Ins1 Gene Up-Regulated in a β-Cell Line Derived from Ins2 Knockout Mice

The authors have derived a new β-cell line (βIns2−/−lacZ) from Ins2−/− mice that carry the lacZ reporter gene under control of the Ins2 promoter. βIns2−/−lacZ cells stained positively using anti-insulin antibody, expressed β-cell–specific genes encoding the transcription factor PDX-1, glucokinase, and Glut-2, retained glucose-responsiveness for insulin secretion, and expressed the lacZ gene. Analysis of Ins1 expression by reverse transcriptase–polymerase chain reaction (RT-PCR) showed that Ins1 transcripts were significantly raised to compensate for the lack of Ins2 transcripts in βIns2−/−lacZ cells, as compared to those found in βTC1 cells expressing both Ins1/Ins2. Thus, transcriptional up-regulation of the remaining functional insulin gene in Ins2−/− mice could potentially contribute to the β-cell adaptation exhibited by these mutants, in addition to the increase in β-cell mass that we previously reported.We have also shown that lacZ expression, as analyzed by determining β-galactosidase activity, was up-regulated by incubating βIns2−/−lacZ cells with GLP-1 and/or IBMX, 2 known stimulators of insulin gene expression. These cells thus represent a new tool for testing of molecules capable of stimulating Ins2 promoter activit

Space QUEST mission proposal: experimentally testing decoherence due to gravity

Models of quantum systems on curved space-times lack sufficient experimental verification. Some speculative theories suggest that quantum correlations, such as entanglement, may exhibit different behavior to purely classical correlations in curved space. By measuring this effect or lack thereof, we can test the hypotheses behind several such models. For instance, as predicted by Ralph et al [5] and Ralph and Pienaar [1], a bipartite entangled system could decohere if each particle traversed through a different gravitational field gradient. We propose to study this effect in a ground to space uplink scenario. We extend the above theoretical predictions of Ralph and coworkers and discuss the scientific consequences of detecting/failing to detect the predicted gravitational decoherence. We present a detailed mission design of the European Space Agency's Space QUEST (Space—Quantum Entanglement Space Test) mission, and study the feasibility of the mission scheme.Peer ReviewedPostprint (published version

Predicting Urban Heat Island Mitigation with Random Forest Regression in Belgian Cities

peer reviewedAn abundance of impervious surfaces like building roofs in densely populated cities make green roofs a suitable solution for urban heat island (UHI) mitigation. Therefore, we employ random forest (RF) regression to predict the impact of green roofs on the surface UHI (SUHI) in Liege, Belgium. While there have been several studies identifying the impact of green roofs on UHI, fewer studies utilize a remote-sensing-based approach to measure impact on Land Surface Temperatures (LST) that are used to estimate SUHI. Moreover, the RF algorithm, can provide useful insights. In this study, we use LST obtained from Landsat-8 imagery and relate it to 2D and 3D morphological parameters that influence LST and UHI effects. Additionally, we utilise parameters that influence wind (e.g., frontal area index). We simulate the green roofs by assigning suitable values of normalised difference-vegetation index and built-up index to the buildings with flat roofs. Results suggest that green roofs decrease the average LST

EFFECTIVENESS OF GREEN ROOFS IN STRENGTHENING ECOLOGICAL NETWORK

peer reviewedImproving biodiversity in urban areas is widely recognised as part of sustainable smart cities development framework. Due to unprecedented urbanisation, there is a lack of adequate green spaces which has in turn affected the urban biodiversity. Green roofs are argued to enhance and support the biodiversity by systematic inclusion into the urban ecological network. However, its connection to the existing natural ecological areas and connectivity are not discussed at a city scale. Thus, in this study, we aim at identifying the connectivity of potential areas for developing green roofs in strengthening the biodiversity and ecological network in cities. Altogether, we observe that the potential roofs are in the near proximity of these zones. The zones with dry lawns and meadows like environment are quite limited and spatially far from each other. Thus, developing green roofs can help in connecting these spaces. In this paper, we mainly focused on bees as they play an important role in pollination and are also declining in the urban areas. Further research can incorporate more detailed analysis on foraging distances of other species. A methodology can be developed to select which zones can be targeted for specific species

Developmental delay and progressive seizures in 2-month-old child with diffuse MRI abnormalities

2 month-old infant presented with seizures, radiological findings of diffuse elevated T2 signal with frontal lobe sparing and extensive symmetrical post contrast enhancement. At autopsy, the brain stem was pale and atrophic, with areas of cystic degeneration. Medullary sections showed perivascular Rosenthal fibre deposition

Stability of the human faecal microbiome in a cohort of adult men

Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics

Imaging Invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion.

Tissue invasion and infiltration by brain tumours poses a clinical challenge, with destruction of structures leading to morbidity. We assessed whether micro-CT could be used to map tumour invasion in adamantinomatous craniopharyngioma (ACP), and whether it could delineate ACPs and their intrinsic components from surrounding tissue.Three anonymised archival frozen ACP samples were fixed, iodinated and imaged using a micro-CT scanner prior to the use of standard histological processing and immunohistochemical techniques.We demonstrate that micro-CT imaging can non-destructively give detailed 3D structural information of tumours in volumes with isotropic voxel sizes of 4-6 microns, which can be correlated with traditional histology and immunohistochemistry.Such information complements classical histology by facilitating virtual slicing of the tissue in any plane and providing unique detail of the three dimensional relationships of tissue compartments

CityRoof -Analogous green roofs for cities in Wallonia

peer reviewedWhy analogous green roofs? Green roofs are becoming increasingly popular owing to the unavailability of land for developing green infrastructure within the urban environment. Green roofs offer multiple ecosystem services, such as maintaining the biodiversity and ecological connectivity between natural areas, regulation of climate and water, and cultural services. Despite the benefits to the ecosystem, the development of green roofs is limited in the cities due to the financial cost. In this project, we unravel the complex interactions among ecological, built, and human environments for a novel ecosystem 'analogous green roofs'-and the way those interactions influence ecosystem delivery for the development of nature-based urban green infrastructures. An analogous habitat is an anthropogenic site hosting indigenous biodiversity due to its structural and functional resemblance to natural ecosystems. The project is conducted by 3 PhD students and studies the urban environment of cities in Wallonia region of Belgium.9. Industry, innovation and infrastructur

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes

Aims: Biomarker‐driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub‐classify iMB, and proffer strategies for personalized, risk‐adapted therapies. Methods: We characterized the iMB molecular landscape, including second‐generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). Results: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second‐generation subtypes II/III/IV. Subtype II strongly associated with large‐cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very‐high‐risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4) and subtype IV tumours were standard risk (80% OS) using upfront CSI‐based therapies; randomized‐controlled trials of upfront radiation‐sparing and/or second‐line radiotherapy should be considered. Seventy‐five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non‐DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH. iMBSHH harboured two distinct subtypes (iMBSHH‐I/II). Within the discriminated favourable‐risk iMBSHH DN/MBEN patient group, iMBSHH‐II had significantly better progression‐free survival than iMBSHH‐I, offering opportunities for risk‐adapted stratification of upfront therapies. Both iMBSHH‐I and iMBSHH‐II showed notable rescue rates (56% combined post‐relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. Conclusions: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup‐dependent survival models highlight opportunities for biomarker‐directed therapies

Transdermal microconduits by microscission for drug delivery and sample acquisition

BACKGROUND: Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 μm diameter areas of human skin in vivo. METHODS: Microscissioning is achieved by a limited flux of accelerated gas: 25 μm inert particles passing through the aperture in a mask held against the stratum corneum. The particles scize (cut) tissue, which is removed by the gas flow with the sensation of a gentle stream of air against the skin. The resulting microconduit is fully open and may be between 50 and 200 μm deep. RESULTS: In vivo adult human tests show that microconduits reduce the electrical impedance between two ECG electrodes from approximately 4,000 Ω to 500 Ω. Drug delivery has been demonstrated in vivo by applying lidocaine to a microconduit from a cotton swab. Sharp point probing demonstrated full anaesthesia around the site within three minutes. Topical application without the microconduit required approximately 1.5 hours. Approximately 180 μm deep microconduits in vivo yielded blood sample volumes of several μl, with a faint pricking sensation as blood enters tissue. Blood glucose measurements were taken with two commercial monitoring systems. Microconduits are invisible to the unaided eye, developing a slight erythematous macule that disappears over days. CONCLUSION: Microscissioned microconduits may provide a minimally invasive basis for delivery of any size molecule, and for extraction of interstitial fluid and blood samples. Such microconduits reduce through-skin electrical impedance, have controllable diameter and depth, are fully open and, after healing, no foreign bodies were visible using through-skin confocal microscopy. In subjects to date, microscissioning is painless and rapid