Origins of host-specific populations of the blast pathogen Magnaporthe oryzae in crop domestication with subsequent expansion of pandemic clones on rice and weeds of rice

Rice, as a widely and intensively cultivated crop, should be a target for parasite host shifts and a source for shifts to co-occurring weeds. Magnaporthe oryzae, of the M. grisea species complex, is the most important fungal pathogen of rice, with a high degree of host specificity. On the basis of 10 loci from six of its seven linkage groups, 37 multilocus haplotypes among 497 isolates of M. oryzae from rice and other grasses were identified. Phylogenetic relationships among isolates from rice (Oryza sativa), millet (Setaria spp.), cutgrass (Leersia hexandra), and torpedo grass (Panicum repens) were predominantly tree like, consistent with a lack of recombination, but from other hosts were reticulate, consistent with recombination. The single origin of rice-infecting M. oryzae followed a host shift from a Setaria millet and was closely followed by additional shifts to weeds of rice, cutgrass, and torpedo grass. Two independent estimators of divergence time indicate that these host shifts predate the Green Revolution and could be associated with rice domestication. The rice-infecting lineage is characterized by high copy number of the transposable element MGR586 (Pot3) and, except in two haplotypes, by a loss of AVR-Co39. Both mating types have been retained in ancestral, well-distributed rice-infecting haplotypes 10 (mainly temperate) and 14 (mainly tropical), but only one mating type was recovered from several derived, geographically restricted haplotypes. There is evidence of a common origin of both ACE1 virulence genotypes in haplotype 14. Host-haplotype association is evidenced by low pathogenicity on hosts associated with other haplotypes.     

Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2',7'-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3(-/-) mice than in SD-fed WT mice. In contrast, HFD-fed NOS3(-/-) developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3(-/-) than in those from HFD-fed WT. N(ω)-nitro-L-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3(-/-) mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.     

Visual configuration of two species of Falconidae with different foraging ecologies

Significant interspecific differences in avian vision occur, even in congeneric species, and these have been correlated with differences in the perceptual challenges associated with foraging. Although diurnal raptors are assumed to be mainly visually guided in their foraging, they differ markedly in their foraging tactics and this may result in different visual demands. Among the Falconidae (Falconiformes), most falcons forage mainly on the wing for highly mobile prey, whereas caracaras forage on the ground for carrion and insects. We assessed whether Saker Falcon Falco cherrug and Southern Caracara Caracara plancus differ in their visual abilities by determining the visual fields and foveal characteristics of both species. Using an ophthalmoscopic reflex technique, we found a higher degree of binocular overlap in the caracaras than in the falcons. The high binocular overlap (47°) of the Southern Caracara may facilitate object manipulation (e.g. moving rocks) when foraging. We used an ultra‐high resolution spectral‐domain optical coherence tomography to determine foveal characteristics. We found two foveas (depressions in the retina where high visual resolution is expected) in the falcons (one central and one temporal) but only a central fovea in the caracaras. The presence of a shallower temporal fovea in Saker Falcons may help to fixate visually upon a highly mobile prey item during pursuit. We conclude that these differences in visual field configurations and foveal characteristics reflect different foraging demands, suggesting that the extraction of visual information is finely tuned to the demands of their foraging tactics.     

Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide: ROLE IN ARGININE AND NITRIC OXIDE PRODUCTION*

Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-de pend ent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, α-methyl-dl-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases.Inhibition of somatic angiotensin-I-converting enzyme (sACE)³ is a widely used approach in the treatment of hypertension. The first available competitive inhibitors of sACE were the naturally occurring proline-rich oligopeptides from the venom of Bothrops jararaca. Clinical studies using Bj-BPP-9a, teprotide, the most efficient of these snake venom peptides, demonstrated the potential of sACE inhibitors as anti-hypertensive drugs (1). Highly potent inhibitors of sACE, which can be administered orally, have subsequently been developed. The first of these, captopril, was designed employing a theoretical model of the active site of sACE, based on its presumed similarity to the active site of carboxypeptidase A and also with reference to the C terminus of venom proline-rich peptides, which compete with sACE substrates (2). Since captopril reproduced all known pharmacological effects and sACE-inhibiting features of the proline-rich peptides (3), the interest to deepen the investigation of the biological properties of these naturally occurring sACE inhibitors dropped dramatically. However, we recently showed that the Bj-BPP-10c (4), displays a strong and sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), independently of the inhibition of sACE (5). This result led us to hypothesize that, besides sACE, another molecule involved in the arterial blood pressure homeostasis could possibly be a target for Bj-BPP-10c. Two reasons prompted us to search the putative target in the kidney: (i) the crucial role played by the kidney in the arterial blood pressure control (6) and (ii) the selective concentration and long lasting permanence of ¹²⁵I-Bj-BPP-10c in the mouse kidney even when a saturating concentration of captopril was administered with the peptide (7).In the present study, we identified the kidney argininosuccinate synthetase (AsS) as a putative target for Bj-BPP10c, and we show results demonstrating that the anti-hypertensive effect of this peptide in SHR is related to the activation of the arginine production in the kidney and of the citrulline-NO cycle in endothelial cells.     

The adaptor function of SHP-2 downstream of the prolactin receptor is required for the recruitment of p29, a substrate of SHP-2

SHP-2, a cytosolic protein tyrosine phosphatase with two SH2 domains and multiple tyrosine phosphorylation sites, contributes to signal transduction as an enzyme and/or adaptor molecule. Here we demonstrate that prolactin (PRL) stimulation of the PRL-responsive Nb2 cells, a rat lymphoma cell line, and T47D cells, a human breast cancer cell line, lead to the complex formation of SHP-2 and growth factor receptor-bound protein-2 (grb2). Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y(546) and Y(584). Furthermore, in this study, we found a highly phosphorylated, 29-kDa protein (p29), a substrate of SHP-2. The recruitment of p29 to SHP-2 requires the carboxy-terminal tyrosine residues of SHP-2 (Y(546) and Y(584)). Together, our results indicate that SHP-2 may function as an adaptor molecule downstream of the PRLR and highlight a new recruitment mechanism of SHP-2 substrates.