Fasciola hepatica cathepsin L-like proteases: biology, function and potential in the development of first generation liver fluke vaccines.

Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit similarities in their substrate specificities to these enzymes they differ in having a wider pH range for activity and an enhanced stability at neutral pH. There are presently 13 Fasciola cathepsin L cDNAs deposited in the public databases representing a gene family of at least seven distinct members, although the temporal and spatial expression of each of these members in the developmental stage of F. hepatica remains unclear. Immunolocalisation and in situ hybridisation studies, using antibody and DNA probes, respectively, show that the vast majority of cathepsin L gene expression is carried out in the epithelial cells lining the parasite gut. Within these cells the enzyme is packaged into secretory vesicles that release their contents into the gut lumen for the purpose of degrading ingested host tissue and blood. Liver flukes also express a novel multi-domain cystatin that may be involved in the regulation of cathepsin L activity. Vaccine trials in both sheep and cattle with purified native FheCL1 and FheCL2 have shown that these enzymes can induce protection, ranging from 33 to 79%, to experimental challenge with metacercariae of F. hepatica, and very potent anti-embryonation/hatch rate effects that would block parasite transmission. In this article we review the vaccine trials carried out over the past 8 years, the role of antibody and T cell responses in mediating protection and discuss the prospects of the cathepsin Ls in the development of first generation recombinant liver fluke vaccines. Author Keywords: Helminths; Trematodes; Parasites; Cathepsins; Proteases; Vaccines; Immunology; Biochemistry

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus.

To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9–59.3) compared with 65.7 Gy (range 65.3–65.9) and 64.2 Gy (range 61.4–65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5% (range 7.0–11.7%) of the volume receiving

Social economy and economic crisis in the basque country abstract

This article examines the socio-economic evolution of the social economy sector in the Basque Country during the 2008-2014 period of economic crisis. Data have been obtained within a framework of collaboration between university, Basque Government and private sector of the social economy. The results suggest that such entities have evolved better, both in terms of number of enterprises and employment, than the general economy of the Basque Country, while the context of public policies aimed at social economy has worsened over the years. However, in economic terms (measured through the Gross Value Added generated), they have not been able to cope with the crisis in equal conditions to the general economy. The main contribution of this research lies in that, unlike similar studies, it discusses the evolution of the whole sector of the social economy, taking as reference a broad period of the current economic crisis.

The influence of gender in the direction of Spanish cooperative societies on profitability and indebtedness: an empirical analysis

In this paper the claim for the market for a new business management to ensure the presence of women in decision -making to respond to new social needs addressed. Thus, this paper analyzes the influence of gender diversity of the directors on the profitability and the level of debt for a sample of 5,199 Spanish cooperatives. Unlike capitalist societies, these organizations have a number of peculiarities in their government, and that the partners are themselves major time, agents and customers. The study focuses on the Spanish context, where there is an open debate on the importance of women's business management, as in other countries, driven by the proliferation of legislation on gender equality, being, in addition, Spain, the pioneer in having specific legislation on Social Economy. The results show that cooperatives with greater female representation in theirs Boards have higher profitability. On the other hand, those Boards with a higher percentage of women show a lower level of indebtedness.

Assessment of fibronectin as a potential new clinical tool in andrology.

In this prospective clinical study, 892 patients with normal and impaired semen were examined in order to investigate the correlation between the concentration of fibronectin in seminal plasma and the motility of spermatozoa. The fibronectin concentration in seminal plasma, total sperm motility and linear sperm motility were measured. We report here a significant negative correlation between the fibronectin concentration in seminal plasma and total sperm motility (r=-0.3474). There was no link between varicocele and vasectomy, or between varicocele and variation in the concentration of fibronectin. It is concluded that higher concentrations of the acute-phase protein fibronectin may be a cause of severe reduction in sperm motility. The investigation of fibronectin concentrations in seminal fluid could be a new and helpful clinical tool in the assessment of male fertility.

Innovation persistence: Survey and case-study evidence

Evidence on the persistence of innovation sheds light on the nature of the innovation process and can guide appropriate policy development. This paper examines innovation persistence in Ireland and Northern Ireland using complementary quantitative and case-study approaches. Panel data derived from innovation surveys is used, and suggests very different results to previous analyses of innovation persistence primarily based on patents data. Product and process innovation are found to exhibit strong general persistence but we find no evidence that persistence is stronger among highly active innovators. Our quantitative evidence is most strongly consistent with a process of cumulative accumulation at plant level. Our case-studies highlight a number of factors which can either interrupt or stimulate this process including market volatility, plants’ organisational context and regulatory changes. Notably, however, the balance of influences on product and process innovation persistence differs, with product innovation persistence linked more strongly to strategic factors and process changes more often driven by market pressures.
© 2007 Elsevier B.V. All rights reserved.

Manual asymmetries in the preparation and control of goal-directed movements

The primary purpose of this experiment was to determine if left hand reaction time advantages in manual aiming result from a right hemisphere attentional advantage or an early right hemisphere role in movement preparation. Right-handed participants were required to either make rapid goal-directed movements to small targets or simply lift their hand upon target illumination. The amount of advance information about the target for a particular trial was manipulated by precuing a subset of potential targets prior to the reaction time interval. When participants were required to make aiming movements to targets in left space, the left hand enjoyed a reaction advantage that was not present for aiming in right space: or simple finger lifts. This advantage was independent of the amount or type of advance information provided by the precue. This finding supports the movement planning hypothesis. With respect to movement execution, participants completed their aiming movements more quickly when aiming with their right hand, particularly in right space. This right hand advantage in right space was due to the time required to decelerate the movement and to make feedback-based adjustments late in the movement trajectory. (C) 2001 Academic Press.

Observations towards early-type stars in the ESO-POP Survey - II. Searches for intermediate- and high-velocity clouds

We present Ca it K and Ti it optical spectra of early-type stars taken mainly from the ultraviolet and visual echelle spectrograph (LIVES) Paranal Observatory Project, plus H 1 21-cm spectra, from the Vila-Elisa and Leiden-Dwingeloo Surveys, which are employed to obtain distances to intermediate- and high-velocity clouds (IHVCs). H I emission at a velocity of -117 km s(-1) towards the sightline HD 30677 (l, b = 190 degrees.2, -22 degrees.2) with column density -1.7 x 10(19) cm(-2) has no corresponding Ca Pi K absorption in the LIVES spectrum, which has a signal-to-noise ratio (S/N) of 610 per resolution element. The star has a spectroscopically determined distance of 2.7 kpc, and hence sets this as a firm lower distance limit towards Anti-Centre cloud ACII. Towards another sightline (HD 46185 with 1, b = 222 0, -10 degrees.1), H1 at a velocity of +122 km s(-1) and column density of 1.2 x 10(19) cm(-2) is seen. The corresponding Ca Pi K spectrum has a S/N of 780, although no absorption is observed at the cloud velocity. This similarly places a firm lower distance limit of 2.9 kpc towards this parcel of gas that may be an intermediate-velocity (IV) cloud. The lack of IV Ca it absorption towards HD 196426 (1, b = 45 degrees.8, -23 degrees.3) at a S/N of 500 reinforces a lower distance limit of -700 pc towards this part of complex gp, where the H I column density is 1.1 x 1019 cm(-2) and velocity is +78 km s(-1). Additionally, no IV Cart is seen in absorption in the spectrum of HD 19445, which is strong in H I with a column density of 8 x 10(19) cm(-2) at a velocity of - -42 km s(-1), placing a firm although uninteresting lower distance limit of 39 pc to this part of IV South. Finally, no high-velocity Call K absorption is seen towards HD 115363 (l, b = 306.0,-1.0) at a S/N of 410, placing a lower distance of -3.2 kpc towards the HVC gas at velocity of - +224 km s(-1) and WE column density of 5.2 x 10(19) cm(-2). This gas is in the same region of the sky as complex WE (Wakker 2001), but at higher velocities. The non-detection of Ca it K absorption sets a lower distance of -3.2 kpc towards the HVC, which is unsurprising if this feature is indeed related to the Magellanic System.