Serotonin in Neurological Diseases

Serotonin (5-HT) is responsible for anxiety, aggression, and stress. Alterations in a serotonergic system play a significant role in pathogenesis of neurological diseases and neuropsychiatric disorders. A wide range of disturbances associated with serotonergic neurotransmission results from different functions of 5-HT in a nervous system. It is believed that 5-HT may be involved in the pathogenesis of migraine, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). In these diseases, disturbances of 5-HT and its metabolites, such as 5-hydroxyindoleacetic acid (5-HIAA), were observed in the plasma, blood platelets, and cerebrospinal fluid (CSF). Changes in the level of this biogenic amine (5-HT) may be associated with malfunction of 5-HT receptors, reuptake transporter for 5-HT (5-HTT, SERT), the enzymes responsible for the synthesis and metabolism of 5-HT, and genetic variants for serotonergic system. It seems that 5-HT and its metabolites may be used as a diagnostic and prognostic marker for neurological diseases or a target for more efficient therapy in neurology in the future

Normal Aging and Dementia

Normal aging begins after 60 years of age. According to Harman, the accumulation of free radicals, which results from weakening of repair and protective mechanisms, takes place in the aging brain. It is believed that especially in the population of the most elderly there is increased incidence of both dementia and depression. The causes of these central nervous system disorders in the aging human body are changes at the molecular level, such as changes in the biochemical parameters, the accumulation of mutations in nuclear and mitochondrial DNA, and epigenetic changes. Biomarkers associated with aging of the brain include accumulated deposits of β-amyloid (Aβ), disturbed cholesterol homeostasis, altered neuroimaging parameters, and impaired glucose metabolism. Genetic factors are also responsible for normal aging, for example, SIRT1, AKT1, and CDKN1A, and among them the longevity genes, such as FOXO3A and CETP. Dementia as well as cognitive decline may be modified by poly-T variants of TOMM40 and APOE alleles via influencing the level of apolipoprotein E (apoE) in the brain and in the plasma as well as by its ability of Aβ clearance

Effect of microencapsulated onion husk extracts on selected properties of wheat bread

Celem badań było określenie wpływu dodatku mikrokapsułkowanego w inulinie lub maltodekstrynie ekstraktu z łuski cebuli na jakość pieczywa pszennego. Proporcje ekstraktu do nośnika w mikrokapsułkach wynosiły 1:1, 1:2, 1:3. Mikrokapsułki dodawano do chleba w ilości równoważnej 0,5% czystego ekstraktu w stosunku do naważki mąki oraz 0,5, 1,0 i 1,5% nośnika odpowiednio do proporcji. Wprowadzenie do chleba ekstraktu z cebuli utrwalanego w maltodekstrynie przyczyniało się do zwiększenia jego wydajności, a dodatek mikrokapsułek z inuliną nie zmieniał tej cechy. Chleby z 0,5-procentowym dodatkiem ekstraktu z cebuli, w porównaniu z chlebami kontrolnymi, zawierającymi tylko nośnik, miały mniejszą objętość. Pieczywo zawierające ekstrakt utrwalany w maltodekstrynie było większe niż to z ekstraktem utrwalanym w inulinie. Dodatek ekstraktu z cebuli powodował kilkakrotny wzrost zawartości polifenoli ogółem i aktywności przeciwutleniającej w pieczywie. Do wzbogacenia chleba w polifenole korzystniejszym nośnikiem była maltodekstryna.The aim of the study was to determine the effect of onion husk microencapsulated with inulin or maltodextrin on wheat bread quality. The proportions of the extract to the carrier in microcapsules were 1:1, 1:2, 1:3. Microcapsules were added to bread in an amount equivalent to 0.5% pure extract in relation to the sample weight of flour and 0.5, 1.0 and 1.5% of a carrier according to the proportion. Inclusions to bread of onion extract with maltodextrin as carries contributed to the increase of its yield, and microcapsules with inulin did not alter this characterisic. Breads with 0.5% onion extract, compared to contol breads that contained only carriers, had a smaller volume. Bread with maltodextrin microcapsules had a bigger volume than bread with inulin microcapsules. The addition of onion extract caused a several fold increase in total polyphenols and antioxidant activity in bread. For the enrichment of bread in polyphenols maltodextrin was a favorable carrier

IR Studies of the Phase Transformation of Fe2O3 → Fe3O4by Magnetomechanical Activation

The phase transformation of hematite αFe2O3 into magnetite Fe3O4 during wet milling in vacuum as a result of mechanochemical process has been investigated by infrared spectroscopy. The FTIR spectra were recorded in the wavenumber range kom 400 to 4000 cm-1. Two very strong bands were generally observed : one in the range 557-577cm-1 with shoulders in 632-693 cm-1, the other at about 475 cm-1. The most important feature is a very strong dependence of the intensities of the main absorption bands on the milling time of the sample. In addition, there was a broad band in the 3000-3700 cm-1 region related to the appearance of a certain number of OH groups in the spinel lattice. The results are discussed assuming the theoretically indicated active IR modes for ferites. A little disorded was interpreted as generated by ball milling and no traces of amorphization were observed

FT-TR, UV-VISIBLE AND X-RAY STUDIES OF COMPLEXES OF PYRIDINE N-OXIDES WITH PENTACHLOROPHENOL

The crystal structure of the 4-methoxy-2,6-dimethylpyridine N-oxide pentachlorophenol complex has been determined by X-ray analysis. The O ... O distance is 2.439(6) Angstrom, the OHO angle is 152.3 degrees and the hydrogen-bonded proton is close to the phenol molecule. The FT-IR spectra of pentachlorophenol complexes with some substituted pyridine N-oxides in the solid state and seven aprotic solvents of different polarity (epsilon from 2.27 to 37.5) show a broad absorption. The broad absorption shows weak dependence upon solvent polarity and is classified as type (ii). UV spectra show that in the investigated complexes protons are not transferred from the phenol to the N-oxides. Formamide (epsilon = 111) is a much stronger proton acceptor than the pyridine N-oxides. Pentachlorophenol in formamide is converted to the phenolate ion

FT-TR, UV-VISIBLE AND X-RAY STUDIES OF COMPLEXES OF PYRIDINE N-OXIDES WITH PENTACHLOROPHENOL

The crystal structure of the 4-methoxy-2,6-dimethylpyridine N-oxide pentachlorophenol complex has been determined by X-ray analysis. The O ... O distance is 2.439(6) Angstrom, the OHO angle is 152.3 degrees and the hydrogen-bonded proton is close to the phenol molecule. The FT-IR spectra of pentachlorophenol complexes with some substituted pyridine N-oxides in the solid state and seven aprotic solvents of different polarity (epsilon from 2.27 to 37.5) show a broad absorption. The broad absorption shows weak dependence upon solvent polarity and is classified as type (ii). UV spectra show that in the investigated complexes protons are not transferred from the phenol to the N-oxides. Formamide (epsilon = 111) is a much stronger proton acceptor than the pyridine N-oxides. Pentachlorophenol in formamide is converted to the phenolate ion

Robust temporal map of human in vitro myelopoiesis using single-cell genomics

We thank the Cellular Genetics wet lab support team, Cellular Genetics IT team, Sanger Sequencing operations and Sanger Cytometry Core facility for their essential help. We thank the Gene Editing team for providing iPSC knock-out lines. We would also like to thank Ruxandra Tesloianu and Luz Garcia-Alonso for their help setting up the scATAC-seq computational analysis. We thank Jana Eliasova for her help with figure design and Christina Usher and Aidan Maartens for their edits in the text. This work was mainly funded by the Open Targets consortium (OTAR026 and OTAR032 project) and the Wellcome Sanger core funding (WT206194) with additional support from Open Targets projects OTAR037, OTAR2065, OTAR2071. The authors are grateful to the funders for their support and additional care given to their members during the COVID-19 pandemic. D.A.-E. thanks CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This study makes use of cell lines and data generated by the HiPSci Consortium, funded by The Wellcome Trust and the MRC (Medical Research Council). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This publication is part of the Human Cell Atlas- www.humancellatlas.org/publications.We thank the Cellular Genetics wet lab support team, Cellular Genetics IT team, Sanger Sequencing operations and Sanger Cytometry Core facility for their essential help. We thank the Gene Editing team for providing iPSC knock-out lines. We would also like to thank Ruxandra Tesloianu and Luz Garcia-Alonso for their help setting up the scATAC-seq computational analysis. We thank Jana Eliasova for her help with figure design and Christina Usher and Aidan Maartens for their edits in the text. This work was mainly funded by the Open Targets consortium (OTAR026 and OTAR032 project) and the Wellcome Sanger core funding (WT206194) with additional support from Open Targets projects OTAR037, OTAR2065, OTAR2071. The authors are grateful to the funders for their support and additional care given to their members during the COVID-19 pandemic. D.A.-E. thanks CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This study makes use of cell lines and data generated by the HiPSci Consortium, funded by The Wellcome Trust and the MRC (Medical Research Council). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This publication is part of the Human Cell Atlas-www.humancellatlas.org/publications.Myeloid cells are central to homeostasis and immunity. Characterising in vitro myelopoiesis protocols is imperative for their use in research, immunotherapies, and understanding human myelopoiesis. Here, we generate a >470K cells molecular map of human induced pluripotent stem cells (iPSC) differentiation into macrophages. Integration with in vivo single-cell atlases shows in vitro differentiation recapitulates features of yolk sac hematopoiesis, before definitive hematopoietic stem cells (HSC) emerge. The diversity of myeloid cells generated, including mast cells and monocytes, suggests that HSC-independent hematopoiesis can produce multiple myeloid lineages. We uncover poorly described myeloid progenitors and conservation between in vivo and in vitro regulatory programs. Additionally, we develop a protocol to produce iPSC-derived dendritic cells (DC) resembling cDC2. Using CRISPR/Cas9 knock-outs, we validate the effects of key transcription factors in macrophage and DC ontogeny. This roadmap of myeloid differentiation is an important resource for investigating human fetal hematopoiesis and new therapeutic opportunities