bluuebunny/crossref_metadata_2025 huggingface dataset:
Diterbium heptanickel: a crystal structure redetermination
Authors: Levytskyy Volodymyr , Babizhetskyy Volodymyr , Kotur Bohdan , Smetana Volodymyr
Published: July 2014

The crystal structure of the title compound, Tb2Ni7, was redetermined from single-crystal X-ray diffraction data. In comparison with previous studies based on powder X-ray diffraction data [Lemaireet al.(1967).C. R. Acad. Sci. Ser. B,265, 1280–1282; Lemaire & Paccard (1969).Bull. Soc. Fr. Mineral. Cristallogr.92, 9–16; Buschow & van der Goot (1970).J. Less-Common Met.22, 419–428], the present redetermination affords refined coordinates and anisotropic displacement parameters for all atoms. A partial occupation for one Tb atom results in the non-stoichiometric composition Tb1.962 (4)Ni7. The title compound adopts the Ce2Ni7structure type and can also be derived from the CaCu5structure type as an intergrowth structure. The asymmetric unit contains two Tb sites (both site symmetries 3m.) and five Ni sites (.m.,mm2, 3m., 3m., -3m.). The two different coordination polyhedra of Tb are a Frank–Kasper polyhedron formed by four Tb and 12 Ni atoms and a pseudo Frank–Kasper polyhedron formed by two Tb and 18 Ni atoms. The four different coordination polyhedra of Ni are Frank–Kasper icosahedra formed by five Tb and seven Ni atoms, four Tb and eight Ni atoms, three Tb and nine Ni atoms, and six Tb and six Ni atoms, respectively.
Experimental manipulation of female reproduction demonstrates its fitness costs in kangaroos
Authors: Gélin Uriel , Wilson Michelle E. , Coulson Graeme , Festa‐Bianchet Marco
Published: July 2014

When resources are scarce, female mammals should face a trade‐off between lactation and other life‐history traits such as growth, survival and subsequent reproduction. Kangaroos are ideal to test predictions about reproductive costs because they may simultaneously lactate and carry a young, and have indeterminate growth and a long breeding season.

An earlier study in three of our five study populations prevented female eastern grey kangaroos (Macropus giganteus) from reproducing during one reproductive season by either inserting contraceptive implants or removing very small pouch young. We explored how individual and environmental variables affect the costs of reproduction over time, combining this experimental reduction of reproductive effort with multi‐year monitoring of 270 marked females. Experimental manipulation should control for individual heterogeneity, revealing the costs of reproduction and their likely sources. We also examined the fitness consequences of reproductive effort and offspring sex among unmanipulated individuals to test whether sex allocation strategies affected trade‐offs.

Costs of reproduction included longer inter‐birth intervals and lower probability of producing a young that survived to 7 months in the subsequent reproductive event. Weaning success, however, did not differ significantly between manipulated and control females. By reducing reproductive effort, manipulation appeared to increase individual condition and subsequent reproductive success.

Effects of offspring sex upon subsequent reproductive success varied according to year and study population. Mothers of sons were generally more likely to have a young that survived to 7 months, compared to mothers of daughters.

The fitness costs of reproduction arise from constraints in both acquisition and allocation of resources. To meet these costs, females delay subsequent parturition and may manipulate offspring sex. Reproductive tactics thus vary according to the amount of resource available to each individual, promoting a wide range in reproductive performance within and among individuals and populations.
Prioritizing barrier removal to improve functional connectivity of rivers
Authors: Branco Paulo , Segurado Pedro , Santos José M. , Ferreira Maria T.
Published: July 2014

Freshwater systems are severely impacted by connectivity reduction due to the construction of dams and weirs. The breach of this longitudinal connectivity imperils freshwater fish species world‐wide. There is thus an increasing need for numerical tools that help decision‐makers correctly allocate resources to prioritize restoration actions.

This study provides a methodology for prioritizing the removal of barriers. It is based on spatial graphs, which represent structural units as nodes and relationships between nodes as links, and uses habitat suitability modelling (Boosted Regression Trees) to weight nodes. To exemplify the application of this procedure, we used the Tagus River network and evaluated the impact of the dams (29 built between 1928 and 2004) on the occurrence of each of two fish species (Iberian barbel Luciobarbus bocagei – representing large potamodromous fish; and southern Iberian chub Squalius pyrenaicus – representing small water‐column residents) and on the combination of both.

Results show that dam construction on the Tagus was responsible for a 48·4–54·4% reduction in river connectivity for different fish species. Actions to promote connectivity in just seven of the dams would increase connectivity by 35·0–37·2%.

The removal of a single barrier chosen through prioritization had a greater overall connectivity increase than the random removal of seven barriers.

Synthesis and applications. The proposed prioritization method, using spatial graphs and habitat suitability modelling, makes it possible to model the impact of the removal or placement of an insurmountable barrier on the overall functional connectivity of a river network, facilitating resource allocation and minimizing the impact of new barrier implementation.
Postoperative chemo‐radiotherapy versus chemotherapy for resected gastric cancer: A systematic review and meta‐analysis
Authors: Soon Yu Yang , Leong Cheng Nang , Tey Jeremy Chee Seong , Tham Ivan Weng Keong , Lu Jiade Jay
Published: July 2014

Introduction

This study conducted a systematic review and meta‐analysis (direct and indirect) of published randomised controlled trials (RCTs) to compare the effects of postoperative chemo‐radiotherapy (ChRT) with chemotherapy (Ch) on overall and disease‐free survival (DFS) for patients with resectable gastric cancer.

Methods

We searched MEDLINE and CENTRAL from the date of inception and annual meeting proceedings of American Society of Clinical Oncology and American Society for Radiation Oncology from 1999 to November 2012 for RCTs comparing postoperative ChRT with Ch, postoperative ChRT with surgery alone and postoperative Ch with surgery alone. The primary outcome was overall survival (OS); secondary outcomes included DFS and toxicity. Hazard ratios (HRs), confidence intervals (CIs) and P values (P) were estimated with fixed effects models using Revman 5.1.

Results

We found six trials comparing postoperative ChRT with Ch (n = 1171). Meta‐analysis of direct comparison trials showed that postoperative ChRT significantly improved both OS (HR 0.80, 95% CI 0.65–0.98, P = 0.03) and DFS (HR 0.76, 95% CI 0.63–0.91, P = 0.003) when compared with Ch. There were no significant differences in toxicity between the two groups.

Conclusions

This study suggests a survival benefit of postoperative ChRT over Ch in patients with resected gastric cancer.
Value of MRI sequences for prediction of invasive breast carcinoma size
Authors: Durur‐Subasi Irmak , Durur‐Karakaya Afak , Karaman Adem , Demirci Elif , Alper Fatih , Yılmazel‐Ucar Elif , Acemoglu Hamit , Akcay Mufide Nuran
Published: July 2014

Introduction

In this retrospective study, we compared transverse short tau inversion recovery (STIR), transverse diffusion‐weighted imaging (DWI), apparent diffusion coefficient (ADC) map and first post‐contrast fat‐saturated fast low‐angle shot (FLASH) 3D T1 with pathology results in terms of their accuracy in estimating breast carcinoma size.

Methods

Magnetic resonance imaging data for 47 patients with invasive breast carcinoma, who were treated surgically, were reviewed. The longest dimension (LD) of the index lesion was measured using STIR, DWI, ADC map and first post‐contrast FLASH 3D T1, and this was compared with the LD measured on the pathology specimen.

Results

All four MRI sequences overestimated the LD by an average of about 1 mm with 95% limits of agreement approximately 0 to 2 mm. This is not considered to be clinically significant in tumours of 10 mm or larger.

Conclusion

Magnetic resonance imaging serves as an accurate tool in sizing breast carcinomas. ADC may be a useful evaluation tool for sizing carcinomas without requiring contrast material.
Understanding the Complexity of the Immune System during Pregnancy
Authors: Racicot Karen , Kwon Ja‐Young , Aldo Paulomi , Silasi Michelle , Mor Gil
Published: July 2014

Progress in our understanding of the role of the maternal immune system during healthy pregnancy will help us better understand the role of the immune system in adverse pregnancy outcomes. In this review, we discuss our present understanding of the ‘immunity of pregnancy’ in the context of the response to cervical and placental infections and how these responses affect both the mother and the fetus. We discuss novel and challenging concepts that help explain the immunological aspects of pregnancy and how the mother and fetus respond to infection.
Involvement of two distinct signalling pathways in IGF‐1‐mediated central control of hypotensive effects in normotensive and hypertensive rats
Authors: Cheng P.‐W. , Kang B.‐H. , Lu P.‐J. , Lin S.‐S. , Ho W.‐Y. , Chen H.‐H. , Hong L.‐Z. , Wu Y.‐S. , Hsiao M. , Tseng C.‐J.
Published: July 2014

Aims

Insulin‐like growth factor‐1 (IGF‐1) is abundantly expressed in the nucleus tractus solitarii (NTS). In a previous study, we revealed that the induction of nitric oxide (NO) production in the NTS reduces blood pressure (BP). It is well known that both acute administration and chronic administration of IGF‐I reduce BP. The aim of this study was to evaluate the short‐term hypotensive effect of IGF‐1 in the NTS and to delineate the underlying molecular mechanisms of IGF‐1 in the NTS of normotensive WKY rats and spontaneously hypertensive rats (SHRs).

Method

Microinjections of the phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 and the MAP kinase‐ERK kinase (MEK) inhibitor PD98059 into the NTS in WKY rats and SHRs were used to study the involvement of IGF‐1‐induced depressor effects.

Result

An IGF‐1 (7.7 pmol) injection into the NTS resulted in a significant decrease in BP and HR in WKY rats and SHRs. Immunoblotting and immunohistochemical analysis showed that the microinjection of LY294002 (0.6 pmol) or PD98059 (3.0 pmol) into the NTS attenuated the IGF‐1‐induced depressor effects and Akt or ERK phosphorylation in WKY rats. An attenuation effect of LY294002, but not PD98059, was found in the SHRs. However, the mRNA and protein expression levels of the IGF‐1R showed no significant differences in the NTS of the WKY rats and the SHRs.

Conclusion

These results suggest that distinct Akt and ERK signalling pathways mediated the IGF‐1 control of the central depressor effects in WKY rats and SHRs. ERK signalling defects may be associated with the development of hypertension.
Apelin‐13 and APJ in paraventricular nucleus contribute to hypertension via sympathetic activation and vasopressin release in spontaneously hypertensive rats
Authors: Zhang F. , Sun H.‐J. , Xiong X.‐Q. , Chen Q. , Li Y.‐H. , Kang Y.‐M. , Wang J.‐J. , Gao X.‐Y. , Zhu G.‐Q.
Published: July 2014

Aims

Apelin is a specific endogenous ligand of orphan G protein‐coupled receptor APJ. This study was designed to determine the roles and mechanisms of apelin‐13 and APJ in paraventricular nucleus (PVN) in renal sympathetic nerve activity (RSNA), arginine vasopressin (AVP) release and mean arterial pressure (MAP) in spontaneously hypertensive rats (SHR).

Method

Acute experiment was carried out in 13‐week‐old male SHR and Wistar‐Kyoto rats (WKY) under anaesthesia. RSNA and MAP responses to the PVN microinjection were determined. Apelin and APJ expressions were examined with quantitative real‐time PCR and Western blot. AVP and noradrenaline were determined with ELISA. Osmotic minipumps were used for chronic PVN infusion in conscious WKY.

Results

Apelin and APJ in the PVN were up‐regulated in SHR. The PVN microinjection of apelin‐13 increased, but APJ antagonist F13A decreased the RSNA, MAP, plasma noradrenaline and AVP levels in SHR. N‐methyl‐D‐aspartate receptor (NMDAR) antagonist plus non‐NMDAR antagonist abolished the apelin‐13‐induced sympathetic activation rather than AVP release. NMDAR antagonist or non‐NMDAR antagonist alone attenuated the apelin‐13‐induced sympathetic activation. Chronic infusion of apelin‐13 into the PVN in normotensive rats induced hypertension, increased plasma noradrenaline and AVP levels and promoted myocardial atrial natriuretic peptide and beta‐myosin heavy chain mRNA expressions, two indicative markers of cardiac hypertrophy.

Conclusion

Apelin‐13 and APJ in the PVN contribute to hypertension via sympathetic activation and AVP release in SHR. The sympatho‐excitatory effect of apeline‐13 is mediated by both NMDAR and non‐NMDAR in the PVN. Persistent activation of APJ in the PVN induces hypertension.
A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers
Authors: Faruqi Shoaib , Wright Caroline , Thompson Rachel , Morice Alyn H.
Published: July 2014

Aims

The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin‐induced cough in healthy volunteers.

Methods

In this randomized, placebo‐controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre‐dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships.

Results

Thirty‐four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate.

Conclusions

We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses.
Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS
Authors: Zeidan Amer M. , Lee Ju‐Whei , Prebet Thomas , Greenberg Peter , Sun Zhuoxin , Juckett Mark , Smith Mitchell R. , Paietta Elisabeth , Gabrilove Janice , Erba Harry P. , Katterling Rhett P. , Tallman Martin S. , Gore Steven D.
Published: July 2014

Reliable clinical or molecular predictors of benefit from azacitidine therapy in patients with myelodysplastic syndromes (MDS) are not defined. Doubling of platelet count at start of second cycle of azacitidine therapy compared to baseline was associated with achieving response and survival advantage in a Dutch cohort. To validate this observation, we analysed a larger cohort of North American patients, whose data was collected in a prospective clinical trial with a longer median follow‐up. We found a significant association between platelet count doubling after first cycle of azacitidine therapy and probability of achieving objective response. Among patients with MDS or oligoblastic acute myeloid leukaemia (<30% bone marrow blasts, n = 102), there was a statistically significant reduction in risk of death for patients who achieved platelet count doubling (n = 23, median OS, 21·0 months) compared to those who did not (n = 79, median OS, 16·7 months, adjusted hazard ratio (no/yes)=1·88, 95% confidence interval, 1·03–3·40, P = 0·04). Nonetheless, the addition of this platelet count doubling variable did not improve the survival prediction provided by the revised International Prognostic Scoring System or the French Prognostic Scoring System. Identification of reliable and consistent predictors for clinical benefit for azacitidine therapy remains an unmet medical need and a top research priority.
Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia
Authors: Dandekar Smita , Romanos‐Sirakis Eleny , Pais Faye , Bhatla Teena , Jones Courtney , Bourgeois Wallace , Hunger Stephen P. , Raetz Elizabeth A. , Hermiston Michelle L. , Dasgupta Ramanuj , Morrison Debra J. , Carroll William L.
Published: July 2014

While childhood acute lymphoblastic leukaemia (ALL) is now highly curable, the dismal prognosis for children who relapse warrants novel therapeutic approaches. Previously, using an integrated genomic analysis of matched diagnosis‐relapse paired samples, we identified overactivation of the Wnt pathway as a possible mechanism of recurrence. To validate these findings and document whether Wnt inhibition may sensitize cells to chemotherapy, we analysed the expression of activated β‐catenin (and its downstream target BIRC5) using multiparameter phosphoflow cytometry and tested the efficacy of a recently developed Wnt inhibitor, iCRT14, in ALL cell lines and patient samples. We observed increased activation of β‐catenin at relapse in 6/10 patients. Furthermore, treatment of leukaemic cell lines with iCRT14 led to significant downregulation of Wnt target genes and combination with traditional chemotherapeutic drugs resulted in a synergistic decrease in viability as well as a significant increase in apoptotic cell death. Finally, pre‐treatment of purified blasts from patients with relapsed leukaemia with the Wnt inhibitor followed by exposure to prednisolone, restored chemosensitivity in these cells. Our results demonstrate that overactivation of the Wnt pathway may contribute to chemoresistance in relapsed childhood ALL and that Wnt‐inhibition may be a promising therapeutic approach.
Microwave‐assisted Synthesis of Cyclic Phosphopeptide on Solid Support
Authors: Qvit Nir
Published: July 2014

Phosphopeptides are important tools for studying intracellular signal transduction events in vitro and in vivo and are also potential drugs due to their direct competition with phosphoprotein recognition elements. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, cyclic phosphopeptide synthesis may not be straightforward due to the sterically hindered phosphorylated side‐chain amino acid derivatives. One option to overcome this hurdle is to use microwave‐assisted synthesis, which has been shown to increase efficiency and reduce synthesis time. Herein, a detailed protocol is provided for synthesizing cyclic phosphopeptides using automated microwave. The overall synthesis duration was reduced and yields increased compared with a manual conventional method. This method provides a general, fast and facile way to synthesize cyclic peptides, demonstrating the synthesis of cyclic phosphorylated peptides which are known to be among the most challenging to produce.
Differences in activities of daily living (ADL) abilities of children across world regions: a validity study of the assessment of motor and process skills
Authors: Gantschnig B. E. , Fisher A. G. , Page J. , Meichtry A. , Nilsson I.
Published: July 2014

Background

One important goal of paediatric occupational therapy services is to improve activities of daily living (ADL) abilities of children. In order to plan and evaluate the effectiveness of targeted interventions, valid assessments are critically needed. The Assessment of Motor and Process Skills (AMPS) is an internationally standardized assessment of ADL performance that has not been validated for use with children in Middle Europe.

Aim

To evaluate for (i) significant differences in mean ADL motor and mean ADL process ability measures among children from Middle Europe compared with children from North America, UK/Republic of Ireland, Nordic countries, Western Europe, Australia/New Zealand and Asia; and (ii) meaningful differences between the international age‐normative means of the AMPS and those for children from Middle Europe.

Method

We analysed data of children across world regions extracted from the international AMPS database using many‐facet Rasch and two‐way anova analyses and by estimating contrasts to evaluate for significant group differences.

Results

anova analyses of data for 11 189 children ages 2–15 revealed significant effects for mean ADL motor and ADL process ability by region [F ≥ 15.32, d.f. = (6, 11 091), MSE ≥ 0.20, P < 0.001, ή2 ≥ 0.008], and age [F ≥ 253.47, d.f. = (13, 11 091), MSE ≥ 0.20, P < 0.001, ή2 ≥ 0.229], and a significant interaction effect for mean ADL process ability [F = 1.48, d.f. = (78, 11 091), P = 0.004, ή2 = 0.010]. Out of 168 estimated contrasts between Middle Europe and the other world regions for mean ADL motor and ADL process ability, seven were statistically significant (4.17%), but none exceeded ±1SE from the international means.

Conclusion

The AMPS remains free of relevant differences in mean ADL ability measures between Middle Europe and other world regions, indicating that the international age‐normative mean values are likely to be applicable to children from Middle Europe. The AMPS can be used internationally to evaluate ADL performance in children and to determine if the child is eligible for occupational therapy services.
The role of partial recording protocols in reporting prevalence and severity of dental fluorosis
Authors: Akinkugbe Aderonke , Iafolla Timothy , Chattopadhyay Amit , Garcia Isabel , Adams Amy , Kingman Albert
Published: July 2014

Objectives

To evaluate the role of partial recording protocols (PRPs) in reporting prevalence and severity of dental fluorosis and assess whether prevalence/severity estimates derived from PRPs differ by race/ethnicity.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999–2004 were analyzed with Stata® v.11. Prevalence of dental fluorosis obtained from a full‐mouth examination (28 teeth gold standard) was compared with estimates derived from four subsets of teeth (maxillary canine‐to‐canine; maxillary first‐premolar‐to‐first‐premolar; all‐premolars; all‐molars). Sensitivity, negative predictive value (NPV), absolute bias, and correction factors were calculated against gold standard estimate. Analysis was stratified according to race/ethnicity to assess differences in estimates derived from PRPs.

Results

All subsets underestimated prevalence albeit to varying degrees. Two subsets (all‐premolars and all‐molars) had prevalence and severity estimates closest to gold standard estimates. The all‐molars subset (eight teeth) recorded the highest sensitivity (84.5%) and the lowest absolute bias (3.5%) of all subsets relative to gold standard. Subsets derived from esthetically relevant teeth produced the lowest fluorosis prevalence. For instance, the maxillary canine‐to‐canine subset underestimated prevalence by 9.5%; incorporating the maxillary first premolars in the span improved prevalence estimate by 31%. Among non‐Hispanic Whites, the all‐premolars subset produced estimates closest to gold standard while the all‐molars subset produced estimates closest to the gold standard among non‐Hispanic Blacks and Hispanics.

Conclusion

While the majority of dental fluorosis in the United States is very mild, concerns regarding its growing prevalence underscore the need for careful monitoring. The use of PRPs offers an alternative method of assessment, with validity of reported prevalence and severity dependent on choice of subset.
Unconventional apoptosis of polymorphonuclear neutrophils (PMN): staurosporine delays exposure of phosphatidylserine and prevents phagocytosis by MΦ-2 macrophages of PMN
Authors: Franz S , Muñoz L E , Heyder P , Herrmann M , Schiller M
Published: July 2014

Apoptosis of polymorphonuclear neutrophils (PMN) and subsequent ‘silent’ removal represents an important check-point for the resolution of inflammation. Failure in PMN clearance resulting in secondary necrosis-driven tissue damage has been implicated in conditions of chronic inflammation and autoimmunity. Apoptotic PMN undergo profound biophysical changes that warrant their efficient recognition and uptake by phagocytes before fading to secondary necrosis. In this study, we demonstrate that staurosporine (STS), a non-selective but potent inhibitor of cyclin-dependent kinase and protein kinase C, exerts a drastic impact on PMN apoptosis. PMN treated with STS underwent an unconventional form of cell death characterized by a delayed exposure of aminophospholipids, including phosphatidylserine (PS) and phosphatidylethanolamine and an increased exposure of neo-glycans. STS caused an impaired cellular fragmentation and accelerated DNA fragmentation. Phagocytosis of STS-treated PMN lacking PS on their surfaces was decreased significantly, which highlights the importance of PS for the clearance of apoptotic PMN. Specific opsonization with immune complexes completely restored phagocytosis of STS-treated PMN, demonstrating the efficiency of back-up clearance pathways in the absence of PS exposure.
Bacteria and their cell wall components uniformly co-activate interleukin-17-producing thymocytes
Authors: Weber A , Zimmermann C , Kieseier B C , Hartung H-P , Hofstetter H H
Published: July 2014

Interleukin (IL)-17-producing T cells play a critical role in the immune response against microbial pathogens. Traditionally, experimental studies have focused upon understanding the activity of IL-17-producing T cells which differentiate from naive T cells in the peripheral immune system. However, we have demonstrated previously that IL-17-producing T cells are also present in the thymus of naive wild-type mice and can be co-activated there by microbial stimuli. Other studies have supported the concept that IL-17-producing thymocytes have a specific role in the immediate defence against microbial pathogens, which is independent from the development of an adaptive immune response. Given an important role of the thymus in systemic bacterial infection and sepsis, in this study we investigate the effect of a broad spectrum of bacteria and cell wall components on thymocyte cytokine production. Surprisingly, we find that all types of bacteria investigated (including non-pathogenic species) uniformly activate IL-17-producing thymocytes upon α-CD3 stimulation. In contrast, there is a heterogeneous effect on IL-6 and interferon (IFN)-γ-production with Gram-negative bacteria inducing far higher frequencies of IL-6- and IFN-γ-producing thymocytes than Gram-positive bacteria. We conclude that IL-17-producing thymocytes constitute a ‘first line of recognition’, but not a ‘first line of defence’ against bacteria in general. Their activity might lead to immune activation, but not necessarily to a pathological inflammatory disease condition. The difference between these two states might be determined by other immunological effector molecules, such as IL-6 and IFN-γ.
Role of adenosine receptors in resveratrol‐induced intraocular pressure lowering in rats with steroid‐induced ocular hypertension
Authors: Razali Norhafiza , Agarwal Renu , Agarwal Puneet , Kumar Sunil , Tripathy Minaketan , Vasudevan Sushil , Crowston Jonathan G , Ismail Nafeeza M
Published: July 2014

Background

Steroid‐induced ocular hypertension is currently treated in the same way as primary open‐angle glaucoma. However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans‐resveratrol in rats with steroid‐induced ocular hypertension and involvement of adenosine receptors (AR) in intraocular pressure (IOP) lowering effect of trans‐resveratrol.

Methods

The oculohypotensive effect of unilateral single‐drop application of various concentrations of trans‐resveratrol was first studied in oculonormotensive rats. Concentration with maximum effect was similarly studied in rats with steroid‐induced ocular hypertension. Involvement of AR was studied by observing the alterations of IOP in response to trans‐resveratrol after pretreating animals with AR subtype‐specific antagonists. Additionally, we used computational methods, including 3D modelling, 3D structure generation and protein–ligand interaction, to determine the AR–trans‐resveratrol interaction.

Results

All concentrations of trans‐resveratrol produced significant IOP reduction in normotensive rat eyes. Maximum mean IOP reduction of 15.1% was achieved with trans‐resveratrol 0.2%. In oculohypertensive rats, trans‐resveratrol 0.2% produced peak IOP reduction of 25.2%. Pretreatment with A1 antagonist abolished the oculohypotensive effect of trans‐resveratrol. Pretreatment with A3 and A2A AR antagonists produced significant IOP reduction in both treated and control eyes, which was further augmented by trans‐resveratrol application in treated eyes. Computational studies showed that trans‐resveratrol has highest affinity for A2B and A1, followed by A2A and A3 AR.

Conclusion

Topically applied trans‐resveratrol reduces IOP in rats with steroid‐induced ocular hypertension. Trans‐resveratrol‐induced oculohypotension involves its agonistic activity at the A1 AR.
Management of diffuse ocular surface squamous neoplasia: efficacy and complications of topical chemotherapy
Authors: Rudkin Adam K , Dempster Lucy , Muecke James S
Published: July 2014

Background

Ocular surface squamous neoplasia (OSSN) characterized by diffuse conjunctival or corneal spread is much less common than localized conjunctival disease. However, it is an important subcategory of the disease because of the difficulty it poses to treatment. It is rarely amenable to simple excision, and a purely surgical approach usually necessitates ocular surface reconstruction. Primary treatment with topical chemotherapy is an alternative, but its efficacy for these lesions is not well understood.

Design

Retrospective case series.

Participants

Thirty‐eight eyes treated for diffuse OSSN, defined as a lesion extending over five or more limbal clock hours or by extensive central or paracentral corneal spread.

Methods

Treatment utilized either topical 5‐FU 1% or mitomycin‐C (MMC) 0.04%.

Main Outcome Measures

(i) Disease remission; (ii) complications.

Results

Thirty‐two patients were treated for a primary diffuse OSSN. Ten patients (31%) required further treatment for disease persistence or recurrence. Thirteen patients had previously undergone a single unsuccessful treatment course for diffuse OSSN. Administration of a second treatment course (whether MMC or 5FU) was successful in 46% (six) of patients. 5‐FU 1% resulted in drug‐related complications in seven of 12 cases, and included a single case of focal paracentral corneal stromal melt. MMC 0.04% resulted in transient drug related complications in 23 of 39 cases.

Conclusion

Diffuse OSSN is often recalcitrant to initial treatment with either 5‐FU 1% or MMC 0.04%, and a pragmatic and vigilant approach to this heterogenous disease is required. Compared to localized disease, diffuse disease often requires multiple treatment efforts.
Are insertion torque and early osseointegration proportional? A histologic evaluation
Authors: Campos Felipe E. B. , Jimbo Ryo , Bonfante Estevam A. , Barbosa Darceny Z. , Oliveira Maiolino T. F. , Janal Malvin N. , Coelho Paulo G.
Published: July 2014

Objectives

The objective of this histologic study was to determine the effect of three drilling protocols (oversized, intermediate, and undersized) on biologic responses to a single implant type at early healing periods (2 weeks in vivo) in a beagle dog model.

Materials and methods

Ten beagle dogs were acquired and subjected to surgeries in the tibia 2 weeks before euthanasia. During surgery, each dog received three Unitite implants, 4 mm in diameter by 10 mm in length, in bone sites drilled to 3.5, 3.75, and 4.0 mm in final diameter. The insertion torque was recorded during surgery, and bone‐to‐implant contact (BIC), and bone area fraction occupied (BAFO) measured from the histology. Each outcome measure was compared between treatment conditions with the Wilcoxon signed‐rank test. Bonferroni‐corrected statistical significance was set to 95%.

Results

Insertion torque increased as an inverse function of drilling diameter, as indicated by significant differences in torque levels between each pair of conditions (P = 0.005). BIC and BAFO levels were highest and statistically similar in the recommended and undersized conditions and significantly reduced in the oversized condition (P < 0.01).

Conclusions

Reduced drilling dimensions resulted in increased insertion torque (primary stability). While BIC and BAFO were maximized when drilling the recommended diameter hole, only the oversized hole resulted in evidence of statistically reduced integration.
Claudin‐2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function
Authors: Tan Xiaohua , Li Dongmei , Wang Xiaobo , Zeng Yan , Yan Yutao , Yang Lei
Published: July 2014

Background

Kaposi sarcoma (KS), caused by the infection of Kaposi sarcoma‐associated herpesvirus (KSHV), is a disease manifested mainly by dark purple skin and mouth nodules. Cancer care studies showed that co‐infection of KSHV and human immunodeficiency virus (HIV) was able to increase the patients' survival, but the underlying mechanisms are still elusive.

Methods

To understand the mechanism underlying the prolonged survival in KSHV‐HIV co‐infected patients, we performed microarray analysis on RNA extracted from biopsies from KS tumors and adjacent healthy tissues in four KS patients. Subsequently, we performed hierarchical clustering, gene ontology (GO) and ingenuity pathway analysis. We then characterized the roles of tight junction protein claudin‐2 in the endothelial barrier function.

Results

Three hundred and forty‐three differentially expressed genes were identified, of which 246 genes exhibited significantly increased expression in the tumor compared to the adjacent healthy tissue and 97 genes showed downregulated expression, including claudin‐2. Knockdown of claudin‐2 in cultured endothelial cells enhances barrier function by altering the charge selectivity, but not the size selectivity.

Conclusion

Claudin‐2 expression is decreased in KS tumors from patients co‐infected with KSHV and HIV. Decreased claudin‐2 enhances endothelial barrier function and may play a role in the prolonged survival of patients with KSHV and HIV co‐infection.
Comparison of percutaneous transhepatic biliary drainage and endoscopic biliary drainage in the management of malignant biliary tract obstruction: A meta‐analysis
Authors: Zhao Xiang‐qian , Dong Jia‐hong , Jiang Kai , Huang Xiao‐qiang , Zhang Wen‐zhi
Published: July 2014

Background and Aim

To compare percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD) for management of malignant biliary tract obstruction (MBTO).

Methods

PubMed, Google Scholar, and the Cochrane database were searched to 31 December 2013. Main outcome measurements were therapeutic success rate, 30‐day mortality rate, overall complications, cholangitis, and pancreatitis.

Results

Eight studies (five retrospective and three randomized controlled trials) were included in the meta‐analysis with a total of 692 participants. Combined odds ratio (OR) = 2.18 revealed no significant difference in therapeutic success between PTBD and EBD (95% confidence interval [CI] = 0.73–6.47, P = 0.162). However, after excluding two studies that appeared to be outliers, PTBD exhibited a better therapeutic success rate than EBD (pooled OR = 4.45, 95% CI = 2.68–7.40, P < 0.001). Patients who underwent PTBD were 0.55 times as likely to have cholangitis as those who underwent EBD, whereas the overall complication rate, pancreatitis rate, and 30‐day mortality were similar between the two procedures.

Conclusions

PTBD may be associated with a better therapeutic success rate and lower incidence of cholangitis than EBD, but the overall complication rate, pancreatitis rate, and 30‐day mortality of the two procedures are similar.
Clinical outcomes of secondary gastroduodenal self‐expandable metallic stent placement by stent‐in‐stent technique for malignant gastric outlet obstruction
Authors: Sasaki Takashi , Isayama Hiroyuki , Nakai Yousuke , Takahara Naminatsu , Hamada Tsuyoshi , Mizuno Suguru , Mohri Dai , Yagioka Hiroshi , Kogure Hirofumi , Arizumi Toshihiko , Togawa Osamu , Matsubara Saburo , Ito Yukiko , Yamamoto Natsuyo , Sasahira Naoki , Hirano Kenji , Toda Nobuo , Tada Minoru , Koike Kazuhiko
Published: July 2014

Background and Aim

To evaluate the efficacy and safety of secondary gastroduodenal stent placement after first stent dysfunction for malignant gastric outlet obstruction.

Methods

We conducted a retrospective analysis to investigate the efficacy and safety of secondary stent‐in‐stent gastroduodenal stent placement.

Results

Among 260 patients who had been treated with first gastroduodenal stent placement for malignant gastric outlet obstruction, 29 patients (11.2%) were treated with secondary gastroduodenal stent placement because of first stent dysfunction. Pancreatic cancer was the major primary cancer (55.2%). A WallFlex duodenal stent was the most frequently inserted stent both as a first stent (75.9%) and as a secondary stent (62.1%). There were 22 patients (75.9%) that received gastroduodenal stents at the bending site (supraduodenal angle or infraduodenal angle). Technical and clinical success rates were 100% and 86.2%, respectively. Median eating period was 3.0 months, and median survival time was 3.5 months. As for related complications, gastrointestinal perforation, insufficient stent expansion, tumor ingrowth, tumor overgrowth, and cholangitis were experienced in 13.8% (four cases), 6.9% (two cases), 6.9% (two cases), 3.4% (one case), and 3.4% (one case), respectively.

Conclusion

Secondary gastroduodenal stent placement might be effective for managing first stent dysfunction in malignant gastric outlet obstruction. However, gastrointestinal perforation was the major complication.
Exacerbation of Pulmonic Regurgitation by Diastolic Tricuspid Regurgitation
Authors: Fan Dali , Makaryus John N. , Wassef Bishoy , Suma Valentin , Masry Mina , Makaryus Amgad N.
Published: July 2014

Few cases of diastolic mitral regurgitation (MR) and tricuspid regurgitation (TR) have been reported in the world literature. We report the case of a 63‐year‐old woman admitted for syncope, with a permanent pacemaker following complete heart block. Echocardiography revealed that the timing of the diastolic TR (and noted MR) coincided with the second phase of the pulmonic insufficiency (PI) jet. The respirometer revealed that the diastolic TR and the second phase of the PI are highly sensitive to respiration (attenuated with inspiration and exacerbated with expiration). The uniqueness of this case is the rare occurrence of the exacerbation of PI as the result of diastolic TR.
Endothelin uncouples gap junctions in sustentacular cells and olfactory ensheathing cells of the olfactory mucosa
Authors: Le Bourhis Mikaël , Rimbaud Stéphanie , Grebert Denise , Congar Patrice , Meunier Nicolas
Published: July 2014

Several factors modulate the first step of odour detection in the rat olfactory mucosa (OM). Among others, vasoactive peptides such as endothelin might play multifaceted roles in the different OM cells. Like their counterparts in the central nervous system, the olfactory sensory neurons are encompassed by different glial‐like non‐neuronal OM cells; sustentacular cells (SCs) surround their cell bodies, whereas olfactory ensheathing cells (OECs) wrap their axons. Whereas SCs maintain both the structural and ionic integrity of the OM, OECs assure protection, local blood flow control and guiding of olfactory sensory neuron axons toward the olfactory bulb. We previously showed that these non‐neuronal OM cells are particularly responsive to endothelin in vitro. Here, we confirmed that the endothelin system is strongly expressed in the OM using in situ hybridization. We then further explored the effects of endothelin on SCs and OECs using electrophysiological recordings and calcium imaging approaches on both in vitro and ex vivo OM preparations. Endothelin induced both robust calcium signals and gap junction uncoupling in both types of cells. This latter effect was mimicked by carbenoxolone, a known gap junction uncoupling agent. However, although endothelin is known for its antiapoptotic effect in the OM, the uncoupling of gap junctions by carbenoxolone was not sufficient to limit the cellular death induced by serum deprivation in OM primary culture. The functional consequence of the endothelin 1‐induced reduction of the gap junctional communication between OM non‐neuronal cells thus remains to be elucidated.
Prioritization of knowledge needs for sustainable aquaculture: a national and global perspective
Authors: Jones Aisla C , Mead Angela , Kaiser Michel J , Austen Melanie C V , Adrian Alex W , Auchterlonie Neil A , Black Kenneth D , Blow Lucy R , Bury Charlotte , Brown Janet H , Burnell Gavin M , Connolly Elaine , Dingwall Alastair , Derrick Simon , Eno N Clare , Gautier Dominique J H , Green Karen A , Gubbins Matthew , Hart Piers R , Holmyard John M , Immink Anton J , Jarrad David L , Katoh Emi , Langley Jeremy C R , Lee Daniel O'C , Le Vay Lewis , Leftwich Chris P , Mitchell Mike , Moore Andrew , Murray Alexander G , McLaren Emma M R , Norbury Hannah , Parker David , Parry Stephen O , Purchase Dawn , Rahman Amanna , Sanver Feyza , Siggs Melanie , Simpson Stephen D , Slaski Richard J , Smith Katie , Syvret Martin Le Q , Tibbott Claire , Thomas Phil C , Turnbull Jimmy , Whiteley Robert , Whittles Matthew , Wilcockson Mary J , Wilson James , Dicks Lynn V , Sutherland William J
Published: July 2014

Aquaculture is currently the fastest expanding global animal food production sector and is a key future contributor to food security. An increase in food security will be dependent upon the development and improvement of sustainable practices. A prioritization exercise was undertaken, focusing on the future knowledge needs to underpin UK sustainable aquaculture (both domestic and imported products) using a ‘task force’ group of 36 ‘practitioners’ and 12 ‘research scientists’ who have an active interest in sustainable aquaculture. A long list of 264 knowledge needs related to sustainable aquaculture was developed in conjunction with the task force. The long list was further refined through a three stage process of voting and scoring, including discussions of each knowledge need. The top 25 knowledge needs are presented, as scored separately by ‘practitioners’ or ‘research scientists’. There was similar agreement in priorities identified by these two groups. The priority knowledge needs will provide guidance to structure ongoing work to make science accessible to practitioners and help to prioritize future science policy needs and funding. The process of knowledge exchange, and the mechanisms by which this can be achieved, effectively emerged as the top priority for sustainable aquaculture. Viable alternatives to wild fish‐based aquaculture feeds, resource constraints that will potentially limit expansion of aquaculture, sustainable offshore aquaculture and the treatment of sea lice also emerged as strong priorities. Although the exercise was focused on UK needs for sustainable aquaculture, many of the emergent issues are considered to have global application.
Fuel consumption of global fishing fleets: current understanding and knowledge gaps
Authors: Parker Robert W R , Tyedmers Peter H
Published: July 2014

Compared to a century ago, the world's fishing fleets are larger and more powerful, are travelling further and are producing higher quality products. These developments come largely at a cost of high‐fossil fuel energy inputs. Rising energy prices, climate change and consumer demand for ‘green’ products have placed energy use and emissions among the sustainability criteria of food production systems. We have compiled all available published and unpublished fuel use data for fisheries targeting all species, employing all gears and fishing in all regions of the world into a Fisheries and Energy Use Database (FEUD). Here, we present results of our analysis of the relative energy performance of fisheries since 1990 and provide an overview of the current state of knowledge on fuel inputs to diverse fishing fleets. The median fuel use intensity of global fishery records since 1990 is 639 litres per tonne. Fuel inputs to fisheries vary by several orders of magnitude, with small pelagic fisheries ranking among the world's most efficient forms of animal protein production and crustaceans ranking among the least efficient. Trends in Europe and Australia since the beginning of the 21st century suggest fuel use efficiency is improving, although this has been countered by a more rapid increase in oil prices. Management decisions, technological improvements and behavioural changes can further reduce fuel consumption in the short term, although the most effective improvement to fisheries energy performance will come as a result of rebuilding stocks where they are depressed and reducing over‐capacity.
Crystal structure of active site mutant of antileukemic l‐asparaginase reveals conserved zinc‐binding site
Authors: Borek Dominika , Kozak Maciej , Pei Jimin , Jaskolski Mariusz
Published: July 2014

The periplasmic enzyme l‐asparaginase type II from Escherichia coli (EcAII) converts l‐asparagine to l‐aspartate and ammonia. EcAII is an important drug in the treatment of childhood acute lymphoblastic leukemia, the most common malignancy in children. Leukemic blast cells lack the ability to synthesize l‐asparagine and rely on other sources of l‐asparagine for protein synthesis. EcAII injections deplete extracellular levels of l‐asparagine, disrupting protein synthesis and inducing apoptosis in the malignant cells. The detailed mechanism of l‐asparaginase catalytic action, the molecular mechanisms of its anticancer activity and the side effects associated with the treatment, including resistance to therapy, are not fully understood despite over 40 years of research. Here, we present X‐ray structures of EcAII with an active site mutation, D90E, in three crystal forms. The region of the mutation is well ordered, allowing precise functional analysis of the consequences of the replacement of Asp90. In all three structures, the mutant protein exhibits an open conformation of the active site. In one of the structures, a zinc cation has been detected. The zinc cation is coordinated in a region of the protein that is implicated in the immunological response to EcAII treatment. A combined sequence‐structure analysis of bacterial‐type l‐asparaginases reveals that the metal coordination may play a role in the response to asparaginase treatment. The observation of a zinc‐binding site in antileukemic l‐asparaginases provides new insight, with consequences for acute lymphoblastic leukemia therapy.

Databases

The atomic coordinates of the monoclinic, orthorhombic and trigonal forms of the D90E mutant of Escherichia coli type II asparaginase have been deposited with the RCSB PDB with accession codes 1JAZ, 1JJA and 1IHD, respectively.

Enzymes

EC 3.5.1.1, l‐asparagine amidohydrolase, l‐asparaginase; EC 3.5.1.38, l‐glutamine (l‐asparagine) amidohydrolase, glutaminase‐asparaginase; EC 6.3.5.6, l‐aspartyl‐tRNAAsn: l‐glutamine amido‐ligase (ADP‐forming), asparaginyl‐tRNA synthase (glutamine‐hydrolysing).