Mechanisms of robustness in gene regulatory networks involved in neural development

The functions of living organisms are affected by different kinds of perturbation, both internal and external, which in many cases have functional effects and phenotypic impact. The effects of these perturbations become particularly relevant for multicellular organisms with complex body patterns and cell type heterogeneity, where transcriptional programs controlled by gene regulatory networks determine, for example, the cell fate during embryonic development. Therefore, an essential aspect of development in these organisms is the ability to maintain the functionality of their genetic developmental programs even in the presence of genetic variation, changing environmental conditions and biochemical noise, a property commonly termed robustness. We discuss the implication of different molecular mechanisms of robustness involved in neurodevelopment, which is characterized by the interplay of many developmental programs at a molecular, cellular and systemic level. We specifically focus on processes affecting the function of gene regulatory networks, encompassing transcriptional regulatory elements and post-transcriptional processes such as miRNA-based regulation, but also higher order regulatory organization, such as gene network topology. We also present cases where impairment of robustness mechanisms can be associated with neurodevelopmental disorders, as well as reasons why understanding these mechanisms should represent an important part of the study of gene regulatory networks driving neural development

Relationship between vascularity, age and survival in non-small-cell lung cancer.

Lung tumours in the elderly show reduced growth potential; impaired angiogenesis may contribute to this phenomenon. Recent studies have suggested that the angiogenic potential of a tumour may be inferred by the vascularity measured in histological sections. The purpose of this study has been to determine whether vascularity is related to age, survival or other clinical parameters in resected non-small-cell lung cancer (NSCLC). A group of 88 consecutive patients with a follow-up period of at least 5 years was selected. The group exhibited a wide age range (37-78 years) and similar survival characteristics to those of the general NSCLC population. Tumour sections were stained with a pan-endothelial antibody (vWF) and vascularity was quantitated, without knowledge of the clinical details, by three methods: highest microvascular density; average microvascular density; and average microvascular volume. The results were analysed by non-parametric statistical tests. A correlation was found between all three methods of quantitation. Vascularity was not associated with age, sex, tumour type, stage, volume, size (TNM-T) nodal status (TNM-N) or survival. However, survival time was generally longer for patients with higher vascularity, reaching borderline significance (P = 0.06) for the average microvascular density values. Higher tumour volume (P = 0.02) and stage (P = 0.05) were associated with lower survival times. Using multivariate survival analysis, tumour volume was the only factor related to survival. We conclude that vascularity is not associated with age and has no significant prognostic value in NSCLC

High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. the results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of ( pro) renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. the increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. the consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.UNIFESP, Div Renal, BR-04023900 São Paulo, BrazilUNIFESP, Div Renal, BR-04023900 São Paulo, BrazilWeb of Scienc

Laser-UV-microirradiation of interphase nuclei and posttreatment with caffeine: a new approach to establish the arrangement of interphase chromosomes

Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small area of the metaphase spread, III) mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus

Covering one eye in fixation-disparity measurement causes slight movement of fellow eye

In the subjective measurement of fixation disparity (FD), the subject fuses contours presented in the peripheral macular areas of both eyes (fusion lock). The position of the eyes relative to each other is monitored by means of two haploscopically seen vertical lines presented in the central macular area, one above and one below a binocularly seen horizontal line. The subject is instructed to shift one of the vertical lines horizontally until the two are aligned, while fixating their intersection with the horizontal line. It has recently been questioned whether the foveolae really are pointed towards the perceived intersection. In this study, we monitored the position of one eye while intermittently covering the fellow eye, while the subject maintained fixation of the intersection of the remaining vertical line and the horizontal line. We found slight differences in position of the measured eye, depending on whether the other eye was covered or not, i.e. depending on the presence or absence of fusion in the macular periphery. These differences were more pronounced in the non-dominant eye

Smoke gets in your eyes:what is sociological about cigarettes?

Contemporary public health approaches increasingly draw attention to the unequal social distribution of cigarette smoking. In contrast, critical accounts emphasize the importance of smokers’ situated agency, the relevance of embodiment and how public health measures against smoking potentially play upon and exacerbate social divisions and inequality. Nevertheless, if the social context of cigarettes is worthy of such attention, and sociology lays a distinct claim to understanding the social, we need to articulate a distinct, positive and systematic claim for smoking as an object of sociological enquiry. This article attempts to address this by situating smoking across three main dimensions of sociological thinking: history and social change; individual agency and experience; and social structures and power. It locates the emergence and development of cigarettes in everyday life within the project of modernity of the nineteenth and twentieth centuries. It goes on to assess the habituated, temporal and experiential aspects of individual smoking practices in everyday lifeworlds. Finally, it argues that smoking, while distributed in important ways by social class, also works relationally to render and inscribe it

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease

Work relations and the multiple dimensions of the work-life boundary: Hairstyling at home

This article proposes a multidimensional approach to analysis of the work-life boundary and examines the affects of particular social and organizational relations on the preservation or porous-ness of different dimensions. In line with Nippert-Eng (1996), it is suggested that different dimensions of the boundary are reinforced or weakened by different social and organizational pressures. Analysis describes a specific type of multidimensional breaching – instances when work is taken outside of the worksite (spatial breaching) and is carried out outside of work-time (temporal breaching). Empirical research was conducted among hairstylists working in salons and barbershops in a city in the North of England. Because of the nature of the tasks involved in hairstyling – that the skills involved are widely exchangeable and so may be employed in extra-work environments and temporalities – hairstylists provide a nice site for investigating the circumstances when this does (or does not) occur. Data collection involved a comprehensive self-completion survey of salons and barbershops in the city (response rate: 40%; N=132) and semi-structured interviews with 70 stylists working in 52 salons or barbershops. Findings demonstrate that work relations (hairstylists’ structural relations of production – whether a worker is an owner-proprietor, chair-renter, on-commission stylist, basic-only stylist, or trainee) are critical in determining both workers’ ability and desire to resist the seepage of work into their social lives as well as the particular dimensions of the boundary that are breached. This is because work relations affect the relative importance of four identified motivations for taking work out of the salon (income production; training; inter-personal reciprocity rooted in social relations; and inter-personal reciprocity rooted in the workplace)