bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant chemotherapy affects molecular classification of colorectal tumors
Authors: Trumpi K , Ubink I , Trinh A , Djafarihamedani M , Jongen J M , Govaert K M , Elias S G , van Hooff S R , Medema J P , Lacle M M , Vermeulen L , Borel Rinkes I H M , Kranenburg O 
Published: July 2017

AbstractThe recent discovery of ‘molecular subtypes’ in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool. We observed considerable discordance (45%) in the classification of primary tumors and their liver metastases. Discordant classification was significantly associated with the use of neoadjuvant chemotherapy. Furthermore, gene expression analysis of chemotherapy-exposed versus chemotherapy naive liver metastases revealed expression of a mesenchymal program in pre-treated tumors. To explore whether chemotherapy could cause gene expression changes influencing molecular subtyping, we exposed patient-derived colonospheres to six short cycles of 5-fluorouracil. Gene expression profiling and signature enrichment analysis subsequently revealed that the expression of signatures identifying mesenchymal-like tumors was strongly increased in chemotherapy-exposed tumor cultures. Unsupervised clustering of large cohorts of human colon tumors with the chemotherapy-induced gene expression program identified a poor prognosis mesenchymal-like subgroup. We conclude that neoadjuvant chemotherapy induces a mesenchymal phenotype in residual tumor cells and that this may influence the molecular classification of colorectal tumors.
Role of insulin receptor substrates in the progression of hepatocellular carcinoma
Authors: Sakurai Yoshitaka , Kubota Naoto , Takamoto Iseki , Obata Atsushi , Iwamoto Masahiko , Hayashi Takanori , Aihara Masakazu , Kubota Tetsuya , Nishihara Hiroshi , Kadowaki Takashi 
Published: July 2017

AbstractSeveral cellular signaling pathways, including insulin/IGF signaling, are known to be activated in hepatocellular carcinoma (HCC). Here, we investigated the roles of insulin receptor substrate (Irs) 1 and Irs2, both of which are the major molecules to be responsible for transducing insulin/IGF signaling in the liver, in the development of HCC by inducing chemical carcinogenesis using diethylnitrosamine (DEN) in mice. The Irs1 mRNA and protein expressions were upregulated in the tumors, along with enhanced insulin signaling. Liver-specific Irs1-knockout (LIrs1KO) mice exhibited suppression of DEN-induced HCC development, accompanied by reduced cancer cell proliferative activity and reduced activation of Akt. Gene expression analyses revealed that the tumors in the DEN-treated LIrs1KO mice showed modest metabolic alterations during hepatocarcinogenesis as well as decreased inflammation and invasion potentials. On the other hand, liver-specific Irs2-knockout (LIrs2KO) mice showed a similar pattern of HCC development to the DEN-treated control wild-type mice. Based on the knowledge that Wnt/β-catenin signaling is activated in HCC, we focused on Wnt/β-catenin signaling and demonstrated that Irs1 expression was induced by Wnt3a stimulation in the primary hepatocytes, associated with insulin-stimulated Akt activation. These data suggest that upregulated Irs1 by Wnt/β-catenin signaling plays a crucial role in the progression of HCC.
Neural correlates of altered feedback learning in women recovered from anorexia nervosa
Authors: Ritschel Franziska , Geisler Daniel , King Joseph A. , Bernardoni Fabio , Seidel Maria , Boehm Ilka , Vettermann Richard , Biemann Ronald , Roessner Veit , Smolka Michael N. , Ehrlich Stefan 
Published: July 2017

AbstractAnorexia nervosa (AN) is associated with exaggerated self-control and altered reward-based decision making, but the underlying neural mechanisms are poorly understood. Consistent with the notion of excessive cognitive control, we recently found increased dorsal anterior cingulate cortex (dACC) activation in acutely ill patients (acAN) on lose-shift trials in a probabilistic reversal learning (PRL) task. However, undernutrition may modulate brain function. In attempt to disentangle trait from state factors, the current fMRI study investigated cognitive control in recovered patients (recAN). Thirty-one recAN and 31 healthy controls (HC) completed a PRL task during fMRI. Based on previous findings, we focused on hemodynamic responses during lose-shift behaviour and conducted supplementary functional connectivity analysis. RecAN showed elevated lose-shift behaviour relative to HC. On the neural level, recAN showed normal dACC responses, but increased activation in fronto-parietal control regions. A trend for increased coupling between frontal and parietal regions of interest was also evident in recAN. The current findings in recAN differ from those in our previous study in acAN. While aberrant dACC response to negative feedback may be a correlate of the underweight state in acAN, impaired behavioural adaptation and elevated activation of cognitive control regions in recAN is suggestive of altered neural efficiency.
Plant recording across two centuries reveals dramatic changes in species diversity of a Mediterranean archipelago
Authors: Chiarucci Alessandro , Fattorini Simone , Foggi Bruno , Landi Sara , Lazzaro Lorenzo , Podani János , Simberloff Daniel 
Published: July 2017

AbstractAlthough islands are model systems for investigating assembly of biological communities, long-term changes in archipelago communities are not well understood because of the lack of reliable data. By using a vast amount of floristic data we assembled a dataset of the plant species occurring on 16 islands of the Tuscan Archipelago, Italy, across two periods, 1830–1950 and 1951–2015. We collected 10,892 occurrence records for 1,831 species. We found major changes in the island plant assemblages between the two periods, with native flora significantly decreasing (−10.7%) and alien flora doubling (+132.1%) in richness. The species–area relationships demonstrated the scale-dependence of the observed changes for native and alien species. The observed floristic changes were dependent on island area, with smaller islands displaying high variability in richness and compositional changes and larger islands having more stable species assemblages. The richness of species associated with open landscapes, that had been maintained for centuries by traditional practices, markedly reduced while the number of woody species, associated with afforestation processes and invasion by alien woody plants, significantly incresed. These results demonstrate the great power of floristic studies, often available in grey literature, for understanding long-term biotic changes in insular ecosystems.
Effects of Lipoic Acid on High-Fat Diet-Induced Alteration of Synaptic Plasticity and Brain Glucose Metabolism: A PET/CT and 13C-NMR Study
Authors: Liu Zhigang , Patil Ishan , Sancheti Harsh , Yin Fei , Cadenas Enrique 
Published: July 2017

AbstractHigh-fat diet (HFD)-induced obesity is accompanied by insulin resistance and compromised brain synaptic plasticity through the impairment of insulin-sensitive pathways regulating neuronal survival, learning, and memory. Lipoic acid is known to modulate the redox status of the cell and has insulin mimetic effects. This study was aimed at determining the effects of dietary administration of lipoic acid on a HFD-induced obesity model in terms of (a) insulin signaling, (b) brain glucose uptake and neuronal- and astrocytic metabolism, and (c) synaptic plasticity. 3-Month old C57BL/6J mice were divided into 4 groups exposed to their respective treatments for 9 weeks: (1) normal diet, (2) normal diet plus lipoic acid, (3) HFD, and (4) HFD plus lipoic acid. HFD resulted in higher body weight, development of insulin resistance, lower brain glucose uptake and glucose transporters, alterations in glycolytic and acetate metabolism in neurons and astrocytes, and ultimately synaptic plasticity loss evident by a decreased long-term potentiation (LTP). Lipoic acid treatment in mice on HFD prevented several HFD-induced metabolic changes and preserved synaptic plasticity. The metabolic and physiological changes in HFD-fed mice, including insulin resistance, brain glucose uptake and metabolism, and synaptic function, could be preserved by the insulin-like effect of lipoic acid.
NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
Authors: Melo-Hanchuk Talita D. , Slepicka Priscila Ferreira , Meirelles Gabriela Vaz , Basei Fernanda Luisa , Lovato Diogo Ventura , Granato Daniela Campos , Pauletti Bianca Alves , Domingues Romenia Ramos , Leme Adriana Franco Paes , Pelegrini Alessandra Luiza , Lenz Guido , Knapp Stefan , Elkins Jonathan M. , Kobarg Jörg 
Published: July 2017

AbstractNEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.
Decreased serum apolipoprotein A1 levels are associated with poor survival and systemic inflammatory response in colorectal cancer
Authors: Sirniö Päivi , Väyrynen Juha P. , Klintrup Kai , Mäkelä Jyrki , Mäkinen Markus J. , Karttunen Tuomo J. , Tuomisto Anne 
Published: July 2017

AbstractRecent studies have reported of an association between high serum apolipoprotein A1 (APOA1) levels and favorable prognosis in several malignancies, while the significance of apolipoprotein B (APOB) in cancer is less well-known. In this study, we analyzed the correlation between serum APOA1 and APOB levels, and APOB/APOA1 ratio, and their associations with clinicopathologic parameters, the levels of twenty systemic inflammatory markers, and survival in 144 colorectal cancer (CRC) patients. We demonstrated that low serum APOA1 levels associated with advanced T-class and TNM-stage but low serum APOB levels did not significantly correlate with tumor characteristics. Serum APOA1 levels showed strong negative correlation with the markers of systemic inflammation including serum CRP and interleukin (IL)-8 levels and blood neutrophil count, whereas high serum APOB levels associated with high serum CCL2 levels. High APOA1 and APOB levels and low APOB/APOA1 ratio associated with improved cancer specific and overall survival. APOA1 had independent prognostic value in Cox regression analysis. In conclusion, low serum APOA1 levels are associated with advanced stage and systemic inflammation, while serum APOB does not significantly correlate with tumor stage. Serum APOA1 represents a promising additional prognostic parameter in CRC.
Molecular inter-kingdom interactions of endophytes isolated from Lychnophora ericoides
Authors: Caraballo-Rodríguez Andrés M. , Dorrestein Pieter C. , Pupo Monica T. 
Published: July 2017

AbstractThe importance of microbial natural products has been widely demonstrated in the search for new antibiotics. However, the functional role of microbial metabolites in nature remains to be deciphered. Several natural products are known to mediate microbial interactions through metabolic exchange. One approach to investigate metabolic exchange in the laboratory is through microbial interactions. Here, we describe the chemical study of selected endophytes isolated from the Brazilian medicinal plant Lychnophora ericoides by pairwise inter-kingdom interactions in order to correlate the impact of co-cultivation to their metabolic profiles. Combining mass spectrometry tools and NMR analyses, a total of 29 compounds were identified. These compounds are members of polyene macrocycles, pyrroloindole alkaloids, angucyclines, and leupeptins chemical families. Two of the identified compounds correspond to a new fungal metabolite (29) and a new actinobacterial angucycline-derivative (23). Our results revealed a substantial arsenal of small molecules induced by microbial interactions, as we begin to unravel the complexity of microbial interactions associated with endophytic systems.
Lipid Driven Nanodomains in Giant Lipid Vesicles are Fluid and Disordered
Authors: Koukalová Alena , Amaro Mariana , Aydogan Gokcan , Gröbner Gerhard , Williamson Philip T. F. , Mikhalyov Ilya , Hof Martin , Šachl Radek 
Published: July 2017

AbstractIt is a fundamental question in cell biology and biophysics whether sphingomyelin (SM)- and cholesterol (Chol)- driven nanodomains exist in living cells and in model membranes. Biophysical studies on model membranes revealed SM and Chol driven micrometer-sized liquid-ordered domains. Although the existence of such microdomains has not been proven for the plasma membrane, such lipid mixtures have been often used as a model system for ‘rafts’. On the other hand, recent super resolution and single molecule results indicate that the plasma membrane might organize into nanocompartments. However, due to the limited resolution of those techniques their unambiguous characterization is still missing. In this work, a novel combination of Förster resonance energy transfer and Monte Carlo simulations (MC-FRET) identifies directly 10 nm large nanodomains in liquid-disordered model membranes composed of lipid mixtures containing SM and Chol. Combining MC-FRET with solid-state wide-line and high resolution magic angle spinning NMR as well as with fluorescence correlation spectroscopy we demonstrate that these nanodomains containing hundreds of lipid molecules are fluid and disordered. In terms of their size, fluidity, order and lifetime these nanodomains may represent a relevant model system for cellular membranes and are closely related to nanocompartments suggested to exist in cellular membranes.
Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma
Authors: Gong Hongli , Shi Yi , Xiao Xiyan , Cao Pengyu , Wu Chunping , Tao Lei , Hou Dongsheng , Wang Yuezhu , Zhou Liang 
Published: July 2017

AbstractThe microbial communities that inhabit the laryngeal mucosa build stable microenvironments and have the potential to influence the health of the human throat. However, the associations between the microbiota structure and laryngeal carcinoma remain uncertain. Here, we explored this question by comparing the laryngeal microbiota structure in laryngeal cancer patients with that in control subjects with vocal cord polyps through high-throughput pyrosequencing. Overall, the genera Streptococcus, Fusobacterium, and Prevotella were prevalent bacterial populations in the laryngeal niche. Tumor tissue samples and normal tissues adjacent to the tumor sites (NATs) were collected from 31 laryngeal cancer patients, and the bacterial communities in laryngeal cancer patients were compared with control samples from 32 subjects. A comparison of the laryngeal communities in the tumor tissues and the NATs showed higher α-diversity in cancer patients than in control subjects, and the relative abundances of seven bacterial genera differed among the three groups of samples. Furthermore, the relative abundances of ten bacterial genera in laryngeal cancer patients differed substantially from those in control subjects. These findings indicate that the laryngeal microbiota profiles are altered in laryngeal cancer patients, suggesting that a disturbance of the microbiota structure might be relevant to laryngeal cancer.
Brain regionalization genes are co-opted into shell field patterning in Mollusca
Authors: Wollesen Tim , Scherholz Maik , Rodríguez Monje Sonia Victoria , Redl Emanuel , Todt Christiane , Wanninger Andreas 
Published: July 2017

AbstractThe ‘brain regionalization genes’ Six3/6, Otx, Pax2/5/8, Gbx, and Hox1 are expressed in a similar fashion in the deuterostome, ecdysozoan, and the cephalopod brain, questioning whether this holds also true for the remaining Mollusca. We investigated developmental Gbx-expression in representatives of both molluscan sister groups, the Aculifera and Conchifera. Gbx is expressed in the posterior central nervous system of an aculiferan polyplacophoran and solenogaster but not in a conchiferan bivalve suggesting that Gbx, together with Six3/6, Otx, Pax2/5/8, and Hox1, is involved in central nervous system regionalization as reported for other bilaterians. Gbx is, however, also expressed in the anterior central nervous system, i.e. the anlagen of the cerebral ganglia, in the solenogaster, a condition not reported for any other bilaterian so far. Strikingly, all Gbx-orthologs and the other ‘posterior brain regionalization genes’ such as Pax2/5/8 and Hox1 are expressed in the mantle that secretes shell(s) and spicules of mollusks (except cephalopods). In bivalves, the ancestral condition has even been lost, with Gbx and Pax2/5/8 not being expressed in the developing central nervous system anymore. This suggests an additional role in the formation of the molluscan shell field(s) and spicule-bearing cells, key features of mollusks.
Inhibition of CTGF ameliorates peritoneal fibrosis through suppression of fibroblast and myofibroblast accumulation and angiogenesis
Authors: Sakai Norihiko , Nakamura Miki , Lipson Kenneth E. , Miyake Taito , Kamikawa Yasutaka , Sagara Akihiro , Shinozaki Yasuyuki , Kitajima Shinji , Toyama Tadashi , Hara Akinori , Iwata Yasunori , Shimizu Miho , Furuichi Kengo , Kaneko Shuichi , Tager Andrew M. , Wada Takashi 
Published: July 2017

AbstractPeritoneal fibrosis (PF) is a serious complication in various clinical settings, but the mechanisms driving it remain to be fully determined. Connective tissue growth factor (CTGF) is known to regulate fibroblast activities. We therefore examined if CTGF inhibition has anti-fibrotic effects in PF. PF was induced by repetitive intraperitoneal injections of chlorhexidine gluconate (CG) in mice with type I pro-collagen promoter-driven green fluorescent protein (GFP) expression to identify fibroblasts. FG-3019, an anti-CTGF monoclonal antibody, was used to inhibit CTGF. CG-induced PF was significantly attenuated in FG-3019-treated mice. CG challenges induced marked accumulations of proliferating fibroblasts and of myofibroblasts, which were both reduced by FG-3019. Levels of peritoneal CTGF expression were increased by CG challenges, and suppressed in FG-3019-treated mice. FG-3019 treatment also reduced the number of CD31+ vessels and VEGF-A-positive cells in fibrotic peritoneum. In vitro studies using NIH 3T3 fibroblasts and peritoneal mesothelial cells (PMCs) showed that CTGF blockade suppressed TGF-β1-induced fibroblast proliferation and myofibroblast differentiation, PMC mesothelial-to-mesenchymal transition, and VEGF-A production. These findings suggest that the inhibition of CTGF by FG-3019 might be a novel treatment for PF through the regulation of fibroblast and myofibroblast accumulation and angiogenesis.
Wave manipulation with magnetically tunable metasurfaces
Authors: Yang Hujiang , Yu Tianlin , Wang Qingmin , Lei Ming 
Published: July 2017

AbstractTunable metasurfaces have emerged as an efficient approach to manipulate the wave propagation. Different from previous work concentrating on electrically tunable mechanisms, here we demonstrate a magnetically tunable metasurface composed of ferrite rods and metallic foils. By tuning the thickness of ferrite rods, metasurfaces with different rod thickness gradients are obtained. The incident wave can propagate through the metasurfaces due to the extraordinary transmission. The deflection angle of the transmission wave is not only influenced by the rod thickness gradient, but also tuned by the applied magnetic field. This approach opens a way for the design of tunable metasurfaces.
Targeting of dopamine transporter to filopodia requires an outward-facing conformation of the transporter
Authors: Ma Shiqi , Cheng Mary H. , Guthrie Daryl A. , Newman Amy H. , Bahar Ivet , Sorkin Alexander 
Published: July 2017

AbstractDopamine transporter (DAT) has been shown to accumulate in filopodia in neurons and non-neuronal cells. To examine the mechanisms of DAT filopodial targeting, we used quantitative live-cell fluorescence microscopy, and compared the effects of the DAT inhibitor cocaine and its fluorescent analog JHC1-64 on the plasma membrane distribution of wild-type DAT and two non-functional DAT mutants, R60A and W63A, that do not accumulate in filopodia. W63A did not bind JHC1-64, whereas R60A did, although less efficiently compared to the wild-type DAT. Molecular dynamics simulations predicted that R60A preferentially assumes an outward-facing (OF) conformation through compensatory intracellular salt bridge formation, which in turn favors binding of cocaine. Imaging analysis showed that JHC1-64-bound R60A mutant predominantly localized in filopodia, whereas free R60A molecules were evenly distributed within the plasma membrane. Cocaine binding significantly increased the density of R60A, but not that of W63A, in filopodia. Further, zinc binding, known to stabilize the OF state, also increased R60A concentration in filopodia. Finally, amphetamine, that is thought to disrupt DAT OF conformation, reduced the concentration of wild-type DAT in filopodia. Altogether, these data indicate that OF conformation is required for the efficient targeting of DAT to, and accumulation in, filopodia.
Selection of complementary foods based on optimal nutritional values
Authors: Sen Partho , Mardinogulu Adil , Nielsen Jens 
Published: July 2017

AbstractHuman milk is beneficial for growth and development of infants. Several factors result in mothers ceasing breastfeeding which leads to introduction of breast-milk substitutes (BMS). In some communities traditional foods are given as BMS, in others they are given as complementary foods during weaning. Improper food selection at this stage is associated with a high prevalence of malnutrition in children under 5 years. Here we listed the traditional foods from four continents and compared them with human milk based on their dietary contents. Vitamins such as thiamine (~[2–10] folds), riboflavin (~[4–10] folds) and ascorbic acid (<2 folds) contents of Asian and African foods were markedly lower. In order to extend the search for foods that includes similar dietary constituents as human milk, we designed a strategy of screening 8654 foods. 12 foods were identified and these foods were evaluated for their ability to meet the daily nutritional requirement of breastfed and non-breastfed infants during their first year of life. Genome-scale models of infant’s hepatocytes, adipocytes and myocytes were then used to simulate in vitro growth of tissues when subjected to these foods. Key findings were that pork ham cured, fish pudding, and egg lean white induced better tissue growth, and quark with fruit, cheese quarg 45% and cheese cream 60% had similar lactose content as human milk.