildrestrand Gunn A. , Rolseth Veslemøy , Kunath Nicolas , Suganthan Rajikala , Jensen Vidar , Bugaj Anna M. , Fernandez-Berrocal Marion S. , Sikko Sunniva B. , Vetlesen Susanne , Kuśnierczyk Anna , Olsen Ann-Karin , Gützkow Kristine B. , Rowe Alexander D. , Wang Wei , Moldestad Olve , Syrstad Monica D. , Slupphaug Geir , Eide Lars , Klungland Arne , Sætrom Pål , Luna Luisa , Ye Jing , Scheffler Katja , Bjørås Magnar 
Published: December 2021

AbstractOxidative DNA damage in the brain has been implicated in neurodegeneration and cognitive decline. DNA glycosylases initiate base excision repair (BER), the main pathway for oxidative DNA base lesion repair. NEIL1 and NEIL3 DNA glycosylases affect cognition in mice, while the role of NEIL2 remains unclear. Here, we investigate the impact of NEIL2 and its potential overlap with NEIL1 on behavior in knockout mouse models. Neil1−/−Neil2−/− mice display hyperactivity, reduced anxiety and improved learning. Hippocampal oxidative DNA base lesion levels are comparable between genotypes and no mutator phenotype is found. Thus, impaired canonical repair is not likely to explain the altered behavior. Electrophysiology suggests reduced axonal activation in the hippocampal CA1 region in Neil1−/−Neil2−/− mice and lack of NEIL1 and NEIL2 causes dysregulation of genes in CA1 relevant for synaptic function. We postulate a cooperative function of NEIL1 and NEIL2 in genome regulation, beyond canonical BER, modulating behavior in mice.
A computational exploration of resilience and evolvability of protein–protein interaction networks
Authors: Klein Brennan , Holmér Ludvig , Smith Keith M. , Johnson Mackenzie M. , Swain Anshuman , Stolp Laura , Teufel Ashley I. , Kleppe April S. 
Published: December 2021

AbstractProtein–protein interaction (PPI) networks represent complex intra-cellular protein interactions, and the presence or absence of such interactions can lead to biological changes in an organism. Recent network-based approaches have shown that a phenotype’s PPI network’s resilience to environmental perturbations is related to its placement in the tree of life; though we still do not know how or why certain intra-cellular factors can bring about this resilience. Here, we explore the influence of gene expression and network properties on PPI networks’ resilience. We use publicly available data of PPIs for E. coli, S. cerevisiae, and H. sapiens, where we compute changes in network resilience as new nodes (proteins) are added to the networks under three node addition mechanisms—random, degree-based, and gene-expression-based attachments. By calculating the resilience of the resulting networks, we estimate the effectiveness of these node addition mechanisms. We demonstrate that adding nodes with gene-expression-based preferential attachment (as opposed to random or degree-based) preserves and can increase the original resilience of PPI network in all three species, regardless of gene expression distribution or network structure. These findings introduce a general notion of prospective resilience, which highlights the key role of network structures in understanding the evolvability of phenotypic traits.
GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening
Authors: Tuffin Jack , Chesor Musleeha , Kuzmuk Valeryia , Johnson Tim , Satchell Simon C. , Welsh Gavin I. , Saleem Moin A. 
Published: December 2021

AbstractThe glomerulus is the filtration unit of the kidney. Injury to any component of this specialised structure leads to impaired filtration and eventually fibrosis and chronic kidney disease. Current two and three dimensional (2D and 3D) models that attempt to recreate structure and interplay between glomerular cells are imperfect. Most 2D models are simplistic and unrepresentative, and 3D organoid approaches are currently difficult to reproduce at scale and do not fit well with current industrial drug-screening approaches. Here we report a rapidly generated and highly reproducible 3D co-culture spheroid model (GlomSpheres), better demonstrating the specialised physical and molecular structure of a glomerulus. Co-cultured using a magnetic spheroid formation approach, conditionally immortalised (CI) human podocytes and glomerular endothelial cells (GEnCs) deposited mature, organized isoforms of collagen IV and Laminin. We demonstrate a dramatic upregulation of key podocyte (podocin, nephrin and podocalyxin) and GEnC (pecam-1) markers. Electron microscopy revealed podocyte foot process interdigitation and endothelial vessel formation. Incubation with pro-fibrotic agents (TGF-β1, Adriamycin) induced extracellular matrix (ECM) dysregulation and podocyte loss, which were attenuated by the anti-fibrotic agent Nintedanib. Incubation with plasma from patients with kidney disease induced acute podocyte loss and ECM dysregulation relative to patient matched remission plasma, and Nintedanib reduced podocyte loss. Finally, we developed a rapid imaging approach to demonstrate the model’s usefulness in higher throughput pharmaceutical screening. GlomSpheres therefore represent a robust, scalable, replacement for 2D in vitro glomerular disease models.
ER-misfolded proteins become sequestered with mitochondria and impair mitochondrial function
Authors: Cortés Sanchón Adrián , Santhosh Kumar Harshitha , Mantovani Matilde , Osinnii Ivan , Mateos José María , Kaech Andres , Shcherbakov Dimitri , Akbergenov Rashid , Böttger Erik C. 
Published: December 2021

AbstractProteostasis is a challenge for cellular organisms, as all known protein synthesis machineries are error-prone. Here we show by cell fractionation and microscopy studies that misfolded proteins formed in the endoplasmic reticulum can become associated with and partly transported into mitochondria, resulting in impaired mitochondrial function. Blocking the endoplasmic reticulum-mitochondria encounter structure (ERMES), but not the mitochondrial sorting and assembly machinery (SAM) or the mitochondrial surveillance pathway components Msp1 and Vms1, abrogated mitochondrial sequestration of ER-misfolded proteins. We term this mitochondria-associated proteostatic mechanism for ER-misfolded proteins ERAMS (ER-associated mitochondrial sequestration). We testify to the relevance of this pathway by using mutant α-1-antitrypsin as an example of a human disease-related misfolded ER protein, and we hypothesize that ERAMS plays a role in pathological features such as mitochondrial dysfunction.
Single-cell transcriptional profiling of splenic fibroblasts reveals subset-specific innate immune signatures in homeostasis and during viral infection
Authors: Pezoldt Joern , Wiechers Carolin , Erhard Florian , Rand Ulfert , Bulat Tanja , Beckstette Michael , Brendolan Andrea , Huehn Jochen , Kalinke Ulrich , Mueller Mathias , Strobl Birgit , Deplancke Bart , Čičin-Šain Luka , Sitnik Katarzyna M. 
Published: December 2021

AbstractOur understanding of the composition and functions of splenic stromal cells remains incomplete. Here, based on analysis of over 20,000 single cell transcriptomes of splenic fibroblasts, we characterized the phenotypic and functional heterogeneity of these cells in healthy state and during virus infection. We describe eleven transcriptionally distinct fibroblastic cell clusters, reassuring known subsets and revealing yet unascertained heterogeneity amongst fibroblasts occupying diverse splenic niches. We further identify striking differences in innate immune signatures of distinct stromal compartments in vivo. Compared to other fibroblasts and to endothelial cells, Ly6C+ fibroblasts of the red pulp were selectively endowed with enhanced interferon-stimulated gene expression in homeostasis, upon systemic interferon stimulation and during virus infection in vivo. Collectively, we provide an updated map of fibroblastic cell diversity in the spleen that suggests a specialized innate immune function for splenic red pulp fibroblasts.
GFI1 tethers the NuRD complex to open and transcriptionally active chromatin in myeloid progenitors
Authors: Helness Anne , Fraszczak Jennifer , Joly-Beauparlant Charles , Bagci Halil , Trahan Christian , Arman Kaifee , Shooshtarizadeh Peiman , Chen Riyan , Ayoub Marina , Côté Jean-François , Oeffinger Marlene , Droit Arnaud , Möröy Tarik 
Published: December 2021

AbstractGrowth factor indepdendent 1 (GFI1) is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation through molecular mechanisms and co-factors that still remain to be clearly identified. Here we show that GFI1 associates with the chromodomain helicase DNA binding protein 4 (CHD4) and other components of the Nucleosome remodeling and deacetylase (NuRD) complex. In granulo-monocytic precursors, GFI1, CHD4 or GFI1/CHD4 complexes occupy sites enriched for histone marks associated with active transcription suggesting that GFI1 recruits the NuRD complex to target genes regulated by active or bivalent promoters and enhancers. GFI1 and GFI1/CHD4 complexes occupy promoters that are either enriched for IRF1 or SPI1 consensus binding sites, respectively. During neutrophil differentiation, chromatin closure and depletion of H3K4me2 occurs at different degrees depending on whether GFI1, CHD4 or both are present, indicating that GFI1 is more efficient in depleting of H3K4me2 and -me1 marks when associated with CHD4. Our data suggest that GFI1/CHD4 complexes regulate histone modifications differentially to enable regulation of target genes affecting immune response, nucleosome organization or cellular metabolic processes and that both the target gene specificity and the activity of GFI1 during myeloid differentiation depends on the presence of chromatin remodeling complexes.