Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene

Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor.

Potential causes of mortality for horseshoe crabs (Limulus polyphemus) during the biomedical bleeding process

Biomedical companies catch and bleed horseshoe crabs for the production of Limulus amebocyte lysate (LAL), a product used for protecting public health (Berkson and Shuster, 1999). LAL is a clotting agent, derived solely from horseshoe crab blood cells, which is used to detect the presence of pathogenic gramnegative bacteria in injectable drugs and implantable medical and dental devices (Mikkelsen, 1988; Novitsky, 1991). In addition, LAL is used in many diagnostic tests for such illnesses as gram-negative bacterial meningitis and typhoid fever (Ding and Ho, 2001). Because the LAL test allows one to detect femtogram levels of endotoxin (Ding and Ho, 2001), it is the most effective test for detecting endotoxin contamination, and its increasing use in medical and pharmaceutical laboratories makes it a highly valued product.

Fisheries potential of village dams in northern Ghana

Results of a twelve-month assessment of the fisheries and aquaculture potential of small waterbodies (SWBs) in the West Gonja District of Northern Ghana are presented. The primary objectives of the project were to established whether the fisheries within the reservoir basins in the West Gonja and Nanumba Districts (Northern Region) could be enhanced and aquaculture associated with the SWBs could be viable.

Reference area as a factor affecting potential yield estimates of coral reef fishes

A compilation of 48 estimates of Caribbean and Pacific coral reef fish catches, ranging from 0.1 to 23.7 t km super(-2) year super(-1), obtained from coral reef areas ranging from 0.1 to nearly 4-10 super(5) km super(2), are used to show that observed catches, and hence potential yield estimates, depend strongly on the reference area. The implications for coral reef fisheries assessments are discussed.

Potential of genetics for aquaculture development in Africa

Aquaculture in Africa is fairly insignificant by world standards and accounts for a mere 0.4 per cent of global aquaculture production. The application of genetics can play an important role in efforts to increase aquaculture production in Africa through methods such as selective breeding, hybridization, chromosome manipulation and use of YY “supermales”. Other issues that need to be addressed are limited genetic research facilities, funding, human capacity and suitable species for aquaculture.

The fisheries of Zanzibar: potential for new investments

Zanzibar, one of the poorest areas of sub-Saharan Africa, has a good potential for foreign investment in offshore (EEZ) marine capture fisheries, in aquaculture and in fi sheries infrastructure. Zanzibar’s fisheries resources could be better managed in an effort to alleviate the poverty of its rural population and to provide food security. At present, Zanzibar’s fisheries are artisanal and its total annual production of fish of just over 20000 t, caught in inshore waters, is consumed locally. The government of Zanzibar has liberalized its policies to make Zanzibar a good environment for foreign investment.

Potential of grouper hybrid (Epinephelus fuscoguttatus x E. polyphekadion) for aquaculture

The marine grouper species are considered high value food fish in several countries. However, controlled breeding and hatchery production of grouper fingerlings for commercial farming is still in its infancy. Investigations on the growth performance of the brown marbled grouper Epinephelus fuscoguttatus (Forskal), camouflage grouper E. polyphekadion (Bleeker) and their hybrid (E. fuscoguttatus x E. polyphekadion) under hatchery and growout culture conditions indicate the potential of grouper hybrids for aquaculture.

Potential for the development of aquaculture in Africa

Aquaculture production in Africa has remained low despite the huge potential that exists on the continent. In order for this potential to be realized, it is necessary to refocus the direction of aquaculture development. This paper concludes that for further growth to occur it is necessary to: (i) widen the range of production systems; (ii) increase production intensities and efficiencies; (iii) develop management technologies for indigenous species that target local niche markets; (iv) put more emphasis on marketing and processing of high value products; (v) promote policy research on how aquaculture production can respond to changing macroeconomic policies; and (vi) accelerate the disengagement of government from activities that can best be done by the private sector.

The potential for crop rotation in controlling diseases in shrimp culture

The use of antibiotics and other chemicals in controlling shrimp pathogens become ineffective as the strains grow more resistant to these chemicals. Moreover, the bacterial pathogen (Vibrio harveyi) produced biofilm coating that protects it from dying and disinfection procedures that are followed during pond preparation. Biological control is being considered as an alternative means of preventing shrimp disease outbreak. The main principle behind biological control is to enhance the growth of beneficial microorganisms which serve as antagonists or target pathogens. The paper discusses shrimp and tilapia crop rotation as a form of effective biological control, a technique which is already being practiced in Indonesia and the Philippines.

Aquaculture potential of seahorses and pipefishes

The characteristics, food and feeding, reproduction and breeding of sea horse and pipefishes (Synanthidae) are presented together with the aspects of syngnathid culture.