bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-FLIP is a target of the E3 ligase deltex1 in gastric cancer
Authors: Hsu Tzu-Sheng , Mo Shu-Ting , Hsu Ping-Ning , Lai Ming-Zong 
Published: January 2018

AbstractThe ubiquitin E3 ligase DELTEX1 (DTX1) is specifically downregulated in gastric cancer tissues, and expression of DTX1 is linked to better prognoses and survival in gastric cancer. Cellular FLICE inhibitory protein (c-FLIP) is known for its pivotal role in the resistance of cancer cells to death receptor-induced cell death. Here, we show that DTX1 is an E3 ligase for c-FLIP in gastric cancer cells. DTX1 promoted c-FLIP downregulation. Overexpression of DTX1 sensitized gastric cancer cells to TRAIL-induced apoptosis, whereas DTX1-knockdown attenuated apoptosis induction. DTX1 binds c-FLIPL and directs it into the endosome-lysosomal pathway for proteasome-independent degradation. Moreover, induction of DTX1 in AGS cells by geldanamycin conferred susceptibility of those cells to TRAIL-induced apoptosis. Our results reveal a tumor-suppressive role for DTX1 and suggest a new approach to increasing TRAIL efficacy by raising DTX1 levels in gastric cancer therapy. DTX1 also enhanced c-FLIP degradation and FasL-induced and TRAIL-induced apoptosis in T cells, suggesting that DTX1 constitutes one of the physiological mechanisms regulating c-FLIP stability.
SIRT1 induces epithelial-mesenchymal transition by promoting autophagic degradation of E-cadherin in melanoma cells
Authors: Sun Ting , Jiao Lin , Wang Yangxia , Yu Yan , Ming Liang 
Published: January 2018

AbstractMelanoma is highly metastatic, and understanding of its molecular mechanism is urgently needed for the development of therapeutic targets and prognostic assessment for metastatic melanoma. SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, belonging to the mammalian sirtuin family. It has been reported that SIRT1 is associated with metastasis in various cancers. However, the molecular mechanism of SIRT1 in melanoma metastasis remains to be clarified. Here we report that SIRT1 induces the epithelial–mesenchymal transition (EMT) by accelerating E-cadherin degradation via autophagy and facilitates melanoma metastasis. Initially, we found that SIRT1 expression was frequently elevated in metastatic melanoma compared with primary melanoma. In addition, SIRT1 induced the EMT and promoted cell migration and invasion by decreasing E-cadherin expression. Further work demonstrated that SIRT1 accelerated the autophagic degradation of E-cadherin through deacetylation of Beclin 1. In addition, inhibition of autophagy recovered E-cadherin expression and suppressed cell migration and invasion by delaying the degradation of E-cadherin in SIRT1-overexpressing cells. Overall, our findings reveal a novel molecular mechanism for SIRT1 in melanoma metastasis, indicating that SIRT1 may serve as a viable therapeutic target for metastatic melanoma.
IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK dipendent autophagy
Authors: Storniolo Antonello , Alfano Vincenzo , Carbotta Sabino , Ferretti Elisabetta , Di Renzo Livia 
Published: January 2018

AbstractSensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase. GSK2606414, a PERK inhibitor, and PERK specific siRNA prevent eIF2α down-regulation and restore cell survival. Degradation of this protein is due to autophagy, as it is prevented by bafilomycin and not by proteasome inhibition. Furthermore, activation of the autophagy flux is PERK dependent. Also the Cathepsin B inhibitor CA074 prevents eIF2α from degradation and reduces cell death. Altogether, these results show that IRE1α deficiency in ER stressed cells leads to an unexpected decrease of eIF2α, an important molecule for protein translation, through PERK dependent autophagy. Thus, IRE1/XBP1 inhibitors may represent a feasible strategy for tumor therapy, while PERK inhibitors may vanish the goal.
Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis
Authors: Matthes Frank , Hettich Moritz M. , Schilling Judith , Flores-Dominguez Diana , Blank Nelli , Wiglenda Thomas , Buntru Alexander , Wolf Hanna , Weber Stephanie , Vorberg Ina , Dagane Alina , Dittmar Gunnar , Wanker Erich , Ehninger Dan , Krauss Sybille 
Published: January 2018

AbstractAlzheimer’s disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA. The underlying mode of action of MID1 involves the mTOR pathway. Thus, inhibition of the MID1 complex reduces the APP protein level in cultures of primary neurons. Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments. Indeed, long-term treatment with metformin decreased APP protein expression levels and consequently Aβ in an AD mouse model. Importantly, we have initiated the metformin treatment late in life, at a time-point where mice were in an already progressed state of the disease, and could observe an improved behavioral phenotype. These findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD.
A cerebellar mechanism for learning prior distributions of time intervals
Authors: Narain Devika , Remington Evan D. , Zeeuw Chris I. De , Jazayeri Mehrdad 
Published: January 2018

AbstractKnowledge about the statistical regularities of the world is essential for cognitive and sensorimotor function. In the domain of timing, prior statistics are crucial for optimal prediction, adaptation and planning. Where and how the nervous system encodes temporal statistics is, however, not known. Based on physiological and anatomical evidence for cerebellar learning, we develop a computational model that demonstrates how the cerebellum could learn prior distributions of time intervals and support Bayesian temporal estimation. The model shows that salient features observed in human Bayesian time interval estimates can be readily captured by learning in the cerebellar cortex and circuit level computations in the cerebellar deep nuclei. We test human behavior in two cerebellar timing tasks and find prior-dependent biases in timing that are consistent with the predictions of the cerebellar model.
Early Cambrian fuxianhuiids from China reveal origin of the gnathobasic protopodite in euarthropods
Authors: Yang Jie , Ortega-Hernández Javier , Legg David A. , Lan Tian , Hou Jin-bo , Zhang Xi-guang 
Published: January 2018

AbstractEuarthropods owe their evolutionary and ecological success to the morphological plasticity of their appendages. Although this variability is partly expressed in the specialization of the protopodite for a feeding function in the post-deutocerebral limbs, the origin of the former structure among Cambrian representatives remains uncertain. Here, we describeAlacaris mirabilisgen. et sp. nov. from the early Cambrian Xiaoshiba Lagerstätte in China, which reveals the proximal organization of fuxianhuiid appendages in exceptional detail. Proximally, the post-deutocerebral limbs possess an antero-posteriorly compressed protopodite with robust spines. The protopodite is attached to an endopod with more than a dozen podomeres, and an oval flap-shaped exopod. The gnathal edges of the protopodites form an axial food groove along the ventral side of the body, indicating a predatory/scavenging autecology. A cladistic analysis indicates that the fuxianhuiid protopodite represents the phylogenetically earliest occurrence of substantial proximal differentiation within stem-group Euarthropoda illuminating the origin of gnathobasic feeding.
Predicting phase behavior of grain boundaries with evolutionary search and machine learning
Authors: Zhu Qiang , Samanta Amit , Li Bingxi , Rudd Robert E. , Frolov Timofey 
Published: January 2018

AbstractThe study of grain boundary phase transitions is an emerging field until recently dominated by experiments. The major bottleneck in the exploration of this phenomenon with atomistic modeling has been the lack of a robust computational tool that can predict interface structure. Here we develop a computational tool based on evolutionary algorithms that performs efficient grand-canonical grain boundary structure search and we design a clustering analysis that automatically identifies different grain boundary phases. Its application to a model system of symmetric tilt boundaries in Cu uncovers an unexpected rich polymorphism in the grain boundary structures. We find new ground and metastable states by exploring structures with different atomic densities. Our results demonstrate that the grain boundaries within the entire misorientation range have multiple phases and exhibit structural transitions, suggesting that phase behavior of interfaces is likely a general phenomenon.
A genome for gnetophytes and early evolution of seed plants
Authors: Wan Tao , Liu Zhi-Ming , Li Ling-Fei , Leitch Andrew R. , Leitch Ilia J. , Lohaus Rolf , Liu Zhong-Jian , Xin Hai-Ping , Gong Yan-Bing , Liu Yang , Wang Wen-Cai , Chen Ling-Yun , Yang Yong , Kelly Laura J. , Yang Ji , Huang Jin-Ling , Li Zhen , Liu Ping , Zhang Li , Liu Hong-Mei , Wang Hui , Deng Shu-Han , Liu Meng , Li Ji , Ma Lu , Liu Yan , Lei Yang , Xu Wei , Wu Ling-Qing , Liu Fan , Ma Qian , Yu Xin-Ran , Jiang Zhi , Zhang Guo-Qiang , Li Shao-Hua , Li Rui-Qiang , Zhang Shou-Zhou , Wang Qing-Feng , Van de Peer Yves , Zhang Jin-Bo , Wang Xiao-Ming 
Published: January 2018

AbstractGnetophytes are an enigmatic gymnosperm lineage comprising three genera, Gnetum, Welwitschia and Ephedra, which are morphologically distinct from all other seed plants. Their distinctiveness has triggered much debate as to their origin, evolution and phylogenetic placement among seed plants. To increase our understanding of the evolution of gnetophytes, and their relation to other seed plants, we report here a high-quality draft genome sequence for Gnetum montanum, the first for any gnetophyte. By using a novel genome assembly strategy to deal with high levels of heterozygosity, we assembled >4 Gb of sequence encoding 27,491 protein-coding genes. Comparative analysis of the G. montanum genome with other gymnosperm genomes unveiled some remarkable and distinctive genomic features, such as a diverse assemblage of retrotransposons with evidence for elevated frequencies of elimination rather than accumulation, considerable differences in intron architecture, including both length distribution and proportions of (retro) transposon elements, and distinctive patterns of proliferation of functional protein domains. Furthermore, a few gene families showed Gnetum-specific copy number expansions (for example, cellulose synthase) or contractions (for example, Late Embryogenesis Abundant protein), which could be connected with Gnetum’s distinctive morphological innovations associated with their adaptation to warm, mesic environments. Overall, the G. montanum genome enables a better resolution of ancestral genomic features within seed plants, and the identification of genomic characters that distinguish Gnetum from other gymnosperms.
Differential depth distribution of microbial function and putative symbionts through sediment-hosted aquifers in the deep terrestrial subsurface
Authors: Probst Alexander J. , Ladd Bethany , Jarett Jessica K. , Geller-McGrath David E. , Sieber Christian M. K. , Emerson Joanne B. , Anantharaman Karthik , Thomas Brian C. , Malmstrom Rex R. , Stieglmeier Michaela , Klingl Andreas , Woyke Tanja , Ryan M. Cathryn , Banfield Jillian F. 
Published: January 2018

AbstractAn enormous diversity of previously unknown bacteria and archaea has been discovered recently, yet their functional capacities and distributions in the terrestrial subsurface remain uncertain. Here, we continually sampled a CO2-driven geyser (Colorado Plateau, Utah, USA) over its 5-day eruption cycle to test the hypothesis that stratified, sandstone-hosted aquifers sampled over three phases of the eruption cycle have microbial communities that differ both in membership and function. Genome-resolved metagenomics, single-cell genomics and geochemical analyses confirmed this hypothesis and linked microorganisms to groundwater compositions from different depths. AutotrophicCandidatus“Altiarchaeum sp.” and phylogenetically deep-branching nanoarchaea dominate the deepest groundwater. A nanoarchaeon with limited metabolic capacity is inferred to be a potential symbiont of theCa. “Altiarchaeum”. Candidate Phyla Radiation bacteria are also present in the deepest groundwater and they are relatively abundant in water from intermediate depths. During the recovery phase of the geyser, microaerophilic Fe- and S-oxidizers have high in situ genome replication rates. AutotrophicSulfurimonassustained by aerobic sulfide oxidation and with the capacity for N2fixation dominate the shallow aquifer. Overall, 104 different phylum-level lineages are present in water from these subsurface environments, with uncultivated archaea and bacteria partitioned to the deeper subsurface.
Silicon based mid-IR super absorber using hyperbolic metamaterial
Authors: Desouky Mai , Mahmoud Ahmed M. , Swillam Mohamed A. 
Published: January 2018

AbstractPerfect absorbers are indispensable components for energy harvesting applications. While many absorbers have been proposed, they encounter inevitable drawbacks including bulkiness or instability over time. The urge for CMOS compatible absorber that can be integrated for on chip applications requires further investigation. We theoretically demonstrate Silicon (Si) based mid IR super absorber with absorption (A) reaching 0.948. Our structure is composed of multilayered N-doped Si/ Si hyperbolic metamaterial (HMM) integrated with sub-hole Si grating. Our proposed structure has tunable absorption peak that can be tuned from 4.5 µm to 11 µm through changing the grating parameters. We also propose two grating designs integrated with N-doped Si/ Si HMM that can achieve wide band absorption. The first grating design is based on Si grating incorporating different holes’ height with (A) varying between 0.83 and 0.97 for wavelength from 5 µm to 7 µm. The second grating design is based on Si grating with variable holes’ diameter; the latter shows broad band absorption with the maximum (A) reaching 0.97. We also show that our structure is omnidirectional. We propose an all Si based absorber which demonstrates a good candidate for thermal harvesting application.
Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression
Authors: Parada Carolina Angelica , Osbun Joshua , Kaur Sumanpreet , Yakkioui Youssef , Shi Min , Pan Catherine , Busald Tina , Karasozen Yigit , Gonzalez-Cuyar Luis Francisco , Rostomily Robert , Zhang Jing , Ferreira Manuel 
Published: January 2018

AbstractThere is a need to better understand meningioma oncogenesis for biomarker discovery and development of targeted therapies. Histological or genetic criteria do not accurately predict aggressiveness. Post-translational studies in meningioma progression are lacking. In the present work, we introduce a combination of mass spectrometry-based phosphoproteomics and peptide array kinomics to profile atypical and anaplastic (high-grade) meningiomas. In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades. AKAP12 knockdown in benign meningioma cells SF4433 increases proliferation, cell cycle, migration, invasion, and confers an anaplastic profile. Differentially regulated pathways were characteristic of high-grade meningiomas. Low AKAP12 expression in a larger cohort of patients (75) characterized tumor invasiveness, recurrence, and progression, indicating its potential as a prognostic biomarker. These results demonstrate AKAP12 as a central regulator of meningioma aggressiveness with a possible role in progression.
Probing the folding pathway of a consensus serpin using single tryptophan mutants
Authors: Yang Li , Irving James A. , Dai Weiwen , Aguilar Marie-Isabel , Bottomley Stephen P. 
Published: January 2018

AbstractConserpin is an engineered protein that represents the consensus of a sequence alignment of eukaryotic serpins: protease inhibitors typified by a metastable native state and a structurally well-conserved scaffold. Previously, this protein has been found to adopt a native inhibitory conformation, possess an atypical reversible folding pathway and exhibit pronounced resistance to inactivation. Here we have designed a version of conserpin, cAT, with the inhibitory specificity of α1-antitrypsin, and generated single-tryptophan variants to probe its folding pathway in more detail. cAT exhibited similar thermal stability to the parental protein, an inactivation associated with oligomerisation rather a transition to the latent conformation, and a native state with pronounced kinetic stability. The tryptophan variants reveal the unfolding intermediate ensemble to consist of an intact helix H, a distorted helix F and ‘breach’ region structurally similar to that of a mesophilic serpin intermediate. A combination of intrinsic fluorescence, circular dichroism, and analytical gel filtration provide insight into a highly cooperative folding pathway with concerted changes in secondary and tertiary structure, which minimises the accumulation of two directly-observed aggregation-prone intermediate species. This functional conserpin variant represents a basis for further studies of the relationship between structure and stability in the serpin superfamily.
msgbsR: An R package for analysing methylation-sensitive restriction enzyme sequencing data
Authors: Mayne Benjamin T. , Leemaqz Shalem Y. , Buckberry Sam , Rodriguez Lopez Carlos M. , Roberts Claire T. , Bianco-Miotto Tina , Breen James 
Published: January 2018

AbstractGenotyping-by-sequencing (GBS) or restriction-site associated DNA marker sequencing (RAD-seq) is a practical and cost-effective method for analysing large genomes from high diversity species. This method of sequencing, coupled with methylation-sensitive enzymes (often referred to as methylation-sensitive restriction enzyme sequencing or MRE-seq), is an effective tool to study DNA methylation in parts of the genome that are inaccessible in other sequencing techniques or are not annotated in microarray technologies. Current software tools do not fulfil all methylation-sensitive restriction sequencing assays for determining differences in DNA methylation between samples. To fill this computational need, we present msgbsR, an R package that contains tools for the analysis of methylation-sensitive restriction enzyme sequencing experiments. msgbsR can be used to identify and quantify read counts at methylated sites directly from alignment files (BAM files) and enables verification of restriction enzyme cut sites with the correct recognition sequence of the individual enzyme. In addition, msgbsR assesses DNA methylation based on read coverage, similar to RNA sequencing experiments, rather than methylation proportion and is a useful tool in analysing differential methylation on large populations. The package is fully documented and available freely online as a Bioconductor package (https://bioconductor.org/packages/release/bioc/html/msgbsR.html).
Synthesis of organic aerogels with tailorable morphology and strength by controlled solvent swelling following Hansen solubility
Authors: Tripathi Anurodh , Parsons Gregory N. , Khan Saad A. , Rojas Orlando J. 
Published: January 2018

AbstractWe introduce a generalized approach to synthesize aerogels that allows remarkable control over its mechanical properties. The Hansen solubility parameters are used to predict and regulate the swelling properties of the precursor gels and, consequently, to achieve aerogels with tailored density and mechanical properties. As a demonstration, crosslinked organogels were synthesized from cellulose esters to generate aerogels. By determination of Hansen’s Relative Energy Difference, it was possible to overcome the limitations of current approaches that solely rely on the choice of precursor polymer concentration to achieve a set of aerogel properties. Hence, from a given concentration, aerogels were produced in a range of mass densities, from 25 to 113 mg/cm3. Consequently, it was possible to tailor the stiffness, toughness and compressive strength of the aerogels, in the ranges between 14–340, 4–103 and 22–373 kPa, respectively. Additionally, unidirectional freeze-drying introduced pore alignment in aerogels with honeycomb morphologies and anisotropy. Interestingly, when the swelling of the polymeric gel was arrested in a non-equilibrium state, it was possible to gain additional control of the property space. The proposed method is a novel and generic solution to achieving full control of aerogel development, which up to now has been an intractable challenge.
Perivascular Spaces Segmentation in Brain MRI Using Optimal 3D Filtering
Authors: Ballerini Lucia , Lovreglio Ruggiero , Valdés Hernández Maria del C. , Ramirez Joel , MacIntosh Bradley J. , Black Sandra E. , Wardlaw Joanna M. 
Published: January 2018

AbstractPerivascular Spaces (PVS) are a feature of Small Vessel Disease (SVD), and are an important part of the brain’s circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. We used ordered logit models and visual rating scales as alternative ground truth for Frangi filter parameter optimization and evaluation. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N = 20) and patients who previously had mild to moderate stroke (N = 48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated well with neuroradiological assessments (Spearman’s ρ = 0.74, p < 0.001), supporting the potential of our proposed method.