Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents

peer-reviewedThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction

The Passive Journalist: How sources dominate the local news

This study explores which sources are “making” local news and whether these sources are simply indicating the type of news that appears, or are shaping newspaper coverage. It provides an empirical record of the extent to which sources are able to dominate news coverage from which future trends in local journalism can be measured. The type and number of sources used in 2979 sampled news stories in four West Yorkshire papers, representing the three main proprietors of local newspapers in the United Kingdom, were recorded for one month and revealed the relatively narrow range of routine sources; 76 per cent of articles cited only a single source. The analysis indicates that journalists are relying less on their readers for news, and that stories of little consequence are being elevated to significant positions, or are filling news pages at the expense of more important stories. Additionally, the reliance on a single source means that alternative views and perspectives relevant to the readership are being overlooked. Journalists are becoming more passive, mere processors of one-sided information or bland copy dictated by sources. These trends indicate poor journalistic standards and may be exacerbating declining local newspaper sales

PCDH10 Promoter Hypermethylation is Frequent in most Histologic Subtypes of Mature Lymphoid Malignancies and Occurs Early in Lymphomagenesis

PCDH10 is epigenetically inactivated in multiple tumor types; however, studies in mature lymphoid malignancies are limited. Here, we have investigated the presence of promoter hypermethylation of the PCDH10 gene in a large cohort of well-characterized subsets of lymphomas. PCDH10 promoter hypermethylation was identified by methylation-specific PCR in 57 to 100% of both primary B- and T-cell lymphoma specimens and cell lines. These findings were further validated by Sequenom Mass-array analysis. Promoter hypermethylation was also identified in 28.6% cases of reactive follicular hyperpla- sia, more commonly occurring in states of immune deregulation and associated with rare presence of clonal karyotypic aberrations, suggesting that PCDH10 methylation occurs early in lymphomagenesis. PCDH10 expression was down regu- lated via promoter hypermethylation in T- and B-cell lymphoma cell lines. The transcriptional down-regulation resulting from PCDH10 methylation could be restored by pharmacologic inhibition of DNA methyltransferases in cell lines. Both T- and B-cell lymphoma cell lines harboring methylation-mediated inactivation of PCDH10 were resistant to doxorubicin treatment, suggesting that hypermethylation of this gene might contribute to chemotherapy response

Smoke, curtains and mirrors: the production of race through time and title registration

This article analyses the temporal effects of title registration and their relationship to race. It traces the move away from the retrospection of pre-registry common law conveyancing and toward the dynamic, future-oriented Torrens title registration system. The Torrens system, developed in early colonial Australia, enabled the production of ‘clean’, fresh titles that were independent of their predecessors. Through a process praised by legal commentators for ‘curing’ titles of their pasts, this system produces indefeasible titles behind its distinctive ‘curtain’ and ‘mirror’, which function similarly to magicians’ smoke and mirrors by blocking particular realities from view. In the case of title registries, those realities are particular histories of and relationships with land, which will not be protected by property law and are thus made precarious. Building on interdisciplinary work which theorises time as a social tool, I argue that Torrens title registration produces a temporal order which enables land market coordination by rendering some relationships with land temporary and making others indefeasible. This ordering of relationships with land in turn has consequences for the human subjects who have those relationships, cutting futures short for some and guaranteeing permanence to others. Engaging with Renisa Mawani and other critical race theorists, I argue that the categories produced by Torrens title registration systems materialise as race

FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer

Background ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours. Methods In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq and western blotting. Endogenous FKBPL protein levels were evaluated using tissue microarrays (TMA). Results ALM201 reduced CSCs in cell lines and primary samples by inducing differentiation. ALM201 treatment of highly vascularised Kuramochi xenografts resulted in tumour growth delay by disruption of angiogenesis and a ten-fold decrease in the CSC population. In contrast, ALM201 failed to elicit a strong antitumour response in non-vascularised OVCAR3 xenografts, due to high levels of IL-6 and vasculogenic mimicry. High endogenous tumour expression of FKBPL was associated with an increased progression-free interval, supporting the protective role of FKBPL in HGSOC. Conclusion FKBPL-based therapy can (i) dually target angiogenesis and CSCs, (ii) target the CD44/STAT3 pathway in tumours and (iii) is effective in highly vascularised HGSOC tumours with low levels of IL-6

Prospective mental imagery as its link with anxiety and depression in prisoners

Mental imagery is known to play a key role in the development and maintenance of depression and anxiety. Prisoners commonly experience psychological distress, but interventions to address this are currently lacking. We aimed to examine the link between prospective mental imagery and anxiety and depression among prisoners. One hundred twenty-three male prisoners from a Category C prison in southwest England participated in the study. They completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the General Anxiety Disorder Scale (GAD-7) to measure whether they experience depression and/or anxiety symptoms. Furthermore, they completed additional questionnaires to evaluate their prospective mental imagery. Results showed that 67.5% of prisoners presented with more depression symptoms and 27.7% with more anxiety symptoms. Supporting earlier findings, our data revealed that some dimensions of prospective mental imagery were significantly related with increased anxiety and depression symptoms in prisoners. Namely, intrusive negative personally relevant imagery was a positive predictor and likelihood of positive events a negative predictor of both anxiety and depression symptoms. The perceived likelihood of negative events was a positive predictor of depression. Intrusive verbal thought was a positive predictor of anxiety. The obtained results suggest the need to develop interventions not only targeting the reduction of prospective negative imagery but also the enhancement of positive mental imagery

The potential for sand dams to increase the adaptive capacity of East African drylands to climate change

Drylands are home to more than two billion people and are characterised by frequent, severe droughts. Such extreme events are expected to be exacerbated in the near future by climate change. A potentially simple and cost-effective mitigation measure against drought periods is sand dams. This little-known technology aims to promote subsoil rainwater storage to support dryland agro-ecosystems. To date, there is little long-term empirical analysis that tests the effectiveness of this approach during droughts. This study addresses this shortcoming by utilising multi-year satellite imagery to monitor the effect of droughts at sand dam locations. A time series of satellite images was analysed to compare vegetation at sand dam sites and control sites over selected periods of drought, using the normalised difference vegetation index. The results show that vegetation biomass was consistently and significantly higher at sand dam sites during periods of extended droughts. It is also shown that vegetation at sand dam sites recovers more quickly from drought. The observed findings corroborate modelling-based research which identified related impacts on ground water, land cover, and socio-economic indicators. Using past periods of drought as an analogue to future climate change conditions, this study indicates that sand dams have potential to increase adaptive capacity and resilience to climate change in drylands. It therefore can be concluded that sand dams enhance the resilience of marginal environments and increase the adaptive capacity of drylands. Sand dams can therefore be a promising adaptation response to the impacts of future climate change on drylands

Migration Status in Relation to Clinical Characteristics and Barriers to Care Among Youth with Diabetes in the US

Migration status and the accompanying diversity in culture, foods and family norms, may be an important consideration for practitioners providing individualized care to treat and prevent complications among youth with diabetes. Approximately 20% of youth in the US have ≥ 1 foreign-born parent. However, the proportion and characteristics of youth with diabetes and ≥ 1 foreign-born parent have yet to be described. Study participants (n = 3,086) were from SEARCH for Diabetes in Youth, a prospective multi-center study in the US. Primary outcomes of interest included HbA1c, body mass index and barriers to care. Multivariable analyses were carried out using logistic regression and analysis of covariance. Approximately 17% of participants with type 1 diabetes (T1D) and 22% with type 2 diabetes (T2D) had ≥ 1 foreign-born parent. Youth with T1D and ≥ 1 foreign-born parent were less likely to have poor glycemic control [adjusted odds ratio (OR) (95% confidence interval): 0.70 (0.53, 0.94)]. Among youth with T2D, those with ≥ 1 foreign-born parent had lower odds of obesity [adjusted OR (95% CI): 0.35 (0.17, 0.70)]. This is the first study to estimate the proportion and characteristics of youth with diabetes exposed to migration in the US. Research into potential mechanisms underlying the observed protective effects is warranted

Epigenetic Effects of Prenatal Stress on 11β-Hydroxysteroid Dehydrogenase-2 in the Placenta and Fetal Brain

Maternal exposure to stress during pregnancy is associated with significant alterations in offspring neurodevelopment and elevated maternal glucocorticoids likely play a central role in mediating these effects. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers the impact of maternal glucocorticoid exposure by converting cortisol/corticosterone into inactive metabolites. However, previous studies indicate that maternal adversity during the prenatal period can lead to a down-regulation of this enzyme. In the current study, we examined the impact of prenatal stress (chronic restraint stress during gestational days 14–20) in Long Evans rats on HSD11B2 mRNA in the placenta and fetal brain (E20) and assessed the role of epigenetic mechanisms in these stress-induced effects. In the placenta, prenatal stress was associated with a significant decrease in HSD11B2 mRNA, increased mRNA levels of the DNA methyltransferase DNMT3a, and increased DNA methylation at specific CpG sites within the HSD11B2 gene promoter. Within the fetal hypothalamus, though we find no stress-induced effects on HSD11B2 mRNA levels, prenatal stress induced decreased CpG methylation within the HSD11B2 promoter and increased methylation at sites within exon 1. Within the fetal cortex, HSD11B2 mRNA and DNA methylation levels were not altered by prenatal stress, though we did find stress-induced elevations in DNMT1 mRNA in this brain region. Within individuals, we identified CpG sites within the HSD11B2 gene promoter and exon 1 at which DNA methylation levels were highly correlated between the placenta and fetal cortex. Overall, our findings implicate DNA methylation as a mechanism by which prenatal stress alters HSD11B2 gene expression. These findings highlight the tissue specificity of epigenetic effects, but also raise the intriguing possibility of using the epigenetic status of placenta to predict corresponding changes in the brain

CITES, wild plants, and opportunities for crime

The illegal trade in endangered plants damages both the environment and local communities by threatening and destroying numerous species and important natural resources. There is very little research which systematically addresses this issue by identifying specific opportunities for crime. This article presents the results of an interdisciplinary study which brings together criminological and conservation science expertise to identify criminal opportunities in the illegal wild plant trade and suggest strategies in order to prevent and mitigate the problem. Methodologically, the study adapts a crime proofing of legislation approach to the UN Convention on the International Trade in Endangered Species of Wild Fauna and Flora and is based on documentary and interview data. Situational crime prevention is used as a framework to provide points for effective intervention