A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium

Neuronogenesis in the neocortical pseudostratified ventricular epithelium (PVE) is initiated rostrolaterally and progresses caudo- medially as development progresses. Here we have measured the cytokinetic parameters and the fractional neuronal output parameter, Q, of laterally located early-maturing regions over the principal embryonic days (E12-E15) of neocortical neuronogenesis in the mouse. These measures are compared with ones previously made of a medial, late- maturing portion of the PVE. Laterally, as medially, the duration of the neuronogenetic interval is 6 days and comprises 11 integer cell cycles. Also, in both lateral and medial areas the length of G1 phase (TG1) increases nearly 4-fold and is the only cell cycle parameter to change. Q progresses essentially identically laterally and medially with respect to the succession of integer cell cycles. Most importantly, from E12 to E13 there is a steeply declining lateral to medial gradient in TG1. The gradient is due both to the lateral to medial graded stage of neuronogenesis and to the stepwise increase in TG1 with each integer cycle during the neuronogenetic interval. To our knowledge this gradient in TG1 of the cerebral PVE is the first cell biological gradient to be demonstrated experimentally in such an extensive proliferative epithelial sheet. We suggest that this gradient in TG1 is the cellular mechanism for positionally encoding a protomap of the neocortex within the PVE.      

Emerging role of the endothelin axis in ovarian tumor progression

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and the ET receptors, ET(A)R and ET(B)R, represents a novel target in tumor treatment. ET-1 may directly contribute to tumor growth and indirectly modulate tumor-host interactions in various tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors and melanoma. Extensive experimental evidence links ET(A)R overexpression with tumor progression in ovarian cancer. ET(A)R engagement can in fact activate multiple signal transduction pathways including protein kinase C, phosphati-dylinositol 3-kinase, mitogen-activated protein kinase and transactivate epidermal growth factor receptor, which play a role in ovarian tumor growth and invasion. The effects of ET(A)R signaling are wide ranging and involve both cancer cells and their surrounding stroma, including the vasculature. Upon being activated, the ET(A)R mediates multiple tumor-promoting activities, including enhanced cell proliferation, escape from apoptosis, angiogenesis, epithelial-mesenchymal transition and increased motility and invasiveness. These findings indicate that activation of ET(A)R by ET-1 is a key mechanism in the cellular signaling network promoting ovarian cancer growth and progression. The predominant role played by ET(A)R in cancer has led to the development of small molecules that antagonize the binding of ET-1 to ET(A)R. The emerging preclinical data presented here provide a rationale for the clinical evaluation of these molecules in which targeting the related signaling cascade via ET(A)R blockade may be advantageous in the treatment of advanced stage ovarian carcinoma.     

Low-level laser therapy for osteonecrotic lesions: effects on osteoblasts treated with zoledronic acid

Purpose

Clinical studies have shown that low-level laser therapy (LLLT) can improve local tissue healing of bisphosphonate-induced osteonecrosis of the jaw. However, the effects of laser irradiation on bisphosphonate-treated osteoblasts have not been completely elucidated.

Methods

Human osteoblasts were cultured in plain culture medium (DMEM). After 48 h, plain DMEM was replaced by DMEM with no fetal bovine serum, for a 24-h incubation followed by addition of zoledronic acid (5 μM) for additional 48 h. Cells were subjected to LLLT (InGaAsP; 780?±?3 nm; 0.025 W) at 0.5, 1.5, 3, 5, and 7 J/cm², three times every 24 h. Cell viability, total protein production, alkaline phosphatase activity (ALP), mineral nodule formation, gene expression of collagen type I and ALP, and cell morphology were evaluated.

Results

LLLT at 0.5 J/cm² increased cell viability of cultured osteoblasts. ALP activity and gene expression, in addition to mineral nodule formation and Col-I gene expression, were not increased by LLLT. LLLT applied to ZA-treated cells increased Col-I expression at 0.5, 1.5, and 3 J/cm² but did not improve any other cell activity assessed.

Conclusion

LLLT showed limited effects on bisphosphonate-treated osteoblasts.     

Vaccine-elicited Human T Cells Recognizing Conserved Protein Regions Inhibit HIV-1

Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4⁺ cells and inhibited HIV-1 replication by up to 5.79 log₁₀. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8⁺ T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.     

Prevalence and risk factors for hypertension and association with ethnicity in Nigeria: results from a national survey

Hypertension is increasingly being recognised as an important public health problem in sub-Saharan Africa, with 26.9% of men and 28.4% of women in 2000 being estimated to have hypertension.1 Although lower than the prevalence in high-income countries (37.4% in men and 37.2% in women), in terms of numbers of people affected, the burden of hypertension in low- and middle-income countries is greater due to the large population.1Hypertension has been recognised as a strong independent risk factor for heart disease and stroke and a predictor of premature death and disability from cardiovascular complications.2 It has been reported that 13.5% of deaths and 6% of disability-adjusted life years (DALYs) were attributed to hypertension globally, and for low- and middle income people, these figures were 12.9 and 5.6%, respectively over the period 1990 to 2001.3 Although infectious diseases remain the leading cause of mortality and morbidity in sub-Saharan Africa, the prevalence of cardiovascular disease and hypertension is rising rapidly.4It has been emphasised that urbanisation is a key reason for the increasing rates of hypertension, as evidenced by the higher prevalence of hypertension in urban areas.4-6 Urban lifestyles, characterised by sedentary living, increased salt intake, obesity and stress contribute to these differences.5 With the urban population in sub-Saharan Africa projected to increase, a greater risk of hypertension is anticipated.Studies on the association between ethnicity and hypertension in high-income countries have documented a higher prevalence of hypertension in black ethnic groups compared to white ethnic groups.7-9 Reasons for this association are complex, unclear and much debated, reflecting genetic and biochemical mechanisms, and environmental and socio-economic factors.10,11 There is limited evidence regarding differences in the prevalence of hypertension between ethnic groups within the broader classification of black ethnicity.6,12,13Studies in Nigeria and sub-Saharan Africa have mainly involved specific geographical areas or have focused on sub-groups of the population.5,14 Surveys from Nigeria report prevalence estimates ranging from 20.2 to 36.6%, but all have involved participants with different age ranges.15-18 To plan services for hypertension in Nigeria, it is essential to have accurate prevalence estimates for the whole population and to identify populations at risk.Nigeria, which is the most populous country in sub-Saharan Africa, is home to over 250 different ethnic groups. Nigeria is experiencing rapid urbanisation of the population, which is likely to increase the population at risk for hypertension.19 The present study is one of the largest population-based surveys in the region and is able to provide a nationally representative estimate of hypertension for Nigeria.     

Curricular Guidelines for Nursing Graduate Course: contexts, changes and perspectives

Research focusing the curricular guidelines for Nursing Faculty in Brazil as approved in 2001 by the Resolution no 03/2001-CNE. The study aimed at contextualizing and rescueing the historical elaboration process of these guidelines, to discuss the approved content supporting elements to guide the construction of politician-pedagogical projects. Bibliographical sources, documents and interviews were used. Pedagogical principles present in the guidelines were verified; the discussion on the research were approached; the nursery licentiature degree, the Unique System of Health as focus of the formation and the performance of the United Net. The context of the private higher education and health, the economic changes (financial globalization, the performance of international agencies) had conformed the scenery of changes in the graduation in Brazil in the 90' and beginning of the 21st century.