bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent genomic and pharmacological evidence of PI3K/GSK3 signaling alterations in neurons from schizophrenia patients
Authors: Stertz Laura , Di Re Jessica , Pei Guangsheng , Fries Gabriel R. , Mendez Emily , Li Shenglan , Smith-Callahan Laura , Raventos Henriette , Tipo Jerricho , Cherukuru Rohan , Zhao Zhongming , Liu Ying , Jia Peilin , Laezza Fernanda , Walss-Bass Consuelo 
Published: December 2020

AbstractHuman-induced pluripotent stem cells (hiPSCs) allow for the establishment of brain cellular models of psychiatric disorders that account for a patient’s genetic background. Here, we conducted an RNA-sequencing profiling study of hiPSC-derived cell lines from schizophrenia (SCZ) subjects, most of which are from a multiplex family, from the population isolate of the Central Valley of Costa Rica. hiPSCs, neural precursor cells, and cortical neurons derived from six healthy controls and seven SCZ subjects were generated using standard methodology. Transcriptome from these cells was obtained using Illumina HiSeq 2500, and differential expression analyses were performed using DESeq2 (|fold change|>1.5 and false discovery rate < 0.3), in patients compared to controls. We identified 454 differentially expressed genes in hiPSC-derived neurons, enriched in pathways including phosphoinositide 3-kinase/glycogen synthase kinase 3 (PI3K/GSK3) signaling, with serum-glucocorticoid kinase 1 (SGK1), an inhibitor of glycogen synthase kinase 3β, as part of this pathway. We further found that pharmacological inhibition of downstream effectors of the PI3K/GSK3 pathway, SGK1 and GSK3, induced alterations in levels of neurite markers βIII tubulin and fibroblast growth factor 12, with differential effects in patients compared to controls. While demonstrating the utility of hiPSCs derived from multiplex families to identify significant cell-specific gene network alterations in SCZ, these studies support a role for disruption of PI3K/GSK3 signaling as a risk factor for SCZ.
NOP10 predicts lung cancer prognosis and its associated small nucleolar RNAs drive proliferation and migration
Authors: Cui Chunhong , Liu Yi , Gerloff Dennis , Rohde Christian , Pauli Cornelius , Köhn Marcel , Misiak Danny , Oellerich Thomas , Schwartz Schraga , Schmidt Lars-Henning , Wiewrodt Rainer , Marra Alessandro , Hillejan Ludger , Bartel Frank , Wickenhauser Claudia , Hüttelmaier Stefan , Göllner Stefanie , Zhou Fengbiao , Edemir Bayram , Müller-Tidow Carsten 
Published: December 2020

AbstractNon-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide underlining the urgent need for new biomarkers and therapeutic targets for this disease. Long noncoding RNAs are critical players in NSCLC but the role of small RNA species is not well understood. In the present study, we investigated the role of H/ACA box small nucleolar RNAs (snoRNAs) and snoRNA-bound ribonucleoproteins (snoRNPs) in the tumorigenesis of NSCLC. H/ACA box snoRNPs including the NOP10 core protein were highly expressed in NSCLC. High levels of either NOP10 mRNA or protein were associated with poor prognosis in NSCLC patients. Loss of NOP10 and subsequent reduction of H/ACA box snoRNAs and rRNA pseudouridylation inhibited lung cancer cell growth, colony formation, migration, and invasion. A focused CRISPR/Cas9 snoRNA knockout screen revealed that genomic deletion of SNORA65, SNORA7A, and SNORA7B reduced proliferation of lung cancer cells. In line, high levels of SNORA65, SNORA7A, and SNORA7B were observed in primary lung cancer specimens with associated changes in rRNA pseudouridylation. Knockdown of either SNORA65 or SNORA7A/B inhibited growth and colony formation of NSCLC cell lines. Our data indicate that specific H/ACA box snoRNAs and snoRNA-associated proteins such as NOP10 have an oncogenic role in NSCLC providing new potential biomarkers and therapeutic targets for the disease.
Perspectives from the Society for Pediatric Research: Probiotic use in urinary tract infections, atopic dermatitis, and antibiotic-associated diarrhea: an overview
Authors: Forster Catherine S. , Hsieh Michael H. , Cabana Michael D. 
Published: December 2020

AbstractProbiotics have received significant attention within both the scientific and lay communities for their potential health-promoting properties, including the treatment or prevention of various conditions in children. In this article, we review the published data on use of specific probiotic strains for three common pediatric conditions: the prevention of urinary tract infections and antibiotic-associated diarrhea and the treatment of atopic dermatitis. Research into the utility of specific probiotic strains is of varying quality, and data are often derived from small studies and case series. We discuss the scientific merit of these studies, their overall findings regarding the utility of probiotics for these indications, issues in reporting of methods, and results from these clinical trials, as well as future areas of investigation.
Seasonality of archaeal proteorhodopsin and associated Marine Group IIb ecotypes (Ca. Poseidoniales) in the North Western Mediterranean Sea
Authors: Pereira Olivier , Hochart Corentin , Boeuf Dominique , Auguet Jean Christophe , Debroas Didier , Galand Pierre E 
Published: December 2020

Abstract
The Archaea Marine Group II (MGII) is widespread in the world’s ocean where it plays an important role in the carbon cycle. Despite recent discoveries on the group’s metabolisms, the ecology of this newly proposed order (Candidatus Poseidoniales) remains poorly understood. Here we used a combination of time-series metagenome-assembled genomes (MAGs) and high-frequency 16S rRNA data from the NW Mediterranean Sea to test if the taxonomic diversity within the MGIIb family (Candidatus Thalassarchaeaceae) reflects the presence of different ecotypes. The MAGs’ seasonality revealed a MGIIb family composed of different subclades that have distinct lifestyles and physiologies. The vitamin metabolisms were notably different between ecotypes with, in some, a possible link to sunlight’s energy. Diverse archaeal proteorhodopsin variants, with unusual signature in key amino acid residues, had distinct seasonal patterns corresponding to changing day length. In addition, we show that in summer, archaea, as opposed to bacteria, disappeared completely from surface waters. Our results shed light on the diversity and the distribution of the euryarchaeotal proteorhodopsin, and highlight that MGIIb is a diverse ecological group. The work shows that time-series based studies of the taxonomy, seasonality, and metabolisms of marine prokaryotes is critical to uncover their diverse role in the ocean.
Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia
Authors: Maziarz Richard T. , Levis Mark , Patnaik Mrinal M. , Scott Bart L. , Mohan Sanjay R. , Deol Abhinav , Rowley Scott D. , Kim Dennis D. H. , Hernandez Daniela , Rajkhowa Trivikram , Haines Kelly , Bonifacio Gaetano , Rine Patrice , Purkayastha Das , Fernandez Hugo F. 
Published: December 2020

AbstractWe evaluated standard-of-care (SOC) treatment with or without midostaurin to prevent relapse following allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with acute myeloid leukemia (AML) harboring internal tandem duplication (ITD) in FLT3. Adults (aged 18–70 years) who received alloHSCT in first complete remission, had achieved hematologic recovery, and were transfusion independent were randomized to receive SOC with or without midostaurin (50 mg twice daily) continuously in twelve 4-week cycles. The primary endpoint was relapse-free survival (RFS) 18 months post-alloHSCT. Sixty patients were randomized (30/arm); 30 completed all 12 cycles (midostaurin + SOC, n = 16; SOC, n = 14). The estimated 18-month RFS (95% CI) was 89% (69–96%) in the midostaurin arm and 76% (54–88%) in the SOC arm (hazard ratio, 0.46 [95% CI, 0.12–1.86]; P = 0.27); estimated relapse rates were 11% and 24%, respectively. Inhibition of FLT3 phosphorylation to <70% of baseline (achieved by 50% of midostaurin-treated patients) was associated with improved RFS. The most common serious adverse events were diarrhea, nausea, and vomiting. Rates of graft-vs-host disease were similar between both arms (midostaurin + SOC, 70%; SOC, 73%). The addition of midostaurin maintenance therapy following alloHSCT may provide clinical benefit in some patients with FLT3-ITD AML. (ClinicalTrials.gov identifier: NCT01883362).
Ubiquitin-dependent and -independent functions of OTULIN in cell fate control and beyond
Authors: Weinelt Nadine , van Wijk Sjoerd J. L. 
Published: December 2020

AbstractUbiquitination, and its control by deubiquitinating enzymes (DUBs), mediates protein stability, function, signaling and cell fate. The ovarian tumor (OTU) family DUB OTULIN (FAM105B) exclusively cleaves linear (Met1-linked) poly-ubiquitin chains and plays important roles in auto-immunity, inflammation and infection. OTULIN regulates Met1-linked ubiquitination downstream of tumor necrosis factor receptor 1 (TNFR1), toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) receptor activation and interacts with the Met1 ubiquitin-specific linear ubiquitin chain assembly complex (LUBAC) E3 ligase. However, despite extensive research efforts, the receptor and cytosolic roles of OTULIN and the distributions of multiple Met1 ubiquitin-associated E3-DUB complexes in the regulation of cell fate still remain controversial and unclear. Apart from that, novel ubiquitin-independent OTULIN functions have emerged highlighting an even more complex role of OTULIN in cellular homeostasis. For example, OTULIN interferes with endosome-to-plasma membrane trafficking and the OTULIN-related pseudo-DUB OTULINL (FAM105A) resides at the endoplasmic reticulum (ER). Here, we discuss how OTULIN contributes to cell fate control and highlight novel ubiquitin-dependent and -independent functions.
Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors
Authors: Alaimo Alessandro , Lorenzoni Marco , Ambrosino Paolo , Bertossi Arianna , Bisio Alessandra , Macchia Alice , Zoni Eugenio , Genovesi Sacha , Cambuli Francesco , Foletto Veronica , De Felice Dario , Soldovieri Maria Virginia , Mosca Ilaria , Gandolfi Francesco , Brunelli Matteo , Petris Gianluca , Cereseto Anna , Villarroel Alvaro , Thalmann George , Carbone Francesco Giuseppe , Kruithof-de Julio Marianna , Barbareschi Mattia , Romanel Alessandro , Taglialatela Maurizio , Lunardi Andrea 
Published: December 2020

AbstractTherapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca2+ cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.
A predicted NEDD8 conjugating enzyme gene identified as a Capsicum candidate Rf gene using bulk segregant RNA sequencing
Authors: Wei Bingqiang , Bosland Paul W. , Zhang Zhenghai , Wang Yongfu , Zhang Gaoyuan , Wang Lanlan , Yu Jihua 
Published: December 2020

AbstractCytoplasmic male sterility (CMS) is an important tool for producing F1hybrids, which can exhibit heterosis. The companion system, restorer-of-fertility (Rf), is poorly understood at the molecular level and would be valuable in producing restorer lines for hybrid seed production. The identity of theRfgene inCapsicum(pepper) is currently unclear. In this study, using bulked segregant RNA sequencing (BSR-seq), a strong candidateRfgene, Capana06g002866, which is annotated as a NEDD8 conjugating enzyme E2, was identified. Capana06g002866 has an ORF of 555 bp in length encoding 184 amino acids; it can be cloned from F1plants from the hybridization of the CMS line 8A and restorer line R1 but is not found in CMS line 8A. With qRT-PCR validation, Capana06g002866 was found to be upregulated in restorer accessions compared to sterile accessions. The relative expression in flower buds increased with the developmental stage in F1plants, while the expression was very low in all flower bud stages of the CMS lines. These results provide new insights into theRfgene in pepper and will be useful for other crops utilizing the CMS system.
Synergistic interactions among growing stressors increase risk to an Arctic ecosystem
Authors: Arrigo K. R. , van Dijken Gert L. , Cameron M. A. , van der Grient J. , Wedding L. M. , Hazen L. , Leape J. , Leonard G. , Merkl A. , Micheli F. , Mills M. M. , Monismith S. , Ouellette N. T. , Zivian A. , Levi M. , Bailey R. M. 
Published: December 2020

AbstractOceans provide critical ecosystem services, but are subject to a growing number of external pressures, including overfishing, pollution, habitat destruction, and climate change. Current models typically treat stressors on species and ecosystems independently, though in reality, stressors often interact in ways that are not well understood. Here, we use a network interaction model (OSIRIS) to explicitly study stressor interactions in the Chukchi Sea (Arctic Ocean) due to its extensive climate-driven loss of sea ice and accelerated growth of other stressors, including shipping and oil exploration. The model includes numerous trophic levels ranging from phytoplankton to polar bears. We find that climate-related stressors have a larger impact on animal populations than do acute stressors like increased shipping and subsistence harvesting. In particular, organisms with a strong temperature-growth rate relationship show the greatest changes in biomass as interaction strength increased, but also exhibit the greatest variability. Neglecting interactions between stressors vastly underestimates the risk of population crashes. Our results indicate that models must account for stressor interactions to enable responsible management and decision-making.
Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies
Authors: Mattsson-Carlgren Niklas , Palmqvist Sebastian , Blennow Kaj , Hansson Oskar 
Published: December 2020

AbstractBiomarkers have revolutionized scientific research on neurodegenerative diseases, in particular Alzheimer’s disease, transformed drug trial design, and are also increasingly improving patient management in clinical practice. A few key cerebrospinal fluid biomarkers have been robustly associated with neurodegenerative diseases. Several novel biomarkers are very promising, especially blood-based markers. However, many biomarker findings have had low reproducibility despite initial promising results. In this perspective, we identify possible sources for low reproducibility of studies on fluid biomarkers for neurodegenerative diseases, with a focus on Alzheimer’s disease. We suggest guidelines for researchers and journal editors, with the aim to improve reproducibility of findings.
Molecular basis of regio- and stereo-specificity in biosynthesis of bacterial heterodimeric diketopiperazines
Authors: Sun Chenghai , Luo Zhenyao , Zhang Wenlu , Tian Wenya , Peng Haidong , Lin Zhi , Deng Zixin , Kobe Bostjan , Jia Xinying , Qu Xudong 
Published: December 2020

AbstractBacterial heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are a growing family of bioactive natural products. They are challenging to prepare by chemical routes due to the polycyclic and densely functionalized backbone. Through functional characterization and investigation, we herein identify a family of three related HTDKP-forming cytochrome P450s (NasbB, NasS1868 and NasF5053) and reveal four critical residues (Qln65, Ala86, Ser284 and Val288) that control their regio- and stereo-selectivity to generate diverse dimeric DKP frameworks. Engineering these residues can alter the specificities of the enzymes to produce diverse frameworks. Determining the crystal structures (1.70–1.47 Å) of NasF5053 (ligand-free and substrate-bound NasF5053 and its Q65I-A86G and S284A-V288A mutants) and molecular dynamics simulation finally elucidate the specificity-conferring mechanism of these residues. Our results provide a clear molecular and mechanistic basis into this family of HTDKP-forming P450s, laying a solid foundation for rapid access to the molecular diversity of HTDKP frameworks through rational engineering of the P450s.
Using antibodies to control DNA-templated chemical reactions
Authors: Baranda Pellejero Lorena , Mahdifar Malihe , Ercolani Gianfranco , Watson Jonathan , Brown Tom , Ricci Francesco 
Published: December 2020

AbstractDNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization. While this strategy has proven advantageous for a variety of applications, including sensing and drug discovery, it has been so far limited to the use of nucleic acids as templating elements. Here, we report the rational design of DNA templated synthesis controlled by specific IgG antibodies. Our approach is based on the co-localization of reactants induced by the bivalent binding of a specific IgG antibody to two antigen-conjugated DNA templating strands that triggers a chemical reaction that would be otherwise too slow under diluted conditions. This strategy is versatile, orthogonal and adaptable to different IgG antibodies and can be employed to achieve the targeted synthesis of clinically-relevant molecules in the presence of specific IgG biomarker antibodies.
Simultaneous interlayer and intralayer space control in two-dimensional metal−organic frameworks for acetylene/ethylene separation
Authors: Shen Jin , He Xin , Ke Tian , Krishna Rajamani , van Baten Jasper M. , Chen Rundao , Bao Zongbi , Xing Huabin , Dincǎ Mircea , Zhang Zhiguo , Yang Qiwei , Ren Qilong 
Published: December 2020

AbstractThree-dimensional metal−organic frameworks (MOFs) are cutting-edge materials in the adsorptive removal of trace gases due to the availability of abundant pores with specific chemistry. However, the development of ideal adsorbents combining high adsorption capacity with high selectivity and stability remains challenging. Here we demonstrate a strategy to design adsorbents that utilizes the tunability of interlayer and intralayer space of two-dimensional fluorinated MOFs for capturing acetylene from ethylene. Validated by X-ray diffraction and modeling, a systematic variation of linker atom oxidation state enables fine regulation of layer stacking pattern and linker conformation, which affords a strong interlayer trapping of molecules along with cooperative intralayer binding. The resultant robust materials (ZUL-100 and ZUL-200) exhibit benchmark capacity in the pressure range of 0.001–0.05 bar with high selectivity. Their efficiency in acetylene/ethylene separation is confirmed by breakthrough experiments, giving excellent ethylene productivities (121 mmol/g from 1/99 mixture, 99.9999%), even when cycled under moist conditions.
Imaging fascicular organization of rat sciatic nerves with fast neural electrical impedance tomography
Authors: Ravagli Enrico , Mastitskaya Svetlana , Thompson Nicole , Iacoviello Francesco , Shearing Paul R. , Perkins Justin , Gourine Alexander V. , Aristovich Kirill , Holder David 
Published: December 2020

AbstractImaging compound action potentials (CAPs) in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles. Existing methods have low resolution, limited imaging depth, or are invasive. Fast neural electrical impedance tomography (EIT) allows fascicular CAP imaging with a resolution of <200 µm, <1 ms using a non-penetrating flexible nerve cuff electrode array. Here, we validate EIT imaging in rat sciatic nerve by comparison to micro-computed tomography (microCT) and histology with fluorescent dextran tracers. With EIT, there are reproducible localized changes in tissue impedance in response to stimulation of individual fascicles (tibial, peroneal and sural). The reconstructed EIT images correspond to microCT scans and histology, with significant separation between the fascicles (p < 0.01). The mean fascicle position is identified with an accuracy of 6% of nerve diameter. This suggests fast neural EIT can reliably image the functional fascicular anatomy of the nerves and so aid selective neuromodulation.
Strain control of layer-resolved negative capacitance in superlattices
Authors: Walter Raymond , Prosandeev Sergey , Paillard Charles , Bellaiche L. 
Published: December 2020

AbstractNegative capacitance in BaTiO3/SrTiO3 superlattices is investigated by Monte Carlo simulations in an atomistic effective Hamiltonian model, using fluctuation formulas for responses to the local macroscopic field that incorporates depolarizing fields. We show that epitaxial strain can tune the negative capacitance of the BaTiO3 ferroelectric layer and the overall capacitance of the system. In addition, we predict and explain an original switching of the negative capacitance from the BaTiO3 layer to the SrTiO3 layer at low temperatures for intermediate strains.
Chromosome-scale, haplotype-resolved assembly of human genomes
Authors: Garg Shilpa , Fungtammasan Arkarachai , Carroll Andrew , Chou Mike , Schmitt Anthony , Zhou Xiang , Mac Stephen , Peluso Paul , Hatas Emily , Ghurye Jay , Maguire Jared , Mahmoud Medhat , Cheng Haoyu , Heller David , Zook Justin M. , Moemke Tobias , Marschall Tobias , Sedlazeck Fritz J. , Aach John , Chin Chen-Shan , Church George M. , Li Heng 
Published: December 2020

AbstractHaplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased ~99.5% of heterozygous sites at 98–99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.