Bentho-pelagic relations in the deep-water part of the Okhotsk Sea by the data of stable isotopes С and N analysis

Composition, abundance, diet and trophic status are analyzed for dominant benthic and pelagic species in the deep-water Okhotsk Sea on the data collected in demersal and pelagic trawl surveys conducted by Pacific Fisheries Research Center (TINRO). Isotope composition of13С and15N is determined for tissues of 107 species of plankton, benthos, demersal fish, and cephalopods, which form a basis of pelagic and benthic communities. The carbon isotope content is significantly different between these groups: d13С ranges from -23.30 to -19.90 ‰ for zooplankton, from -18.90 to -13.33 ‰ for benthos, from -22.10 to -18.90 ‰ for fish (mean values), and from -20.08 to -15.75 ‰ for cephalopods. It depends mainly on proportion of pelagic and benthic food in their diet. Following to these values, 30 % of examined species of demersal fishes and cephalopods use resources of detritus food chain as the base of their diet. The range of d15N is from 6.79 ( Megayoldia thraciaeformis ), 6.88 ( Eucalanus bungii ) to 18.26 ‰ ( Molpadia roretzii ). Its highest level is observed for 4 species of benthic invertebrates and 8 species of demersal fishes on the continental slope characterized by high tropic level (≥5) and included to the bentho-pelagic food chain, that corresponds with their d13С values. Trophic relations in the deep-water Okhotsk Sea demonstrates high dependence between benthic and pelagiс communities, as far as many dominant species of pelagic and demersal nekton consume both benthic and pelagic food. Feeding about of 70 % of dominant species of demersal fishes and cephalopods is based on grazing rather than on detritus food

Новая мутация в гене TYMP: клинико-морфологическая характеристика пациента с синдромом MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G>T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.Синдром митохондриальной нейрогастроинтестинальной энцефаломиопатии – редкое (1–9:1000000, Orphanet, 2021) генетическое мультисистемное заболевание, обусловленное мутациями в ядерном гене TYMP, кодирующем фермент тимидинфосфорилазу.Представлены данные 13‑летнего наблюдения пациентки Д., 40 лет, с синдромом митохондриальной нейрогастроинтестинальной энцефаломиопатии, связанным с ранее не описанной миссенс‑заменой c.1301G>T (p.Gly434Val) в гене TYMP. Диагноз синдрома митохондриальной нейрогастроинтестинальной энцефаломиопатии был поставлен на основании клинических проявлений (дисфункция желудочно‑кишечного тракта, кахексия, блефароптоз, офтальмопарез, периферическая полинейропатия и лейкоэнцефалопатия), результатов электронейромиографии (демиелинизация с вторичной аксонопатией), а также повышения уровня дигидротимина в сыворотке крови при нормальных уровнях тимидина и дезоксиуридина. Патогистологическое исследование выявило атрофию продольного (наружного) мышечного слоя тонкой и толстой кишок и значимое уменьшение количества CD117+‑клеток (телоцитов), поражение скелетных мышц смешанного характера с преобладанием миогенного паттерна, а также деструкцию миелиновых оболочек периферических нервов. Исследование S100‑положительных вегетативных образований кишечной стенки не выявило патологических изменений. При гистохимическом исследовании не были обнаружены «рваные красные волокна», характерные для митохондриопатий. Трансмиссионная электронная микроскопия продемонстрировала наличие полиморфизма митохондрий кардиомиоцитов и мегаломитохондрий лейомиоцитов кишечника

Причины ложной диагностики полимиозита у пациентов с дисферлинопатией: клинический случай

Differential diagnosis of inflammatory myopathies with hereditary muscular dystrophies accompanied by a secondary inflammatory process is a time‑consuming clinical and pathomorphological task. In particular, false diagnosis of polymyositis in patients with dysferlinopathy reaches 25 % of cases.A 40‑year‑old female patient with a limb‑girdle phenotype of dysferlinopathy, initially diagnosed as polymyositis, is presented. The reasons that led to the erroneous diagnosis were: sporadic case; subacute onset; proximal muscle weakness; myalgia, which stopped on the glucocorticosteroid therapy; high levels of creatine phosphokinase (up to 17 times); the presence of lymphocytic‑macrophage infiltrate in the muscle biopsy and the absence of magnetic resonance imaging data in primary examination of the patient.The refractoriness of clinical and laboratory signs to complex immunosuppressive therapy was the reason for revising the muscle biopsy with typing of the inflammatory infiltrate. The predominantly unexpressed perivascular infiltrate was characterized by the predominance of macrophages and, to a lesser extent, CD4+, which indicated the secondary nature of the inflammation in the muscle observed in some hereditary muscular dystrophies. When conducting an immunohistochemical reaction, the absence of the dysferlin protein in the sarcoplasmic membrane was revealed.Whole‑exome sequencing (NGS) revealed a mutation in exon 39 of the DYSF gene (p.Gln1428Ter) in the heterozygous state, which leads to the appearance of a stop codon and premature termination of protein translation. MLPA method registered 3 copies of exons 18, 19, 20, 22, 24 of the DYSF gene.Thus, this clinical example reflects the main methodological errors and possible effects of immunosuppressive therapy in patients with dysferlinopathy.Дифференциальная диагностика воспалительных миопатий, сопровождающихся вторичным воспалительным процессом, с наследственными мышечными дистрофиями является сложной и трудоемкой клинико‑патоморфологической задачей. В частности, ложная диагностика полимиозита у пациентов с дисферлинопатией достигает 25 % случаев.Представлена пациентка 40 лет с поясно‑конечностным фенотипом дисферлинопатии, первично диагностированной как полимиозит. Причины, повлекшие ошибочную диагностику: спорадическое происхождение; подострый дебют; проксимальная мышечная слабость; миалгия, купировавшаяся на фоне глюкокортикостероидной терапии; повышение уровня креатинфосфокиназы (до 17 раз); наличие лимфоцитарно‑макрофагального инфильтрата в мышечном биоптате и отсутствие данных магнитно‑резонансной томографии при первичном обследовании.Рефрактерность клинико‑лабораторных признаков к комплексной иммуносупрессивной терапии послужила причиной пересмотра результатов биопсии мышцы с типированием воспалительного инфильтрата. Невыраженный, преимущественно периваскулярный инфильтрат характеризовался преобладанием макрофагов и, в меньшей степени, CD4+, что указывало на вторичный характер воспаления в мышечной ткани, наблюдаемого при некоторых наследственных мышечных дистрофиях. При проведении иммуногистохимической реакции выявлено отсутствие белка дисферлина в саркоплазматической мембране.В ходе полноэкзомного секвенирования (NGS) выявлена мутация в 39‑м экзоне гена DYSF (p.Gln1428Ter) в гетерозиготном состоянии, приводящая к появлению стоп‑кодона и преждевременной терминации трансляции белка. Методом MLPA зарегистрировано по 3 копии 18, 19, 20, 22, 24‑го экзонов гена DYSF. Клинический случай отражает основные ошибки оценки результатов обследования и эффективности иммуносупрессивной терапии у пациентов с дисферлинопатией

Piezo modulated active grating for selecting X ray pulses separated by one nanosecond

We present a novel method of temporal modulation of X-ray radiation for time resolved experiments. To control the intensity of the X-ray beam, the Bragg reflection of a piezoelectric crystal is modified using comb-shaped electrodes deposited on the crystal surface. Voltage applied to the electrodes induces a periodic deformation of the crystal that acts as a diffraction grating, splitting the original Bragg reflection into several satellites. A pulse of X-rays can be created by rapidly switching the voltage on and off. In our prototype device the duty cycle was limited to similar to 1 ns by the driving electronics. The prototype can be used to generate X-ray pulses from a continuous source. It can also be electrically correlated to a synchrotron light source and be activated to transmit only selected synchrotron pulses. Since the device operates in a non-resonant mode, different activation patterns and pulse durations can be achieved. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License

he amyloid hypothesis of Alzheimer's disease: past and present, hopes and disappointments

In 1887, S.A. Belyakov, a physician of the Imperial Medical and Surgical Academy, first described amyloid deposits in the brain of patients with dementia. Later, in 1906, A. Alzheimer revealed amyloid plaques and tau tangles in a patient with clinical signs of dementia. Over the following 100 years, the development of the concept of the amyloid origin of Alzheimer's disease (AD) confirmed numerous relationships between the brain accumulation of APs and cognitive decline. And if at the beginning of the amyloid era many researchers considered that the disease was caused by amyloid beta (Aβ) protein overproduction, in recent years they have increasingly pointed to a defect in the mechanisms of Aβ clearance, especially after the discovery of the lymphatic system of the brain. The role of disturbed homeostasis of redox-active metals, primarily iron and copper, in the development of the disease is also considered.The amyloid hypothesis of AD has served as the basis for several areas in the design of drugs, such as secretase inhibitors, immunomodulatory drugs for active and passive immunization. However, only one drug (Akatinol memantine, an inhibitor of NMDA receptors and glutamatergic excitotoxicity) for the treatment of AD has been introduced into clinical practice over the past 20 years. Of interest are the data obtained in new studies of Akatinol memantine, which suggest that the latter is able to some extent affect the main pathophysiological processes underlying the development of cognitive impairment in Alzheimer-type pathology