bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental and evolutionary novelty in the serrated teeth of theropod dinosaurs
Authors: Brink K. S. , Reisz R. R. , LeBlanc A. R. H. , Chang R. S. , Lee Y. C. , Chiang C. C. , Huang T. , Evans D. C. 
Published: July 2015

AbstractTooth morphology and development can provide valuable insights into the feeding behaviour and evolution of extinct organisms. The teeth of Theropoda, the only clade of predominantly predatory dinosaurs, are characterized by ziphodonty, the presence of serrations (denticles) on their cutting edges. Known today only in varanid lizards, ziphodonty is much more pervasive in the fossil record. Here we present the first model for the development of ziphodont teeth in theropods through histological, SEM and SR-FTIR analyses, revealing that structures previously hypothesized to prevent tooth breakage instead first evolved to shape and maintain the characteristic denticles through the life of the tooth. We show that this novel complex of dental morphology and tissues characterizes Theropoda, with the exception of species with modified feeding behaviours, suggesting that these characters are important for facilitating the hypercarnivorous diet of most theropods. This adaptation may have played an important role in the initial radiation and subsequent success of theropods as terrestrial apex predators.
Rapid parallel measurements of macroautophagy and mitophagy in mammalian cells using a single fluorescent biosensor
Authors: Sargsyan A. , Cai J. , Fandino L. B. , Labasky M. E. , Forostyan T. , Colosimo L. K. , Thompson S. J. , Graham T. E. 
Published: July 2015

AbstractMitochondrial dysfunction is implicated in many human diseases and occurs in normal aging. Mitochondrial health is maintained through organelle biogenesis and repair or turnover of existing mitochondria. Mitochondrial turnover is principally mediated by mitophagy, the trafficking of damaged mitochondria to lysosomes via macroautophagy (autophagy). Mitophagy requires autophagy, but is itself a selective process that relies on specific autophagy-targeting mechanisms and thus can be dissociated from autophagy under certain circumstances. Therefore, it is important to assess autophagy and mitophagy together and separately. We sought to develop a robust, high-throughput, quantitative method for monitoring both processes in parallel. Here we report a flow cytometry-based assay capable of rapid parallel measurements of mitophagy and autophagy in mammalian cells using a single fluorescent protein biosensor. We demonstrate the ability of the assay to quantify Parkin-dependent selective mitophagy in CCCP-treated HeLa cells. In addition, we show the utility of the assay for measuring mitophagy in other cell lines, as well as for Parkin-independent mitophagy stimulated by deferiprone. The assay makes rapid measurements (10,000 cells per 6 seconds) and can be combined with other fluorescent indicators to monitor distinct cell populations, enabling design of high-throughput screening experiments to identify novel regulators of mitophagy in mammalian cells.
Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions
Authors: Ma Lei , Jia Ji , Niu Wen , Jiang Tao , Zhai Qian , Yang Lei , Bai Fuhai , Wang Qiang , Xiong Lize 
Published: July 2015

AbstractMitochondrial dysfunction contributes to cell death after cerebral ischemia/reperfusion (I/R) injury. Cannabinoid CB1 receptor is expressed in neuronal mitochondrial membranes (mtCB1R) and involved in regulating mitochondrial functions under physiological conditions. However, whether mtCB1R affords neuroprotection against I/R injury remains unknown. We used mouse models of cerebral I/R, primary cultured hippocampal neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) and Ca2+-induced injury in purified neuronal mitochondria to investigate the role of mtCB1R in neuroprotection. Our results showed selective cell-permeant CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), significantly up-regulated the expression of mtCB1R protein in hippocampal neurons and tissue.In vitro, ACEA restored cell viability, inhibited generation of reactive oxygen species (ROS), decreased lactate dehydrogenase (LDH) release and reduced apoptosis, improved mitochondrial function.In vivo, ACEA ameliorated neurological scores, diminished the number of TUNEL-positive neurons and decreased the expression of cleaved caspase-3. However, ACEA-induced benefits were blocked by the selective cell-permeant CB1 receptor antagonist AM251, but just partially by the selective cell-impermeant CB1 receptor antagonist hemopressin. In purified neuronal mitochondria, mtCB1R activation attenuated Ca2+-induced mitochondrial injury. In conclusion, mtCB1R is involved in ACEA-induced protective effects on neurons and mitochondrial functions, suggesting mtCB1R may be a potential novel target for the treatment of brain ischemic injury.
The Cipher Code of Simple Sequence Repeats in “Vampire Pathogens”
Authors: Zou Geng , Bello-Orti Bernardo , Aragon Virginia , Tucker Alexander W. , Luo Rui , Ren Pinxing , Bi Dingren , Zhou Rui , Jin Hui 
Published: July 2015

AbstractBlood inside mammals is a forbidden area for the majority of prokaryotic microbes; however, red blood cells tropism microbes, like “vampire pathogens” (VP), succeed in matching scarce nutrients and surviving strong immunity reactions. Here, we found VP of Mycoplasma, Rhizobiales and Rickettsiales showed significantly higher counts of (AG)n dimeric simple sequence repeats (Di-SSRs) in the genomes, coding and non-coding regions than non Vampire Pathogens (N_VP). Regression analysis indicated a significant correlation between GC content and the span of (AG)n-Di-SSR variation. Gene Ontology (GO) terms with abundance of (AG)3-Di-SSRs shared by the VP strains were associated with purine nucleotide metabolism (FDR < 0.01), indicating an adaptation to the limited availability of purine and nucleotide precursors in blood. Di-amino acids coded by (AG)n-Di-SSRs included all three six-fold code amino acids (Arg, Leu and Ser) and significantly higher counts of Di-amino acids coded by (AG)3, (GA)3 and (TC)3 in VP than N_VP. Furthermore, significant differences (P < 0.001) on the numbers of triplexes formed from (AG)n-Di-SSRs between VP and N_VP in Mycoplasma suggested the potential role of (AG)n-Di-SSRs in gene regulation.
Mieap suppresses murine intestinal tumor via its mitochondrial quality control
Authors: Tsuneki Masayuki , Nakamura Yasuyuki , Kinjo Takao , Nakanishi Ruri , Arakawa Hirofumi 
Published: July 2015

AbstractMieap, a novel p53-inducible protein, plays a key role in maintaining healthy mitochondria in various pathophysiological states. Here, we show that Mieap deficiency in ApcMin/+ mice is strikingly associated with the malignant progression of murine intestinal tumors. To understand the role that Mieap plays in in vivo tumorigenesis, we generated Mieap heterozygous (ApcMin/+ Mieap+/−) and homozygous (ApcMin/+ Mieap−/−) ApcMin/+ mice. Interestingly, the ApcMin/+ mice with the Mieap+/− and Mieap−/− genetic background revealed remarkable shortening of the lifetime compared to ApcMin/+ mice because of severe anemia. A substantial increase in the number and size of intestinal polyps was associated with Mieap gene deficiency. Histopathologically, intestinal tumors in the Mieap-deficient ApcMin/+ mice clearly demonstrated advanced grades of adenomas and adenocarcinomas. We demonstrated that the significant increase in morphologically unhealthy mitochondria and trace accumulations of reactive oxygen species may be mechanisms underlying the increased malignant progression of the intestinal tumors of Mieap-deficient ApcMin/+ mice. These findings suggest that the Mieap-regulated mitochondrial quality control plays a critical role in preventing mouse intestinal tumorigenesis.
Environmentally Driven Migration in a Social Network Game
Authors: Takano Masanori , Wada Kazuya , Fukuda Ichiro 
Published: July 2015

AbstractCooperative behaviors are common in humans and they are the fundamental basis of our society. Theoretical and experimental studies have modeled environments where the behaviors of humans, or agents, have been restricted to analyze their social behavior. However, it is important that such studies can be generalized to a less restrictive environment in order to understand human society. Social network games (SNGs) provide a powerful tool for the quantitative study of human behavior using a less restrictive environment than in previous studies. We focused on multilevel selection, one of the theoretical frameworks used to study the evolution of cooperation. The evolution of cooperation by multilevel selection requires that the continual assortment between cooperators and noncooperators is generated; thus, humans may have acquired mechanisms that ensure assortment (e.g., migration between groups). This study aims to investigate this mechanism in a less restrictive environment. For this purpose, we researched the effect of migration based on data analysis in an SNG where the players could behave more freely than was possible in the environments used in the previous studies. We showed that players maintained assortment between cooperators and defectors in this SNG, where it appears that environmentally driven migration generated the assortment.
Seagrass meadows (Posidonia oceanica) distribution and trajectories of change
Authors: Telesca Luca , Belluscio Andrea , Criscoli Alessandro , Ardizzone Giandomenico , Apostolaki Eugenia T. , Fraschetti Simonetta , Gristina Michele , Knittweis Leyla , Martin Corinne S. , Pergent Gérard , Alagna Adriana , Badalamenti Fabio , Garofalo Germana , Gerakaris Vasilis , Louise Pace Marie , Pergent-Martini Christine , Salomidi Maria 
Published: July 2015

AbstractPosidonia oceanica meadows are declining at alarming rates due to climate change and human activities. Although P. oceanica is considered the most important and well-studied seagrass species of the Mediterranean Sea, to date there has been a limited effort to combine all the spatial information available and provide a complete distribution of meadows across the basin. The aim of this work is to provide a fine-scale assessment of (i) the current and historical known distribution of P. oceanica, (ii) the total area of meadows and (iii) the magnitude of regressive phenomena in the last decades. The outcomes showed the current spatial distribution of P. oceanica, covering a known area of 1,224,707 ha and highlighted the lack of relevant data in part of the basin (21,471 linear km of coastline). The estimated regression of meadows amounted to 34% in the last 50 years, showing that this generalised phenomenon had to be mainly ascribed to cumulative effects of multiple local stressors. Our results highlighted the importance of enforcing surveys to assess the status and prioritize areas where cost-effective schemes for threats reduction, capable of reversing present patterns of change and ensuring P. oceanica persistence at Mediterranean scale, could be implemented.
PKCζ Promotes Breast Cancer Invasion by Regulating Expression of E-cadherin and Zonula Occludens-1 (ZO-1) via NFκB-p65
Authors: Paul Arindam , Danley Marsha , Saha Biswarup , Tawfik Ossama , Paul Soumen 
Published: July 2015

AbstractAtypical Protein Kinase C zeta (PKCζ) forms Partitioning-defective (PAR) polarity complex for apico-basal distribution of membrane proteins essential to maintain normal cellular junctional complexes and tissue homeostasis. Consistently, tumor suppressive role of PKCζ has been established for multiple human cancers. However, recent studies also indicate pro-oncogenic function of PKCζ without firm understanding of detailed molecular mechanism. Here we report a possible mechanism of oncogenic PKCζ signaling in the context of breast cancer. We observed that depletion of PKCζ promotes epithelial morphology in mesenchymal-like MDA-MB-231 cells. The induction of epithelial morphology is associated with significant upregulation of adherens junction (AJ) protein E-cadherin and tight junction (TJ) protein Zonula Occludens-1 (ZO-1). Functionally, depletion of PKCζ significantly inhibits invasion and metastatic progression. Consistently, we observed higher expression and activation of PKCζ signaling in invasive and metastatic breast cancers compared to non-invasive diseases. Mechanistically, an oncogenic PKCζ– NFκB-p65 signaling node might be involved to suppress E-cadherin and ZO-1 expression and ectopic expression of a constitutively active form of NFκB-p65 (S536E-NFκB-p65) significantly rescues invasive potential of PKCζ-depleted breast cancer cells. Thus, our study discovered a PKCζ - NFκB-p65 signaling pathway might be involved to alter cellular junctional dynamics for breast cancer invasive progression.
Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65
Authors: Sun Xin , Li Pan P. , Zhu Shanshan , Cohen Rachael , Marque Leonard O. , Ross Christopher A. , Pulst Stefan M. , Chan Ho Yin Edwin , Margolis Russell L. , Rudnicki Dobrila D. 
Published: July 2015

AbstractHuntington’s disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non-mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and HTT RNA-triggered mechanisms. Here we provide further evidence for the role of expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is cytotoxic in the absence of any translation and that the extent of cytotoxicity is similar to the cytotoxicity of an expHTT protein fragment encoded by a transcript of similar length and with a similar repeat size. In addition, full-length (FL) expHTT is retained in the nucleus. Overexpression of the splicing factor muscleblind-like 1 (MBNL1) increases nuclear retention of expHTT and decreases the expression of expHTT protein in the cytosol. The splicing and nuclear export factor U2AF65 has the opposite effect, decreasing expHTT nuclear retention and increasing expression of expHTT protein. This suggests that MBNL1 and U2AF65 play a role in nuclear export of expHTT RNA.
Human xylosyltransferases – mediators of arthrofibrosis? New pathomechanistic insights into arthrofibrotic remodeling after knee replacement therapy
Authors: Faust Isabel , Traut Philipp , Nolting Frank , Petschallies Jan , Neumann Elena , Kunisch Elke , Kuhn Joachim , Knabbe Cornelius , Hendig Doris 
Published: July 2015

AbstractTotal knee replacement (TKR) is a common therapeutic option to restore joint functionality in chronic inflammatory joint diseases. Subsequent arthrofibrotic remodeling occurs in 10%, but the underlying pathomechanisms remain unclear. We evaluated the association of xylosyltransferases (XT), fibrotic mediators catalyzing glycosaminoglycan biosynthesis, leading to arthrofibrosis as well as the feasibility of using serum XT activity as a diagnostic marker. For this purpose, synovial fibroblasts (SF) were isolated from arthrofibrotic and control synovial biopsies. Basal α-smooth muscle actin expression revealed a high fibroblast-myofibroblast transition rate in arthrofibrotic fibroblasts. Fibrotic remodeling marked by enhanced XT activity, α-SMA protein expression as well as xylosyltransferase-I, collagen type III-alpha-1 and ACTA2 mRNA expression was stronger in arthrofibrotic than in control fibroblasts treated with transforming growth factor-β1 (TGF-β1). Otherwise, no differences between serum levels of XT-I activity or common fibrosis markers (galectin-3 and growth differentiation factor-15 levels (GDF-15)) were found between 95 patients with arthrofibrosis and 132 controls after TKR. In summary, XT-I was initially investigated as a key cellular mediator of arthrofibrosis and a target for therapeutic intervention. However, the blood-synovial-barrier makes arthrofibrotic molecular changes undetectable in serum. Future studies on monitoring or preventing arthrofibrotic remodeling should therefore rely on local instead of systemic parameters.
Brain plasticity in aphasic patients: intra- and inter-hemispheric reorganisation of the whole linguistic network probed by N150 and N350 components
Authors: Spironelli Chiara , Angrilli Alessandro 
Published: July 2015

AbstractThe present study examined linguistic plastic reorganization of language through Evoked Potentials in a group of 17 non-fluent aphasic patients who had suffered left perisylvian focal lesions and showed a good linguistic recovery. Language reorganisation was probed with three linguistic tasks (Phonological, Semantic, Orthographic), the early word recognition potential (N150) and the later phonological-related component (N350). Results showed the typical left-lateralised posterior N150 in healthy controls (source: left Fusiform Gyrus), that was bilateral (Semantic) or right sided (Phonological task) in patients (sources: right Inferior/Middle Temporal and Fusiform Gyri). As regards N350, controls revealed different intra- and inter-hemispheric linguistic activation across linguistic tasks, whereas patients exhibited greater activity in left intact sites, anterior and posterior to the damaged area, in all tasks (sources: Superior Frontal Gyri). A comprehensive neurofunctional model is presented, describing how complete intra- and inter-hemispheric reorganisation of the linguistic networks occurs after aphasic damage in the strategically dominant left perisylvian linguistic centres.
Melting Temperature Mapping Method: A Novel Method for Rapid Identification of Unknown Pathogenic Microorganisms within Three Hours of Sample Collection
Authors: Niimi Hideki , Ueno Tomohiro , Hayashi Shirou , Abe Akihito , Tsurue Takahiro , Mori Masashi , Tabata Homare , Minami Hiroshi , Goto Michihiko , Akiyama Makoto , Yamamoto Yoshihiro , Saito Shigeru , Kitajima Isao 
Published: July 2015

AbstractAcquiring the earliest possible identification of pathogenic microorganisms is critical for selecting the appropriate antimicrobial therapy in infected patients. We herein report the novel “melting temperature (Tm) mapping method” for rapidly identifying the dominant bacteria in a clinical sample from sterile sites. Employing only seven primer sets, more than 100 bacterial species can be identified. In particular, using the Difference Value, it is possible to identify samples suitable for Tm mapping identification. Moreover, this method can be used to rapidly diagnose the absence of bacteria in clinical samples. We tested the Tm mapping method using 200 whole blood samples obtained from patients with suspected sepsis, 85% (171/200) of which matched the culture results based on the detection level. A total of 130 samples were negative according to the Tm mapping method, 98% (128/130) of which were also negative based on the culture method. Meanwhile, 70 samples were positive according to the Tm mapping method and of the 59 suitable for identification, 100% (59/59) exhibited a “match” or “broad match” with the culture or sequencing results. These findings were obtained within three hours of whole blood collection. The Tm mapping method is therefore useful for identifying infectious diseases requiring prompt treatment.
High Pressure Phase-Transformation Induced Texture Evolution and Strengthening in Zirconium Metal: Experiment and Modeling
Authors: Yu Xiaohui , Zhang Ruifeng , Weldon David , Vogel Sven C. , Zhang Jianzhong , Brown Donald W. , Wang Yanbin , Reiche Helmut M. , Wang Shanmin , Du Shiyu , Jin Changqing , Zhao Yusheng 
Published: July 2015

AbstractWe studied the phase-transition induced texture changes and strengthening mechanism for zirconium metal under quasi-hydrostatic compression and uni-axial deformation under confined high pressure using the deformation-DIA (D-DIA) apparatus. It is shown that the experimentally obtained texture for ω-phase Zr can be qualitatively described by combining a subset of orientation variants previously proposed in two different models. The determined flow stress for the high-pressure ω-phase is 0.5–1.2 GPa, more than three times higher than that of the α-phase. Using first-principles calculations, we investigated the mechanical and electronic properties of the two Zr polymorphs. We find that the observed strengthening can be attributed to the relatively strong directional bonding in the ω phase, which significantly increases its shear plastic resistance over the α-phase Zr. The present findings provide an alternate route for Zr metal strengthening by high-pressure phase transformation.
Quantitative reflection phase mesoscopy by remote coherence tuning of phase-shift interference patterns
Authors: Arbel Elad , Bilenca Alberto 
Published: July 2015

AbstractConventional low-magnification phase-contrast microscopy is an invaluable, yet a qualitative, imaging tool for the interrogation of transparent objects over a mesoscopic millimeter-scale field-of-view in physical and biological settings. Here, we demonstrate that introducing a compact, unbalanced phase-shifting Michelson interferometer into a standard reflected brightfield microscope equipped with low-power infinity-corrected objectives and white light illumination forms a phase mesoscope that retrieves remotely and quantitatively the reflection phase distribution of thin, transparent and weakly scattering samples with high temporal (1.38 nm) and spatial (0.87 nm) axial-displacement sensitivity and micrometer lateral resolution (2.3 μm) across a mesoscopic field-of-view (2.25 × 1.19 mm2). Using the system, we evaluate the etch-depth uniformity of a large-area nanometer-thick glass grating and show quantitative mesoscopic maps of the optical thickness of human cancer cells without any area scanning. Furthermore, we provide proof-of-principle of the utility of the system for the quantitative monitoring of fluid dynamics within a wide region.
Different gap junction-propagated effects on cisplatin transfer result in opposite responses to cisplatin in normal cells versus tumor cells
Authors: Zhang Yuan , Tao Liang , Fan Lixia , Peng Yuexia , Yang Kefan , Zhao Yifan , Song Qi , Wang Qin 
Published: July 2015

AbstractPrevious work has shown that gap junction intercellular communication (GJIC) enhances cisplatin (Pt) toxicity in testicular tumor cells but decreases it in non-tumor testicular cells. In this study, these different GJIC-propagated effects were demonstrated in tumor versus non-tumor cells from other organ tissues (liver and lung). The downregulation of GJIC by several different manipulations (no cell contact, pharmacological inhibition and siRNA suppression) decreased Pt toxicity in tumor cells but enhanced it in non-tumor cells. The in vivo results using xenograft tumor models were consistent with those from the above-mentioned cells. To better understand the mechanism(s) involved, we studied the effects of GJIC on Pt accumulation in tumor and non-tumor cells from the liver and lung. The intracellular Pt and DNA-Pt adduct contents clearly increased in non-tumor cells but decreased in tumor cells when GJIC was downregulated. Further analysis indicated that the opposite effects of GJIC on Pt accumulation in normal versus tumor cells from the liver were due to its different effects on copper transporter1 and multidrug resistance-associated protein2, membrane transporters attributed to intracellular Pt transfer. Thus, GJIC protects normal organs from cisplatin toxicity while enhancing it in tumor cells via its different effects on intracellular Pt transfer.