Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination.

Otto Warburg described tumour cells as displaying enhanced aerobic glycolysis whilst maintaining defective oxidative phosphorylation (OXPHOS) for energy production almost 100 years ago [1, 2]. Since then, the 'Warburg effect' has been widely accepted as a key feature of rapidly proliferating cancer cells [3-5]. What is not clear is how early "Warburg metabolism" initiates in cancer and whether changes in energy metabolism might influence tumour progression ab initio.

PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation.

Melanocytes, replenished throughout life by melanocyte stem cells (MSCs), play a critical role in pigmentation and melanoma. Here, we reveal a function for the metastasis-associated phosphatase of regenerating liver 3 (PRL3) in MSC regeneration. We show that PRL3 binds to the RNA helicase DDX21, thereby restricting productive transcription by RNAPII at master transcription factor (MITF)-regulated endolysosomal vesicle genes.

Feather arrays are patterned by interacting signalling and cell density waves.

Feathers are arranged in a precise pattern in avian skin. They first arise during development in a row along the dorsal midline, with rows of new feather buds added sequentially in a spreading wave. We show that the patterning of feathers relies on coupled fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signalling together with mesenchymal cell movement, acting in a coordinated reaction-diffusion-taxis system.

Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate.

Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. hybridization studies reveal EDAR pathway components including in the developing prostate and localize these factors to prostatic bud epithelium where CTNNB1 target genes are co-expressed.

Hierarchical patterning modes orchestrate hair follicle morphogenesis.

Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction-diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern.

Foxf2 is required for secondary palate development and Tgfβ signaling in palatal shelf mesenchyme.

The secondary palate separates the oral from the nasal cavity and its closure during embryonic development is sensitive to genetic perturbations. Mice with deleted Foxf2, encoding a forkhead transcription factor, are born with cleft palate, and an abnormal tongue morphology has been proposed as the underlying cause. Here, we show that Foxf2(-/-) maxillary explants cultured in vitro, in the absence of tongue and mandible, failed to close the secondary palate.

A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features.

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness.

Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron.

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis.

Longitudinal medical records as a complement to routine drug safety signal analysis.

Purpose: To explore whether and how longitudinal medical records could be used as a source of reference in the early phases of signal detection and analysis of novel adverse drug reactions (ADRs) in a global pharmacovigilance database.

Methods: Drug and ADR combinations from the routine signal detection process of VigiBase® in 2011 were matched to combinations in The Health Improvement Network (THIN). The number and type of drugs and ADRs from the data sets were investigated.

Regionalisation of the skin.

The skin displays marked anatomical variation in thickness, colour and in the appendages that it carries. These regional distinctions arise in the embryo, likely founded on a combinatorial positional code of transcription factor expression. Throughout adult life, the skin's distinct anatomy is maintained through both cell autonomous epigenetic processes and by mesenchymal-epithelial induction.