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.     

Immobile survival of motoneuron (SMN) protein stored in Cajal bodies can be mobilized by protein interactions

Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-2²³) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-2²³ depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-2²³ accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-2²³ caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-2²³, leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly.     

The role of estrogen receptor α in the regulation of bone and growth plate cartilage

Estrogens are important endocrine regulators of skeletal growth and maintenance in both females and males. Studies have demonstrated that the estrogen receptor (ER)-α is the main mediator of these estrogenic effects in bone. Therefore, estrogen signaling via ERα is a target both for affecting longitudinal bone growth and bone remodeling. However, treatment with estradiol (E2) leads to an increased risk of side effects such as venous thromboembolism and breast cancer. Thus, an improved understanding of the signaling pathways of ERα will be essential in order to find better bone specific treatments with minimal adverse effects for different estrogen-related bone disorders. This review summarizes the recent data regarding the intracellular signaling mechanisms, in vivo, mediated by the ERα activation functions (AFs), AF-1 and AF-2, and the effect on bone, growth plate and other estrogen responsive tissues. In addition, we review the recent cell-specific ERα-deleted mouse models lacking ERα specifically in neuronal cells or growth plate cartilage. The newly characterized signaling pathways of estrogen, described in this review, provide a better understanding of the ERα signaling pathways, which may facilitate the design of new, bone-specific treatment strategies with minimal adverse effects.     

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.