Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis

BACKGROUND: APC (Adenomatous polyposis coli) plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process. METHODS: To elucidate the biological dysregulation underlying adenoma formation we examined global gene expression profiles of adenomas and corresponding normal mucosa from an FAP patient. Differential expression of the most significant gene identified in this study was further validated by mRNA in situ hybridization, reverse transcriptase PCR and Northern blotting in different sets of adenomas, tumours and cancer cell lines. RESULTS: Eighty four genes were differentially expressed between all adenomas and corresponding normal mucosa, while only seven genes showed differential expression within the adenomas. The first group included pregnancy specific β-1 glycoprotein 9 (PSG9) (p < 0.006). PSG9 is a member of the carcinoembryonic antigen (CEA)/PSG family and is produced at high levels during pregnancy, mainly by syncytiotrophoblasts. Further analysis of sporadic and familial colorectal cancer confirmed that PSG9 is ectopically upregulated in vivo by cancer cells. In total, deregulation of PSG9 mRNA was detected in 78% (14/18) of FAP adenomas and 75% (45/60) of sporadic colorectal cancer cases tested. CONCLUSION: Detection of PSG9 expression in adenomas, and at higher levels in FAP cases, indicates that germline APC mutations and defects in Wnt signalling modulate PSG9 expression. Since PSG9 is not found in the non-pregnant adult except in association with cancer, and it appears to be an early molecular event associated with colorectal cancer monitoring of its expression may be useful as a biomarker for the early detection of this disease

Micro-spectroscopic investigation of selenium-bearing minerals from the Western US Phosphate Resource Area

Mining activities in the US Western Phosphate Resource Area (WPRA) have released Se into the environment. Selenium has several different oxidation states and species, each having varying degrees of solubility, reactivity, and bioavailability. In this study we are investigating the speciation of Se in mine-waste rocks. Selenium speciation was determined using bulk and micro-x-ray absorption spectroscopy (XAS), as well as micro-x-ray fluorescence mapping. Rocks used for bulk-XAS were ground into fine powders. Shale used for micro-XAS was broken along depositional planes to expose unweathered surfaces. The near edge region of the XAS spectra (XANES) for the bulk rock samples revealed multiple oxidation states, with peaks indicative of Se(-II), Se(IV), and Se(+VI) species. Micro-XANES analysis of the shale indicated that three unique Se-bearing species were present. Using the XANES data together with ab initio fitting of the extended x-ray absorption fine structure region of the micro-XAS data (micro-EXAFS) the three Se-bearing species were identified as dzharkenite, a di-selenide carbon compound, and Se-substituted pyrite. Results from this research will allow for a better understanding of the biogeochemical cycling of Se in the WPRA

Enzymatic hydrolysis of sorghum straw using native cellulase produced by T. reesei NCIM 992 under solid state fermentation using rice straw

Cellulose is a major constituent of renewable lignocellulosic waste available in large quantities and is considered the most important reservoir of carbon for the production of glucose, for alternative fuel and as a chemical feedstock. Over the past decade, the emphasis has been on the enzymatic hydrolysis of cellulose to glucose and the efficiency of which depends on source of cellulosic substrate, its composition, structure, pretreatment process, and reactor design. In the present study, efforts were made to produce cellulase enzyme using rice straw. The produced enzyme was used for the hydrolysis of selected lignocellulosic substrate, i.e., sorghum straw. When rice straw was used as a substrate for cellulase production under solid state fermentation, the highest enzyme activity obtained was 30.7 FPU/gds, using T. reesei NCIM 992. 25 FPU/g of cellulase was added to differently treated (native, alkali treated, alkali treated followed by 3% acid treated and alkali treated followed by 3 and 5% acid treated) sorghum straw and hydrolysis was carried out at 50 °C for 60 h. 42.5% hydrolysis was obtained after 36 h of incubation. Optimization of enzyme loading, substrate concentration, temperature, time and buffer yielded a maximum of 546.00 ± 0.55 mg/g sugars (54.60 ± 0.44 g/l) with an improved hydrolysis efficiency of 70 ± 0.45%. The enzymatic hydrolyzate can be used for fermentation of ethanol by yeasts

Establishment creation and destruction across business density cycles: US evidence

This paper investigates how business establishment entry and exit are affected by cycles in business density. We assess how entry/exit behave when markets over and under shoot a dynamic equilibrium number of businesses and whether these effects differ between manufacturing and service industries. Overall, we find persistent cycles where the actual number of business establishments is typically not equal to the dynamic equilibrium number even though it gravitates towards it. We uncover a systematic pattern which indicates that in disequilibrium entry is dis-equilibrating while closure is equilibrating. For example, the entry rate plays a dis-equilibrating role by accelerating in an overshoot, however as exits accelerate even faster in an overshoot they help move the industry towards an equilibrium. Overall, the results indicate that entrepreneurs and corporations operate with a herd instinct thereby increasing establishments in a cyclical business density over shoot and decreasing them in an under shoot. In terms of economic policy, the results question whether government policy aimed at promoting business creation and expansion ought to have a counter business density cyclical dimension. In other words, should business start-up and growth be promoted more strongly in business density under shoots than over shoots

Comparing the Functional Independence Measure and the interRAI/MDS for use in the functional assessment of older adults: a review of the literature

<p>Abstract</p> <p>Background</p> <p>The rehabilitation of older persons is often complicated by increased frailty and medical complexity - these in turn present challenges for the development of health information systems. Objective investigation and comparison of the effectiveness of geriatric rehabilitation services requires information systems that are comprehensive, reliable, valid, and sensitive to clinically relevant changes in older persons. The Functional Independence Measure is widely used in rehabilitation settings - in Canada this is used as the central component of the National Rehabilitation Reporting System of the Canadian Institute of Health Information. An alternative system has been developed by the interRAI consortium. We conducted a literature review to compare the development and measurement properties of these two systems.</p> <p>Methods</p> <p>English language literature published between 1983 (initial development of the FIM) and 2008 was searched using Medline and CINAHL databases, and the reference lists of retrieved articles. Relevant articles were summarized and charted using the criteria proposed by Streiner. Additionally, attention was paid to the ability of the two systems to address issues particularly relevant to older rehabilitation clients, such as medical complexity, comorbidity, and responsiveness to small but clinically meaningful improvements.</p> <p>Results</p> <p>In total, 66 articles were found that met the inclusion criteria. The majority of FIM articles studied inpatient rehabilitation settings; while the majority of interRAI/MDS articles focused on nursing home settings. There is evidence supporting the reliability of both instruments. There were few articles that investigated the construct validity of the interRAI/MDS.</p> <p>Conclusion</p> <p><b>A</b>dditional psychometric research is needed on both the FIM and MDS, especially with regard to their use in different settings and with different client groups.</p

Visual attention and action: How cueing, direct mapping, and social interactions drive orienting

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated

The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia