Role of ovarian cancer antigen CA125/MUC16 in development and cancer

Cancer antigen 125 (CA125) is a tumor antigen that is routinely used to monitor the disease progress and the outcome of treatment in ovarian cancer patients. Elevated serum levels of CA125 are detected in over 80% of epithelial ovarian cancer patients. CA125 is a high molecular weight (>1M Dalton) mucin-type glycoprotein encoded by the MUC16 gene on human chromosome 19. Although MUC16 has served as the best serum marker for monitoring growth of ovarian cancer, roles for MUC16 in normal physiology and ovarian cancer are largely unknown. To understand the biological functions of MUC16, I characterized a mouse Muc16 homolog on chromosome 9 by means of expression pattern profiling, phenotype analysis of Muc16 knockout mice, and in vitro and in vivo studies of Muc16 null transformed ovarian surface epithelial (OSE) cells. ^ The mouse Muc16 homolog shares a conserved genomic structure with human MUC16. In addition to being expressed in mouse ovarian cancer, mouse Muc16 mRNA and protein were expressed in the mesothelia covering the heart, lung, ovary, oviduct, spleen, testis, and uterus. The conserved genomic structure and expression pattern of mouse Muc16 to human MUC16 suggests that mouse Muc16 is the ortholog of human MUC16. To understand the biological functions of Muc16, I generated Muc16 knockout mice. Muc16 knockout mice were viable, fertile and normal by one year of age. However, between 18 and 24 months of age, Muc16 knockout mice developed various tissue abnormalities such as ovarian cysts and tumors of the liver and other peritoneal organs. To determine the role of MUC16 in ovarian cancer progression, I established Muc16 null transformed ovarian surface epithelial (OSE) cell lines, following the same method to develop mouse model of epithelial ovarian cancer (Orsulic et al., 2002). Loss of Muc16 did not affect cell morphology, cell proliferation rate, or tumorigenic potential. However, Muc16-null OSE cells showed decreased attachment to extracellular matrix proteins as well as to primary mouse peritoneal mesothelial cells. Peritoneal mesothelia are the most frequent implantation sites of ovarian cancer. Furthermore, a pilot transplantation assay suggests that Muc16 null transformed OSE cells formed less disseminated tumors in the peritoneal cavity compared to wild-type OSE cells. ^ In conclusion, these results demonstrate that MUC16 is not required for normal mouse development or reproduction, but plays important roles in tissue homeostasis, ovarian cancer cell adhesion and dissemination. This study provides the first in vivo evidence of the roles of MUC16 in development, as well as ovarian cancer progression and dissemination. These studies offer valuable insights into possible mechanisms of ovarian cancer development and potential molecular targets for ovarian cancer treatment. ^

A prototype from the Solar Decathlon Competition becomes an educational building in sustanaible architecture

In 2008, the City Council of Rivas-Vaciamadrid (Spain) decided to promote the construction of “Rivasecopolis”, a complex of sustainable buildings in which a new prototype of a zero-energy house would become the office of the Energy Agency. According to the initiative of the City Council, it was decided to recreate the dwelling prototype “Magic-box” which entered the 2005 Solar Decathlon Competition. The original project has been adapted to a new necessities programme, by adding the necessary spaces that allows it to work as an office. A team from university has designed and carried out the direction of the construction site. The new Solar House is conceived as a “testing building”. It is going to become the space for attending citizens in all questions about saving energy, energy efficiency and sustainable construction, having a permanent small exhibition space additional to the working places for the information purpose. At the same time, the building includes the use of experimental passive architecture systems and a monitoring and control system. Collected data will be sent to University to allow developing research work about the experimental strategies included in the building. This paper will describe and analyze the experience of transforming a prototype into a real durable building and the benefits for both university and citizens in learning about sustainability with the building

Construction cost and energy consumption resulting from energy retrofitting in an apartment building in Madrid (Spain).

This theoretical study analyzes the relation between the measures necessesary for the energy retrofitting of a residential building constructed in Madrid, their cost and the improvement of the energy rating of the dwellings. The aim of this work is to establish an evaluation methodology that allows developers and architects to obtain conclusions and orientates therm in the decisioin-making process. It will allow finding the most suitable cost-effective solutions in each case. This paper describes the methodology and the findings obtained. Energy retrofitting and the improvement of the energy behaviour of the building depend on the selection of the retrofitting solutions and also on the investment. In this case study to achieve the best energy rates it is necessary to improve the thermal performance of the envelope as well as the energy systems. Energy retrofitting means an increase in property value but it can't only be considered in economic terms. It is necessary to take into account unquantifiable aspects as increased comfort, improved sound insulation, livability, health, or the elimination of energy poverty situations.

Testing the performance of a green wall system on an experimental building in the summer

It is known that a green wall brings some advantages to a building. It constitutes a barrier against solar radiation, thus decreasing and delaying the incoming heat flux. The aim of this study is to quantify such advantages through analytical comparison between two facades, a vegetal facade and a conventional facade. Both were highly insulated (U-value = 0.3 W/m2K) and installed facing south on the same building in the central territory of Spain. In order to compare their thermal trend, a series of sensors were used to register superficial and indoor air temperature. The work was carried out between 17th August 2012 and 1st October 2012, with a temperature range of 12°C-36°C and a maximum horizontal radiation of 1020 W/m2. Results show that the indoor temperature of the green wall module was lower than the other. Besides, comparing superficial outdoor and indoor temperatures of the two walls to outdoor air temperatures, it was noticed that, due to the shading plants, the green wall superficial temperature was 5 °C lower on the facade, while the bare wall temperature was 15 °C higher. The living wall module temperature was 1.6 °C lower than the outdoor, while the values of the conventional one were similar to the outdoor air temperature.

Cross Ventilation CFD Modeling: Characterization and Study of Different Façade Openings Configurations at the Refurbishment of a Residential Building in Málaga (Spain)

The opening of new windows on the façade is proposed as a refurbishment strategy in an existing building in Málaga to facilitate cross ventilation of dwellings. The building is a residential block of 140 public housing units for rent for people with low income in Málaga (Spain), property of the City Council. By modeling with Computational Fluid Dynamics (CFD), eleven configurations of openings are studied in two different areas of the main housing type of the building. The quantity of introduced/extracted air into/from the room and the generated airflow patterns are obtained. The modeling allows comparing the different openings configurations to determine the most appropriate ventilation option for every room.

Youth participation in development planning: case study of Sayausí (Rural Parish) Cuenca-Ecuador

Young people now represent the highest percentage of the world population. Soon, they will be seniors and they will take decisions for a more orderly and equitable world. For this reason, the participation of young people in development planning is very important and many countries are trying to promote it through various measures. This article analyzes the trajectory of youth participation in the Latin American region and specifically the profile of youth participation in Ecuador, country in which the Constitution recognizes the strategic role of youth in development. The case study of Sayausí rural parish in canton Cuenca is analyzed, through surveys, interviews and an Empowerment Evaluation workshop to young people and decentralized government. The results obtained allow to propose strategies to help improve the participation of youth in the community.

The role of private sector in development: The relation between public-private investment in infrastructure and agricultural exports in developing countries

Increasing foreign private investment in developing countries explains why the Public-Private Investment (PPI) is becoming a key tool to reach the development goal. This article analyzes the relation between PPI in infrastructure and agricultural exports in developing countries. We use the panel data approach (52 countries and 17 years). Results show that PPI in infrastructure has a positive impact on agricultural exports of developing countries. The impact is greater in developing countries with higher income rates. This suggests that the lower income countries require the intervention of public sector without which private investment cannot help to economic development.

The insect neuropeptide prothoracicotropic hormone is released with a daily rhythm: re-evaluation of its role in development.

Prothoracicotropic hormone (PTTH) is the central cerebral neurohormone in insect development. Its release has been believed for decades to be confined to one (or two) critical moments early in each developmental stage at which time it triggers prolonged activation of the prothoracic glands to synthesize and release the steroid molting hormones (ecdysteroids), which elicit developmental responses in target tissues. We used an in vitro assay for PTTH released from excised brains of the bug Rhodnius prolixus and report that release of PTTH does occur at the expected time on day 6, but that this release is merely the first in a daily rhythm of release that continues throughout most of the 21 days of larval-adult development. This finding, together with reports of circadian control of ecdysteroid synthesis and titer throughout this time, raises significant challenges to several features of the current understanding of the hormonal control of insect development. New questions are raised concerning the function(s) of PTTH, its relationship with the prothoracic glands, and the significance of circadian rhythmicity throughout this endocrine axis. The significance of the reported observations derives from the set of entirely new questions they raise concerning the regulation of insect development.

Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors.

The observed in vitro and in vivo benefit of combination treatment with anti-human immunodeficiency virus (HIV) agents prompted us to examine the potential of resistance development when two protease inhibitors are used concurrently. Recombinant HIV-1 (NL4-3) proteases containing combined resistance mutations associated with BMS-186318 and A-77003 (or saquinavir) were either inactive or had impaired enzyme activity. Subsequent construction of HIV-1 (NL4-3) proviral clones containing the same mutations yielded viruses that were severely impaired in growth or nonviable, confirming that combination therapy may be advantageous. However, passage of BMS-186318-resistant HIV-1 (RF) in the presence of either saquinavir or SC52151, which represented sequential drug treatment, produced viable viruses resistant to both BMS-186318 and the second compound. The predominant breakthrough virus contained the G48V/A71T/V82A protease mutations. The clone-purified RF (G48V/A71T/V82A) virus, unlike the corresponding defective NL4-3 triple mutant, grew well and displayed cross-resistance to four distinct protease inhibitors. Chimeric virus and in vitro mutagenesis studies indicated that the RF-specific protease sequence, specifically the Ile at residue 10, enabled the NL4-3 strain with the triple mutant to grow. Our results clearly indicate that viral genetic background will play a key role in determining whether cross-resistance variants will arise.

Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.