A Permanent Automated Real-Time Passive Acoustic Monitoring System for Bottlenose Dolphin Conservation in the Mediterranean Sea

Within the framework of the EU Life+ project named LIFE09 NAT/IT/000190 ARION, a permanent automated real-time passive acoustic monitoring system for the improvement of the conservation status of the transient and resident population of bottlenose dolphin (Tursiops truncatus) has been implemented and installed in the Portofino Marine Protected Area (MPA), Ligurian Sea. The system is able to detect the simultaneous presence of dolphins and boats in the area and to give their position in real time. This information is used to prevent collisions by diffusing warning messages to all the categories involved (tourists, professional fishermen and so on). The system consists of two gps-synchronized acoustic units, based on a particular type of marine buoy (elastic beacon), deployed about 1 km off the Portofino headland. Each one is equipped with a four-hydrophone array and an onboard acquisition system which can record the typical social communication whistles emitted by the dolphins and the sound emitted by boat engines. Signals are pre-filtered, digitized and then broadcast to the ground station via wi-fi. The raw data are elaborated to get the direction of the acoustic target to each unit, and hence the position of dolphins and boats in real time by triangulation.     

Optimal design of airlift fermenters

In this article a modeling of a draft-tube airlift fermentor (ALF) based on perfect backmixing of liquid and plugflow for gas bubbles has been carried out to optimize the design and operation of fermentation units at different working capacities. With reference to a whey fermentation by yeasts the economic optimization has led to a slim ALF with an aspect ration of about 15. As far as power expended per unit of oxygen transfer is concerned, the responses of the model are highly influenced by k_La However, a safer use of the model has been suggested in order to assess the feasibility of the fermentation process under study.     

The molecular mode of action and species specificity of canakinumab,a human monoclonal antibody neutralizing IL-1β

Interleukin-1β (IL-1β) plays a key role in autoinflammatory diseases, such as systemic juvenile idiopathic arthritis (sJIA) or cryopyrin-associated periodic syndrome (CAPS). Canakinumab, a human monoclonal anti-IL-1β antibody, was recently approved for human use under the brand name Ilaris®. Canakinumab does not cross-react with IL-1β from mouse, rat, rabbit, or macaques. The crystal structure of the canakinumab Fab bound to human IL-1β was determined in an attempt to rationalize the species specificity. The X-ray analysis reveals a complex surface epitope with an intricate network of well-ordered water molecules at the antibody-antigen interface. The canakinumab paratope is largely pre-organized, as demonstrated by the structure determination of the free Fab. Glu 64 of human IL-1β is a pivotal epitope residue explaining the exquisite species specificity of canakinumab. We identified marmoset as the only non-human primate species that carries Glu 64 in its IL-1β and demonstrates full cross-reactivity of canakinumab, thereby enabling toxicological studies in this species. As demonstrated by the X-ray structure of the complex with IL-1β, canakinumab binds IL-1β on the opposite side with respect to the IL-1RAcP binding site, and in an approximately orthogonal orientation with respect to IL-1RI. However, the antibody and IL-1RI binding sites slightly overlap and the V_H region of canakinumab would sterically interfere with the D1 domain of IL-1RI, as shown by a structural overlay with the IL-1β:IL-1RI complex. Therefore, direct competition with IL-1RI for IL-1β binding is the molecular mechanism of neutralization by canakinumab, which is also confirmed by competition assays with recombinant IL-1RI and IL-1RII.     

Serum Adiponectin and Glomerular Filtration Rate in Patients with Type 2 Diabetes

High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation) was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR) and 365 from Foggia (FG). Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE) for 1 standard deviation (SD) of adiponectin = -3.26 (0.64)] and in FG [β(SE)=-5.70(1.28)] sample, as well as in the two studies combined [β(SE)=-3.99(0.59)];(p<0.0001 for all). In this combined analysis, the association was still significant after adjusting for sex, smoking habits, body mass index (BMI), waist circumference, diabetes duration, glycated hemoglobin (HbA1c), albumin creatinine ratio (ACR) and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments [β (SE)= -2.19 (0.59), p = 0.0001]. A stronger association between each SD adiponectin increment and low eGFR was observed among patients with micro-/macro-albuminuria, as compared to those with normo-albuminuria [adjusted β(SE)=-4.42(1.16) ml/min/1.73m² vs. -1.50 (0.67) ml/min/1.73m², respectively; p for adiponectin-by-albuminuric status = 0.022]. For each adiponectin SD increment, the odds of having eGFR < 60 ml/min/1.73m² increased by 41% (odds ratio, OR = 1.41; 95% confidence interval, CI 1.21–1.64) in SGR sample, 53% (OR = 1.53; 95% CI 1.21–1.94) in FG sample, and 44% (OR = 1.44; 95%CI 1.27–1.64) in the two studies considered together (p<0.0001 for all). In the combined sample, further adjustment for the above mentioned covariates did not change the observed association (OR = 1.36; 95%CI 1.16–1.60; p<0.0001). Our study, so far the largest addressing the relationship between serum adiponectin and GFR in T2D, strongly suggests that the paradoxical inverse association, previously reported in different clinical sets, is also observed in diabetic patients. Further studies are needed to unravel the biology underlying this counterintuitive relationship.     

Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein 2

Articular cartilage progenitor cells (ACPCs) represent a new and potentially powerful alternative cell source to commonly used cell sources for cartilage repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells (MSCs). This is particularly due to the apparent resistance of ACPCs to hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs) are responsive towards mechanical stimulation and/or adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2). hACPCs were cultured in fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro-permissive medium, lacking exogenous growth factors. Constructs were cultured, for 7 or 28 days, under free-swelling conditions or with the application of complex mechanical stimulation, using a custom built bioreactor that is able to generate joint-like movements. Outcome parameters were quantification of BMP-2 and transforming growth factor beta 1 (TGF-β1) concentration within the cell culture medium, biochemical and gene expression analyses, histology and immunohistochemistry. The application of mechanical stimulation alone resulted in the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive. This was evidenced by increased GAG production, lack of expression of hypertrophic markers and a promising gene expression profile (significant up-regulation of cartilaginous marker genes, specifically collagen type II, accompanied by no increase in the hypertrophic marker collagen type X or the osteogenic marker alkaline phosphatase). To further investigate the resistance of ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic differentiation, BMP-2, was investigated. A novel, three-dimensional, transduction protocol was used to transduce cells with an adenovirus coding for BMP-2. Over-expression of BMP-2, independent of load, led to an increase in markers associated with hypertropy. Taken together ACPCs represent a potential alterative cell source for cartilage tissue engineering applications.     

Inhibition of Breast Cancer Cell Proliferation and In Vitro Tumorigenesis by a New Red Apple Cultivar

Purpose

The aim of this study was to evaluate the antiproliferative activity in breast cancer cells and the inhibition of tumorigenesis in pre-neoplastic cells of a new apple cultivar with reddish pulp, called the Pelingo apple.

Methods

The antiproliferative activity was evaluated in MCF-7 and MDA-MB-231 human breast cancer cells. The inhibition of tumorigenesis was performed in JB6 promotion-sensitive (P+) cells.

Results

Results showed that Pelingo apple juice is characterized by a very high polyphenol content and strongly inhibited breast cancer cell proliferation. Its antiproliferative activity was found to be higher than the other five apple juices tested. Pelingo juice induced cell accumulation in the G2/M phase of the cell cycle and autophagy through overexpression of p21, inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) activity and an increase in lipidated microtubule-associated protein-1 light chain-3 beta (LC3B). Remarkably, Pelingo juice inhibited the 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)-induced tumorigenesis of JB6 P+ cells, suppressing colony formation in semi-solid medium and TPA-induced ERK1/2 phosphorylation.

Conclusions

Our data indicate that the Pelingo apple is rich in food components that can markedly inhibit in vitro tumorigenesis and growth of human breast cancer cells and could provide natural bioactive non-nutrient compounds, with potential chemopreventive activity.     

Melanins and melanogenesis: from pigment cells to human health and technological applications

During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine‐based multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi‐tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications.     

Physical Forcing Mechanisms Controlling the Variability of Chlorophyll-a over the Royal-Charlotte and Abrolhos Banks—Eastern Brazilian Shelf

The Abrolhos Bank is part of the so-called Eastern Brazilian Shelf and is an area of high ecological and economic importance. The bank supports the largest and richest coral reefs in the South Atlantic and the largest rhodolith bed in the world. The spatial and seasonal variation of phytoplankton concentration, however, and the dynamic processes controlling that variability have remained poorly known. The present study investigates the seasonal and spatial distributions of chlorophyll-a (Chl-a) and water conditions by analyzing nine years (2003–2011) of level-3 Moderate-resolution Imaging Spectroradiometer (MODIS) derived Chl-a, National Centers for Environmental Prediction (NCEP)/ETA model-derived winds, NCEP model-derived heat fluxes, thermohaline and velocity results from the Hybrid Circulation Ocean Model (HYCOM) 1/12^o assimilated simulation. The results show that low/high concentrations occurred in austral spring-summer (wet season)/autumn-winter (dry season), with the highest values observed in the northern portion of the Abrolhos Bank. The typical meteorological and oceanographic conditions during austral summer favor the development of strong stratification. These conditions are 1) N-NE winds that favor an upwelling-type Ekman circulation; 2) coupling between the open ocean and the continental shelf through the western boundary current, which promotes cooler subsurface water to rise onto the shelf break; and 3) positive net heat flux. In contrast, the S-SE winds during autumn are in the opposite direction of the predominant current system over the Abrolhos Bank, thus reducing their speed and inducing an inverse shear. The warmer ocean and a somewhat cool and dry atmosphere promote the evaporative cooling of the surface layer. The above processes drive mixed layer cooling and deepening that reaches its maximum in winter. The blooming of phytoplankton in the Abrolhos Bank waters appears to be regulated by changes in the mixed layer depth, with Chl-a levels that start to increase during autumn and reach their peak in June-July.     

A Human Deciduous Tooth and New 40Ar/39Ar Dating Results from the Middle Pleistocene Archaeological Site of Isernia La Pineta,Southern Italy

Isernia La Pineta (south-central Italy, Molise) is one of the most important archaeological localities of the Middle Pleistocene in Western Europe. It is an extensive open-air site with abundant lithic industry and faunal remains distributed across four stratified archaeosurfaces that have been found in two sectors of the excavation (3c, 3a, 3s10 in sect. I; 3a in sect. II). The prehistoric attendance was close to a wet environment, with a series of small waterfalls and lakes associated to calcareous tufa deposits. An isolated human deciduous incisor (labelled IS42) was discovered in 2014 within the archaeological level 3 coll (overlying layer 3a) that, according to new ⁴⁰Ar/³⁹Ar measurements, is dated to about 583–561 ka, i.e. to the end of marine isotope stage (MIS) 15. Thus, the tooth is currently the oldest human fossil specimen in Italy; it is an important addition to the scanty European fossil record of the Middle Pleistocene, being associated with a lithic assemblage of local raw materials (flint and limestone) characterized by the absence of handaxes and reduction strategies primarily aimed at the production of small/medium-sized flakes. The faunal assemblage is dominated by ungulates often bearing cut marks. Combining chronology with the archaeological evidence, Isernia La Pineta exhibits a delay in the appearance of handaxes with respect to other European Palaeolithic sites of the Middle Pleistocene. Interestingly, this observation matches the persistence of archaic morphological features shown by the human calvarium from the Middle Pleistocene site of Ceprano, not far from Isernia (south-central Italy, Latium). In this perspective, our analysis is aimed to evaluate morphological features occurring in IS42.