Spin separation in cyclotron motion

Charged carriers with different spin states are spatially separated in a two-dimensional hole gas. Due to strong spin-orbit interaction holes at the Fermi energy have different momenta for two possible spin states travelling in the same direction and, correspondingly, different cyclotron orbits in a weak magnetic field. Two point contacts, acting as a monochromatic source of ballistic holes and a narrow detector in the magnetic focusing geometry are demonstrated to work as a tunable spin filter.Comment: 4 pages, 2 figure

Genome-wide association studies targeting the yield of extraembryonic fluid and production traits in Russian White chickens

Background: The Russian White is a gene pool breed, registered in 1953 after crossing White Leghorns with local populations and, for 50 years, selected for cold tolerance and high egg production (EL). The breed has great potential in meeting demands of local food producers, commercial farmers and biotechnology sector of specific pathogen-free (SPF) eggs, the former valuing the breed for its egg weight (EW), EL, age at first egg (AFE), body weight (BW), and the latter for its yield of extraembryonic fluid (YEF) in 12.5-day embryos, ratio of extraembryonic fluid to egg weight, and embryo mass. Moreover, its cold tolerance has been presumably associated with day-old chick down colour (DOCDC) white rather than yellow, the genetic basis of these traits being however poorly understood. Results: We undertook genome-wide association studies (GWASs) for eight performance traits using single nucleotide polymorphism (SNP) genotyping of 146 birds and an Illumina 60KBeadChip. Several suggestive associations (p <5.16*10(-5)) were found for YEF, AFE, BW and EW. Moreover, on chromosome 2, an association with the white DOCDC was found where there is an linkage disequilibrium block of SNPs including genes that are responsible not for colour, but for immune resistance. Conclusions: The obtained GWAS data can be used to explore the genetics of immunity and carry out selection for increasing YEF for SPF eggs production.Peer reviewe

Genetic variability in local and imported germplasm chicken populations as revealed by analyzing runs of homozygosity

Simple Summary To maintain the uniqueness of conserved chicken populations of local and imported breeds is of great importance. In this study, we genotyped small populations belonging to 14 breeds and 7 crossbreds using an Illumina Chicken 60K SNP (Single Nucleotide Polymorphisms) BeadChip and looked for appropriate methods to characterize their purity/variability. It was not straightforward to identify crossbred individuals, and the best approach was based on calculating the length and number of homozygous regions, or runs of homozygosity (ROH), in the populations studied. The latter enabled most accurate identification of crossbreds and can be served as an effective tool in testing genome-wide purity of chicken breeds. Abstract Preserving breed uniqueness and purity is vitally important in developing conservation/breeding programs for a germplasm collection of rare and endangered chicken breeds. The present study was aimed at analyzing SNP genetic variability of 21 small local and imported purebred and F1 crossbred populations and identifying crossbreeding events via whole-genome evaluation of runs of homozygosity (ROH). The admixture models more efficiently reflected population structure, pinpointing crossbreeding events in the presence of ancestral populations but not in their absence. Multidimensional scaling and FST-based analyses did not discriminate properly between purebred populations and F1 crossbreds, especially when comparing related breeds. When applying the ROH-based approach, more and longer ROHs were revealed in purebred individuals/populations, suggesting this as an effective implement in genome-wide analysis of germplasm breed purity

Possibilities of radionuclide visualization of HER2/neu-positive breast cancer using a radiopharmaceutical based on recombinant targeting molecules DARPin9_29

Epidermal growth receptor HER2/neu is still of great interest, the overexpression of which is most often observed in patients with breast cancer and accounts for 15–20 % of cases. Present methods of HER2/neu determination have a number of significant drawbacks. In recent years, alternative framework proteins are used for the targeted radionuclide imaging. Molecules of DARPin (Design Ankyrin Repeat Protein) are one of representatives of scaffolds. Material and methods. The study included 4 breast cancer patients (T1-2N0-1M0) who were not receiving systemic therapy at the time of the study: in 2 patients, HER2/neu overexpression was noted, in 2 patients – not detected. HER2/neu status was determined using an immunohistochemical method and a FISH assay. At the preclinical stage, radiopharmaceutical 99mTc-DARPin9_29 was injected intravenously to all patients, «WholeBody» scintigraphy and single-photon emission computed tomography were performed 2 hours after injection. Results. The distribution of radiopharmaceuticals in organs 2 hours after injection revealed the greatest accumulation in the liver and kidneys. In studying of tumor/background indicator it was revealed that values of the studied parameter in patients with overexpression of HER2 receptors are more than 3 times higher than the values in the subgroup of patients with negative expression of this marker. Conclusion. According to the results of preliminary studies, the 99mTc-DARPin9_29 demonstrated significant differences between tumors with and without HER2/neu overexpression

Assessing the effects of rare alleles and linkage disequilibrium on estimates of genetic diversity in the chicken populations

Phenotypic diversity in poultry has been mainly driven by artificial selection and genetic drift. These led to the adaptation to the environment and the development of specific phenotypic traits of chickens in response to their economic use. This study evaluated genetic diversity within and between Russian breeds and populations using Illumina Chicken 60 K SNP iSelect BeadChip by analysing genetic differences between populations with Hudson's fixation index (FST statistic) and heterozygosity. We estimated the effect of rare alleles and linkage disequilibrium (LD) on these measurements. To assess the effect of LD on the genetic diversity population, we carried out the LD-based pruning (LD < 0.5 and LD < 0.1) for seven chicken populations combined (I) or separately (II). LD pruning was specific for different dataset groups. Because of the noticeably large sample size in the RussianWhite RG population, pruningwas substantial for Dataset I, and FST valueswere only positivewhen LD< 0.1 pruning was applied. For Dataset II, the LD pruning results were confirmed by examining heterozygosity and alleles' frequency distribution. LD between single nucleotide polymorphisms was consistent across the seven chicken populations, except the RussianWhite RG populationwith the smallest r2 values and the largest effective population size. Our findings suggest to study variability in each population LD pruning has to be carried separately not after merging to avoid bias in estimates

Альтернативные каркасные белки в радионуклидной диагностике злокачественных образований

This review discusses a relatively new class of targeted molecules that is being actively studied for radionuclide diagnosis and treatment of malignancies. The full-size antibodies used so far have non-optimal pharmacological properties, slow distribution in the body, poor penetration into the tissue and kidney excretion, and high immunogenicity, which significantly complicates their use in clinical practice. Over the past decade, a new class of targeted molecules, called “non-immunoglobulin scaffolds” have become popular; they have all the requirements for optimal delivery of a radionuclide to tumor cells. Scaffolds usually are smaller in size in comparison with antibodies, but they are larger than peptides, and are characterized by high affinity and optimal biochemical, biophysical, biological, and economic features. The advantages of such proteins are their stable structure, good penetration into tissues, the possibility of additional functionalization and expression in the bacterial system, which ensures low production costs.The results of preclinical and clinical studies for diagnosis of malignancies using such proteins as affibody, adnectin, DARPins, etc., have demonstrated their high specificity, affinity, good tolerance and low immunogenicity. В настоящем обзоре обсуждается относительно новый класс направленных адресных молекул, активно исследующийся в отношении радионуклидной диагностики и лечения злокачественных образований. Используемые до настоящего времени полноразмерные антитела обладают неоптимальными фармакологическими свойствами, медленным распределением в организме, плохим проникновением в ткани, выведением почками и высокой иммуногенностью, что существенно затрудняет их применение в клинической практике. В течение последнего десятилетия большую популярность приобретают таргетные молекулы, получившие название «альтернативные каркасные белки» (АКБ) или «скаффолды» и отвечающие всем требованиям для оптимальной доставки радионуклида к опухолевым клеткам. Обычно АКБ имеют меньшие размеры по сравнению с антителом, но большие, чем пептиды, и характеризуются высокой аффинностью и оптимальными биохимическими, биофизическими, биологическими и экономическими характеристиками. Преимуществами таких белков являются их стабильная структура, хорошее проникновение в ткани, возможность дополнительной функционализации и ýкспрессия в бактериальной системе, обеспечивающая низкую стоимость производства.Результаты проведенных к настоящему моменту доклинических и клинических исследований для диагностики злокачественных образований с использованием таких представителей АКБ, как аффибоди, аднектин, дарпины и пр., продемонстрировали высокую специфичность, аффинность, хорошую переносимость и низкую иммуногенность используемых препаратов.

Evolutionary subdivision of domestic chickens: implications for local breeds as assessed by phenotype and genotype in comparison to commercial and fancy breeds

To adjust breeding programs for local, commercial, and fancy breeds, and to implement molecular (marker-assisted) breeding, a proper comprehension of phenotypic and genotypic variation is a sine qua non for breeding progress in animal production. Here, we investigated an evolutionary subdivision of domestic chickens based on their phenotypic and genotypic variability using a wide sample of 49 different breeds/populations. These represent a significant proportion of the global chicken gene pool and all major purposes of breed use (according to their traditional classification model), with many of them being characterized by a synthetic genetic structure and notable admixture. We assessed their phenotypic variability in terms of body weight, body measurements, and egg production. From this, we proposed a phenotypic clustering model (PCM) including six evolutionary lineages of breed formation: egg-type, meat-type, dual purpose (egg-meat and meat-egg), game, fancy, and Bantam. Estimation of genotypic variability was carried out using the analysis of five SNPs, i.e., at the level of genomic variation at the NCAPG-LCORL locus. Based on these data, two generally similar genotypic clustering models (GCM1 and GCM2) were inferred that also had several overlaps with PCM. Further research for SNPs associated with economically important traits can be instrumental in marker-assisted breeding programs

[Genetic variation of the NCAPG-LCORL locus in chickens of local breeds based on SNP genotyping data] Генетическая изменчивость локуса NCAPG-LCORL у кур локальных пород на основе данных SNP-генотипирования

Using SNP analysis, genomic variation of the NCAPG-LCORL locus in chickens of 49 gene pool breeds and crossbreds from the Genetic Collection of Rare and Endangered Chicken Breeds was analyzed. Genotyping was performed using an Illumina Chicken 60K SNP iSelect BeadChip. As a result of SNP scanning, five significant SNPs were identified in the NCAPG-LCORL region in all breeds and crossbreds of the analyzed groups of chickens for GGA4. Cluster analysis of admixture models revealed a subdivision of individuals according to their origin at K = 5. Chickens of the egg and meat types formed two separate clusters, which is consistent with the results of genotype frequencies. When analyzing genetic differentiation between groups of chickens with different utility types on the basis of pairwise FST values, significant differences (p < 0.05) were found for the group of egg-type chickens in comparison with meat-type (0.330), dual purpose (meat-egg, 0.178), game (0.225 ) and dual purpose (egg-meat, 0.237) chickens, as well as for meat-type relative to fancy chickens (0.153). The results showed that the compared groups differ genetically from each other, which is confirmed by the data on genotype frequencies. The population specificity of the linkage disequilibrium structure at the NCAPG-LCORL locus was revealed for 11 chicken breeds. В ходе исследования с помощью анализа однонуклеотидного полиморфизма (SNP) была проанализирована геномная изменчивость локуса NCAPG-LCORL у кур 49 генофондных пород и гибридных форм из «Генетической коллекции редких и исчезающих пород кур». Генотипирование проводили с помощью чипа Illumina Chicken 60K SNP iSelect BeadChip. В результате SNP-сканирования у всех пород и гибридов анализируемых групп кур на GGA4 в регионе, включающем NCAPG-LCORL, и в области рядом с этим регионом определено пять значимых SNPs, которые могут быть кандидатами для селекции с помощью маркеров (MAS). Кластерный анализ адмикс-моделей обнаружил разделение особей соответственно их происхождению при К=5. Куры яичного и мясного направления продуктивности сформировали два обособленных кластера, что согласуется с результатами частот генотипов. При анализе генетической дифференциации между группами кур различного направления продуктивности на основе попарных FST-значений отмечены достоверные различия (p < 0,05) для группы кур яичного направления продуктивности в сравнении с мясными (0,330), мясо-яичными (0,178), бойцовыми (0,225) и яично-мясными (0,237), а также для кур мясного направления продуктивности относительно декоративных (0,153). Результаты показали, что сравниваемые группы отличаются генетически друг от друга, что подтверждается данными о частотах генотипов. Выявлена популяционная специфичность структуры неравновесия по сцеплению (LD) по локусу NCAPG-LCORL для 11 пород кур

Способ получения и изучение биологических свойств меченной йодом-123 производной аминоглюкозы

Search and synthesis of glucose derivatives for nuclear medicine is of great current interest. Being a promising analogue of glucose, D-glucosamine iodine labeled glucose derivatives can be applied in rheumatoid arthritis radionuclide diagnostics and therapy as a radiopharmaceutical.The purpose of the study. Synthesis of a new iodine labeled D-glucosamine derivative; development of the iodine-123 labeling method and the obtained glucose derivative biostudy.Materials and methods. Synthesis of 2-N-(6-iodohexanoyl)-D-glucosamine was carried out through established techniques in organic chemistry. Infrared spectroscopy and nuclear magnetic resonance spectroscopy were used to establish the test compound structure. Isotope change between iodine-127 and iodine-123 of glucosamine derivative was conducted using the heating of mix of the compound and Na123I in acetone. The radio-TLC method was applied to estimate the radiochemical purity of 2-N- (6-iod-123-hexanoyl) -D-glucosamine. The safe application and test of drug pharmacokinetic parameters study was performed on intact Wistar male rats.Results. An original 2-N-(6-iodohexanoyl)-D-glucosamine synthesis method was proposed. According to the method, an intermediate synthesis succimide-1-yl 6-iodohexanoate was obtained by the cyclohexanone oxidative cleavage reaction. The radiochemical purity of 2-N-(6-iodo-123-hexanoyl)-D-glucosamine was more than 97%.Conclusion. 2-N-(6-iodohexanoyl)-D-glucosamine was synthesized and iodine-123 labeled. When investigating the proposed radiopharmaceutical safety and pharmacokinetics, it was shown the drug lacks acute toxicity through intravenous injection and is excreted renally by glomerular filtration.В настоящее время являются актуальными поиск и синтез производных глюкозы для ядерной медицины. В последние годы D-глюкозамин является перспективным аналогом глюкозы, модифицированные йодпроизводные которого, возможно, могут быть применены в радионуклидной диагностики, и радиойодтерапии ревматоидного артрита в качестве радиофармацевтического препарата (РФП).Цель исследования. Синтез нового йодсодержащего производного D-глюкозамина, разработка методики его мечения йодом-123 и биологическое изучение свойств полученного препарата.Материалы и методы. Синтез 2-N-(6-йодгексаноил)-D-глюкозамина проводили с использованием общепринятых приемов в органической химии. Для установления структуры исследуемого соединения использовали инфракрасную спектроскопию и спектроскопию ядерно-магнитного резонанса. Изотопный обмен стабильного йода-127, присутствующего в алифатической цепи, на его радиоактивный аналог – йод-123 проводили при нагревании смеси полученного производного D-глюкозамина с натрий йодидом Na123I в ацетоне с последующим синтезом в твердой фазе. Для оценки радиохимической чистоты 2-N-(6-йод123гексаноил)-D-глюкозамина использовали метод хроматографии в тонком слое сорбента. Изучение безопасности применения и фармакокинетических параметров исследуемого препарата производилось на интактных самцах крыс линии Вистар.Результаты. Была предложена оригинальная методика синтеза 2-N-(6-йодгексаноил)-D-глюкозамина, по которой промежуточный продукт синтеза сукцимид-1-ил 6-йодгексаноат был получен по реакции окислительного расщепления циклогексанона, являющейся экологически безопасной. Радиохимическая чистота 2-N-(6-йод123гексаноил)-D-глюкозамина составила более 97%. Заключение. Синтезирован 2-N-(6-йодгексаноил)-D-глюкозамин и проведено его мечение йодом-123. При исследовании безопасности применения и изучении фармакокинетики предлагаемого РФП было показано, что препарат не обладает острой токсичностью при внутривенном введении и выводится почками путем клубочковой фильтрации

Разработка способа получения производного октреотида для диагностики нейроэндокринных опухолей

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.The purpose of the study was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.Materials and methods. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.Results. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.Conclusion. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors. Введение. В настоящее время разработка технологии мечения аналогов соматостатина технецием99м (99mTc) для радинуклидной диагностики нейроэндокринных опухолей активно проводится по всему миру. Аналоги соматостатина, к которым относится октреотид, связываются с 99mTc только путем предварительного присоединения к ним хелатирующего агента. Поэтому актуальным является модификация октреотида прекурсорами с высокой хелатирующей способностью для прочного связывания 99mTc. В качестве таких прекурсоров успешно могут применяться ω-бис(пиридин-2- илметил)амино)алифатические кислоты.Цель исследования. Разработка способа получения нового производного октреотида, пригодного для диагностики нейроýндокринных опухолей.Материалы и методы. В качестве объекта исследования использовали октреотид – аналог соматостатина. В качестве бифункционального хелатирующего агента использовали сукцинимид-1-ил 6-(бис(пиридин-2-илметил)амино)гексаноат, синтезированный по модифицированной методике с учетом специфики агента. Для разделения и анализа синтезированных соединений применяли методы высокоýффективной жидкостной хроматографии и масс-спектрометрии.Результаты исследования. Предложен способ получения производного октреотида с применением хелатирующего агента сукцинимид-1-ил 6-(бис(пиридин-2-илметил)амино)гексаноата в среде 10 ммоль PBS (рН = 6,0) с добавлением 20%-го ацетонитрила в течение 24 ч. Разработаны условия для анализа и очистки активного производного октреотида с использованием аналитической и полупрепаративной жидкостной хроматографии.Заключение. Впервые в результате модификации октреотида по остатку D-фенилаланина создан центр хелатирования для технеция-99м на основе ω-бис(пиридин-2-илметил)амино)алифатических кислот. Производное октреотида является перспективным для дальнейшего изучения его функциональной пригодности для диагностики нейроэндокринных опухолей.