bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors
Authors: Wang Tingting , Wang Dangge , Yu Haijun , Feng Bing , Zhou Fangyuan , Zhang Hanwu , Zhou Lei , Jiao Shi , Li Yaping 
Published: April 2018

AbstractVaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes. A mechanical study reveals that NIR light-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to the satisfied therapeutic effect. Furthermore, PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. The PVAX model might provide novel insights for postoperative immunotherapy.
TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin
Authors: Montero Juan J. , López-Silanes Isabel , Megías Diego , F. Fraga Mario , Castells-García Álvaro , Blasco Maria A. 
Published: April 2018

AbstractTERRAs are long non-coding RNAs generated from the telomeres. Lack of TERRA knockout models has hampered understanding TERRAs’ functions. We recently identified chromosome 20q as one of the main origins of human TERRAs, allowing us to generate the first 20q-TERRA knockout models and to demonstrate that TERRAs are essential for telomere length maintenance and protection. Here, we use ALT 20q-TERRA knockout cells to address a direct role of TERRAs in telomeric heterochromatin formation. We find that 20q-TERRAs are essential for the establishment of H3K9me3, H4K20me3, and H3K27me3 heterochromatin marks at telomeres. At the mechanistic level, we find that TERRAs bind to PRC2, responsible for catalyzing H3K27 tri-methylation, and that its localization to telomeres is TERRA-dependent. We further demonstrate that PRC2-dependent H3K27me3 at telomeres is required for the establishment of H3K9me3, H4K20me3, and HP1 binding at telomeres. Together, these findings demonstrate an important role for TERRAs in telomeric heterochromatin assembly.
Atomically thin noble metal dichalcogenide: a broadband mid-infrared semiconductor
Authors: Yu Xuechao , Yu Peng , Wu Di , Singh Bahadur , Zeng Qingsheng , Lin Hsin , Zhou Wu , Lin Junhao , Suenaga Kazu , Liu Zheng , Wang Qi Jie 
Published: April 2018

AbstractThe interest in mid-infrared technologies surrounds plenty of important optoelectronic applications ranging from optical communications, biomedical imaging to night vision cameras, and so on. Although narrow bandgap semiconductors, such as Mercury Cadmium Telluride and Indium Antimonide, and quantum superlattices based on inter-subband transitions in wide bandgap semiconductors, have been employed for mid-infrared applications, it remains a daunting challenge to search for other materials that possess suitable bandgaps in this wavelength range. Here, we demonstrate experimentally for the first time that two-dimensional (2D) atomically thin PtSe2 has a variable bandgap in the mid-infrared via layer and defect engineering. Here, we show that bilayer PtSe2 combined with defects modulation possesses strong light absorption in the mid-infrared region, and we realize a mid-infrared photoconductive detector operating in a broadband mid-infrared range. Our results pave the way for atomically thin 2D noble metal dichalcogenides to be employed in high-performance mid-infrared optoelectronic devices.
Structural basis of epilepsy-related ligand–receptor complex LGI1–ADAM22
Authors: Yamagata Atsushi , Miyazaki Yuri , Yokoi Norihiko , Shigematsu Hideki , Sato Yusuke , Goto-Ito Sakurako , Maeda Asami , Goto Teppei , Sanbo Makoto , Hirabayashi Masumi , Shirouzu Mikako , Fukata Yuko , Fukata Masaki , Fukai Shuya 
Published: April 2018

AbstractEpilepsy is a common brain disorder throughout history. Epilepsy-related ligand–receptor complex, LGI1–ADAM22, regulates synaptic transmission and has emerged as a determinant of brain excitability, as their mutations and acquired LGI1 autoantibodies cause epileptic disorders in human. Here, we report the crystal structure of human LGI1–ADAM22 complex, revealing a 2:2 heterotetrameric assembly. The hydrophobic pocket of the C-terminal epitempin-repeat (EPTP) domain of LGI1 binds to the metalloprotease-like domain of ADAM22. The N-terminal leucine-rich repeat and EPTP domains of LGI1 mediate the intermolecular LGI1–LGI1 interaction. A pathogenic R474Q mutation of LGI1, which does not exceptionally affect either the secretion or the ADAM22 binding, is located in the LGI1–LGI1 interface and disrupts the higher-order assembly of the LGI1–ADAM22 complex in vitro and in a mouse model for familial epilepsy. These studies support the notion that the LGI1–ADAM22 complex functions as the trans-synaptic machinery for precise synaptic transmission.
Neural-like computing with populations of superparamagnetic basis functions
Authors: Mizrahi Alice , Hirtzlin Tifenn , Fukushima Akio , Kubota Hitoshi , Yuasa Shinji , Grollier Julie , Querlioz Damien 
Published: April 2018

AbstractIn neuroscience, population coding theory demonstrates that neural assemblies can achieve fault-tolerant information processing. Mapped to nanoelectronics, this strategy could allow for reliable computing with scaled-down, noisy, imperfect devices. Doing so requires that the population components form a set of basis functions in terms of their response functions to inputs, offering a physical substrate for computing. Such a population can be implemented with CMOS technology, but the corresponding circuits have high area or energy requirements. Here, we show that nanoscale magnetic tunnel junctions can instead be assembled to meet these requirements. We demonstrate experimentally that a population of nine junctions can implement a basis set of functions, providing the data to achieve, for example, the generation of cursive letters. We design hybrid magnetic-CMOS systems based on interlinked populations of junctions and show that they can learn to realize non-linear variability-resilient transformations with a low imprint area and low power.
Artificial two-dimensional polar metal at room temperature
Authors: Cao Yanwei , Wang Zhen , Park Se Young , Yuan Yakun , Liu Xiaoran , Nikitin Sergey M. , Akamatsu Hirofumi , Kareev M. , Middey S. , Meyers D. , Thompson P. , Ryan P. J. , Shafer Padraic , N’Diaye A. , Arenholz E. , Gopalan Venkatraman , Zhu Yimei , Rabe Karin M. , Chakhalian J. 
Published: April 2018

AbstractPolar metals, commonly defined by the coexistence of polar crystal structure and metallicity, are thought to be scarce because the long-range electrostatic fields favoring the polar structure are expected to be fully screened by the conduction electrons of a metal. Moreover, reducing from three to two dimensions, it remains an open question whether a polar metal can exist. Here we report on the realization of a room temperature two-dimensional polar metal of the B-site type in tri-color (tri-layer) superlattices BaTiO3/SrTiO3/LaTiO3. A combination of atomic resolution scanning transmission electron microscopy with electron energy-loss spectroscopy, optical second harmonic generation, electrical transport, and first-principles calculations have revealed the microscopic mechanisms of periodic electric polarization, charge distribution, and orbital symmetry. Our results provide a route to creating all-oxide artificial non-centrosymmetric quasi-two-dimensional metals with exotic quantum states including coexisting ferroelectric, ferromagnetic, and superconducting phases.
Motion model ultrasound localization microscopy for preclinical and clinical multiparametric tumor characterization
Authors: Opacic Tatjana , Dencks Stefanie , Theek Benjamin , Piepenbrock Marion , Ackermann Dimitri , Rix Anne , Lammers Twan , Stickeler Elmar , Delorme Stefan , Schmitz Georg , Kiessling Fabian 
Published: April 2018

AbstractSuper-resolution imaging methods promote tissue characterization beyond the spatial resolution limits of the devices and bridge the gap between histopathological analysis and non-invasive imaging. Here, we introduce motion model ultrasound localization microscopy (mULM) as an easily applicable and robust new tool to morphologically and functionally characterize fine vascular networks in tumors at super-resolution. In tumor-bearing mice and for the first time in patients, we demonstrate that within less than 1 min scan time mULM can be realized using conventional preclinical and clinical ultrasound devices. In this context, next to highly detailed images of tumor microvascularization and the reliable quantification of relative blood volume and perfusion, mULM provides multiple new functional and morphological parameters that discriminate tumors with different vascular phenotypes. Furthermore, our initial patient data indicate that mULM can be applied in a clinical ultrasound setting opening avenues for the multiparametric characterization of tumors and the assessment of therapy response.
Olfactory inputs modulate respiration-related rhythmic activity in the prefrontal cortex and freezing behavior
Authors: Moberly Andrew H. , Schreck Mary , Bhattarai Janardhan P. , Zweifel Larry S. , Luo Wenqin , Ma Minghong 
Published: April 2018

AbstractRespiration and airflow through the nasal cavity are known to be correlated with rhythmic neural activity in the central nervous system. Here we show in rodents that during conditioned fear-induced freezing behavior, mice breathe at a steady rate (~4 Hz), which is correlated with a predominant 4-Hz oscillation in the prelimbic prefrontal cortex (plPFC), a structure critical for expression of conditioned fear behaviors. We demonstrate anatomical and functional connections between the olfactory pathway and plPFC via circuit tracing and optogenetics. Disruption of olfactory inputs significantly reduces the 4-Hz oscillation in the plPFC, but leads to prolonged freezing periods. Our results indicate that olfactory inputs can modulate rhythmic activity in plPFC and freezing behavior.
Single synaptic inputs drive high-precision action potentials in parvalbumin expressing GABA-ergic cortical neurons in vivo
Authors: Jouhanneau Jean-Sébastien , Kremkow Jens , Poulet James F. A. 
Published: April 2018

AbstractA defining feature of cortical layer 2/3 excitatory neurons is their sparse activity, often firing in singlets of action potentials. Local inhibitory neurons are thought to play a major role in regulating sparseness, but which cell types are recruited by single excitatory synaptic inputs is unknown. Using multiple, targeted, in vivo whole-cell recordings, we show that single uEPSPs have little effect on the firing rates of excitatory neurons and somatostatin-expressing GABA-ergic inhibitory neurons but evoke precisely timed action potentials in parvalbumin-expressing inhibitory neurons. Despite a uEPSP decay time of 7.8 ms, the evoked action potentials were almost completely restricted to the uEPSP rising phase (~0.5 ms). Evoked parvalbumin-expressing neuron action potentials go on to inhibit the local excitatory network, thus providing a pathway for single spike evoked disynaptic inhibition which may enforce sparse and precisely timed cortical signaling.
Short-term activation of the Jun N-terminal kinase pathway in apoptosis-deficient cells of Drosophila induces tumorigenesis
Authors: Pinal Noelia , Martín María , Medina Izarne , Morata Ginés 
Published: April 2018

AbstractIn Drosophila, the JNK pathway eliminates by apoptosis aberrant cells that appear in development. It also performs other functions associated with cell proliferation, but analysis of the latter is hindered by the pro-apoptotic activity. We report the response of apoptosis-deficient cells to transient activation of JNK and show that it causes persistent JNK function during the rest of the development. As a consequence, there is continuous activity of the downstream pathways JAK/STAT, Wg and Dpp, which results in tumour overgrowths. We also show that the oncogenic potential of the Ras-MAPK pathway resides largely on its ability to suppress apoptosis. It has been proposed that a hallmark of tumour cells is that they can evade apoptosis. In reverse, we propose that, in Drosophila, apoptosis-deficient cells become tumorigenic due to their property of acquiring persistent JNK activity after stress events that are inconsequential in tissues in which cells are open to apoptosis.
Random sequences rapidly evolve into de novo promoters
Authors: Yona Avihu H. , Alm Eric J. , Gore Jeff 
Published: April 2018

AbstractHow new functions arise de novo is a fundamental question in evolution. We studied de novo evolution of promoters in Escherichia coli by replacing the lac promoter with various random sequences of the same size (~100 bp) and evolving the cells in the presence of lactose. We find that ~60% of random sequences can evolve expression comparable to the wild-type with only one mutation, and that ~10% of random sequences can serve as active promoters even without evolution. Such a short mutational distance between random sequences and active promoters may improve the evolvability, yet may also lead to accidental promoters inside genes that interfere with normal expression. Indeed, our bioinformatic analyses indicate that E. coli was under selection to reduce accidental promoters inside genes by avoiding promoter-like sequences. We suggest that a low threshold for functionality balanced by selection against undesired targets can increase the evolvability by making new beneficial features more accessible.
An automated skin segmentation of Breasts in Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Authors: Lee Chia-Yen , Chang Tzu-Fang , Chang Nai-Yun , Chang Yeun-Chung 
Published: April 2018

AbstractDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to diagnose breast disease. Obtaining anatomical information from DCE-MRI requires the skin be manually removed so that blood vessels and tumors can be clearly observed by physicians and radiologists; this requires considerable manpower and time. We develop an automated skin segmentation algorithm where the surface skin is removed rapidly and correctly. The rough skin area is segmented by the active contour model, and analyzed in segments according to the continuity of the skin thickness for accuracy. Blood vessels and mammary glands are retained, which remedies the defect of removing some blood vessels in active contours. After three-dimensional imaging, the DCE-MRIs without the skin can be used to see internal anatomical information for clinical applications. The research showed the Dice’s coefficients of the 3D reconstructed images using the proposed algorithm and the active contour model for removing skins are 93.2% and 61.4%, respectively. The time performance of segmenting skins automatically is about 165 times faster than manually. The texture information of the tumors position with/without the skin is compared by the paired t-test yielded all p < 0.05, which suggested the proposed algorithm may enhance observability of tumors at the significance level of 0.05.
Measurement of metabolite variations and analysis of related gene expression in Chinese liquorice (Glycyrrhiza uralensis) plants under UV-B irradiation
Authors: Zhang Xiao , Ding Xiaoli , Ji Yaxi , Wang Shouchuang , Chen Yingying , Luo Jie , Shen Yingbai , Peng Li 
Published: April 2018

AbstractPlants respond to UV-B irradiation (280–315 nm wavelength) via elaborate metabolic regulatory mechanisms that help them adapt to this stress. To investigate the metabolic response of the medicinal herb Chinese liquorice (Glycyrrhiza uralensis) to UV-B irradiation, we performed liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomic analysis, combined with analysis of differentially expressed genes in the leaves of plants exposed to UV-B irradiation at various time points. Fifty-four metabolites, primarily amino acids and flavonoids, exhibited changes in levels after the UV-B treatment. The amino acid metabolism was altered by UV-B irradiation: the Asp family pathway was activated and closely correlated to Glu. Some amino acids appeared to be converted into antioxidants such as γ-aminobutyric acid and glutathione. Hierarchical clustering analysis revealed that various flavonoids with characteristic groups were induced by UV-B. In particular, the levels of some ortho-dihydroxylated B-ring flavonoids, which might function as scavengers of reactive oxygen species, increased in response to UV-B treatment. In general, unigenes encoding key enzymes involved in amino acid metabolism and flavonoid biosynthesis were upregulated by UV-B irradiation. These findings lay the foundation for further analysis of the mechanism underlying the response of G. uralensis to UV-B irradiation.
Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin
Authors: Saraiva Raúl G. , Huitt-Roehl Callie R. , Tripathi Abhai , Cheng Yi-Qiang , Bosch Jürgen , Townsend Craig A. , Dimopoulos George 
Published: April 2018

AbstractThe Chromobacterium sp. Panama bacterium has in vivo and in vitro anti-Plasmodium properties. To assess the nature of the Chromobacterium-produced anti-Plasmodium factors, chemical partition was conducted by bioassay-guided fractionation where different fractions were assayed for activity against asexual stages of P. falciparum. The isolated compounds were further partitioned by reversed-phase FPLC followed by size-exclusion chromatography; high resolution UPLC and ESI/MS data were then collected and revealed that the most active fraction contained a cyclic depsipeptide, which was identified as romidepsin. A pure sample of this FDA-approved HDAC inhibitor allowed us to independently verify this finding, and establish that romidepsin also has potent effect against mosquito stages of the parasite’s life cycle. Genomic comparisons between C. sp. Panama and multiple species within the Chromobacterium genus further demonstrated a correlation between presence of the gene cluster responsible for romidepsin production and effective antiplasmodial activity. A romidepsin-null Chromobacterium spp. mutant loses its anti-Plasmodium properties by losing the ability to inhibit P. falciparum HDAC activity, and romidepsin is active against resistant parasites to commonly deployed antimalarials. This independent mode of action substantiates exploring a chromobacteria-based approach for malaria transmission-blocking.
Acoustic fine structure may encode biologically relevant information for zebra finches
Authors: Prior Nora H. , Smith Edward , Lawson Shelby , Ball Gregory F. , Dooling Robert J. 
Published: April 2018

AbstractThe ability to discriminate changes in the fine structure of complex sounds is well developed in birds. However, the precise limit of this discrimination ability and how it is used in the context of natural communication remains unclear. Here we describe natural variability in acoustic fine structure of male and female zebra finch calls. Results from psychoacoustic experiments demonstrate that zebra finches are able to discriminate extremely small differences in fine structure, which are on the order of the variation in acoustic fine structure that is present in their vocal signals. Results from signal analysis methods also suggest that acoustic fine structure may carry information that distinguishes between biologically relevant categories including sex, call type and individual identity. Combined, our results are consistent with the hypothesis that zebra finches can encode biologically relevant information within the fine structure of their calls. This study provides a foundation for our understanding of how acoustic fine structure may be involved in animal communication.
A systems biology approach to predict and characterize human gut microbial metabolites in colorectal cancer
Authors: Wang QuanQiu , Li Li , Xu Rong 
Published: April 2018

AbstractColorectal cancer (CRC) is the second leading cause of cancer-related deaths. It is estimated that about half the cases of CRC occurring today are preventable. Recent studies showed that human gut microbiota and their collective metabolic outputs play important roles in CRC. However, the mechanisms by which human gut microbial metabolites interact with host genetics in contributing CRC remain largely unknown. We hypothesize that computational approaches that integrate and analyze vast amounts of publicly available biomedical data have great potential in better understanding how human gut microbial metabolites are mechanistically involved in CRC. Leveraging vast amount of publicly available data, we developed a computational algorithm to predict human gut microbial metabolites for CRC. We validated the prediction algorithm by showing that previously known CRC-associated gut microbial metabolites ranked highly (mean ranking: top 10.52%; median ranking: 6.29%; p-value: 3.85E-16). Moreover, we identified new gut microbial metabolites likely associated with CRC. Through computational analysis, we propose potential roles for tartaric acid, the top one ranked metabolite, in CRC etiology. In summary, our data-driven computation-based study generated a large amount of associations that could serve as a starting point for further experiments to refute or validate these microbial metabolite associations in CRC cancer.
Detecting liver fibrosis with Gd-EOB-DTPA-enhanced MRI: A confirmatory study
Authors: Verloh Niklas , Utpatel Kirsten , Haimerl Michael , Zeman Florian , Beyer Lukas , Fellner Claudia , Brennfleck Frank , Dahlke Marc H , Stroszczynski Christian , Evert Matthias , Wiggermann Philipp 
Published: April 2018

AbstractStrong correlations between the grade of fibrosis and cirrhosis, classified using the Ishak scoring system, and the uptake characteristics of Gd-EOB-DTPA with the relative enhancement (RE) of the liver parenchyma have been reported. To confirm the results of a retrospective analysis, patients undergoing liver surgery were prospectively examined with Gd-EOB-DTPA-enhanced liver 3 Tesla MRI to determine the degree of liver fibrosis. Correlations between the grade of fibrosis and cirrhosis, classified using the Ishak scoring system, and RE were investigated and compared with those derived from an initial retrospective study. After validating the cut-off values in the retrospective study (Ishak ≥ 1, RE-cut-off 0.90; Ishak ≥ 2, RE-cut-off 0.79; Ishak ≥ 4, RE-cut-off 0.60; and Ishak = 6, RE-cut-off 0.47), we showed that Gd-EOB-DTPA has a high sensitivity (≥86%) and a high positive predictive value (≥86%). These results support the use of Gd-EOB-DTPA-enhanced liver MRI as a non-invasive method for determining the degree of liver fibrosis and cirrhosis.