bluuebunny/crossref_metadata_2025_split huggingface dataset:
APC protein immunoexpression in colorectal adenoma and adenocarcinoma
Authors: Bourroul Vivian Sati Oba , Bourroul Guilherme Muniz , Toloi Giovanna Canato , Palma Rogério Tadeu , Oshima Celina Tizuko Fujiyama , Gomes Thiago Simão , Ihara Sílvia Saiuli Miki , Waisberg Jaques 
Published: November 2013

Abstract
Background activation of the Wnt pathway by mutated APC gene is considered the initial event in colorectal carcinogenesis. The identification of these mutations can improve the specific treatment of the adenocarcinoma.
Objective detect and evaluate wild-type APC protein in tissue from colorectal adenoma, adenocarcinoma and adjacent mucosa.
Methods 42 patients that underwent surgery for adenocarcinoma and 53 patients with resected adenomas were studied. Tissue samples from the adenocarcinoma were obtained from the tumor and from adjacent non-neoplastic mucosa located 10 cm from the proximal margin of the tumor. Adenoma tissue was obtained from representative areas. Blocks of tissue microarray (TMA) were submitted to immunohistochemistry with anti-APC, with readings of positivity and intensity of immunostaining and the score of immune expression of APC protein was obtained.
Results the APC protein immune expression score showed a significantly lower expression of APC protein in the adenoma when compared with the adenocarcinoma (p < 0.0001) and adjacent mucosa (p < 0.0001). The APC protein immune expression score in the colorectal mucosa and adjacent to the adenocarcinoma showed no significant difference (p = 0.24).
Conclusions the finding of decreased expression of APC protein in adenoma tissue may indicate that the mutated APC gene may contribute to the changes in the adenoma-carcinoma process of carcinogenesis sequence. The strong expression of protein APC in tissues from the carcinoma and adjacent mucosa suggests that in most patients in this series, the mutation of the APC gene did not participate in the oncogenesis mechanism.
Ex vivo sentinel lymph node investigation in colorectal cancer
Authors: Freitas Antônio Hilário Alves , Wainstein Alberto Julius Alves , Nunes Tarcizo Afonso 
Published: November 2013

AbstractIntroduction In Brazil, about 26,000 cases of colorectal cancer are diagnosed per year. Pa- tients considered at the early stage of disease (without lymph node) evolve with tumor relapse or recurrence in up to a quarter of cases, probably due to understaging.Objective Research on ex vivo sentinel lymph node in patients with colorectal adenocarcinoma.Materials and methods We studied 37 patients who underwent curative surgical resection. The marker used to identify lymph nodes was patent blue dye injected into the peritu- moral submucosa of the open surgical specimen immediately after its removal from the abdominal cavity.Results  Ex vivo identification of sentinel lymph node with marker occurred in 13 (35.1%) patients. The sensitivity was 40% and 60% false negative. The detailed histological examina- tion of sentinel lymph nodes with multilevel section and immunohistochemistry showed metastasis in one (4.3%) individual, considered ultra-staging.Conclusion The ex vivo identification of sentinel lymph node had questionable benefits, and worse results when include patients with rectal cancer. Restaging of one patient was possible after multilevel section and immunohistochemistry of the sentinel lymph node, but more research is needed to evaluate the role of micrometastases in patients with colorectal cancer.
The contribution of biotechnology to improving post-harvest chilling tolerance in fruits and vegetables using heat-shock proteins
Authors: AGHDAM M. S. , SEVILLANO L. , FLORES F. B. , BODBODAK S. 
Published: November 2013

SUMMARYFresh fruits and vegetables have a short post-harvest life and are prone to post-harvest losses due to mechanical injury, physiological causes and decay. Low-temperature storage is widely used as post-harvest treatment applied for delaying senescence in vegetables and ornamentals and ripening in fruits, upholding their post-harvest quality. But the refrigerated storage of tropical and subtropical crop plant species provokes a set of physiological alterations known as chilling injury that negatively affect their quality and frequently renders the product not saleable. Membrane damage and reactive oxygen species (ROS) accumulation are the main adverse effects of chilling injury impact in sensitive horticultural products. The chilling injury tolerance of certain plant species is attributed to their ability to accumulate heat-shock proteins (HSP). The beneficial action of HSP in chilling tolerance is due to their chaperone activity but, besides this biological function, small HSP (sHSP) are able to function as membrane stabilizers and ROS scavengers, or synergistically with cell antioxidant systems. Also, biosynthesis of osmolytes such as raffinose and proline is under the regulation of heat-shock transcription factors (HSTF). These molecules are critical for osmotic adjustment since low temperatures also provoke a secondary osmotic stress. The use of biotechnological strategies can be envisaged, with the aim of generating engineered crop plants of horticultural interest to induce the production and action of HSP and HSTF, in order to assure the beneficial effects of these proteins in promoting chilling injury tolerance during their post-harvest refrigerated storage. In particular, induction of HSTF expression using biotechnology has significant potential and interest for reducing the impact of chilling injury on sensitive produce, avoiding the practical difficulties of applying the classic post-harvest technologies based on heat treatment.
On the Trail and Trial of a Palestinian Diaspora: Mapping South America in the Arab–Israeli Conflict, 1967–1972
Authors: KARAM JOHN TOFIK 
Published: November 2013

AbstractCentred around a May 1970 shooting at the Israeli embassy in Asunción, this article traces a chain of actions and reactions that began with Israel's victory in the Six-Day War in June 1967 and ended after the June 1972 verdict of a Paraguayan court regarding two Palestinians. Situated among Israeli officials, Palestinian refugees and Syrian-Lebanese elites, authoritarian Paraguay was not only encompassed by but also accommodated the post-1967 Arab–Israeli conflict, revealing the connection between the ‘areas’ of South America and the Middle East through ideas about relocating Palestinians as well as their actual displacement.
Early development of Betta splendens under stereomicroscopy and scanning electron microscopy
Authors: Valentin Fernanda Nogueira , do Nascimento Nivaldo Ferreira , da Silva Regiane Cristina , Fernandes João Batista Kochenborger , Giannecchini Luiz Gustavo , Nakaghi Laura Satiko Okada 
Published: November 2013

SummaryBetta splendens is a very important ornamental species. The current paper describes the embryonic and larval development of B. splendens under stereomicroscopy and scanning electron microscopy. Eggs and larvae from natural spawning were collected at different developmental stages at previously established intervals and analysed. The eggs of B. splendens are yellowish, clear, spherical, demersal, translucent and telolecithal with a large amount of yolk. Between 0–2 h post-initial collection (hpIC), the eggs were at the egg cell, first cleavage and morula stages. The blastula stage was identified at 2–3 hpIC and the early gastrula phase was observed at 3–4 hpIC with 20% epiboly, which was finalized after 13–18 hpIC. When the pre-larvae were ready to hatch, the appearance of somites and the free tail were observed, at 23–25 hpIC. At 29 hpIC, the majority of larvae had already hatched at an average temperature of 28.4 ± 0.2°C. The newly hatched larvae measured 2.47 ± 0.044 mm total length. The mouth opened at 23 h post-hatching (hPH) and the yolk sac was totally absorbed at 73 hPH. After 156 hPH, the heart was pumping blood throughout the entire larval body. The caudal fin, operculum and eyes were well developed at 264 hPH. When metamorphosis was complete at 768 hPH, the larvae became juveniles. The current study presents the first results about early development of B. splendens and provides relevant information for its reproduction, rearing and biology.
Coincident Electron Channeling and Cathodoluminescence Studies of Threading Dislocations in GaN
Authors: Naresh-Kumar Gunasekar , Bruckbauer Jochen , Edwards Paul R. , Kraeusel Simon , Hourahine Ben , Martin Robert W. , Kappers Menno J. , Moram Michelle A. , Lovelock Stephen , Oliver Rachel A. , Humphreys Colin J. , Trager-Cowan Carol 
Published: November 2013

AbstractWe combine two scanning electron microscopy techniques to investigate the influence of dislocations on the light emission from nitride semiconductors. Combining electron channeling contrast imaging and cathodoluminescence imaging enables both the structural and luminescence properties of a sample to be investigated without structural damage to the sample. The electron channeling contrast image is very sensitive to distortions of the crystal lattice, resulting in individual threading dislocations appearing as spots with black–white contrast. Dislocations giving rise to nonradiative recombination are observed as black spots in the cathodoluminescence image. Comparison of the images from exactly the same micron-scale region of a sample demonstrates a one-to-one correlation between the presence of single threading dislocations and resolved dark spots in the cathodoluminescence image. In addition, we have also obtained an atomic force microscopy image from the same region of the sample, which confirms that both pure edge dislocations and those with a screw component (i.e., screw and mixed dislocations) act as nonradiative recombination centers for the Si-dopedc-plane GaN thin film investigated.
Future public pensions and changing employment patterns across birth cohorts
Authors: GEYER JOHANNES , STEINER VIKTOR 
Published: November 2013

AbstractWe analyse the impacts of changing employment patterns and pension reforms on the future level of public pensions across birth cohorts in Germany. The analysis is based on a microsimulation model and a rich data set that combines household survey data from the German Socio-Economic Panel Study (SOEP) and process-produced microdata from the German pension insurance. We account for cohort effects in individual employment and unemployment affecting earnings over the life cycle as well as the differential impact of recent pension reforms. For individuals born between 1937 and 1971, cohort effects vary greatly by region, gender and education, and strongly affect life cycle earnings profiles. The largest effects can be observed for younger cohorts in East Germany and for the low educated. Using simulated life cycle employment and income profiles, we project gross future pensions across cohorts taking into account changing demographics and recent pension reforms. Simulations show that pension levels for East German men and women will fall dramatically among younger birth cohorts, not only because of policy reforms but also due to higher cumulated unemployment. For West German men, the small reduction of average pension levels among younger birth cohorts is mainly driven by the impact of pension reforms, while future pension levels of West German women are increasing or stable due to rising labour market participation of younger birth cohorts.
Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species
Authors: Pohjoismäki Jaakko L. O. , Williams Siôn L. , Boettger Thomas , Goffart Steffi , Kim Johnny , Suomalainen Anu , Moraes Carlos T. , Braun Thomas 
Published: November 2013

SignificanceIn the present work, we show that overexpression of TWINKLE helicase reduces the amount of ROS-induced mtDNA mutations and ameliorates cardiomyopathy in Sod2+/−mice. We demonstrate that increased ROS in mitochondria result in a rise of base transversions and mtDNA rearrangements. Increased TWINKLE availability improves mtDNA integrity and protects cardiomyocytes by inhibiting apoptosis via p21. Our findings offer unique approaches to limit the loss of cardiomyocytes due to oxidative stress, a common problem in various disease conditions and during normal aging.
Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition
Authors: Kirkpatrick Donald S. , Bustos Daisy J. , Dogan Taner , Chan Jocelyn , Phu Lilian , Young Amy , Friedman Lori S. , Belvin Marcia , Song Qinghua , Bakalarski Corey E. , Hoeflich Klaus P. 
Published: November 2013

Significance
Growing evidence suggests that successful intervention in many human cancers will require combinations of therapeutic agents. Critical to this effort will be a detailed understanding of the crosstalk between signaling networks that modulate proliferation, cell death, drug sensitivity, and acquired resistance. Here we investigated DNA-damage signaling elicited by small-molecule inhibitors against MAP/ERK kinase (MEK) and PI3K in melanoma cells. This work, performed using cutting-edge mass spectrometry proteomics, uncovered a burst of signaling among proteins in the DNA-damage pathway upon initiation of the cell-death program by agents targeting the RAS–RAF–MEK and PI3K–AKT–mTOR pathways. These signals may prove important to the short- and long-term sensitivity of tumor cells to MEK- and PI3K-targeted therapies.
Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy
Authors: Ohara-Imaizumi Mica , Kim Hail , Yoshida Masashi , Fujiwara Tomonori , Aoyagi Kyota , Toyofuku Yukiko , Nakamichi Yoko , Nishiwaki Chiyono , Okamura Tadashi , Uchida Toyoyoshi , Fujitani Yoshio , Akagawa Kimio , Kakei Masafumi , Watada Hirotaka , German Michael S. , Nagamatsu Shinya 
Published: November 2013

Significance
During pregnancy, maternal insulin secretion increases markedly. This increase is not simply a response to increased demand, as it precedes the insulin resistance that develops late in pregnancy, nor is it solely a result of increased β cell mass, as secretion per beta cell increases as well. Here we show that the increased islet serotonin induced by pregnancy signals through the 5-HT3 receptor (Htr3) to increase insulin secretion dramatically. Htr3 signaling increases the excitability of the β cell membrane, thereby decreasing the threshold for insulin secretion. These studies elucidate the mechanism for pregnancy-induced increase in insulin release.
Structural insights into the histone H1-nucleosome complex
Authors: Zhou Bing-Rui , Feng Hanqiao , Kato Hidenori , Dai Liang , Yang Yuedong , Zhou Yaoqi , Bai Yawen 
Published: November 2013

Significance
Linker H1 histones control the accessibility of linker DNA between two neighbor nucleosomes to DNA-binding proteins and regulate chromatin folding. We investigated the structure of the H1–nucleosome complex through a combination of multidimensional nuclear magnetic resonance spectroscopy, site-directed mutagenesis-isothermal-titration calorimetry and computational design/modeling. The results lead to a unique structural model for the globular domain of H1 in complex with the nucleosome that contains residue-level information and have implications for the dynamics of chromatin in vivo. In addition, our approach will be useful for testing the hypothesis that the globular domain of H1 variants might have distinct binding geometries within the nucleosome, and thereby contribute to the heterogeneity of chromatin structure.
Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration
Authors: Peng Yu-Ching , Levine Charles M. , Zahid Sarwar , Wilson E. Lynette , Joyner Alexandra L. 
Published: November 2013

Significance
Sonic hedgehog (SHH) signaling regulates adult stem cells in many self-renewing organs. However, whether SHH also regulates adult stem cells in tissues like the prostate is unclear. Improving therapy for prostate diseases, including benign prostatic hyperplasia and prostate cancer, will require a better understanding of the key signaling pathways that regulate prostate homeostasis and regeneration. We show that SHH signals from basal epithelial cells to the surrounding stroma in the adult prostate. Moreover, SHH responding cells repopulate the stroma and exhibit long-term self-renewal capacity during multiple rounds of involution and regeneration. Furthermore, we identified four stromal subtypes and present evidence for a model in which the three ductal stromal subtypes are maintained largely by distinct unipotent stem/progenitor cells.
The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway
Authors: Tan Dongyan , Cai Yiying , Wang Juan , Zhang Jinzhong , Menon Shekar , Chou Hui-Ting , Ferro-Novick Susan , Reinisch Karin M. , Walz Thomas 
Published: November 2013

Significance
Rab GTPases are critical determinants of membrane identity in eukaryotic cells. Typically, each GTPase is activated by a single guanine nucleotide exchange factor (GEF), but the Ypt1/Rab1 GTPase is activated by three related GEFs, transport protein particle (TRAPP) I, TRAPPII, and TRAPPIII, that function in distinct trafficking pathways. TRAPPIII is recruited to the phagophore assembly site when macroautophagy is induced. Here, we present the single-particle electron microscopy structure of TRAPPIII and evidence that TRAPPIII binds the coat protein complex (COP) II coat. We also show that the ER-Golgi fusion machinery that is present on COPII vesicles is needed for macroautophagy. Our results imply that TRAPPIII recruits COPII vesicles to the PAS and that COPII vesicles may provide one of the membrane sources used in autophagosome formation.
BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer’s disease
Authors: Burke Rebecca M. , Norman Timothy A. , Haydar Tarik F. , Slack Barbara E. , Leeman Susan E. , Blusztajn Jan Krzysztof , Mellott Tiffany J. 
Published: November 2013

Significance
Bone morphogenetic protein 9 (BMP9) is a trophic factor for basal forebrain cholinergic neurons (BFCN) and constitutes a candidate therapeutic molecule for diseases characterized by BFCN dysfunction. A prominent example of such an illness, for which effective therapies are critically needed, is Alzheimer’s disease (AD). A decline in BFCN function and diminished cholinergic marker expression occurs in brains of patients with AD and is observed in AD animal models. We report that BMP9 administration is effective in reducing the amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for cholinergic neurons in a mouse model of AD, thus providing evidence that the BMP9-signaling pathway may constitute a novel therapeutic target in AD.
Correct developmental expression level of Rai1 in forebrain neurons is required for control of body weight, activity levels and learning and memory
Authors: Cao Lei , Molina Jessica , Abad Clemer , Carmona-Mora Paulina , Cárdenas Oyarzo Areli , Young Juan I. , Walz Katherina 
Published: November 2013

Abstract
Potocki–Lupski syndrome (PTLS) is a genomic disorder associated with an ∼3 Mb duplication in 17p11.2. Clinical features include leanness, intellectual disability, autistic features and developmental deficits. RAI1 gene dosage is associated with the PTLS phenotypes. To understand where and when Rai1 overexpression is detrimental, we generated a mouse that over-expresses Rai1 conditionally in forebrain neurons (I-Rai1). Phenotypic characterization of I-Rai1 mice showed significant underweight, hyperactivity and impaired learning and memory ability compared with wild-type littermates. Doxycycline administration can turn off the transgene expression allowing the restoration of Rai1 normal expression levels. When the transgene was turned off from conception to 3 months of age, no phenotypic differences were observed between I-Rai1 and their wild-type littermates. Surprisingly, we found that turning off the transgene expression before the onset of the phenotypes (1–3 months) or after the onset of the phenotypes (3–5 months) cannot prevent nor reverse the phenotypic outcomes. Our results indicate that Rai1 dosage in forebrain neurons is critical during the development and is related to body weight regulation, activity levels and learning and memory.
Comparative receptor tyrosine kinase profiling identifies a novel role for AXL in human stem cell pluripotency
Authors: Son Mi-Young , Seol Binna , Han Yong-Mahn , Cho Yee Sook 
Published: November 2013

Abstract
The extensive molecular characterization of human pluripotent stem cells (hPSCs), human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) is required before they can be applied in the future for personalized medicine and drug discovery. Despite the efforts that have been made with kinome analyses, we still lack in-depth insights into the molecular signatures of receptor tyrosine kinases (RTKs) that are related to pluripotency. Here, we present the first detailed and distinct repertoire of RTK characteristic for hPSC pluripotency by determining both the expression and phosphorylation profiles of RTKs in hESCs and hiPSCs using reverse transcriptase–polymerase chain reaction with degenerate primers that target conserved tyrosine kinase domains and phospho-RTK array, respectively. Among the RTKs tested, the up-regulation of EPHA1, ERBB2, FGFR4 and VEGFR2 and the down-regulation of AXL, EPHA4, PDGFRB and TYRO3 in terms of both their expression and phosphorylation levels were predominantly related to the maintenance of hPSC pluripotency. Notably, the specific inhibition of AXL was significantly advantageous in maintaining undifferentiated hESCs and hiPSCs and for the overall efficiency and kinetics of hiPSC generation. Additionally, a global phosphoproteomic analysis showed that ∼30% of the proteins (293 of 970 phosphoproteins) showed differential phosphorylation upon AXL inhibition in undifferentiated hPSCs, revealing the potential contribution of AXL-mediated phosphorylation dynamics to pluripotency-related signaling networks. Our findings provide a novel molecular signature of AXL in pluripotency control that will complement existing pluripotency-kinome networks.
Discover context-specific combinatorial transcription factor interactions by integrating diverse ChIP-Seq data sets
Authors: Teng Li , He Bing , Gao Peng , Gao Long , Tan Kai 
Published: November 2013

AbstractCombinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. Current knowledge about combinatorial regulation is rather limited due to the lack of suitable experimental technologies and bioinformatics tools. The rapid accumulation of ChIP-Seq data has provided genome-wide occupancy maps for a large number of TFs and chromatin modification marks for identifying enhancers without knowing individual TF binding sites. Integration of the two data types has not been researched extensively, resulting in underused data and missed opportunities. We describe a novel method for discovering frequent combinatorial occupancy patterns by multiple TFs at enhancers. Our method is based on probabilistic item set mining and takes into account uncertainty in both types of ChIP-Seq data. By joint analysis of 108 TFs in four human cell types, we found that cell–type-specific interactions among TFs are abundant and that the majority of enhancers have flexible architecture. We show that several families of transposable elements disproportionally overlap with enhancers with combinatorial patterns, suggesting that these transposable element families play an important role in the evolution of combinatorial regulation.