bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of AMPK in regulating the degradation of MAD2B under high glucose in neuronal cells
Authors: Meng Xianfang , Chu Guangpin , Ye Chen , Tang Hui , Qiu Ping , Hu Yue , Li Man , Zhang Chun 
Published: December 2016

AbstractAlthough our recent study has demonstrated that mitotic spindle assembly checkpoint protein (MAD2B) mediates high glucose‐induced neuronal apoptosis, the mechanisms for MAD2B degradation under hyperglycaemia have not yet been elucidated. In this study, we first found that the activation of adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK) was decreased in neurons, accompanied with the increased expression of MAD2B. Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B. Moreover, activation of AMPK prevented neuronal cells from high glucose‐induced injury as demonstrated by the reduced expression of cyclin B1 and percentage of apoptosis as detected by TUNEL. We further found that when total protein synthesis was suppressed by chlorhexidine, the degradation of MAD2B was slower in high glucose‐treated neurons and was mainly dependent on the ubiquitin–proteasome system. Finally, it was indicated that high glucose inhibited the ubiquitination of MAD2B, which could be reversed by activation of AMPK. Collectively, this study demonstrates that AMPK acts as a key regulator of MAD2B expression, suggesting that activation of AMPK signalling might be crucial for the treatment of high glucose‐induced neuronal injury.
MiR‐199b‐5p inhibits osteogenic differentiation in ligamentum flavum cells by targeting JAG1 and modulating the Notch signalling pathway
Authors: Qu Xiaochen , Chen Zhongqiang , Fan Dongwei , Sun Chuiguo , Zeng Yan , Guo Zhaoqing , Qi Qiang , Li Weishi 
Published: December 2016

AbstractOssification of the ligamentum flavum (OLF) is a pathology almost only reported in East Asian countries. The leading cause of OLF is thoracic spinal canal stenosis and myelopathy. In this study, the role of miR‐199b‐5p and jagged 1 (JAG1) in primary ligamentum flavum cell osteogenesis was examined. MiR‐199b‐5p was found to be down‐regulated during osteogenic differentiation in ligamentum flavum cells, while miR‐199b‐5p overexpression inhibited osteogenic differentiation. In addition, JAG1 was found to be up‐regulated during osteogenic differentiation in ligamentum flavum cells, while JAG1 knockdown via RNA interference caused an inhibition of Notch signalling and osteogenic differentiation. Moreover, target prediction analysis and dual luciferase reporter assays supported the notion that JAG1 was a direct target of miR‐199b‐5p, with miR‐199b‐5p found to down‐regulate both JAG1 and Notch. Further, JAG1 knockdown was demonstrated to block the effect of miR‐199b‐5p inhibition. These findings imply that miR‐199b‐5p performs an inhibitory role in osteogenic differentiation in ligamentum flavum cells by potentially targeting JAG1 and influencing the Notch signalling pathway.
GRAIN INCOMPLETE FILLING 2 regulates grain filling and starch synthesis during rice caryopsis development
Authors: Wei Xiangjin , Jiao Guiai , Lin Haiyan , Sheng Zhonghua , Shao Gaoneng , Xie Lihong , Tang Shaoqing , Xu Qingguo , Hu Peisong 
Published: December 2016

AbstractRice grain filling determines grain weight, final yield and grain quality. Here, a rice defective grain filling mutant, gif2, was identified. Grains of gif2 showed a slower filling rate and a significant lower final grain weight and yield compared to wild‐type. The starch content in gif2 was noticeably decreased and its physicochemical properties were also altered. Moreover, gif2 endosperm cells showed obvious defects in compound granule formation. Positional cloning identified GIF2 to encode an ADP‐glucose pyrophosphorylase (AGP) large subunit, AGPL2; consequently, AGP enzyme activity in gif2 endosperms was remarkably decreased. GIF2 is mainly expressed in developing grains and the coded protein localizes in the cytosol. Yeast two hybrid assay showed that GIF2 interacted with AGP small subunits OsAGPS1, OsAGPS2a and OsAGPS2b. Transcript levels for granule‐bound starch synthase, starch synthase, starch branching enzyme and starch debranching enzyme were distinctly elevated in gif2 grains. In addition, the level of nucleotide diversity of the GIF2 locus was extremely low in both cultivated and wild rice. All of these results suggest that GIF2 plays important roles in the regulation of grain filling and starch biosynthesis during caryopsis development, and that it has been preserved during selection throughout domestication of modern rice.
Fitness consequences of altering floral circadian oscillations forNicotiana attenuata
Authors: Yon Felipe , Kessler Danny , Joo Youngsung , Cortés Llorca Lucas , Kim Sang‐Gyu , Baldwin Ian T. 
Published: December 2016

AbstractEcological interactions between flowers and pollinators are all about timing. Flower opening/closing and scent emissions are largely synchronized with pollinator activity, and a circadian clock regulates these rhythms. However, whether the circadian clock increases a plant's reproductive success by regulating these floral rhythms remains untested. Flowers ofNicotiana attenuata,a wild tobacco, diurnally and rhythmically open, emit scent and move vertically through a 140° arc to interact with nocturnal hawkmoths. We tethered flowers to evaluate the importance of flower positions forManduca sexta‐mediated pollinations; flower position dramatically influenced pollination. We examined the pollination success of phase‐shifted flowers, silenced in circadian clock genes, NaZTL, NaLHY, and NaTOC1, by RNAi. Circadian rhythms inN.attenuataflowers are responsible for altered seed set from outcrossed pollen.
In situ experimental formation and growth of Fe nanoparticles and vesicles in lunar soil
Authors: Thompson Michelle S. , Zega Thomas J. , Howe Jane Y. 
Published: December 2016

AbstractWe report the results of the first dynamic, in situ heating of lunar soils to simulate micrometeorite impacts on the lunar surface. We performed slow‐ and rapid‐heating experiments inside the transmission electron microscope to understand the chemical and microstructural changes in surface soils resulting from space‐weathering processes. Our slow‐heating experiments show that the formation of Fe nanoparticles begins at ~575 °C. These nanoparticles also form as a result of rapid‐heating experiments, and electron energy‐loss spectroscopy measurements indicate the Fe nanoparticles are composed entirely of Fe0, suggesting this simulation accurately mimics micrometeorite space‐weathering processes occurring on airless body surfaces. In addition to Fe nanoparticles, rapid‐heating experiments also formed vesiculated textures in the samples. Several grains were subjected to repeated thermal shocks, and the measured size distribution and number of Fe nanoparticles evolved with each subsequent heating event. These results provide insight into the formation and growth mechanisms for Fe nanoparticles in space‐weathered soils and could provide a new methodology for relative age dating of individual soil grains from within a sample population.
Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor‐alpha
Authors: Brock C. , Brock B. , Aziz Q. , Møller H. J. , Pfeiffer Jensen M. , Drewes A. M. , Farmer A. D. 
Published: December 2016

AbstractThe vagus nerve is a central component of cholinergic anti‐inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t‐VNS) on validated parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t‐VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor‐α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t‐VNS exerts an autonomic and a subtle antitumor necrosis factor‐α effect, which warrants further evaluation in larger controlled studies.
Spatial analysis for regional behavior of patients with mental disorders in Japan
Authors: Takahashi Kunihiko , Tachimori Hisateru , Kan Chiemi , Nishi Daisuke , Okumura Yasuyuki , Kato Naohiro , Takeshima Tadashi 
Published: December 2016

AimThe aim of our study was to clarify the geographical movement of patients treated in psychiatric facilities, which can provide important information on the resources and health‐care system of psychiatric services.MethodsWe conducted an analysis of nationwide data on psychiatric patients, collected as an additional survey to the conventional ‘630 survey’ in 2014. For the 151 848 initially admitted inpatients during 6 months and the 144 401 outpatients on a specific day, we identified whether a patient was admitted to a psychiatric facility located in the same medical area as his/her residence. We estimated percentages of being from (i) within the medical area, (ii) within the prefecture, and (iii) outside the prefecture, using a Bayesian statistical approach for each secondary medical area.ResultsThe inpatients moved across wider areas than did the outpatients. Almost all inpatients and outpatients received their medical treatment at hospitals/clinics within their prefecture of residence.ConclusionThe current mental health medical system in Japan has been operating according to prefecture unit; thus, it may be appropriate to plan a medical system at a prefectural level.
Impaired intention‐to‐treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years’ experience from the Nordic countries
Authors: Malenicka S. , Ericzon B.‐G. , Jørgensen M. H. , Isoniemi H. , Karlsen T. H. , Krantz M. , Naeser V. , Olausson M. , Rasmussen A. , Rönnholm K. , Sanengen T. , Scholz T. , Fischler B. , Nemeth A. 
Published: December 2016

AbstractBiliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention‐to‐treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 μmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention‐to‐treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the “sickest children first” allocation policy and correction of malnutrition before surgery.
Bogen's Critique of Linear‐No‐Threshold Default Assumptions
Authors: Crump Kenny S. 
Published: December 2016

AbstractIn an article recently published in this journal, Bogen(1) concluded that an NRC committee's recommendations that default linear, nonthreshold (LNT) assumptions be applied to dose– response assessment for noncarcinogens and nonlinear mode of action carcinogens are not justified. Bogen criticized two arguments used by the committee for LNT: when any new dose adds to a background dose that explains background levels of risk (additivity to background or AB), or when there is substantial interindividual heterogeneity in susceptibility (SIH) in the exposed human population. Bogen showed by examples that SIH can be false. Herein is outlined a general proof that confirms Bogen's claim. However, it is also noted that SIH leads to a nonthreshold population distribution even if individual distributions all have thresholds, and that small changes to SIH assumptions can result in LNT. Bogen criticizes AB because it only applies when there is additivity to background, but offers no help in deciding when or how often AB holds. Bogen does not contradict the fact that AB can lead to LNT but notes that, even if low‐dose linearity results, the response at higher doses may not be useful in predicting the amount of low‐dose linearity. Although this is theoretically true, it seems reasonable to assume that generally there is some quantitative relationship between the low‐dose slope and the slope suggested at higher doses. Several incorrect or misleading statements by Bogen are noted.
Angiotensin II reduces the surface abundance of KV1.5 channels in arterial myocytes to stimulate vasoconstriction
Authors: Kidd Michael W. , Bulley Simon , Jaggar Jonathan H. 
Published: December 2016

Key points
Several different voltage‐dependent K+ (KV) channel isoforms are expressed in arterial smooth muscle cells (myocytes).
Vasoconstrictors inhibit KV currents, but the isoform selectivity and mechanisms involved are unclear.
We show that angiotensin II (Ang II), a vasoconstrictor, stimulates degradation of KV1.5, but not KV2.1, channels through a protein kinase C‐ and lysosome‐dependent mechanism, reducing abundance at the surface of mesenteric artery myocytes.
The Ang II‐induced decrease in cell surface KV1.5 channels reduces whole‐cell KV1.5 currents and attenuates KV1.5 function in pressurized arteries.
We describe a mechanism by which Ang II stimulates protein kinase C‐dependent KV1.5 channel degradation, reducing the abundance of functional channels at the myocyte surface.
AbstractSmooth muscle cells (myocytes) of resistance‐size arteries express several different voltage‐dependent K+ (KV) channels, including KV1.5 and KV2.1, which regulate contractility. Myocyte KV currents are inhibited by vasoconstrictors, including angiotensin II (Ang II), but the mechanisms involved are unclear. Here, we tested the hypothesis that Ang II inhibits KV currents by reducing the plasma membrane abundance of KV channels in myocytes. Angiotensin II (applied for 2 h) reduced surface and total KV1.5 protein in rat mesenteric arteries. In contrast, Ang II did not alter total or surface KV2.1, or KV1.5 or KV2.1 cellular distribution, measured as the percentage of total protein at the surface. Bisindolylmaleimide (BIM; a protein kinase C blocker), a protein kinase C inhibitory peptide or bafilomycin A (a lysosomal degradation inhibitor) each blocked the Ang II‐induced decrease in total and surface KV1.5. Immunofluorescence also suggested that Ang II reduced surface KV1.5 protein in isolated myocytes; an effect inhibited by BIM. Arteries were exposed to Ang II or Ang II plus BIM (for 2 h), after which these agents were removed and contractility measurements performed or myocytes isolated for patch‐clamp electrophysiology. Angiotensin II reduced both whole‐cell KV currents and currents inhibited by Psora‐4, a KV1.5 channel blocker. Angiotensin II also reduced vasoconstriction stimulated by Psora‐4 or 4‐aminopyridine, another KV channel inhibitor. These data indicate that Ang II activates protein kinase C, which stimulates KV1.5 channel degradation, leading to a decrease in surface KV1.5, a reduction in whole‐cell KV1.5 currents and a loss of functional KV1.5 channels in myocytes of pressurized arteries.
How useful are ARFI elastography cut-off values proposed by meta-analysis for predicting the significant fibrosis and compensated liver cirrhosis?
Authors: Bota Simona , Sporea Ioan , Sirli Roxana , Popescu Alina , Gradinaru-Tașcău Oana 
Published: December 2016

Aim: To evaluate how often do we “miss” chronic hepatitis C patients with at least significant fibrosis (F≥2) and those with compensated cirrhosis, by using Acoustic Radiation Force Impulse (ARFI) elastography cut-off values proposed by meta-analysis. Material and methods: Our study included 132 patients with chronic hepatitis C, evaluated by means of ARFI and liver biopsy (LB), in the same session. Reliable measurements were defined as: median value of 10 liver stiffness (LS) measurements with a success rate≥60% and an interquartile range interval<30%. For predicting F≥2 and F=4 we used the LS cut-offs proposed in the last published meta-analysis: 1.35 m/s and 1.87 m/s, respectively. Results: Reliable LS measurements by means of ARFI were obtained in 117 patients (87.9%). In our study, 58 patients (49.6%) had LS values <1.35 m/s; from these 75.8% had F≥2 in LB. From the 59 patients (50.4%) with LS values≥1.35 m/s, only 6.8% had F0 or F1 in LB. Also, in our study, 88 patients (75.3%) had LS values <1.87 m/s; from these only 2.2 % had F4 in LB. From the 29 patients (24.7%) with LS values≥1.87 m/s, 41.3% had F4 in LB. Both for prediction of at least significant fibrosis and liver cirrhosis, higher aminotransferases levels were associated with wrongly classified patients, in univariate and multivariate analysis. Conclusions: ARFI elastography had a very good positive predictive value (93.2%) for predicting the presence of significant fibrosis and excellent negative predictive value (97.8%) for excluding the presence of compensated liver cirrhosis.
Cephem Potentiation by Inactivation of Nonessential Genes Involved in Cell Wall Biogenesis of β-Lactamase-Producing Escherichia coli
Authors: Baker Kristin R. , Sigurðardóttir Helga Høeg , Jana Bimal , Guardabassi Luca 
Published: December 2016

ABSTRACT

Reversal of antimicrobial resistance is an appealing and largely unexplored strategy in drug discovery. The objective of this study was to identify potential targets for “helper” drugs reversing cephem resistance in
Escherichia coli
strains producing β-lactamases. A CMY-2-encoding plasmid was transferred by conjugation to seven isogenic deletion mutants exhibiting cephem hypersusceptibility. The effect of each mutation was evaluated by comparing the MICs in the wild type and the mutant harboring the same plasmid. Mutation of two genes encoding proteins involved in cell wall biosynthesis,
dapF
and
mrcB
, restored susceptibility to cefoxitin (FOX) and reduced the MICs of cefotaxime and ceftazidime, respectively, from the resistant to the intermediate category according to clinical breakpoints. The same mutants harboring a CTX-M-1-encoding plasmid fell into the intermediate or susceptible category for all three drugs. Individual deletion of
dapF
and
mrcB
in a clinical isolate of CTX-M-15-producing
E. coli
sequence type 131 (ST131) resulted in partial reversal of ceftazidime and cefepime resistance but did not reduce MICs below susceptibility breakpoints. Growth curve analysis indicated no fitness cost in a Δ
mrcB
mutant, whereas a Δ
dapF
mutant had a 3-fold longer lag phase than the wild type, suggesting that drugs targeting DapF may display antimicrobial activity, in addition to synergizing with selected cephems. DapF appeared to be a potential FOX helper drug target candidate, since
dapF
inactivation resulted in synergistic potentiation of FOX in the genetic backgrounds tested. The study showed that individual inactivation of two nonessential genes involved in cell wall biogenesis potentiates cephem activity according to drug- and strain-specific patterns.
Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit Strong
In Vitro
Activity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds
Authors: Schell W. A. , Jones A. M. , Garvey E. P. , Hoekstra W. J. , Schotzinger R. J. , Alexander B. D. 
Published: December 2016

ABSTRACT

The
in vitro
activities of fungal CYP51 inhibitors VT-1161 and VT-1129 were determined for
Candida glabrata
(
n
= 34) and
C. krusei
(
n
= 50).
C. glabrata
isolates were screened for FKS gene mutations. All isolates were resistant clinically and/or
in vitro
to at least one standard antifungal compound. VT-1161 and VT-1129 MICs for all isolates were at least 5-fold below achievable human plasma levels for VT-1161. VT-1161 and VT-1129 are promising for the treatment of resistant
C. glabrata
and
C. krusei
infections.
Chromosome-Encoded Broad-Spectrum Ambler Class A β-Lactamase RUB-1 from Serratia rubidaea
Authors: Bonnin Rémy A. , Didi Jennifer , Ergani Ayla , Lima Sandra , Naas Thierry 
Published: December 2016

ABSTRACT

Whole-genome sequencing of
Serratia rubidaea
CIP 103234
T
revealed a chromosomally located Ambler class A β-lactamase gene. The gene was cloned, and the β-lactamase, RUB-1, was characterized. RUB-1 displayed 74% and 73% amino acid sequence identity with the GIL-1 and TEM-1 penicillinases, respectively, and its substrate profile was similar to that of the latter β-lactamases. Analysis by 5′ rapid amplification of cDNA ends revealed promoter sequences highly divergent from the
Escherichia coli
σ
70
consensus sequence. This work further illustrates the heterogeneity of β-lactamases among
Serratia
spp.
Inventory of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study
Authors: Robin F. , Beyrouthy R. , Bonacorsi S. , Aissa N. , Bret L. , Brieu N. , Cattoir V. , Chapuis A. , Chardon H. , Degand N. , Doucet-Populaire F. , Dubois V. , Fortineau N. , Grillon A. , Lanotte P. , Leyssene D. , Patry I. , Podglajen I. , Recule C. , Ros A. , Colomb-Cotinat M. , Ponties V. , Ploy M. C. , Bonnet R. 
Published: December 2016

ABSTRACT

The objective of this study was to perform an inventory of the extended-spectrum-β-lactamase (ESBL)-producing
Enterobacteriaceae
isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing
Enterobacteriaceae
strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in
Escherichia coli
(37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in
Klebsiella pneumoniae
(81.1%). SHV-12 was associated with ESBL-encoding
Enterobacter cloacae
strains (37.9%).
qnrB
,
aac(6
′
)-Ib-cr
, and
aac(3)-II
genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in
K. pneumoniae
and
E. cloacae
. However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the
Enterobacteriaceae
species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the
Enterobacteriaceae
species.