bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2
Authors: Das Lopamudra , Kokate Shrikant Babanrao , Rath Suvasmita , Rout Niranjan , Singh Shivaram Prasad , Crowe Sheila Eileen , Mukhopadhyay Asish K. , Bhattacharyya Asima 
Published: April 2016

Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose.
Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells
Authors: Marcus Elizabeth A. , Tokhtaeva Elmira , Turdikulova Shahlo , Capri Joseph , Whitelegge Julian P. , Scott David R. , Sachs George , Berditchevski Fedor , Vagin Olga 
Published: April 2016

Septins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear. The hypothesis tested here is that septins contribute to cancer by stabilizing the receptor tyrosine kinase ErbB2, an important target for cancer treatment. Septins and ErbB2 were highly over-expressed in gastric cancer cells. Immunoprecipitation followed by MS analysis identified ErbB2 as a septin-interacting protein. Knockdown of septin-2 or cell exposure to forchlorfenuron (FCF), a well-established inhibitor of septin oligomerization, decreased surface and total levels of ErbB2. These treatments had no effect on epidermal growth factor receptor (EGFR), emphasizing the specificity and functionality of the septin–ErbB2 interaction. The level of ubiquitylated ErbB2 at the plasma membrane was elevated in cells treated with FCF, which was accompanied by a decrease in co-localization of ErbB2 with septins at the membrane. Cathepsin B inhibitor, but not bafilomycin or lactacystin, prevented FCF-induced decrease in total ErbB2 by increasing accumulation of ubiquitylated ErbB2 in lysosomes. Therefore, septins protect ErbB2 from ubiquitylation, endocytosis and lysosomal degradation. The FCF-induced degradation pathway is distinct from and additive with the degradation induced by inhibiting ErbB2 chaperone Hsp90. These results identify septins as novel regulators of ErbB2 expression that contribute to the remarkable stabilization of the receptor at the plasma membrane of cancer cells and may provide a basis for the development of new ErbB2-targeting anti-cancer therapies.
Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer
Authors: Wang Wenjing , Shi Yanhua , Li Jing , Cui Wei , Yang Baozhi 
Published: April 2016

Kinesin family member 14 (KIF14) is a member of kinesin family proteins which have been found to be dysregulated in various cancer types. However, the expression of KIF14 and its potential prognostic significance have not been investigated in cervical cancer. Real-time PCR was performed to assess the expression levels of KIF14 in 47 pairs of cervical cancer tissues and their matched normal tissues from patients who had not been exposed to chemotherapy as well as tissue samples from 57 cervical cancer patients who are sensitive to paclitaxel treatment and 53 patients who are resistant. The association between KIF14 expression levels in tissue and clinicopathological features or chemosensitivity was examined. Kaplan–Meier analysis and Cox proportional hazards model were applied to assess the correlation between KIF14 expression levels and overall survival (OS) of cervical cancer patients. KIF14 expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues and it was higher in tissues of patients who are chemoresistant compared with those who are chemosensitive. KIF14 expression was positively associated with high tumour stage (P=0.0044), lymph node metastasis (P=0.0034) and chemoresistance (P&lt;0.0001). Kaplan–Meier analysis showed that high KIF14 expression levels predicted poor survival in patients with (P=0.0024) or without (P=0.0028) paclitaxel treatment. Multivariate analysis revealed that KIF14 was an independent prognostic factor for OS. Our study suggests that KIF14 may serve as a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer.
Smooth muscle titin formsin vitroamyloid aggregates
Authors: Bobylev Alexandr G. , Galzitskaya Oxana V. , Fadeev Roman S. , Bobyleva Liya G. , Yurshenas Darya A. , Molochkov Nikolay V. , Dovidchenko Nikita V. , Selivanova Olga M. , Penkov Nikita V. , Podlubnaya Zoya A. , Vikhlyantsev Ivan M. 
Published: April 2016

Amyloids are insoluble fibrous protein aggregates, and their accumulation is associated with amyloidosis and many neurodegenerative diseases, including Alzheimer's disease. In the present study, we report that smooth muscle titin (SMT; 500 kDa) from chicken gizzard forms amyloid aggregates in vitro. This conclusion is supported by EM data, fluorescence analysis using thioflavin T (ThT), Congo red (CR) spectroscopy and X-ray diffraction. Our dynamic light scattering (DLS) data show that titin forms in vitro amyloid aggregates with a hydrodynamic radius (Rh) of approximately 700–4500 nm. The initial titin aggregates with Rh approximately 700 nm were observed beyond first 20 min its aggregation that shows a high rate of amyloid formation by this protein. We also showed using confocal microscopy the cytotoxic effect of SMT amyloid aggregates on smooth muscle cells from bovine aorta. This effect involves the disorganization of the actin cytoskeleton and result is cell damage. Cumulatively, our results indicate that titin may be involved in generation of amyloidosis in smooth muscles.
An Item Response Theory–Based, Computerized Adaptive Testing Version of the MacArthur–Bates Communicative Development Inventory: Words & Sentences (CDI:WS)
Authors: Makransky Guido , Dale Philip S. , Havmose Philip , Bleses Dorthe 
Published: April 2016

Purpose
This study investigated the feasibility and potential validity of an item response theory (IRT)–based computerized adaptive testing (CAT) version of the MacArthur–Bates Communicative Development Inventory: Words & Sentences (CDI:WS; Fenson et al., 2007) vocabulary checklist, with the objective of reducing length while maintaining measurement precision.

Method
Parent-reported vocabulary for the American CDI:WS norming sample consisting of 1,461 children between the ages of 16 and 30 months was used to investigate the fit of the items to the 2-parameter logistic IRT model and to simulate CDI-CAT versions with 400, 200, 100, 50, 25, 10, and 5 items.

Results
All but 14 items fit the 2-parameter logistic IRT model, and real data simulations of CDI-CATs with at least 50 items recovered full CDI scores with correlations over .95. Furthermore, the CDI-CATs with at least 50 items had similar correlations with age and socioeconomic status as the full CDI:WS.

Conclusion
These results provide strong evidence that a CAT version of the CDI:WS has the potential to reduce length while maintaining the accuracy and precision of the full instrument.
The role of neoantigens in response to immune checkpoint blockade
Authors: Riaz Nadeem , Morris Luc , Havel Jonathan J. , Makarov Vladimir , Desrichard Alexis , Chan Timothy A. 
Published: April 2016

Abstract
Immune checkpoint blockade has demonstrated substantial promise for the treatment of several advanced malignancies. These agents activate the immune system to attack tumor cells. For example, agents targeting CTLA4 and programmed cell death 1 (PD-1) have resulted in impressive response rates and, in some cases, durable remissions. Neoantigens are mutations that encode immunologically active proteins that can cause the immune system to recognize the affected cell as foreign. Recent data have made it clear that these mutations are, in large part, the functional targets of immune checkpoint blockade. This review summarizes the key discoveries leading up to this important conclusion and discusses possible applications of neoantigens in cancer therapy.
The new primary X-ray component confirmed in the Seyfert I galaxy IC 4329A
Authors: Miyake Katsuma , Noda Hirofumi , Yamada Shin'ya , Makishima Kazuo , Nakazawa Kazuhiro 
Published: April 2016

Abstract
The bright and highly variable Seyfert I active galactic nucleus IC 4329A was observed with Suzaku five times in 2007 August, with intervals of ∼5 days and a net exposure of 24–31 ks each. Another longer observation was carried out in 2012 August with a net exposure of 118 ks. In the six observations, a source was detected in 2–45 keV with an average 2–10 keV fluxes of (0.67–1.2) × 10−10 erg cm−2 s−1. Its intensity changed by a factor of 2 among the five observations in 2007, and 1.5 within the 2012 observation. A difference of spectrum among these observations revealed that the variability of IC 4329A was carried mainly by a power-law component with a photon index Γ ∼ 2.0. However, in addition to this primary component and its associated reflection, the broad-band Suzaku data required another, harder, and less-variable component with Γ ∼ 1.4. The presence of this new continuum was also confirmed by analyzing the same six data sets through the spectral decomposition technique developed by Noda et al. (2013a, ApJ, 771, 100). This Γ ∼ 1.4 continuum is considered to be a new primary component that has not been recognized in the spectra of IC 4329A so far, although it was recently identified in those of several other Seyfert I galaxies (Noda et al. 2013a, ApJ, 771, 100; Noda et al. 2014, ApJ, 794, 2).
Wide genome involvement in response to long-term selection for antibody response in an experimental population of White Leghorn chickens
Authors: Lillie Mette , Sheng Zheya , Honaker Christa , Dorshorst Ben , Siegel Paul , Carlborg Örjan 
Published: April 2016

AbstractLong-term selection experiments provide a powerful approach to gain empirical insights into adaptation. They allow researchers to uncover the targets of selection and how these contribute to the mode and tempo of adaptation. Here we report results from a pooled genome re-sequencing study to investigate the consequences of 39 generations of bidirectional selection in White Leghorn chickens on a humoral immune trait: antibody response to sheep red blood cells. We observed wide genome involvement in response to this selection regime, with over 200 candidate sweep regions characterised by spans of high genetic differentiation (FST). These sweep signatures, encompassing almost 20% of the chicken genome (208.8 Mb), are primarily the result from bidirectional selection on haplotypes present in the base population. These extensive genomic changes highlight both the extent of standing genetic variation at immune loci available at the onset of selection, as well as how the long-term selection response results from selection on a highly polygenic genetic architecture. Furthermore, we present three examples of strong candidate genes that may have contributed to the profound phenotypic response to selection.Data AvailabilityPooled genome data generated for this study will become available via SRA upon acceptance of manuscript
Zfp423regulates Sonic hedgehog signaling via primary cilium function
Authors: Hong Chen-Jei , Hamilton Bruce A. 
Published: April 2016

AbstractZfp423encodes a 30-zinc finger transcription factor that intersects several canonical signaling pathways.Zfp423mutations result in ciliopathy-related phenotypes, including agenesis of the cerebellar vermis in mice and Joubert syndrome (JBTS19) and nephronophthisis (NPHP14) in humans. Unlike most ciliopathy genes,Zfp423encodes a nuclear protein and its developmental expression is complex, leading to alternative proposals for cellular mechanisms. Here we show thatZfp423is expressed by cerebellar granule cell precursors, that loss ofZfp423in these precursors leads to cell-intrinsic reduction in proliferation, loss of response to Shh, and primary cilia abnormalities that include diminished frequency of both Smoothened and IFT88 localization. Loss ofZfp423alters expression of several genes encoding key cilium components, including increased expression ofTulp3.Tulp3is a direct binding target ofZfp423and reducing the overexpression ofTulp3inZfp423-deficient cells suppresses Smoothened translocation defects. These results defineZfp423deficiency as a bona fide ciliopathy, acting upstream of Shh signaling, and indicate a mechanism intrinsic to granule cell precursors for the resulting cerebellar hypoplasia.Author SummaryCiliopathies are a broad group of individually rare genetic disorders that share overlapping phenotypes and mutations in genes that make components of the primary cilium. Mutations inZNF423are an exception. Patients and mouse models show characteristic hypoplasia of the cerebellar midline (Joubert syndrome), but the gene encodes a nuclear transcription factor. The mouse gene,Zfp423, is expressed in a dynamic developmental pattern, leaving the cellular mechanism for this brain malformation unresolved. One report suggested reduced Purkinje cell expression of Shh, a key mitogen for cerebellar granule cell precursors (GCPs) whose signal transduction occurs at the primary cilium, as the key event. We show thatZfp423mutants expressed normal Shh levels, but thatZfp423-depleted GCPs were unable to respond. Primary cilia onZfp423-mutant GCPs in situ typically had a wider base and longer extension. ZNF423-depletion in a human cell culture model resulted in defective translocation of Smoothened, a key event in Shh signaling, and of the intraflagellar transport protein IFT88. RNA-Seq and RT-qPCR experiments identified known ciliopathy genes as potential conserved targets ofZNF423andZfp423. One of these,TULP3, was both up-regulated inZNF423/Zfp423-deficient cells and directly bound by Zfp423 in granule cell precursors. Reversing the overexpression of TULP3 in ZNF423-depleted human cell culture model reversed the defect in Smoothened translocation.
CoSMoMVPA: multi-modal multivariate pattern analysis of neuroimaging data in Matlab / GNU Octave
Authors: Oosterhof Nikolaas N. , Connolly Andrew C. , Haxby James V. 
Published: April 2016

AbstractRecent years have seen an increase in the popularity of multivariate pattern (MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much lesser extent, magneto-and electro-encephalography (M/EEG) data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens.CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and across: space, time, frequency bands, neuroimaging modalities, individuals, and species.It uses a uniform data representation of fMRI data in the volume or on the surface, and of M/EEG data at the sensor and source level. Through various external toolboxes, it directly supports reading and writing a variety of fMRI and M/EEG neuroimaging formats, and, where applicable, can convert between them. As a result, it can be integrated readily in existing pipelines and used with existing preprocessed datasets.CoSMoMVPA overloads the traditional volumetric searchlight concept to support neighborhoods for M/EEG and surface-based fMRI data, which supports localization of multivariate effects of interest across space, time, and frequency dimensions. CoSMoMVPA also provides a generalized approach to multiple comparison correction across these dimensions using Threshold-Free Cluster Enhancement with state-of-the-art clustering and permutation techniques.CoSMoMVPA is highly modular and uses abstractions to provide a uniform interface for a variety of MVP measures. Typical analyses require a few lines of code, making it accessible to beginner users. At the same time, expert programmers can easily extend its functionality.CoSMoMVPA comes with extensive documentation, including a variety of runnable demonstration scripts and analysis exercises (with example data and solutions). It uses best software engineering practices including version control, distributed development, an automated test suite, and continuous integration testing. It can be used with the proprietary Matlab and the free GNU Octave software, and it complies with open source distribution platforms such as NeuroDebian.CoSMoMVPA is Free/Open Source Software under the permissive MIT license.Website:https://cosmomvpa.orgSource code:https://github.com/CoSMoMVPA/CoSMoMVPA
Predictions shape confidence in right inferior frontal gyrus
Authors: Sherman Maxine T. , Seth Anil K. , Kanai Ryota 
Published: April 2016

AbstractIt is clear that prior expectations shape perceptual decision-making, yet their contribution to the construction of subjective decision confidence remains largely unexplored. We recorded fMRI data while participants made perceptual decisions and confidence judgements, controlling for potential confounds of attention. Results show that subjective confidence increases as perceptual prior expectations increasingly support the decision, and that this relationship is associated with BOLD activity in right inferior frontal gyrus (rIFG). Specifically, rIFG is sensitive to the discrepancy between expectation and decision (mismatch), and, crucially, higher mismatch responses are associated with lower decision confidence. Connectivity analyses revealed the source of the expectancy information to be bilateral orbitofrontal cortex (OFC) and the source of sensory signals to be intracalcarine sulcus. Altogether, our results indicate that predictive information is integrated into subjective confidence in rIFG, and reveal an occipital-frontal network that constructs confidence from top-down and bottom-up signals. This interpretation was further supported by exploratory findings that the white matter density of intracalcarine sulcus and OFC negatively predicted their respective contributions to the construction of confidence. Our findings advance our understanding of the neural basis of subjective perceptual processes by revealing an occipito-frontal functional network that integrates prior beliefs into the construction of confidence.
Potential for Zika virus to establish a sylvatic transmission cycle in the Americas
Authors: Althouse Benjamin M. , Vasilakis Nikos , Sall Amadou A. , Diallo Mawlouth , Weaver Scott C. , Hanley Kathryn A. 
Published: April 2016

AbstractZika virus (ZIKV) originated and continues to circulate in a sylvatic transmission cycle between non-human primate hosts and arboreal mosquitoes in tropical Africa. Recently ZIKV invaded the Americas, where it poses a threat to human health, especially to pregnant women and their infants. Here we examine the risk that ZIKV will establish a sylvatic cycle in the Americas, focusing on Brazil. We review the natural history of sylvatic ZIKV and present a mathematical dynamic transmission model to assess the probability of establishment of a sylvatic ZIKV transmission cycle in non-human primates and/or other mammals and arboreal mosquito vectors in Brazil. Brazil is home to multiple species of primates and mosquitoes potentially capable of ZIKV transmission, though direct assessment of host competence (ability to mount viremia sufficient to infect a feeding mosquito) and vector competence (ability to become infected with ZIKV and disseminate and transmit upon subsequent feedings) of New World species is lacking. Modeling reveals a high probability of establishment of sylvatic ZIKV across a large range of biologically plausible parameters. Probability of establishment is dependent on host population sizes and birthrates and ZIKV force of infection, but a network of as few as 6,000 primates with 10,000 mosquitoes is capable of supporting establishment of a ZIKV sylvatic cycle. Research on the susceptibility of New World monkeys or other small mammals to ZIKV, on the vector competence of New WorldAedes, Sabethes, andHaemagogusmosquitoes for ZIKV, and on the geographic range of these species is urgently needed. A sylvatic cycle of ZIKV would make future elimination efforts in the Americas practically impossible, and paints a dire situation for the epidemiology of ZIKV and ending the ongoing outbreak of congenital Zika syndrome.