Expression of heterogeneous nuclear ribonucleoprotein A2/B1 changes with critical stages of mammalian lung development

Recent reports have demostrated a link between expression of members of the family of heterogeneous nuclear ribonucleoproteins (hnRNPs) and cancer. Overexpression of hnRNP A2/B1 correlated with the eventual development of lung cancer in three different clinical cohorts. We have studied the expression of hnRNP A2/B1 messenger RNA (mRNA) and protein during mammalian development. The expression of hnRNP A2/B1 mRNA and protein are parallel but change dynamically during critical periods in mouse pulmonary development. hnRNP A2/B1 is first detected in the lung in the early pseudoglandular period, peaks at the beginning of the canalicular period, and remains high during the saccular (alveolar) period. In mouse and rat, hnRNP A2/B1 expression is first evident in the earliest lung buds. As lung development progresses, the cuboidal epithelial cells of the distal primitive alveoli show high levels of the ribonucleoprotein, which is almost undetectable in the proximal conducting airways. The expression of hnRNP A2/ B1 is restricted in mature lung. Similar dynamic pattern of expression through lung development was also found in rat and human lung. Upregulated expression of hnRNP A2/B1 at critical periods of lung development was comparable to the level of expression found in lung cancers and preneoplastic lesions and is consistent with hnRNP A2/B1 overexpression playing an oncodevelopmental role

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959+/-0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G(1)/G(0) cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms

A Sweet Killer: Mesoporous Polysaccharide Confined Silver Nanoparticles for Antibacterial Applications

Silver nanoparticles (AgNP) confined within porous starch have been prepared in a simple, green and efficient manner, utilising the nanoporous structure of predominantly mesoporous starch (MS) to act as nanoparticle stabiliser, support and reducing surface. MS/AgNP materials present high surface areas (SBET > 150 m2 g−1) and mesopore volumes (Vmeso > 0.45 cm3 g−1). The interaction of the AgNP precursor and forming nanoparticle nuclei with the mesoporous domains of the porous polysaccharide, direct porosity to increasingly narrower and more defined pore size distributions, indicative of a degree of cooperative assembly. Transmission electron microscopy images indicated the presence of spherical AgNP of a size reflective of the porous polysaccharide mesopore diameter (e.g., 5–25 nm), whilst XPS analysis confirmed the metallic Ag0 state. Materials were prepared at relatively low Ag loadings (<0.18 mmol g−1), demonstrating excellent antimicrobial activity in solid and liquid phase testing against Gram negative (E. coli) and positive (S. aureus) model bacteria. The resulting materials are biocompatible and present a useful solid porous carbohydrate-based polymer vehicle to control the AgNP size regime and facilitate transference to a biological environment

Bonsais in a Wild Forest? A Historical Interpretation of the Longevity of Large Spanish Family Firms

En este artículo se presentan los primeros resultados de una investigación en curso sobre la longevidad de las grandes empresas familiares españolas. Su principal objetivo es proporcionar datos sólidos sobre un tema en el que abundan más las opiniones que las estadísticas científicas, así como identificar las claves de la supervivencia y competitividad de las cerca de 250 empresas en que se basa el estudio. Se concluye que esta realidad no es sólo el resultado de dos décadas de integración económica en Europa o de una buena dotación de recursos naturales, sino también de un largo período de aprendizaje y de la combinación de dos factores: la especialización en nichos de mercado que no fueron objeto de interés estratégico por parte del Estado, y la habilidad para consolidar redes personales de cooperación e influencia dentro y fuera del país.This study presents the first results of an on-going study of longevity of large Spanish family firms. Its main objective is to provide solid data for a topic in which opinions are more abundant than scientific statistics, as well as to identify the keys to the survival and competitiveness of the almost 250 firms included in the study. It concludes that this reality is not just the result of two decades of integration in Europe or a fortunate endowment with some natural resources, but the outcome of a long learning process and the combination of two factors: specialization in market niches in which the state had no strategic interests and the creation of personal networks of cooperation and influence within and outside Spain

Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study

Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer’s disease. However, how sleep apnea affects longitudinal risk for Alzheimer’s disease is less well understood. Objectives: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. Measurements and Main Results: We found that severity of OSA indices (AHIall [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively). Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A review of the effects of colour and light on non-image function in humans

This paper reviews current knowledge on non-image-forming aspects of vision. Developments in the last 20 years have included the discovery of a fifth class of human visual pigment (melanopsin), in addition to the three classes of photopsin to be found in the cones and rhodopsin in the rods in the human retina. Melanopsin is found in a small number of retinal ganglion cells which then, in addition to receiving input from rods and cones, are intrinsically photosensitive. These retinal ganglion cells send their input primarily to the hypothalamus, where they help to regulate the circadian system (daily rhythms of sleep patterns, body temperature, heart rate, etc.). The discovery of the anatomical basis of non-image-forming vision has led to a great deal of research into the effects of light on sleep, depression and mood, retinal photodamage and well-being, amongst other factors. Given that recent technological innovations in LED lighting now give us greater control over environmental lighting, it is timely to review the non-visual effects of light in humans in order to inform lighting design in the future

Current benzodiazepine issues

This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral effects. Reviews of epidemiological, clinical and experimental literature indicated that the previous conclusion about abuse of these drugs still holds: the vast majority of the use of benzodiazepines is appropriate. Problems of nonmedical use arise nearly exclusively among people who abuse other drugs. Nevertheless, there are reasons for concern about patients who take benzodiazepines regularly for long periods of time. These drugs can produce physiological dependence when taken chronicaly, and although this does not appear to result in dose escalation or other evidence of “psychological dependence,” physiological dependence can result in patient discomfort if drug use is abruptly discontiniued. Also, physicians are currently prescribing shorter-acting benzodiazepines in preference to longer-acting benzodiazepines. The shorter-acting drugs can produce a more intense withdrawal syndrome following chronic administration. Furthermore, rates of use of benzodiazepines increase with age, and elderly patients are more likely than younger ones to take the drug chronically. The clearest adverse effect of benzodiazepines is impairment of memory. This, too, may be particular concern in older patients whose recall in the absence of drug is typically impaired relative to younger individuals, and who are more compromised following drug administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46347/1/213_2005_Article_BF02245824.pd