Vertebrate Tracksites in the Middle Jurassic-Upper Cretaceous of South Tunisia

Four vertebrate tracksites from the Middle Jurassic and Upper Cretaceous in the Tataouine basin of southern Tunisia are described. Approximately 130 tridactyl footprints distributed over an area of 200 square meters, preserved on Callovian beds exposed at the Beni Ghedir site, represent the oldest evidence of a dinosaur fauna in Tunisia. In addition, three tracksites—Chenini, Ksar Ayaat, and Jebel Boulouha—have been discovered in the Cretaceous beds of the upper Continental Intercalaire, previously considered as a strictly marine depositional sequence. In addition to dinosaur tracks, the Chenini tracksite (late Albian) includes poorly preserved crocodilian tracks, and footprints assigned to a pleurodiran turtle have been recovered at the Ksar Ayaat locality (early Cenomanian). The Jebel Boulouha tracksite is dominated by well-preserved tridactyl tracks referred to small-sized theropods. Depositional settings of each tracksite have been defined on stratigraphic and sedimentologic data, and tracks were ascribed to different ichnocoenoses in relation to their paleoenvironments. This new and differentiated track record gives important information on how the fossil vertebrate fauna changed in southern Tunisia during mid-Jurassic to mid-Cretaceous times. These data provide a unique and useful census of tetrapod associations along the southern margin of the peri-Mediterranean area.     

Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause

Menopause is associated with endothelial dysfunction and oxidative stress. In this condition, reduced n-3 polyunsaturated fatty acids (n-3 PUFAs) contribute to cardiovascular disease. We investigated whether treatment with n-3 PUFA reverses endothelial dysfunction and oxidative stress in experimental menopause. Thirty female rats underwent either sham-surgery or bilateral ovariectomy or bilateral ovariectomy+oral n-3 PUFA (0.8 g kg^-1 day^-1 for 2 months).Ovariectomy caused endothelial dysfunction to acetylcholine, which was reversed by superoxide scavenger Tiron. Erythrocyte membrane lipid composition was characterized by reduced n-3 PUFA total content and omega-3 index, and by concomitant increase in n-6:n-3 PUFA ratio. Ovariectomy-related oxidative stress, demonstrated by both enhanced superoxide production and 3-nitrotyrosine expression in aorta, was associated with increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NOX-4 protein expression. Endothelial nitric oxide synthase (eNOS) functional inhibition by l-NG-nitroarginine methyl ester, protein expression and activity did not change.In ovariectomized rats, treatment with n-3 PUFA increased n-3 PUFA total content and omega-3 index and decreased n-6:n-3 PUFA ratio in erythrocyte membrane, reversed vascular oxidative stress, endothelial dysfunction, aortic 3-nitrotyrosine and markedly lowered NOX-4 protein expression; eNOS protein expression also increased, paralleled by reversal of inhibitory binding to Caveolin-1, while ex-vivo functional inhibition and NOS synthesis were unchanged.These findings demonstrate in vivo a therapeutic benefit of n-3 PUFA on menopause-associated endothelial dysfunction by reversal of alterations in membrane lipid composition induced by ovariectomy and by reduction of vascular oxidative stress. In this setting they also identify NOX-4 as a potential target to reduce oxidative stress-mediated vascular complications.     

(+)-Usnic acid enamines with remarkable cicatrizing properties

Wound healing is a significant concern in many pathologies (post-surgeries, burns, scars) and the search for new chemical entities is advisable. The lichen compound (+)-usnic acid (1) has found application in dermatological and cosmetic preparations, due to its bacteriostatic and antioxidant activities. The compound has also been shown to stimulate the wound closure of keratinocyte monolayers at subtoxic doses. Here we describe the design and synthesis of usnic acid enamines (compounds 2–11), obtained through nucleophilic attack of amino acids or decarboxyamino acids at the acyl carbonyl of the enolized 1,3 diketone. The wound repair properties of these derivatives were evaluated using in vitro and in vivo assays. Compounds 8 and 9 combine low cytotoxicity with high wound healing performance, suggesting their possible use in wound healing-promoting or antiage skin preparations.     

Ecological costs of climate change on marine predator–prey population distributions by 2050

Identifying and quantifying the effects of climate change that alter the habitat overlap of marine predators and their prey population distributions is of great importance for the sustainable management of populations. This study uses Bayesian joint models with integrated nested Laplace approximation (INLA) to predict future spatial density distributions in the form of common spatial trends of predator–prey overlap in 2050 under the “business‐as‐usual, worst‐case” climate change scenario. This was done for combinations of six mobile marine predator species (gray seal, harbor seal, harbor porpoise, common guillemot, black‐legged kittiwake, and northern gannet) and two of their common prey species (herring and sandeels). A range of five explanatory variables that cover both physical and biological aspects of critical marine habitat were used as follows: bottom temperature, stratification, depth‐averaged speed, net primary production, and maximum subsurface chlorophyll. Four different methods were explored to quantify relative ecological cost/benefits of climate change to the common spatial trends of predator–prey density distributions. All but one future joint model showed significant decreases in overall spatial percentage change. The most dramatic loss in predator–prey population overlap was shown by harbor seals with large declines in the common spatial trend for both prey species. On the positive side, both gannets and guillemots are projected to have localized regions with increased overlap with sandeels. Most joint predator–prey models showed large changes in centroid location, however the direction of change in centroids was not simply northwards, but mostly ranged from northwest to northeast. This approach can be very useful in informing the design of spatial management policies under climate change by using the potential differences in ecological costs to weigh up the trade‐offs in decisions involving issues of large‐scale spatial use of our oceans, such as marine protected areas, commercial fishing, and large‐scale marine renewable developments.     

Holocene vegetation history and human impact in the eastern Italian Alps: a multi-proxy study on the Coltrondo peat bog,Comelico Superiore,Italy

Vegetation History and Archaeobotany - The present study aims to reconstruct vegetation development, climate changes and human impact using an ombrotrophic peat core from the Coltrondo bog in the...     

Molecular modelling studies,synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors

A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N,N′-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)]propane-2-ethanediamine (9) and the N,N′-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)]butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours π–π stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 μM concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation.     

5-Arylidene-2-phenylimino-4-thiazolidinones as PTP1B and LMW-PTP inhibitors

As part of a project aimed at identifying effective low molecular weight nonphosphorus monoanionic inhibitors of PTPs, we have synthesized 4-[(5-arylidene-4-oxo-2-phenyliminothiazolidin-3-yl)methyl]benzoic acids (4) and evaluated their inhibitory activity against human PTP1B and LMW-PTP enzymes. The introduction of a 2-phenylimino moiety onto the 4-thiazolidinone ring was designed to enhance the inhibitor/enzyme affinity by means of further favourable interactions with residues of the active site and the surrounding loops. Some of the compounds (4a–d, f) showed interesting inhibition levels in the low micromolar range. The 5-arylidene moiety of acids 4 proved to markedly influence the potency of these inhibitors. Molecular modeling experiments inside the binding sites of both enzymes were performed.