bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering cell signaling using tunable CRISPR–Cpf1-based transcription factors
Authors: Liu Yuchen , Han Jinghong , Chen Zhicong , Wu Hanwei , Dong Hongsong , Nie Guohui 
Published: December 2017

AbstractThe catalytically dead Cpf1 endonuclease from Acidaminococcus sp. BV3L6 (dAsCpf1) has been used to construct effective transcriptional repressors in bacteria and plants. However, it is still unclear if dAsCpf1 can function in human cells as a transcriptional regulator or a signal conductor. Here, we repurpose the dAsCpf1 system in human cells for a variety of functions, including the activation or repression of gene transcription. Moreover, we construct programmable ligand-controlled dAsCpf1 systems either by coupling crRNAs with engineered riboswitches or by fusing dAsCpf1 proteins with G protein-coupled receptors. These generalizable approaches allow us to regulate the transcription of endogenous genes in response to diverse classes of ligands, thus constructing artificial signaling pathways with rewired cellular input–output behaviors. The systems exhibit signal amplification, an important feature in cell signaling, when multiple crRNAs are processed from a single transcript. The results provide a robust and efficient platform for engineering customized cell signaling circuits.
Machine learning in materials informatics: recent applications and prospects
Authors: Ramprasad Rampi , Batra Rohit , Pilania Ghanshyam , Mannodi-Kanakkithodi Arun , Kim Chiho 
Published: December 2017

AbstractPropelled partly by the Materials Genome Initiative, and partly by the algorithmic developments and the resounding successes of data-driven efforts in other domains, informatics strategies are beginning to take shape within materials science. These approaches lead to surrogate machine learning models that enable rapid predictions based purely on past data rather than by direct experimentation or by computations/simulations in which fundamental equations are explicitly solved. Data-centric informatics methods are becoming useful to determine material properties that are hard to measure or compute using traditional methods—due to the cost, time or effort involved—but for which reliable data either already exists or can be generated for at least a subset of the critical cases. Predictions are typically interpolative, involving fingerprinting a material numerically first, and then following a mapping (established via a learning algorithm) between the fingerprint and the property of interest. Fingerprints, also referred to as “descriptors”, may be of many types and scales, as dictated by the application domain and needs. Predictions may also be extrapolative—extending into new materials spaces—provided prediction uncertainties are properly taken into account. This article attempts to provide an overview of some of the recent successful data-driven “materials informatics” strategies undertaken in the last decade, with particular emphasis on the fingerprint or descriptor choices. The review also identifies some challenges the community is facing and those that should be overcome in the near future.
Relation between Fractal Inhomogeneity and In/Nb-Arrangement in Pb(In1/2Nb1/2)O3
Authors: Tsukada Shinya , Ohwada Kenji , Ohwa Hidehiro , Mori Shigeo , Kojima Seiji , Yasuda Naohiko , Terauchi Hikaru , Akishige Yukikuni 
Published: December 2017

AbstractRelaxor ferroelectrics show substantial responses to electric fields. The key difference from normal ferroelectrics is a temperature-dependent inhomogeneous structure and its dynamics. The lead-based complex perovskite Pb(In1/2Nb1/2)O3is an intriguing system in which the inhomogeneous structure can be controlled by thermal treatment. Herein, we report investigations of the phase transitions in single crystals of Pb(In1/2Nb1/2)O3via changing the degree of randomness in which In and Nb occupy the B site of the ABO3perovskite structure. We studied the dynamic properties of the structure using inelastic light scattering and the static properties using diffuse X-ray scattering. These properties depend on the degree of randomness with which the B site is occupied. When the distribution of occupied In/Nb sites is regular, the antiferroelectric phase is stabilised by a change in the collective transverse-acoustic wave, which suppresses long-range ferroelectric order and the growth of the inhomogeneous structure. However, when the B site is occupied randomly, a fractal structure grows as the temperature decreases belowT*~475 K, and nanosized ferroelectric domains are produced by the percolation of self-similar and static polar nanoregions.
Molecular cloning and expression analysis of two key genes, HDS and HDR, in the MEP pathway in Pyropia haitanensis
Authors: He Yuan , Yan Zhihong , Du Yu , Ma Yafeng , Shen Songdong 
Published: December 2017

AbstractThe 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase (HDS) gene and the 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) gene are two important genes in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. In this study, we reported the isolation and characterization of full-length HDS (MF101802) and HDR (MF159558) from Pyropia haitanensis. Characteristics of 3-D structures of the PhHDS and PhHDR proteins were analysed respectively. The results showed that the full-length cDNA of PhHDS, which is 1801 bp long, contained a 1455 bp open reading frame (ORF) encoding a putative 484 amino acid residue protein with a predicted molecular mass of 51.60 kDa. Meanwhile, the full-length cDNA of PhHDR was 1668 bp and contained a 1434 bp ORF encoding a putative 477 amino acid 2 residue protein with a predicted molecular mass of 51.49 kDa. The expression levels of the two genes were higher in conchocelis than that in leafy thallus. Additionally, the expression levels could be influenced by light, temperature and salinity and induced by methyl jasmonate (MJ) and salicylic acid (SA). This study contributed to our in-depth understanding of the roles of PhHDS and PhHDR in terpenoid biosynthesis in Pyropia haitanensis and the regulation of the two genes by external environments.
Small molecules related to adrenomedullin reduce tumor burden in a mouse model of colitis-associated colon cancer
Authors: Ochoa-Callejero Laura , García-Sanmartín Josune , Martínez-Herrero Sonia , Rubio-Mediavilla Susana , Narro-Íñiguez Judit , Martínez Alfredo 
Published: December 2017

AbstractTo investigate the contribution of adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), to the progression and potential treatment of colon cancer we studied the effects of four small molecules (SM) related to AM and PAMP on a mouse model of colon cancer. For each SM, four experimental groups of male mice were used: (i) Control group; (ii) SM group; (iii) DSS group (injected with azoxymethane [AOM] and drank dextran sulfate sodium [DSS]); and (iv) DSS + SM group (treated with AOM, DSS, and the SM). None of the mice in groups i and ii developed tumors, whereas all mice in groups iii and iv developed colon neoplasias. No significant differences were found among mice treated with PAMP modulators (87877 and 106221). Mice that received the AM negative modulator, 16311, had worse colitis symptoms than their control counterparts, whereas mice injected with the AM positive modulator, 145425, had a lower number of tumors than their controls. SM 145425 regulated the expression of proliferation marker Lgr5 and had an impact on microbiota, preventing the DSS-elicited increase of the Bacteroides/Prevotella ratio. These results suggest that treatment with AM or with positive modulator SMs may represent a novel strategy for colon cancer.
Inactivation of the dnaK gene in Clostridium difficile 630 Δerm yields a temperature-sensitive phenotype and increases biofilm-forming ability
Authors: Jain Shailesh , Smyth Deborah , O’Hagan Barry M. G. , Heap John T. , McMullan Geoff , Minton Nigel P. , Ternan Nigel G. 
Published: December 2017

AbstractClostridium difficile infection is a growing problem in healthcare settings worldwide and results in a considerable socioeconomic impact. New hypervirulent strains and acquisition of antibiotic resistance exacerbates pathogenesis; however, the survival strategy of C. difficile in the challenging gut environment still remains incompletely understood. We previously reported that clinically relevant heat-stress (37–41 °C) resulted in a classical heat-stress response with up-regulation of cellular chaperones. We used ClosTron to construct an insertional mutation in the dnaK gene of C. difficile 630 Δerm. The dnaK mutant exhibited temperature sensitivity, grew more slowly than C. difficile 630 Δerm and was less thermotolerant. Furthermore, the mutant was non-motile, had 4-fold lower expression of the fliC gene and lacked flagella on the cell surface. Mutant cells were some 50% longer than parental strain cells, and at optimal growth temperatures, they exhibited a 4-fold increase in the expression of class I chaperone genes including GroEL and GroES. Increased chaperone expression, in addition to the non-flagellated phenotype of the mutant, may account for the increased biofilm formation observed. Overall, the phenotype resulting from dnaK disruption is more akin to that observed in Escherichia coli dnaK mutants, rather than those in the Gram-positive model organism Bacillus subtilis.
Stress-induced release of the S100A8/A9 alarmin is elevated in coronary artery disease patients with impaired cortisol response
Authors: Jonasson L. , Grauen Larsen H. , Lundberg A. K. , Gullstrand B. , Bengtsson A. A. , Schiopu A. 
Published: December 2017

AbstractPsychological stress is thought to be an important trigger of cardiovascular events, yet the involved pathways and mediators are largely unknown. Elevated systemic levels of the pro-inflammatory alarmin S100A8/A9 correlate with poor prognosis in coronary artery disease (CAD) patients. Here, we investigated the links between S100A8/A9 release and parameters of anti-inflammatory glucocorticoid secretion in two different cohorts subjected to a psychological stress test. In the first cohort of 60 CAD patients, psychological stress induced a rapid increase of circulating S100A8/A9. This rapid S100A8/A9 response strongly correlated with elevated evening saliva cortisol levels, suggesting an association with a dysregulated hypothalamic–pituitary–adrenal (HPA) axis. In the second cohort of 27 CAD patients and 28 controls, elevated S100A8/A9 levels were still detectable 24 h after stress in 40% of patients and 36% of controls, with a tendency for higher levels in patients. The sustained S100A8/A9 response was associated with a poor rapid cortisol release after stress in patients, but not in the control group. Our findings reveal for the first time that acute psychological stress induces elevated levels of S100A8/A9. We also provide hypothesis-generating evidence that dysregulated cortisol secretion in CAD patients might be associated with an exaggerated pro-inflammatory S100A8/A9 response.
Comprehensive analysis of the catalytic and structural properties of a mu-class glutathione s-transferase from Fasciola gigantica
Authors: Kalita Jupitara , Shukla Rohit , Shukla Harish , Gadhave Kundlik , Giri Rajanish , Tripathi Timir 
Published: December 2017

AbstractGlutathione S‒transferases (GSTs) play an important role in the detoxification of xenobiotics. They catalyze the nucleophilic addition of glutathione (GSH) to nonpolar compounds, rendering the products water-soluble. In the present study, we investigated the catalytic and structural properties of a mu-class GST fromFasciola gigantica(FgGST1). The purified recombinant FgGST1 formed a homodimer composed of 25 kDa subunit. Kinetic analysis revealed that FgGST1 displays broad substrate specificity and shows high GSH conjugation activity toward 1-chloro-2,4-dinitrobenzene, 4-nitroquinoline-1-oxide, and trans-4-phenyl-3-butene-2-one and peroxidase activity towards trans-2-nonenal and hexa-2,4-dienal. The FgGST1 was highly sensitive to inhibition by cibacron blue. The cofactor (GSH) and inhibitor (cibacron blue) were docked, and binding sites were identified. The molecular dynamics studies and principal component analysis indicated the stability of the systems and the collective motions, respectively. Unfolding studies suggest that FgGST1 is a highly cooperative molecule because, during GdnHCl-induced denaturation, a simultaneous unfolding of the protein without stabilization of any partially folded intermediate is observed. The protein is stabilized with a conformational free energy of about 10 ± 0.3 kcal mol−1. Additionally, the presence of conserved Pro-53 and structural motifs such as N-capping box and hydrophobic staple, further aided in the stability and proper folding of FgGST1.
Production of lignin based insoluble polymers (anionic hydrogels) by C. versicolor
Authors: Brzonova Ivana , Kozliak Evguenii I. , Andrianova Anastasia A. , LaVallie Audrey , Kubátová Alena , Ji Yun 
Published: December 2017

AbstractUnlike previous lignin biodegradation studies, white rot fungi were used to produce functional biopolymers from Kraft lignin. Lignin-based polymers (hydrogel precursors) partially soluble in both aqueous and organic solvents were produced employing a relatively fast (6 days) enzymation of Kraft lignin with basidiomycetes, primarily Coriolus versicolor, pre-grown on kenaf/lignin agar followed by either vacuum evaporation or acid precipitation. After drying followed by a treatment with alkaline water, this intermediate polymer became a pH-sensitive anionic hydrogel insoluble in either aqueous or organic solvents. The yield of this polymer increased from 20 to 72 wt% with the addition of 2% dimethylsulfoxide to distilled water used as a medium. The mechanical stability and buffering capacity of this hydrogel can be adjusted by washing the intermediate polymer/hydrogel precursor prior to drying with solvents of different polarity (water, methanol or ethanol). Any of these polymers featured a significant thermal resilience assessed as a high thermostable “coked” fraction in thermal carbon analysis, apparently resulting from significant covalent cross-linking that occurs during the treatment of their intermediate precursors.
Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium
Authors: Yüksel Esra , Nazıroğlu Mustafa , Şahin Mehmet , Çiğ Bilal 
Published: December 2017

AbstractFibromyalgia (FM) results in pain characterized by low selenium (Se) levels, excessive Ca2+ influx, reactive oxygen species (ROS) production, and acidic pH. TRPM2 and TRPV1 are activated by ROS and acid; nevertheless, their roles have not been elucidated in FM. Therefore, we investigated the contribution of TRPM2 and TRPV1 to pain, oxidative stress, and apoptosis in a rat model of FM and the therapeutic potential of Se. Thirty-six rats were divided into four groups: control, Se, FM, and FM + Se. The Se treatment reduced the FM-induced increase in TRPM2 and TRPV1 currents, pain intensity, intracellular free Ca2+, ROS, and mitochondrial membrane depolarization in the sciatic (SciN) and dorsal root ganglion (DRGN) neurons. Furthermore, Se treatment attenuated the FM-induced decrease in cell viability in the DRGN and SciN, glutathione peroxidase, and reduced glutathione and α-tocopherol values in the DRGN, SciN, brain, muscle, and plasma; however, lipid peroxidation levels were decreased. Se also attenuated PARP1, caspase 3, and 9 expressions in the SciN, DRGN, and muscle. In conclusion, Se treatment decreased the FM-induced increase in hyperalgesia, ROS, apoptosis, and Ca2+ entry through TRPM2 and TRPV1 in the SciN and DRGN. Our findings may be relevant to the elucidation and treatment of FM.
Blood-Brain Glucose Transfer in Alzheimer’s disease: Effect of GLP-1 Analog Treatment
Authors: Gejl Michael , Brock Birgitte , Egefjord Lærke , Vang Kim , Rungby Jørgen , Gjedde Albert 
Published: December 2017

AbstractThere are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer’s disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD to treatment with liraglutide (n = 18) or placebo (n = 20) for 6 months, and determined the blood-brain glucose transfer capacity (Tmax) in the two groups and a healthy age matched control group (n = 6). In both AD groups at baseline, Tmax estimates correlated inversely with the duration of AD, as did the estimates of CMRglc that in turn were positively correlated with cognition. The GLP-1 analog treatment, compared to placebo, highly significantly raised the Tmax estimates of cerebral cortex from 0.72 to 1.1 umol/g/min, equal to Tmax estimates in healthy volunteers. The result is consistent with the claim that GLP-1 analog treatment restores glucose transport at the BBB.
Identification of MYLK3 mutations in familial dilated cardiomyopathy
Authors: Tobita Takashige , Nomura Seitaro , Morita Hiroyuki , Ko Toshiyuki , Fujita Takanori , Toko Haruhiro , Uto Kenta , Hagiwara Nobuhisa , Aburatani Hiroyuki , Komuro Issei 
Published: December 2017

AbstractDilated cardiomyopathy (DCM) is a primary cause of heart failure, life-threatening arrhythmias, and cardiac death. Pathogenic mutations have been identified at the loci of more than 50 genes in approximately 50% of DCM cases, while the etiologies of the remainder have yet to be determined. In this study, we applied whole exome sequencing in combination with segregation analysis to one pedigree with familial DCM, and identified a read-through mutation (c.2459 A > C; p.*820Sext*19) in the myosin light chain kinase 3 gene (MYLK3). We then conducted MYLK3 gene screening of 15 DCM patients (7 familial and 8 sporadic) who were negative for mutation screening of the previously-reported cardiomyopathy-causing genes, and identified another case with a MYLK3 frameshift mutation (c.1879_1885del; p.L627fs*41). In vitro experiments and immunohistochemistry suggested that the MYLK3 mutations identified in this study result in markedly reduced levels of protein expression and myosin light chain 2 phosphorylation. This is the first report that MYLK3 mutations can cause DCM in humans. The clinical phenotypes of DCM patients were consistent with MYLK3 loss-of-function mouse and zebrafish models in which cardiac enlargement and heart failure are observed. Our findings highlight an essential role for cardiac myosin light chain kinase in the human heart.
Biodegradable Bisvinyl Sulfonemethyl-crosslinked Gelatin Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats
Authors: Ko Chien-Hsin , Shie Ming-You , Lin Jia-Horng , Chen Yi-Wen , Yao Chun-Hsu , Chen Yueh-Sheng 
Published: December 2017

AbstractIn our previous study, we found that gelatin-based materials exhibit good conductivity and are non-cytotoxic. In this study, gelatin was cross-linked with bisvinyl sulfonemethyl (BVSM) to fabricate a biodegradable conduit for peripheral nerve repair. First, BVSM on the prepared conduit was characterized to determine its mechanical properties and contact angle. The maximum tensile strength and water contact angle of the gelatin-BVSM conduits were 23 ± 4.8 MPa and 74.7 ± 9°, which provided sufficient mechanical strength to resist muscular contraction; additionally, the surface was hydrophilic. Cytotoxicity and apoptosis assays using Schwann cells demonstrated that the gelatin-BVSM conduits are non-cytotoxic. Next, we examined the neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide localization and expression, as well as the expression levels of nerve regeneration-related proteins. The number of fluorogold-labelled cells and histological analysis of the gelatin-BVSM nerve conduits was similar to that observed with the clinical use of silicone rubber conduits after 8 weeks of repair. Therefore, our results demonstrate that gelatin-BVSM conduits are promising substrates for application as bioengineered grafts for nerve tissue regeneration.
A generic standard additions based method to determine endogenous analyte concentrations by immunoassays to overcome complex biological matrix interference
Authors: Pang Susan , Cowen Simon 
Published: December 2017

AbstractWe describe a novel generic method to derive the unknown endogenous concentrations of analyte within complex biological matrices (e.g. serum or plasma) based upon the relationship between the immunoassay signal response of a biological test sample spiked with known analyte concentrations and the log transformed estimated total concentration. If the estimated total analyte concentration is correct, a portion of the sigmoid on a log-log plot is very close to linear, allowing the unknown endogenous concentration to be estimated using a numerical method. This approach obviates conventional relative quantification using an internal standard curve and need for calibrant diluent, and takes into account the individual matrix interference on the immunoassay by spiking the test sample itself. This technique is based on standard additions for chemical analytes. Unknown endogenous analyte concentrations within even 2-fold diluted human plasma may be determined reliably using as few as four reaction wells.
Leveraging ectopic Hsp90 expression to assay the presence of tumor cells and aggressive tumor phenotypes in breast specimens
Authors: Crouch Brian , Murphy Helen , Belonwu Stella , Martinez Amy , Gallagher Jennifer , Hall Allison , Soo Mary Scott , Lee Marianne , Hughes Philip , Haystead Timothy , Ramanujam Nirmala 
Published: December 2017

AbstractHsp90 has been studied extensively as a therapeutic target in breast cancer in pre-clinical and clinical trials, demonstrating a variety of roles in metastatic progression. The evidence to date suggests a compelling opportunity to leverage attributes of Hsp90 expression beyond therapeutics with potential applications in breast cancer diagnosis, prognosis, and recurrence risk assessment. In this study, we developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay Hsp90 expression on intact tissue specimens with comparable contrast to in vivo administration routes, and demonstrate the feasibility of our approach in breast cancer patients. In addition to Hsp90 inhibition being most effective in glycolytic tumors, we found ectopic Hsp90 expression to be highest in glycolytic tumors reinforcing its role as an indicator of aggressive disease. This work sets the stage for immediately using Hsp90 to improve outcomes for breast cancer patients without affecting traditional care pathways.