bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Joint Soil‐Vegetation‐Atmospheric Water Tagging Procedure With WRF‐Hydro: Implementation and Application to the Case of Precipitation Partitioning in the Upper Danube River Basin
Authors: Arnault Joël , Wei Jianhui , Rummler Thomas , Fersch Benjamin , Zhang Zhenyu , Jung Gerlinde , Wagner Sven , Kunstmann Harald 
Published: July 2019

AbstractAtmospheric models such as the Weather Research and Forecasting (WRF) model provide a tool to evaluate the behavior of regional hydrological cycle components, including precipitation, evapotranspiration, soil water storage, and runoff. Recent model developments have focused on coupled atmospheric‐hydrological modeling systems, such as WRF‐Hydro, in order to account for subsurface, overland, and river flow and potentially improve the representation of land‐atmosphere interactions. The aim of this study is to investigate the contribution of lateral terrestrial water flow to the regional hydrological cycle, with the help of a joint soil‐vegetation‐atmospheric water tagging procedure newly developed in the so‐called WRF‐tag and WRF‐Hydro‐tag models. An application of both models for the high precipitation event on 15 August 2008 in the German and Austrian parts of the upper Danube river basin (94,100 km2) is presented. The precipitation that fell in the basin during this event is considered as a water source, is tagged, and subsequently tracked for a 40‐month period until December 2011. At the end of the study period, in both simulations, approximately 57% of the tagged water has run off, while 41% has evaporated back to the atmosphere, including 2% that has recycled in the upper Danube river basin as precipitation. In WRF‐Hydro‐tag, the surface evaporation of tagged water is slightly enhanced by surface flow infiltration and slightly reduced by subsurface lateral water flow in areas with low topography gradients. This affects the source precipitation recycling only in a negligible amount.
Molecular basis for hierarchical histone de-β-hydroxybutyrylation by SIRT3
Authors: Zhang Xingrun , Cao Ruili , Niu Jinrong , Yang Shumin , Ma Huida , Zhao Shuai , Li Haitao 
Published: July 2019

AbstractChemical modifications on histones constitute a key mechanism for gene regulation in chromatin context. Recently, histone lysine β-hydroxybutyrylation (Kbhb) was identified as a new form of histone acylation that connects starvation-responsive metabolism to epigenetic regulation. Sirtuins are a family of NAD+-dependent deacetylases. Through systematic profiling studies, we show that human SIRT3 displays class-selective histone de-β-hydroxybutyrylase activities with preference for H3 K4, K9, K18, K23, K27, and H4K16, but not for H4 K5, K8, K12, which distinguishes it from the Zn-dependent HDACs. Structural studies revealed a hydrogen bond-lined hydrophobic pocket favored for the S-form Kbhb recognition and catalysis. β-backbone but not side chain-mediated interactions around Kbhb dominate sequence motif recognition, explaining the broad site-specificity of SIRT3. The observed class-selectivity of SIRT3 is due to an entropically unfavorable barrier associated with the glycine-flanking motif that the histone Kbhb resides in. Collectively, we reveal the molecular basis for class-selective histone de-β-hydroxybutyrylation by SIRT3, shedding lights on the function of sirtuins in Kbhb biology through hierarchical deacylation.
Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders
Authors: Pua Emmanuel Peng Kiat , Ball Gareth , Adamson Chris , Bowden Stephen , Seal Marc L. 
Published: July 2019

AbstractThe neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.58) was strictly matched to a control participant (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures (Social Responsiveness Scale) were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features,p = 0.01, n = 5000 permutations; 10 surface area features,p = 0.006, n = 5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.
The Pol β variant containing exon α is deficient in DNA polymerase but has full dRP lyase activity
Authors: Dai Da-Peng , Prasad Rajendra , Strauss Phyllis R. , Wilson Samuel H. 
Published: July 2019

AbstractDNA polymerase (Pol) β is a key enzyme in base excision repair (BER), an important repair system for maintaining genomic integrity. We previously reported the presence of a Pol β transcript containing exon α (105-nucleotide) in normal and colon cancer cell lines. The transcript carried an insertion between exons VI and VII and was predicted to encode a ~42 kDa variant of the wild-type 39 kDa enzyme. However, little is known about the biochemical properties of the exon α-containing Pol β (exon α Pol β) variant. Here, we first obtained evidence indicating expression of the 42 kDa exon α Pol β variant in mouse embryonic fibroblasts. The exon α Pol β variant was then overexpressed in E. coli, purified, and characterized for its biochemical properties. Kinetic studies of exon α Pol β revealed that it is deficient in DNA binding to gapped DNA, has strongly reduced polymerase activity and higher Km for dNTP during gap-filling. On the other hand, the 5′-dRP lyase activity of the exon α Pol β variant is similar to that of wild-type Pol β. These results indicate the exon α Pol β variant is base excision repair deficient, but does conduct 5′-trimming of a dRP group at the gap margin. Understanding the biological implications of this Pol β variant warrants further investigation.
Environment shapes sleep patterns in a wild nocturnal primate
Authors: Reinhardt Kathleen D. , Vyazovskiy Vladyslav V. , Hernandez-Aguilar R. Adriana , Imron Muhammad Ali , Nekaris K. Anne-Isola 
Published: July 2019

AbstractAmong primates, the suborder Haplorhini is considered to have evolved a consolidated monophasic sleep pattern, with diurnal species requiring a shorter sleep duration than nocturnal species. Only a few primate species have been systematically studied in their natural habitat where environmental variables, including temperature and light, have a major influence on sleep and activity patterns. Here we report the first sleep study on a nocturnal primate performed in the wild. We fitted seven wild Javan slow lorises (Nycticebus javanicus) in West Java, Indonesia with accelerometers that collected activity data, and installed climate loggers in each individual’s home range to collect ambient temperature readings (over 321 days in total). All individuals showed a strictly nocturnal pattern of activity and displayed a striking synchronisation of onset and cessation of activity in relation to sunset and sunrise. The longest consolidated rest episodes were typically clustered near the beginning and towards the end of the light period, and this pattern was inversely related to daily fluctuations of the ambient temperature. The striking relationship between daily activity patterns, light levels and temperature suggests a major role of the environment in shaping the daily architecture of waking and sleep. We concluded that well-known phenotypic variability in daily sleep amount and architecture across species may represent an adaptation to changes in the environment. Our data suggest that the consolidated monophasic sleep patterns shaped by environmental pressures observed in slow lorises represent phylogenetic inertia in the evolution of sleep patterns in humans.
Structural changes within the bifunctional cryptochrome/photolyase CraCRY upon blue light excitation
Authors: Franz-Badur Sophie , Penner Alexander , Straß Simon , von Horsten Silke , Linne Uwe , Essen Lars-Oliver 
Published: July 2019

AbstractCryptochromes (CRYs) are an ubiquitously occurring class of photoreceptors, which are important for regulating the circadian rhythm of animals via a time-delayed transcription-translation feedback loop (TTFL). Due to their protein architecture and common FAD chromophore, they belong to the same superfamily as photolyases (PHLs), an enzyme class that repairs UV-induced DNA lesions upon blue light absorption. Apart from their different functions the only prominent structural difference between CRY and PHL is the highly variable C-terminal extension (CTE) of the former. The nature of the CTE is still unclear and highly speculated. In this study, we show by hydrogen/deuterium exchange and subsequent mass-spectrometric analysis that the CTE of the animal-like cryptochrome from the green algae Chlamydomonas reinhardtii (CraCRY) binds to the surface of the photolyase homology region, which flanks the DNA binding site. We also compared the fully oxidized and fully reduced states of the flavoprotein and designed a tool, so called light chamber, for automated HDX-MS measurements of photoreceptors in defined photostates. We could observe some striking differences between the two photostates and propose a model for light-dependent switching of this bifunctional cryptochrome.
Tunable magnetoplasmonics in lattices of Ni/SiO2/Au dimers
Authors: Pourjamal Sara , Kataja Mikko , Maccaferri Nicolò , Vavassori Paolo , van Dijken Sebastiaan 
Published: July 2019

AbstractWe present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By considering the excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically demonstrate that the magnetoplasmonic response of dimer lattices is governed by a complex interplay of near- and far-field interactions. Near-field coupling between dipoles in Ni and low-loss Au enhances the polarizabilty of single dimers compared to that of isolated Ni nanodisks. Far-field diffractive coupling in periodic lattices of these two particle types enlarges the difference in effective polarizability further. This effect is explained by an inverse relationship between the damping of collective surface lattice resonances and the imaginary polarizability of individual scatterers. Optical reflectance measurements, magneto-optical Kerr effect spectra, and finite-difference time-domain simulations confirm the analytical results. Hybrid dimer arrays supporting intense plasmon excitations are a promising candidate for active magnetoplasmonic devices.
Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms
Authors: Slater Ross T. , Frost Lucy R. , Jossi Sian E. , Millard Andrew D. , Unnikrishnan Meera 
Published: July 2019

AbstractThe anaerobic gut pathogen, Clostridioides difficile, forms adherent biofilms that may play an important role in recurrent C. difficile infections. The mechanisms underlying C. difficile community formation and inter-bacterial interactions are nevertheless poorly understood. C. difficile produces AI-2, a quorum sensing molecule that modulates biofilm formation across many bacterial species. We found that a strain defective in LuxS, the enzyme that mediates AI-2 production, is defective in biofilm development in vitro. Transcriptomic analyses of biofilms formed by wild type (WT) and luxS mutant (luxS) strains revealed a downregulation of prophage loci in the luxS mutant biofilms compared to the WT. Detection of phages and eDNA within biofilms may suggest that DNA release by phage-mediated cell lysis contributes to C. difficile biofilm formation. In order to understand if LuxS mediates C. difficile crosstalk with other gut species, C. difficile interactions with a common gut bacterium, Bacteroides fragilis, were studied. We demonstrate that C. difficile growth is significantly reduced when co-cultured with B. fragilis in mixed biofilms. Interestingly, the absence of C. difficile LuxS alleviates the B. fragilis-mediated growth inhibition. Dual species RNA-sequencing analyses from single and mixed biofilms revealed differential modulation of distinct metabolic pathways for C. difficile WT, luxS and B. fragilis upon co-culture, indicating that AI-2 may be involved in induction of selective metabolic responses in B. fragilis. Overall, our data suggest that C. difficile LuxS/AI-2 utilises different mechanisms to mediate formation of single and mixed species communities.
A general non-rectangular hyperbola equation for photosynthetic light response curve of rice at various leaf ages
Authors: Xu Junzeng , Lv Yuping , Liu Xiaoyin , Wei Qi , Qi Zhiming , Yang Shihong , Liao Linxian 
Published: July 2019

AbstractPhotosynthetic light response (PLR) curves of leaves are usually fitted by non-rectangular hyperbola (NRH) equation, and those fitted NRH parameters may change with leaf aging. The objectives of this study were 1) to reveal the response of NRH parameters of rice leaves, light-saturated net photosynthetic rate (Pnmax), quantum yield of assimilation (φ), dark respiration rate (Rd) and convexity of the curve (k), to leaf age; and 2) to improve the performance of NRH equation in simulating the PLR curves for leaves at various ages. The PLR for rice leaves at ages of 3–53 days were measured, and the general NRH equation was developed by incorporating the relationship between NRH parameters and leaf age into the NRH equation. The results showed that the NRH parameters of Pnmax, φ and Rd increased rapidly to maximum at approximately 10 days and then declined linearly toward the age of 53 days. However, the value of k was not sensitive to leaf age. The general NRH equation can be used to simulate leaf PLR continuously along with leaf aging.
Discovery of novel oestrogen receptor α agonists and antagonists by screening a revisited privileged structure moiety for nuclear receptors
Authors: Masuya Takahiro , Iwamoto Masaki , Liu Xiaohui , Matsushima Ayami 
Published: July 2019

AbstractBisphenol A (BPA) is used as an industrial raw material for polycarbonate plastics and epoxy resins; however, various concerns have been reported regarding its status as an endocrine-disrupting chemical. BPA interacts not only with oestrogen receptors (ERs) but constitutive androstane receptor, pregnane X receptor, and oestrogen-related receptor γ (ERRγ); therefore, the bisphenol structure represents a privileged structure for the nuclear-receptor superfamily. Here, we screen 127 BPA-related compounds by competitive-binding assay using [3H]oestradiol and find that 20 compounds bind to ERα with high affinity. We confirm most of these as ERα agonists; however, four compounds, including bisphenol M and bisphenol P act as novel antagonists. These structures harbour three benzene rings in tandem with terminal hydroxy groups at para-positions, with this tandem tri-ring bisphenol structure representing a novel privileged structure for an ERα antagonist. Additionally, we perform an ab initio calculation and develop a new clipping method for halogen bonding or non-covalent interaction using DV-Xα evaluation for biomolecules.
Dual Kit/Aur Inhibitors as Chemosensitizing Agents for the Treatment of Melanoma: Design, Synthesis, Docking Studies and Functional Investigation
Authors: Quattrini Luca , Coviello Vito , Sartini Stefania , Di Desidero Teresa , Orlandi Paola , Ke Yi-Yu , Liu Kai-Lun , Hsieh Hsing-Pang , Bocci Guido , La Motta Concettina 
Published: July 2019

AbstractMelanoma is the most serious form of skin cancer but its medication is still far from being safe and thoroughly effective. The search of novel therapeutic approaches represents therefore a health emergency to push through eagerly. In this study, we describe a novel class of dual c-Kit/Aur inhibitors, characterized by a 1,2,4-triazole core and developed by a structure-based optimization of a previously developed hit, and report the evidence of their significance as drug candidates for the treatment of melanoma. Compound6a, merging the best inhibitory profile against the target kinases, showed anti-proliferative efficacy against the human melanoma cell lines A2058, expressing the BRAF V600D mutation, and WM266-4, expressing BRAF V600E. Significantly, it displayed also a highly synergistic profile when tested in combination with vemurafenib, thus proving its efficacy not onlyper sebut even in a combination therapy, which is nowadays acknowledged as the cornerstone approach of the forthcoming tumour management.
Bio-enzymes for inhibition and elimination of Escherichia coli O157:H7 biofilm and their synergistic effect with sodium hypochlorite
Authors: Lim Eun Seob , Koo Ok Kyung , Kim Min-Jeong , Kim Joo-Sung 
Published: July 2019

AbstractEscherichia coli O157:H7 is one of the most important pathogens worldwide. In this study, three different kinds of enzymes, DNase I, proteinase K and cellulase were evaluated for inhibitory or degrading activity against E. coli O157:H7 biofilm by targeting extracellular DNA, proteins, and cellulose, respectively. The cell number of biofilms formed under proteinase K resulted in a 2.43 log CFU/cm2 reduction with an additional synergistic 3.72 log CFU/cm2 reduction after NaClO post-treatment, while no significant reduction occurred with NaClO treatment alone. It suggests that protein degradation could be a good way to control the biofilm effectively. In preformed biofilms, all enzymes showed a significant reduction of 16.4–36.7% in biofilm matrix in 10-fold diluted media (p < 0.05). The sequential treatment with proteinase K, cellulase, and NaClO showed a significantly higher synergistic inactivation of 2.83 log CFU/cm2 compared to 1.58 log CFU/cm2 in the sequence of cellulase, proteinase K, and NaClO (p < 0.05). It suggests that the sequence of multiple enzymes can make a significant difference in the susceptibility of biofilms to NaClO. This study indicates that the combination of extracellular polymeric substance-degrading enzymes with NaClO could be useful for the efficient control of E. coli O157:H7 biofilms.
Human Schwann cells are susceptible to infection with Zika and yellow fever viruses, but not dengue virus
Authors: Dhiman Gaurav , Abraham Rachy , Griffin Diane E. 
Published: July 2019

AbstractZika virus (ZIKV) is a re-emerged flavivirus transmitted by Aedes spp mosquitoes that has caused outbreaks of fever and rash on islands in the Pacific and in the Americas. These outbreaks have been associated with neurologic complications that include congenital abnormalities and Guillain-Barré syndrome (GBS). The pathogenesis of ZIKV-associated GBS, a potentially life-threatening peripheral nerve disease, remains unclear. Because Schwann cells (SCs) play a central role in peripheral nerve function and can be the target for damage in GBS, we characterized the interactions of ZIKV isolates from Africa, Asia and Brazil with human SCs in comparison with the related mosquito-transmitted flaviviruses yellow fever virus 17D (YFV) and dengue virus type 2 (DENV2). SCs supported sustained replication of ZIKV and YFV, but not DENV. ZIKV infection induced increased SC expression of IL-6, interferon (IFN)β1, IFN-λ, IFIT-1, TNFα and IL-23A mRNAs as well as IFN-λ receptors and negative regulators of IFN signaling. SCs expressed baseline mRNAs for multiple potential flavivirus receptors and levels did not change after ZIKV infection. SCs did not express detectable levels of cell surface Fcγ receptors. This study demonstrates the susceptibility and biological responses of SCs to ZIKV infection of potential importance for the pathogenesis of ZIKV-associated GBS.
Human intestinal spheroids cultured using Sacrificial Micromolding as a model system for studying drug transport
Authors: Samy Karen E. , Levy Elizabeth S. , Phong Kiet , Demaree Benjamin , Abate Adam R. , Desai Tejal A. 
Published: July 2019

AbstractIn vitro models of the small intestine are crucial tools for the prediction of drug absorption. The Caco-2 monolayer transwell model has been widely employed to assess drug absorption across the intestine. However, it is now well-established that 3D in vitro models capture tissue-specific architecture and interactions with the extracellular matrix and therefore better recapitulate the complex in vivo environment. However, these models need to be characterized for barrier properties and changes in gene expression and transporter function. Here, we report that geometrically controlled self-assembling multicellular intestinal Caco-2 spheroids cultured using Sacrificial Micromolding display reproducible intestinal features and functions that are more representative of the in vivo small intestine than the widely used 2D transwell model. We show that Caco-2 cell maturation and differentiation into the intestinal epithelial phenotype occur faster in spheroids and that they are viable for a longer period of time. Finally, we were able to invert the polarity of the spheroids by culturing them around Matrigel beads allowing superficial access to the apical membrane and making the model more physiological. This robust and reproducible in vitro intestinal model could serve as a valuable system to expedite drug screening as well as to study intestinal transporter function.
Development of orthotopic tumour models using ultrasound-guided intrahepatic injection
Authors: McVeigh L. E. , Wijetunga I. , Ingram N. , Marston G. , Prasad R. , Markham A. F. , Coletta P. L. 
Published: July 2019

AbstractMouse models of human diseases are an essential part of the translational pipeline. Orthotopic tumour mouse models are increasingly being used in cancer research due to their increased clinical relevance over subcutaneous xenograft models, particularly in relation to metastatic disease. In this study, we have developed orthotopic colorectal cancer liver metastases (CRCLM) and primary cholangiocarcinoma (CCA) models in BALB/c nude mice using minimally invasive ultrasound-guided intrahepatic injection. Due to its minimally invasive nature, the method reduced risk from surgical complications whilst being fast and easy to perform and resulted in measurable tumour volumes 1 to 3 weeks post-injection. Tumour volumes were monitored in vivo by weekly high-frequency ultrasound (HF-US) and/or twice weekly bioluminescence imaging (BLI) and confirmed with end-point histology. Take rates were high for human CRC cells (>73%) and for CCA cells (90%). We have demonstrated that this method reliably induces CRCLM and CCAs, in which tumour volume can be monitored throughout using HF-US and/or BLI. This provides a promising experimental tool for future testing of cancer therapeutics in an orthotopic model.