Connective-Tissue Growth Factor (CTGF/CCN2) Induces Astrogenesis and Fibronectin Expression of Embryonic Neural Cells In Vitro

Connective-tissue growth factor (CTGF) is a modular secreted protein implicated in multiple cellular events such as chondrogenesis, skeletogenesis, angiogenesis and wound healing. CTGF contains four different structural modules. This modular organization is characteristic of members of the CCN family. The acronym was derived from the first three members discovered, cysteine-rich 61 (CYR61), CTGF and nephroblastoma overexpressed (NOV). CTGF is implicated as a mediator of important cell processes such as adhesion, migration, proliferation and differentiation. Extensive data have shown that CTGF interacts particularly with the TGFβ, WNT and MAPK signaling pathways. The capacity of CTGF to interact with different growth factors lends it an important role during early and late development, especially in the anterior region of the embryo. ctgf knockout mice have several cranio-facial defects, and the skeletal system is also greatly affected due to an impairment of the vascular-system development during chondrogenesis. This study, for the first time, indicated that CTGF is a potent inductor of gliogenesis during development. Our results showed that in vitro addition of recombinant CTGF protein to an embryonic mouse neural precursor cell culture increased the number of GFAP- and GFAP/Nestin-positive cells. Surprisingly, CTGF also increased the number of Sox2-positive cells. Moreover, this induction seemed not to involve cell proliferation. In addition, exogenous CTGF activated p44/42 but not p38 or JNK MAPK signaling, and increased the expression and deposition of the fibronectin extracellular matrix protein. Finally, CTGF was also able to induce GFAP as well as Nestin expression in a human malignant glioma stem cell line, suggesting a possible role in the differentiation process of gliomas. These results implicate ctgf as a key gene for astrogenesis during development, and suggest that its mechanism may involve activation of p44/42 MAPK signaling. Additionally, CTGF-induced differentiation of glioblastoma stem cells into a less-tumorigenic state could increase the chances of successful intervention, since differentiated cells are more vulnerable to cancer treatments.     

Application of a predictive approach to estimate exposure to non‐smoking urban sub‐populations to background levels of Benzene in Ontario

An indirect approach was used to estimate exposure to background levels of atmospheric benzene for a selection of Ontario non‐smoking urban sub‐populations. Activity codes obtained from nationally representative time‐budget surveys were allocated to five general microenvironments (home, work (or school), outdoors, commuting, and other indoors) and further combined with inhalation rates corresponding to specific levels of physical activity in order to develop average activity patterns for six sub‐populations believed to be differently exposed to atmospheric benzene in urban areas (children, teenagers, office workers, outdoor workers, transit workers, and seniors). These activity patterns were then combined with representative concentrations of benzene measured in the selected microenvironments in Ontario in order to evaluate exposure. Two metrics were used for this purpose, integrated exposure and potential average daily dose (intake). Potential lifetime average daily doses were also estimated for three composite sub‐groups representing average office, outdoor, and transit workers. A probabilistic approach using a Monte‐Carlo sampling procedure was used in order to estimate possible ranges of exposures experienced by the various sub‐populations. Results obtained suggested that the highest daily integrated exposure (mean: 131 μg‐hrs/m³) was associated with the average transit worker while comparable levels were estimated for the other sub‐populations investigated (mean: 77–86 μg‐hrs/m³). These levels corresponded to 24‐hours time‐weighted average (TWA)‐equivalent concentrations of 5.5 μg/m³ and 3.5 μg/m³, respectively. Statistical distributions of integrated exposures obtained with the probabilistic approach indicated levels as high as 343 μg‐hrs/m³ (97.5th percentile) in the case of the average transit worker, corresponding to TWA‐equivalents in excess of 15 μg/m³. When levels of physical activities and inhalation rates were integrated in the calculation of exposure, the highest potential average daily dose was found to be associated with the average child (mean: 3.1 μg/kg‐day; 97.5th percentile: 6.0 μg/kg‐day) whereas comparable amounts were estimated for teenager and transit workers (mean: 2.1 μg/kg‐day; 97.5th: 4.1 and 6.9 μg/kg‐day, respectively). Indoor microenvironments (home, office/school, other indoors) were identified as the major contributors to total exposure and intake of benzene (≥50%) although their relative importance varied depending on the exposure metric utilized. Potential lifetime average daily doses estimated for transit workers varied from 2.1 (mean) to 5.4 (97.5th) μg/kg‐day. This was slightly higher than those estimated for the average office and outdoor workers (mean: 1.5–1.7 μg/kg‐day). These projections suggest that average non‐smoking children and teenagers are the most exposed sub‐populations among those investigated to background levels of atmospheric benzene as a result of their daily activities. However, these projections must be interpreted with caution in view of uncertainties associated with some of the assumptions adopted, the limited database used to document benzene levels, and as a result of unaccounted sources of emissions which, under certain circumstances, can significantly modify these conclusions.     

Identification and characterization of DUSP27, a novel dual-specific protein phosphatase

A novel human dual-specific protein phosphatase (DSP), designated DUSP27, is here described. The DUSP27 gene contains three exons, rather than the predicted 4-14 exons, and encodes a 220 amino acid protein. DUSP27 is structurally similar to other small DSPs, like VHR and DUSP13. The location of DUSP27 on chromosome 10q22, 50 kb upstream of DUSP13, suggests that these two genes arose by gene duplication. DUSP27 is an active enzyme, and its kinetic parameters and were determined. DUSP27 is a cytosolic enzyme, expressed in skeletal muscle, liver and adipose tissue, suggesting its possible role in energy metabolism.     

Interaction between double helix DNA fragments and the new antitumor agent sabarubicin,Men10755

Among the disaccharide derivatives of the antitumor anthracycline doxorubicin, sabarubicin (Men10755) is more active and less cytotoxic than doxorubicin. It showed a strong in vivo antitumor activity in all preclinical models examined, in conjunction with a better tolerability, and is now in phase II clinical trials.The interaction of sabarubicin and Men10749 (a similar disaccharide with a different configuration at C-4′ of the proximal sugar) with the hexanucleotides d(CGTACG)₂ and d(CGATCG)₂ was studied by a combined use of 2D-¹H and ³¹P NMR techniques. Both ¹H and ³¹P chemical shifts of imino protons and phosphates allowed to established the intercalation sites between the CG base pairs, as it occurs for other anthracyclines of the series. The dissociation rate constants (k_off) of the slow step of the intercalation process were measured for Men10755 and Men10749, by NMR NOE-exchange experiments. The increase of k_off , with respect of doxorubicin, showed that the intercalation process is significantly faster for both drugs, leading to an average residence time for sabarubicin into d(CGTACG)₂ sixfold shorter than for doxorubicin. This could give account of both higher cytoplasmic/nuclear ratio and lower cellular uptake of sabarubicin in comparison with doxorubicin and accordingly of the lower cytotoxicity of these disaccharide analogues.A relevant number of NOE interactions allowed the structure of the complexes in solution to be derived through restrained MD calculations. NMR-DOSY experiments were performed with several drug/oligonucleotide mixtures in order to determine the structure and the dimension of the aggregates.     

Chelating derivatives of chitosan obtained by reaction with ascorbic acid

Ascorbic acid immediately dissolves Euphausia superba chitosan upon mixing and forms chitosan ascorbate; during the 6-h period after dissolution in water at pH 5–7, ascorbate is oxidized to dehydroascorbate which undergoes Schiff reaction with the amino groups of chitosan, thus yielding a viscous solution of a polymeric ketimine. The latter is characterized by infrared spectrometry, circular dichroism spectropolarimetry, viscometry and alkalimetry. When brought into contact with transition metal ions, the chitosan ascorbate ketimine yields insoluble metal chelates. Upon reduction with sodium cyanoborohydride, the water-insoluble N-[2-(1,2-dihydroxyethyl)tetrahydrofuryl] chitosan (NDTC) is obtained, which shows enhanced capacity for uranium, up to 800 mg U/g from solutions at pH 4·5.     

Interface processes between protected and unprotected areas: A global review and ways forward

Land‐use changes and the expansion of protected areas (PAs) have amplified the interaction between protected and unprotected areas worldwide. In this context, ‘interface processes' (human–nature and cross‐boundary interactions inside and around PAs) have become central to issues around the conservation of biodiversity and ecosystem services. This scientific literature review aimed to explore current knowledge and research gaps on interface processes regarding terrestrial PAs. At first, 3,515 references related to the topic were extracted through a standardized search on the Web of Science and analyzed with scientometric techniques. Next, a full‐text analysis was conducted on a sample of 240 research papers. A keyword analysis revealed a wide diversity of research topics, from ‘pure' ecology to sociopolitical research. We found a bias in the geographical distribution of research, with half the papers focusing on eight countries. Additionally, we found that the spatial extent of cross‐boundary interactions was rarely assessed, preventing any clear delimitation of PA interactive zones. In the 240 research papers we scanned, we identified 403 processes that were studied. The ecological effects of PAs were well documented and appeared to be positive overall. In contrast, the effects of PAs on local communities were understudied and, according to the literature focusing on these, were very variable according to local contexts. Our findings highlight key research advances on interface processes, especially regarding the ecological outcomes of PAs, the influence of human activities on biodiversity, and PA governance issues. In contrast, main knowledge gaps concern the spatial extent of interactive zones, as well as the interactions between local people and conservation actions and how to promote synergies between them. While the review was limited to terrestrial PAs, its findings allow us to propose research priorities for tackling environmental and socioeconomic challenges in the face of a rapidly changing world.     

The future of ecolabels

The International Journal of Life Cycle Assessment -     

Dinosaur Tracks as Paleogeographic Constraints: New Scenarios for the Cretaceous Geography of the Periadriatic Region

A really unexpected finding of sauropod and theropod footprints in southern Latium raises to four the number of the trampled levels recognized in central and southern Italy. After the recent findings in Latest Jurassic and Early, mid and Late Cretaceous carbonate platform deposits of the Periadriatic region, dinosaur footprints seem to provide very important paleogeographic constraints for reconstructing the geodynamic history of the Mediterranean area. The presence of a varied ichnoassociation makes acceptance of the current paleogeographic models concerning the relative and absolute position of the Laziale-Abruzzese-Campano and of Apulian-Dinaric domains during the Late Cretaceous more and more problematic. Dinosaur footprints, combined with other paleontological data, demonstrate that these areas were never completely pulled apart by deep seaways, while frequent or continuous links between them, and to southern and northern mainlands, probably persisted. These data also allowed us to improve our understanding of the timing of the Mesozoic plate motion in this segment of the Western Tethys.     

Author and type of the name Iris cengialti (Iridaceae)

Abstract

A. Kerner is correctly the author of the name Iris cengialti previously ascribed to Ambrosi, and consequently the type of the species is here selected, as lectotype, among Kerner's original material kept in WU.