Structural basis of bacterial defense against g-type lysozyme-based innate immunity

Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double ‘key-lock’ mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG.     

Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.     

Enhancing momentum investment strategy using leverage

Previous studies examine investment strategies based on leverage and momentum; none investigates both variables jointly as an investment strategy. This paper is the first incorporating leverage and momentum together. We show that low past returns (losers) forecast future negative abnormal returns only among stocks with high leverage levels, but not among stocks with low leverage levels. However, high past returns (winners) forecast future positive abnormal returns independently of leverage level. As a result, the negative relation between leverage and future abnormal returns is only observed among loser stocks, and the positive relation between past returns and future abnormal returns is only shown among non‐low leverage stocks. Our results are important in achieving better investment strategies: buying winners' stocks (independently of their level of leverage) and short‐selling losers' stocks with high leverage yield higher abnormal returns than strategies based on only one of these variables. Our two‐dimensional strategy yields risk‐adjusted abnormal returns of 15.66% per annum, whereas the single leverage or momentum strategies yield 7.70% and 7.96% per annum, respectively. The difference is nearly 8% and economically significant. If leverage is considered as proxy for default risk, our results, contrary to previous evidence, show that momentum profits are not exclusive of default stocks, and that momentum returns are not only driven by negative returns yielded by distress stocks.     

The occurrence and function of the sphragis in the zerynthiine genera Zerynthia,Allancastria and Bhutanitis (Lepidoptera: Papilionoidea: Papilionidae)

In some butterfly species males attach a large external mating plug termed a sphragis to the female abdomen during mating. This is derived from male accessory secretions and covers the female ostium bursae and surrounding areas, thus preventing or delaying remating. Specimens of all 12 species of the genera Zerynthia, Allancastria and Bhutanitis (Lepidoptera: papilionidae), which form a natural clade within the Zerynthiini, were examined for presence or absence of a sphragis and their male and female genitalia were studied. In all three genera female genitalia lack a typical sinus vaginalis and the sterigma is modified to form an exposed, shiny, well-sclerotized genital plate, derived from the fusion and expansion of the lamellae ante- and postvaginales. The exposed ostium bursae is situated near the posterior end of the genital plate in Zerynthia, whereas in Allancastria and Bhutanitis it is near the anterior end. A crude irregularly formed sphragis was found at least facultatively in all species. The sphragides of Zerynthia and Bhutanitis were generally poorly developed, in most cases only partially covering the female genital plate. In Allancastria the sphragis mostly covered the genital plate entirely, and generally incorporated numerous long scales derived from the male’s 8th abdominal segment; scales were sometimes sparse or absent, probably due to depletion from repeated matings by males. In Zerynthia, males lacked the dense terminal abdominal tuft of elongated scales found in Allancastria, and their sphragis lacked scales. The sphragis of Bhutanitis thaidina incorporated scales from the male valves, whereas in the B. lidderdalii sphragis (and probably B. ludlowi) the scales derived from the male’s 8th abdominal segment. The role of the scales and possible reasons for the difference in the development of the sphragis among these genera are discussed.     

Parasite community of the golden cownose ray Rhinoptera steindachneri Evermann and Jenkins 1891 (Chondrichthyes: Myliobatidae), in Acapulco Bay,Guerrero, Mexico

The parasite community of the ray Rhinoptera steindachneri from Acapulco Bay was examined and quantified; analyses were based on the sex of the host and the date of sampling. A total of 171 specimens of R. steindachneri were examined during July–August of 2010, and May and July of 2012. Twenty-one species of parasites were found: three species of Monogenea; eight adult and one larval species of Cestoda; one larval species of Nematoda; five species of Copepoda; two species of Isopoda; and one species of Hirudinea. Cestodes had the greatest species richness (43% of the total species), followed by the copepods (24%). Two species of cestode, Glyphobothrium sp. and Rhinebothrium sp., were collected only from adult rays. At the component community level, species richness showed statistically significant variation between 13 and 16 species, which is similar to previous reports for other species of rays. The parasite component communities and infracommunities of R. steindachneri exhibited similar patterns: high species number and low numerical dominance by a particular species of parasite. The differences of body size of male vs. female rays, and a change in diet and feeding behaviour with the age of R. steindachneri, are likely important factors in the structuring of their parasite communities.     

Intrinsically disordered proteins in crowded milieu: when chaos prevails within the cellular gumbo

Effects of macromolecular crowding on structural and functional properties of ordered proteins, their folding, interactability, and aggregation are well documented. Much less is known about how macromolecular crowding might affect structural and functional behaviour of intrinsically disordered proteins (IDPs) or intrinsically disordered protein regions (IDPRs). To fill this gap, this review represents a systematic analysis of the available literature data on the behaviour of IDPs/IDPRs in crowded environment. Although it was hypothesized that, due to the excluded-volume effects present in crowded environments, IDPs/IDPRs would invariantly fold in the presence of high concentrations of crowding agents or in the crowded cellular environment, accumulated data indicate that, based on their response to the presence of crowders, IDPs/IDPRs can be grouped into three major categories, foldable, non-foldable, and unfoldable. This is because natural cellular environment is not simply characterized by the presence of high concentration of “inert” macromolecules, but represents an active milieu, components of which are engaged in direct physical interactions and soft interactions with target proteins. Some of these interactions with cellular components can cause (local) unfolding of query proteins. In other words, since crowding can cause both folding and unfolding of an IDP or its regions, the outputs of the placing of a query protein to the crowded environment would depend on the balance between these two processes. As a result, and because of the spatio-temporal heterogeneity in structural organization of IDPs, macromolecular crowding can differently affect structures of different IDPs. Recent studies indicate that some IDPs are able to undergo liquid–liquid-phase transitions leading to the formation of various proteinaceous membrane-less organelles (PMLOs). Although interiors of such PMLOs are self-crowded, being characterized by locally increased concentrations of phase-separating IDPs, these IDPs are minimally foldable or even non-foldable at all (at least within the physiologically safe time-frame of normal PMLO existence).     

Sex-dependence in triglyceride metabolism in response to dietary carbohydrates.

In humans, as well as in mice, fed on high carbohydrate diets, there was a significant sex difference in the plasma tirglycerides in that males had higher levels than females. This was mainly due to the difference in their removal rate of circulating triglycerides in the animals of both sexes. In mice, males had higher levels of liver triglycerides as well as higher rate of incorporation of U- 14C-glucose into liver triglycerides when compared to females.