Dysregulated protease activated receptor 1 (PAR1) promotes metastatic phenotype in breast cancer through HMGA2.

As the majority of patients with basal-like breast carcinoma present with invasive, metastatic disease that do not respond to available therapies, it is essential to identify new therapeutic targets that impact invasion and metastasis. Protease-activated receptor 1 (PAR1), a G-protein coupled receptor has been shown to act as an oncogene, but underlying mechanisms are not well understood. Here, we show that ectopic expression of functionally active PAR1 in MCF-7 cells induced a hormone-refractory, invasive phenotype representative of advanced basal-like breast carcinoma that readily formed metastatic lesions in lungs of mice. PAR1 was found to globally upregulate mesenchymal markers, including vimentin, a direct target of PAR1, and downregulate the epithelial markers including E-cadherin, as well as estrogen receptor. In contrast, non-signaling PAR1 mutant receptor did not lead to an invasive, hormone refractory phenotype. PAR1 expression increased spheroid formation and the level of stemness markers and self-renewal capacity in human breast cancer cells. We identified HMGA2 (high mobility group A2) as an important regulator of PAR1-mediated invasion. Inhibition of PAR1 signaling suppresses HMGA2-driven invasion in breast cancer cells. HMGA2 gene and protein are highly expressed in metastatic breast cancer cells. Overall, our results show that PAR1/HMGA2 pathway may present a novel therapeutic target.

The MRI findings of a de Garengeot hernia.

The presence of the appendix within a femoral hernia is rare. It was first described by the French surgeon Jacques Croissant de Garengeot in 1731. This phenomenon accounts for 0.8-1% of all femoral hernias. Acute appendicitis occurring within a femoral hernia is even rarer and is difficult to diagnose pre-operatively. This type of hernia is termed a de Garengeot hernia. The ultrasonographic and CT imaging features of de Garengeot hernias have been described previously. We report a case of a 57-year-old female who presented with a painful right-sided groin mass. She underwent MRI of the inguinal region, which successfully diagnosed this rare hernia pre-operatively. To our knowledge, this is the first description of a de Garengeot hernia diagnosed using MRI.

First evidence of azaspiracids (AZAs): A family of lipophilic polyether marine toxins in scallops (Argopecten purpuratus) and mussels (Mytilus chilensis) collected in two regions of Chile.

Azaspiracids are a family of lipophilic polyether marine biotoxins that have caused a number of human intoxication incidents in Europe since 1995 following the consumption by consumers of intoxicated shellfish (Mytilus edulis). These azaspiracids have now been identified in mussels (Mytilus chilensis) and scallops (Argopecten purpuratus) from two Chilean locations. This is the first report of the occurrence of azaspiracid toxins in these species (Mytilus chilensis and Argopecten purpuratus) from Chile. The areas studied were Bahía Inglesa (III Region, 27 degrees SL) and Chiloé Archipelago, both important scallop and mussels farming areas. Separation of azaspiracid (AZA1), azaspiracid isomer (AZA6) and its analogues, 8-methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3), was achieved using reversed-phase LC and toxins were identified using a turbo electrospray ionisation (ESI) source, to a triple quadrupole mass spectrometer. In mussels, AZA1 was the predominant toxin in mussel hepatopancreas with AZA2, AZA3 and AZA6 present in approximate equivalent amounts in the remaining tissues, 20-30% of the AZA1 level. AZA2 predominated in the scallop samples with the toxin almost entirely present in the hepatopancreas (digestive gland). AZA1 was only observed in some of the scallop samples and was present at 12-15% of the AZA2 levels. Whilst the levels of AZAs in Chilean samples are below the EU regulatory limit of 160mug/kg, it is significant that this toxin is present in Pacific Ocean species. Consequently measures should be taken by regulatory authorities to implement regular seafood monitoring to ensure safety of harvested product.

A self-fertile species of Steinernema from Indonesia: further evidence of convergent evolution amongst entomopathogenic nematodes?

More than 20 species of the entomopathogenic nematode Steinernema have been described; to date, all reproduce exclusively by cross-fertilization of male and female individuals. Steinernema sp. strain T87 from Indonesia was found to consist largely of self-fertile hermaphrodites. Progeny were produced by morphological females both in insects (Galleria mellonella) and in hanging drops of insect haemolymph inoculated with a single infective juvenile. Sperm were present in the oviduct of unmated morphological females. Approximately 1% of infective juveniles developed into males, and males were also present in the second generation where they constituted 1-6% of the population. Under the same conditions the related species Steinernema longicaudum strain CB2B displayed typical steinernematid reproduction: cross-fertilization and a 1:1 sex ratio. It is argued that the development of hermaphroditism in Steinernema sp. T87 represents convergent evolution with Heterorhabditis, the other major genus of entomopathogenic nematode.

Azorhizobium caulinodans ORS571 colonizes the xylem of Arabidopsis thaliana.

Improved conditions were used for the aseptic growth of Arabidopsis thaliana to investigate whether xylem colonization of A. thaliana by Azorhizobium caulinodans ORS571 might occur. When seedlings were inoculated with ORS571 (pXLGD4) tagged with the lacZ reporter gene, nearly all of the plants showed blue regions of ORS571 colonization at lateral root cracks (LRC). The flavonoids naringenin and liquiritigenin significantly stimulated colonization of LRC by ORS571. Blue bands of ORS571 (pXLGD4) bacteria were observed histochemically in the xylem of intact roots of inoculated plants. Detailed microscopic analysis of sections of primary and lateral roots from inoculated A. thaliana confirmed xylem colonization. Xylem colonization also occurred with an ORS571 nodC mutant deficient in nodulation factors. There was no significant difference in the percentage of plants with xylem colonization or in the mean length of xylem colonized per plant between plants inoculated with either ORS571 (pXLGD4) or ORS571::nodC (pXLGD4), with or without naringenin.

Effects of glucosinolates and flavonoids on colonization of the roots of Brassica napus by Azorhizobium caulinodans ORS571.

Plants of Brassica napus were assessed quantitatively for their susceptibility to lateral root crack colonization by Azorhizobium caulinodans ORS571(pXLGD4) (a rhizobial strain carrying the lacZ reporter gene) and for the concentration of glucosinolates in their roots by high-pressure liquid chromatography (HPLC). High- and low-glucosinolate-seed (HGS and LGS) varieties exhibited a relatively low and high percentage of colonized lateral roots, respectively. HPLC showed that roots of HGS plants contained a higher concentration of glucosinolates than roots of LGS plants. One LGS variety showing fewer colonized lateral roots than other LGS varieties contained a higher concentration of glucosinolates than other LGS plants. Inoculated HGS plants treated with the flavonoid naringenin showed significantly more colonization than untreated HGS plants. This increase was not mediated by a naringenin-induced lowering of the glucosinolate content of HGS plant roots, nor did naringenin induce bacterial resistance to glucosinolates or increase the growth of bacteria. The erucic acid content of seed did not appear to influence colonization by azorhizobia. Frequently, leaf assays are used to study glucosinolates and plant defense; this study provides data on glucosinolates and bacterial colonization in roots and describes a bacterial reporter gene assay tailored easily to the study of ecologically important phytochemicals that influence bacterial colonization. These data also form a basis for future assessments of the benefits to oilseed rape plants of interaction with plant growth-promoting bacteria, especially diazotrophic bacteria potentially able to extend the benefits of nitrogen fixation to nonlegumes.

The xylem of rice (Oryza sativa) is colonized by Azorhizobium caulinodans.

Following inoculation with Azorhizobium caulinodans ORS571 (pXLGD4), lateral root development of rice and colonization of lateral root cracks by bacteria were shown to be stimulated by the flavonoid naringenin. Rice seedlings growing aseptically in the presence of naringenin were inoculated with ORS571 (pXLGD4), carrying the lacZ reporter gene. By microscopic analysis of sections of inoculated rice roots, it has been demonstrated that the xylem of rice roots can be colonized by Azorhizobium caulinodans. We discuss whether this colonization of the xylem of rice roots by azorhizobia could provide a suitable niche for endophytic nitrogen fixation.

A medico-social survey of over-75's in a rural practice.

A survey of patients in a Donegal practice showed that 7.9% (n = 198) were over 75 years of age. Of these, 20% lived alone, many of whom lived in poor housing, less than one third of these attended the nearest day centre. Sixteen per cent of the group studied had an inappropriate diet. Fourteen per cent suffered significant physical disability, 30% showed evidence of mental impairment and 28% were taking three or more drugs on a regular basis. Most support for the elderly was provided by friends and relatives. General practitioners are well placed to identify mental and physical disability and social problems and should be actively involved in developing community support services.

Passive accessory movement at the elbow: a roentgenographic analysis.

Longitudinal movement of the radius, in relation to the ulna, occurring during abduction and adduction of the elbow, and during radial and ulnar deviation of the wrist, was examined roet-genographically on five students. A fixation device was designed to stabilize the humerus while the passive movements were carried out, and all measurements were done with the arm in 0° extension. The average movement from full adduction to full abduction was 10.4° and, at the same time, the radius moved an average of 1.6 mm distally in relation to the ulna. When the wrist was moved from full radial deviation to full ulnar deviation the radius moved an average of 0.1 mm in relation to the ulna. The importance of assessing passive accessory movements at the elbow in the examination and treatment of elbow lesions is discussed.