Disruption of tuftelin 1, a desmosome associated protein, causes skin fragility, woolly hair and palmoplantar keratoderma

Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss of function variants in desmosomal genes lead to a variety of skin and heart related phenotypes. Here, we report tuftelin 1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair and mild palmoplantar keratoderma, but without a cardiac phenotype, we identified a homozygous splice site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of tuftelin 1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that tuftelin 1 is positioned within the desmosome and its location dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1 knock-out mouse model mimicked the patients' phenotypes. Altogether, this study reveals tuftelin 1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair and palmoplantar keratoderma

Cardiovascular and metabolic influences of fetal smoke exposure

Many epidemiological studies showed associations of low birth weight with cardiovascular disease, type 2 diabetes and obesity. The associations seem to be consistent and stronger among subjects with a postnatal catch up growth. It has been suggested that developmental changes in response to adverse fetal exposures might lead to changes in the fetal anatomy and physiology. These adaptations may be beneficial for short term, but may lead to common diseases in adulthood. Maternal smoking during pregnancy is one of the most important adverse fetal exposures in Western countries, and is known to be associated with a 150–200 g lower birth weight. An accumulating body of evidence suggests that maternal smoking during pregnancy might be involved in pathways leading to both low birth weight and common diseases, including cardiovascular disease, type 2 diabetes and obesity, in adulthood. In this review, we discuss epidemiological studies focused on the associations of maternal smoking with fetal growth and development and cardiovascular and metabolic disease in later life. We also discuss potential biological mechanisms, and challenges for future epidemiological studies

Molecular characterization of Cryptosporidium spp. from wild rats and mice from rural communities in the Philippines

In order to examine the prevalence of Cryptosporidium in wild rodents in the Philippines and understand the role wild rodents play in the transmission of this parasite to humans and livestock, 194 fecal samples from wild rats and mice from Luzon and Mindoro islands were examined. Molecular screening at the 18S and actin gene loci identified an overall prevalence of 25.8% (95%CI: 19.8, 32.5). Sequence and phylogenetic analysis of both loci identified C. parvum, C. muris, C. scrofarum, rat genotypes I-IV and a C. suis-like genotype in the rat-derived isolates and is the first report of C. suis-like and C. scrofarum in rats. Mixed infections were identified in 24% of the Cryptosporidium positive isolates. Rat genotypes II, III and IV showed high intragenotypic variation at the 18S gene locus compared to the actin locus

Human cryptosporidiosis diagnosed in Western Australia: A mixed infection with Cryptosporidium meleagridis, the Cryptosporidium mink genotype, and an unknown Cryptosporidium species

This report describes a case of cryptosporidiosis from an immunocompetent patient from Perth, Western Australia, suffering from diarrhea and a spectrum of other symptoms. Molecular identification revealed that this patient was infected with three Cryptosporidium species-Cryptosporidium meleagridis, the Cryptosporidium mink genotype, and an unknown Cryptosporidium species

Investigation of a swimming pool-associated cryptosporidiosis outbreak in the Kimberley region of Western Australia

Cryptosporidiosis is a gastroenteric disease caused by the protozoan parasite Cryptosporidium, which manifests primarily as watery diarrhoea. Transmitted via the faecal-oral route, infection with the parasite can occur through ingestion of water, food or other fomites contaminated with its infective oocyst stage. In the months of November and December 2012, there were 18 notified cases of cryptosporidiosis from Broome, Western Australia. The 5-year average for the Kimberley region for this period is <1 case. Interviews conducted by Broome local government staff on the notified cases revealed that 11/18 cases had been swimming at the Broome public swimming pool. Molecular analyses of extracted DNA performed on 8/18 microscopy-positive faecal samples from interviewed cases and three water samples from different locations at the hypervariable glycoprotein 60 (gp60) gene, identified the C. hominis IbA10G2 subtype in all human samples and one water sampl

Differences in the occurrence and epidemiology of cryptosporidiosis in Aboriginal and non-Aboriginal people in Western Australia (2002 − 2012)

Cryptosporidiosis is a diarrhoeal illness caused by the protozoan parasite Cryptosporidium. In Australia, very little is known about the epidemiology of cryptosporidiosis in Aboriginal peoples. The present study analysed long-term cryptosporidiosis patterns across Western Australia (WA) (2001 − 2012), combined with genotyping and subtyping data at the 18S and glycoprotein 60 (gp60) loci respectively. Comparison of cryptosporidiosis notifications between Aboriginal and non-Aboriginal people in WA, revealed that notification rates among Aboriginal people were up to 50 times higher compared to non-Aboriginal people, highlighting the burden of the disease in this population. More than 90% of notifications were in Aboriginal children aged 00–04 years, who had a notification rate 20.5 times higher than non-Aboriginal children in the same age group. Cryptosporidium hominis was the predominant species infecting both Aboriginal and non-Aboriginal people. However, Aboriginal people were mainly infected with the C. hominis IdA15G1 subtype, whereas non-Aboriginal people were predominantly infected with the IbA10G2 subtype. To control cryptosporidiosis in Aboriginal populations in Australia, effective health interventions/promotions need to be a priority for public health research and action

Metabolomic profiling of faecal extracts from cryptosporidium parvum infection in experimental mouse models

Cryptosporidiosis is a gastrointestinal disease in humans and animals caused by infection with the protozoan parasite Cryptosporidium. In healthy individuals, the disease manifests mainly as acute self-limiting diarrhoea, but may be chronic and life threatening for those with compromised immune systems. Control and treatment of the disease is challenged by the lack of sensitive diagnostic tools and broad-spectrum chemotherapy. Metabolomics, or metabolite profiling, is an emerging field of study, which enables characterisation of the end products of regulatory processes in a biological system. Analysis of changes in metabolite patterns reflects changes in biochemical regulation, production and control, and may contribute to understanding the effects of Cryptosporidium infection in the host environment. In the present study, metabolomic analysis of faecal samples from experimentally infected mice was carried out to assess metabolite profiles pertaining to the infection. Gas-chromatography mass spectrometry (GC-MS) carried out on faecal samples from a group of C. parvum infected mice and a group of uninfected control mice detected a mean total of 220 compounds. Multivariate analyses showed distinct differences between the profiles of C. parvum infected mice and uninfected control mice,identifying a total of 40 compounds, or metabolites that contributed most to the variance between the two groups. These metabolites consisted of amino acids (n = 17), carbohydrates (n = 8), lipids (n = 7), organic acids (n = 3) and other various metabolites (n = 5), which showed significant differences in levels of metabolite abundance between the infected and uninfected mice groups (p < 0.05). The metabolites detected in this study as well as the differences in abundance between the C. parvum infected and the uninfected control mice, highlights the effects of the infection on intestinal permeability and the fate of the metabolites as a result of nutrient scavenging by the parasite to supplement its streamlined metabolism

Identification of novel and zoonotic Cryptosporidium species in fish from Papua New Guinea

There is still limited information on the distribution of Cryptosporidium species and genotypes in fish. The present study investigated the prevalence of Cryptosporidium species in cultured freshwater (n = 132), wild freshwater (n = 206) and wild marine (n = 276) fish in Papua New Guinea (PNG) by PCR screening at the 18S rRNA locus. A total of seven fish (2 cultured freshwater, 1 wild freshwater and 4 wild marine fish) were identified as positive for Cryptosporidium. Specifically, Cryptosporidium was found in four different host species (Nile tilapia, Oreochromis niloticus; silver barb, Puntius gonionotus; mackerel scad, Decapterus maracellus and oblong silver biddy, Gerres oblongus), giving an overall prevalence of 1.14% (95% CI: 0.3-2%, n = 7/614). Of the seven positive isolates, five were identified as C. parvum and two were a novel piscine genotype, which we have named piscine genotype 8. Piscine genotype 8 was identified in two marine oblong silver biddies and exhibited 4.3% genetic distance from piscine genotype 3 at the 18S locus. Further subtyping of C. parvum isolates at the 60 kDa glycoprotein (gp60) locus identified 3 C. parvum subtypes (IIaA14G2R1, IIaA15G2R1 and IIaA19G4R1) all of which are zoonotic and a C. hominis subtype (IdA15G1). The zoonotic Cryptosporidium were identified in fish samples from all three groups; cultured and wild freshwater and wild marine fish. Detection of Cryptosporidium among aquaculture fingerlings warrants further research to gain a better understanding of the epidemiology of Cryptosporidium infection in cultured fish. The identification of zoonotic Cryptosporidium genotypes in fish from PNG has important public health implications and should be investigated further

Longitudinal prevalence, oocyst shedding and molecular characterisation of Cryptosporidium species in sheep across four states in Australia

The prevalence of Cryptosporidium in sheep in the eastern states of Australia has not been well described, therefore a study of the prevalence, oocyst concentration, species and subtypes of Cryptosporidium were assessed from lamb faecal samples at three sampling periods (weaning, post-weaning and pre-slaughter) from eight farms across South Australia, New South Wales, Victoria and Western Australia. A total of 3412 faecal samples were collected from approximately 1182 lambs across the four states and screened for the presence of Cryptosporidium using a quantitative PCR (qPCR) at the actin locus. Positives were typed at the 18S locus and at a second locus using C. parvum and C. hominis specific qPCR primers. The overall prevalence was 16.9% (95% CI: 15.6-18.1%) and of the 576 positives, 500 were successfully genotyped. In general, the prevalence of Cryptosporidium was higher in WA than the eastern states. Cryptosporidium prevalence peaked at 43.9% and 37.1% at Pingelly (WA2) and Arthur River (WA1), respectively during weaning and at Pingelly (WA2) during pre-slaughter (36.4%). The range of oocyst shedding at weaning overall across all states was 63-7.9 × 106 and the median was 3.2 × 104 oocysts g-1. The following species were identified; C. xiaoi (69%-345/500), C. ubiquitum (17.6%-88/500), C. parvum (9.8%-49/500), C. scrofarum (0.8%-4/500), mixed C. parvum and C. xiaoi (2.4%-12/500), C. andersoni (0.2%-1/500) and sheep genotype 1 (0.2%-1/500). Subtyping of C. parvum and C. ubiquitum isolates identified IIa and IId subtype families within C. parvum (with IId as the dominant subtype) and XIIa within C. ubiquitum. This is the first published description of C. parvum subtypes detected in lambs in Australia