Assignment of the prealbumin (PALB) gene (familial amyloidotic polyneuropathy) to human chromosome region 18q11.2–q12.1

Summary The assignment of the human prealbumin (PALB) gene to chromosome region 18q11–q12.1 has been achieved using a human genomic probe in the study of human-mouse somatic cell hybrids and by in situ hybridization. Because familial amyloidotic polyneuropathy was reported previously to be due to a mutation in prealbumin, it can be inferred that the gene for this disorder also maps to 18q11.2–q12.1.     

Warming and drought do not influence the palatability of Quercus pubescens Willd. leaves of four European provenances

In the context of global warming, the impact of extreme drought events on trees and biotic interactions with herbivore insects is widely unknown. A faster range expansion of insects in a changing climate could lead to mass propagations of pests in forests. Therefore, the aim was to investigate the influence of climatic alterations on leaf palatability. We exposed juvenile Quercus pubescens Willd. individuals of four European provenances (Bulgaria, Germany, Hungary, and Italy) to warming and drought. In addition, we conducted a palatability experiment with the pre-exposed Q. pubescens leaves and the caterpillars of the generalist forest pest Lymantria dispar L. (gypsy moth). Consumed leaf dry material, density of trichomes, and specific leaf area were examined. Surprisingly, neither warming nor drought affected the leaf palatability, but palatability was related to the density of trichomes. The Bulgarian provenance of Q. pubescens, which had the lowest density of trichomes, was most palatable. These findings suggest that global warming and drought might not lead to more frequent infestations of the four tested European Q. pubescens provenances by L. dispar caterpillars in the future.     

Protein sorting into multivesicular endosomes

Multivesicular endosomes are important as compartments for receptor downregulation and as intermediates in the formation of secretory lysosomes. Work during the past year has shed light on the molecular mechanisms of protein sorting into multivesicular endosomes and yielded information about the machinery involved in multivesicular endosome formation. Monoubiquitination functions as a signal for sorting transmembrane proteins into intraluminal vesicles of multivesicular endosomes and subsequent delivery to lysosomes. A molecular machinery that contains the ubiquitin-binding protein Hrs/Vps27 appears to be central in this sorting process. Three conserved multisubunit complexes, ESCRT-I, -II and -III, are essential for both sorting and multivesicular endosomes formation. Enveloped RNA viruses such as HIV can redirect these complexes from multivesicular endosomes to the plasma membrane to facilitate viral budding.     

“Following,” an Alternative Mating Strategy Used by Male Olive Baboons (Papio hamadryas anubis): Quantitative Behavioral and Functional Description

Recent data reveal that high-ranking males are unable to monopolize sexual access to fertile females, suggesting the potential evolutionary significance of alternative strategies across many taxa. We examined a well known behavior, “following” of a consortship by adult male olive baboons (Papio hamadryas anubis), that has received little empirical attention. Four consort takeover tactics have been suggested, for both follower and nonfollower males: takeover of an abandoned consort female, individual aggressive challenge to oust the consort male, coalitionary challenge to oust the consort male, or an opportunistic consort takeover relying on the consort male being distracted. We addressed the following questions: 1) How does the behavior of followers differ from nonfollowers? 2) Is following an effective alternative mating strategy? 3) What tactics do followers use to obtain access to fertile females? 4) Do dominance rank and female cycle day influence tactic expression? We studied two habituated groups of olive baboons from September 2009 to July 2010 in Kenya. Followers had a higher rate of agonistic interactions with the consort male and affiliative interactions with other followers. Overall, 74% of consort takeovers were executed by follower males of the targeted consortships. Each of the four consort takeover tactics were used by both follower and nonfollower males, although followers used the individual aggressive challenge and coalitionary challenge tactics more often than nonfollowers. Dominance rank, but not female cycle day, influenced the expression of consort takeover tactics. Our findings indicate that following provides males with sexual access to females.     

Confidence from uncertainty - A multi-target drug screening method from robust control theory

Background  

Robustness is a recognized feature of biological systems that evolved as a defence to environmental variability. Complex diseases such as diabetes, cancer, bacterial and viral infections, exploit the same mechanisms that allow for robust behaviour in healthy conditions to ensure their own continuance. Single drug therapies, while generally potent regulators of their specific protein/gene targets, often fail to counter the robustness of the disease in question. Multi-drug therapies offer a powerful means to restore disrupted biological networks, by targeting the subsystem of interest while preventing the diseased network from reconciling through available, redundant mechanisms. Modelling techniques are needed to manage the high number of combinatorial possibilities arising in multi-drug therapeutic design, and identify synergistic targets that are robust to system uncertainty.     

ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins

ADAM12, adisintegrin and metalloprotease, has been demonstrated to be upregulated in human malignant tumors and to accelerate the malignant phenotype in a mouse model for breast cancer. ADAM12 is a substrate for beta1 integrins and may affect tumor and stromal cell behavior through its binding to beta1 integrins. Here, we report that cells deficient in beta1 integrin or overexpressing beta3 integrin can bind to recombinant full-length human ADAM12 via beta3 integrin. Furthermore, cell binding to ADAM12 via beta3 integrin results in the formation of focal adhesions, which are not formed upon beta1 integrin-mediated cell attachment. We also show that RhoA is involved in beta3 integrin-mediated focal adhesion formation.     

The Salmonella transmembrane effector SteD hijacks AP1-mediated vesicular trafficking for delivery to antigen-loading MHCII compartments

SteD is a transmembrane effector of the Salmonella SPI-2 type III secretion system that inhibits T cell activation by reducing the amounts of at least three proteins –major histocompatibility complex II (MHCII), CD86 and CD97 –from the surface of antigen-presenting cells. SteD specifically localises at the trans-Golgi network (TGN) and MHCII compartments; however, the targeting, membrane integration and trafficking of SteD are not understood. Using systematic mutagenesis, we identify distinct regions of SteD that are required for these processes. We show that SteD integrates into membranes of the ER/Golgi through a two-step mechanism of membrane recruitment from the cytoplasm followed by integration. SteD then migrates to and accumulates within the TGN. From here it hijacks the host adaptor protein (AP)1-mediated trafficking pathway from the TGN to MHCII compartments. AP1 binding and post-TGN trafficking require a short sequence in the N-terminal cytoplasmic tail of SteD that resembles the AP1-interacting dileucine sorting signal, but in inverted orientation, suggesting convergent evolution.