Within-species correlations in leaf traits of three boreal plant species along a latitudinal gradient

Evergreen boreal plant species express high variability in their leaf traits. It remains controversial whether this within-species variability is constrained to the same leaf trait relationships as has been observed across species. We sampled leaves of three boreal evergreen woody species along a latitudinal gradient (from 57o56′N to 69o55′N). Leaf longevity (LL) of Pinus sylvestris L. and Vaccinium vitis-idaea L. correlated negatively with mean annual air temperature (MAT), whereas the LL of Ledum palustre L. was not affected by MAT. V. vitis-idaea and L. palustre had a negative relationship between leaf mass per area (LMA) and MAT. In P. sylvestris, the LMA–MAT relationship was positive. A negative correlation between LL and LMA was significant only for P. sylvestris. Leaf nitrogen concentration was positively related to leaf phosphorus concentration in all three species. Leaf potassium concentration was related to nitrogen concentration only in L. palustre, and to phosphorus concentration in P. sylvestris and L. palustre. Our results demonstrate that although within the studied species the variation in some of the leaf traits may have the same degree as interspecific variation, there is no such intercorrelation of leaf traits within the studied species as has been observed across species.     

Dual Cyclin-Binding Domains Are Required for p107 To Function as a Kinase Inhibitor

The retinoblastoma (pRB) family of proteins includes three proteins known to suppress growth of mammalian cells. Previously we had found that growth suppression by two of these proteins, p107 and p130, could result from the inhibition of associated cyclin-dependent kinases (cdks). One important unresolved issue, however, is the mechanism through which inhibition occurs. Here we present in vivo and in vitro evidence to suggest that p107 is a bona fide inhibitor of both cyclin A-cdk2 and cyclin E-cdk2 that exhibits an inhibitory constant (K_i) comparable to that of the cdk inhibitor p21/WAF1. In contrast, pRB is unable to inhibit cdks. Further reminiscent of p21, a second cyclin-binding site was mapped to the amino-terminal portions of p107 and p130. This amino-terminal domain is capable of inhibiting cyclin-cdk2 complexes, although it is not a potent substrate for these kinases. In contrast, a carboxy-terminal fragment of p107 that contains the previously identified cyclin-binding domain serves as an excellent kinase substrate although it is unable to inhibit either kinase. Clustered point mutations suggest that the amino-terminal domain is functionally important for cyclin binding and growth suppression. Moreover, peptides spanning the cyclin-binding region are capable of interfering with p107 binding to cyclin-cdk2 complexes and kinase inhibition. Our ability to distinguish between p107 and p130 as inhibitors rather than simple substrates suggests that these proteins may represent true inhibitors of cdks.     

<Emphasis Type="Italic">In vitro</Emphasis> Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K _p), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K _p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.     

Software Replica of Minimal Living Processes

There is a long tradition of software simulations in theoretical biology to complement pure analytical mathematics which are often limited to reproduce and understand the self-organization phenomena resulting from the non-linear and spatially grounded interactions of the huge number of diverse biological objects. Since John Von Neumann and Alan Turing pioneering works on self-replication and morphogenesis, proponents of artificial life have chosen to resolutely neglecting a lot of materialistic and quantitative information deemed not indispensable and have focused on the rule-based mechanisms making life possible, supposedly neutral with respect to their underlying material embodiment. Minimal life begins at the intersection of a series of processes which need to be isolated, differentiated and duplicated as such in computers. Only software developments and running make possible to understand the way these processes are intimately interconnected in order for life to appear at the crossroad. In this paper, I will attempt to set out the history of life as the disciples of artificial life understand it, by placing these different lessons on a temporal and causal axis, showing which one is indispensable to the appearance of the next and how does it connect to the next. I will discuss the task of artificial life as setting up experimental software platforms where these different lessons, whether taken in isolation or together, are tested, simulated, and, more systematically, analyzed. I will sketch some of these existing software platforms: chemical reaction networks, Varela’s autopoietic cellular automata, Ganti’s chemoton model, whose running delivers interesting take home messages to open-minded biologists.     

Skipper impoverishment on large West Mediterranean islands (Lepidoptera Hesperioidea): deterministic,historical and stochastic factors

Biogeographical analyses are applied to skipper (Hesperioidea) presence/absence data from the Western Mediterranean mainland and the three largest islands (Sardinia, Corsica and Sicily) in order to identify potential conservation issues. The analyses performed on species, both collectively and individually, indicate that regional species richness and occurrence in the Mediterranean zone are largely predicted by latitude and area but that islands have impoverished faunas. Several species, predicted to be present on these islands from logistic regression of their continental distributions, are actually absent. The number of species predicted to be present from logistic regression analyses for each island, closely matched the number of species predicted to occur in regional-focused multiple regression analysis. This suggests that missing species have been identified. When compared with species that occur in Sicily and Corsica, the missing species are shown to differ for ecological traits, mainly those linked to altitudinal tolerance. No ecological distinctions were disclosed for Sardinian skippers suggesting a mainly stochastic colonisation. These results, and those from an analogous study carried out on Papilionoidea, point to Hesperioidea having (i) overall more impoverished faunas on islands and (ii) being subject to stochastic or historical colonisation events more than Papilionoidea. Species not predicted to occur on islands based on their mainland distributions and ecological traits, are foci for conservation attention. However, as many species becoming extinct on the islands may be irreplaceable, all species, in particular the Sardinian ones, deserve to be conserved.     

An antigenic HIV-1 peptide sequence engineered into the surface structure of transferrin does not elicit an antibody response.

One novel approach for the biological delivery of peptide drugs is to incorporate the sequence of the peptide into the structure of a natural transport protein such as human serum transferrin (HST). However, a potential drawback is that the HST may increase the immunoreactivity of the peptide, in the same way that carrier proteins can be used to generate highly immunogenic peptide hapten conjugates. In this study we have generated a recombinant HST carrier protein that contains a peptide substrate of HIV-1 protease (VSQNYPIVL). The protein retained native HST function, and the peptide was surface exposed since it was immunoreactive in native dot blots, and was cleaved by HIV-1 protease. Immunisation of rabbits with the recombinant protein elicited only a very poor anti-peptide immune response. In contrast, strong anti-peptide immune responses were raised against both the peptide alone, and a chemical conjugate of the peptide with HST. These data demonstrate that it is possible to attenuate the immune response normally directed against an immunogenic peptide sequence by engineering into a surface exposed loop of HST. These findings may have an important impact on the future design of peptide delivery systems.     

Analysis of Flow Phenomena in Gastric Contents Induced by Human Gastric Peristalsis Using CFD

This paper uses computational fluid dynamics to simulate and analyze intragastric fluid motions induced by human peristalsis. We created a two-dimensional computational domain of the distal stomach where peristalsis occurs. The motion of the gastric walls induced by an antral contraction wave (ACW) on the wall of the computational domain was well simulated using a function defined in this study. Retropulsive flow caused by ACW was observed near the occluded region, reaching its highest velocity of approximately 12 mm/s in the narrowest region. The viscosity of the model gastric contents applied in this study hardly affected the highest velocity, but greatly affected the velocity profile in the computational domain. The shear rate due to gastric fluid motion was calculated using the numerical output data. The shear rate reached relatively high values of approximately 20 s⁻¹ in the most occluded region. The shear rate profile was almost independent of the fluid viscosity. We also simulated mass transfer of a gastric digestive enzyme (pepsin) in model gastric content when peristalsis occurs on the gastric walls. The visualized simulation results suggest that gastric peristalsis is capable of efficiently mixing pepsin secreted from the gastric walls with an intragastric fluid.     

An efficient chemical approach to bispecific antibodies and antibodies of high valency

Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with β-lactam equipped mono- and bifunctional targeting modules, including a cyclic-RGD peptide linked to either the peptide (d-Lys⁶)-LHRH or another cyclic RGD unit and a small-molecule integrin inhibitor SCS-873 conjugated to (d-Lys⁶)LHRH. We also prepared monofunctional targeting modules containing either cyclic RGD or (d-Lys⁶)-LHRH peptides. Binding of the chemically programmed antibodies to integrin receptors α(v)β(3) and α(v)β(5) and to the luteinizing hormone releasing hormone receptor were evaluated. The bifunctional and bivalent c-RGD/LHRH and SCS-783/LHRH, the monofunctional and tetravalent c-RGD/c-RGD, and the monofunctional bivalent c-RGD chemically programmed antibodies bound specifically to the isolated integrin receptor proteins as well as to integrins expressed on human melanoma M-21 cells. c-RGD/LHRH, SCS-783/LHRH, and LHRH chemically programmed antibodies bound specifically to the LHRH receptors expressed on human ovarian cancer cells. This approach provides an efficient, versatile, and economically viable route to high-valency therapeutic antibodies that target defined combinations of specific receptors. Additionally, this approach should be applicable to chemically programmed vaccines.     

A catalogue of <Emphasis Type="Italic">Triticum monococcum</Emphasis> genes encoding toxic and immunogenic peptides for celiac disease patients

The celiac disease (CD) is an inflammatory condition characterized by injury to the lining of the small-intestine on exposure to the gluten of wheat, barley and rye. The involvement of gluten in the CD syndrome has been studied in detail in bread wheat, where a set of “toxic” and “immunogenic” peptides has been defined. For wheat diploid species, information on CD epitopes is poor. In the present paper, we have adopted a genomic approach in order to understand the potential CD danger represented by storage proteins in diploid wheat and sequenced a sufficiently large number of cDNA clones related to storage protein genes of Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides were found. All the classes of storage proteins were shown to contain harmful sequences. The major conclusion is that einkorn has the full potential to induce the CD syndrome, as already evident for polyploid wheats. In addition, a complete overview of the storage protein gene arsenal in T. monococcum is provided, including a full-length HMW x-type sequence and two partial HMW y-type sequences. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Background  

Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.