Biology subjects

Ramos, R.

Publications and source records attributed to Ramos, R..

3 recordsLinked to original sources

bioRxiv2018

A gate-and-switch model for head orientation behaviors in C. elegans

The nervous system seamlessly integrates perception and action. This ability is essential for stable representation of and appropriate responses to the external environment. How the sensorimotor integration underlying this ability occurs at the level of individual neurons is of keen interest. In Caenorhabditis elegans, RIA interneurons receive input from sensory pathways and have reciprocal connections with head motor neurons. Through separate physiological mechanisms, RIA simultaneously encodes both head orientation and sensory stimuli. Based on these observations, we proposed a model for how RIA may integrate these two signals to detect the spatial distribution of stimuli across head sweeps and generate directional head responses. Here, we show that blocking synaptic release from RIA disrupts head orientation behaviors in response to unilaterally presented stimuli. We found that sensory encoding in RIA is gated according to head orientation. This dependence on head orientation is independent of motor encoding in RIA, suggesting a second, posture-dependent pathway upstream of RIA. This gating mechanism may allow RIA to selectively attend to stimuli that are asymmetric across head sweeps. Attractive odor removal during head bends triggers rapid head withdrawal in the opposite direction. Unlike sensory encoding, this directional response is dependent on motor inputs to and synaptic output from RIA. Together, these results suggest that RIA is part of a sensorimotor pathway that is dynamically regulated according to head orientation at two levels: the first is a gate that filters sensory representations in RIA, and the second is a switch that routes RIA synaptic output to dorsal or ventral head motor neurons.

neuroscience↗

bioRxiv2018

Improving Metagenomic Assemblies Through Data Partitioning: a GC content approach

Assembling metagenomic data sequenced by NGS platforms poses significant computational challenges, especially due to large volumes of data, sequencing errors, and variations in size, complexity, diversity and abundance of organisms present in a given metagenome. To overcome these problems, this work proposes an open-source, bioinfor-matic tool called GCSplit, which partitions metagenomic sequences into subsets using a computationally inexpensive metric: the GC content. Experiments performed on real data show that preprocessing short reads with GCSplit prior to assembly reduces memory consumption and generates higher quality results, such as an increase in the N50 metric and the reduction in both the L50 value and the total number of contigs produced in the assembly. GCSplit is available at https://github.com/mirand863/gcsplit.

bioinformatics↗

bioRxiv2017

A novel combination of cyclophosphamide and anti-ICOS mAb prevents tumor growth by affecting regulatory T cells in mice with a human immune system

Mice reconstituted with a human immune system and bearing human tumors represent a promising model for developing novel cancer immunotherapies. Here, we used mass cytometry and multi-parametric flow cytometry to characterize human leukocytes infiltrating a human breast cancer tumor model in immunocompromised NOD.SCID.{gamma}c-null mice reconstituted with a human immune system and compared it to samples of breast cancer patients. We observed highly activated human CD4+ and CD8+ T cells in the tumor, as well as minor subsets of innate immune cells in both settings. We also report that ICOS+ CD4+ regulatory T cells (Treg) were enriched in the tumor relative to the periphery in humanized mice and patients, providing a target to affect Treg and tumor growth. Indeed, administration of a neutralizing mAb to human ICOS reduced Treg proportions and numbers and improved CD4+ T cell proliferation in humanized mice. Moreover, a combination of the anti-ICOS mAb with cyclophosphamide reduced tumor growth, and that was associated with an improved CD8 to Treg ratio. However, depletion of human CD8+ T cells only marginally affected tumor control whereas depletion of murine myeloid cells abrogated the effect of the combination therapy. Altogether, our results indicate that a combination of anti-ICOS mAb and chemotherapy controls tumor growth in humanized mice and highlight the crucial implication of innate immunity in treatment efficacy, opening new perspectives for the treatment of breast cancer.\n\nOne sentence summaryICOS expressed on Tregs is a promising target to improve tumor immunity in humans\n\nAbbreviations

immunology↗