scholarly journals Structural Connectivity-Based Parcellation of the Dopaminergic Midbrain in Healthy Subjects and Schizophrenic Patients

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 686
Author(s):  
Gianpaolo Antonio Basile ◽  
Alessia Bramanti ◽  
Salvatore Bertino ◽  
Giuseppina Cutroneo ◽  
Antonio Bruno ◽  
...  

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients.

2020 ◽  
Vol 61 (6) ◽  
pp. 816-829 ◽  
Author(s):  
Naoko Sawada ◽  
Takashi Obama ◽  
Shinji Koba ◽  
Takashi Takaki ◽  
Sanju Iwamoto ◽  
...  

Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(−)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(−) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(−) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(−) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(−) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(−) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.


2020 ◽  
Vol 27 (9) ◽  
pp. 1405-1419 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Maria Rosa Loffredo ◽  
Francesca Ghirga ◽  
Maria Luisa Mangoni

Antimicrobial Peptides (AMPs) are the key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs, and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying Damino acids in order to reduce the peptide’s cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPs to the direction of peptide-based drugs for clinical use.


Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3600-3608 ◽  
Author(s):  
Jiquan Zhang ◽  
Anna Raper ◽  
Noriko Sugita ◽  
Ravi Hingorani ◽  
Mariolina Salio ◽  
...  

We describe the cloning and characterization of Siglec-H, a novel murine CD33-related siglec-like molecule with 2 immunoglobulin domains. Unlike other CD33-related siglecs, Siglec-H lacks tyrosine-based signaling motifs in its cytoplasmic tail. Although Siglec-H has the typical structural features required for sialic acid binding, no evidence for carbohydrate recognition was obtained. Specific monoclonal and polyclonal antibodies (Abs) were raised to Siglec-H and used to define its cellular expression pattern and functional properties. By flow cytometry, Siglec-H was expressed specifically on plasmacytoid dendritic cell (pDC) precursors in bone marrow, spleen, blood, and lymph nodes. Staining of tissue sections showed that Siglec-H was also expressed in a subset of marginal zone macrophages in the spleen and in medullary macrophages in lymph nodes. Using bone marrow-derived pDC precursors that express Siglec-H, addition of Abs did not influence cytokine production, either in the presence or absence of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG). In comparison, Siglec-H functioned as an endocytic receptor and mediated efficient internalization of anti–Siglec-H Abs. By immunizing mice with ovalbumin-conjugated anti–Siglec-H Ab in the presence of CpG, we demonstrate generation of antigen-specific CD8 T cells in vivo. Targeting Siglec-H may therefore be a useful way of delivering antigens to pDC precursors for cross-presentation.


Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 1029-1038 ◽  
Author(s):  
T Papayannopoulou ◽  
B Nakamoto ◽  
S Kurachi ◽  
M Tweeddale ◽  
H Messner

Detailed characterization of the composite phenotype of two newly established erythroleukemia lines (OCIM1, OCIM2) shows that these lines share many of their erythroid markers (ie, surface antigens and globin program) as well as several of their nonerythroid properties (myeloid/monocytic/megakaryocytic) with the two known erythroleukemia lines (K562, HEL). In addition, each displays novel and instructive features. We argue that the surface and globin phenotype of all erythroleukemia lines is nonrandom and that it may be of physiologic relevance; it could represent the most prevalent phenotype of cells transformed by leukemia in vivo, and it raises the possibility that cells with similar potentials exist transiently during normal hematopoietic differentiation before their irreversible commitment to a single lineage. As such, these cells demonstrate a greater phenotypic adaptability in vitro than do their single lineage-committed counterparts since they can differentiate toward more than one lineage.


2007 ◽  
Vol 53 (7) ◽  
pp. 888-900 ◽  
Author(s):  
Adnan A. Alatoom ◽  
Ricardo Aburto ◽  
Abdul N. Hamood ◽  
Jane A. Colmer-Hamood

The vceCAB (vce) operon encodes the multidrug resistance pump VceCAB (VCE), which contributes to resistance of Vibrio cholerae to carbonyl cyanide m-chlorophenylhydrazine (CCCP), deoxycholate, and pentachlorophenol by several-fold. vceR, which encodes the TetR-type repressor VceR and is divergently transcribed from vce, has been characterized in Escherichia coli . Detailed characterization of vceR in V. cholerae 569B confirmed the repressive effect of VceR on VCE function and indicated several novel features of VceR. Deletion of vceR increased resistance of strain 569B to CCCP and deoxycholate modestly, but did not affect resistance to pentachlorophenol. Transcriptional analysis revealed that vce expression was not only increased in strain 569BΔvceR::Ω by 2-fold but continued to rise throughout the growth cycle. Using a vceR–lux transcriptional fusion plasmid, we examined whether vceR is autoregulated in strain 569B. Expression of vceR from the vceR–lux fusion was significantly lower in strain 569BΔvceR::Ω than in strain 569B. In addition, exposure to CCCP reduced vceR expression from the vceR–lux fusion in strain 569B but not in strain 569BΔvceR::Ω. Despite differences in the VceR binding site in strain 569B from the previously recognized 28 bp sequence in V. cholerae CVD101, purified recombinant VceR bound to the 24 bp sequence from strain 569B. We propose that VceR modulates vce expression by binding in vivo to the 24 bp sequence within the vceR–vce intergenic region; unlike many TetR repressors that are negatively autoregulated, VceR positively regulates vceR expression in trans.


Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 1029-1038 ◽  
Author(s):  
T Papayannopoulou ◽  
B Nakamoto ◽  
S Kurachi ◽  
M Tweeddale ◽  
H Messner

Abstract Detailed characterization of the composite phenotype of two newly established erythroleukemia lines (OCIM1, OCIM2) shows that these lines share many of their erythroid markers (ie, surface antigens and globin program) as well as several of their nonerythroid properties (myeloid/monocytic/megakaryocytic) with the two known erythroleukemia lines (K562, HEL). In addition, each displays novel and instructive features. We argue that the surface and globin phenotype of all erythroleukemia lines is nonrandom and that it may be of physiologic relevance; it could represent the most prevalent phenotype of cells transformed by leukemia in vivo, and it raises the possibility that cells with similar potentials exist transiently during normal hematopoietic differentiation before their irreversible commitment to a single lineage. As such, these cells demonstrate a greater phenotypic adaptability in vitro than do their single lineage-committed counterparts since they can differentiate toward more than one lineage.


2006 ◽  
Vol 53 (3) ◽  
pp. 585-589 ◽  
Author(s):  
Joanna Skórko-Glonek ◽  
Anna Sobiecka-Szkatuła ◽  
Barbara Lipińska

DsbA is the major oxidase responsible for generation of disulfide bonds in proteins of E. coli envelope. In the present work we provided the first detailed characterization of disulfide exchange between DsbA and its natural substrate, HtrA protease. We demonstrated that HtrA oxidation relies on DsbA, both in vivo and in vitro. We followed the disulfide exchange between these proteins spectrofluorimetrically and found that DsbA oxidizes HtrA with a 1:1 stoichiometry. The calculated second-order apparent rate constant (kapp) of this reaction was 3.3x10(4)+/-0.6x10(4) M-1s-1. This value was significantly higher than the values obtained for nonfunctional disulfide exchanges between DsbA and DsbC or DsbD and it was comparable to the kapp values calculated for in vitro oxidation of certain non-natural DsbA substrates of eukaryotic origin.


2011 ◽  
Vol 21 (1) ◽  
pp. 19
Author(s):  
Phung Kim Phu ◽  
Nguyen Minh Thuan ◽  
Tran Nam Trung ◽  
Nguyen Van Minh

We present the synthesis and detailed characterization of RbxMn[Fe(CN)]6 and Mn3[Cr(CN)6]2 compounds. The composition of the materials significantly depends on the preparation conditions. Analysis of Raman spectroscopic results and X-ray powder diffraction data yielded a further assessment of the changes in structural features. The characteristic individual magnetic behavior, as well as the metal-to-metal charge-transfer capabilities of the various samples, could be related to significant changes within the structure that appear to be associated with the synthesis method used.


Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


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