miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development

MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased β-cell and increased α-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal β-cell mass and function. Selective re-expression of miR-375 in β-cells of miR-375KO mice normalizes both, α- and β-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of β-cells to the total plasma miR-375 levels. Only a small proportion (≈1 %) of circulating miR-375 originates from β-cells. Furthermore, acute and profound β-cell destruction is sufficient to detect elevations of miR-375 levels in the blood. These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients. Together, our data support an essential role for miR-375 in the maintenance of β-cell mass and provide in vivo evidence for release of miRNAs from pancreatic β-cells. The small contribution of β-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for β-cell function but suggests a utility for the detection of acute β-cell death for autoimmune diabetes

Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack

BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment

Utilising green and bluespace to mitigate urban heat island intensity.

It has long been recognised that cities exhibit their own microclimate and are typically warmer than the surrounding rural areas. This 'mesoscale' influence is known as the urban heat island (UHI) effect and results largely from modification of surface properties leading to greater absorption of solar radiation, reduced convective cooling and lower water evaporation rates. Cities typically contain less vegetation and bodies of water than rural areas, and existing green and bluespace is often under threat from increasing population densities. This paper presents a meta-analysis of the key ways in which green and bluespace affect both urban canopy- and boundary-layer temperatures, examined from the perspectives of city-planning, urban climatology and climate science. The analysis suggests that the evapotranspiration-based cooling influence of both green and bluespace is primarily relevant for urban canopy-layer conditions, and that tree-dominated greenspace offers the greatest heat stress relief when it is most needed. However, the magnitude and transport of cooling experienced depends on size, spread, and geometry of greenspaces, with some solitary large parks found to offer minimal boundary-layer cooling. Contribution to cooling at the scale of the urban boundary-layer climate is attributed mainly to greenspace increasing surface roughness and thereby improving convection efficiency rather than evaporation. Although bluespace cooling and transport during the day can be substantial, nocturnal warming is highlighted as likely when conditions are most oppressive. However, when both features are employed together they can offer many synergistic ecosystem benefits including cooling. The ways in which green and bluespace infrastructure is applied in future urban growth strategies, particularly in countries expected to experience rapid urbanisation, warrants greater consideration in urban planning policy to mitigate the adverse effects of the UHI and enhance climate resilience

Simultaneous Orthogonal Planarity

We introduce and study the $\textit{OrthoSEFE}-k$ problem: Given $k$ planar graphs each with maximum degree 4 and the same vertex set, do they admit an OrthoSEFE, that is, is there an assignment of the vertices to grid points and of the edges to paths on the grid such that the same edges in distinct graphs are assigned the same path and such that the assignment induces a planar orthogonal drawing of each of the $k$ graphs? We show that the problem is NP-complete for $k \geq 3$ even if the shared graph is a Hamiltonian cycle and has sunflower intersection and for $k \geq 2$ even if the shared graph consists of a cycle and of isolated vertices. Whereas the problem is polynomial-time solvable for $k=2$ when the union graph has maximum degree five and the shared graph is biconnected. Further, when the shared graph is biconnected and has sunflower intersection, we show that every positive instance has an OrthoSEFE with at most three bends per edge.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Effects of dental probing on occlusal surfaces - A scanning electron microscopy evaluation

The aim of this clinical-morphological study was to investigate the effects of dental probing on occlusal surfaces by scanning electron microscopy (SEM). Twenty sound occlusal surfaces of third molars and 20 teeth with initial carious lesions of 17- to 26-year-old patients (n = 18) were involved. Ten molars of each group were probed with a sharp dental probe (No. 23) before extraction; the other molars served as negative controls. After extraction of the teeth, the crowns were separated and prepared for the SEM study. Probing-related surface defects, enlargements and break-offs of occlusal pits and fissures were observed on all occlusal surfaces with initial carious lesions and on 2 sound surfaces, respectively. No traumatic defects whatsoever were visible on unprobed occlusal surfaces. This investigation confirms findings of light-microscopic studies that using a sharp dental probe for occlusal caries detection causes enamel defects. Therefore, dental probing should be considered as an inappropriate procedure and should be replaced by a meticulous visual inspection. Critical views of tactile caries detection methods with a sharp dental probe as a diagnostic tool seem to be inevitable in undergraduate and postgraduate dental education programmes. Copyright (c) 2007 S. Karger AG, Basel