A comparison of the immune response and pathogenesis in sheep and cattle to Toxoplasma gondii infection

Toxoplasma gondii is an extremely successful parasite capable of infecting all warm blooded animals. However, there is a wide variation between different animal species in their vulnerability to infection, providing a fascinating opportunity for comparative studies on the host/parasite relationship.The main purpose of this thesis was to compare primary oral Toxoplasma gondii infection in two animal species, sheep and cattle, which are thought to differ in their respective vulnerability to infection. The parameters examined were the immune responses, pathogenesis and persistence of the parasite within tissuesThe rationale behind this study was based on reports that cattle seem to be more resistant to the outcome of Toxoplasma infection. Congenital disease is rarely reported and cattle are thought to harbour fewer parasite tissue cysts which may not persist for the life time of the host. Whereas in sheep, a primary infection usually results in the host remaining chronically infected for life and may result in abortion if primary infection occurs during pregnancy. It was hoped that these studies may indicate the critical factors involved in controlling T. gondii infection and increase our understanding of the events leading to persistence of the parasite within tissue cysts in the muscles and central nervous system of infected food animals. T. gondii tissue cysts in animal meat are an important source of infection for people, and recrudescence of parasites within tissue cysts in the central nervous system of immunosuppressed people, is one of the most common causes of death in AIDS patients. Host immune responses, in particular T cells and IFNγ, are known to play an important role in determining the outcome of Toxoplasma infection. Much of the data on host immune responses is derived from the study of laboratory mice which are extremely vulnerable to infection. There is comparatively little data from other animal species.An initial experiment was conducted to determine an appropriate dose of T. gondii oocysts which would consistently produce detectable amounts of parasite cysts in sheep tissues. Groups of sheep were orally infected with a titrated dose of oocysts ranging from 10³ to 10⁵ and their tissues were examined 6 weeks later at post mortem. An infective dose of 10⁵ sporulated oocysts gave the best result with T. gondii parasites being detected consistently in samples of heart and brain tissues. Two further experiments were conducted to compare T. gondii infection and host immune response in groups of sheep and cattle which were orally infected with either 10³ or 10⁵ T. gondii oocysts. Clinical responses, humoral and cell mediated immune responses were examined along with parasitaemia and the presence of T. gondii in various tissues at post mortem. The most striking difference between the sheep and the cattle was that T. gondii was more frequently and consistently detected in ovine tissues, in particular within brain and heart tissues, whereas parasites were not detected in the cattle samples. Although there was a marked difference in parasite detection, negative results do not necessarily exclude the possibility of persistent infection due to the limitations of sample size. Infection of sheep and cattle with either a low (10³) or high (10⁵) dose of oocysts provoked no more than a mild clinical response. The sheep developed an earlier febrile response which persisted longer than in the cattle. T. gondii was more frequently detected in the blood of sheep and cattle given the high dose of oocysts (10⁵). Both, cattle and sheep, seroconverted following oral infection with antibody titres appearing to correlate with the infective dose. The higher the infective dose the higher the antibody titre. Specific antibody was detected earlier in sheep given 10⁵ oocysts compared with 10⁴ or 10³. In agreement with previous studies on the immune response of sheep to T. gondii, an increase in the ratio of CD8⁺: CD4⁺ T cells occurred in peripheral blood following Toxoplasma infection. In cattle there was an early, brief increase in the percentage of CD4⁺ T cells. The cytokine IFNγ was more frequently detected in blood plasma samples from cattle compared to sheep in the 3 weeks following infection with either 10³ or 10⁵ oocysts. In addition when in vivo primed peripheral blood lymphocytes were stimulated in vitro with specific T. gondii antigen the cells from cattle showed stronger proliferative activity which was detected more frequently compared with the sheep cells under the same conditions. There was more IFNγ present in supernatants from activated cattle cells compared to sheep cells.It is difficult to draw any precise conclusion as to why cattle may be less vulnerable to T. gondii infection than sheep. In general the cattle appear to be better able to control the parasitaemia resulting in fewer T. gondii cysts being detected in their tissues compared with sheep. Interestingly the cytokine IFNγ was more frequently detected either from plasma or activated cell supernatants in the infected cattle compared to the sheep. This cytokine is known to play an important role in protection against T. gondii and has been implicated as a factor involved in the differentiation of tachyzoites to bradyzoites (tissue cyst stage). Recent data would suggest that production of IFNγ can occur via NK cells very early in infection and that this may have a profound effect on the ability of the host to withstand infection. Future studies should perhaps focus on local responses at the very early stages of infection as measurement of peripheral immune responses may not be sufficiently sensitive

Diseño de las infraestructuras frigoríficas en países en vías de desarrollo

En los países subdesarrollados y en vías de desarrollo, los recursos alimenticios no llegan a todos los sectores de la población entre otras razones porque se pierde buena parte de los alimentos producidos. Los informes de la FAO sobre estos países son preocupantes pues dan cifras de pérdidas de alimentos en el sector hortofrutícola superiores al 50%, en el cárnico al 20% y en el piscícola al 60%. La carencia de infraestructuras frigoríficas adecuadas y en algunos países inexistentes, son causa en gran medida de esta situación. Por tanto, el fundamento de establecer estas infraestructuras es conseguir el máximo aprovechamiento de los recursos propios de productos perecederos alimenticios, destinados al consumo de la población..

Presentation of the results of the Banco de España statistics user satisfaction survey

The Banco de España Statistics Department has conducted a survey to ascertain the level of satisfaction of the users of its statistics and to improve the quality of their production and disseminatio

A new integrated methodology for characterizing and assessing suitable areas for viticulture: A case study in Northwest Spain

.In 2018, Spain was the third largest producer and the leading exporter of wine in the world. Viticulture is an important economic activity in the Castilla y León region, and is an element capable of halting the flight from the countryside and favouring demographic settlement in rural areas. A new integrated methodology for characterizing and delimitating areas suitable for vineyard cultivation is proposed here. The approach combines traditional climate indices with others used in bioclimatology and with soil variables, and applies various statistical analyses to select the predictors that best characterize the vineyards. These predictors are then integrated in species distribution models and a geographic information system. The methodology was tested in the Denomination of Origin León (hereafter DO León) in northwest Spain. Ten single models using the maximum entropy modelling algorithm were run for each of the six wine-grape varieties. Single-model projections built as a consensus of the ten models into an ensemble-forecasting approach were later used to generate maps of suitable areas for each variety. The results confirm the delimitation of the DO León as a Denomination of Origin. The bioclimatic variables Compensated Thermicity Index and Continentality Index and the soil variables pH, Clay Content, Soil Retention Capacity and Soil Saturation Humidity are defining for all the varieties studied. Garnacha and Mencía were the most different varieties in relation to their bioclimatic and soil requirements. Suitability maps revealed that the DO could be extended into neighbouring areas up to 30 km around it. The proposed methodology is a useful tool for agronomic and oenological management; it allows a more effective selection of sites for new vineyards, improves vineyard management, and can even be used to protect territories with a historical and cultural heritage of grape cultivation, thus favouring demographic settlement in rural areas and avoiding depopulation.S

Clinical Significance of Langerhans Cells in Squamous Cell Carcinoma of the Larynx

Langerhans cells (LCs) may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50) and also in metastases (6 out of 10) and recurrences (2 out of 3), but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells

Análisis de sostenibilidad de una propuesta de aprovechamiento integral de residuos en una zona cafetera

El café es una de las actividades económicas más importantes de Colombia. Aporta al producto interno bruto nacional 6,1 % y ha hecho conocer al país en el mundo. Sin embargo, esta actividad genera un desequilibrio económico en las familias de cafeteros, ya que de los tres dólares que se obtienen por cada taza de café vendida, el campesino solamente recibe 0,001 dólares de ganancia. Por otro lado, el 99,8 % de la biomasa vegetal se desecha y el mínimo restante se aprovecha para satisfacer la demanda social de café. Cada año se producen alrededor de 16 millones de toneladas de residuos orgánicos en las plantaciones de café, que no se aprovechan, con las implicaciones ambientales que esto conlleva. Mientras, los cafetaleros y comunidades solo se benefician económicamente del grano de café, que cuando el precio no es con suficiencia alto, solo les permite atender sus necesidades básicas

Regulator of calcineurin 1 modulates vascular contractility and stiffness through the upregulation of COX-2-derived prostanoids

Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1+/+) and Rcan1-deficient (Rcan1-/-) mice untreated or treated with the COX-2 inhibitor rofecoxib were used. Vascular function and structure were analysed by myography. COX-2 and phospo-p65 expression were studied by western blotting and immunohistochemistry and TXA2 production by ELISA. We found that Rcan1 deficiency increases COX-2 and IL-6 expression and NF-κB activation in arteries and vascular smooth muscle cells (VSMC). Adenoviral-mediated re-expression of Rcan1.4 in Rcan1-/- VSMC normalized COX-2 expression. Phenylephrine-induced vasoconstrictor responses were greater in aorta from Rcan1-/- compared to Rcan1+/+ mice. This increased response were diminished by etoricoxib, furegrelate, SQ 29548, cyclosporine A and parthenolide, inhibitors of COX-2, TXA2 synthase, TP receptors, calcineurin and NF-κB, respectively. Endothelial removal and NOS inhibition increased phenylephrine responses only in Rcan1+/+ mice. TXA2 levels were greater in Rcan1-/- mice. In small mesenteric arteries, vascular function and structure were similar in both groups of mice; however, vessels from Rcan1-/- mice displayed an increase in vascular stiffness that was diminished by rofecoxib. In conclusion, our results suggest that Rcan1 might act as endogenous negative modulator of COX-2 expression and activity by inhibiting calcineurin and NF-kB pathways to maintain normal contractility and vascular stiffness in aorta and small mesenteric arteries, respectively. Our results uncover a new role for Rcan1 in vascular contractility and mechanical properties.This study was supported by Ministerio de Economia, Industria y Competitividad (MINECO) (SAF2012-36400 and SAF2016-80305-P), Institute de Salud Carlos III (ISCIII) (Red de Investigacion Cardiovascular, RD12/0042/0022 and RD12/0042/0024, CiberCV CB16/11/00286 and CB16/11/00264 and PI13/01488) Fondo Europeo de Desarrollo Regional (FEDER) a way to build Europe, Comunidad de Madrid (B2017/BMD-3676), COST BM1301 and Roche-IdiPaz. VE was supported by the Ramon y Cajal Program (RYC-2013-12880).S

Initial Fitness Recovery of HIV-1 Is Associated with Quasispecies Heterogeneity and Can Occur without Modifications in the Consensus Sequence

BACKGROUND: Fitness recovery of HIV-1 "in vitro" was studied using viral clones that had their fitness decreased as a result of plaque-to-plaque passages. PRINCIPAL FINDINGS: After ten large population passages, the viral populations showed an average increase of fitness, although with wide variations among clones. While 5 clones showed significant fitness increases, 3 clones showed increases that were only marginally significant (p<0.1), and 4 clones did not show any change. Fitness recovery was not accompanied by an increase in p24 production, but was associated with an increase in viral titer. Few mutations (an average of 2 mutations per genome) were detected in the consensus nucleotide sequence of the entire genome in all viral populations. Five of the populations did not fix any mutation, and three of them displayed marginally significant fitness increases, illustrating that fitness recovery can occur without detectable alterations of the consensus genomic sequence. The investigation of other possible viral factors associated with the initial steps of fitness recovery, showed that viral quasispecies heterogeneity increased between the initial clones and the passaged populations. A direct statistical correlation between viral heterogeneity and viral fitness was obtained. CONCLUSIONS: Thus, the initial fitness recovery of debilitated HIV-1 clones was mediated by an increase in quasispecies heterogeneity. This observation, together with the invariance of the consensus sequence despite fitness increases demonstrates the relevance of quasispecies heterogeneity in the evolution of HIV-1 in cell culture

Comparison of four strategies of ram management in a semen collection centre

Thirty Merino rams were used to determine the effect of four management systems of rams on semen quality during the anoestrous season. Animals were divided into four groups: Artificial-Photoperiod group (AP; n = 8), which were isolated from females and exposed to artificial long days (16 hr/d) from 1 Feb to 15 Mar; Natural-Photoperiod (NP; n = 8), isolated from females and exposed to the natural photoperiod throughout the experiment; Oestrous-Ewe group (EE; n = 7), housed in a pen adjacent to another pen that housed three ewes in oestrus, and Anestric-Ewe group (AE; n = 7), housed adjacent to another pen that housed three ovariectomized ewes. From 20 Mar to the end of May (10 weeks), semen samples were collected weekly, and blood samples were collected to determine plasma testosterone concentrations. Mean plasma testosterone concentrations, ejaculate volume and reaction time were not affected either by treatment or week. There was a significant effect (p < .01) of ram treatment on sperm concentration, and both TM y PM, and their interaction, were significantly affected by group and week (p < .001). Rams exposed to ewes in oestrus presented the largest sperm concentration (p < .05) compared with the other three groups, although they had the lowest total and progressive motilities (p < .01). In conclusion, management strategy in spring affects semen quality of rams, with the presence of ewes in oestrus being the best plan to increase sperm concentration