bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the planetary dynamo go cycling on? Re-examining the evidence for cycles in magnetic reversal rate
Authors: Melott Adrian L. , Pivarunas Anthony , Meert Joseph G. , Lieberman Bruce S.
Published: March 2017

The record of reversals of the geomagnetic field has played an integral role in the development of plate tectonic theory. Statistical analyses of the reversal record are aimed at detailing patterns and linking those patterns to core–mantle processes. The geomagnetic polarity timescale is a dynamic record and new paleomagnetic and geochronologic data provide additional detail. In this paper, we examine the periodicity revealed in the reversal record back to 375 million years ago (Ma) using Fourier analysis. Four significant peaks were found in the reversal power spectra within the 16–40-million-year range (Myr). Plotting the function constructed from the sum of the frequencies of the proximal peaks yield a transient 26 Myr periodicity, suggesting chaotic motion with a periodic attractor. The possible 16 Myr periodicity, a previously recognized result, may be correlated with ‘pulsation’ of mantle plumes and perhaps; more tentatively, with core–mantle dynamics originating near the large low shear velocity layers in the Pacific and Africa. Planetary magnetic fields shield against charged particles, which can give rise to radiation at the surface and ionize the atmosphere, which is a loss mechanism particularly relevant to M stars. Understanding the origin and development of planetary magnetic fields can shed light on the habitable zone.
Quantification of galantamine in Narcissus tazetta and Galanthus nivalis (Amaryllidaceae) populations growing wild in Iran
Authors: Rahimi Khonakdari Majid , Mirjalili Mohammad Hossein , Gholipour Abbas , Rezadoost Hassan , Moridi Farimani Mahdi
Published: March 2017

Galantamine (GAL), a morphine-like alkaloid produced by some members of the Amaryllidaceae plant family, is a possible therapeutic agent in Alzheimer's disease because of its central cholinergic effects. GAL has been extracted from the plant sources or produced synthetically for pharmaceutical use. Limited supply of the natural source and high cost of synthetic production has led to a search for alternative sources of this valuable compound. In the present study, a total of six Galanthus nivalis populations (GNPs) and 11 Narcissus tazetta populations (NTPs) were collected across different regions of Iran and were then subjected to the high-performance liquid chromatography analysis for their GAL quantification. The GAL content ranged from 0.05 to 0.36 mg/g dry weight (DW) in the bulbs of GNPs, and from 0.03 to 0.33 mg/g DW in the bulbs of NTPs. Maximum content of GAL (0.36 and 0.33 mg/g DW) was measured in the Zirab population of G. nivalis and Ghaemshahr population of N. tazetta, respectively. Our results provided a suitable material for further agronomical and biotechnological strategies for enhanced production of valuable GAL compound on a large scale.
Health plan choice in the Netherlands: restrictive health plans preferred by young and healthy individuals
Authors: Bes Romy E. , Curfs Emile C. , Groenewegen Peter P. , de Jong Judith D.
Published: March 2017

In a health care system based on managed competition, health insurers negotiate on quality and price with care providers and are allowed to offer restrictive health plans. It is crucial that enrolees who need care choose restrictive health plans, as otherwise health insurers cannot channel patients to contracted providers and they will lose their bargaining power in negotiations with providers. We aim to explain enrolees’ choice of a restrictive health plan in exchange for a lower premium. In 2014 an online survey with an experimental design was conducted on members of an access panel (response 78%;n=3,417). Results showed 37.4% of respondents willing to choose a restrictive health plan in exchange for a lower premium. This fell to 22% when the restrictive health plan also included a longer travelling time. Enrolees who choose a restrictive health plan are younger and healthier, or on lower incomes, than those preferring a non-restrictive one. This means that enrolees who use care will be unlikely to choose a restrictive health plan and, therefore, health insurers will not be able to channel them to contracted care providers. This undermines the goals of the health care system based on managed competition.
Role and mechanism of action of leucine-rich repeat kinase 1 in bone
Authors: Xing Weirong R , Goodluck Helen , Zeng Canjun , Mohan Subburaman
Published: March 2017

Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1 deficiency-induced skeletal phenotypes, LRRK1 structure–function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.
Development of SH2 probes and pull‐down assays to detect pathogen‐induced, site‐specific tyrosine phosphorylation of the TLR adaptor SCIMP
Authors: Luo Lin , Tong Samuel J , Wall Adam A , Khromykh Tatiana , Sweet Matthew J , Stow Jennifer L
Published: March 2017

Protein tyrosine phosphorylation guides many molecular interactions for cellular functions. SCIMP is a transmembrane adaptor protein (TRAP) family member that mediates selective proinflammatory cytokine responses generated by pathogen‐activated Toll‐like receptor (TLR) pathways in macrophages. TLR activation triggers SCIMP phosphorylation and selective phosphorylation of distinct tyrosine residues on this adaptor offers the potential for regulating or biasing inflammatory responses. To analyze site‐specific phosphorylation events, we developed three probes based on the SH2 domains of known SCIMP effectors, and used them for pull‐downs from macrophage extracts. CRISPR‐mediated SCIMP‐deficient RAW264.7 macrophage‐like cells were reconstituted with various phosphorylation‐deficient (Y58F, Y96F, Y120F) SCIMPs, and used to demonstrate the specificity of LPS/TLR4‐induced, site‐specific phosphorylation of SCIMP for the temporal recruitment of the effectors Grb2, Csk and SLP65. Our findings reveal potential for differential SCIMP phosphorylation and specific effectors to influence TLR signaling and inflammatory programs. Furthermore, the use of Csk‐SH2 pull‐downs to identify additional known and new Csk targets in LPS‐activated macrophages reveals the wider utility of our SH2 probes.
Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival
Authors: Nelson Marin E. , Lahiri Sujoy , Chow Jenny D. Y. , Byrne Frances L. , Hargett Stefan R. , Breen David S. , Olzomer Ellen M. , Wu Lindsay E. , Cooney Gregory J. , Turner Nigel , James David E. , Slack-Davis Jill K. , Lackner Carolin , Caldwell Stephen H. , Hoehn Kyle L.
Published: March 2017

The metabolic pathway of de novo lipogenesis is frequently upregulated in human liver tumours, and its upregulation is associated with poor prognosis. Blocking lipogenesis in cultured liver cancer cells is sufficient to decrease cell viability; however, it is not known whether blocking lipogenesis in vivo can prevent liver tumorigenesis. Herein, we inhibit hepatic lipogenesis in mice by liver-specific knockout of acetyl-CoA carboxylase (ACC) genes and treat the mice with the hepatocellular carcinogen diethylnitrosamine (DEN). Unexpectedly, mice lacking hepatic lipogenesis have a twofold increase in tumour incidence and multiplicity compared to controls. Metabolomics analysis of ACC-deficient liver identifies a marked increase in antioxidants including NADPH and reduced glutathione. Importantly, supplementing primary wild-type hepatocytes with glutathione precursors improves cell survival following DEN treatment to a level indistinguishable from ACC-deficient primary hepatocytes. This study shows that lipogenesis is dispensable for liver tumorigenesis in mice treated with DEN, and identifies an important role for ACC enzymes in redox regulation and cell survival.
Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice
Authors: Yu Wenhan , Mookherjee Suddhasil , Chaitankar Vijender , Hiriyanna Suja , Kim Jung-Woong , Brooks Matthew , Ataeijannati Yasaman , Sun Xun , Dong Lijin , Li Tiansen , Swaroop Anand , Wu Zhijian
Published: March 2017

In retinitis pigmentosa, loss of cone photoreceptors leads to blindness, and preservation of cone function is a major therapeutic goal. However, cone loss is thought to occur as a secondary event resulting from degeneration of rod photoreceptors. Here we report a genome editing approach in which adeno-associated virus (AAV)-mediated CRISPR/Cas9 delivery to postmitotic photoreceptors is used to target the Nrl gene, encoding for Neural retina-specific leucine zipper protein, a rod fate determinant during photoreceptor development. Following Nrl disruption, rods gain partial features of cones and present with improved survival in the presence of mutations in rod-specific genes, consequently preventing secondary cone degeneration. In three different mouse models of retinal degeneration, the treatment substantially improves rod survival and preserves cone function. Our data suggest that CRISPR/Cas9-mediated NRL disruption in rods may be a promising treatment option for patients with retinitis pigmentosa.
A young child with a history of wheeze
Authors: Paton James , Bindels Patrick , McMurray Ann , Biggins Jodie , Nantanda Rebecca , Østergaard Marianne Stubbe
Published: March 2017

The parents of a 3-year old boy are anxious about their son who has recurring episodes of wheezing. They are frustrated that no one seems to be able to give them answers to their questions and would like a referral to a specialist. Does their son have asthma and what is the prognosis; how can the recurrent wheezing be managed and can the risk of asthma be reduced; are there lifestyle changes that could improve the environment and avoid triggers? Communication and support from the family practice team were essential. Listening to the parents’ concerns, explaining the diagnostic uncertainty, being realistic about what drug treatments could achieve, and providing practical advice on inhaler use and trigger avoidance reassured the parents that there was a strategy for managing their son’s wheeze. The specialist referral was postponed.
Correction: Corrigendum: Epileptiform activity in the mouse visual cortex interferes with cortical processing in connected areas
Authors: Petrucco L. , Pracucci E. , Brondi M. , Ratto G. M. , Landi S.
Published: March 2017

Scientific Reports 7: Article number: 40054; published online: 10 January 2017; updated: 14 March 2017 This Article contains typographical errors in the Results section under subheading ‘ISs fragment the up states in the opposite hemisphere’. “The presence of ISs in Hem 2 was associated with a change of the statistics of the slow-wave oscillations in Hem 1; in particular, as shown in Fig.
Correction: Corrigendum: The citrus flavanone naringenin impairs dengue virus replication in human cells
Authors: Frabasile Sandra , Koishi Andrea Cristine , Kuczera Diogo , Silveira Guilherme Ferreira , Verri Waldiceu Aparecido , Duarte dos Santos Claudia Nunes , Bordignon Juliano
Published: March 2017

Scientific Reports 7: Article number: 41864; published online: 03 February 2017; updated: 14 March 2017 In the original version of this Article, Claudia Nunes Duarte dos Santos and Juliano Bordignon were incorrectly affiliated with ‘Sección Virologia, Facultad de Ciencias, Universidad de La República, 11400, Montevideo, Uruguay’.
Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer
Authors: Wang Yi-Ting , Pan Szu-Hua , Tsai Chia-Feng , Kuo Ting-Chun , Hsu Yuan-Ling , Yen Hsin-Yung , Choong Wai-Kok , Wu Hsin-Yi , Liao Yen-Chen , Hong Tse-Ming , Sung Ting-Yi , Yang Pan-Chyr , Chen Yu-Ju
Published: March 2017

Although EGFR tyrosine kinase inhibitors (TKIs) have demonstrated good efficacy in non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, most patients develop intrinsic and acquired resistance. We quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant NSCLC cells under gefitinib treatment. The construction of a dose-dependent responsive kinase-substrate network of 1548 phosphoproteins and 3834 proteins revealed CK2-centric modules as the dominant core network for the potential gefitinib resistance-associated proteins. CK2 knockdown decreased cell survival in gefitinib-resistant NSCLCs. Using motif analysis to identify the CK2 core sub-network, we verified that elevated phosphorylation level of a CK2 substrate, HMGA1 was a critical node contributing to EGFR-TKI resistance in NSCLC cell. Both HMGA1 knockdown or mutation of the CK2 phosphorylation site, S102, of HMGA1 reinforced the efficacy of gefitinib in resistant NSCLC cells through reactivation of the downstream signaling of EGFR. Our results delineate the TKI resistance-associated kinase-substrate network, suggesting a potential therapeutic strategy for overcoming TKI-induced resistance in NSCLC.
Creation of nano eye-drops and effective drug delivery to the interior of the eye
Authors: Ikuta Yoshikazu , Aoyagi Shigenobu , Tanaka Yuji , Sato Kota , Inada Satoshi , Koseki Yoshitaka , Onodera Tsunenobu , Oikawa Hidetoshi , Kasai Hitoshi
Published: March 2017

Nano eye-drops are a new type of ophthalmic treatment with increased potency and reduced side effects. Compounds in conventional eye-drops barely penetrate into the eye because the cornea, located at the surface of eye, has a strong barrier function for preventing invasion of hydrophilic or large-sized materials from the outside. In this work, we describe the utility of nano eye-drops utilising brinzolamide, a commercially available glaucoma treatment drug, as a target compound. Fabrication of the nanoparticles of brinzolamide prodrug increases the eye penetration rate and results in high drug efficacy, compared with that of commercially available brinzolamide eye-drops formulated as micro-sized structures. In addition, the resulting nano eye-drops were not toxic to the corneal epithelium after repeated administration for 1 week. The nano eye-drops may have applications as a next-generation ophthalmic treatment.
Thermal transport in nanocrystalline Si and SiGe by ab initio based Monte Carlo simulation
Authors: Yang Lina , Minnich Austin J.
Published: March 2017

Nanocrystalline thermoelectric materials based on Si have long been of interest because Si is earth-abundant, inexpensive, and non-toxic. However, a poor understanding of phonon grain boundary scattering and its effect on thermal conductivity has impeded efforts to improve the thermoelectric figure of merit. Here, we report an ab-initio based computational study of thermal transport in nanocrystalline Si-based materials using a variance-reduced Monte Carlo method with the full phonon dispersion and intrinsic lifetimes from first-principles as input. By fitting the transmission profile of grain boundaries, we obtain excellent agreement with experimental thermal conductivity of nanocrystalline Si [Wang et al. Nano Letters 11, 2206 (2011)]. Based on these calculations, we examine phonon transport in nanocrystalline SiGe alloys with ab-initio electron-phonon scattering rates. Our calculations show that low energy phonons still transport substantial amounts of heat in these materials, despite scattering by electron-phonon interactions, due to the high transmission of phonons at grain boundaries, and thus improvements in ZT are still possible by disrupting these modes. This work demonstrates the important insights into phonon transport that can be obtained using ab-initio based Monte Carlo simulations in complex nanostructured materials.
Structural Basis of Eco1-Mediated Cohesin Acetylation
Authors: Chao William C. H. , Wade Benjamin O. , Bouchoux Céline , Jones Andrew W. , Purkiss Andrew G. , Federico Stefania , O’Reilly Nicola , Snijders Ambrosius P. , Uhlmann Frank , Singleton Martin R.
Published: March 2017

Sister-chromatid cohesion is established by Eco1-mediated acetylation on two conserved tandem lysines in the cohesin Smc3 subunit. However, the molecular basis of Eco1 substrate recognition and acetylation in cohesion is not fully understood. Here, we discover and rationalize the substrate specificity of Eco1 using mass spectrometry coupled with in-vitro acetylation assays and crystallography. Our structures of the X. laevis Eco2 (xEco2) bound to its primary and secondary Smc3 substrates demonstrate the plasticity of the substrate-binding site, which confers substrate specificity by concerted conformational changes of the central β hairpin and the C-terminal extension.
Inhibition of leukotriene B4 receptor 1 attenuates lipopolysaccharide-induced cardiac dysfunction: role of AMPK-regulated mitochondrial function
Authors: Sun Meng , Wang Rui , Han Qinghua
Published: March 2017

Leukotriene B4 (LTB4)-mediated leukocyte recruitment and inflammatory cytokine production make crucial contributions to chronic inflammation and sepsis; however, the role of LTB4 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains unclear. Therefore, the present study addressed this issue using an LTB4 receptor 1 (BLT1) inhibitor. Administration of LPS to mice resulted in decreased cardiovascular function. Inhibition of LTB4/BLT1 with the BLT1 inhibitor U75302 significantly improved survival and attenuated the LPS-induced acute cardiac dysfunction. During LPS challenge, the phosphorylated AMPK/ACC signaling pathway was slightly activated, and this effect was enhanced by U75302. Additionally, pNF-κB, Bax and cleaved caspase-3 were upregulated by LPS, and Bcl-2, IκB-α, mitochondrial complex I, complex II, and OPA1 were downregulated; however, these effects were reversed by U75302. The results indicated that the BLT1 antagonist suppressed cardiac apoptosis, inflammation, and mitochondrial impairment. Furthermore, the protection provided by the BLT1 inhibitor against LPS-induced cardiac dysfunction was significantly reversed by the AMPK inhibitor Compound C. In conclusion, inhibiting the LTB4/BLT1 signaling pathway via AMPK activation is a potential treatment strategy for septic cardiac dysfunction because it efficiently attenuates cardiac apoptosis, which may occur via the inhibition of inflammation and mitochondrial dysfunction.
Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
Authors: Carrillo-Salinas F. J. , Mestre L. , Mecha M. , Feliú A. , del Campo R. , Villarrubia N. , Espejo C. , Montalbán X. , Álvarez-Cermeño J. C. , Villar L. M. , Guaza C.
Published: March 2017

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+and CD8+T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.
A phylogenetically distinctive and extremely heat stable light-driven proton pump from the eubacterium Rubrobacter xylanophilus DSM 9941T
Authors: Kanehara Kanae , Yoshizawa Susumu , Tsukamoto Takashi , Sudo Yuki
Published: March 2017

Rhodopsins are proteins that contain seven transmembrane domains with a chromophore retinal and that function as photoreceptors for light-energy conversion and light-signal transduction in a wide variety of organisms. Here we characterized a phylogenetically distinctive new rhodopsin from the thermophilic eubacterium Rubrobacter xylanophilus DSM 9941T that was isolated from thermally polluted water. Although R. xylanophilus rhodopsin (RxR) is from Actinobacteria, it is located between eukaryotic and archaeal rhodopsins in the phylogenetic tree. Escherichia coli cells expressing RxR showed a light-induced decrease in environmental pH and inhibition by a protonophore, indicating that it works as a light-driven outward proton pump. We characterized purified RxR spectroscopically, and showed that it has an absorption maximum at 541 nm and binds nearly 100% all-trans retinal. The pKa values for the protonated retinal Schiff base and its counterion were estimated to be 10.7 and 1.3, respectively. Time-resolved flash-photolysis experiments revealed the formation of a red-shifted intermediate. Of note, RxR showed an extremely high thermal stability in comparison with other proton pumping rhodopsins such as thermophilic rhodopsin TR (by 16-times) and bacteriorhodopsin from Halobacterium salinarum (HsBR, by 4-times).
Quantification of arthritic bone degradation by analysis of 3D micro-computed tomography data
Authors: Svensson Carl-Magnus , Hoffmann Bianca , Irmler Ingo M. , Straßburger Maria , Figge Marc Thilo , Saluz Hans Peter
Published: March 2017

The use of animal models of arthritis is a key component in the evaluation of therapeutic strategies against the human disease rheumatoid arthritis (RA). Here we present quantitative measurements of bone degradation characterised by the cortical bone profile using glucose-6-phosphate isomerase (G6PI) induced arthritis. We applied micro-computed tomography (μCT) during three arthritis experiments and one control experiment to image the metatarsals of the hind paws and to investigate the effect of experimental arthritis on their cortical bone profile. For measurements of the cortical profile we automatically identified slices that are orthogonal to individual metatarsals, thereby making the measurements independent of animal placement in the scanner. We measured the average cortical thickness index (CTI) of the metatarsals, as well as the thickness changes along the metatarsal. In this study we introduced the cortical thickness gradient (CTG) as a new measure and we investigated how arthritis affects this measure. We found that in general both CTI and CTG are able to quantify arthritic progression, whilst CTG was found to be the more sensitive measure.
Acquisition of the capsule locus by horizontal gene transfer in Neisseria meningitidis is often accompanied by the loss of UDP-GalNAc synthesis
Authors: Bartley Stephanie N. , Mowlaboccus Shakeel , Mullally Christopher A. , Stubbs Keith A. , Vrielink Alice , Maiden Martin C. J. , Harrison Odile B. , Perkins Timothy T. , Kahler Charlene M.
Published: March 2017

Pathogenic meningococci have acquired a 24 kb capsule synthesis island (cps) by horizontal gene transfer which consists of a synthetic locus and associated capsule transport genes flanked by repetitive Regions D and D’. Regions D and D’ contain an intact gene encoding a UDP-galactose epimerase (galE1) and a truncated remnant (galE2), respectively. In this study, GalE protein alleles were shown to be either mono-functional, synthesising UDP-galactose (UDP-Gal), or bi-functional, synthesising UDP-Gal and UDP-galactosamine (UDP-GalNAc). Meningococci possessing a capsule null locus (cnl) typically possessed a single bi-functional galE. Separation of functionality between galE1 and galE2 alleles in meningococcal isolates was retained for all serogroups except serogroup E which has a synthetic requirement for UDP-GalNAc. The truncated galE2 remnant in Region D’ was also phylogenetically related to the bi-functional galE of the cnl locus suggesting common ancestry. A model is proposed in which the illegitimate recombination of the cps island into the galE allele of the cnl locus results in the formation of Region D’ containing the truncated galE2 locus and the capture of the cps island en bloc. The retention of the duplicated Regions D and D’ enables inversion of the synthetic locus within the cps island during bacterial growth.
Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling
Authors: Lai Jinsheng , Chen Fuqiong , Chen Jing , Ruan Guoran , He Mengying , Chen Chen , Tang Jiarong , Wang Dao Wen
Published: March 2017

Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro.
Mapping cell surface adhesion by rotation tracking and adhesion footprinting
Authors: Li Isaac T. S. , Ha Taekjip , Chemla Yann R.
Published: March 2017

Rolling adhesion, in which cells passively roll along surfaces under shear flow, is a critical process involved in inflammatory responses and cancer metastasis. Surface adhesion properties regulated by adhesion receptors and membrane tethers are critical in understanding cell rolling behavior. Locally, adhesion molecules are distributed at the tips of membrane tethers. However, how functional adhesion properties are globally distributed on the individual cell’s surface is unknown. Here, we developed a label-free technique to determine the spatial distribution of adhesive properties on rolling cell surfaces. Using dark-field imaging and particle tracking, we extract the rotational motion of individual rolling cells. The rotational information allows us to construct an adhesion map along the contact circumference of a single cell. To complement this approach, we also developed a fluorescent adhesion footprint assay to record the molecular adhesion events from cell rolling. Applying the combination of the two methods on human promyelocytic leukemia cells, our results surprisingly reveal that adhesion is non-uniformly distributed in patches on the cell surfaces. Our label-free adhesion mapping methods are applicable to the variety of cell types that undergo rolling adhesion and provide a quantitative picture of cell surface adhesion at the functional and molecular level.
Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients
Authors: Shi Jijing , Zhao Juanjuan , Zhang Xin , Cheng Yongqian , Hu Jinhua , Li Yuanyuan , Zhao Xin , Shang Qinghua , Sun Yanling , Tu Bo , Shi Lei , Gao Bin , Wang Fu-Sheng , Zhang Zheng
Published: March 2017

Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate cells (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics and regulatory mechanisms by HSCs remain to be determined, especially in livers from HBV-infected liver cirrhosis (LC) patients. We analyzed frequency, phenotype and anti-fibrotic function of hepatic and peripheral NK subsets in 43 HBV-LC patients. We found that hepatic NK subsets from LC patients displayed a decreased frequency, activation status and anti-fibrotic activity compared with those from chronic hepatitis B patients, which were mainly mediated by increased intrahepatic tumour-growth factor (TGF)-β because blockade of TGF-β significantly reversed NK anti-fibrotic function in vitro. In vivo, hepatic NK cells were enriched in proximity to the α-smooth muscle actin (α-SMA+) area within mild fibrosis regions; while in severe fibrotic areas, they were either directly attached to or separated from the α-SMA+ region. NK cells from LC patients could enter HSCs to form emperipolesis (a cell-in-cell structure) and become apoptotic; anti-TGF-β treatment ameliorated this emperipolesis. This finding suggested a novel mechanism by which activated HSCs impair NK cells’ anti-fibrosis capacity through a TGF-β-dependent emperipolesis in LC patients, providing an anti-fibrotic rational by enhancing NK cell activity.
Tailoring the electronic and magnetic properties of monolayer SnO by B, C, N, O and F adatoms
Authors: Tao Junguang , Guan Lixiu
Published: March 2017

Recently, SnO has attracted more and more attention, because it is a bipolar electronic material holding great potential in the design of p-n junction. In this paper, we examine the effect of extrinsic point defects on modifying the electronic and magnetic properties of SnO using density functionals theory (DFT). The surface adatoms considered are B, C, N, O and F with a [He] core electronic configuration. All adatoms are found energetically stable. B, C, N and F adatoms will modify the band gap and introduce band gap states. In addition, our calculations show that N, B and F can introduce stable local magnetic moment to the lattice. Our results, therefore, offer a possible route to tailor the electronic and magnetic properties of SnO by surface functionalization, which will be helpful to experimentalists in improving the performance of SnO-based electronic devices and opening new avenue for its spintronics applications.
Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders
Authors: Lemonnier E , Villeneuve N , Sonie S , Serret S , Rosier A , Roue M , Brosset P , Viellard M , Bernoux D , Rondeau S , Thummler S , Ravel D , Ben-Ari Y
Published: March 2017

In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl−)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3–11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2–18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.
Integrated transcriptome and methylome analysis in youth at high risk for bipolar disorder: a preliminary analysis
Authors: Fries G R , Quevedo J , Zeni C P , Kazimi I F , Zunta-Soares G , Spiker D E , Bowden C L , Walss-Bass C , Soares J C
Published: March 2017

First-degree relatives of patients with bipolar disorder (BD), particularly their offspring, have a higher risk of developing BD and other mental illnesses than the general population. However, the biological mechanisms underlying this increased risk are still unknown, particularly because most of the studies so far have been conducted in chronically ill adults and not in unaffected youth at high risk. In this preliminary study we analyzed genome-wide expression and methylation levels in peripheral blood mononuclear cells from children and adolescents from three matched groups: BD patients, unaffected offspring of bipolar parents (high risk) and controls (low risk). By integrating gene expression and DNA methylation and comparing the lists of differentially expressed genes and differentially methylated probes between groups, we were able to identify 43 risk genes that discriminate patients and high-risk youth from controls. Pathway analysis showed an enrichment of the glucocorticoid receptor (GR) pathway with the genesMED1,HSPA1L,GTF2A1andTAF15, which might underlie the previously reported role of stress response in the risk for BD in vulnerable populations. Cell-based assays indicate a GR hyporesponsiveness in cells from adult BD patients compared to controls and suggest that these GR-related genes can be modulated by DNA methylation, which poses the theoretical possibility of manipulating their expression as a means to counteract the familial risk presented by those subjects. Although preliminary, our results suggest the utility of peripheral measures in the identification of biomarkers of risk in high-risk populations and further emphasize the potential role of stress and DNA methylation in the risk for BD in youth.
Introduction to High Pressure CO2 and H2O Technologies in Sustainable Biomass Processing
Authors: Questell-Santiago Ydna M. , Luterbacher Jeremy S.
Published: March 2017

Biomass is an attractive source of renewable carbon-based fuels and chemicals and their production is envisaged within the framework of integrated biorefineries. Multiple research efforts to make biorefineries more economically competitive and sustainable are ongoing. In this context the use of high-pressure CO2 and CO2/H2O mixtures for biomass conversion is especially attractive. These mixtures are cheap, renewable, environmentally benign and allow tuning of various processing parameters by varying temperature, pressure and CO2 loading. This chapter presents a broad introduction of the principal processes and conversion routes being considered within biorefineries, and how high-pressure CO2 and CO2/H2O mixtures could help address certain challenges associated with biomass conversion. Some of the principle advantages associated with high-pressure CO2 and CO2/H2O mixtures that we highlight here are their abilities to act as green substitutes for unsustainable solvents, to enhance acid-catalysed reaction rates by in situ carbonic acid formation, to reduce mass transfer-limitations, and to increase access to substrates and catalysts. We discuss these advantages in the context of the trade-offs associated with implementing large-scale high-pressure systems including safety concerns and increased capital costs. With this introduction, we highlight both the principal benefits and challenges associated with the use of high-pressure CO2 and CO2/H2O mixtures, which are further detailed in subsequent chapters.
Pre-treatment of Biomass Using CO2-based Methods
Authors: Ramos Luiz P. , De León Mayorga Fayer M. , Silveira Marcos H. L. , Galvão Célia M. A. , Corazza Marcos L.
Published: March 2017

This chapter is focused on the role of high-pressure CO2 as a tool for biomass pre-treatment to enhance the selective fractionation of the main components of the plant cell wall and their subsequent conversion to fuels, chemicals and materials. In particular, the influence of different properties and process conditions on pre-treatment efficiency, such as CO2 pressure, water content, CO2-to-biomass ratio, the use of a co-solvent and biomass recalcitrance, among others, is described. Some fundamental thermo-physical properties of CO2 are presented and discussed near and at the supercritical region to address the CO2 application for process developments using supercritical technologies. In addition, pre-treatment with water only will be discussed and the advantages and disadvantages of CO2 addition will be given, along with the advantages of using scCO2 in the presence of co-solvents. Finally, relevant issues related to the conditions for scaling up of scCO2 biomass processing facility are discussed with a biorefinery background.
Perspectives of the Development of High-pressure Technologies in Biomass Processing
Authors: Lukasik Rafal M.
Published: March 2017

Consumer demands are a driving force of the chemical industry. The necessities for novel, more sustainable and less environmentally hazardous processes turn the interest of industry towards natural resources. Lignocellulosic biomass is one of such resources. Hence, economically beneficial and environmentally friendly processing of the different biopolymers constituting lignocellulosic biomass towards diverse products is a major interest. High-pressure fluids e.g. CO2, water and others have been demonstrated to be excellent reaction media for biomass processing. Additionally, high-pressure fluids have been demonstrated to be interesting alternatives for current technologies making biomass processing more sustainable and greener. However, great improvements are still needed as some of the challenges listed in this chapter must be addressed to make high-pressure fluid technologies an industrial reality.
Nucleation and growth of 2D covalent organic frameworks: polymerization and crystallization of COF monomers
Authors: Koo B. T. , Heden R. F. , Clancy P.
Published: March 2017

First computational study of the nucleation of a prototypical covalent organic framework from its building blocks.
A robust and active hybrid catalyst for facile oxygen reduction in solid oxide fuel cells
Authors: Chen Yu , Chen Yan , Ding Dong , Ding Yong , Choi YongMan , Zhang Lei , Yoo Seonyoung , Chen Dongchang , deGlee Ben , Xu Han , Lu Qiyang , Zhao Bote , Vardar Gulin , Wang Jiayue , Bluhm Hendrik , Crumlin Ethan J. , Yang Chenghao , Liu Jiang , Yildiz Bilge , Liu Meilin
Published: March 2017

A hybrid catalyst coating dramatically enhances the electrocatalytic activity and durability of a solid oxide fuel cell cathode.
The nature of the conserved basic amino acid sequences found among 437 heparin binding proteins determined by network analysis
Authors: Rudd Timothy R. , Preston Mark D. , Yates Edwin A.
Published: March 2017

Heparin/HS binding sites on proteins are composed of manifold small and flexible, basic amino acid sequences, that occur in many members of the proteome.
Marine natural products
Authors: Blunt John W. , Copp Brent R. , Keyzers Robert A. , Munro Murray H. G. , Prinsep Michèle R.
Published: March 2017

This review of marine natural products for 2015 describes 1340 new compounds and reports structural revisions or assignments of absolute configuration for previously reported compounds. Other aspects of marine natural products research over the three sesquidecades from 1971 are also examined and contrasted against the 2015 discovery of the source of ET-743, also known as the anti-cancer drug Yondelis®(trabectedin).
Towards high visible light photocatalytic activity in rare earth and N co-doped SrTiO3: a first principles evaluation and prediction
Authors: Zhang Chao , Jiang Nan , Xu Shiai , Li Zheng , Liu Xingliang , Cheng Tianle , Han Aixia , Lv Haitang , Sun Wenliang , Hou Yunlei
Published: March 2017

The band structure and photocatalytic activity of RE (La, Ce, Pr or Nd) mono-doped and RE–N co-doped SrTiO3 for band gap reduction are studied systematically using first principles calculations.
Rectangular and hexagonal doping of graphene with B, N, and O: a DFT study
Authors: Ullah Saif , Hussain Akhtar , Sato Fernando
Published: March 2017

First-principles density functional theory (DFT) calculations were carried out to investigate the rectangular and hexagonal doping of graphene with B, N, and O.
Development of an analytical method for the determination of N-nitrosamines in tobacco by GC-NCD after solid phase extraction
Authors: Soares F. A. , Chiapetta S. C. , Pacheco W. F.
Published: March 2017

In this paper an analytical method was developed for the determination of some tobacco specific N-nitrosamines (TSNAs) in cigarettes, and applied to cigarettes purchased in the city of Rio de Janeiro/RJ (Brazil).
Phenylamine-functionalized mesoporous silica supported PdAg nanoparticles: a dual heterogeneous catalyst for formic acid/CO2-mediated chemical hydrogen delivery/storage
Authors: Mori Kohsuke , Masuda Shinya , Tanaka Hiromasa , Yoshizawa Kazunari , Che Michel , Yamashita Hiromi
Published: March 2017

PdAg nanoparticles supported on phenylamine-grafted mesoporous silica acted as a dual heterogeneous catalyst for the interconversion of H2 and CO2.
Metallic reductant-free synthesis of α-substituted propionic acid derivatives through hydrocarboxylation of alkenes with a formate salt
Authors: Takaya Jun , Miyama Ko , Zhu Chuan , Iwasawa Nobuharu
Published: March 2017

Newly designed PGeP–palladium complex-catalyzed hydrocarboxylation of alkenes with a formate salt.
Two metal–organic frameworks sharing the same basic framework show distinct interpenetration degrees and different performances in CO2 catalytic conversion
Authors: Li Pei-Zhou , Wang Xiao-Jun , Liu Jia , Liang Jie , Chen Jie Yi Jalyn , Zhao Yanli
Published: March 2017

Two metal–organic frameworks having the same basic framework but different interpenetration degrees show different catalytic activities in CO2 cycloaddition reactions.
Protein conformation in pure and hydrated deep eutectic solvents
Authors: Sanchez-Fernandez A. , Edler K. J. , Arnold T. , Alba Venero D. , Jackson A. J.
Published: March 2017

Deep eutectic solvents as media for protein stabilisation: conformation in the absence and presence of water.
Pegylated and folic acid functionalized carbon nanotubes as pH controlled carriers of doxorubicin. Molecular dynamics analysis of the stability and drug release mechanism
Authors: Wolski Pawel , Nieszporek Krzysztof , Panczyk Tomasz
Published: March 2017

p-Phenylenediamine release from pegylated carbon nanotubes at acidic pH.
Crystallization of supercooled fenofibrate studied at ambient and elevated pressures
Authors: Szklarz Grzegorz , Adrjanowicz Karolina , Knapik-Kowalczuk Justyna , Jurkiewicz Karolina , Paluch Marian
Published: March 2017

Investigation of the thermodynamic history in the T,p-plane of the crystallization process of a supercooled liquid.
On the relation between carbonyl stretching frequencies and the donor power of chelating diphosphines in nickel dicarbonyl complexes
Authors: Fusè Marco , Rimoldi Isabella , Cesarotti Edoardo , Rampino Sergio , Barone Vincenzo
Published: March 2017

We unravel the mechanisms of chelation-bond formation in nickel dicarbonyl complexes with bidentate phosphines and demonstrate that σ donation drives the carbonyl stretching response to the metal–ligand bond formation.
A study of the water molecule using frequency control over nuclear dynamics in resonant X-ray scattering
Authors: Vaz da Cruz Vinícius , Ertan Emelie , Couto Rafael C. , Eckert Sebastian , Fondell Mattis , Dantz Marcus , Kennedy Brian , Schmitt Thorsten , Pietzsch Annette , Guimarães Freddy F. , Ågren Hans , Gel'mukhanov Faris , Odelius Michael , Föhlisch Alexander , Kimberg Victor
Published: March 2017

We report a full analysis of the resonant inelastic X-ray scattering spectra of H2O, D2O and HDO.
The role of coordinated solvent on Co(ii) ions in tuning the single molecule magnet properties in a {CoII2DyIII2} system
Authors: Peng Yan , Mereacre Valeriu , Anson Christopher E. , Powell Annie K.
Published: March 2017

The anisotropy of a single DyIII can be steered through subtle changes in the coordination geometry of the CoII ions in CoII2DyIII2 butterfly compounds resulting from changing the coordinated solvent molecule on the CoII ion.
Harvesting the photoexcited holes on a photocatalytic proton reduction metal–organic framework
Authors: Santaclara J. G. , Olivos-Suarez A. I. , du Fossé I. , Houtepen A. , Hunger J. , Kapteijn F. , Gascon J. , van der Veen M. A.
Published: March 2017

The highly porous titanium based metal–organic framework NH2-MIL-125(Ti) has recently attracted significant attention in the field of photocatalysis as a promising material for H+ reduction. This work reveals charge transfer upon visible light illumination from this MOF to two different charge acceptors, as an alternative to sacrificial electron donors. Charge transfer is demonstrated through a combined spectroscopic study between this MOF and: (1) 2-(1H-pyrazol-3-yl)phenol, a molecule that functionally mimics the tyrosine–histidine pair, responsible for shuttling the holes to the oxygen evolving centre in natural photosynthesis, and (2) TEMPO, a well known and stable radical. Charge transfer of the holes from the MOF to these occluded molecules takes place on the picosecond time scale. This work suggests that, by coupling a stable and recyclable charge acceptor to the photogenerated holes, the charges can be utilised for oxidation reactions and, thus, link the reduction to the oxidation reactions in water splitting.
Recent applications of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for biological sample analysis: a follow-up review
Authors: Pozebon D. , Scheffler G. L. , Dressler V. L.
Published: March 2017

Information provided by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in the analysis of biological tissues is expanding.
Optimisation of the dibromomaleimide (DBM) platform for native antibody conjugation by accelerated post-conjugation hydrolysis
Authors: Morais Maurício , Nunes João P. M. , Karu Kersti , Forte Nafsika , Benni Irene , Smith Mark E. B. , Caddick Stephen , Chudasama Vijay , Baker James R.
Published: March 2017

Dibromomaleimide (DBM) reagents are described which hydrolyse rapidly post-conjugation, representing an optimised platform for homogeneous and stable antibody conjugation.
Structural diversification of the aminobicyclo[4.3.0]nonane skeleton using alkynylsilyl-derived allylic trichloroacetimidates
Authors: Mostafa Mohamed A. B. , McMillan Angus E. , Sutherland Andrew
Published: March 2017

The late-stage synthesis of aminobicyclo[4.3.0]nonane analogues has been achieved from a key vinylsilane intermediate, prepared in turn by a one-pot multi-step process using an alkynylsilyl-derived allylic trichloroacetimidate.
Dual-sensitive and biodegradable core-crosslinked HPMA copolymer–doxorubicin conjugate-based nanoparticles for cancer therapy
Authors: Tang Manling , Zhou Minglu , Huang Yuan , Zhong Jiaju , Zhou Zhou , Luo Kui
Published: March 2017

The nanoplatform of biosafe crosslinked copolymer-NPs efficiently delivers anticancer drugs to tumor cellsviablood circulation.