Expression and function of tumour necrosis factor-alpha-converting enzyme in the central nervous system

Tumour necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE/ADAM17) is a membrane protein belonging to the ADAM (a disintegrin and a metalloprotease) family able to cleave various membrane proteins, including the transmembrane form of TNF-alpha at its physiological processing site. Being an ADAM, TACE may mediate not only proteolysis but also adhesive interactions; however, the role of the disintegrin domain of TACE has not been studied. In the central nervous system (CNS), little is known about the physiological role of TACE, but some important pathophysiological functions have been reported recently, with both neurotoxic and neuroprotective repercussions. This article discusses and reviews the main contributions to this field of investigation addressing the expression and function of TACE in the CNS.     

The organization of the microbial biodegradation network from a systems-biology perspective

Microbial biodegradation of environmental pollutants is a field of growing importance because of its potential use in bioremediation and biocatalysis. We have studied the characteristics of the global biodegradation network that is brought about by all the known chemical reactions that are implicated in this process, regardless of their microbial hosts. This combination produces an efficient and integrated suprametabolism, with properties similar to those that define metabolic networks in single organisms. The characteristics of this network support an evolutionary scenario in which the reactions evolved outwards from the central metabolism. The properties of the global biodegradation network have implications for predicting the fate of current and future environmental pollutants.     

Soil-transmitted helminth infections: updating the global picture

Public health workers and parasitologists have long been interested in estimating numbers infected with particular parasite species. Recent changes in social and economic conditions, in addition to implementation of control in some regions of the world, have changed the global picture of soil-transmitted helminth infections. This article brings global estimates up to date, reveals some interesting new trends and discusses the future for control.     

Beclomethasone rapidly ablates allergen-induced beta 2-adrenoceptor pathway dysfunction in human isolated bronchi

Bronchial rings from nonatopic humans were passively sensitized with serum from allergic subjects. Allergen challenge significantly reduced the relaxant effect of salbutamol on carbachol-induced contractions, suggesting beta(2)-adrenoceptor (beta(2)-AR) pathway dysfunction. Incubation of challenged rings for 3 h with 3 x 10(-6) M beclomethasone dipropionate (BDP) restored the relaxant effect, suggesting reversal of beta(2)-AR pathway dysfunction. Incubation with the G(s)alpha protein-stimulating cholera toxin attenuated contractile responses to carbachol significantly less in challenged than in unchallenged rings. Treatment of challenged rings with BDP resulted in an inhibitory effect of cholera toxin that was similar to the effect in unchallenged rings. G(s)alpha protein expression was not significantly altered by BDP, suggesting that the activity of G(s)alpha protein was increased. Relaxation of challenged rings by forskolin was not significantly affected by BDP, suggesting that beta(2)-AR pathway dysfunction was proximal to the adenylyl cyclase. In conclusion, short-term (3-h) treatment with BDP after allergen challenge ablated beta(2)-AR pathway dysfunction by increasing the activity of the G(s)alpha protein in human isolated bronchi.     

The C-terminal extension of a hybrid immunoglobulin A/G heavy chain is responsible for its Golgi-mediated sorting to the vacuole

We have assessed the ability of the plant secretory pathway to handle the expression of complex heterologous proteins by investigating the fate of a hybrid immunoglobulin A/G in tobacco cells. Although plant cells can express large amounts of the antibody, a relevant proportion is normally lost to vacuolar sorting and degradation. Here we show that the synthesis of high amounts of IgA/G does not impose stress on the plant secretory pathway. Plant cells can assemble antibody chains with high efficiency and vacuolar transport occurs only after the assembled immunoglobulins have traveled through the Golgi complex. We prove that vacuolar delivery of IgA/G depends on the presence of a cryptic sorting signal in the tailpiece of the IgA/G heavy chain. We also show that unassembled light chains are efficiently secreted as monomers by the plant secretory pathway.     

Detection of Listeria monocytogenes in Italian-style soft cheeses

AIMS: A rapid detection system specific for Listeria monocytogenes and based on the polymerase chain reaction (PCR) was developed. METHODS AND RESULTS: Primers annealing to the coding region of the actA gene, critically involved in virulence and capable of discrimination between two different alleles naturally occurring in L. monocytogenes, have been utilized. The procedure was applied to recover L. monocytogenes cells in artificially contaminated fresh Italian soft cheeses (mozzarella, crescenza and ricotta). Low levels of L. monocytogenes were detected in mozzarella and crescenza homogenates (0.04-0.4 and 4 CFU g(-1), respectively) whereas in ricotta the detection limit was higher (40 CFU g(-1)). CONCLUSIONS: This PCR-based assay is highly specific as primers used recognize the DNA from different L. monocytogenes strains of clinical and food origin, while no amplification products result with any other Listeria spp. strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlighted a low-cost and rapid procedure that can be appropriated for the detection in real time of low L. monocytogenes levels in soft cheese.     

Adaptation to the land: The skin of reptiles in comparison to that of amphibians and endotherm amniotes

The adaptation to land from amphibians to amniotes was accompanied by drastic changes of the integument, some of which might be reconstructed by studying the formation of the stratum corneum during embryogenesis. As the first amniotes were reptiles, the present review focuses on past and recent information on the evolution of reptilian epidermis and the stratum corneum. We aim to generalize the discussion on the evolution of the skin in amniotes. Corneous cell envelopes were absent in fish, and first appeared in adult amphibian epidermis. Stem reptiles evolved a multilayered stratum corneum based on a programmed cell death, intensified the production of matrix proteins (e.g., HRPs), corneous cell envelope proteins (e.g., loricrine-like, sciellin-like, and transglutaminase), and complex lipids to limit water loss. Other proteins were later produced in association to the soft or hairy epidermis in therapsids (e.g., involucrin, profilaggrin-filaggrin, trichohyalin, trichocytic keratins), or to the hard keratin of hairs, quills, horns, claws (e.g., tyrosine-rich, glycine-rich, sulphur-rich matrix proteins). In sauropsids special proteins associated to hard keratinization in scales (e.g., scale beta-keratins, cytokeratin associated proteins) or feathers (feather beta-keratins and HRPs) were originated. The temporal deposition of beta-keratin in lepidosaurian reptiles originated a vertical stratified epidermis and an intraepidermal shedding layer. The evolutions of the horny layer in Therapsids (mammals) and Saurospids (reptiles and birds) are discussed. The study of the molecules involved in the dermo-epidermal interactions in reptilian skin and the molecular biology of epidermal proteins are among the most urgent future areas of research in the biology of reptilian skin.     

Endothelin-B (ET(B)) receptor distribution in tissues of the lizard Podarcis sicula

Although the structural and pharmacological properties of endothelin (ET) receptors have been studied, little is known concerning their physiological significance, even if each subtype is supposed to have a distinct physiological action. Thus, to further elucidate the physiological function of this receptor, we examined the presence and distribution of the endothelin-B receptor (ET(B)) subtype in tissues of the lizard Podarcis sicula, using immunoblotting and immunohistochemistry. Immunoblotting indicated that, although the ET(B) receptor appears to be ubiquitous, it is present at different levels in the tissues examined. Furthermore, immunohistochemistry showed that this receptor is very abundant in endothelial cells of all tissues, suggesting that there is an ET(B)-mediated autocrine system of endothelin, which plays an important role in the regulation of endothelial cell function. On the other hand, the presence of ET(B) immunoreactivity also in endocrine systems such as adrenal and thyroid glands suggests an involvement also in the paracrine system of these organs.     

Defective dendrite elongation but normal fertility in mice lacking the Rho-like GTPase activator Dbl

Dbl is the prototype of a large family of GDP-GTP exchange factors for small GTPases of the Rho family. In vitro, Dbl is known to activate Rho and Cdc42 and to induce a transformed phenotype. Dbl is specifically expressed in brain and gonads, but its in vivo functions are largely unknown. To assess its role in neurogenesis and gametogenesis, targeted deletion of the murine Dbl gene was accomplished in embryonic stem cells. Dbl-null mice are viable and did not show either decreased reproductive performances or obvious neurological defects. Histological analysis of mutant testis showed normal morphology and unaltered proliferation and survival of spermatogonia. Dbl-null brains indicated a correct disposition of the major neural structures. Analysis of cortical stratification indicated that Dbl is not crucial for neuronal migration. However, in distinct populations of Dbl-null cortical pyramidal neurons, the length of dendrites was significantly reduced, suggesting a role for Dbl in dendrite elongation.