bluuebunny/crossref_metadata_2025_split huggingface dataset:
PARP1 rs1805407 Increases Sensitivity to PARP1 Inhibitors in Cancer Cells Suggesting an Improved Therapeutic Strategy
Authors: Abecassis Irina , Sedgewick Andrew J. , Romkes Marjorie , Buch Shama , Nukui Tomoko , Kapetanaki Maria G. , Vogt Andreas , Kirkwood John M. , Benos Panayiotis V. , Tawbi Hussein 
Published: March 2019

AbstractPersonalized cancer therapy relies on identifying patient subsets that benefit from a therapeutic intervention and suggest alternative regimens for those who don’t. A new data integrative approach, based on graphical models, was applied on our multi-modal –omics, and clinical data cohort of metastatic melanoma patients. We found that response to chemotherapy is directly linked to ten gene expression, four methylation variables and PARP1 SNP rs1805407. PARP1 is a DNA repair gene critical for chemotherapy response and for which FDA-approved inhibitors are clinically available (olaparib). We demonstrated that two PARP inhibitors (ABT-888 and olaparib) make SNP carrier cancer cells of various histologic subtypes more sensitive to alkylating agents, but they have no effect in wild-type cells. Furthermore, PARP1 inhibitors act synergistically with chemotherapy in SNP carrier cells (especially in ovarian cancer for which olaparib is FDA-approved), but they are additive at best in wild-type cancer cells. Taken together, our results suggest that the combination of chemotherapy and PARP1 inhibition may benefit the carriers of rs1805407 in the future and may be used in personalized therapy strategies to select patients that are more likely to respond to PARP inhibitors.
Terahertz emission from gold nanorods irradiated by ultrashort laser pulses of different wavelengths
Authors: Takano Keisuke , Asai Motoki , Kato Kosaku , Komiyama Hideaki , Yamaguchi Akihisa , Iyoda Tomokazu , Tadokoro Yuzuru , Nakajima Makoto , Bakunov Michael I. 
Published: March 2019

AbstractElectron photoemission and ponderomotive acceleration by surface enhanced optical fields is considered as a plausible mechanism of terahertz radiation from metallic nanostructures under ultrafast laser excitation. To verify this mechanism, we studied experimentally terahertz emission from an array of gold nanorods illuminated by intense (~10–100 GW/cm2) femtosecond pulses of different central wavelengths (600, 720, 800, and 1500 nm). We found for the first time that the order of the dependence of the terahertz fluence on the laser intensity is, unexpectedly, almost the same (~4.5–4.8) for 720, 800, and 1500 nm and somewhat higher (~6.6) for 600 nm. The results are explained by tunneling currents driven by plasmonically enhanced laser field. In particular, the pump-intensity dependence of the terahertz fluence is more consistent with terahertz emission from the sub-cycle bursts of the tunneling current rather than with the ponderomotive mechanism.
Functional analysis of ZmMADS1a reveals its role in regulating starch biosynthesis in maize endosperm
Authors: Dong Qing , Wang Fang , Kong Jingjing , Xu Qianqian , Li Tingchun , Chen Long , Chen Hongjian , Jiang Haiyang , Li Cheng , Cheng Beijiu 
Published: March 2019

AbstractMADS-box family proteins play an important role in grain formation and flower development; however, the molecular mechanisms by which transcription factors regulate the starch metabolism pathway are unclear in maize. Here, we report a transcription factor, ZmMADS1a, that controls starch biosynthesis in maize (Zea mays L.). We demonstrate the expression of ZmMADS1a in tassel, silk, and endosperm, and show that the protein is localized to the cell nucleus. Compared with the control, seeds of overexpressing ZmMADS1a increased starch content (especially amylose content), had smaller starch granules and altered chemical structure. Meanwhile, overexpression of ZmMADS1a resulted in increases in the contents of soluble sugars and reducing sugars in maize. ZmMADS1a plays a positive regulatory role in the starch biosynthesis pathway by up-regulating several starch biosynthesis related genes. We also show that ZmMADS1a has a similar adjustment mechanism of starch biosynthesis in rice. Collectively, our study suggests that ZmMADS1a functions as a positive regulator of starch biosynthesis by regulating the expression of key starch metabolism genes during seed development.
The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/ HIF-1α axis signals
Authors: Wu Tsai-Kun , Wei Chyou-Wei , Pan Ying-Ru , Hsu Ren-Jun , Wu Chung-Yi , Yu Yung-Luen 
Published: March 2019

Abstractp-Cresyl sulfate (pCS), a uremic toxin, can cause renal damage and dysfunction. Studies suggest that renal dysfunction increases the prevalence of renal cancer. However, the effect of pCS on the proliferation and migration of renal cancer is unclear. Clear cell renal cell carcinoma (ccRCC) expresses mutant von Hippel-Lindau gene and is difficult to treat. Hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-α and miR-21 in ccRCC remains unclear. Therefore, the effects of pCS on ccRCC cells were investigated for HIF-α and miR-21 signals. Our results showed that pCS induced overexpression of HIF-1α and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells. pCS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked pCS-induced proliferation and migration. Taken together, the present results demonstrate that pCS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21/HIF-1α signaling pathways.
Parallel colonization of subalpine habitats in the central European mountains by Primula elatior
Authors: Konečná Veronika , Nowak Michael D. , Kolář Filip 
Published: March 2019

AbstractThe island-like distribution of subalpine habitats across mountain ranges can trigger the parallel evolution of locally adapted ecotypes. Such naturally replicated scenarios allow testing hypotheses on how elevational differentiation structures genetic diversity within species. Nevertheless, the parallel colonization of subalpine habitats across different mountain ranges has only rarely been documented with molecular data. We chose Primula elatior (Primulaceae), naturally spanning entire elevation range in multiple mountain regions of central Europe, to test for the origin of its scattered subalpine populations. Nuclear microsatellite variation revealed three genetic groups corresponding with the distinct study regions. We found that genetic differentiation between foothill and subalpine populations within each region was relatively low, suggesting that the colonization of subalpine habitats occurred independently within each mountain range. Furthermore, the strongest differentiation was usually found between the subalpine populations suggesting that mountain ridges may act as migration barriers that can reduce gene flow more strongly than elevational differences between foothill and subalpine populations. Finally, we found that subalpine colonization did not result in a loss of genetic diversity relative to foothill populations in agreement with the high migration rates that we document here between the subalpine and the foothill populations. In summary, our study shows subalpine Primula elatior populations are genetically diverse and distinct results of parallel colonization events from multiple foothill gene pools.
Frequent pattern mining in multidimensional organizational networks
Authors: Gadár László , Abonyi János 
Published: March 2019

AbstractNetwork analysis can be applied to understand organizations based on patterns of communication, knowledge flows, trust, and the proximity of employees. A multidimensional organizational network was designed, and association rule mining of the edge labels applied to reveal how relationships, motivations, and perceptions determine each other in different scopes of activities and types of organizations. Frequent itemset-based similarity analysis of the nodes provides the opportunity to characterize typical roles in organizations and clusters of co-workers. A survey was designed to define 15 layers of the organizational network and demonstrate the applicability of the method in three companies. The novelty of our approach resides in the evaluation of people in organizations as frequent multidimensional patterns of multilayer networks. The results illustrate that the overlapping edges of the proposed multilayer network can be used to highlight the motivation and managerial capabilities of the leaders and to find similarly perceived key persons.
HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503
Authors: Gorbatenko Andrej , Søkilde Rolf , Sorensen Ester E. , Newie Inga , Persson Helena , Morancho Beatriz , Arribas Joaquin , Litman Thomas , Rovira Carlos , Pedersen Stine Falsig 
Published: March 2019

AbstractThe HER2 oncogene and its truncated form p95HER2 play central roles in breast cancer. Here, we show that although HER2 and p95HER2 generally elicit qualitatively similar changes in miRNA profile in MCF-7 breast cancer cells, a subset of changes are distinct and p95HER2 shifts the miRNA profile towards the basal breast cancer subtype. High-throughput miRNA profiling was carried out 15, 36 and 60 h after HER2 or p95HER2 expression and central hits validated by RT-qPCR. miRNAs strongly regulated by p95HER2 yet not by HER2, included miR-221, miR-222, miR-503, miR-29a, miR-149, miR-196 and miR-361. Estrogen receptor-α (ESR1) expression was essentially ablated by p95HER2 expression, in a manner recapitulated by miR-221/-222 mimics. c-Myb family transcription factors MYB and MYBL1, but not MYBL2, were downregulated by p95HER2 and by miR-503 or miR-221/-222 mimics. MYBL1 3′UTR inhibition by miR-221/222 was lost by deletion of a single putative miR-221/222 binding sites. p95HER2 expression, or knockdown of either MYB protein, elicited upregulation of tissue inhibitor of matrix metalloprotease-2 (TIMP2). miR-221/222 and -503 mimics increased, and TIMP2 knockdown decreased, cell migration and invasion. A similar pathway was operational in T47D- and SKBr-3 cells. This work reveals important differences between HER2- and p95HER2- mediated miRNA changes in breast cancer cells, provides novel mechanistic insight into regulation of MYB family transcription factors by p95HER2, and points to a role for a miR-221/222– MYB family–TIMP2 axis in regulation of motility in breast cancer cells.
Dietary Lutein Plus Zeaxanthin Intake and DICER1 rs3742330 A > G Polymorphism Relative to Colorectal Cancer Risk
Authors: Kim Jimi , Lee Jeonghee , Oh Jae Hwan , Chang Hee Jin , Sohn Dae Kyung , Kwon Oran , Shin Aesun , Kim Jeongseon 
Published: March 2019

AbstractIt is unclear whether dietary lutein/zeaxanthin intake in colorectal cancer is associated with microRNA processing involved in DICER1 cleavage for messenger RNA translation. We investigated whether dietary lutein/zeaxanthin intake affects colorectal cancer risk in patients with a DICER1 rs3742330 polymorphism. In this hospital-based case-control study, we recruited 923 colorectal cancer patients and 1,846 controls based on eligibility criteria, a semiquantitative food frequency questionnaire and the DICER1 rs3742330 genotype. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for confounders. The highest quartile of lutein/zeaxanthin consumption was inversely associated with a reduced colorectal cancer risk (OR, 95% CI = 0.25, 0.18–0.36). Carrying G allele (AG + GG) showed a significantly reduced colorectal cancer incidence compared with that of AA carriers (OR, 95% CI = 0.71, 0.55–0.91). Those carrying the G allele (AG + GG) along with high lutein/zeaxanthin consumption were markedly associated with a decreased colorectal cancer risk (OR, 95% CI = 0.32, 0.22–0.46, P for interaction = 0.018), particularly for rectal cancer (OR, 95% CI = 0.24, 0.15–0.39, P for interaction = 0.004), compared with that of AA carriers with low lutein/zeaxanthin intakes. In conclusion, colorectal cancer risk was related to an interactive effect between dietary lutein/zeaxanthin intake and the DICER1 rs3742330 polymorphism.
Crystal structure investigation of La5.4W1−yMoyO12−δ for gas separation by high-resolution transmission electron microscopy
Authors: Ran K. , Deibert W. , Ivanova M. E. , Meulenberg W. A. , Mayer J. 
Published: March 2019

AbstractLanthanum tungstate (LWO) and LWO with 20 at.% and 35 at.% molybdenum substituting tungsten were prepared by the Pechini method. Phase purity and successful Mo substitution inside these dense LWO membrane materials were confirmed by conventional and high resolution transmission electron microscopy techniques. The split of La2/W2 site by around 0.3 Å was proven. Extra reflections show up in the diffraction patterns from Mo-substituted LWO, and together with simulations, these reflections were recognized as forbidden reflections in a non-substituted LWO system, while the extinction rules are broken by Mo substitution due to the different scattering factors of W and Mo. Energy-dispersive X-ray chemical mapping allowed direct visualization of individual atomic columns, and revealed that all Mo is located at the W1 sites in the Mo-substituted LWO. Moreover, the diffuse scattering in diffraction patterns provides direct evidence of short range clustering of oxygen vacancies and could be further related to the oxygen conduction of the LWO membranes.
Coherence and pulse duration characterization of the PAL-XFEL in the hard X-ray regime
Authors: Yun Kyuseok , Kim Sungwon , Kim Dongjin , Chung Myungwoo , Jo Wonhyuk , Hwang Hyerim , Nam Daewoong , Kim Sangsoo , Kim Jangwoo , Park Sang-Youn , Kim Kyung Sook , Song Changyong , Lee Sooheyong , Kim Hyunjung 
Published: March 2019

AbstractWe characterize the spatial and temporal coherence properties of hard X-ray pulses from the Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL, Pohang, Korea). The measurement of the single-shot speckle contrast, together with the introduction of corrections considering experimental conditions, allows obtaining an intrinsic degree of transverse coherence of 0.85 ± 0.06. In the Self-Amplified Spontaneous Emission regime, the analysis of the intensity distribution of X-ray pulses also provides an estimate for the number of longitudinal modes. For monochromatic and pink (i.e. natural bandwidth provided by the first harmonic of the undulator) beams, we observe that the number of temporal modes is 6.0 ± 0.4 and 90.0 ± 7.2, respectively. Assuming a coherence time of 2.06 fs and 0.14 fs for the monochromatic and pink beam respectively, we estimate an average X-ray pulse duration of 12.6 ± 1.0 fs.
Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function
Authors: Fang Qiaojun , Zhang Yuhua , Da Peng , Shao Buwei , Pan Haolai , He Zuhong , Cheng Cheng , Li Dan , Guo Jiaqi , Wu Xiaohan , Guan Ming , Liao Menghui , Zhang Yuan , Sha Suhua , Zhou Zikai , Wang Jian , Wang Tian , Su Kaiming , Chai Renjie , Chen Fangyi 
Published: March 2019

AbstractInherited hearing loss is associated with gene mutations that result in sensory hair cell (HC) malfunction. HC structure is defined by the cytoskeleton, which is mainly composed of actin filaments and actin-binding partners. LIM motif-containing protein kinases (LIMKs) are the primary regulators of actin dynamics and consist of two members: LIMK1 and LIMK2. Actin arrangement is directly involved in the regulation of cytoskeletal structure and the maturation of synapses in the central nervous system, and LIMKs are involved in structural plasticity by controlling the activation of the actin depolymerization protein cofilin in the olfactory system and in the hippocampus. However, the expression pattern and the role of LIMKs in mouse cochlear development and synapse function also need to be further studied. We show here that the Limk genes are expressed in the mouse cochlea. We examined the morphology and the afferent synapse densities of HCs and measured the auditory function in Limk1 and Limk2 double knockout (DKO) mice. We found that the loss of Limk1 and Limk2 did not appear to affect the overall development of the cochlea, including the number of HCs and the structure of hair bundles. There were no significant differences in auditory thresholds between DKO mice and wild-type littermates. However, the expression of p-cofilin in the DKO mice was significantly decreased. Additionally, no significant differences were found in the number or distribution of ribbon synapses between the DKO and wild-type mice. In summary, our data suggest that the Limk genes play a different role in the development of the cochlea compared to their role in the central nervous system.
Feature-tracking myocardial strain in healthy adults- a magnetic resonance study at 3.0 tesla
Authors: Mangion Kenneth , Burke Nicole M. M. , McComb Christie , Carrick David , Woodward Rosemary , Berry Colin 
Published: March 2019

AbstractWe analyzed feature-tracking derived circumferential and longitudinal strain in healthy volunteers who underwent cardiac magnetic resonance imaging (CMR) at 3.0 T. 88 healthy adults (44.6 ± 18.0 years old, 49% male), without prior cardiovascular disease, underwent CMR at 3.0 T including cine, and late gadolinium enhancement in subjects >45 years. LV functional analysis and feature-tracking strain analyses were carried out. Global strain had better reproducibility than segmental strain. There was a sex specific difference global longitudinal strain (mean ± SD, −18.48 ± 3.65% (male), −21.91 ± 3.01% (female), p < 0.001), but not global circumferential strain (mean ± SD, −25.41 ± 4.50% (male), −27.94 ± 3.48% (female), p = 0.643). There was no association of strain with ageing after accounting for sex for both global longitudinal and circumferential strain. Feature-tracking strain analysis is feasible at 3.0 T. Healthy female volunteers demonstrated higher magnitudes of global longitudinal strain when compared to male counterparts. Whilst global cine-strain has good reproducibility, segmental strain does not.
Mutational convergence acts as a major player in adaptive parallel evolution of Shigella spp.
Authors: Thomas Achsah K. , Preetha Sruthy , Omanakuttan Anjana , Vidyullata Lakkaraju , Ashokan Anjaly , Rajachandran Vyshakh , Chattopadhyay Sujay 
Published: March 2019

AbstractShigella spp., emerging from multiple origins of Escherichia coli, poses a significant health threat as a causative agent of bacillary dysentery. While multiple serotypes of four different species have evolved via independent lineages, Shigella spp. are designated as a single pathotype, primarily because of their common mode of pathogenesis. Convergent horizontal transfer events have so far been attributed to the commonalities in the evolution of virulence across diverse lineages. However, the role of mutational convergence in such parallel evolution is not yet well understood. Here we have carried out a genome-wide analysis of Shigella strains from all four species to detect the core genes (i.e. the ones present in all analyzed strains) acquiring convergent mutations of evolutionarily recent origin. Simulation studies show non-neutral accumulation of these convergent mutations across species, suggesting their adaptive role in the evolution of Shigella virulence. S. dysenteriae strain 197, representing highly virulent type 1 (Sd1) clone, carries excessively high number of core genes with recent convergent mutations compared to other analyzed strains. We propose that this high frequency of adaptive convergence in S. dysenteriae strain 197 could be linked to recent re-emergence of the Sd1 clone and its increased resistance to antimicrobials.
Fe-Sn nanocrystalline films for flexible magnetic sensors with high thermal stability
Authors: Satake Y. , Fujiwara K. , Shiogai J. , Seki T. , Tsukazaki A. 
Published: March 2019

AbstractThe interplay of magnetism and spin-orbit coupling on an Fe kagome lattice in Fe3Sn2 crystal produces a unique band structure leading to an order of magnitude larger anomalous Hall effect than in conventional ferromagnetic metals. In this work, we demonstrate that Fe-Sn nanocrystalline films also exhibit a large anomalous Hall effect, being applicable to magnetic sensors that satisfy both high sensitivity and thermal stability. In the films prepared by a co-sputtering technique at room temperature, the partial development of crystalline lattice order appears as nanocrystals of the Fe-Sn kagome layer. The tangent of Hall angle, the ratio of Hall resistivity to longitudinal resistivity, is maximized in the optimal alloy composition of close to Fe3Sn2, implying the possible contribution of the kagome origin even though the films are composed of nanocrystal and amorphous-like domains. These ferromagnetic Fe-Sn films possess great advantages as a Hall sensor over semiconductors in thermal stability owing to the weak temperature dependence of the anomalous Hall responses. Moreover, the room-temperature fabrication enables us to develop a mechanically flexible Hall sensor on an organic substrate. These demonstrations manifest the potential of ferromagnetic kagome metals as untapped reservoir for designing new functional devices.
Haida Gwaii (British Columbia, Canada): a Phanerozoic analogue of a subduction-unrelated Archean greenstone belt
Authors: Shellnutt J. Gregory , Dostal Jaroslav 
Published: March 2019

AbstractUnderstanding the formation and evolution of Precambrian greenstone belts is hampered by gaps in the rock record and the uncertainty of the tectonic regime that was operating at the time. Thus identifying a modern analogue of a Precambrian greenstone belt can be problematic. In this paper we present geological, geochemical and petrological evidence outlining the case for Haida Gwaii (British Columbia, Canada) as a modern example of a greenstone belt. Haida Gwaii is comprised of two rift-related volcano-sedimentary sequences. The older (Early Triassic) Karmutsen volcanic sequence consists of subaqueous ultramafic-mafic volcanic rocks that are capped by marine carbonate and siliciclastic rocks. The younger (Paleogene) Masset bimodal volcanic sequence consists of tholeiitic and calc-alkaline basalt along with calc-alkaline silicic volcanic and intrusive rocks that are capped by epiclastic sandstones. The Karmutsen and Masset volcanic rocks have indistinguishable Sr-Nd-Pb isotopes demonstrating they were derived from a similar mantle source. Some of the Masset calc-alkaline rocks are compositionally similar to magnesian andesites (SiO2 = 56–64 wt%; Mg# = 0.50–0.64) that are typical of subduction-related Archean greenstone belts. We show that the calc-alkaline signature observed in the bimodal sequence of the Masset Formation is likely due to fractional crystallization of a tholeiitic parental magma under relatively oxidizing (ΔFMQ + 0.7) conditions indicating that a calc-alkaline signature is not prima facie evidence of a subduction setting. Given the geological and geochemical evidence, Haida Gwaii represents one of the best analogues of a modern subduction-unrelated Archean greenstone belt.