bluuebunny/crossref_metadata_2025 huggingface dataset:
Entamoeba and Giardia parasites implicated as hosts of CRESS viruses
Authors: Kinsella Cormac M. , Bart Aldert , Deijs Martin , Broekhuizen Patricia , Kaczorowska Joanna , Jebbink Maarten F. , van Gool Tom , Cotten Matthew , van der Hoek Lia
Published: September 2020

Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance. Here, we address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. Recombination between viruses provides evidence of a shared host, in which genetic exchange occurs. We utilise networks of viral recombination to delimit virus-host clusters, which are then anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements. This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. The trio supplements five CRESS virus families already known to infect eukaryotes, extending the CRESS virus host range to protozoa. Phylogenetic analysis implies CRESS viruses infecting multicellular life have evolved independently on at least three occasions.
Gradient tantalum-doped hematite homojunction photoanode improves both photocurrents and turn-on voltage for solar water splitting
Authors: Zhang Hemin , Li Dongfeng , Byun Woo Jin , Wang Xiuli , Shin Tae Joo , Jeong Hu Young , Han Hongxian , Li Can , Lee Jae Sung
Published: September 2020

Hematite has a great potential as a photoanode for photoelectrochemical (PEC) water splitting by converting solar energy into hydrogen fuels, but the solar-to-hydrogen conversion efficiency of state-of-the-art hematite photoelectrodes are still far below the values required for practical hydrogen production. Here, we report a core-shell formation of gradient tantalum-doped hematite homojunction nanorods by combination of hydrothermal regrowth strategy and hybrid microwave annealing, which enhances the photocurrent density and reduces the turn-on voltage simultaneously. The unusual bi-functional effects originate from the passivation of the surface states and intrinsic built-in electric field by the homojunction formation. The additional driving force provided by the field can effectively suppress charge–carrier recombination both in the bulk and on the surface of hematite, especially at lower potentials. Moreover, the synthesized homojunction shows a remarkable synergy with NiFe(OH)x cocatalyst with significant additional improvements of photocurrent density and cathodic shift of turn-on voltage. The work has nicely demonstrated multiple collaborative strategies of gradient doping, homojunction formation, and cocatalyst modification, and the concept could shed light on designing and constructing the efficient nanostructures of semiconductor photoelectrodes in the field of solar energy conversion.
Robust rapid-setting antibacterial liquid bandages
Authors: Bastos Carlos A. P. , Thom William D. , Reilly Beth , Batalha Iris L. , Burge Rogers Maedee L. , McCrone Ian S. , Faria Nuno , Powell Jonathan J.
Published: September 2020

Bandaging is a steadfast but time-consuming component of wound care with limited technical advancements to date. Bandages must be changed and infection risk managed. Rapid-set liquid bandages are efficient alternatives but lack durability or inherent infection control. We show here that antibacterial zinc (Zn) and copper (Cu) species greatly enhance the barrier properties of the natural, waterproof, bio-adhesive polymer, shellac. The material demonstrated marked antibacterial contact properties and, in ex-vivo studies, effectively locked-in pre-applied therapeutics. When challenged in vivo with the polybacterial bovine wound infection ‘digital dermatitis’, Zn/Cu-shellac adhered rapidly and robustly over pre-applied antibiotic. The bandage self-degraded, appropriately, over 7 days despite extreme conditions (faecal slurry). Treatment was well-tolerated and clinical improvement was observed in animal mobility. This new class of bandage has promise for challenging topical situations in humans and other animals, especially away from controlled, sterile clinical settings where wounds urgently require protection from environmental and bacterial contamination.
Recent atmospheric drying in Siberia is not unprecedented over the last 1,500 years
Authors: Churakova Sidorova O. V. , Corona C. , Fonti M. V. , Guillet S. , Saurer M. , Siegwolf R. T. W. , Stoffel M. , Vaganov E. A.
Published: September 2020

Newly developed millennial δ13C larch tree-ring chronology from Siberia allows reconstruction of summer (July) vapor pressure deficit (VPD) changes in a temperature-limited environment. VPD increased recently, but does not yet exceed the maximum values reconstructed during the Medieval Warm Anomaly. The most humid conditions in the Siberian North were recorded in the Early Medieval Period and during the Little Ice Age. Increasing VPD under elevated air temperature affects the hydrology of these sensitive ecosystems by greater evapotranspiration rates. Further VPD increases will significantly affect Siberian forests most likely leading to drought and forest mortality even under additional access of thawed permafrost water. Adaptation strategies are needed for Siberian forest ecosystems to protect them in a warming world.
Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach
Authors: Verma Anukriti , Sharda Shivani , Rathi Bhawna , Somvanshi Pallavi , Pandey Bimlesh Dhar
Published: September 2020

Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g.Salmonella,Shigella,Yersinia,Campylobacter,Chlamydiahave been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe ‘interspecies communication’, using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA.

Our study identified Na(+)/H(+)anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.
Molecular mechanisms underlying AMH elevation in hyperoestrogenic states in males
Authors: Valeri Clara , Lovaisa María M. , Racine Chrystèle , Edelsztein Nadia Y. , Riggio Marina , Giulianelli Sebastián , Venara Marcela , Bedecarrás Patricia , Ballerini María G. , di Clemente Nathalie , Lamb Caroline A. , Schteingart Helena F. , Rey Rodolfo A.
Published: September 2020

Anti-Müllerian hormone (AMH) is secreted by Sertoli cells of the testes from early fetal life until puberty, when it is downregulated by androgens. In conditions like complete androgen insensitivity syndrome (CAIS), AMH downregulation does not occur and AMH increases at puberty, due in part to follicle-stimulating hormone (FSH) effect. However, other conditions like Peutz-Jeghers syndrome (PJS), characterised by low FSH, also have increased AMH. Because both CAIS and PJS may present as hyperoestrogenic states, we tested the hypothesis that oestradiol (E2) upregulates AMH expression in peripubertal Sertoli cells and explored the molecular mechanisms potentially involved. The results showed that E2 is capable of inducing an upregulation of endogenous AMH and of the AMH promoter activity in the prepubertal Sertoli cell line SMAT1, signalling through ERα binding to a specific ERE sequence present on the hAMH promoter. A modest action was also mediated through the membrane oestrogen receptor GPER. Additionally, the existence of ERα expression in Sertoli cells in patients with CAIS was confirmed by immunohistochemistry. The evidence presented here provides biological plausibility to the hypothesis that testicular AMH production increases in clinical conditions in response to elevated oestrogen levels.
A first-principles analysis of the charge transfer in magnesium corrosion
Authors: Würger Tim , Feiler Christian , Vonbun-Feldbauer Gregor B. , Zheludkevich Mikhail L. , Meißner Robert H.
Published: September 2020

Magnesium is the lightest structural engineering material and bears high potential to manufacture automotive components, medical implants and energy storage systems. However, the practical use of untreated magnesium alloys is restricted as they are prone to corrosion. An essential prerequisite for the control or prevention of the degradation process is a deeper understanding of the underlying corrosion mechanisms. Prior investigations of the formation of gaseous hydrogen during the corrosion of magnesium indicated that the predominant mechanism for this process follows the Volmer–Heyrovský rather than the previously assumed Volmer–Tafel pathway. However, the energetic and electronic states of both reaction paths as well as the charge state of dissolved magnesium have not been fully unraveled yet. In this study, density functional theory calculations were employed to determine these parameters for the Volmer, Tafel and Heyrovský steps to gain a comprehensive understanding of the major corrosion mechanisms responsible for the degradation of magnesium.
StoneMod: a database for kidney stone modulatory proteins with experimental evidence
Authors: Sassanarakkit Supatcha , Peerapen Paleerath , Thongboonkerd Visith
Published: September 2020

Better understanding of molecular mechanisms for kidney stone formation is required to improve management of kidney stone disease with better therapeutic outcome. Recent kidney stone research has indicated critical roles of a group of proteins, namely ‘stone modulators’, in promotion or inhibition of the stone formation. Nevertheless, such information is currently dispersed and difficult to obtain. Herein, we present the kidney stone modulator database (StoneMod), which is a curated resource by obtaining necessary information of such stone modulatory proteins, which can act as stone promoters or inhibitors, with experimental evidence from previously published studies. Currently, the StoneMod database contains 10, 16, 13, 8 modulatory proteins that affect calcium oxalate crystallization, crystal growth, crystal aggregation, and crystal adhesion on renal tubular cells, respectively. Informative details of each modulatory protein and PubMed links to the published articles are provided. Additionally, hyperlinks to other protein/gene databases (e.g., UniProtKB, Swiss-Prot, Human Protein Atlas, PeptideAtlas, and Ensembl) are made available for the users to obtain additional in-depth information of each protein. Moreover, this database provides a user-friendly web interface, in which the users can freely access to the information and/or submit their data to deposit or update. Database URL:https://www.stonemod.org.
Development of screening methods for functional characterization of UGTs from Stevia rebaudiana
Authors: Petit Eva , Berger Monique , Camborde Laurent , Vallejo Veronica , Daydé Jean , Jacques Alban
Published: September 2020

Glycosylation is a key modification that contributes to determine bioactivity and bioavailability of plant natural products, including that of terpenoids and steviol glycosides (SVglys). It is mediated by uridine-diphosphate glycosyltransferases (UGTs), that achieve their activity by transferring sugars on small molecules. Thus, the diversity of SVglys is due to the number, the position and the nature of glycosylations on the hydroxyl groups in C-13 and C-19 of steviol. Despite the intense sweetener property of SVglys and the numerous studies conducted, the SVglys biosynthetic pathway remains largely unknown. More than 60 SVglys and 68 putative UGTs have been identified in Stevia rebaudiana. This study aims to provide methods to characterize UGTs putatively involved in SVglys biosynthesis. After agroinfiltration-based transient gene expression in Nicotiana benthamiana, functionality of the recombinant UGT can be tested simply and directly in plants expressing it or from a crude extract. The combined use of binary vectors from pGWBs series to produce expression vectors containing the stevia's UGT, enables functionality testing with many substrates as well as other applications for further analysis, including subcellular localization.
Computational mechanistic study of the unimolecular dissociation of ethyl hydroperoxide and its bimolecular reactions with atmospheric species
Authors: Almatarneh Mansour H. , Alnajajrah Asmaa , Altarawneh Mohammednoor , Zhao Yuming , Halim Mohammad A.
Published: September 2020

A detailed computational study of the atmospheric reaction of the simplest Criegee intermediate CH2OO with methane has been performed using the density functional theory (DFT) method and high-level calculations. Solvation models were utilized to address the effect of water molecules on prominent reaction steps and their associated energies. The structures of all proposed mechanisms were optimized using B3LYP functional with several basis sets: 6-31G(d), 6-31G (2df,p), 6-311++G(3df,3pd) and at M06-2X/6-31G(d) and APFD/6-31G(d) levels of theory. Furthermore, all structures were optimized at the B3LYP/6-311++G(3df,3pd) level of theory. The intrinsic reaction coordinate (IRC) analysis was performed for characterizing the transition states on the potential energy surfaces. Fifteen different mechanistic pathways were studied for the reaction of Criegee intermediate with methane. Both thermodynamic functions (ΔH and ΔG), and activation parameters (activation energies Ea, enthalpies of activation ΔHǂ, and Gibbs energies of activation ΔGǂ) were calculated for all pathways investigated. The individual mechanisms for pathways A1, A2, B1, and B2, comprise two key steps: (i) the formation of ethyl hydroperoxide (EHP) accompanying with the hydrogen transfer from the alkanes to the terminal oxygen atom of CIs, and (ii) a following unimolecular dissociation of EHP. Pathways from C1 → H1 involve the bimolecular reaction of EHP with different atmospheric species. The photochemical reaction of methane with EHP (pathway E1) was found to be the most plausible reaction mechanism, exhibiting an overall activation energy of 7 kJ mol−1, which was estimated in vacuum at the B3LYP/6-311++G(3df,3pd) level of theory. All of the reactions were found to be strongly exothermic, expect the case of the sulfur dioxide-involved pathway that is predicted to be endothermic. The solvent effect plays an important role in the reaction of EHP with ammonia (pathway F1). Compared with the gas phase reaction, the overall activation energy for the solution phase reaction is decreased by 162 and 140 kJ mol−1 according to calculations done with the SMD and PCM solvation models, respectively.
In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia
Authors: Farrell Jordan S. , Colangeli Roberto , Dudok Barna , Wolff Marshal D. , Nguyen Sarah L. , Jackson Jesse , Dickson Clayton T. , Soltesz Ivan , Teskey G. Campbell
Published: September 2020

Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizures per se, are associated with memory impairment after temporal lobe seizures. While this observation suggests a key pathophysiological role for insufficient energy delivery, it is unclear how the networks that underlie episodic memory respond to vascular constraints that ultimately give rise to amnesia. Here, we focused on cellular/network level analyses in the CA1 of hippocampus in vivo to determine if neural activity, network oscillations, synaptic transmission, and/or synaptic plasticity are impaired following kindled seizures. Importantly, the induction of severe postictal hypoperfusion/hypoxia was prevented in animals treated by a COX-2 inhibitor, which experimentally separated seizures from their vascular consequences. We observed complete activation of CA1 pyramidal neurons during brief seizures, followed by a short period of reduced activity and flattening of the local field potential that resolved within minutes. During the postictal state, constituting tens of minutes to hours, we observed no changes in neural activity, network oscillations, and synaptic transmission. However, long-term potentiation of the temporoammonic pathway to CA1 was impaired in the postictal period, but only when severe local hypoxia occurred. Lastly, we tested the ability of rats to perform object-context discrimination, which has been proposed to require temporoammonic input to differentiate between sensory experience and the stored representation of the expected object-context pairing. Deficits in this task following seizures were reversed by COX-2 inhibition, which prevented severe postictal hypoxia. These results support a key role for hypoperfusion/hypoxia in postictal memory impairments and identify that many aspects of hippocampal network function are resilient during severe hypoxia except for long-term synaptic plasticity.
Seasonality of moisture supplies to precipitation over the Third Pole: a stable water isotopic perspective
Authors: Yang Xiaoxin , Yao Tandong
Published: September 2020

This study integrated isotopic composition in precipitation at 50 stations on and around the Tibetan Plateau (TP) and demonstrated the distinct seasonality of isotopic composition in precipitation across the study period. The potential effect of water vapor isotopes on precipitation isotopes is studied by comparing the station precipitation data with extensive isotopic patterns in atmospheric water vapor, revealing the close linkage between the two. The analysis of contemporary water vapor transport and potential helps confirm the different mechanisms behind precipitation isotopic compositions in different areas, as the southern TP is more closely related to large-scale atmospheric circulation such as local Hadley and summer monsoon circulations during other seasons than winter, while the northern TP is subject to the westerly prevalence and advective moisture supply and precipitation processes. The new data presented in this manuscript also enrich the current dataset for the study of precipitation isotopes in this region and together provide a valuable database for verification of the isotope-integrated general circulation model and explanation of related physical processes.
Viromers as carriers for mRNA-mediated expression of therapeutic molecules under inflammatory conditions
Authors: Jansig Edith , Geissler Stefanie , Rieckmann Vera , Kuenemund Anja , Hietel Benjamin , Schenk Mathias , Wussow Sebastian , Kreideweiss Patrick , Panzner Steffen , Reinsch Christian , Cynis Holger
Published: September 2020

Therapeutic mRNA delivery has been described for several treatment options, such as vaccination and cancer immunotherapy. However, mRNA delivery has to be accompanied by the development and testing of suitable carrier materials due to the instability of mRNAs in human body fluids. In the present study, we investigated the ability of recently developed Viromers to deliver mRNAs in a classical inflammatory setting. We tested mRNAs coding for active components of preclinical (7ND) and approved (sTNF-RII) biologics, in vitro and in vivo. 7ND is an established blocker of the CCR2 axis, whereas sTNF-RII is the active component of the approved drug Etanercept. Viromer/mRNA complexes were transfected into murine macrophages in vitro. Protein expression was analysed using Luciferase reporter expression and mainly identified in spleen, blood and bone marrow in vivo. 7ND-mRNA delivery led to efficient blockage of monocytes infiltration in thioglycolate-induced peritonitis in mice, underlining the ability of Viromers to deliver a therapeutic mRNA cargo without overt toxicity. Therefore, we propose Viromer-based mRNA delivery as a suitable option for the treatment of inflammatory disorders beyond infusion of biological molecules.
Advantage of fat-derived CD73 positive cells from multiple human tissues, prospective isolated mesenchymal stromal cells
Authors: Suto Eriko G. , Mabuchi Yo , Toyota Saki , Taguchi Miyu , Naraoka Yuna , Itakura Natsumi , Matsuoka Yoh , Fujii Yasuhisa , Miyasaka Naoyuki , Akazawa Chihiro
Published: September 2020

Somatic stem cells have been isolated from multiple human tissues for their potential usefulness in cell therapy. Currently, mesenchymal stromal cells (MSCs) are prepared after several passages requiring a few months of cell culture. In this study, we used a prospective isolation method of somatic stem cells from gestational or fat tissues, which were identified using CD73 antibody. CD73-positive population from various tissues existed individually in flowcytometric pattern, especially subcutaneous fat- and amniotic-derived cells showed the highest enrichment of CD73-positive cells. Moreover, the cell populations isolated with the prospective method showed higher proliferative capacity and stem cell marker expression, compared to the cell populations which isolated through several passages of culturing whole living cells: which we named “conventional method” in this paper. Furthermore, the therapeutic potential of CD73-positive cells was evaluated in vivo using a mouse model of pulmonary fibrosis. After intranasal administration, murine CD73-positive cells reduced macrophage infiltration and inhibited fibrosis development. These results suggest that further testing using CD73-positive cells may be beneficial to help establish the place in regenerative medicine use.
Spatial structure, parameter nonlinearity, and intelligent algorithms in constructing pedotransfer functions from large-scale soil legacy data
Authors: Chakraborty Poulamee , Das Bhabani S. , Vasava Hitesh B. , Panigrahi Niranjan , Santra Priyabrata
Published: September 2020

Pedotransfer function (PTF) approach is a convenient way for estimating difficult-to-measure soil properties from basic soil data. Typically, PTFs are developed using a large number of samples collected from small (regional) areas for training and testing a predictive model. National soil legacy databases offer an opportunity to provide soil data for developing PTFs although legacy data are sparsely distributed covering large areas. Here, we examined the Indian soil legacy (ISL) database to select a comprehensive training dataset for estimating cation exchange capacity (CEC) as a test case in the PTF approach. Geostatistical and correlation analyses showed that legacy data entail diverse spatial and correlation structure needed in building robust PTFs. Through non-linear correlation measures and intelligent predictive algorithms, we developed a methodology to extract an efficient training dataset from the ISL data for estimating CEC with high prediction accuracy. The selected training data had comparable spatial variation and nonlinearity in parameters for training and test datasets. Thus, we identified specific indicators for constructing robust PTFs from legacy data. Our results open a new avenue to use large volume of existing soil legacy data for developing region-specific PTFs without the need for collecting new soil data.
A data-driven typology of asthma medication adherence using cluster analysis
Authors: Tibble Holly , Chan Amy , Mitchell Edwin A. , Horne Elsie , Doudesis Dimitrios , Horne Rob , Mizani Mehrdad A. , Sheikh Aziz , Tsanas Athanasios
Published: September 2020

Asthma preventer medication non-adherence is strongly associated with poor asthma control. One-dimensional measures of adherence may ignore clinically important patterns of medication-taking behavior. We sought to construct a data-driven multi-dimensional typology of medication non-adherence in children with asthma. We analyzed data from an intervention study of electronic inhaler monitoring devices, comprising 211 patients yielding 35,161 person-days of data. Five adherence measures were extracted: the percentage of doses taken, the percentage of days on which zero doses were taken, the percentage of days on which both doses were taken, the number of treatment intermissions per 100 study days, and the duration of treatment intermissions per 100 study days. We applied principal component analysis on the measures and subsequently applied k-means to determine cluster membership. Decision trees identified the measure that could predict cluster assignment with the highest accuracy, increasing interpretability and increasing clinical utility. We demonstrate the use of adherence measures towards a three-group categorization of medication non-adherence, which succinctly describes the diversity of patient medication taking patterns in asthma. The percentage of prescribed doses taken during the study contributed to the prediction of cluster assignment most accurately (84% in out-of-sample data).
Left hemispheric α band cerebral oscillatory changes correlate with verbal memory
Authors: Araki Toshihiko , Watanabe Yoshiyuki , Hirata Masayuki
Published: September 2020

Event-related synchronisation (ERS) and event-related desynchronisation (ERD) have been observed via magnetoencephalography (MEG) in the language-dominant hemisphere. However, the relationship between ERS/ERD and clinical language indices is unclear. Therefore, the present study evaluated brain activity utilising MEG during a verb generation task in 36 subjects and determined ERS/ERD power values in θ, α, β, low γ and high γ frequency bands. To measure clinical language indices, we adopted Wechsler Memory Scale-revised. We observed ERD in the α band from the bilateral occipital to the left central brain region, in the β band from the bilateral occipital to the left frontal region and in the low γ band a high-power signal in the left frontal region. We also observed ERS in the θ band in bilateral frontal region and in the high γ band in bilateral occipital region. Furthermore, we found a significant negative correlation between α-band ERD power at the left postcentral gyrus and medial superior frontal gyrus and verbal memory score (correlation coefficients =  − 0.574 and − 0.597, respectively). These results suggest that individuals with lower linguistic memory have less desynchronised α-band ERD power and α-band ERD power in the left hemisphere may be a neurophysiological biomarker for verbal memory.
Characterization of rare ABCC8 variants identified in Spanish pulmonary arterial hypertension patients
Authors: Lago-Docampo Mauro , Tenorio Jair , Hernández-González Ignacio , Pérez-Olivares Carmen , Escribano-Subías Pilar , Pousada Guillermo , Baloira Adolfo , Arenas Miguel , Lapunzina Pablo , Valverde Diana
Published: September 2020

Pulmonary Arterial Hypertension (PAH) is a rare and fatal disease where knowledge about its genetic basis continues to increase. In this study, we used targeted panel sequencing in a cohort of 624 adult and pediatric patients from the Spanish PAH registry. We identified 11 rare variants in the ATP-binding Cassette subfamily C member 8 (ABCC8) gene, most of them with splicing alteration predictions. One patient also carried another variant in SMAD1 gene (c.27delinsGTAAAG). We performed an ABCC8 in vitro biochemical analyses using hybrid minigenes to confirm the correct mRNA processing of 3 missense variants (c.211C > T p.His71Tyr, c.298G > A p.Glu100Lys and c.1429G > A p.Val477Met) and the skipping of exon 27 in the novel splicing variant c.3394G > A. Finally, we used structural protein information to further assess the pathogenicity of the variants. The results showed 11 novel changes in ABCC8 and 1 in SMAD1 present in PAH patients. After in silico and in vitro biochemical analyses, we classified 2 as pathogenic (c.3288_3289del and c.3394G > A), 6 as likely pathogenic (c.211C > T, c.1429G > A, c.1643C > T, c.2422C > A, c.2694 + 1G > A, c.3976G > A and SMAD1 c.27delinsGTAAAG) and 3 as Variants of Uncertain Significance (c.298G > A, c.2176G > A and c.3238G > A). In all, we show that coupling in silico tools with in vitro biochemical studies can improve the classification of genetic variants.
Flexible ZnO-mAb nanoplatforms for selective peripheral blood mononuclear cell immobilization
Authors: Babu K. Sowri , Pinheiro Pedro F. , Marques Cátia F. , Justino Gonçalo C. , Andrade Suzana M. , Alves Marta M.
Published: September 2020

Cancer is the second cause of death worldwide. This devastating disease requires specific, fast, and affordable solutions to mitigate and reverse this trend. A step towards cancer-fighting lies in the isolation of natural killer (NK) cells, a set of innate immune cells, that can either be used as biomarkers of tumorigenesis or, after autologous transplantation, to fight aggressive metastatic cells. In order to specifically isolate NK cells (which express the surface NKp30 receptor) from peripheral blood mononuclear cells, a ZnO immunoaffinity-based platform was developed by electrodeposition of the metal oxide on a flexible indium tin oxide (ITO)-coated polyethylene terephthalate (PET) substrate. The resulting crystalline and well-aligned ZnO nanorods (NRs) proved their efficiency in immobilizing monoclonal anti-human NKp30 antibodies (mAb), obviating the need for additional procedures for mAb immobilization. The presence of NK cells on the peripheral blood mononuclear cell (PBMCs) fraction was evaluated by the response to their natural ligand (B7-H6) using an acridine orange (AO)-based assay. The successful selection of NK cells from PBMCs by our nanoplatform was assessed by the photoluminescent properties of AO. This easy and straightforward ZnO-mAb nanoplatform paves the way for the design of biosensors for clinic diagnosis, and, due to its inherent biocompatibility, for the initial selection of NK cells for autotransplantation immunotherapies.
Horizontal ‘gene drives’ harness indigenous bacteria for bioremediation
Authors: French Katherine E. , Zhou Zhongrui , Terry Norman
Published: September 2020

Engineering bacteria to clean-up oil spills is rapidly advancing but faces regulatory hurdles and environmental concerns. Here, we develop a new technology to harness indigenous soil microbial communities for bioremediation by flooding local populations with catabolic genes for petroleum hydrocarbon degradation. Overexpressing three enzymes (almA, xylE, p450cam) in Escherichia coli led to degradation of 60–99% of target hydrocarbon substrates. Mating experiments, fluorescence microscopy and TEM revealed indigenous bacteria could obtain these vectors from E. coli through several mechanisms of horizontal gene transfer (HGT), including conjugation and cytoplasmic exchange through nanotubes. Inoculating petroleum-polluted sediments with E. coli carrying the vector pSF-OXB15-p450camfusion showed that the E. coli cells died after five days but a variety of bacteria received and carried the vector for over 60 days after inoculation. Within 60 days, the total petroleum hydrocarbon content of the polluted soil was reduced by 46%. Pilot experiments show that vectors only persist in indigenous populations when under selection pressure, disappearing when this carbon source is removed. This approach to remediation could prime indigenous bacteria for degrading pollutants while providing minimal ecosystem disturbance.
Gene signatures and prognostic values of m1A-related regulatory genes in hepatocellular carcinoma
Authors: Shi Qingmiao , Xue Chen , Yuan Xin , He Yuting , Yu Zujiang
Published: September 2020

Hepatocellular carcinoma (HCC) ranks fourth in cancer-related mortality worldwide. N1-methyladenosine (m1A), a methylation modification on RNA, is gaining attention for its role across diverse biological processes. However, m1A-related regulatory genes expression, its relationship with clinical prognosis, and its role in HCC remain unclear. In this study, we utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to investigate alterations within 10 m1A-related regulatory genes and observed a high mutation frequency (23/363). Cox regression analysis and least absolute shrinkage and selection operator were used to explore the association between m1A-related regulatory genes expression and HCC patient survival and identified four regulators that were remarkably associated with HCC patient prognosis. Additionally, an independent cohort from International Cancer Genome Consortium was studied to validate our discoveries and found to be consistent with those in the TCGA dataset. In terms of mechanism, gene set enrichment analysis linked these four genes with various physiological roles in cell division, the MYC pathway, protein metabolism, and mitosis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that PI3K/Akt signaling pathway had potential relevance to m1A-related regulatory genes in HCC. These findings indicate that m1A-related regulatory genes may play crucial roles in regulating HCC progression and be exploited for diagnostic and prognostic purposes.
Continuous preparation of antimony nanocrystals with near infrared photothermal property by pulsed laser ablation in liquids
Authors: Kou Juanrong , Wang Yongkai , Liu Xiaoyu , Zhang Xianju , Chen Gaoyu , Xu Xiangxing , Bao Jianchun , Yang Kaili , Yuwen Lihui
Published: September 2020

Antimony nanocrystals (Sb NCs) are of interest in energy storage, catalysis and cancer therapy for its special physical, chemical and biomedical properties. However, methodology challenges still remain in preparation of colloidal Sb NCs, due to the restricted reaction solution systems, high temperature and time costing for common routes. Herein, size controllable colloidal Sb NCs were continuously prepared by pulsed laser ablation of Sb target in different solvents, owning to the metal nanodroplet explosive ejection and thermal evaporation mechanisms. These well dispersed and stable Sb NCs showed excellent photothermal property in the near-infrared-II window.
Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans
Authors: Lee Mi-Kyung , Son Ye-Eun , Park Hee-Soo , Alshannaq Ahmad , Han Kap-Hoon , Yu Jae-Hyuk
Published: September 2020

McrA is a key transcription factor that functions as a global repressor of fungal secondary metabolism in Aspergillus species. Here, we report that mcrA is one of the VosA-VelB target genes and McrA governs the cellular and metabolic development in Aspergillus nidulans. The deletion of mcrA resulted in a reduced number of conidia and decreased mRNA levels of brlA, the key asexual developmental activator. In addition, the absence of mcrA led to a loss of long-term viability of asexual spores (conidia), which is likely associated with the lack of conidial trehalose and increased β-(1,3)-glucan levels in conidia. In supporting its repressive role, the mcrA deletion mutant conidia contain more amounts of sterigmatocystin and an unknown metabolite than the wild type conidia. While overexpression of mcrA caused the fluffy-autolytic phenotype coupled with accelerated cell death, deletion of mcrA did not fully suppress the developmental defects caused by the lack of the regulator of G-protein signaling protein FlbA. On the contrary to the cellular development, sterigmatocystin production was restored in the ΔflbA ΔmcrA double mutant, and overexpression of mcrA completely blocked the production of sterigmatocystin. Overall, McrA plays a multiple role in governing growth, development, spore viability, and secondary metabolism in A. nidulans.
Information content best characterises the hemispheric selectivity of the inferior parietal lobe: a meta-analysis
Authors: Gray Oliver , Fry Lewis , Montaldi Daniela
Published: September 2020

Our understanding of the inferior parietal lobe (IPL) remains challenged by inconsistencies between neuroimaging and neuropsychological perspectives. To date, others assume that hemispheric specialisation of the IPL is linked with the type of processing; attention processing in the right hemisphere; memory retrieval and semantic judgement in the left hemisphere. Here, we provide compelling evidence associating the type of information being processed with the recruitment of each hemisphere’s IPL. In a meta-analysis, we classify 121 previous fMRI reports of IPL activity arising from episodic memory retrieval, according to the type of information that characterises each fMRI contrast. We demonstrate that the left IPL is more consistently associated with retrieval of the semantic (95% of eligible contrasts) than perceptual aspects of memory (83%). In contrast, the right IPL is more consistently associated with the retrieval of perceptual (97%), than semantic aspects of memory (43%). This work revises assumptions of how the IPL contributes to healthy cognition and has major implications for IPL-related neuropsychological deficits.
Electronic decoupling of polyacenes from the underlying metal substrate by sp3 carbon atoms
Authors: Mohammed Mohammed S. G. , Colazzo Luciano , Robles Roberto , Dorel Ruth , Echavarren Antonio M. , Lorente Nicolás , de Oteyza Dimas G.
Published: September 2020

On-surface synthesis is becoming an increasingly popular approach to obtain new organic materials. In this context, metallic surfaces are the most commonly used substrates. However, their hybridization with the adsorbates often hinder a proper characterization of the molecule’s intrinsic electronic and magnetic properties. Here we report a route to electronically decouple molecules from their supporting substrates. In particular, we have used a Ag(001) substrate and hydrogenated heptacene molecules, in which the longest conjugated segment determining its frontier molecular orbitals amounts to five consecutive rings. The non-planarity that sp3 atoms impose on the carbon backbone results in electronically decoupled molecules, as demonstrated by scanning tunneling spectroscopy measurements. The charging resonances of the latter imply the presence of double tunneling barriers. We further explain the existing relation between the charging resonance energy and their contrast, as well as with the presence or absence of additional Kondo resonances.
Living optical random neural network with three dimensional tumor spheroids for cancer morphodynamics
Authors: Pierangeli D. , Palmieri V. , Marcucci G. , Moriconi C. , Perini G. , De Spirito M. , Papi M. , Conti C.
Published: September 2020

Optical neural networks process information at the speed of light and are energetically efficient. Photonic artificial intelligence allows speech recognition, image classification, and Ising machines. Modern machine learning paradigms, as extreme learning machines, reveal that disordered and biological materials may realize optical neural networks with thousands of nodes trained only at the input and at the readout. May we use living matter for machine learning? Here, we employ living three-dimensional tumor brain models to demonstrate a random optical learning machine (ROM) for the investigation of glioblastoma. The tumor spheroid act as a computational reservoir. The ROM detects cancer morphodynamics by laser-induced hyperthermia, quantifies chemotherapy, and cell metabolism. The ROM is a sensitive noninvasive smart probe for cytotoxicity assay and enables real-time investigation of tumor dynamics. We hence design and demonstrate a novel bio-hardware for optical computing and the study of light/complex matter interaction.
A quantitative hydroclimatic context for the European Great Famine of 1315–1317
Authors: Baek Seung H. , Smerdon Jason E. , Dobrin George-Costin , Naimark Jacob G. , Cook Edward R. , Cook Benjamin I. , Seager Richard , Cane Mark A. , Scholz Serena R.
Published: September 2020

The European Great Famine of 1315–1317 triggered one of the worst population collapses in European history and ranks as the single worst European famine in mortality as a proportion of population. Historical records point to torrential rainfall, land saturation, crop failure, and prolonged flooding as important causes of the famine. Here we use the tree-ring based Old World Drought Atlas (OWDA) to show that the average of each growing season preceding the Great Famine years (1314–1316) was the fifth wettest over Europe from 1300 to 2012 C.E. The spatial and temporal characteristics of our OWDA-estimated anomalies are in excellent agreement with available historical accounts. We also characterize a mode of European hydroclimate variability that is associated with the Great Famine, which we term the “Great Famine mode.” This mode emerges as the leading mode of European hydroclimate variability from 1300–2012 and is strongly associated with extreme wet and dry events in Europe over the last millennium.
Direct monitoring of protease activity using an integrated microchip coated with multilayered fluorogenic nanofilms
Authors: Yu Dan , Chen Yuting , Ahrens Caroline C. , Wang Yinggui , Ding Zhenya , Lim HyunTaek , Fell Cody , Rumbaugh Kendra P. , Wu Jiangyu , Li Wei
Published: September 2020

A microchip coated with fluorogenic nanofilms demonstrates the potential to provide real-time information about protease activity using small sample volumes.
Cold atmospheric plasma induces stress granule formation via an eIF2α-dependent pathway
Authors: Motaln Helena , Čerček Urša , Recek Nina , Bajc Česnik Ana , Mozetič Miran , Rogelj Boris
Published: September 2020

Cold atmospheric plasma treatment of FlpIn SH-SY5Y cells with an inducible expression of G3BP1 results in stress granule assembly resembling a cellular oxidative stress response that has been shown to be eIF2α-signaling dependent and inhibited by an ISRIB inhibitor.
Biopolymers-calcium phosphate antibacterial coating reduces the pathogenicity of internalized bacteria by mesenchymal stromal cells
Authors: Dubus Marie , Varin-Simon Jennifer , Prada Pierre , Scomazzon Loïc , Reffuveille Fany , Alem Halima , Boulmedais Fouzia , Mauprivez Cédric , Rammal Hassan , Kerdjoudj Halima
Published: September 2020

Coating made of calcium phosphate/chitosan/hyaluronic acid, proposed as an antibacterial substrate for stromal cell adhesion.
Silver-decorated, light-activatable polymeric antimicrobials for combined chemo-photodynamic therapy of drug-resistant bacterial infection
Authors: Hou Xiaoxue , Yang Lijun , Liu Jinjian , Zhang Yumin , Chu Liping , Ren Chunyan , Huang Fan , Liu Jianfeng
Published: September 2020

In this article, we describe a silver-decorated, light-activatable polymeric antimicrobial with strong synergistic chemo-photodynamic effect to combat bacterial infections.
An alpha/beta chimeric peptide molecular brush for eradicating MRSA biofilms and persister cells to mitigate antimicrobial resistance
Authors: Xiao Ximian , Zhang Si , Chen Sheng , Qian Yuxin , Xie Jiayang , Cong Zihao , Zhang Danfeng , Zou Jingcheng , Zhang Wenjing , Ji Zhemin , Cui Ruxin , Qiao Zhongqian , Jiang Weinan , Dai Yidong , Wang Yun , Shao Xiaoyan , Sun Yun , Xia Jiang , Fei Jian , Liu Runhui
Published: September 2020

An α/β chimeric polypeptide molecular brush shows excellent performance in eradicating established biofilms, persister cells, and clinically isolated multi-drug resistant Gram-positive bacteria.
β-FeOOH/Fe-TiO2 heterojunctions on Ti for bacteria inactivation under light irradiation and biosealing
Authors: Li Kai , Xue Yang , Zhang Lan , Han Yong
Published: September 2020

Upon light irradiation, β-FeOOH/Fe-TiO2 heterojunctions efficiently eliminate bacteria and enhance the biosealing of Ti implants in an infection model.
A novel, rationally designed lanthanoid chelating tag delivers large paramagnetic structural restraints for biomolecular NMR
Authors: Joss Daniel , Winter Florine , Häussinger Daniel
Published: September 2020

A novel, rationally designed lanthanoid chelating tag enables fast ligation to biomacromolecules and delivers long-range structural restraints by NMR.
FeS/FeNC decorated N,S-co-doped porous carbon for enhanced ORR activity in alkaline media
Authors: Chen Zirun , Liu Ruliang , Liu Shaohong , Huang Junlong , Chen Luyi , Nadimicherla Reddeppa , Wu Dingcai , Fu Ruowen
Published: September 2020

A novel strategy is developed to produce an FeS–FeNC-decorated hierarchical porous N,S-co-doped carbon (FeS–FeNC@NSC) electrocatalyst via introducing volatile FeCl3 into a porphyrin polymer framework followed by carbonization.
Black phosphorus-modified sulfurized polyacrylonitrile with high C-rate and cycling performance in ether-based electrolyte for lithium sulfur batteries
Authors: Ma Shaobo , Wang Yang , Fu Chuankai , Ma Yulin , Gao Yunzhi , Yin Geping , Zuo Pengjian
Published: September 2020

Black phosphorus modified sulfurized polyacrylonitrile was reported for the first time with enhanced C-rate and cycling stability performance in ether electrolyte.
Efficient construction of diverse 3-cyanoindoles under novel tandem catalysis
Authors: Wu Jun , Liu Jiabin , Zhou Kerui , He Zhenni , Wang Qian , Wu Fen , Miao Tingting , Qian Jinjie , Shi Qian
Published: September 2020

A novel and rapid construction of 3-cyanoindoles by palladium-catalyzed tandem reactions has been developed.
Copper-catalyzed chemoselective C–H functionalization of quinoxalin-2(1H)-ones with hexafluoroisopropanol
Authors: Su Hai-Yan , Zhu Xiao-Lei , Huang Yangen , Xu Xiu-Hua , Qing Feng-Ling
Published: September 2020

New applications of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) were reported in the copper-catalyzed chemoselective C–H hydroxyhexafluoroisobutylation and hexafluoroisopropoxylation of quinoxalin-2(1H)-ones.
Polarised covalent thorium(iv)– and uranium(iv)–silicon bonds
Authors: Réant Benjamin L. L. , Berryman Victoria E. J. , Seed John A. , Basford Annabel R. , Formanuik Alasdair , Wooles Ashley J. , Kaltsoyannis Nikolas , Liddle Stephen T. , Mills David P.
Published: September 2020

We report thorium- and uranium–silicon bonds in structurally analogous complexes with surprisingly similar actinide–silicon bonding regimes.
Formation of well-organized, concentric-ringed spherulites of four-arm star symmetric PEO-b-PCL via confined evaporative crystallization
Authors: Wei Jing , Wu Lin , Zhu Hao , Li Yiguo , Wang Zongbao
Published: September 2020

Toluene solvent-assisted topology confinement facilitates PCL block templated rhythmic crystallization into concentric-ringed spherulites of star symmetric P(EO2.5k-b-CL2.7k)4.