bluuebunny/crossref_metadata_2025 huggingface dataset:
First discovery of Eocene coastal-estuarine ostracods from Japan, with the geological history of the migration of estuarine genera in the Far East
Authors: TANAKA GENGO , HENMI YASUHISA , KOMATSU TOSHIFUMI , HIROSE KOJI , UGAI HIROAKI , KAWANO SHIGEHIRO , MAEDA HARUYOSHI
Published: September 2017

The genusNeomonoceratina, which dominated the ostracod assemblage in the uppermost part of the Akasaki Formation (Miroku Group) of the Kyushu Island, Japan, is associated with the benthic foraminiferAmmonia cf.beccarii, molluscaTerebralia? sp. andAnomiasp., and the oogonium of Charophyceae, indicating a marine-to-brackish estuarine environment involving inflowing freshwater. This is the first record of Eocene coastal-estuarine ostracods from the eastern margin of the Eurasian continent and demonstrates that different pre-Neogene coastal-estuarine ostracod assemblages flourished in this region. The assemblages comprised five ostracod species (including one novel species) assigned to the generaNeomonoceratina,Paijeiborchella,PropontocyprisandParakrithella. These species exhibited genus-level links with the Eocene borehole cores along the continental shelf of the East China Sea and other areas of Kyushu. Fossil data of characteristic Eocene coastal-estuarine genera collected worldwide indicate that different characteristic genera inhabited each region. For example,Neomonoceratinaoriginated on the Indian subcontinent by the Early Paleocene period at the latest, along with the northern drift of the Indian subcontinent. These species subsequently diversified west and east with the equatorial current and counter-current via the Tethys and reached the eastern margin of the Eurasian continent among the various eastwards-migrating species, where one genus ultimately adapted to the coastal-estuarine environment. Notably, the coastal-estuarine ostracod assemblage of the eastern margin of the Eurasian continent differs completely from that of the Tethys during the Eocene period. Our results suggest that coastal-estuarine ostracod assemblages are a powerful tool for palaeogeographic reconstruction.
The value of Admiral Matelieff's writings for studying the history of Southeast Asia,c.1600–1620
Authors: Borschberg Peter
Published: September 2017

Cornelis Matelieff de Jonge (also Cornelis Cornelisz. Matelief) was a director of the Dutch East India Company (VOC) and fleet commander of a voyage to the East Indies in 1605–08. On his return to the Dutch Republic in September 1608, he wrote a series of epistolary memorials, or ‘discourses’, in which he recommended sweeping reforms in the way in which the VOC conducted business in Asia. Not only did these recommendations serve as a blueprint for subsequent developments of the VOC during the early seventeenth century, the documents also made astute observations about the dynamics of trade, geopolitics, agency of the Asian rulers as well as political power on the Malay Peninsula, Java, Maluku and Borneo. This article problematises these primary sources and demonstrates how they can be profitably mined for the history of trade and diplomacy of early seventeenth century Southeast Asia.
Subclinical levels of anxiety but not depression are associated with planning performance in a large population-based sample
Authors: Unterrainer J. M. , Domschke K. , Rahm B. , Wiltink J. , Schulz A. , Pfeiffer N. , Lackner K. J. , Münzel T. , Wild P. S. , Beutel M.
Published: September 2017

Background

Major depression and anxiety disorders are known to negatively influence cognitive performance. Moreover, there is evidence for greater cognitive decline in older adults with generalized anxiety disorder. Except for clinical studies, complex executive planning functions and subclinical levels of anxiety have not been examined in a population-based sample with a broad age range.

Methods

Planning performance was assessed using the Tower of London task in a population-based sample of 4240 participants aged 40–80 years from the Gutenberg Health Study (GHS) and related to self-reported anxiety and depression by means of multiple linear regression analysis.

Results

Higher anxiety ratings were associated with lower planning performance (β= −0.20;p< 0.0001) independent of age (β= 0.03;p= 0.47). When directly comparing the predictive value of depression and anxiety on cognition, only anxiety attained significance (β= −0.19;p= 0.0047), whereas depression did not (β= −0.01;p= 0.71).

Conclusions

Subclinical levels of anxiety but not of depression showed negative associations with cognitive functioning independent of age. Our results demonstrate that associations observed in clinical groups might differ from those in population-based samples, also with regard to the trajectory across the life span. Further studies are needed to uncover causal interrelations of anxiety and cognition, which have been proposed in the literature, in order to develop interventions aimed at reducing this negative affective state and to improve executive functioning.
INTEGRATE-HTA: THE PERSPECTIVE OF EUnetHTA
Authors: Lampe Kristian , Schnell-Inderst Petra
Published: September 2017

The HTA Core Model (HTACM) of EUnetHTA and the INTEGRATE-HTA Model (IHTAM) both provide HTA experts with advanced guidance on how to assess health technologies. In this study, we examine the similarities and differences of the two models, identifying synergies and opportunities for future collaboration. We also consider how such an alignment of the HTACM and IHTAM might be done in practice and present some alternative practical approaches. Overall the two models share several similarities, primarily the perception of HTA as a multidisciplinary analysis that needs to be adjusted according to the properties of the technology under assessment.
The benefits of exotic food crops cultivated by small-scale growers in the UK
Authors: Kell S. , Rosenfeld A. , Cunningham S. , Dobbie S. , Maxted N.
Published: September 2017

Exotic crops—plant species grown in relatively small quantities and not traditionally cultivated in a country or region—are often intimately linked with the ethnic origins of their maintainers and are a principal source of culinary and nutritional diversity for many people. Recognizing that a wealth of exotic crop diversity and associated knowledge is held by small-scale growers in the UK, Garden Organic initiated the Sowing New Seeds project to capture and preserve some of this valuable resource by building a seed collection and knowledge base. To establish a sample of this diversity and knowledge, we undertook a survey at 31 allotment sites in the Midlands region of the UK with the objectives of identifying the exotic crops cultivated, characterizing the demography of those who grow them, understanding their direct use values, and assessing their potential indirect use value for the diversification and improvement of other crops. Results reveal that 26% of the food crops recorded are exotic and that they are grown by people belonging to 13 different ethnic groups. The majority save their own seed, indicating that these crops are performing well in the UK, with grower selection providing the basis for their continuing success. Further, most maintainers swap seed with other growers, indicating that exotic crops are likely to be gradually diversifying in response to different growing conditions—a positive sign for their value for local food security and as national genetic resources with potential for use in crop improvement programs. The research highlights the multitude of benefits that growers obtain through cultivating exotic crops, which are not only related to nutrition and culinary requirements, but also to general health and well-being, culture, and a range of other forms of life enrichment. It is critical that growers are encouraged and supported in continuing to cultivate, save and pass on their exotic crops to younger generations, as well as to protect allotments from development in order to maintain this important diversity adapted to local growing conditions. Importantly, many exotic crops currently grown on a small scale may enter into commerce, and thus expand the diversity of the UK's food crop base. Such a shift may be particularly important in the face of the increasingly detrimental impacts of climate change on crop production. We conclude that exotic crop diversity could be more important for future nutrition, health and food security than we currently appreciate.
Das Belastungs-EKG
Authors: Kottmann Wilhard , Veress Réka
Published: September 2017

Zusammenfassung. Das Belastungs-EKG ist zur Erfassung einer Myokardischämie und der Leistungsfähigkeit das am weitesten verbreitete Standardverfahren in Klinik und Praxis der Kardiologie und zählt nach wie vor zu den wichtigsten Funktionsuntersuchungen des Herz-Kreislauf-Systems. Ein Belastungs-EKG sollte symptomlimitiert durchgeführt werden und ca. 10 min dauern, damit eine hohe Leistung mit möglichst hohem Doppelprodukt und damit eine möglichst hohe Aussagekraft des Tests bezüglich Ischämie und Prognose erreicht wird. Sollarbeitskapazität und Herzfrequenz sind als Abbruchkriterien nicht geeignet. Verbesserte Interpretationsmöglichkeiten durch Einbeziehung neuer Variablen (Hyper-Q) können die Diagnosegenauigkeit bei Patienten mit mittlerer Vortestwahrscheinlichkeit erhöhen. Trotz hochentwickelter bildgebender Verfahren mit grösserer Sensitivität und Spezifität bleibt ein korrekt durchgeführtes Belastungs-EKG aufgrund der ubiquitären Verfügbarkeit und des guten Kosten-Nutzen-Verhältnisses ein fester Bestandteil der Basisdiagnostik.
Pharmakologische und nicht-pharmakologische Therapie der idiopathischen Lungenfibrose
Authors: Schertel Anke , Funke-Chambour Manuela , Geiser Thomas
Published: September 2017

Zusammenfassung. Trotz der Verfügbarkeit neuer Antifibrotika, mit denen eine Verlangsamung der Krankheitsprogression erreicht werden kann, bleibt die idiopathische Lungenfibrose eine invalidisierende, progressive Erkrankung mit schlechter Prognose. Mit dem Ziel einer Verbesserung der Lebensqualität und der Vermeidung von Komplikationen werden deshalb neben der antifibrotischen Therapie auch die Behandlung von Komorbiditäten sowie nicht-medikamentöse Therapieansätze eingesetzt, welche im Folgenden vorgestellt werden.
Geometrically-controlled polarisation processing in femtosecond-laser-written photonic circuits
Authors: Pitsios Ioannis , Samara Farid , Corrielli Giacomo , Crespi Andrea , Osellame Roberto
Published: September 2017

Polarisation of light is a powerful and widely used degree of freedom to encode information, both in classical and quantum applications. In particular, quantum information technologies based on photons are being revolutionised by the use of integrated photonic circuits. It is therefore very important to be able to manipulate the polarisation of photons in such circuits. We experimentally demonstrate the fabrication by femtosecond laser micromachining of components such as polarisation insensitive and polarising directional couplers, operating at 1550 nm wavelength, where the two opposite behaviours are achieved just by controlling the geometric layout of the photonic circuits, being the waveguides fabricated with the same irradiation recipe. We expect to employ this approach in complex integrated photonic devices, capable of a full control of the photons polarisation for quantum cryptography, quantum computation and quantum teleportation experiments.
Three novel structural phenomena in the cellular ontogeny of Oenococcus oeni from northern China
Authors: Wang Yun , Liu Shuwen , Su Jing , Zhang Yu , Li Jing , Sui Yin-Qiang , Li Ying-Ying , Wang Hua , Li Hua
Published: September 2017

Stress resistance and growth are important aspects to consider when engineeringOenococcus oenistrains for winemaking. We identified 3 previously unreported structural phenomena in the cell ontogeny ofO.oenisampled in northern China. We show that budding and binary fission (BBF) occur simultaneously in the growth process; that a novel ‘pomegranate-shaped structure’ (PSS) occurs mainly in the stationary and death phases; and that symbiosis and cyclical phenomena (SCP) occur throughout the various cell growth phases. These observations add to the current knowledge of the cell growth process ofO.oeni. BBF, PSS, and SCP sufficiently describe the characteristics of the cellular ontogeny ofO.oeni. We highlight a newly identified structure that explains the complex cell growth process. These findings will help understand the growth and development ofO.oeni, supplementing the knowledge base of the established phases and providing new perspectives into its complex growth patterns.
Photobleaching in STED nanoscopy and its dependence on the photon flux applied for reversible silencing of the fluorophore
Authors: Oracz Joanna , Westphal Volker , Radzewicz Czesław , Sahl Steffen J. , Hell Stefan W.
Published: September 2017

In STED (stimulated emission depletion) nanoscopy, the resolution and signal are limited by the fluorophore de-excitation efficiency and photobleaching. Here, we investigated their dependence on the pulse duration and power of the applied STED light for the popular 750 nm wavelength. In experiments with red- and orange-emitting dyes, the pulse duration was varied from the sub-picosecond range up to continuous-wave conditions, with average powers up to 200 mW at 80 MHz repetition rate, i.e. peak powers up to 1 kW and pulse energies up to 2.5 nJ. We demonstrate the dependence of bleaching on pulse duration, which dictates the optimal parameters of how to deliver the photons required for transient fluorophore silencing. Measurements with the dye ATTO647N reveal that the bleaching of excited molecules scales with peak power with a single effective order ~1.4. This motivates peak power reduction while maintaining the number of STED-light photons, in line with the superior resolution commonly achieved for nanosecond STED pulses. Other dyes (ATTO590, STAR580, STAR635P) exhibit two distinctive bleaching regimes for constant pulse energy, one with strong dependence on peak power, one nearly independent. We interpret the results within a photobleaching model that guides quantitative predictions of resolution and bleaching.
Characterization of a new pathway that activates lumisterol in vivo to biologically active hydroxylumisterols
Authors: Slominski Andrzej T. , Kim Tae-Kang , Hobrath Judith V. , Janjetovic Zorica , Oak Allen S. W. , Postlethwaite Arnold , Lin Zongtao , Li Wei , Takeda Yukimasa , Jetten Anton M. , Tuckey Robert C.
Published: September 2017

Using LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum and epidermis, and the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of human skin cells in a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also inhibited melanoma proliferation in both monolayer and soft agar. 20-Hydroxylumisterol stimulated the expression of several genes, including those associated with keratinocyte differentiation and antioxidative responses, while inhibiting the expression of others includingRORAandRORC. Molecular modeling and studies on VDRE-transcriptional activity excludes action through the genomic site of the VDR. However, their favorable interactions with the A-pocket in conjunction with VDR translocation studies suggest they may act on this non-genomic VDR site. Inhibition of RORα and RORγ transactivation activities in a Tet-on CHO cell reporter system, RORα co-activator assays and inhibition of (RORE)-LUC reporter activity in skin cells, in conjunction with molecular modeling, identified RORα and RORγ as excellent receptor candidates for the hydroxylumisterols. Thus, we have discovered a new biologically relevant, lumisterogenic pathway, the metabolites of which display biological activity. This opens a new area of endocrine research on the effects of the hydroxylumisterols on different pathways in different cells and the mechanisms involved.
Oscillations of ultra-weak photon emission from cancer and non-cancer cells stressed by culture medium change and TNF-α
Authors: Madl Pierre , Verwanger Thomas , Geppert Mark , Scholkmann Felix
Published: September 2017

Cells spontaneously emit photons in the UV to visible/near-infrared range (ultra-weak photon emission, UPE). Perturbations of the cells’ state cause changes in UPE (evoked UPE). The aim of the present study was to analyze the evoked UPE dynamics of cells caused by two types of cell perturbations (stressors): (i) a cell culture medium change, and (ii) application of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α). Four types of human cell lines were used (squamous cell carcinoma cells, A431; adenocarcinomic alveolar basal epithelial cells, A549; p53-deficient keratinocytes, HaCaT, and cervical cancer cells, HeLa). In addition to the medium change, TNF-α was applied at different concentrations (5, 10, 20, and 40 ng/mL) and UPE measurements were performed after incubation times of 0, 30, 60, 90 min, 2, 5, 12, 24, 48 h. It was observed that (i) the change of cell culture medium (without added TNF-α) induces a cell type-specific transient increase in UPE with the largest UPE increase observed in A549 cells, (ii) the addition of TNF-α induces a cell type-specific and dose-dependent change in UPE, and (iii) stressed cell cultures in general exhibit oscillatory UPE changes.
Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity
Authors: Kapoor Abhijeet , Martinez-Rosell Gerard , Provasi Davide , de Fabritiis Gianni , Filizola Marta
Published: September 2017

While the therapeutic effect of opioids analgesics is mainly attributed to µ-opioid receptor (MOR) activation leading to G protein signaling, their side effects have mostly been linked to β-arrestin signaling. To shed light on the dynamic and kinetic elements underlying MOR functional selectivity, we carried out close to half millisecond high-throughput molecular dynamics simulations of MOR bound to a classical opioid drug (morphine) or a potent G protein-biased agonist (TRV-130). Statistical analyses of Markov state models built using this large simulation dataset combined with information theory enabled, for the first time: a) Identification of four distinct metastable regions along the activation pathway, b) Kinetic evidence of a different dynamic behavior of the receptor bound to a classical or G protein-biased opioid agonist, c) Identification of kinetically distinct conformational states to be used for the rational design of functionally selective ligands that may eventually be developed into improved drugs; d) Characterization of multiple activation/deactivation pathways of MOR, and e) Suggestion from calculated transition timescales that MOR conformational changes are not the rate-limiting step in receptor activation.
Laminarinase from Flavobacterium sp. reveals the structural basis of thermostability and substrate specificity
Authors: Qin Hui-Min , Miyakawa Takuya , Inoue Akira , Nakamura Akira , Nishiyama Ryuji , Ojima Takao , Tanokura Masaru
Published: September 2017

Laminarinase from Flavobacterium sp. strain UMI-01, a new member of the glycosyl hydrolase 16 family of a marine bacterium associated with seaweeds, mainly degrades β-1,3-glucosyl linkages of β-glucan (such as laminarin) through the hydrolysis of glycosidic bonds. We determined the crystal structure of ULam111 at 1.60-Å resolution to understand the structural basis for its thermostability and substrate specificity. A calcium-binding motif located on the opposite side of the β-sheet from catalytic cleft increased its degrading activity and thermostability. The disulfide bridge Cys31-Cys34, located on the β2-β3 loop near the substrate-binding site, is responsible for the thermostability of ULam111. The substrates of β-1,3-linked laminarin and β-1,3-1,4-linked glucan bound to the catalytic cleft in a completely different mode at subsite -3. Asn33 and Trp113, together with Phe212, formed hydrogen bonds with preferred substrates to degrade β-1,3-linked laminarin based on the structural comparisons. Our structural information provides new insights concerning thermostability and substrate recognition that will enable the design of industrial biocatalysts.
Unexpected viscoelastic deformation of tight sandstone: Insights and predictions from the fractional Maxwell model
Authors: Ding Xiang , Zhang Guangqing , Zhao Bo , Wang Yan
Published: September 2017

Tight gas is one important unconventional hydrocarbon resource that is stored in tight sandstone, whose mechanical property greatly influences the tight gas production process and is commonly believed to be simply elastic when designing the stimulation plan. However, the experimental evidence provided in this work surprisingly shows that tight sandstone can deform in a viscoelastic way. Such an unexpected observation poses a challenge in accurately modelling the deformation process. We solve this problem by adopting the fractional Maxwell model to successfully derive the constitutive equation of tight sandstone, based on which not only all the experimental data can be interpreted quantitatively, but also reasonable and consistent predictions as to tight sandstone’s long-term deformation behaviour can be made. We then investigate the typicality of our results in China’s Changqing oilfield, which is one major centre of tight gas production and where the rock samples for experiments are obtained. It is estimated that a non-negligible portion of 18% tight sandstone samples in this area will probably display viscoelasticity. Finally, our work implies that the mechanical properties of other materials may also need further scrutiny to possibly uncover any unexpected behaviour, overlooking which may result in misleading predictions.
Mechanistic insight into internal conversion process within Q-bands of chlorophyll a
Authors: Meneghin Elena , Leonardo Cristina , Volpato Andrea , Bolzonello Luca , Collini Elisabetta
Published: September 2017

The non-radiative relaxation of the excitation energy from higher energy states to the lowest energy state in chlorophylls is a crucial preliminary step for the process of photosynthesis. Despite the continuous theoretical and experimental efforts to clarify the ultrafast dynamics of this process, it still represents the object of an intense investigation because the ultrafast timescale and the congestion of the involved states makes its characterization particularly challenging. Here we exploit 2D electronic spectroscopy and recently developed data analysis tools to provide more detailed insights into the mechanism of internal conversion within the Q-bands of chlorophyll a. The measurements confirmed the timescale of the overall internal conversion rate (170 fs) and captured the presence of a previously unidentified ultrafast (40 fs) intermediate step, involving vibronic levels of the lowest excited state.
Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702
Authors: Chin Alex W. H. , Leong Nathaniel K. C. , Nicholls John M. , Poon Leo L. M.
Published: September 2017

The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range. Limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells. Notably, some mutants displayed enhanced polymerase activity, yet their replication kinetics were comparable to the wild-type virus. Surface electrostatic charge predication on the PB2 structural model revealed that the viral polymerase activity in mammalian cells generally increases as this region becomes more positively charged. One of the mutants (701A/702E) showed much reduced pathogenicity in mice while others had a pathogenicity similar to the wild-type level. Distinct tissue tropisms of the PB2-701/702 mutants were observed in infected chicken embryos. Overall, this study demonstrates that the PB2-701/702 region has a high degree of sequence plasticity and sequence changes in this region can alter virus phenotypes in vitro and in vivo.
Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice
Authors: Gomez John C. , Dang Hong , Kanke Matthew , Hagan Robert S. , Mock Jason R. , Kelada Samir N. P. , Sethupathy Praveen , Doerschuk Claire M.
Published: September 2017

The complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and performed in depth in silico analyses. Lung neutrophils were isolated 24 hours after intratracheal instillation of PBS or S. pneumoniae, and differentially expressed (DE) mRNAs and miRs were identified. Lung neutrophils from mice with S. pneumoniae pneumonia contained 4127 DE mRNAs, 36% of which were upregulated at least 2-fold. During pneumonia, lung neutrophils increase expression of pattern recognition receptors, receptors for inflammatory mediators, transcription factors including NF-κB and AP-1, Nrf2 targets, cytokines, chemokines and other inflammatory mediators. Interestingly, neutrophils responded to Type I interferons, whereas they both produced and responded to Type II interferon. Expression of regulators of the inflammatory and immune response was verified at the mRNA and protein level. Of approximately 1100 miRs queried, 31 increased and 67 decreased more than 2-fold in neutrophils from S. pneumoniae pneumonia. Network analyses of potential DE miR-target DE mRNA interactions revealed candidate key regulatory miRs. Thus, S. pneumoniae modulates mRNA and miR expression by lung neutrophils, increasing their ability to respond and facilitating host defense.
Adolescent THC Exposure Causes Enduring Prefrontal Cortical Disruption of GABAergic Inhibition and Dysregulation of Sub-Cortical Dopamine Function
Authors: Renard Justine , Szkudlarek Hanna J. , Kramar Cecilia P. , Jobson Christina E. L. , Moura Kyra , Rushlow Walter J. , Laviolette Steven R.
Published: September 2017

Chronic adolescent marijuana use has been linked to the later development of psychiatric diseases such as schizophrenia. GABAergic hypofunction in the prefrontal cortex (PFC) is a cardinal pathological feature of schizophrenia and may be a mechanism by which the PFC loses its ability to regulate sub-cortical dopamine (DA) resulting in schizophrenia-like neuropsychopathology. In the present study, we exposed adolescent rats to Δ-9-tetra-hydrocannabinol (THC), the psychoactive component in marijuana. At adulthood, we characterized the functionality of PFC GABAergic neurotransmission and its regulation of sub-cortical DA function using molecular, behavioral andin-vivoelectrophysiological analyses. Our findings revealed a persistent attenuation of PFC GABAergic function combined with a hyperactive neuronal state in PFC neurons and associated disruptions in cortical gamma oscillatory activity. These PFC abnormalities were accompanied by hyperactive DAergic neuronal activity in the ventral tegmental area (VTA) and behavioral and cognitive abnormalities similar to those observed in psychiatric disorders. Remarkably, these neuronal and behavioral effects were reversed by pharmacological activation of GABAAreceptors in the PFC. Together, these results identify a mechanistic link between dysregulated frontal cortical GABAergic inhibition and sub-cortical DAergic dysregulation, characteristic of well-established neuropsychiatric endophenotypes.
Clinical characteristics and risk factors for developing bone metastases in patients with breast cancer
Authors: Chen Wen-Zhao , Shen Jun-Feng , Zhou Yang , Chen Xuan-Yin , Liu Jia-Ming , Liu Zhi-Li
Published: September 2017

The risk factors for predicting bone metastases in patients with breast cancer are still controversial. Here, a total of 2133 patients with breast cancer, including 327 with bone metastases (15.33%) and 1806 without bone metastases (84.67%) were retrospective reviewed from January 2005 to December 2015. The spine was found to be the most common site for bone metastases, followed by ribs (57.5%), pelvis (54.1%) and sternum (44.3%). The results indicated that axillary lymph node metastases and the concentrations of CA125, CA153, ALP and hemoglobin were the independent risk factors for bone metastases in patients with breast cancer. The receiver operating characteristics (ROC) curves showed that combined axillary lymph node metastases, high CA153 and ALP, with low hemoglobin were the most accurate biomarkers for predicting bone metastases in breast cancer [area under the curve = 0.900], and the sensitivity and specificity for the prediction were 78.5% and 87.8%, respectively. Therefore, breast cancer patients with more axillary lymph node metastases, high serum concentrations of CA125, CA153, ALP and low level of hemoglobin were closely related to bone metastases. Combined axillary lymph node metastases, CA153, ALP with hemoglobin have the highest predictive accuracy for bone metastases in breast cancer.
Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration
Authors: Wang Junling , Han Xuemei , Leu Nicolae Adrian , Sterling Stephanie , Kurosaka Satoshi , Fina Marie , Lee Virginia M. , Dong Dawei W. , Yates John R. , Kashina Anna
Published: September 2017

Alpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acidic side chains of E46 and E83. Lack of arginylation leads to increased α-syn aggregation and causes the formation of larger pathological aggregates in neurons, accompanied by impairments in its ability to be cleared via normal degradation pathways. In the mouse brain, lack of arginylation leads to an increase in α-syn’s insoluble fraction, accompanied by behavioral changes characteristic for neurodegenerative pathology. Our data show that lack of arginylation in the brain leads to neurodegeneration, and suggests that α-syn arginylation can be a previously unknown factor that facilitates normal α-syn folding and function in vivo.
Pixelated Checkerboard Metasurface for Ultra-Wideband Radar Cross Section Reduction
Authors: Haji-Ahmadi Mohammad-Javad , Nayyeri Vahid , Soleimani Mohammad , Ramahi Omar M.
Published: September 2017

In this paper we designed and fabricated a metasurface working as a radar cross section (RCS) reducer over an ultra wide band of frequency from 3.8 to 10.7 GHz. The designed metasurface is a chessboard-like surface made of alternating tiles, with each tile composed of identical unit cells. We develop a novel, simple, highly robust and fully automated approach for designing the unit cells. First, a topology optimization algorithm is used to engineer the shape of the two unit cells. The area of each unit cell is pixelated. A particle swarm optimization algorithm is applied wherein each pixel corresponds to a bit having a binary value of 1 or 0 indicating metallization or no metallization. With the objective of reducing the RCS over a specified frequency range, the optimization algorithm is then linked to a full wave three-dimensional electromagnetic simulator. To validate the design procedure, a surface was designed, fabricated and experimentally tested showing significantly enhanced performance than previous works. Additionally, angular analysis is also presented showing good stability and wide-angle behavior of the designed RCS reducer. The automated design procedure has a wide range of applications and can be easily extended to design surfaces for antennas, energy harvesters, noise mitigation in electronic circuit boards amongst others.
Highly Effective Broad Spectrum Chimeric Larvicide That Targets Vector Mosquitoes Using a Lipophilic Protein
Authors: Bideshi Dennis K. , Park Hyun-Woo , Hice Robert H. , Wirth Margaret C. , Federici Brian A.
Published: September 2017

Two mosquitocidal bacteria, Bacillus thuringiensis subsp. israelensis (Bti) and Lysinibacillus sphaericus (Ls) are the active ingredients of commercial larvicides used widely to control vector mosquitoes. Bti’s efficacy is due to synergistic interactions among four proteins, Cry4Aa, Cry4Ba, Cry11Aa, and Cyt1Aa, whereas Ls’s activity is caused by Bin, a heterodimer consisting of BinA, the toxin, and BinB, a midgut-binding protein. Cyt1Aa is lipophilic and synergizes Bti Cry proteins by increasing midgut binding. We fused Bti’s Cyt1Aa to Ls’s BinA yielding a broad-spectrum chimeric protein highly mosquitocidal to important vector species including Anopheles gambiae, Culex quinquefasciatus, and Aedes aegypti, the latter an important Zika and Dengue virus vector insensitive to Ls Bin. Aside from its vector control potential, our bioassay data, in contrast to numerous other reports, provide strong evidence that BinA does not require conformational interactions with BinB or microvillar membrane lipids to bind to its intracellular target and kill mosquitoes.
Characterization and Identification of a woody lesion mimic mutant lmd, showing defence response and resistance to Alternaria alternate in birch
Authors: Li Ranhong , Chen Su , Liu Guifeng , Han Rui , Jiang Jing
Published: September 2017

Lesion mimic mutants (LMM) usually show spontaneous cell death and enhanced defence responses similar to hypersensitive response (HR) in plants. Many LMM have been reported in rice, wheat, maize, barley, Arabidopsis, etc., but little was reported in xylophyta. BpGH3.5 is an early auxin-response factor which regulates root elongation in birch. Here, we found a T-DNA insertion mutant in a BpGH3.5 transgenic line named lmd showing typical LMM characters and early leaf senescence in Betula platyphylla × B. pendula. lmd showed H2O2 accumulation, increased SA level and enhanced resistance to Alternaria alternate, compared with oe21 (another BpGH3.5 transgenic line) and NT (non-transgenic line). Cellular structure observation showed that programmed cell death occurred in lmd leaves. Stereomicroscope observation and Evans’ blue staining indicated that lmd is a member of initiation class of LMM. Transcriptome analysis indicated that defence response-related pathways were enriched. Southern-blot indicated that there were two insertion sites in lmd genome. Genome re-sequencing and thermal asymmetric interlaced PCR (TAIL-PCR) confirmed the two insertion sites, one of which is a T-DNA insertion in the promoter of BpEIL1 that may account for the lesion mimic phenotype. This study will benefit future research on programmed cell death, HR and disease resistance in woody plants.
Analysis and comparison of the wolf microbiome under different environmental factors using three different data of Next Generation Sequencing
Authors: Wu Xiaoyang , Zhang Huanxin , Chen Jun , Shang Shuai , Yan Jiakuo , Chen Yao , Tang Xuexi , Zhang Honghai
Published: September 2017

Next Generation Sequencing has been widely used to characterize the prevalence of fecal bacteria in many different species. In this study, we attempted to employ a low-cost and high-throughput sequencing model to discern information pertaining to the wolf microbiota. It is hoped that this model will allow researchers to elucidate potential protective factors in relation to endangered wolf species. We propose three high-throughput sequencing models to reveal information pertaining to the micro-ecology of the wolf. Our analyses advised that, among the three models, more than 100,000 sequences are more appropriate to retrieve the communities’ richness and diversity of micro-ecology. In addition, the top five wolf microbiome OTUs (99%) were members of the following five phyla: Bacteroidetes, Fusobacteria, Firmicutes, Proteobacteria, and Actinobacteria. While Alloprevotella, Clostridium_sensu_stricto_1, Anaerobiospirillum, Faecalibactreium and Streptococcus were shared by all samples, their relative abundances were differentially represented between domestic dogs and other wolves. Our findings suggest that altitude, human interference, age, and climate all contribute towards the micro-ecology of the wolf. Specifically, we observed that genera Succinivibrio and Turicibacter are significantly related to altitude and human interference (including hunting practices).
Reevaluating the prognostic significance of male gender for papillary thyroid carcinoma and microcarcinoma: a SEER database analysis
Authors: Liu Chunping , Chen Tianwen , Zeng Wen , Wang Shuntao , Xiong Yiquan , Liu Zeming , Huang Tao
Published: September 2017

The prognostic significance of gender remains controversial for papillary thyroid carcinoma (PTC). In this study, we investigated the associations between gender and prognosis in a large cohort of patients with PTC or PTMC that was diagnosed in 2010–2013 and recorded in the Surveillance, Epidemiology, and End Results cancer registry. The mean ± standard deviation duration of survival for all patients with PTC during the study period was 21.47 ± 14.04 months. In Kaplan-Meier analyses of the entire cohort of PTC patients, survival curves for all-cause death and cancer-specific death declined more sharply for men than for women. Similar results were observed in analyses of patients with PTCs > 1 cm and PTMC. After adjusting for potential confounders, hazard rates indicated significantly elevated all-cause mortality for men in analyses of all PTCs, PTCs > 1 cm, and PTMCs. However, in a confounder-adjusted analysis of patients with PTMC, the hazard rate did not indicate significantly higher mortality for men than for women. Our study demonstrated that male gender is an independent poor prognostic factor for all PTCs and for PTCs > 1 cm. However, gender is not an independent prognostic factor for cause-specific survival in PTMC.
Lasing by driven atoms-cavity system in collective strong coupling regime
Authors: Sawant Rahul , Rangwala S. A.
Published: September 2017

The interaction of laser cooled atoms with resonant light is determined by the natural linewidth of the excited state. An optical cavity is another optically resonant system where the loss from the cavity determines the resonant optical response of the system. The near resonant combination of an optical Fabry-Pérot cavity with laser cooled and trapped atoms couples two distinct optical resonators via light and has great potential for precision measurements and the creation of versatile quantum optics systems. Here we show how driven magneto-optically trapped atoms in collective strong coupling regime with the cavity leads to lasing at a frequency red detuned from the atomic transition. Lasing is demonstrated experimentally by the observation of a lasing threshold accompanied by polarization and spatial mode purity, and line-narrowing in the outcoupled light. Spontaneous emission into the cavity mode by the driven atoms stimulates lasing action, which is capable of operating as a continuous wave laser in steady state, without a seed laser. The system is modeled theoretically, and qualitative agreement with experimentally observed lasing is seen. Our result opens up a range of new measurement possibilities with this system.
Siglec-5 is a novel marker of critical limb ischemia in patients with diabetes
Authors: Li Ju-yi , Yang Xiao-yan , Wang Xiu-fang , Jia Xiong , Wang Zhong-jing , Deng Ai-ping , Bai Xiang-li , Zhu Lin , Li Bing-hui , Feng Zi-bo , Li Ye , Wang Ling , Jin Si
Published: September 2017

Critical Limb Ischemia (CLI) is common but uncommonly diagnosed. Improved recognition and early diagnostic markers for CLI are needed. Therefore, the aim of our study was to identify plasma biomarkers of CLI in patients with type 2 diabetes mellitus (T2DM). In this study, antibody-coated glass slide arrays were used to determine the plasma levels of 274 human cytokines in four matched cases of diabetes with and without CLI. Potential biomarkers were confirmed in an independent cohort by ELISA. After adjusting for confounding risk factors, only plasma level of Siglec-5 remained significantly associated with an increased odds ratio (OR) for diabetes with CLI by binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off points for Siglec-5 was 153.1 ng/ml. After entering Siglec-5, the AUC was 0.99, which was higher than that of confounding risk factors only (AUC = 0.97, P < 0.05). Siglec-5 was expressed in plaques, but not in healthy artery wall in T2DM patients. Elevated plasma Siglec-5 was independently associated with CLI in T2DM. Plasma Siglec-5 levels are implicated as an early diagnostic marker of CLI in T2DM patients and it may become a target for the prevention or treatment of CLI in diabetes.
Metagenomic insight into the microbial networks and metabolic mechanism in anaerobic digesters for food waste by incorporating activated carbon
Authors: Zhang Jingxin , Mao Liwei , Zhang Le , Loh Kai-Chee , Dai Yanjun , Tong Yen Wah
Published: September 2017

Powdered activated carbon (AC) is commonly used as an effective additive to enhance anaerobic digestion (AD), but little is known about how the metabolic pathways resulting from adding AC change the microbial association network and enhance food waste treatment. In this work, the use of AC in an anaerobic digestion system for food waste was explored. Using bioinformatics analysis, taxonomic trees and the KEGG pathway analysis, changes in microbial network and biometabolic pathways were tracked. The overall effect of these changes were used to explain and validate improved digestion performance. The results showed that AC accelerated the decomposition of edible oil in food waste, enhancing the conversion of food waste to methane with the optimized dosage of 12 g AC per reactor. Specifically, when AC was added, the proponoate metabolic pathway that converts propanoic acid to acetic acid became more prominent, as measured by 16S rRNA in the microbial community. The other two metabolic pathways, Lipid Metabolism and Methane Metabolism, were also enhanced. Bioinformatics analysis revealed that AC promoted the proliferation of syntrophic microorganisms such as Methanosaeta and Geobacter, forming a highly intensive syntrophic microbial network.
Effect of efflux pump inhibition on Pseudomonas aeruginosa transcriptome and virulence
Authors: Rampioni Giordano , Pillai Cejoice Ramachandran , Longo Francesca , Bondì Roslen , Baldelli Valerio , Messina Marco , Imperi Francesco , Visca Paolo , Leoni Livia
Published: September 2017

Efflux pumps of the resistance-nodulation-cell-division (RND) family increase antibiotic resistance in many bacterial pathogens, representing candidate targets for the development of antibiotic adjuvants. RND pumps have also been proposed to contribute to bacterial infection, implying that efflux pump inhibitors (EPIs) could also act as anti-virulence drugs. Nevertheless, EPIs are usually investigated only for their properties as antibiotic adjuvants, while their potential anti-virulence activity is seldom taken into account. In this study it is shown that RND efflux pumps contribute to Pseudomonas aeruginosa PAO1 pathogenicity in an insect model of infection, and that the well-characterized EPI Phe-Arg-β-naphthylamide (PAβN) is able to reduce in vivo virulence of the P. aeruginosa PAO1 laboratory strain, as well as of clinical isolates. The production of quorum sensing (QS) molecules and of QS-dependent virulence phenotypes is differentially affected by PAβN, depending on the strain. Transcriptomic and phenotypic analyses showed that the protection exerted by PAβN from P. aeruginosa PAO1 infection in vivo correlates with the down-regulation of key virulence genes (e.g. genes involved in iron and phosphate starvation). Since PAβN impacts P. aeruginosa virulence, anti-virulence properties of EPIs are worthy to be explored, taking into account possible strain-specificity of their activity.
COPT2, a plasma membrane located copper transporter, is involved in the uptake of Au in Arabidopsis
Authors: Tiwari Manish , Venkatachalam Perumal , Penarrubia Lola , Sahi Shivendra V.
Published: September 2017

The mechanism of gold nanoparticle formation and genes involved in such processes, especially Au transport in plants are not understood. Previous reports pointed to the probable role of COPT2 in Au transport based on the transcript accumulation of COPT2 under Au exposure. Here, we provide evidence revealing the additional role of COPT2 for Au mobilization in yeast and Arabidopsis. The COPT2 transcripts significantly accumulated in the root of Arabidopsis under Au exposure. The expression of COPT2 restores Cu uptake ability in ctr1Δctr3Δ mutants and leads to Au sensitivity in yeast, which is comparable to Cu in growth kinetics experiments. The metal measurement data showed that the Au level was increased in COPT2, expressing yeast cells compared to vector transformed control. The copt2 mutant of Arabidopsis displayed a similar growth pattern to that of Col-0 under Au treatment. However, a notable phenotypic difference was noticed in three-week-old plants treated with and without Au. Consistent with yeast, Au uptake was reduced in the copt2 mutant of Arabidopsis. Together, these results clearly reveal the Au uptake capability of COPT2 in yeast and Arabidopsis. This is the first report showing the potential role of any transporter towards uptake and accumulation of Au in plants.
High extinction ratio electromagnetically induced transparency analogue based on the radiation suppression of dark modes
Authors: Xie JingYa , Zhu Xi , Zang XiaoFei , Cheng QingQing , Ye YangYang , Zhu YiMing
Published: September 2017

A high extinction ratio (ER) electromagnetically induced transparency (EIT) analogue based on single-layer metamaterial is designed and experimentally demonstrated in this paper. This design involves four mirror-like symmetrically coupled split ring resonators (SRRs) that exhibit a bright-dark-dark-bright mode configuration. The EIT-like effect is realized by coupling between the bright resonators and dark resonators. The high ER feature is achieved from the suppression of radiative losses, due to opposite directions of electric and magnetic dipoles of two dark modes in the unit cell. Classical coupled resonator model is used to theoretically analyze the device transmission performances and to characterize parameter influence of the ER. Both numerical simulation and experiment results demonstrate that the ER of this device can reach more than 21 dB, which is 11 dB higher than that of conventional bright-dark coupling SRR arrangement. Finally, the potential multi-channel sensing utility of this device is demonstrated to show the importance of high ER feature.