Supplementing honey bee (Hymenoptera: Apidae) colonies with pollen increases their pollinating activity on nectariferous crops with anthers isolated from stigmas.

The western honey bee (Apis mellifera L.) is the most globally used managed pollinator species, but it can have limited pollinating activity on nectariferous crops displaying anthers isolated from stigmas, i.e., when anthers are spatially or temporally separated from stigma within or between flowers. We supplemented honey bee colonies with pollen in the combs or in paste form laid on top of the hive frames to test if these treatments could reduce their pollen foraging and increase their pollinating activity in a monoecious and nectariferous cultivar of cantaloupe melon (Cucumis melo L.), in comparison with control colonies not supplemented. We recorded the pollen forager density per flower, the number of pollen grains deposited per stigma and their resulting fruit set, seed set and fruit mass, before and after the colony pollen supplementations. The number of pollen grains deposited by honey bees on stigmas increased gradually after pollen supplementation in the combs. But pollen foraging decreased only moderately, and no effect could be observed on any yield component except the seed set. On the other hand, there was no effect of the pollen paste laid on top of the frames either on stigmatic pollen loads, on colony pollen foraging or on any yield component. Supplementing honey bee colonies with pollen in the combs can therefore be an effective means for increasing their pollinating activity in nectariferous crops displaying anthers isolated from stigmas, e.g., Amaryllidaceae, Apiaceae, Cucurbitaceae, avocado, all hybrid seed productions. The context for the potential use of pollen substitutes is discussed.

Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss.

SMARCA4 (BRG1) and SMARCA2 (BRM) are the two paralogous ATPases of the SWI/SNF chromatin remodeling complexes frequently inactivated in cancers. Cells deficient in either ATPase have been shown to depend on the remaining counterpart for survival. Contrary to this paralog synthetic lethality, concomitant loss of SMARCA4/2 occurs in a subset of cancers associated with very poor outcomes. Here, we uncover that SMARCA4/2-loss represses expression of the glucose transporter GLUT1, causing reduced glucose uptake and glycolysis accompanied with increased dependency on oxidative phosphorylation (OXPHOS); adapting to this, these SMARCA4/2-deficient cells rely on elevated SLC38A2, an amino acid transporter, to increase glutamine import for fueling OXPHOS. Consequently, SMARCA4/2-deficient cells and tumors are highly sensitive to inhibitors targeting OXPHOS or glutamine metabolism. Furthermore, supplementation of alanine, also imported by SLC38A2, restricts glutamine uptake through competition and selectively induces death in SMARCA4/2-deficient cancer cells. At a clinically relevant dose, alanine supplementation synergizes with OXPHOS inhibition or conventional chemotherapy eliciting marked antitumor activity in patient-derived xenografts. Our findings reveal multiple druggable vulnerabilities of SMARCA4/2-loss exploiting a GLUT1/SLC38A2-mediated metabolic shift. Particularly, unlike dietary deprivation approaches, alanine supplementation can be readily applied to current regimens for better treatment of these aggressive cancers.

The collaborative development through multidisciplinary and advocate consensus of an accessible notice of rights for people with intellectual disabilities in police custody.

Background People with intellectual disabilities are over-represented in the criminal justice system. The United Nations' Convention on the Rights of Persons with Disabilities (UNCRPD) enshrines a right to equal access to justice for persons with disabilities (Article 13, UNCRPD). Accessible information is a key aspect of exercising this right. Yet, many jurisdictions, including Ireland, are yet to develop accessible information for disabled people who may be arrested. Aims This paper describes the collaborative development through multidisciplinary and advocate consensus of an accessible (Easy -to- Read) Notice of Rights (ERNR) for people with intellectual disabilities in police custody in Ireland. Methods Guidelines developed by Ireland's representative organisation for people with intellectual disabilities and examples of international practice were used to develop a draft ERNR by the primary researcher in partnership with an expert from a representative organisation for people with intellectual disabilities. The ERNR was developed thereafter through two focus groups with a view to achieving consensus with a focus on accessibility, accuracy and layout. This included a multidisciplinary focus group with participants from a representative organisation for people with intellectual disabilities, psychology, speech and language therapy, the police force, public health, forensic psychiatry, mental health, law and, subsequently, a focus group of people with lived experience of intellectual disability. Results Progressive development of the ERNR resulted in incremental improvements in textual accuracy as well as the inclusion of more accessible language and imagery. Originality/value This is the first attempt at developing an easy-to-read document relating to the legal rights of suspects in police custody in Ireland and, accordingly, this procedural innovation promises to assist, not just persons with intellectual disabilities, but also those with limited literacy at the point of arrest. The methodology used in the preparation of the document, employing a focus group to achieve consensus with participation from both multiple disciplines and persons with an intellectual disability, is in harmony with the ethos of the UNCPRD. This methodology may usefully be employed by other member states that have ratified the Convention but have yet to develop accessible version of the legal rights and entitlements that extend to arrested persons under their domestic law.

Impact of the type of dialysis membranes on the circulating concentration of markers of vitamin D metabolism.

INTRODUCTION: Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend vitamin D supplementation in hemodialyzed patients to monitor 25(OH)-vitamin D 25(OH)D levels. However, patient-to-patient inconsistency can be observed in response to the treatment. In this study, we aimed to evaluate the impact of the dialysis membrane on 25(OH)D, albumin (Alb) and vitamin D-binding protein (VDBP), the major players of vitamin D transport and storage. MATERIAL AND METHODS: Alb (Cobas), VDBP (R&D) and 25(OH)D (liquid chromatography-tandem mass spectrometry) were measured in 75 patients before and after a 4-hour dialysis session. Ten dialysis membranes were used: FX10, FX80, FX800, BK-2.1F, BG-2.1U, Rexeed 15 A, Rexeed 21 A, TS 1.8 SL and TS 2.1 SL manque la ELISIO 21H. Accordingly, 13 patients were dialyzed with membranes possessing high adsorption and high cut-off properties (BK), 17 with membranes possessing high adsorption but usual cut-off properties (BG) and all the remaining 45 patients with polysufone (PS) membranes with usual adsorptive and cut-off properties. Among these 45 patients treated with PS, we compared those treated by classical dialysis (HD) (n = 14) and hemodiafiltration (HDF) (n = 31). Results were corrected for total extracellular volume to take into consideration the hemoconcentration after dialysis. RESULTS: The 3 analytes showed a decreased concentration after the dialysis session. The decrease of ALB, VDBP and 25(OH)D was similar with the adsorptive (BG) and PS membranes. However, patients treated with adsorptive and high cut-off membrane (BK) presented a significantly higher decrease values of Alb (-9.6%[-15.1; -7.5]), of VDBP (-20.6%[-36.6; -17.2] and 25(OH)D (-17%[-27.3; -12.3]) compared to other membranes (BG and PS).When we limited our study to PS membranes, we did not observe any significant difference between the HD or HDF modalities in the decrease for any of the studied parameters. CONCLUSIONS: A significant loss of Alb, VDBP and 25(OH)D occurs after a dialysis session. This loss is significantly more important when patients are dialyzed with high adsorption and high cut-off dialysis membranes.

Strong antineoplastic effects of metformin in preclinical models of liver carcinogenesis.

Studies suggest that metformin, widely used for treating Type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma (HCC), metformin may provide antitumoral effects. We evaluated the impact of metformin on tumour growth and visceral fat composition using relevant preclinical models of metabolic syndrome. Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow (SC) diet, 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured HCC slices. Visceral fatty acid composition was analysed by magnetic resonance imaging (MRI). Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways. Tumour engraftment rates were higher in HFD mice than SC mice (hepatic: 79% compared with 25%, P=0.02) and FR mice (subcutaneous: 86% compared with 50%, P=0.04). Subcutaneous tumour volume was increased in HFD mice (+64% compared with FR and SC, P=0.03). Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis. In ex vivo tumour slices, metformin treatment led to increased necrosis, decreased cyclin D1 and increased carbonic anhydrase-9 (CA-9). Metformin caused qualitative changes in visceral fat composition of HFD mice, with decreased proportions of polyunsaturated fatty acids (14.6% ± 2.3% compared with 17.9% ± 3.0%, P=0.04). The potent antitumoral effects of metformin in multiple preclinical models implicating several molecular mechanisms provide a strong rationale for clinical trials including combination studies in HCC patients.

Variations in the Availability of Pollen Resources Affect Honey Bee Health.

Intensive agricultural systems often expose honey bees (Apis mellifera L.) to large temporal variations in the availability (quantity, quality and diversity) of nutritional resources. Such nutritional irregularity is expected to affect honey bee health. We therefore tested under laboratory conditions the effect of such variation in pollen availability on honey bee health (survival and nursing physiology-hypopharyngeal gland development and vitellogenin expression). We fed honey bees with different diets composed of pollen pellets collected by honey bees in an agricultural landscape of western France. Slight drops (5-10%) in the availability of oilseed rape (Brassica napus L.) pollen resulted in significant reductions of all tested variables. Despite some variations in taxonomic diversity and nutritional quality, the pollen mixes harvested over the season had a similar positive influence on honey bee health, except for the one collected in late July that induced poor survival and nursing physiology. This period coincided with the mass-flowering of maize (Zea mays L.), an anemophilous crop which produces poor-quality pollen. Therefore, changes in bee health were not connected to variations in pollen diversity but rather to variations in pollen depletion and quality, such as can be encountered in an intensive agricultural system of western France. Finally, even though pollen can be available ad libitum during the mass-flowering of some crops (e.g. maize), it can fail to provide bees with diet adequate for their development.

A comprehensive and comparative GC-MS metabolomics study of non-volatiles in Tanzanian grown mango, pineapple, jackfruit, baobab and tamarind fruits.

Tropical fruits contribute significantly to the total fruit intake worldwide. However, their metabolomes have not yet been investigated comprehensively, as most previous studies revealed only volatile and bulk compositions. This study compares non-volatile metabolites of five fruits grown in Tanzania. A new methodology is developed for broad-spectrum GC-MS metabolomics in fruits using a new derivatization and a two dimensional peak deconvolution techniques. A total of 92 peaks were detected from fruits of which 45 were identified. Jackfruits contained the highest amount of carbohydrates, while baobab contained the highest amount of fatty acids. The highest content of organic acids was detected in tamarind. Principal component analysis revealed insights into metabolic differences and similarities, while hierarchical cluster analysis correctly grouped the fruits according to their relationships in plants' phylogenetic tree. The developed methodology could potentially be applied in large-scale studies on fruit quality, authenticity/variety, optimization of post-harvest processing and storage.

Efficiency of delivery observed treatment in hemodialysis patients: the example of the native vitamin D therapy.

INTRODUCTION: Adherence to therapy is a relevant challenge in chronic hemodialysis patients. The directly observed therapy (DOT) could be an effective method to increase adherence for specific therapies. We aimed to study the performance of DOT versus home medication. We follow the impact of providing native vitamin D directly by the nurse after a dialysis session on the 25-hydroxyvitamin [25(OH)D] concentrations. METHODS: In this observational study, we included 38 dialysis patients treated by stable dosage of cholecalciferol. DOT was implemented in December 2010. We considered the concentrations of 25-OH vitamin D three times before (T1 = June 2010, T2 = July 2010 and T3 = September 2010) and three times after the modification of prescription (T4 = February 2011, T5 = March 2011 and T6 = April 2011). RESULTS: Median age was 72 [62; 79] years and 48 % were diabetics. Mean body mass index was 26 ± 5 kg/m(2) and median dialysis vintage was 20 [8; 46] months. The patients were compared to themselves. Before DOT, median concentrations of 25(OH)D were 27 (14-36), 23 (17-31), 31 (22-38) ng/mL at T1, T2 and T3, respectively. When DOT was effective, the concentrations significantly increased to 34 (28-44), 35 (29-41), 39 (32-47) ng/mL at T4, T5 and T6, respectively. Before DOT, 19 patients (50 %) reached the target of 30 ng/mL. After DOT, 29 patients (76 %) reached the target concentration of 30 ng/mL. CONCLUSIONS: In hemodialysis patients, DOT is both simple and effective to increase the therapeutic impact to native vitamin D.

Quantification of the triglyceride fatty acid composition with 3.0 T MRI.

The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was performed with a 3D spoiled gradient multiple echo sequence. A specific phase correction algorithm was implemented to correct the native phase images for wrap, zero- and first-order phase and rebuild the real part images. Then, using a model of a fat (1)H MR spectrum integrating nine components, the number of double bonds (ndb) and the number of methylene-interrupted double bonds (nmidb) were derived. The chain length (CL) was obtained from these parameters using heuristic approximation. Validations were performed on different vegetable oils whose theoretical fatty acid composition was used as reference and in five human subjects. In vivo measurements were made in the liver and in the subcutaneous and visceral adipose tissues. Linear regressions showed strong correlations between ndb and nmidb quantified with MRI and the theoretical values calculated using oil composition. Mean ndb/nmidb/CL were 1.80 ± 0.25/0.51 ± 0.21/17.43 ± 0.07, 2.72 ± 0.31/0.94 ± 0.16/17.47 ± 0.08 and 2.53 ± 0.21/0.84 ± 0.14/17.43 ± 0.07 in the liver, subcutaneous and visceral adipose tissues respectively. The results suggest that the triglyceride fatty acid composition can be assessed in human fatty liver and adipose tissues with a clinically relevant MRI method at 3.0 T.

Insect pollination enhances seed yield, quality, and market value in oilseed rape.

The relationships between landscape intensification, the abundance and diversity of pollinating insects, and their contributions to crop yield, quality, and market value are poorly studied, despite observed declines in wild and domesticated pollinators. Abundance and species richness of pollinating insects were estimated in ten fields of spring oilseed rape, Brassica napus var. SW Stratos™, located along a gradient of landscape compositions ranging from simple landscapes dominated by arable land to heterogeneous landscapes with extensive cover of semi-natural habitats. In each field, we assessed the contribution of wind and insect pollination to seed yield, seed quality (individual seed weight and oil and chlorophyll contents), and market value in a block experiment with four replicates and two treatments: (1) all flowers were accessible to insects, self and wind pollination, and (2) flowers enclosed in tulle net bags (mesh: 1 × 1 mm) were accessible only to wind and self pollination. Complex landscapes enhanced the overall abundance of wild insects as well as the abundance and species richness of hoverflies. This did not translate to a higher yield, probably due to consistent pollination by honey bees across all fields. However, the pollination experiment showed that insects increased seed weight per plant by 18% and market value by 20%. Seed quality was enhanced by insect pollination, rendering heavier seeds as well as higher oil and lower chlorophyll contents, clearly showing that insect pollination is required to reach high seed yield and quality in oilseed rape. Our study demonstrates considerable and previously underestimated contributions from pollinating insects to both the yield and the market value of oilseed rape.

Complementary and alternative medicine in the management of hypertension in an urban Nigerian community.

BACKGROUND: Hypertension is a common non communicable condition worldwide. In developing countries (including Nigeria), the use of complementary and alternative medicine (CAM) is common. This study investigated the frequency and factors associated with use of CAM among hypertensive subjects in an urban Nigerian community. Perspectives about the management of hypertension were obtained from CAM practitioners in the community. METHODS: Four hundred and forty hypertensive subjects in Idikan community, Ibadan, were interviewed using a semi-structured survey instrument. Association between categorical variables was tested using the chi-square test. Logistic regression analysis was done to identify independent predictor variables of CAM use, with CAM use as the outcome variable and the demographic and belief items as predictor variables. In-depth interviews were conducted with all known CAM practitioners in the community on issues relating to their beliefs, knowledge, practice and experiences in managing patients with hypertension in the community. RESULTS: In the study sample, 29% used CAM in the management of their hypertension. Among those using CAM, the most common forms used were herbs (63%) and garlic (21%). Logistic regression analysis revealed that four variables were independent predictors of CAM use: being male (OR 2.58, p < 0.0001), belief in supernatural causes of hypertension (OR 2.11, p = 0.012), lack of belief that hypertension is preventable (OR 0.57, p = 0.014) and having a family history of hypertension (OR1.78, p = 0.042). Other factors such as age, educational level and occupation were not independent predictors of CAM use. Interviews with CAM practitioners revealed that they believed hypertension was caused by evil forces, stress or "too much blood in the body". They also thought they could cure hypertension but that reduced costs (compared to hospitals) was one of the reasons most of their clients consult them. CONCLUSIONS: The use of CAM is common among hypertensive subjects in this urban Nigerian community. Men were more than twice as likely to use CAM and belief in supernatural causes of hypertension was the most notable belief predicting CAM use. Interviews with CAM practitioners yielded useful perspectives about the role they play in hypertension management in the community. This study adds to the small but growing literature about the use of CAM in hypertension in sub Saharan Africa. Further studies in hypertension and other non communicable disease are needed.

Early detection of steatohepatitis in fatty rat liver by using MR elastography.

PURPOSE: To assess the potential value of magnetic resonance (MR) elastographic imaging to help detect nonalcoholic steatohepatitis in the fatty rat liver. MATERIALS AND METHODS: This study was approved by the regional ethics committee. Fifty-four rats were imaged after being fed either a standard diet, a choline-deficient diet for up to 8 weeks to induce steatohepatitis, or a 2-week orotic acid diet to induce steatosis; or were imaged 48 hours after carbon tetrachloride injection to model acute liver injury. MR elastography was performed at 7.0 T to assess viscoelastic liver parameters. Steatosis and fibrosis were quantified with morphometric and biochemical analysis. Myofibroblast activation was assessed with morphometric analysis of alpha-smooth muscle actin. Expression of transforming growth factor beta1 and procollagens 1 and 3 as markers of fibrogenesis was evaluated with real-time reverse transcription polymerase chain reaction. Inflammation was scored at histologic analysis. RESULTS: In rats with steatohepatitis, mean elasticity (2.24 kPa +/- 0.19 [standard deviation] vs 1.82 kPa +/- 0.22) and mean viscosity (0.86 kPa +/- 0.10 vs 0.59 kPa +/- 0.12) increased significantly (P < .005) after the 2-week orotic acid diet, while steatosis, inflammation, myofibroblast activation, and increase of other fibrogenesis markers were observed. Fibrosis appeared only after 5 weeks. In rats with steatosis, viscosity increased (0.77 kPa +/- 0.11, P < .005), elasticity remained constant. In rats with acute liver injury, elasticity (2.96 kPa +/- 0.63) and viscosity (0.85 kPa +/- 0.22) increased (P < .005), while fibrogenesis and inflammation were observed without substantial fibrosis or steatosis. At multivariate analysis in all rats, liver elasticity correlated only with myofibroblast activation (P < .001, r > 0.6). CONCLUSION: The results suggest that in nonalcoholic fatty rat liver, MR elastography may be useful in the early detection of steatohepatitis by showing increased elasticity and appearing before fibrosis development, which was linked to myofibroblast activation. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2523081817/-/DC1.

Importance of pollinators in changing landscapes for world crops.

The extent of our reliance on animal pollination for world crop production for human food has not previously been evaluated and the previous estimates for countries or continents have seldom used primary data. In this review, we expand the previous estimates using novel primary data from 200 countries and found that fruit, vegetable or seed production from 87 of the leading global food crops is dependent upon animal pollination, while 28 crops do not rely upon animal pollination. However, global production volumes give a contrasting perspective, since 60% of global production comes from crops that do not depend on animal pollination, 35% from crops that depend on pollinators, and 5% are unevaluated. Using all crops traded on the world market and setting aside crops that are solely passively self-pollinated, wind-pollinated or parthenocarpic, we then evaluated the level of dependence on animal-mediated pollination for crops that are directly consumed by humans. We found that pollinators are essential for 13 crops, production is highly pollinator dependent for 30, moderately for 27, slightly for 21, unimportant for 7, and is of unknown significance for the remaining 9. We further evaluated whether local and landscape-wide management for natural pollination services could help to sustain crop diversity and production. Case studies for nine crops on four continents revealed that agricultural intensification jeopardizes wild bee communities and their stabilizing effect on pollination services at the landscape scale.

131I-Labelled-iodized oil for palliative treatment of hepatocellular carcinoma.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is growing in western countries. Poor liver status and tumour size make curative options scarce. Palliative treatments such as chemo-embolization are improving survival in selected patients, but side-effects are frequent. There is a need for the validation of alternative treatments. Metabolic radiotherapy using lipiodol labelled with 131I-iodine (I-131-lipiodol) is one of these treatments. OBJECTIVES: To analyse the effect of I-131-lipiodol in a population of advanced HCC patients and to define the potential prognostic factors in this setting. METHODS: A retrospective analysis of the effect of I-131-lipiodol on 29 patients bearing multifocal tumours was performed. An analysis of two subgroups, defined by a Cancer of the Liver Italian Program (CLIP) score of 2 or less (n=20) or greater than 2 (n=9) was performed to assess the prognostic significance of the score in this setting. RESULTS: Overall median survival in the entire study population was 203 days (95% confidence interval 83-322 days). Median survival was significantly better in the group with CLIP scores of 2 or less than in the group with CLIP scores greater than 2 (453 versus 60 days, P< or =0.001). Treatment-related mortality was 6.9% (one interstitial pneumonia and one acute liver failure). CONCLUSION: The survival of patients treated with I-131-lipiodol in this series compared favourably with published data. Stratification according to the CLIP score was useful to predict survival. In particular, patients with portal vein thrombosis should only be considered for I-131-lipiodol if the CLIP score is lower than 2.

ATP-sensitive potassium channels induced in liver cells after transfection with insulin cDNA and the GLUT 2 transporter regulate glucose-stimulated insulin secretion.

As part of our research into the liver-directed gene therapy of Type I diabetes, we have engineered a human hepatoma cell line (HEPG2ins/g cells) to store and secrete insulin to a glucose stimulus. The aim of the present study was to determine whether HEPG2ins/g cells respond to glucose via signaling pathways that depend on ATP-sensitive potassium channels (KATP). Using patch-clamp electrophysiology with symmetrical KCl solutions, the single-channel conductance of KATP was 61pS. KATP was inhibited by ATP (1 mM) or cAMP (50 microM) applied to the cytosolic side of the membrane. Single KATP channels and macroscopic whole-cell currents were inhibited by glucose (20 mM) and glibenclamide (20 microM) and were activated by diazoxide (150 microM). Immunoprecipitation and Western blot analysis confirmed the presence of Kir6.2 KATP channel subunit protein in HEPG2ins/g and HEPG2ins cells. Using radioimmunoassay techniques, we report that exposure of the cells to tolbutamide (100 microM) resulted in an increase in insulin secretion from 0.3 +/- 0.05 to 1.8 +/- 0.2 pmol insulin/10(6) cells and glibenclamide (20 microM) from 0.4 +/- 0.06 to 2.1 +/- 0.3 (n=4), similar to what is seen on glucose (20 mM) stimulation. Diazoxide (150 microM) completely inhibited glucose-stimulated insulin release. Glucose 20 mM and glibenclamide 100 microM increased intracellular Ca2+ level in the HEPG2ins/g cells. However, glucose 20 mM did not stimulate a rise in intracellular Ca2+ in the un-transfected parent cell-line HEPG2. We used confocal microscopy to confirm that glucose (20 mM) stimulated the release of insulin from the fluorescently labeled secretion granules in the cells. Furthermore, glibenclamide (20 microM) also stimulated the release of insulin from fluorescently labeled secretion granules, and diazoxide (150 microM) blocked that stimulated release of insulin. Our results suggest that HEPG2ins/g cells respond to glucose via signaling pathways that depend on KATP, similar to a normal pancreatic beta cell.