Ecological drivers of flower-leaf sequences: aridity and proxies for pollinator attraction select for flowering-first in the American plums.

Across temperate forests, many tree species produce flowers before their leaves emerge. This flower-leaf phenological sequence, known as hysteranthy, is generally described as an adaptation for wind pollination. However, this explanation does not address why hysteranthy is also common in biotically pollinated taxa. We quantified flower-leaf sequence variation in the American plums (Prunus, subg. Prunus sect. Prunocerasus), a clade of insect-pollinated trees, using herbaria specimens and Bayesian hierarchical modeling. We tested two common, but rarely interrogated hypotheses - that hysteranthy confers aridity tolerance and/or pollinator visibility - by modeling the associations between hysteranthy and related traits. To understand how these phenology-trait associations were sensitive to taxonomic scale and flower-leaf sequence classification, we then extended these analyses to all Prunus species in North America. Our findings across two taxonomic levels support the hypotheses that hysteranthy may help temporally partition hydraulic demand to reduce water stress and increase pollinator visibility - thereby reducing selective pressure on inflorescence size. Our results provide foundational insights into the evolution of flower-leaf sequences in the genus Prunus, with implications for understanding these patterns in biotically pollinated plants in general. Our approach suggests a path to advance these hypotheses to other clades, but teasing out drivers fully will require new experiments.

The bigger picture: young children's perception of fatness in the context of other physical differences.

BACKGROUND: Negative obesity stereotypes and anti-fat attitudes have been observed in children from age three. It is uncertain whether this is specific to fatness or generalizable to other visible differences. OBJECTIVES: To determine whether young children base decisions about qualities in others and friendship choices more on fatness than other visible differences between people. METHODS: Using a personal construct theory approach, 85 children (mean age 5.7, 42 girls) completed a simple repertory grid. The children were asked about differences (constructs) between four illustrations (elements) that showed children as healthy weight, fat, the opposite gender and in a wheelchair. Children were also asked about friendship with the illustrated children and self-image preferences. Their answers were grouped using thematic analysis. RESULTS: The fat, opposite gender and wheelchair-bound characters were equally chosen by children as different to the standard character. When identifying differences, fatness or body shape was referred to significantly less than gender or being in a wheelchair. Children were more likely to reject an opposite gender character as a friend, or as someone they would like to be, than to reject the fat character. Only one child, themselves overweight, voiced strong anti-fat attitudes. CONCLUSIONS: Apparent negativity towards fatness is fostered by failure to consider other visible differences and by children's 'like me' peer preferences. It was less desirable in the eyes of most 5-year old girls to be a boy than to be fat. This offers some reassurance to those working to improve children's health literacy in obesity.

Experiences of mental health nursing staff working with voice hearers in an acute setting: An interpretive phenomenological approach.

WHAT IS KNOWN ON THE SUBJECT?: Community mental health staff and their service users have reported mixed views on the importance of talking about the content of voices. Community staff have reported feeling that they do not have the skills to explore voice content and worry about making things worse. Voice hearers experiencing extreme distress due to the content of their voices can access support through acute inpatient mental health services. No previous studies have focused on the experiences of staff who nurse voice hearers at a time of acute distress. WHAT DOES THIS STUDY ADD TO EXISTING KNOWLEDGE?: MHNs and HSWs working with voice hearers in acute distress report feeling powerless and helpless, as they feel that they cannot lessen the distress experienced by the voice hearer. Despite these difficult feelings, staff report finding ways of coping, including using structured tools to help make sense of their service users' voice-hearing experiences and accessing reflective practice forums. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Due to the current context of increased acuity and limited resources in acute services, there may be a need to further protect time for staff to access reflective practice groups and supervision forums to help them manage the difficult feelings arising from their work with voice hearers. ABSTRACT: Introduction Mental health nursing (MHN) staff in acute settings work with voice hearers at times of crises when they experience high levels of distress. Previous research has focused on community mental health staff's experiences and their service users views on exploring the content of voices. No studies have explored this from an acute mental health service perspective. Aim This study therefore sought to explore the experiences of staff working with voice hearers in an acute mental health service. Method Due to the exploratory nature of the research, a qualitative design was chosen. Three MHNs and five healthcare support workers (HSWs) were interviewed. The data were analysed using Interpretative Phenomenological Analysis. Results A group analysis elicited three master themes: "It's quite scary really, not unlike a horror movie;" "I can only influence what's in front of me;" and "Just chipping away". Discussion Staff working with voice hearers in acute settings experience feelings of powerlessness and helplessness, as they feel unable to reduce the distress experienced by voice hearers in their care. Staff employ coping strategies to help manage these difficult feelings, including using structured tools in their work with voice hearers and attending reflective practice forums. Implications for Practice Acute mental health services may need to protect time for staff to access regular reflective practice and other supervision forums to help manage their feelings of powerlessness and helplessness arising from their work with voice hearers.

'Thin people they're healthy': young children's understanding of body weight change.

BACKGROUND: While research has investigated negative stereotyping of fat body shapes, little has focused on young children's understanding of the mechanisms, motivations and consequences of weight change. OBJECTIVES: To investigate children's understanding of how weight change is achieved, people's motivation for weight change, and the consequences of weight loss or weight gain. METHODS: One hundred children (mean age 5.2, 38 girls) read a book in which one of the main characters (male/female according to the child's sex) was either healthy weight or overweight. Afterwards, this character was described as gaining or losing weight, and drawings which depicted the child in the story as either healthy weight or overweight were presented to the child and discussed. An audio-recorded semi-structured interview followed and transcripts were analysed using thematic analysis. RESULTS: Nearly all children described the weight/shape change and attributed this to food more frequently than exercise. Weight loss was viewed positively and both motivations and consequences grouped under two master themes (physical and social reasons). No clear gender differences were observed in these responses. CONCLUSIONS: Talking with 5-year-olds showed them to be observant and knowledgeable, especially about motivations for and consequences of weight change. For those working to improve children's health literacy, this suggests receptiveness to early and fact-based education.

Multivesicular exocytosis in rat pancreatic beta cells.

AIMS/HYPOTHESIS: To establish the occurrence, modulation and functional significance of compound exocytosis in insulin-secreting beta cells. METHODS: Exocytosis was monitored in rat beta cells by electrophysiological, biochemical and optical methods. The functional assays were complemented by three-dimensional reconstruction of confocal imaging, transmission and block face scanning electron microscopy to obtain ultrastructural evidence of compound exocytosis. RESULTS: Compound exocytosis contributed marginally (<5% of events) to exocytosis elicited by glucose/membrane depolarisation alone. However, in beta cells stimulated by a combination of glucose and the muscarinic agonist carbachol, 15-20% of the release events were due to multivesicular exocytosis, but the frequency of exocytosis was not affected. The optical measurements suggest that carbachol should stimulate insulin secretion by ∼40%, similar to the observed enhancement of glucose-induced insulin secretion. The effects of carbachol were mimicked by elevating [Ca(2+)](i) from 0.2 to 2 µmol/l Ca(2+). Two-photon sulforhodamine imaging revealed exocytotic events about fivefold larger than single vesicles and that these structures, once formed, could persist for tens of seconds. Cells exposed to carbachol for 30 s contained long (1-2 µm) serpentine-like membrane structures adjacent to the plasma membrane. Three-dimensional electron microscopy confirmed the existence of fused multigranular aggregates within the beta cell, the frequency of which increased about fourfold in response to stimulation with carbachol. CONCLUSIONS/INTERPRETATION: Although contributing marginally to glucose-induced insulin secretion, compound exocytosis becomes quantitatively significant under conditions associated with global elevation of cytoplasmic calcium. These findings suggest that compound exocytosis is a major contributor to the augmentation of glucose-induced insulin secretion by muscarinic receptor activation.

Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.

AIMS/HYPOTHESIS: Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected. METHODS: Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy. RESULTS: Culture at 15 mmol/l glucose increased islet glucagon content by approximately 50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by approximately 50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in <10% of non-beta cells but in >80% of the beta cells. CONCLUSIONS/INTERPRETATION: Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.

Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations.

AIMS/HYPOTHESIS: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. Several reports suggest that genetic variants in the adiponectin gene are associated with circulating levels of adiponectin, insulin sensitivity and type 2 diabetes risk. Recently two receptors for adiponectin have been cloned. Genetic studies have yielded conflicting results on the role of these genes and type 2 diabetes predisposition. In this study we aimed to evaluate the potential role of genetic variation in these genes in syndromes of severe insulin resistance, type 2 diabetes and in related metabolic traits in UK Europid populations. MATERIALS AND METHODS: Exons and splice junctions of the adiponectin receptor 1 and 2 genes (ADIPOR1; ADIPOR2) were sequenced in patients from our severe insulin resistance cohort (n=129). Subsequently, 24 polymorphisms were tested for association with type 2 diabetes in population-based type 2 diabetes case-control studies (n=2,127) and with quantitative traits in a population-based longitudinal study (n=1,721). RESULTS: No missense or nonsense mutations in ADIPOR1 and ADIPOR2 were detected in the cohort of patients with severe insulin resistance. None of the 24 polymorphisms (allele frequency 2.3-48.3%) tested was associated with type 2 diabetes in the case-control study. Similarly, none of the polymorphisms was associated with fasting plasma insulin, fasting and 2-h post-load plasma glucose, 30-min insulin increment or BMI. CONCLUSIONS/INTERPRETATION: Genetic variation in ADIPOR1 and ADIPOR2 is not a major cause of extreme insulin resistance in humans, nor does it contribute in a significant manner to type 2 diabetes risk and related traits in UK Europid populations.

Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8.

AIMS/HYPOTHESIS: Genetic investigations in the spontaneously diabetic (Type 2) Goto Kakizaki (GK) rat have identified quantitative trait loci (QTL) for diabetes-related phenotypes. The aims of this study were to refine the chromosomal mapping of a QTL ( Nidd/gk5) identified in chromosome 8 of the GK rat and to define a pathophysiological profile of GK gene variants underlying the QTL effects in congenics. METHODS: Genetic linkage analysis was carried out with chromosome 8 markers genotyped in a GKxBN F2 intercross previously used to map diabetes QTL. Two congenic strains were designed to contain GK haplotypes in the region of Nidd/gk5 transferred onto a Brown Norway (BN) genetic background, and a broad spectrum of diabetes phenotypes were characterised in the animals. RESULTS: Results from QTL mapping suggest that variations in glucose-stimulated insulin secretion in vivo, and in body weight are controlled by different chromosome 8 loci (LOD3.53; p=0.0004 and LOD4.19; p=0.00007, respectively). Extensive physiological screening in male and female congenics at 12 and 24 weeks revealed the existence of GK variants at the locus Nidd/gk5, independently responsible for significantly enhanced insulin secretion and increased levels of plasma triglycerides, phospholipids and HDL, LDL and total cholesterol. Sequence polymorphisms detected between the BN and GK strains in genes encoding ApoAI, AIV, CIII and Lipc do not account for these effects. CONCLUSIONS/INTERPRETATION: We refined the localisation of the QTL Nidd/gk5 and its pathophysiological characteristics in congenic strains derived for the locus. These congenic strains provide novel models for testing the contribution of a subset of GK alleles on diabetes phenotypes and for identifying diabetes susceptibility genes.

Homocysteine potentiates beta-amyloid neurotoxicity: role of oxidative stress.

The cause of neuronal degeneration in Alzheimer's disease (AD) has not been completely clarified, but has been variously attributed to increases in cytosolic calcium and increased generation of reactive oxygen species (ROS). The beta-amyloid fragment (Abeta) of the amyloid precursor protein induces calcium influx, ROS and apoptosis. Homocysteine (HC), a neurotoxic amino acid that accumulates in neurological disorders including AD, also induces calcium influx and oxidative stress, which has been shown to enhance neuronal excitotoxicity, leading to apoptosis. We examined the possibility that HC may augment Abeta neurotoxicity. HC potentiated the Abeta-induced increase in cytosolic calcium and apoptosis in differentiated SH-SY-5Y human neuroblastoma cells. The antioxidant vitamin E and the glutathione precursor N-acetyl-L-cysteine blocked apoptosis following cotreatment with HC and Abeta, indicating that apoptosis is associated with oxidative stress. These findings underscore that moderate accumulation of excitotoxins at concentrations that alone do not appear to initiate adverse events may enhance the effects of other factors known to cause neurodegeneration such as Abeta.

A high-resolution consensus linkage map of the rat, integrating radiation hybrid and genetic maps.

We have constructed a high-resolution consensus genetic map of the rat in a single large intercross, which integrates 747 framework markers and 687 positions of our whole-genome radiation hybrid (RH) map of the rat. We selected 136 new gene markers from the GenBank database and assigned them either genetically or physically to rat chromosomes to evaluate the accuracy of the integrated linkage-RH maps in the localization of new markers and to enrich existing comparative mapping data. These markers and 631 D-Got- markers, which are physically mapped but still uncharacterized for evidence of polymorphism, were tested for allele variations in a panel of 16 rat strains commonly used in genetic studies. The consensus linkage map constructed in the GK x BN cross now comprises 1620 markers of various origins, defining 840 resolved genetic positions with an average spacing of 2.2 cM between adjacent loci, and includes 407 gene markers. This whole-genome genetic map will contribute to the advancement of genetic studies in the rat by incorporating gene/EST maps, physical mapping information, and sequence data generated in rat and other mammalian species into genetic intervals harboring disease susceptibility loci identified in rat models of human genetic disorders.

Detailed comparative gene map of rat chromosome 1 with mouse and human genomes and physical mapping of an evolutionary chromosomal breakpoint.

We report the localization of 92 new gene-based markers assigned to rat chromosome 1 by linkage or radiation hybrid mapping. The markers were chosen to enrich gene mapping data in a region of the rat chromosome known to contain several of the principal quantitative trait loci in rodent models of human multifactorial disease. The composite map reported here provides map information on a total of 139 known genes, including 80 that have been localized in mouse and 109 that have been localized in human, and integrates the gene-based markers with anonymous microsatellites. The evolutionary breakpoints identifying 16 segments that are homologous regions in the human genome are defined. These data will facilitate genetic and comparative mapping studies and identification of novel candidate genes for the quantitative trait loci that have been localized to the region.

Voltage-gated potassium channels and the control of membrane potential in human platelets.

1. Human platelets were studied using a combination of patch-clamp and fluorescent indicators of membrane potential and [Ca2+]i. 2. Whole-cell and cell-attached patch recordings showed voltage-gated channels selective for K+ (IK(V]. These channels were activated by depolarization at a threshold close to the platelet resting potential and were blocked by the venom charybdotoxin (CTX; 10-20 nM). Several different conductance states were observed, ranging from 5 to 34 pS, with isotonic KCl in the patch pipette and bath. 3. Measurements with the potential-sensitive dye 3,3'-dipropylthia-dicarbocyanine, diS-C3-(5), in platelet suspensions showed that CTX depolarized the resting potential by approximately 25 mV. Thus, CTX-sensitive, voltage-gated K+ channels appear to play a major part in setting the resting potential. 4. ADP-evoked Ca2+ influx, monitored with Fura-2, was reduced by 10 nM-CTX. Restoration of a large negative membrane potential with valinomycin reversed this effect of CTX. These results suggest that the Ca2+ influx depends on the negative membrane potential and that K+ channels may be important in maintaining this potential during activation.

School catering: the place for change.

The 1944 Education Act marked the foundation of the modern School Catering Service. A statutory duty is imposed on Local Education Authorities (LEAs) to provide a 'mid-day dinner...suitable in all respects as the main meal of the day'. LEAs are free to provide meals consistent with broad nutritional guidelines of the Department of Education and Science but financial pressures have a large bearing on this. The traditional 2-course meal is still the norm, although there is a multi-choice menu for the majority of secondary schoolchildren. But a wide choice of food is incompatible with closely prescribed nutritional standards and pupils need to be aware of the implications for their health in the choice of food. The adoption of dietary recommendations for prevention of coronary heart disease would not generate serious practical difficulties for the professional caterer. The technical problems arising from minor adaptations in catering practice would be minimal in comparison to those of cost, education and hence modification of consumer demand. The move away from nutritional standards is likely to accelerate if, owing to financial constraints, the Government withdraws nutritional guidelines or removes the obligation on LEAs to provide a catering service. The danger is that financial considerations will override those of nutrition and a unique opportunity for health education by guidance and example in the schools may be lost.