Biomedical subjects

Pablo Alvarez

Publications and source records attributed to Pablo Alvarez.

4 recordsLinked to original sources

PubMed2006

Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.

The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies.

Base Sequence↗

PubMed2005

Genome sequence, comparative analysis and haplotype structure of the domestic dog.

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

Animals↗

PubMed2002

Hippocampal formation lesions impair performance in an odor-odor association task independently of spatial context.

The rodent hippocampal system is known to play an important role in memory. Evidence that this role is not limited to spatial memory has come from studies using a variety of non-spatial memory tasks. One example is the social transmission of food preference paradigm, a task in which rats learn an odor-odor association with no explicit spatial memory component. However, because training and testing in this task typically take place in the same environment, it is possible that memory for the spatial context in which odors are experienced during training is critical to subsequent retention performance. If this is the case, it might be expected that lesions of the hippocampal system would impair memory performance by disrupting the establishment of a representation of the training environment. We addressed this issue by training rats in one spatial context and then testing them either in the same or a different spatial context. Normal control rats performed equally well when tested in an environment that was the same or different from that used during training, and the retention impairment exhibited by rats with hippocampus plus subiculum lesions was equivalent in the two test environments. These results support the view that the hippocampal system is necessary for the flexible expression of nonspatial memories even when the spatial context in which the memory is acquired is not critical to retrieval.

Animals↗

PubMed2002

Representations of odors in the rat orbitofrontal cortex change during and after learning.

Cells in the orbitofrontal cortex (OF) respond to odors and their associated rewards. To determine how these responses are acquired and maintained, the authors recorded single OF units in rats performing an odor discrimination task. Approximately 64% of all cells differentiated between rewarded and nonrewarded odors. These odor valence responses changed during learning in 26% of all cells, and these changes were positively correlated with improving performance, supporting the idea that the information provided by these cells is used in learning the task. However, changes in odor valence responses were also observed after learning, and included not only increases in odor discrimination, but also decreases or mixed increases and decreases. Thus, only some of the changes in firing reflected acquisition of the task. The results suggest that learning triggers a continuing reorganization of OF neural ensembles representing odors and their rewards.

Action Potentials↗