Dermoscopic and Reflectance Confocal Microscopic Presentation of Hailey‐Hailey Disease: a Case Series

Background/purpose: Hailey-Hailey disease is a rare inherited acantholytic skin disorder characterized by heterogeneous clinical presentation. Its differential diagnosis might be wide, including other genodermatoses, inflammatory, and infectious skin diseases. Although histopathology remains as diagnostic gold standard, noninvasive techniques such as dermoscopy and reflectance confocal microscopy may assist clinical examination. Herein, we aim to further characterize the dermoscopic and reflectance confocal microscopic presentation of Hailey-Hailey disease with histologic correlation. Methods: Eight patients with Hailey-Hailey disease were consecutively recruited. All patients were examined using dermoscopy and reflectance confocal microscopy. Results: In all cases, dermoscopy enabled the visualization of polymorphous vessels, including glomerular and linear-looped vessels, within a pink-whitish background. Reflectance confocal microscopy revealed wide suprabasilar partial acantholysis and clefting, crusts, dilated papillae with tortuous vessels, and inflammatory cells. Dyskeratosis, uplocated papillae, and adnexal sparing were also observed. Conclusion: Although definite diagnosis was obtained by histopathology in all cases, dermoscopy and reflectance confocal microscopy allowed the identification of common features (even in cases with dissimilar clinical presentation) that may support an early diagnosis of Hailey-Hailey disease, and its differentiation from other more frequent skin disorders.info:eu-repo/semantics/publishedVersio

Analysis of RNA Expression Profiles Identifies Dysregulated Vesicle Trafficking Pathways in Creutzfeldt-Jakob Disease

Functional genomics applied to the study of RNA expression profiles identified several abnormal molecular processes in experimental prion disease. However, only a few similar studies have been carried out to date in a naturally occurring human prion disease. To better characterize the transcriptional cascades associated with sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, we investigated the global gene expression profile in samples from the frontal cortex of 10 patients with sCJD and 10 non-neurological controls by microarray analysis. The comparison identified 333 highly differentially expressed genes (hDEGs) in sCJD. Functional enrichment Gene Ontology analysis revealed that hDEGs were mainly associated with synaptic transmission, including GABA (q value = 0.049) and glutamate (q value = 0.005) signaling, and the immune/inflammatory response. Furthermore, the analysis of cellular components performed on hDEGs showed a compromised regulation of vesicle-mediated transport with mainly up-regulated genes related to the endosome (q value = 0.01), lysosome (q value = 0.04), and extracellular exosome (q value < 0.01). A targeted analysis of the retromer core component VPS35 (vacuolar protein sorting-associated protein 35) showed a down-regulation of gene expression (p value= 0.006) and reduced brain protein levels (p value= 0.002). Taken together, these results confirm and expand previous microarray expression profile data in sCJD. Most significantly, they also demonstrate the involvement of the endosomal-lysosomal system. Since the latter is a common pathogenic pathway linking together diseases, such as Alzheimer’s and Parkinson’s, it might be the focus of future studies aimed to identify new therapeutic targets in neurodegenerative diseases

The Global Lake Ecological Observatory Network (GLEON): the evolution of grassroots network science

Nine years later, with over 380 members from 40 countries, and 50 publications to its credit, GLEON is growing at a rapid pace and pushing the boundaries of the practice of network science. GLEON is really three networks: a network of lakes, data, and peopl

A Global lake ecological observatory network (GLEON) for synthesising high-frequency sensor data for validation of deterministic ecological models

A Global Lake Ecological Observatory Network (GLEON; www.gleon.org) has formed to provide a coordinated response to the need for scientific understanding of lake processes, utilising technological advances available from autonomous sensors. The organisation embraces a grassroots approach to engage researchers from varying disciplines, sites spanning geographic and ecological gradients, and novel sensor and cyberinfrastructure to synthesise high-frequency lake data at scales ranging from local to global. The high-frequency data provide a platform to rigorously validate processbased ecological models because model simulation time steps are better aligned with sensor measurements than with lower-frequency, manual samples. Two case studies from Trout Bog, Wisconsin, USA, and Lake Rotoehu, North Island, New Zealand, are presented to demonstrate that in the past, ecological model outputs (e.g., temperature, chlorophyll) have been relatively poorly validated based on a limited number of directly comparable measurements, both in time and space. The case studies demonstrate some of the difficulties of mapping sensor measurements directly to model state variable outputs as well as the opportunities to use deviations between sensor measurements and model simulations to better inform process understanding. Well-validated ecological models provide a mechanism to extrapolate high-frequency sensor data in space and time, thereby potentially creating a fully 3-dimensional simulation of key variables of interest

The data paper: a mechanism to incentivize data publishing in biodiversity science

<p/> <p>Background</p> <p>Free and open access to primary biodiversity data is essential for informed decision-making to achieve conservation of biodiversity and sustainable development. However, primary biodiversity data are neither easily accessible nor discoverable. Among several impediments, one is a lack of incentives to data publishers for publishing of their data resources. One such mechanism currently lacking is recognition through conventional scholarly publication of enriched metadata, which should ensure rapid discovery of 'fit-for-use' biodiversity data resources.</p> <p>Discussion</p> <p>We review the state of the art of data discovery options and the mechanisms in place for incentivizing data publishers efforts towards easy, efficient and enhanced publishing, dissemination, sharing and re-use of biodiversity data. We propose the establishment of the 'biodiversity data paper' as one possible mechanism to offer scholarly recognition for efforts and investment by data publishers in authoring rich metadata and publishing them as citable academic papers. While detailing the benefits to data publishers, we describe the objectives, work flow and outcomes of the pilot project commissioned by the Global Biodiversity Information Facility in collaboration with scholarly publishers and pioneered by Pensoft Publishers through its journals <it>Zookeys</it>, <it>PhytoKeys</it>, <it>MycoKeys</it>, <it>BioRisk</it>, <it>NeoBiota</it>, <it>Nature Conservation</it> and the forthcoming <it>Biodiversity Data Journal</it>. We then debate further enhancements of the data paper beyond the pilot project and attempt to forecast the future uptake of data papers as an incentivization mechanism by the stakeholder communities.</p> <p>Conclusions</p> <p>We believe that in addition to recognition for those involved in the data publishing enterprise, data papers will also expedite publishing of fit-for-use biodiversity data resources. However, uptake and establishment of the data paper as a potential mechanism of scholarly recognition requires a high degree of commitment and investment by the cross-sectional stakeholder communities.</p

TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons

Nuclear clearance of TDP-43 into cytoplasmic aggregates is a key driver of neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but the mechanisms are unclear. Here, we show that TDP-43 knockdown specifically reduces the number and motility of RAB11-positive recycling endosomes in dendrites, while TDP-43 overexpression has the opposite effect. This is associated with delayed transferrin recycling in TDP-43-knockdown neurons and decreased 2-transferrin levels in patient CSF. Whole proteome quantification identified the upregulation of the ESCRT component VPS4B upon TDP-43 knockdown in neurons. Luciferase reporter assays and chromatin immunoprecipitation suggest that TDP-43 represses VPS4B transcription. Preventing VPS4B upregulation or expression of its functional antagonist ALIX restores trafficking of recycling endosomes. Proteomic analysis revealed the broad reduction in surface expression of key receptors upon TDP-43 knockdown, including ErbB4, the neuregulin 1 receptor. TDP-43 knockdown delays the surface delivery of ErbB4. ErbB4 overexpression, but not neuregulin 1 stimulation, prevents dendrite loss upon TDP-43 knockdown. Thus, impaired recycling of ErbB4 and other receptors to the cell surface may contribute to TDP-43-induced neurodegeneration by blocking trophic signaling

Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants.

Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls. Results: TOMM40-L/APOE-ε4 alleles were associated with DLB (OR TOMM40 -L = 3.61; P value = 3.23 × 10-9; OR APOE -ε4 = 3.75; P value = 4.90 × 10-10) and earlier age at onset of DLB (HR TOMM40 -L = 1.33, P value = .031; HR APOE -ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L = 4.40, P value = 1.15 × 10-6; OR APOE -ε4 = 5.65, P value = 2.97 × 10-8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10-99; ORDLB+AD = 5.36, P value = 1.56 × 10-47). Discussion: APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB

Open data platforms and their usability: Proposing a framework for evaluating citizen intentions

Governments across the world are releasing public data in an effort to increase transparency of how public services are managed whilst also enticing citizens to participate in the policy decision-making processes. The channel for making open data available to citizens in the UK is the data.gov.uk platform, which brings together data relating to various public services in one searchable website. The data.gov.uk platform currently offers access to 25,500 datasets that are organized across key public service themes including health, transport, education, environment, and public spending in towns and cities. While the website reports 5,438,159 site visits as of June 2015, the average time spent on the site has been recorded at just 02:12 min per visitor. This raises questions regarding the actual use and usability of open data platforms and the extent to which they fulfill the stated outcomes of open data. In this paper, the authors examine usability issues surrounding open data platforms and propose a framework that can be used to evaluate their usability

Towards a data publishing framework for primary biodiversity data: challenges and potentials for the biodiversity informatics community

Background: Currently primary scientific data, especially that dealing with biodiversity, is neither easily discoverable nor accessible. Amongst several impediments, one is a lack of professional recognition of scientific data publishing efforts. A possible solution is establishment of a ‘Data Publishing Framework’ which would encourage and recognise investments and efforts by institutions and individuals towards management, and publishing of primary scientific data potentially on a par with recognitions received for scholarly publications. Discussion: This paper reviews the state-of-the-art of primary biodiversity data publishing, and conceptualises a ‘Data Publishing Framework’ that would help incentivise efforts and investments by institutions and individuals in facilitating free and open access to biodiversity data. It further postulates the institutionalisation of a ‘Data Usage Index (DUI)’, that would attribute due recognition to multiple players in the data collection/creation, management and publishing cycle. Conclusion: We believe that institutionalisation of such a ‘Data Publishing Framework’ that offers socio-cultural, legal, technical, economic and policy environment conducive for data publishing will facilitate expedited discovery and mobilisation of an exponential increase in quantity of ‘fit-for-use’ primary biodiversity data, much of which is currently invisible