Fumonisin-induced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion.

We review the hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides(= Fusarium moniliforme) strain MRC 826 in male BD IX rats. Subsequent chemical analyses of the fumonisin B (FB) mycotoxin content in the culture material used and long-term carcinogenesis studies with purified FB1 provide information about dose-response effects, relevance of hepatotoxicity during FB1-induced carcinogenesis, and the existence of a no-effect threshold. Fumonisin intake levels of between 0.08 and 0.16 mg FB/100 g body weight (bw)/day over approximately 2 years produce liver cancer in male BD IX rats. Exposure levels < 0.08 mg FB/100 g bw/day fail to induce cancer, although mild toxic and preneoplastic lesions are induced. The nutritional status of the diets used in the long-term experiments was marginally deficient in lipotropes and vitamins and could have played an important modulating role in fumonisin-induced hepatocarcinogenesis. Short-term studies in a cancer initiation/promotion model in rat liver provided important information about the possible mechanisms involved during the initial stages of cancer development by this apparently nongenotoxic mycotoxin. These studies supported the findings of long-term investigations indicating that a cytotoxic/proliferative response is required for cancer induction and that a no-effect threshold exists for cancer induction. The mechanisms proposed for cancer induction are highlighted and include the possible role of oxidative damage during initiation and the disruption of lipid metabolism, integrity of cellular membranes, and altered growth-regulatory responses as important events during promotion

Platforms to differentiate exotic pathovars of plant bacteria

Many of the EPPs that pose the biggest threat to the biosecurity of Australia’s plant industries are bacterial, but difficulties in identification to the subspecific or ‘ pathovar ’ level can seriously delay incursion management and affect market access. Pathovars are defined by host specificity so bio assays remain the definitive means of identification, but these require high level physical containment and can be slow and subjective , delaying diagnosis . Some pathovar - specific serological and molecular tests are available but better diagnostic methods are often required. This project used proteomics and metabolomics, platforms that identify functional molecules potentially associated with plant - pathogen interactions, to identify biomarkers that differentiate pathovars in species of Xanthomonas . Membrane - associated proteins from a collection of bacterial isolates were compared on 2Dimensional gels. Proteins that were found to be differentially expressed between distinct pathovars may be important modulators of host specificity so they were identified and the genes that encode them located by reference to genomic sequences . DNA - based assays targeting these genes were designed and validated for their specificity to the pathovar level . We have developed two new assays that provide levels of specificity not reported elsewhere in the literature. These assays specifically target the bacteria causing the different forms of citrus canker, but without cross - reaction to the closely - related organisms causing bacterial blight on cotton and Citrus Bacterial Spot. The molecular assays will be incorporated into the National Diagnostic Protocol for citrus canker through the SPHDS process. The metabolomics component has analysed metabolite expression in selected bacterial pathovars. Results showed separation between the different pathovars based on differential levels of expression of particular metabolites. These metabolites may be important determinants of pathogenicity. Neither proteomics nor metabolomics had been implemented before in the study of phytopathogenic bacteria and whilst both proved to be technically demanding, each delivered new biomarkers that differentiate phytopathogenic bacteria to a subspecific level . This confirmed the viability of these approaches as platforms to discover novel diagnostic targets. The new methods developed will be implemented into the national incursion response capability , improving the specificity of diagnostic testing available and reducing the possibility of false positive diagnosis . The project has fostered new collaborative partnerships both nationally (NSW, Victoria, WA) and internationally (to Thailand and the USA). The next phase of this work will provide a strong start - up project to the Plant Biosecurity Cooperative Research Centre ( PBCRC ) . This project has directly enhanced the plant bacteriology capacity of NSW and Australia trough the recruitment and training of science professionals and an undergraduate student , and supported the specialist training of a Thai scientist through allied project CRC20093

Clinical, biochemical, and genetic spectrum of MADD in a South African cohort: an ICGNMD study

\ua9 2024, The Author(s).Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. Methods: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. Results: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G &gt; A];c.[1067G &gt; A] and compound heterozygous c.[976G &gt; C];c.[1067G &gt; A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G &gt; A];c.[1448C &gt; T], c.[740G &gt; T];c.[1448C &gt; T], and c.[287dupA*];c.[1448C &gt; T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C &gt; T];c.[1448C &gt; T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G &gt; A] and c.[1448C &gt; T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of &lt; 0.00067–0.00084%. Conclusions: This study reveals the first extensive genotype–phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population

The Lingering Environmental Impact of Repressive Governance: The Environmental Legacy of the Apartheid Era for the New South Africa

This article aims to explore the historical link between contemporary environmental problems and the environmental, economic and political policies of the apartheid government. The analysis draws on an examination of the detrimental environmental impacts of the apartheid era and how international isolation impacted on governmental environmental management in the country, before turning attention to the way in which the ANC government has managed the South African natural and human environments in the period after 1994. The article shows that despite many important new developments since 1994, that there are high levels of continuity between the environmental management practices of the old and the new regimes. This state of affairs negatively impacts on the ability of the ANC government to provide every South African citizen with the clean and safe environment guaranteed to all within the 1996 Bill of Rights.This article also appeared unchanged as a chapter in the following edited collection: Jan Oosthoek and Barry K. Gills (eds), _The Globalization of Environmental Crisis_ (Abingdon: Routledge, 2008), pp. 109-120

International Paediatric Mitochondrial Disease Scale

Objective: There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study. Methods: A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6–16 years) from five different expert centres from four different continents were evaluated in this study. Results: The feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23–0.99). Conclusion: In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials

Exploring the components, asymmetry and distribution of relationship quality in wild Barbary macaques (Macaca sylvanus)

Social relationships between group members are a key feature of many animal societies. The quality of social relationships has been described by three main components: value, compatibility and security, based on the benefits, tenure and stability of social exchanges. We aimed to analyse whether this three component structure could be used to describe the quality of social relationships in wild Barbary macaques (Macaca sylvanus). Moreover, we examined whether relationship quality was affected by the sex, age and rank differences between social partners, and investigated the asymmetric nature of social relationships. We collected over 1,900 hours of focal data on seven behavioural variables measuring relationship quality, and used principal component analysis to investigate how these variables clustered together. We found that relationship quality in wild Barbary macaques can be described by a three component structure that represents the value, compatibility and security of a relationship. Female-female dyads had more valuable relationships and same-age dyads more compatible relationships than any other dyad. Rank difference had no effect on the quality of a social relationship. Finally, we found a high degree of asymmetry in how members of a dyad exchange social behaviour. We argue that the asymmetry of social relationships should be taken into account when exploring the pattern and function of social behaviour in animal societies

Sexual dimorphism in postcranial skeletal shape suggests male‐biased specialization for physical competition in anthropoid primates

Sexual dimorphism often arises as a response to selection on traits that improve a male's ability to physically compete for access to mates. In primates, sexual dimorphism in body mass and canine size is more common in species with intense male–male competition. However, in addition to these traits, other musculoskeletal adaptations may improve male fighting performance. Postcranial traits that increase strength, agility, and maneuverability may also be under selection. To test the hypothesis that males, as compared to females, are more specialized for physical competition in their postcranial anatomy, we compared sex‐specific skeletal shape using a set of functional indices predicted to improve fighting performance. Across species, we found significant sexual dimorphism in a subset of these indices, indicating the presence of skeletal shape sexual dimorphism in our sample of anthropoid primates. Mean skeletal shape sexual dimorphism was positively correlated with sexual dimorphism in body size, an indicator of the intensity of male–male competition, even when controlling for both body mass and phylogenetic relatedness. These results suggest that selection on male fighting ability has played a role in the evolution of postcranial sexual dimorphism in primates

Human bocavirus (HBoV) in children with respiratory tract infection by enzyme linked immunosorbent assay (ELISA) and qualitative polymerase chain reaction (PCR)

<p>Abstract</p> <p>Background</p> <p>Human bocavirus (HBoV) is a recently discovered parvovirus associated with mild to severe lower respiratory tract infections in children, the aim of the work was determination of human bocavirus in nasopharyngeal aspirate (NPA) of infants by qualitative PCR and determination of acute human bocavirus infection by estimation of immunoglobulin M (IgM) antibodies in serum by enzyme linked immunosorbent assay.</p> <p>Results</p> <p>Twenty two (22%) out of the 100 NPA specimens of the patients with respiratory manifestations were positive for HBoV by qualitative PCR, while ELISA revealed positive HBoV IgM antibodies in 18 (18%) patients who were also positive by PCR. Non of the controls were positive by both techniques. The correlation study between ELISA and PCR revealed high significant association, (p < 0.001, X²= 36 and agreement = 96%). Also PCR detected 4 (18.1%) NPA samples as HBoV positive cases among the patients that were not identified by ELISA. This could be due to high sensitivity and efficacy of PCR. ELISA being less sensitive than RT-PCR, sensitivity was (81.8% vs 100%), the efficacy was 97.7% in ELISA versus 99.7% for RT-PCR.</p> <p>Conclusion</p> <p>HBoV infections could be diagnosed in NPA of children by conventional PCR as a rapid and sensitive technique. While ELISA was a reliable serologic analysis for diagnosis of acute HBoV infection by estimation IgM antibodies in serum.</p