Unravelling the photoprotective mechanisms of nature-inspired ultraviolet filters using ultrafast spectroscopy

There are several drawbacks with the current commercially available ultraviolet (UV) filters used in sunscreen formulations, namely deleterious human and ecotoxic effects. As a result of the drawbacks, a current research interest is in identifying and designing new UV filters. One approach that has been explored in recent years is to use nature as inspiration, which is the focus of this review. Both plants and microorganisms have adapted to synthesize their own photoprotective molecules to guard their DNA from potentially harmful UV radiation. The relaxation mechanism of a molecule after it has been photoexcited can be unravelled by several techniques, the ones of most interest for this review being ultrafast spectroscopy and computational methods. Within the literature, both techniques have been implemented on plant-, and microbial-inspired UV filters to better understand their photoprotective roles in nature. This review aims to explore these findings for both families of nature-inspired UV filters in the hope of guiding the future design of sunscreens

Achieving continuity of care: facilitators and barriers in community mental health teams.

BACKGROUND: The integration of mental health and social services for people diagnosed with severe mental illness (SMI) has been a key aspect of attempts to reform mental health services in the UK and aims to minimise user and carer distress and confusion arising from service discontinuities. Community mental health teams (CMHTs) are a key component of UK policy for integrated service delivery, but implementing this policy has raised considerable organisational challenges. The aim of this study was to identify and explore facilitators and barriers perceived to influence continuity of care by health and social care professionals working in and closely associated with CMHTs. METHODS: This study employed a survey design utilising in-depth, semi-structured interviews with a proportionate, random sample of 113 health and social care professionals and representatives of voluntary organisations. Participants worked in two NHS Mental Health Trusts in greater London within eight adult CMHTs and their associated acute in-patient wards, six local general practices, and two voluntary organisations. RESULTS: Team leadership, decision making, and experiences of teamwork support were facilitators for cross boundary and team continuity; face-to-face communication between teams, managers, general practitioners, and the voluntary sector were facilitators for information continuity. Relational, personal, and longitudinal continuity were facilitated in some local areas by workforce stability. Barriers for cross boundary and team continuity were specific leadership styles and models of decision making, blurred professional role boundaries, generic working, and lack of training for role development. Barriers for relational, personal, and longitudinal continuity were created by inadequate staffing levels, high caseloads, and administrative duties that could limit time spent with users. Incompatibility of information technology systems hindered information continuity. Flexible continuity was challenged by the increasingly complex needs of service users. CONCLUSIONS: Substantive challenges exist in harnessing the benefits of integrated CMHT working to deliver continuity of care. Team support should be prioritised in terms of IT provision linked to a review of current models of administrative support. Investment in education and training for role development, leadership, workforce retention, and skills to meet service users' complex needs are recommended

A perspective on femtosecond pump–probe spectroscopy in the development of future sunscreens

Given the negative impacts of overexposure to ultraviolet radiation (UVR) on humans, sunscreens have become a widely used product. Certain ingredients within sunscreens are responsible for photoprotection and these are known, collectively herein, as ultraviolet (UV) filters. Generally speaking, organic UV filters work by absorbing the potentially harmful UVR and dissipating this energy as harmless heat. This process happens on picosecond time scales and so femtosecond pump–probe spectroscopy (FPPS) is an ideal technique for tracking this energy conversion in real time. Coupling FPPS with complementary techniques, including steady-state spectroscopy and computational methods, can provide a detailed mechanistic picture of how UV filters provide photoprotection. As such, FPPS is crucial in aiding the future design of UV filters. This Perspective sheds light on the advancements made over the past two years on both approved and nature-inspired UV filters. Moreover, we suggest where FPPS can be further utilized within sunscreen applications for future considerations

A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

<p>Abstract</p> <p>Background</p> <p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis caused by more than 500 different mutations in the <it>COL7A1 </it>gene and characterized by blistering of the skin following a minimal friction or mechanical trauma.</p> <p>The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation.</p> <p>Methods</p> <p>Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs) throughout the <it>COL7A1 </it>gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin.</p> <p>Results</p> <p>Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation.</p> <p>Conclusion</p> <p>Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (<b><it>CCGCTCAAA_6527insC</it></b>), thus suggesting the presence of a common ancestor.</p

The potential of unmanned aerial systems for sea turtle research and conservation: A review and future directions

This is the final version. Available on open access from Inter Research via the DOI in this recordThe use of satellite systems and manned aircraft surveys for remote data collection has been shown to be transformative for sea turtle conservation and research by enabling the collection of data on turtles and their habitats over larger areas than can be achieved by surveys on foot or by boat. Unmanned aerial vehicles (UAVs) or drones are increasingly being adopted to gather data, at previously unprecedented spatial and temporal resolutions in diverse geographic locations. This easily accessible, low-cost tool is improving existing research methods and enabling novel approaches in marine turtle ecology and conservation. Here we review the diverse ways in which incorporating inexpensive UAVs may reduce costs and field time while improving safety and data quality and quantity over existing methods for studies on turtle nesting, at-sea distribution and behaviour surveys, as well as expanding into new avenues such as surveillance against illegal take. Furthermore, we highlight the impact that high-quality aerial imagery captured by UAVs can have for public outreach and engagement. This technology does not come without challenges. We discuss the potential constraints of these systems within the ethical and legal frameworks which researchers must operate and the difficulties that can result with regard to storage and analysis of large amounts of imagery. We then suggest areas where technological development could further expand the utility of UAVs as data-gathering tools; for example, functioning as downloading nodes for data collected by sensors placed on turtles. Development of methods for the use of UAVs in sea turtle research will serve as case studies for use with other marine and terrestrial taxa

Deficient Plakophilin-1 Expression Due to a Mutation in PKP1 Causes Ectodermal Dysplasia-Skin Fragility Syndrome in Chesapeake Bay Retriever Dogs

In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children

Candidate target genes for loss of heterozygosity on human chromosome 17q21

Loss of heterozygosity (LOH) on chromosome 17q21 has been detected in 30% of primary human breast tumours. The smallest common region deleted occurred in an interval between the D17S746 and D17S846 polymorphic sequences tagged sites that are located on two recombinant PI-bacteriophage clones of chromosome 17q21: 122F4 and 50H1, respectively. To identify the target gene for LOH, we defined a map of this chromosomal region. We found the following genes: JUP, FK506BP10, SC65, Gastrin (GAS) and HAP1. Of the genes that have been identified in this study, only JUP is located between D17S746 and D17S846. This was of interest since earlier studies have shown that JUP expression is altered in breast, lung and thyroid tumours as well as cell lines having LOH in chromosome 17q21. However, no mutations were detected in JUP using single-strand conformation polymorphism analysis of primary breast tumour DNAs having LOH at 17q21. We could find no evidence that the transcription promoter for JUP is methylated in tumour DNAs having LOH at 17q21. We suspect that the target gene for LOH in primary human breast tumours on chromosome 17q21 is either JUP and results in a haploinsufficiency for expression or may be an unidentified gene located in the interval between D17S846 and JUP. © 2004 Cancer Research UK

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases