bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose promotes cell growth by suppressing branched-chain amino acid degradation
Authors: Shao Dan , Villet Outi , Zhang Zhen , Choi Sung Won , Yan Jie , Ritterhoff Julia , Gu Haiwei , Djukovic Danijel , Christodoulou Danos , Kolwicz Stephen C. , Raftery Daniel , Tian Rong 
Published: July 2018

AbstractGlucose and branched-chain amino acids (BCAAs) are essential nutrients and key determinants of cell growth and stress responses. High BCAA level inhibits glucose metabolism but reciprocal regulation of BCAA metabolism by glucose has not been demonstrated. Here we show that glucose suppresses BCAA catabolism in cardiomyocytes to promote hypertrophic response. High glucose inhibits CREB stimulated KLF15 transcription resulting in downregulation of enzymes in the BCAA catabolism pathway. Accumulation of BCAA through the glucose-KLF15-BCAA degradation axis is required for the activation of mTOR signaling during the hypertrophic growth of cardiomyocytes. Restoration of KLF15 prevents cardiac hypertrophy in response to pressure overload in wildtype mice but not in mutant mice deficient of BCAA degradation gene. Thus, regulation of KLF15 transcription by glucose is critical for the glucose-BCAA circuit which controls a cascade of obligatory metabolic responses previously unrecognized for cell growth.
The science of food security
Authors: Cole Martin Barry , Augustin Mary Ann , Robertson Michael John , Manners John Michael 
Published: July 2018

AbstractWe need to feed an estimated population in excess of 9 billion by 2050 with diminishing natural resources, whilst ensuring the health of people and the planet. Herein we connect the future global food demand to the role of agricultural and food science in producing and stabilising foods to meet the global food demand. We highlight the challenges to food and agriculture systems in the face of climate change and global megatrends that are shaping the future world. We discuss the opportunities to reduce food loss and waste, and recover produce that is currently wasted to make this the new raw ingredient supply for the food industry. Our systems-based perspective links food security to agricultural productivity, food safety, health and nutrition, processing and supply chain efficiency in the face of global and industry megatrends. We call for a collaborative, transdisciplinary approach to the science of food security, with a focus on enabling technologies within a context of social, market and global trends to achieve food and nutritional security.
Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
Authors: Bergonzi Celine , Schwab Michael , Naik Tanushree , Daudé David , Chabrière Eric , Elias Mikael 
Published: July 2018

AbstractQuorum quenching lactonases are enzymes that are capable of disrupting bacterial signaling based on acyl homoserine lactones (AHL) via their enzymatic degradation. In particular, lactonases have therefore been demonstrated to inhibit bacterial behaviors that depend on these chemicals, such as the formation of biofilms or the expression of virulence factors. Here we characterized biochemically and structurally a novel representative from the metallo-β-lactamase superfamily, named AaL that was isolated from the thermoacidophilic bacterium Alicyclobacillus acidoterrestris. AaL is a potent quorum quenching enzyme as demonstrated by its ability to inhibit the biofilm formation of Acinetobacter baumannii. Kinetic studies demonstrate that AaL is both a proficient and a broad spectrum enzyme, being capable of hydrolyzing a wide range of lactones with high rates (kcat/KM > 105 M−1.s−1). Additionally, AaL exhibits unusually low KM values, ranging from 10 to 80 µM. Analysis of AaL structures bound to phosphate, glycerol, and C6-AHL reveals a unique hydrophobic patch (W26, F87 and I237), involved in substrate binding, possibly accounting for the enzyme’s high specificity. Identifying the specificity determinants will aid the development of highly specific quorum quenching enzymes as potential therapeutics.
SVM-SulfoSite: A support vector machine based predictor for sulfenylation sites
Authors: AL-barakati Hussam J. , McConnell Evan W. , Hicks Leslie M. , Poole Leslie B. , Newman Robert H. , KC Dukka B. 
Published: July 2018

AbstractProteinS-sulfenylation, which results from oxidation of free thiols on cysteine residues, has recently emerged as an important post-translational modification that regulates the structure and function of proteins involved in a variety of physiological and pathological processes. By altering the size and physiochemical properties of modified cysteine residues, sulfenylation can impact the cellular function of proteins in several different ways. Thus, the ability to rapidly and accurately identify putative sulfenylation sites in proteins will provide important insights into redox-dependent regulation of protein function in a variety of cellular contexts. Though bottom-up proteomic approaches, such as tandem mass spectrometry (MS/MS), provide a wealth of information about global changes in the sulfenylation state of proteins, MS/MS-based experiments are often labor-intensive, costly and technically challenging. Therefore, to complement existing proteomic approaches, researchers have developed a series of computational tools to identify putative sulfenylation sites on proteins. However, existing methods often suffer from low accuracy, specificity, and/or sensitivity. In this study, we developed SVM-SulfoSite, a novel sulfenylation prediction tool that uses support vector machines (SVM) to identify key determinants of sulfenylation among five feature classes: binary code, physiochemical properties, k-space amino acid pairs, amino acid composition and high-quality physiochemical indices. Using 10-fold cross-validation, SVM-SulfoSite achieved 95% sensitivity and 83% specificity, with an overall accuracy of 89% and Matthew’s correlation coefficient (MCC) of 0.79. Likewise, using an independent test set of experimentally identified sulfenylation sites, our method achieved scores of 74%, 62%, 80% and 0.42 for accuracy, sensitivity, specificity and MCC, with an area under the receiver operator characteristic (ROC) curve of 0.81. Moreover, in side-by-side comparisons, SVM-SulfoSite performed as well as or better than existing sulfenylation prediction tools. Together, these results suggest that our method represents a robust and complementary technique for advanced exploration of protein S-sulfenylation.
Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells
Authors: Zhang Hong-Wei , Hu Jin-Jiao , Fu Ruo-Qiu , Liu Xin , Zhang Yan-Hao , Li Jing , Liu Lei , Li Yu-Nong , Deng Qin , Luo Qing-Song , Ouyang Qin , Gao Ning 
Published: July 2018

AbstractAnticancer activities of flavonoids derived from Tephroseris kirilowii (Turcz.) Holub. were evaluated in human cancer cells. We isolated and identified, for the first time, eight flavonoids from T. kirilowii and found that three of them (IH: isorhamnetin, GN: genkwanin, and Aca: acacetin) inhibited cell proliferation in a variety of human cancer cell lines. These active flavonoids caused cell cycle arrest at G2/M phase and induced apoptosis and autophagy in human breast cancer cells. Molecular docking revealed that these flavonoids dock in the ATP binding pocket of PI3Kγ. Importantly, treatment with these flavonoids decreased the levels of PI3Kγ-p110, phospho-PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6K, and phospho-ULK. Pretreatment with PI3Kγ specific inhibitor AS605240 potentiated flavonoids-mediated inactivation of AKT, mTOR, p70S6K, ULK, and apoptosis. Taken together, these findings represent a novel mechanism by which downregulation of PI3Kγ-p110 and consequent interruption of PI3K/AKT/mTOR/p70S6K/ULK signaling pathway might play a critical functional role in these flavonoids-induced cell cycle arrest at G2/M phase, apoptosis, and autophagy. Our studies provide novel insights into the anticancer activities of selected flavonoids and their potential uses in anticancer therapy.
Defining the frequency of human papillomavirus and polyomavirus infection in urothelial bladder tumours
Authors: Llewellyn Matthew A. , Gordon Naheema S. , Abbotts Ben , James Nicholas D. , Zeegers Maurice P. , Cheng K. K. , Macdonald Andrew , Roberts Sally , Parish Joanna L. , Ward Douglas G. , Bryan Richard T. 
Published: July 2018

AbstractGiven the contradictory nature of the literature regarding the role of human papillomaviruses and polyomaviruses in the pathogenesis of urothelial bladder cancer (UBC), we sought to investigate the frequency of their involvement in a large cohort of primary UBCs. DNA was extracted from 689 fresh-frozen UBC tissues and screened for the presence of high-risk human papillomavirus (HPV) types 16 and 18 and BKV/JCV genomic DNA by qPCR. In positive cases, viral identity was confirmed by Sanger sequencing and viral gene expression was analysed by RT-PCR or immunohistochemistry. All 689 UBCs were negative for HPV18. One UBC from a female patient with areas of squamous differentiation was positive for HPV16. The qPCR data indicated variable levels of polyomavirus in 49 UBCs. In the UBCs with low Cts we were able to confirm that 23 were BKV and 6 were JCV by Sanger sequencing. Polyomavirus large T antigen expression was low but detectable in 70% of the sequencing-confirmed polyomavirus positive samples. Thus, in United Kingdom patients, the presence of HPV DNA sequences is extremely rare in UBC (<1% of cases). Polyomavirus DNA (predominantly BKV) is more common in UBC, but still only detectable in 7% of cases and in many of these cases at low copy number. We have performed the largest virus screening to date in UBC, finding that HPV16, HPV18 and HPyV are unlikely to be common causative agents in UBC.
Zn2+-triggered self-assembly of Gonadorelin [6-D-Phe] to produce nanostructures and fibrils
Authors: Yordanova Yordanka , Vanderlinden Willem , Stoll Raphael , Rüdiger Daniel , Tosstorff Andreas , Zaremba Wolfgang , Winter Gerhard , Zahler Stefan , Friess Wolfgang 
Published: July 2018

AbstractA synthetic derivative, GnRH [6-D-Phe], stable against enzymatic degradation, self-assembles and forms nanostructures and fibrils upon a pH shift in the presence of different concentrations of Zn2+in vitro. Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR–FTIR) revealed the existence of higher order assembly of Zn2+: GnRH [6-D-Phe]. Nuclear Magnetic Resonance spectroscopy (NMR) indicated a weak interaction between Zn2+ and GnRH [6-D-Phe]. Atomic Force Microscopy (AFM) showed the existence of GnRH [6-D-Phe] oligomers and fibrils. Molecular Dynamic (MD) simulation of the 10:1 Zn2+: GnRH [6-D-Phe] explored the interaction and dimerization processes. In contrast to already existing short peptide fibrils, GnRH [6-D-Phe] nanostructures and fibrils form in a Tris-buffered pH environment in a controlled manner through a temperature reduction and a pH shift. The lyophilized Zn2+: GnRH [6-D-Phe] assembly was tested as a platform for the sustained delivery of GnRH [6-D-Phe] and incorporated into two different oil vehicle matrices. The in vitro release was slow and continuous over 14 days and not influenced by the oil matrix.
Questioning Seasonality of Neuronal Plasticity in the Adult Avian Brain
Authors: Pozner Tatyana , Vistoropsky Yulia , Moaraf Stan , Heiblum Rachel , Barnea Anat 
Published: July 2018

AbstractTo date, studies that reported seasonal patterns of adult neurogenesis and neuronal recruitment have correlated them to seasonal behaviors as the cause or as a consequence of neuronal changes. The aim of our study was to test this correlation, and to investigate whether there is a seasonal pattern of new neuronal recruitment that is not correlated to behavior. To do this, we used adult female zebra finches (songbirds that are not seasonal breeders), kept them under constant social, behavioral, and spatial environments, and compared neuronal recruitment in their brains during two seasons, under natural and laboratory conditions. Under natural conditions, no significant differences were found in the pattern of new neuronal recruitment across seasons. However, under artificial indoor conditions that imitated the natural conditions, higher neuronal recruitment occurred in late summer (August) compared to early spring (February). Moreover, our data indicate that “mixing” temperature and day length significantly reduces new neuronal recruitment, demonstrating the importance of the natural combination of temperature and day length. Taken together, our findings show, for the first time, that neuroplasticity changes under natural vs. artificial conditions, and demonstrate the importance of both laboratory and field experiments when looking at complex biological systems.
Galvanomagnetic properties of the putative type-II Dirac semimetal PtTe2
Authors: Pavlosiuk Orest , Kaczorowski Dariusz 
Published: July 2018

AbstractPlatinum ditelluride has recently been characterized, based on angle-resolved photoemission spectroscopy data and electronic band structure calculations, as a possible representative of type-II Dirac semimetals. Here, we report on the magnetotransport behavior (electrical resistivity, Hall effect) in this compound, investigated on high-quality single-crystalline specimens. The magnetoresistance (MR) of PtTe2 is large (over 3000% at T = 1.8 K in B = 9 T) and unsaturated in strong fields in the entire temperature range studied. The MR isotherms obey a Kohler’s type scaling with the exponent m = 1.69, different from the case of ideal electron-hole compensation. In applied magnetic fields, the resistivity shows a low-temperature plateau, characteristic of topological semimetals. In strong fields, well-resolved Shubnikov – de Haas (SdH) oscillations with two principle frequencies were found, and their analysis yielded charge mobilities of the order of 103 cm2 V−1 s−1 and rather small effective masses of charge carriers, 0.11 me and 0.21 me. However, the extracted Berry phases point to trivial character of the electronic bands involved in the SdH oscillations. The Hall effect data corroborated a multi-band character of the electrical conductivity in PtTe2, with moderate charge compensation.
Tear eicosanoids in healthy people and ocular surface disease
Authors: Ambaw Yohannes Abere , Chao Cecilia , Ji Shanshan , Raida Manfred , Torta Federico , Wenk Markus R. , Tong Louis 
Published: July 2018

AbstractMeibomian gland (MG) dysfunction is the leading cause of evaporative dry eye and it leads to inflammation of the ocular surface. Eicosanoids may be involved in inflammation of dry eye. This study aimed to profile tear eicosanoid levels in healthy individuals and those with MG dysfunction, and to examine if these levels are associated with clinical factors and expressibility of MG. Forty participants with MG dysfunction and 30 healthy controls were recruited in this study. Clinical signs of MG dysfunction were assessed, and tear lactoferrin concentration was evaluated. Tear eicosanoids were extracted from Schirmer’s strips and analyzed using mass spectrometry. We were able to quantify 38 tear eicosanoids and levels were increased in older individuals. In participants with MG dysfunction, higher 5-HETE, LTB4, 18-HEPE, 12-HEPE and 14-HDoHE were associated with poorer MG expressibility. The eicosanoids PGF2α, 18-HEPE, 20-HDoHE and 17-HDoHE were elevated with increased corneal staining; higher 5-HETE, LTB4 were associated with lower tear lactoferrin levels. The receiver-operating-characteristics analysis shows higher levels of 5-HETE, LTB4 and 18-HEPE were able to predict poor expressibility of MGs. In conclusion, tear eicosanoid levels are age-dependent and specific eicosanoids may be indicators of clinical obstruction of MG or the severity of ocular surface damage.
Response of phytoplankton to heavy cloud cover and turbidity in the northern Bay of Bengal
Authors: Jyothibabu R. , Arunpandi N. , Jagadeesan L. , Karnan C. , Lallu K. R. , Vinayachandran P. N. 
Published: July 2018

AbstractAn interesting physiological response of phytoplankton to large fluctuations in underwater photosynthetically active radiation (PAR) levels in the northern Bay of Bengal has been presented here. This study is primarily based on a 12-day time series observation in the northern Bay of Bengal during the peak Southwest Monsoon (July 2012), when the study region was recurrently exposed to alternating cloudy and sunny sky conditions. On overcast days, the PAR available underwater at the time series location (TSL) drastically decreased, with the noontime PAR at the surface water (2 m) usually being ~600 µmol m−2 s−1 on sunny days and declining to ~50 µmol m−2 s−1 on heavily overcast days. Closely linked with the sunny and cloudy days at TSL, chlorophyll a concentration in the water column showed noticeable features; it increased in the upper water column (surface-40 m) and decreased in the lower water column (41–80 m) on cloudy days, while the reverse was the case on sunny days. Based on in-situ and laboratory experimental data, it was observed that these temporal changes in the vertical distribution of chlorophyll a in the northern Bay of Bengal were due to the short-term physiological acclimation of phytoplankton to large changes in underwater PAR.
Small litter size impairs spatial memory and increases anxiety- like behavior in a strain-dependent manner in male mice
Authors: Salari Ali-Akbar , Samadi Hanieh , Homberg Judith R. , Kosari-Nasab Morteza 
Published: July 2018

AbstractEarly life overfeeding is associated with cognitive decline and anxiety-like behaviors in later life. It is not clear whether there are individual differences in the effects of early life overfeeding and what the underlying mechanistic pathways are. We investigated the long-lasting effects of small litter size, an experimental manipulation to induce neonatal overfeeding, in two strains of mice, C57BL/6 and NMRI. We measured body weight, learning and memory, anxiety-related behaviors, interleukin-(IL)-1β and brain-derived-neurotrophic-factor (BDNF) levels in the hippocampus, and both basal and stress corticosterone levels in adult mice which have been nursed in small litters compared with those from control litters. Our findings showed that small litter size led to increased body weight in both strains of mice. Small litter size significantly decreased spatial memory and hippocampal BDNF levels, and increased hippocampal IL-1β, in NMRI mice, but not C57BL/6 mice. Interestingly, we found that small litter size resulted in a significant increase in anxiety-like behaviors and stress-induced corticosterone in NMRI mice, whereas small litter size reduced anxiety-like symptoms and stress-induced corticosterone levels in C57BL/6 mice. These data show that small litter size, which is life-long associated with increased body weight, affects memory and anxiety-related behaviors in a strain-dependent manner in male mice. This suggests that there are individual differences in the developmental consequences of early life overfeeding.
Quantitative Profiling of the Lymph Node Clearance Capacity
Authors: Clement Cristina C. , Wang Wei , Dzieciatkowska Monika , Cortese Marco , Hansen Kirk C. , Becerra Aniuska , Thangaswamy Sangeetha , Nizamutdinova Irina , Moon Jee-Young , Stern Lawrence J. , Gashev Anatoliy A. , Zawieja David , Santambrogio Laura 
Published: July 2018

AbstractTransport of tissue-derived lymphatic fluid and clearance by draining lymph nodes are pivotal for maintenance of fluid homeostasis in the body and for immune-surveillance of the self- and non-self-proteomes. Yet a quantitative analysis of nodal filtration of the tissue-derived proteome present in lymphatic fluid has not been reported. Here we quantified the efficiency of nodal clearance of the composite proteomic load using label-free and isotope-labeling proteomic analysis of pre-nodal and post-nodal samples collected by direct cannulation. These results were extended by quantitation of the filtration efficiency of fluorophore-labeled proteins, bacteria, and beads infused at physiological flow rates into pre-nodal lymphatic collectors and collected by post-nodal cannulation. We developed a linear model of nodal filtration efficiency dependent on pre-nodal protein concentrations and molecular weight, and uncovered criteria for disposing the proteome incoming from defined anatomical districts under physiological conditions. These findings are pivotal to understanding the maximal antigenic load sustainable by a draining node, and promote understanding of pathogen spreading and nodal filtration of tumor metastasis, potentially helping to improve design of vaccination protocols, immunization strategies and drug delivery.
Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia bavariensis
Authors: Brangulis Kalvis , Akopjana Inara , Petrovskis Ivars , Kazaks Andris , Kraiczy Peter , Tars Kaspars 
Published: July 2018

AbstractBorrelia (B.) bavariensis, B. burgdorferi, B. afzelii, B. garinii, B. spielmanii, and B. mayonii are the causative agents in Lyme disease. Lyme disease spirochetes reside in infected Ixodes ticks and are transferred to mammalian hosts during tick feeding. Once transmitted, spirochetes must overcome the first line of defense of the innate immune system either by binding complement regulators or by terminating the formation of the membrane attack complex (MAC). In B. bavariensis, the proteins BGA66 and BGA71 inhibit complement activation by interacting with the late complement components C7, C8, and C9, as well as with the formed MAC. In this study, we have determined the crystal structure of the potent MAC inhibitor BGA71 at 2.9 Ǻ resolution. The structure revealed a cysteine cross-linked homodimer. Based on the crystal structure of BGA71 and the structure-based sequence alignment with CspA from B. burgdorferi, we have proposed a potential binding site for C7 and C9, both of which are constituents of the formed MAC. Our results shed light on the molecular mechanism of immune evasion developed by the human pathogenic Borrelia species to overcome innate immunity. These results will aid in the understanding of Lyme disease pathogenesis and pave the way for the development of new strategies to prevent Lyme disease.
Assessment of High Thermal Effects on Carbon Nanotube (Cnt)- Reinforced Concrete
Authors: Elkady Hala , Hassan Ahmed 
Published: July 2018

AbstractThis paper presents the outcome of a project funded by Beni-suef University targeting the assessment of the addition of carbon nanotubes (CNTs) to reinforced concrete beams on exposure to elevated temperatures. Tests were carried out in compliance to ASTM E119-95a. Besides, pre and post their exposure to elevated temperature tests, the maximum bending capacity of the beams are evaluated. Standard reinforced concrete beams are cast- with and without Carbon Nanotube (CNT). Tests were performed at two temperature levels 400 °C and 600 °C working around temperature ranges expected to have significant effect on concrete endurance, using both one and two hours exposure. Results proved a positive effect for adding CNT to beams at room temperature. This improvement is slightly affected at 400 °C exposure for 2 hr. On the other hand, exposing CNT beams for 600 °C for two hours reduced the beams capacity by 14% compared to a similar reinforced beam without CNT. It is worth notice that CNT was not burnt but suffered de-bonding. Finally, this investigation implies that CNT can be used as an enhancing element to concrete ductility, with no deterioration in other mechanical characteristics on exposure to drastic thermal conditions.