Redescription of the enigmatic long-tailed rat Sigmodontomys aphrastus (Cricetidae: Sigmodontinae) with comments on taxonomy and natural history

Sigmodontomys aphrastus, the long-tailed rat, is an exceedingly rare rodent species from montane regions of Central and South America of which very little is known ecologically or systematically. It has been variously placed in the genera Oryzomys, Nectomys, and Sigmodontomys based on the five previously known specimens. Recent phylogenetic analyses (Weksler 2006) have shown that S. aphrastus occurs in a monophyletic clade composed of S. alfari and Melanomys caliginosus with M. caliginosus as the proposed sister taxon. Two new individuals were collected in northwestern Costa Rica’s Cordillera de Tilarán. These new specimens and the other five known specimens are used to redescribe the species, detail measurements of external and cranial morphology, and compare S. aphrastus to similar appearing, sympatric species (Nephelomys albigularis and N. devius) and proposed closely related species (Sigmodontomys alfari, Mindomys hammondi, and Melanomys caliginosus). New ecological data is presented and the general knowledge of its natural history is summarized. The phylogenetic relatedness of S. aphrastus with purported sister taxa remains unresolved until combined molecular and morphological analyses are conducted.Resumen—Sigmodontomys aphrastus, la rata de cola larga, es una especie rara de rodedor de las montañas de America Central y Sur de la cual se conoce muy poco acerca de su ecología y sistemática. Esta especie ha sido clasificada en el género Oryzomys, Nectomys, y Sigmodontomys basado en solo cinco especímenes. Análisis filogenéticos recientes (Weksler 2006) han demonstrado que S. aphrastus se encuentra en un clado monofilético compuesto de S. alfari y Melanomys caliginosus con M. caliginosus propuesto como la especie hermana. Dos nuevos individuos fueron recolectados en el noreste de Costa Rica en la Cordillera de Tilarán. Estos dos nuevos especímenes y junto con los cinco anteriores son usados a describir nuevamente la especie, detallar sus medidas morfométricas externas y craneales, y comparar S. aphrastus con especies simpátricas similares (Nephelomys albigularis and N. devius) y especies que han sido propuestas como dentro del mismo clado (Sigmodontomys alfari, Mindomys hammondi, y Melanomys caliginosus). Presentamos nuevos datos ecológicos y resumimos el conocimiento de su historia natural. La relación filogenética de S. aphrastus con las especies propuestas como del mismo clado no sera resuelto hasta que analisis moleculares y morfologicos sean llevados a cabo

A newly recognized clade of trans-Andean Oryzomyini (Rodentia: Cricetidae), with description of a new genus.

We expand upon recent studies on relationships within the Oryzomyini, in particular, those involving taxa currently assigned to the genus Sigmodontomys. In recent years, Sigmodontomys has been treated as including 2 species, alfari (J. A. Allen, 1897) and aphrastus (Harris, 1932), but throughout their complicated taxonomic history both species also have been placed in the genus Oryzomys, and alfari independently in Nectomys. Using morphological (98 external, cranial, dental, and postcranial) and molecular (nuclear interphotoreceptor retinoid-binding protein gene and mitochondrial cytochrome-b and ribosomal 12S RNA genes) characters, we infer the phylogenetic position of these 2 species within Oryzomyini. We document that alfari and aphrastus do not form a monophyletic group. Sigmodontomys alfari is most closely related to Melanomys, and aphrastus is either the sister to that clade, or to the extinct Caribbean genus Megalomys. Thus, aphrastus is best regarded as representing a new genus, which is described and named herein. This new genus falls within the Sigmodontomys–Melanomys–Aegialomys–Nesoryzomys clade, which forms a monophyletic group of mainly southern Central American and northern South American taxa primarily restricted to lowland to midelevation montane trans-Andean habitats and possessing a marked ability to cross expanses of salt water. The new genus occurs in middle elevations from north-central Costa Rica to northwestern Ecuador and along with some populations of Aegialomys and Melanomys occupies the highest elevations for members of this group. Resumen—A partir de estudios recientes, profundizamos acerca de las relaciones filogenéticas dentro de Oryzomyini (Rodentia: Cricetidae), en particular aquellas que involucran taxa actualmente atribuidos al género Sigmodontomys. Recientemente se ha considerado que Sigmodontomys incluye dos especies—alfari (J. A. Allen, 1897) y aphrastus (Harris, 1932), sin embargo, a través de su complicada historia taxonómica, ambas especies también han sido incluidas dentro del género Oryzomys, y alfari independientemente dentro del género Nectomys. Usando caracteres morfológicos (98 externos, craneales, dentales y postcraneales) y moleculares (citocromo b, 12S y IRBP), inferimos la posición filogenética de estas dos especies dentro de Oryzomyini. Documentamos que alfari y aphrastus no forman un grupo monofilético. Sigmodontomys alfari es el taxón hermano de Melanomys, mientras aphrastus es hermano de dicho grupo, o del género caribeño extinto Megalomys. Por consiguiente, consideramos a aphrastus como un nuevo género que describimos y nombramos a continuación. Este nuevo género está incluido dentro del clado formado por Sigmodontomys–Melanomys–Aegialomys–Nesoryzomys, el cual representa un grupo monofilético bien sustentado principalmente del sur de Centroamérica y norte de Sudamérica, restringido principalmente a hábitats de tierras bajas a elevaciones intermedias trasandinas, y caracterizado por su habilidad de cruzar barreras de agua salada. El nuevo género se encuentra en elevaciones medianas y altas desde el centro y norte de Costa Rica hasta el noroeste de Ecuador y, junto con algunas poblaciones de Aegialomys y Melanomys, ocupa las elevaciones más altas de cualquier miembro de este grupo

Stagnation point reverse flow combustor

A method for combusting a combustible fuel includes providing a vessel having an opening near a proximate end and a closed distal end defining a combustion chamber. A combustible reactants mixture is presented into the combustion chamber. The combustible reactants mixture is ignited creating a flame and combustion products. The closed end of the combustion chamber is utilized for directing combustion products toward the opening of the combustion chamber creating a reverse flow of combustion products within the combustion chamber. The reverse flow of combustion products is intermixed with combustible reactants mixture to maintain the flame

Karyology of the Atlantic forest rodent Juliomys (Cricetidae): A new karyotype from southern Brazil

Juliomys is a small rodent from the family Cricetidae which inhabits the Atlantic forest and forests from Argentina to eastern Brazil. The three species recognized so far have different karyotypes. In this paper, we describe a new karyotype with 2n = 32, FN = 48 found in Juliomys specimens from a high-altitude area in the Atlantic forest of southern Brazil. The karyotype was analyzed after G- and C-banding and silver staining of the nucleolus organizer regions (Ag-NOR) and its G-banding patterns were compared with those of the newly described species Juliomys ossitenuis (2n = 20, FN = 36). The 2n = 32 karyomorph presented peculiar features and was very different from those of the other species of the genus: J. pictipes (2n = 36, FN = 34), J. rimofrons (2n = 20, FN = 34) and J. ossitenuis (2n = 20, FN = 36). Differences were mostly due to centric and tandem fusions, pericentric inversion and loss of heterochromatin. The karyotype represents a powerful tool to differentiate Juliomys species and our data suggest that the karyotype described herein belongs to a new species

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

High Levels of Receptor Tyrosine Kinases in CCM3-Deficient Cells Increase Their Susceptibility to Tyrosine Kinase Inhibition

Cerebral cavernous malformations (CCMs) are vascular malformations that can be the result of the deficiency of one of the CCM genes. Their only present treatment is surgical removal, which is not always possible, and an alternative pharmacological strategy to eliminate them is actively sought. We have studied the effect of the lack of one of the CCM genes, CCM3, in endothelial and non-endothelial cells. By comparing protein expression in control and CCM3-silenced cells, we found that the levels of the Epidermal Growth Factor Receptor (EGFR) are higher in CCM3-deficient cells, which adds to the known upregulation of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in these cells. Whereas VEGFR2 is upregulated at the mRNA level, EGFR has a prolonged half-life. Inhibition of EGFR family members in CCM3-deficient cells does not revert the known cellular effects of lack of CCM genes, but it induces significantly more apoptosis in CCM3-deficient cells than in control cells. We propose that the susceptibility to tyrosine kinase inhibitors of CCM3-deficient cells can be harnessed to kill the abnormal cells of these lesions and thus treat CCMs pharmacologically

Identification of Peptide Ligands for Targeting to the Blood-Brain Barrier

PurposeTransport of drugs to the brain is limited by the blood-brain barrier. New, specific brain endothelium ligands can facilitate brain-specific delivery of drugs. MethodsWe used phage display in an in situ brain perfusion model to screen for new brain endothelium peptide ligands. ResultsTwo phage clones, displaying 15 amino acid-peptides (GLA and GYR) that were selected for brain binding in the mouse model, showed significant binding to human brain endothelium (hCMEC/D3), compared to a random control phage. This binding was not seen for other human endothelial cells (HUVEC). Binding to hCMEC/D3 cells was dose dependent. When phage GLA and GYR were individually perfused through the murine brain, their ability to bind to the brain was 6-fold (GLA) and 5-fold (GYR) higher than the control phage. When compared to lung perfusion, phage showed an 8.5-fold (GYR) and 48-fold (GLA) preference for brain over lung compared to the control. ConclusionsThese results indicate that two new peptide ligands have been identified that may be used for specific targeting of drugs to the blood-brain barrier