Characterization of three novel pathogenic SLC40A1 mutations and genotype/phenotype correlations in 7 Italian families with type 4 hereditary hemochromatosis

Mutations of SLC40A1 encoding ferroportin (Fpn), the unique cellular iron exporter, severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations. This disease can be classified as type 4A, better known as “ferroportin disease”, which is due to “loss of function” mutations that lead to decreased iron export from cells, or as type 4B hemochromatosis, which is caused by “gain of function” mutations, conferring partial or complete resistance to hepcidin-mediated Fpn degradation.In this work, we discuss clinical and molecular findings on a group of patients in whom a SLC40A1 single copy missense variant was identified. Three novel variants, p.D181N, p.G204R and p.R296Q were functionally characterized. Fpn D181N and R296Q mutants can be classified as full or partial loss of function, respectively. Replacement of G204 with arginine appears to cause a more complex defect with impact both on iron export function and hepcidin sensitivity. This finding confirms the difficulty of predicting the effect of a mutation on the molecular properties of Fpn in order to provide an exhaustive explanation to the wide variability of the phenotype in type 4 hereditary hemochromatosis.     

Rabies in the Baltic States: Decoding a Process of Control and Elimination

Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries—Estonia, Latvia and Lithuania—to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005–2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North-East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles).     

Trend in ambient ozone and an attempt to detect its effect on biota in forest ecosystem. Step I of Lithuanian studies

The presented study aimed to explore the relationships between ambient ozone (O3) and tree defoliation, specific diversity, and abundance of soil microarthropods, stream macroinvertebrates, and small mammals (mainly rodents) in order to test the hypothesis that changes in the considered objects of the forest ecosystem could be related to changes in ambient O3, concentration of which is below critical level. The observations were carried out from 1994 at three integrated monitoring stations. The obtained data revealed that only peak O3 concentrations (from 125-215 microg x m(-3)) had significant effect on changes in the considered components of forest biota.     

46,XX,der(2)t(2;10)(2pter-->2q37::10p13-->10pter)[127]/45,X,der(2)t(2;10) (2pter-->2q37::10p13-->10pter)[23]. Karyotype-phenotype correlation and genetic counselling in complex karyotypes

We describe a female child with complex cytogenetic anomalies consisting in partial trisomy of the short arm of chromosome 10, terminal deletion of the long arm of chromosome 2 and--at the same time--a mosaicism for X monosomy. To our knowledge, this is the first case reported in which 10p trisomy is associated to a 2qter deletion. Due to the scarcity of cases reported with pure trisomy, it has not been possible to define the 10p+ syndrome precisely yet. Comparison of our proband's phenotype to both the 2q37 deletion and 10p trisomy showed more features described in 2q37- subjects than in 10p+ ones. We also discuss the difficulties of genetic counseling in children with complex aberrations.     

Comparison of Alnus,Corylus, Betula pollen seasons in Riga,Moscow and Vilnius

Research characterizes differences and similarities of the seasonal behaviour of Alnus, Betula, Corylus pollen in Riga, Moscow and Vilnius. An important uniting factor dealing with the research is that on the selected territories in spring there are abundance of Alnus, Corylus and Betula airborne pollen. The study is based on the 2004–2011 atmospheric pollen records. Differences and similarities of the analysed territories include the following: (1) the beginning of the Alnus and Corylus pollen season usually coincided in Riga and Vilnius, whereas significantly differed between Riga and Moscow; (2) no significant differences among separate stations have been estimated concerning the beginning of the Betula pollen season; (3) Moscow differed by the shortest period of pollen season, independently of the pollen type; (4) the biennial cycle of Betula pollen is characteristic to Riga only; (5) in the spectrum of spring plants’ pollen, Corylus pollen was found in the least amount (10–23 pgm^?3 per day on the average); (6) average concentration of Betula pollen per day significantly differed in all locations of the survey, in Moscow, the concentration (853 pgm^?3) was twice higher that in Riga and Vilnius; (7) Alnus, Corylus and Betula pollen seasons overlap each other in all locations surveyed, thus creating additional load of pollen; (8) in each of the stations, there were 13–15 days when concentration of Betula pollen exceeded 100 pgm^?3.     

Comparison of physicochemical properties of chitins isolated from an insect (Melolontha melolontha) and a crustacean species (Oniscus asellus)

The chitin structures of two common European species belonging to Insecta (Melolontha melolontha) and Crustacea (Oniscus asellus) were isolated. The same procedure is followed for chitin isolations for both the species. First, HCl was used for removing of minerals in the organisms, and then, the protein structure was removed by using NaOH. Chitins obtained from these two species were characterized physicochemically. Physicochemical properties of chitins isolated from the insect and the crustacean were compared to each other. The chitin content for dry weights of M. melolontha and O. asellus were recorded as 13–14 and 6–7 %, respectively. The results of Fourier transform infrared spectroscopy, thermogravimetric analysis and X-ray diffraction analysis were found to be more or less similar. The surface morphologies of chitins were examined via environmental scanning electron microscopy and nanofibers, and pore structures were observed. While the chitin nanofibers of O. asellus were adherent to each other, nanofibers of M. melolontha were non-adherent. On the other hand, the number of pores was much higher in the chitin from M. melolontha than in the chitin from O. asellus. Looking at the elemental analysis results, the M. melolontha chitin was found to be more pure than the O. asellus chitin. For this reason, M. melolontha has been considered more attractive source for chitin than O. asellus.     

The course of diabetes in children,adolescents and young adults: does the autoimmunity status matter?

Background

Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes.The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0–25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies.

Methods

Cross-sectional population-based study was performed covering 100% of pediatric (n?=?860) and 70% of 18–25 years old adult patients (n?=?349) with type 1 diabetes in Lithuania.

Results

No antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p?<?0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p?<?0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p?>?0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p?<?0.05).

Conclusion

Antibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.