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Nature Aug 2015The E3 ubiquitin ligase PARKIN (encoded by PARK2) and the protein kinase PINK1 (encoded by PARK6) are mutated in autosomal-recessive juvenile Parkinsonism (AR-JP) and...
The E3 ubiquitin ligase PARKIN (encoded by PARK2) and the protein kinase PINK1 (encoded by PARK6) are mutated in autosomal-recessive juvenile Parkinsonism (AR-JP) and work together in the disposal of damaged mitochondria by mitophagy. PINK1 is stabilized on the outside of depolarized mitochondria and phosphorylates polyubiquitin as well as the PARKIN ubiquitin-like (Ubl) domain. These phosphorylation events lead to PARKIN recruitment to mitochondria, and activation by an unknown allosteric mechanism. Here we present the crystal structure of Pediculus humanus PARKIN in complex with Ser65-phosphorylated ubiquitin (phosphoUb), revealing the molecular basis for PARKIN recruitment and activation. The phosphoUb binding site on PARKIN comprises a conserved phosphate pocket and harbours residues mutated in patients with AR-JP. PhosphoUb binding leads to straightening of a helix in the RING1 domain, and the resulting conformational changes release the Ubl domain from the PARKIN core; this activates PARKIN. Moreover, phosphoUb-mediated Ubl release enhances Ubl phosphorylation by PINK1, leading to conformational changes within the Ubl domain and stabilization of an open, active conformation of PARKIN. We redefine the role of the Ubl domain not only as an inhibitory but also as an activating element that is restrained in inactive PARKIN and released by phosphoUb. Our work opens up new avenues to identify small-molecule PARKIN activators.
Topics: Animals; Binding Sites; Conserved Sequence; Crystallography, X-Ray; Enzyme Activation; Humans; Models, Molecular; Mutation; Parkinsonian Disorders; Pediculus; Phosphates; Phosphoproteins; Phosphorylation; Protein Binding; Protein Kinases; Protein Structure, Tertiary; Structure-Activity Relationship; Ubiquitin; Ubiquitin-Protein Ligases
PubMed: 26161729
DOI: 10.1038/nature14879 -
The Journal of Investigative Dermatology Mar 2014Head-louse infestation remains a public health problem. Despite published randomized-controlled trials, no consensus-based clinical practice guidelines for its... (Review)
Review
Head-louse infestation remains a public health problem. Despite published randomized-controlled trials, no consensus-based clinical practice guidelines for its management emerged because of the heterogeneity of trial methodologies. Our study was undertaken to attempt to find an optimal trial framework: minimizing the risk of bias, while taking feasibility into account. To do so, we used the vignette-based method. A systematic review first identified trials on head-louse infestation; 49 were selected and their methodological constraints assessed. Methodological features were extracted and combined by arborescence to generate a broad spectrum of potential designs, called vignettes, yielding 357 vignettes. A panel of 48 experts then rated one-on-one comparisons of those vignettes to obtain a ranking of the designs. Methodological items retained for vignette generation were income level of the population, types of treatments compared, randomization unit, blinding, treatment-administration site, diagnosis method and criteria, and primary outcome measure. The expert panel selected vignettes with cluster randomization, centralized treatment administration, and blinding of the outcome assessor. The vignette method identified optimal designs to standardize future head-louse treatment trials, thereby obtaining valid conclusions and comparable data from future trials, and appears to be a reliable way to generate evidence-based guidelines.
Topics: Animals; Bias; Evidence-Based Medicine; Humans; Lice Infestations; Pediculus; Randomized Controlled Trials as Topic
PubMed: 24121401
DOI: 10.1038/jid.2013.414 -
Emerging Infectious Diseases Sep 2008
Review
Topics: Animals; Global Health; Humans; Lice Infestations; Pediculus
PubMed: 18760032
DOI: 10.3201/eid1409.080368 -
Parasitology Research May 2021Head lice (Pediculus humanus capitis) are worldwide obligate human ectoparasites, with high implications in pediatrics. In Europe, first-line topical neurotoxic...
Head lice (Pediculus humanus capitis) are worldwide obligate human ectoparasites, with high implications in pediatrics. In Europe, first-line topical neurotoxic insecticidal therapeutic strategies are being replaced by topical physically acting agents as the first-choice treatment. Safety of the active ingredients and high efficacy in a one-time single-dose treatment with a brief treatment application time are key issues for consumer use and effective compliance. The aim of this study was to assess the in vitro efficacy of a newly developed squalane and dimethicone-based pediculicidal formula, against motile head lice and eggs after 2 and 5 min immersion in the product, as well as its skin tolerance and acceptability under dermatological and pediatric expert control in children with atopic skin. The results indicate that at both time points, 100% mortality rate of head lice crawling stages and late-stage eggs was achieved. The formula was well tolerated and suitable for children with atopic skin from 12 months of age. Showing high in vitro efficacy and good skin acceptability, this solution is presented as a new safe alternative therapy for treatment of head lice infestations.
Topics: Animals; Child, Preschool; Dimethylpolysiloxanes; Europe; Female; Humans; Infant; Insecticides; Lice Infestations; Male; Pediculus; Skin; Squalene
PubMed: 33797611
DOI: 10.1007/s00436-021-07113-y -
Medicina (Kaunas, Lithuania) Nov 2022Background and Objectives: Pediculosis, or head lice infestation, is a widespread health problem that can affect anyone, regardless of gender, age, or social background....
Background and Objectives: Pediculosis, or head lice infestation, is a widespread health problem that can affect anyone, regardless of gender, age, or social background. The purpose of this study was to clarify the occurrence of pediculosis among Estonian preschool- and primary school-aged children according to their parents and the parent’s awareness of pediculosis and related behaviors. Materials and Methods: An online questionnaire was completed by the parents of the preschool children (n = 1141) in 2019 and the parents of the elementary school children (n = 362) in 2021. For the descriptive data, t-test, Mann−Whitney or χ2 test, linear regression, and logistic regression analyses were applied. Results: According to the parents, pediculosis had occurred in 34.7% of the children, and more than one-third of pediculosis patients had experienced it more than twice. Lice were mainly acquired from elementary school or preschool and less often from friends, relatives, or training environments. Parents’ knowledge of head lice was rather good; the average score of the correct answers was 14.0 ± 3.4 (max. 20). In the multivariate analysis, higher age (coefficient 0.07, p < 0.001), healthcare education (coefficient 1.19, p < 0.001), and a previous occurrence of pediculosis in a family (coefficient 1.95; p < 0.001) were factors influencing better knowledge. In order to treat the infestation, antilice shampoo and combing were the most often used methods. Conclusion: Despite parents’ awareness, pediculosis infestations continue to be common among our children.
Topics: Animals; Humans; Child, Preschool; Child; Lice Infestations; Estonia; Pediculus; Parents; Surveys and Questionnaires; Prevalence
PubMed: 36556975
DOI: 10.3390/medicina58121773 -
Frontiers in Veterinary Science 2023To obtain new data on the species diversity, host associations and spatiotemporal occurrence of flies and blood-sucking lice of veterinary importance in Malta,...
An update on the occurrence of flies (Diptera: Muscidae, Calliphoridae) and sucking lice (Phthiraptera: Anoplura) of veterinary importance in Malta: First record of and .
To obtain new data on the species diversity, host associations and spatiotemporal occurrence of flies and blood-sucking lice of veterinary importance in Malta, ectoparasites were collected at cattle, sheep and goat, pig farms, as well as dog shelters, and in two places in the absence of domestic animals. The species were identified morphologically, but voucher specimens were also analyzed with molecular-phylogenetic methods following DNA extraction. Altogether 3,095 flies (Diptera: Muscidae, Calliphoridae) were collected at farms and kennels near domestic animals, as well as 37 blowflies (Calliphoridae) in rural and urban areas without animals nearby. Regarding Muscidae, the great majority of flies ( = 3,084) were identified as the common housefly (). Eight flies represented the stable fly (). Three blowflies associated with dogs and small ruminants belonged to . By contrast, all 37 blowflies collected without domestic animals nearby, were identified as . In addition, 22 sucking lice were collected from goats, and all belonged to . Molecular identification of 28 flies and four lice confirmed the above species. Considering the sex ratio of among samples collected randomly at cattle farms, females predominated in the whole study period, but the abundance of males increased significantly toward the autumn. was associated with cattle and dogs, whereas was found near small ruminants and dogs. To our knowledge, this is the first study including the molecular analysis of flies and lice of veterinary-medical importance from Malta. The most important finding of this study is the first evidence for the autochthonous occurrence of in Malta. The exclusive presence of at animal-keeping facilities in rural areas and association of with urban areas void of livestock might reflect similar habitat preference of these species in Malta to what was reported in South Africa. Based on the sucking-louse burden in the examined goat herds, the situation in Malta was similar to northern Africa where the exclusive presence of was reported, unlike toward the north in the Mediterranean Basin where populations of this species are mixed with .
PubMed: 36998639
DOI: 10.3389/fvets.2023.1143800 -
Turkiye Parazitolojii Dergisi Jun 2015This study aimed to examine scientific articles performed in Turkey on the prevalence and management of PK (diagnosis, contagion, prevention, treatment) from a critical... (Review)
Review
This study aimed to examine scientific articles performed in Turkey on the prevalence and management of PK (diagnosis, contagion, prevention, treatment) from a critical perspective. The population of the systematic review consisted of total 63 published and unpublished theses or dissertations and peer-reviewed articles published in Turkish or English in national or foreign scientific journals from studies performed in Turkey between 1982 and 2012 years. It reached 578,938 people in 63 studies. Seventy-eight percent of the studies were related to the prevalence of PK and/or associated factors. The number of the studies was limited regarding diagnosis, prevention, contagion, treatment compliance, difficulties and causes of failure. Of the studies, 90.5% had been performed in public schools, almost exclusively elementary schools. The prevalence of PK was 0.3-34.1%, 0-35.4%, and it was 0.3-34.1% in elementary school children. It increased with years of education. It was double that of the boys in the girls (p<0.05). The prevalence among the subjects with low economic status were 1.9-42.3%, and it increased with worsening economic status (p<0.05). The prevalence reached up to 44.1% among children with illiterate mother. Basic recommendations include increasing the number of studies on the diagnosis, prevention, contagion, treatment compliance and efficacy, treatment failures and difficulties; public health workers also should prioritize investigation of head lice infestation.
Topics: Animals; Child; Female; Humans; Lice Infestations; Male; Mothers; Patient Compliance; Pediculus; Prevalence; Scalp Dermatoses; Schools; Socioeconomic Factors; Treatment Failure; Turkey
PubMed: 26081888
DOI: 10.5152/tpd.2015.3628 -
Revue Scientifique Et Technique... Apr 2015Among the many complex relationships between insects and microorganisms such as viruses, bacteria and parasites, some have resulted in the establishment of biological...
Among the many complex relationships between insects and microorganisms such as viruses, bacteria and parasites, some have resulted in the establishment of biological systems within which the insects act as a biological vector for infectious agents. It is therefore advisable to understand the identity and biology of these vectors in depth, in order to define procedures for epidemiological surveillance and anti-vector control. The following are successively reviewed in this article: Anoplura (lice), Siphonaptera (fleas), Heteroptera (bugs: Cimicidae, Triatoma, Belostomatidae), Psychodidae (sandflies), Simuliidae (black flies), Ceratopogonidae (biting midges), Culicidae (mosquitoes), Tabanidae (horseflies) and Muscidae (tsetse flies, stable flies and pupipara). The authors provide a rapid overview of the morphology, systematics, development cycle and bio-ecology of each of these groups of vectors. Finally, their medical and veterinary importance is briefly reviewed.
Topics: Animals; Communicable Diseases; Feeding Behavior; Insect Vectors; Insecta
PubMed: 26470450
DOI: No ID Found -
Acta Dermatovenerologica Alpina,... Dec 2008Head lice infestation, or pediculosis capitis, caused by Pediculus humanus capitis, is a common health concern. In the US, where pediculosis capitis is the most... (Review)
Review
Head lice infestation, or pediculosis capitis, caused by Pediculus humanus capitis, is a common health concern. In the US, where pediculosis capitis is the most prevalent parasitic infestation of children, 6 to 12 million people are affected every year. Pediculosis capitis remains confined to the scalp. Scalp pruritus is the cardinal symptom, although patients with lice can be asymptomatic. Pruritus with impetiginization should prompt the physician to look for lice or viable nits. All close contacts should be examined. Treatment directed at killing the lice and the ova should be considered only if active lice or viable eggs are observed. The three fundamental effective treatment options for head lice are topical pediculicides, wet combing, and oral therapy. Spraying or fogging a home with insecticides or pediculicides is not recommended.
Topics: Animals; Child; Humans; Insecticides; Lice Infestations; Pediculus; Pyrethrins; Scalp Dermatoses
PubMed: 19104739
DOI: No ID Found -
PLoS Genetics Aug 2018Ivermectin has emerged as very promising pediculicide, particularly in cases of resistance to commonly used pediculicides. Recently, however, the first field-evolved...
Ivermectin has emerged as very promising pediculicide, particularly in cases of resistance to commonly used pediculicides. Recently, however, the first field-evolved ivermectin-resistance in lice was reported. To gain insight into the mechanisms underlying ivermectin-resistance, we both looked for mutations in the ivermectin-target site (GluCl) and searched the entire proteome for potential new loci involved in resistance from laboratory susceptible and ivermectin-selected resistant body lice. Polymorphism analysis of cDNA GluCl showed no non-silent mutations. Proteomic analysis identified 22 differentially regulated proteins, of which 13 were upregulated and 9 were downregulated in the resistant strain. We evaluated the correlation between mRNA and protein levels by qRT-PCR and found that the trend in transcriptional variation was consistent with the proteomic changes. Among differentially expressed proteins, a complexin i.e. a neuronal protein which plays a key role in regulating neurotransmitter release, was shown to be the most significantly down-expressed in the ivermectin-resistant lice. Moreover, DNA-mutation analysis revealed that some complexin transcripts from resistant lice gained a premature stop codon, suggesting that this down-expression might be due, in part, to secondary effects of a nonsense mutation inside the gene. We further confirmed the association between complexin and ivermectin-resistance by RNA-interfering and found that knocking down the complexin expression induces resistance to ivermectin in susceptible lice. Our results provide evidence that complexin plays a significant role in regulating ivermectin resistance in body lice and represents the first evidence that links complexin to insecticide resistance.
Topics: Amino Acid Sequence; Animals; Cloning, Molecular; Gene Expression Regulation; Insect Proteins; Insecticide Resistance; Insecticides; Ivermectin; Lice Infestations; Nerve Tissue Proteins; Pediculus; Proteomics; RNA, Messenger; Sequence Analysis, DNA
PubMed: 30080859
DOI: 10.1371/journal.pgen.1007569