Most of Plečnik’s work was achieved in the strict urban core, mainly on the edge joining the historical medieval core with the new city. Plečnik gradually created a composition of places surrounding ...the old city that became important connecting elements between the medieval and modern city, at that time in its first development surge. From his work it is clear that he achieved his imaginary city gradually and methodically, with architectural emphasis and based on ties between particular key places in the city. He recognised these key spaces in the city, tied them together with axes and merged them into the present urban tissue.
Večina Plečnikovih del je nastala v ožjem mestnem jedru, predvsem na stiku starega srednjeveškega jedra z nastajajočim mestom. Plečnik je postopno ustvaril kompozicijo prostorov, ki so obdajali staro ...mesto oziroma bili pomembni povezovalni členi med srednjeveškim in modernim mestom, takrat v prvem razmahu. Iz njegovega dela je razvidno, da je svoje domišljijsko mesto realiziral metodično in postopno, z arhitekturnimi poudarki in na podlagi povezav med posameznimi ključnimi točkami mesta. V mestnem prostoru je prepoznaval ključne točke mesta, jih povezoval v prostorske osi in zraščal v tedanje mestno tkivo.
Plečnik’s rearrangement of the centre of Ljubljana is a process, which had already begun in the time of his journey to Italy. The process developed alongside the architectural and urban design plan. ...The planning of Novi trg (New market) as an important public place shows the development of an architectural idea trough a long period by which a space was monumentalized and idea connections with the city found.
Plečnikovo preoblikovanje središča Ljubljane je proces, katerega izhodišče sega že v čas študijskega potovanja po Italiji in je potekal sočasno ter z medsebojnimi vplivi v okviru arhitekturnega in ...urbanističnega načrta. Pri načrtu za preoblikovanje Novega trga kot pomembnega mestnega prostora gre za razvoj arhitekturne ideje, ki jo lahko spremljamo skozi daljše časovno obdobje, v smislu monumentalizacije in približevanja idealni povezavi z mestom.
Plečnikovo preoblikovaiye središča Ljubljane je proces. katerega izhodišče sega že v čas študijskega potovanja po Italiji inje potekal sočasno ter z medsebojnimi vplivi v okviru arhitekturnega in ...urbanističnega načrta. Pri načrtu za preoblikovanje Novega trga kot pomembnega mestnega prostora gre za razvoj arhitekturne ideje, ki jo lahko spremljamo skozi daljše časovno obdobje, v smislu monumentalizacije in približevanja idealni povezavi z mestom. Plečnik's rearrangement of the centre of Ljubljana is a process. which had already begun in the time of his journey to Italy. This process developed alongside the architectural and urban design plan. The planning of Novi trg (New market) as an important public place shows the development of an architectural idea through a long period by which a space was monumentalised and ideal connections with the city found.
Proline‐specific endoproteases have been successfully used in, for example, the in‐situ degradation of gluten, the hydrolysis of bitter peptides, the reduction of haze during beer production, and the ...generation of peptides for mass spectroscopy and proteomics applications. Here we present the crystal structure of the extracellular proline‐specific endoprotease from Aspergillus niger (AnPEP), a member of the S28 peptidase family with rarely observed true proline‐specific endoprotease activity. Family S28 proteases have a conventional Ser‐Asp‐His catalytic triad, but their oxyanion‐stabilizing hole shows a glutamic acid, an amino acid not previously observed in this role. Since these enzymes have an acidic pH optimum, the presence of a glutamic acid in the oxyanion hole may confine their activity to an acidic pH. Yet, considering the presence of the conventional catalytic triad, it is remarkable that the A. niger enzyme remains active down to pH 1.5. The determination of the primary cleavage site of cytochrome c along with molecular dynamics‐assisted docking studies indicate that the active site pocket of AnPEP can accommodate a reverse turn of approximately 12 amino acids with proline at the S1 specificity pocket. Comparison with the structures of two S28‐proline‐specific exopeptidases reveals not only a more spacious active site cavity but also the absence of any putative binding sites for amino‐ and carboxyl‐terminal residues as observed in the exopeptidases, explaining AnPEP's observed endoprotease activity.
The ATP-binding cassette (ABC) transporter GlnPQ is an essential uptake system for amino acids in gram-positive pathogens and related nonpathogenic bacteria. The transporter has tandem ...substrate-binding domains (SBDs) fused to each transmembrane domain, giving rise to four SBDs per functional transporter complex. We have determined the crystal structures and ligand-binding properties of the SBDs of GlnPQ from Enterococcus faecalis, Streptococcus pneumoniae, and Lactococcus lactis. The tandem SBDs differ in substrate specificity and affinity, allowing cells to efficiently accumulate different amino acids via a single ABC transporter. The combined structural, functional, and thermodynamic analysis revealed the roles of individual residues in determining the substrate affinity. We succeeded in converting a low-affinity SBD into a high-affinity receptor and vice versa. Our data indicate that a small number of residues that reside in the binding pocket constitute the major affinity determinants of the SBDs.
•Crystal structures of liganded and unliganded receptor domains•Molecular basis of high-affinity amino acid binding•Tandem ligand-binding domains operate independent from each other•Dual specificity and dual affinity transport
The ATP-binding cassette transporter GlnPQ is an essential uptake system for amino acids in Gram-positive bacteria. Fulyani et al. show that a small number of residues that reside in the binding pocket of the receptor domains of GlnPQ constitute the major affinity determinants for transport.
Metabolic brain biomarkers have been incorporated in various diagnostic guidelines of neurodegenerative diseases, recently. To improve their diagnostic accuracy a biologically and clinically ...homogeneous sample is needed for their identification. Alzheimer's disease-related pattern (ADRP) has been identified previously in cohorts of clinically diagnosed patients with dementia due to Alzheimer's disease (AD), meaning that its diagnostic accuracy might have been reduced due to common clinical misdiagnosis. In our study, we aimed to identify ADRP in a cohort of AD patients with CSF confirmed diagnosis, validate it in large out-of-sample cohorts and explore its relationship with patients' clinical status. For identification we analyzed 2-
FFDG PET brain scans of 20 AD patients and 20 normal controls (NCs). For validation, 2-
FFDG PET scans from 261 individuals with AD, behavioral variant of frontotemporal dementia, mild cognitive impairment and NC were analyzed. We identified an ADRP that is characterized by relatively reduced metabolic activity in temporoparietal cortices, posterior cingulate and precuneus which co-varied with relatively increased metabolic activity in the cerebellum. ADRP expression significantly differentiated AD from NC (AUC = 0.95) and other dementia types (AUC = 0.76-0.85) and its expression correlated with clinical measures of global cognition and neuropsychological indices in all cohorts.
•Fifteen hemp cultivars were grown and 13 cannabinoids were determined.•Big differences in cannabinoid content between cultivars were found.•All cultivars corresponded to < 0.2 % limit of total ...tetrahydrocannabinol.•Tetrahydrocannabinol/cannabidiol ratio > 1:30 was found in four cultivars.•Bracts from upper and lower inflorescence contains similar cannabinoids content.
Cannabinoid content in different hemp varieties from the Common catalogue of varieties of agricultural plant species is not well known. Hemp (Cannabis sativa L., subsp. sativa) contains a wide range of cannabinoids, where cannabidiol (CBD) and (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) are the constituents with known therapeutic activity. Also, Δ9-THC is recognized as an illicit drug; therefore, cultivation of hemp is restricted to a 0.2 % limit of THC content in many European countries. In this study, the cannabinoid profiles of 15 hemp varieties, accessible to our research group, were analysed. The content of 13 cannabinoids was determined with HLPC (high-performance liquid chromatography) analysis. Large variations in cannabinoid content among varieties that grew in uniform conditions (ANOVA p < 0.05) and also within a single variety were found, which shows on un-uniform genetic profiles of the seed material. The varieties Fedora 17, USO 31, Tisza, Tiborszallasi, and Antal all displayed good response to growth conditions, related to cannabinoid content, in Slovenia.
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