Influence of Caloric Restriction on Constitutive Expression of NF-κB in an Experimental Mouse Astrocytoma

Many of the current standard therapies employed for the management of primary malignant brain cancers are largely viewed as palliative, ultimately because these conventional strategies have been shown, in many instances, to decrease patient quality of life while only offering a modest increase in the length of survival. We propose that caloric restriction (CR) is an alternative metabolic therapy for brain cancer management that will not only improve survival but also reduce the morbidity associated with disease. Although we have shown that CR manages tumor growth and improves survival through multiple molecular and biochemical mechanisms, little information is known about the role that CR plays in modulating inflammation in brain tumor tissue.Phosphorylation and activation of nuclear factor κB (NF-κB) results in the transactivation of many genes including those encoding cycloxygenase-2 (COX-2) and allograft inflammatory factor-1 (AIF-1), both of which are proteins that are primarily expressed by inflammatory and malignant cancer cells. COX-2 has been shown to enhance inflammation and promote tumor cell survival in both in vitro and in vivo studies. In the current report, we demonstrate that the p65 subunit of NF-κB was expressed constitutively in the CT-2A tumor compared with contra-lateral normal brain tissue, and we also show that CR reduces (i) the phosphorylation and degree of transcriptional activation of the NF-κB-dependent genes COX-2 and AIF-1 in tumor tissue, as well as (ii) the expression of proinflammatory markers lying downstream of NF-κB in the CT-2A malignant mouse astrocytoma, [e.g. macrophage inflammatory protein-2 (MIP-2)]. On the whole, our date indicate that the NF-κB inflammatory pathway is constitutively activated in the CT-2A astrocytoma and that CR targets this pathway and inflammation.CR could be effective in reducing malignant brain tumor growth in part by inhibiting inflammation in the primary brain tumor

Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

BACKGROUND: To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH). METHODS: Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. RESULTS: We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase. CONCLUSION: Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively

A hydrogeomorphological approach to quantification of groundwater discharge to streams in South Africa

In South Africa, the flow requirements for maintaining the normal functioning of aquatic ecosystems is termed the "ecological reserve", and these should be determined when a licence application for water allocation is processed. Determination of the ecological reserve entails investigation of the relationship between the major interactive components of the hydrologic cycle, namely groundwater and surface water bodies including rivers, lakes and estuaries. Information on groundwater discharge towards surface water bodies is critical for the water resource manager to make a decision regarding the amount of groundwater allocation that can be licensed without causing a negative impact on aquatic ecosystems. Existing techniques of hydrograph-separation are too subjective either due to the fact that assumptions of the techniques cannot be met in reality or that the parameters used in models do not have physical meanings. This paper presents a geomorphologic framework under which the quantification of groundwater from a hydrograph is discussed. A focus is placed on hydrogeomorphological typing that can be used to guide a process of separating groundwater discharge time series from hydrographs where a monthly groundwater discharge time series is required for comparison with instream flow requirements. For generating monthly groundwater discharge time series, a generic procedure is proposed, which is applied in a case study. WaterSA Vol.28(4) 2002: 375-38

An indicator-based approach for cross-realm coastal biodiversity assessments

Ecosystem status assessments are generally separated into realm-specific analyses (terrestrial, freshwater, estuarine or marine), but without integrating these into a coherent assessment of coastal biodiversity across the land–sea interface. Trends in assessment indicators in coastal versus non-coastal areas have also rarely been considered. In this study we aimed to compile the first cross-realm national biodiversity assessment for the South African coast using three key indicators. The ecological condition, ecosystem threat status, and ecosystem protection level of coastal ecosystem types (n = 186) were determined and compared with those of non-coastal ecosystem types (n = 444). Nearly half (46.9%) of the South African coastal habitat has been degraded compared with 20% of non-coastal areas. Proportionately, there are three-times (60%) as many threatened coastal ecosystem types (or 55% by area) as there are threatened non-coastal ecosystem types (19%, 6% by area). Despite the impacted state of coastal biodiversity, protection levels are generally higher in the coastal zone (87% of ecosystem types have some protection) compared with non-coastal areas (75%), although fewer coastal ecosystem types have met their biodiversity targets (24%, vs 28% for non-coastal ecosystem types). These results illustrate the importance of using a cross-realm approach for status assessments, management and conservation of coastal biodiversity. The assessment methods described are flexible and widely applicable to other regions

Textural history of recent basaltic-andesites and plutonic inclusions from Merapi volcano

Mt. Merapi in Central Java is one of the most active stratovolcanoes on Earth and is underlain by a multistage plumbing system. Crystal size distribution analyses (CSD) were carried out on recent Merapi basaltic-andesites and co-eruptive magmatic and plutonic inclusions to characterise the crystallisation processes that operate during storage and ascent and to obtain information on respective time scales. The basaltic-andesites exhibit log-linear, kinked-upwards CSD curves for plagioclase and clinopyroxene that can be separated into two main textural populations. Large plagioclase phenocrysts (≥1.6 mm) make up one population, but correspond to crystals with variable geochemical composition and reflect a period of crystal growth at deep to mid-crustal levels. This population was subsequently influenced by crystal accumulation and the onset of crustal assimilation, including the incorporation of high-Ca skarn-derived xenocrysts. Textural re-equilibration is required for these crystals to form a single population in CSD. A second episode of crystal growth at shallower levels is represented by chemically homogenous plagioclase crystals <1.6 mm in size. Crustal assimilation is indicated by, for example, oxygen isotopes and based on the CSD data, crystallisation combined with contamination is likely semi-continuous in these upper crustal storage chambers. The CSD data observed in the basaltic-andesite samples are remarkably consistent and require a large-volume steady state magmatic system beneath Merapi in which late textural equilibration plays a significant role. Plagioclase CSDs of co-eruptive magmatic and plutonic inclusions may contain a third crystal population (<1 mm) not found in the lavas. This third population has probably formed from enhanced degassing of portions of basaltic-andesite magma at shallow crustal levels which resulted in increased crystallinity and basaltic-andesite mush inclusions. A suite of coarse plutonic inclusions is also present that reflects crystallisation and accumulation of crystals in the deep Merapi plumbing system, as deduced from CSD patterns and mineral assemblages