bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of carbofuran and deltamethrin on acetylcholinesterase activity in brain and muscle of the common carp
Authors: Ensibi Cherif , Hernández‐Moreno David , Míguez Santiyán M. Prado , Daly Yahya Mohamed Néjib , Rodríguez Francisco Soler , Pérez‐López Marcos
Published: March 2012

This work investigated the effect from exposure to insecticides carbofuran and deltamethrin on acetylcholinesterase (AChE) activity in the brain and muscle of common carp (Cyprinus carpio). Both pesticides were evaluated through two separate experiments, and carp were exposed in a semi‐static system to three different concentrations of carbofuran (10, 50, and 100 μg/L) and deltamethrin (0.08, 0.4, and 0.8 μg/L) during a month with sampling times at 0, 4, 15, and 30 days (n = 7 from each aquarium). AChE activity was significantly inhibited in both organs of carps exposed to carbofuran at all sampling times depending on dose and time, reaching inhibition values of 73.5 and 67.1%, in brain and muscle tissues respectively, after 30 days with the highest concentration. On the contrary, AChE activity was not significantly affected after deltamethrin exposure at all concentrations and times of the assay. This study shows that the measurement of brain and muscle AChE activity in Cyprinus carpio is a useful biomarker of carbamates exposure and/or effects, but has no application with pyrethroids. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 386–393, 2014.
Proposal for a morphological classification of intraductal papillary neoplasm of the bile duct (IPN‐B)
Authors: Kato Hiroyuki , Tabata Masami , Azumi Yoshinori , Osawa Ichiro , Kishiwada Masashi , Hamada Takashi , Mizuno Shugo , Usui Masanobu , Sakurai Hiroyuki , Isaji Shuji
Published: March 2012

Purpose

We propose a morphological classification of intraductal papillary neoplasm of the bile duct (IPN‐B).

Methods

A retrospective analysis of 16 patients with IPN‐B who had undergone surgical resection was conducted. These 16 cases were classified into three types based on the primary lesion's anatomical location: branch duct type (6 cases), main duct type (5 cases) and mixed type (5 cases). In this paper we have analyzed the characteristics of IPN‐B according to our new classification.

Results

All branch duct type IPN‐B was located in the left lobe and 5 of them were resected by left hepatectomy without extrahepatic bile duct resection (EBDR). On the other hand, all patients with main duct and mixed type IPN‐B underwent EBDR in addition to hepatectomy or pancreatoduodenectomy. Microscopically, 2 of 6 patients with branch duct type IPN‐B had no malignant component and, in the remaining 4 patients, cancer invasion was restricted to within the ductal wall. There were no cases of branch duct type IPN‐B with lymph node metastasis and superficial intraductal tumor spread. In contrast, all patients with main duct and mixed duct type IPN‐B had the malignant component. In all cases, lymph node metastasis was not observed, but superficial intraductal tumor spread was frequently found in extrahepatic bile duct lesions: 3 of main duct type and 3 of mixed type. Four patients with superficial intraductal spread had non‐curative resection due to a cancer‐positive ductal margin. Most patients with IPN‐B obtained a good prognosis, but two patients with a cancer‐positive ductal margin developed local recurrence.

Conclusions

Our classification vividly reflects clinical and pathological characteristics of IPN‐B and is useful to determine appropriate surgical strategy.
A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma
Authors: Yau Thomas , Cheng P. N. , Chan Pierre , Chan William , Chen Li , Yuen Jimmy , Pang Roberta , Fan S. T. , Poon Ronnie T.
Published: March 2012

Background Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced HCC patients. Methods Eligibility criteria included advanced HCC with measurable lesions, Child-Pugh A or B, and adequate organ function. Initial single IV bolus was followed by weekly doses of peg-rhArgI escalated from 500 U/kg to 2500 U/kg in a 3 + 3 design. Results Fifteen patients were enrolled at weekly doses of 500 U/kg (n = 3), 1000 U/kg (n = 3), 1600 U/kg (n = 3) and 2500 U/kg (n = 6). The median age was 57 years (33–74); 87% were hepatitis B carriers and 47% had prior systemic treatment. The most commonly reported drug-related non-haematological adverse events (AEs) were diarrhea (13.3%), abdominal discomfort (6.7%) and nausea (6.7%). No drug-related haematological AEs were seen. Only 1 of the six patients that received 2500U/kg peg-rhArg1 experienced DLT (grade 4 bilirubin elevation) and thus the maximum tolerated dose was 2500 U/kg. PK and PD analysis indicated that peg-rhArg1 was efficacious in inducing arginine depletion in a dose-dependent manner. Adequate arginine depletion dose was achieved in the 1,600–2,500 U/kg range and therefore the optimal biological dose was at 1600 U/kg, which was chosen as the recommended dose. The best response was stable disease for >8 weeks in 26.7% of the enrolled patients. Conclusion Peg-rhArg1 has manageable safety profile and preliminary evidence of activity in advanced HCC patients.
The use of TachoSil for the prevention of postoperative complications after groin dissection in cases of gynecologic malignancy
Authors: Buda Alessandro , Fruscio Robert , Pirovano Cecilia , Signorelli Mauro , Betti Marta , Milani Rodolfo
Published: March 2012

Objective

To evaluate the effect of TachoSil in preventing postoperative complications after groin dissection performed for primary or recurrent gynecologic malignancy.

Methods

In a case–control analysis, the incidence of postoperative complications—including lymphocyst formation, wound breakdown and/or infection, and chronic lymphedema—was examined among 8 patients who received TachoSil and 16 controls (standard technique) treated for vulvar cancer or recurrent ovarian/breast cancer at San Gerardo Hospital, Monza, Italy, from 2008 to 2011.

Results

Thirty‐eight inguinal dissections were performed in the 24 patients. Bilateral groin dissection was performed in 14 patients (n = 4 in the study group; n = 10 in the control group). Patients in the study group had a lower mean daily drainage volume than those in the control group (133 mL [range, 50–356 mL] vs 320 mL [range, 67–472 mL]; P < 0.001) and a lower incidence of lymphocyst requiring drainage (25.0% vs 62.5%), cellulitis (12.0% vs 25.0%), and wound infection (0.0% vs 25.0%).

Conclusion

The use of TachoSil seems to be effective in reducing the rate of postoperative complications after inguinofemoral lymphadenectomy in cases of gynecologic malignancy.
Mutual fund corporate culture and performance
Authors: Gottesman Aron , Morey Matthew
Published: March 2012

In this paper we test if a mutual fund's own corporate culture predicts fund performance. To do this we use Morningstar's corporate culture ratings for mutual funds and then examine the ability of these corporate culture ratings to predict risk‐adjusted performance of domestic equity funds over the period 2005–2010. Using methods that are robust to survivorship bias, we find there is little significant evidence that corporate culture predicts better fund performance. Indeed, we find that no individual component of the Morningstar stewardship rating including board quality, fees, manager incentives and regulatory issues is able to consistently predict fund performance.
On least-order flow representations for aerodynamics and aeroacoustics
Authors: Schlegel Michael , Noack Bernd R. , Jordan Peter , Dillmann Andreas , Gröschel Elmar , Schröder Wolfgang , Wei Mingjun , Freund Jonathan B. , Lehmann Oliver , Tadmor Gilead
Published: March 2012

We propose a generalization of proper orthogonal decomposition (POD) for optimal flow resolution of linearly related observables. This Galerkin expansion, termed ‘observable inferred decomposition’ (OID), addresses a need in aerodynamic and aeroacoustic applications by identifying the modes contributing most to these observables. Thus, OID constitutes a building block for physical understanding, least-biased conditional sampling, state estimation and control design. From a continuum of OID versions, two variants are tailored for purposes of observer and control design, respectively. Firstly, the most probable flow state consistent with the observable is constructed by a ‘least-residual’ variant. This version constitutes a simple, easily generalizable reconstruction of the most probable hydrodynamic state to preprocess efficient observer design. Secondly, the ‘least-energetic’ variant identifies modes with the largest gain for the observable. This version is a building block for Lyapunov control design. The efficient dimension reduction of OID as compared to POD is demonstrated for several shear flows. In particular, three aerodynamic and aeroacoustic goal functionals are studied: (i) lift and drag fluctuation of a two-dimensional cylinder wake flow; (ii) aeroacoustic density fluctuations measured by a sensor array and emitted from a two-dimensional compressible mixing layer; and (iii) aeroacoustic pressure monitored by a sensor array and emitted from a three-dimensional compressible jet. The most ‘drag-related’, ‘lift-related’ and ‘loud’ structures are distilled and interpreted in terms of known physical processes.
Size exclusion and reversed-phase high-performance liquid chromatography/UV for routine control of thermal processing of cows' and donkey milk major proteins
Authors: Pinho Carina , Martins Zita E. , Petisca Catarina , Figurska Agata M. , Pinho Olívia , Ferreira Isabel M.P.L.V.O.
Published: March 2012

Cows' and donkey milks (raw and thermally processed) and respective whey were analysed for quantification of major proteins. Two different chromatographic approaches, size exclusion (SE-HPLC) and reversed-phase high performance liquid chromatography (RP-HPLC) both coupled to UV detection were used. Usefulness of these methods for routine control of the effect of thermal processing was evaluated. The external standard method was used to calibrate the SE-HPLC and RP-HPLC systems. Concerning quantification of β-lactoglobulin (β-lg), α-lactalbumin (α-la), lysozyme (lys), and total casein (cn), no significant differences between results obtained by SE-HPLC and by RP-HPLC (t-test, P>0·05) were observed for raw milks and whey. Heating of cows' milk promoted aggregation of denatured proteins as observed by SE-HPLC, whereas α-la and β-lg from donkey milk were stable to thermal processing at 100°C (5 min). Lys was quantified in donkey raw milk and whey however, in thermally processed donkey milk lys was denatured and could not be quantified by HPLC.
Environmental influences predominate in remission from alcohol use disorder in young adult twins
Authors: McCutcheon V. V. , Grant J. D. , Heath A. C. , Bucholz K. K. , Sartor C. E. , Nelson E. C. , Madden P. A. F. , Martin N. G.
Published: March 2012

Background

Familial influences on remission from alcohol use disorder (AUD) have been studied using family history of AUD rather than family history of remission. The current study used a remission phenotype in a twin sample to examine the relative contributions of genetic and environmental influences to remission.

Method

The sample comprised 6183 twins with an average age of 30 years from the Australian Twin Registry. Lifetime history of alcohol abuse and dependence symptoms and symptom recency were assessed with a structured telephone interview. AUD was defined broadly and narrowly as history of two or more or three or more abuse or dependence symptoms. Remission was defined as absence of symptoms at time of interview among individuals with lifetime AUD. Standard bivariate genetic analyses were conducted to derive estimates of genetic and environmental influences on AUD and remission.

Results

Environmental influences alone accounted for remission in males and for 89% of influences on remission in females, with 11% due to genetic influences shared with AUD, which decreased the likelihood of remission. For women, more than 80% of influences on remission were distinct from influences on AUD, and environmental influences were from individual experiences only. For men, just over 50% of influences on remission were distinct from those on AUD, and the influence of environments shared with the co-twin were substantial. The results for the broad and narrow phenotypes were similar.

Conclusions

The current study establishes young adult remission as a phenotype distinct from AUD and highlights the importance of environmental influences on remission.
Non-Three-Colourable Common Graphs Exist
Authors: HATAMI HAMED , HLADKÝ JAN , KRÁL' DANIEL , NORINE SERGUEI , RAZBOROV ALEXANDER
Published: March 2012

A graph H is called common if the sum of the number of copies of H in a graph G and the number in the complement of G is asymptotically minimized by taking G to be a random graph. Extending a conjecture of Erdős, Burr and Rosta conjectured that every graph is common. Thomason disproved both conjectures by showing that K4 is not common. It is now known that in fact the common graphs are very rare. Answering a question of Sidorenko and of Jagger, Št'ovíček and Thomason from 1996 we show that the 5-wheel is common. This provides the first example of a common graph that is not three-colourable.
An Alternative to Generating Alternative Interpretations in Social Cognitive Therapy for Psychosis
Authors: Roberts David L. , Kleinlein Petra , Stevens Bruce
Published: March 2012

Background: Generating alternative interpretations is a widely used technique in cognitively-oriented treatments for psychosis, including social cognitive treatments. However, research on judgment and decision-making suggests that this technique may backfire among individuals with cognitive deficits. Aims: Mary/Eddie/Bill (MEB) was developed as an alternative approach to help improve Theory of Mind, attributional bias and Jumping to Conclusions in psychosis. An initial pilot trial was conducted to evaluate the tolerability and potential efficacy of MEB. Method: Twenty-four outpatients with psychotic disorders participated in an uncontrolled trial. Social cognition, social functioning, and participant feedback were assessed. Results: Treatment completers exhibited statistically significant improvements in Theory of Mind, social cognitive overconfidence and self-reported social engagement, and reported positive experiences with MEB. No improvements were observed in attributional bias. Conclusions: Given that there are risks associated with the use of traditional generating-alternatives techniques, the current findings support ongoing development of MEB and similar approaches.
Consensus Social Movements and the Catholic Worker
Authors: Stock Paul V.
Published: March 2012

This article proposes a revised conceptual definition of consensus social movement. By using the example of the Catholic Worker, I construct a workable concept of a consensus social movement based on Quaker consensus and indigenous decision-making. The new definition of consensus social movement brings theoretical strength as demonstrated in the illustration of the Catholic Worker. The concept of a consensus social movement offers a revised theoretical tool for the social movement literature toolkit.
The Emerging Practice of Global Environmental Law
Authors: Yang Tseming
Published: March 2012

Since the 1972 Stockholm Conference on the Human Environment, ecological pressures on our planet have grown more acute. Yet, modern environmental law has also continued to evolve and spread within international as well as among national legal systems. With the paths of international and national environmental law becoming increasingly intertwined over the years, international environmental legal norms and principles are now penetrating deeper into national legal systems, and environmental treaties are increasingly incorporating or referencing national legal norms and practices. The shifting legal landscape is also changing contemporary environmental law practice, creating greater needs for domestic environmental lawyers to be informed by international law and vice versa. This essay describes how domestic environmental law practice is increasingly informed by international legal norms, while the effective practice of international environmental law more and more requires enhanced awareness, and even understanding, of national environmental regulatory and governance systems. It illustrates these trends with the historical role and work of the United States Environmental Protection Agency’s Office of General Counsel.
Magnetosphere response to high‐speed solar wind streams: A comparison of weak and strong driving and the importance of extended periods of fast solar wind
Authors: Denton M. H. , Borovsky J. E.
Published: March 2012

Much attention has been focused on the reaction of the magnetosphere to the solar wind during the recent extended solar minimum (2006–2010). Although this period was exceptionally quiet when categorized by some parameters (e.g., the number of sunspots) the solar wind still contained features which impacted the Earth's magnetosphere and caused geomagnetic disturbances. Recurrent corotating interaction regions (CIRs) and associated high‐speed solar wind streams (HSSs) are typically associated with the declining phase of the solar cycle and were a regular feature of the solar wind during the most recent solar minimum. Here we compare and contrast strong and weak HSSs in the solar wind and their subsequent effect within the Earth's magnetosphere. We find significant differences between strong and weak HSS effects in the plasmasphere, in the ion and electron plasma sheets, and in the outer electron radiation belt. A density‐temperature description of the outer radiation belt is shown to shed light on why the radiation belt flux is observed to return at a higher level after the arrival of strong HSSs than before strong HSSs and why the flux is observed to return at a lower level after the arrival of weak HSSs than before weak HSSs.
A new class of SUMO proteases
Authors: Gillies Jennifer , Hochstrasser Mark
Published: March 2012

A new class of SUMO protease, DeSUMOylating enzyme (DeSI)—that has different substrates and localization to SENP SUMO proteases—is characterized in this issue of EMBO reports. The implications for the field are discussed here.
Rac1 Is a Possible Link Between Obesity and Oxidative Stress in Chinese Overweight Adolescents
Authors: Sun Mingxiao , Huang Xiuqing , Yan Yi , Chen Junfei , Wang Zhengzhen , Xie Minhao , Li Jian
Published: March 2012

Enhanced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in the monocytes occurred in metabolic syndrome, hypertension, diabetes and obese patients in adults. However, whether NADPH oxidase is involved in the oxidative stress of overweight adolescents without comorbidities is still unclear. This study aimed to identify whether and how NADPH oxidase plays a crucial role in overweight adolescents. The study was performed in 93 overweight adolescents and 31 normal weight controls. Moreover, 87 overweight adolescents were enrolled in weight‐loss program. Demographics characteristics, anthropometrics, composition and clinical characteristics were analyzed. Oxidative stress indexes including the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in plasma and the expression of NADPH oxidase in the monocytes were examined. Overweight adolescents showed a higher oxidative stress state, as indicated by decreased SOD activity and elevated MDA level (P < 0.01). Furthermore, increased NADPH oxidase activity in the monocytes was accompanied by Rac1 upregulation. A significant positive bivariate correlation was found between Rac1 expression and MDA (r = 0.289). There also was a significant positive bivariate correlation between Rac1 expression and obesity‐related indexes including BMI (r = 0.227) and percentage of trunk fat (r = 0.233). Data from weight‐loss program reinforced the results. Partial correlation analysis indicated that obesity‐induced oxidative stress and Rac1 expression is a consequence of aberrant glucose‐lipid metabolism in overweight adolescents. In conclusion, we provided novel data showing that NADPH oxidase in the monocytes was highly activated by enhancing Rac1 expression in Chinese overweight adolescents and Rac1 may act as a link between obesity and oxidative stress in overweight adolescents.
Metabolic Effects of Short-term GLP-1 Treatment in Insulin Resistant Heart Failure Patients
Authors: Nielsen R. , Wiggers H. , Halbirk M. , Bøtker H. , Holst J. , Schmitz O. , Frandsen E. , Nielsen S. , Møller N. , Nørrelund H.
Published: March 2012

We studied the metabolic effects of 48-h GLP-1 treatment in insulin resistant heart failure patients.

In a randomized placebo-controlled double-blinded cross-over study, 11 non-diabetic HF patients with IHD received 48-h GLP-1 and placebo-infusion. We applied OGTT, hyperinsulinemic clamp, indirect calorimetry, forearm, and tracer methods.

7 insulin resistant HF (EF 28%±2) patients completed the protocol. GLP-1 decreased plasma glucose levels (p=0.048) and improved glucose tolerance. 4 patients had hypoglycemic events during GLP-1 vs. none during placebo. GLP-1 treatment tended to increase whole body protein turnover (p=0.08) but did not cause muscle wasting. No significant changes in circulating levels of insulin, glucagon, free fatty acids or insulin sensitivity were detected.

GLP-1 treatment decreased glucose levels and increased glucose tolerance in insulin resistant HF patients with IHD. Hypoglycemia was common and may limit the use of GLP-1 in these patients. Insulin sensitivity, lipid-, and protein metabolism remained unchanged.

Data were collected at the examinational laboratories of Department of Endocrinology and Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
Morphology and biochemical characteristics of pistils in the staminate flowers of yellow horn during selective abortion
Authors: Zhou Yan , Gao Shumin , Zhang Xiaofang , Gao Hua , Hu Qing , Song Yanru , Jiao Yanhong , Gao Hongbo
Published: March 2012

Yellow horn (Xanthoceras sorbifolia Bunge), an andromonoecious woody plant, has both hermaphrodite and staminate flowers. Both stamens and pistils in hermaphrodite flowers develop normally, but the pistils are aborted and the stamens develop normally in staminate flowers. To investigate the anatomical and biochemical characteristics of the aborted pistils in staminate flowers, anatomical and biochemical assays were carried out. Microstructure, ultrastructure and their histochemistry were analysed. The hypotheses that amylase and endogenous hormones are involved in pistil abortion were tested by comparing the homochronous pistil tissues in both hermaphrodite and staminate flowers. We conclude that pistil abortion occurs at the meiosis stage of megasporocyte cells and programmed cell death in staminate flowers. Simultaneously, we observed that starch grains and protein abundance are of benefit to megasporocyte meiosis. Our study indicates that the low activity of amylase isozymes α3 and α4 will result in insufficient soluble sugars for pistil development. The endogenous hormones gibberellic acid (GA3) and abscisic acid (ABA) in the pistil of both staminate and hermaphrodite flowers at four stages were measured by gas chromatography–mass spectrometry. The results suggested that both ABA and GA3 are related to pistil abortion. In addition, a high ratio of GA3 and ABA exists in the stage of megasporocyte cells until the stage of megasporocyte meiosis I, which affects the normal activity of sucrose invertase and pistil development in staminate flowers. These results suggest that starch grains, proteins and endogenous hormones are important for pistil development and, as well, that pistil abortion in staminate flowers is related to the level of endogenous hormones and the activity of amylase isozymes.
Direct observation of multiple misfolding pathways in a single prion protein molecule
Authors: Yu Hao , Liu Xia , Neupane Krishna , Gupta Amar Nath , Brigley Angela M. , Solanki Allison , Sosova Iveta , Woodside Michael T.
Published: March 2012

Protein misfolding is a ubiquitous phenomenon associated with a wide range of diseases. Single-molecule approaches offer a powerful tool for deciphering the mechanisms of misfolding by measuring the conformational fluctuations of a protein with high sensitivity. We applied single-molecule force spectroscopy to observe directly the misfolding of the prion protein PrP, a protein notable for having an infectious misfolded state that is able to propagate by recruiting natively folded PrP. By measuring folding trajectories of single PrP molecules held under tension in a high-resolution optical trap, we found that the native folding pathway involves only two states, without evidence for partially folded intermediates that have been proposed to mediate misfolding. Instead, frequent but fleeting transitions were observed into off-pathway intermediates. Three different misfolding pathways were detected, all starting from the unfolded state. Remarkably, the misfolding rate was even higher than the rate for native folding. A mutant PrP with higher aggregation propensity showed increased occupancy of some of the misfolded states, suggesting these states may act as intermediates during aggregation. These measurements of individual misfolding trajectories demonstrate the power of single-molecule approaches for characterizing misfolding directly by mapping out nonnative folding pathways.
Divergent role of the Hox gene
Antennapedia
in spiders is responsible for the convergent evolution of abdominal limb repression
Authors: Khadjeh Sara , Turetzek Natascha , Pechmann Matthias , Schwager Evelyn E. , Wimmer Ernst A. , Damen Wim G. M. , Prpic Nikola-Michael
Published: March 2012

Evolution often results in morphologically similar solutions in different organisms, a phenomenon known as convergence. However, there is little knowledge of the processes that lead to convergence at the genetic level. The genes of the Hox cluster control morphology in animals. They may also be central to the convergence of morphological traits, but whether morphological similarities also require similar changes in Hox gene function is disputed. In arthropods, body subdivision into a region with locomotory appendages (“thorax”) and a region with reduced appendages (“abdomen”) has evolved convergently in several groups, e.g., spiders and insects. In insects, legs develop in the expression domain of the Hox gene
Antennapedia
(
Antp
), whereas the Hox genes
Ultrabithorax
(
Ubx
) and
abdominal-A
mediate leg repression in the abdomen. Here, we show that, unlike
Antp
in insects, the
Antp
gene in the spider
Achaearanea tepidariorum
represses legs in the first segment of the abdomen (opisthosoma), and that
Antp
and
Ubx
are redundant in the following segment. The down-regulation of
Antp
in
A. tepidariorum
leads to a striking 10-legged phenotype. We present evidence from ectopic expression of the spider
Antp
gene in
Drosophila
embryos and imaginal tissue that this unique function of
Antp
is not due to changes in the Antp protein, but likely due to divergent evolution of cofactors, Hox collaborators or target genes in spiders and flies. Our results illustrate an interesting example of convergent evolution of abdominal leg repression in arthropods by altering the role of distinct Hox genes at different levels of their action.
Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell–cell adhesion and signaling mechanism that requires
cis-trans
receptor clustering
Authors: Stengel Katharina F. , Harden-Bowles Kristin , Yu Xin , Rouge Lionel , Yin Jianping , Comps-Agrar Laëtitia , Wiesmann Christian , Bazan J. Fernando , Eaton Dan L. , Grogan Jane L.
Published: March 2012

Nectins (nectin1–4) and Necls [nectin-like (Necl1–5)] are Ig superfamily cell adhesion molecules that regulate cell differentiation and tissue morphogenesis. Adherens junction formation and subsequent cell–cell signaling is initiated by the assembly of higher-order receptor clusters of cognate molecules on juxtaposed cells. However, the structural and mechanistic details of signaling cluster formation remain unclear. Here, we report the crystal structure of poliovirus receptor (PVR)/Nectin-like-5/CD155) in complex with its cognate immunoreceptor ligand T-cell-Ig-and-ITIM-domain (TIGIT). The TIGIT/PVR interface reveals a conserved specific “lock-and-key” interaction. Notably, two TIGIT/PVR dimers assemble into a heterotetramer with a core TIGIT/TIGIT
cis
-homodimer, each TIGIT molecule binding one PVR molecule. Structure-guided mutations that disrupt the TIGIT/TIGIT interface limit both TIGIT/PVR-mediated cell adhesion and TIGIT-induced PVR phosphorylation in primary dendritic cells. Our data suggest a
cis-trans
receptor clustering mechanism for cell adhesion and signaling by the TIGIT/PVR complex and provide structural insights into how the PVR family of immunoregulators function.
Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity
Authors: Lovatt Ditte , Xu Qiwu , Liu Wei , Takano Takahiro , Smith Nathan A. , Schnermann Jurgen , Tieu Kim , Nedergaard Maiken
Published: March 2012

Adenosine is a potent anticonvulsant acting on excitatory synapses through A1 receptors. Cellular release of ATP, and its subsequent extracellular enzymatic degradation to adenosine, could provide a powerful mechanism for astrocytes to control the activity of neural networks during high-intensity activity. Despite adenosine's importance, the cellular source of adenosine remains unclear. We report here that multiple enzymes degrade extracellular ATP in brain tissue, whereas only Nt5e degrades AMP to adenosine. However, endogenous A1 receptor activation during cortical seizures in vivo or heterosynaptic depression in situ is independent of Nt5e activity, and activation of astrocytic ATP release via Ca
2+
photolysis does not trigger synaptic depression. In contrast, selective activation of postsynaptic CA1 neurons leads to release of adenosine and synaptic depression. This study shows that adenosine-mediated synaptic depression is not a consequence of astrocytic ATP release, but is instead an autonomic feedback mechanism that suppresses excitatory transmission during prolonged activity.
Sleeping Beauty
mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma
Authors: Mann Karen M. , Ward Jerrold M. , Yew Christopher Chin Kuan , Kovochich Anne , Dawson David W. , Black Michael A. , Brett Benjamin T. , Sheetz Todd E. , Dupuy Adam J. ,   Australian Pancreatic Cancer Genome Initiative, Chang David K. , Biankin Andrew V. , Waddell Nicola , Kassahn Karin S. , Grimmond Sean M. , Rust Alistair G. , Adams David J. , Jenkins Nancy A. , Copeland Neal G.
Published: March 2012

Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and development of improved diagnostic tools and therapeutics. We have conducted a mutagenic screen using
Sleeping Beauty
(
SB
) in mice to identify new candidate cancer genes in pancreatic cancer. By combining
SB
with an oncogenic
Kras
allele, we observed highly metastatic pancreatic adenocarcinomas. Using two independent statistical methods to identify loci commonly mutated by
SB
in these tumors, we identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these CCGs, including
Mll3
and
Ptk2
, have known mutations in human pancreatic cancer. We identified point mutations in human pancreatic patient samples for another 11 CCGs, including
Acvr2a
and
Map2k4
. Importantly, 10% of the CCGs are involved in chromatin remodeling, including
Arid4b
,
Kdm6a
, and
Nsd3
, and all
SB
tumors have at least one mutated gene involved in this process; 20 CCGs, including
Ctnnd1
,
Fbxo11
, and
Vgll4
, are also significantly associated with poor patient survival.
SB
mutagenesis provides a rich resource of mutations in potential cancer drivers for cross-comparative analyses with ongoing sequencing efforts in human pancreatic adenocarcinoma.
Leonardo Sciascia's L'affaire Moro: Re-writing fact, which can be stranger than fiction
Authors: Francese Joseph
Published: March 2012

The author contends that Leonardo Sciascia's L'affaire Moro is not a work of non-fiction, as Sciascia proposed, but of historical fiction, and that Sciascia's Moro is a literary character, more a spokesperson for Sciascia's political views than a reflection of the historical figure. Sciascia's Moro embodies the same qualities as many of Sciascia's other protagonists, such as a radical individualism and willingness to sacrifice all in order to protect their dignity and liberty. What emanates from the text is a ‘postmodern’ blend that interprets and imposes a narrative hierarchy on events, and conveys a mental reality that need not necessarily coincide with what can be proven with evidence. In fact, Sciascia combines factual information and his own ‘conjectural knowledge’ to convince his reader of the ‘moral truth’ of his argument. Sciascia's is indeed a strong narrative in that it succeeded in shaping how the Italian public views to this day a critical juncture in its recent history.
(3aR*,6S*,7aR*)-7a-Chloro-6-methyl-2-(4-methylphenylsulfonyl)-2,3,3a,6,7,7a-hexahydro-3a,6-epoxy-1H-isoindole
Authors: Temel Ersin , Demircan Aydın , Beyazova Gözde , Büyükgüngör Orhan
Published: March 2012

In the title compound, C16H18ClNO3S, the six-membered ring has a boat conformation. The two five-membered rings with the bridging O atom adopt envelope conformations, whereas the N-containing five-membered ring adopts a twisted conformation. In the crystal, C—H...O hydrogen bonds link the molecules into a three-dimensional network.
(2E,4E)-Ethyl 5-(phenylsulfonyl)penta-2,4-dienoate
Authors: Sankar Ulaganathan , Sabari V. , Suresh G. , Uma Ramakrishnan , Aravindhan S.
Published: March 2012

In the title compound, C13H14O4S, both C=C double bonds adopt anEconformation. In the crystal, molecules are linked into centrosymmetricR22(14) dimersviapairs of C—H...O hydrogen bonds.
Bis(azido-κN)bis[6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine-κ2N1,N6]manganese(II)
Authors: Wang Kun-Miao , Liu Zhi-Hua , Zheng Qi , Liu Chun-Bo , Miao Ming-Ming
Published: March 2012

In the title complex, [Mn(N3)2(C8H8N6)2], the complete molecule is generated by the application of twofold symmetry, and is in a distorted octahedral environment, coordinated by four N atoms of two bidentate 6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine ligands and two N atoms from two azide anions. The two chelated 6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine ligands form a dihedral angle 74.75 (5)°. The mononuclear molecules are alternatively linked into layers parallel to theacplaneviaN—H...N hydrogen bonds. Adjacent layers are connected into a three-dimensional supramolecular framework by futher N—H...N hydrogen-bonding interactions.
Non-centrosymmetric Na3Nb4As3O19
Authors: Chérif Saïda Fatma , Hizaoui Khaled , Zid Mohamed Faouzi , Driss Ahmed
Published: March 2012

A new non-centrosymmetric compound, trisodium tetraniobium triarsenic nonadecaoxide, Na3Nb4As3O19, has been synthesized by a solid-state reaction at 1123 K. The structure consists of AsO4tetrahedra and NbO6octahedra sharing corners to form a three-dimensional framework containing two types of tunnels running along thecaxis, in which the sodium ions are located. Na+cations occupying statistically several sites, respectively, are surrounded by seven, six and four O atoms at distances ranging from 2.08 (1) to 2.88 (4) Å. The title structure is compared with those containing the same groups,viz.M2XO13andM2X2O17(M= transition metal, andX= As or P).
N-[Amino(imino)methyl]uronium tetrafluoroborate
Authors: Fridrichová Michaela , Fábry Jan , Fejfarová Karla , Krupková Radmila , Vaněk Přemysl
Published: March 2012

In the title compound, C2H7N4O+·BF4−, intermolecular N—H...O hydrogen bonds connect the cations into chains parallel to thecaxis, with graph-set motifC(4). These chains are in turn connected into a three-dimensional network by intermolecular N—H...F hydrogen bonds. The B—F distances distances in the anion are not equal.
2,3,5,6-Tetrafluoro-1,4-bis(trimethylsilyl)benzene
Authors: Finze Maik , Reiss Guido J. , Frohn Hermann-Josef
Published: March 2012

The asymmetric unit of the title compound, C12H18F4Si2, contains two independent molecules, both lying on inversion centers. The Carene—Si distances are significantly longer than in the analogous non-fluorinated compound. The packing of the molecules results in a herringbone motif in theacplane.
(E)-BenzaldehydeO-{[3-(pyridin-3-yl)isoxazol-5-yl]methyl}oxime
Authors: Moreno-Fuquen Rodolfo , Loaiza Alix Elena , Diaz-Velandia John , Kennedy Alan R. , Morrison Catriona A.
Published: March 2012

The asymmetric unit of the title compound, C16H13N3O2, contains two independent molecules in which the pyridine and benzene rings form dihedral angles of 81.7 (2) and 79.8 (2)°, indicating the twist in the molecules. In the crystal, weak C—H...N interactions link molecules into chains along [100].
3,6-Dibromo-7-ethylamino-4-methyl-2H-chromen-2-one
Authors: Zhang Ting , Xing Huai-jie , Miao Chun-bao , Sun Xiao-qiang , Xi Hai-tao
Published: March 2012

In title compound, C12H11Br2NO2, the coumarin ring system is almost planar, the two rings being inclined to one another by 1.40 (15)°. There are two short intramolecular interactions (N—H...Br and C—H...Br) involving the Br atoms. In the crystal, molecules stack along thea-axis directionviaπ–π interactions; the centroid–centroid distances vary from 3.6484 (19) to 3.7942 (19) Å.
trans-Diaquabis(L-phenylalaninato-κ2N,O)nickel(II)
Authors: Ghorbanloo Massomeh , Shahbakhsh Nahid , Choquesillo-Lazarte Duane
Published: March 2012

In the title compound, [Ni(C9H10NO2)2(H2O)2], the coordination geometry around the NiIIion can be described as distorted octahedral, with two N atoms and two O atoms from phenylalaninate ligands in the basal plane and two aqua O atoms at the axial sites. The crystal packing is stabilized by intermolecular O—H...O and N—H...O hydrogen bonds.
(2,9-Dimethyl-1,10-phenanthroline-κ2N,N′)bis(2-methoxybenzoato-κ2O1,O1′)cadmium
Authors: Zhang Heng , Zhao Pei-Zheng
Published: March 2012

In the title compound, [Cd(C8H7O3)2(C14H12N2)], the CdIIion is coordinated by two N atoms from a 2,9-dimethyl-1,10-phenanthroline (dmphen) ligand and four O atoms from two 2-methoxybenzoate anions in a distorted octahedral environment. Two O atoms of one bidentate 2-methoxybenzoate ligand are each disordered over two positions, with site-occupancy factors of 0.579 (4) and 0.421 (4). In the crystal, molecules are linked by C—H...O hydrogen bonds, forming a two-dimensional network lieing parallel to thebcplane. The crystal packing is further stablized by π–π stacking interactions between the dmphen rings of neighboring molecules, with distances between their parallel dmphen ring planes of 3.517 (3) and 3.610 (3) Å.
Chlorido{4-cyclohexyl-1-[1-(pyridin-2-yl-κN)ethylidene]thiosemicarbazidato-κ2N1,S}diphenyltin(IV)
Authors: Affan Md. Abu , Salam Md. Abdus , Jusoh Ismail , Ng Seik Weng , Tiekink Edward R. T.
Published: March 2012

The distorted octahedral geometry about the SnIVatom in the title compound, [Sn(C6H5)2(C14H19N4S)Cl], is defined by theN,N,S-tridentate Schiff base ligand, two mutuallytrans ipso-C atoms of the Sn-bound phenyl groups, and the Cl atom which istransto the azo N atom. The two five-membered chelate rings and pyridyl ring are almost coplanar with the dihedral angle between the outer five-membered chelate and pyridine rings being 5.39 (8)°. Centrosymmetric dimers feature in the crystal packing mediated by N—H...S hydrogen bonds, leading to eight-membered {...HNCS}2synthons. The dimeric aggregates are connected into a three-dimensional architecture by C—H...Cl and C—H...π interactions, as well as π–π interactions occurring between centrosymmetrically related pyridine rings [centroid–centroid distance = 3.6322 (13) Å].
City of One: A Qualitative Study Examining the Participation of Young People in Care in a Theatre and Music Initiative
Authors: Salmon Debra , Rickaby Caroline
Published: March 2012

Young people's engagement with the arts can facilitate skills development, improve mental health and strengthen resilience. This article reports on a qualitative study exploring the experiences and involvement of ten young people in care in the development of a musical play exploring life in the care system. The project was viewed as successful in a number of ways: involving young people who had not previously taken part in drama; developing skills, confidence and resilience, and improving feelings of social connectedness. Extending work on participatory arts approaches, this study identifies factors that influence young people's ability to maintain involvement and the implications for carers and professionals supporting them.
Immunity induced by Staphylococcus aureus surface protein A was protective against lethal challenge of Staphylococcus aureus in BALB/c mice
Authors: Yi Shao‐Qiong , Zhang Xiao‐Yan , Yang Yi‐Long , Yang Yue , Liu Shu‐Ling , Fu Ling , Yu Chang‐Ming , Chen Wei
Published: March 2012

Staphylococcus aureus is the most common cause of hospital‐acquired bacteremia. Due to emergence of antibiotic‐resistant strains, these infections present a serious public health threat. In this study, to develop a broadly protective vaccine, we tested whether immune responses induced by several proteins associated with S. aureus toxicity could protect mice from lethal challenge with human clinical S. aureus isolate USA300. We found that the surface protein A (SasA) of S. aureus could protect mice from lethal challenge of the bacteria.
Fine‐mapping the POLL locus in Brahman cattle yields the diagnostic marker CSAFG29
Authors: Mariasegaram Maxy , Harrison Blair E. , Bolton Jennifer A. , Tier Bruce , Henshall John M. , Barendse William , Prayaga Kishore C.
Published: March 2012

The POLL locus has been mapped to the centromeric region of bovine chromosome 1 (BTA1) in both taurine breeds and taurine–indicine crosses in an interval of approximately 1 Mb. It has not yet been mapped in pure‐bred zebu cattle. Despite several efforts, neither causative mutations in candidate genes nor a singular diagnostic DNA marker has been identified. In this study, we genotyped a total of 68 Brahman cattle and 20 Hereford cattle informative for the POLL locus for 33 DNA microsatellites, 16 of which we identified de novo from the bovine genome sequence, mapping the POLL locus to the region of the genes IFNAR2 and SYNJ1. The 303‐bp allele of the new microsatellite, CSAFG29, showed strong association with the POLL allele. We then genotyped 855 Brahman cattle for CSAFG29 and confirmed the association between the 303‐bp allele and POLL. To determine whether the same association was found in taurine breeds, we genotyped 334 animals of the Angus, Hereford and Limousin breeds and 376 animals of the Brangus, Droughtmaster and Santa Gertrudis composite taurine–zebu breeds. The association between the 303‐bp allele and POLL was confirmed in these breeds; however, an additional allele (305 bp) was also associated but not fully predictive of POLL. Across the data, CSAFG29 was in sufficient linkage disequilibrium to the POLL allele in Australian Brahman cattle that it could potentially be used as a diagnostic marker in that breed, but this may not be the case in other breeds. Further, we provide confirmatory evidence that the scur phenotype generally occurs in animals that are heterozygous for the POLL allele.
How could undergraduate education prepare new graduates to be safer prescribers?
Authors: McLellan Lucy , Tully Mary Patricia , Dornan Tim
Published: March 2012

This review examines the extent to which undergraduate prescribing education prepares graduates for the complexities of prescribing in the workplace context. In order to prescribe safely, it is important for medical students to acquire prescribing expertise. We have developed a theoretical model, based on theories of expertise development, which acknowledges the inherent complexity of the task itself, the social context and the relationship between the two. We have examined the empirical evidence on educational interventions for prescribing by reviewing the extent to which the interventions acknowledge the different components of our theoretical model. Fifteen empirical studies met our inclusion criteria and were reviewed in detail. All the studies were conducted between 2002 and 2010, six were controlled trials, six were before and after studies and three were prospective observational studies. We found that most studies focused on improving and evaluating students' knowledge and skills, although they used different approaches to doing so. These aspects of prescribing only constitute a small part of our theoretical model of prescribing expertise. Other important components, such as social context, metacognition and training transfer, were neglected. We suggest that educational interventions need to account for the integrated nature of learning to prescribe and take a more contextualized approach which considers the task as a whole, rather than isolated constituent parts. In doing so, prescribing education could equip graduates with the necessary expertise to judge and respond to situations, enabling them to prescribe safely, or seek the help to do so, in the unpredictable and complex context of workplaces.
The antioxidant paradox: less paradoxical now?
Authors: Halliwell Barry
Published: March 2012

The term ‘antioxidant paradox’ is often used to refer to the observation that oxygen radicals and other reactive oxygen species are involved in several human diseases, but giving large doses of dietary antioxidant supplements to human subjects has, in most studies, demonstrated little or no preventative or therapeutic effect. Why should this be? First, the role of reactive oxygen species in the origin and/or progression of most human diseases is unclear, although they are probably important in cancer, neurodegenerative diseases and perhaps some others. Second, the endogenous antioxidant defences in the human body are complex, interlocking and carefully regulated. The body's ‘total antioxidant capacity’ seems unresponsive to high doses of dietary antioxidants, so that the amount of oxidative damage to key biomolecules is rarely changed. Indeed, manipulation of endogenous antioxidant levels (e.g. by supplying weak pro‐oxidants) may be a more useful approach to treatment and prevention of diseases in which reactive oxygen species are important than is consumption of large doses of dietary antioxidants.