Cornell University

About: Cornell University is a education organization based out in Ithaca, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 102246 authors who have published 235546 publications receiving 12283673 citations. The organization is also known as: Cornell & CUI.

High density molecular linkage maps of the tomato and potato genomes.

Abstract: High density molecular linkage maps, comprised of more than 1000 markers with an average spacing between markers of approximately 1.2 cM (ca. 900 kb), have been constructed for the tomato and potato genomes. As the two maps are based on a common set of probes, it was possible to determine, with a high degree of precision, the breakpoints corresponding to 5 chromosomal inversions that differentiate the tomato and potato genomes. All of the inversions appear to have resulted from single breakpoints at or near the centromeres of the affected chromosomes, the result being the inversion of entire chromosome arms. While the crossing over rate among chromosomes appears to be uniformly distributed with respect to chromosome size, there is tremendous heterogeneity of crossing over within chromosomes. Regions of the map corresponding to centromeres and centromeric heterochromatin, and in some instances telomeres, experience up to 10-fold less recombination than other areas of the genome. Overall, 28% of the mapped loci reside in areas of putatively suppressed recombination. This includes loci corresponding to both random, single copy genomic clones and transcribed genes (detected with cDNA probes). The extreme heterogeneity of crossing over within chromosomes has both practical and evolutionary implications. Currently tomato and potato are among the most thoroughly mapped eukaryotic species and the availability of high density molecular linkage maps should facilitate chromosome walking, quantitative trait mapping, marker-assisted breeding and evolutionary studies in these two important and well studied crop species.

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype

Abstract: Both genome-wide genetic and epigenetic alterations are fundamentally important for the development of cancers, but the interdependence of these aberrations is poorly understood. Glioblastomas and other cancers with the CpG island methylator phenotype (CIMP) constitute a subset of tumours with extensive epigenomic aberrations and a distinct biology. Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathogenicity, but the molecular basis of G-CIMP remains unresolved. Here we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), establishes G-CIMP by remodelling the methylome. This remodelling results in reorganization of the methylome and transcriptome. Examination of the epigenome of a large set of intermediate-grade gliomas demonstrates a distinct G-CIMP phenotype that is highly dependent on the presence of IDH mutation. Introduction of mutant IDH1 into primary human astrocytes alters specific histone marks, induces extensive DNA hypermethylation, and reshapes the methylome in a fashion that mirrors the changes observed in G-CIMP-positive lower-grade gliomas. Furthermore, the epigenomic alterations resulting from mutant IDH1 activate key gene expression programs, characterize G-CIMP-positive proneural glioblastomas but not other glioblastomas, and are predictive of improved survival. Our findings demonstrate that IDH mutation is the molecular basis of CIMP in gliomas, provide a framework for understanding oncogenesis in these gliomas, and highlight the interplay between genomic and epigenomic changes in human cancers.

On the generality of the laws of learning

Abstract: That all events are equally associable and obey common laws is a central assumption of general process learning theory. A continuum of preparedness is denned which holds that organisms are prepared to associate certain events, unprepared for some, and contraprepared for others. A review of data from the traditional learning paradigms shows that the assumption of equivalent associability is false: in classical conditioning, rats are prepared to associate tastes with illness even over very long delays of reinforcement, but are contraprepared to associate tastes with footshock. In instrumental training, pigeons acquire key pecking in the absence of a contingency between pecking and grain (prepared), while cats, on the other hand, have trouble learning to lick themselves to escape, and dogs do not yawn for food (contraprepared). In discriminatio n, dogs are contraprepared to learn that different locations of discriminativ e stimuli control go-no go responding, and to learn that different qualities control directional responding. In avoidance, responses from the natural defensive repertoire are prepared for avoiding shock, while those from the appetitive repertoire are contraprepared. Language acquisition and the functional autonomy of motives are also viewed using the preparedness continuum. Finally, it is speculated that the laws of learning themselves may vary with the preparedness of the organism for the association and that different physiological and cognitive mechanisms may covary with the dimension. Sometimes we forget why psychologists ever trained white rats to press bars for little pellets of flour or sounded metronomes followed by meat powder for domestic dogs. After all, when in the real world do rats encounter levers which they learn to press in order to eat, and when do our pet dogs ever come across metronomes whose clicking signals meat powder ? It may be useful now to remind ourselves about a basic premise which gave rise to such bizarre endeavors, and to see if we still have reason to believe this premise.

Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease

Abstract: Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.

Dynamic Logic

Abstract: From the Publisher: Among the many approaches to formal reasoning about programs, Dynamic Logic enjoys the singular advantage of being strongly related to classical logic. Its variants constitute natural generalizations and extensions of classical formalisms. For example, Propositional Dynamic Logic (PDL) can be described as a blend of three complementary classical ingredients: propositional calculus, modal logic, and the algebra of regular events. In First-Order Dynamic Logic (DL), the propositional calculus is replaced by classical first-order predicate calculus. Dynamic Logic is a system of remarkable unity that is theoretically rich as well as of practical value. It can be used for formalizing correctness specifications and proving rigorously that those specifications are met by a particular program. Other uses include determining the equivalence of programs, comparing the expressive power of various programming constructs, and synthesizing programs from specifications. This book provides the first comprehensive introduction to Dynamic Logic. It is divided into three parts. The first part reviews the appropriate fundamental concepts of logic and computability theory and can stand alone as an introduction to these topics. The second part discusses PDL and its variants, and the third part discusses DL and its variants. Examples are provided throughout, and exercises and a short historical section are included at the end of each chapter.