Explore the vast range of titles available.

When the animals on Miss Leoparda's bus route abandon the bus for cars, traffic jams and deforestation ensue, prompting Miss Leoparda to help her community rediscover the importance of nature and togetherness.

Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant \"RASopathy\" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in mice harboring the PTPN11 mutation Y279C, one of the most common NSML alleles; these now-termed SHP2Y279C/+ mice recapitulate the human disorder and develop hypertrophic cardiomyopathy (HCM) by 12 weeks of age. Functionally, heart and/or cardiomyocyte lysates from SHP2Y279C/+ mice exhibit increased basal and agonist-induced AKT and mTOR activities. Here, we sought to determine whether we could reverse the hypertrophy in SHP2Y279C/+ mice using ARQ 092, an oral and selective allosteric AKT inhibitor currently in clinical trials for patients with PI3K/AKT-driven tumors or Proteus syndrome. We obtained echocardiographs of SHP2Y279C/+ and wildtype (SHP2+/+) littermates, either in the presence or absence of ARQ 092 at 12, 14, and 16 weeks of age. While SHP2Y279C/+ mice developed significant left ventricular hypertrophy by 12 weeks, as indicated by decreased chamber dimension and increased posterior wall thickness, treatment of SHP2Y279C/+ mice with ARQ 092 normalized the hypertrophy in as early as 2 weeks following treatment, with hearts comparable in size to those in wildtype (SHP2+/+) mice. In addition, we observed an increase in fractional shortening (FS%) in SHP2Y279C/+ mice, an effect of increased compensatory hypertrophy, which was not apparent in SHP2Y279C/+ mice treated with ARQ 092, suggesting functional improvement of HCM upon treatment with the AKT inhibitor. Finally, we found that ARQ 092 specifically inhibited AKT activity, as well as its downstream effectors, PRAS and S6RP in NSML mice. Taken together, these data suggest ARQ 092 may be a promising novel therapy for treatment of hypertrophy in NSML patients.

Is a lion still a lion if he ... wears a hat? And carries an umbrella? Is a lion still a lion if he asks for a dance? Is so polite ... but then asks for lunch?!

iPS cell model of LEOPARD syndrome Patient-specific iPS (induced pluripotent stem) cells are seen as key to modelling genetic disorders and developing new treatments for them. Now iPS cell lines have been generated by nuclear reprogramming from patients with LEOPARD syndrome, a rare developmental disorder characterized by skin lesions, heart abnormalities and deafness. Cardiomyocytes derived from the resulting LEOPARD iPS cells have hypertrophic properties resembling those typical of the disease — cardiac hypertrophy occurs in 90% of children with the syndrome. The reprogrammed cells feature extensive alterations in various signal transduction pathway components, including RAS–MAPK, some previously described in association with cardiac hypertrophy. Using these cell lines, together with robust differentiation protocols, it may be possible to identify compounds that reverse diseased cellular phenotypes. The generation of induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders promises to help the basic understanding of complex diseases and the development of therapeutics. Here iPSCs have been generated from patients with LEOPARD syndrome, a developmental disorder with pleiomorphic effects on several tissues and organs. The iPSCs are characterized and the phenotype of cardiomyocytes derived from these cells is investigated. The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS–mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems 1 , 2 . The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro -derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.

A little orphaned elephant is adopted by a lion, King of the Beasts, but grows bigger and more capable than the lion, caring for the king in the latter's old age.

Time and space are essential niche dimensions along which species tend to coexist. We assessed spatiotemporal resource partitioning between leopards and lions and hypothesized the differential use of spatiotemporal resources by leopards with respect to lions. We used a systematic camera trap survey to collect the data at 50 sites. The data were analyzed using overlap indices, and non-parametric test statistics to assess the spatiotemporal associations. Leopard and lion were crepuscular and nocturnal in their activity pattern. They did not segregate temporally and showed substantially high overlap and strong temporal association. Leopard segregates with lion spatially by overlapping less and showing no association in space use at specific camera trap sites. Leopards showed preference for dense habitats, while the lion preferred both dense and open habitats. Leopard showed moderate-overlap and positive association with key prey species, i.e., chital and sambar. Lion, however showed low site-specific overlap and negative association with its crucial prey species, i.e., sambar and wild pig. We conclude that site-specific spatial partitioning along with differential affinities for habitat is helping leopards to partition their spatio-temporal resources with lions and hence facilitate coexistence of leopards with lions in Gir forest.

\"When a circus train derails in the middle of a big city in 1925, a lion escapes and finds shelter in a sprawling city park. No one knows about the creature except for Sadie Menken, the feisty daughter of a pie-maker. As various squirrels, dogs and an expensive peacock meet unfortunate ends, and the park \"beast\" is spotted by visitors, the lion's presence draws the attention of the authorities. Can a creature that is wild at heart live in harmony with humans? Sadie must decide who to trust to help her find a happy ending for an unlikely friend\"--Jacket flap.

Time and space are essential niche dimensions along which species tend to coexist. We assessed spatiotemporal resource partitioning between leopards and lions and hypothesized the differential use of spatiotemporal resources by leopards with respect to lions. We used a systematic camera trap survey to collect the data at 50 sites. The data were analyzed using overlap indices, and non-parametric test statistics to assess the spatiotemporal associations. Leopard and lion were crepuscular and nocturnal in their activity pattern. They did not segregate temporally and showed substantially high overlap and strong temporal association. Leopard segregates with lion spatially by overlapping less and showing no association in space use at specific camera trap sites. Leopards showed preference for dense habitats, while the lion preferred both dense and open habitats. Leopard showed moderate-overlap and positive association with key prey species, i.e., chital and sambar. Lion, however showed low site-specific overlap and negative association with its crucial prey species, i.e., sambar and wild pig. We conclude that site-specific spatial partitioning along with differential affinities for habitat is helping leopards to partition their spatio-temporal resources with lions and hence facilitate coexistence of leopards with lions in Gir forest.

\"In this illustrated early chapter book, Angelica allows a new friend to believe she is a part-time lion trainer in training.\"-- Provided by publisher.

LEOPARD syndrome (LS) is an autosomal dominant \"RASopathy\" that manifests with congenital heart disease. Nearly all cases of LS are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11) gene that encodes the SH2 domain-containing PTP-2 (SHP2). RASopathies typically affect components of the RAS/MAPK pathway, yet it remains unclear how PTPN11 mutations alter cellular signaling to produce LS phenotypes. We therefore generated knockin mice harboring the Ptpn11 mutation Y279C, one of the most common LS alleles. Ptpn11(Y279C/+) (LS/+) mice recapitulated the human disorder, with short stature, craniofacial dysmorphia, and morphologic, histologic, echocardiographic, and molecular evidence of hypertrophic cardiomyopathy (HCM). Heart and/or cardiomyocyte lysates from LS/+ mice showed enhanced binding of Shp2 to Irs1, decreased Shp2 catalytic activity, and abrogated agonist-evoked Erk/Mapk signaling. LS/+ mice also exhibited increased basal and agonist-induced Akt and mTor activity. The cardiac defects in LS/+ mice were completely reversed by treatment with rapamycin, an inhibitor of mTOR. Our results demonstrate that LS mutations have dominant-negative effects in vivo, identify enhanced mTOR activity as critical for causing LS-associated HCM, and suggest that TOR inhibitors be considered for treatment of HCM in LS patients.