bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward an Energetically Consistent, Resolution Aware Parameterization of Ocean Mesoscale Eddies
Authors: Jansen Malte F. , Adcroft Alistair , Khani Sina , Kong Hailu 
Published: August 2019

AbstractA subgrid‐scale eddy parameterization is developed, which makes use of an explicit eddy kinetic energy budget and can be applied at both “non‐eddying” and “eddy‐permitting” resolutions. The subgrid‐scale eddies exchange energy with the resolved flow in both directions via a parameterization of baroclinic instability (based on the established formulation of Gent and McWilliams) and biharmonic and negative Laplacian viscosity terms. This formulation represents the turbulent cascades of energy and enstrophy consistent with our current understanding of the turbulent eddy energy cycle. At the same time, the approach is simple and general enough to be readily implemented in ocean climate models, without adding significant computational cost. The closure has been implemented in the Modular Ocean Model Version 6 and tested in the “Neverworld” configuration, which employs an idealized analytically defined topography designed as a testbed for mesoscale eddy parameterizations. The parameterization performs well over a range of resolutions, seamlessly connecting non‐eddying and eddy‐resolving regimes.
Late-stage peptide C–H alkylation for bioorthogonal C–H activation featuring solid phase peptide synthesis
Authors: Schischko Alexandra , Kaplaneris Nikolaos , Rogge Torben , Sirvinskaite Giedre , Son Jongwoo , Ackermann Lutz 
Published: August 2019

AbstractMethods for the late-stage diversification of structurally complex peptides hold enormous potential for advances in drug discovery, agrochemistry and pharmaceutical industries. While C–H arylations emerged for peptide modifications, they are largely limited to highly reactive, expensive and/or toxic reagents, such as silver(I) salts, in superstoichiometric quantities. In sharp contrast, we herein establish the ruthenium(II)-catalyzed C–H alkylation on structurally complex peptides. The additive-free ruthenium(II)carboxylate C–H activation manifold is characterized by ample substrate scope, racemization-free conditions and the chemo-selective tolerance of otherwise reactive functional groups, such as electrophilic ketone, bromo, ester, amide and nitro substituents. Mechanistic studies by experiment and computation feature an acid-enabled C–H ruthenation, along with a notable protodemetalation step. The transformative peptide C–H activation regime sets the stage for peptide ligation in solution and proves viable in a bioorthogonal fashion for C–H alkylations on user-friendly supports by means of solid phase peptide syntheses.
Sulfenamide-enabled ortho thiolation of aryl iodides via palladium/norbornene cooperative catalysis
Authors: Li Renhe , Zhou Yun , Yoon Ki-Young , Dong Zhe , Dong Guangbin 
Published: August 2019

AbstractPoly-substituted aromatic sulfur compounds are widely found in pharmaceuticals, agrochemicals and organic materials. However, the position that a sulfur moiety can be introduced to is largely restricted to a pre-functionalized site; otherwise, use of electronically biased substrates or auxiliary groups that direct catalysis is required. Here we report a general ortho thiolation of common aryl and heteroaryl iodides via palladium-norbornene cooperative catalysis. Using this approach, an aryl or alky sulfur moiety can be site-selectively introduced at the arene ortho position without using sterically or electronically biased substrates. The arene ipso functionalization is simultaneously achieved through Heck, Suzuki or Sonogashira termination. The reaction is enabled by a unique class of electrophiles in palladium-norbornene cooperative catalysis, which are sulfenamides derived from seven-membered lactams. The broad substrates scope and high chemoselectivity could make this method attractive for synthesis of complex sulfur-containing aromatic compounds.
ARID1A and PI3-kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion
Authors: Wilson Mike R. , Reske Jake J. , Holladay Jeanne , Wilber Genna E. , Rhodes Mary , Koeman Julie , Adams Marie , Johnson Ben , Su Ren-Wei , Joshi Niraj R. , Patterson Amanda L. , Shen Hui , Leach Richard E. , Teixeira Jose M. , Fazleabas Asgerally T. , Chandler Ronald L. 
Published: August 2019

AbstractARID1A and PI3-Kinase (PI3K) pathway alterations are common in neoplasms originating from the uterine endometrium. Here we show that monoallelic loss of ARID1A in the mouse endometrial epithelium is sufficient for vaginal bleeding when combined with PI3K activation. Sorted mutant epithelial cells display gene expression and promoter chromatin signatures associated with epithelial-to-mesenchymal transition (EMT). We further show that ARID1A is bound to promoters with open chromatin, but ARID1A loss leads to increased promoter chromatin accessibility and the expression of EMT genes. PI3K activation partially rescues the mesenchymal phenotypes driven by ARID1A loss through antagonism of ARID1A target gene expression, resulting in partial EMT and invasion. We propose that ARID1A normally maintains endometrial epithelial cell identity by repressing mesenchymal cell fates, and that coexistent ARID1A and PI3K mutations promote epithelial transdifferentiation and collective invasion. Broadly, our findings support a role for collective epithelial invasion in the spread of abnormal endometrial tissue.
Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
Authors: Werner Tessa R. , Kunze Ann-Cathrin , Stenzig Justus , Eschenhagen Thomas , Hirt Marc N. 
Published: August 2019

AbstractAfterload enhancement (AE) of rat engineered heart tissue (EHT) in vitro leads to a multitude of changes that in vivo are referred to as pathological cardiac hypertrophy: e.g., cardiomyocyte hypertrophy, contractile dysfunction, reactivation of fetal genes and fibrotic changes. Moreover AE induced the upregulation of 22 abundantly expressed microRNAs. Here, we aimed at evaluating the functional effect of inhibiting 7 promising microRNAs (miR-21-5p, miR-146b-5p, miR-31a-5p, miR-322-5p, miR-450a-5p, miR-140-3p and miR-132-3p) in a small-range screen. Singular transfection of locked nucleic acid (LNA)-based anti-miRs at 100 nM (before the one week AE-procedure) led to a powerful reduction of the targeted microRNAs. Pretreatment with anti-miR-146b-5p, anti-miR-322-5p or anti-miR-450a-5p did not alter the AE-induced contractile decline, while anti-miR-31a-5p-pretreatment even worsened it. Anti-miR-21-5p and anti-miR-132-3p partially attenuated the AE-effect, confirming previous reports. LNA-anti-miR against miR-140-3p, a microRNA recently identified as a prognostic biomarker of cardiovascular disease, also attenuated the AE-effect. To simplify future in vitro experiments and to create an inhibitor for in vivo applications, we designed shorter miR-140-3p-inhibitors and encountered variable efficiency. Only the inhibitor that effectively repressed miR-140-3p was also protective against the AE-induced contractile decline. In summary, in a small-range functional screen, miR-140-3p evolved as a possible new target for the attenuation of afterload-induced pathological cardiac hypertrophy.
Correlations between obstructive sleep apnea and adenotonsillar hypertrophy in children of different weight status
Authors: Wang Jing , Zhao Yu , Yang Wen , Shen Tian , Xue Pei , Yan Xiaohong , Chen Danni , Qiao Yixin , Chen Min , Ren Rong , Ren Jianjun , Xu Yang , Zheng Yongbo , Zou Jian , Tang Xiangdong 
Published: August 2019

AbstractThe present study aimed to evaluate the relationship between OSA and adenotonsillar size in children of different weight status. A total of 451 patients aged 2–13 years with suspected OSA were retrospectively enrolled in the study. Correlations between the apnea-hypopnea index (AHI) and adenotonsillar size in different weight status were investigated. The adenoidal/nasopharyngeal (A/N) ratio of underweight children was significantly higher than that of normal-weight children (P = 0.027). Both adenoid and tonsil size were positively correlated with logAHI in children of normal weight (r = 0.210, P = 0.001; and r = 0.212, P = 0.001) but uncorrelated in the other groups. Gender (OR = 1.49, 95% CI: 1.01–2.20, P = 0.043), obese (OR = 1.93, 95% CI: 1.10–3.40, P = 0.012), A/N ratio (OR = 1.55, 95% CI: 1.28–1.88, P < 0.001) and tonsil size (OR = 1.36, 95% CI: 1.18–1.57, P < 0.001) were all associated with the severity of OSA. Adenotonsillar hypertrophy contributed to OSA in normal-weight children. In children of abnormal weight, instead of treatment for adenotonsillar hypertrophy, appropriate treatments for other factors are required.
The genetic ancestry of American Creole cattle inferred from uniparental and autosomal genetic markers
Authors: Ginja Catarina , Gama Luis Telo , Cortés Oscar , Burriel Inmaculada Martin , Vega-Pla Jose Luis , Penedo Cecilia , Sponenberg Phil , Cañón Javier , Sanz Arianne , do Egito Andrea Alves , Alvarez Luz Angela , Giovambattista Guillermo , Agha Saif , Rogberg-Muñoz Andrés , Lara Maria Aparecida Cassiano ,   BioBovis Consortium, Afonso Sónia , Aguirre Lenin , Armstrong Eileen , Vallejo Maria Esperanza Camacho , Canales Amado , Cassamá Bernardo , Contreras Gloria , Cordeiro J. M. Moras , Dunner Susana , Elbeltagy Ahmed , Fioravanti Maria Clorinda Soares , Carpio Mayra Gómez , Gómez Mariano , Hernández Antonio , Hernandez Darwin , Juliano Raquel Soares , Landi Vincenzo , Marques Ribamar , Martínez Rubén D. , Martínez O. Roberto , Melucci Lilia , Flores Baldomero Molina , Mújica Fernando , Parés i Casanova Pere-Miquel , Quiroz Jorge , Rodellar Clementina , Tjon Gerald , Adebambo Tumininu , Uffo Odalys , Vargas Julio César , Villalobos Axel , Zaragoza Pilar , Delgado Juan Vicente , Martinez Amparo 
Published: August 2019

AbstractCattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development.
Predator-induced fear causes PTSD-like changes in the brains and behaviour of wild animals
Authors: Zanette Liana Y. , Hobbs Emma C. , Witterick Lauren E. , MacDougall-Shackleton Scott A. , Clinchy Michael 
Published: August 2019

AbstractPredator-induced fear is both, one of the most common stressors employed in animal model studies of post-traumatic stress disorder (PTSD), and a major focus of research in ecology. There has been a growing discourse between these disciplines but no direct empirical linkage. We endeavoured to provide this empirical linkage by conducting experiments drawing upon the strengths of both disciplines. Exposure to a natural cue of predator danger (predator vocalizations), had enduring effects of at least 7 days duration involving both, a heightened sensitivity to predator danger (indicative of an enduring memory of fear), and elevated neuronal activation in both the amygdala and hippocampus – in wild birds (black-capped chickadees,Poecile atricapillus), exposed to natural environmental and social experiences in the 7 days following predator exposure. Our results demonstrate enduring effects on the brain and behaviour, meeting the criteria to be considered an animal model of PTSD – in awildanimal, which are of a nature and degree which can be anticipated could affect fecundity and survival in free-living wildlife. We suggest our findings support both the proposition that PTSD is not unnatural, and that long-lasting effects of predator-induced fear, with likely effects on fecundity and survival, are the norm in nature.
Interneuronal correlations at longer time scales predict decision signals for bistable structure-from-motion perception
Authors: Wasmuht D. F. , Parker A. J. , Krug K. 
Published: August 2019

AbstractPerceptual decisions are thought to depend on the activation of task-relevant neurons, whose activity is often correlated in time. Here, we examined how the temporal structure of shared variability in neuronal firing relates to perceptual choices. We recorded stimulus-selective neurons from visual area V5/MT while two monkeys (Macaca mulatta) made perceptual decisions about the rotation direction of structure-from-motion cylinders. Interneuronal correlations for a perceptually ambiguous cylinder stimulus were significantly higher than those for unambiguous cylinders or for random 2D motion during passive viewing. Much of the difference arose from correlations at relatively long timescales (hundreds of milliseconds). Choice-related neural activity (quantified as choice probability; CP) for ambiguous cylinders was positively correlated with interneuronal correlations and was specifically associated with their long timescale component. Furthermore, the slope of the long timescale - but not the instantaneous - component of the correlation predicted higher CPs towards the end of the trial i.e. close to the decision. Our results suggest that the perceptual stability of structure-from-motion cylinders may be controlled by enhanced interneuronal correlations on longer timescales. We propose this as a potential signature of top-down influences onto V5/MT processing that shape and stabilize the appearance of 3D-motion percepts.
Real-Time Selective Sequencing with RUBRIC: Read Until with Basecall and Reference-Informed Criteria
Authors: Edwards Harrison S. , Krishnakumar Raga , Sinha Anupama , Bird Sara W. , Patel Kamlesh D. , Bartsch Michael S. 
Published: August 2019

AbstractThe Oxford MinION, the first commercial nanopore sequencer, is also the first to implement molecule-by-molecule real-time selective sequencing or “Read Until”. As DNA transits a MinION nanopore, real-time pore current data can be accessed and analyzed to provide active feedback to that pore. Fragments of interest are sequenced by default, while DNA deemed non-informative is rejected by reversing the pore bias to eject the strand, providing a novel means of background depletion and/or target enrichment. In contrast to the previously published pattern-matching Read Until approach, our RUBRIC method is the first example of real-time selective sequencing where on-line basecalling enables alignment against conventional nucleic acid references to provide the basis for sequence/reject decisions. We evaluate RUBRIC performance across a range of optimizable parameters, apply it to mixed human/bacteria and CRISPR/Cas9-cut samples, and present a generalized model for estimating real-time selection performance as a function of sample composition and computing configuration.
Multifunctionalizing the marine diatom Phaeodactylum tricornutum for sustainable co-production of omega-3 long chain polyunsaturated fatty acids and recombinant phytase
Authors: Pudney Alex , Gandini Chiara , Economou Chloe K. , Smith Richard , Goddard Paul , Napier Johnathan A. , Spicer Andrew , Sayanova Olga 
Published: August 2019

AbstractThere is an urgent requirement for sustainable sources of food and feed due to world population growth. Aquaculture relies heavily on the fish meal and fish oils derived from capture fisheries, challenging sustainability of the production system. Furthermore, substitution of fish oil with vegetable oil and fish meal with plant seed meals in aquaculture feeds reduces the levels of valuable omega-3 long chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, and lowers the nutritional value due to the presence of phytate. Addition of exogenous phytase to fish feed is beneficial for enhancing animal health and reducing phosphorus pollution. We have engineered the marine diatom Phaeodactylum tricornutum, accumulating high levels of EPA and DHA together with recombinant proteins: the fungal Aspergillus niger PhyA or the bacterial Escherichia coli AppA phytases. The removal of the N-terminal signal peptide further increased phytase activity. Strains engineered with fcpA and CIP1 promoters showed the highest level of phytase activity. The best engineered strain achieved up to 40,000 phytase activity units (FTU) per gram of soluble protein, thus demonstrating the feasibility of development of multifunctionalized microalgae to simultaneously produce industrially useful proteins and fatty acids to meet the demand of intensive fish farming activity.
Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells
Authors: Bomfim Larissa M. , de Araujo Fênix A. , Dias Rosane B. , Sales Caroline B. S. , Rocha Clarissa A. Gurgel , Correa Rodrigo S. , Soares Milena B. P. , Batista Alzir A. , Bezerra Daniel P. 
Published: August 2019

AbstractRuthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)2(PPh3)2] (1) and [Ru(6m2tu)2(dppb)] (2) (where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane; and 6m2tu = 6-methyl-2-thiouracil) are potent cytotoxic agents and able to bind DNA. The aim of this study was to evaluate in vitro cellular underlying mechanism and in vivo effectiveness of these ruthenium(II) complexes in human acute promyelocytic leukemia HL-60 cells. Both complexes displayed potent and selective cytotoxicity in myeloid leukemia cell lines, and were detected into HL-60 cells. Reduction of the cell proliferation and augmented phosphatidylserine externalization, caspase-3, -8 and -9 activation and loss of mitochondrial transmembrane potential were observed in HL-60 cells treated with both complexes. Cotreatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced Ru(II) complexes-induced apoptosis. In addition, both metal complexes induced phosphorylation of histone H2AX (S139), JNK2 (T183/Y185) and p38α (T180/Y182), and cotreatment with JNK/SAPK and p38 MAPK inhibitors reduced complexes-induced apoptosis, indicating DNA double-strand break and activation of caspase-mediated apoptosis through JNK/p38 pathways. Complex 1 also reduced HL-60 cell growth in xenograft model. Overall, the outcome indicated the ruthenium(II) complexes with 6-methyl-2-thiouracil as a novel promising antileukemic drug candidates.
Short Interruptions of Imposed Hyperopic Defocus Earlier in Treatment are More Effective at Preventing Myopia Development
Authors: Benavente-Perez Alexandra , Nour Ann , Troilo David 
Published: August 2019

AbstractThe purpose of this study was to evaluate the effect of interrupting negative lens wear for short periods early or late during the development of lens-induced myopia in marmosets. Sixteen marmosets were reared with a −5D contact lens on their right eye (plano on contralateral eye) for 8 weeks. Eight marmosets had lenses removed for 30 mins twice/day during the first four weeks (early interruption) and eight during the last four weeks (late interruption). Data were compared to treated controls that wore lenses continuously (N = 12) and untreated controls (N = 10). Interocular differences (IOD) in vitreous chamber (VC) depth and central and peripheral mean spherical refractive error (MSE) were measured at baseline and after four (T4) and eight (T8) weeks of treatment. Visual experience during the interruptions was monitored by measuring refraction while marmosets were seated at the center of a 1 m radius viewing cylinder. At T4 the eyes that were interrupted early were not different from untreated controls (p = 0.10) and at T8 had grown less and were less myopic than those interrupted later (IOD change from baseline, VC: +0.07 ± 0.04 mm vs +0.20 ± 0.03 mm, p < 0.05; MSE: −1.59 ± 0.26D vs −2.63 ± 0.60D, p = 0.13). Eyes interrupted later were not different from treated controls (MSE, p = 0.99; VC, p = 0.60) and grew at the same rate as during the first four weeks of uninterrupted lens wear (T4 − T0: 3.67 ± 1.1 µm/day, T8 − T4: 3.56 ± 1.3 µm/day p = 0.96). Peripheral refraction was a predictive factor for the amount of myopia developed only when the interruption was not effective. In summary, interrupting hyperopic defocus with short periods of myopic defocus before compensation occurs prevents axial myopia from developing. After myopia develops, interruption is less effective.
Molecular mechanisms of lncRNAs in regulating cancer cell radiosensitivity
Authors: Zhu Jiamin , Chen Shusen , Yang Baixia , Mao Weidong , Yang Xi , Cai Jing 
Published: August 2019

AbstractRadiotherapy is one of the main modalities of cancer treatment. However, tumor recurrence following radiotherapy occurs in many cancer patients. A key to solving this problem is the optimization of radiosensitivity. In recent years, long non-coding RNAs (lncRNAs), which affect the occurrence and development of tumors through a variety of mechanisms, have become a popular research topic. LncRNAs have been found to influence radiosensitivity by regulating various mechanisms, including DNA damage repair, cell cycle arrest, apoptosis, cancer stem cells regulation, epithelial–mesenchymal transition, and autophagy. LncRNAs are expected to become a potential therapeutic target for radiotherapy in the future. This article reviews recent advances in the role and mechanism of lncRNAs in tumor radiosensitivity.