Supply chain and marketing of sea grapes,Caulerpa racemosa (Forsskål) J. Agardh (Chlorophyta: Caulerpaceae) in Fiji,Samoa and Tonga

This report describes for the first time the supply chain of Caulerpa racemosa in three Pacific Island countries. The harvesting and marketing of C. racemosa are important subsistence activities for villagers in Fiji and Samoa, less so in Tonga. At least 150 harvesters are involved in Fiji, some 100 in Samoa and only a handful in Tonga. The annual combined crop is of some 123 t valued at around US$266,492. In Fiji, it is projected that supply does not meet local demand and there is a potential export market that is currently operating at a pilot project level. In Samoa, the supply is considered adequate for the current market. In Tonga, harvesting is carried out by a few families and supplies a niche market in that country. The possibilities of field cultivation of Caulerpa have been explored but, at present, with only limited success in Samoa. The supply chain is simple in all three countries, and only in Fiji are middlemen involved in the distribution process. The limitations for marketing include the fact that only a few sites supply most of the crop in all the three countries, that all sites need to be conserved through sustainable harvesting methods, the short shelf life of the crop and a lack of information on the carrying capacity of harvest sites. Caulerpa remains a crop that fulfils a niche market but has the potential to be scaled up for additional livelihood development in the future.     

Arc1p organizes the yeast aminoacyl-tRNA synthetase complex and stabilizes its interaction with the cognate tRNAs

Eukaryotic aminoacyl-tRNA synthetases, in contrast to their prokaryotic counterparts, are often part of high molecular weight complexes. In yeast, two enzymes, the methionyl- and glutamyl-tRNA synthetases associate in vivo with the tRNA-binding protein Arc1p. To study the assembly and function of this complex, we have reconstituted it in vitro from individually purified recombinant proteins. Our results show that Arc1p can readily bind to either or both of the two enzymes, mediating the formation of the respective binary or ternary complexes. Under competition conditions, Arc1p alone exhibits broad specificity and interacts with a defined set of tRNA species. Nevertheless, the in vitro reconstituted Arc1p-containing enzyme complexes can bind only to their cognate tRNAs and tighter than the corresponding monomeric enzymes. These results demonstrate that the organization of aminoacyl-tRNA synthetases with general tRNA-binding proteins into multimeric complexes can stimulate their catalytic efficiency and, therefore, offer a significant advantage to the eukaryotic cell.     

Molecular determinants of the yeast Arc1p-aminoacyl-tRNA synthetase complex assembly

Eukaryotic aminoacyl-tRNA synthetases are usually organized into high-molecular-weight complexes, the structure and function of which are poorly understood. We have previously described a yeast complex containing two aminoacyl-tRNA synthetases, methionyl-tRNA synthetase and glutamyl-tRNA synthetase, and one noncatalytic protein, Arc1p, which can stimulate the catalytic efficiency of the two synthetases. To understand the complex assembly mechanism and its relevance to the function of its components, we have generated specific mutations in residues predicted by a recent structural model to be located at the interaction interfaces of the N-terminal domains of all three proteins. Recombinant wild-type or mutant forms of the proteins, as well as the isolated N-terminal domains of the two synthetases, were overexpressed in bacteria, purified and used for complex formation in vitro and for determination of binding affinities using surface plasmon resonance. Moreover, mutant proteins were expressed as PtA or green fluorescent protein fusion polypeptides in yeast strains lacking the endogenous proteins in order to monitor in vivo complex assembly and their subcellular localization. Our results show that the assembly of the Arc1p-synthetase complex is mediated exclusively by the N-terminal domains of the synthetases and that the two enzymes bind to largely independent sites on Arc1p. Analysis of single-amino-acid substitutions identified residues that are directly involved in the formation of the complex in yeast cells and suggested that complex assembly is mediated predominantly by van der Waals and hydrophobic interactions, rather than by electrostatic forces. Furthermore, mutations that abolish the interaction of methionyl-tRNA synthetase with Arc1p cause entry of the enzyme into the nucleus, proving that complex association regulates its subcellular distribution. The relevance of these findings to the evolution and function of the multienzyme complexes of eukaryotic aminoacyl-tRNA synthetases is discussed.     

Imaging for distant metastases in women with early-stage breast cancer: a population-based cohort study

Background:

Practice guidelines recommend that imaging to detect metastatic disease not be performed in the majority of patients with early-stage breast cancer who are asymptomatic. We aimed to determine whether practice patterns in Ontario conform with these recommendations.

Methods:

We used provincial registry data to identify a population-based cohort of Ontario women in whom early-stage, operable breast cancer was diagnosed between 2007 and 2012. We then determined whether imaging of the skeleton, thorax, and abdomen or pelvis had been performed within 3 months of tissue diagnosis. We calculated rates of confirmatory imaging of the same body site.

Results:

Of 26 547 patients with early-stage disease, 22 811 (85.9%) had at least one imaging test, and a total of 83 249 imaging tests were performed (mean of 3.7 imaging tests per patient imaged). Among patients with pathologic stage I and II disease, imaging was performed in 79.6% (10 921/13 724) and 92.7% (11 882/12 823) of cases, respectively. Of all imaging tests, 19 784 (23.8%) were classified as confirmatory investigations. Imaging was more likely for patients who were younger, had greater comorbidity, had tumours of higher grade or stage or had undergone preoperative breast ultrasonography, mastectomy or surgery in the community setting.

Interpretation:

Despite recommendations from multiple international guidelines, most Ontario women with early-stage breast cancer underwent imaging to detect distant metastases. Inappropriate imaging in asymptomatic patients with early-stage disease is costly and may lead to harm. The use of population datasets will allow investigators to evaluate whether or not strategies to implement practice guidelines lead to meaningful and sustained change in physician practice.Most women with newly diagnosed breast cancer present with early-stage, potentially curable disease.¹ Among patients whose disease is restricted to the breast and axillary lymph nodes, without signs or symptoms of metastatic disease, the likelihood of having radiologically evident metastases in pathologic stage I and II disease is about 0.2% and 1.2%, respectively.² This low frequency has not changed significantly, even with the increasing use of magnetic resonance imaging (MRI) and positron emission tomography.^2,3 For this reason, most provincial, national and international guidelines do not recommend imaging for all patients with early-stage breast cancer who are asymptomatic.^4–8Despite these evidence-based guidelines, imaging for distant metastases in patients with a new diagnosis of breast cancer remains common.^2,9–12 In response to the Choosing Wisely campaign of the American Board of Internal Medicine Foundation,¹³ the American Society of Clinical Oncology (ASCO) published its inaugural “top 5” list for choosing wisely in oncology.¹⁴ It recommended against routine imaging for staging purposes in women with early breast cancer, because “such imaging adds little benefit to patient care and has the potential to cause harm.”¹⁴ In 2014, Choosing Wisely Canada was launched in an effort to encourage physicians and patients to engage in conversations about unnecessary tests, treatments and procedures, to help ensure that patients receive the highest-quality care.¹⁵The ASCO Choosing Wisely recommendation¹⁴ is similar to the Cancer Care Ontario guideline,⁴ which has been in existence for over a decade. Whereas ASCO in its Choosing Wisely campaign recommends no imaging for patients with stage I or II disease, the Cancer Care Ontario guideline recommends no imaging for patients with stage I disease and a bone scan for those with stage II disease. A recent study at a large Canadian academic cancer centre showed that, despite publication of both a provincial guideline and the ASCO recommendations, most patients with primary operable (early-stage) breast cancer undergo imaging for distant metastases.¹⁰ We hypothesized that despite the provincial guideline, this practice may be more widespread. We undertook this population-based study to determine whether physician practice patterns in Ontario regarding imaging of patients with early-stage breast cancer are in keeping with the published Cancer Care Ontario guideline.     

Low Serum Hepcidin in Patients with Autoimmune Liver Diseases

Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients’ sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.     

A modified phase-fitted and amplification-fitted Runge-Kutta-Nyström method for the numerical solution of the radial Schrödinger equation

A new Runge-Kutta-Nyström method, with phase-lag and amplification error of order infinity, for the numerical solution of the Schrödinger equation is developed in this paper. The new method is based on the Runge-Kutta-Nyström method with fourth algebraic order, developed by Dormand, El-Mikkawy and Prince. Numerical illustrations indicate that the new method is much more efficient than other methods derived for the same purpose.     

Intra-peritoneal application of catechins and EGCG as in vivo inhibitors of ozone-induced oxidative stress

Oxidative stress is considered as a prominent feature of many acute and chronic diseases as well as of the normal aging process. We examined the effects of intra-peritoneal administration of catechins and EGCG as in vivo inhibitors of oxidative stress induced by ozone administration in two groups of Wistar rats. The first group was treated by intra-peritoneal administration of catechins and EGCG after the administration of ozone and the second group was pretreated by intra-peritoneal administration of catechins and EGCG prior to ozone administration. We determined in blood the activity of the enzymes superoxide dismutase and glutathione peroxidase, total antioxidant capacity, levels of copper and zinc and in urine malonaldehyde contents. Ozone administration resulted in significant reduction of glutathione peroxidase activity, plasma zinc levels and plasma and Red Blood Cells antioxidant capacity. Catechins and EGCG upregulate superoxide dismutase activity and maintain plasma and Red Blood Cells antioxidant capacity. Malonaldehyde levels at the end of the study were significantly increased only in the first group. Our data demonstrate that treatment with catechins and EGCG cannot reverse or prevent the effects of oxidative stress although some modulation occurs.     

A P-stable exponentially-fitted method for the numerical integration of the Schrödinger equation

In this paper we present a P-stable exponentially-fitted four-step method for the numerical integration of the radial Schrödinger equation. More specifically we present a method than satisfies the property of P-stability and also integrates exactly any linear combination of the functions {1, x, exp( ± w x), x exp( ± w x), x ²exp( ± w x)}. We tested the efficiency of our newly developed scheme against well known methods, with excellent results. The numerical illustration showed that our method is considerably more efficient compared to well‐known methods used for the numerical integration of resonance problem of the radial Schrödinger equation.