bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene
Authors: Ono Hiroyuki , Saitsu Hirotomo , Horikawa Reiko , Nakashima Shinichi , Ohkubo Yumiko , Yanagi Kumiko , Nakabayashi Kazuhiko , Fukami Maki , Fujisawa Yasuko , Ogata Tsutomu 
Published: January 2018

AbstractAlthough partial androgen insensitivity syndrome (PAIS) is caused by attenuated responsiveness to androgens, androgen receptor gene (AR) mutations on the coding regions and their splice sites have been identified only in <25% of patients with a diagnosis of PAIS. We performed extensive molecular studies including whole exome sequencing in a Japanese family with PAIS, identifying a deep intronic variant beyond the branch site at intron 6 of AR (NM_000044.4:c.2450−42 G > A). This variant created the splice acceptor motif that was accompanied by pyrimidine-rich sequence and two candidate branch sites. Consistent with this, reverse transcriptase (RT)-PCR experiments for cycloheximide-treated lymphoblastoid cell lines revealed a relatively large amount of aberrant mRNA produced by the newly created splice acceptor site and a relatively small amount of wildtype mRNA produced by the normal splice acceptor site. Furthermore, most of the aberrant mRNA was shown to undergo nonsense mediated decay (NMD) and, if a small amount of aberrant mRNA may have escaped NMD, such mRNA was predicted to generate a truncated AR protein missing some functional domains. These findings imply that the deep intronic mutation creating an alternative splice acceptor site resulted in the production of a relatively small amount of wildtype AR mRNA, leading to PAIS.
A sequence polymorphism on 8q24 is associated with survival in hepatocellular carcinoma patients who received radiation therapy
Authors: Zhao Xiao-Mei , Xiang Zuo-Lin , Chen Yi-Xing , Yang Ping , Hu Yong , Zeng Zhao-Chong 
Published: January 2018

AbstractThere is a growing consensus that genetic variation in candidate genes can influence cancer progression and treatment effects. In this study, we genotyped the rs9642880 G > T polymorphism using DNA isolated from blood samples of 271 hepatocellular carcinoma (HCC) patients who received radiotherapy treatment. We found that patients who carried the GT or TT genotypes had significantly shorter median survival times (MSTs) compared to patients with the GG genotype (14.6 vs.21.4 months). The multivariate P value was 0.027, the hazard ratio (HR) was 1.38, and the 95% confidence interval was 1.04–1.84. Further analysis revealed that patients with the variant genotypes had an increased risk of poor tumour response to radiotherapy (P = 0.036 and 0.002 for stable disease and progressive disease, respectively) and higher incidence of multiple intrahepatic lesions (P = 0.026) and BCLC C stage (P = 0.027). Moreover, further stratified survival analyses revealed that at least radioresponse and BCLC stage contributed to the association between the rs9642880 G > T polymorphism and survival of HCC patients in this study (P value, 0.017 vs 0.053 for BCLC C stage vs B stage; 0.011 vs 0.531 for radioresponse SD + PD vs CR + PR). These results illustrate the potential association between rs9642880 G > T and survival in HCC patients who received radiotherapy treatment.
Temporal reprogramming of calcium signalling via crosstalk of gonadotrophin receptors that associate as functionally asymmetric heteromers
Authors: Jonas K. C. , Chen S. , Virta M. , Mora J. , Franks S. , Huhtaniemi I. , Hanyaloglu A. C. 
Published: January 2018

AbstractSignal crosstalk between distinct G protein-coupled receptors (GPCRs) is one mechanism that underlies pleiotropic signalling. Such crosstalk is also pertinent for GPCRs activated by gonadotrophic hormones; follicle-stimulating hormone (FSH) and luteinising hormone (LH), with specific relevance to female reproduction. Here, we demonstrate that gonadotrophin receptor crosstalk alters LH-induced Gαq/11-calcium profiles. LH-induced calcium signals in both heterologous and primary human granulosa cells were prolonged by FSHR coexpression via influx of extracellular calcium in a receptor specific manner. LHR/FSHR crosstalk involves Gαq/11 activation as a Gαq/11 inhibitor abolished calcium responses. Interestingly, the enhanced LH-mediated calcium signalling induced by FSHR co-expression was dependent on intracellular calcium store release and involved Gβγ. Biophysical analysis of receptor and Gαq interactions indicated that ligand-dependent association between LHR and Gαq was rearranged in the presence of FSHR, enabling FSHR to closely associate with Gαq following LHR activation. This suggests that crosstalk may occur via close associations as heteromers. Super-resolution imaging revealed that LHR and FSHR formed constitutive heteromers at the plasma membrane. Intriguingly, the ratio of LHR:FSHR in heterotetramers was specifically altered following LH treatment. We propose that functionally significant FSHR/LHR crosstalk reprograms LH-mediated calcium signalling at the interface of receptor-G protein via formation of asymmetric complexes.
Contractile Skeletal Muscle Cells Cultured with a Conducting Soft Wire for Effective, Selective Stimulation
Authors: Nagamine Kuniaki , Sato Hirotaka , Kai Hiroyuki , Kaji Hirokazu , Kanzaki Makoto , Nishizawa Matsuhiko 
Published: January 2018

AbstractContractile skeletal muscle cells were cultured so as to wrap around an electrode wire to enable their selective stimulation even when they were co-cultured with other electrically-excitable cells. Since the electrode wire was composed of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and polyurethane (PU), which is soft and highly capacitive (~10 mF cm−2), non-faradaic electrical stimulation with charge/discharge currents could be applied to the surrounding cells without causing significant damage even for longer periods (more than a week). The advantage of this new culture system was demonstrated in the study of chemotactic interaction of monocytes and skeletal muscle cells via myokines.
Determining the Rate of Carbonic Anhydrase Reaction in the Human Brain
Authors: Li Shizhe , An Li , Duan Qi , Ferraris Araneta Maria , Johnson Christopher S. , Shen Jun 
Published: January 2018

AbstractCarbonic anhydrase plays important role in life. This study sought to demonstrate the feasibility of detecting carbonic anhydrase activity in the human brain in vivo. After oral administration of [U-13C6]glucose, 13C saturation transfer experiments were performed with interleaved control spectra and carbon dioxide saturation spectra. Proton nuclear Overhauser effect pulses were used to increase signal to noise ratio; no proton decoupling was applied. Results showed that the 13C signal of bicarbonate was reduced by 72% ± 0.03 upon saturating carbon dioxide. The unidirectional dehydration rate constant of the carbonic anhydrase reaction was found to be 0.28 ± 0.02 sec−1 in the human brain. These findings demonstrate the feasibility of measuring carbonic anhydrase activity in vivo in the human brain, which makes it possible to characterize this important enzyme in patients with brain disorders.
Magnetization reversal in trilayer structures consisting of GaMnAs layers with opposite signs of anisotropic magnetoresistance
Authors: Lee Kyung Jae , Lee Sangyeop , Bac Seul-Ki , Choi Seonghoon , Lee Hakjoon , Chang Jihoon , Choi Suho , Chongthanaphisut Phunvira , Lee Sanghoon , Liu X. , Dobrowolska M. , Furdyna J. K. 
Published: January 2018

AbstractMagnetization reversal in a GaMnAs trilayer system consisting of two GaMnAs layers separated by a Be-doped GaAs spacer was investigated by magnetotransport measurements. The rotation of magnetization in the two GaMnAs layers is observed as two abrupt independent transitions in planar Hall resistance (PHR). Interestingly, one GaMnAs layer manifests a positive change in PHR, while the other layer shows a negative change for the same rotation of magnetization. Such opposite behavior of the two layers indicates that anisotropic magnetoresistance (AMR) has opposite signs in the two GaMnAs layers. Owing to this opposite behavior of AMR, we are able to identify the sequence of magnetic alignments in the two GaMnAs layers during magnetization reversal. The PHR signal can then be decomposed into two independent contributions, which reveal that the magnetic anisotropy of the GaMnAs layer with negative AMR is predominantly cubic, while it is predominantly uniaxial in the layer with positive AMR. This investigation suggests the ability of engineering the sign of AMR in GaMnAs multilayers, thus making it possible to obtain structures with multi-valued PHR, that can be used as multinary magnetic memory devices.
The MRPS18-2 protein levels correlate with prostate tumor progression and it induces CXCR4-dependent migration of cancer cells
Authors: Mushtaq Muhammad , Jensen Lasse , Davidsson Sabina , Grygoruk Oleksandr V. , Andrén Ove , Kashuba Vladimir , Kashuba Elena 
Published: January 2018

AbstractWe have earlier found abnormal expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) in endometrial cancer, compared to the expression in hyperplasia and in normal endometrium. Here we report that expression of S18-2 was increased with disease progression in clinical specimens of prostate cancer (PCa). The level of induction of epithelial to mesenchymal cell transition (EMT) correlated with the expression level of S18-2 in PCa cell lines. Moreover, cells acquired increased ability of migration upon S18-2 overexpression, as was evaluated in zebrafish embryo model and in trans-well assay. We found that this is due to increased CXCR4 cell surface expression. Neutralizing CXCR4 protein or abrogating S18-2 expression in cells significantly reduced their migratory ability directed toward CXCL12. The mRNA expression of TWIST2, encoding one of transcription factors that induce EMT upon CXCR4 increase, positively correlated with the S18-2 protein level. Together, these data suggest that the S18-2 protein induces EMT through the TWIST2/E-cadherin signalling and, consequently, CXCR4-mediated migration of PCa cells.
Nonthermal plasma treated solution inhibits adipocyte differentiation and lipogenesis in 3T3-L1 preadipocytes via ER stress signal suppression
Authors: Kang Sung Un , Kim Haeng Jun , Kim Dae Ho , Han Chang Hak , Lee Yun Sang , Kim Chul-Ho 
Published: January 2018

AbstractThe accumulation and differentiation of adipocytes contribute to the development of obesity and metabolic diseases. It is well-known that interactions of transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and endoplasmic reticulum (ER) stress are required for adipogenesis. Recently, use of nonthermal atmospheric plasma (NTP) is expanding from the biomedical field into various other fields. In this study, we investigated whether nonthermal plasma-treated solution (NTS) has an inhibitory effect on adipogenesis and elucidated its mechanisms. Our results demonstrated that NTS significantly inhibited pre-adipocyte differentiation into adipocytes based on Oil Red O staining and triglyceride accumulation. Moreover, NTS treatment suppressed the mRNA and protein expression levels of key adipogenic transcription factors, and adipocyte-specific genes. NTS also down-regulated endoplasmic reticulum stress-related proteins. Consistent with in vitro studies, an animal study using a mouse model of diet-induced obesity showed that NTS treatment reduced body weight and fat, ER stress/UPR, triglyceride, and adipogenic marker level without altering food intake. These findings indicate that NTS inhibits adipogenic differentiation, and provide a mechanistic explanation of the inhibitory effect of NTS on adipogenesis. Taken together, our results suggest that NTS might be useful to treat obesity and obesity-related diseases.
Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening
Authors: Lo Chun-Yeung , Li Olive Tin-Wai , Tang Wen-Ping , Hu Chun , Wang Guo Xin , Ngo Jacky Chi-Ki , Wan David Chi-Cheong , Poon Leo Lit-Man , Shaw Pang-Chui 
Published: January 2018

AbstractCurrently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals to combat this virus. The influenza polymerase with three proteins, PA, PB1 and PB2, is a crucial component of the viral ribonucleoprotein (RNP) complex. Here, we report the identification of a hit compound 221 by surface plasmon resonance (SPR) direct binding screening on the C-terminal of PA (PAC). Compound 221 can subdue influenza RNP activities and attenuate influenza virus replication. Its analogs were subsequently investigated and twelve of them could attenuate RNP activities. One of the analogs, compound 312, impeded influenza A virus replication in Madin-Darby canine kidney cells with IC50 of 27.0 ± 16.8 μM. In vitro interaction assays showed that compound 312 bound directly to PAC with Kd of about 40 μM. Overall, the identification of novel PAC-targeting compounds provides new ground for drug design against influenza virus in the future.
The first identification of genomic loci in plants associated with resistance to galling insects: a case study in Eucalyptus L'Hér. (Myrtaceae)
Authors: Zhang Miaomiao , Zhou Changpin , Song Zhijiao , Weng Qijie , Li Mei , Ji Hongxia , Mo Xiaoyong , Huang Huanhua , Lu Wanhong , Luo Jianzhong , Li Fagen , Gan Siming 
Published: January 2018

AbstractGenomic loci related with resistance to gall-inducing insects have not been identified in any plants. Here, association mapping was used to identify molecular markers for resistance to the gall wasp Leptocybe invasa in two Eucalyptus species. A total of 86 simple sequence repeats (SSR) markers were screened out from 839 SSRs and used for association mapping in E. grandis. By applying the mixed linear model, seven markers were identified to be associated significantly (P ≤ 0.05) with the gall wasp resistance in E. grandis, including two validated with a correction of permutation test (P ≤ 0.008). The proportion of the variance in resistance explained by a significant marker ranged from 3.3% to 37.8%. Four out of the seven significant associations in E. grandis were verified and also validated (P ≤ 0.073 in a permutation test) in E. tereticornis, with the variation explained ranging from 24.3% to 48.5%. Favourable alleles with positive effect were also mined from the significant markers in both species. These results provide insight into the genetic control of gall wasp resistance in plants and have great potential for marker-assisted selection for resistance to L. invasa in the important tree genus Eucalyptus.
Intercalation pseudocapacitance of expanded graphite in sodium‐ion capacitors
Authors: Zhang Zhendong , Zhao Jiachang , Guo Chaofei , Xu Jingli 
Published: January 2018

The intercalation pseudocapacitance of expanded graphite (EG) which was prepared by a process of oxidation and partial reduction on pristine graphite was investigated in this work. The structure of EG was characterised by X‐ray diffraction (XRD) and high‐resolution transmission electron microscope (HRTEM), and the electrochemical performance of EG was measured by cyclic voltammetry, galvanostatic charge–discharge and electrochemical impedance spectroscopy. The interlayer distance of EG is enlarged from 0.34 to 0.40 nm, which is demonstrated by XRD and HRTEM. EG electrode exhibits a specific capacitance of 228 F/g at current density of 0.5 A/g. Moreover, the material shows excellent cycle stability after 2000 charge–discharge cycles at a current density of 1 A/g. EG could be a very promising material for the supercapacitors industry.
Well-defined EUV wave associated with a CME-driven shock
Authors: Cunha-Silva R. D. , Selhorst C. L. , Fernandes F. C. R. , Oliveira e Silva A. J. 
Published: January 2018

Aims. We report on a well-defined EUV wave observed by the Extreme Ultraviolet Imager (EUVI) on board the Solar Terrestrial Relations Observatory (STEREO) and the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory (SDO). The event was accompanied by a shock wave driven by a halo CME observed by the Large Angle and Spectrometric Coronagraph (LASCO-C2/C3) on board the Solar and Heliospheric Observatory (SOHO), as evidenced by the occurrence of type II bursts in the metric and dekameter-hectometric wavelength ranges. We investigated the kinematics of the EUV wave front and the radio source with the purpose of verifying the association between the EUV wave and the shock wave.
Methods. The EUV wave fronts were determined from the SDO/AIA images by means of two appropriate directions (slices). The heights (radial propagation) of the EUV wave observed by STEREO/EUVI and of the radio source associated with the shock wave were compared considering the whole bandwidth of the harmonic lane of the radio emission, whereas the speed of the shock was estimated using the lowest frequencies of the harmonic lane associated with the undisturbed corona, using an appropriate multiple of the Newkirk (1961, ApJ, 133, 983) density model and taking into account the H/F frequency ratio fH∕fF = 2. The speed of the radio source associated with the interplanetary shock was determined using the Mann et al. (1999, A&A, 348, 614) density model.
Results. The EUV wave fronts determined from the SDO/AIA images revealed the coexistence of two types of EUV waves, a fast one with a speed of ~560 km s−1, and a slower one with a speed of ~250 km s−1, which corresponds approximately to one-third of the average speed of the radio source (~680 km s−1). The radio signature of the interplanetary shock revealed an almost constant speed of ~930 km s−1, consistent with the linear speed of the halo CME (950 km s−1) and with the values found for the accelerating coronal shock (~535–823 km s−1), taking into account the gap between the radio emissions.
LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect
Authors: Xiang Shaoxun , Gu Hao , Jin Lei , Thorne Rick F. , Zhang Xu Dong , Wu Mian 
Published: January 2018

Significance
We report in this article that c-Myc-mediated repression of lncRNA IDH1-AS1 sustains activation of the Warburg effect by HIF1α under normoxic conditions. IDH1-AS1 would otherwise enhance IDH1 enzymatic activity through promoting its homodimerization, leading to increased production of α-KG, which, along with decreases in ROS levels similarly resulting from increased IDH1 activity, causes down-regulation of HIF1a and a reduction in glycolysis. Collectively, our results have identified a signaling axis c-Myc-(IDH1-AS1)-IDH1-αKG/ROS-HIF1α that is important for activation of the Warburg effect under normoxia. Moreover, the results reveal IDH1 as a member of c-Myc-responsive metabolic enzymes and demonstrate that c-Myc plays an important part in balancing mitochondrial respiration and glycolysis to ensure glycolysis be executed efficiently in cancer cells under normoxia.
Method to generate highly stable D-amino acid analogs of bioactive helical peptides using a mirror image of the entire PDB
Authors: Garton Michael , Nim Satra , Stone Tracy A. , Wang Kyle Ethan , Deber Charles M. , Kim Philip M. 
Published: January 2018

Significance
Using D-amino acids as the building blocks for bioactive peptides can dramatically increase their potency. However, simply swapping regular levorotary amino acids for dextrorotary (D)-amino acids alters the peptide surface topology and function is lost. Current methods to overcome this are not generally applicable and exclude the majority of therapeutic targets. By creating a mirror image of all 111,867 protein structures in the Protein Data Bank (PDB), we convert this repository into a D-peptide database with 2.8 million D-peptide structures. This D-PDB can be searched to find therapeutically active topologies, demonstrated here by the discovery of D-peptide GLP1R and PTH1R agonists. Evaluation of D-PDB coverage suggests that it holds candidates for most therapeutic targets and, thus, potentially contains hundreds of potent drug leads.
On the complex dynamics of savanna landscapes
Authors: Touboul Jonathan David , Staver Ann Carla , Levin Simon Asher 
Published: January 2018

Significance
This paper makes a significant contribution both to ecological theory and to an understanding more generally regarding how complex dynamics can emerge in mathematical models from quite simple underlying assumptions. Empirical and theoretical work has suggested that savanna–forest systems exhibit bistability, potentially flipping from one state to another in the face of environmental change. Here, we show that the dynamics of those systems may be much more complicated (periodic and endogenously driven) and present surprising responses to environmental variability. From a mathematical point of view, the models that we explore exhibit a rich array of behaviors and responses to random perturbations, and we suggest that such dynamics may arise in a variety of contexts.
Effects of rapamycin on growth hormone receptor knockout mice
Authors: Fang Yimin , Hill Cristal M. , Darcy Justin , Reyes-Ordoñez Adriana , Arauz Edwin , McFadden Samuel , Zhang Chi , Osland Jared , Gao John , Zhang Tian , Frank Stuart J. , Javors Martin A. , Yuan Rong , Kopchick John J. , Sun Liou Y. , Chen Jie , Bartke Andrzej 
Published: January 2018

Significance
In various animal species, including mammals, longevity can be extended by rapamycin, an inhibitor of mTOR (mechanistic target of rapamycin). mTOR acts through two complexes: mTORC1 and mTORC2. Antiaging effects of rapamycin are mediated by suppression of mTORC1, while the role of mTORC2 in aging remains to be elucidated. Here, we report that mTORC2 plays a positive role in regulating longevity via maintenance, or enhancement, of whole-body homeostasis. When mTORC2-mediated homeostasis was disrupted by rapamycin in the remarkably long-lived GHR-KO mice (in which mTORC1 signaling is low, while mTORC2 signaling is elevated), their life span was shortened. Hence, a selective approach toward mTORC1 inhibition without impairing mTORC2 is important in devising a strategy for slowing aging.
Disease-causing mutation in α-actinin-4 promotes podocyte detachment through maladaptation to periodic stretch
Authors: Feng Di , Notbohm Jacob , Benjamin Ava , He Shijie , Wang Minxian , Ang Lay-Hong , Bantawa Minaspi , Bouzid Mehdi , Del Gado Emanuela , Krishnan Ramaswamy , Pollak Martin R. 
Published: January 2018

Significance
Point mutations in α-actinin-4 (ACTN4) cause a form of kidney disease in humans. Although we know these mutations affect kidney podocytes, the mechanism by which they lead to podocyte dysfunction remains unclear. Here, we show that homozygous mutant Actn4 podocytes developed irrecoverable reductions in their contraction and irreparable disruptions in their actin cytoskeletons when subjected to periodic stretch. This maladaptive response is akin to failure of a brittle material under deformation. Our results clarify the mechanism by which mutations in ACTN4 leave the podocyte more vulnerable to detachment in the progression of kidney disease.