Recent changes in body weight and wing length among some British passerine birds

We tested the prediction that global warming has caused recent decreases in body weight (Bergmann's rule) and increases in wing length (Allen's rule) in 14 species of passerine birds at two localities in England: Wicken Fen (1968–2003) and Treswell Wood (1973–2003).
Predicted long-term linear decreases in residual body weight occurred in four species: dunnocks (Wicken Fen), and great tits, blue tits and bullfinches (Treswell Wood). Non-linear decreases also occurred in reed warblers and blackcaps at Wicken Fen, which also had a surprising linear increase in residual body weight in blackbirds.
Residual wing lengths increased linearly, as predicted, in six of seven species at Wicken Fen. Whereas there were non-linear long-term increases in wrens, dunnocks and blackbirds in Treswell Wood. Unexpected linear decreases also occurred in residual wing lengths in willow warblers (Wicken Fen), and blue tits, great tits and chaffinches (Treswell Wood).
The most parsimonious explanation for such long-term changes in body weight is global warming, as predicted by Bergmann's rule. Greater site and species-specific effects on wing length (e.g. non-linear changes plus shorter wings in the woodland habitat) suggest a less straightforward conclusion concerning Allen's rule, probably because wing length involved variation in both bone and feather growth.
Changes in residual body weights and wing lengths often differed between species and were sometimes non-linear, perhaps reflecting short-term modifications in selection pressures. Human-induced influences are discussed, such as avian predator population densities and land-use change. Short-term variation in temperature had little effect, but rainfall did explain the unusual increase in blackbird body weight, possibly as a result of improving food (earthworm) availability.     

Symmetry breaking and convergent extension in early chordate development

The initiation of axis, polarity, cell differentiation, and gastrulation in the very early chordate development is due to the breaking of radial symmetry. It is believed that this occurs by an external signal. We suggest instead spontaneous symmetry breaking through the agency of the Turing-Child field. Increased size or decreased diffusivity, both brought about by mitotic activity, cause the spontaneous loss of stability of the homogeneous state and the evolution of the metabolic pattern during development. The polar metabolic pattern is the cause of polar gene expression, polar morphogenesis (gastrulation), and polar mitotic activity. The Turing-Child theory explains not only the spontaneous formation of the invagination in gastrulation but also the coherent cell movement observed in convergence and extension during gastrulation and neurulation. The theory is demonstrated with respect to experimental observations on the early development of fish, amphibian, and the chick. The theory can explain a multitude of experimental details. For example, it explains the splayed polar progression of reduction in the fish blastoderm. Reduction starts on that side of the blastoderm margin, which will initiate invagination several hours later. It progresses toward the blastoderm center and somewhat laterally from this future "dorsal lip". This is precisely as predicted by a Turing-Child system in a circle. And for a fish like zebrafish with a blastoderm that is slightly oval, reduction is observed to progress along the long axis of the ellipse, which is what Turing-Child theory predicts. In general the shape and the chemical nature of the experimental patterns are the same as predicted by the Turing couple (cAMP, ATP). Embryological polarity and convergent extension are based on polar eigenfunction and saddle-shaped eigenfunction, respectively.     

ARNO through its coiled-coil domain regulates endocytosis at the apical surface of polarized epithelial cells

ARNO is a guanine-nucleotide exchange protein for the ARF family of GTPases. Here we show that in polarized epithelial cells, ARNO is localized exclusively to the apical plasma membrane, where it regulates endocytosis. Expression of ARNO stimulates apical endocytosis of the polymeric immunoglobulin receptor, and coexpression of ARF6 with ARNO leads to a synergistic stimulation of apical endocytosis. Expression of a dominant negative ARF6 mutant, ARF6-T27N, antagonizes this stimulatory effect. Deletion of the N-terminal coiled-coil (CC) domain of ARNO causes the mutant ARNO to localize to both the apical and basolateral plasma membranes. Expression of the CC domain alone abolishes ARNO-induced apical endocytosis as well as co-localization of IgA-receptor complexes with ARNO and clathrin. These results suggest that the CC domain contributes to the specificity of apical localization of ARNO through association with components of the apical plasma membrane. We conclude that ARNO acts together with ARF6 to regulate apical endocytosis.     

The NRAMP family of metal-ion transporters

The family of NRAMP metal ion transporters functions in diverse organisms from bacteria to human. NRAMP1 functions in metal transport across the phagosomal membrane of macrophages, and defective NRAMP1 causes sensitivity to several intracellular pathogens. DCT1 (NRAMP2) transport metal ions at the plasma membrane of cells of both the duodenum and in peripheral tissues, and defective DCT1 cause anemia. The driving force for the metal-ion transport is proton gradient (protonmotive force). In DCT1 the stoichiometry between metal ion and proton varied at different conditions due to a mechanistic proton slip. Though the metal ion transport by Smf1p, the yeast homolog of DCT1, is also a protonmotive force, a slippage of sodium ions was observed. The mechanism of the above phenomena could be explained by a combination between transporter and channel mechanisms.     

Osmotic swelling and residual stress in cardiovascular tissues

Osmotic swelling (OS) and residual stress (RS) significantly affect the function of cardiovascular (CVS) tissues and organs. The physical mechanisms of OS and RS are reviewed and analyzed with focus on the theoretical background and related experimental evidence. It will be shown that swelling of CVS tissues stems from the presence of charged proteoglycan macro-molecules in these tissues, and that this swelling is a key determinant of RS. In view of OS and RS functional significance in mechanical function, modeling attempts which incorporate them in CVS stress analysis will be presented and discussed.     

Peptide Derived from HIV-1 TAT Protein Destabilizes a Monolayer of Endothelial Cells in an in Vitro Model of the Blood-Brain Barrier and Allows Permeation of High Molecular Weight Proteins

Most chemotherapeutic agents are blood-brain barrier (BBB) impermeants. HIV-1-derived TAT protein variants contain a transmembrane domain, which may enable them to cross the BBB and reach the brain. Here we synthesized CAYGRKKRRQRRR, a peptide containing a cysteine moiety attached to the N terminus of the transmembrane domain (C-TAT peptide), and studied its effects in an in vitro BBB model, which we found to reflect penetration by a receptor-independent pathway. Incubation of the brain capillary endothelial cell monolayer with 0.3–0.6 μmol/ml of this C-TAT peptide, for a period of 1–2 h, destabilizes brain capillary endothelial cell monolayer and introduces the ability of impermeant therapeutic agents including high molecular weight proteins to penetrate it substantially. The cysteinyl moiety at position 1 of the C-TAT peptide contributes largely to the destabilizing potency and the penetration efficacy of impermeant substances. The destabilizing effect was reversed using heparin. In summary, experimental conditions allowing a significant increase in entry of impermeant low and high molecular weight substances from the luminal (blood) to the abluminal side (brain) were found in an in vitro BBB model reflecting in vivo protein penetrability by a receptor-independent pathway.     

Identification of a Novel Pathway of Transforming Growth Factor-β1 Regulation by Extracellular NAD+ in Mouse Macrophages: IN VITRO AND IN SILICO STUDIES

Extracellular β-nicotinamide adenine dinucleotide (NAD(+)) is anti-inflammatory. We hypothesized that NAD(+) would modulate the anti-inflammatory cytokine Transforming Growth Factor (TGF)-β1. Indeed, NAD(+) led to increases in both active and latent cell-associated TGF-β1 in RAW 264.7 mouse macrophages as well as in primary peritoneal macrophages isolated from both C3H/HeJ (TLR4-mutant) and C3H/HeOuJ (wild-type controls for C3H/HeJ) mice. NAD(+) acts partially via cyclic ADP-ribose (cADPR) and subsequent release of Ca(2+). Treatment of macrophages with the cADPR analog 3-deaza-cADPR or Ca(2+) ionophores recapitulated the effects of NAD(+) on TGF-β1, whereas the cADPR antagonist 8-Br-cADPR, Ca(2+) chelation, and antagonism of L-type Ca(2+) channels suppressed these effects. The time and dose effects of NAD(+) on TGF-β1 were complex and could be modeled both statistically and mathematically. Model-predicted levels of TGF-β1 protein and mRNA were largely confirmed experimentally but also suggested the presence of other mechanisms of regulation of TGF-β1 by NAD(+). Thus, in vitro and in silico evidence points to NAD(+) as a novel modulator of TGF-β1.     

Intraspecific directed deterrence by the mustard oil bomb in a desert plant

Plant secondary metabolites (SMs) acting as defensive chemicals in reproductive organs such as fruit tissues play roles in both mutualistic and antagonistic interactions between plants and seed dispersers/predators. The directed-deterrence hypothesis states that SMs in ripe fruits deter seed predators but have little or no effect on seed dispersers. Indeed, studies have demonstrated that birds are able to cope with fruit SMs whereas rodents are deterred by them. However, this mechanism was only demonstrated at the class level, i.e., between birds and mammals, based on differences in the vanilloid receptors. Here we present experimental and behavioral data demonstrating the use of the broad-range, class-independent "mustard oil bomb" mechanism in Ochradenus baccatus fruits to force a behavioral change at an ecological timescale, converting rodents from seed predators to seed dispersers. This is achieved by a unique compartmentalization of the mustard oil bomb, causing activation of the system only upon seed and pulp coconsumption, encouraging seed dispersal via seed spitting by rodents. Our findings demonstrate the power of SMs to shift the animal-plant relationship from predation to mutualism and provide support for the directed-deterrence hypothesis at the intraspecific level, in addition to the interspecific level.