bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioactivity descriptors for uncharacterized chemical compounds
Authors: Bertoni Martino , Duran-Frigola Miquel , Badia-i-Mompel Pau , Pauls Eduardo , Orozco-Ruiz Modesto , Guitart-Pla Oriol , Alcalde Víctor , Diaz Víctor M. , Berenguer-Llergo Antoni , Brun-Heath Isabelle , Villegas Núria , de Herreros Antonio García , Aloy Patrick
Published: June 2021

Chemical descriptors encode the physicochemical and structural properties of small molecules, and they are at the core of chemoinformatics. The broad release of bioactivity data has prompted enriched representations of compounds, reaching beyond chemical structures and capturing their known biological properties. Unfortunately, bioactivity descriptors are not available for most small molecules, which limits their applicability to a few thousand well characterized compounds. Here we present a collection of deep neural networks able to infer bioactivity signatures for any compound of interest, even when little or no experimental information is available for them. Our signaturizers relate to bioactivities of 25 different types (including target profiles, cellular response and clinical outcomes) and can be used as drop-in replacements for chemical descriptors in day-to-day chemoinformatics tasks. Indeed, we illustrate how inferred bioactivity signatures are useful to navigate the chemical space in a biologically relevant manner, unveiling higher-order organization in natural product collections, and to enrich mostly uncharacterized chemical libraries for activity against the drug-orphan target Snail1. Moreover, we implement a battery of signature-activity relationship (SigAR) models and show a substantial improvement in performance, with respect to chemistry-based classifiers, across a series of biophysics and physiology activity prediction benchmarks.
Spearheading future omics analyses using dyngen, a multi-modal simulator of single cells
Authors: Cannoodt Robrecht , Saelens Wouter , Deconinck Louise , Saeys Yvan
Published: June 2021

We present dyngen, a multi-modal simulation engine for studying dynamic cellular processes at single-cell resolution. dyngen is more flexible than current single-cell simulation engines, and allows better method development and benchmarking, thereby stimulating development and testing of computational methods. We demonstrate its potential for spearheading computational methods on three applications: aligning cell developmental trajectories, cell-specific regulatory network inference and estimation of RNA velocity.
Unsplit superconducting and time reversal symmetry breaking transitions in Sr2RuO4 under hydrostatic pressure and disorder
Authors: Grinenko Vadim , Das Debarchan , Gupta Ritu , Zinkl Bastian , Kikugawa Naoki , Maeno Yoshiteru , Hicks Clifford W. , Klauss Hans-Henning , Sigrist Manfred , Khasanov Rustem
Published: June 2021

There is considerable evidence that the superconducting state of Sr2RuO4 breaks time reversal symmetry. In the experiments showing time reversal symmetry breaking, its onset temperature, TTRSB, is generally found to match the critical temperature, Tc, within resolution. In combination with evidence for even parity, this result has led to consideration of a dxz ± idyz order parameter. The degeneracy of the two components of this order parameter is protected by symmetry, yielding TTRSB = Tc, but it has a hard-to-explain horizontal line node at kz = 0. Therefore, s ± id and d ± ig order parameters are also under consideration. These avoid the horizontal line node, but require tuning to obtain TTRSB ≈ Tc. To obtain evidence distinguishing these two possible scenarios (of symmetry-protected versus accidental degeneracy), we employ zero-field muon spin rotation/relaxation to study pure Sr2RuO4 under hydrostatic pressure, and Sr1.98La0.02RuO4 at zero pressure. Both hydrostatic pressure and La substitution alter Tc without lifting the tetragonal lattice symmetry, so if the degeneracy is symmetry-protected, TTRSB should track changes in Tc, while if it is accidental, these transition temperatures should generally separate. We observe TTRSB to track Tc, supporting the hypothesis of dxz ± idyz order.
The origin of the high electrochemical activity of pseudo-amorphous iridium oxides
Authors: Elmaalouf Marine , Odziomek Mateusz , Duran Silvia , Gayrard Maxime , Bahri Mounib , Tard Cédric , Zitolo Andrea , Lassalle-Kaiser Benedikt , Piquemal Jean-Yves , Ersen Ovidiu , Boissière Cédric , Sanchez Clément , Giraud Marion , Faustini Marco , Peron Jennifer
Published: June 2021

Combining high activity and stability, iridium oxide remains the gold standard material for the oxygen evolution reaction in acidic medium for green hydrogen production. The reasons for the higher electroactivity of amorphous iridium oxides compared to their crystalline counterpart is still the matter of an intense debate in the literature and, a comprehensive understanding is needed to optimize its use and allow for the development of water electrolysis. By producing iridium-based mixed oxides using aerosol, we are able to decouple the electronic processes from the structural transformation, i.e. Ir oxidation from IrO2 crystallization, occurring upon calcination. Full characterization using in situ and ex situ X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and transmission electron microscopy allows to unambiguously attribute their high electrochemical activity to structural features and rules out the iridium oxidation state as a critical parameter. This study indicates that short-range ordering, corresponding to sub-2nm crystal size for our samples, drives the activity independently of the initial oxidation state and composition of the calcined iridium oxides.
Frontopolar theta oscillations link metacognition with prospective decision making
Authors: Soutschek Alexander , Moisa Marius , Ruff Christian C. , Tobler Philippe N.
Published: June 2021

Prospective decision making considers the future consequences of actions and therefore requires agents to represent their present subjective preferences reliably across time. Here, we test the link of frontopolar theta oscillations to both metacognitive ability and prospective choice behavior. We target these oscillations with transcranial alternating current stimulation while participants make decisions between smaller-sooner and larger-later monetary rewards and rate their choice confidence after each decision. Stimulation designed to enhance frontopolar theta oscillations increases metacognitive accuracy in reports of subjective uncertainty in intertemporal decisions. Moreover, the stimulation also enhances the willingness of participants to restrict their future access to short-term gratification by strengthening the awareness of potential preference reversals. Our results suggest a mechanistic link between frontopolar theta oscillations and metacognitive knowledge about the stability of subjective value representations, providing a potential explanation for why frontopolar cortex also shields prospective decision making against future temptation.
Approximate Bayesian Computation of radiocarbon and paleoenvironmental record shows population resilience on Rapa Nui (Easter Island)
Authors: DiNapoli Robert J. , Crema Enrico R. , Lipo Carl P. , Rieth Timothy M. , Hunt Terry L.
Published: June 2021

Examining how past human populations responded to environmental and climatic changes is a central focus of the historical sciences. The use of summed probability distributions (SPD) of radiocarbon dates as a proxy for estimating relative population sizes provides a widely applicable method in this research area. Paleodemographic reconstructions and modeling with SPDs, however, are stymied by a lack of accepted methods for model fitting, tools for assessing the demographic impact of environmental or climatic variables, and a means for formal multi-model comparison. These deficiencies severely limit our ability to reliably resolve crucial questions of past human-environment interactions. We propose a solution using Approximate Bayesian Computation (ABC) to fit complex demographic models to observed SPDs. Using a case study from Rapa Nui (Easter Island), a location that has long been the focus of debate regarding the impact of environmental and climatic changes on its human population, we find that past populations were resilient to environmental and climatic challenges. Our findings support a growing body of evidence showing stable and sustainable communities on the island. The ABC framework offers a novel approach for exploring regions and time periods where questions of climate-induced demographic and cultural change remain unresolved.
Chronic obstructive pulmonary disease as a risk factor in primary care: a Canadian retrospective cohort study
Authors: Cave Andrew , Pham Anh , Lindeman Cliff , Soos Boglarka , Williamson Tyler , Drummond Neil
Published: June 2021

Chronic obstructive pulmonary disease (COPD) is a complex disease that is predicted to be the third most common cause of death by 2030. In Canada, the care and management of chronic conditions is largely provided by primary care providers. Although there is emerging research and initiatives that describe the prevalence of COPD in Canadian primary care settings, to our knowledge, there have been no efforts to use a large pan-Canadian database to analyze COPD as a risk factor for other common chronic conditions managed in primary care. We report the risk of developing comorbidities after the onset of COPD, that is, the extent to which COPD is a risk factor for developing common chronic conditions (heart failure, depression, anxiety, coronary artery disease, diabetes, anemia, hypertension, ischemic heart disease, underweight, and osteoporosis). After adjusting for age, sex, urban vs rural residence, and smoking status, the relative risks for patients with COPD at baseline were significantly higher for subsequent incidence of anemia, anxiety, diabetes, depression, heart failure, ischemic heart disease, lung cancer, osteoporosis, sleep apnea, underweight, and hypertension than patients without COPD. Using a cut-point of a 200% increase in relative risk as indicative of particular clinical relevance, COPD has a statistically and clinically significant association with developing lung cancer, becoming underweight, and developing heart failure.
Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome
Authors: Nayfach Stephen , Páez-Espino David , Call Lee , Low Soo Jen , Sberro Hila , Ivanova Natalia N. , Proal Amy D. , Fischbach Michael A. , Bhatt Ami S. , Hugenholtz Philip , Kyrpides Nikos C.
Published: June 2021

Bacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available human stool metagenomes. Over 75% of genomes represent double-stranded DNA phages that infect members of the Bacteroidia and Clostridia classes. Based on sequence clustering we identified 54,118 candidate viral species, 92% of which were not found in existing databases. The Metagenomic Gut Virus catalogue improves detection of viruses in stool metagenomes and accounts for nearly 40% of CRISPR spacers found in human gut Bacteria and Archaea. We also produced a catalogue of 459,375 viral protein clusters to explore the functional potential of the gut virome. This revealed tens of thousands of diversity-generating retroelements, which use error-prone reverse transcription to mutate target genes and may be involved in the molecular arms race between phages and their bacterial hosts.
Dataset and validation of the approaches to study skills inventory for students
Authors: Dedos Skarlatos G. , Fouskakis Dimitris
Published: June 2021

There exists a vast amount of research on how students, in higher education, approach their studying and learning. Such research resulted in a multitude of questionnaires and tools to capture the way students perform in higher education institutions. One of these tools is the Approaches to Study Skills Inventory for Students (ASSIST) that was developed in the ’80 s and ’90 s. This inventory broadly classifies students, as approaching their study, in a deep, a strategic and/or a surface manner. Although it has gone through rigorous validation in many studies, there exist no publicly available dataset of the results of these studies and so the raw datasets cannot be re-used or integrated with other similar datasets. Here, we report and make publicly available the raw data of an 8-year longitudinal survey using this inventory in a cohort study of 1181 students from a department of a higher education institution. We validated our dataset using reliability analyses that confirmed, and compared well, with the results of previous studies.
Radiocarbon dating of lead white: novel application in the study of polychrome sculpture
Authors: Sá Sara , Hendriks Laura , Pombo Cardoso Isabel , Hajdas Irka
Published: June 2021

Recently, radiocarbon dating underwent considerable technological advances allowing unprecedented sample size downscaling. These achievements introduced novel opportunities in dating cultural heritage objects. Within this pioneering research, the possibility of a direct 14C dating of lead white pigment and organic binder in paint samples was investigated on polychrome sculptures, a foremost artistic expression in human history. The polychromy, an indivisible part of polychrome sculpture, holds a key role in the interpretation and understanding of these artworks. Unlike in other painted artworks, the study of polychromies is repeatedly hampered by repaints and degradation. The omnipresence of lead white within the original polychromy was thus pursued as dating proxy. Thermal decomposition allowed bypassing geologic carbonate interferences caused by the object's support material, while an added solvent extraction successfully removed conservation products. This radiocarbon dating survey of the polychromy from 16 Portuguese medieval limestone sculptures confirmed that some were produced within the proposed chronologies while others were revised. Within this multidisciplinary study, the potential of radiocarbon dating as a complementary source of information about these complex paint systems guiding their interpretation is demonstrated. The challenges of this innovative approach are highlighted and improvements on sampling and sample preparation are discussed.
The best temperature range to acquire reliable thermal infrared spectra from orbit
Authors: Nestola F. , Ferrari S. , Pamato M. G. , Redhammer G. , Helbert J. , Alvaro M. , Domeneghetti M. C.
Published: June 2021

Solar System bodies undergo to daily and periodical variations of temperature that mainly depend on their closeness to the Sun. It is known that mineral expansion and contraction due to such variations modify the thermal infrared spectra acquired on solid surfaces. Therefore, it becomes crucial to know the best temperature range at which the acquisition itself should be carried out to get reliable information on the mineralogy of such bodies. Here we provide the thermal expansion of olivine between 20 and 298 K determined by X-ray diffraction. Our data reveal the non-linear behaviour of silicates that undergo to low temperatures, where volume variations appear positively correlated with temperatures. Subtle bond-length variations occurring at low temperatures are then expected to minimally affect vibrational absorption positions. We suggest that thermal infrared spectra of those Solar-System surfaces that are not exceeding 300 K provide reliable information about not only the silicate mineral identification but also on their chemical composition, regardless of the instantaneous temperature.
The mineralocorticoid receptor leads to increased expression of EGFR and T-type calcium channels that support HL-1 cell hypertrophy
Authors: Stroedecke Katharina , Meinel Sandra , Markwardt Fritz , Kloeckner Udo , Straetz Nicole , Quarch Katja , Schreier Barbara , Kopf Michael , Gekle Michael , Grossmann Claudia
Published: June 2021

The EGF receptor (EGFR) has been extensively studied in tumor biology and recently a role in cardiovascular pathophysiology was suggested. The mineralocorticoid receptor (MR) is an important effector of the renin–angiotensin–aldosterone-system and elicits pathophysiological effects in the cardiovascular system; however, the underlying molecular mechanisms are unclear. Our aim was to investigate the importance of EGFR for MR-mediated cardiovascular pathophysiology because MR is known to induce EGFR expression. We identified a SNP within the EGFR promoter that modulates MR-induced EGFR expression. In RNA-sequencing and qPCR experiments in heart tissue of EGFR KO and WT mice, changes in EGFR abundance led to differential expression of cardiac ion channels, especially of the T-type calcium channel CACNA1H. Accordingly, CACNA1H expression was increased in WT mice after in vivo MR activation by aldosterone but not in respective EGFR KO mice. Aldosterone- and EGF-responsiveness of CACNA1H expression was confirmed in HL-1 cells by Western blot and by measuring peak current density of T-type calcium channels. Aldosterone-induced CACNA1H protein expression could be abrogated by the EGFR inhibitor AG1478. Furthermore, inhibition of T-type calcium channels with mibefradil or ML218 reduced diameter, volume and BNP levels in HL-1 cells. In conclusion the MR regulates EGFR and CACNA1H expression, which has an effect on HL-1 cell diameter, and the extent of this regulation seems to depend on the SNP-216 (G/T) genotype. This suggests that the EGFR may be an intermediate for MR-mediated cardiovascular changes and that SNP analysis can help identify subgroups of patients that will benefit most from MR antagonists.
Sodium lignosulfonate improves shoot growth of Oryza sativa via enhancement of photosynthetic activity and reduced accumulation of reactive oxygen species
Authors: Kok Andrew De-Xian , Wan Abdullah Wan Muhamad Asrul Nizam , Tang Chu-Nie , Low Lee-Yoon , Yuswan Mohd Hafis , Ong-Abdullah Janna , Tan Ngai-Paing , Lai Kok-Song
Published: June 2021

Lignosulfonate (LS) is a by-product obtained during sulfite pulping process and is commonly used as a growth enhancer in plant growth. However, the underlying growth promoting mechanism of LS on shoot growth remains largely unknown. Hence, this study was undertaken to determine the potential application of eco-friendly ion-chelated LS complex [sodium LS (NaLS) and calcium LS (CaLS)] to enhance recalcitrant indica rice MR 219 shoot growth and to elucidate its underlying growth promoting mechanisms. In this study, the shoot apex of MR 219 rice was grown on Murashige and Skoog medium supplemented with different ion chelated LS complex (NaLS and CaLS) at 100, 200, 300 and 400 mg/L The NaLS was shown to be a better shoot growth enhancer as compared to CaLS, with optimum concentration of 300 mg/L. Subsequent comparative proteomic analysis revealed an increase of photosynthesis-related proteins [photosystem II (PSII) CP43 reaction center protein, photosystem I (PSI) iron-sulfur center, PSII CP47 reaction center protein, PSII protein D1], ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), carbohydrate metabolism-related proteins (glyceraldehyde-3-phosphate dehydrogenase 3, fructose-bisphosphate aldolase) and stress regulator proteins (peptide methionine sulfoxide reductase A4, delta-1-pyrroline-5-carboxylate synthase 1) abundance in NaLS-treated rice as compared to the control (MSO). Consistent with proteins detected, a significant increase in biochemical analyses involved in photosynthetic activities, carbohydrate metabolism and protein biosynthesis such as total chlorophyll, rubisco activity, total sugar and total protein contents were observed in NaLS-treated rice. This implies that NaLS plays a role in empowering photosynthesis activities that led to plant growth enhancement. In addition, the increased in abundance of stress regulator proteins were consistent with low levels of peroxidase activity, malondialdehyde content and phenylalanine ammonia lyase activity observed in NaLS-treated rice. These results suggest that NaLS plays a role in modulating cellular homeostasis to provide a conducive cellular environment for plant growth. Taken together, NaLS improved shoot growth of recalcitrant MR 219 rice by upregulation of photosynthetic activities and reduction of ROS accumulation leading to better plant growth.
Molecular characterization of sequence-driven peptide glycation
Authors: Berger Michelle T. , Hemmler Daniel , Walker Alesia , Rychlik Michael , Marshall James W. , Schmitt-Kopplin Philippe
Published: June 2021

Peptide glycation is an important, yet poorly understood reaction not only found in food but also in biological systems. The enormous heterogeneity of peptides and the complexity of glycation reactions impeded large-scale analysis of peptide derived glycation products and to understand both the contributing factors and how this affects the biological activity of peptides. Analyzing time-resolved Amadori product formation, we here explored site-specific glycation for 264 peptides. Intensity profiling together with in-depth computational sequence deconvolution resolved differences in peptide glycation based on microheterogeneity and revealed particularly reactive peptide collectives. These peptides feature potentially important sequence patterns that appear in several established bio- and sensory-active peptides from independent sources, which suggests that our approach serves system-wide applicability. We generated a pattern peptide map and propose that in peptide glycation the herein identified molecular checkpoints can be used as indication of sequence reactivity.
Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19
Authors: Redhead Martin A. , Owen C. David , Brewitz Lennart , Collette Amelia H. , Lukacik Petra , Strain-Damerell Claire , Robinson Sean W. , Collins Patrick M. , Schäfer Philipp , Swindells Mark , Radoux Chris J. , Hopkins Iva Navratilova , Fearon Daren , Douangamath Alice , von Delft Frank , Malla Tika R. , Vangeel Laura , Vercruysse Thomas , Thibaut Jan , Leyssen Pieter , Nguyen Tu-Trinh , Hull Mitchell , Tumber Anthony , Hallett David J. , Schofield Christopher J. , Stuart David I. , Hopkins Andrew L. , Walsh Martin A.
Published: June 2021

Effective agents to treat coronavirus infection are urgently required, not only to treat COVID-19, but to prepare for future outbreaks. Repurposed anti-virals such as remdesivir and human anti-inflammatories such as barcitinib have received emergency approval but their overall benefits remain unclear. Vaccines are the most promising prospect for COVID-19, but will need to be redeveloped for any future coronavirus outbreak. Protecting against future outbreaks requires the identification of targets that are conserved between coronavirus strains and amenable to drug discovery. Two such targets are the main protease (Mpro) and the papain-like protease (PLpro) which are essential for the coronavirus replication cycle. We describe the discovery of two non-antiviral therapeutic agents, the caspase-1 inhibitor SDZ 224015 and Tarloxotinib that target Mpro and PLpro, respectively. These were identified through extensive experimental screens of the drug repurposing ReFRAME library of 12,000 therapeutic agents. The caspase-1 inhibitor SDZ 224015, was found to be a potent irreversible inhibitor of Mpro (IC50 30 nM) while Tarloxotinib, a clinical stage epidermal growth factor receptor inhibitor, is a sub micromolar inhibitor of PLpro (IC50 300 nM, Ki 200 nM) and is the first reported PLpro inhibitor with drug-like properties. SDZ 224015 and Tarloxotinib have both undergone safety evaluation in humans and hence are candidates for COVID-19 clinical evaluation.
Genome-scale comparative analysis for host resistance against sea lice between Atlantic salmon and rainbow trout
Authors: Cáceres Pablo , Barría Agustín , Christensen Kris A. , Bassini Liane N. , Correa Katharina , Garcia Baltasar , Lhorente Jean P. , Yáñez José M.
Published: June 2021

Sea lice (Caligus rogercresseyi) is an ectoparasite which causes major production losses in the salmon aquaculture industry worldwide. Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) are two of the most susceptible salmonid species to sea lice infestation. The objectives of this study were to: (1) identify genomic regions associated with resistance toCaligus rogercresseyiin Atlantic salmon and rainbow trout by performing single-step Genome-Wide Association studies (ssGWAS), and (2) identify candidate genes related to trait variation based on exploring orthologous genes within the associated regions across species. A total of 2626 Atlantic salmon and 2643 rainbow trout were challenged and genotyped with 50 K and 57 K SNP panels, respectively. We ran two independent ssGWAS for sea lice resistance on each species and identified 7 and 13 regions explaining more than 1% of the genetic variance for the trait, with the most important regions explaining 3% and 2.7% for Atlantic salmon and rainbow trout, respectively. We identified genes associated with immune response, cytoskeleton function, and cell migration when focusing on important genomic regions for each species. Moreover, we found 15 common orthogroups which were present in more than one associated genomic region, within- or between-species; however, only one orthogroup showed a clear potential biological relevance in the response against sea lice. For instance,dual-specificity protein phosphatase 10-like(dusp10) anddual-specificity protein phosphatase 8(dusp8) were found in genomic regions associated with lice density in Atlantic salmon and rainbow trout, respectively.Dusp10anddusp8are modulators of the MAPK pathway and might be involved in the differences of the inflammation response between lice resistant and susceptible fish from both species. Our results provide further knowledge on candidate genes related to sea lice resistance and may help establish better control for sea lice in fish populations.
Transposon sequencing analysis of Bradyrhizobium diazoefficiens 110spc4
Authors: Baraquet Claudine , Dai Weijun , Mendiola Jose , Pechter Kieran , Harwood Caroline S.
Published: June 2021

Bradyrhizobium diazoefficiens USDA110 is one of the most effective nitrogen-fixing symbionts of soybeans. Here we carried out a large-scale transposon insertion sequencing (Tn-seq) analysis of strain Bd110spc4, which is derived from USDA110, with the goal of increasing available resources for identifying genes crucial for the survival of this plant symbiont under diverse conditions. We prepared two transposon (Tn) insertion libraries of Bd110spc4 with 155,042 unique Tn insertions when the libraries were combined, which is an average of one insertion every 58.7 bp of the reference USDA110 genome. Application of bioinformatic filtering steps to remove genes too small to be expected to have Tn insertions, resulted in a list of genes that were classified as putatively essential. Comparison of this gene set with genes putatively essential for the growth of the closely related alpha-proteobacterium, Rhodopseudomonas palustris, revealed a small set of five genes that may be collectively essential for closely related members of the family Bradyrhizobiaceae. This group includes bacteria with diverse lifestyles ranging from plant symbionts to animal-associated species to free-living species.
Fms-like tyrosine kinase 3-internal tandem duplications epigenetically activates checkpoint kinase 1 in acute myeloid leukemia cells
Authors: Zhang Yudong , Yuan Lingli
Published: June 2021

It is not clear how Fms-like tyrosine kinase 3-internal tandem duplications (FLT3-ITD) regulates checkpoint kinase 1 (CHK1) in acute myeloid leukemia (AML). In this study, we investigated the regulatory effect of FLT3-ITD on CHK1. Our results showed that CHK1 was highly expressed in FLT3-ITD positive AML. The overall survival rate and disease-free survival rate of AML patients with high CHK1 level were lower than those of patients with low CHK1 level. Mechanistically, FLT3-ITD recruited p300 to the CHK1 promoter and subsequently acetylated H3K27, thereby enhancing the transcription of CHK1. Interfering with the expression of CHK1 significantly inhibited the cell proliferation and induced cell apoptosis in FLT3-ITD positive MV4-11 cells. In addition, CHK1 knockdown promoted the sensitivity of MV4-11 cells to the epigenetic inhibitors JQ1 and C646. This study discovers a new therapeutic target for FLT3-ITD + AML and provided evidence for the combination of epigenetic inhibitors for AML treatment.
Analysis of the dark proteome of Chandipura virus reveals maximum propensity for intrinsic disorder in phosphoprotein
Authors: Sharma Nishi R. , Gadhave Kundlik , Kumar Prateek , Saif Mohammad , Khan Md. M. , Sarkar Debi P. , Uversky Vladimir N. , Giri Rajanish
Published: June 2021

Chandipura virus (CHPV, a member of the Rhabdoviridae family) is an emerging pathogen that causes rapidly progressing influenza-like illness and acute encephalitis often leading to coma and death of the human host. Given several CHPV outbreaks in Indian sub-continent, recurring sporadic cases, neurological manifestation, and high mortality rate of this infection, CHPV is gaining global attention. The ‘dark proteome’ includes the whole proteome with special emphasis on intrinsically disordered proteins (IDP) and IDP regions (IDPR), which are proteins or protein regions that lack unique (or ordered) three-dimensional structures within the cellular milieu. These proteins/regions, however, play a number of vital roles in various biological processes, such as cell cycle regulation, control of signaling pathways, etc. and, therefore, are implicated in many human diseases. IDPs and IPPRs are also abundantly found in many viral proteins enabling their multifunctional roles in the viral life cycles and their capability to highjack various host systems. The unknown abundance of IDP and IDPR in CHPV, therefore, prompted us to analyze the dark proteome of this virus. Our analysis revealed a varying degree of disorder in all five CHPV proteins, with the maximum level of intrinsic disorder propensity being found in Phosphoprotein (P). We have also shown the flexibility of P protein using extensive molecular dynamics simulations up to 500 ns (ns). Furthermore, our analysis also showed the abundant presence of the disorder-based binding regions (also known as molecular recognition features, MoRFs) in CHPV proteins. The identification of IDPs/IDPRs in CHPV proteins suggests that their disordered regions may function as potential interacting domains and may also serve as novel targets for disorder-based drug designs.
Determining the burden of fungal infections in Zimbabwe
Authors: Pfavayi Lorraine T. , Denning David W. , Baker Stephen , Sibanda Elopy N. , Mutapi Francisca
Published: June 2021

Zimbabwe currently faces several healthcare challenges, most notably HIV and associated infections including tuberculosis (TB), malaria and recently outbreaks of cholera, typhoid fever and COVID-19. Fungal infections, which are also a major public health threat, receive considerably less attention. Consequently, there is dearth of data regarding the burden of fungal diseases in the country. We estimated the burden of fungal diseases in Zimbabwe based on published literature and ‘at-risk’ populations (HIV/AIDS patients, survivors of pulmonary TB, cancer, chronic obstructive pulmonary disease, asthma and patients receiving critical care) using previously described methods. Where there was no data for Zimbabwe, regional, or international data was used. Our study revealed that approximately 14.9% of Zimbabweans suffer from fungal infections annually, with 80% having tinea capitis. The annual incidence of cryptococcal meningitis andPneumocystis jiroveciipneumonia in HIV/AIDS were estimated at 41/100,000 and 63/100,000, respectively. The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) was 2,739/100,000. The estimated burden of fungal diseases in Zimbabwe is high in comparison to other African countries, highlighting the urgent need for increased awareness and surveillance to improve diagnosis and management.
Cell-fate decision of mesenchymal stem cells toward osteocyte differentiation is committed by spheroid culture
Authors: Kim Jeonghyun , Adachi Taiji
Published: June 2021

Osteocytes are mechanosensory commander cells to regulate bone remodeling throughout the lifespan. While the osteocytes are known as terminally differentiated cells derived from mesenchymal stem cells, the detailed mechanisms of osteocyte differentiation remain unclear. In this study, we fabricated 3D self-organized spheroids using human mesenchymal stem cells (MSCs). Under the osteogenesis induction medium, the spheroid culture model exerted the osteocyte-likeness within 2 days compared to a conventional 2D monolayer model. Moreover, we showed that an inhibition of actin polymerization in the spheroid further up-regulated the osteocyte gene expressions. Notably, we represented that the cell condensed condition acquired in the 3D spheroid culture model determined a differentiation fate of MSCs to osteocytes. Taken together, we suggest that our self-organized spheroid model can be utilized as a new in vitro model to represent the osteocyte and to recapitulate an in vitro ossification process.
Trends in use of e-cigarette device types and heated tobacco products from 2016 to 2020 in England
Authors: Tattan-Birch Harry , Brown Jamie , Shahab Lion , Jackson Sarah E.
Published: June 2021

This study examined use trends of e-cigarette devices types, heated tobacco products (HTPs) and e-liquid nicotine concentrations in England from 2016 to 2020. Data were from a representative repeat cross-sectional survey of adults aged 16 or older. Bayesian logistic regression was used to estimate proportions and 95% credible intervals (CrIs). Of 75,355 participants, 5.3% (weighted = 5.5%) were currently using e-cigarettes or HTPs, with the majority (98.7%) using e-cigarettes. Among e-cigarette users, 53.7% (CrI 52.0–55.1%) used tank devices, 23.7% (22.4–25.1%) mods, 17.3% (16.1–18.4%) pods, and 5.4% (4.7–6.2%) disposables. Tanks were the most widely used device type throughout 2016–2020. Mods were second until 2020, when pods overtook them. Among all e-cigarette/HTP users, prevalence of HTP use remains rare (3.4% in 2016 versus 4.2% in 2020), whereas JUUL use has risen from 3.4% in 2018 to 11.8% in 2020. Across all years, nicotine concentrations of ≤ 6 mg/ml were most widely (41.0%; 39.4–42.4%) and ≥ 20 mg/ml least widely used (4.1%; 3.4–4.9%). Among e-cigarette/HTP users, ex-smokers were more likely than current smokers to use mod and tank e-cigarettes, but less likely to use pods, disposables, JUUL and HTPs. In conclusion, despite growing popularity of pods and HTPs worldwide, refillable tank e-cigarettes remain the most widely used device type in England.
Fabrication of 2D-MoSe2 incorporated NiO Nanorods modified electrode for selective detection of glucose in serum samples
Authors: Jeevanandham Gayathri , Vediappan Kumaran , ALOthman Zeid A. , Altalhi Tariq , Sundramoorthy Ashok K.
Published: June 2021

Layered molybdenum diselenide (MoSe2) nanosheets were formed by the weak Van der Waals forces of attraction between Se and Mo atoms. MoSe2has a larger space between the adjacent layers and smaller band gaps in the range of 0.85 to ~ 1.6 eV. In this study, MoSe2nanosheets decorated nickel oxide (NiO) nanorods have been synthesized by hydrothermal method using sodium molybdate and selenium metal powder. NiO/MoSe2composite formation was confirmed by powder X-ray diffraction analysis. In addition, the presence of MoSe2nanosheets on NiO nanorods were confirmed by field emission scanning electron microscopy, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy. The Nyquist plots of NiO/MoSe2coated glassy carbon electrode (GCE) was indicated that it had lower charge transfer resistance compared to NiO/GCE and MoSe2/GCE. Furthermore, as-prepared NiO/MoSe2/GCE was used to detect glucose in alkaline solution by cyclic voltammetry and amperometry techniques. The NiO/MoSe2/GCE was exhibited a linear response for the oxidation of glucose from 50 µM to 15.5 mM (R2 = 0.9842) at 0.5 V by amperometry. The sensor response time and the limit of detection were found to be 2 s and 0.6 µM for glucose. Moreover, selectivity of the NiO/MoSe2sensor was tested in the presence of common interferent molecules such as hydrogen peroxide, fructose, lactose, ascorbic acid, uric acid, and dopamine. It was found that NiO/MoSe2/GCE did not respond to these interfering biomolecules. In addition, NiO/MoSe2/GCE had shown high stability, reproducibility and repeatability. Finally, the practical application of the sensor was demonstrated by detecting glucose in human blood serum with the acceptable recovery.
Interactions of nasal epithelium with macrophages and dendritic cells variously alter urban PM-induced inflammation in healthy, asthma and COPD
Authors: Paplinska-Goryca Magdalena , Misiukiewicz-Stepien Paulina , Proboszcz Malgorzata , Nejman-Gryz Patrycja , Gorska Katarzyna , Zajusz-Zubek Elwira , Krenke Rafal
Published: June 2021

Urban particulate matter (UPM) is an important trigger of airway inflammation. The cross-talk between the external and internal matrix in the respiratory tract occurs due to the transepithelial network of macrophages/dendritic cells. This study characterized the immune processes induced by the epithelium after UPM exposure in special regard to interactions with monocyte-derived dendritic cells (moDCs) and monocyte-derived macrophages (moMφs) in obstructive lung diseases. A triple-cell co-culture model (8 controls, 10 asthma, and 8 patients with COPD) utilized nasal epithelial cells, along with moMφs, and moDCs was exposed to UPM for 24 h. The inflammatory response of nasal epithelial cells to UPM stimulation is affected differently by cell–cell interactions in healthy people, asthma or COPD patients of which the interactions with DCs had the strongest impact on the inflammatory reaction of epithelial cells after UPM exposure. The epithelial remodeling and DCs dysfunction might accelerate the inflammation after air pollution exposure in asthma and COPD.
Profiling temporal dynamics of acetogenic communities in anaerobic digesters using next-generation sequencing and T-RFLP
Authors: Singh Abhijeet , Müller Bettina , Schnürer Anna
Published: June 2021

Acetogens play a key role in anaerobic degradation of organic material and in maintaining biogas process efficiency. Profiling this community and its temporal changes can help evaluate process stability and function, especially under disturbance/stress conditions, and avoid complete process failure. The formyltetrahydrofolate synthetase (FTHFS) gene can be used as a marker for acetogenic community profiling in diverse environments. In this study, we developed a new high-throughput FTHFS gene sequencing method for acetogenic community profiling and compared it with conventional terminal restriction fragment length polymorphism of the FTHFS gene, 16S rRNA gene-based profiling of the whole bacterial community, and indirect analysis via 16S rRNA profiling of the FTHFS gene-harbouring community. Analyses and method comparisons were made using samples from two laboratory-scale biogas processes, one operated under stable control and one exposed to controlled overloading disturbance. Comparative analysis revealed satisfactory detection of the bacterial community and its changes for all methods, but with some differences in resolution and taxonomic identification. FTHFS gene sequencing was found to be the most suitable and reliable method to study acetogenic communities. These results pave the way for community profiling in various biogas processes and in other environments where the dynamics of acetogenic bacteria have not been well studied.
GREB1L overexpression correlates with prognosis and immune cell infiltration in lung adenocarcinoma
Authors: Yu Yilin , Wang Zhiping , Zheng Qunhao , Li Jiancheng
Published: June 2021

GREB1L is a protein-coding gene that is an important paralog of GREB1. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of GREB1L in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between GREB1L and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, HPA, TIMER, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, GREB1L expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high GREB1L expression levels were correlated with a poor OS in LUAD. Additionally, GREB1L expression was independently associated with OS through a multivariate Cox analysis. GSEA analysis revealed enrichment in cell cycle, immune regulation, and methylation. Moreover, high GREB1L expression was associated with poor survival. We also found that the methylation and genetic alteration level was associated with prognosis in patients with LUAD. Finally, an analysis of immune infiltration showed that GREB1L is correlated with immune cell infiltration, PD-1, and PD-L1. In summary, these results indicate that GREB1L is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.
An urgent need for improving thalassemia care due to the wide gap in current real-life practice and clinical practice guidelines
Authors: Ekwattanakit Supachai , Hantaweepant Chattree , Khuhapinant Archrob , Siritanaratkul Noppadol , Viprakasit Vip
Published: June 2021

Based on Thalassemia International Federation clinical practice guidelines (CPG) for non-transfusion dependent and transfusion dependent thalassemia, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications for early detection and proper clinical management. To evaluate the prevalence and the performance of routine surveillance for thalassemia related complications during 2 periods; before and after published CPGs (2012–2014 vs 2015–2017), data from 524 adult thalassemia patients attended at Siriraj hospital were compared among different treating physician groups; thalassemia, private hematology, and internal medicine clinics. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). Iron overload has been widely evaluated (93.1%) followed by liver function test (82.3%). However, the rate of evaluation for other complications were significantly reduced and < 25% of patients were evaluated in several complications. Comparing among clinics, the surveillance rate has increased significantly for several endocrine complications only in patients treated at thalassemia clinic but not in others. This study was the first study that evaluated real-world practical management of thalassemia patient in terms of complication surveillance. This different clinical practice has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand.
Comparative analyses of Mikania (Asteraceae: Eupatorieae) plastomes and impact of data partitioning and inference methods on phylogenetic relationships
Authors: Thode Verônica A. , Oliveira Caetano T. , Loeuille Benoît , Siniscalchi Carolina M. , Pirani José R.
Published: June 2021

We assembled new plastomes of 19 species ofMikaniaand ofAgeratina fastigiata,Litothamnus nitidus,andStevia collina, all belonging to tribe Eupatorieae (Asteraceae). We analyzed the structure and content of the assembled plastomes and used the newly generated sequences to infer phylogenetic relationships and study the effects of different data partitions and inference methods on the topologies. Most phylogenetic studies with plastomes ignore that processes like recombination and biparental inheritance can occur in this organelle, using the whole genome as a single locus. Our study sought to compare this approach with multispecies coalescent methods that assume that different parts of the genome evolve at different rates. We found that the overall gene content, structure, and orientation are very conserved in all plastomes of the studied species. As observed in other Asteraceae, the 22 plastomes assembled here contain two nested inversions in the LSC region. The plastomes show similar length and the same gene content. The two most variable regions withinMikaniaarerpl32-ndhFandrpl16-rps3, while the three genes with the highest percentage of variable sites areycf1,rpoA, andpsbT. We generated six phylogenetic trees using concatenated maximum likelihood and multispecies coalescent methods and three data partitions: coding and non-coding sequences and both combined. All trees strongly support that the sampledMikaniaspecies form a monophyletic group, which is further subdivided into three clades. The internal relationships within each clade are sensitive to the data partitioning and inference methods employed. The trees resulting from concatenated analysis are more similar among each other than to the correspondent tree generated with the same data partition but a different method. The multispecies coalescent analysis indicate a high level of incongruence between species and gene trees. The lack of resolution and congruence among trees can be explained by the sparse sampling (~ 0.45% of the currently accepted species) and by the low number of informative characters present in the sequences. Our study sheds light into the impact of data partitioning and methods over phylogenetic resolution and brings relevant information for the study ofMikaniadiversity and evolution, as well as for the Asteraceae family as a whole.
Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
Authors: Di Carlo Claudia , Sousa Bebiana C. , Manfredi Marcello , Brandi Jessica , Dalla Pozza Elisa , Marengo Emilio , Palmieri Marta , Dando Ilaria , Wakelam Michael J. O. , Lopez-Clavijo Andrea F. , Cecconi Daniela
Published: June 2021

Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.