Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation

Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.     

Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin’s role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT₁ receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT₁ antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT₁ cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.     

Il Potenziale di Ossido-Riduzione e le sue applicazioni in Batteriologia ed in Igiene

Summary After a short reference to the fundamental principles of the oxidation-reduction potential and the meaning of the symbolr _H introduced byClark, the author proceeds to set out, among the numerous applications which this important notion has found in various scientific fields, those found in Bacteriology and Hygiene.As regards Bacteriology, the oxidation-reduction potential of the sterile culture media and of various aerobic and anaerobic micro-organisms has been investigated in connection with their growth. The oxidation-reduction potential has proved to be a very good means of classification and identification of the various bacterial strains.Moreover, although the studies performed are not numerous the said oxidation-reduction potential has also been shown to have a great importance in the determination of the immunisation processes of the organism and in its serological behaviour.The oxidation-reduction potential, furthermore, has found very large applications in the field of alimentation, from the problem of fermentations, such as the alcoholic fermentation and the bread fermentation, to the distinction between raw and boiled milk by means ofSchardinger's reaction.In the future, the possibilities for application and development of the oxidation-reduction potential appear to be even more considerable.     

Directing neural stem cell fate with biomaterial parameters for injured brain regeneration

The discovery of neural stem cells (NSCs), which have the ability to self-renew and differentiate into all types of neural lineages, offers promising prospect for the treatment of brain neurological disorders such as stroke/cerebral ischemia, traumatic brain injury and neurodegenerative disorders. However, only limited number of NSCs could survive or propagate due to tissue inflammation or blood-brain barrier. Therefore, it is necessary to develop an appropriate culture system that highly mimics the natural NSCs niche to direct stem cell fate and behavior for nerve regeneration. Both biophysical and biochemical properties of the NSC niche, including topology, mechanical properties, bioactive molecules, and their spatial and temporal presentations should be considered for the design of functionalized scaffolds, which could not only serve as the delivery vehicles of NSCs but also stimulate specific cellular responses at the molecular level, such as support endogenous or exogenous cells proliferation, migration and homing, even promote the growth of axon at the injured brain site. This review attempts to outline the varieties of biomaterial     

欧洲产毒真菌及毒枝菌素研究进展

过去的十多年里，随着人类对自身健康的日益关注，人们对产毒真菌及毒枝菌素研究也在不断深入。欧洲一些与农业相关的研究领域，如植物、食品和饲料等，积累了大量有关产毒真菌及毒枝菌素方面的信息。由于欧洲国家之间环境条件的差异（如温度、光照、降雨等）和自然条件下栽培的作物（谷物品种等）的不同，导致特定产毒真菌在地区分布上的差异，同时也带来了一系列有关真菌毒理学方面的问题。此外，由于世界经济的全球化，农产品的全球贸易对农业有毒真菌的迁移及其可能引发的新疾病，以及地方种群的遗传多样性都将带来深刻的影响。为了便于读者了解过去10—15年间，欧洲有毒真菌及毒枝菌素研究的最新进展，2003年10月25日在意大利举行的“COST-835”会议，本书的编委将这次会议上各国代表的研究论文汇编成册，以飨食读者。     

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila

Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background. Here we re-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C. elegans and Drosophila. In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression abrogated the longevity increase, but did not abrogate sir-2.1 overexpression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low-copy-number sir-2.1 overexpression also abrogated longevity. A Drosophila strain with ubiquitous overexpression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported, but was not long-lived relative to the appropriate transgenic controls, and nor was a new line with stronger overexpression of dSir2. These findings underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life-extending effect of dietary restriction on ageing in Drosophila has also been reported to be dSir2 dependent. We found that dietary restriction increased fly lifespan independently of dSir2. Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila.     

Taxonomic review of the Amazonian millipede genus Parastenonia Hoffman, 1977 and description of a new species from iron-ore caves (Polydesmida: Chelodesmidae)

ABSTRACT

The Amazonian genus Parastenonia Hoffman, 1977 is here revised. The species P. carajas sp. nov. is described from Brazilian iron-ore caves and P. aurae (Schubart, 1947) is considered junior synonym of P. parae (Cook, 1895). In addition, the known geographic distribution of the genus is presented with the inclusion of new occurrence data.

http://www.zoobank.org/urn:lsid:zoobank.org:act:CCBEED10-DCB4-48C9-A71D-CED3462DD72A