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1.
More than 50 hereditary lysosomal storage disorders (LSDs) are currently described. Most of these disorders are due to a deficiency of certain hydrolases/glycosidases and subsequent accumulation of nonhydrolyzable carbohydrate-containing compounds in lysosomes. Such accumulation causing hypertrophy of the lysosomal compartment is a characteristic feature of affected cells in LSDs. The investigation of biochemical and cellular parameters is of particular interest for understanding “life” of lysosomes in the normal state and in LSDs. This review highlights the wide spectrum of biochemical and morphological changes during developing LSDs that are extremely critical for many metabolic processes inside the various cells and tissues of affected persons. The data presented will help establish new complex strategies for metabolic correction of LSDs. 相似文献
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Human organ-on-a-chip systems for drug screening have evolved as feasible alternatives to animal models, which are unreliable, expensive, and at times erroneous. While chips featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of the organ-on-a-chip technology is revealed by connecting multiple organs on one chip to create a single integrated system for sophisticated fundamental biological studies and devising therapies for disease. Furthermore, since most organ-on-a-chip systems require special protocols with organ-specific media for the differentiation and maturation of the tissues, multi-organ systems will need to be temporally customizable and flexible in terms of the time point of connection of the individual organ units. We present a customizable Lego®-like plug & play system, μOrgano, which enables initial individual culture of single organ-on-a-chip systems and subsequent connection to create integrated multi-organ microphysiological systems. As a proof of concept, the μOrgano system was used to connect multiple heart chips in series with excellent cell viability and spontaneously physiological beat rates. 相似文献
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Nóra Kutszegi ágnes F. Semsei András Gézsi Judit C. Sági Viktória Nagy Katalin Csordás Zsuzsanna Jakab Orsolya Lautner-Csorba Krisztina Míta Gábor Gábor T. Kovács Dániel J. Erdélyi Csaba Szalai 《PloS one》2015,10(10)
L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect. 相似文献
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Travis Park Felix G. Marx Erich M. G. Fitzgerald Alistair R. Evans 《Journal of morphology》2017,278(6):801-809
The pygmy right whale, Caperea marginata , is the least understood extant baleen whale (Cetacea, Mysticeti). Knowledge on its basic anatomy, ecology, and fossil record is limited, even though its singular position outside both balaenids (right whales) and balaenopteroids (rorquals + grey whales) gives Caperea a pivotal role in mysticete evolution. Recent investigations of the cetacean cochlea have provided new insights into sensory capabilities and phylogeny. Here, we extend this advance to Caperea by describing, for the first time, the inner ear of this enigmatic species. The cochlea is large and appears to be sensitive to low‐frequency sounds, but its hearing limit is relatively high. The presence of a well‐developed tympanal recess links Caperea with cetotheriids and balaenopteroids, rather than balaenids, contrary to the traditional morphological view of a close Caperea‐balaenid relationship. Nevertheless, a broader sample of the cetotheriid Herpetocetus demonstrates that the presence of a tympanal recess can be variable at the specific and possibly even the intraspecific level. 相似文献
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Fabio Moda Thanh-Nhat T. Le Suzana Auli? Edoardo Bistaffa Ilaria Campagnani Tommaso Virgilio Antonio Indaco Luisa Palamara Olivier Andréoletti Fabrizio Tagliavini Giuseppe Legname 《PLoS pathogens》2015,11(12)
Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrPSc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrPSc were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties. 相似文献
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