Stereoselective Synthesis of N-Propargyl Alkynes and Axial Chiral N-Allenes with Epimeric Imidazolone Auxiliaries

This thesis describes the synthesis of an N-propargyl pyrroloimidazolone chiral auxiliary/directing group with syn or anti stereochemistry derived from L-proline hydantoin and its diastereoselective lithiation for the synthesis of central chiral alkynes and axial chiral allenamides. Lithiation followed by quench with alkylating electrophiles or aldehydes/ketones gives access to chiral propargyl or allene derivatives respectively, both in high diastereomeric ratio (>95:5 dr). Use of the anti epimer of the aforementioned imidazolone chiral auxiliary results in the reversal of stereochemistry at the propargyl position of the products, again with high diastereoselectivity. This conclusion was confirmed by the synthesis and comparison of the solely central chiral alkynes from both the syn and anti series, obtained via acid-induced elimination of the labile silyloxy protecting group. Therefore, this method allows for the preparation of both enantiomeric propargyl products without the need to prepare additional starting materials from more expensive unnatural D-proline. X-Ray analysis of an allene derivative confirmed that lithiation of the syn pyrroloimidazolone followed by direct quench with prochiral benzaldehydes led to axial chiral allenamides in high selectivity (>95:5 dr) with atypical stereochemistry of the resulting benzylic alcohol. Lithiation followed by transmetalation to a titanium triisopropoxide intermediate before benzaldehyde quench gave epimeric allenamides with opposite stereochemistry at the benzylic alcohol. Density Functional Theory (DFT) computational modelling explained this reversal of stereochemistry at the benzylic position as arising from stereofacial attack in 6,5-bicyclic or 6-membered transition states in the lithium or titanium series, respectively

Water quality evaluation in Mediterranean Lagoons using the Multimetric Phytoplankton Index (MPI): study cases from Sardinia

1 - Water quality in four Sardinian lagoons (western Mediterranean Sea) was assessed using the Multimetric Phytoplankton Index (MPI), which is consistent with the EU Water Framework Directive. The index was developed using data on phytoplankton abundances, species structure and chlorophyll a concentrations in Venice Lagoon, Italy. 2 - The aim of this study was to test the MPI on a larger geographical scale and across a range of lagoon types. Therefore, it was applied to assess water quality in the Cabras, S’Ena Arrubia, Santa Giusta and Calich lagoons in Sardinia. These lagoons are all “choked”, but exhibit a range of sizes and morphometric features. They are directly affected by human activity within the lagoons themselves, such as fisheries, aquaculture and the construction of dams and canals, and are indirectly affected by anthropogenic activities in their catchments, including intensive agriculture, industrial activity and urban development. 3 - The data used in the present study were collected monthly over a period of 4 years (Calich, Santa Giusta and S’Ena Arrubia) to 7 years (Cabras). Samples were collected at three stations at each of the Cabras, Santa Giusta and Calich lagoons, and at two stations at the S’Ena Arrubia Lagoon, providing a total of 220 samples. 4 - The water quality in three of the four lagoons investigated (Cabras, S’Ena Arrubia and Calich) was classified as bad using the MPI. Among these three, water in Cabras Lagoon exhibited the worst condition. Water quality in Santa Giusta Lagoon was classified as poor using the MPI. 5 - Although we present preliminary results that require further verification, the index appears to be a useful tool for assessing the ecological status of typical Mediterranean lagoons

A Numerical index for evaluating phytoplankton response to changes in nutrient levels in deep Mediterranean reservoirs

This paper proposes a new ecological index based on phytoplankton (MedPTI) as suggested by the European Directive 2000/60/CE, Water Framework Directive (WFD). The index is a useful tool to verify the impacts of eutrophication in Mediterranean reservoirs belonging to different categories of the WFD. Multiple data sets were employed to develop the MedPTI index. The calibration data set included data collected from 30 Sardinian reservoirs in 1994. A list of 44 selected taxa was obtained and used for index calculation. A second dataset including 48 averaged annual values from 10 reservoirs was used. Results showed good correlation between MedPTI and concentration of total phosphorus, which was the limiting nutrient in these reservoirs. The trophic classifications determined using the index agreed with the results from the OECD probabilistic model on the same series of data. Finally, the index was included in an international exercise to compare the definition of reference conditions and quality class boundaries against indices used in other Mediterranean countries

Identification of GOLPH3 Partners in <i>Drosophila</i> Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders.

Golgi phosphoprotein 3 (GOLPH3) is a highly conserved peripheral membrane protein localized to the Golgi apparatus and the cytosol. GOLPH3 binding to Golgi membranes depends on phosphatidylinositol 4-phosphate [PI(4)P] and regulates Golgi architecture and vesicle trafficking. GOLPH3 overexpression has been correlated with poor prognosis in several cancers, but the molecular mechanisms that link GOLPH3 to malignant transformation are poorly understood. We recently showed that PI(4)P-GOLPH3 couples membrane trafficking with contractile ring assembly during cytokinesis in dividing Drosophila spermatocytes. Here, we use affinity purification coupled with mass spectrometry (AP-MS) to identify the protein-protein interaction network (interactome) of Drosophila GOLPH3 in testes. Analysis of the GOLPH3 interactome revealed enrichment for proteins involved in vesicle-mediated trafficking, cell proliferation and cytoskeleton dynamics. In particular, we found that dGOLPH3 interacts with the Drosophila orthologs of Fragile X mental retardation protein and Ataxin-2, suggesting a potential role in the pathophysiology of disorders of the nervous system. Our findings suggest novel molecular targets associated with GOLPH3 that might be relevant for therapeutic intervention in cancers and other human diseases

Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders.

Golgi phosphoprotein 3 (GOLPH3) is a highly conserved peripheral membrane protein localized to the Golgi apparatus and the cytosol. GOLPH3 binding to Golgi membranes depends on phosphatidylinositol 4-phosphate [PI(4)P] and regulates Golgi architecture and vesicle trafficking. GOLPH3 overexpression has been correlated with poor prognosis in several cancers, but the molecular mechanisms that link GOLPH3 to malignant transformation are poorly understood. We recently showed that PI(4)P-GOLPH3 couples membrane trafficking with contractile ring assembly during cytokinesis in dividing Drosophila spermatocytes. Here, we use affinity purification coupled with mass spectrometry (AP-MS) to identify the protein-protein interaction network (interactome) of Drosophila GOLPH3 in testes. Analysis of the GOLPH3 interactome revealed enrichment for proteins involved in vesicle-mediated trafficking, cell proliferation and cytoskeleton dynamics. In particular, we found that dGOLPH3 interacts with the Drosophila orthologs of Fragile X mental retardation protein and Ataxin-2, suggesting a potential role in the pathophysiology of disorders of the nervous system. Our findings suggest novel molecular targets associated with GOLPH3 that might be relevant for therapeutic intervention in cancers and other human diseases

Efficacy of Fractional Versus Fully Ablative CO2 Laser for Distolateral Onychomycosis: Experience With 20 Patients

Introduction: Oral antifungals are the treatment choice for onychomycosis, and topical therapies are favored in cases of limited nail involvement. Recently, carbon dioxide (CO2) laser treatment has emerged as an option to enhance the effectiveness of topical therapies. Objective: Our objective was to compare the efficacy of fractional ablative and fully ablative CO2 laser treatments for distolateral subungual onychomycosis affecting a single toenail and caused by dermatophytes. Method: The records of 10 patients treated with a single fully ablative CO2 session were matched with those of 10 patients who underwent a single CO2 fractional treatment. All had previously failed topical antifungal lacquers and were discharged with the prescription of topical ciclopirox nail lacquer (8%) for 3 months. Results: The overall clinical response was 80% versus 60% in the fully ablative compared to the fractional group, with a mean onychomycosis severity index drop of 6.9±5.4 in the fully ablative group and 3.6 ±6.6 in the fractional group computed from baseline to 8.6±1.6 weeks after treatment completion. The relapse rate among responders was 12.5% in the fully ablative and 33.3% in the fractional group after a mean follow-up time of 29.4±2.3 weeks. Conclusion: Fractional and fully ablative CO2 laser in combination with ciclopirox lacquer could increase theresponse rate in onychomycosis resistant to topical antifungals when systemic therapy is contraindicated or not yet pursued. Fully ablative mode therapy is significantly more effective than fractional (p<0.05). Further studies are needed to identify prognostic response factors and assess the long-term effectiveness of CO2 laser treatment

Le Problematiche degli Harmful Algal Blooms (HABs) in Sardegna = Harmful Algal Blooms in Sardinia

Harmful Algal Blooms are events that produce damage to the environment and/or risk to the health of humans and aquatic life. A part of the responsible species acts through toxins whereas other no toxic species can grow to high biomass, causing different consequences. The different typologies of HABs is signalled also along Sardinian coast. Indications on specific events are reported

Long-term ecological studies on phytoplankton in Mediterranean reservoirs: a case study from Sardinia (Italy)

Artificial lakes are strategic water resources in the Mediterranean region but are one of the most vulnerable areas to the impacts of climate change, particularly to the expected significant decrease in water resources; therefore, enhancing the ability of water management to improve water quality is crucial. This study contributes to the knowledge of the long-term ecological features of Mediterranean artificial lakes based on a case study of Bidighinzu Lake in Sardinia, Italy, a warm, monomitic and hypereutrophic reservoir mainly used for drinking water. Among the different restoration actions carried out in Bidighinzu Lake to improve water quality is the reduction of nutrient loads from the watershed. To study multiannual trends of the trophic state, a long-term series (1988–2012) of both environmental variables and phytoplankton was analysed. Mann-Kendall tests revealed increasing trends for total nitrogen to total phosphorus ratios (TN:TP; significant in spring, summer, and winter) and decreasing trends for ammonium (winter and autumn), TP (all seasons), orthophosphate (spring, summer, and winter), reactive silica (autumn), and pH (summer). Among phytoplankton, significant increasing trends were assessed in biomass of Bacillariophyceae, Chlorophyceae, Dinophyceae, and Chrysophyceae. Cyanobacteria did not show a clear trend, although at the order level, Chroococcales significantly increased in summer and decreased in winter. Despite these major tendencies, the lake did not show significant improvement in its eutrophic state, probably due to an inherent resistance and the insufficient and/or not well calibrated or applied recovery actions

Indici per la valutazione della qualit? ecologica dei laghi

Methods are presented to evaluate the biological quality of Italian lakes based on phytoplankton, macrophytes, fishes, benthic fauna and hydromorphology