bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis C virus NS5A drives a PTEN‐PI3K/Akt feedback loop to support cell survival
Authors: Cheng Du , Zhang Leiliang , Yang Guangbo , Zhao Lei , Peng Feng , Tian Yi , Xiao Xinqiang , Chung Raymond T. , Gong Guozhong
Published: November 2014

Background & Aims

Decreased levels of phosphatase and tensin homologue (PTEN) are associated with hepatocellular carcinoma (HCC) pathogenesis and poor prognosis in hepatitis C virus (HCV)‐infected HCC patients. The molecular processes governing the reduction in PTEN and outcome of PTEN dysfunction in hepatocytes are poorly understood.

Methods

The levels of proteins and mRNA were assessed by real time PCR and immunoblot. PTEN promoter activity was measured by reporter assay. Signalling pathways were perturbed using siRNAs or pharmacological inhibitors.

Results

Here, we report that HCV down‐regulates PTEN expression at the transcriptional level by decreasing its promoter activity, mRNA transcription, and protein levels. We further identify NS5A protein as a key determinant of PTEN reduction among HCV proteins. NS5A‐mediated down‐regulation of PTEN occurs through a cooperation of reactive oxygen species (ROS)‐dependent Nuclear Factor‐ kappa B (NF‐κB) and ROS‐independent phosphoinositol‐3‐kinase (PI3K) pathways. Moreover, NS5A protects cells against apoptosis. In addition, we found that down‐regulation of PTEN relieves its inhibitory effect on PI3K‐Akt pathway and triggers cumulative activation of Akt. This PTEN‐PI3K/Akt feedback network mediates the suppression of cell apoptosis caused by NS5A.

Conclusions

These data demonstrate that HCV NS5A down‐regulates PTEN expression through a cooperation of ROS‐dependent and ‐independent pathways that subsequently drives a PTEN‐PI3K/Akt feedback loop to support cell survival. Our findings provide new insights suggesting that NS5A contributes to HCV‐related hepatocarcinogenesis.
A two‐component, multimeric endolysin encoded by a single gene
Authors: Proença Daniela , Velours Christophe , Leandro Clara , Garcia Miguel , Pimentel Madalena , São‐José Carlos
Published: November 2014

Bacteriophage endolysins are bacterial cell wall degrading enzymes whose potential to fight bacterial infections has been intensively studied. Endolysins from Gram‐positive systems are typically described as monomeric and as having a modular structure consisting of one or two N‐terminal catalytic domains (CDs) linked to a C‐terminal region responsible for cell wall binding (CWB). We show here that expression of the endolysin gene lys170 of the enterococcal phage F170/08 results in two products, the expected full length endolysin (Lys170FL) and a C‐terminal fragment corresponding to the CWB domain (CWB170). The latter is produced from an in‐frame, alternative translation start site. Both polypeptides interact to form the fully active endolysin. Biochemical data strongly support a model where Lys170 is made of one monomer of Lys170FL associated with up to three CWB170 subunits, which are responsible for efficient endolysin binding to its substrate. Bioinformatics analysis indicates that similar secondary translation start signals may be used to produce and add independent CWB170‐like subunits to different enzymatic specificities. The particular configuration of endolysin Lys170 uncovers a new mode of increasing the number of CWB motifs associated to CD modules, as an alternative to the tandem repetition typically found in monomeric cell wall hydrolases.
Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale
Authors: Cockburn Darrell W. , Orlovsky Nicole I. , Foley Matthew H. , Kwiatkowski Kurt J. , Bahr Constance M. , Maynard Mallory , Demeler Borries , Koropatkin Nicole M.
Published: November 2014

Eubacterium rectale is a prominent human gut symbiont yet little is known about the molecular strategies this bacterium has developed to acquire nutrients within the competitive gut ecosystem. Starch is one of the most abundant glycans in the human diet, and E. rectale increases in vivo when the host consumes a diet rich in resistant starch, although it is not a primary degrader of this glycan. Here we present the results of a quantitative proteomics study in which we identify two glycoside hydrolase 13 family enzymes, and three ABC transporter solute‐binding proteins that are abundant during growth on starch and, we hypothesize, work together at the cell surface to degrade starch and capture the released maltooligosaccharides. EUR_21100 is a multidomain cell wall anchored amylase that preferentially targets starch polysaccharides, liberating maltotetraose, whereas the membrane‐associated maltogenic amylase EUR_01860 breaks down maltooligosaccharides longer than maltotriose. The three solute‐binding proteins display a range of glycan‐binding specificities that ensure the capture of glucose through maltoheptaose and some α1,6‐branched glycans. Taken together, we describe a pathway for starch utilization by E. rectale DSM 17629 that may be conserved among other starch‐degrading Clostridium cluster XIVa organisms in the human gut.
Role of the aminotransferase domain in Bacillus subtilis GabR, a pyridoxal 5′‐phosphate‐dependent transcriptional regulator
Authors: Okuda Keita , Kato Shiro , Ito Tomokazu , Shiraki Shunsuke , Kawase Yumiko , Goto Masaru , Kawashima Susumu , Hemmi Hisashi , Fukada Harumi , Yoshimura Tohru
Published: November 2014

MocR/GabR family proteins are widely distributed prokaryotic transcriptional regulators containing pyridoxal 5′‐phosphate (PLP), a coenzyme form of vitamin B6. The Bacillus subtilis GabR, probably the most extensively studied MocR/GabR family protein, consists of an N‐terminal DNA‐binding domain and a PLP‐binding C‐terminal domain that has a structure homologous to aminotransferases. GabR suppresses transcription of gabR and activates transcription of gabT and gabD, which encode γ‐aminobutyrate (GΑΒΑ) aminotransferase and succinate semialdehyde dehydrogenase, respectively, in the presence of PLP and GABA. In this study, we examined the mechanism underlying GabR‐mediated gabTD transcription with spectroscopic, crystallographic and thermodynamic studies, focusing on the function of the aminotransferase domain. Spectroscopic studies revealed that GABA forms an external aldimine with the PLP in the aminotransferase domain. Isothermal calorimetry demonstrated that two GabR molecules bind to the 51‐bp DNA fragment that contains the GabR‐binding region. GABA minimally affected ΔGbinding upon binding of GabR to the DNA fragment but greatly affected the contributions of ΔH and ΔS to ΔGbinding. GABA forms an external aldimine with PLP and causes a conformational change in the aminotransferase domain, and this change likely rearranges GabR binding to the promoter and thus activates gabTD transcription.
V. THE DIFFERENTIAL ASSOCIATION OF ADIPOSITY AND FITNESS WITH COGNITIVE CONTROL IN PREADOLESCENT CHILDREN
Authors: Pontifex Matthew B. , Kamijo Keita , Scudder Mark R. , Raine Lauren B. , Khan Naiman A. , Hemrick Bonnie , Evans Ellen M. , Castelli Darla M. , Frank Kenneth A. , Hillman Charles H.
Published: November 2014

With the increasing prevalence of sedentary behaviors during childhood, a greater understanding of the extent to which excess adiposity and aerobic fitness relate to cognitive health is of increasing importance. To date, however, the vast majority of research in this area has focused on adiposity or fitness, rather than the possible inter‐relationship, as it relates to cognition. Accordingly, this study examined the differential associations between body composition, aerobic fitness, and cognitive control in a sample of 204 (96 female) preadolescent children. Participants completed a modified flanker task (i.e., inhibition) and a switch task (i.e., cognitive flexibility) to assess two aspects of cognitive control. Findings from this study indicate that fitness and adiposity appear to be separable factors as they relate to cognitive control, given that the interaction of fitness and adiposity was observed to be nonsignificant for both the flanker and switch tasks. Fitness exhibited an independent association with both inhibition and cognitive flexibility whereas adiposity exhibited an independent association only with cognitive flexibility. These results suggest that while childhood obesity and fitness appear to both be related to cognitive control, they may be differentially associated with its component processes.
VI. THE ROLE OF PHYSICAL ACTIVITY IN REDUCING BARRIERS TO LEARNING IN CHILDREN WITH DEVELOPMENTAL DISORDERS
Authors: Pontifex Matthew B. , Fine Jodene G. , da Cruz Katelin , Parks Andrew C. , Smith Alan L.
Published: November 2014

Emerging research suggests that physical activity may be an effective non‐pharmaceutical intervention approach for childhood developmental disorders. Findings indicate that both single bouts of activity and chronic physical activity associate with improved mental health and classroom performance in children with attention‐deficit/hyperactivity disorder and children with autism spectrum disorders. This review describes the research in this area and identifies limitations and challenges to the translation of these findings to promote physical activity in clinical practice and educational policy.
MECHANISMS AND CORRELATES OF A HEALTHY BRAIN: A COMMENTARY
Authors: Cheatham Carol L.
Published: November 2014

In this monograph, the message is that early inactivity and obesity lead to later chronic disease, and, as such, physical inactivity should be recognized as a public health crisis. Sedentary behavior, to some extent, serves a purpose in our current culture (e.g., keeping children indoors keeps them safe), and, as such, may not be amenable to change. Thus, it is important that we understand the underpinnings of later‐developing chronic disease as this complex public health issue may have roots that go deeper than sedentary behavior. In this commentary, I speculate on the mechanisms for physical activity exacting positive changes on cognitive abilities. Three potential mechanisms are discussed: glucose transport, postnatal neurogenesis, and vitamin synthesis, all of which are inextricably linked to nutrition. This discussion of mechanisms is followed by a discussion of tractable correlates of the progression to non‐communicable disease in the adult.
Knowing your friends and foes – plant receptor‐like kinases as initiators of symbiosis or defence
Authors: Antolín‐Llovera Meritxell , Petutsching Elena Kristin , Ried Martina Katharina , Lipka Volker , Nürnberger Thorsten , Robatzek Silke , Parniske Martin
Published: November 2014

The decision between defence and symbiosis signalling in plants involves alternative and modular plasma membrane‐localized receptor complexes. A critical step in their activation is ligand‐induced homo‐ or hetero‐oligomerization of leucine‐rich repeat (LRR)‐ and/or lysin motif (LysM) receptor‐like kinases (RLKs). In defence signalling, receptor complexes form upon binding of pathogen‐associated molecular patterns (PAMPs), including the bacterial flagellin‐derived peptide flg22, or chitin. Similar mechanisms are likely to operate during the perception of microbial symbiont‐derived (lipo)‐chitooligosaccharides. The structurally related chitin‐oligomer ligands chitooctaose and chitotetraose trigger defence and symbiosis signalling, respectively, and their discrimination involves closely related, if not identical, LysM‐RLKs. This illustrates the demand for and the challenges imposed on decision mechanisms that ensure appropriate signal initiation. Appropriate signalling critically depends on abundance and localization of RLKs at the cell surface. This is regulated by internalization, which also provides a mechanism for the removal of activated signalling RLKs. Abundance of the malectin‐like domain (MLD)‐LRR‐RLK Symbiosis Receptor‐like Kinase (SYMRK) is additionally controlled by cleavage of its modular ectodomain, which generates a truncated and rapidly degraded RLK fragment. This review explores LRR‐ and LysM‐mediated signalling, the involvement of MLD‐LRR‐RLKs in symbiosis and defence, and the role of endocytosis in RLK function.
Functional equivalence, competitive hierarchy and facilitation determine species coexistence in highly invaded grasslands
Authors: Gross Nicolas , Liancourt Pierre , Butters Robyn , Duncan Richard P. , Hulme Philip E.
Published: November 2014

Alien and native plant species often differ in functional traits. Trait differences could lead to niche differences that minimize competitive interactions and stabilize coexistence. However, trait differences could also translate into average fitness differences, leading to a competitive hierarchy that prevents coexistence.

We tested whether trait differences between alien and native species translated into average fitness or stabilizing niche differences, and whether competition could explain observed coexistence within invaded grassland communities (New Zealand).

Trait differences reflected marked competitive hierarchy, suggesting average fitness differences. Species coexistence was determined by a trade‐off between species susceptibility to herbivory vs competitive hierarchy and facilitation. Importantly, although aliens and natives differed in their trait values, they did not differ in their competitive response, highlighting the importance of equalizing mechanisms in structuring invaded communities. Only a few alien species with a particular set of traits were able to jeopardize species coexistence when grazing was ceased.

Our study explains why some alien species coexist with natives, whereas others have strong impacts on native communities. It highlights that trait differences can underlie several coexistence processes and that the demonstration of trait differences between aliens and natives is only a first step to understanding the role of biotic interactions in structuring invaded communities.
Association of TGF‐β1 −509C/T, +869T/C, and +915G/C polymorphisms with periodontitis susceptibility
Authors: Huang J , Ding C , Chen X , He R , Chen N
Published: November 2014

Objectives

To investigate the potential association of TGF‐β1 −509C/T (rs1800469), +869T/C (rs1800470), and +915G/C (rs1800471) polymorphisms with susceptibility to periodontitis.

Materials and Methods

Several electronic databases were searched for eligible articles. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were calculated to assess the strength of relationship between the TGF‐β1 polymorphisms and periodontitis risk.

Results

Eleven studies were searched without any language restriction. Pooled estimates showed that TGF‐β1 −509C/T polymorphism was associated with decreased risk of periodontitis. Subgroup analysis revealed that −509C/T T allele was associated with decreased risk of chronic periodontitis (CP) in Asians (T allele vs C allele: OR = 0.81, 95% CI = 0.69–0.97, Pheterogeneity = 0.25). Furthermore, the +915G/C CC genotype might be associated with elevated risk of CP in Caucasians (CC vs GG: OR = 9.14, 95% CI = 1.01–82.50, Pheterogeneity = 0.49). Concerning +869T/C polymorphism, no evidence of significant association was identified.

Conclusion

This meta‐analysis suggested that TGF‐β1 −509C/T T allele was associated with decreased risk of CP in Asians, while +915G/C CC genotype might contribute to increased CP risk in Caucasians. Replication studies of our results in independent large populations are necessary to validate this association in diverse populations.
Plant growth response to direct and indirect temperature effects varies by vegetation type and elevation in a subarctic tundra
Authors: De Long Jonathan R. , Kardol Paul , Sundqvist Maja K. , Veen G. F. (Ciska) , Wardle David A.
Published: November 2014

There has been growing recent use of elevational gradients as tools for assessing effects of temperature changes on vegetation properties, because these gradients enable temperature effects to be considered over larger spatial and temporal scales than is possible through conventional experiments. While many studies have explored the direct effects of temperature, the indirect effects of temperature through its long‐term influence on soil abiotic or biotic properties remain essentially unexplored. We performed two climate chamber experiments using soils from a subarctic elevational gradient in Abisko, Sweden to investigate the direct effects of temperature, and indirect effects of temperature via soil legacies, on growth of two grass species. The soils were collected from each of two vegetation types (heath, dominated by dwarf shrubs, and meadow, dominated by graminoids and herbs) at each of three elevations. We found that plants responded to both the direct effect of temperature and its indirect effect via soil legacies, and that direct and indirect effects were largely decoupled. Vegetation type was a major determinant of plant responses to both the direct and indirect effects of temperature; responses to soils from increasing elevation were stronger and showed a more linear decline for meadow than for heath soils. The influence of soil biota on plant growth was independent of elevation, with a positive influence across all elevations regardless of soil origin for meadow soils but not for heath soils. Taken together, this means that responses of plant growth to soil legacy effects of temperature across the elevational gradient were driven primarily by soil abiotic, and not biotic, factors. These findings emphasize that vegetation type is a strong determinant of how temperature variation across elevational gradients impacts on plant growth, and highlight the need for considering both direct and indirect effects of temperature on plant responses to future climate change.
Pain Intensity as Prognostic Factor in Cancer Pain Management
Authors: Mercadante Sebastiano , Porzio Giampiero , Adile Claudio , Aielli Federica , Cortegiani Andrea , Caruselli Amanda , Casuccio Alessandra
Published: November 2014

Aim

The aim of this study was to prospectively assess the prognostic value of initial pain intensity and its duration in advanced cancer patients.

Methods

A prospective study was conducted in a sample of patients with cancer requiring pain control. Patients underwent standard analgesic strategies used in our palliative care units. Pain intensity was measured at admission (T0) and after successful dose titration or opioid/route switching within a week (Ts). Patients were also asked about their pain intensity reported 15 days before admission (T‐15). Doses of opioids and duration of opioid use were recorded.

Patients were also assessed for the presence of incident pain, neuropathic pain, alcoholism, delirium, and symptom intensity, including items representing psychological distress. One week after or at time of stabilization (Ts), the opioid response was clinically graded as follows: (1) good pain control; (2) adequate pain control requiring more aggressive opioid escalation; (3) adequate pain control associated with the occurrence of adverse effects; (4) incapacity to achieve pain control within a week. Opioid escalation indexes and days for dose finding were also recorded.

Results

Pain intensity at T0 and at T‐15, opioid doses, duration of opioid therapy, and age were associated with more complex analgesic therapies, which were effective in almost all patients within a week.

Conclusion

High levels of pain intensity, often due to previous undertreatment, are predictive of more complex analgesic treatment. Opioid tolerance, as well as younger age, may also play a role.
The role of attachment style, attachment to therapist, and working alliance in response to psychological therapy
Authors: Taylor Peter J. , Rietzschel Julia , Danquah Adam , Berry Katherine
Published: November 2014

Objectives

Working alliance (WA) has been shown to be an important process influencing the success of therapy. The association of clients' underlying attachment representations with WA and the subsequent success of therapy has increasingly been recognized. This study explores the association between adult attachment representations, specific attachment to the therapist and WA in patients receiving psychological therapy.

Method

Fifty‐eight participants due to receive therapy were recruited from primary care psychological services. Participants completed self‐report measures of attachment, WA, and psychopathology.

Results

Patients with greater secure attachment to the therapist showed significantly greater WA. In a subset of participants completing therapy, change in outcome was also correlated with baseline attachment towards the therapist.

Conclusions

The study suggests that attachment towards the therapist is an important predictor of WA. The results suggest that in terms of WA, attachment to the therapist may be more important than pre‐existing attachment representations.

Practitioner points

A more secure attachment to the therapist was associated with greater WA and improvement in therapy.

Clinicians should be mindful of signs of an insecure attachment to themselves, reflecting a difficulty around trusting the therapist and viewing them as a secure base. Missed sessions and an ongoing reluctance to disclose personal information to the therapist may be signs of an insecure attachment.

This may be the case even in cognitive–behavioural approaches to therapy where relational processes are not necessarily a focus of therapy.

Incorporating attachment processes in the formulation, including attachment to the therapist, may provide one way of exploring these issues in therapy.
White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study
Authors: Ota Miho , Noda Takamasa , Sato Noriko , Hattori Kotaro , Hori Hiroaki , Sasayama Daimei , Teraishi Toshiya , Nagashima Anna , Obu Satoko , Higuchi Teruhiko , Kunugi Hiroshi
Published: November 2014

Aim

The DSM‐IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes.

Methods

Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age‐ and sex‐matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel‐by‐voxel basis among the two diagnostic groups and healthy subjects.

Results

There were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto‐occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD.

Conclusion

Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD.
Resistance to a highly aggressive isolate of Sclerotinia sclerotiorum in a Brassica napus diversity set
Authors: Taylor A. , Coventry E. , Jones J. E. , Clarkson J. P.
Published: November 2014

Sclerotinia stem rot (SSR) of oilseed rape (OSR, Brassica napus), caused by Sclerotinia sclerotiorum, is a serious problem in the UK and worldwide. As fungicide‐based control approaches are not always reliable, identifying host resistance is a desirable and sustainable approach to disease management. This research initially examined the aggressiveness of 18 Sclerotinia isolates (17 S. sclerotiorum, one S. subarctica) on cultivated representatives of B. rapa, B. oleracea and B. napus using a young plant test. Significant differences were observed between isolates and susceptibility of the brassica crop types, with B. rapa being the most susceptible. Sclerotinia sclerotiorum isolates from crop hosts were more aggressive than those from wild buttercup (Ranunculus acris). Sclerotinia sclerotiorum isolates P7 (pea) and DG4 (buttercup), identified as ‘aggressive’ and ‘weakly aggressive’, respectively, were used to screen 96 B. napus lines for SSR resistance in a young plant test. A subset of 20 lines was further evaluated using the same test and also in a stem inoculation test on flowering plants. A high level of SSR resistance was observed for five lines and, although there was some variability between tests, one winter OSR (line 3, Czech Republic) and one rape kale (line 83, UK) demonstrated consistent resistance. Additionally, one swede (line 69, Norway) showed an outstanding level of resistance in the stem test. Resistant lines also had fewer sclerotia forming in stems. New pre‐breeding material for the production of SSR resistant OSR cultivars relevant to conditions in the UK and Europe has therefore been identified.
Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?
Authors: Davenport Andrew
Published: November 2014

The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over‐hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area.
Economic Dominance, the “American Dream,” and Homicide: A Cross‐National Test of Institutional Anomie Theory
Authors: Hughes Lorine A. , Schaible Lonnie M. , Gibbs Benjamin R.
Published: November 2014

This article presents a cross‐national test of Messner and Rosenfeld's (1994) institutional anomie theory. Drawing on multiple data sources, including the United Nations, World Bank, World Values Survey, and Heritage Foundation, we examine relationships between economic dominance, indicators of culture, and homicide among a sample of 50 nations. Additionally, we assess the thesis of “American exceptionalism,” a unique cultural complex implicated by Messner and Rosenfeld as a cause of high rates of serious crime in the United States. Results from OLS regression models provide mixed support for the theory. While none of the theoretical predictors exhibits a statistically significant direct effect on homicide, findings suggest that homicide occurs most often in countries where free‐market principles and practices drive the economy and where core cultural commitments are oriented toward achievement, individualism, fetishism of money, and universalism. However, contrary to expectations, the impact of a market‐driven economy is not more pronounced in countries with weakened non‐economic institutions, and results provide only limited evidence in support of the American exceptionalism thesis. The theoretical implications of these findings are discussed.
Generalized Clausal Modifiers in Thai Noun Phrases
Authors: Jenks Peter
Published: November 2014

The Thai particlethîiintroduces relative clauses and noun‐complement clauses but does not introduce clausal complements of verbs. This paper provides a unified analysis for these two noun phrase‐internal clauses as modifiers, proposing thatthîiis a complementizer that is interpreted as a lambda‐operator that derives CP‐sized properties. This analysis is extended to the use ofthîiin factive complements of verbs, contrastive clefts, and infinitives. Arguments are presented against the analysis ofthîiby den Dikken & Singhapreecha (2004) as alinker, a reflex of DP‐internal predicate inversion.
CLUMSY VEIN, the Arabidopsis DEAH‐box Prp16 ortholog, is required for auxin‐mediated development
Authors: Tsugeki Ryuji , Tanaka‐Sato Nana , Maruyama Nozomi , Terada Shiho , Kojima Mikiko , Sakakibara Hitoshi , Okada Kiyotaka
Published: November 2014

Pre‐messenger RNA (pre‐mRNA) splicing is essential in eukaryotic cells. In animals and yeasts, the DEAH‐box RNA‐dependent ATPase Prp16 mediates conformational change of the spliceosome, thereby facilitating pre‐mRNA splicing. In yeasts, Prp16 also plays an important role in splicing fidelity. Conversely, PRP16 orthologs in Chlamydomonas reinhardtii and nematode do not have an important role in general pre‐mRNA splicing, but are required for gene silencing and sex determination, respectively. Functions of PRP16 orthologs in higher plants have not been described until now. Here we show that the CLUMSY VEIN (CUV) gene encoding the unique Prp16 ortholog in Arabidopsis thaliana facilitates auxin‐mediated development including male‐gametophyte transmission, apical–basal patterning of embryonic and gynoecium development, stamen development, phyllotactic flower positioning, and vascular development. cuv‐1 mutation differentially affects splicing and expression of genes involved in auxin biosynthesis, polar auxin transport, auxin perception and auxin signaling. The cuv‐1 mutation does not have an equal influence on pre‐mRNA substrates. We propose that Arabidopsis PRP16/CUV differentially facilitates expression of genes, which include genes involved in auxin biosynthesis, transport, perception and signaling, thereby collectively influencing auxin‐mediated development.
Impact of priming on the response of neutrophils to human neutrophil alloantigen‐3a antibodies
Authors: Berthold Tom , Muschter Stefan , Schubert Nicole , Wesche Jan , Ameling Sabine , Teumer Alexander , Reil Angelika , Bux Jürgen , Bakchoul Tamam , Greinacher Andreas
Published: November 2014

Background

Human neutrophil alloantigen‐3a (HNA‐3a) antibodies can induce transfusion‐related acute lung injury (TRALI). The severity of TRALI varies largely among the affected patients. Severe comorbidity seems to increase the susceptibility for TRALI, potentially by priming of neutrophils. Thus, the impact of neutrophil priming on HNA‐3a antibody–mediated neutrophil aggregation and CD11b surface expression was investigated.

Study Design and Methods

Neutrophils were primed using formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or bacterial lipopolysaccharide (LPS). Granulocyte aggregation and CD11b surface expression were evaluated by the granulocyte agglutination test and by flow cytometry (FC), respectively. Priming‐induced changes in the surface expression of choline transporter‐like protein 2 (CTL2) and the CTL2 mRNA expression were assessed by FC and quantitative real‐time polymerase chain reaction, respectively.

Results

Priming of neutrophils lowered the amount of HNA‐3a antibodies required for inducing granulocyte aggregation in a dose‐dependent manner by 50% to 75%. The priming agent concentration necessary for this response differed between donors. Priming slightly enhanced binding of HNA‐3a antibodies to neutrophils. However, CTL2 de novo synthesis was not induced after priming with LPS, indicating that increased HNA‐3a antibody binding was likely caused by translocation of intracellular CTL2 to the surface or by increased affinity of HNA‐3a antibodies to CTL2. HNA‐3a antibodies influenced CD11b surface expression on neutrophils only marginally, which was also not potentiated by priming with fMLP or LPS.

Conclusion

This study provides experimental evidence supporting the “threshold model” of TRALI. Priming of neutrophils with fMLP or LPS increases their aggregation response to HNA‐3a antibodies by lowering the required antibody amount.
Efficacy of plasmapheresis on donor‐specific antibody reduction by HLA specificity in post–kidney transplant recipients
Authors: Yamada Chisa , Ramon Daniel S. , Cascalho Marilia , Sung Randall S. , Leichtman Alan B. , Samaniego Milagros , Davenport Robertson D.
Published: November 2014

Background

Donor‐specific antibodies (DSAs) to HLA antigens can cause acute antibody‐mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction rates are inconsistent. We investigated DSA reduction rates by HLA specificity and clinical outcome.

Study Design and Methods

Sixty‐four courses of TPE for 56 kidney Txp recipients with high DSA were investigated. Dates of TPE procedures and Txp, patients' age, sex, race, creatinine (Cr), and mean fluorescent intensity (MFI) of DSA were retrieved. MFI reduction rate after one to three TPE and four to six TPE procedures were calculated by HLA DSA specificity in each patient, and the mean reduction rates were compared. The relationship of TPE treatment, MFI or Cr improvement rate, and graft age was also investigated.

Results

Patients received a mean 6.0 TPE procedures. Most received intravenous immunoglobulin after TPE and immunosuppressives. Forty‐two cases (65.6%) had DSA to HLA Class I and 54 cases (84.4%) to Class II, including 32 cases (50.0%) to both. Mean MFI reduction rates after one to three TPE and four to six TPE procedures were 25.7 and 37.1% in HLA Class I, 25.1 and 34.2% in Class II, and 14.3 and 19.9% in DR51‐53. The mean Cr improvements at the end of TPE and 3 and 6 months after TPE were 3.41, −0.37, and −0.72%, respectively.

Conclusion

Six TPE procedures decreased DSA more than three TPE procedures, but reduction rate was lower by the second three TPE procedures than the first three TPE procedures. Although the mean Cr improvement was minimal, the treatment has good potential to stop further deterioration of kidney function. Better Cr improvement rate is correlated with the graft age.
Decolonizing Encounters of the Third Kind: Alternative Futuring in Native Science Fiction Film
Authors: Lempert William
Published: November 2014

In the last few years, Native filmmakers have begun drawing explicitly on the science fiction genre. Engaging recent short films depicting noncolonial encounters of the third kind and alternative utopian–dystopian futures, I argue that Native science fiction film provides a creative subversive mode of representation, uniquely positioning indigenous filmmakers to vividly reimagine a multiplicity of futures for their communities while critically addressing contemporary issues. Synthesizing scholarship in visual anthropology, afro and feminist futurism, and indigenous methodologies, I attempt to further develop an indigenous futurist analytical framework as part of a larger argument for increased anthropological engagement with Native futures.
Heterotopic gastric mucosa associated with abdominal abscess formation, hypotension, and acute abdominal pain in a puppy
Authors: Tobleman Bridget N. , Sinnott Virginia B.
Published: November 2014

Objective

To describe the presence of heterotopic gastric mucosa forming an abscess associated with acute abdominal pain and shock in a puppy.

Case Summary

A 7‐month‐old male intact Shih‐Tzu was presented to the emergency service for evaluation of a 12‐hour history of vomiting and lethargy progressing to weakness. On presentation, the puppy was obtunded and hypotensive. Radiographs revealed an ill‐defined mid‐ventral abdominal mass. Ultrasound revealed an echogenic, fluid‐filled mass associated with the jejunum. The puppy had an exploratory celiotomy and a 2 × 4 cm oval fluid‐filled soft tissue mass was found to be intimately associated, but not communicating with, a section of the mid‐jejunum. The mass and associated jejunum were removed via enterectomy. Histopathology of the resected mass revealed heterotopic gastric mucosa; bacterial culture of the fluid contained in the mass revealed heavy growth of Escherichia coli. The puppy recovered from surgery, was discharged from the hospital, and has had no further complications from this episode.

Unique Information Provided

Heterotopic gastric mucosa is commonly found incidentally on necropsy. When it has been associated with acute gastrointestinal signs, mechanical intestinal obstruction with or without perforation was noted. To the authors' knowledge, this is the first reported case of heterotopic gastric mucosa leading to abscess formation and acute abdominal pain in the dog.
Facing the challenge of mammalian neural microcircuits: taking a few breaths may help
Authors: Feldman Jack L. , Kam Kaiwen
Published: November 2014

Breathing in mammals is a seemingly straightforward behaviour controlled by the brain. A brainstem nucleus called the preBötzinger Complex sits at the core of the neural circuit generating respiratory rhythm. Despite the discovery of this microcircuit almost 25 years ago, the mechanisms controlling breathing remain elusive. Given the apparent simplicity and well‐defined nature of regulatory breathing behaviour, the identification of much of the circuitry, and the ability to study breathing in vitro as well as in vivo, many neuroscientists and physiologists are surprised that respiratory rhythm generation is still not well understood. Our view is that conventional rhythmogenic mechanisms involving pacemakers, inhibition or bursting are problematic and that simplifying assumptions commonly made for many vertebrate neural circuits ignore consequential detail. We propose that novel emergent mechanisms govern the generation of respiratory rhythm. That a mammalian function as basic as rhythm generation arises from complex and dynamic molecular, synaptic and neuronal interactions within a diverse neural microcircuit highlights the challenges in understanding neural control of mammalian behaviours, many (considerably) more elaborate than breathing. We suggest that the neural circuit controlling breathing is inimitably tractable and may inspire general strategies for elucidating other neural microcircuits.
Ageing and neurotrophic signalling effects on diaphragm neuromuscular function
Authors: Greising Sarah M. , Ermilov Leonid G. , Sieck Gary C. , Mantilla Carlos B.
Published: November 2014

Key points

Sarcopenia of the diaphragm muscle, i.e. loss of muscle force and size with increasing age, may contribute to respiratory impairment in old age but the exact mechanisms underlying this are currently unknown.

Across the lifespan in mice there is worsening neuromuscular function of the diaphragm muscle, specifically reduced force and impaired neuromuscular transmission.

We tested the hypothesis that age‐related changes to the diaphragm muscle depend on brain‐derived neurotrophic factor (BDNF), acting through its high affinity receptor.

BDNF improves neuromuscular transmission in the diaphragm muscle into early old age, but not older ages. Inhibition of BDNF signalling impairs neuromuscular transmission only in young adult mice.

Our results suggest that the loss of endogenous BDNF precedes reduced activity of the high affinity receptor tropomyosin‐related kinase receptor B in the ageing mouse diaphragm muscle.

The age‐related mechanisms underlying sarcopenia are largely unknown. We hypothesize that age‐related neuromuscular changes depend on brain‐derived neurotrophic factor (BDNF) acting through the tropomyosin‐related kinase receptor B (TrkB). Maximal specific force and neuromuscular transmission failure were assessed at 6, 18 and 24 months following control, BDNF or phosphoprotein phosphatase 1 derivative (1NMPP1) treatment in male TrkBF616A mice. Phosphoprotein phosphatase‐1 derivatives such as 1NMPP1 inhibit TrkB kinase activity as a result of this single amino acid mutation in the ATP binding domain. Maximal twitch and isometric tetanic force were reduced at 24 months compared to 6 and 18 months (P < 0.001). Neuromuscular transmission failure significantly increased at 18 and 24 months compared to 6 months (age × treatment interaction: P < 0.001). Neuromuscular transmission was improved following BDNF at 6 and 18 months and was impaired only at 6 months following 1NMPP1 treatment. Age and inhibition of TrkB kinase activity had similar effects on neuromuscular transmission failure, supporting a critical role for BDNF/TrkB signalling on neuromuscular changes in ageing. These results suggest that an age‐related loss of endogenous BDNF precedes reductions in TrkB kinase activity in the diaphragm muscle.
Contributions of white and brown adipose tissues and skeletal muscles to acute cold‐induced metabolic responses in healthy men
Authors: Blondin Denis P. , Labbé Sébastien M. , Phoenix Serge , Guérin Brigitte , Turcotte Éric E. , Richard Denis , Carpentier André C. , Haman François
Published: November 2014

Key points

Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering.

Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men.

Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized.

Cold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold‐defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U‐13C]‐palmitate and [3‐3H]‐glucose tracer methodologies coupled with positron emission tomography using 11C‐acetate and 18F‐fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold‐induced increase in whole‐body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold‐induced increase in non‐esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 ± 124 vs. 12 ± 8 μmol min−1, respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WAT lipolysis is closely associated with BAT metabolic activation upon acute cold exposure in healthy men. In humans, muscle glucose utilization during shivering contributes to a much greater extent than BAT to systemic glucose utilization during acute cold exposure.
Control of vascular smooth muscle function by Src‐family kinases and reactive oxygen species in health and disease
Authors: MacKay Charles E. , Knock Greg A.
Published: November 2014

Reactive oxygen species (ROS) are now recognised as second messenger molecules that regulate cellular function by reversibly oxidising specific amino acid residues of key target proteins. Amongst these are the Src‐family kinases (SrcFKs), a multi‐functional group of non‐receptor tyrosine kinases highly expressed in vascular smooth muscle (VSM). In this review we examine the evidence supporting a role for ROS‐induced SrcFK activity in normal VSM contractile function and in vascular remodelling in cardiovascular disease. VSM contractile responses to G‐protein‐coupled receptor stimulation, as well as hypoxia in pulmonary artery, are shown to be dependent on both ROS and SrcFK activity. Specific phosphorylation targets are identified amongst those that alter intracellular Ca2+ concentration, including transient receptor potential channels, voltage‐gated Ca2+ channels and various types of K+ channels, as well as amongst those that regulate actin cytoskeleton dynamics and myosin phosphatase activity, including focal adhesion kinase, protein tyrosine kinase‐2, Janus kinase, other focal adhesion‐associated proteins, and Rho guanine nucleotide exchange factors. We also examine a growing weight of evidence in favour of a key role for SrcFKs in multiple pro‐proliferative and anti‐apoptotic signalling pathways relating to oxidative stress and vascular remodelling, with a particular focus on pulmonary hypertension, including growth‐factor receptor transactivation and downstream signalling, hypoxia‐inducible factors, positive feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK and NADPH oxidase dependent ROS production. We also discuss evidence for and against the potential therapeutic targeting of SrcFKs in the treatment of pulmonary hypertension.
Further Results on Exponential Robust Stability Analysis for Recurrent Neural Networks With Time-Varying Delay
Authors: Liu Pin-Lin
Published: November 2014

In this paper, the problems of determining the robust exponential stability and estimating the exponential convergence rate for recurrent neural networks (RNNs) with parametric uncertainties and time-varying delay are studied. The relationship among the time-varying delay, its upper bound, and their difference is taken into account. The developed stability conditions are in terms of linear matrix inequalities (LMIs) and the integral inequality approach (IIA), which can be checked easily by recently developed algorithms solving LMIs. Furthermore, the proposed stability conditions are less conservative than some recently known ones in the literature, and this has been demonstrated via four examples with simulation.
When Crowdsourcing Fails: A Study of Expertise on Crowdsourced Design Evaluation
Authors: Burnap Alex , Ren Yi , Gerth Richard , Papazoglou Giannis , Gonzalez Richard , Papalambros Panos Y.
Published: November 2014

Crowdsourced evaluation is a promising method of evaluating engineering design attributes that require human input. The challenge is to correctly estimate scores using a massive and diverse crowd, particularly when only a small subset of evaluators has the expertise to give correct evaluations. Since averaging evaluations across all evaluators will result in an inaccurate crowd evaluation, this paper benchmarks a crowd consensus model that aims to identify experts such that their evaluations may be given more weight. Simulation results indicate this crowd consensus model outperforms averaging when it correctly identifies experts in the crowd, under the assumption that only experts have consistent evaluations. However, empirical results from a real human crowd indicate this assumption may not hold even on a simple engineering design evaluation task, as clusters of consistently wrong evaluators are shown to exist along with the cluster of experts. This suggests that both averaging evaluations and a crowd consensus model that relies only on evaluations may not be adequate for engineering design tasks, accordingly calling for further research into methods of finding experts within the crowd.