Prolactin delays hair regrowth in mice

Mammalian hair growth is cyclic, with hair-producing follicles alternating between active (anagen) and quiescent (telogen) phases. The timing of hair cycles is advanced in prolactin receptor (PRLR) knockout mice, suggesting that prolactin has a role in regulating follicle cycling. In this study, the relationship between profiles of circulating prolactin and the first post-natal hair growth cycle was examined in female Balb/c mice. Prolactin was found to increase at 3 weeks of age, prior to the onset of anagen 1 week later. Expression of PRLR mRNA in skin increased fourfold during early anagen. This was followed by upregulation of prolactin mRNA, also expressed in the skin. Pharmacological suppression of pituitary prolactin advanced dorsal hair growth by 3.5 days. Normal hair cycling was restored by replacement with exogenous prolactin for 3 days. Increasing the duration of prolactin treatment further retarded entry into anagen. However, prolactin treatments, which began after follicles had entered anagen at 26 days of age, did not alter the subsequent progression of the hair cycle. Skin from PRLR-deficient mice grafted onto endocrine-normal hosts underwent more rapid hair cycling than comparable wild-type grafts, with reduced duration of the telogen phase. These experiments demonstrate that prolactin regulates the timing of hair growth cycles in mice via a direct effect on the skin, rather than solely via the modulation of other endocrine factors

Increasing the spatial resolution of agricultural land cover maps using a Hopfield neural network

Land cover class composition of remotely sensed image pixels can be estimated using soft classification techniques increasingly available in many GIS packages. However, their output provides no indication of how such classes are distributed spatially within the instantaneous field of view represented by the pixel. Techniques that attempt to provide an improved spatial representation of land cover have been developed, but not tested on the difficult task of mapping from real satellite imagery. The authors investigated the use of a Hopfield neural network technique to map the spatial distributions of classes reliably using information of pixel composition determined from soft classification previously. The approach involved designing the energy function to produce a ‘best guess’ prediction of the spatial distribution of class components in each pixel. In previous studies, the authors described the application of the technique to target identification, pattern prediction and land cover mapping at the sub-pixel scale, but only for simulated imagery.We now show how the approach can be applied to Landsat Thematic Mapper (TM) agriculture imagery to derive accurate estimates of land cover and reduce the uncertainty inherent in such imagery. The technique was applied to Landsat TM imagery of small-scale agriculture in Greece and largescale agriculture near Leicester, UK. The resultant maps provided an accurate and improved representation of the land covers studied, with RMS errors for the Landsat imagery of the order of 0.1 in the new fine resolution map recorded. The results showed that the neural network represents a simple efficient tool formapping land cover from operational satellite sensor imagery and can deliver requisite results and improvements over traditional techniques for the GIS analysis of practical remotely sensed imagery at the sub pixel scale

The influence of prior relationship on perceptions of stalking: A comparison of laypersons, non-specialist police officers and specialist police officers

The current research examined the influence of prior relationship on perceptions of stalking, and compared the perceptions of laypersons, nonspecialist police officers, and specialist police officers. Two studies employed experimental designs where participants were presented with one of three vignettes in which the nature of the prior relationship was manipulated so that the perpetrator and victim were portrayed as strangers, acquaintances, or ex-partners. Participants comprised 101 nonspecialist police officers and 108 laypersons in Study 1, and 49 specialist police officers and 49 nonspecialist police officers in Study 2. Findings indicate that nonspecialist police officers and laypersons shared the common misperception that stranger stalkers present a greater threat to the personal safety of their victims than acquaintance or ex-partner stalkers. Specialist police officers were less susceptible to common misperceptions and believed that intervention was more necessary. Specialist police officers also believed that the perpetrator’s behavior would cause the victim more alarm or personal distress than nonspecialist police officers

Dehydroepiandrosterone sulfate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya

In areas where Plasmodium falciparum malaria is endemic, parasite density, morbidity, and mortality decrease with increasing age, which supports the view that years of cumulative exposure are necessary for the expression of maximal protective immunity. Developmental changes in the host also have been implicated in the expression of maximal resistance. To further evaluate the contribution of host developmental factors in malaria resistance, we examined the relationship between P. falciparum parasitemia and pubertal development in a cross-sectional sample of 12 - 18-year-old schoolgirls from an area of intense transmission in western Kenya. Among pubertal girls, dehydroepiandrosterone sulfate (DHEAS) levels were significantly associated with decreased parasite density, even after adjustment for age. DHEAS levels also were related to increased hemoglobin levels, even after accounting for age and other determinants of hemoglobin level. These findings support the hypothesis that host pubertal development, independent of age and, by proxy, cumulative exposure, is necessary for maximal expression of resistance to malarial infection and morbidity, as assessed by hemoglobin leve

A terminal assessment of stages theory : introducing a dynamic states approach to entrepreneurship

Stages of Growth models were the most frequent theoretical approach to understanding entrepreneurial business growth from 1962 to 2006; they built on the growth imperative and developmental models of that time. An analysis of the universe of such models (N=104) published in the management literature shows no consensus on basic constructs of the approach, nor is there any empirical confirmations of stages theory. However, by changing two propositions of the stages models, a new dynamic states approach is derived. The dynamic states approach has far greater explanatory power than its precursor, and is compatible with leading edge research in entrepreneurship

IGF-1 does not moderate the time-dependent transcriptional patterns of key homeostatic genes induced by sustained compression of bovine cartilage

Objective To determine changes in chondrocyte transcription of a range of anabolic, catabolic and signaling genes following simultaneous treatment of cartilage with Insulin-like growth factor-1 (IGF-1) and ramp-and-hold mechanical compression, and compare with effects on biosynthesis. Methods Explant disks of bovine calf cartilage were slowly compressed (unconfined) over 3-min to their 1 mm cut-thickness (0%-compression) or to 50%-compression with or without 300 ng/ml IGF-1. Expression of 24 genes involved in cartilage homeostasis was measured using qPCR at 2, 8, 24, 32, 48 h after compression ±IGF-1. Clustering analysis was used to identify groups of co-expressed genes to further elucidate mechanistic pathways. Results IGF-1 alone stimulated gene expression of aggrecan and collagen II, but simultaneous 24h compression suppressed this effect. Compression alone up-regulated expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 and transforming growth factor (TGF)-β, an effect not reversed by simultaneous IGF-1 treatment. Temporal changes in expression following IGF-1 treatment were generally slower than that following compression. Clustering analysis revealed five distinct groups within which the pairings, tissue inhibitor of metalloproteinase (TIMP)-3 and ADAMTS-5, MMP-1 and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed, suggesting inherent regulation and feedback in chondrocyte gene expression. While aggrecan synthesis was transcriptionally regulated by IGF-1, inhibition of aggrecan synthesis by sustained compression appeared post-transcriptionally regulated. Conclusion Sustained compression markedly altered the effects of IGF-1 on expression of genes involved in cartilage homeostasis, while IGF-1 was largely unable to moderate the transcriptional effects of compression alone. The demonstrated co-expressed gene pairings suggest a balance of anabolic and catabolic activity following simultaneous mechanical and growth factor stimuli.National Institutes of Health (U.S.) (grant R01-AR33236)National Institutes of Health (U.S.) (grant R01-HG003352)National Institutes of Health (U.S.) (grant P42-ES04699)National Institutes of Health (U.S.) (grant T32-EB006348

Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function

The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipulated cells or those with different surface levels of PODXL define that this axis controls metastasis in vivo. Clinically, interplay between PODXL-GAL3 stratifies prostate cancer patients with poor outcome. Our studies define the molecular mechanisms and context in which PODXL promotes invasion and metastasis

Supermassive Black Hole Binaries: The Search Continues

Gravitationally bound supermassive black hole binaries (SBHBs) are thought to be a natural product of galactic mergers and growth of the large scale structure in the universe. They however remain observationally elusive, thus raising a question about characteristic observational signatures associated with these systems. In this conference proceeding I discuss current theoretical understanding and latest advances and prospects in observational searches for SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA)

Objective: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients. Method: This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32mg delivered dose, N=63) or TAcs (1 mL, 40mg, N=18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week1, Week6, Week12, Week16 or Week20; TAcs: Week6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means), pharmacokinetics (non-compartmental analysis models), and adverse events (AEs) were assessed. Results: SF TA concentrations following FX006 were quantifiable through Week12 (pg/mL: 231,328.9 at Week1; 3590.0 at Week6; 290.6 at Week12); post-TAcs, only 2 of 8 patients had quantifiable SF TA at Week6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 hours and slowly declined to <110 pg/mL over Weeks12-20; following TAcs, plasma TA peaked at 4 hours (9,628.8 pg/mL), decreased to 4,991.1 pg/mL at 24 hours, and was 149.4 pg/mL at Week6, the last post-treatment time point assessed. AEs were similar between groups. Conclusion: In knee OA patients, microsphere-based TA delivery via a single IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs