Control of the adaptive response of the heart to stress via the Notch1 receptor pathway.

In the damaged heart, cardiac adaptation relies primarily on cardiomyocyte hypertrophy. The recent discovery of cardiac stem cells in the postnatal heart, however, suggests that these cells could participate in the response to stress via their capacity to regenerate cardiac tissues. Using models of cardiac hypertrophy and failure, we demonstrate that components of the Notch pathway are up-regulated in the hypertrophic heart. The Notch pathway is an evolutionarily conserved cell-to-cell communication system, which is crucial in many developmental processes. Notch also plays key roles in the regenerative capacity of self-renewing organs. In the heart, Notch1 signaling takes place in cardiomyocytes and in mesenchymal cardiac precursors and is activated secondary to stimulated Jagged1 expression on the surface of cardiomyocytes. Using mice lacking Notch1 expression specifically in the heart, we show that the Notch1 pathway controls pathophysiological cardiac remodeling. In the absence of Notch1, cardiac hypertrophy is exacerbated, fibrosis develops, function is altered, and the mortality rate increases. Therefore, in cardiomyocytes, Notch controls maturation, limits the extent of the hypertrophic response, and may thereby contribute to cell survival. In cardiac precursors, Notch prevents cardiogenic differentiation, favors proliferation, and may facilitate the expansion of a transient amplifying cell compartment.

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Two new mermithidis (Nematoda: Mermithidae) parasites of Simulium wolffhuegeli Roubaud and S. jujuyense (Paterson & Shannon) (Diptera: Simuliidae) in Argentina

Two new species of mermithids (Nematoda: Mermithidae), Gastromermis doloresi n. sp. a parasite of Simulium wolffhuegeli Roubaud and Hydromermis doloresi n. sp. a parasite of S. jujuyense (Paterson & Shannon) from Córdoba, Argentina, are described and illustrated. G. doloresi n. sp. is characterized by having medium sized, pear-shaped and oval amphids, eight hypodermal chords all around the body, cylindrical S-shaped vagina, single long spicule 528 [mi]m, whith teh sculpture tip, three rows of genital papillae in which the middle row contains 17 pre-anal and 9 post-anal papillae, and lateral rows contain 18 papillae. Hydromermis doloresi n. sp. can be distinghished by the following: medium sized, pear-shaped amphids, eight hypodermal chords, a cylindrical, S-shaped vagina, one short curved spicule with sculpture and genital papillae in three rows. The medium ventral row of papillae has 4 double and 9 single pre-anal papillae and 3 double and 6 single port-anal papillae, lateral rows have 18 single papillae each.

Life history of Pygidiopsis crassus n. sp. (Trematoda, Digenea, Heterophyidae) in the neotropical region

The life cycle of Pygidiopsis crassus n. sp. was experimentally reproduced, starting from cercariae from naturally infected Littoridina parchappei collected from Lujan River and different ponds in Buenos Aires Province, Argentina. Metacercariae were found encysted in the body cavity of experimentally and naturally infected fishes Cnesterodon decemmaculatus and naturally infected Jenynsia lineata. Adults were obtained experimentally in chicks and mice. The natural host is unknown. The new species is compared with Pygidiopsis macrostomum Travassos 1928, from Rattus norvegicus and from Noctilio leporinus mastivus, differing in body and egg sizes, in the size relation of oral and ventral sucker and the shape of excretory vesicle.

Identification of cancer stem cells in Ewing's sarcoma

Summary : Cancer stem cells (CSC) that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been demonstrated to date. Here, we .identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESPY), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in NOD/SCID mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic and chondrogenic lineages. Quantitative Real-Time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133- counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells (ET-CSC) and demonstration of their mesenchymal stem cell properties, a critical step toward a better biological understanding and rational therapeutic targeting of these tumors. Résumé : Des cellules souches tumorales avec des propriétés exclusives d'initiation tumorale ont récemment été identifiées dans différents types de cancers, permettant ainsi d'espérer le développement de thérapies plus efficaces. Cependant, l'existence de telles cellules dans les sarcomes, un sous-groupe de cancers d'origine mésenchymateuse très agressifs, n'a pas encore été démontrée. Dans ce travail de recherche, nous identifions et caractérisons des cellules souches tumorales dans le sarcome d'Ewing, une tumeur pédiatrique très agressive vraisemblablement dérivée de cellules souches mésenchymateuses (MSC). Afin de séparer des populations cellulaires dans des échantillons primaires de sarcome d'Ewing, nous avons utilisé des billes magnétiques couplées à des anticorps monoclonaux. Ceci nous a permis d'isoler une sous-population de cellules tumorales CD133+ qui ont la capacité d'initier et de maintenir la croissance tumorale dans des xénotransplantations en série effectuées dans des souris immunodéficientes NOD/SCID. Ces cellules reétablissent à chaque passage in vivo le phénotype de la tumeur d'origine ainsi que son organisation hiérarchique. En accord avec la plasticité des MSC, des tests de différentiation in vitro ont montré que les cellules CD133+ maintiennent la capacité de se différentier en adipocytes, ostéocytes et chondrocytes. Une analyse par PCR quantitative de gènes impliqués dans le maintien des cellules souches a montré que les cellules CD133+ expriment un niveau beaucoup plus élevé de OCT4 and NANOG que les cellules CD133-. En résumé, nos observations constituent la première identification de cellules souches tumorales dans le sarcome d'Ewing et démontrent leur propriété de cellules souches mésenchymateuses. Ceci constitue une étape clé vers une meilleure compréhension biologique et une meilleure approche thérapeutique de ces tumeurs.

Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.

Mammary carcinomas developing in SV40 transgenic WAP-T mice arise in two distinct histological phenotypes: as differentiated low-grade and undifferentiated high-grade tumors. We integrated different types of information such as histological grading, analysis of aCGH-based gene copy number and gene expression profiling to provide a comprehensive molecular description of mammary tumors in WAP-T mice. Applying a novel procedure for the correlation of gene copy number with gene expression on a global scale, we observed in tumor samples a global coherence between genotype and transcription. This coherence can be interpreted as a matched transcriptional regulation inherited from the cells of tumor origin and determined by the activity of cancer driver genes. Despite common recurrent genomic aberrations, e.g. gain of chr. 15 in most WAP-T tumors, loss of chr. 19 frequently occurs only in low-grade tumors. These tumors show features of "basal-like" epithelial differentiation, particularly expression of keratin 14. The high-grade tumors are clearly separated from the low-grade tumors by strong expression of the Met gene and by coexpression of epithelial (e.g. keratin 18) and mesenchymal (e.g. vimentin) markers. In high-grade tumors, the expression of the nonmutated Met protein is associated with Met-locus amplification and Met activity. The role of Met as a cancer driver gene is supported by the contribution of active Met signaling to motility and growth of mammary tumor-derived cells. Finally, we discuss the independent origin of low- and high-grade tumors from distinct cells of tumor origin, possibly luminal progenitors, distinguished by Met gene expression and Met signaling.

Neotropical Monogenoidea. 24. Rhinoxenus bulbovaginatus n. sp. (Dactylogyridae, Ancyrocephalinae) from the nasal cavity of Salminus maxillosus (Osteichthyes, Characidae) from the Rio Paraná, Paraná, Brazil

Rhinoxenus bulbovaginatus n. sp. is described from the nose of Salminus maxillosus (Characidae) collected in the basin of the rio Paraná, near the city of Porto Rico, state of Paraná, Brazil. The new species can be differentiated from the other three species in the genus by the morphology of the copulatory complex, vagina, and ventral anchor. The sister group relationship of the known species of Rhinoxenus was determined using techniques of Phylogenetic Systematics (Cladism). The resulting cladogram (C.I.=100%) indicates that the new species is most closely related to R. piranhus Kritsky, Boeger and Thatcher, 1988. The other two species of the genus, R. arietinus Kritsky, Boeger and Thatcher, 1988 and R. nyttus Kritsky, Boeger and Thatcher, 1988, both parasites of Anostomidae fishes, have a paraphyletic position in the cladogram, suggesting that the origin of at least one of them can not be associated to cospeciation.

Morphological Aspects of the Larval Instars of Chrysomya albiceps (Diptera, Calliphoridae) Reared in the Laboratory

In order to study the morphology of young Chrysomya albiceps forms, newly hatched larvae were collected at 2 hr intervals, during the first 56 hr; after this time the collection was made at 12 hr intervals. For identification and drawing, larvae were placed between a slide and a coverslip. The cephalopharyngeal skeletons along with the first and last segments were cut off for observation of their structures and spiracles. The larvae present microspines, which are distributed randomly throughout the 12 segments of the body surface; the cephalopharyngeal skeleton varies in shape and extent of sclerotization according to larval instar; the second and third instars have relatively long processes (tubercles) on the dorsal, lateral and ventral surfaces, with microspine circles on the terminal portion

Limnomermis subtropicalis n. sp. (Nematoda:Mermithidae) a Parasite of Larvae of Simulium orbitale Lutz (Diptera:Simuliidae) in Argentina

Limnomermis subtropicalis n. sp. (Nematoda: Mermithidae) a parasite of Simulium orbitale Lutz (Diptera: Simuliidae) found in Argentina is described and illustrated. This species is characterized by having medium sized amphids, pocket-shaped, medium sized vagina, sculptured spicule, and by having 9 preanal, 7 postanal papillae in the ventral row, and 12 papillae in the lateral rows

Morphological Study of Adult Male Worms of Schistosoma mansoni Sambon, 1907 by Scanning Electron Microscopy

Tubercles, spines and sensory receptors are the most studied structures of adult male worms of Schistosoma mansoni isolated in other countries. The purpose of this investigation was to properly define these structures in Brazilian worms. Specimens 7-8 weeks after infection were recovered from albino SW mice and from a wild rodent (Nectomys squamipes) and processed for scanning electron microscopy studies. Photomicrographs of the anterior region with the aspects related to the outer and inner regions of both suckers were considered. The ventral portion of the middle region was represented by the anterior of gynaecophoric canal while the dorsal surface was studied in its ventral and dorsal regions mainly focusing the aspect of the tubercles, spines and sensorial papillae. The outer surface of the oral sucker is spiny and spines are bigger, sharp with sensory receptors in their posterior edge. Tubercles with spines or receptors are more concentrated in the middle region and in one of the margins of the gynaecophoric canal. An excretory pore-like structure in the posterior portion was observed. The gynaecophoric canal has few sensory structures, spines broadned in their mid-region and are sharp pointed at the distal end. It was concluded that the presently studied characters are similar to those previously reported

Let-7a Is a Direct EWS-FLI-1 Target Implicated in Ewing's Sarcoma Development.

Ewing's sarcoma family tumors (ESFT) are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA) expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC) and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

Adult human adipose tissue contains several types of multipotent cells.

Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria.

Aplectana artigasi n.sp. (Nematoda: Cosmocercidae) from the Frog Eupsophus calcaratus (Anura: Leptodactylidae) in Southern Chile

A new species of nematode found in the intestine of Eupsophus calcaratus (Anura: Leptodactylidae) from Yaldad, Chile (45° 5'S;73° 43'W) is described. This new nematode is compared with other South American species of the genus. Aplectana artigasi differs from the only known Chilean species, Aplectana chilensis, as the former has a greater number of postanal papillae and a double papilla in the ventral region of the tail

Giardia agilis: Ultrastructure of the Trophozoites in the Frog Intestine

Intestine samples of Bufo sp. tadpoles with parasitism confirmed for Giardia agilis were studied by transmission electron microscopy. The G. agilis trophozoites were long and thin. The plasma membrane was sometimes undulated and the cytoplasm, adjacent to the dorsal and ventral regions, showed numerous vacuoles. The two nuclei presented prominent nucleoli. The cytoplasm was electron-dense with free ribosomes, glycogen and rough endoplasmic reticulum-like structures. Polyhedral inclusions were observed in the cytoplasm and outside the protozoan; some of these inclusions exhibited membrane disruption. The flagella ultrastructure is typical, with the caudal pair accompanied by the funis. Next to the anterior pair, osmiophilic material was noticed. The ventro-lateral flange was short and thick, supported by the marginal plates that penetrated into its distal extremity; only its distal portion had adjacent osmiophilic filament. The G. agilis trophozoites showed the general subcellular feature of the genus. However, the ventro-lateral flange ultrastructure was an intermediate type between G. muris and G. duodenalis.