Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis

Background

Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation.

Methodology/Principal Findings

Magic-Factor 1 (Met-Activating Genetically Improved Chimeric Factor-1 or Magic-F1) is an HGF-derived, engineered protein that contains two Met-binding domains repeated in tandem. It has a reduced affinity for Met and, in contrast to HGF it elicits activation of the AKT but not the ERK signaling pathway. As a result, Magic-F1 is not mitogenic but conserves the ability to promote cell survival. Here we show that Magic-F1 protects myogenic precursors against apoptosis, thus increasing their fusion ability and enhancing muscular differentiation. Electrotransfer of Magic-F1 gene into adult mice promoted muscular hypertrophy and decreased myocyte apoptosis. Magic-F1 transgenic mice displayed constitutive muscular hypertrophy, improved running performance and accelerated muscle regeneration following injury. Crossing of Magic-F1 transgenic mice with α-sarcoglycan knock-out mice –a mouse model of muscular dystrophy– or adenovirus-mediated Magic-F1 gene delivery resulted in amelioration of the dystrophic phenotype as measured by both anatomical/histological analysis and functional tests.

Conclusions/Significance

Because of these features Magic-F1 represents a novel molecular tool to counteract muscle wasting in major muscular diseases such as cachexia or muscular dystrophy.     

The influence of host plant diversity and food quality on larval survival of plant feeding heteropteran bugs

Abstract. 1. In a laboratory experiment, the influence of host plant diversity and food quality, in terms of nitrogen content, on the larval survival of two oligophagous bug species (Heteroptera, Miridae: Leptopterna dolobrata L., Notostira erratica L.) was investigated. Both species are strictly phytophagous and capable of feeding on a wide range of grass species. Moreover, they typically change their host plants during ontogenesis; it has been suggested that this behaviour is a response to the changing protein content of the hosts.
2. To investigate the importance of host plant diversity for these insects, the development of insects reared on grass monocultures was compared with that on mixtures of four grass species. In addition, the host grasses were grown under two nitrogen regimes to test whether nitrogen content is the key factor determining host plant switching.
3. Both species had a significantly higher survival rate when feeding on several host plants but only L. dolobrata showed a significant response to food nitrogen content. Furthermore, there was no correlation between the nitrogen content of the host plants and the survival rate of N. erratica larvae.
4. The study suggests that at least some Stenodemini need a variety of host plants during larval development but that the level of host plant nitrogen is not the main factor responsible for the observed diversity effect.     

Low-density lipoprotein receptors in the uptake of tumour photosensitizers by human and rat transformed fibroblasts.

Low-density lipoproteins (LDL) increase the selectivity of tumour targeting by drugs, including sensitisers for photodynamic therapy, because of the enhanced expression of specific LDL receptors in many types of transformed as compared with non-transformed cells. This investigation aims at gaining more information on the role of LDL receptors in the accumulation of photosensitizer-LDL complexes by human and rat transformed fibroblasts, and the interference of the photosensitizer with LDL recognition by the specific receptors. Both an amphiphilic hematoporphyrin IX (Hp) and a hydrophobic Zn(II)-phthalocyanine (ZnPc) photosensitizers bind to human LDL with molar ratios of 5-6:1 and 10-12:1, respectively. The hematoporphyrin-LDL complex is accumulated by human HT1080 fibroblasts mainly through the high affinity LDL receptors, while the Zn-phthalocyanine-LDL complex is internalised through non specific endocytosis because of changes in the apoB LDL structure induced by phthalocyanine association, as suggested by spectroscopic studies. The uptake of LDL-delivered hematoporphyrin, but not Zn-phthalocyanine, is about 4-fold higher in HT1080 cells stimulated for maximal expression of LDL receptors as compared with non-stimulated cells. This difference is abolished by LDL acetylation. Human LDL-bound hematoporphyrin and Zn-phthalocyanine are up taken by stimulated and non-stimulated 4R rat fibroblasts with similar efficiency. Scatchard plot analysis of human (125)I-LDL binding to 4R cells shows the presence of only low affinity receptors while 350,000 high affinity receptors are expressed per HT1080 cell. It is concluded that a careful evaluation of the lack of conformational changes of LDL is critical for guaranteeing the selectivity and efficiency of photosensitizer delivery to tumour cells.     

Rhinoglena frontalis (Rotifera,Monogononta): a scanning electron microscopic study

Females and males of Rhinoglena frontalis (Monogononta, Epiphanidae) are observed by SEM and their external morphologies are compared. The two sexes differ in size and shape of the body. The female body is fusiform with a short, conical foot, while the male body is more slender and has a rather long foot. The rotatory apparatus (or corona) of both sexes is similar with only minor differences and consists of rows and tufts of cilia arranged around the mouth opening. The corona is made of two paired lobes lateral to the mouth and of a third prominent dorsal lobe, usually called proboscis. The three lobes are lined externally by dense rows of cilia, which constitute the cingulum, used for swimming. The central surface of the proboscis is covered with numerous longitudinal rows of cilia bent towards the mouth. The lateral lobes show, on their central surfaces, two concentric arcs of cirri (made of tightly packed cilia) bent towards the mouth. The similar organization of the rotatory apparatus of both sexes is related to the fact that the male, in this species, is able to feed and has a developed mastax and digestive system. The trophi of both sexes are illustrated and compared.     

A carnivorous bdelloid rotifer, Abrochtha carnivora n.sp.

Abstract. Here we describe a new bdelloid rotifer, Abrochtha carnivora n.sp., that preys on other bdelloids and monogonont rotifers. This is the first report of predatory behavior in bdelloids. Despite this extraordinary behavior, A. carnivora displays no major structural deviation from the standard body plan for members of the bdelloid family Philodinavidae: body with head (with ciliated corona), trunk, and foot, mastax with ramate trophi. The finding of such a carnivorous species, unique for the class, appears to contradict the common assumption that the wholly parthenogenetic bdelloids are evolutionary dead-ends.