bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders
Authors: Seidlitz Jakob , Nadig Ajay , Liu Siyuan , Bethlehem Richard A. I. , Vértes Petra E. , Morgan Sarah E. , Váša František , Romero-Garcia Rafael , Lalonde François M. , Clasen Liv S. , Blumenthal Jonathan D. , Paquola Casey , Bernhardt Boris , Wagstyl Konrad , Polioudakis Damon , de la Torre-Ubieta Luis , Geschwind Daniel H. , Han Joan C. , Lee Nancy R. , Murphy Declan G. , Bullmore Edward T. , Raznahan Armin
Published: July 2020

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.
Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways
Authors: Pichler Michael Jakob , Yamada Chihaya , Shuoker Bashar , Alvarez-Silva Camila , Gotoh Aina , Leth Maria Louise , Schoof Erwin , Katoh Toshihiko , Sakanaka Mikiyasu , Katayama Takane , Jin Chunsheng , Karlsson Niclas G. , Arumugam Manimozhiyan , Fushinobu Shinya , Abou Hachem Maher
Published: July 2020

The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here, we describe catabolic pathways that support the growth of Roseburia and Eubacterium members on distinct human milk oligosaccharides (HMOs). The HMO pathways, which include enzymes with a previously unknown structural fold and specificity, were upregulated together with additional glycan-utilization loci during growth on selected HMOs and in co-cultures with Akkermansia muciniphila on mucin, suggesting an additional role in enabling cross-feeding and access to mucin O-glycans. Analyses of 4599 Roseburia genomes underscored the preponderance and diversity of the HMO utilization loci within the genus. The catabolism of HMOs by butyrate-producing Clostridiales may contribute to the competitiveness of this group during the weaning-triggered maturation of the microbiota.
Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells
Authors: Su Chun , Johnson Matthew E. , Torres Annabel , Thomas Rajan M. , Manduchi Elisabetta , Sharma Prabhat , Mehra Parul , Le Coz Carole , Leonard Michelle E. , Lu Sumei , Hodge Kenyaita M. , Chesi Alessandra , Pippin James , Romberg Neil , Grant Struan F. A. , Wells Andrew D.
Published: July 2020

Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of SLE variant accessibility and gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear antibodies characteristic of SLE. Of the ~400 potential regulatory variants identified, 90% exhibit spatial proximity to genes distant in the 1D genome sequence, including variants that loop to regulate the canonical TFH genes BCL6 and CXCR5 as confirmed by genome editing. SLE ‘variant-to-gene’ maps also implicate genes with no known role in TFH/SLE disease biology, including the kinases HIPK1 and MINK1. Targeting these kinases in TFH inhibits production of IL-21, a cytokine crucial for class-switched B cell antibodies. These studies offer mechanistic insight into the SLE-associated regulatory architecture of the human genome.
Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase
Authors: Wilkes M. C. , Siva K. , Chen J. , Varetti G. , Youn M. Y. , Chae H. , Ek F. , Olsson R. , Lundbäck T. , Dever D. P. , Nishimura T. , Narla A. , Glader B. , Nakauchi H. , Porteus M. H. , Repellin C. E. , Gazda H. T. , Lin S. , Serrano M. , Flygare J. , Sakamoto K. M.
Published: July 2020

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.
Low thermal conductivity of iron-silicon alloys at Earth’s core conditions with implications for the geodynamo
Authors: Hsieh Wen-Pin , Goncharov Alexander F. , Labrosse Stéphane , Holtgrewe Nicholas , Lobanov Sergey S. , Chuvashova Irina , Deschamps Frédéric , Lin Jung-Fu
Published: July 2020

Earth’s core is composed of iron (Fe) alloyed with light elements, e.g., silicon (Si). Its thermal conductivity critically affects Earth’s thermal structure, evolution, and dynamics, as it controls the magnitude of thermal and compositional sources required to sustain a geodynamo over Earth’s history. Here we directly measured thermal conductivities of solid Fe and Fe–Si alloys up to 144 GPa and 3300 K. 15 at% Si alloyed in Fe substantially reduces its conductivity by about 2 folds at 132 GPa and 3000 K. An outer core with 15 at% Si would have a conductivity of about 20 W m−1 K−1, lower than pure Fe at similar pressure–temperature conditions. This suggests a lower minimum heat flow, around 3 TW, across the core–mantle boundary than previously expected, and thus less thermal energy needed to operate the geodynamo. Our results provide key constraints on inner core age that could be older than two billion-years.
Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation
Authors: Conte Mattia , Fiorillo Luca , Bianco Simona , Chiariello Andrea M. , Esposito Andrea , Nicodemi Mario
Published: July 2020

The spatial organization of chromosomes has key functional roles, yet how chromosomes fold remains poorly understood at the single-molecule level. Here, we employ models of polymer physics to investigate DNA loci in human HCT116 and IMR90 wild-type and cohesin depleted cells. Model predictions on single-molecule structures are validated against single-cell imaging data, providing evidence that chromosomal architecture is controlled by a thermodynamics mechanism of polymer phase separation whereby chromatin self-assembles in segregated globules by combinatorial interactions of chromatin factors that include CTCF and cohesin. The thermodynamics degeneracy of single-molecule conformations results in broad structural and temporal variability of TAD-like contact patterns. Globules establish stable environments where specific contacts are highly favored over stochastic encounters. Cohesin depletion reverses phase separation into randomly folded states, erasing average interaction patterns. Overall, globule phase separation appears to be a robust yet reversible mechanism of chromatin organization where stochasticity and specificity coexist.
A sequential methodology for the rapid identification and characterization of breast cancer-associated functional SNPs
Authors: Zhao Yihan , Wu Di , Jiang Danli , Zhang Xiaoyu , Wu Ting , Cui Jing , Qian Min , Zhao Jean , Oesterreich Steffi , Sun Wei , Finkel Toren , Li Gang
Published: July 2020

GWAS cannot identify functional SNPs (fSNP) from disease-associated SNPs in linkage disequilibrium (LD). Here, we report developing three sequential methodologies including Reel-seq (Regulatory element-sequencing) to identify fSNPs in a high-throughput fashion, SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify fSNP-bound proteins and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to detect allele-specific protein:fSNP binding. We first apply Reel-seq to screen a library containing 4316 breast cancer-associated SNPs and identify 521 candidate fSNPs. As proof of principle, we verify candidate fSNPs on three well-characterized loci: FGFR2, MAP3K1 and BABAM1. Next, using SDCP-MS and AIDP-Wb, we rapidly identify multiple regulatory factors that specifically bind in an allele-imbalanced manner to the fSNPs on the FGFR2 locus. We finally demonstrate that the factors identified by SDCP-MS can regulate risk gene expression. These data suggest that the sequential application of Reel-seq, SDCP-MS, and AIDP-Wb can greatly help to translate large sets of GWAS data into biologically relevant information.
Collective dipole effects in ionic transport under electric fields
Authors: Salles N. , Martin-Samos L. , de Gironcoli S. , Giacomazzi L. , Valant M. , Hemeryck A. , Blaise P. , Sklenard B. , Richard N.
Published: July 2020

In the context of ionic transport in solids, the variation of a migration barrier height under electric fields is traditionally assumed to be equal to the classical electric work of a point charge that carries the transport charge. However, how reliable is this phenomenological model and how does it fare with respect to Modern Theory of Polarization? In this work, we show that such a classical picture does not hold in general as collective dipole effects may be critical. Such effects are unraveled by an appropriate polarization decomposition and by an expression that we derive, which defines the equivalent polarization-work charge. The equivalent polarization-work charge is not equal neither to the transported charge, nor to the Born effective charge of the migrating atom alone, but it is defined by the total polarization change at the transition state. Our findings are illustrated by oxygen charged defects in MgO and in SiO2.
Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth
Authors: Ishak Gabra Mari B. , Yang Ying , Li Haiqing , Senapati Parijat , Hanse Eric A. , Lowman Xazmin H. , Tran Thai Q. , Zhang Lishi , Doan Linda T. , Xu Xiangdong , Schones Dustin E. , Fruman David A. , Kong Mei
Published: July 2020

Tumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Metabolomic analysis reveals that dietary uptake of glutamine effectively increases the concentration of glutamine in tumours and its downstream metabolite, αKG, without increasing biosynthetic intermediates necessary for cell proliferation. Mechanistically, we find that glutamine supplementation uniformly alters the transcriptome in tumours. Our data further demonstrate that increase in intra-tumoural αKG concentration drives hypomethylation of H3K4me3, thereby suppressing epigenetically-activated oncogenic pathways in melanoma. Therefore, our findings provide evidence that glutamine supplementation can serve as a potential dietary intervention to block melanoma tumour growth and sensitize tumours to targeted therapy via epigenetic reprogramming.
A Keplerian Ag90 nest of Platonic and Archimedean polyhedra in different symmetry groups
Authors: Su Yan-Min , Wang Zhi , Schein Stan , Tung Chen-Ho , Sun Di
Published: July 2020

Polyhedra are ubiquitous in chemistry, biology, mathematics and other disciplines. Coordination-driven self-assembly has created molecules mimicking Platonic, Archimedean and even Goldberg polyhedra, however, nesting multiple polyhedra in one cluster is challenging, not only for synthesis but also for determining the alignment of the polyhedra. Here, we synthesize a nested Ag90 nanocluster under solvothermal condition. This pseudo-Th symmetric Ag90 ball contains three concentric Ag polyhedra with apparently incompatible symmetry. Specifically, the inner (Ag6) and middle (Ag24) shells are octahedral (Oh), an octahedron (a Platonic solid with six 3.3.3.3 vertices) and a truncated octahedron (an Archimedean solid with twenty-four 4.6.6 vertices), whereas the outer (Ag60) shell is icosahedral (Ih), a rhombicosidodecahedron (an Archimedean solid with sixty 3.4.5.4 vertices). The Ag90 nanocluster solves the apparent incompatibility with the most symmetric arrangement of 2- and 3-fold rotational axes, similar to the arrangement in the model called Kepler’s Kosmos, devised by the mathematician John Conway.
Rational flux-tuning of Halomonas bluephagenesis for co-production of bioplastic PHB and ectoine
Authors: Ma Hong , Zhao Yiqing , Huang Wuzhe , Zhang Lizhan , Wu Fuqing , Ye Jianwen , Chen Guo-Qiang
Published: July 2020

Ectoine, a compatible solute synthesized by many halophiles for hypersalinity resistance, has been successfully produced by metabolically engineeredHalomonas bluephagenesis, which is a bioplastic poly(3-hydroxybutyrate) producer allowing open unsterile and continuous conditions. Here we report a de novo synthesis pathway for ectoine constructed into the chromosome ofH. bluephagenesisutilizing two inducible systems, which serve to fine-tune the transcription levels of three clusters related to ectoine synthesis, includingectABC,lysCandasdbased on a GFP-mediated transcriptional tuning approach. Combined with bypasses deletion, the resulting recombinantH. bluephagenesisTD-ADEL-58 is able to produce 28 g L−1ectoine during a 28 h fed-batch growth process. Co-production of ectoine and PHB is achieved to 8 g L−1ectoine and 32 g L−1dry cell mass containing 75% PHB after a 44 h growth.H. bluephagenesisdemonstrates to be a suitable co-production chassis for polyhydroxyalkanoates and non-polymer chemicals such as ectoine.
Three-terminal Weyl complex with double surface arcs in a cubic lattice
Authors: Huang Zhenqiao , Chen Zhongjia , Zheng Baobing , Xu Hu
Published: July 2020

Exploring unconventional topological quasiparticles and their associated exotic physical properties has become a hot topic in condensed matter physics, thus stimulating extensive interest in recent years. Here, in contrast to the double-Weyl phonons (the topological chiral charge +2) in the trigonal and hexagonal crystal systems, we propose that the unconventional double-Weyl without counterparts in high-energy physics can emerge in the phonons of cubic structures, i.e., SrSi2. Employing a two-band k ⋅ p Hamiltonian, we prove that the quadratic double-Weyl nodes are protected by the fourfold screw rotational symmetry $${\tilde{C}}_{4}$$

C

̃

4

. Strikingly, we find that the surface arcs are terminated with the Weyl nodes that possess unequal topological charges with opposite sign (i.e., +2 and −1), leading to unique three-terminal Weyl complex (one quadratic double-Weyl and two linear single-Weyl) with double surface arcs in SrSi2. In addition, we apply a uniaxial tensile strain along z-axis to examine the evolution of the three-terminal Weyl complex when the corresponding symmetries are broken. Our work not only provides an ideal candidate for the realization of the quadratic double-Weyl and the corresponding unique surface arc states, but also broadens the understanding of topological Weyl physics.
Probabilistic identification of saccharide moieties in biomolecules and their protein complexes
Authors: Dashti Hesam , Westler William M. , Wedell Jonathan R. , Demler Olga V. , Eghbalnia Hamid R. , Markley John L. , Mora Samia
Published: July 2020

The chemical composition of saccharide complexes underlies their biomedical activities as biomarkers for cardiometabolic disease, various types of cancer, and other conditions. However, because these molecules may undergo major structural modifications, distinguishing between compounds of saccharide and non-saccharide origin becomes a challenging computational problem that hinders the aggregation of information about their bioactive moieties. We have developed an algorithm and software package called “Cheminformatics Tool for Probabilistic Identification of Carbohydrates” (CTPIC) that analyzes the covalent structure of a compound to yield a probabilistic measure for distinguishing saccharides and saccharide-derivatives from non-saccharides. CTPIC analysis of the RCSB Ligand Expo (database of small molecules found to bind proteins in the Protein Data Bank) led to a substantial increase in the number of ligands characterized as saccharides. CTPIC analysis of Protein Data Bank identified 7.7% of the proteins as saccharide-binding. CTPIC is freely available as a webservice at (http://ctpic.nmrfam.wisc.edu).
Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis
Authors: Kano Michiko , Grinsvall Cecilia , Ran Qian , Dupont Patrick , Morishita Joe , Muratsubaki Tomohiko , Mugikura Shunji , Ly Huynh Giao , Törnblom Hans , Ljungberg Maria , Takase Kei , Simrén Magnus , Van Oudenhove Lukas , Fukudo Shin
Published: July 2020

Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.
A Multidimensional Approach of Surgical Mortality Assessment and Stratification (Smatt Score)
Authors: Cutti Sara , Klersy Catherine , Favalli Valentina , Cobianchi Lorenzo , Muzzi Alba , Rettani Marco , Tavazzi Guido , Delmonte Maria Paola , Peloso Andrea , Arbustini Eloisa , Marena Carlo
Published: July 2020

Surgical mortality is the most significant measure of outcome in surgical healthcare. The objective was to assess surgical 30 days mortality and improve the identification of predictors for personalized risk stratification of patients undergoing elective and emergency surgery. The study was conducted as a single-center cohort retrospective observational study, based on the analysis of data collected from patients surgically treated from 2002 to 2014 in a multi-disciplinary research and care referral hospital with global case mix of 1.27. The overall in-hospital mortality rate was 1.89% (95% CI 1.82–1.95). In the univariable analysis, numerous predictors were significantly associated with in-hospital death following surgery. In the multivariable model, age, BMI (Body Mass Index), ASA score, department, planned surgical complexity, surgical priority, previous surgeries in the same hospitalization, cardiovascular, pulmonary, hepato-renal comorbidities, drug intolerance, cancer and AIDS were independently associated with mortality after surgery. At logistic regression, the computed SMATT score (graded 0–100), generated on the basis of multivariate analysis, demonstrated a good discrimination (10-fold cross-validated AUC-ROC 0.945, 95%CI 0.941–0.948) and correctly classified 98.5% of those admissions with a probability of death >50%. The novel SMATT score, based on individual preoperative and surgical factors, accurately predicts mortality and provides dynamic information of the risk in redo/reoperative surgery.
Computational studies on the gas phase reaction of methylenimine (CH2NH) with water molecules
Authors: Ali Mohamad Akbar
Published: July 2020

In this work, we used quantum chemical methods and chemical kinetic models to answer the question of whether or not formaldehyde (CH2O) and ammonia (NH3) can be produced from gas phase hydration of methylenimine (CH2NH). The potential energy surfaces (PESs) of CH2NH + H2O → CH2O + NH3 and CH2NH + 2H2O → CH2O + NH3 + H2O reactions were computed using CCSD(T)/6–311++G(3d,3pd)//M06-2X/6–311++G(3d,3pd) level. The temperature-and pressure-dependent rate constants were calculated using variational transition state theory (VTST), microcanonical variational transition state theory $$(\mu VTST)$$(μVTST) and Rice–Ramsperger–Kassel–Marcus/master equation (RRKM/ME) simulations. The PES along the reaction path forming a weakly bound complex (CH2NH⋯H2O) was located using VTST and $$\mu$$μVTST, however, the PES along the tight transition state was characterized by VTST with small curvature tunneling (SCT) approach. The results show that the formation of CH2NH + H2O → CH2NH⋯H2O is pressure -and temperature-dependent. The calculated atmospheric lifetimes of CH2NH⋯H2O (~ 8 min) are too short to undergo secondary bimolecular reactions with other atmospheric species. Our results suggest that the formation of CH2O and NH3 likely to occur in the combustion of biomass burning but the rate of formation CH2O and NH3 is predicted to be negligible under atmospheric conditions. When a second water molecule is added to the reaction, the results suggest that the rates of formation of CH2O and NH3 remain negligible.
Observational evidence of wildfire-promoting soil moisture anomalies
Authors: O Sungmin , Hou Xinyuan , Orth Rene
Published: July 2020

Wildfires can destroy property and vegetation, thereby threatening people’s livelihoods and food security. Soil moisture and biomass are important determinants of wildfire hazard. Corresponding novel satellite-based observations therefore present an opportunity to better understand these disasters globally and across different climate regions. We sampled 9,840 large wildfire events from around the globe, between 2001 and 2018, along with respective surface soil moisture and biomass data. Using composites across fire events in similar climate regions, we show contrasting soil moisture anomalies in space and time preceding large wildfires. In arid regions, wetter-than-average soils facilitate sufficient biomass growth required to fuel large fires. In contrast, in humid regions, fires are typically preceded by dry soil moisture anomalies, which create suitable ignition conditions and flammability in an otherwise too wet environment. In both regions, soil moisture anomalies continuously decrease in the months prior to fire occurrence, often from above-normal to below-normal. These signals are most pronounced in sparsely populated areas with low human influence, and for larger fires. Resolving natural soil moisture–fire interactions supports fire modelling and facilitates improved fire predictions and early warning.
Effects of Roundup and its main component, glyphosate, upon mammalian sperm function and survival
Authors: Nerozzi Chiara , Recuero Sandra , Galeati Giovanna , Bucci Diego , Spinaci Marcella , Yeste Marc
Published: July 2020

The wide use of glyphosate-based herbicides (GBHs) has become a matter of concern due to its potential harmful effects on human health, including men fertility.
This study sought to investigate, using the pig as a model, the impact of pure glyphosate and its most known commercial formulation, Roundup, on sperm function and survival. With this purpose, fresh commercial semen doses were incubated with different concentrations (0–360 µg/mL) of glyphosate (GLY; exp. 1) or Roundup, at the equivalent GLY concentration (exp. 2), at 38 °C for 3 h. Glyphosate at 360 µg/mL significantly (P < 0.05) decreased sperm motility, viability, mitochondrial activity and acrosome integrity but had no detrimental effect at lower doses. On the other hand, Roundup did significantly (P < 0.05) reduce sperm motility at ≥ 5 µg/mL GLY-equivalent concentration; mitochondrial activity at ≥ 25 µg/mL GLY-equivalent concentration; and sperm viability and acrosome integrity at ≥ 100 µg/mL GLY-equivalent concentration as early as 1 h of incubation. In a similar fashion, GLY and Roundup did not inflict any detrimental effect on sperm DNA integrity. Taken together, these data indicate that, while both glyphosate and Roundup exert a negative impact on male gametes, Roundup is more toxic than its main component, glyphosate.
Machine learning-based prediction of acute severity in infants hospitalized for bronchiolitis: a multicenter prospective study
Authors: Raita Yoshihiko , Camargo Carlos A. , Macias Charles G. , Mansbach Jonathan M. , Piedra Pedro A. , Porter Stephen C. , Teach Stephen J. , Hasegawa Kohei
Published: July 2020

We aimed to develop machine learning models to accurately predict bronchiolitis severity, and to compare their predictive performance with a conventional scoring (reference) model. In a 17-center prospective study of infants (aged < 1 year) hospitalized for bronchiolitis, by using routinely-available pre-hospitalization data as predictors, we developed four machine learning models: Lasso regression, elastic net regression, random forest, and gradient boosted decision tree. We compared their predictive performance—e.g., area-under-the-curve (AUC), sensitivity, specificity, and net benefit (decision curves)—using a cross-validation method, with that of the reference model. The outcomes were positive pressure ventilation use and intensive treatment (admission to intensive care unit and/or positive pressure ventilation use). Of 1,016 infants, 5.4% underwent positive pressure ventilation and 16.0% had intensive treatment. For the positive pressure ventilation outcome, machine learning models outperformed reference model (e.g., AUC 0.88 [95% CI 0.84–0.93] in gradient boosted decision tree vs 0.62 [95% CI 0.53–0.70] in reference model), with higher sensitivity (0.89 [95% CI 0.80–0.96] vs. 0.62 [95% CI 0.49–0.75]) and specificity (0.77 [95% CI 0.75–0.80] vs. 0.57 [95% CI 0.54–0.60]). The machine learning models also achieved a greater net benefit over ranges of clinical thresholds. Machine learning models consistently demonstrated a superior ability to predict acute severity and achieved greater net benefit.
A novel self-seeding method for particle image velocimetry measurements of subsonic and supersonic flows
Authors: Nematollahi Omid , Samsam-Khayani Hadi , Nili-Ahmadabadi Mahdi , Yoon Sang Youl , Kim Kyung Chun
Published: July 2020

A self-seeding particle method is proposed for particle image velocimetry measurements in closed cycles such as Organic Rankine Cycles. Condensed droplets of vapor are used as tracers in a closed cycle for both subsonic and supersonic regimes. A free jet of R245fa in the vapor phase is examined in a case study with two different nozzle pressure ratios of 5.1 and 2.1 to evaluate the tracer particles in both supersonic and subsonic conditions. A simple turbulent jet in subsonic conditions and an under-expanded jet are observed in high supersonic conditions. The flow structures of the under-expanded jet are captured using the proposed method, and vivid images of the Mach disk and shock cells are obtained. A series of Schlieren photography experiments are performed to validate the proposed method. The results show that the method can be a good candidate for tracer particles in the closed cycles where condensation of the working fluid is possible.
Development of fluorescence oligonucleotide probes based on cytosine- and guanine-rich sequences
Authors: Dembska Anna , Świtalska Angelika , Fedoruk-Wyszomirska Agnieszka , Juskowiak Bernard
Published: July 2020

The properties of cytosine- and guanine-rich oligonucleotides contributed to employing them as sensing elements in various biosensors. In this paper, we report our current development of fluorescence oligonucleotide probes based on i-motif or G-quadruplex forming oligonucleotides for cellular measurements or bioimaging applications. Additionally, we also focus on the spectral properties of the new fluorescent silver nanoclusters based system (ChONC12-AgNCs) that is able to anchor at the Langmuir monolayer interface, which is mimicking the surface of living cells membrane.
Bax and Bak jointly control survival and dampen the early unfolded protein response in pancreatic β-cells under glucolipotoxic stress
Authors: White Sarah A. , Zhang Lisa S. , Pasula Daniel J. , Yang Yu Hsuan Carol , Luciani Dan S.
Published: July 2020

ER stress and apoptosis contribute to the loss of pancreatic β-cells under pro-diabetic conditions of glucolipotoxicity. Although activation of canonical intrinsic apoptosis is known to require pro-apoptotic Bcl-2 family proteins Bax and Bak, their individual and combined involvement in glucolipotoxic β-cell death are not known. It has also remained an open question if Bax and Bak in β-cells have non-apoptotic roles in mitochondrial function and ER stress signaling, as suggested in other cell types. Using mice with individual or combined β-cell deletion of Bax and Bak, we demonstrated that glucolipotoxic β-cell death in vitro occurs by both non-apoptotic and apoptotic mechanisms, and the apoptosis could be triggered by either Bax or Bak alone. In contrast, they had non-redundant roles in mediating staurosporine-induced apoptosis. We further established that Bax and Bak do not affect normal glucose-stimulated β-cell Ca2+ responses, insulin secretion, or in vivo glucose tolerance. Finally, our experiments revealed that combined deletion of Bax and Bak amplified the unfolded protein response in islets during the early stages of chemical- or glucolipotoxicity-induced ER stress. These findings shed new light on roles of the core apoptosis machinery in β-cell survival and stress signals of importance for the pathobiology of diabetes.
A regression algorithm for accelerated lattice QCD that exploits sparse inference on the D-Wave quantum annealer
Authors: Nguyen Nga T. T. , Kenyon Garrett T. , Yoon Boram
Published: July 2020

We propose a regression algorithm that utilizes a learned dictionary optimized for sparse inference on a D-Wave quantum annealer. In this regression algorithm, we concatenate the independent and dependent variables as a combined vector, and encode the high-order correlations between them into a dictionary optimized for sparse reconstruction. On a test dataset, the dependent variable is initialized to its average value and then a sparse reconstruction of the combined vector is obtained in which the dependent variable is typically shifted closer to its true value, as in a standard inpainting or denoising task. Here, a quantum annealer, which can presumably exploit a fully entangled initial state to better explore the complex energy landscape, is used to solve the highly non-convex sparse coding optimization problem. The regression algorithm is demonstrated for a lattice quantum chromodynamics simulation data using a D-Wave 2000Q quantum annealer and good prediction performance is achieved. The regression test is performed using six different values for the number of fully connected logical qubits, between 20 and 64. The scaling results indicate that a larger number of qubits gives better prediction accuracy.
NRAS mutant E132K identified in young-onset sporadic colorectal cancer and the canonical mutants G12D and Q61K affect distinct oncogenic phenotypes
Authors: Yu Ryan Timothy D. , Garcia Reynaldo L.
Published: July 2020

Recent data show a global increase in colorectal cancer (CRC) cases among younger demographics, which portends poorer prognosis. The cause of rising incidence is uncertain, and its mutational landscape remains largely unexplored, including those in genes of the epidermal growth factor receptor pathway. Among these are NRAS mutants where there is paucity of functional studies compared to KRAS. Here, the novel NRAS mutant E132K, identified in three tumor samples from Filipino young-onset, sporadic colorectal cancer patients, was investigated for its effects on different cancer hallmarks, alongside the NRAS canonical mutants G12D and Q61K which are yet poorly characterized in the context of CRC. The novel NRAS mutant E132K and the canonical G12D and Q61K mutants show resistance to apoptosis, cytoskeletal reorganization, and loss of adhesion. In contrast to activating KRAS mutations, including the analogous KRAS G12D and Q61K mutations, all three NRAS mutants have no apparent effect on cell proliferation and motility. The results highlight the need to characterize isoform- and mutation-specific oncogenic phenotypes which can have repercussions in disease management and choice of therapeutic intervention. Further analyses of young-onset versus late-onset CRC datasets are necessary to qualify NRAS E132K as a biomarker for the young-onset subtype.
Proteome analysis revealed the essential functions of protein phosphatase PP2A in the induction of Th9 cells
Authors: Roy Suyasha , Goel Renu , Aggarwal Suruchi , Asthana Shailendra , Yadav Amit Kumar , Awasthi Amit
Published: July 2020

Proteomic analysis identifies post-translational functions of proteins, which remains obscure in transcriptomics. Given the important functions of Th9 cells in anti-tumor immunity, we performed proteome analysis of Th9 cells to understand the involvement of proteins that might be crucial for the anti-tumor functions of Th9 cells. Here we performed a comprehensive proteomic analysis of murine Th0 and Th9 cells, and identified proteins that are enriched in Th9 cells. Pathway analysis identified an abundance of phosphoproteins in the proteome of Th9 cells as compared to Th0 cells. Among upregulated phosphoproteins, Ppp2ca (catalytic subunit of protein phosphatase, PP2A) was found to be highly enriched in Th9 cells. Although the role of PP2A has been shown to regulate the differentiation and functions of Th1, Th2, Th17 and Tregs, its role in the differentiation and functions of Th9 cells is not identified yet. Here we found that PP2A is required for the induction of Th9 cells, as PP2A inhibition leads to the suppression of IL-9 and expression of key transcription factors of Th9 cells. PP2A inhibition abrogates Th9 cell-mediated anti-tumor immune response in B16-OVA melanoma tumor model. Thus, we report that PP2A is essential for the differentiation and anti-tumor functions of Th9 cells.
Chloroplast DNA analysis of the invasive weed, Himalayan balsam (Impatiens glandulifera), in the British Isles
Authors: Kurose Daisuke , Pollard Kathryn M. , Ellison Carol A.
Published: July 2020

Impatiens glanduliferaor Himalayan balsam (HB), is an invasive alien weed throughout the British Isles (BI). Classical biological control of HB in the BI using a rust fungus from the Himalayan native range was implemented in 2014. However, not all HB populations are susceptible to the two rust strains currently released. Additional strains are needed that infect resistant populations in order to achieve successful control. These are best sourced from the historical collecting sites. A molecular analysis was conducted using six chloroplast DNA sequences from leaf material from across the BI and the native range. Herbarium samples collected in the Himalayas between 1881 and 1956 were also included. Phylogenetic analyses resulted in the separation of two distinct groups, one containing samples from the BI and the native range, and the other from the BI only; suggesting that HB was introduced into the BI on at least two occasions. The former group is composed of two subgroups, indicating a third introduction. Ten and 15 haplotypes were found in the introduced and native range respectively, and with two of these found in both regions. Results show where to focus future surveys in the native range to find more compatible rust strains.
Smoking and Epstein–Barr virus infection in multiple sclerosis development
Authors: Hedström Anna Karin , Huang Jesse , Brenner Nicole , Butt Julia , Hillert Jan , Waterboer Tim , Kockum Ingrid , Olsson Tomas , Alfredsson Lars
Published: July 2020

It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p < 0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2–0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI − 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004–0.4), but not between past smoking and IM history (AP − 0.06, 95% CI − 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved.
Spectrum of biopsy proven renal diseases in Central China: a 10-year retrospective study based on 34,630 cases
Authors: Hu Ruimin , Quan Songxia , Wang Yingzi , Zhou Yali , Zhang Ying , Liu Lu , Zhou Xin J. , Xing Guolan
Published: July 2020

Chronic kidney diseases have become a major issue worldwide. The spectrum of biopsy proven renal diseases differs between locations and changes over time. It is therefore essential to describe the local epidemiological trends and the prevalence of renal biopsy in various regions to shine new light on the pathogenesis of various renal diseases and provide a basis for further hypothesis-driven research. We retrospectively analyzed 34,630 hospitalized patients undergoing native renal biopsy between January 1, 2009 and December 31, 2018. Indications for renal biopsy and histological diagnosis were analyzed to describe the prevalence of renal biopsy, and changing prevalence between period 1 (2009–2013) and period 2 (2014–2018) were further analyzed. Nephrotic syndrome (NS) was the most common indication for biopsy. Membranous nephropathy (MN, 24.96%) and IgA nephropathy (IgAN, 24.09%) were the most common primary glomerulonephritis (PGN). MN was most common in adults, with IgAN more prevalent in children. Lupus nephritis (LN) was the most common secondary glomerulonephritis (SGN) in adults, while Henöch–Schönlein purpura nephritis (HSPN) in children. The prevalence of MN increased significantly and nearly doubled from period 1 (15.98%) to period 2 (30.81%) (P = 0.0004). The same trend appeared with membranoproliferative glomerulonephritis (MPGN), diabetic nephropathy (DN) and obesity-related glomerulopathy (ORG), while the frequencies of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), LN and hepatitis B associated glomerulonephritis (HBV-GN) significantly decreased between the two intervals. NS was the most common indication for biopsy across all age groups and genders. MN has overtaken IgAN to become the most common PGN in adults, while IgAN was the most common PGN in children. LN was the most common SGN in adults, and HSPN the most common in children.
HEBE, a novel positive regulator of senescence in Solanum lycopersicum
Authors: Forlani Sara , Cozzi Carolina , Rosa Stefano , Tadini Luca , Masiero Simona , Mizzotti Chiara
Published: July 2020

Leaf senescence and plant aging are traits of great interest for breeders. Senescing cells undergo important physiological and biochemical changes, while cellular structures such as chloroplasts are degraded with dramatic metabolic consequences for the whole plant. The possibility of prolonging the photosynthetic ability of leaves could positively impact the plant’s life span with benefits for biomass production and metabolite accumulation; plants with these characteristics display a stay-green phenotype. A group of plant transcription factors known as NAC play a pivotal role in controlling senescence: here we describe the involvement of the tomato NAC transcription factor Solyc12g036480, which transcript is present in leaves and floral buds. Since its silencing delays leaf senescence and prevents plants from ageing, we renamed Solyc12g0364 HḖBĒ, for the Greek goddess of youth. In this manuscript we describe how HEB downregulation negatively affects the progression of senescence, resulting in changes in transcription of senescence-promoting genes, as well as the activity of enzymes involved in chlorophyll degradation, thereby explaining the stay-green phenotype.
Measured resting metabolic rate, respiratory quotient, and body composition in patients with narcolepsy: a preliminary report of a case–control study
Authors: Abulmeaty Mahmoud M. A. , BaHammam Ahmed S. , Aljuraiban Ghadeer S. , Almajwal Ali M. , Aldosari Mona S.
Published: July 2020

This case–control study compared the body composition, resting metabolic rate (RMR), and respiratory quotient (RQ) of narcolepsy patients with those of body mass index (BMI)- gender and age-matched controls. This study included 14 male patients with narcolepsy and 14 matched controls. The narcolepsy patients were subdivided into two subgroups (n = 7/each): those with cataplexy (NT1) and those without cataplexy (NT2). Anthropometric measurements, bioelectric impedance analysis, and indirect calorimetry were used in addition to the calculation of common body-composition indices (conicity index, abdominal volume index, and body adiposity index). Our results showed no significant difference in fat percentage, fat mass, fat-free mass, and TBW among NT1, NT2, and controls (p > 0.05). Compared to matched controls, there was a reduction of muscle mass in both NT1 and NT2 subgroups. The RMR was similar in all groups, while patients in the NT1/NT2 subgroups had a lower RQ, used more fat and fewer carbohydrates during the fasting period. These findings give an insight into the distinctive state of altered metabolism in patients with narcolepsy, especially the resting metabolic rate, which was not altered in NT1 vs. NT2 compared to the controls when matched for BMI, age, and gender.
Synthesis of mesoporous SnO2/NiO nanocomposite using modified sol–gel method and its electrochemical performance as electrode material for supercapacitors
Authors: Varshney Bhaskar , Siddiqui M. J. , Anwer A. Hakeem , Khan M. Zain , Ahmed Faheem , Aljaafari Abdullah , Hammud Hassan H. , Azam Ameer
Published: July 2020

In this research work, SnO2, NiO and SnO2/NiO nanocomposites were synthesized at low temperature by modified sol–gel method using ultrasonication. Prepared samples were investigated for their properties employing various characterization techniques. X-ray diffraction (XRD) patterns confirmed the purity and phase of the samples as no secondary phase was detected. The average crystallite size of the nanocomposites was found to decrease from 19.24 to 4.53 nm with the increase in NiO concentration. It was confirmed from SEM micrographs that the material has mesoporous morphology. This mesoporous morphology resulted in the increase of the surface to mass ratio of the material, which in turn increases the specific capacitance of the material. The UV–Visible spectra showed the variation in the band gap of SnO2/NiO at different weight ratio ranging from 3.49 to 3.25 eV on increasing NiO concentration in the samples. These composites with different mass ratio of SnO2 and NiO were also characterized by FT-IR spectroscopy that showed shifting of the peaks centered at 545 cm−1 in the spectra for NiO/SnO2 nanocomposite. The analysis of the electrochemical performance of the material was done with the help of cyclic voltammetry and Galvanostatic charge–discharge. The specific capacitance of the synthesized samples with different concentration of SnO2 and NiO was analyzed at different scan rates of 5 to 100 mV/s. Interestingly, 7:1 mass ratio of NiO and SnO2 (SN7) nanocomposite exhibited a maximum specific capacitance of ~ 464 F/g at a scan rate of 5 mV/s and good capacitance retention of 87.24% after 1,000 cycles. These excellent electrochemical properties suggest that the SnO2/NiO nanocomposite can be used for high energy density supercapacitor electrode material.
Human-like maternal left-cradling bias in monkeys is altered by social pressure
Authors: Boulinguez-Ambroise Grégoire , Pouydebat Emmanuelle , Disarbois Éloïse , Meguerditchian Adrien
Published: July 2020

About 66–72% of human mothers cradle their infants on their left side. Given that left-cradling exposes the baby’s face to the mother’s left visual field (i.e., mainly projected to her right hemisphere) and is altered by emotional states such as stress, maternal left-cradling was interpreted as reflecting right-hemispheric dominance for emotional processing. Whether this phenomenon is unique to human evolution is still in debate. In the present study we followed 44 olive baboon (Papio anubis) mothers and their infants in different social groups. We found that a maternal cradling bias exists and is predominantly towards the left in a similar proportion as in humans, but shifts toward a right bias in mothers living in high density groups. The sensitivity of left-cradling to social pressure highlights its potential links with the mother’s stress as reported in humans. Our finding clearly illustrates the phylogenetic continuity between humans and Old-World monkeys concerning this lateralization and its potential links with hemispheric specialization for emotions, inherited from a common ancestor 25–35 million years ago.