bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole Exome Screening Identifies Novel and Recurrent WISP3 Mutations Causing Progressive Pseudorheumatoid Dysplasia in Jammu and Kashmir-India
Authors: Rai Ekta , Mahajan Ankit , Kumar Parvinder , Angural Arshia , Dhar Manoj K , Razdan Sushil , Thangaraj Kumarasamy , Wise Carol A. , Ikegawa Shiro , Pandita Kamal Kishore , Sharma Swarkar 
Published: June 2016

AbstractWe report identification and genetic characterization of a rare skeletal disorder that remained unidentified for decades in a village of Jammu and Kashmir, India. The population residing in this region is highly consanguineous and a lack of understanding of the disorder has hindered clinical management and genetic counseling for the many affected individuals in the region. We collected familial information and identified two large extended multiplex pedigrees displaying apparent autosomal recessive inheritance of an uncharacterized skeletal dysplasia. Whole exome sequencing (WES) in members of one pedigree revealed a rare mutation in WISP3:c.156C > A (NP_003871.1:p.Cys52Ter), that perfectly segregated with the disease in the family. To our surprise, Sanger sequencing the WISP3 gene in the second family identified a distinct, novel splice site mutation c.643 + 1G > A, that perfectly segregated with the disease. Combining our next generation sequencing data with careful clinical documentation (familial histories, genetic data, clinical and radiological findings), we have diagnosed the families with Progressive Pseudorheumatoid Dysplasia (PPD). Our results underscore the utility of WES in arriving at definitive diagnoses for rare skeletal dysplasias. This genetic characterization will aid in genetic counseling and management, critically required to curb this rare disorder in the families.
Luteolin inhibits GABAA receptors in HEK cells and brain slices
Authors: Shen Mei-Lin , Wang Chen-Hung , Chen Rita Yu-Tzu , Zhou Ning , Kao Shung-Te , Wu Dong Chuan 
Published: June 2016

AbstractModulation of the A type γ-aminobutyric acid receptors (GABAAR) is one of the major drug targets for neurological and psychological diseases. The natural flavonoid compound luteolin (2-(3,4-Dihydroxyphenyl)- 5,7-dihydroxy-4-chromenone) has been reported to have antidepressant, antinociceptive and anxiolytic-like effects, which possibly involve the mechanisms of modulating GABA signaling. However, as yet detailed studies of the pharmacological effects of luteolin are still lacking, we investigated the effects of luteolin on recombinant and endogenous GABAAR-mediated current responses by electrophysiological approaches. Our results showed that luteolin inhibited GABA-mediated currents and slowed the activation kinetics of recombinant α1β2, α1β2γ2, α5β2 and α5β2γ2 receptors with different degrees of potency and efficacy. The modulatory effect of luteolin was likely dependent on the subunit composition of the receptor complex: the αβ receptors were more sensitive than the αβγ receptors. In hippocampal pyramidal neurons, luteolin significantly reduced the amplitude and slowed the rise time of miniature inhibitory postsynaptic currents (mIPSCs). However, GABAAR-mediated tonic currents were not significantly influenced by luteolin. These data suggested that luteolin has negative modulatory effects on both recombinant and endogenous GABAARs and inhibits phasic rather than tonic inhibition in hippocampus.
AtDOF5.4/OBP4, a DOF Transcription Factor Gene that Negatively Regulates Cell Cycle Progression and Cell Expansion in Arabidopsis thaliana
Authors: Xu Peipei , Chen Haiying , Ying Lu , Cai Weiming 
Published: June 2016

AbstractIn contrast to animals, plant development involves continuous organ formation, which requires strict regulation of cell proliferation. The core cell cycle machinery is conserved across plants and animals, but plants have developed new mechanisms that precisely regulate cell proliferation in response to internal and external stimuli. Here, we report that the DOF transcription factorOBP4negatively regulates cell proliferation and expansion. OBP4 is a nuclear protein. Constitutive and inducible overexpression ofOBP4reduced the cell size and number, resulting in dwarf plants. Inducible overexpression ofOBP4inArabidopsisalso promoted early endocycle onset and inhibited cell expansion, while inducible overexpression ofOBP4fused to the VP16 activation domain inArabidopsisdelayed endocycle onset and promoted plant growth. Furthermore, gene expression analysis showed that cell cycle regulators and cell wall expansion factors were largely down-regulated in theOBP4overexpression lines. Short-term inducible analysis coupled within vivoChIP assays indicated thatOBP4targets theCyclinB1;1,CDKB1;1andXTHgenes. These results strongly suggest thatOBP4is a negative regulator of cell cycle progression and cell growth. These findings increase our understanding of the transcriptional regulation of the cell cycle in plants.
Empathy Modulates the Rewarding Effect of Mimicry
Authors: Neufeld J. , Chakrabarti B. 
Published: June 2016

AbstractWe tend to like those who mimic us. In this study we formally test if mimicry changes the reward value of the mimicker, using gaze bias as a proxy for reward. Previous research has demonstrated that people show gaze bias towards more rewarding targets, suggesting that gaze bias can be considered a proxy for relative reward value. Forty adults participated in a conditioning task, where they were mimicked by one face and ‘anti-mimicked’ by another. Subsequently, they were found to show gaze-bias towards faces that mimicked them compared to those that did not, in a preferential looking task. The strength of this effect correlated positively with individual levels of trait empathy. In a separate, similar task, these participants showed a gaze bias for faces paired with high vs low monetary rewards, thus validating the use of gaze bias as a proxy for learnt reward. Together, these results demonstrate that mimicry changes the reward value of social stimuli and empathy influences the extent of this change. This can potentially inform conditions marked by deficits in forming social bonds, such as Autism.
Cbx7 is epigenetically silenced in glioblastoma and inhibits cell migration by targeting YAP/TAZ-dependent transcription
Authors: Nawaz Zahid , Patil Vikas , Arora Anjali , Hegde Alangar S. , Arivazhagan Arimappamagan , Santosh Vani , Somasundaram Kumaravel 
Published: June 2016

AbstractGlioblastomas (GBM) are the most malignant form of astrocytomas which are difficult to treat and portend a grave clinical course and poor prognosis. In this study, we identified Chromobox homolog 7 (Cbx7), a member of Polycomb Repressive Complex 1 (PRC1), as a downregulated gene in GBM owing to its promoter hypermethylation. Bisulphite sequencing and methylation inhibitor treatment established the hypermethylation of Cbx7 in GBM. Exogenous overexpression of Cbx7 induced cell death, inhibited cell proliferation, colony formation and migration/invasion of the glioma cells. GSEA of Cbx7 regulated genes identified Cbx7 as a repressor of transcription co-activators YAP/TAZ, the inhibitory targets of the Hippo signalling pathway. In good correlation, the exogenous expression of Cbx7 repressed the YAP/TAZ-dependent transcription and downregulated CTGF, a bonafide YAP/TAZ target. We also observed reduced levels of phospho-JNK in Cbx7 expressing cells. Additionally, CTGF silencing and pharmacological inhibition of JNK also inhibited glioma cell migration. Further, Cbx7 failed to inhibit cell migration significantly in the presence of exogenously overexpressed CTGF or constitutively active JNK. Thus, our study identifies Cbx7 as an inhibitor of glioma cell migration through its inhibitory effect on YAP/TAZ-CTGF-JNK signalling axis and underscores the importance of epigenetic inactivation of Cbx7 in gliomagenesis.
The hidden teeth of sloths: evolutionary vestiges and the development of a simplified dentition
Authors: Hautier Lionel , Gomes Rodrigues Helder , Billet Guillaume , Asher Robert J. 
Published: June 2016

AbstractXenarthrans are unique among mammals in retaining simplified teeth that are rootless and homodont, which makes it difficult to determine dental homologies. We apply computerized tomography to prenatal developmental series of extant sloths,BradypusandCholoepus, to further elucidate the patterns of morphological variation in their dentition. We also propose new criteria based on sequences of dental mineralization and the presence of vestigial teeth, to distinguish between caniniforms and postcaniniforms. We report for the first time the presence of vestigial incisors inBradypus. We also show the presence of a vestigial tooth in front of the lower caniniform in both extant sloth genera and the existence of two generations for the upper caniniform inCholoepus. The study of their sequence of mineralization indicates that the lower and upper caniniform teeth are not homologous in sloths and suggests that upper caniniforms are not homologous between the two extant sloth genera. Our results show that assessing the developmental processes and functional constraints remains crucial to understand the dental variations observed in sloths and more generally, tooth class homology issues in mammals. Applied to the tooth row of all extinct sloths, these developmental data illuminate a potentially ancestral dental formula for sloths.
FAM20A binds to and regulates FAM20C localization
Authors: Ohyama Yoshio , Lin Ju-Hsien , Govitvattana Nattanan , Lin I-Ping , Venkitapathi Sundharamani , Alamoudi Ahmed , Husein Dina , An Chunying , Hotta Hak , Kaku Masaru , Mochida Yoshiyuki 
Published: June 2016

AbstractMutations in the Family with sequence similarity (FAM) 20 gene family are associated with mineralized tissue phenotypes in humans. Among these genes, FAM20A mutations are associated with Amelogenesis Imperfecta (AI) with gingival hyperplasia and nephrocalcinosis, while FAM20C mutations cause Raine syndrome, exhibiting bone and craniofacial/dental abnormalities. Although it has been demonstrated that Raine syndrome associated-FAM20C mutants prevented FAM20C kinase activity and secretion, overexpression of the catalytically inactive D478A FAM20C mutant was detected in both cell extracts and the media. This suggests that FAM20C secretion doesn’t require its kinase activity, and that another molecule(s) may control the secretion. In this study, we found that extracellular FAM20C localization was increased when wild-type (WT), but not AI-forms of FAM20A was co-transfected. On the other hand, extracellular FAM20C was absent in the conditioned media of mouse embryonic fibroblasts (MEFs) derived from Fam20a knock-out (KO) mouse, while it was detected in the media from WT MEFs. We also showed that cells with the conditioned media of Fam20a WT MEFs mineralized, but those with the conditioned media of KO MEFs failed to mineralize in vitro. Our data thus demonstrate that FAM20A controls FAM20C localization that may assist in the extracellular function of FAM20C in mineralized tissues.
CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii
Authors: Shin Sung-Eun , Lim Jong-Min , Koh Hyun Gi , Kim Eun Kyung , Kang Nam Kyu , Jeon Seungjib , Kwon Sohee , Shin Won-Sub , Lee Bongsoo , Hwangbo Kwon , Kim Jungeun , Ye Sung Hyeok , Yun Jae-Young , Seo Hogyun , Oh Hee-Mock , Kim Kyung-Jin , Kim Jin-Soo , Jeong Won-Joong , Chang Yong Keun , Jeong Byeong-ryool 
Published: June 2016

AbstractGenome editing is crucial for genetic engineering of organisms for improved traits, particularly in microalgae due to the urgent necessity for the next generation biofuel production. The most advanced CRISPR/Cas9 system is simple, efficient and accurate in some organisms; however, it has proven extremely difficult in microalgae including the model alga Chlamydomonas. We solved this problem by delivering Cas9 ribonucleoproteins (RNPs) comprising the Cas9 protein and sgRNAs to avoid cytotoxicity and off-targeting associated with vector-driven expression of Cas9. We obtained CRISPR/Cas9-induced mutations at three loci including MAA7, CpSRP43 and ChlM, and targeted mutagenic efficiency was improved up to 100 fold compared to the first report of transgenic Cas9-induced mutagenesis. Interestingly, we found that unrelated vectors used for the selection purpose were predominantly integrated at the Cas9 cut site, indicative of NHEJ-mediated knock-in events. As expected with Cas9 RNPs, no off-targeting was found in one of the mutagenic screens. In conclusion, we improved the knockout efficiency by using Cas9 RNPs, which opens great opportunities not only for biological research but also industrial applications in Chlamydomonas and other microalgae. Findings of the NHEJ-mediated knock-in events will allow applications of the CRISPR/Cas9 system in microalgae, including “safe harboring” techniques shown in other organisms.
Evolutionary and developmental analysis reveals KANK genes were co-opted for vertebrate vascular development
Authors: Hensley Monica R. , Cui Zhibin , Chua Rhys F. M. , Simpson Stefanie , Shammas Nicole L. , Yang Jer-Yen , Leung Yuk Fai , Zhang GuangJun 
Published: June 2016

AbstractGene co-option, usually after gene duplication, in the evolution of development is found to contribute to vertebrate morphological innovations, including the endothelium-based vascular system. Recently, a zebrafish kank gene was found expressed in the vascular vessel primordium, suggesting KANK genes are a component of the developmental tool kit for the vertebrate vascular system. However, how the KANK gene family is involved in vascular vessel development during evolution remains largely unknown. First, we analyzed the molecular evolution of the KANK genes in metazoan, and found that KANK1, KANK2, KANK3 and KANK4 emerged in the lineage of vertebrate, consistent with the two rounds of vertebrate whole-genome duplications (WGD). Moreover, KANK genes were further duplicated in teleosts through the bony-fish specific WGD, while only kank1 and kank4 duplicates were retained in some of the examined fish species. We also found all zebrafish kank genes, except kank1b, are primarily expressed during embryonic vascular development. Compared to invertebrate KANK gene expression in the central nervous system, the vascular expression of zebrafish kank genes suggested KANK genes were co-opted for vertebrate vascular development. Given the cellular roles of KANK genes, our results suggest that this co-option may facilitate the evolutionary origin of vertebrate vascular vessels.
Glipizide suppresses prostate cancer progression in the TRAMP model by inhibiting angiogenesis
Authors: Qi Cuiling , Bin Li  , Yang Yang , Yang Yongxia , Li Jialin , Zhou Qin , Wen Yinxin , Zeng Cuiling , Zheng Lingyun , Zhang Qianqian , Li Jiangchao , He Xiaodong , Zhou Jia , Shao Chunkui , Wang Lijing 
Published: June 2016

AbstractDrug repurposing of non-cancer drugs represents an attractive approach to develop new cancer therapy. Using the TRAMP transgenic mouse model, glipizide, a widely used drug for type 2 diabetes mellitus, has been identified to suppress prostate cancer (PC) growth and metastasis. Angiogenesis is intimately associated with various human cancer developments. Intriguingly, glipizide significantly reduces microvessel density in PC tumor tissues, while not inhibiting prostate cancer cell proliferation from the MTT assay and flow cytometry investigation. Moreover, glipizide inhibits the tubular structure formation of human umbilical vein endothelial cells by regulating the HMGIY/Angiopoietin-1 signaling pathway. Taken together, these results demonstrate that glipizide has the potential to be repurposed as an effective therapeutic for the treatment of PC by targeting tumor-induced angiogenesis.
Effect of desertification on productivity in a desert steppe
Authors: Tang Zhuangsheng , An Hui , Deng Lei , Wang Yingying , Zhu Guangyu , Shangguan Zhouping 
Published: June 2016

AbstractDesertification, one of the most severe types of land degradation in the world, is of great importance because it is occurring, to some degree, on approximately 40% of the global land area and is affecting more than 1 billion people. In this study, we used a space-for-time method to quantify the impact of five different desertification regimes (potential (PD), light (LD), moderate (MD), severe (SD), and very severe (VSD)) on a desert steppe ecosystem in northern China to examine the relationship between the productivity of the vegetation and soil properties and to determine the mechanism underlying the effects of desertification on productivity. Our results showed that the effects of desertification on TP (total phosphorus) and AP (available phosphorus) were not significant, and desertification decreased productivity in the desert steppe as a result of direct changes to soil physical properties, which can directly affect soil chemical properties. Therefore, intensive grassland management to improve soil quality may result in the long-term preservation of ecosystem functions and services.
Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs
Authors: Lee Eun Jung , Kim Ji Young , Oh Sang Ho 
Published: June 2016

AbstractAccumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation.
Anomalous photoluminescence in InP1−xBix
Authors: Wu Xiaoyan , Chen Xiren , Pan Wenwu , Wang Peng , Zhang Liyao , Li Yaoyao , Wang Hailong , Wang Kai , Shao Jun , Wang Shumin 
Published: June 2016

AbstractLow temperature photoluminescence (PL) from InP1−xBix thin films with Bi concentrations in the 0–2.49% range reveals anomalous spectral features with strong and very broad (linewidth of 700 nm) PL signals compared to other bismide alloys. Multiple transitions are observed and their energy levels are found much smaller than the band-gap measured from absorption measurements. These transitions are related to deep levels confirmed by deep level transient spectroscopy, which effectively trap free holes and enhance radiative recombination. The broad luminescence feature is beneficial for making super-luminescence diodes, which can theoretically enhance spatial resolution beyond 1 μm in optical coherent tomography (OCT).
Transparent ferromagnetic and semiconducting behavior in Fe-Dy-Tb based amorphous oxide films
Authors: Taz H. , Sakthivel T. , Yamoah N. K. , Carr C. , Kumar D. , Seal S. , Kalyanaraman R. 
Published: June 2016

AbstractWe report a class of amorphous thin film material comprising of transition (Fe) and Lanthanide metals (Dy and Tb) that show unique combination of functional properties. Films were deposited with different atomic weight ratio (R) of Fe to Lanthanide (Dy + Tb) using electron beam co-evaporation at room temperature. The films were found to be amorphous, with grazing incidence x-ray diffraction and x-ray photoelectron spectroscopy studies indicating that the films were largely oxidized with a majority of the metal being in higher oxidation states. Films with R = 0.6 were semiconducting with visible light transmission due to a direct optical band-gap (2.49 eV), had low resistivity and sheet resistance (7.15 × 10−4 Ω-cm and ~200 Ω/sq respectively) and showed room temperature ferromagnetism. A metal to semiconductor transition with composition (for R < 11.9) also correlated well with the absence of any metallic Fe0 oxidation state in the R = 0.6 case as well as a significantly higher fraction of oxidized Dy. The combination of amorphous microstructure and room temperature electronic and magnetic properties could lead to the use of the material in multiple applications, including as a transparent conductor, active material in thin film transistors for display devices and in spin-dependent electronics.
Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
Authors: Martinez-Cruzado Lucia , Tornin Juan , Santos Laura , Rodriguez Aida , García-Castro Javier , Morís Francisco , Rodriguez Rene 
Published: June 2016

AbstractTumors evolve from initial tumorigenic events into increasingly aggressive behaviors in a process usually driven by subpopulations of cancer stem cells (CSCs). Mesenchymal stromal/stem cells (MSCs) may act as the cell-of-origin for sarcomas and CSCs that present MSC features have been identified in sarcomas due to their ability to grow as self-renewed floating spheres (tumorspheres). Accordingly, we previously developed sarcoma models using human MSCs transformed with relevant oncogenic events. To study the evolution/emergence of CSC subpopulations during tumor progression, we compared the tumorigenic properties of bulk adherent cultures and tumorsphere-forming subpopulations both in the sarcoma cell-of-origin models (transformed MSCs) and in their corresponding tumor xenograft-derived cells. Tumor formation assays showed that the tumorsphere cultures from xenograft-derived cells, but not from the cell-of-origin models, were enriched in CSCs, providing evidence of the emergence of bona fide CSCs subpopulations during tumor progression. Relevant CSC-related factors, such as ALDH1 and SOX2, were increasingly upregulated in CSCs during tumor progression and importantly, the increased levels and activity of ALDH1 in these subpopulations were associated with enhanced tumorigenicity. In addition to being a CSC marker, our findings indicate that ALDH1 could also be useful for tracking the malignant potential of CSC subpopulations during sarcoma evolution.
New materials for Li-ion batteries: synthesis and spectroscopic characterization of Li2(FeMnCo)SiO4 cathode materials
Authors: Ferrari Stefania , Mozzati Maria Cristina , Lantieri Marco , Spina Gabriele , Capsoni Doretta , Bini Marcella 
Published: June 2016

AbstractImproving cathode materials is mandatory for next-generation Li-ion batteries. Exploring polyanion compounds with high theoretical capacity such as the lithium metal orthosilicates, Li2MSiO4 is of great importance. In particular, mixed silicates represent an advancement with practical applications. Here we present results on a rapid solid state synthesis of mixed Li2(FeMnCo)SiO4 samples in a wide compositional range. The solid solution in the P21/n space group was found to be stable for high iron concentration or for a cobalt content up to about 0.3 atom per formula unit. Other compositions led to a mixture of polymorphs, namely Pmn21 and Pbn21. All the samples contained a variable amount of Fe3+ ions that was quantified by Mössbauer spectroscopy and confirmed by the TN values of the paramagnetic to antiferromagnetic transition. Preliminary characterization by cyclic voltammetry revealed the effect of Fe3+ on the electrochemical response. Further work is required to determine the impact of these electrode materials on lithium batteries.