bluuebunny/crossref_metadata_2025_split huggingface dataset:
A partially-open inward-facing intermediate conformation of LeuT is associated with Na+ release and substrate transport
Authors: Terry Daniel S. , Kolster Rachel A. , Quick Matthias , LeVine Michael V. , Khelashvili George , Zhou Zhou , Weinstein Harel , Javitch Jonathan A. , Blanchard Scott C. 
Published: January 2018

AbstractNeurotransmitter:sodium symporters (NSS), targets of antidepressants and psychostimulants, clear neurotransmitters from the synaptic cleft through sodium (Na+)-coupled transport. Substrate and Na+ are thought to be transported from the extracellular to intracellular space through an alternating access mechanism by coordinated conformational rearrangements in the symporter that alternately expose the binding sites to each side of the membrane. However, the mechanism by which the binding of ligands coordinates conformational changes occurring on opposite sides of the membrane is not well understood. Here, we report the use of single-molecule fluorescence resonance energy transfer (smFRET) techniques to image transitions between distinct conformational states on both the extracellular and intracellular sides of the prokaryotic NSS LeuT, including partially open intermediates associated with transport activity. The nature and functional context of these hitherto unidentified intermediate states shed new light on the allosteric mechanism that couples substrate and Na+ symport by the NSS family through conformational dynamics.
A bony-crested Jurassic dinosaur with evidence of iridescent plumage highlights complexity in early paravian evolution
Authors: Hu Dongyu , Clarke Julia A. , Eliason Chad M. , Qiu Rui , Li Quanguo , Shawkey Matthew D. , Zhao Cuilin , D’Alba Liliana , Jiang Jinkai , Xu Xing 
Published: January 2018

AbstractThe Jurassic Yanliao theropods have offered rare glimpses of the early paravian evolution and particularly of bird origins, but, with the exception of the bizarre scansoriopterygids, they have shown similar skeletal and integumentary morphologies. Here we report a distinctive new Yanliao theropod species bearing prominent lacrimal crests, bony ornaments previously known from more basal theropods. It shows longer arm and leg feathers than Anchiornis and tail feathers with asymmetrical vanes forming a tail surface area even larger than that in Archaeopteryx. Nanostructures, interpreted as melanosomes, are morphologically similar to organized, platelet-shaped organelles that produce bright iridescent colours in extant birds. The new species indicates the presence of bony ornaments, feather colour and flight-related features consistent with proposed rapid character evolution and significant diversity in signalling and locomotor strategies near bird origins.
Electric-field control of anomalous and topological Hall effects in oxide bilayer thin films
Authors: Ohuchi Yuki , Matsuno Jobu , Ogawa Naoki , Kozuka Yusuke , Uchida Masaki , Tokura Yoshinori , Kawasaki Masashi 
Published: January 2018

AbstractOne of the key goals in spintronics is to tame the spin-orbit coupling (SOC) that links spin and motion of electrons, giving rise to intriguing magneto-transport properties in itinerant magnets. Prominent examples of such SOC-based phenomena are the anomalous and topological Hall effects. However, controlling them with electric fields has remained unachieved since an electric field tends to be screened in itinerant magnets. Here we demonstrate that both anomalous and topological Hall effects can be modulated by electric fields in oxide heterostructures consisting of ferromagnetic SrRuO3 and nonmagnetic SrIrO3. We observe a clear electric field effect only when SrIrO3 is inserted between SrRuO3 and a gate dielectric. Our results establish that strong SOC of nonmagnetic materials such as SrIrO3 is essential in electrical tuning of these Hall effects and possibly other SOC-related phenomena.
Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke
Authors: Liu Yu-Chuan , Tsai Yung-Hsu , Tang Sung-Chun , Liou Houng-Chi , Kang Kai-Hsiang , Liou Horng-Huei , Jeng Jiann-Shing , Fu Wen-Mei 
Published: January 2018

AbstractIschemic stroke is a devastating disease with limited therapeutic options. It is very urgent to find a new target for drug development. Here we found that the blood level of MIF in ischemic stroke patients is upregulated. To figure out the pathological role of MIF in ischemic stroke, both in vitro and in vivo studies were conducted. For in vitro studies, primary cortical neuron cultures and adult rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation (OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were used for in vivo studies. The results show that MIF exerts no direct neuronal toxicity in primary culture but disrupts tight junction in ARBECs. Furthermore, administration of MIF following MCAo shows the deleterious influence on stroke-induced injury by destroying the tight junction of blood-brain barrier and increasing the infarct size. In contrast, administration of MIF antagonist ISO-1 has the profound neuroprotective effect. Our results demonstrate that MIF might be a good drug target for the therapy of stroke.
Mapping the epidemic changes and risks of hemorrhagic fever with renal syndrome in Shaanxi Province, China, 2005–2016
Authors: Liang Weifeng , Gu Xu , Li Xue , Zhang Kangjun , Wu Kejian , Pang Miaomiao , Dong Jianhua , Merrill Hunter R. , Hu Tao , Liu Kun , Shao Zhongjun , Yan Hong 
Published: January 2018

AbstractHemorrhagic fever with renal syndrome (HFRS) is a major rodent-borne zoonosis. Each year worldwide, 60,000–100,000 HFRS human cases are reported in more than seventy countries with almost 90% these cases occurring in China. Shaanxi Province in China has been among the most seriously affected areas since 1955. During 2009–2013, Shaanxi reported 11,400 human cases, the most of all provinces in China. Furthermore, the epidemiological features of HFRS have changed over time. Using long-term data of HFRS from 2005 to 2016, we carried out this retrospective epidemiological study combining ecological assessment models in Shaanxi. We found the majority of HFRS cases were male farmers who acquired infection in Guanzhong Plain, but the geographic extent of the epidemic has slowly spread northward. The highest age-specific attack rate since 2011 was among people aged 60–74 years, and the percentage of HFRS cases among the elderly increased from 12% in 2005 to 25% in 2016. We highly recommend expanding HFRS vaccination to people older than 60 years to better protect against the disease. Multivariate analysis revealed artificial area, cropland, pig and population density, GDP, and climate conditions (relative humidity, precipitation, and wind speed) as significant risk factors in the distribution of HFRS.
Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 /PET
Authors: Monazzam Azita , Lau Joey , Velikyan Irina , Li Su-Chen , Razmara Masoud , Rosenström Ulrika , Eriksson Olof , Skogseid Britt 
Published: January 2018

AbstractMultiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.
Dual functional dinuclear platinum complex with selective reactivity towards c-myc G-quadruplex
Authors: He Lei , Meng Zhenyu , Xu Dechen , Shao Fangwei 
Published: January 2018

AbstractG-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising targets for developing anticancer therapeutic molecules. However, the current drug development mainly focused on non-covalent dynamic binders to stabilize GQ structures, while the covalent targeting from inorganic complexes via chelating principles, as a potent therapeutic strategy was surprisingly lack of exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)2(μ-diamine)](NO3)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain two dual-functional Pt cores connected by an alkyl linkage. Pt3 with nonanediamine linkage optimized the specific binding towards c-myc G-quadruplex via dual functional clamp on GQ as 1) non-covalently π-stacking of aromatic ligands, and 2) two Pt(II) cores covalently chelated to guanines at both 3′- and 5′-ends.
Bacterial and Fungal Community Composition and Functional Activity Associated with Lake Wetland Water Level Gradients
Authors: Ma Yantian , Li Jinqian , Wu Juan , Kong Zhaoyu , Feinstein Larry M. , Ding Xia , Ge Gang , Wu Lan 
Published: January 2018

AbstractThe water regime is often the primary force driving the evolution of freshwater lakes, but how soil microbes responded to this process is far from understood. This study sampled wetland soils from a shallow lake that experienced water regime changes, Poyang Lake of China, to explore the features of bacterial and fungal community in response to water level changes. The soil physicochemical properties, T-RFLP based community structures and soil activities (including basal respiration, microbial biomass and enzymes) were all determined. Soil microbial eco-function was captured by testing the carbon metabolism with Biolog-Ecoplate. The results showed remarkable influence of the water level gradients on the soil physicochemical properties, microbial community structures and soil activities. However, the carbon utilization profile exhibited weak connections with the environmental variables and microbial community structures (p > 0.05). The microbial activities were significantly correlated with both bacterial and fungal community structures. Our results also emphasized the ascendant role of the deterministic process in the assemblages of microbial community structures and functions in wetland. In conclusion, this study revealed the discrepancy between community structures and eco-functions in response to water level gradients, and a relatively stable eco-function helped to maintain the ecosystem function of wetland from a long-term perspective.
Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by Spectral Phasor Analysis
Authors: Sameni Sara , Malacrida Leonel , Tan Zhiqun , Digman Michelle A. 
Published: January 2018

AbstractHuntington disease (HD) is a late-onset genetic neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide in the exon 1 of the gene encoding the polyglutamine (polyQ). It has been shown that protein degradation and lipid metabolism is altered in HD. In many neurodegenerative disorders, impaired lipid homeostasis is one of the early events in the disease onset. Yet, little is known about how mutant huntingtin may affect phospholipids membrane fluidity. Here, we investigated how membrane fluidity in the living cells (differentiated PC12 and HEK293 cell lines) are affected using a hyperspectral imaging of widely used probes, LAURDAN. Using phasor approach, we characterized the fluorescence of LAURDAN that is sensitive to the polarity of the immediate environment. LAURDAN is affected by the physical order of phospholipids (lipid order) and reports the membrane fluidity. We also validated our results using a different fluorescent membrane probe, Nile Red (NR). The plasma membrane in the cells expressing expanded polyQ shows a shift toward increased membrane fluidity revealed by both LAURDAN and NR spectral phasors. This finding brings a new perspective in the understanding of the early stages of HD that can be used as a target for drug screening.
Label-free photoacoustic imaging of human palmar vessels: a structural morphological analysis
Authors: Matsumoto Y. , Asao Y. , Yoshikawa A. , Sekiguchi H. , Takada M. , Furu M. , Saito S. , Kataoka M. , Abe H. , Yagi T. , Togashi K. , Toi M. 
Published: January 2018

AbstractWe analysed the vascular morphology of the palm using a photoacoustic tomography (PAT) instrument with a hemispherical detector array. The three-dimensional (3D) morphology of blood vessels was determined noninvasively. Overall, 12 females and 11 males were recruited as healthy volunteers. Their ages were distributed almost evenly from 22 to 59 years. In all cases, many vascular networks were observed just beneath the skin and were determined to be veins anatomically. To analyse the major arteries, the layer containing the subcutaneous venous network was removed from the image. The analysis focused on the common and proper palmar digital arteries. We used the curvature of these arteries as a parameter to analyse their morphologies. There was no significant difference in the curvature between genders when comparing the subjects as a whole. The blood vessel curvature increased with age. Good agreement was found between the 3D numerical analysis results and the subjective evaluation of the two-dimensional (2D) projection image. The PAT system enabled visualization of the 3D features of blood vessels in the palm and noninvasive analysis of arterial tortuousness.
Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice
Authors: Shi Yanan , Sun Xinfeng , Zhang Liping , Sun Kaoxiang , Li Keke , Li Youxin , Zhang Qiang 
Published: January 2018

AbstractTo improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest encapsulation efficiency of exenatide in the NPs was greater than 80%. Fc-conjugated NPs permeated Caco-2 cells faster and to a greater extent compared to unmodified NPs, as verified by CLSM and flow cytometry. Hypoglycemic effect studies demonstrated that oral administration of exenatide-loaded PEG-PLGA NPs modified by an Fc group extended the hypoglycemic effects compared with s.c. injection of the exenatide solution. Fluorescence-labeled NPs were used to investigate the effects of Fc targeting, and the results demonstrated that the NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with the unmodified NPs, as shown by the whole-body fluorescence images and fluorescence images of the dissected organs detected by in vivo imaging in live mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral peptide/protein drug delivery.
Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL
Authors: Bhalla Kavita , Jaber Sausan , Nahid M. Nanaji , Underwood Karen , Beheshti Afshin , Landon Ari , Bhandary Binny , Bastian Paul , Evens Andrew M. , Haley John , Polster Brian , Gartenhaus Ronald B. 
Published: January 2018

AbstractPublished molecular profiling studies in patients with lymphoma suggested the influence of hypoxia inducible factor-1 alpha (HIF1α) targets in prognosis of DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We observed that activation of HIF1α resulted in global translation repression during hypoxic stress in DLBCL. Protein translation efficiency as measured using 35S-labeled methionine incorporation revealed a ≥50% reduction in translation upon activation of HIF1α. Importantly, translation was not completely inhibited and expression of clinically correlated hypoxia targets such as GLUT1, HK2, and CYT-C was found to be refractory to translational repression under hypoxia in DLBCL cells. Notably, hypoxic induction of these genes was not observed in normal primary B-cells. Translational repression was coupled with a decrease in mitochondrial function. Screening of primary DLBCL patient samples revealed that expression of HK2, which encodes for the enzyme hexokinase 2, was significantly correlated with DLBCL phenotype. Genetic knockdown studies demonstrated that HK2 is required for promoting growth of DLBCL under hypoxic stress. Altogether, our findings provide strong support for the direct contribution of HK2 in B-cell lymphoma development and suggest that HK2 is a key metabolic driver of the DLBCL phenotype.
Engineering Yarrowia lipolytica to Simultaneously Produce Lipase and Single Cell Protein from Agro-industrial Wastes for Feed
Authors: Yan Jinyong , Han Bingnan , Gui Xiaohua , Wang Guilong , Xu Li , Yan Yunjun , Madzak Catherine , Pan Dujie , Wang Yaofeng , Zha Genhan , Jiao Liangcheng 
Published: January 2018

AbstractLipases are scarcely exploited as feed enzymes in hydrolysis of lipids for increasing energy supply and improving nutrient use efficiency. In this work, we performed homologous overexpression, in vitro characterization and in vivo assessment of a lipase from the yeast Yarrowia lipolytica for feed purpose. Simultaneously, a large amount of yeast cell biomass was produced, for use as single cell protein, a potential protein-rich feed resource. Three kinds of low cost agro-industrial wastes were tested as substrates for simultaneous production of lipase and single cell protein (SCP) as feed additives: sugarcane molasses, waste cooking oil and crude glycerol from biodiesel production. Sugarcane molasses appeared as the most effective cheap medium, allowing production of 16420 U/ml of lipase and 151.2 g/L of single cell protein at 10 liter fermentation scale. In vitro characterization by mimicking a gastro-intestinal environment and determination of essential amino acids of the SCP, and in vivo oral feeding test on fish all revealed that lipase, SCP and their combination were excellent feed additives. Such simultaneous production of this lipase and SCP could address two main concerns of feed industry, poor utilization of lipid and shortage of protein resource at the same time.
TerraClimate, a high-resolution global dataset of monthly climate and climatic water balance from 1958–2015
Authors: Abatzoglou John T. , Dobrowski Solomon Z. , Parks Sean A. , Hegewisch Katherine C. 
Published: January 2018

AbstractWe present TerraClimate, a dataset of high-spatial resolution (1/24°, ~4-km) monthly climate and climatic water balance for global terrestrial surfaces from 1958–2015. TerraClimate uses climatically aided interpolation, combining high-spatial resolution climatological normals from the WorldClim dataset, with coarser resolution time varying (i.e., monthly) data from other sources to produce a monthly dataset of precipitation, maximum and minimum temperature, wind speed, vapor pressure, and solar radiation. TerraClimate additionally produces monthly surface water balance datasets using a water balance model that incorporates reference evapotranspiration, precipitation, temperature, and interpolated plant extractable soil water capacity. These data provide important inputs for ecological and hydrological studies at global scales that require high spatial resolution and time varying climate and climatic water balance data. We validated spatiotemporal aspects of TerraClimate using annual temperature, precipitation, and calculated reference evapotranspiration from station data, as well as annual runoff from streamflow gauges. TerraClimate datasets showed noted improvement in overall mean absolute error and increased spatial realism relative to coarser resolution gridded datasets.
Properties of active galaxies at the extreme of Eigenvector 1
Authors: Śniegowska M. , Czerny B. , You B. , Panda S. , Wang J.-M. , Hryniewicz K. , Wildy C. 
Published: January 2018

Context. Eigenvector 1 (EV1) is the formal parameter which allows the introduction of some order in the properties of the unobscured type 1 active galaxies.
Aims. We aim to understand the nature of this parameter by analyzing the most extreme examples of quasars with the highest possible values of the corresponding eigenvalues RFe.
Methods. We selected the appropriate sources from the Sloan Digital Sky Survey (SDSS) and performed detailed modeling, including various templates for the Fe II pseudo-continuum and the starlight contribution to the spectrum.
Results. Out of 27 sources with RFe larger than 1.3 and with the measurement errors smaller than 20% selected from the SDSS quasar catalog, only six sources were confirmed to have a high value of RFe, defined as being above 1.3. All other sources have an RFe of approximately 1. Three of the high RFe objects have a very narrow Hβ line, below 2100 km s−1 but three sources have broad lines, above 4500 km s−1, that do not seem to form a uniform group, differing considerably in black hole mass and Eddington ratio; they simply have a very similar EW([OIII]5007) line. Therefore, the interpretation of the EV1 remains an open issue.
Myelomeningocele with Unilateral Right Renal Agenesis: A Case Report
Authors: Maeda Hajime , Go Hayato , Sakuma Jun , Imamura Takashi , Sato Maki , Momoi Nobuo , Hosoya Mitsuaki 
Published: January 2018

AbstractCongenital anomalies of the spine may occur with malformations of the central nervous, cardiovascular, gastrointestinal, respiratory, and genitourinary systems. This is a case of myelomeningocele with unilateral right renal agenesis in a newborn. The patient suffered complications of cerebrospinal fluid leak and meningitis, but was successfully treated and discharged on day 86. In this case, unilateral right renal agenesis represented a significant surgical risk because failure of the remaining kidney could result in renal failure. Because congenital anomalies of the spine may be associated with malformations of the genitourinary system, and additional surgeries were necessary in our case following birth, it is very important that the presence of genitourinary malformations be evaluated.