Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis

A mutual coordination of size between developing arteries and veins is essential for establishing proper connections between these vessels and, ultimately, a functional vasculature; however, the cellular and molecular regulation of this parity is not understood. Here, we demonstrate that the size of the developing dorsal aorta and cardinal vein is reciprocally balanced. Mouse embryos carrying gain-of-function Notch alleles show enlarged aortae and underdeveloped cardinal veins, whereas those with loss-of-function mutations show small aortae and large cardinal veins. Notch does not affect the overall number of endothelial cells but balances the proportion of arterial to venous endothelial cells, thereby modulating the relative sizes of both vessel types. Loss of ephrin B2 or its receptor EphB4 also leads to enlarged aortae and underdeveloped cardinal veins; however, endothelial cells with venous identity are mislocalized in the aorta, suggesting that ephrin B2/EphB4 signaling functions distinctly from Notch by sorting arterial and venous endothelial cells into their respective vessels. Our findings provide mechanistic insight into the processes underlying artery and vein size equilibration during angiogenesis.     

Changing reference frames during the encoding of tactile events

The mindless act of swatting a mosquito on the hand poses a remarkable challenge for the brain. Given that the primary somatosensory cortex maps skin location independently of arm posture [1, 2], the brain must realign tactile coordinates in order to locate the origin of the stimuli in extrapersonal space. Previous studies have highlighted the behavioral relevance of such an external mapping of touch, which results from combining somatosensory input with proprioceptive and visual cues about body posture [3-7]. However, despite the widely held assumption about the existence of this remapping process from somatotopic to external space and various findings indirectly suggesting its consequences [8-11], a demonstration of its changing time course and nature was lacking. We examined the temporal course of this multisensory interaction and its implications for tactile awareness in humans using a crossmodal cueing paradigm [12, 13]. What we show is that before tactile events are referred to external locations [12-15], a fleeting, unconscious image of the tactile sensation abiding to a somatotopic frame of reference rules performance. We propose that this early somatotopic "glimpse" arises from the initial feed-forward sweep of neural activity to the primary somatosensory cortex, whereas the later externally-based, conscious experience reflects the activity of a somatosensory network involving recurrent connections from association areas.     

Brassinosteroids Alleviate Heat-Induced Inhibition of Photosynthesis by Increasing Carboxylation Efficiency and Enhancing Antioxidant Systems in <Emphasis Type="Italic">Lycopersicon esculentum</Emphasis>

To investigate the effects of exogenously applied brassinosteroids on the thermotolerance of plants, leaf CO₂ assimilation, chlorophyll fluorescence parameters, and antioxidant enzyme metabolism were examined in tomato (Lycopersicon esculentum Mill. cv. 9021) plants with or without 24-epibrassinolide (EBR) application. Tomato plants were exposed to 40/30°C for 8 days and then returned to optimal conditions for 4 days. High temperature significantly decreased the net photosynthetic rate (P _n), stomatal conductance (G _s), and maximum carboxylation rate of Rubisco (V _cmax), the maximum potential rate of electron transport contributed to ribulose-1,5-bisphosphate (RuBP), as well as the relative quantum efficiency of PSII photochemistry (Ф_PSII), photochemical quenching (q _P), and increased nonphotochemical quenching (NPQ). However, only slight reversible photoinhibition occurred during heat stress. Interestingly, EBR pretreatment significantly alleviated high-temperature-induced inhibition of photosynthesis. The activities of antioxidant enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPOD), and catalase (CAT) increased during heat treatments, and these increases proved to be more significant in EBR-treated plants. EBR application also reduced total hydrogen peroxide (H₂O₂) and malonaldehyde (MDA) contents, while significantly increasing shoot weight following heat stress. It was concluded that EBR could alleviate the detrimental effects of high temperatures on plant growth by increasing carboxylation efficiency and enhancing antioxidant enzyme systems in leaves.     

A pulse--radiolysis approach to fast reductive cleavage of a disulfide bond to uncage enzyme activity

The essential thiol of the enzyme papain has been caged by linking to an aromatic thiol. The resulting caged protein is inactive but enzymatic activity is fully restored upon chemical cleavage of the protective disulfide bond. We have exploited the chemistry of this disulfide bond to uncage papain by pulse radiolysis. We have shown that up to 10% of the enzyme activity can be restored by reductive pulse radiolysis. This approach has been tested on a small-molecule model system, and experiments on this model compound show that pulse radiolysis of the mixed cysteine-aromatic disulfide results in selective reduction of the disulfide bond to generate a thiol in 10-20% yield, consistent with the radiolytically restored activity of the caged papain quantified by the biochemical assay.     

DNA-damage induction by eight metal compounds in TK6 human lymphoblastoid cells: results obtained with the alkaline Comet assay

Metal compounds are long-lived and can react with different macromolecules, producing a wide range of biological effects, including DNA damage. Since their reactivity is associated with their chemical structure, it is important to obtain information on more than one compound from the same metal. In this study, the DNA-damaging potential of two mercury compounds (mercury chloride and methyl mercury chloride), two nickel compounds (nickel chloride and potassium hexafluoronickelate), two palladium compounds (ammonium tetrachloropalladate and ammonium hexachloropalladate), and two tellurium compounds (sodium tellurite and sodium tellurate) was evaluated in human lymphoblastoid TK6 cells by use of the alkaline version of the Comet assay. As the use of computerized image-analysis systems to collect comet data has increased, the metric used for quantifying DNA damage was the Olive tail moment. Treatments lasted for 3h and the range of concentrations tested was different for each metal compound, depending on its toxicity. Both mercury agents produced DNA damage in TK6 cells, with mercury chloride producing considerably more DNA damage than methyl mercury chloride. Of the two nickel compounds, only nickel chloride (a Ni(II) compound) induced DNA breaks. Similarly, of the two palladium compounds, only the Pd(II) compound (ammonium tetrachloropalladate) was positive in the assay. Sodium tellurite was clearly positive, producing concentration-related increases in DNA damage, while sodium tellurate gave a negative response. In conclusion, the ability of inducing DNA damage by the selected metal compounds in human TK6 cells, when measured with the Comet assay, was dependent on the chemical form and, in general, compounds containing the metal in the lower valence state displayed the greater DNA-damaging ability.     

Role of DHEA-S on body fat distribution: gender- and depot-specific stimulation of adipose tissue lipolysis

The objective of this work was to study the possible impact of DHEA-S on body fat distribution and the specific action of the hormone on lipolysis from visceral and subcutaneous human adipose tissue. First, a clinical evaluation was performed in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed tomography (CT) anthropometric parameters of abdominal fat distribution. In a second experiment, subcutaneous and visceral adipose tissue samples were obtained from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation with DHEA-S to further assess a possible effect of this hormone on adipose tissue lipolysis. Serum DHEA-S was inversely and specifically associated with visceral fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In vitro, DHEA-S increased lipolysis in women's subcutaneous adipose tissue at 2 h, while in men, the effect was evident in visceral tissue and after 24 h of treatment. In conclusion, DHEA-S contributes to gender-related differences in body fat distribution probably by a differential lipolytic action. We have demonstrated for the first time in vitro that DHEA-S stimulates lipolysis preferably in subcutaneous fat in women and in visceral fat in men.     

Early lipoic acid intake protects retina of diabetic mice

The aim of this study was to test the effect of lipoic acid treatment on the retina after a short diabetic insult. Diabetes was induced by alloxan and mice were divided into sub-groups; control, diabetic, diabetic+insulin and all groups received+/-lipoic acid (100 mg/kg body weight) for 3 weeks. GSH content, MDA concentration, GPx activity were measured and electroretinograms (ERG) were recorded. Early administration of lipoic acid to diabetic mice prevented the statistically significant decreases of GSH content and GPx activity and normalized MDA concentration. Moreover, lipoic acid restored electroretinogram b-wave amplitude of diabetic animals to control values. Lipoic acid has a protective effect on the diabetic retina.     

Bosque: integrated phylogenetic analysis software

Phylogenetic analyses today involve dealing with computer files in different formats and often several computer programs. Although some widely used applications have integrated important functionalities for such analyses, they still work with local resources only: input/output files (users have to manage them) and local computing (users have sometimes to leave their programs, on their desktop computers, running for extended periods of time). To address these problems we have developed 'Bosque', a multi-platform client-server software that performs standard phylogenetic tasks either locally or remotely on servers, and integrates the results on a local relational database. Bosque performs sequence alignments and graphical visualization and editing of trees, thus providing a powerful environment that integrates all the steps of phylogenetic analyses. AVAILABILITY: http://bosque.udec.cl