bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of palbociclib and radiotherapy for glioblastoma
Authors: Whittaker Shane , Madani Daniel , Joshi Swapna , Chung Sylvia A , Johns Terrance , Day Bryan , Khasraw Mustafa , McDonald Kerrie L 
Published: July 2017

AbstractThe cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic.
Characterization of forced localization of disordered weakly coupled micromechanical resonators
Authors: Zhang Hemin , Chang Honglong , Yuan Weizheng 
Published: July 2017

AbstractThe mode localization phenomenon of disordered weakly coupled resonators (WCRs) is being used as a novel transduction scheme to further enhance the sensitivity of micromechanical resonant sensors. In this paper, two novel characteristics of mode localization are described. First, we found that the anti-resonance loci behave as a linear function of the stiffness perturbation. The anti-resonance behavior can be regarded as a new manifestation of mode localization in the frequency domain, and mode localization occurs at a deeper level as the anti-resonance approaches closer to the resonance. The anti-resonance loci can be used to identify the symmetry of the WCRs and the locations of the perturbation. Second, by comparing the forced localization responses of the WCRs under both the single-resonator-driven (SRD) scheme and the double-resonator-driven (DRD) scheme, we demonstrated that the DRD scheme extends the linear measurement scale while sacrificing a certain amount of sensitivity. We also demonstrated experimentally that the amplitude ratio-based sensitivity under the DRD scheme is approximately an order of magnitude lower than that under the SRD scheme, that is, the amplitude ratio-based sensitivity is −70.44% (N m−1)−1 under the DRD scheme, while it is −785.6% (N m−1)−1 under the SRD scheme. These characteristics of mode localization are valuable for the design and control of WCR-based sensors.
Revising the hygroscopicity of inorganic sea salt particles
Authors: Zieger P. , Väisänen O. , Corbin J. C. , Partridge D. G. , Bastelberger S. , Mousavi-Fard M. , Rosati B. , Gysel M. , Krieger U. K. , Leck C. , Nenes A. , Riipinen I. , Virtanen A. , Salter M. E. 
Published: July 2017

AbstractSea spray is one of the largest natural aerosol sources and plays an important role in the Earth’s radiative budget. These particles are inherently hygroscopic, that is, they take-up moisture from the air, which affects the extent to which they interact with solar radiation. We demonstrate that the hygroscopic growth of inorganic sea salt is 8–15% lower than pure sodium chloride, most likely due to the presence of hydrates. We observe an increase in hygroscopic growth with decreasing particle size (for particle diameters <150 nm) that is independent of the particle generation method. We vary the hygroscopic growth of the inorganic sea salt within a general circulation model and show that a reduced hygroscopicity leads to a reduction in aerosol-radiation interactions, manifested by a latitudinal-dependent reduction of the aerosol optical depth by up to 15%, while cloud-related parameters are unaffected. We propose that a value of κs=1.1 (at RH=90%) is used to represent the hygroscopicity of inorganic sea salt particles in numerical models.
A point-of-care microfluidic biochip for quantification of CD64 expression from whole blood for sepsis stratification
Authors: Hassan U. , Ghonge T. , Reddy B. , Patel M. , Rappleye M. , Taneja I. , Tanna A. , Healey R. , Manusry N. , Price Z. , Jensen T. , Berger J. , Hasnain A. , Flaugher E. , Liu S. , Davis B. , Kumar J. , White K. , Bashir R. 
Published: July 2017

AbstractSepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. Leukocyte count and CD64 expression on neutrophils (nCD64) are known to correlate strongly with improved sensitivity and specificity of sepsis diagnosis at its onset. A major challenge is the lack of a rapid and accurate point-of-care (PoC) device that can perform these measurements from a minute blood sample. Here, we report a PoC microfluidic biochip to enumerate leukocytes and quantify nCD64 levels from 10 μl of whole blood without any manual processing. Biochip measurements have shown excellent correlation with the results from flow cytometer. In clinical studies, we have used PoC biochip to monitor leukocyte counts and nCD64 levels from patients’ blood at different times of their stay in the hospital. Furthermore, we have shown the biochip’s utility for improved sepsis diagnosis by combining these measurements with electronic medical record (EMR).
Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism
Authors: Biancur Douglas E. , Paulo Joao A. , Małachowska Beata , Quiles Del Rey Maria , Sousa Cristovão M. , Wang Xiaoxu , Sohn Albert S. W. , Chu Gerald C. , Gygi Steven P. , Harper J. Wade , Fendler Wojciech , Mancias Joseph D. , Kimmelman Alec C. 
Published: July 2017

AbstractPancreatic ductal adenocarcinoma is a notoriously difficult-to-treat cancer and patients are in need of novel therapies. We have shown previously that these tumours have altered metabolic requirements, making them highly reliant on a number of adaptations including a non-canonical glutamine (Gln) metabolic pathway and that inhibition of downstream components of Gln metabolism leads to a decrease in tumour growth. Here we test whether recently developed inhibitors of glutaminase (GLS), which mediates an early step in Gln metabolism, represent a viable therapeutic strategy. We show that despite marked early effects on in vitro proliferation caused by GLS inhibition, pancreatic cancer cells have adaptive metabolic networks that sustain proliferation in vitro and in vivo. We use an integrated metabolomic and proteomic platform to understand this adaptive response and thereby design rational combinatorial approaches. We demonstrate that pancreatic cancer metabolism is adaptive and that targeting Gln metabolism in combination with these adaptive responses may yield clinical benefits for patients.
Quantum Nuclear Dynamics of Protons within Layered Hydroxides at High Pressure
Authors: Dupuis Romain , Dolado Jorge S. , Benoit Magali , Surga Jose , Ayuela Andrés 
Published: July 2017

AbstractStudies of the structure of hydroxides under pressure using neutron diffraction reveal that the high concentration of hydrogen is distributed in a disordered network. The disorder in the hydrogen-bond network and possible phase transitions are reported to occur at pressures within the range accessible to experiments for layered calcium hydroxides, which are considered to be exemplary prototype materials. In this study, the static and dynamical properties of these layered hydroxides are investigated using a quantum approach describing nuclear motion, shown herein to be required particularly when studying diffusion processes involving light hydrogen atoms. The effect of high-pressure on the disordered hydrogen-bond network shows that the protons tunnel back and forth across the barriers between three potential minima around the oxygen atoms. At higher pressures the structure has quasi two-dimensional layers of hydrogen atoms, such that at low temperatures this causes the barrier crossing of the hydrogen to be significantly rarefied. Furthermore, for moderate values of both temperature and pressure this process occurs less often than the usual mechanism of proton transport via vacancies, limiting global proton diffusion within layers at high pressure.
Organization and hierarchy of the human functional brain network lead to a chain-like core
Authors: Mastrandrea Rossana , Gabrielli Andrea , Piras Fabrizio , Spalletta Gianfranco , Caldarelli Guido , Gili Tommaso 
Published: July 2017

AbstractThe brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.
Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses
Authors: Moon Ho-Jin , Nikapitiya Chamilani , Lee Hyun-Cheol , Park Min-Eun , Kim Jae-Hoon , Kim Tae-Hwan , Yoon Ji-Eun , Cho Won-Kyung , Ma Jin Yeul , Kim Chul-Joong , Jung Jae U. , Lee Jong-Soo 
Published: July 2017

AbstractThe antiviral activities of synthesized Kα2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi’s sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the Kα2-helix peptide, the present study showed that treatment with the Kα2 peptide fused with the TAT peptide significantly inhibited IAV replication and transmission. Moreover, TAT-Kα2 peptide protected the mice, that were challenged with lethal doses of highly pathogenic influenza A H5N1 or H1N1 viruses. Mechanistically, we found that TAT-Kα2 peptide destabilized the viral membranes, depending on their lipid composition of the viral envelop. In addition to IAV, the Kα2 peptide inhibited infections with enveloped viruses, such as Vesicular Stomatitis Virus (VSV) and Respiratory Syncytial Virus (RSV), without cytotoxicity. These results suggest that TAT-Kα2 peptide is a potential antiviral agent for controlling emerging or re-emerging enveloped viruses, particularly diverse subtypes of IAVs.
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria
Authors: Zarkan Ashraf , Macklyne Heather-Rose , Chirgadze Dimitri Y. , Bond Andrew D. , Hesketh Andrew R. , Hong Hee-Jeon 
Published: July 2017

AbstractVancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors.
Dynamic responses to silicon in Thalasiossira pseudonana - Identification, characterisation and classification of signature genes and their corresponding protein motifs
Authors: Brembu Tore , Chauton Matilde Skogen , Winge Per , Bones Atle M. , Vadstein Olav 
Published: July 2017

AbstractThe diatom cell wall, or frustule, is a highly complex, three-dimensional structure consisting of nanopatterned silica as well as proteins and other organic components. While some key components have been identified, knowledge on frustule biosynthesis is still fragmented. The model diatomThalassiosira pseudonanawas subjected to silicon (Si) shift-up and shift-down situations. Cellular and molecular signatures, dynamic changes and co-regulated clusters representing the hallmarks of cellular and molecular responses to changing Si availabilities were characterised. Ten new proteins with silaffin-like motifs, two kinases and a novel family of putatively frustule-associated transmembrane proteins induced by Si shift-up with a possible role in frustule biosynthesis were identified. A separate cluster analysis performed on all significantly regulated silaffin-like proteins (SFLPs), as well as silaffin-like motifs, resulted in the classification of silaffins, cingulins and SFLPs into distinct clusters. A majority of the genes in the Si-responsive clusters are highly divergent, but positive selection does not seem to be the driver behind this variability. This study provides a high-resolution map over transcriptional responses to changes in Si availability inT. pseudonana. Hallmark Si-responsive genes are identified, characteristic motifs and domains are classified, and taxonomic and evolutionary implications outlined and discussed.
3D free-standing nitrogen-doped reduced graphene oxide aerogel as anode material for sodium ion batteries with enhanced sodium storage
Authors: Zhang Jiao , Li Chuanqi , Peng Zhikun , Liu Yushan , Zhang Jianmin , Liu Zhongyi , Li Dan 
Published: July 2017

AbstractSodium ion batteries have drawn extensive attentions for large-scale energy storage to replace lithium ion batteries primarily due to the natural abundance of sodium resource and low cost, but their energy density and electrochemical performance are hindered by the sluggish diffusion kinetics of sodium ion. Herein, free-standing nitrogen-doped graphene aerogel has been fabricated via hydrothermal reaction as the potential anode material for sodium ion batteries. The three dimensional porous network structure of the graphene aerogel provides sufficient interstitial space for sodium ion accommodation, allowing fast and reversible ion intercalation/de-intercalation. The nitrogen doping could introduce defects on the graphene sheets, making the feasible transport of large-sized sodium ion. Benefiting from the effective structure and nitrogen doping, the obtained material demonstrates high reversible capacities, good cycling performance (287.9 mA h g−1 after 200 cycles at a current density of 100 mA g−1), especially superior rate capability (151.9 mA h g−1 at a high current density of 5 A g−1).
X-Ray snapshots of a pyridoxal enzyme: a catalytic mechanism involving concerted [1,5]-hydrogen sigmatropy in methionine γ-lyase
Authors: Sato Dan , Shiba Tomoo , Karaki Tsuyoshi , Yamagata Wataru , Nozaki Tomoyoshi , Nakazawa Takashi , Harada Shigeharu 
Published: July 2017

AbstractPyridoxal 5′-phosphate (PLP)-enzymes are essentially involved in amino acid and amine metabolism of a wide variety of organisms. Despite their extensive biochemical studies, there are little evidence and structural data to comprehensively elaborate the catalytic mechanism. We obtained X-ray snapshots of l-methionine γ-lyase from Entamoeba histolytica (EhMGL), a PLP-enzyme catalyzing the γ-elimination reaction of methionine. Here, we suggest a catalytic mechanism of EhMGL by using the X-ray snapshots covering all stages of this multistep catalysis reaction. Initial formation of a Michaelis complex is followed by the migration of double bond from the C4′=Nα–Cα moiety in an intermediate PLP-methionine imine to C4′–Nα=Cα in pyridoxamine 5′-phosphate (PMP)-α,β-dehydromethionine imine without intervention of a putative quinonoid intermediate. The enzyme can facilitate the subsequent γ-elimination of methanethiol by the possible general acid-base catalysis of Tyr108 for the E1cB mechanism, enabling to form the ene-imine C4′–Nα=Cα–Cβ=Cγ structure with the s-cis conformation, which is prerequisite for the non-enzymatic symmetry-allowed suprafacial [1,5]-hydrogen shift to complete the catalytic cycle by releasing α-ketobutyrate. The mechanism based on the X-ray snapshots is consistent with the reactivity of MGL toward methionine analogues. The generality of such a mechanism involving non-enzymatic concerted reaction in other PLP enzymes is discussed.
Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
Authors: Wang Chun , Xu Can-Xin , Alippe Yael , Qu Chao , Xiao Jianqiu , Schipani Ernestina , Civitelli Roberto , Abu-Amer Yousef , Mbalaviele Gabriel 
Published: July 2017

AbstractSkeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.
DNA Barcoding studies on Thrips in India: Cryptic species and Species complexes
Authors: Tyagi Kaomud , Kumar Vikas , Singha Devkant , Chandra Kailash , Laskar Boni Amin , Kundu Shantanu , Chakraborty Rajasree , Chatterjee Sumantika 
Published: July 2017

AbstractThrips are one of the major sucking pest and vector of plant viruses causing huge economic loss in agriculture. The accurate identification of thrips is crucial for effective pest management strategies. However, morphology based identification has limitations and warrants integration of molecular data. We attempted the largest DNA barcoding initiative on 370 sequences of 89 thrips morphospecies including 104 novel sequences from 39 morphospecies, including the type specimens of four species. The results of multiple species delimitation methods (BIN, ABGD, GMYC and bPTP) were consistent for 73 species (82%) with their morphological identifications. A total of 107 molecular operational taxonomic units (MOTUs) was recovered for 89 morphospecies by superimposing multiple methods and applying a three level nomenclature system. We detected more than one MOTU in 14 morphospecies indicating to have cryptic diversity including, two major vector species (Frankliniella schultzei and Thrips palmi). However, four morphospecies (Thrips moundi, Thrips carthami, Haplothrips andersi and Haplothrips gowdeyi) showed low genetic distances between them with overlapping in barcode gap that requires further analysis with multiple molecular markers and more specimens from wide geographical areas for better taxonomic judgment. We also presented the advantage of simultaneous use of multiple delimitation methods for detection and identification of cryptic species.
Serum TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer
Authors: Ishibashi Yuko , Ohtsu Hiroshi , Ikemura Masako , Kikuchi Yasuko , Niwa Takayoshi , Nishioka Kotoe , Uchida Yoshihiro , Miura Hirona , Aikou Susumu , Gunji Toshiaki , Matsuhashi Nobuyuki , Ohmoto Yasukazu , Sasaki Takeshi , Seto Yasuyuki , Ogawa Toshihisa , Tada Keiichiro , Nomura Sachiyo 
Published: July 2017

AbstractBreast cancer remains a common malignancy in women, but the take-up for breast cancer screening programs in Japan is still low, possibly due to its perceived inconvenience. TFF1 and TFF3 are expressed in both breast cancer tissue and normal breast. Serum trefoil proteins were reported as cancer screening markers for gastric, prostate, lung, pancreatic cancer and cholangio carcinoma. The purpose of this study was to examine whether serum trefoil proteins could be screening biomarkers for breast cancer. Serum trefoil proteins in 94 breast cancer patients and 84 health check females were measured by ELISA. Serum TFF1 and TFF3 were significantly higher and serum TFF2 was significantly lower in breast cancer patients. Area under the curve of receiver operating characteristic of TFF1, TFF2, and TFF3 was 0.69, 0.83, and. 0.72, respectively. AUC of the combination of TFF1, TFF2, and TFF3 was 0.96. Immunohistochemically, TFF1 expression was positive in 56.5% and TFF3 was positive in 73.9% of breast cancers, while TFF2 was negative in all tumors. Serum TFF1 had positive correlation with expression of TFF1 in breast cancer tissue. Serum concentrations of TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer.
Effects of suspended sediments on the sponge holobiont with implications for dredging management
Authors: Pineda Mari-Carmen , Strehlow Brian , Sternel Miriam , Duckworth Alan , Jones Ross , Webster Nicole S. 
Published: July 2017

AbstractDredging can cause high suspended sediment concentrations (SSC) in the water column, posing a hazard to filter feeding organisms like sponges as sediment may clog their aquiferous systems and reduce feeding. In order to provide pressure−response values for sponges to SSC and tease apart the cause:effect pathways of dredging pressures, five heterotrophic and phototrophic species were experimentally exposed to a range of dredging-relevant SSC of up to 100 mg L−1, with light compensation across treatments to ensure that SSC was the primary physical parameter. This study shows that some sponge species exposed to high SSC (≥23 mg L−1) for extended periods (28 d) have lower survival, increased necrosis and depletion of energy reserves. In contrast, SSC of ≤10 mg L−1caused few, if any, negative effects and is thus suggested as a prudent sub-lethal threshold for sponges. Microbial communities did not change significantly among SSC treatments, although a nutritional shift from mixotrophy towards increased phototrophy was detected for some sponge species exposed to high SSC. Importantly however, it is expected that the combined effect of SSC with low light availability and sediment smothering as occurs during dredging operations will increase the negative effects on sponges.