Neuromyelitis optica spectrum disorders and systemic lupus erythematosus: A case series from a university center.

Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory diseases of the central nervous system (CNS), which preferentially affect the optic nerves and the spinal cord. Anti-aquaporin 4 antibody is a specific serological marker. Systemic lupus erythematosus (SLE) is a rheumatologic disease that may affect the CNS. There are several reports about the coexistence of NMOSD and autoimmune diseases, mainly those of rheumatologic origin. We describe three different cases in which SLE and NMOSD subsequently occurred, drawing attention to the clinical heterogeneity, the challenge and the importance of recognizing this possible association.

Assessment of weight gain and control of parasitism by Rhipicephalus microplus in dairy cattle in the field using organosynthetic parasiticide, phytotherapics and homeopathy / Avaliação do ganho de peso e controle do parasitismo por Rhipicephalus microplus em bovinos leiteiros a campo usando parasiticida organosintético, fitoterápicos e homeopatia

The goal of this research was to compare the effect of the following products on dairy cattle, parasitized by Rhipicephalus microplus: organosynthetics - Clorfenvinfós and Ivermectina (OG); phytotherapics - Eucalyptus oil (EG) and Neem cake (NG); Homeopathy (HG); The control group (CG) received no treatment. Infestation was by R. microplus (MIC) and weight gain (GP) were evaluated. The study included 60 animals (5 groups) from ­ Dutch / Zebu, aged between 25-44 months and initial weight between 211-477kg. EG and NG showed MIC 84.9% and 14.0% greater than CG, respectively (P <0.05; P = 0). HG and OG had MIC less than CG 24.4% and 16.9%, respectively (P<0.05; P <0.05). EG, NG and OG obtained GP lower than CG in 7.9%, 8.9% and 8.06% (P <0.05) respectively. The HG GP was 4.9% higher (P <0.05) than CG. This was the first research to prove parasitism control by R. microplus in a field test, using homeopathy. The methodology for choosing Homeopathy for the control of enzooties, developed and tested for the first time in this study, proved to be adequate and efficient, opening the possibility for establishing a new methodology for strategic control of parasitism by R. microplus.(AU)

O objetivo desta pesquisa foi comparar o efeito dos seguintes produtos sobre bovinos leiteiros, parasitados por Rhipicephalus microplus: organossintéticos - clorfenvinfós e ivermectina (OG); fitoterápicos - óleo de eucalipto (EG) e torta de Neem (NG) e homeopatia (HG). O grupo controle (CG) não recebeu tratamento. Foram avaliados infestação por R. microplus (MIC) e ganho de peso/grupo (GP) em 60 animais (5 grupos), a partir de ­ holandês/zebu, com idade entre 25 e 44 meses e peso inicial entre 211 e 477kg. EG e NG apresentaram MIC 84,9% e 14,0% maior que CG, respectivamente (P<0,05; P=0). HG e OG apresentaram MIC menor que CG 24,4% e 16,9%, respectivamente (P<0,05; P<0,05). EG, NG e OG obtiveram GP menor que CG em 7,9%, 8,9% e 8,06% (P<0,05), respectivamente. O GP do HG foi 4,9% maior (P<0,05) que o CG. Esta foi a primeira pesquisa a comprovar controle do parasitismo por R. microplus em teste a campo, usando homeopatia. A metodologia para escolha de medicamentos homeopáticos para controle de enzootias, desenvolvida e testada pela primeira vez neste estudo, mostrou-se adequada e eficiente, abrindo a possibilidade para estabelecimento de nova metodologia para controle estratégico do parasitismo por R. microplus.(AU)

Anti-inflammatory and immune properties of the peltatoside, isolated from the leaves of Annona crassiflora Mart., in a new experimental model zebrafish.

Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.

Alanyl-glutamine protects the intestinal barrier function in trained rats against the impact of acute exhaustive exercise.

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.

Alanyl-glutamine protects the intestinal barrier function in trained rats against the impact of acute exhaustive exercise

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.

Renal Alterations Induced by the Venom of Colombian Scorpion Centruroides Margaritatus.

BACKGROUND: Scorpion venom causes renal injury and affects vascular ion-channels function. Centruroides margaritatus scorpion is found in Colombia and is frequently the cause of envenomation accidents; however, its renal impact has never been investigated. OBJECTIVE: To evaluate the effects of C. margaritatus venom (CmV) on renal parameters using isolated rat kidney and renal cell culture models. METHODS: Wistar rats (n = 5, weighing 240-300 g) were first perfused with Krebs-Henseleit solution containing 6 g 100 mL-1 bovine serum albumin. After 30 minutes, the kidneys were perfused with CmV to a final concentration of 10 µgmL-1; evaluation was performed by measuring Perfusion Pressure (PP), Renal Vascular Resistance (RVR), Urinary Flow (UF), Glomerular Filtration Rate (GFR), and percentage of electrolyte tubular transport. Moreover, kidney histological analyses and cell cytotoxicity in renal tubule epithelial cells (MDCK) and proximal tubular cells (LLC-MK2) were assessed. RESULTS: CmV increased PP and RVR 60 min after perfusion. On the other hand, UF, GFR, and the percentages of sodium, potassium and chloride tubular transport decreased after experimental envenomation. UF dropped after 120 min, while GFR and percentage of electrolyte tubular transport diminished after 60, 90 and 120 min. CmV was not toxic to MDCK cell line but reduced the viability of LLC-MK2 cells at concentrations ranging from 6.25 to 200 µgmL-1. Histological analyses disclosed hydropic degeneration, edema, and protein deposits. Flow cytometry disclosed that cell death occurred predominantly by necrosis. CONCLUSION: Our results suggest that C. margaritatus venom can trigger renal impairment, mainly in the proximal kidney tubule.

Expression of myo-inositol cotransporters in the sciatic nerve and dorsal root ganglia in experimental diabetes.

The transport of myo-inositol is the main mechanism for the maintenance of its high intracellular levels. We aimed to measure the mRNA and protein levels of myo-inositol cotransporters in the sciatic nerve (SN) and dorsal root ganglia (DRG) during experimental diabetes. Streptozotocin-induced (STZ; 4, 8, and 12 weeks; 65 mg/kg; ip) diabetic rats (DB) and age-matched euglycemic (E) rats were used for the analysis of mRNA and protein levels of sodium myo-inositol cotransporters 1, 2 (SMIT1, SMIT2) or H+/myo-inositol cotransporter (HMIT). There was a significant reduction in the mRNA levels for SMIT1 in the SN and DRG (by 36.9 and 31.0%) in the 4-week DB (DB4) group compared to the E group. SMIT2 was not expressed in SN. The mRNA level for SMIT2 was up-regulated only in the DRG in the DB4 group. On the other hand, the protein level of SMIT1 decreased by 42.5, 41.3, and 44.8% in the SN after 4, 8, and 12 weeks of diabetes, respectively. In addition, there was a decrease of 64.3 and 58.0% of HMIT in membrane and cytosolic fractions, respectively, in the SN of the DB4 group. In the DRG, there was an increase of 230 and 86.3% for SMIT1 and HMIT, respectively, in the DB12 group. The levels of the main inositol transporters, SMIT1 and HMIT, were greatly reduced in the SN but not in the DRG. SMIT-1 was selectively reduced in the sciatic nerve during experimental STZ-induced diabetes.

Experimental and Monte Carlo characterization of radionuclidic impurities originated from proton irradiation of [18O]H2O in a modern medical cyclotron.

In this work we present a characterization of the radionuclidic impurities originated by proton irradiation of enriched water [18O]H2O in a medical cyclotron through Monte Carlo simulations and experimental measurements. A set of standard samples of enriched water loaded in the cyclotron target cell have been irradiated at 30 µA proton current for 1 h each and, after an appropriate cooling time, measured by HPGe gamma spectrometry. In this way it was possible to study the direct release of radionuclidic impurities from target components as well as the release as a function of target ageing. Previously to experimental measurements, Monte Carlo calculations with the PHITS Code have been carried out to estimate the radionuclides generated within the target components (in particular Havar® foil) with the aim to identify the nuclides expected to be found in the irradiated water due to cell-to-water transmission mechanisms. Comparison between simulations data and experimental measurements by gamma spectrometry showed that only a very small amount of the radionuclides produced in the target window are released in the enriched water through corrosion/erosion effects, while the release decreases with increasing aging of the target.

Expression of myo-inositol cotransporters in the sciatic nerve and dorsal root ganglia in experimental diabetes

The transport of myo-inositol is the main mechanism for the maintenance of its high intracellular levels. We aimed to measure the mRNA and protein levels of myo-inositol cotransporters in the sciatic nerve (SN) and dorsal root ganglia (DRG) during experimental diabetes. Streptozotocin-induced (STZ; 4, 8, and 12 weeks; 65 mg/kg; ip) diabetic rats (DB) and age-matched euglycemic (E) rats were used for the analysis of mRNA and protein levels of sodium myo-inositol cotransporters 1, 2 (SMIT1, SMIT2) or H+/myo-inositol cotransporter (HMIT). There was a significant reduction in the mRNA levels for SMIT1 in the SN and DRG (by 36.9 and 31.0%) in the 4-week DB (DB4) group compared to the E group. SMIT2 was not expressed in SN. The mRNA level for SMIT2 was up-regulated only in the DRG in the DB4 group. On the other hand, the protein level of SMIT1 decreased by 42.5, 41.3, and 44.8% in the SN after 4, 8, and 12 weeks of diabetes, respectively. In addition, there was a decrease of 64.3 and 58.0% of HMIT in membrane and cytosolic fractions, respectively, in the SN of the DB4 group. In the DRG, there was an increase of 230 and 86.3% for SMIT1 and HMIT, respectively, in the DB12 group. The levels of the main inositol transporters, SMIT1 and HMIT, were greatly reduced in the SN but not in the DRG. SMIT-1 was selectively reduced in the sciatic nerve during experimental STZ-induced diabetes.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains.

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Radiation resistance of elastomeric O-rings in mixed neutron and gamma fields: Testing methodology and experimental results.

Materials and components employed in the presence of intense neutron and gamma fields are expected to absorb high dose levels that may induce deep modifications of their physical and mechanical properties, possibly causing loss of their function. A protocol for irradiating elastomeric materials in reactor mixed neutron and gamma fields and for testing the evolution of their main mechanical and physical properties with absorbed dose has been developed. Four elastomeric compounds used for vacuum O-rings, one fluoroelastomer polymer (FPM) based and three ethylene propylene diene monomer rubber (EPDM) based, presently available on the market have been selected for the test. One EPDM is rated as radiation resistant in gamma fields, while the other elastomers are general purpose products. Particular care has been devoted to dosimetry calculations, since absorbed dose in neutron fields, unlike pure gamma fields, is strongly dependent on the material composition and, in particular, on the hydrogen content. The products have been tested up to about 2 MGy absorbed dose. The FPM based elastomer, in spite of its lower dose absorption in fast neutron fields, features the largest variations of properties, with a dramatic increase in stiffness and brittleness. Out of the three EPDM based compounds, one shows large and rapid changes in the main mechanical properties, whereas the other two feature more stable behaviors. The performance of the EPDM rated as radiation resistant in pure gamma fields does not appear significantly better than that of the standard product. The predictive capability of the accelerated irradiation tests performed as well as the applicable concepts of threshold of radiation damage is discussed in view of the use of the examined products in the selective production of exotic species facility, now under construction at the Legnaro National Laboratories of the Italian Istituto Nazionale di Fisica Nucleare. It results that a careful account of dose rate effects and oxygen penetration in the material, both during test irradiations and in operating conditions, is needed to obtain reliable predictions.

Characterisation of the secondary neutron field generated by a compact PET cyclotron with MCNP6 and experimental measurements.

The production of the most common used PET radioisotope Fluorine-18 with commercial cyclotrons is obtained from the 18O(p,n)18F nuclear reaction when 18O-enriched water is bombarded with a proton beam. We present the characterization of the secondary neutron field spectra produced by this reaction in different locations around the cyclotron, through a comparison between MCNP6 Monte Carlo simulation results and experimental data obtained with Neutron Activation Analysis (NAA) of thin target foils of different materials.

Molluscicidal potential of Heterorhabditis baujardi (Rhabditida: Heterorhabditidae), strain LPP7, on Lymnaea columella (Gastropoda: Pulmonata): An alternative for biological control of fasciolosis.

This study elucidated for the first time, under laboratory conditions, the susceptibility of Lymnaea columella to infective juveniles of Heterorhabditis baujardi LPP7. Exposure to the nematodes induced an average mortality rate of 66.66% in the population of L. columella, with the highest values attained from the second week after exposure onward. In addition, all the reproductive parameters analyzed (total number of eggs, number of egg masses, number of eggs laid/snail, embryo hatching rate and content of galactogen stored in the albumen gland) changed as a result of the infection. The results indicate the occurrence of the phenomenon of parasitic castration in L. columella infected by H. baujardi LPP7, probably through depletion of energy reserves such as galactogen, necessary to meet the intense metabolic demands of the nematode's larval stages. Finally, histopathological analysis demonstrated an intense process of cell disorganization, characterized by the occurrence of granulomatous inflammatory reactions in tissues of exposed snails, induced by the spoliative action of the bacteria/nematode. The results suggest the use of H. baujardi LPP7 as an alternative for biological control of the population of this intermediate host, and thus of the diseases in whose epidemiological chain it participates, especially fasciolosis, in line with the recommendations of the World Health Organization (WHO).

Impact of acute undernutrition on growth, ileal morphology and nutrient transport in a murine model.

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.

Zika virus infections imported from Brazil to Portugal, 2015.

Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present.

Impact of acute undernutrition on growth, ileal morphology and nutrient transport in a murine model

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.

Genetic parameters for milk production traits and breeding goals for Gir dairy cattle in Brazil.

To implement an animal breeding program, it is important to define the production circumstances of the animals of interest to determine which traits of economic interest will be selected for the breeding goal. The present study defined breeding goals and proposed selection indices for milk production and quality traits of Gir dairy cattle. First, a bioeconomic model was developed to calculate economic values. The genetic and phenotypic parameters were estimated based on records from 22,468 first-lactation Gir dairy cows and their crosses for which calving occurred between 1970 and 2011. Statistical analyses were carried out for the animal model, with multitrait analyses using the restricted maximum likelihood method. Two situations were created in the present study to define the breeding goals: 1) including only milk yield in the breeding goal (HGL1) and 2) including fat and protein in addition to the milk yield (HGL2). The heritability estimates for milk, protein, and fat production were 0.33 ± 0.02, 0.26 ± 0.02, and 0.24 ± 0.02, respectively. All phenotypic and genetic correlations were highly positive. The economic values for milk, fat, and protein were US$0.18, US$0.27, and US$7.04, respectively. The expected economic responses for HGL2 and for HGL1 were US$126.30 and US$79.82, respectively. These results indicate that milk component traits should be included in a selection index to rank animals evaluated in the National Gir Dairy Breeding Program developed in Brazil.

Neutron flux characterisation of the Pavia TRIGA Mark II research reactor for radiobiological and microdosimetric applications.

Nowadays the Pavia TRIGA reactor is available for national and international collaboration in various research fields. The TRIGA Mark II nuclear research reactor of the Pavia University offers different in- and out-core neutron irradiation channels, each characterised by different neutron spectra. In the last two years a campaign of measurements and simulations has been performed in order to guarantee a better characterisation of these different fluxes and to meet the demands of irradiations that require precise information on these spectra in particular for radiobiological and microdosimetric studies. Experimental data on neutron fluxes have been collected analysing and measuring the gamma activity induced in thin target foils of different materials irradiated in different TRIGA experimental channels. The data on the induced gamma activities have been processed with the SAND II deconvolution code and finally compared with the spectra obtained with Monte Carlo simulations. The comparison between simulated and measured spectra showed a good agreement allowing a more precise characterisation of the neutron spectra and a validation of the adopted method.

Molecular and computational analyses of genes involved in mannose 6-phosphate independent trafficking.

The newly-synthesized lysosomal enzymes travel to the trans-Golgi network (TGN) and are then driven to the acidic organelle. While the best-known pathway for TGN-to-endosome transport is the delivery of soluble hydrolases by the M6P receptors (MPRs), additional pathways do exist, as showed by the identification of two alternative receptors: LIMP-2, implicated in the delivery of ß-glucocerebrosidase; and sortilin, involved in the transport of the sphingolipid activator proteins prosaposin and GM2AP, acid sphingomyelinase and cathepsins D and H. Disruption of the intracellular transport and delivery pathways to the lysosomes may result in lysosomal dysfunction, predictably leading to a range of clinical manifestations of lysosomal storage diseases. However, for a great percentage of patients presenting such manifestations, no condition is successfully diagnosed. To analyse if, in this group, phenotypes could be determined by impairments in the known M6P-independent receptors, we screened the genes that encode for LIMP-2 and sortilin. No pathogenic mutations were identified. Other approaches will be needed to clarify whether sortilin dysfunction may cause disease.