bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOXP3 inhibits angiogenesis by downregulating VEGF in breast cancer
Authors: Li Xiaoju , Gao Yuan , Li Jialin , Zhang Kuo , Han Jun , Li Weina , Hao Qiang , Zhang Wangqian , Wang Shuning , Zeng Cheng , Zhang Wei , Zhang Yingqi , Li Meng , Zhang Cun 
Published: July 2018

AbstractForkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer angiogenesis remain unclear. Here we found that the clinical expression of nuclear FOXP3 was inversely correlated with breast cancer angiogenesis. Moreover, the animal study demonstrated that FOXP3 significantly reduced the microvascular density of MDA-MB-231 tumors transplanted in mice. The cytological experiments showed that the supernatant from FOXP3-overexpressing cells exhibited a diminished ability to stimulate tube formation and sprouting in HUVECs in vitro. In addition, expression of vascular endothelial growth factor (VEGF) was downregulated by FOXP3 in breast cancer cell lines. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that FOXP3 can directly interact with the VEGF promoter via specific forkhead-binding motifs to suppress its transcription. Importantly, the inhibitory effects of FOXP3 in the supernatant on tube formation and sprouting in HUVECs could be reversed by adding VEGF in vitro. Nuclear FOXP3 expression was inversely correlated with VEGF expression in clinical breast cancer tissues, and FOXP3 downregulation and VEGF upregulation were both correlated with reduced survival in breast cancer data sets in the Kaplan–Meier plotter. Taken together, our data demonstrate that FOXP3 suppresses breast cancer angiogenesis by downregulating VEGF expression.
AAV vector-mediated in vivo reprogramming into pluripotency
Authors: Senís Elena , Mosteiro Lluc , Wilkening Stefan , Wiedtke Ellen , Nowrouzi Ali , Afzal Saira , Fronza Raffaele , Landerer Henrik , Abad Maria , Niopek Dominik , Schmidt Manfred , Serrano Manuel , Grimm Dirk 
Published: July 2018

AbstractIn vivo reprogramming of somatic cells into induced pluripotent stem cells (iPSC) holds vast potential for basic research and regenerative medicine. However, it remains hampered by a need for vectors to express reprogramming factors (Oct-3/4, Klf4, Sox2, c-Myc; OKSM) in selected organs. Here, we report OKSM delivery vectors based on pseudotyped Adeno-associated virus (AAV). Using the AAV-DJ capsid, we could robustly reprogram mouse embryonic fibroblasts with low vector doses. Swapping to AAV8 permitted to efficiently reprogram somatic cells in adult mice by intravenous vector delivery, evidenced by hepatic or extra-hepatic teratomas and iPSC in the blood. Notably, we accomplished full in vivo reprogramming without c-Myc. Most iPSC generated in vitro or in vivo showed transcriptionally silent, intronic or intergenic vector integration, likely reflecting the increased host genome accessibility during reprogramming. Our approach crucially advances in vivo reprogramming technology, and concurrently facilitates investigations into the mechanisms and consequences of AAV persistence.
The effectiveness of virtual reality based interventions for symptoms of anxiety and depression: A meta-analysis
Authors: Fodor Liviu A. , Coteț Carmen D. , Cuijpers Pim , Szamoskozi Ștefan , David Daniel , Cristea Ioana A. 
Published: July 2018

AbstractWe report a meta-analysis of virtual reality (VR) interventions for anxiety and depression outcomes, as well as treatment attrition. We included randomized controlled trials comparing VR interventions, alone or in combination, to control conditions or other active psychological interventions. Effects sizes (Hedges’ g) for anxiety and depression outcomes, as post-test and follow-up, were pooled with a random-effects model. Drop-outs were compared using odds ratio (OR) with a Mantel-Haenszel model. We included 39 trials (52 comparisons). Trial risk of bias was unclear for most domains, and high for incomplete outcome data. VR-based therapies were more effective than control at post-test for anxiety, g = 0.79, 95% CI 0.57 to 1.02, and depression, g = 0.73, 95% CI 0.25 to 1.21, but not for treatment attrition, OR = 1.34, 95% CI 0.95 to 1.89. Heterogeneity was high and there was consistent evidence of small study effects. There were no significant differences between VR-based and other active interventions. VR interventions outperformed control conditions for anxiety and depression but did not improve treatment drop-out. High heterogeneity, potential publication bias, predominant use of waitlist controls, and high or uncertain risk of bias of most trials question the reliability of these effects.
Mass Cytometry Reveals Distinct Platelet Subtypes in Healthy Subjects and Novel Alterations in Surface Glycoproteins in Glanzmann Thrombasthenia
Authors: Blair Thomas A. , Michelson Alan D. , Frelinger Andrew L. 
Published: July 2018

AbstractMass cytometry (MC) uses mass spectrometry to simultaneously detect multiple metal-conjugated antibodies on single cells, thereby enabling the detailed study of cellular function. Here, for the first time, we applied MC to the analysis of platelets. We developed a panel of 14 platelet-specific metal-tagged antibodies (targeting cluster of differentiation [CD] 9, CD29, CD31, CD36, CD41, CD42a, CD42b, CD61, CD62P, CD63, CD107a, CD154, glycoprotein [GP] VI and activated integrin αIIbβ3) and compared this panel with two fluorescence flow cytometry (FFC) panels (CD41, CD42b, and CD61; or CD42b, CD62P, and activated integrin αIIbβ3) in the evaluation of activation-dependent changes in glycoprotein expression on healthy subject and Glanzmann thrombasthenia (GT) platelets. High-dimensional analysis of surface markers detected by MC identified previously unappreciated subpopulations of platelets in healthy donors. As expected, MC and FFC revealed that GT platelets had significantly reduced CD41, CD61, and activated integrin αIIbβ3 surface expression. MC also revealed that surface expression of CD9, CD42a and CD63 were elevated, CD31, CD154 and GPVI were reduced and CD29, CD36, CD42b, CD62P and CD107a were similar on GT platelets compared to healthy donor platelets. In summary, MC revealed distinct platelet subtypes in healthy subjects and novel alterations in surface glycoproteins on GT platelets.
Lateral optical confinement of GaN-based VCSEL using an atomically smooth monolithic curved mirror
Authors: Hamaguchi Tatsushi , Tanaka Masayuki , Mitomo Jugo , Nakajima Hiroshi , Ito Masamichi , Ohara Maho , Kobayashi Noriko , Fujii Kentaro , Watanabe Hideki , Satou Susumu , Koda Rintaro , Narui Hironobu 
Published: July 2018

AbstractWe demonstrate the lateral optical confinement of GaN-based vertical-cavity surface-emitting lasers (GaN-VCSELs) with a cavity containing a curved mirror that is formed monolithically on a GaN wafer. The output wavelength of the devices is 441–455 nm. The threshold current is 40 mA (Jth = 141 kA/cm2) under pulsed current injection (Wp = 100 ns; duty = 0.2%) at room temperature. We confirm the lateral optical confinement by recording near-field images and investigating the dependence of threshold current on aperture size. The beam profile can be fitted with a Gaussian having a theoretical standard deviation of σ = 0.723 µm, which is significantly smaller than previously reported values for GaN-VCSELs with plane mirrors. Lateral optical confinement with this structure theoretically allows aperture miniaturization to the diffraction limit, resulting in threshold currents far lower than sub-milliamperes. The proposed structure enabled GaN-based VCSELs to be constructed with cavities as long as 28.3 µm, which greatly simplifies the fabrication process owing to longitudinal mode spacings of less than a few nanometers and should help the implementation of these devices in practice.
N-mixture models reliably estimate the abundance of small vertebrates
Authors: Ficetola Gentile Francesco , Barzaghi Benedetta , Melotto Andrea , Muraro Martina , Lunghi Enrico , Canedoli Claudia , Lo Parrino Elia , Nanni Veronica , Silva-Rocha Iolanda , Urso Arianna , Carretero Miguel Angel , Salvi Daniele , Scali Stefano , Scarì Giorgio , Pennati Roberta , Andreone Franco , Manenti Raoul 
Published: July 2018

AbstractAccurate measures of species abundance are essential to identify conservation strategies. N-mixture models are increasingly used to estimate abundance on the basis of species counts. In this study we tested whether abundance estimates obtained using N-mixture models provide consistent results with more traditional approaches requiring capture (capture-mark recapture and removal sampling). We focused on endemic, threatened species of amphibians and reptiles in Italy, for which accurate abundance data are needed for conservation assessments: the Lanza’s Alpine salamander Salamandra lanzai, the Ambrosi’s cave salamander Hydromantes ambrosii and the Aeolian wall lizard Podarcis raffonei. In visual counts, detection probability was variable among species, ranging between 0.14 (Alpine salamanders) and 0.60 (cave salamanders). For all the species, abundance estimates obtained using N-mixture models showed limited differences with the ones obtained through capture-mark-recapture or removal sampling. The match was particularly accurate for cave salamanders in sites with limited abundance and for lizards, nevertheless non-incorporating heterogeneity of detection probability increased bias. N-mixture models provide reliable abundance estimates that are comparable with the ones of more traditional approaches, and offer additional advantages such as a smaller sampling effort and no need of manipulating individuals, which in turn reduces the risk of harming animals and spreading diseases.
Annexins induce curvature on free-edge membranes displaying distinct morphologies
Authors: Boye Theresa Louise , Jeppesen Jonas Camillus , Maeda Kenji , Pezeshkian Weria , Solovyeva Vita , Nylandsted Jesper , Simonsen Adam Cohen 
Published: July 2018

AbstractAnnexins are a family of proteins characterized by their ability to bind anionic membranes in response to Ca2+-activation. They are involved in a multitude of cellular functions including vesiculation and membrane repair. Here, we investigate the effect of nine annexins (ANXA1-ANXA7, ANXA11, ANXA13) on negatively charged double supported membrane patches with free edges. We find that annexin members can be classified according to the membrane morphology they induce and matching a dendrogam of the annexin family based on full amino acid sequences. ANXA1 and ANXA2 induce membrane folding and blebbing initiated from membrane structural defects inside patches while ANXA6 induces membrane folding originating both from defects and from the membrane edges. ANXA4 and ANXA5 induce cooperative roll-up of the membrane starting from free edges, producing large rolls. In contrast, ANXA3 and ANXA13 roll the membrane in a fragmented manner producing multiple thin rolls. In addition to rolling, ANXA7 and ANXA11 are characterized by their ability to form fluid lenses localized between the membrane leaflets. A shared feature necessary for generating these morphologies is the ability to induce membrane curvature on free edged anionic membranes. Consequently, induction of membrane curvature may be a significant property of the annexin protein family that is important for their function.
Integrated Brain Atlas for Unbiased Mapping of Nervous System Effects Following Liraglutide Treatment
Authors: Salinas Casper Bo Gravesen , Lu Tess Tsai-Hsiu , Gabery Sanaz , Marstal Kasper , Alanentalo Tomas , Mercer Aaron Jeffrey , Cornea Anda , Conradsen Knut , Hecksher-Sørensen Jacob , Dahl Anders Bjorholm , Knudsen Lotte Bjerre , Secher Anna 
Published: July 2018

AbstractLight Sheet Fluorescence Microscopy (LSFM) of whole organs, in particular the brain, offers a plethora of biological data imaged in 3D. This technique is however often hindered by cumbersome non-automated analysis methods. Here we describe an approach to fully automate the analysis by integrating with data from the Allen Institute of Brain Science (AIBS), to provide precise assessment of the distribution and action of peptide-based pharmaceuticals in the brain. To illustrate this approach, we examined the acute central nervous system effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Peripherally administered liraglutide accessed the hypothalamus and brainstem, and led to activation in several brain regions of which most were intersected by projections from neurons in the lateral parabrachial nucleus. Collectively, we provide a rapid and unbiased analytical framework for LSFM data which enables quantification and exploration based on data from AIBS to support basic and translational discovery.
Repurposing drugs to target the malaria parasite unfolding protein response
Authors: Chen Yun , Murillo-Solano Claribel , Kirkpatrick Melanie G. , Antoshchenko Tetyana , Park Hee-Won , Pizarro Juan C. 
Published: July 2018

AbstractDrug resistant Plasmodium falciparum parasites represent a major obstacle in our efforts to control malaria, a deadly vector borne infectious disease. This situation creates an urgent need to find and validate new drug targets to contain the spread of the disease. Several genes associated with the unfolded protein response (UPR) including Glucose-regulated Protein 78 kDa (GRP78, also known as BiP) have been deemed potential drug targets. We explored the drug target potential of GRP78, a molecular chaperone that is a regulator of the UPR, for the treatment of P. falciparum parasite infection. By screening repurposed chaperone inhibitors that are anticancer agents, we showed that GRP78 inhibition is lethal to drug-sensitive and -resistant P. falciparum parasite strains in vitro. We correlated the antiplasmodial activity of the inhibitors with their ability to bind the malaria chaperone, by characterizing their binding to recombinant parasite GRP78. Furthermore, we determined the crystal structure of the ATP binding domain of P. falciparum GRP78 with ADP and identified structural features unique to the parasite. These data suggest that P. falciparum GRP78 can be a valid drug target and that its structural differences to human GRP78 emphasize potential to generate parasite specific compounds.
Glucose and glutamine handling in the Sertoli cells of transgenic rats overexpressing regucalcin: plasticity towards lactate production
Authors: Mateus Inês , Feijó Mariana , Espínola Luís M. , Vaz Cátia V. , Correia Sara , Socorro Sílvia 
Published: July 2018

AbstractSertoli cells (SCs) possess the unparalleled ability to provide the germ line with growth factors and nutrients. Although SCs can oxidize amino acids, e.g., glutamine, they mostly metabolize glucose, producing high amounts of lactate, the germ cells preferential substrate. Regucalcin (RGN) is a calcium-binding protein that has been indicated as a regulator of cell metabolism. In this study, we investigated glucose and glutamine handling in the SCs of transgenic rats overexpressing RGN (Tg-RGN) comparatively with wild-type (Wt) littermates. Primary SCs isolated from adult Tg-RGN animals and maintained in culture for 24 hours, produced and exported more lactate, despite consuming less glucose. These observations were underpinned by increased expression of alanine transaminase, and augmented glutamine consumption, suggesting that alternative routes are contributing to the enhanced lactate production in the SCs of Tg-RGN rats. Moreover, lactate seems to be used by germ cells, with diminished apoptosis being detected in the seminiferous tubules of Tg-RGN animals cultured ex vivo. The obtained results showed a distinct metabolism in the SCs of Wt and Tg-RGN rats widening the roles assigned to RGN in spermatogenesis. These findings also highlighted the plasticity of SCs metabolism, a feature that would be exploited in the context of male infertility.
Comparison of Systematic Ticagrelor-Based Dual Antiplatelet Therapy to Selective Triple Antithrombotic Therapy for Left Ventricle Dysfunction Following Anterior STEMI
Authors: Bastiany Alexandra , Matteau Alexis , El-Turaby Fady , Angers-Goulet Alexandre , Mansour Samer , Daneault Benoit , Potter Brian J. 
Published: July 2018

AbstractAntithrombotic management of STEMI patients with apical dysfunction, but without demonstrable thrombus, is controversial. Triple antithrombotic therapy (TATT, defined as the addition of oral anticoagulation to dual antiplatelet therapy, or DAPT) may be associated with increased bleeding, while DAPT alone may not adequately protect against cardio-embolic events. We undertook a dual-center study of anterior STEMI patients treated with primary PCI (pPCI) from 2013 to 2015 and presenting presumed new apical dysfunction. The Centre hospitalier de l’Université de Montréal (CHUM) uses a strategy of selective TATT, whereas the Centre hospitalier universitaire de Sherbrooke (CHUS) has favored ticagrelor-based DAPT for all patients since 2013. The primary composite outcome consisted of death, MI, stroke, revascularization, and BARC 3 to 5 bleeding up to 4-months follow-up. We identified 177 cases (69 CHUM; 108 CHUS). Baseline characteristics were similar and procedural success was high (97%). There was no difference in post-procedure LVEF (39 ± 9% vs 37 ± 9%) or the extent of apical dysfunction. The primary composite outcome occurred in 27% with the selective TATT strategy compared to 19% with ticagrelor-DAPT (p = 0.342). Thus, this retrospective dual-center analysis does not support a strategy of conventional TATT over ticagrelor-based DAPT for patients with apical dysfunction following anterior STEMI treated with pPCI. A pragmatic randomized trial is needed to provide a definitive answer to this clinical conundrum.
Bacillus amyloliquefaciens strain MBI600 induces salicylic acid dependent resistance in tomato plants against Tomato spotted wilt virus and Potato virus Y
Authors: Beris Despoina , Theologidis Ioannis , Skandalis Nicholas , Vassilakos Nikon 
Published: July 2018

AbstractPlant growth promoting rhizobacteria have been proposed as effective biocontrol agents against several fungal and bacterial plant pathogens. However, there is limited knowledge regarding their effect against viruses. In this study, Bacillus amyloliquefaciens strain MBI600 (MBI600), active ingredient of the biological fungicide Serifel® (BASF SE), was tested for its antiviral action in tomato plants. Drench, foliar or soil amendment applications of MBI600 reduced up to 80% the incidence of Tomato spotted wilt virus under two different sets of environmental conditions. In addition, drench application of MBI600 delayed Potato virus Y systemic accumulation. Transcriptional analysis of a range of genes associated with salicylic acid (SA)- or jasmonic acid - related defense, priming or basal defense against viruses, revealed the induction of the SA signaling pathway in tomato after MBI600 treatment, and discrete gene expression patterns in plant response to TSWV and PVY infection.
Data analysis and uncertainty estimation in supercontinuum laser absorption spectroscopy
Authors: Emmert Johannes , Blume Niels Göran , Dreizler Andreas , Wagner Steven 
Published: July 2018

AbstractA set of algorithms is presented that facilitates the evaluation of super continuum laser absorption spectroscopy (SCLAS) measurements with respect to temperature, pressure and species concentration without the need for simultaneous background intensity measurements. For this purpose a non-linear model fitting approach is employed. A detailed discussion of the influences on the instrument function of the spectrometer and a method for the in-situ determination of the instrument function without additional hardware are given. The evaluation procedure is supplemented by a detailed measurement precision assessment by applying an error propagation through the non-linear model fitting approach. While the algorithms are tailored to SCLAS, they can be transferred to other spectroscopic methods, that similarly require an instrument function. The presented methods are validated using gas cell measurements of methane in the near infrared region at pressures up to 8.7 bar.
Nurse-led hypertension management was well accepted and non-inferior to physician consultation in a Chinese population: a randomized controlled trial
Authors: Yip Benjamin Hon Kei , Lee Eric Kam Pui , Sit Regina Wing Shan , Wong Carmen , Li Xue , Wong Eliza Lai Yi , Wong Martin Chi sang , Chung Roger Yat Nork , Chung Vincent Chi ho , Kung Kenny , Wong Samuel Yeung shan 
Published: July 2018

AbstractThe objective of this study is to evaluate if nurse-led repeated prescription (NRP) could ensure non-inferior disease control and would be accepted in Chinese patients with controlled hypertension (HT) in primary care clinics. A 12-month follow-up non-inferiority randomized trial was conducted. The non-inferior margins for systolic and diastolic blood pressure were 6.6 mmHg and 3.7 mmHg, respectively. Eligible patients (>18 years of age) with HT were randomized to the NRP and usual care (UC) groups for their regular clinical follow-up. We used ANCOVA to study the difference-of-difference of the blood pressures between the two groups. The levels of patient acceptance and experience of NRP were assessed by the observed opt-out rate and a qualitative analysis. We found no statistically significant differences in BP blood pressure between the NRP (N = 194) and UC (N = 199) groups. Only 4 of the participants in the NRP group opted out due to a preference for assessment by a physician. The interviewed participants (N = 12) felt positive about NRP, because they experienced more relaxed communication with the nurse and believed that the eligibility to join the NRP program was an indication of optimal BP control. We observed no adverse events. The findings show that NRP was well accepted and found to be non-inferior to physician consultation for HT management.
Cobra Venom Factor-induced complement depletion protects against lung ischemia reperfusion injury through alleviating blood-air barrier damage
Authors: Haihua Chang , Wei Wang , Kun Huang , Yuanli Liao , Fei Lin 
Published: July 2018

AbstractThe purpose of this study was to study whether complement depletion induced by pretreatment with Cobra Venom Factor (CVF) could protect against lung ischemia reperfusion injury (LIRI) in a rat model and explore its molecular mechanisms. Adult Sprague-Dawley rats were randomly assigned to five groups (n = 6): Control group, Sham-operated group, I/R group, CVF group, I/R + CVF group. CVF (50 μg/kg) was injected through the tail vein 24 h before anesthesia. Lung ischemia reperfusion (I/R) was induced by clamping the left hilus pulmonis for 60 minutes followed by 4 hours of reperfusion. Measurement of complement activity, pathohistological lung injury score, inflammatory mediators, pulmonary permeability, pulmonary edema, integrity of tight junction and blood-air barrier were performed. The results showed that pretreatment with CVF significantly reduced complement activity in plasma and BALF. Evaluation in histomorphology showed that complement depletion induced by CVF significantly alleviated the damage of lung tissues and inhibited inflammatory response in lung tissues and BALF. Furthermore, CVF pretreatment had the function of ameliorating pulmonary permeability and preserving integrity of tight junctions in IR condition. In conclusion, our results indicated that complement depletion induced by CVF could inhibit I/R-induced inflammatory response and alleviate lung I/R injury. The mechanisms of its protective effects might be ameliorated blood-air barrier damage.