SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration

After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.     

Observations and comments on the reliability of muscle reconstruction in fossil vertebrates

In Canis and Ursus the largest proportion of attachments of muscles of the shoulder and brachium on the scapula and humerus is direct; fewer attachments are aponeurotic or tendinous. In both genera most attachments can be associated with superficial osteological features (scars or delimitable surfaces); attachments that lack such features are direct. Most aponeurotic attachments are associated with rugose scarring whereas tendinous attachments are often associated with smooth surfaces. Although most attachments can be associated with osteological features the areal extent of attachment is often not inferrable from the bone. The inference of muscle size or functional significance from osteological features is problematic. The amount of myological information that can be deciphered from the osteology in Canis and Ursus is greater than that reported for particular members of other vertebrate groups which suggests that there may be differences in the degree to which muscles can be reconstructed from superficial osteology alone. Nonetheless, even in mammals such as the Carnivora, detailed muscular reconstructions in extinct taxa cannot be achieved without reference to the musculature of extant relatives. Such reconstructions rely on assumptions, that often have not been adequately tested, regarding the similarity of musculature in closely related taxa. This testing and well corroborated hypotheses of phylogenetic relationship are essential for the evaluation of the accuracy of reconstructions of the musculature in fossil vertebrates.     

Losses of female song with changes from tropical to temperate breeding in the New World blackbirds

Birds in which both sexes produce complex songs are thought to be more common in the tropics than in temperate areas, where typically only males sing. Yet the role of phylogeny in this apparent relationship between female song and latitude has never been examined. Here, we reconstruct evolutionary changes in female song and breeding latitude in the New World blackbirds (Icteridae), a family with both temperate and tropical representatives. We provide strong evidence that members of this group have moved repeatedly from tropical to temperate breeding ranges and, furthermore, that these range shifts were associated with losses of female song more often than expected by chance. This historical perspective suggests that male-biased song production in many temperate species is the result not of sexual selection for complex song in males but of selection against such songs in females. Our results provide new insights into the differences we see today between tropical and temperate songbirds, and suggest that the role of sexual selection in the evolution of bird song might not be as simple as we think.     

Analysis of non-peptidic compounds as potential malarial inhibitors against Plasmodial cysteine proteases via integrated virtual screening workflow

Falcipain-2 (FP-2) and falcipain-3 (FP-3), haemoglobin-degrading enzymes in Plasmodium falciparum, are validated drug targets for the development of effective inhibitors against malaria. However, no commercial drug-targeting falcipains has been developed despite their central role in the life cycle of the parasites. In this work, in silico approaches are used to identify key structural elements that control the binding and selectivity of a diverse set of non-peptidic compounds onto FP-2, FP-3 and homologues from other Plasmodium species as well as human cathepsins. Hotspot residues and the underlying non-covalent interactions, important for the binding of ligands, are identified by interaction fingerprint analysis between the proteases and 2-cyanopyridine derivatives (best hits). It is observed that the size and chemical type of substituent groups within 2-cyanopyridine derivatives determine the strength of protein–ligand interactions. This research presents novel results that can further be exploited in the structure-based molecular-guided design of more potent antimalarial drugs.     

Oligomerized backbone pilin helps piliated Lactococcus lactis to withstand shear flow

The present work focuses on the role of pili present at the cell surface of Lactococcus lactis in bacterial adhesion to abiotic (hydrophobic polystyrene) and biotic (mucin-coated polystyrene) surfaces. Native pili-displaying strains and isogenic derivatives in which pilins or sortase C structural genes had been modified were used. Surface physico-chemistry, morphology and shear-flow-induced detachment of lactococcal cells were evaluated. The involvement of pili in L. lactis adhesion was clearly demonstrated, irrespective of the surface characteristics (hydrophobic/hydrophilic, presence or not of specific binding sites). The accessory pilin, PilC, and the backbone pilin, PilB, were revealed to play a major role in adhesion, provided that the PilB was present in its polymerized form. Within the population fraction that remained attached to the surface under increasing shear flow, different association behaviors were observed, showing that pili could serve as anchoring sites thus hampering the effect of shear flow on cell orientation and detachment.     

Second-harmonic generation from organic molecules incorporated in sol-gel matrices

Orientation of optically nonlinear organic molecules inside sol-gel matrices upon application of an external D.C. electrical field is demonstrated for the first time. The quadratic nonlinear response of silicon oxide or transition metal oxide based gels containing organic molecules has been determined from Electric Field Induced Second Harmonic (EFISH) measurements. Large concentrations of Optically Nonlinear Organic Molecules (ONOM) have been either incorporated inside the macromolecular network or chemically bonded to the oxide backbone of the gels. These results demonstrate the feasibility of permanently poled doped sol-gel matrices. Moreover, EFISH measurements performed on organic molecules appear to be a useful tool for monitoring the changes occurring during sol-gel transformations.