bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development and Evolution of Family Therapy Research: Its Impact on Practice, Current Status, and Future Directions
Authors: Sexton Thomas L. , Datchi Corinne
Published: June 2014

Science has always been a central part of family therapy. Research by early pioneers focused on studying the efficacy of both couple and family interventions from a systemic perspective. Today we know more now than ever before about the processes of diverse families and the therapeutic outcomes of family therapy practices. Despite the acknowledged importance of family therapy research, there are still questions about its impact on “real life” practice. Despite all the flaws of each, research and practice are critical interacting elements of a dialectic relationship: High‐quality practice combines reliable scientific knowledge with individual clinical judgment made by family therapists in the context of their dynamic transactions with a family or couple. Future research can help uncover the mechanisms we have yet to know and test the ones we have identified while the dynamic interaction of research and practice that can lead to further innovations and developments central to the future of family therapy.
The structure of a PII signaling protein from a halophilic archaeon reveals novel traits and high‐salt adaptations
Authors: Palanca Carles , Pedro‐Roig Laia , Llácer José Luis , Camacho Mónica , Bonete María J. , Rubio Vicente
Published: June 2014

To obtain insights into archaeal nitrogen signaling and haloadaptation of the nitrogen/carbon/energy‐signaling protein PII, we determined crystal structures of recombinantly produced GlnK2 from the extreme halophilic archaeon Haloferax mediterranei, complexed with AMP or with the PII effectors ADP or ATP, at respective resolutions of 1.49 Å, 1.45 Å, and 2.60 Å. A unique trait of these structures was a three‐tongued crown protruding from the trimer body convex side, formed by an 11‐residue, N‐terminal, highly acidic extension that is absent from structurally studied PII proteins. This extension substantially contributed to the very low pI value, which is a haloadaptive trait of H. mediterranei GlnK2, and participated in hexamer‐forming contacts in one crystal. Similar acidic N‐extensions are shown here to be common among PII proteins from halophilic organisms. Additional haloadaptive traits prominently represented in H. mediterranei GlnK2 are a very high ratio of small residues to large hydrophobic aliphatic residues, and the highest ratio of polar to nonpolar exposed surface for any structurally characterized PII protein. The presence of a dense hydration layer in the region between the three T‐loops might also be a haloadaptation. Other unique findings revealed by the GlnK2 structure that might have functional relevance are: the adoption by its T‐loop of a three‐turn α‐helical conformation, perhaps related to the ability of GlnK2 to directly interact with glutamine synthetase; and the firm binding of AMP, confirmed by biochemical binding studies with ATP, ADP, and AMP, raising the possibility that AMP could be an important PII effector, at least in archaea.

Database

The atomic coordinates and structure factors have been deposited in the Protein Data Bank under the accession numbers 4OZL (hmGlnK2–AMP), 4OZJ (hmGlnK2–ADP), and 4OZN (hmGlnK2–ATP).

Structured digital abstract

hmGlnK2 and hmGlnK2 bind by x-ray crystallography (View interaction)
Implicit gradient and integral average effective stresses: relationships and numerical approximations
Authors: Maggiolini E. , Livieri P. , Tovo R.
Published: June 2014

This paper investigates two possible definitions of a non‐local effective stress: the weighted average value and the implicit gradient solution. These definitions are usually applied for strength assessment, particularly in the high cycle fatigue regime, in the presence of notches, defects, cracks or welded joint toes or roots. The present research analyses their general relationship in plane notches. Then, the paper presents a numerical method for their assessment by means of a general FE tool. Different solutions are calculated and compared by evaluating the results obtained from different finite element method commercial software.
Managing microcystin: identifying national‐scale thresholds for total nitrogen and chlorophyll a
Authors: Yuan Lester L. , Pollard Amina I. , Pather Santhiska , Oliver Jacques L. , D'Anglada Lesley
Published: June 2014

The occurrence of high cyanotoxin concentrations can severely impair the use of a waterbody for drinking water and recreational purposes. Cyanotoxins are likely to occur under specific environmental conditions, and so identifying these conditions can facilitate management of the waterbody to reduce the likelihood of high cyanotoxin concentrations.

We analysed data collected from lakes across the contiguous United States to identify environmental variables that are strongly associated with occurrence of high concentrations of a common cyanotoxin, microcystin (MC).

Since many different environmental variables covary and are associated with high MC, we used least absolute shrinkage and selection operator (LASSO) regression to identify a few variables that provided accurate predictions of high MC (≥1 μg L−1).

Our analysis indicated that total nitrogen (TN) and chlorophyll a (chl a) concentrations yielded a parsimonious model that accurately predicted the occurrence of high MC. Based on this model, we identified management thresholds for TN and chl a that would maintain the probability of high MC at or below 10 and 5%.
Methyl CpG Binding Domain Ultra‐Sequencing: a novel method for identifying inter‐individual and cell‐type‐specific variation in DNA methylation
Authors: Li X. , Baker‐Andresen D. , Zhao Q. , Marshall V. , Bredy T. W.
Published: June 2014

Experience‐dependent changes in DNA methylation can exert profound effects on neuronal function and behaviour. A single learning event can induce a variety of DNA modifications within the neuronal genome, some of which may be common to all individuals experiencing the event, whereas others may occur in a subset of individuals. Variations in experience‐induced DNA methylation may subsequently confer increased vulnerability or resilience to the development of neuropsychiatric disorders. However, the detection of experience‐dependent changes in DNA methylation in the brain has been hindered by the interrogation of heterogeneous cell populations, regional differences in epigenetic states and the use of pooled tissue obtained from multiple individuals. Methyl CpG Binding Domain Ultra‐Sequencing (MBD Ultra‐Seq) overcomes current limitations on genome‐wide epigenetic profiling by incorporating fluorescence‐activated cell sorting and sample‐specific barcoding to examine cell‐type‐specific CpG methylation in discrete brain regions of individuals. We demonstrate the value of this method by characterizing differences in 5‐methylcytosine (5mC) in neurons and non‐neurons of the ventromedial prefrontal cortex of individual adult C57BL/6 mice, using as little as 50 ng of genomic DNA per sample. We find that the neuronal methylome is characterized by greater CpG methylation as well as the enrichment of 5mC within intergenic loci. In conclusion, MBD Ultra‐Seq is a robust method for detecting DNA methylation in neurons derived from discrete brain regions of individual animals. This protocol will facilitate the detection of experience‐dependent changes in DNA methylation in a variety of behavioural paradigms and help identify aberrant experience‐induced DNA methylation that may underlie risk and resiliency to neuropsychiatric disease.
Use of recombinant activated factor VII in patients with Glanzmann's thrombasthenia: a review of the literature
Authors: Rajpurkar M. , Chitlur M. , Recht M. , Cooper D. L.
Published: June 2014

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder characterized by a quantitative or qualitative defect of glycoprotein IIb/IIIa on the platelet membrane. Managing bleeding episodes is often difficult, and a variety of modalities have been used, including platelet transfusions, recombinant factor VIIa (rFVIIa), and other supportive care. The aim of this review was to present the clinical experience with rFVIIa bolus infusion (rFVIIa BI) for treatment of bleeding episodes and prevention of bleeding during surgical procedures in patients with GT. A literature search was performed to identify rFVIIa‐treated patients with GT. Overall, one international survey, one open‐label study, and 40 case reports identified 172 bleeding episodes treated with rFVIIa and 62 procedures covered with rFVIIa. In the international survey, rFVIIa BI was used for 96 bleeding episodes in 59 patients. Recombinant FVIIa was effective in 76 bleeding episodes (79%). Of 34 surgical procedures, 25 procedures received rFVIIa BI with 92% bleeding‐prevention efficacy. The open‐label study reported 28 patients with 28 rFVIIa BI‐treated bleeds, and 26 (93%) bleeding episodes responded to rFVIIa. Published case reports revealed that 25 (69%) of 36 bleeds and 27 (96%) of 28 surgeries responded to rFVIIa BI treatment. Overall, 26 adverse events were reported in 19 patients, including five thromboembolic events in two patients where a possible relationship with rFVIIa could not be excluded. Two large studies and 40 case reports provide a literature base to support the efficacy and safety of rFVIIa BI in patients with GT.
Pyogenic liver abscess in end‐stage renal disease patients: A nationwide longitudinal study
Authors: Tsai Lung‐Wen , Chao Pei‐Wen , Ou Shuo‐Ming , Chen Yung‐Tai , Shih Chia‐Jen , Li Szu‐Yuan , Chen Tzen‐Wen , Chen Tzeng‐Ji , Liu Chien‐Tsai
Published: June 2014

End‐stage renal disease (ESRD) patients are more prone to infectious disease because of their immunocompromised status. However, the association between pyogenic liver abscess (PLA) and ESRD remains not clear. The aim of our study is to evaluate the incidence, risk factors, and outcomes of PLA in ESRD patients. We recruited all incident ESRD patients from the Taiwan National Health Insurance database from 1998 to 2006. The incidence rate of PLA in ESRD patients was compared with that of a randomly selected non‐ESRD control group matched for age, sex gender, Charlson comorbidity score, diabetes mellitus, and cirrhosis. Among the 57,761 incident dialysis patients, there were 538 cases of PLA. The incidence rate of PLA was 18.20 per 10,000 person‐years in the ESRD cohort and 6.34 per 10,000 person‐years in matched control cohort. The rate of PLA was significantly higher in the ESRD cohort (hazard ratio 3.63, 95% confidence interval 2.83–4.65, P < 0.001). The mortality rates of PLA were higher in the ESRD cohort than those in matched control cohort. Diabetes mellitus was an independent risk factor for mortality of PLA. Compared with non‐ESRD patients, ESRD patients have a higher risk of PLA and poorer outcomes.
What are the patients' preferences for the Chronic Care Model? An application to the obstructive sleep apnoea syndrome
Authors: Krucien Nicolas , Le Vaillant Marc , Pelletier‐Fleury Nathalie
Published: June 2014

Context

The Chronic Care Model (CCM) has been developed to improve the quality of medical care delivered by general practitioners to patients with multiple chronic conditions. Despite an increasing use of this model, it remains unclear to what extent the different recommendations are valued by the patients.

Objective

This study aims to identify the preferences of patients with multiple chronic conditions for recommendations of the Chronic Care Model.

Methods

The patients' preferences were identified with a discrete choice experiment. The hypothetical general practice cares were described using 10 recommendations of the Chronic Care Model (i.e. shared decision making; informational continuity (INF); regular follow‐up; planned care; communication; collaboration with a nurse; advices on health habits; patient empowerment; psychological support; coordination). Respondents were consecutively recruited in a hospital setting during routine follow‐up visits to their pulmonary specialist. The sample of respondents included 150 patients with multiple chronic conditions in addition to an obstructive sleep apnoea syndrome.

Results

The INF is highly valued by the patients. At the opposite, patients do not appear to value collaboration between nurses and GPs. To a large extent, the patients' preferences for the recommendations of the CCM depend on their gender, number of chronic conditions and self‐perceived health condition.

Discussion

The INF appeared to be a minimal requirement to ensure high‐quality general practice care. The significant interactions between the patients' socio‐demographic characteristics and their preferences for the CCM highlighted the necessity to deliver personalized services.
Patient‐centred care – what is it and how is it practised in the dental surgery?
Authors: Scambler Sasha , Gupta Adyya , Asimakopoulou Koula
Published: June 2014

Objectives

This paper explores the understanding and practice of patient‐centred care (PCC) within dentistry. The aim of the research was to explore the nature of PCC, how PCC is taught and how it is practiced within a dental setting.

Methods

The results of a qualitative, interview‐based study of dental professionals working across clinical and teaching positions within a dental school are presented.

Results

Results suggest that a shared understanding of PCC revolves round a basic sense of humanity (‘being nice to patients’), giving information that is judged, by the clinician, to be in the patient's best interest and ‘allowing’ patient choice from a set of choices made available to patients by the clinicians themselves.

Conclusions

This research suggests that significant work is needed if dentists are going to conform to the General Dental Council guidelines on patient‐centred practice and a series of recommendations are made to this end.
Diagnostic utility of bone marrow examination for the assessment of patients with fever of unknown origin: a 10‐year single‐centre experience
Authors: Labrador J. , Pérez‐López E. , Martín A. , Cabrero M. , Puig N. , Díez‐Campelo M.
Published: June 2014

Bone marrow (BM) examination is included in the diagnostic algorithm of fever of unknown origin (FUO), although its role is not clearly determined. The purpose of this study was to assess the role of BM studies in patients with FUO. We retrospectively reviewed 45 consecutive patients (25% human immunodeficiency virus‐positive) with FUO who underwent a BM study in the University Hospital of Salamanca from 2000 to 2010. We analysed the diagnostic role of BM smears, multiparameter flow cytometry analysis, histology and microbiological cultures. Five patients (11%) were finally diagnosed by BM study (three had an infectious disease and two were found to have haematological malignancies), all of whom were immunocompetent patients. Histology was the most useful study (diagnosis was obtained in 4/5 patients), while BM cultures did not establish the final diagnosis in any patient. Flow cytometry established the diagnosis in one patient, although this patient was also diagnosed by histology. In conclusion, BM study is useful for establishing the aetiology of FUO. BM biopsy for histological examination should be always mandatory if a BM examination is performed.
CORB is the best pneumonia severity score for elderly hospitalised patients with suspected pneumonia
Authors: Williams E. , Girdwood J. , Janus E. , Karunajeewa H.
Published: June 2014

Pneumonia severity scoring systems have been developed to identify patients at highest mortality risk, and are used in guidelines to limit use of broad‐spectrum antibiotics to patients with severe community‐acquired pneumonia. A retrospective audit of hospitalised general internal medicine patients with pneumonia was performed to assess the diagnostic performance of various pneumonia severity scores in an elderly general internal medicine population.
New oral anticoagulants: a practical guide on prescription, laboratory testing and peri‐procedural/bleeding management
Authors: Tran H. , Joseph J. , Young L. , McRae S. , Curnow J. , Nandurkar H. , Wood P. , McLintock C.
Published: June 2014

New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non‐valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in‐depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or ‘reverse’ the anticoagulant effects for urgent invasive procedures.
Foam dressing with epidermal growth factor for severe radiation dermatitis in head and neck cancer patients
Authors: Lee Jihyo , Lee Sang‐wook , Hong Joon Pio , Shon Myeong Wha , Ryu Seung‐Hee , Ahn Seung Do
Published: June 2014

This study was conducted to evaluate the effects of foam dressing with human recombinant human epidermal growth factor (rhEGF) on the healing process in head and neck cancer patients who experience radiation‐induced dermatitis (RID). Seven patients, including three with oropharyngeal, two with nasopharyngeal and one each with hypopharyngeal and laryngeal carcinoma, who underwent radiotherapy (RT) for head and neck cancer at the Asan Medical Center from March to December 2008 were prospectively included in this study. Patients who showed severe RID (more than wet desquamation) on the supraclavicular fossa or neck areas were treated by wound cleaning and debridement of granulation tissue, followed by daily rhEGF spray and foam dressing. Median time to stop exudates and reepithelialisation was 4 days. Within 14 days (median 8 days), all patients showed complete healing of RID and no longer required dressings. This new method of treatment with dressing containing rhEGF may have the potential to accelerate the healing process in patients with RID. A case–control study is needed to confirm this finding.
Pro‐healing effects of bilirubin in open excision wound model in rats
Authors: Ahanger Azad A , Leo Marie D , Gopal Anu , Kant Vinay , Tandan Surendra K , Kumar Dinesh
Published: June 2014

Bilirubin, a by‐product of heme degradation, has an important role in cellular protection. Therefore, we speculated that bilirubin could be of potential therapeutic value in wound healing. To validate the hypothesis, we used a full‐thickness cutaneous wound model in rats. Bilirubin (30 mg/kg) was administered intraperitoneally every day for 9 days. The surface area of the wound was measured on days 0, 2, 4, 7 and 10 after the creation of the wound. The granulation tissue was collected on day 10 post‐wounding for analysing various parameters of wound healing. Bilirubin treatment accelerated wound contraction and increased hydroxyproline and glucosamine contents. mRNA expression of pro‐inflammatory factors such as intercellular cell adhesion molecule‐1 (ICAM‐1) and tumour necrosis factor‐α (TNF‐α) were down‐regulated and that of anti‐inflammatory cytokine interleukin‐10 (IL‐10) was up‐regulated. The findings suggest that bilirubin could be a new agent for enhancing cutaneous wound healing.
Durán of Huesca (c. 1160–1230): A Waldensian Seeking a Remedy to Heresy
Authors: Hoose Adam L.
Published: June 2014

Despite the debates about the nature of medieval heresy, especially the Cathars and the Waldensians, in recent scholarship, very little attention has been given to Durán of Huesca, a Spanish Waldensian who wrote two anti‐heretical treatises before and after he was reconciled with the Roman Church in 1207. This article examines how Durán's decisions to join the Waldensians and later to return to the Catholic Church were motivated by his commitment to defending the sacraments and the Incarnation against what he saw as dualist heresy. That his major decisions were in response to this heresy suggests that while old scholarship might overemphasise the cohesiveness of heresy in the south of France, it is important not to dismiss the existence of explicit heretical belief altogether. Moreover, the centrality of the Incarnation and the sacraments in Durán's shifts in association reveals that the Waldensians were active, rather than passive, participants in shaping how the Church hierarchy and other dissident groups perceived and categorised them.
Biophysical Parameters During Radiofrequency Catheter Ablation of Scar‐Mediated Ventricular Tachycardia: Epicardial and Endocardial Applications via Manual and Magnetic Navigation
Authors: BOURKE TARA , BUCH ERIC , MATHURIA NILESH , MICHOWITZ YOAV , YU RICKY , MANDAPATI RAVI , SHIVKUMAR KALYANAM , TUNG RODERICK
Published: June 2014

Ablation Effectiveness and Biophysical Parameters

Background

There is a paucity of data on biophysical parameters during radiofrequency ablation of scar‐mediated ventricular tachycardia (VT).

Methods and Results

Data were collected from consecutive patients undergoing VT ablation with open‐irrigation. Complete data were available for 372 lesions in 21 patients. The frequency of biophysical parameter changes were: >10Ω reduction (80%), bipolar EGM reduction (69%), while loss of capture was uncommon (32%). Unipolar injury current was seen in 72% of radiofrequency applications. Both EGM reduction and impedance drop were seen in 57% and a change in all 3 parameters was seen in only 20% of lesions. Late potentials were eliminated in 33%, reduced/modified in 56%, and remained after ablation in 11%. Epicardial lesions exhibited an impedance drop (90% vs. 76%, P = 0.002) and loss of capture (46% vs. 27%, P < 0.001) more frequently than endocardial lesions. Lesions delivered manually exhibited a >10Ω impedance drop (83% vs. 71%, P = 0.02) and an EGM reduction (71% vs. 40%, P < 0.001) more frequently than lesions applied using magnetic navigation, although loss of capture, elimination of LPs, and a change in all 3 parameters were similarly observed.

Conclusions

VT ablation is inefficient as the majority of radiofrequency lesions do not achieve more than one targeted biophysical parameter. Only one‐third of RF applications targeted at LPs result in complete elimination. Epicardial ablation within scar may be more effective than endocardial lesions, and lesions applied manually may be more effective than lesions applied using magnetic navigation. New technologies directed at identifying and optimizing ablation effectiveness in scar are clinically warranted.
Commentary: Improving treatment for youth with callous‐unemotional traits through the intersection of basic and applied science – reflections on Dadds et al. (2014)
Authors: Hyde Luke W. , Waller Rebecca , Burt S. Alexandra
Published: June 2014

There is increasing evidence that callous‐unemotional (CU) traits delineate a distinctive group of youth with antisocial behavior (AB). While controversies surrounding the construct of CU traits remain, the Dadds et al. (2014) study in this issue is emblematic of recent research that has focused on understanding the development of CU traits among antisocial youth. We explore four pertinent issues in the study of youth AB highlighted by this study, and highlight this study as exemplar research program that will ultimately help youth and families through translation from the lab to the clinic.
Linking signal fidelity and the efficiency costs of communication
Authors: Hackett S. , Schaefer H. M. , Ruxton G. D.
Published: June 2014

The handicap principle has been the overarching framework to explain the evolution and maintenance of communication. Yet, it is becoming apparent that strategic costs of signalling are not the only mechanism maintaining signal honesty. Rather, the fidelity of detecting signals can itself be strongly selected. Specifically, we argue that the fidelity of many signals will be constrained by the investment in signal generation and reception by the signaller and perceiver, respectively. Here, we model how investments in signal fidelity influence the emergence and stability of communication using a simple theoretical framework. The predictions of the model indicate that high‐cost communication can be stable whereas low‐cost intermediates are generally selected against. This dichotomy suggests that the most parsimonious route to the evolution of communication is for initial investment in communicative traits to be driven by noncommunicative functions. Such cues can appeal to pre‐existing perceptual biases and thereby stimulate signal evolution. We predict that signal evolution will vary between systems in ways that can be linked to the economics of communication to the two parties involved.
Identification and characterization of Mini1, a gene regulating rice shoot development
Authors: Fang Yunxia , Hu Jiang , Xu Jie , Yu Haiping , Shi Zhenyuan , Xiong Guosheng , Zhu Li , Zeng Dali , Zhang Guangheng , Gao Zhenyu , Dong Guojun , Yan Meixian , Guo Longbiao , Wang Yonghong , Qian Qian
Published: June 2014

The aerial parts of higher plants are generated from the shoot apical meristem (SAM). In this study, we isolated a small rice (Oryza sativa L.) mutant that showed premature termination of shoot development and was named mini rice 1 (mini1). The mutant was first isolated from a japonica cultivar Zhonghua11 (ZH11) subjected to ethyl methanesulfonate (EMS) treatment. With bulked segregant analysis (BSA) and map‐based cloning method, Mini1 gene was finally fine‐mapped to an interval of 48.6 kb on chromosome 9. Sequence analyses revealed a single base substitution from G to A was found in the region, which resulted in an amino acid change from Gly to Asp. The candidate gene Os09g0363900 was predicted to encode a putative adhesion of calyx edges protein ACE (putative HOTHEAD precursor) and genetic complementation experiment confirmed the identity of Mini1. Os09g0363900 contains glucose‐methanol‐choline (GMC) oxidoreductase and NAD(P)‐binding Rossmann‐like domain, and exhibits high similarity to Arabidopsis HOTHEAD (HTH). Expression analysis indicated Mini1 was highly expressed in young shoots but lowly in roots and the expression level of most genes involved in auxin biosynthesis and signal transduction were reduced in mutant. We conclude that Mini1 plays an important role in maintaining SAM activity and promoting shoot development in rice.
SVCT2 transporter expression is post‐natally induced in cortical neurons and its function is regulated by its short isoform
Authors: Salazar Katterine , Cerda Gustavo , Martínez Fernando , Sarmiento José M. , González Carlos , Rodríguez Federico , García‐Robles María , Tapia Juan Carlos , Cifuentes Manuel , Nualart Francisco
Published: June 2014

Different studies have demonstrated the importance of micronutrients, such as vitamins, for normal adult brain function and development. Vitamin C is not synthesized in the brain, but high levels are detected in this organ because of the existence of specific uptake mechanisms, which concentrate ascorbic acid from the bloodstream to the cerebrospinal fluid and then into neurons and glial cells. Two different isoforms of sodium–vitamin C cotransporters (SVCT1 and SVCT2) have been cloned. SVCT2 expression has been observed in the adult hippocampus and cortical neurons by in situ hybridization. In addition, the localization of SVCT2 in the rat fetal brain has been studied by immunohistochemistry and in situ hybridization, demonstrating that SVCT2 is highly expressed in the ventricular and subventricular areas of the brain cortex. However, there are currently no immunohistochemical data regarding SVCT2 expression and function in the post‐natal brain. Therefore, we analyzed SVCT2 expression in the developing brain cortex of mice, and demonstrated an increase in SVCT2 mRNA in mice at 1–15 days of age. The expression of a short isoform, SVCT2sh, was also detected within the same period. SVCT2 expression was concentrated in neurons within the inner layer of the brain cortex. Both SVCT2 isoforms were coexpressed in N2a cells to obtain functional data. Fluorescence resonance energy transfer analysis revealed a molecular interaction between SVCT2wt and SVCT2sh. Finally, differences in transport ratios suggested that SVCT2sh expression inhibited ascorbic acid uptake in N2a cells when both isoforms were coexpressed.

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The sodium–vitamin C cotransporter, SVCT2, is induced in neurons within the inner layer of the brain cortex during post‐natal development, mainly in pyramidal cortex neurons. Two different isoforms, SVCT2wt and SVCT2sh, were detected. Using in vitro studies, we suggest a molecular interaction between SVCT2wt and SVCT2sh, which may regulate the affinity of vitamin C uptake.
Ectonucleotide pyrophosphatase/phosphodiesterase activity in Neuro‐2a neuroblastoma cells: changes in expression associated with neuronal differentiation
Authors: Gómez‐Villafuertes Rosa , Pintor Jesús , Miras‐Portugal María Teresa , Gualix Javier
Published: June 2014

Neuro‐2a (N2a) neuroblastoma cells display an ectoenzymatic hydrolytic activity capable of degrading diadenosine polyphosphates. The ApnA‐cleaving activity has been analysed with the use of the fluorogenic compound BODIPY® FL guanosine 5′‐O‐(3‐thiotriphosphate) thioester. Hydrolysis of this dinucleotide analogue showed a hyperbolic kinetic with a Km value of 4.9 ± 1.3 μM. Diadenosine pentaphosphate, diadenosine tetraphosphate, diadenosine triphosphate, and the nucleoside monophosphate AMP behaved as an inhibitor of BODIPY® FL guanosine 5′‐O‐(3‐thiotriphosphate) thioester extracellular degradation. Ectoenzymatic activity shared the typical characteristics of the ectonucleotide pyrophosphatase/phosphodiesterase family, as hydrolysis reached maximal activity at alkaline pH and was dependent on the presence of divalent cations, being strongly inhibited by EDTA and activated by Zn2+ ions. Both NPP1 and NPP3 isozymes are expressed in N2a cells, their expression levels substantially changing when cells differentiate into a neuronal‐like phenotype. In this sense, it is relevant to point the expression pattern of the NPP3 protein, whose levels were drastically reduced in the differentiated cells, being almost completely absent after 24 h of differentiation. Enzymatic activity assays carried out with differentiated N2a cells showed that NPP1 is the main isozyme involved in the extracellular degradation of dinucleotides in these cells, this enzyme reducing its activity and changing its subcellular location following neuronal differentiation.

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We described the presence of an ectoenzymatic activity able to hydrolyse diadenosine polyphosphates (ApnA) in N2a cells. This activity displays biochemical features that are typical of the ectonucleotide pyrophosphatase/phosphodiesterase (E‐NPP) family members, as demonstrated by the use of the fluorogenic compound BODIPY‐FL‐GTPγS. Both NPP1 and NPP3 ectoenzymes are expressed in N2a cells, their levels dramatically changing when cells differentiate into a neuronal‐like phenotype. Activity assays in differentiated cells showed that the ApnA‐hydrolytic activity largely depends on the NPP1 isozyme.
Hypoxia‐inducible factor‐1α mediates up‐regulation of neprilysin by histone deacetylase‐1 under hypoxia condition in neuroblastoma cells
Authors: Wang Hecheng , Sun Miao , Yang Huan , Tian Xiaosheng , Tong Yawei , Zhou Ting , Zhang Tao , Fu Yaoyun , Guo Xiangyang , Fan Dongsheng , Yu Albert , Fan Ming , Wu Xuefei , Xiao Weizhong , Chui Dehua
Published: June 2014

Hypoxia‐inducible factor (HIF)‐1 is the key transcriptional activator mediating both adaptive and pathological responses to hypoxia. The purpose of this study was to find the role of HIF‐1 in regulating neprilysin (NEP) at the early stage of hypoxia and explore the underlying mechanism. In this study, we demonstrated that both NEP mRNA and protein levels in neuroblastoma cells were elevated in early stages of hypoxia. Over‐expression of HIF‐1α gene increased NEP mRNA/protein levels, as well as enzyme activity while knockdown of HIF‐1α decreased them. Meanwhile, HIF‐1α was shown to bind to histone deacetylase (HDAC)‐1 and reduced the association of HDAC‐1 with NEP promoter, thus activating NEP gene transcription in a de‐repression way. In summary, our results indicated that hypoxia in the early stages would up‐regulate NEP expression, in which interaction of HIF‐1α and HDAC‐1 may play a role. This study suggested that NEP up‐regulation might be an adaptive response to hypoxia, which was mediated by HIF‐1α binding to HDAC‐1 at the early stage of hypoxia.

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HIF‐1 binded to and disassociated HDAC‐1 from NEP promoter, activating NEP gene expression at early stage of hypoxia. HDAC‐1 protein level was elevated at late stage of hypoxia that exceeded the binding capacity of HIF‐1 to prevent association of HDAC‐1 from NEP promoter, leading to suppression of NEP.
Differential protein–protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways
Authors: Reyniers Lauran , Del Giudice Maria Grazia , Civiero Laura , Belluzzi Elisa , Lobbestael Evy , Beilina Alexandra , Arrigoni Giorgio , Derua Rita , Waelkens Etienne , Li Yan , Crosio Claudia , Iaccarino Ciro , Cookson Mark R. , Baekelandt Veerle , Greggio Elisa , Taymans Jean‐Marc
Published: June 2014

Genetic studies show that LRRK2, and not its closest paralogue LRRK1, is linked to Parkinson's disease. To gain insight into the molecular and cellular basis of this discrepancy, we searched for LRRK1‐ and LRRK2‐specific cellular processes by identifying their distinct interacting proteins. A protein microarray‐based interaction screen was performed with recombinant 3xFlag‐LRRK1 and 3xFlag‐LRRK2 and, in parallel, co‐immunoprecipitation followed by mass spectrometry was performed from SH‐SY5Y neuroblastoma cell lines stably expressing 3xFlag‐LRRK1 or 3xFlag‐LRRK2. We identified a set of LRRK1‐ and LRRK2‐specific as well as common interactors. One of our most prominent findings was that both screens pointed to epidermal growth factor receptor (EGF‐R) as a LRRK1‐specific interactor, while 14‐3‐3 proteins were LRRK2‐specific. This is consistent with phosphosite mapping of LRRK1, revealing phosphosites outside of 14‐3‐3 consensus binding motifs. To assess the functional relevance of these interactions, SH‐SY5Y‐LRRK1 and ‐LRRK2 cell lines were treated with LRRK2 kinase inhibitors that disrupt 14‐3‐3 binding, or with EGF, an EGF‐R agonist. Redistribution of LRRK2, not LRRK1, from diffuse cytoplasmic to filamentous aggregates was observed after inhibitor treatment. Similarly, EGF induced translocation of LRRK1, but not of LRRK2, to endosomes. Our study confirms that LRRK1 and LRRK2 can carry out distinct functions by interacting with different cellular proteins.

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LRRK1 and LRRK2 (leucine‐rich repeat kinase) interaction partners were identified by two different protein‐protein interaction screens. These confirmed epidermal growth factor receptor (EGR‐R) as a LRRK1‐specific interactor, while 14‐3‐3 proteins were LRRK2‐specific. Functional analysis of these interactions and the pathways they mediate shows that LRRK1 and LRRK2 signaling do not intersect, reflective of the differential role of both LRRKs in Parkinson's disease.
A functional variant in the 5′‐flanking region of the chicken serotonin transporter gene is associated with increased body weight and locomotor activity
Authors: Phi‐van Loc , Holtz Marlis , Kjaer Joergen B. , van Phi Valerie D. , Zimmermann Katrin
Published: June 2014

In this study, we identified a polymorphism in the 5′‐flanking region of the chicken serotonin transporter (5‐HTT) gene. Sequencing analysis revealed that in comparison with the wild‐type variant (W), a deleted variant (D) is generated by deletion of four nucleotides (5′‐AATT‐3′) and a single nucleotide change (A→T). Using a polyacrylamide gel electrophoresis system, we found that the 360‐bp DNA fragment containing the W variant with the wild‐type sequence 5′‐AATTAATT‐3′ shows intrinsic DNA curvature while the 356‐bp fragment containing the D variant lacking the four base pairs AATT is not curved. Quantitative real‐time RT‐PCR and ELISA demonstrated that the expression of 5‐HTT in D/D chickens was higher than that in W/W and W/D chickens. In addition, transient transfection experiments with chloramphenicol acetyltransferase reporter gene constructs revealed increased 5‐HTT promoter activity mediated by the D variant and a silencer activity of the W variant. Interestingly, females and males with D/D genotype showed significant greater increase in body weight from 6 weeks and 16 weeks of age, respectively, and higher body mass index. Moreover, we found that D/D chickens of both genders were physically more active than W/W and W/D chickens.

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We identified a polymorphism in the 5'‐flanking region of the chicken serotonin transporter (5‐HTT) gene. The expression of 5‐HTT in D/D chickens was higher than that in W/W and W/D chickens. D/D females showed significant greater increase in body weight from 6 weeks of age, higher body mass index and higher content of intra‐abdominal fat. The presence of D/D alleles resulted in increase in physical activity.
Localization of RANK, RANKL and osteoprotegerin during healing of surgically created periodontal defects in sheep
Authors: Baharuddin N. A. , Coates D. E. , Cullinan M. , Seymour G. , Duncan W.
Published: June 2014

Background and Objective

Modeling of periodontal bone regeneration in a large animal enables better examination of the spatial and temporal regulation of osteogenesis and the remodeling of the healing defect. RANK, RANKL and osteoprotegerin (OPG) are known to be important regulators of bone healing. The aim of this study was to create periodontal defects surgically in a large animal model and to examine bone regeneration and the expression of RANK, RANKL and OPG proteins in the defect site during bone regeneration.

Material and Methods

Periodontal defects were made in the furcation of the second mandibular premolar of sheep. Wound healing was examined 6 h, and 1, 4 and 6 wk after surgery and in control tissue. The teeth and defect region were decalcified and paraffin embedded. Immunohistochemistry for RANK, RANKL and OPG was conducted. Osteoclasts were identified using TRAP staining.

Results

The defects were examined at different time points after surgery and by 6 wk the defect region had fully regenerated with new bone, albeit less dense than that in the unwounded controls. RANK‐positive osteoclasts were present at the edge of the wound from week 1 and were found within the defect at week 6, corresponding to osteoclast activation and bone remodeling. RANKL staining increased from week 1 compared with unwounded tissue, and peaked at 4 and 6 wk, as the osteoblast numbers increased. At the same time, OPG immunostaining was high in controls and at week 6, suggesting that it may act to block RANKL and control the bone remodeling within the defect.

Conclusion

Distinctive temporal and spatial expression patterns for RANK, RANKL and OPG proteins were observed during healing of surgically created periodontal wounds in a sheep model. The research identifies possible therapeutic approaches to periodontal bone repair via modulation of these members of the tumor necrosis factor family.
Mechanical induction of interleukin‐11 regulates osteoblastic/cementoblastic differentiation of human periodontal ligament stem/progenitor cells
Authors: Monnouchi S. , Maeda H. , Yuda A. , Hamano S. , Wada N. , Tomokiyo A. , Koori K. , Sugii H. , Serita S. , Akamine A.
Published: June 2014

Background and Objective

The periodontal ligament (PDL) is continually exposed to mechanical loading caused by mastication or occlusion. Physiological loading is thus considered a key regulator of PDL tissue homeostasis; however, it remains unclear how this occurs. We recently reported that an appropriate magnitude of mechanical stretch can maintain PDL tissue homeostasis via the renin–angiotensin system. In the present study, we investigated the expression of interleukin‐11 (IL‐11) in human primary PDL cells (HPDLCs) exposed to stretch loading, the contribution of angiotensin II (Ang II) to this event and the effects of IL‐11 on osteoblastic/cementoblastic differentiation of human PDL progenitor cells (cell line 1‐17).

Material and Methods

Human primary PDL cells, derived from human tissues, with or without antagonists against the Ang II receptors AT1 or AT2, were subjected to cyclical stretch loading with 8% elongation for 1 h. Expression of IL‐11 was measured by ELISA in these cultures and by immunohistochemistry in the sectioned maxillae of rats. The osteoblastic/cementoblastic potential of cell line 1‐17 was determined using cell proliferation, gene expression and Alizarin Red staining.

Results

Positive staining for IL‐11 was observed in the PDL of rat maxillae and in cultures of HPDLCs. In HPDLCs exposed to stretch, expression of the IL11 gene and the IL‐11 protein were up‐regulated, concomitant with an increase in Ang II and via AT2. Recombinant human IL‐11 (rhIL‐11) stimulated an increase in expression of mRNA for the cementoblast‐specific marker, CP‐23, and for the osteoblastic markers, osteopontin and bone sialoprotein, and promoted proliferation in cell line 1‐17. In addition, rhIL‐11 also increased the degree of mineralized nodule formation in cell line 1‐17 cultures treated with CaCl2.

Conclusion

Mechanical loading appears to control proliferation and osteoblastic/cementoblastic differentiation of human PDL stem/progenitor cells through the regulation of Ang II and AT2 by IL‐11.
Synthetic hexaploid wheat enhances variation and adaptive evolution of bread wheat in breeding processes
Authors: LI Jun , WAN Hong‐Shen , YANG Wu‐Yun
Published: June 2014

Synthetic hexaploid wheat (SHW) that combines novel and elite genes from the tetraploid wheat Triticum turgidum L. and wild ancestor Aegilops tauschii Coss., has been used to genetically improve hexaploid common wheat. The abundant genetic diversity in SHW can effectively make breakthroughs in wheat genetic improvement through the inclusion of increased variation. In this paper, we reviewed the current advances in research and utilization of the primary SHW lines and SHW‐derived wheat varieties that have enhanced evolution of modern wheat under conditions of natural and artificial selection in southwestern China. Using primary SHW lines, four high‐yielding wheat varieties have been developed. In addition, using the SHW‐derived varieties as breeding parents, 12 new wheat varieties were also developed. Results of genotype–phenotype and fingerprint analysis showed that the introgressed alleles from SHW lines have contributed a great number of elite characters to the new wheat varieties, and these elite characters include disease resistance, more spikes per plant, more grains per spike, larger grains, and higher grain‐yield potential. We found that the primary SHW lines and SHW‐derived varieties have identifiable effects to enhance genetic variation and adaptive evolution of modern hexaploid wheat, which significantly increased the grain yields of hexaploid wheat in recent years. These findings have significant implications in the breeding of high‐yielding wheat varieties resistant to biotic and abiotic stresses using SHW as genetic resources.
Evolution of the cyclin gene family in plants
Authors: JIA Rui‐Dong , GUO Chun‐Ce , XU Gui‐Xia , SHAN Hong‐Yan , KONG Hong‐Zhi
Published: June 2014

Cyclins are key regulators of cell cycle progression. Previous studies have shown that cyclin genes in plants can be divided into 10 groups. However, because those studies only focused on genes from two well‐known model plants (i.e., Arabidopsis thaliana (L.) Heynh. and Oryza sativa L.), it remains unclear whether the 10 groups are reasonably defined. In this study, by analyzing the genomes of 10 representative plants (Chlamydomonas reinhardtii P. A. Dang, Physcomitrella patens (Hedw.) Bruch & Schimp., Selaginella moellendorffii Hieron., Picea abies (L.) H. Karst., Amborella trichopoda Baill., A. thaliana, Populus trichocarpa Torr. & A. Gray ex Hook., Vitis vinifera L., O. sativa, and Sorghum bicolor (L.) Moench), we estimated the phylogenetic relationships of plant cyclins and investigated their evolutionary patterns. We confirmed that plant cyclins can be classified into 10 groups, although only eight ancestral genes may have existed in the most recent common ancestor of extant green plants. We also found that, due to the frequent occurrences of gene duplication events, several groups have expanded extensively in seed plants and, particularly, flowering plants, so that multiple genes belonging to different subgroups are present in a species. Reconciliation of the evolutionary histories of these groups and subgroups further led to the identification of evolutionarily highly conserved and rapidly duplicating gene lineages. These results will guide the classification and nomenclature of plant cyclins and help understand the conservativeness and variation in their functions.
Comparative analysis of Stowaway‐like miniature inverted repeat transposable elements in wheat group 7 chromosomes: Abundance, composition, and evolution
Authors: LU Yun‐Ze , WANG Le , YUE Hong , WANG Meng‐Xing , DENG Ping‐Chuan , EDWARDS David , WEINING Song
Published: June 2014

Miniature inverted repeat transposable elements (MITEs) are the most ubiquitous transposable elements in eukaryotic genomes; they play a prominent role in sequence divergence and genome evolution. There are many well‐characterized Stowaway‐like MITE families in wheat, but their distribution, abundance, and composition at the chromosome level are still not well understood. In this study, we systematically investigated the Stowaway‐like MITEs in wheat group 7 chromosomes based on the survey sequences of isolated wheat chromosomes, to compare them at the chromosome level and to reveal their evolutionary role on wheat polyploidization. In summary, 2026 MITEs were identified, of which 587, 714, and 725 were distributed on 7A, 7B, and 7D chromosomes, respectively. There are more MITEs present on 7D, compared to 7A and 7B, suggesting A and B subgenomes eliminated some repetitive elements during two hybridization processes. Furthermore, some chromosome/arm‐specific MITEs were also identified, providing information on the function and evolution of MITEs in wheat genomes. The sequence diversity of the MITE insertions was also investigated. This study for the first time investigated the abundance and composition of MITEs at the chromosome level, which will be beneficial to improve our understanding of the distribution of wheat MITEs and their evolutionary role in polyploidization.
MULTIVARIATE SUBORDINATION OF MARKOV PROCESSES WITH FINANCIAL APPLICATIONS
Authors: Mendoza‐Arriaga Rafael , Linetsky Vadim
Published: June 2014

This paper develops the procedure of multivariate subordination for a collection of independent Markov processes with killing. Starting from d independent Markov processes with killing and an independent d‐dimensional time change , we construct a new process by time, changing each of the Markov processes with a coordinate . When is a d‐dimensional Lévy subordinator, the time changed process is a time‐homogeneous Markov process with state‐dependent jumps and killing in the product of the state spaces of . The dependence among jumps of its components is governed by the d‐dimensional Lévy measure of the subordinator. When is a d‐dimensional additive subordinator, Y is a time‐inhomogeneous Markov process. When with forming a multivariate Markov process, is a Markov process, where each plays a role of stochastic volatility of . This construction provides a rich modeling architecture for building multivariate models in finance with time‐ and state‐dependent jumps, stochastic volatility, and killing (default). The semigroup theory provides powerful analytical and computational tools for securities pricing in this framework. To illustrate, the paper considers applications to multiname unified credit‐equity models and correlated commodity models.