Differential carnitine/acylcarnitine translocase expression defines distinct metabolic signatures in skeletal muscle cells

Import of acylcarnitine into mitochondrial matrix through carnitine/acylcarnitine-translocase (CACT) is fundamental for lipid catabolism. To probe the effect of CACT down-expression on lipid metabolism in muscle, human myocytes were stably transfected with CACT-antisense construct. In presence of low concentration of palmitate, transfected cells showed decreased palmitate oxidation and acetyl-carnitine content, increased palmitoyl-carnitine level, and reduced insulin-dependent decrease of fatty acylcarnitine-to-fatty acyl-CoA ratio. The augmented palmitoyl-carnitine synthesis, also in the presence of insulin, could be related to an altered regulation of carnitine-palmitoyl-transferase 1 (CPT 1) by malonyl-CoA, whose synthesis is dependent by the availability of cytosolic acetyl-groups. Indeed, all the described effects were completely overcome by CACT neo-expression by recombinant adenovirus vector or by addition of acetyl-carnitine to cultures. Acetyl-carnitine effect was related to an increase of malonyl-CoA and was abolished by down-expression, via antisense RNA strategy, of acetyl-CoA carboxylase-beta, the mitochondrial membrane enzyme involved in the direct CPT 1 inhibition via malonyl-CoA synthesis. Thus, in our experimental model the modulation of CACT expression has consequences for CPT 1 activity, while the biologic effects of acetyl-carnitine are not associated with a generic supply of energy compounds but to the anaplerotic property of the molecule.     

Spermiogenesis in a Scutariellid (Platyhelminthes)

Spermiogenesis and spermatozoa were studied by transmission and scanning electron microscopy in Troglocaridicolasp., a scutariellid epizoic on a cavernicolous freshwater shrimp. Spermiogenesis involves elongation of the spermatid in which the nucleus elongates, but remains close to the common cytoplasmic mass. Flagella first grow in opposite direction and at a right angle to the cytoplasmic shaft, and centrioles show associate structures. Later, the two centrioles rotate and the flagella emerge parallel, but still perpendicular to the shaft. An apical process elongates at the extremity of the spermatid shaft. The spermatozoon shows active flagellar beating and undulations of the sperm body. The spermatozoon comprises an anterior ‘corkscrew’ region, the flagellar insertion region, a cytoplasmic region and a posterior nuclear region. The corkscrew contains an electron dense structure, not membrane-bound, originating from the apical process of the spermatid. The flagella show the 9+‘1’ pattern, usual in Platyhelminthes. The cytoplasmic and nuclear regions show a cortical row of about 50 twisted longitudinal microtubules surrounding a row of electron dense, and not membrane-bound, 25-nm granules. These granules are original structures and seem to be known only in a few Platyhelminthes species in which a non-flagellar movement of the spermatozoon occurs. Thus, it is hypothesised that the 25-nm granules play a role in cellular motility. Sperm ultrastructure in Troglocaridicolashows major differences to that in the temnocephalids. It is therefore concluded that the phylogenetic position of the scutariellids within the Temnocephalidea should be reinvestigated.     

The Spermatozoon of Brachionus plicatilis(Rotifera,Monogononta) With Some Notes on Sperm Ultrastructure in Rotifera

The spermatozoon of B. plicatilisis a thread–like cell with an anterior flagellar portion and a posterior cell body. The flagellum has a lateral ‘undulating membrane’, containing a folded longitudinal cisterna and an axoneme. The basal body of the axoneme is at the anterior tip. The axoneme lacks outer dynein arms and extends through the entire flagellar region and most of the cell body. The main portion of the flagellum and of the cell body contains a series of vesicles with tightly packed tubules that may serve as a cytoskeleton. The cell body contains a partly condensed nucleus, several mitochondria and some cytoplasm. Some elongated mitochondria are arranged in the postnuclear region. When the spermatozoon moves, the undulations propagate from the basal body at the flagellar tip. Late spermatids can be recognized by the nucleus and the flagellum being coiled and enclosed within a common cell membrane. As in other rotifers, there are cigar–like cell products (‘rods’) in the testes. The general organization of the cell, including the absence of an evident acrosome, resembles that of the other known monogonont sperm types.     

Rotatory apparatus in Bdelloids

All Bdelloid Rotifers have the same body plan: elongated body, ciliated apical region (rotatory apparatus or corona), telescopically retractable foot and head with pseudosegments, paired gonads, single dorsal antenna, apical rostrum, ramate mastax. Bdelloids use the rotatory apparatus for both locomotion and collecting food and therefore the shape of the corona and arrangement of the cilia, both related to the animal's life style, probably are important for the fitness of the rotifers. We have analyzed the fine morphology of the corona and the rostrum from species belonging to the four families, Habrotrochidae, Philodinidae, Adinetidae and Philodinavidae, each with its own form of feeding and locomotion. In the rostrum one can distinguish a sensorial area and a ciliated area. The former is common to all bdelloids, while the latter is lacking in the Adinetidae. Three models of corona can be recognized: 1) a simple ciliated field of undifferentiated cilia (Adinetidae), 2) a well developed ciliated field with specialized cilia forming the paired trochi on the disks and the cingulum (Habrotrochidae and Philodinidae), and 3) a ciliated field with a single trochus encompassing rudimentary pedicels and cingulum (Abrochtha). We propose (1) to no longer use Digononta as a taxon, (2) to assign the class rank to Bdelloidea, (3) to distinguish three orders, grouping Philodinidae and Habrotrochidae under a single order and (4) to retain the current families.     

Defective growth in vitro of Duchenne Muscular Dystrophy myoblasts: the molecular and biochemical basis

As the molecular basis of Duchenne Muscular Dystrophy (DMD) was being discovered, increasing focus was placed on the mechanisms of progressive failure of myoregeneration. In this study, we propose a pathogenesis model for DMD, where an autocrine growth factor release of TGF-beta1-from necrotic myofibers-could contribute to the increasing loss of muscle regeneration. In fact, we report evidence that DMD myoblasts reduce their proliferation rate, in time and later cultures; in connection with this, we observed TGF-beta1 increase in conditioned media of DMD myoblasts, able to control the myoblast growth by reducing fusion and differentiation of DMD satellite 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.     

Iron supplementation is sufficient to rescue skeletal muscle mass and function in cancer cachexia

Cachexia is a wasting syndrome characterized by devastating skeletal muscle atrophy that dramatically increases mortality in various diseases, most notably in cancer patients with a penetrance of up to 80%. Knowledge regarding the mechanism of cancer‐induced cachexia remains very scarce, making cachexia an unmet medical need. In this study, we discovered strong alterations of iron metabolism in the skeletal muscle of both cancer patients and tumor‐bearing mice, characterized by decreased iron availability in mitochondria. We found that modulation of iron levels directly influences myotube size in vitro and muscle mass in otherwise healthy mice. Furthermore, iron supplementation was sufficient to preserve both muscle function and mass, prolong survival in tumor‐bearing mice, and even rescues strength in human subjects within an unexpectedly short time frame. Importantly, iron supplementation refuels mitochondrial oxidative metabolism and energy production. Overall, our findings provide new mechanistic insights in cancer‐induced skeletal muscle wasting, and support targeting iron metabolism as a potential therapeutic option for muscle wasting diseases.