Vaccination of lambs against Haemonchus contortus infection with a somatic protein (Hc23) from adult helminths

A somatic protein from adult Haemonchus contortus (Hc23), the most abundant component in a low molecular weight fraction with known immunizing effect against experimental haemonchosis, has been purified by immunochromatography. The immunoprophylactic value of Hc23 was tested in groups of 5–6 months old Assaf lambs using Al(OH)₃ or Escherichia coli lipopolysaccharide + inactivated Propionibacterium acnes as adjuvant and the results compared with uninfected control, uninfected and challenged or infected and challenged lambs. Immunization with Hc23 in either adjuvant elicited significant reductions in fecal egg counts after challenge with 15,000 L3s (70.67%–85.64%, respectively) and reduced (67.1% and 86%) abomasal worm counts (45 days post-challenge). Immunized lambs displayed higher peripheral eosinophil counts, were less anaemic and had weight gains than challenged controls. The results suggest that the Hc23 antigen can induce a partially protective response against haemonchosis in lambs.     

Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines

At the end of 2005, six European countries had implemented public immunization campaigns with serogroup C conjugate vaccines, and all had experienced substantial declines in the incidence of serogroup C disease. A quadrivalent ACWY meningococcal vaccine is in use in the USA, but serogroup A is extremely rare in Europe and serogroups Y and W135 are infrequent causes of disease. This paper outlines recommendations on the use of conjugate vaccines in Europe based on the experience with meningococcal C conjugate (MCC) vaccines so far.     

Amphiphilic,glycophosphatidylinositol-specific phospholipase C (PI-PLC)-insensitive monomers and dimers of acetylcholinesterase

1. In a recent study, we distinguished two classes of amphiphilic AChE3 dimers in Torpedo tissues: class I corresponds to glycolipid-anchored dimers and class II molecules are characterized by their lack of sensitivity to PI-PLC and PI-PLD, relatively small shift in sedimentation with detergent, and absence of aggregation without detergent. 2. In the present report, we analyze the amphiphlic or nonamphiphilic properties of globular AChE forms in T28 murine neural cells, rabbit muscle, and chicken muscle. The molecular forms were identified by sucrose gradient sedimentation in the presence and absence of detergent and analyzed by nondenaturing charge-shift electrophoresis. Some amphiphilic forms showed an abnormal electrophoretic migration in the absence of detergent, because of the retention of detergent micelles. 3. We show that the amphiphilic monomers (G1a) from these tissues, as well as the amphiphilic dimers (G2a) from chicken muscle, resemble the class II dimers of Torpedo AChE. We cannot exclude that these molecules possess a glycolipidic anchor but suggest that their hydrophobic domain may be of a different nature. We discuss their relationship with other cholinesterase molecular forms.     

Defense activation triggers differential expression of phospholipase-C (PLC) genes and elevated temperature induces phosphatidic acid (PA) accumulation in tomato

Recently, we provided the first genetic evidence for the requirement of tomato PLC4 and PLC6 genes in defense activation and disease resistance. The encoded enzymes were catalytically active as they were able to degrade phosphatidylinositol (PI), thereby producing diacylglycerol (DG). Here we report differential PLC gene expression following the initiation of defense signaling by the interaction between Cladosporium fulvum resistance (R) protein Cf-4 and its matching effector Avr4 in tomato hybrid seedlings that express both Cf-4 and Avr4. Furthermore, we observed that PLC3 and PLC6 gene expression is upregulated by elevated temperature in the control seedlings. This upregulation coincides with an increase in the levels of phosphatidic acid (PA) and a decrease in the levels of PI and phosphatidylinositol phosphate (PIP). The decrease in PI and PIP levels matches with the activation of PLC. In addition, the levels of the structural phospholipids phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) declined transiently during recovery after the exposure to elevated temperature., Further studies will be required to explain the mechanism causing the sustained accumulation of PA during recovery, combined with a reduction in the levels of structural phospholipids.     

Digenic/multilocus aetiology of multiple self-healing squamous epithelioma (Ferguson-Smith disease): TGFBR1 and a second linked locus

Multiple self-healing squamous epithelioma (MSSE) is a rare familial skin cancer in which multiple tumours resembling crateriform squamous carcinomas are locally invasive but regress spontaneously after several months, leaving deep disfiguring facial scars and shallower scars on the limbs. First identified in a number of Scottish families, the condition has since been reported more widely. We review here the investigations leading to the discovery of loss of function mutations in TGFBR1 that are responsible for the disease. Loss of heterozygosity in tumours reveals that TGFBR1 acts as a tumour suppressor gene. TGFBR1 was initially excluded as the MSSE gene because it lies outside an extensive chromosome 9 haplotype shared by Scottish families. MSSE can now be regarded as a digenic/multilocus disease in view of the evidence of a second linked locus necessary for pathogenesis located within the Scottish haplotype.This article is part of a Directed Issue entitled: Rare Cancers.     

Vitamin D receptor gene polymorphisms (TaqI and ApaI) in relation to 25-hydroxyvitamin D levels and coronary artery disease incidence

Abstract

Context/objective: Previous studies have illustrated the association of the ApaI and TaqI polymorphisms of the vitamin D receptor gene, located in non-coding and coding regions, respectively, with diseases such as cancer and cardiovascular disease; however, investigating such association in Egyptian patients with coronary artery disease (CAD) has never been formerly attempted. Materials and methods: Male patients (n?=?137), 35–50 years of age, with verified CAD, were recruited alongside age- and sex-matched controls (n?=?58). Genotyping and 25-hydroxyvitamin D [25(OH)D] measurement were performed by polymerase chain reaction RFLP and HPLC, respectively. Results: Comparison of the genotypic distribution of both the TaqI and ApaI polymorphisms between patients and controls yielded insignificant results (p?=?0.55 and 0.7, respectively). Comparison of the allelic distribution of both polymorphisms also yielded insignificant results. The TaqI polymorphism was not found to predict 25(OH)D levels, whereas the wild-type genotype of the ApaI polymorphism was associated with greater levels of 25(OH)D (p?=?0.02), taking all subjects into consideration. Discussion/conclusion: This study presents the ApaI and TaqI polymorphisms as non-influencing players in the pathogenesis of CAD in Egyptian males and the ability of only the ApaI polymorphism to predict 25(OH)D levels, thus warranting further investigations of the triangular relationship between the polymorphisms, 25(OH)D and CAD incidence.     

Genetic polymorphisms of vitamin D receptor (VDR) in Fabry disease

Fabry disease, an X-linked inborn error of metabolism, is characterized by multi-organ involvement including cardiac signs of left ventricular hypertrophy and abnormal intima-medial (IMT) thickening of arteries, progressive renal failure, neurological involvement, and more. The vitamin D receptor (VDR) and an enzyme producing vitamin D3 result in an autocrine loop with direct effects on blood vessels. The purpose of this study is to assess VDR polymorphisms (BsmI, FokI, ApaI, and TaqI) relative to clinically important disease parameters using a disease-specific severity score (MSSI) and haplotype analysis. There were statistically significant differences between females (43% of 74 patients) and males in MSSI total scores, and in general and neurologic sub-scores. There appears to be a protective effect of the TaqI tt genotype so that there were significantly lower scores in clinical categories between those with the tt genotype versus those with the TT genotype. Multivariate models of haplotypes with MSSI scores reveal that T-A-f-B and t-a-F-b haplotypes of the VDR gene polymorphisms are significantly associated with variation in the Fabry phenotype. Despite the limitations of using the MSSI score as a clinical correlate, these results are provocative and further studies in larger cohorts with more males are recommended.     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR?=?1.12, 95% CI: 0.88–1.44, p?=?0.36; BB genotype: OR?=?1.15, 95% CI: 0.81–1.62, p?=?0.43; bb genotype: OR?=?0.86, 95% CI: 0.61–1.20, p?=?0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.     

Screening and biochemical characterisation of resistant and susceptible citrus species against dry root rot disease (Fusarium solani)

Fourteen citrus species were screened for their resistance against dry root rot under artificial inoculation conditions and classified as resistant (RHRL-122, RHRL-124, Australian sour, Sour dig, Balaji, Rangpurlime), moderately resistant (PKM-1, AL-Srirampur, Rough lemon), Susceptible (TAL 95/1, TAL 95/2, TAL 95/3, Nalgonda selection) and highly susceptible (TAL 94/13). The higher polyphenol oxidase (PPO) activity was observed in all infected leaves and roots of citrus species when compared to healthy leaves and roots at 15 and 30 days after inoculation (DAI). Higher PPO activity was observed in Balaji, Australian sour and Rangpurlime whereas lowest PPO activity was observed in TAL 94/13. In the case of leaf Peroxidase (PEO) isozyme profile an additional band which was darker and thicker was observed at an Em value of 0.24 in the case of Australia sour, Balaji and AL-Srirampur. In roots the PEO isozyme profile has the induction of single thick and darker additional band with an Em value of 0.47 was observed in Australian sour and Balaji. The banding profiles of estarase in leaves showed the induction of an extra band in the ase of Australian sour at Em 0.1, and at Em 0.53 in the case of Rangpurlime and Sourdig when compared to other species. The banding profile of esterase in roots was well expressed in Australian sour, PKM-1, Rough lemon, TAL-95/3, Rangpurlime and Sour dig. However, a minor band at Em 0.27 in Australian sour, TAL 95/1 and at Em 0.33 in Balaji was observed.     

Forecasting infections of the red rot disease on Porphyra yezoensis Ueda (Rhodophyta) cultivation farms

Pythium porphyrae is a fungal pathogen responsible for red rot disease of the seaweed Porphyra (Rhodophyta). Infection forecasts of Porphyra by P. porphyrae were estimated from the epidemiological observations of Porphyra thalli and numbers of zoospore of P. porphyrae in laboratory and cultivation areas. Four features of forecasting infections were determined by relating zoospore concentrations to the incidence of thallus infection; infection (in more than 1000 zoospores L⁻¹), microscopic infection [less than 2 mm in diameter of lesion (in from 2000 to 3000 zoospores L⁻¹)], macroscopic infection [more than 2 mm in diameter of lesion (in from 3000 to 4000 zoospores L⁻¹), and thallus disintegration (in more than 4000 zoospores L⁻¹). High zoospore concentrations led to more infection. The tendency that zoospore concentration of P. porphyrae increased with the rate of infection of Porphyra thalli was generally observed in forecasting infections in both the laboratory and in cultivation areas. Based on the Porphyra cultivation areas, the accuracy and consistency of forecasting infections suggest that this method could be employed to manage and control red rot disease.     

Comparative proteomic analysis in children with idiopathic short stature (ISS) before and after short‐term recombinant human growth hormone (rhGH) therapy

This study was undertaken to identify growth hormone (GH) responsive proteins and protein expression patterns by short‐term recombinant human growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS) using proteomic analysis. Seventeen children (14 males and three females) with ISS were included. They were treated with rhGH at a dose of 0.31 ± 0.078 mg/kg/week for 3 months. Immunodepletion of six highly‐abundant serum proteins followed by 2D DIGE analysis, and subsequent MALDI TOF MS, were employed to generate a panel of proteins differentially expressed after short‐term rhGH therapy and verify the differences in serum levels of specific proteins by rhGH therapy. Fourteen spots were differentially expressed after rhGH treatment. Among them, apo E and apo L‐1 expression were consistently enhanced, whereas serum amyloid A was reduced after rhGH therapy. The differential expressions of these proteins were subsequently verified by Western blot analysis using sera of the before and after rhGH treatment. This study suggests that rhGH therapy influences lipoprotein metabolism and enhances apo L‐1 protein expression in ISS patients.     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease (ESRD) from the published reports is still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the iPTH level among patients with ESRD. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with iPTH level among patients with ESRD. In this meta-analysis, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations (Bb versus bb: OR?=?61.40, 95% CI: 19.65–103.16, p?=?0.004). However, the iPTH level in ESRD patients carrying BB genotype was not significant different from that in ESRD patients with Bb genotype and bb genotype in overall populations (BB versus Bb: OR?=??18.30, 95% CI: ?126.28–89.69, p?=?0.74; BB versus bb: OR?=?22.85, 95% CI: ?70.81–116.51, p?=?0.63). Furthermore, the results for Caucasians were similar to those in overall populations. In conclusion, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations and in Caucasians. However, more studies should be conducted to confirm it.     

Chitosan-induced defence responses in tomato plants against early blight disease caused by Alternaria solani (Ellis and Martin) Sorauer

The in vitro antifungal properties of chitosan and its role in protection of tomato from early blight disease were evaluated. Chitosan inhibited the radial and submerged growth of Alternaria solani at 1 mg/ml, and controls tomato plants from blight pathogen. Chitosan induces the level of chitinase activity and new isoforms of chitinase resulting in the reduction of early blight disease severity in tomato leaves. These results suggested the role of chitosan in activation of defence responses as well as protecting tomato plants from A. solani infection.     

Activation of phospholipases A2 and D of a human neuroblastoma cell line (LA-N-2) by N-dodecyl-L-lysine amide (compound 24), a putative G protein activator: characteristics of inhibition by (-)-nicotine

Compound 24, an alkyl-substituted amino acid amide, previously found to activate pertussis toxin-sensitive G proteins in cell membranes and membrane protein fractions, was used as a tool to determine the mechanism/location of nicotine inhibition of amyloid peptide-stimulated phospholipase A₂ and D activities in a human neuroblastoma cell line, LA-N-2, in vitro. In contrast to our previous findings with amyloid peptide, these phospholipase activations by compound 24 were not inhibited by (–)-nicotine, cholera toxin or tetanus toxin pretreatment. The contrasting activation of these phospholipases by amyloid peptide and compound 24 are discussed.     

Chitosan-induced defence responses in tomato plants against early blight disease caused by Alternaria solani (Ellis and Martin) Sorauer

The in vitro antifungal properties of chitosan and its role in protection of tomato from early blight disease were evaluated. Chitosan inhibited the radial and submerged growth of Alternaria solani at 1?mg/ml and control tomato plants from blight pathogen. Chitosan was able to induce the level of chitinase activity and new isoforms of chitinase, resulting in the reduction of early blight disease severity in tomato leaves. These results suggested the role of chitosan in activation of defence responses as well as protecting tomato plants from A. solani infection.     

Cerebrospinal fluid-optimized two-dimensional difference gel electrophoresis (2-D DIGE) facilitates the differential diagnosis of Creutzfeldt-Jakob disease

So far only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is included in the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). However, this assay cannot be used for screening because of the high rate of false positive results in sCJD, and often negative results in variant CJD. To facilitate the differential diagnosis of CJD, we applied 2-D differential gel-electrophoresis (2-D DIGE) as a quantitative proteomic screening system for CSF proteins. We compared 36 patients suffering from sCJD with 30 patients suffering from other neurodegenerative diseases. Sample preparation was optimized in consideration of the fact that CSF is composed of blood- and brain-derived proteins, and an improved 2-D DIGE protocol was established. Using this method in combination with protein identification by MALDI-TOF-MS, several known surrogate markers of sCJD like 14-3-3 protein, neuron-specific enolase, and lactate dehydrogenase were readily identified. Moreover, a not yet identified protein with an approximate molecular mass of 85 kDa was found as marker for sCJD with high diagnostic specificity and sensitivity. We conclude that our proteomic approach is useful to differentiate CJD from other neurodegenerative diseases and expect that CSF-optimized 2-D DIGE will find broad application in the search for other brain derived proteins in CSF.