bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of the R2R3-MYB Transcription Factor TaMYB14 fromTrifolium arvenseActivates Proanthocyanidin Biosynthesis in the LegumesTrifolium repensandMedicago sativa
Authors: Hancock Kerry R. , Collette Vern , Fraser Karl , Greig Margaret , Xue Hong , Richardson Kim , Jones Chris , Rasmussen Susanne
Published: May 2012

Proanthocyanidins (PAs) are oligomeric flavonoids and one group of end products of the phenylpropanoid pathway. PAs have been reported to be beneficial for human and animal health and are particularly important in pastoral agricultural systems for improved animal production and reduced greenhouse gas emissions. However, the main forage legumes grown in these systems, such as Trifolium repens and Medicago sativa, do not contain any substantial amounts of PAs in leaves. We have identified from the foliar PA-accumulating legume Trifolium arvense an R2R3-MYB transcription factor, TaMYB14, and provide evidence that this transcription factor is involved in the regulation of PA biosynthesis in legumes. TaMYB14 expression is necessary and sufficient to up-regulate late steps of the phenylpropanoid pathway and to induce PA biosynthesis. RNA interference silencing of TaMYB14 resulted in almost complete cessation of PA biosynthesis in T. arvense, whereas Nicotiana tabacum, M. sativa, and T. repens plants constitutively expressing TaMYB14 synthesized and accumulated PAs in leaves up to 1.8% dry matter. Targeted liquid chromatography-multistage tandem mass spectrometry analysis identified foliar PAs up to degree of polymerization 6 in leaf extracts. Hence, genetically modified M. sativa and T. repens plants expressing TaMYB14 provide a viable option for improving animal health and mitigating the negative environmental impacts of pastoral animal production systems.
Mutation inTERMINAL FLOWER1Reverses the Photoperiodic Requirement for Flowering in the Wild StrawberryFragaria vesca
Authors: Koskela Elli A. , Mouhu Katriina , Albani Maria C. , Kurokura Takeshi , Rantanen Marja , Sargent Daniel J. , Battey Nicholas H. , Coupland George , Elomaa Paula , Hytönen Timo
Published: May 2012

Photoperiodic flowering has been extensively studied in the annual short-day and long-day plants rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), whereas less is known about the control of flowering in perennials. In the perennial wild strawberry, Fragaria vesca (Rosaceae), short-day and perpetual flowering long-day accessions occur. Genetic analyses showed that differences in their flowering responses are caused by a single gene, SEASONAL FLOWERING LOCUS, which may encode the F. vesca homolog of TERMINAL FLOWER1 (FvTFL1). We show through high-resolution mapping and transgenic approaches that FvTFL1 is the basis of this change in flowering behavior and demonstrate that FvTFL1 acts as a photoperiodically regulated repressor. In short-day F. vesca, long photoperiods activate FvTFL1 mRNA expression and short days suppress it, promoting flower induction. These seasonal cycles in FvTFL1 mRNA level confer seasonal cycling of vegetative and reproductive development. Mutations in FvTFL1 prevent long-day suppression of flowering, and the early flowering that then occurs under long days is dependent on the F. vesca homolog of FLOWERING LOCUS T. This photoperiodic response mechanism differs from those described in model annual plants. We suggest that this mechanism controls flowering within the perennial growth cycle in F. vesca and demonstrate that a change in a single gene reverses the photoperiodic requirements for flowering.
Common data elements for substance use disorders in electronic health records: the NIDA Clinical Trials Network experience
Authors: Ghitza Udi E. , Gore‐Langton Robert E. , Lindblad Robert , Shide David , Subramaniam Geetha , Tai Betty
Published: May 2012

Aims  Electronic health records (EHRs) are essential in improving quality and enhancing efficiency of health‐care delivery. By 2015, medical care receiving service reimbursement from US Centers for Medicare and Medicaid Services (CMS) must show ‘meaningful use’ of EHRs. Substance use disorders (SUD) are grossly under‐detected and under‐treated in current US medical care settings. Hence, an urgent need exists for improved identification of and clinical intervention for SUD in medical settings. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) has leveraged its infrastructure and expertise and brought relevant stakeholders together to develop consensus on brief screening and initial assessment tools for SUD in general medical settings, with the objective of incorporation into US EHRs.

Methods  Stakeholders were identified and queried for input and consensus on validated screening and assessment for SUD in general medical settings to develop common data elements to serve as shared resources for EHRs on screening, brief intervention and referral to treatment (SBIRT), with the intent of supporting interoperability and data exchange in a developing Nationwide Health Information Network.

Results  Through consensus of input from stakeholders, a validated screening and brief assessment instrument, supported by Clinical Decision Support tools, was chosen to be used at out‐patient general medical settings.

Conclusions  The creation and adoption of a core set of validated common data elements and the inclusion of such consensus‐based data elements for general medical settings will enable the integration of SUD treatment within mainstream health care, and support the adoption and ‘meaningful use’ of the US Office of the National Coordinator for Health Information Technology (ONC)‐certified EHRs, as well as CMS reimbursement.
The majority of allergen‐specific IgE in the blood of allergic patients does not originate from blood‐derived B cells or plasma cells
Authors: Eckl‐Dorna J. , Pree I. , Reisinger J. , Marth K. , Chen K.‐W. , Vrtala S. , Spitzauer S. , Valenta R. , Niederberger V.
Published: May 2012

Background

The production of allergen‐specific IgE antibodies is a hallmark of IgE‐mediated allergy but the contribution of blood cells to allergen‐specific IgE production in allergic patients has not been studied in detail.

Objective

Aim of this study was the characterization of IgE‐producing cells in the blood of allergic patients and the determination of the amount of IgE antibodies which are produced by these cells in relation to total amounts of circulating specific IgE.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from allergic patients and cell populations were purified or depleted using magnetically labelled antibodies directed against specific cell surface markers (CD19, CD20, CD22, CD27, CD38, CD126, CD138, CD203c). Allergen‐specific IgE was measured in serum samples and cell culture supernatants by quantitative ImmunoCAP measurements and by ELISA using purified recombinant allergens. IgE transcripts were detected using RT‐PCR with primers specific for human IgE.

Results

We found that allergen‐specific IgE levels in PBMC supernatants correlated strongly with specific serum IgE but represented less than 1% of circulating IgE. Depletion of basophils resulted in substantial reduction of allergen‐specific IgE levels in PBMC culture supernatants suggesting that an important source of allergen‐specific IgE in PBMC supernatants could be IgE derived from the surface of basophils. Newly synthesized IgE was derived from CD138+ plasma cells, but not from B and B memory cells, and accounted for only approximately 0.2% of circulating IgE in blood.

Conclusion and Clinical Relevance

Our finding that the majority of allergen‐specific IgE in the peripheral blood is not derived from IgE‐secreting cells in the blood suggests local IgE production in tissues as a major source for allergen‐specific IgE and possible target for therapeutic intervention.
Impaired development of melanoblasts in the black‐eyed white Mitfmi‐bw mouse, a model for auditory–pigmentary disorders
Authors: Hozumi Hiroki , Takeda Kazuhisa , Yoshida‐Amano Yasuko , Takemoto Yuji , Kusumi Ryota , Fukuzaki‐Dohi Urara , Higashitani Atsushi , Yamamoto Hiroaki , Shibahara Shigeki
Published: May 2012

Microphthalmia‐associated transcription factor (Mitf) is a regulator for differentiation of melanoblasts that are derived from the neural crest. The mouse homozygous for the black‐eyed white (Mitfmi‐bw) allele is characterized by the white coat color and deafness, with black eye that is associated with the lack of melanocytes in skin and inner ear. The Mitfmi‐bw mutation is an insertion of the LINE1 retrotransposable element into intron 3 of the Mitf gene that causes the selective deficiency of the melanocyte‐specific Mitf isoform, Mitf‐M. Here, we show the expression of Mitf‐M mRNA in the trunk region of the homozygous Mitfmi‐bw (bw) mouse at embryonic days (E) 11.5 and E12.5, but Mitf‐M mRNA is undetectable at E13.5. In addition, using bw mouse that carries the lacZ transgene under the control of a melanoblast‐specific promoter, we show that the number of migrating melanoblasts in bw embryos was less than 10% of that in control embryos at E11.5 and E12.5, and melanoblasts disappear by E13.5. The loss of melanoblasts in bw embryos was probably caused by apoptosis. Finally, forced expression of Mitf‐M in the cultured neural tube of bw embryos ensured the differentiation of melanoblasts. Therefore, the correct dose of Mitf‐M is required for the normal development of melanoblasts.
Muscle wasting in animal models of severe illness
Authors: Holecek Milan
Published: May 2012

Muscle wasting is a serious complication of various clinical conditions that significantly worsens the prognosis of the illnesses. Clinically relevant models of muscle wasting are essential for understanding its pathogenesis and for selective preclinical testing of potential therapeutic agents. The data presented here indicate that muscle wasting has been well characterized in rat models of sepsis (endotoxaemia, and caecal ligation and puncture), in rat models of chronic renal failure (partial nephrectomy), in animal models of intensive care unit patients (corticosteroid treatment combined with peripheral denervation or with administration of neuromuscular blocking drugs) and in murine and rat models of cancer (tumour cell transplantation). There is a need to explore genetically engineered mouse models of cancer. The degree of protein degradation in skeletal muscle is not well characterized in animal models of liver cirrhosis, chronic heart failure and chronic obstructive pulmonary disease. The major difficulties with all models are standardization and high variation in disease progression and a lack of reflection of clinical reality in some of the models. The translation of the information obtained by using these models to clinical practice may be problematic.
Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction
Authors: de Almeida Prado Patrícia S. , Soares Maria Fernanda , Lima Flávio O. , Schor Nestor , Teixeira Vicente P.C.
Published: May 2012

Infravesical obstruction (IVO) secondary to benign prostatic hypertrophy can affect up to 50% of men over 50 years old and may cause serious and irreversible alterations throughout the urinary tract, especially in the bladder. Therapeutic approaches are currently limited. Amitriptyline has recently been described as an analgesic, anti‐inflammatory and myorelaxant in some experimental models. The objective of this study was to investigate the effects of amitriptyline hydrochloride on the process of fibrosis in a bladder outlet obstruction model in rats. Male Wistar rats were subjected to IVO and studied at intervals of 1 and 14 days postprocedure. The rats were randomly divided into five groups: sham, IVO1‐T, IVO1‐NT, IVO14‐T and IVO14‐NT. Bladder tissue was processed for histopathology, immunohistochemistry and RT‐PCR. The IVO14 groups presented bladder fibrosis, smooth muscle cell hypertrophy and bladder wall thickening. The IVO14‐T group demonstrated a higher intensity of fibrosis, higher macrophage infiltration rate and higher gene expression of Transforming growth factor (TGF) Tgf‐β1. Thus this data shows that in this experimental mode amitriptyline had an amplifying effect on the process of fibrosis as a whole.
Prediction of storage quality of fresh‐cut green peppers using artificial neural network
Authors: Meng Xiangyong , Zhang Min , Adhikari Benu
Published: May 2012

To extend the shelf‐life of fresh‐cut fruits and vegetables, it is essential to develop models that can accurately predict their storage quality. In view of this, an artificial neural network (ANN) model based on back propagation (BP) algorithm was developed to predict the storage quality (degree of yellowness, water loss, textural firmness and vitamin C content) of fresh‐cut green peppers. The prediction accuracy of ANN was compared with that of multiple linear regression‐based models. The root mean square error (RMSE), mean absolute error (MAE), sum of squared residuals (SSR) and standard error of prediction (SEP) were used as comparison parameters. The results showed that the accuracy and goodness of fit of the storage quality parameters predicted by ANN were better than those predicted by multiple linear regression‐based models. The RMSE, MAE, SSR and SEP values obtained from the former were much lower than those obtained from the latter.
Optimisation of lactic acid fermentation of York cabbage for the development of potential probiotic products
Authors: Jaiswal Amit K. , Gupta Shilpi , Abu‐Ghannam Nissreen
Published: May 2012

In this study, York cabbage was used as the sole substrate for the lactic acid (LA) fermentation with Lactobacillus plantarum. York cabbage was blanched at 95 °C for 12 min to inactivate surface microflora prior to fermentation. To achieve an optimal fermentation condition that would result in higher release of phytochemicals and antioxidant (AO) capacity in the broth, Box‐Behnken design integrating a desirability approach was used. A second‐order polynomial equation was developed, indicating the effect of solute/liquid ratio, agitation rate and fermentation time on desired parameters. The optimised factors were used for fermenting York cabbage to obtain maximum bacterial growth, LA, polyphenols and AO capacity. There was ≈5 log cfu mL−1 increment in bacterial growth after fermentation, whereas LA production reached up to 4.97 mg mL−1. Results showed that fermentation retains 95–98% and 90–95% of TPC and AO capacity, respectively. During refrigerated storage (4 °C), the cell numbers, bioactive components and acidity were maintained till 15‐day storage.
Comparison of enhancement in bioaccessible iron and zinc in native and fortified high‐phytate oilseed and cereal composites by activating endogenous phytase
Authors: Shilpa K. S. , Jyothi lakshmi A.
Published: May 2012

In developing countries, iron and zinc deficiencies are mostly attributable to poor bioavailability of iron and zinc. The study aimed at enhancing the bioaccessibility of minerals in high‐phytate oilseed and cereal flour mixes by activating the intrinsic phytase of wheat flour. The flour mixes were fortified with iron and zinc separately for comparison. The flour mixes were incubated at optimum conditions of temperature and pH for phytase activation. Phytase activation enhanced bioaccessible iron by 43–162% in native and 40–168% in fortified wheat–soya, 83–192% in native and 97–240% in fortified wheat–groundnut flour mixes in relation to control flour mixes. Bioaccessible zinc was enhanced by 87–183% in native and 30–113% in fortified wheat–soya, 31–65% in native and 61–186% in fortified wheat–groundnut flour mixes. Endogenous phytase activation was effective in enhancing bioaccessibility of iron and zinc in native and fortified flour composites economically.
Variation in phenotypic plasticity and selection patterns in blue tit breeding time: between‐ and within‐population comparisons
Authors: Porlier Melody , Charmantier Anne , Bourgault Patrice , Perret Philippe , Blondel Jacques , Garant Dany
Published: May 2012

1. Phenotypic plasticity, the response of individual phenotypes to their environment, can allow organisms to cope with spatio‐temporal variation in environmental conditions. Recent studies have shown that variation exists among individuals in their capacity to adjust their traits to environmental changes and that this individual plasticity can be under strong selection. Yet, little is known on the extent and ultimate causes of variation between populations and individuals in plasticity patterns.

2. In passerines, timing of breeding is a key life‐history trait strongly related to fitness and is known to vary with the environment, but few studies have investigated the within‐species variation in individual plasticity.

3. Here, we studied between‐ and within‐population variation in breeding time, phenotypic plasticity and selection patterns for this trait in four Mediterranean populations of blue tits (Cyanistes caeruleus) breeding in habitats varying in structure and quality.

4. Although there was no significant warming over the course of the study, we found evidence for earlier onset of breeding in warmer years in all populations, with reduced plasticity in the less predictable environment. In two of four populations, there was significant inter‐individual variation in plasticity for laying date. Interestingly, selection for earlier laying date was significant only in populations where there was no inter‐individual differences in plasticity.

5. Our results show that generalization of plasticity patterns among populations of the same species might be challenging even at a small spatial scale and that the amount of within‐individual variation in phenotypic plasticity may be linked to selective pressures acting on these phenotypic traits.
Opening up to learning spiritual care of patients: a grounded theory study of nursing students
Authors: Giske Tove , Cone Pamela H
Published: May 2012

Aim.  To determine undergraduate nursing students’ perspectives on spiritual care and how they learn to assess and provide spiritual care to patients.

Background.  Nursing is concerned with holistic care. Systematic teaching and supervision of students to prepare them to assist patients spiritually is a growing focus. However, there is limited consensus about the competences students need to develop and little is written related to students learning processes.

Design.  Grounded theory was used to identify students’ main concern and develop a substantive grounded theory.

Method.  Data collected during semi‐structured interviews at three Norwegian University Colleges in eight focus groups with 42 undergraduate nursing students were analysed through constant comparison of transcribed interviews until categories were saturated.

Results.  The participants’ main concern was ‘How to create a professional relationship with patients and maintain rapport when spiritual concerns were recognised’. Participants resolved this by ‘Opening up to learning spiritual care’. This basic social process has three iterative phases that develop as a spiral throughout the nursing programme: ‘Preparing for connection’, ‘Connecting with and supporting patients’ and ‘Reflecting on experiences’.

Conclusion.  Nurses need a wide range of competences to fulfil the nursing focus on holistic patient care. Nursing education should prepare students to recognise and act on spiritual cues. A trusting relationship and respectful and sensitive communication assist students to discover what is important to patients. An educational focus on spiritual and existential themes throughout the nursing programme will assist students to integrate theoretical learning into clinical practice.

Relevance to clinical practice.  Study participants reported seeing few role models in clinical settings. Making spiritual assessment and interventions more visible and explicit would facilitate student learning in clinical practice. Evaluative discussions in clinical settings that include spiritual concerns will enhance holistic care.
Costs and outcomes over 36 years of patients with phenylketonuria who do and do not remain on a phenylalanine‐restricted diet
Authors: Guest J. F. , Bai J. J. , Taylor R. R. , Sladkevicius E. , Lee P. J. , Lachmann R. H.
Published: May 2012

Background  To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine‐restricted diet for life.

Methods  A computer‐based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co‐morbidities and the levels of healthcare resource use and corresponding costs over the 36 years.

Results  Patients who remained on a phenylalanine‐restricted diet accounted for 38% of the cohort. Forty‐seven per cent of patients discontinued their phenylalanine‐restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine‐restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received.

Conclusion  The findings suggest that the majority of patients with PKU were under‐treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long‐term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.
Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata)
Authors: MIYABE‐NISHIWAKI T. , MASUI K. , KANEKO A. , NISHIWAKI K. , NISHIO T. , KANAZAWA H.
Published: May 2012

Miyabe‐Nishiwaki, T., Masui, K., Kaneko, A., Nishiwaki, K., Nishio, T., Kanazawa, H. Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata). J. vet. Pharmacol. Therap. 36, 169–173.

Propofol is a short‐acting intravenous anesthetic used for induction/maintenance anesthesia. The objective of this study was to assess a population pharmacokinetic (PPK) model for Japanese macaques during a step‐down infusion of propofol. Five male Japanese macaques were immobilized with ketamine (10 mg/kg) and atropine (0.02 mg/kg). A bolus dose of propofol (5 mg/kg) was administrated intravenously (360 mg/kg/h) followed by step‐down infusion at 40 mg/kg/h for 10 min, 20 mg/kg/h for 10 min, and then 15 mg/kg/h for 100 min. Venous blood samples were repeatedly collected following the administration. The plasma concentration of propofol (Cp) was measured by high‐speed LC‐FL. PPK analyses were performed using NONMEM VII. Median absolute prediction error and median prediction error (MDPE), the indices of prediction inaccuracy and bias, respectively, were calculated, and PE − individual MDPE vs. time was depicted to show the variability of prediction errors. In addition, we developed another population pharmacokinetic model using previous and current datasets. The previous PK model achieved stable prediction of propofol Cp throughout the study period, although it underestimates Cp. The step‐down infusion regimen described in this study would be feasible in macaques during noninvasive procedures.
Capturing the dynamics of systemic Renin‐Angiotensin‐Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs
Authors: MOCHEL J. P. , PEYROU M. , FINK M. , STREHLAU G. , MOHAMED R. , GIRAUDEL J. M. , PLOEGER B. , DANHOF M.
Published: May 2012

Mochel, J. P., Peyrou, M, Fink, M, Strehlau, G, Mohamed, R, Giraudel, J. M., Ploeger, B, Danhof, M. Capturing the dynamics of systemic Renin‐Angiotensin‐Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs.J. vet. Pharmacol. Therap. 36, 174–180.

In dogs, activation of the Renin‐Angiotensin‐Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long‐term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin‐converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low‐sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC24 hours) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC24 hoursof plasma renin activity (+90%), angiotensin I (+43%), and AII (−53%) were found between benazepril and placebo‐treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs.
HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype
Authors: Yamamura T. , Hikita J. , Bleakley M. , Hirosawa T. , Sato‐Otsubo A. , Torikai H. , Hamajima T. , Nannya Y. , Demachi‐Okamura A. , Maruya E. , Saji H. , Yamamoto Y. , Takahashi T. , Emi N. , Morishima Y. , Kodera Y. , Kuzushima K. , Riddell S. R. , Ogawa S. , Akatsuka Y.
Published: May 2012

Minor histocompatibility (H) antigens are targets of graft‐vs‐host disease and graft‐vs‐tumor responses after human leukocyte antigen matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium blocks that encoded novel minor H antigens using the large dataset from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B‐lymphoid cell line by minor H antigen‐specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single‐nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as ‘HapMap SNP Scanner’, and can incorporate T‐cell recognition and other data with genotyping datasets from CEU, JPT, CHB, and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP‐based customized therapies.
Spontaneous expression of FRA16B in a non‐consanguineous couple experiencing multiple fetal losses
Authors: Aswini Sivasankaran , Jegatheesan ThankaNadar , Chandra Nallathambi
Published: May 2012

The association between fragile sites and human genetic diseases is still debatable. Although FRAXA and FRAXE have been found to be associated with mental retardation and FRA11B possibly with Jacobsen syndrome, no other autosomal fragile site has yet been found to have a direct correlation with a genetic disorder; however, the frequency of fragile sites in infertile couples has been reported to be higher than in a control group. The occurrence of a fragile site can therefore be a possible risk factor causing considerable anxiety to the clinician and probably requires follow up with appropriate genetic counseling. The present study reports heterozygosity for FRA16B in both partners of an infertile non‐consanguineous couple married for 9 years. They had been referred for cytogenetic evaluation with the complaint of multiple fetal losses.
Cutaneous metastasis from primary adenocarcinoma of the vagina: A case report
Authors: Nakai Hidekastu , Watanabe Yoh , Etoh Tomomaro , Kimura Masatomo , Hoshiai Hiroshi
Published: May 2012

Cutaneous metastasis in vaginal cancer is an extremely rare event and no cases of cutaneous metastasis from primary vaginal adenocarcinoma have been found. We report the clinicopathologic features, including cytopathologic findings, of the first case of cutaneous metastasis to the anterior chest wall from a sporadic‐type advanced primary vaginal adenocarcinoma. Our present case suggested that cytopathologic examination should be performed as soon as possible when a patient exhibits multiple subcutaneous nodules or a painful cutaneous ulcer during treatment of advanced gynecologic cancer.
Presynaptic inhibition of glutamate transmission by α2 receptors in the VTA
Authors: Jiménez‐Rivera Carlos A. , Figueroa Johnny , Vázquez‐Torres Rafael , Vélez‐Hernandez María E. , Schwarz David , Velásquez‐Martinez María C. , Arencibia‐Albite Francisco
Published: May 2012

The ventral tegmental area (VTA) forms part of the mesocorticolimbic system and plays a pivotal role in reward and reinforcing actions of drugs of abuse. Glutamate transmission within the VTA controls important aspects of goal‐directed behavior and motivation. Noradrenergic receptors also present in the VTA have important functions in the modulation of neuronal activity. Here we studied the effects of α2 noradrenergic receptor activation in the alteration of glutamate neurotransmission in VTA dopaminergic neurons from male Sprague–Dawley rats. We used whole‐cell patch‐clamp recordings from putative VTA dopaminergic neurons and measured excitatory postsynaptic currents. Clonidine (40 μm) and UK 14,304 (40 μm), both α2 receptor agonists, reduced (approximately 40%) the amplitude of glutamate‐induced excitatory postsynaptic currents. After clonidine administration, there was a dose‐dependent reduction over the concentration range of 15–40 μm. Using yohimbine (20 μm) and two other α2 adrenergic receptor antagonists, idaxozan (40 μm) and atipemazole (20 μm), we demonstrated that the inhibitory action is specifically mediated by α2 receptors. Moreover, by inhibiting protein kinases with H‐7 (75 μm), Rp‐adenosine 3′,5′‐cyclic (11 μm) and chelerythrine (1 μm) it was shown that the clonidine‐induced inhibition seems to involve a selective activation of the protein kinase C intracellular pathway. Increased paired‐pulse ratios and changes in spontaneous and miniature excitatory postsynaptic current frequencies but not amplitudes indicated that the effect of the α2 agonist was presynaptically mediated. It is suggested that the suppression of glutamate excitatory inputs onto VTA dopaminergic neurons might be relevant in the regulation of reward and drug‐seeking behaviors.
Species abundance patterns of coccinellid communities associated with olive, chestnut and almond crops in north‐eastern Portugal
Authors: Santos Sónia A. P. , Raimundo Armando , Bento Albino , Pereira José A.
Published: May 2012

The patterns of abundance of coccinellid species associated to the main agricultural tree crops of north‐eastern Portugal namely olive, chestnut and almond were studied.

During three to four crop seasons, eight olive, five chestnut and one almond groves were sampled. In each grove, five samples were collected from 10 randomly selected trees using the beating technique and the coccinellids were counted and identified to species. Principal component analysis was used to establish associations among crop and coccinellid species.

The mean species richness was higher in chestnut, with 15 ± 3.81 species/grove, followed by olive and almond, with 13 ± 2.76 and 10 ± 2.97 species/grove, respectively. Scymnus mediterraneus was the most abundant species in olive and almond, whereas Scymnus interruptus was dominant in chestnut. Brumus quadripustulatus, Chilocorus bipustulatus, Scymnus subvillosus, S. mediterraneus and Rhyzobius chrysomeloides were associated with olive, whereas S. interruptus, Coccinella septempunctata and Adalia decempunctata were associated with chestnut and Hippodamia variegata, Oenopia conglobata and Adalia bipunctata with almond. Both Stethorus punctillum and Scymnus apetzi species were similarly associated with chestnut and almond.

The differences in coccinellid communities could have been related to the kind of prey item present in the different trees. This knowledge can be used to develop integrated pest management programmes that encourage greater natural enemy biodiversity in agroecosystems.
Prevalence, transmission and mortality associated with Nosema fumiferanae infections in field populations of spruce budworm Choristoneura fumiferana
Authors: Eveleigh Eldon S. , Lucarotti Christopher J. , McCarthy Peter C. , Morin Benoit
Published: May 2012

The prevalence, intensity and transmission of Nosema fumiferanae (Thomson) (Microsporidae) infections and potential impacts on the survival of field populations of spruce budworm Choristoneura fumiferana (Clem.) were examined in three plots in New Brunswick, Canada, from 1983 to 1992.

The highest prevalence of N. fumiferanae infection in post‐hibernation second‐instar larvae occurred in the plot where prevalence in female pupae was the highest in the previous generation, suggesting higher rates of vertical transmission. There was little change in the prevalence of N. fumiferanae infections between the second and sixth instars in the later generations. In the two other plots, N. fumiferanae prevalence increased by approximately 25% from the second to sixth larval stadia. Coincident with the changes in N. fumiferanae prevalence were substantial declines in the populations of spruce budworms, making it difficult to determine rates of horizontal transfer of the disease.

In all plots and in all years, there were progressive increases in the intensity of N. fumiferanae infections (spore loads/individual) from the second to sixth instars and pupae.

Annual spruce budworm mortality associated with N. fumiferanae was ≤15% of all mortality in reared specimens and was positively correlated with but generally less than 30% of annual N. fumiferanae prevalence.
Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic β‐cell mass in a streptozotocin‐induced mouse model of type 2 diabetes
Authors: Poucher S. M. , Cheetham S. , Francis J. , Zinker B. , Kirby M. , Vickers S. P.
Published: May 2012

Aims

We examined the effects of the oral dipeptidyl peptidase‐4 (DPP‐4) inhibitor saxagliptin on glycaemic control and pancreatic β‐cell mass and morphology in a mouse model of type 2 diabetes mellitus (T2DM).

Methods

Male C57BL/6 mice (n = 12/group) aged 4 to 6 weeks and weighing >15 g received a high‐fat diet throughout this 45‐day study. After a 7‐day handling period, baseline levels of plasma glucose, plasma insulin and glycated haemoglobin (HbA1c) were assessed. Animals were allocated to one of six groups: compound vehicle control, intraperitoneal streptozotocin (STZ, 50 mg/kg)‐treated control and saxagliptin (10 mg/kg) or sitagliptin (10 mg/kg, positive control) initiated 7 days before or 1 day after STZ administration. Endpoints included changes in body weight, food and water consumption, glucose tolerance (approximately 3 weeks post‐STZ), fasting glucose and HbA1c and immunohistochemical analyses of the pancreas.

Results

Body weight, weight gain and food intake were reduced in STZ versus control mice. DPP‐4 inhibitor treatment did not affect these changes, but the increase in water intake observed post‐STZ administration was significantly attenuated with DPP‐4 inhibitors whether initiated before or after STZ injury. Small but significant improvements in glycaemic control were observed with DPP‐4 inhibitors versus the STZ control. Improved β‐cell mass and morphology were observed with saxagliptin given pre‐ or post‐STZ and sitagliptin given post‐STZ.

Conclusions

Saxagliptin mitigated damage to β‐cells and improved glycaemic control in this mouse model of T2DM.
COMMON DRIVERS OF TRANSNATIONAL TERRORISM: PRINCIPAL COMPONENT ANALYSIS
Authors: KHUSRAV GAIBULLOEV , TODD SANDLER , DONGGYU SUL
Published: May 2012

This article applies principal component analysis to decompose transnational terrorism during 1970–2007 into common (worldwide) and idiosyncratic (country‐specific) factors. Regardless of alternative thresholds and filtering procedures, a single common factor is related to individual countries' transnational terrorist events. Based on a conventional criterion, Lebanon's transnational terrorism is the key common driver of global transnational terrorist incidents. With a more conservative criterion, four additional countries—United States, Germany, Iraq, and the United Kingdom—are core countries in explaining cross‐sectional correlation across 106 countries' transnational terrorism. The analysis shows that there is a marked cross‐sectional dependence among transnational terrorist incidents worldwide. (JEL C38, H56)
There's Nothing New in Dying Now: Will Welfare Attorney Decision Making at End of Life Make a Real Difference?
Authors: Samanta Jo
Published: May 2012

Advance care planning is a way to express value‐based preferences in order to guide future treatment decisions following loss of decision‐making capacity. It aims to ensure that one's critical values continue to influence healthcare decisions, particularly at end of life. The Mental Capacity Act 2005 permits adults with capacity to appoint welfare attorneys to act as their proxy decision‐makers following loss of capacity. A focus group study was used to explore the views and perceptions of lawyers and health professionals to attorney decision making at end of life. Whilst participants gave a guarded welcome to the introduction of healthcare and welfare attorneys, potential challenges were identified, based upon professional norms and expectations. A shared consensus was that the realization of the full potential of proxy decision making was likely to be a theoretical, rather than real, benefit. Opinions were divided on elemental tenets such as prospective autonomy, best interests, and the potential for conflict.
Whither the Law and the Law Books? From Prescription to Possibility
Authors: Brownsword Roger
Published: May 2012

This article is a contribution to the occasional series dealing with major books that have influenced the authors. Previous contributors include Stewart Macaulay, John Griffith, William Twining, Carol Harlow, Geoffrey Bindman, Harry Arthurs, André‐Jean Arnaud, Alan Hunt, Michael Adler, Lawrence O. Gostin, and John P. Heinz
Antecedents of Board Composition: The Role of Nomination Committees
Authors: Kaczmarek Szymon , Kimino Satomi , Pye Annie
Published: May 2012

Manuscript Type: Empirical

Research Question/Issue: The global financial crisis in 2008 has generated increasing recognition of the importance of board diversity reflected amidst the capabilities and skills of directors on a board. As the primary institutional mechanism designed to strengthen the director selection process, nomination committees (NCs) occupy centre stage of this discussion. However, there is a dearth of studies which focus either specifically on NCs or on diversity as a board composition outcome. In this study, we examine the research question of the likely antecedents in terms of NC characteristics of two board composition outcomes, i.e., diversity as variety in terms of gender and nationality, and diversity as separation in terms of a board demographic faultline.

Research Findings/Insights: For a panel of FTSE350 companies from 1999 to 2008, we find that the increasing presence on the NC of females or non‐British nationals is likely to have a positive impact on the level of board gender and nationality diversity, respectively. In addition, we report that the presence of the chief executive officer (CEO) on the NC is found to interact with the NC independence, as a result of which a board demographic faultline is likely to emerge.

Theoretical/Academic Implications: We bring together three concepts from social psychology research to create the theoretical basis for our study of the influence of NCs on board diversity: these are similarity‐attraction, homosocial reproduction, and social identity. The strong empirical findings suggest that these socio‐psychological dimensions are applicable to the operations of NCs, which has implications for the outcomes of the director nomination and selection process, and consequently also for board composition.

Practitioner/Policy Implications: Our research indicates that NC characteristics are significant antecedents of board diversity, hence composition of the NC is an important step and pre‐requisite for assembling a diverse board. For example, appointing females and/or non‐nationals to the NC increases the likelihood of greater representation of females and/or non‐nationals on the entire board. At the same time, our evidence suggests that the presence of the CEO amidst the majority of non‐executive directors (NEDs) on the NC is detrimental for board cohesiveness.
Intelligent tutoring systems: An overview
Authors: YAZDANI MASOUD
Published: May 2012

Abstract: In this paper we look at the evolutionary development of Computer Assisted Instruction from the early days of ‘linear programs’ up to the use of ‘expert systems’ in education and training. We present the basic principles of Intelligent Tutoring Systems (ITS) which are capable of rich interaction with the student, which know how to teach, and who and what they are teaching. We point out the need for knowledge representation formalisms which can support ITS and present one such formalism (production systems). In the framework presented we describe systems developed for the teaching of modern languages, electronic trouble shooting and computer programming. Finally we point out the shortcomings of ITS and identify areas where a consensus of opinion does not exist.
Fertility, Female Labor Supply, and Family Policy‡
Authors: Fehr Hans , Ujhelyiova Daniela
Published: May 2012

The present paper develops an overlapping generations general equilibrium model for Germany in order to study the impact of public policy on household labor supply and fertility decisions. Starting from a benchmark equilibrium which reflects the current German family policy regime we introduce various reforms of the tax and child benefit system and quantify the consequences for birth rates and female labor supply. Our simulations indicate three central results: First, higher transfers to families (either direct, in-kind or via family splitting) may increase birth rates significantly, but they may come at the cost of lower female employment. Second, the introduction of individual taxation (instead of joint taxation of couples) would increase female employment but might further reduce current birth rates in Germany. Third, it is possible to increase birth rates and female employment rates simultaneously if the government invests in child care facilities for children of all ages.
Predation of Atlantic Petrel chicks by house mice on Gough Island
Authors: Wanless R. M. , Ratcliffe N. , Angel A. , Bowie B. C. , Cita K. , Hilton G. M. , Kritzinger P. , Ryan P. G. , Slabber M.
Published: May 2012

The impacts of predation by invasive mammals on island fauna are a major driver of insular biodiversity loss. Devastating, hitherto unsuspected impacts of predatory house mice on breeding seabirds have been described recently. We studied the fate of 178 Atlantic Petrel Pterodroma incerta nests at Gough Island, over four seasons, from October 2003 to January 2008. Introduced house mice Mus musculus were found in all study burrows checked for mouse visits. From October 2003 to September 2004, we video‐recorded attacks by mice on six (of 13) live, healthy Atlantic Petrel chicks and on one (of three) great shearwater Puffinus gravis chicks. In all years, chicks died from mouse attacks. Stage‐specific daily nest survival rates were modelled, from which estimates of breeding success were derived that accounted for the variable exposure periods studied among years. Average daily survival rate of eggs was 0.998, and hatching success through the entire incubation period (55.5 days) was 0.924 [95% confidence interval (CI) 0.903–0.940]. Daily chick survival rates were 0.990, which gave a modelled fledging success of 0.247 (CI 0.165–0.338) over the 138‐day chick period, and average annual breeding success (chicks fledged per breeding attempt) of 0.228 (CI 0.150–0.318), which is low compared with congeners. Productivity estimates were used as a parameter in a population simulation model, which predicted a population multiplication rate (λ) of 0.993 (CI = 0.966–1.021). However, in the one season studied from laying to fledging (2007), from 58 nests, only one chick fledged (1.7%). This suggests the wide errors on the model results may obscure a more severe reality. More than 60% of model simulations resulted in an International Union for Conservation of Nature classification of Endangered. Our results add support to calls to eradicate mice from Gough Island. More generally, mice cannot be ignored as a potential threat to island fauna, and island restoration and management plans should routinely include eradication of introduced mice.
On the function of placental corticotropin‐releasing hormone: a role in maternal‐fetal conflicts over blood glucose concentrations
Authors: Gangestad Steven W. , Caldwell Hooper Ann E. , Eaton Melissa A.
Published: May 2012

Throughout the second and third trimesters, the human placenta (and the placenta in other anthropoid primates) produces substantial quantities of corticotropin‐releasing hormone (placental CRH), most of which is secreted into the maternal bloodstream. During pregnancy, CRH concentrations rise over 1000‐fold. The advantages that led selection to favour placental CRH production and secretion are not yet fully understood. Placental CRH stimulates the production of maternal adrenocorticotropin hormone (ACTH) and cortisol, leading to substantial increases in maternal serum cortisol levels during the third trimester. These effects are puzzling in light of widespread theory that cortisol has harmful effects on the fetus. The maternal hypothalamic‐pituitary‐adrenal (HPA) axis becomes less sensitive to cortisol during pregnancy, purportedly to protect the fetus from cortisol exposure. Researchers, then, have often looked for beneficial effects of placental CRH that involve receptors outside the HPA system, such as the uterine myometrium (e.g. the placental clock hypothesis). An alternative view is proposed here: the beneficial effect of placental CRH to the fetus lies in the fact that it does stimulate the production of cortisol, which, in turn, leads to greater concentrations of glucose in the maternal bloodstream available for fetal consumption. In this view, maternal HPA insensitivity to placental CRH likely reflects counter‐adaptation, as the optimal rate of cortisol production for the fetus exceeds that for the mother. Evidence pertaining to this proposal is reviewed.