bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-disease analysis of Alzheimer’s disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases
Authors: Caberlotto Laura , Nguyen T.-Phuong , Lauria Mario , Priami Corrado , Rimondini Roberto , Maioli Silvia , Cedazo-Minguez Angel , Sita Giulia , Morroni Fabiana , Corsi Mauro , Carboni Lucia 
Published: March 2019

AbstractEvidence is accumulating that the main chronic diseases of aging Alzheimer’s disease (AD) and type-2 diabetes mellitus (T2DM) share common pathophysiological mechanisms. This study aimed at applying systems biology approaches to increase the knowledge of the shared molecular pathways underpinnings of AD and T2DM. We analysed transcriptomic data of post-mortem AD and T2DM human brains to obtain disease signatures of AD and T2DM and combined them with protein-protein interaction information to construct two disease-specific networks. The overlapping AD/T2DM network proteins were then used to extract the most representative Gene Ontology biological process terms. The expression of genes identified as relevant was studied in two AD models, 3xTg-AD and ApoE3/ApoE4 targeted replacement mice. The present transcriptomic data analysis revealed a principal role for autophagy in the molecular basis of both AD and T2DM. Our experimental validation in mouse AD models confirmed the role of autophagy-related genes. Among modulated genes, Cyclin-Dependent Kinase Inhibitor 1B, Autophagy Related 16-Like 2, and insulin were highlighted. In conclusion, the present investigation revealed autophagy as the central dys-regulated pathway in highly co-morbid diseases such as AD and T2DM allowing the identification of specific genes potentially involved in disease pathophysiology which could become novel targets for therapeutic intervention.
Bcl-xL inhibition enhances Dinaciclib-induced cell death in soft-tissue sarcomas
Authors: Rello-Varona Santi , Fuentes-Guirado Miriam , López-Alemany Roser , Contreras-Pérez Aida , Mulet-Margalef Núria , García-Monclús Silvia , Tirado Oscar M. , García del Muro Xavier 
Published: March 2019

AbstractSoft-tissue sarcomas (STS) are an uncommon and heterogeneous group of malignancies that result in high mortality. Metastatic STS have very bad prognosis due to the lack of effective treatments. Dinaciclib is a model drug for the family of CDK inhibitors. Its main targets are cell cycle regulator CDK1 and protein synthesis controller CDK9. We present data supporting Dinaciclib ability to inactivate in vitro different STS models at nanomolar concentrations. Moreover, the different rhythms of cell death induction allow us to further study into the mechanism of action of the drug. Cell death was found to respond to the mitochondrial pathway of apoptosis. Anti-apoptotic Bcl-xL was identified as the key regulator of this process. Already natural low levels of pro-apoptotic proteins BIM and PUMA in tolerant cell lines were insufficient to inhibit Bcl-xL as this anti-apoptotic protein showed a slow decay curve after Dinaciclib-induced protein synthesis disruption. Combination of Dinaciclib with BH3-mimetics led to quick and massive apoptosis induction in vitro, but in vivo assessment was prevented due to liver toxicity. Additionally, Bcl-xL inhibitor A-1331852 also synergized with conventional chemotherapy drugs as Gemcitabine. Thus, Bcl-xL targeted therapy arises as a major opportunity to the treatment of STS.
Provisional Tic Disorder is not so transient
Authors: Kim Soyoung , Greene Deanna J. , Bihun Emily C. , Koller Jonathan M. , Hampton Jacqueline M. , Acevedo Haley , Reiersen Angela M. , Schlaggar Bradley L. , Black Kevin J. 
Published: March 2019

AbstractMotor and vocal tics are common in childhood. The received wisdom among clinicians is that for most children the tics are temporary, disappearing within a few months. However, that common clinical teaching is based largely on biased and incomplete data. The present study was designed to prospectively assess outcome of children with what the current nomenclature calls Provisional Tic Disorder. We identified 43 children with recent onset tics (mean 3.3 months since tic onset) and re-examined 39 of them on the 12-month anniversary of their first tic. Tic symptoms improved on a group level at the 12-month follow-up, and only two children had more than minimal impairment due to tics. Remarkably, however, tics were present in all children at follow-up, although in several cases tics were apparent only when the child was observed remotely by video. Our results suggest that remission of Provisional Tic Disorder is the exception rather than the rule. We also identified several clinical features present at the first examination that predict one-year outcome; these include baseline tic severity, subsyndromal autism spectrum symptoms, and the presence of an anxiety disorder.
Toxicity and neurophysiological impacts of plant essential oil components on bed bugs (Cimicidae: Hemiptera)
Authors: Gaire Sudip , Scharf Michael E. , Gondhalekar Ameya D. 
Published: March 2019

AbstractBed bugs (Cimex lectulariusL.) are globally important human parasites. Integrated pest management (IPM) approaches, which include the use of essential oil-based insecticidal compounds, have been proposed for their control. This study aimed to define insecticidal activity and neurophysiological impacts of plant essential oil constituents. The topical and fumigant toxicity of 15 compounds was evaluated against adult male bed bugs. Neurological effects of the 6 most toxicologically active compounds were also determined. In both topical and fumigant bioassays, carvacrol and thymol were the most active compounds. The potency of bifenthrin (a pyrethroid insecticide) in topical bioassays was 72,000 times higher than carvacrol, while vapors of dichlorvos (an organophosphate insecticide) were 445 times more potent than thymol. Spontaneous electrical activity measurements of the bed bug nervous system demonstrated neuroinhibitory effects of carvacrol, thymol and eugenol, whereas linalool produced an excitatory effect. Although citronellic acid and (±)-camphor increased baseline activity of the nervous system their effects were not statistically significant. Bifenthrin also caused neuroexcitation, which is consistent with its known mode of action. These comparative toxicity and neurological impact findings provide new information for formulating effective essential oil-based insecticides for bed bug IPM and conducting mode-of-action studies on individual essential oil components.
Daiokanzoto (Da-Huang-Gan-Cao-Tang) is an effective laxative in gut microbiota associated with constipation
Authors: Takayama Kento , Takahara Chiho , Tabuchi Norihiko , Okamura Nobuyuki 
Published: March 2019

AbstractInterindividual differences affect the purgative activities of sennoside A (SA) and Daiokanzoto (Da-Huang-Gan-Cao-Tang, DKT). In this study, we manipulated gut microbiota in mice to establish laxative responders and non-responders by feeding them a high-carbohydrate, a high-fat or a high-fibre diet. To assess the relationship between laxatives and gut microbiota, we monitored the gut microbiota before and after administering laxatives. Twenty mice per diet were divided into four groups of five mice to evaluate purgative activities of four laxative preparations, DKT, SA, SA plus rhein 8-O-β-D-glucopyranoside (SA + RG), and SA plus liquiritin (SA + LQ). Gut microbiota changes were monitored by next-generation sequencing of 16 S rRNA gene amplicons. In high-carbohydrate and high-fat diet-fed mice, DKT exerted a significantly higher purgative activity than SA alone, and RG contributed to this activity. DKT and SA + RG administration increased the Enterobacteriaceae content of gut microbiota, which was associated with an increased purgative activity. In contrast, DKT activity was significantly suppressed by high-fibre diet. Hence, diet-induced differences in gut microbiota determined the effect of DKT, which is interesting, considering that Oriental medicines are formulated for a specific functional state or “pattern”. These results demonstrated that the purgative activity of anthranoid laxatives is susceptible to diet-induced alterations in gut microbiota.
Solid-phase synthesis of molecularly imprinted polymer nanolabels: Affinity tools for cellular bioimaging of glycans
Authors: Medina Rangel Paulina X. , Laclef Sylvain , Xu Jingjing , Panagiotopoulou Maria , Kovensky José , Tse Sum Bui Bernadette , Haupt Karsten 
Published: March 2019

AbstractHyaluronic acid (HA) is a glycosaminoglycan that plays many roles in health and disease and is a key biomarker of certain cancers. Therefore, its detection at an early stage, by histochemical methods, is of importance. However, intracellular HA can be masked by other HA-binding macromolecules, rendering its visualization somehow problematic. We show that fluorescent molecularly imprinted polymer nanogels (MIP-NPs), can localize and detect intracellular HA. MIP-NPs were synthesized by solid-phase synthesis on glass beads (GBs). GBs were functionalized with terminal alkyne groups on which an azide derivative of the template molecule glucuronic acid was immobilized via click chemistry. Immobilization via the anomeric carbon left the template’s carboxyl moiety free to enable strong stoichiometric electrostatic interactions with a benzamidine-based functional monomer, to confer selective recognition to the MIP-NPs. Due to the two-point orientation of the template, the resulting MIP-NPs were endowed with improved binding site homogeneity and specificity, reminiscent of monoclonal antibodies. These synthetic antibodies were then applied for probing and staining HA, of which glucuronic acid is a substructure (epitope), on human epidermal cells. Their excellent sensitivity, small size and water compatibility, enabled the MIP-NPs to visualize HA, as evidenced by confocal fluorescence micrographs.
The prevalence of nonlinearity and detection of ecological breakpoints across a land use gradient in streams
Authors: D’Amario Sarah C. , Rearick Daniel C. , Fasching Christina , Kembel Steven W. , Porter-Goff Emily , Spooner Daniel E. , Williams Clayton J. , Wilson Henry F. , Xenopoulos Marguerite A. 
Published: March 2019

AbstractHuman activities can alter aquatic ecosystems through the input of nutrients and carbon, but there is increasing evidence that these pressures induce nonlinear ecological responses. Nonlinear relationships can contain breakpoints where there is an unexpected change in an ecological response to an environmental driver, which may result in ecological regime shifts. We investigated the occurrence of nonlinearity and breakpoints in relationships between total dissolved nitrogen (TDN), total dissolved phosphorus (TDP), and total dissolved carbon (DOC) concentrations and ecological responses in streams with varying land uses. We calculated breakpoints using piecewise regression, two dimensional Kolmogorov-Smirnov (2DKS), and significant zero crossings (SiZer) methods. We found nonlinearity was common, occurring in half of all analyses, with some evidence of multiple breakpoints. Linearity, by contrast, occurred in less than 14% of cases, on average. Breakpoints were related to land use gradients, with 34–43% agricultural cover associated with DOC and TDN breakpoints, and 15% wetland and 9.5% urban land associated with DOC and nutrient breakpoints, respectively. While these breakpoints are likely specific to our study area, our study contributes to the growing literature of the prevalence and location of ecological breakpoints in streams, providing watershed managers potential criteria for catchment land use thresholds.
Ultra-dense (~20 Tdot/in2) nanoparticle array from an ordered supramolecular dendrimer containing a metal precursor
Authors: Kwon Kiok , Suh Bong Lim , Park Kangho , Kim Jihan , Jung Hee-Tae 
Published: March 2019

AbstractThe fabrication of an ultra-dense, highly periodic nanoparticle array from a soft template is one of the most important issues in the fields of material science and nanotechnology. To date, block copolymer (BCP) structures have been primarily used as templates for fabricating highly periodic nanoparticle arrays with high areal densities. Herein, we demonstrate for the first time the use of a supramolecular dendrimer assembly for the formation of a highly ordered nanoparticle array with a high areal density of ~20 Tdot/in2, four times larger than that of the currently reported BCP-based nanoparticle arrays. By the simple thermal annealing of a dendrimers containing a metal precursor between two flat, solid substrates, a hexagonal array of small gold nanoparticles (with a diameter of ~1.6 nm and center-to-center distance of ~5.3 nm), oriented normal to the bottom, was achieved. Density functional theory calculations demonstrated that the gold cation strongly bound to the head group of the dendrimer. This structure served as a building block for self-assembly into a stable cylindrical structure. We anticipate that this study will lead to the creation of a large family of supramolecular dendrimers that can be utilized as soft templates for creating periodic, ultra-dense nanoparticle arrays.
Previously published drug interaction models predict loss of response for transoesophageal echocardiography sedation well but not response to oesophageal instrumentation
Authors: Su Fu-Wei , Ting Chien-Kun , Liou Jing-Yang , Chen Yi-Chang , Tsou Mei-Yung , Wang Shen-Chih 
Published: March 2019

AbstractResponse surface models (RSMs) were used to predict effects of multiple drugs interactions. Our study was aimed to validate accuracy of the previous published volunteer models during transoesophageal echocardiography (TEE). This is a cross-sectional study with 20 patients scheduled for transesophageal echocardiography in Taipei Veterans General Hospital, Taiwan. Effect-site concentration pairs of alfentanil and propofol were recorded and converted to equivalent remifentanil and propofol effect-site concentrations. Observer’s Assessment of Alertness/Sedation (OAA/S) scores were assessed every 2 minutes. Using these data, previous published models of loss of response (LOR), intolerable ventilatory depression (IVD), and loss of response to esophageal instrumentation (LREI) were then estimated. Accuracy of prediction is assessed by calculating the difference between the true response and the model-predicted probability. Clinical events such as interruption of TEE were recorded. The average procedure time was 11 minutes. Accuracy for prediction of LOR and LREI is 63.6% and 38.5%, respectively. There were four patients experienced desaturation for less than 1 minute, which were not predicted by IVD model, and one interruption of TEE due to involuntary movement. The previous published drug-interaction RSMs predict LOR well but not LREI for TEE sedation. Further studies using response surface methodology are needed to improve quality for TEE sedation and clinical implementation.
Risk Factors and Outcomes of Choroidal Neovascularization Secondary to Central Serous Chorioretinopathy
Authors: Lee Ga-In , Kim A. Young , Kang Se Woong , Cho Soo Chang , Park Kyu Hyung , Kim Sang Jin , Kim Kyung Tae 
Published: March 2019

AbstractWe identified clinical characteristics and risk factors of choroidal neovascularization (CNV) in eyes with prior episode of central serous chorioretinopathy (CSC). This retrospective case-control study included those initially diagnosed with CSC and developed CNV secondarily (Group 1, n = 16), those diagnosed with CNV in eyes of previous putative CSC (Group 2, n = 14), and those initially diagnosed with CSC, and did not develop CNV secondarily, as a control group for Group 1 (Group 3, n = 250). Clinical characteristics including treatment outcomes were assessed. Demographics and multimodal imaging at the time of CSC diagnosis of secondary CNV were compared between the groups to identify risk factors. Duration from diagnosis of CSC to development of CNV in Group 1 was 40.2 ± 42.0 months. Classic CNV was noted in 23 (76.7%) eyes. After treatment with intravitreal antiangiogenics with average of 4.9 times, visual acuity improved in Group 1 and Group 2 (p = 0.002). Multivariate analysis revealed that systemic hypertension, pigmentary changes, and double layer sign were associated with development of CNV secondary to CSC (p < 0.05). Hypertension, pigmentary changes, and double layer sign were independent risk factors for CNV secondary to CSC. The CNV’s responded well to treatment, resulting in improved vision.
Key role of excess atomic volume in structural rearrangements at the front of moving partial dislocations in copper nanocrystals
Authors: Psakhie S. G. , Zolnikov K. P. , Kryzhevich D. S. , Korchuganov A. V. 
Published: March 2019

AbstractHere we report on a molecular dynamics simulation of the atomic volume distribution in fcc copper with moving partial dislocations 1/6 〈112〉 {111}. The simulation shows that the leading and trailing partial dislocations surrounding a stacking fault move via local fcc→hcp and hcp→fcc transformations and that a fcc–hcp transition zone exists in which the atomic volume is larger than that in the perfect close-packed structure. The excess volume is five to seven percent, which compares with volume jumps on melting. The simulation results agree with experimental data showing that the nucleation of dislocations is preceded by the formation of regions with an excess atomic volume.
Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride
Authors: Takizawa Hotake , Hara Yuko , Mizobe Yoshitaka , Ohno Taisuke , Suzuki Sadafumi , Inoue Ken , Takeshita Eri , Shimizu-Motohashi Yuko , Ishiyama Akihiko , Hoshino Mikio , Komaki Hirofumi , Takeda Shin’ichi , Aoki Yoshitsugu 
Published: March 2019

AbstractDuchenne muscular dystrophy (DMD) is a severe muscle disorder characterised by mutations in the DMD gene. Recently, we have completed a phase I study in Japan based on systemic administration of the morpholino antisense that is amenable to exon-53 skipping, successfully. However, to achieve the effective treatment of DMD, in vitro assays on patient muscle cells to screen drugs and patient eligibility before clinical trials are indispensable. Here, we report a novel MYOD1-converted, urine-derived cells (UDCs) as a novel DMD muscle cell model. We discovered that 3-deazaneplanocin A hydrochloride, a histone methyltransferase inhibitor, could significantly promote MYOGENIN expression and myotube differentiation. We also demonstrated that our system, based on UDCs from DMD patients, could be used successfully to evaluate exon-skipping drugs targeting DMD exons including 44, 50, 51, and 55. This new autologous UDC-based disease modelling could lead to the application of precision medicine for various muscle diseases.
Higher ventricular rate during atrial fibrillation relates to increased cerebral hypoperfusions and hypertensive events
Authors: Saglietto Andrea , Scarsoglio Stefania , Ridolfi Luca , Gaita Fiorenzo , Anselmino Matteo 
Published: March 2019

AbstractAtrial fibrillation (AF) is associated with cognitive impairment/dementia, independently of clinical cerebrovascular events (stroke/TIA). One of the plausible mechanisms is the occurrence of AF-induced transient critical hemodynamic events; however, it is presently unknown, if ventricular response rate during AF may impact on cerebral hemodynamics. AF was simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) by two coupled lumped parameter validated models (systemic and cerebral circulation), and compared to corresponding control normal sinus rhythm simulations (NSR). Hemodynamic outcomes and occurrence of critical events (hypoperfusions and hypertensive events) were assessed along the internal carotid artery-middle cerebral artery pathway up to the capillary-venous bed. At the distal cerebral circle level (downstream middle cerebral artery), increasing ventricular rates lead to a reduced heart rate-related dampening of hemodynamic signals compared to NSR (p = 0.003 and 0.002 for flow rate and pressure, respectively). This response causes a significant progressive increase in critical events in the distal cerebral circle (p < 0.001) as ventricular rate increases during AF. On the other side, at the lowest ventricular response rates (HR 50 bpm), at the systemic-proximal cerebral circle level (up to middle cerebral artery) hypoperfusions (p < 0.001) occur more commonly, compared to faster AF simulations. This computational study suggests that higher ventricular rates relate to a progressive increase in critical cerebral hemodynamic events (hypoperfusions and hypertensive events) at the distal cerebral circle. Thus, a rate control strategy aiming to around 60 bpm could be beneficial in terms on cognitive outcomes in patients with permanent AF.
Fast spectrally encoded Mueller optical scanning microscopy
Authors: Rivet Sylvain , Dubreuil Matthieu , Bradu Adrian , Le Grand Yann 
Published: March 2019

AbstractMueller microscopes enable imaging of the optical anisotropic properties of biological or non-biological samples, in phase and amplitude, at sub-micrometre scale. However, the development of Mueller microscopes poses an instrumental challenge: the production of polarimetric parameters must be sufficiently quick to ensure fast imaging, so that the evolution of these parameters can be visualised in real-time, allowing the operator to adjust the microscope while constantly monitoring them. In this report, a full Mueller scanning microscope based on spectral encoding of polarization is presented. The spectrum, collected every 10 μs for each position of the optical beam on the specimen, incorporates all the information needed to produce the full Mueller matrix, which allows simultaneous display of all the polarimetric parameters, at the unequalled rate of 1.5 Hz (for an image of 256 × 256 pixels). The design of the optical blocks allows for the real-time display of linear birefringent images which serve as guidance for the operator. In addition, the instrument has the capability to easily switch its functionality from a Mueller to a Second Harmonic Generation (SHG) microscope, providing a pixel-to-pixel matching of the images produced by the two modalities. The device performance is illustrated by imaging various unstained biological specimens.
Development of an inducible lytic system for functional metagenomic screening
Authors: Cárcel-Márquez Jara , Flores Amando , Martín-Cabello Guadalupe , Santero Eduardo , Camacho Eva M. 
Published: March 2019

AbstractFunctional metagenomic is a powerful tool that allows the discovery of new enzymes with biotechnological potential. During functional screenings of enzymes, the ability of the substrate to enter the surrogate host or the ability of this bacterium to export heterologous extracellular enzymes may hamper the technique. Here we have used an inducible autolysis system that lyses bacteria thus releasing its content in both, liquid and solid cultures, in response to anhydrotetracycline. The lytic cluster is tightly regulated to prevent impaired bacterial growth in absence of the inducer and produced very efficient though not complete bacterial lysis upon induction, which allowed the recovery of live bacteria. The system can be used in combination with specialised fosmids and E. coli strains that maximize transcription of metagenomic DNA. Our results show that colony-lysis on plates allows detection of an endogenous intracellular amylase activity naturally present in E. coli and clearly increased detection of clones coding for cellulase activities in a metagenomic screening, while allowing recovery of survivor positive clones from the lysed colonies in all cases. Therefore, this tool represents an important step towards the effective access to the extraordinary potential of the uncultivated bacteria genetic resources.