bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of large-cell neuroendocrine carcinoma harboring rare ALK fusion with initial response to the ALK inhibitor crizotinib and acquired F1174L mutation after resistance
Authors: Wang Ye , Tian Panwen , Wang Weiya , Li Yalun , Wang Yu , Li Weimin 
Published: March 2019

Abstract
A 51-year-old, male, non-smoker with a 3.4 cm mass in the right middle lobe was diagnosed with large cell neuroendocrine carcinoma (LCNEC). Fluorescence in situ hybridization revealed anaplastic lymphoma kinase (ALK) gene translocation, in agreement with the immunohistochemistry result obtained with use of ALK-Ventana. Radiographic examinations showed both bone and brain metastasis. After two cycles of chemotherapy consisting of etoposide and cisplatin, the patient achieved stable disease, and was subsequently switched to crizotinib. Both computed tomography and magnetic resonance imaging revealed partial response after 4 months of crizotinib, but progressed after treatment for 10 months, when several hard lymph nodes were palpable in the left supraclavicular fossa. Lymph node biopsy showed similar histology of tumor cells and targeted next-generation sequencing revealed ALK F1174L on exon 23 with two rare forms of ALK rearrangements. This case provides evidence of responsiveness of ALK inhibitors for a rare pattern of ALK-rearranged LCNEC, and suggests that F1174L, a common resistant mutation found in non-small-cell lung cancer, also causes crizotinib resistance in LCNEC.
Estimation with Aggregate Shocks
Authors: Hahn Jinyong , Kuersteiner Guido , Mazzocco Maurizio 
Published: March 2019

AbstractAggregate shocks affect most households’ and firms’ decisions. Using three stylized models, we show that inference based on cross-sectional data alone generally fails to correctly account for decision making of rational agents facing aggregate uncertainty. We propose an econometric framework that overcomes these problems by explicitly parameterizing the agents’ decision problem relative to aggregate shocks. Our framework and examples illustrate that the cross-sectional and time-series aspects of the model are often interdependent. Therefore, estimation of model parameters in the presence of aggregate shocks requires the combined use of cross-sectional and time-series data. We provide easy-to-use formulas for test statistics and confidence intervals that account for the interaction between the cross-sectional and time-series variation. Lastly, we perform Monte Carlo simulations that highlight the properties of the proposed method and the risks of not properly accounting for the presence of aggregate shocks.
Effects of distillers dried grains with solubles on amino acid digestibility, growth performance, and carcass characteristics of growing pigs1
Authors: Curry Shelby M , Blavi Laia , Wiseman Julian , Stein Hans H 
Published: March 2019

AbstractTwo experiments were conducted to compare the standardized ileal digestibility (SID) of AA by growing pigs in European distillers dried grains with solubles (DDGS) produced from wheat, maize, or wheat–maize mixtures and to test the effect of increasing the inclusion levels of wheat DDGS on growth performance of growing-finishing pigs fed diets balanced for NE and SID Lys. In Exp. 1, 12 barrows (initial BW: 23.0 ± 2.2 kg) were surgically equipped with a T-cannula in the distal ileum and randomly allotted to a replicated 6 × 6 Latin square design with six diets and six periods. Five sources of European DDGS were used: wheat DDGS from 2011, wheat DDGS from 2012, wheat-80 DDGS (80% wheat and 20% maize), wheat-70 DDGS (70% wheat and 30% maize), and maize DDGS. Each diet contained one source of DDGS as the sole source of AA and an N-free diet was used to determine basal endogenous losses of AA. Results indicated that the SID of CP was greater (P &lt; 0.05) in maize DDGS compared with wheat DDGS from 2011, wheat DDGS from 2012, and wheat-70 DDGS. The SID of all indispensable AA except Trp was also greater (P &lt; 0.05) in maize DDGS compared with all other DDGS sources used in this experiment. For Trp, the SID in wheat-80 DDGS, wheat DDGS from 2011, and wheat DDGS from 2012 were not different from maize DDGS, but were greater (P &lt; 0.05) than in wheat-70 DDGS. The SID for all indispensable AA except Ile and Trp in wheat-70 DDGS were not different from the values calculated for wheat DDGS from 2011 and wheat DDGS from 2012, and no differences between SID values for AA in wheat DDGS from 2011 and wheat DDGS from 2012 were observed. In Exp. 2, 36 growing pigs (initial BW: 38.3 ± 1.97 kg) were randomly allotted to one of four dietary treatments (one pig/pen and nine replicate pigs/treatment) in a 2-phase feeding program (35 to 65, and 35 to 105 kg BW). The four dietary treatments included diets containing 0%, 10%, 20%, or 30% wheat DDGS. Results indicated that there was no effect of wheat DDGS on pig growth performance or carcass quality. However, addition of wheat DDGS increased linearly (P &lt; 0.015) the indole concentration in the carcasses of the pigs. In conclusion, the SID of AA in maize DDGS produced in Europe is greater than in European wheat DDGS and DDGS produced from mixtures of wheat and maize, but inclusion of 30% wheat DDGS in diets fed to growing-finishing pigs did not affect growth performance or carcass quality.
The effects of maternal dietary supplementation of cholecalciferol (vitamin D3) and 25(OH)D3 on sow and progeny performance1
Authors: Thayer Morgan T , Nelssen Jim L , Langemeier Austin J , Morton Jodi M , Gonzalez John M , Kruger Stephanie R , Ou Zhining , Makowski Andrew J , Bergstrom Jon R 
Published: March 2019

Abstract
A total of 69 sows (DNA Line 200 × 400) and their progeny were used to determine if feeding a combination of vitamin D3 and 25(OH)D3 influences neonatal and sow vitamin D status, muscle fiber morphometrics at birth and weaning, and subsequent growth performance. Within 3 d of breeding, sows were allotted to one of three dietary treatments fortified with 1,500 IU/kg vitamin D3 (CON), 500 IU/kg vitamin D3 + 25 μg/kg 25(OH)D3 (DL), or 1,500 IU/kg vitamin D3 + 50 μg/kg 25(OH)D3 (DH). When pigs were sacrificed at birth, there were no treatment effects for all fiber morphometric measures (P &gt; 0.170), except primary fiber number and the ratio of secondary to primary muscle fibers (P &lt; 0.016). Pigs from CON fed sows had fewer primary fibers than pigs from sows fed the DH treatment (P = 0.014), with pigs from sows fed DL treatment not differing from either (P &gt; 0.104). Pigs from CON and DL fed sows had a greater secondary to primary muscle fiber ratio compared to pigs from DH sows (P &lt; 0.022) but did not differ from each other (P = 0.994). There were treatment × time interactions for all sow and pig serum metabolites (P &lt; 0.001). Therefore, treatment means were compared within the time period. At all time periods, sow serum 25(OH)D3 concentrations differed for all treatments with the magnitude of difference largest at weaning (P &lt; 0.011), where serum 25(OH)D3 concentration was always the greatest when sows were fed the DH diet. At birth, piglets from DH fed sows had greater serum 25(OH)D3 concentrations than piglets from sows fed the DL treatment (P = 0.003), with piglets from sows fed CON treatment not differing from either (P &gt; 0.061). At weaning, serum concentrations of 25(OH)D3 in piglets from all sow treatments were different (P &lt; 0.001), with the greatest concentration in piglets from DH sows, followed by CON, and followed by DL. There were no treatment × time interactions for any of the metabolites measured in milk and no treatment or time main effects for 24,25(OH)2D3 concentration (P &gt; 0.068). Colostrum collected within 12 h of parturition contained less (P = 0.001) 25(OH)D3 than milk collected on day 21 of lactation. Regardless of time, concentrations of 25(OH)D3 in milk were different (P &lt; 0.030), with the largest 25(OH)D3 concentration from DH fed sows, followed by DL, and then CON. In conclusion, combining vitamin D3 and 25(OH)D3 in the maternal diet improves the vitamin D status of the dam and progeny and it increases primary muscle fiber number at birth.
Magnetic resonance imaging suggests functional role of previous year vessels and fibres in ring-porous sap flow resumption
Authors: Copini Paul , Vergeldt Frank J , Fonti Patrick , Sass-Klaassen Ute , den Ouden Jan , Sterck Frank , Decuyper Mathieu , Gerkema Edo , Windt Carel W , Van As Henk 
Published: March 2019

Abstract
Reactivation of axial water flow in ring-porous species is a complex process related to stem water content and developmental stage of both earlywood-vessel and leaf formation. Yet empirical evidence with non-destructive methods on the dynamics of water flow resumption in relation to these mechanisms is lacking. Here we combined in vivo magnetic resonance imaging and wood-anatomical observations to monitor the dynamic changes in stem water content and flow during spring reactivation in 4-year-old pedunculate oaks (Quercus robur L.) saplings. We found that previous year latewood vessels and current year developing earlywood vessels form a functional unit for water flow during growth resumption. During spring reactivation, water flow shifted from latewood towards the new earlywood, paralleling the formation of earlywood vessels and leaves. At leaves' full expansion, volumetric water content of previous rings drastically decreased due to the near-absence of water in fibre tissue. We conclude (i) that in ring-porous oak, latewood vessels play an important hydraulic role for bridging the transition between old and new water-conducting vessels and (ii) that fibre and parenchyma provides a place for water storage.
Resolving multisensory and attentional influences across cortical depth in sensory cortices
Authors: Gau Remi , Bazin Pierre-Louis , Trampel Robert , Turner Robert , Noppeney Uta 
Published: March 2019

ABSTRACTIn our environment our senses are bombarded with a myriad of signals, only a subset of which is relevant for our goals. Using sub-millimeter-resolution fMRI at 7T we resolved BOLD-response and activation patterns across cortical depth in early sensory cortices to auditory, visual and audiovisual stimuli under auditory or visual attention. In visual cortices, auditory stimulation induced widespread inhibition irrespective of attention, whereas auditory relative to visual attention suppressed mainly central visual field representations. In auditory cortices, visual stimulation suppressed activations, but amplified responses to concurrent auditory stimuli, in a patchy topography. Critically, multisensory interactions in auditory cortices were stronger in deeper laminae, while attentional influences were greatest at the surface. These distinct depth-dependent profiles suggest that multisensory and attentional mechanisms regulate sensory processing via partly distinct circuitries. Our findings are crucial for understanding how the brain regulates information flow across senses to interact with our complex multisensory world.
RBPSponge: genome-wide identification of lncRNAs that sponge RBPs
Authors: HafezQorani Saber , Houdjedj Aissa , Arici Mehmet , Said Abdesselam , Kazan Hilal 
Published: March 2019

AbstractSummaryLong noncoding RNAs (lncRNAs) can act as molecular sponges or decoys for an RNA-binding protein (RBP) through their RBP binding sites, thereby modulating the expression of all target genes of the corresponding RBP of interest. Here, we present a web tool named RBPSponge to explore lncRNAs based on their potential to act as a sponge for an RBP of interest. RBPSponge identifies the occurrences of RBP binding sites and CLIP peaks on lncRNAs, and enables users to run statistical analyses to investigate the regulatory network between lncRNAs, RBPs and targets of RBPs.AvailabilityThe web server is available athttps://www.RBPSponge.comContacthilal.kazan@antalya.edu.tr
Cell-type specific innervation of cortical pyramidal cells at their apical tufts
Authors: Karimi Ali , Odenthal Jan , Drawitsch Florian , Boergens Kevin M. , Helmstaedter Moritz 
Published: March 2019

ABSTRACTWe investigated the synaptic innervation of apical tufts of cortical pyramidal cells in a region between layers 1 and 2 using 3-D electron microscopy (3D-EM) applied to four cortical regions in mouse. Across all cortices, we found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 3-fold stronger for layer 2 pyramidal cells than for all other pyramidal cells. Towards the distal tuft dendrites in upper layer 1, however, the relative inhibitory input was about 2-fold stronger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input density. The inhibitory to excitatory synaptic balance is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either layer 2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites in the upper layers of the cerebral cortex and point to differential computational properties of layer 2, layer 3 and layer 5 pyramidal cells in cortex.
Zn2+ intoxication of Mycobacterium marinum during Dictyostelium discoideum infection is counteracted by induction of the pathogen Zn2+ exporter CtpC
Authors: Lefrançois Louise H. , Kalinina Vera , Cardenal-Muñoz Elena , Hanna Nabil , Koliwer-Brandl Hendrik , Appiah Joddy , Leuba Florence , Hilbi Hubert , Soldati Thierry , Barisch Caroline 
Published: March 2019

ABSTRACTMacrophages use diverse strategies to kill or restrict intracellular pathogens. Some of these strategies involve the deprivation of bacteria from (micro)nutrients such as transition metals, and the bacteria intoxication through metal accumulation. Little is known about the chemical warfare between Mycobacterium marinum, a close relative of the human pathogen M. tuberculosis, and its hosts. Here we use the professional phagocyte Dictyostelium discoideum to investigate the role of Zn2+ during M. marinum infection. We show that M. marinum infection induces the accumulation of Zn2+ inside the Mycobacterium-containing vacuole (MCV), achieved by the induction and recruitment of the D. discoideum Zn2+ efflux pumps ZntA and ZntB. In cells lacking the ZntA detoxifying transporter there is further attenuation of M. marinum growth, possibly due to a compensatory efflux of Zn2+ into the MCV. This efflux is presumably carried out by ZntB, the main Zn2+ transporter in endosomes and phagosomes. Counterintuitively, M. marinum growth is also impaired in zntB KO cells, where MCVs accumulate less Zn2+. We also demonstrate that M. marinum senses toxic levels of Zn2+ and responds by upregulating its Zn2+ exporter CtpC, which supports bacteria survival under these restrictive conditions. Attenuation of M. marinum intracellular proliferation in zntA and zntB KO cells is accentuated in the absence of CtpC, confirming that mycobacteria face noxious levels of Zn2+. Altogether, we show for the first time that M. marinum infection induces a deleterious Zn2+ elevation in D. discoideum, which is counteracted by the bacteria with the induction of its Zn2+ exporter CtpC.
High-Affinity Binding of Chemokine Analogs that Display Ligand Bias at the HIV-1 Co-receptor CCR5
Authors: Rico Carlos A. , Berchiche Yamina A. , Horioka Mizuho , Peeler Jennifer C. , Lorenzen Emily , Tian He , Kazmi Manija A. , Fürstenberg Alexandre , Gaertner Hubert , Hartley Oliver , Sakmar Thomas P. , Huber Thomas 
Published: March 2019

ABSTRACTThe chemokine receptor CCR5 is a drug target to prevent transmission of HIV/AIDS. We studied four analogs of the native chemokine RANTES (CCL5) that have anti-HIV potencies of around 25 pM, which is more than four orders-of-magnitude higher than that of RANTES itself. It has been hypothesized that the ultra-high potency of the analogs is due to their ability to bind populations of receptors not accessible to native chemokines. To test this hypothesis, we developed a homogeneous dual-color fluorescence cross-correlation spectroscopy (FCCS) assay for saturation and competition binding experiments. The FCCS assay has the advantage that it does not rely on competition with radioactively labeled native chemokines used in conventional assays. We prepared site-specifically labeled fluorescent analogs using native chemical ligation of synthetic peptides, followed by bioorthogonal fluorescent labeling. We engineered a mammalian cell expression construct to provide fluorescently labeled CCR5, which was purified using a tandem immunoaffinity and size-exclusion chromatography approach to obtain monomeric fluorescent CCR5 in detergent solution. We found subnanomolar binding affinities for the two analogs 5P12-RANTES and 5P14-RANTES, and about twenty-fold reduced affinities for PSC-RANTES and 6P4-RANTES. Using homologous and heterologous competition experiments with unlabeled chemokine analogs, we conclude that the analogs all bind at the same binding site; whereas, the native chemokines (RANTES and MIP1α) fail to displace bound fluorescent analogs even at tens of micromolar concentrations. Our results can be rationalized withde novostructural models of the N-terminal tails of the synthetic chemokines that adopt a different binding mode as compared to the parent compound.
Genetic variation in apolipoprotein A-I concentrations and risk of coronary artery disease
Authors: Karjalainen Minna K. , Holmes Michael V. , Wang Qin , Anufrieva Olga , Kähönen Mika , Lehtimäki Terho , Havulinna Aki S. , Kristiansson Kati , Salomaa Veikko , Perola Markus , Viikari Jorma S. , Raitakari Olli T. , Järvelin Marjo-Riitta , Ala-Korpela Mika , Kettunen Johannes 
Published: March 2019

ABSTRACTRationaleApolipoprotein A-I (apoA-I) infusions represent a potential novel therapeutic approach for the prevention of coronary artery disease (CAD) with phase III cardiovascular outcome trials currently underway. Although circulating apoA-I levels inversely associate with risk of CAD, the evidence base of this representing a causal relationship is lacking.ObjectiveTo assess the causal role of apoA-I in CAD using human genetics.Methods and ResultsWe identified a variant (rs12225230) in APOA1 locus that associated with circulating apoA-I concentrations at GWAS significance (P<5×10−8) in 20,370 Finnish participants and meta-analyzed our data with a previous genome-wide association study of apoA-I. We obtained genetic estimates of CAD from UK Biobank and CARDIoGRAMplusC4D (totaling 122,733 CAD cases) and conducted a two-sample Mendelian randomization analysis. We compared our genetic findings to observational associations of apoA-I with risk of CAD in 918 incident CAD cases among 11,535 individuals from population-based prospective cohorts. We also summarized the available evidence from randomized controlled trials (RCTs) of apoA-I infusion therapies reporting CAD events. ApoA-I was associated with a lower risk of CAD in observational analyses (HR 0.81; 95%CI: 0.75, 0.88; per 1-SD higher apoA-I), with the association showing a dose-response relationship. Rs12225230 associated with apoA-I concentrations (per-C allele beta 0.076 SD; SE: 0.013; P=1.5×10−9) but not with potential confounders. In Mendelian randomization analyses, apoA-I was not related to risk of CAD (OR 1.13; 95%CI: 0.98, 1.30 per 1-SD higher apoA-I), which was different to the observational association (P-het<0.001). RCTs of apoA-I infusions did not show an effect on the risk of CAD.ConclusionsGenetic evidence fails to support a cardioprotective role for apoA-I. This casts doubt on the likely benefit of apoA-I infusion therapy in the ongoing phase III cardiovascular outcome trial.
HiLDA: a statistical approach to investigate differences in mutational signatures
Authors: Yang Zhi , Pandey Priyatama , Shibata Darryl , Conti David V. , Marjoram Paul , Siegmund Kimberly D. 
Published: March 2019

ABSTRACTWe propose a hierarchical latent Dirichlet allocation model (HiLDA) for characterizing somatic mutation data in cancer. The method allows us to infer mutational patterns and their relative frequencies in a set of tumor mutational catalogs and to compare the estimated frequencies between tumor sets. We apply our method to somatic mutations in colon cancer with mutations classified by the time of occurrence, before or after tumor initiation. Applying the methods to 16 colon cancers, we found significant associations between the relative frequencies of mutational patterns and the time of occurrence of mutations. Our novel method provides higher statistical power for detecting differences in mutational signatures.
Variation of human neural stem cells generating organizer statesin vitrobefore committing to cortical excitatory or inhibitory neuronal fates
Authors: Micali Nicola , Kim Suel-Kee , Diaz-Bustamante Marcelo , Stein-O’Brien Genevieve , Seo Seungmae , Shin Joo-Heon , Rash Brian G. , Ma Shaojie , Wang Yanhong , Olivares Nicolas A. , Arellano Jon , Maynard Kristen R. , Fertig Elana J. , Cross Alan J. , Burli Roland , Brandon Nicholas J. , Weinberger Daniel R. , Chenoweth Joshua G. , Hoeppner Daniel J. , Sestan Nenad , Rakic Pasko , Colantuoni Carlo , McKay Ronald D. 
Published: March 2019

SUMMARYBetter understanding the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here we used RNA-sequencing, cell imaging and lineage tracing of mouse and humanin vitroNSCs to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs developed from pluripotencyin vitro, they first transitioned through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines varied in these early patterning states leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analysis of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon.
Hypothalamic-extended amygdala circuit regulates temporal discounting
Authors: Rossi Mark A. , Li Haofang E. , Watson Glenn W. , Moore H. Gregory , Cai Min Tong , Kim Namsoo , Vokt Katrina A. , Lu Dongye , Bartholomew Ryan A. , Yin Henry H. 
Published: March 2019

AbstractChoice behavior is characterized by temporal discounting, i.e., preference for immediate rewards over delayed rewards. Temporal discounting is often dysfunctional in psychiatric disorders, addiction, and eating disorders. However, the underlying neural mechanisms governing temporal discounting are still poorly understood. We found that food deprivation resulted in steep temporal discounting of food rewards, whereas satiation abolished discounting. In addition, optogenetic activation of AgRP-expressing neurons in the arcuate nucleus or their axon terminals in the posterior bed nucleus of stria terminalis (BNST) restored temporal discounting in sated mice. Activation of postsynaptic neuropeptide Y receptors (Y1Rs) within the BNST, which is influenced by neuropeptide released by AgRP neurons, was sufficient to restore temporal discounting. These results demonstrate for the first time a profound effect of motivational signals from hypothalamic feeding circuits on temporal discounting and reveal a novel neural circuit that regulates choice behavior.