bluuebunny/crossref_metadata_2025_split huggingface dataset:
SACRED LANDSCAPES AND BUILDING PRACTICES AT UCI, KANCAB, AND UCANHA, YUCATAN, MEXICO
Authors: Hutson Scott R. , Welch Jacob A. 
Published: January 2015

AbstractDuring the emergence of regional hierarchy around the site of Uci in northwest Yucatan, Mexico, ordinary people affected power relations in at least two ways. First, in the Late Preclassic and Early Classic periods, Uci had the largest ceremonial center and the largest population within a 20 km radius. Uci also physically linked itself to smaller settlements, such as Kancab and Ucanha, by means of a broad stone causeway. Yet Kancab and Ucanha's quadripartite placement of causeways and central plaza suggests that its households created a sacred landscape that gave them a degree of ritual autonomy. Ordinary people impacted power relations a second way by participating in the development of the megalithic architectural style, which was used in the region's most authoritative buildings. The use of this style in domestic platforms illustrates the ability of modest households to make their own decisions and to act in ways that constituted society at large.
DAC can restore expression of NALP1 to suppress tumor growth in colon cancer
Authors: Chen C , Wang B , Sun J , Na H , Chen Z , Zhu Z , Yan L , Ren S , Zuo Y 
Published: January 2015

AbstractDespite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.
Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: an in vitro and in vivo study
Authors: Li H-Y , Zhang J , Sun L-L , Li B-H , Gao H-L , Xie T , Zhang N , Ye Z-M 
Published: January 2015

AbstractOsteosarcoma is the most common primary malignant tumor of bone, the long-term survival of which has stagnated in the past several decades. Celastrol, a triterpene from traditional Chinese medicine, has been proved to possess potent anti-tumor effect on various cancers. However, the effect of celastrol on human osteosarcoma and the underlying mechanisms remains to be elucidated. We reported here that celastrol could inhibit cell proliferation by causing G2/M phase arrest. Exposure to celastrol resulted in the activation of caspase-3, -8, and -9, indicating that celastrol induced apoptosis through both extrinsic and intrinsic pathways. Autophagy occurred in celastrol-treated cells as evidenced by formation of autophagosome and accumulation of LC3B-II. The celastrol-induced cell death was remarkably restored by the combination of autophagy and apoptosis inhibitors. Furthermore, inhibition of apoptosis enhanced autophagy while suppression of autophagy diminished apoptosis. Celastrol also induced JNK activation and ROS generation. The JNK inhibitor significantly attenuated celastrol-triggered apoptosis and autophagy while ROS scavenger could completely reverse them. The ROS scavenger also prevented G2/M phase arrest and phosphorylation of JNK. Importantly, we found that celastrol had the similar effects on primary osteosarcoma cells. Finally, in vivo, celastrol suppressed tumor growth in the mouse xenograft model. Taken together, our results revealed that celastrol caused G2/M phase arrest, induced apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells. Celastrol is therefore a promising candidate for development of antitumor drugs targeting osteosarcoma.
Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer
Authors: Vishnubalaji R , Hamam R , Abdulla M-H , Mohammed M A V , Kassem M , Al-Obeed O , Aldahmash A , Alajez N M 
Published: January 2015

AbstractDespite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-β pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R2=0.56, P=0.0001) and hsa-let-7b-5p (R2=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC.
BMCC1, which is an interacting partner of BCL2, attenuates AKT activity, accompanied by apoptosis
Authors: Tatsumi Y , Takano R , Islam M S , Yokochi T , Itami M , Nakamura Y , Nakagawara A 
Published: January 2015

AbstractBNIP2 and Cdc42GAP homology (BCH) motif-containing molecule at the carboxyl-terminal region 1 (BMCC1) gene is highly expressed in patients with favorable neuroblastoma (NB). It encodes a 340-kDa protein with a conserved BCH scaffold domain that may regulate signaling networks and multiple cellular functions, including apoptosis. In this study, we determined the mechanism by which BMCC1 promotes apoptosis in human NB and non-NB cells, as BMCC1 is normally expressed in various organs, particularly in neuronal and epithelial tissues. We demonstrated in this report that BMCC1 was induced by DNA damage, one of the triggers of intrinsic apoptosis. Accordingly, we investigated whether BMCC1 expression impacts intracellular signals in the regulation of apoptosis via its C-terminal region containing BCH scaffold domain. BMCC1 decreased phosphorylation of survival signals on AKT and its upstream kinase PDK1. BMCC1 upregulation was correlated with the activation of forkhead box-O3a (FOXO3a) (a downstream inducer of apoptosis, which is suppressed by AKT) and induction of BCL2 inhibitor BIM, suggesting that BMCC1 negatively regulates phosphorylation pathway of AKT, resulted in apoptosis. In addition, we found that BNIP2 homology region of BMCC1 interacts with BCL2. Intrinsic apoptosis induced by DNA damage was enhanced by BMCC1 overexpression, and was diminished by knockdown of BMCC1. Taken together, we conclude that BMCC1 promotes apoptosis at multiple steps in AKT-mediated survival signal pathway. These steps include physical interaction with BCL2 and attenuation of AKT-dependent inhibition of FOXO3a functions, such as transcriptional induction of BIM and phosphorylation of ataxia telangiectasia-mutated (ATM) after DNA damage. We propose that downregulation of BMCC1 expression, which is frequently observed in unfavorable NB and epithelial-derived cancers, may facilitate tumor development by abrogating DNA damage repair and apoptosis.
A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation
Authors: Gao X , Ma W , Nie J , Zhang C , Zhang J , Yao G , Han J , Xu J , Hu B , Du Y , Shi Q , Yang Z , Huang X , Zhang Y 
Published: January 2015

AbstractG-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we investigated the distribution of G4 structures in mouse testis and identified their alterations during spermatogenesis. Meanwhile, we studied the function of RNA helicase associated with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ-cell-specific knockout mouse model. The results showed that the ablation of RHAU in germ cells caused the increase of G4 structures and thus resulted in the decrease of spermatogonial differentiation. c-kit, a spermatogonia differentiation-related gene, contains two G4 DNA motifs on its promoter. We found its expression was significantly downregulated in RHAU conditional knockout testis. A further analysis demonstrated that RHAU directly bound to the G4 structures to activate c-kit expression. We concluded that RHAU regulates spermatogonia differentiation by promoting c-kit expression via directly binding to the G4 DNA motifs c-kit promoter.
ING1b negatively regulates HIF1α protein levels in adipose-derived stromal cells by a SUMOylation-dependent mechanism
Authors: Bigot N , Guérillon C , Loisel S , Bertheuil N , Sensebé L , Tarte K , Pedeux R 
Published: January 2015

AbstractHypoxic niches help maintain mesenchymal stromal cell properties, and their amplification under hypoxia sustains their immature state. However, how MSCs maintain their genomic integrity in this context remains elusive, since hypoxia may prevent proper DNA repair by downregulating expression of BRCA1 and RAD51. Here, we find that the ING1b tumor suppressor accumulates in adipose-derived stromal cells (ADSCs) upon genotoxic stress, owing to SUMOylation on K193 that is mediated by the E3 small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated STAT protein γ (PIAS4). We demonstrate that ING1b finely regulates the hypoxic response by triggering HIF1α proteasomal degradation. On the contrary, when mutated on its SUMOylation site, ING1b failed to efficiently decrease HIF1α levels. Consistently, we observed that the adipocyte differentiation, generally described to be downregulated by hypoxia, was highly dependent on ING1b expression, during the early days of this process. Accordingly, contrary to what was observed with HIF1α, the absence of ING1b impeded the adipogenic induction under hypoxic conditions. These data indicate that ING1b contributes to adipogenic induction in adipose-derived stromal cells, and thus hinders the phenotype maintenance of ADSCs.
MiR-34c suppresses tumor growth and metastasis in nasopharyngeal carcinoma by targeting MET
Authors: Li Y-Q , Ren X-Y , He Q-M , Xu Y-F , Tang X-R , Sun Y , Zeng M-S , Kang T-B , Liu N , Ma J 
Published: January 2015

AbstractOur previous microarray analysis indicated that miR-34c was downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the function and molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be significantly downregulated in NPC cell lines and clinical tissues. Ectopic expression of miR-34c suppressed NPC cell viability, colony formation, anchorage-independent growth, cell migration and invasion in vitro, and inhibited xenograft tumor growth and lung metastasis in vivo. MET proto-oncogene (MET) was identified as a direct target of miR-34c using luciferase reporter assays, quantitative RT-PCR, western blotting and immunofluorescent staining. Overexpression of miR-34c markedly reduced MET expression at both the mRNA and protein levels. Knockdown of MET suppressed NPC cell proliferation, migration and invasion, whereas the restoration of MET rescued the suppressive effects of miR-34c. The demethylation agent 5-aza-2′-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell lines. The promoter region of miR-34c was hypermethylated in NPC cells. In conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting MET. The newly identified miR-34c/MET pathway provides further insights into the development and progression of NPC, and may represent a novel therapeutic target for NPC treatment.
Structural analysis of herpes simplex virus by optical super-resolution imaging
Authors: Laine Romain F. , Albecka Anna , van de Linde Sebastian , Rees Eric J. , Crump Colin M. , Kaminski Clemens F. 
Published: January 2015

AbstractHerpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.
A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Authors: Byron Adam , Askari Janet A. , Humphries Jonathan D. , Jacquemet Guillaume , Koper Ewa J. , Warwood Stacey , Choi Colin K. , Stroud Matthew J. , Chen Christopher S. , Knight David , Humphries Martin J. 
Published: January 2015

AbstractIntegrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling.
Thermal conductivity of skutterudite CoSb3 from first principles: Substitution and nanoengineering effects
Authors: Guo Ruiqiang , Wang Xinjiang , Huang Baoling 
Published: January 2015

AbstractCoSb3-based skutterudites are promising intermediate-temperature thermoelectric materials and fundamental understanding of the thermal transport in CoSb3 is crucial for further improving its performance. We herein calculate the lattice thermal conductivity κL of CoSb3 with first-principles methods and conduct a comprehensive analysis on phonon mode contribution, relaxation time and mean free path (MFP) distributions. The contribution of optical phonons is found to be significant (28% at 300 K) and important optical modes usually involve two or more pnicogen atoms moving synchronously. The MFP (~135 nm at 300 K) corresponding to 50% κL accumulation in CoSb3 is much larger than that predicted from the kinetic theory (~4 nm), providing an opportunity to reduce κL by nanoengineering. The effects of elemental substitution and nanoengineering on κL are therefore investigated. A 10% substitution of Sb by As results in 57% reduction of κL while the in-plane (cross-plane) κL of a 50-nm CoSb3 thin film is only 56% (33%) of the bulk κL at 300 K. The impurity scattering and boundary scattering mainly suppress phonons in different frequency regimes. By combining these two effects, κL can be reduced by more than 70% at 300 K, potentially leading to much improved ZT near room temperature.
Yo‐Yo Intermittent Endurance Test‐Level 1 to monitor changes in aerobic fitness in pre‐pubertal boys
Authors: Fernandes Luís , Krustrup Peter , Silva Gustavo , Rebelo Antonio , Oliveira José , Brito João 
Published: January 2015

AbstractThe present study aimed to examine the performance and heart rate responses during the Yo‐Yo Intermittent Endurance Test‐Level 1 (Yo‐Yo IE1) in children under the age of 10. One hundred and seven male children (7–9 years) performed the Yo‐Yo IE1 at the beginning (M1), middle (M2) and end (M3) of the school year. Data from individual heart rate curves of the Yo‐Yo IE1 were analysed in order to detect the inflection point between an initial phase of fast rise in heart rate values and a second phase in which the rise of the heart rate values is much smaller. The distance covered in the Yo‐Yo IE1 improved from M1 to M3 (884 ± 496 vs. 1032 ± 596 m; p < 0.05; d = 0.27), with intermediate values for M2 (962 ± 528 m). Peak heart rate (HRpeak) decreased from M1 to M2 and M3 (204 ± 9, 202 ± 9 and 200 ± 9 bpm, respectively; p < 0.05; d = 0.25–0.42). The 7th shuttle of the test (280 m), corresponding to 2.5 min, was identified as the inflection point between the two phases. Also, absolute heart rate at the 7th shuttle decreased progressively throughout the year (185 ± 9, 183 ± 10, and 179 ± 10 bpm; p < 0.05; d = 0.31–0.61). The present study provides evidence of the usefulness of a maximal as well as a submaximal version of Yo‐Yo IE1 as a tool to monitor changes in aerobic fitness in pre‐pubertal children.
Introduction
Authors: Moravcsik Edith 
Published: January 2015

AbstractFirst, the concept of competing motivations is introduced as conflicting tendencies whose effects are detectable in grammar and in language use. Second, the basic issues involved in researching competing motivations are listed: what motivations compete? how are they manifested in synchronic structure and in the processes of language use, language acquisition, and historical change? what are possible ways in which competitions can be resolved? and what may explain the existence of competing motivations in language? Third, past research on the topic is surveyed, followed by summaries of the chapters with comments on the connections among the papers and on how the papers address the basic issues of the study of competing motivations.
Resolving alignment conflicts: A competing motivations approach
Authors: Malchukov Andrej 
Published: January 2015

AbstractThe present chapter addresses a thorny question of whether individual constructions reveal alignment preferences with respect to monotransitive (accusative vs. ergative) and ditransitive (indirective vs. secundative) alignment. It is argued that typological variation in this domain can be explained through interaction of two general factors, Harmony embodying the analogical tendency for coding/behavior matching, and Bias embodying intrinsic alignment preferences dictated by functional properties of individual constructions. It is shown that interaction between these two factors can both explain the crosslinguistically recurrent patterns of alignment (arising in situations when both motivations prefer the same alignment pattern) and crosslinguistic variation (arising in situations when the two motivations are in conflict).
Why move? How weight and discourse factors combine to predict relative clause extraposition in English
Authors: Francis Elaine J. , Michaelis Laura A. 
Published: January 2015

AbstractIn relative clause extraposition (RCE) in English, a subject-modifying relative clause appears after the verb phrase, as in Some research was conducted that supports the existing theory. Previous studies have revealed that both grammatical weight and discourse factors induce speakers to use RCE. However, the current study is the first to examine the interaction of the two. A quantitative analysis of RCE and comparable non-RCE tokens in the International Corpus of English–Great Britain (ICE-GB) showed a strong effect of weight: there is a strong preference for RCE when the relative clause is at least five times longer than the verb phrase, and a strong preference for canonical (non-RCE) order when the relative clause is the same length or shorter than the verb phrase. However, for those tokens with length ratios falling between these limits, choice of structure depends primarily on discourse factors.
Competing motivations in children's omission of subjects? The interaction between verb finiteness and referent accessibility
Authors: Hughes Mary E. , Allen Shanley E. M. 
Published: January 2015

AbstractChildren acquiring a first language omit sentential subjects more frequently than their adult counterparts. The posited motivation for this non‐target‐like omission differs across theoretical accounts: nativists claim that subjects are omitted when the accompanying verb is non‐finite, while usage‐based theorists claim that subjects are omitted when referents are accessible. Given the lack of dialogue between theories, these motivations are seen as competing, meaning that only one account provides the correct explanation. This chapter demonstrates that these two motivations interact rather than compete. Spontaneous speech data from monolingual English‐speaking children and their caregivers shows that subjects are more likely omitted when their referents are accessible in both finite and non‐finite contexts, and that subjects are more likely omitted in non‐finite contexts both when they are maximally accessible and when they are maximally inaccessible.