Pigmentation: Watching hair turn grey

Analysing changes in hair pigmentation may lead to a better understanding of the impacts of ‘life events’ on human biology and aging

Fluorimetricex vivoquantification of protease debriding efficacy on natural substrate

Debridement is the process of removal of necrotic and infected tissue to clean a wound or burn and expedite healing. Proteases such as papain, bromelain and collagenase that promote debridement by degrading proteins in the dead tissue are in use today. However, the only method to measure debriding efficacy in vitro is the fluorescent monitoring of the digestion of an Artificial Wound Eschar (AWE) substrate. This AWE substrate contains a pellet of only three eschar matrix proteins collagen, elastin, and fibrin which do not account for the complexity and the composition of necrotic tissue. Here, we describe an ex vivo method using dry necrotic full thickness human skin and ortho-phthalaldehyde (OPA), a molecule commonly used for sensitive fluorimetric protein detection to monitor debridement activity. We advocate this simple yet sensitive approach to detect debridement efficacy that can readily be used commercially to benchmark products prior to in vivo testing. This article is protected by copyright. All rights reserved

Biotin-tagged fluorescent sensor to visualize "mobile' Zn2+ in cancer cells

A cancer cell-targeting fluorescent sensor has been developed to image mobile Zn2+ by introducing a biotin group. It shows a highly selective response to Zn2+ in vitro, no toxicity in cellulo and images 'mobile' Zn2+ specifically in cancer cells. We believe this probe has the potential to help improve our understanding of the role of Zn2+ in the processes of cancer initiation and development

Can the skin make you fat? A role for the skin in regulating adipose tissue function and whole-body glucose and lipid homeostasis

This work was supported by the following funding: BBSRC-LIDO Studentship (PWC, MPP and EE); Diabetes UK project grant (15/0005154) (PWC); British Skin Foundation (RFH, MP); MedCity (RFH)

Early growth response 2 (EGR2) is a novel regulator of the senescence programme.

Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up-regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down-regulates p16 levels and increases the pool of p16- p21- 'reversed' cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence

Clusters of ant colonies and robust criticality in a tropical agroecosystem

Although sometimes difficult to measure at large scales, spatial pattern is important in natural biological spaces as a determinant of key ecological properties such as species diversity, stability, resiliency and others(1-6). Here we demonstrate, at a large spatial scale, that a common species of tropical arboreal ant forms clusters of nests through a combination of local satellite colony formation and density- dependent control by natural enemies, mainly a parasitic fly. Cluster sizes fall off as a power law consistent with a so-called robust critical state(7). This endogenous cluster formation at a critical state is a unique example of an insect population forming a non- random pattern at a large spatial scale. Furthermore, because the species is a keystone of a larger network that contributes to the ecosystem function of pest control, this is an example of how spatial dynamics at a large scale can affect ecosystem service at a local level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62598/1/nature06477.pd

GLI2 Is a Regulator of beta-Catenin and Is Associated with Loss of E-Cadherin, Cell Invasiveness, and Long-Term Epidermal Regeneration

Research Advisory Board of the Barts and the London Charity (Grant DERG1D8R

MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

Fight For Sight Fellowship, UK; National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHSFoundation Trust and UCL Institute of Ophthalmology. J.W. and C.C. acknowledge support from Cancer Research UK Centre of Excellence Award to Barts Cancer Centre [C16420/A18066

MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets

A Clinical and Biological Guide for Understanding Chemotherapy-Induced Alopecia and its Prevention

Chemotherapy-induced alopecia (CIA) is the most visibly distressing side effect of commonly administered chemotherapeutic agents. As psychological health has huge relevance on lifestyle, diet and self-esteem, it is important for clinicians to fully appreciate the psychological burden that CIA can place on patients. Here, for the first time, we provide a comprehensive review encompassing the molecular characteristics of the human hair follicle (HF), how different anticancer agents damage the HF to cause CIA, subsequent HF pathophysiology and we assess known and emerging prevention modalities that have aimed to reduce or prevent CIA. We argue that, at present, scalp cooling is the only safe and FDA-cleared modality available, and we highlight the extensive available clinical and experimental (biological) evidence for its efficacy. The likelihood of a patient that uses scalp cooling during chemotherapy maintaining enough hair to not require a wig is approximately 50%. This is despite different types of chemotherapy regimens, patient-specific differences and possible lack of staff experience in effectively delivering scalp cooling. The increased use of scalp cooling and an understanding of how to deliver it most effectively to patients has enormous potential to ease the psychological burden of CIA, until other, more efficacious, equally safe treatments become available