bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Synthesis, SAR and Molecular Modeling Studies of Novel Imidazo[2,1‐b][1,3,4]Thiadiazole Derivatives as Highly Potent Antimicrobial Agents
Authors: Tahtaci Hakan , Karacık Hatice , Ece Abdulilah , Er Mustafa , Şeker Mine Gül 
Published: September 2017

AbstractIn this study, a novel series of phenyl substituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives were synthesized, characterized and explored for antibacterial activity against Gram‐negative Escherichia coli, Gram‐positive Staphylococcus aureus and Bacillus subtilis and antifungal activity against Candida albicans. Most of the synthesized compounds exhibited remarkable antimicrobial activities, some of which being ten times more potent than positive controls. The most promising compound showed excellent activity with MIC value of 0.03 μg/ml against both S. aureus and B. subtilis (MIC values of positive compound Chloramphenicol are 0.4 μg/ml and 0.85 μg/ml, respectively). Furthermore, structure‐activity relationship was also investigated with the help of computational tools. Some physicochemical and ADME properties of the compounds were calculated too. The combination of electronic structure calculations performed at PM6 level and molecular docking simulations using Glide extra‐precision mode showed that the hydrophobic nature of keto aryl ring with no electron withdrawing substituents at para position enhances activity while electron‐donating substituents at the second aryl ring is detrimental to activity.
Identification of Signaling Pathways Targeted by the Food Contaminant FB1: Transcriptome and Kinome Analysis of Samples from Pig Liver and Intestine
Authors: Régnier Marion , Gourbeyre Pascal , Pinton Philippe , Napper Scott , Laffite Joëlle , Cossalter Anne‐Marie , Bailly Jean‐Denis , Lippi Yannick , Bertrand‐Michel Justine , Bracarense Ana Paula F.R.L. , Guillou Hervé , Loiseau Nicolas , Oswald Isabelle P. 
Published: September 2017

ScopeFumonisin B1 (FB1) is a mycotoxin produced by Fusarium species. In mammals, this toxin causes widespread organ‐specific damage; it promotes hepatotoxicity, is immunotoxic, alters intestinal functions etc. Despite its inhibitory effect on de novo ceramide synthesis, its molecular mechanism of action and toxicity is not totally elucidated.Methods and resultsTo explore the mechanism of FB1 toxicity, we analyzed the transcriptome and the kinome of two organs targeted by FB1: the liver and the jejunum. Pigs were fed for 4 weeks a control diet or a FB1‐contaminated diet (10 mg/kg). As expected, FB1‐exposed pigs gained less weight and displayed a higher sphinganine/sphingosine ratio. Comparison of the transcriptomes and the kinomes of treated versus control pigs showed striking differences. Among the disrupted pathways in liver and jejunum, we highlight Protein Kinase B (AKT) / Phosphatase and tensin homolog (PTEN) at the intersection of the FB1‐modulated pathways.ConclusionMost of the effects of FB1 are mediated by the regulation of ceramide level, which influences protein phosphatase 2 (PP2A) and the phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway. This pathway might be a new target to counteract toxic effect of Fumonisin B1, which is one of the most spread food contaminant in the world.
Clinical features and evolution of juvenile myasthenia gravis in a French cohort
Authors: Barraud Coline , Desguerre Isabelle , Barnerias Christine , Gitiaux Cyril , Boulay Christophe , Chabrol Brigitte 
Published: September 2017

ABSTRACTIntroductionIn this study we determined the clinical, paraclinical, and treatment‐related features of juvenile myasthenia gravis (JMG) as well as the clinical course in a cohort of French children.MethodsWe conducted a retrospective study of 40 patients with JMG at 2 French pediatric neurology departments from April 2004 to April 2014.ResultsAmong the patients, 70% had generalized JMG, 52% had positive acetylcholine receptor antibodies, 8% had muscle‐specific kinase antibodies, and 40% were seronegative. Treatment with acetylcholinesterase inhibitors was effective and sufficient in 47% of patients. The 6 patients with generalized JMG treated with rituximab and/or immunoadsorption showed improvement. Thirty percent of the patients required hospitalization in an intensive care unit during follow‐up (mean 4.7 years). Remission without treatment occurred in 18% of patients.DiscussionAs with adults, JMG has high morbidity, particularly among children with generalized symptoms, and rituximab should be considered early in the course of the disease as a second‐line treatment. Muscle Nerve 57: 603–609, 2018
Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon
Authors: Saito Kanako , Kawasoe Ryotaro , Sasaki Hiroshi , Kawaguchi Ayano , Miyata Takaki 
Published: September 2017

AbstractSpatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.
Tidal modulation of ice shelf buttressing stresses
Authors: Robel Alexander A. , Tsai Victor C. , Minchew Brent , Simons Mark 
Published: September 2017

ABSTRACT
Ocean tides influence the flow of marine-terminating glaciers. Observations indicate that the large fortnightly variations in ice flow at Rutford Ice Stream in West Antarctica originate in the floating ice shelf. We show that nonlinear variations in ice shelf buttressing driven by tides can produce such fortnightly variations in ice flow. These nonlinearities in the tidal modulation of buttressing stresses can be caused by asymmetries in the contact stress from migration of the grounding line and bathymetric pinning points beneath the ice shelf. Using a simple viscoelastic model, we demonstrate that a combination of buttressing and hydrostatic stress variations can explain a diverse range of tidal variations in ice shelf flow, including the period, phase and amplitude of flow variations observed at Rutford and Bindschadler Ice Streams.
Growth performance, nutrient utilisation and carcass composition respond to dietary protein concentrations in broiler chickens but responses are modified by dietary lipid levels
Authors: Liu Sonia Y. , Selle Peter H. , Raubenheimer David , Gous Rob M. , Chrystal Peter V. , Cadogan David J. , Simpson Stephen J. , Cowieson Aaron J. 
Published: September 2017

AbstractA total of ten experimental diets with protein concentrations ranging from 154 to 400 g/kg and two lipid levels (46 and 85 g/kg) with identical energy densities were offered to 240 male Ross 308 broilers from 7 to 28 d post-hatch. Growth performance was monitored and nutrient utilisation (apparent metabolisable energy (AME), N-corrected AME (AMEn), AME daily intake, AME:gross energy ratios, N retention) was determined. The weight gain response of broiler chickens to dietary protein concentrations in diets containing high and low lipid levels was diverse, with the relevant quadratic regressions being significantly different (P<0·05). With low lipid levels, the predicted maximum weight gain of 1809 g/bird equated to 342 g/kg dietary protein, whereas, for high lipid levels the predicted maximum weight gain of 1694 g/bird equated to 281 g/kg dietary protein. AME was linearly correlated with dietary protein concentration but regressions in diets with different lipid content were not significantly different (P>0·05). AMEn was also linearly (P<0·0001) increased with dietary protein concentrations but regressions in diets with low and high lipid content were significantly different (P<0·03). Carcass protein content increased linearly with dietary protein content in diets containing high lipid concentrations (r 0·933, P<0·0001); by contrast, this relationship was quadratic (R2=0·93, P<0·0001) in diets with low lipid levels. In conclusion, predictably, the effects of dietary protein concentrations on broiler performance were profound; however, the impact of dietary protein on performance in broiler chickens was modified by dietary lipid concentrations.
Premorbid social adjustment and association with attenuated psychotic symptoms in clinical high-risk and help-seeking youth
Authors: Tarbox-Berry S. I. , Perkins D. O. , Woods S. W. , Addington J. 
Published: September 2017

BackgroundAttenuated positive symptom syndrome (APSS), characterized by ‘putatively prodromal’ attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of ‘true’ prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals.MethodAssociation between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis.ResultsPremorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria.ConclusionsPredictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.
Rapid global ocean-atmosphere response to Southern Ocean freshening during the last glacial
Authors: Turney Chris S. M. , Jones Richard T. , Phipps Steven J. , Thomas Zoë , Hogg Alan , Kershaw A. Peter , Fogwill Christopher J. , Palmer Jonathan , Bronk Ramsey Christopher , Adolphi Florian , Muscheler Raimund , Hughen Konrad A. , Staff Richard A. , Grosvenor Mark , Golledge Nicholas R. , Rasmussen Sune Olander , Hutchinson David K. , Haberle Simon , Lorrey Andrew , Boswijk Gretel , Cooper Alan 
Published: September 2017

AbstractContrasting Greenland and Antarctic temperatures during the last glacial period (115,000 to 11,650 years ago) are thought to have been driven by imbalances in the rates of formation of North Atlantic and Antarctic Deep Water (the ‘bipolar seesaw’). Here we exploit a bidecadally resolved 14C data set obtained from New Zealand kauri (Agathis australis) to undertake high-precision alignment of key climate data sets spanning iceberg-rafted debris event Heinrich 3 and Greenland Interstadial (GI) 5.1 in the North Atlantic (~30,400 to 28,400 years ago). We observe no divergence between the kauri and Atlantic marine sediment 14C data sets, implying limited changes in deep water formation. However, a Southern Ocean (Atlantic-sector) iceberg rafted debris event appears to have occurred synchronously with GI-5.1 warming and decreased precipitation over the western equatorial Pacific and Atlantic. An ensemble of transient meltwater simulations shows that Antarctic-sourced salinity anomalies can generate climate changes that are propagated globally via an atmospheric Rossby wave train.
Comparison of quality of life between Billroth-І and Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: A randomized controlled trial
Authors: Yang Kun , Zhang Wei-Han , Liu Kai , Chen Xin-Zu , Zhou Zong-Guang , Hu Jian-Kun 
Published: September 2017

AbstractStudies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) anastomosis are still lacking and inconsistent. The aim of this trial was to compare the quality of life (QoL) of B-I with R-Y reconstruction after curative distal gastrectomy for gastric cancer. A total of 140 patients were randomly assigned to the B-I group (N = 70) and R-Y group (N = 70) with the comparable baseline characteristics. The overall postoperative morbidity rates were 18.6% and 25.7% in the B-I group and R-Y group without significant difference. More estimated blood loss and longer surgical duration were found in the R-Y group. At the postoperative 1 year time point, the B-I group had a higher score in pain, but lower score in global health. However, the R-Y anastomosis was associated with lower incidence of reflux symptoms at postoperative 6 months (P = 0.002) and postoperative 9 months (P = 0.007). The multivariable analyses of variance did not show any interactions between the time trend and grouping. For the results of endoscopic examination, the degree and extent of remnant gastritis were milder significantly in the R-Y group. The stronger anti-reflux capability of R-Y anastomosis contributes to the higher QoL by reducing the reflux related gastritis and pain symptoms, and promotes a better global health.
Nectin-like molecule-4/cell adhesion molecule 4 inhibits the ligand-induced dimerization of ErbB3 with ErbB2
Authors: Mizutani Kiyohito , Kedashiro Shin , Maruoka Masahiro , Ueda Yuki , Takai Yoshimi 
Published: September 2017

AbstractThe ligand-induced dimerization of cell surface single-transmembrane receptors is essential for their activation. However, physiological molecules that inhibit their dimerization and activation have not been identified. ErbB3 dimerizes with ErbB2 upon binding of heregulin (HRG) to ErbB3, causing the ErbB2-catalyzed tyrosine phosphorylation of ErbB3, which leads to the activation of the signalling pathways for cell movement and survival. Genetic disorders of this receptor cause tumorigenesis and metastasis of cancers. We show here that nectin-like molecule-4/cell adhesion molecule 4, known to serve as a tumour suppressor, interacts with ErbB3 in the absence of HRG and inhibits the HRG-induced dimerization of ErbB3 with ErbB2 and its activation. The third immunoglobulin-like domain of nectin-like molecule-4 cis-interacts with the extracellular domain 3 of ErbB3. We describe here a novel regulatory mechanism for the activation and signalling of cell surface single-transmembrane receptors.
Genetic Ablation of Fgf23 or Klotho Does not Modulate Experimental Heart Hypertrophy Induced by Pressure Overload
Authors: Slavic Svetlana , Ford Kristopher , Modert Magalie , Becirovic Amarela , Handschuh Stephan , Baierl Andreas , Katica Nejla , Zeitz Ute , Erben Reinhold G. , Andrukhova Olena 
Published: September 2017

AbstractLeft ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage. Aldosterone receptor blocker spironolactone normalizes serum intact Fgf23 levels after TAC by reducing bony Fgf23 transcription. Notably, genetic Fgf23 or Klotho deficiency does not influence TAC-induced hypertrophic remodelling, LV functional impairment, or LV fibrosis. Despite the profound, aldosterone-mediated increase in circulating intact Fgf23 after TAC, our data do not support an essential role of Fgf23 or Klotho in the pathophysiology of pressure overload-induced cardiac hypertrophy.
A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients
Authors: Tsai Hui-Jen , Jiang Shih Sheng , Hung Wen-Chun , Borthakur Gautam , Lin Sheng-Fung , Pemmaraju Naveen , Jabbour Elias , Bomalaski John S. , Chen Ya-Ping , Hsiao Hui-Hua , Wang Ming-Chung , Kuo Ching-Yuan , Chang Hung , Yeh Su-Peng , Cortes Jorge , Chen Li-Tzong , Chen Tsai-Yun 
Published: September 2017

AbstractExogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 μM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.
The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
Authors: Kosack Lindsay , Gawish Riem , Lercher Alexander , Vilagos Bojan , Hladik Anastasiya , Lakovits Karin , Bhattacharya Anannya , Schliehe Christopher , Mesteri Ildiko , Knapp Sylvia , Bergthaler Andreas 
Published: September 2017

AbstractLipid metabolism is increasingly being appreciated to affect immunoregulation, inflammation and pathology. In this study we found that mice infected with lymphocytic choriomeningitis virus (LCMV) exhibit global perturbations of circulating serum lipids. Mice lacking the lipid-sensing surface receptor triggering receptor expressed on myeloid cells 2 (Trem2−/−) were protected from LCMV-induced hepatitis and showed improved virus control despite comparable virus-specific T cell responses. Non-hematopoietic expression of TREM2 was found to be responsible for aggravated hepatitis, indicating a novel role for TREM2 in the non-myeloid compartment. These results suggest a link between virus-perturbed lipids and TREM2 that modulates liver pathogenesis upon viral infection. Targeted interventions of this immunoregulatory axis may ameliorate tissue pathology in hepatitis.
Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial
Authors: Matsuzaki Sachiko , Vernis Lise , Bonnin Martine , Houlle Celine , Fournet-Fayard Aurelie , Rosano Giuseppe , Lafaye Anne Laure , Chartier Christian , Barriere Agnes , Storme Brigitte , Bazin Jean-Etienne , Canis Michel , Botchorishvili Revaz 
Published: September 2017

AbstractLaparoscopic surgery technology continues to advance. However, much less attention has been focused on how alteration of the laparoscopic surgical environment might improve clinical outcomes. We conducted a randomized, 2 × 2 factorial trial to evaluate whether low intraperitoneal pressure (IPP) (8 mmHg) and/or warmed, humidified CO2 (WH) gas are better for minimizing the adverse impact of a CO2 pneumoperitoneum on the peritoneal environment during laparoscopic surgery and for improving clinical outcomes compared to the standard IPP (12 mmHg) and/or cool and dry CO2 (CD) gas. Herein we show that low IPP and WH gas may decrease inflammation in the laparoscopic surgical environment, resulting in better clinical outcomes. Low IPP and/or WH gas significantly lowered expression of inflammation-related genes in peritoneal tissues compared to the standard IPP and/or CD gas. The odds ratios of a visual analogue scale (VAS) pain score >30 in the ward was 0.18 (95% CI: 0.06, 0.52) at 12 hours and 0.06 (95% CI: 0.01, 0.26) at 24 hours in the low IPP group versus the standard IPP group, and 0.16 (95% CI: 0.05, 0.49) at 0 hours and 0.29 (95% CI: 0.10, 0.79) at 12 hours in the WH gas group versus the CD gas group.
Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion
Authors: Daimon Makoto , Kamba Aya , Murakami Hiroshi , Mizushiri Satoru , Osonoi Sho , Matsuki Kota , Sato Eri , Tanabe Jutaro , Takayasu Shinobu , Matsuhashi Yuki , Yanagimachi Miyuki , Terui Ken , Kageyama Kazunori , Tokuda Itoyo , Kurauchi Shizuka , Nakaji Shigeyuki 
Published: September 2017

AbstractHow the association between the hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based 2015 Iwaki study were enrolled (n: 1,016; age: 54.4 ± 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-β). Univariate linear regression analyses showed a correlation between PC2 and HOMA-β (β = −0.248, p < 0.0001), but not between PC1 and HOMA-β (β = −0.004, p = 0.9048). The correration between PC2 and HOMA-β persisted after adjustment for multiple factors (β = −0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-β (≤68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35–2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population.