Morphology, ecology and distribution of threatened species in Cacatuidae family

Neprestani negativni antropogeni utjecaj dovodi do ugroženosti vrsta i povećanog rizika od izumiranja istih. Ovaj rad donosi kratak pregled ugroženih vrsta iz porodice Cacatuidae, uključujući njihovu morfologiju, ekologiju, distribuciju te kategoriju i razloge ugroženosti. Kao glavni razlozi ugroženosti navode se kontinuirana deforestacija, krivolov i ilegalna trgovina te globalno zatopljenje. Navedeni problemi uzrokuju smanjenje populacija, često bez mogućnosti oporavka te zbog toga brojnost vrsta kontinuirano pada. Kako bi se usporio nestanak vrsta, provode se brojne edukacije, istraživanja i projekti, a na nacionalnoj i internacionalnoj razini donose se propisi i mjere za zaštitu vrsta i njihovih staništa.Continuous negative anthropogenic influence leads to endangered species and increased risk of extinction. This paper provides a brief overview of the endangered species of the Cacatuidae family, including their morphology, ecology, distribution, and the category and causes of endangerment. The main threats include continuous deforestation, poaching, illegal trade and global warming. These problems cause decline of populations, often with no recovery potential, and therefore the number of species continues to decline. To slow down the disappearance of species, numerous education and research projects are carried out, while regulations and measures for the protection of species and their habitats are adopted at national and international level

Morphology, ecology and distribution of threatened species in Cacatuidae family

Neprestani negativni antropogeni utjecaj dovodi do ugroženosti vrsta i povećanog rizika od izumiranja istih. Ovaj rad donosi kratak pregled ugroženih vrsta iz porodice Cacatuidae, uključujući njihovu morfologiju, ekologiju, distribuciju te kategoriju i razloge ugroženosti. Kao glavni razlozi ugroženosti navode se kontinuirana deforestacija, krivolov i ilegalna trgovina te globalno zatopljenje. Navedeni problemi uzrokuju smanjenje populacija, često bez mogućnosti oporavka te zbog toga brojnost vrsta kontinuirano pada. Kako bi se usporio nestanak vrsta, provode se brojne edukacije, istraživanja i projekti, a na nacionalnoj i internacionalnoj razini donose se propisi i mjere za zaštitu vrsta i njihovih staništa.Continuous negative anthropogenic influence leads to endangered species and increased risk of extinction. This paper provides a brief overview of the endangered species of the Cacatuidae family, including their morphology, ecology, distribution, and the category and causes of endangerment. The main threats include continuous deforestation, poaching, illegal trade and global warming. These problems cause decline of populations, often with no recovery potential, and therefore the number of species continues to decline. To slow down the disappearance of species, numerous education and research projects are carried out, while regulations and measures for the protection of species and their habitats are adopted at national and international level

Morphology, ecology and distribution of threatened species in Cacatuidae family

Neprestani negativni antropogeni utjecaj dovodi do ugroženosti vrsta i povećanog rizika od izumiranja istih. Ovaj rad donosi kratak pregled ugroženih vrsta iz porodice Cacatuidae, uključujući njihovu morfologiju, ekologiju, distribuciju te kategoriju i razloge ugroženosti. Kao glavni razlozi ugroženosti navode se kontinuirana deforestacija, krivolov i ilegalna trgovina te globalno zatopljenje. Navedeni problemi uzrokuju smanjenje populacija, često bez mogućnosti oporavka te zbog toga brojnost vrsta kontinuirano pada. Kako bi se usporio nestanak vrsta, provode se brojne edukacije, istraživanja i projekti, a na nacionalnoj i internacionalnoj razini donose se propisi i mjere za zaštitu vrsta i njihovih staništa.Continuous negative anthropogenic influence leads to endangered species and increased risk of extinction. This paper provides a brief overview of the endangered species of the Cacatuidae family, including their morphology, ecology, distribution, and the category and causes of endangerment. The main threats include continuous deforestation, poaching, illegal trade and global warming. These problems cause decline of populations, often with no recovery potential, and therefore the number of species continues to decline. To slow down the disappearance of species, numerous education and research projects are carried out, while regulations and measures for the protection of species and their habitats are adopted at national and international level

Impaired Retromer Function in Niemann-Pick Type C Disease Is Dependent on Intracellular Cholesterol Accumulation

Niemann-Pick type C disease (NPC) is a rare inherited neurodegenerative disorder characterized by an accumulation of intracellular cholesterol within late endosomes and lysosomes due to NPC1 or NPC2 dysfunction. In this work, we tested the hypothesis that retromer impairment may be involved in the pathogenesis of NPC and may contribute to increased amyloidogenic processing of APP and enhanced BACE1-mediated proteolysis observed in NPC disease. Using NPC1-null cells, primary mouse NPC1-deficient neurons and NPC1-deficient mice (BALB/cNctr-Npc1m1N), we show that retromer function is impaired in NPC. This is manifested by altered transport of the retromer core components Vps26, Vps35 and/or retromer receptor sorLA and by retromer accumulation in neuronal processes, such as within axonal swellings. Changes in retromer distribution in NPC1 mouse brains were observed already at the presymptomatic stage (at 4-weeks of age), indicating that the retromer defect occurs early in the course of NPC disease and may contribute to downstream pathological processes. Furthermore, we show that cholesterol depletion in NPC1-null cells and in NPC1 mouse brains reverts retromer dysfunction, suggesting that retromer impairment in NPC is mechanistically dependent on cholesterol accumulation. Thus, we characterized retromer dysfunction in NPC and propose that the rescue of retromer impairment may represent a novel therapeutic approach against NPC

Impaired Retromer Function in Niemann-Pick Type C Disease Is Dependent on Intracellular Cholesterol Accumulation

Niemann-Pick type C disease (NPC) is a rare inherited neurodegenerative disorder characterized by an accumulation of intracellular cholesterol within late endosomes and lysosomes due to NPC1 or NPC2 dysfunction. In this work, we tested the hypothesis that retromer impairment may be involved in the pathogenesis of NPC and may contribute to increased amyloidogenic processing of APP and enhanced BACE1-mediated proteolysis observed in NPC disease. Using NPC1-null cells, primary mouse NPC1-deficient neurons and NPC1-deficient mice (BALB/cNctr-Npc1m1N), we show that retromer function is impaired in NPC. This is manifested by altered transport of the retromer core components Vps26, Vps35 and/or retromer receptor sorLA and by retromer accumulation in neuronal processes, such as within axonal swellings. Changes in retromer distribution in NPC1 mouse brains were observed already at the presymptomatic stage (at 4-weeks of age), indicating that the retromer defect occurs early in the course of NPC disease and may contribute to downstream pathological processes. Furthermore, we show that cholesterol depletion in NPC1-null cells and in NPC1 mouse brains reverts retromer dysfunction, suggesting that retromer impairment in NPC is mechanistically dependent on cholesterol accumulation. Thus, we characterized retromer dysfunction in NPC and propose that the rescue of retromer impairment may represent a novel therapeutic approach against NPC

Distribution of BACE1 substrates in the endosomal fractions isolated from the brain regions of wild type (NCP1+/+) and NPC1-/- disease mouse model

Niemann-Pickova bolest tipa C (NPC) nasljedna je, rijetka neurodegenerativna bolest nakupljanja lipida uzrokovana mutacijama u genu NPC1, a rjeđe NPC2. NPC dijeli niz karakteristika s kompleksnom Alzheimerovom bolesti (AB), ukazujući na postojanje zajedničkih patoloških procesa. Neke od zajedničkih karakteristika su disfunkcija endolizosomalnog puta te nedavno otkrivena povećana proteoliza supstrata β-sekretaze (BACE1) – enzima ključnog u patogenezi AB. Cilj rada bio je ispitati hipotezu da je povećana proteoliza supstrata BACE1 u moždanim regijama miševa NPC1 (NPC1-/-) u odnosu na miševe divljeg tipa (WT, NPC1+/+) posljedica nakupljanja supstrata i/ili enzima BACE1 u endosomima – organelima odgovornima za cijepanje BACE1. Metodom ultracentrifugiranja u diskontinuiranom gradijentu saharoze, izdvojene su frakcije ranih endosoma te kasnih endosoma/lizosoma iz malog mozga i hipokampusa devet tjedana starih miševa NPC1 i WT te su analizirane metodom western blotting, a dobiveni signali kvantificirani su softwareom ImageJ. Rezultati pokazuju različitu distribuciju i razinu biljega ranih endosoma i kasnih endosoma/lizosoma u moždanim regijama NPC1 u odnosu na WT miševe. Također, uočeno je značajno nakupljanje BACE1 supstrata Sez6L u ranim endosomima moždanih regija miševa NPC1 vs. WT. Zaključno, rezultati ukazuju da je Alzheimeru sličan fenotip u bolesti NPC jednim dijelom vjerojatno posljedica poremećaja transporta u endolizosomalnom putu te nakupljanja i povećanog cijepanja supstrata BACE1 u endosomima.Niemann-Pick type C disease (NPC) is a rare, inherited, neurodegenerative lipid storage disorder caused by mutations in NPC1 or NPC2 gene. NPC shares several features with the complex Alzheimer's disease (AD), including endolysosomal dysfunction and the increased proteolysis of the substrates of β-secretase (BACE1), a key protease in AD pathogenesis. The goal of this work was to test the hypothesis that increased proteolysis of BACE1 substrates in brain regions of NPC1 (NPC1-/-) compared to wild-type mice (WT, NPC1+/+) is due to accumulation of BACE1 substrates and/or enzyme BACE1 in endosomes. Ultracentrifugation in a discontinuous sucrose gradient was used to isolate fractions of early and late endosomes/lysosomes from the cerebellum and hippocampus of nine-week-old NPC1 and WT mice. The fractions were analyzed by western blotting, and the obtained signals were quantified using ImageJ software. Different distribution and level of markers of early and late endosomes/lysosomes in the brain regions of NPC1 vs. WT mice was observed. Also, significant accumulation of BACE1 substrate Sez6L was detected in early endosomes in brains of NPC1 mice. In conclusion, the results suggest that the Alzheimer-like phenotype in NPC disease is likely due to endolysosomal dysfunction causing accumulation and increased cleavage of BACE1 substrates in endosomes

Distribution of BACE1 substrates in the endosomal fractions isolated from the brain regions of wild type (NCP1+/+) and NPC1-/- disease mouse model

Niemann-Pickova bolest tipa C (NPC) nasljedna je, rijetka neurodegenerativna bolest nakupljanja lipida uzrokovana mutacijama u genu NPC1, a rjeđe NPC2. NPC dijeli niz karakteristika s kompleksnom Alzheimerovom bolesti (AB), ukazujući na postojanje zajedničkih patoloških procesa. Neke od zajedničkih karakteristika su disfunkcija endolizosomalnog puta te nedavno otkrivena povećana proteoliza supstrata β-sekretaze (BACE1) – enzima ključnog u patogenezi AB. Cilj rada bio je ispitati hipotezu da je povećana proteoliza supstrata BACE1 u moždanim regijama miševa NPC1 (NPC1-/-) u odnosu na miševe divljeg tipa (WT, NPC1+/+) posljedica nakupljanja supstrata i/ili enzima BACE1 u endosomima – organelima odgovornima za cijepanje BACE1. Metodom ultracentrifugiranja u diskontinuiranom gradijentu saharoze, izdvojene su frakcije ranih endosoma te kasnih endosoma/lizosoma iz malog mozga i hipokampusa devet tjedana starih miševa NPC1 i WT te su analizirane metodom western blotting, a dobiveni signali kvantificirani su softwareom ImageJ. Rezultati pokazuju različitu distribuciju i razinu biljega ranih endosoma i kasnih endosoma/lizosoma u moždanim regijama NPC1 u odnosu na WT miševe. Također, uočeno je značajno nakupljanje BACE1 supstrata Sez6L u ranim endosomima moždanih regija miševa NPC1 vs. WT. Zaključno, rezultati ukazuju da je Alzheimeru sličan fenotip u bolesti NPC jednim dijelom vjerojatno posljedica poremećaja transporta u endolizosomalnom putu te nakupljanja i povećanog cijepanja supstrata BACE1 u endosomima.Niemann-Pick type C disease (NPC) is a rare, inherited, neurodegenerative lipid storage disorder caused by mutations in NPC1 or NPC2 gene. NPC shares several features with the complex Alzheimer's disease (AD), including endolysosomal dysfunction and the increased proteolysis of the substrates of β-secretase (BACE1), a key protease in AD pathogenesis. The goal of this work was to test the hypothesis that increased proteolysis of BACE1 substrates in brain regions of NPC1 (NPC1-/-) compared to wild-type mice (WT, NPC1+/+) is due to accumulation of BACE1 substrates and/or enzyme BACE1 in endosomes. Ultracentrifugation in a discontinuous sucrose gradient was used to isolate fractions of early and late endosomes/lysosomes from the cerebellum and hippocampus of nine-week-old NPC1 and WT mice. The fractions were analyzed by western blotting, and the obtained signals were quantified using ImageJ software. Different distribution and level of markers of early and late endosomes/lysosomes in the brain regions of NPC1 vs. WT mice was observed. Also, significant accumulation of BACE1 substrate Sez6L was detected in early endosomes in brains of NPC1 mice. In conclusion, the results suggest that the Alzheimer-like phenotype in NPC disease is likely due to endolysosomal dysfunction causing accumulation and increased cleavage of BACE1 substrates in endosomes

Impaired Retromer Function in Niemann-Pick Type C Disease Is Dependent on Intracellular Cholesterol Accumulation

Niemann-Pick type C disease (NPC) is a rare inherited neurodegenerative disorder characterized by an accumulation of intracellular cholesterol within late endosomes and lysosomes due to NPC1 or NPC2 dysfunction. In this work, we tested the hypothesis that retromer impairment may be involved in the pathogenesis of NPC and may contribute to increased amyloidogenic processing of APP and enhanced BACE1-mediated proteolysis observed in NPC disease. Using NPC1-null cells, primary mouse NPC1-deficient neurons and NPC1-deficient mice (BALB/cNctr-Npc1m1N), we show that retromer function is impaired in NPC. This is manifested by altered transport of the retromer core components Vps26, Vps35 and/or retromer receptor sorLA and by retromer accumulation in neuronal processes, such as within axonal swellings. Changes in retromer distribution in NPC1 mouse brains were observed already at the presymptomatic stage (at 4-weeks of age), indicating that the retromer defect occurs early in the course of NPC disease and may contribute to downstream pathological processes. Furthermore, we show that cholesterol depletion in NPC1-null cells and in NPC1 mouse brains reverts retromer dysfunction, suggesting that retromer impairment in NPC is mechanistically dependent on cholesterol accumulation. Thus, we characterized retromer dysfunction in NPC and propose that the rescue of retromer impairment may represent a novel therapeutic approach against NPC.</jats:p

Genetics of Pediatric Epilepsy: Next-Generation Sequencing in Clinical Practice

Epilepsy is one of the most common neurological disorders with diverse phenotypic characteristics and high genetic heterogeneity. Epilepsy often occurs in childhood, so timely diagnosis and adequate therapy are crucial for preserving quality of life and unhindered development of a child. Next-generation-sequencing (NGS)-based tools have shown potential in increasing diagnostic yield. The primary objective of this study was to evaluate the impact of genetic testing and to investigate the diagnostic utility of targeted gene panel sequencing. This retrospective cohort study included 277 patients aged 6 months to 17 years undergoing NGS with an epilepsy panel covering 142 genes. Of 118 variants detected, 38 (32.2%) were not described in the literature. We identified 64 pathogenic or likely pathogenic variants with an overall diagnostic yield of 23.1%. We showed a significantly higher diagnostic yield in patients with developmental delay (28.9%). Furthermore, we showed that patients with variants reported as pathogenic presented with seizures at a younger age, which led to the conclusion that such children should be included in genomic diagnostic procedures as soon as possible to achieve a correct diagnosis in a timely manner, potentially leading to better treatment and avoidance of unnecessary procedures. Describing and discovering the genetic background of the disease not only leads to a better understanding of the mechanisms of the disorder but also opens the possibility of more precise and individualized treatment based on stratified medicine