bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen sulphide exacerbates acute pancreatitis by over‐activating autophagy viaAMPK/mTOR pathway
Authors: Ji Liang , Li Le , Qu Fengzhi , Zhang Guangquan , Wang Yongwei , Bai Xuewei , Pan Shangha , Xue Dongbo , Wang Gang , Sun Bei 
Published: July 2016

AbstractPreviously, we have shown that hydrogen sulphide (H2S) might be pro‐inflammatory during acute pancreatitis (AP) through inhibiting apoptosis and subsequently favouring a predominance of necrosis over apoptosis. In this study, we sought to investigate the detrimental effects of H2S during AP specifically with regard to its regulation on the impaired autophagy. The incubated levels of H2S were artificially intervened by an administration of sodium hydrosulphide (NaHS) or DL‐propargylglycine (PAG) after AP induction. Accumulation of autophagic vacuoles and pre‐mature activation of trypsinogen within acini, which indicate the impairment of autophagy during AP, were both exacerbated by treatment with NaHS but attenuated by treatment with PAG. The regulation that H2S exerted on the impaired autophagy during AP was further attributed to over‐activation of autophagy rather than hampered autophagosome–lysosome fusion. To elucidate the molecular mechanism that underlies H2S‐mediated over‐activation of autophagy during AP, we evaluated phosphorylations of AMP‐activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR). Furthermore, Compound C (CC) was introduced to determine the involvement of mTOR signalling by evaluating phosphorylations of downstream effecters including p70 S6 kinase (P70S6k) and UNC‐51‐Like kinase 1 (ULK1). Our findings suggested that H2S exacerbated taurocholate‐induced AP by over‐activating autophagy via activation of AMPK and subsequently, inhibition of mTOR. Thus, an active suppression of H2S to restore over‐activated autophagy might be a promising therapeutic approach against AP‐related injuries.
Deactivation in anterior cingulate cortex during facial processing in young individuals with high familial risk and early development of depression: fMRI findings from the Scottish Bipolar Family Study
Authors: Chan Stella W.Y. , Sussmann Jessika E. , Romaniuk Liana , Stewart Tiffany , Lawrie Stephen M. , Hall Jeremy , McIntosh Andrew M. , Whalley Heather C. 
Published: July 2016

BackgroundStudies have identified perturbations in facial processing in bipolar disorder and major depressive disorder (MDD), but their relationship to genetic risk and early development of illness is unclear.MethodsThe Scottish Bipolar Family Study is a prospective longitudinal investigation examining young individuals (age 16–25) at familial risk of mood disorder. Participants underwent functional MRI using an implicit facial processing task employing angry and neutral faces. An explicit facial expression recognition task was completed outside the scanner. Clinical outcomes obtained 2 years after the scan were used to categorise participants into controls (n = 54), high‐risk individuals who had developed MDD (HR MDD; n = 30) and high‐risk individuals who remained well (HR Well, n = 43).ResultsAll groups demonstrated activation patterns typically observed during facial processing, including activation of the amygdala, hippocampus, fusiform gyrus and middle frontal regions. Notably, the HR MDD group showed reduced activation of the anterior cingulate gyrus versus both the control and HR Well group for angry faces, and versus the HR Well group for neutral faces. Outside the scanner, the HR MDD group was less accurate in recognising fearful expressions than the HR Well group.ConclusionsHere, we demonstrate functional abnormalities of the anterior cingulate cortex alongside facial emotional recognition deficits in high‐risk individuals in the early stages of depression compared with both controls and at‐risk individuals who remained well. These neural changes were associated with a current or future diagnosis of MDD and were not simply associated with increased familial risk.
Surveillance of patients with long‐segment Barrett's esophagus: A multicenter prospective cohort study in Japan
Authors: Matsuhashi Nobuyuki , Sakai Eiji , Ohata Ken , Ishimura Norihisa , Fujisaki Junko , Shimizu Tomoki , Iijima Katsunori , Koike Tomoyuki , Endo Takao , Kikuchi Takefumi , Inayoshi Tatsuya , Amano Yuji , Furuta Takahisa , Haruma Ken , Kinoshita Yoshikazu 
Published: July 2016

AbstractBackground and AimThe incidence of esophageal adenocarcinoma (EAC) in cases with long‐segment Barrett's esophagus (BE) has not been investigated in Japan. The aim of this study is to investigate the incidence of EAC in Japanese cases with long‐segment BE prospectively.MethodsThis is a multicenter prospective cohort study investigating the incidence rate of EAC in patients with BE with a length of at least 3 cm. Study subjects received index esophagogastroduodenoscopy at the time of enrollment, and they were instructed to undergo yearly follow‐up esophagogastroduodenoscopy. Patients in whom EAC was diagnosed in the endoscopic examinations underwent subsequent treatment, and their prognosis was observed.ResultsOf 215 enrolled patients, six (2.8%) were initially diagnosed with EAC at the enrollment. Among the remaining 209 patients, 132 received at least one follow‐up esophagogastroduodenoscopy. In this follow‐up, three EACs developed in 251 observed patient‐years (incidence rate: 1.2% per year). Most of the EACs detected at the initial endoscopic examination (5/6, 83%) were already at advanced stages. Meanwhile, all the three lesions detected in the follow‐up esophagogastroduodenoscopies were identified as early cancers and subjected to curative resection.ConclusionsThe incidence rate of EAC in Japanese cases with long‐segment BE was calculated to be 1.2% in a year.
Plasma hypercoagulability in the presence of thrombomodulin but not of activated protein C in patients with cirrhosis
Authors: Lebreton Aurélien , Sinegre Thomas , Pereira Bruno , Lamblin Géraldine , Duron Cédric , Abergel Armand 
Published: July 2016

AbstractBackground and AimsCirrhosis significantly changes all hemostasis steps. Recent studies suggest that cirrhosis is associated with a coagulopathy leading to a hypercoagulable state. The underlying mechanisms are not fully understood, but protein C deficiency is probably a major determinant of this phenotype. The aim of this study was to compare the results of thrombin generation assays performed with addition of thrombomodulin or activated protein C to assess the effect of by‐passing the protein C activation step in cirrhotic patients and healthy controls.MethodsFifty‐eight patients with cirrhosis and 26 healthy controls were prospectively included in this study. Thrombin generation was determined in platelet‐poor plasma using 5 pM of tissue factor and 4 nM of phospholipids, without and with external addition of 1 nM thrombomodulin or 4 nM activated protein C. All results were normalized with the values of a pool of normal plasma samples to limit inter‐plate variability.ResultsWhen thrombin generation assays were performed in the presence of thrombomodulin, endogenous thrombin potential (ETP) and ETP with/ETP without TM ratio were significantly higher in cirrhotic patients than in healthy controls (P < 0.0001). Moreover, these values progressively increased with cirrhosis severity. When thrombin generation assays were performed with activated protein C, all thrombin generation parameters were comparable between healthy controls and cirrhotic patients, despite an acquired protein S deficiency.ConclusionIn the presence of activated protein C, no hypercoagulability was observed, adding to the current evidence that acquired protein C deficiency plays a key role in the coagulation imbalance.
Pharmacokinetics of the MRI contrast agent gadobutrol in common marmoset monkeys (Callithrix jacchus)
Authors: Helms Gunther , Schlumbohm Christina , Garea‐Rodriguez Enrique , Dechent Peter , Fuchs Eberhard 
Published: July 2016

AbstractBackgroundThis study determined the pharmacokinetics of the contrast agent gadobutrol in marmosets by quantitative MRI to derive guidelines for neuroimaging protocols.MethodsLocal concentrations of gadobutrol were determined from consecutive gradient echo‐based mapping of the relaxation rate R1 on a clinical 3T MRI scanner. Half‐time of renal elimination was measured after injection of a triple dose of gadobutrol (0.3 mmol/kg) into the saphenous vein. A first‐order single‐compartment model was fitted to the measured R1 values and verified by blood analysis.ResultsSlow injection (1.5 minutes) resulted in an elimination half‐time of 26±4 minutes. After bolus injection (15 seconds), elimination was much slower (62±8 minutes) with 45% larger distribution volumes. Importantly, more gadobutrol entered the cerebrospinal fluid.ConclusionsSlow injection and a latency of about 20 minutes are recommended to avoid extravasation. Application of a triple dose of gadobutrol compensates for the fast elimination in healthy marmosets.
Novel molecular insights into the critical role of sulfatide in myelin maintenance/function
Authors: Palavicini Juan Pablo , Wang Chunyan , Chen Linyuan , Ahmar Sareen , Higuera Juan Diego , Dupree Jeffrey L. , Han Xianlin 
Published: July 2016

AbstractCerebroside sulfotransferase (CST) catalyzes the production of sulfatide, a major class of myelin‐specific lipids. CST knockout (CST−/−) mice in which sulfatide is completely depleted are born healthy, but display myelin abnormalities and progressive tremors starting at 4–6 weeks of age. Although these phenotypes suggest that sulfatide plays a critical role in myelin maintenance/function, the underlying mechanisms remain largely unknown. We analyzed the major CNS myelin proteins and the major lipids enriched in the myelin in a spatiotemporal manner. We found a one‐third reduction of the major compact myelin proteins (myelin basic protein, myelin basic protein, and proteolipid protein, PLP) and an equivalent post‐developmental loss of myelin lipids, providing the molecular basis behind the thinner myelin sheaths. Our lipidomics data demonstrated that the observed global reduction of myelin lipid content was not because of an increase of lipid degradation but rather to the reduction of their synthesis by oligodendrocytes. We also showed that sulfatide depletion leads to region‐specific effects on non‐compact myelin, dramatically affecting the paranode (neurofascin 155) and the major inner tongue myelin protein (myelin‐associated glycoprotein). Moreover, we demonstrated that sulfatide promotes the interaction between adjacent PLP extracellular domains, evidenced by a progressive decline of high molecular weight PLP complexes in CST−/− mice, providing an explanation at a molecular level regarding the uncompacted myelin sheaths. Finally, we proposed that the dramatic losses of neurofascin 155 and PLP interactions are responsible for the progressive tremors and eventual ataxia. In summary, we unraveled novel molecular insights into the critical role of sulfatide in myelin maintenance/function.
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Cerebroside sulfotransferase (CST) catalyzes the production of sulfatide, a major class of myelin‐specific lipids. CST knockout (CST−/−) mice in which sulfatide is completely depleted are born healthy, but display myelin abnormalities We show in our study that sulfatide depletion leads to losses of myelin proteins and lipids, and impairment of myelin functions, unraveling novel molecular insights into the critical role of sulfatide in myelin maintenance/function.
Glycine release from astrocytes via functional reversal of GlyT1
Authors: Shibasaki Koji , Hosoi Nobutake , Kaneko Ryosuke , Tominaga Makoto , Yamada Katsuya 
Published: July 2016

AbstractIt was previously reported that functional glycine receptors were expressed in neonatal prefrontal cortex; however, the glycine‐releasing cells were unknown. We hypothesized that astrocytes might be a major glycine source, and examined the glycine release properties of astrocytes. We also hypothesized that dopamine (DA) might be a trigger for the astrocytic glycine release, as numerous DA terminals localize in the cortex. We combined two different methods to confirm the glycine release from astrocytes. Firstly, we analyzed the supernatant of astrocytes by amino acid analyzer after DA stimulation, and detect significant glycine peak. Furthermore, we utilized a patch‐clamp biosensor method to confirm the glycine release from astrocytes by using GlyRα1 and Glyβ‐expressing HEK293T cells, and detected significant glycine‐evoked current upon DA stimulation. Thus, we clearly demonstrated that DA induces glycine release from astrocytes. Surprisingly, DA caused a functional reversal of astrocytic glycine transporter 1, an astrocytic type of glycine transporter, causing astrocytes to release glycine. Hence, astrocytes transduce pre‐synaptic DA signals to glycine signals through a reversal of astrocytic glycine transporter 1 to regulate neuronal excitability.
imageCover Image for this issue: doi: 10.1111/jnc.13785.
Doxycycline reduces the expression and activity of matrix metalloproteinase‐2 in the periodontal ligament of the rat incisor without altering the eruption process
Authors: Gomes J. R. , Omar N. F. , Neves J. d. S , Novaes P. D. 
Published: July 2016

Background and ObjectiveDoxycycline is an antibiotic agent that inhibits the activity of matrix metalloproteinases (MMPs) present in the extracellular matrix. In this study, the rat incisor was submitted to a hypofunctional condition, and the effects of doxycycline (80 mg/kg/d) on the expression and activity of MMP‐2, as well as on eruption rate, were determined in the odontogenic region and in the periodontal ligament for 14 d.Material and MethodsRats were distributed into four groups: normofunctional (NF); doxycyline normofunctional (DNF); hypofunctional (HP); and doxycyline hypofunctional (DHP). The left lower incisors of 10 rats were shortened every 2 d, using a high‐rotation drill, to produce the HP and DHP groups, after starting doxycycline treatment (80 mg/kg) by gavage. Eruption was measured using a millimeter ocular, from the gingival margin to the top of the tooth in the HP and DHP groups, and also by a mark made in the tooth previously, in the NF and DNF groups. The hemimandibles were removed and the teeth were extracted to collect the periodontal and odontogenic tissues for immunohistochemical analyses and zymography.ResultsThe eruption rates were higher in the HP and the DHP groups than in the NF and DNF groups, respectively (p < 0.05). In the odontogenic region, neither of the treatments changed the expression and activity of MMP‐2. In the HP group, the shortening treatment decreased the expression, but not the activity, of MMP‐2, while doxycycline was able to inhibit the increase of expression and activity of MMP‐2.ConclusionWe conclude that the inhibition of MMP‐2 by doxycycline, during incisor shortening, was not enough to alter the eruption rate, which suggests that MMP‐2 may have an important role in the turnover of extracellular matrix of the periodontal ligament during the tooth‐eruption process.
Hip bone morphometrics of bottlenose dolphins (Tursiops truncatus) from Adriatic Sea: Sex determination and postnatal development
Authors: Đuras Martina , Jagar Ivona , Gomerčić Tomislav , Watson Alastair , Škrtić Darinka , Galov Ana 
Published: July 2016

AbstractBones are frequently the only cetacean samples available in the wild and may be useful for determination of sex, physical maturity, body length, and body mass. We analyzed the postnatal morphological development and morphometric characteristics of the cleaned and dried, paired hip bone (os coxae) from 131 bottlenose dolphins, Tursiops truncatus, (61 females, 70 males; total body length 117–322 cm) ranging in age from neonates to 28 yr, salvaged from Croatian waters of the eastern Adriatic Sea. Adult dolphins exhibited sexual dimorphism in their hip bone morphology and morphometrics: fully‐formed hip bones from males were significantly longer, heavier, and more robust than those from females. Moreover, the fully formed hip bone from males featured a prominent bony tuberosity protruding dorsolaterally from the caudal half that was significantly wider and higher than in females. Morphometric measurements were used to generate classification functions for reliable sex determination (97%). In addition, hip bone length in both sexes correlated tightly with total body length, allowing one measurement to be calculated from the other. Only a single ossification developed in all hip bones although soft tissue attachments and comparative review suggests homological equivalence with the tripartite terrestrial mammal hip bone.
Reconsidering Intentions
Authors: Tenenbaum Sergio 
Published: July 2016

AbstractThis paper argues that the principles of instrumental rationality apply primarily to extended action through time. Most philosophers assume that rational requirements and principles govern in the first instance momentary mental states, as opposed to governing extended intentional actions directly. In the case of instrumental rationality, the relevant mental states or attitudes would typically be preferences, decisions, or intentions. In fact, even those who recognize the extended nature of our agency still assume that rational requirements apply primarily to mental states at a moment in time. Such views try to do justice to the extended nature of our agency by postulating rational requirements that apply in the first instance to plans, policies, and intentions more generally. The paper focuses on the central case of requirements and reasons governing the reconsideration of intentions and argues that these requirements or reasons are either superfluous or invalid.I argue that a proper conception of instrumental reasoning that applies directly to actions turn out to have surprising consequences. In fact, this conception allows us to see that policies, projects and the like are best understood as instances of extended actions, and that the instrumental requirements that apply to projects and policies are exactly the same as the instrumental requirements that apply to ordinary extended actions. Finally, I argue that the resulting theory of instrumental rationality is a significant improvement over theories that rely on principles governing intentions.
Expression‐level support for gene dosage sensitivity in three Glycine subgenus Glycine polyploids and their diploid progenitors
Authors: Coate Jeremy E. , Song Michael J. , Bombarely Aureliano , Doyle Jeff J. 
Published: July 2016

Summary

Retention or loss of paralogs following duplication correlates strongly with the function of the gene and whether the gene was duplicated by whole‐genome duplication (WGD) or by small‐scale duplication. Selection on relative gene dosage (to maintain proper stoichiometry among interacting proteins) has been invoked to explain these patterns of duplicate gene retention and loss. In order for gene dosage to be visible to natural selection, there must necessarily be a correlation between gene copy number and gene expression level (transcript abundance), but this has rarely been examined.

We used RNA‐Seq data from seven Glycine subgenus Glycine species (three recently formed allotetraploids and their four diploid progenitors) to determine if expression patterns and gene dosage responses at the level of transcription are consistent with selection on relative gene dosage.

As predicted, metabolic pathways and gene ontologies that are putatively dosage‐sensitive based on duplication history exhibited reduced expression variance across species, and more coordinated expression responses to recent WGD, relative to putatively dosage‐insensitive networks.

We conclude that selection on relative dosage has played an important role in shaping gene networks in Glycine.
Lifestyle intervention can reduce the risk of gestational diabetes: a meta‐analysis of randomized controlled trials
Authors: Song C. , Li J. , Leng J. , Ma R. C. , Yang X. 
Published: July 2016

SummaryThis study aimed to examine the effect of lifestyle intervention on the risk of gestational diabetes mellitus (GDM). We searched PubMed, Springer and other databases to retrieve articles published in English and Chinese up to 30 September 2015. The inclusion criteria were randomized controlled trials evaluating the effects of lifestyle intervention on risk of GDM. Exclusion criteria were studies with prepregnancy diabetes mellitus or interventions with nutrient supplements. Random‐effect and fixed‐effect model analyses were used to obtain pooled relative risks and 95% confidence intervals (CIs) of diet and physical activity on the risk of GDM. Subgroup analyses were performed to check the consistency of effect sizes across groups where appropriate. We identified 29 randomized controlled trials with 11,487 pregnant women, addressing the effect of lifestyle intervention on the risk of GDM. In the pooled analysis, either diet or physical activity resulted in an 18% (95%CI 5–30%) reduction in the risk of GDM (P = 0.0091). Subgroup analysis showed that such intervention was effective among women with intervention before the 15th gestational week (relative risk: 0.80, 95%CI 0.66–0.97), but not among women receiving the intervention afterwards. We conclude that lifestyle modification during pregnancy, especially before the 15th gestational week, can reduce the risk of GDM. © 2016 World Obesity
Advice for Noncognitivists
Authors: Willer Malte 
Published: July 2016

AbstractMetaethical noncognitivists have trouble arriving at a respectable semantic theory for moral language. The goal of this article is to make substantial progress toward demonstrating that these problems may be overcome. Replacing the predominant expressivist semantic agenda in metaethics with a dynamic perspective on meaning and communication allows noncognitivists to provide a satisfying analysis of negation and other constructions that have been argued to be problematic for metaethical noncognitivism, including disjunctions. The resulting proposal preserves some of the key insights from recent work on the semantics of expressivism while highlighting the widely neglected early noncognitivists' sympathies to the kind of dynamic story I intend to tell here. A comparison between the advertised dynamic semantic story and current proposals that treat expressivism as a pragmatic rather than semantic theory about moral language is provided.
Reduced paucimannosidic N‐glycan formation by suppression of a specific β‐hexosaminidase from Nicotiana benthamiana
Authors: Shin Yun‐Ji , Castilho Alexandra , Dicker Martina , Sádio Flavio , Vavra Ulrike , Grünwald‐Gruber Clemens , Kwon Tae‐Ho , Altmann Friedrich , Steinkellner Herta , Strasser Richard 
Published: July 2016

SummaryPlants are attractive hosts for the production of recombinant glycoproteins for therapeutic use. Recent advances in glyco‐engineering facilitate the elimination of nonmammalian‐type glycosylation and introduction of missing pathways for customized N‐glycan formation. However, some therapeutically relevant recombinant glycoproteins exhibit unwanted truncated (paucimannosidic) N‐glycans that lack GlcNAc residues at the nonreducing terminal end. These paucimannosidic N‐glycans increase product heterogeneity and may affect the biological function of the recombinant drugs. Here, we identified two enzymes, β‐hexosaminidases (HEXOs) that account for the formation of paucimannosidic N‐glycans in Nicotiana benthamiana, a widely used expression host for recombinant proteins. Subcellular localization studies showed that HEXO1 is a vacuolar protein and HEXO3 is mainly located at the plasma membrane in N. benthamiana leaf epidermal cells. Both enzymes are functional and can complement the corresponding HEXO‐deficient Arabidopsis thaliana mutants. In planta expression of HEXO3 demonstrated that core α1,3‐fucose enhances the trimming of GlcNAc residues from the Fc domain of human IgG. Finally, using RNA interference, we show that suppression of HEXO3 expression can be applied to increase the amounts of complex N‐glycans on plant‐produced human α1‐antitrypsin.