The Origanum Collection of Gaetano Savi (1769-1844) in the Herbarium Horti Pisani (PI)

The Origanum Collection of Gaetano Savi (1769-1844) in the Herbarium Horti Pisani (PI). The collection of exsiccata of the genus Origanum, studied by Gaetano Savi and kept in the Herbarium Horti Pisani (PI) represents a valuable document of Savi's work as a taxonomist. It provides useful news for researchers of systematics and history of botany. The collection is enriched by some original drawings and includes the lectotypes of Origanum confertum Savi and O. fortuitum Savi

Lectotypification of two Origanum names (Lamiaceae) described by Gaetano Savi

Origanum confertum Savi and O. fortuitum Savi are typified on herbarium specimens kept in PI. These taxa are identifiable, as heterotypic synonyms, with O. majorana L. and O. xpaniculatum W.D.J.Koch, respectively

Lightning performance evaluation of Italian 150 kV sub-transmission lines

A significant majority of overhead transmission lines' (OHLs) outages is due to backflashovers caused by direct lightning strikes: the realistic assessment of the lightning performance is thus an important task. The paper presents the analysis of the lightning performance of an existing 150kVItalian OHL, namely, its backflashover rate (BFOR), carried out by means of anATP-EMTP-based Monte Carlo procedure. Among other features, the procedure makes use of a simplified pi-circuit for line towers' grounding system, allowing a very accurate reproduction of transient behaviours at a very low computational cost. Tower grounding design modifications, aimed at improving the OHL lightning performance, are also proposed and discussed

Arthrobacter sp. Inoculation Improves Cactus Pear Growth, Quality of Fruits, and Nutraceutical Properties of Cladodes

A study was undertaken to determine the effects of a strain of Arthrobacter sp., a Plant Growth-Promoting Bacteria (PGPB), on plant phenology and qualitative composition of Opuntia ficus-indica (L.) Mill. fruits and cladodes. The strain was inoculated in soil, and its effects on cactus pear plants were detected and compared to nontreated plants. Compared to the latter, the treatment with bacteria promoted an earlier plant sprouting (2 months before the control) and fruitification, ameliorating fruit quality (i.e., improved fresh and dry weight: + 24% and + 26%, respectively, increased total solid content by 30% and polyphenols concentrations by 22%). The quality and quantity of monosaccharides of cladodes were also increased by Arthrobacter sp. with a positive effect on their nutraceutical value. In summer, the mean values of xylose, arabinose, and mannose were significantly higher in treated compared to not treated plants (+ 3.54; + 7.04; + 4.76 mg/kg d.w. respectively). A similar trend was observed in autumn, when the cladodes of inoculated plants had higher contents, i.e., 33% xylose, 65% arabinose, and 40% mannose, respect to the controls. In conclusion, Arthrobacter sp. plays a role in the improvement of nutritional and nutraceutical properties of cactus pear plants due to its capabilities to promote plant growth. Therefore, these results open new perspectives in PGPB application in the agro-farming system as alternative strategy to improve cactus pear growth, yield, and cladodes quality, being the latter the main by-product to be utilized for additional industrial uses

Structure-based virtual screening of novel natural alkaloid derivatives as potential binders of h-telo and c-myc DNA G-quadruplex conformations

Several ligands can bind to the non-canonical G-quadruplex DNA structures thereby stabilizing them. These molecules can act as effective anticancer agents by stabilizing the telomeric regions of DNA or by regulating oncogene expression. In order to better interact with the quartets of G-quadruplex structures, G-binders are generally characterized by a large aromatic core involved in pi-pi stacking. Some natural flexible cyclic molecules from Traditional Chinese Medicine have shown high binding affinity with G-quadruplex, such as berbamine and many other alkaloids. Using the structural information available on G-quadruplex structures, we performed a high throughput in silico screening of commercially available alkaloid derivative databases by means of a structure-based approach based on docking and molecular dynamics simulations against the human telomeric sequence d[AG(3)(T(2)AG(3))(3)] and the c-myc promoter structure. We identified 69 best hits reporting an improved theoretical binding affinity with respect to the active set. Among them, a berberine derivative, already known to remarkably inhibit telomerase activity, was related to a better theoretical affinity versus c-myc

5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action

In the effort to identify and develop new HIV-1 inhibitors endowed with innovative mechanisms, we focused our attention on the possibility to target more than one viral encoded enzymatic function with a single molecule. In this respect, we have previously identified by virtual screening a new indolinone-based scaffold for dual allosteric inhibitors targeting both reverse transcriptase-associated functions: polymerase and RNase H. Pursuing with the structural optimization of these dual inhibitors, we synthesized a series of 35 new 3-[2-(4-aryl-1,3-thiazol-2-ylidene)hydrazin-1-ylidene]1-indol-2-one and 3-[3-methyl-4-arylthiazol-2-ylidene)hydrazine-1-ylidene)indolin-2-one derivatives, which maintain their dual inhibitory activity in the low micromolar range. Interestingly, compounds 1a, 3a, 10a, and 9b are able to block HIV-1 replication with EC50 < 20 µM. Mechanism of action studies showed that such compounds could block HIV-1 integrase. In particular, compound 10a is the most promising for further multitarget compound development

New Dihydrothiazole Benzensulfonamides: Looking for Selectivity toward Carbonic Anhydrase Isoforms I, II, IX, and XII

In the present study we investigated the structure-activity relationships of a new series of 4-[(3-ethyl-4-aryl-2,3-dihydro-1,3-thiazol-2-ylidene)amino]benzene-1-sulfonamides (EMAC10101a-m). All synthesized compounds, with the exception of compound EMAC10101k, preferentially inhibit off-target hCA II isoform. Within the series, compound EMAC10101d, bearing a 2,4-dichorophenyl substituent in position 4 of the dihydrothiazole ring, was the most potent and selective toward hCA II with an inhibitory activity in the low nanomolar range

Ribonuclease H/DNA polymerase HIV-1 reverse transcriptase dual inhibitor: mechanistic studies on the allosteric mode of action of isatin-based compound RMNC6

The DNA polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) are needed for the replication of the viral genome and are validated drug targets. However, there are no approved drugs inhibiting RNase H and the efficiency of DNA polymerase inhibitors can be diminished by the presence of drug resistance mutations. In this context, drugs inhibiting both activities could represent a significant advance towards better anti-HIV therapies. We report on the mechanisms of allosteric inhibition of a newly synthesized isatin-based compound designated as RMNC6 that showed IC50 values of 1.4 and 9.8 μM on HIV-1 RT-associated RNase H and polymerase activities, respectively. Blind docking studies predict that RMNC6 could bind two different pockets in the RT: one in the DNA polymerase domain (partially overlapping the non-nucleoside RT inhibitor [NNRTI] binding pocket), and a second one close to the RNase H active site. Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI) in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6. In addition, despite being naturally resistant to NNRTIs, the polymerase activity of HIV-1 group O RT was efficiently inhibited by RMNC6. The compound was also an inhibitor of the RNase H activity of wild-type HIV-1 group O RT, although we observed a 6.5-fold increase in the IC50 in comparison with the prototypic HIV-1 group M subtype B enzyme. Mutagenesis studies showed that RT RNase H domain residues Asn474 and Tyr501, and in a lesser extent Ala502 and Ala508, are critical for RMNC6 inhibition of the endonuclease activity of the RT, without affecting its DNA polymerization activity. Our results show that RMNC6 acts as a dual inhibitor with allosteric sites in the DNA polymerase and the RNase H domains of HIV-1 R

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors

Evaluation of an automatic HPLC analyser for thalassemia and haemoglobin variants screening

In this paper the authors report the evolution of a new automatic HPLC analyser for screening haemoglobinopathies. HbA2 and F determinations are accurate and reproducible. The analysis time is short (6.5 min) and there is a good separation between the HbA2 values of β-thalassemia carriers from normals and α-thalassemia carriers, with no overlap between these groups. In addition, the system is also able to detect and quantitate most of the haemoglobin variants, particularly those (HbS, HbC, HbE and Hb Lepore) able to interact with β-thalassemia and could make haemoglobin electrophoresis unnecessary in all samples. The ease of operation and the limited technical work make this system especially suitable for laboratories with a high workload and allow the cost of screening to be reduced