Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells.

SummaryIncreasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of “disallowed” genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans

The soil-dwelling earthworm Allolobophora chlorotica modifies its burrowing behaviour in response to carbendazim applications

Carbendazim-amended soil was placed above or below unamended soil. Control tests comprised two layers of unamended soil. Allolobophora chlorotica earthworms were added to either the upper or the unamended soil. After 72 h vertical distributions of earthworms were compared between control and carbendazim-amended experiments. Earthworm distributions in the carbendazim-amended test containers differed significantly from the ‘normal’ distribution observed in the control tests. In the majority of the experiments, earthworms significantly altered their burrowing behaviour to avoid carbendazim. However, when earthworms were added to an upper layer of carbendazim-amended soil they remained in this layer. This non-avoidance is attributed to (1) the earthworms’ inability to sense the lower layer of unamended soil and (2) the toxic effect of carbendazim inhibiting burrowing. Earthworms modified their burrowing behaviour in response to carbendazim in the soil. This may explain anomalous results observed in pesticide field trials when carbendazim is used as a control substance

A Physical Interpretation of Stagnation Pressure and Enthalpy Changes in Unsteady Flow

This paper provides a physical interpretation of the mechanism of stagnation enthalpy and stagnation pressure changes in turbomachines due to unsteady flow, the agency for all work transfer between a turbomachine and an inviscid fluid. Examples are first given to illustrate the direct link between the time variation of static pressure seen by a given fluid particle and the rate of change of stagnation enthalpy for that particle. These include absolute stagnation temperature rises in turbine rotor tip leakage flow, wake transport through downstream blade rows, and effects of wake phasing on compressor work input. Fluid dynamic situations are then constructed to explain the effect of unsteadiness, including a physical interpretation of how stagnation pressure variations are created by temporal variations in static pressure; in this it is shown that the unsteady static pressure plays the role of a time-dependent body force potential. It is further shown that when the unsteadiness is due to a spatial nonuniformity translating at constant speed, as in a turbomachine, the unsteady pressure variation can be viewed as a local power input per unit mass from this body force to the fluid particle instantaneously at that point

The person-based nature of prejudice: Individual difference predictors of intergroup negativity

Person-based factors influence a range of meaningful life outcomes, including intergroup processes, and have long been implicated in explaining prejudice. In addition to demonstrating significant heritability, person-based factors are evident in expressions of generalised prejudice, a robust finding that some people (relative to others) consistently score higher in prejudice towards multiple outgroups. Our contemporary review includes personality factors, ideological orientations (e.g., authoritarianism), religiosity, anxiety, threat, disgust sensitivity, and cognitive abilities and styles. Meta-analytic syntheses demonstrate that such constructs consistently predict prejudice, often at the upper bounds of effect sizes observed in psychological research. We conclude that prejudice theories need to better integrate person- and situation-based factors, including their interaction, to capture the complexity of prejudice and inform intervention development

COVID-19 health misinformation: using design-based research to develop a theoretical framework for intervention

Purpose: Because health misinformation pertaining to COVID-19 is a serious threat to public health, the purpose of this study is to develop a framework to guide an online intervention into some of the drivers of health misinformation online. This framework can be iterated upon through the use of design-based research to continue to develop further interventions as needed. Design/methodology/approach: Using design-based research methods, in this paper, the authors develop a theoretical framework for addressing COVID-19 misinformation. Using a heuristic analysis of research on vaccine misinformation and hesitancy, the authors propose a framework for education interventions that use the narrative effect of transportation as a means to increase knowledge of the drivers of misinformation online. Findings: This heuristic analysis determined that a key element of narrative transportation includes orientation towards particular audiences. Research indicates that mothers are the most significant household decision-makers with respect to vaccines and family health in general; the authors suggest narrative interventions should be tailored specifically to meet their interests and tastes, and that this may be different for mothers of different backgrounds and cultural communities. Originality/value: While there is a significant body of literature on vaccine hesitancy and vaccine misinformation, more research is needed that helps people understand the ways in which misinformation works upon social media users. The framework developed in this research guided the development of an education intervention meant to facilitate this understanding

Expression of schizophrenia in black Xhosa-speaking and white English-speaking South Africans

Objective. To inv:estigate whether schizophrenia manifests itself differently in  Xhosa-speaking South Africans, compared with English-speaking white South  Africans.Design. A comparative study ·of the presentation of schizophrenia in two groups of patients.Settings and subjects. A sample of 63 patients (43 Xhosaspeaking and 20 English-speaking) admitted to a large psychiatric hospital for the first time with a diagnosis of schizophrenia.Outcome measures. The Present State Examination (PSE) was used to confirm the clinical diagnosis of schizophrenia. The Relatives' Rating of Symptoms and Social Behaviour (KAS-R) was used to obtain information on the behavioural and emotional expression of schizophrenia.Results. A significantly higher prevalence of aggressive and disruptive behaviour was reported by relatives of Xhosaspeaking patients with schizophrenia of recent onset compared with English-speaking patients. The PSE elicited significantly more delusions of persecution, sexual and fantastic delusions, self-neglect and irritability in the Xhosaspeaking patients.Canclusion. Significant differences in the presentation of schizophrenia, but not its core symptoms, were identified in . Xhosa-speaking blacks and English-speaking whites

Aspects of Transition in Turbomachines

This talk provides a description of several types of transition encountered in turbomachines. It is based largely on personal experience of the detection of transition in turbomachines. Examples are taken from axial compressors, axial turbines and radial turbines. The illustrations are concerned with transition in steady and unsteady boundary layers that develop under the influence of two-dimensional and three-dimensional flow fields

Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states

The state of metabolic dormancy has fascinated people for hundreds of years, leading to research exploring the identity of natural molecular components that may induce and maintain this state. Many animals lower their metabolism in response to high temperatures and/or arid conditions, a phenomenon called aestivation. The biological significance for this is clear; by strongly suppressing metabolic rate to low levels, animals minimize their exposure to stressful conditions. Understanding blood or hemolymph metabolite changes that occur between active and aestivated animals can provide valuable insights relating to those molecular components that regulate hypometabolism in animals, and how they afford adaptation to their different environmental conditions. In this study, we have investigated the hemolymph metabolite composition from the land snail Theba pisana, a remarkably resilient mollusc that displays an annual aestivation period. Using LC-MS-based metabolomics analysis, we have identified those hemolymph metabolites that show significant changes in relative abundance between active and aestivated states. We show that certain metabolites, including some phospholipids [e.g. LysoPC(14:0)], and amino acids such as l-arginine and l-tyrosine, are present at high levels within aestivated snails. Further investigation of our T. pisana RNA-sequencing data elucidated the entire repertoire of phospholipid-synthesis genes in the snail digestive gland, as a precursor towards future comparative investigation between the genetic components of aestivating and non-aestivating species. In summary, we have identified a large number of metabolites that are elevated in the hemolymph of aestivating snails, supporting their role in protecting against heat or desiccation

Metal bioaccumulation and cellular fractionation in an epigeic earthworm (Lumbricus rubellus): the interactive influences of population exposure histories, site-specific geochemistry and mitochondrial genotype

Subcellular fractionation techniques were used to describe temporal changes (at intervals from T0 to T70 days) in the Pb, Zn and P partitioning profiles of Lumbricus rubellus populations from one calcareous (MDH) and one acidic (MCS) geographically isolated Pb/Zn-mine sites and one reference site (CPF). MDH and MCS individuals were laboratory maintained on their native field soils; CPF worms were exposed to both MDH and MCS soils. Site-specific differences in metal partitioning were found: notably, the putatively metal-adapted populations, MDH and MCS, preferentially partitioned higher proportions of their accumulated tissue metal burdens into insoluble CaPO4-rich organelles compared with naive counterparts, CPF. Thus, it is plausible that efficient metal immobilization is a phenotypic trait characterising metal tolerant ecotypes. Mitochondrial cytochrome oxidase II (COII) genotyping revealed that the populations indigenous to mine and reference soils belong to distinct genetic lineages, differentiated by 13%, with 7 haplotypes within the reference site lineage but fewer (3 and 4, respectively) in the lineage common to the two mine sites. Collectively, these observations raise the possibility that site-related genotype differences could influence the toxico-availability of metals and, thus, represent a potential confounding variable in field-based eco-toxicological assessments