Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model.

Altered neuronal excitability is emerging as an important feature in Alzheimer's disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca(2+)]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1-dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD-related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain

Language-Related Skills in Bilingual Children With Specific Learning Disorders

Purpose: The purpose of this study is to better understand the characteristics of the language-related skills of bilingual children with specific learning disorders (SLD). The aim is achieved by analyzing language-related skills in a sample of bilingual (Italian plus another language) and Italian monolingual children, with and without SLD. Patients and methods: A total of 72 minors aged between 9 and 11 were recruited and divided into four groups: 18 Italian monolingual children with SLD, 18 bilingual children with SLD, 18 Italian monolingual children without SLD, and 18 bilingual children without SLD. Each child underwent tests to evaluate different aspects of language skills: lexical and grammar, metalanguage and executive functions. Results: With regard to lexical and grammatical skills, the conditions of SLD and bilingualism both impact naming in terms of total number of errors for words with low frequency of use, while the condition of SLD has an effect on semantic errors for words with low frequency of use. The condition of bilingualism impacts on the total errors for words with high frequency of use and on circumlocution-type errors for words with low frequency of use. There were significant effects of bilingualism and SLD on the metalinguistic test for understanding implicit meaning, and an impact of SLD on phonological awareness was also found. Conclusion: The results suggest that both SLD and bilingualism have an effect on some lexical skills, in particular for words with low frequency of use. Both conditions, bilingualism and SLD, seem to impact on metalinguistic abilities that depend on lexical knowledge. These findings reinforce the importance of improving understanding of the neuropsychological profile of bilingual children with SLD

Інновації у технологіях приготування страв із використанням нетрадиційної сировини

The priority direction of the development of food industries of the 21st century is the production of healthy-prophylactic, functional purpose food, which get due to using the innovation technologies and also the use of non- traditional plant raw materials, including the wild plants, with the aim improving the qualitative adequacy of food rations namely ensuring compliance their chemical composition to the physiological needs of human body, improvement of their taste, aroma and other properties. Nowadays, the action of biologically active substances of plant origin for the creation of dishes with a health-improving, preventive functional effect remains insufficiently studied. Therefore, one of new recipes with an improved composition of raw materials, and also using new methods of processing and preparation of products which will allows to keep all nutrients and enriching the body with the necessary nutrients. In this context, in order to expand the range of dishes, we searched for non-traditional raw materials with a significant content of biologically active substances among the biodiversity of the vegetation of the Carpathian region and improved the technologies for the introduction them into Ukrainian cuisine. The properties of non-traditional raw materials of local origin are considered and proposed the priority of directions its use in the development of dishes with health-improving properties for sanatorium – resort complex and restaurants. Changes have been made to innovative manufacturing technologies dishes using traditional vegetable raw materials. Llingonberry and cranberry berries, and green leaves of stinging nettle were used as innovative ingredients taken to improve and expand the assortment of dishes with health-improving properties. Using innovative ingredients with the application of high technologies expands the possibilities of obtaining a technologically new product enriched with biologically active substances, macro- and micronutrients, vitamins, dietary fibers, and other functional additives. The nutritional and biological value of food products using unconventional raw materials of plant origin is given, and the priority directions of its use in the development of dishes with health-improving properties for sanatorium-resort complexes and restaurant establishments of the Western region of Ukraine are proposed.Пріоритетним напрямом розвитку харчових виробництв  ХХІ століття є виробництво продуктів харчування оздоровчо-профілактичного і функціонального призначення, які одержують за інноваційними технологіями, а також внаслідок використання нетрадиційної рослинної сировини, в тому числі дикорослої, з метою поліпшення якісної адекватності харчових раціонів, тобто на забезпечення відповідності їхнього хімічного складу фізіологічним потребам організму людини, поліпшення їх смакових, ароматичних та інших властивостей. На сьогодні недостатньо вивченою залишається дія біологічно активних речовин рослинного походження для створення страв оздоровчої, профілактичної та функціональної дії. Тому одним із способів вирішенням цієї проблеми є розробка нових рецептур з удосконаленим складом сировини, а також застосування нових методів обробки і приготування продукції, які дозволять зберегти всі поживні речовини та збагатити організм необхідними нутрієнтами. У цьому контексті з метою розширення асортименту страв проведено пошук нетрадиційної сировини зі значним вмістом біологічно активних речовин серед біорозмаїття рослинного покрову Карпатського регіону та вдосконалено технології щодо їх введення у страви української кухні. Розглянуто властивості нетрадиційної сировини місцевого походження та запропоновано пріоритетні напрямки її використання в розробці страв з оздоровчими властивостями для санаторно-курортних комплексів і закладів ресторанного господарства. Внесено зміни у технології виготовлення інноваційних страв із використанням натрадиційної рослинної сировини. Як інноваційні інгредієнти – взяті для вдосконалення та розширення асортименту страв із оздоровчими властивостями ягоди брусниці та журавлини і зелене листя кропиви дводомної. Використання інноваційних інгредієнтів із використанням високих технологій розширює можливості отримати технологічно новий продукт, збагачений біологічно активними речовинами, макро- і мікронутрієнтами, вітамінами, харчовими волокнами та іншими функціональними добавками. Наведена харчова і біологічна цінність харчових виробів із використанням нетрадиційної сировини рослинного походження та запропоновано пріоритетні напрями її використання в розробці страв з оздоровчими властивостями для санаторно-курортних комплексів і закладів ресторанного господарства західного регіону України

Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3

Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We repor

Beneficial modification of functional renal parameters in 5/6 nephrectomized rats by nutraceutical : in view of a kidney-protective intervention

The objective of this study is to ascertain the potential beneficial effects of a novel phytoterapeutic formula (DTS, Kyotsu Jigyo, Japan) on renal function and morphological structure in 5/6 nephrectomized rats. Male Spraque-Dawley rats, 240-280 g, were divided into sham control (Group A) and nephrectomized (Group B and Group C) groups. The 5/6 nephrectomy was performed by removal of the right kidney and 2/3 ligation of left renal artery. After surgery, the animals were kept in individual cage for 6 weeks. Rats in Group A and Group B were fed with a normal protein diet only while those in Group C were fed normal protein diet added with DTS (10 mg/rat/day). The DTS supplementation was started a day after surgery. After 5 weeks, all rats were subjected to renal function study and then their left kidneys were isolated for morphological study. There were no significant differences in body weight, blood pressure, and heart rate among groups. DTS supplementation significantly increased (p < 0.05) plasma creatinine concentration, glomerular filtration rate, effective renal plasma flow, and urine flow rate in nephrectomized rats when compared to sham control (Group A) and untreated nephrectomized (Group B) controls. In contrast, plasma urea concentration and morphological structure were not significantly modified by DTS supplementation in nephrectomized animals. These data suggest that feeding with a normal protein diet and DTS supplementation improves renal function without any morphological effect in 5/6 nephrectomized rats if not a slight preservation

Low levels of taurine introgression in the current Brazilian Nelore and Gir indicine cattle populations

Background: Nelore and Gir are the two most important indicine cattle breeds for production of beef and milk in Brazil. Historical records state that these breeds were introduced in Brazil from the Indian subcontinent, crossed to local taurine cattle in order to quickly increase the population size, and then backcrossed to the original breeds to recover indicine adaptive and productive traits. Previous investigations based on sparse DNA markers detected taurine admixture in these breeds. High-density genome-wide analyses can provide high-resolution information on the genetic composition of current Nelore and Gir populations, estimate more precisely the levels and nature of taurine introgression, and shed light on their history and the strategies that were used to expand these breeds. Results: We used the high-density Illumina BovineHD BeadChip with more than 777 K single nucleotide polymorphisms (SNPs) that were reduced to 697 115 after quality control filtering to investigate the structure of Nelore and Gir populations and seven other worldwide populations for comparison. Multidimensional scaling and model-based ancestry estimation clearly separated the indicine, European taurine and African taurine ancestries. The average level of taurine introgression in the autosomal genome of Nelore and Gir breeds was less than 1% but was 9% for the Brahman breed. Analyses based on the mitochondrial SNPs present in the Illumina BovineHD BeadChip did not clearly differentiate taurine and indicine haplotype groupings. Conclusions: The low level of taurine ancestry observed for both Nelore and Gir breeds confirms the historical records of crossbreeding and supports a strong directional selection against taurine haplotypes via backcrossing. Random sampling in production herds across the country and subsequent genotyping would be useful for a more complete view of the admixture levels in the commercial Nelore and Gir populations.(VLID)90707

Utjecaj različitih površinski aktivnih tvari i njihovih koncentracija na kontrolirano oslobađanje kaptoprila iz polimernih matriksa

Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC 1:1 matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.Postoje različite metode formuliranja vodotopljivih lijekova u dozirane ljekovite oblike s polaganim oslobađanjem. Jedan od načina postizanja kontroliranog otpuštanja, a prema tome i produljenog učinka je upotreba hidrofilnih i lipofilnih polimera. U ovom radu proučavan je utjecaj različitih polimera poput hidroksipropil metilceluloze (HPMC), etilceluloze (EC) i natrijeve soli karboksimetilceluloze (NaCMC) i površinski aktivnih tvari (natrijevog lauril-sulfata, cetiltrimetilamonijevog bromida i Arlacela 60) na oslobađanje kaptoprila. Rezultati pokazuju da povećanje količine HPMC K15M ima za posljedicu smanjenje oslobađanja kaptoprila iz matriksa. Ako se HPMC djelomično zamijeni s NaCMC (omjer HPMC/NaCMC 5:1), oslobađanje ljekovite tvari značajno se smanjuje. Međutim, nema značajne razlike u oslobađanju kaptoprila iz matriksa s omjerom HPMC/NaCMC 5:1 i 2:1. Prisutnost laktoze u matriksu koji sadrži HPMC i NaCMC povećalo je oslobađanje kaptoprila. Iako djelomična zamjena HPMC s EC smanjuje oslobađanje ljekovite tvari (omjer HPMC/EC 2:1), oslobađanje se povećava uz omjer HPMC/EC 1:1. Nadalje, ispitivan je utjecaj površinski aktivnih tvari na oslobađanje kaptoprila iz matriksa u kojima je omjer HPMC/EC (1:1). Može se zaključiti da površinski aktivne tvari ne utječu značajno na oslobađanje ljekovite tvari. U sklopu istraživanja određen je i kinetički model oslobađanja kaptoprila. Analiza kinetičkih podataka ukazuje da dodatak površinski aktivnih tvari u HPMC/EC matrikse ne slijedi kinetiku nultog reda

Analysis of B. taurus and B. indicus admixture in Uganda as revealed by the Illumina BovineSNP50 Genotyping BeadChip

The NextGen project investigates disease resistance in indigenous Ugandan cattle. Since population structure and stratification may produce biased results, We have investigated the genomic structure of sampled animals genotyped with the BovineSNP50 Genotyping Beadchip. A total of 788 animals from 9 populations belonging to Ankole (crossbred between B. indicus and B. taurus), Zebu and Ankole-Zebu crosses have been sampled in 52 grid cells throughout the country (Table 1). We merged this data whit other 400 Italian Holstein Cattle, genotyped in the framework of SELMOL project to seek for a likely introgression of European B. taurus. The data were filtered with the following exclusion criteria: MAF < 0.01, genotype call rate (SNPs) < 0.95, genotype call rate (Animals) < 0.95. The resulting working dataset were composed of 43494 SNPs and 1188 animals. Hidden genetic structures were investigated by a Bayesian clustering approach with the ADMIXTURE software (Novembre et al. 2010). The software Admixture identified four ancestral genomic components. Three of them likely correspond to European taurine, African indicine and African taurine components (Figure 2). The fourth has a still unidentified origin (Yellow, Figure 2d). Most Ugandan individuals investigated have a remarkable level of admixture. Overall, about 20% of the Zebu genome is of African taurine origin, confirming previous data on the foundation of African Zebu. The European taurine (Blue, Figure 2) is a minor component of African genomes, rare in Zebu and evenly distributed in Ankole, other taurine subgroups and Ankole- Zebu crosses. Indicine and taurine components show a clear geographical structure, the former being predominant in north-eastern Uganda, and the latter in the south-west. Holstein Fresian introgression is spread mostly in south-western Uganda, while the fourth component is located in restricted geographical area in the East (Figure 3). The Ugandan cattle population is a complex admixture of African taurine (green in Figure 2) and zebuine (red) genomes, with a minor component of European origin (blue) and a rare but relevant contribution (yellow) from a still unidentified source. This complexity is to be accounted for in the following GWAS and selection signatures analyses planned within the NextGen project

An atlas of genetic scores to predict multi-omic traits

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics. Here we examine a large cohort (the INTERVAL study; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores