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1.
2.
G. Ricci L. Volpi L. Pasquali L. Petrozzi G. Siciliano 《Journal of biological physics》2009,35(4):317-336
Astrocytes have long been considered as just providing trophic support for neurons in the central nervous system, but recently
several studies have highlighted their importance in many functions such as neurotransmission, metabolite and electrolyte
homeostasis, cell signaling, inflammation, and synapse modulation. Astrocytes are, in fact, part of a bidirectional crosstalk
with neurons. Moreover, increasing evidence is stressing the emerging role of astrocyte dysfunction in the pathophysiology
of neurological disorders, including neurodegenerative disease, stroke, epilepsy, migraine, and neuroinflammatory diseases. 相似文献
3.
Rashi Verma Monika Yadav Rajabrata Bhuyan Shweta Aggarwal Arnab Nayek 《Journal of receptor and signal transduction research》2016,36(6):601-616
Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen–antibody (Ag???Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag???Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases. 相似文献
4.
N. Theret P. Boulenguer B. Fournet J. C. Fruchart J. M. Bourre † C. Delbart 《Journal of neurochemistry》1988,50(3):883-888
Acylgalactosylceramides (AGC) from forebrains of normal and dysmyelinating (quaking and shiverer) mice were purified by Florisil column chromatography and preparative TLC. These procedures resolved the AGC on the basis of their Rf values into two main fractions which co-nigrate with their homologs from rat forebrains. In control animals, AGC were detectable in mouse forebrains from the eighth postnatal day and reached maximal values within 20 days. The same developmental pattern was obtained in dysmyelinating shiverer mice but the AGC content was reduced to approximately 30% of control values. In quaking mutants, the AGC were hardly detected. They were also present in sciatic nerve of normal mice and to a lesser extent in trembler mice. Gas chromatography-mass spectrometry analysis of both ester- and amide-linked fatty acids isolated from AGC of normal and shiverer mice shows that the shiverer mutant AGC display a chemical structure similar to that of normal AGC. AGC constituents of control myelin are reduced by approximately 70% in shiverer myelin, indicating that these molecules can be considered as early markers of oligodendrocyte differentiation. The early arrest of myelinogenesis in the quaking animals and the near absence of AGC are in good agreement with this proposal. Moreover, the reduced amount of AGC in the trembler PNS indicates that AGC could also be early markers for differentiation of the Schwann cell. 相似文献
5.
The pigment of substantia nigra human brain has been extracted by a mild procedure consisting of washes with phosphate buffer, methanol and incubation with SDS-proteinase. Pyrolisis gas chromatography mass spectrometry infrared spectrometry, termogravimetric analysis and elemental analysis were the techniques used for the chemical characterization. An indole moiety bound to a sulfur containing amino acid and to palmitic acid were the main aspects found in the structure. The presence of a 7% inorganic component was observed. This probably contains Fe, Cu, Zn and Cr which are also relevant, for the formation and the role of melanin in substantia nigra neurons. The fatty acid moiety is chemically bound to the indole structure as it was not eliminated by repeated methanol washing. The same situation occurs for the sulfur containing gropu. Considering these data and the most abundant molecules present in substantia nigra the precursor of neuromelanin seems to be a cysteinyl-cethecol, to which is then bound a palmityl group. 相似文献
6.
In West Africa, rice is grown in three constrasting ecosystems, upland, phreatic, and lowland, which is characterized by differing
water availability and soil properties. These ecosystems influence the predisposition of rice to disease problems, including
the grain discoloration complex. Discoloration of the hull was found to be most severe in the upland, less in the phreatic,
and least in the water-saturated lowland ecosystem. Caryopsis discoloration, however, showed no consistent pattern in relation
to the three ecosystems and was not correlated with hull discoloration, indicating that other factors are involved. 相似文献
7.
Josiane Arnaud Pierre Bourlard Bernard Denis Alain E. Favier 《Biological trace element research》1996,53(1-3):129-136
This study was carried out to assess manganese (Mn) status after an acute episode of myocardial infarction. Plasma and erythrocyte
Mn concentrations were measured from admission to hospital to day 15 postadmission in 21 patients suffering from acute myocardial
infarction and in three control groups. The determination of Mn in these biological fluids was performed by electrothermal
atomic absorption spectrometry. Plasma Mn was higher (p<0.01) and erythrocyte Mn was similar in the acute myocardial infarction group compared to healthy age-matched control group.
Plasma and erythrocyte Mn remained unchanged during the 2 wk after acute myocardial infarction and were not correlated to
enzyme activities. A decrease of erythrocyte Mn with age, expressed in nmol/L, was noted (p<0.02). These results suggest that plasma and erythrocyte Mn do not provide an indication of myocardial damage. Nonetheless,
Mn status in elderly merits further attention. 相似文献
8.
Many deterministic models of sexually transmitted diseases, as well as population models in general, contain elements of stochastic or statistical reasoning. An example of such a model is that of Dietz and Hadeler (1988) concerning sexually transmitted diseases in which there is partnership formation and dissolution. Among the interesting formulas in this paper, which enter into the analysis of the model, are those for the expected number of partners a male or female has during a lifetime. To a probabilist such formulas suggest the possibility that some stochastic process may be constructed so as to yield these formulas as well as others that may be of interest. The principal purpose of this paper is to demonstrate that such a stochastic process does indeed exist in the form of a three state semi-Markov process in continuous time with stationary laws of evolution and with a one-step density matrix determined by four parameters which were interpreted as constant latent risk functions in the classical theory of competing risks. This construction of a semi-Markov process not only provides a framework for the systematic derivation of the formulas of Dietz and Hadeler but also suggests pathways,for extensions to the age-dependent case.This research was partially supported by NATO Grant D.890350 相似文献
9.
Lev G. Goldfarb Paul Brown Larisa Cervenakova D. Carleton Gajdusek 《Molecular neurobiology》1994,8(2-3):89-97
Genetic study of over 200 cases of Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), and kuru have brought a reliable body of evidence that the familial forms of CJD and all known cases of GSS and FFI are linked to germline mutations in the coding region of the PRNP gene on chromosome 20, either point substitutions or expansion of the number of repeat units. No pathogenic mutations have so far been found in sporadic or infectious forms of CJD, although there are features of genetic predisposition in iatrogenic CJD and kuru. In FFI and familial CJD, clinically and pathologically distinct syndromes that are both linked to the 178Asp→Asn substitution, phenotypic expression is dependent on a polymorphism at codon 129. Synthetic peptides homologous to several regions of PrP spontaneously form insoluble amyloid fibrils with unique morphological characteristics and polymerization tendencies. Peptides homologous to mutated regions of PrP exhibit enhanced fibrilogenic properties and, if mixed with the wild-type peptide, produce even more abundant and larger fibrous aggregates. A similar process in vivo may lead to amyloid accumulation and disease, and transmission of “baby fibrils” may induce disease in other hosts. 相似文献
10.
Ilan Hammel Joseph Alroy Vibha Goyal Stephen J. Galli 《Virchows Archiv. B, Cell pathology including molecular pathology》1993,64(1):83-89
The effect of lysosomal storage diseases on the ultrastructure of human mast cells has not previously been reported. Indeed,
there has been little published evidence indicating that mast cells contain typical lysosomes. However, mast cell cytoplasmic
granules contain hydrolases similar to those found in lysosomes, but which differ from lysosomal hydrolases in exhibiting
optimal activity at higher pH. We therefore examined by transmission electron microscopy the dermal mast cells in 58 biopsies
of patients exhibiting 1 of 29 different lysosomal storage diseases. We found mast cells containing abnormal lysosomes in
16 of these disorders. In 6 of these 16 diseases, the mast cells' cytoplasmic granules appeared normal. These observations
indicate that human mast cells can contain lysosomes, and provide evidence that the enzymes affected by lysosomal storage
diseases are active in mast cells. 相似文献