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231.
Bertini S Ghilardi E Asso V Granchi C Minutolo F Pineschi M Di Bussolo V Bortolato A Moro S Saba A Macchia M 《Bioorganic & medicinal chemistry》2010,18(22):7991-7996
β-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC(50) values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules. 相似文献
232.
Viganò MA Lamartine J Testoni B Merico D Alotto D Castagnoli C Robert A Candi E Melino G Gidrol X Mantovani R 《The EMBO journal》2006,25(21):5105-5116
233.
Matteo Pizzolon Eva Giacomello Laura Marri Daniela Marchini Francesco Pascoli Carlotta Mazzoldi Maria Berica Rasotto 《Functional ecology》2010,24(1):141-148
1. Egg and offspring resistance to pathogens is a major determinant of survival and has been mainly ascribed to maternal factors. However, paternal production of antimicrobials was recently suggested to increase offspring survival in species where males perform egg care.
2. In the peacock blenny, Salaria pavo , a demersal spawning species where males exhibit a pair of anal glands producing lysozyme-like compounds, we tested the antimicrobial activity and the egg protection efficacy of these glands. The anal gland secretion (AGS) has an inhibitory effect on the growth of both Gram-negative and Gram-positive bacteria, including those causing the most severe fish diseases in marine culture. The egg clutches cared for by males deprived of anal glands have a significantly lower survival rate than those cared for by sham-operated males and non-viable eggs showed clear signs of bacterial infection.
3. Anal gland secretion production and its protein content are proportional to gland size. In species where male parental care plays a crucial role in offspring survival, females are expected to assess mates selecting those traits that are reliably associated with parental ability. Hence, we experimentally challenged females with dummy males differing in anal gland size. Females definitely preferred dummy males with larger anal glands, suggesting that their choice is driven by the pursuit of direct fecundity benefits.
4. These findings indicate that antimicrobial production is a crucial component of male parental care. The contribution of antimicrobials to male performance as fathers suggests that the development of traits devoted to this function may influence male attractiveness and be sexually selected. 相似文献
2. In the peacock blenny, Salaria pavo , a demersal spawning species where males exhibit a pair of anal glands producing lysozyme-like compounds, we tested the antimicrobial activity and the egg protection efficacy of these glands. The anal gland secretion (AGS) has an inhibitory effect on the growth of both Gram-negative and Gram-positive bacteria, including those causing the most severe fish diseases in marine culture. The egg clutches cared for by males deprived of anal glands have a significantly lower survival rate than those cared for by sham-operated males and non-viable eggs showed clear signs of bacterial infection.
3. Anal gland secretion production and its protein content are proportional to gland size. In species where male parental care plays a crucial role in offspring survival, females are expected to assess mates selecting those traits that are reliably associated with parental ability. Hence, we experimentally challenged females with dummy males differing in anal gland size. Females definitely preferred dummy males with larger anal glands, suggesting that their choice is driven by the pursuit of direct fecundity benefits.
4. These findings indicate that antimicrobial production is a crucial component of male parental care. The contribution of antimicrobials to male performance as fathers suggests that the development of traits devoted to this function may influence male attractiveness and be sexually selected. 相似文献
234.
235.
Gaetano Di Bari Eugenia Gentile Tiziana Latronico Giuseppe Corriero Anna Fasano Carlotta Nonnis Marzano Grazia Maria Liuzzi 《PloS one》2015,10(6)
The aim of this study was to evaluate whether water soluble compounds present in aqueous extracts from seven Mediterranean demosponges exert biological activity towards matrix metalloproteinases (MMPs), which represent important pathogenic factors of human diseases. Aqueous extracts were tested on LPS-activated cultured rat astrocytes, and levels and expression of MMP-2 and MMP-9 were assessed by zymography and RT-PCR, respectively. Our results demonstrated that the studied extracts contain water soluble compounds able to inhibit MMP-2 and MMP-9 activity and expression. We also compared the anti-MMP activities present in aqueous extracts from wild and reared specimens of Tethya aurantium and T. citrina. The results obtained revealed that the reared sponges maintain the production of bioactive compounds with inhibitory effect on MMP-2 and MMP-9 for all the duration of the rearing period. Taken together, our results indicate that the aqueous extracts from the selected Mediterranean demosponges possess a variety of water-soluble bioactive compounds, which are able to inhibit MMPs at different levels. The presence of biological activity in aqueous extracts from reared specimens of T. aurantium and T. citrina strongly encourage sponge aquaculture as a valid option to supply sponge biomass for drug development on a large scale. 相似文献
236.
237.
NRAGE Mediates p38 Activation and Neural Progenitor Apoptosis via the Bone Morphogenetic Protein Signaling Cascade 下载免费PDF全文
238.
The present work reports the observations on numerical and structural changes in 7 embryonic cell lines, derived from two stocks marked by reciprocal and heterozygous translocations between the Y and chromosome 3. Karyological analyses were carried out by using different techniques, such as Q-, C- banding and autoradiography, capable to define the distribution of heterochromatin and to identify individual chromosomes. These procedures, considering also synaptic prophases, provided characteristics for distinguishing each line, besides some very similar features common to all cells. Of particular interest was the appearance of various unusual chromosome morphological variants, characterized by centromeric and interstitial or terminal displaced heterochromatic segments, observed never before in Drosophila lines, whereas the original translocation was not found. Moreover, cell lines were found which had been exclusively polyploid since their establishment, irrespective of the length of their quiescence period. These observations confirm previous findings. The probable origin of the marker chromosomes, as well as a possible correlation between the chromosomal constitution of the cultured cells and the original parental karyotype, are discussed.This paper is dedicated to Prof. Dr. Hans Bauer for his 75th anniversary 相似文献
239.
Anne Filipe Alexander Chernorudskiy Sandrine Arbogast Ersilia Varone Rocío-Nur Villar-Quiles Diego Pozzer Maryline Moulin Stefano Fumagalli Eva Cabet Swati Dudhal Maria-Grazia De Simoni Raphaël Denis Nathalie Vadrot Corinne Dill Matteo Giovarelli Luke Szweda Clara De Palma Paolo Pinton Carlotta Giorgi Carlo Viscomi Emilio Clementi Sonia Missiroli Simona Boncompagni Ester Zito Ana Ferreiro 《Cell death and differentiation》2021,28(1):123
SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired.Subject terms: Chaperones, Respiratory tract diseases 相似文献