Carlos Aguilar - Academia.edu (original) (raw)
Papers by Carlos Aguilar
Cell Reports, 2020
During aging, there is a progressive loss of volume and function in skeletal muscle that impacts ... more During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [MuSCs]), but in aging, MuSCs decrease in numbers
SUMMARYThroughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a p... more SUMMARYThroughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission and muscle contraction have been well characterized, little is known on the reciprocal crosstalk between neural cells and MuSCs within the muscle microenvironment. Here, we report that mild peripheral nerve injury enhances MuSC myogenic function and muscle regeneration by synergistically augmenting MuSC mitochondrial bioenergetics and upregulating anabolic protein synthesis pathways. We also demonstrate that chronic disruption or degeneration of neuromuscular synapses, such as in muscular dystrophy and biological aging, abolishes MuSC and motor neuron interactions, causing s...
Reproductive Toxicology, 2015
Protein Expression and Purification, 2001
and folded TcP0, a very hydrophobic protein with a The P0 protein is part of the ribosomal eukary... more and folded TcP0, a very hydrophobic protein with a The P0 protein is part of the ribosomal eukaryotic high tendency to aggregation. ᭧ 2001 Academic Press stalk, which is an elongated lateral protuberance of the large ribosomal subunit involved in the translocation step of protein synthesis. P0 is the minimal portion The ribosomal stalk is a structural feature present of the stalk that is able to support accurate protein in the large subunit of eukaryotic and prokaryotic ribosynthesis. The P0 C-terminal peptide is highly antisomes that is involved in the interaction of elongation genic and a major target of the antibody response in factors with the ribosome. Although the structure of patients with systemic lupus erythematosus and the large ribosomal subunit has been described for bacpatients suffering chronic heart disease produced by teria at atomic resolution (1) there is not clear electronic the Trypanosoma cruzi parasite. The T. cruzi P0 (TcP0) density for the ribosomal stalk proteins. Electron miprotein was cloned into the pRSET A vector and croscopy and low-resolution X-ray studies have sugexpressed in Escherichia coli fused to a His-tag. The gested that the ribosomal stalk is an elongated and identity of the protein was confirmed by immunoblothighly flexible lateral protuberance on the large riboting. Due to the formation of inclusion bodies the prosomal subunit (2). The prokaryotic stalk is made up of tein was purified using the following steps: (i) two dimers of the 12-kDa acidic ribosomal proteins L7/ differential centrifugation to separate the inclusion L12, forming a very stable complex with protein L10 bodies from soluble proteins and (ii) affinity chroma-(3). In eukaryotes this pentamer is formed by the family tography under denaturing conditions. TcP0 showed of ribosomal P proteins, P0, P1, and P2, which show no high tendency to aggregation during refolding assays. significant sequence identity with the analogous bacte-However, TcP0 could be efficiently folded in the presrial proteins L10 and L7/L12. ence of a low concentration of SDS. The folding of the The ribosomal stalk has been proposed to play a role protein was confirmed using urea gradient electrophoin the translocation step of protein synthesis (2, 4). resis, limited proteolysis, circular dichroism, and tryp-Moreover, it has been shown to be involved in the activtophan fluorescence. Native electrophoresis showed ity of the elongation factors in both bacteria (5) and that the folded TcP0 (and not a folding intermediate) eukaryotes (6, 7). A direct interaction between the ribowas the cause of aggregation in the absence of SDS. somal stalk and EF-Tu and EF-G has been recently The protocol described here permitted us to obtain confirmed by electron microscopy (8, 9). large amounts (up to 30 mg per culture liter) of pure The small P proteins (P1 and P2) interact via their N-terminal domains with a region close to the C-terminus of P0 (10, 11). The C-terminal domains of P1 and
Neuron, 2010
Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradi... more Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradiance) for the circadian clock, the pupillomotor system, and other influential behavioral/physiological responses. mRGCs are activated both by their intrinsic phototransduction cascade and by the rods and cones. However, the individual contribution of each photoreceptor class to irradiance responses remains unclear. We address this deficit using mice expressing human red cone opsin, in which rod-, cone-, and melanopsin-dependent responses can be identified by their distinct spectral sensitivity. Our data reveal an unexpectedly important role for rods. These photoreceptors define circadian responses at very dim ''scotopic'' light levels but also at irradiances at which pattern vision relies heavily on cones. By contrast, cone input to irradiance responses dissipates following light adaptation to the extent that these receptors make a very limited contribution to circadian and pupillary light responses under these conditions. Our data provide new insight into retinal circuitry upstream of mRGCs and optimal stimuli for eliciting irradiance responses.
Journal of Molecular Biology, 1992
Dinucleotides containing guanine, when soaked into crystals of bovine pancreatic ribonuclease, ha... more Dinucleotides containing guanine, when soaked into crystals of bovine pancreatic ribonuclease, have been found to bind in an unexpected manner, quite unlike interpretations of earlier X-ray diffraction studies. This finding has prompted a reexamination of three mononucleotide-RNase complexes from this laboratory resulting in a re-interpretation of the complex that involved a guanine mononucleotide.
Journal of Bacteriology, 2000
Gene expression of the flagellar system is tightly controlled by external stimuli or intracellula... more Gene expression of the flagellar system is tightly controlled by external stimuli or intracellular signals. A general picture of this regulation has been obtained from studies of Salmonella enterica serovar Typhimurium. However, these regulatory mechanisms do not apply to all bacterial groups. In this study, we have investigated regulation of the flagellar genetic system inRhodobacter sphaeroides. Deletion analysis, site-directed mutagenesis, and 5′-end mapping were conducted in order to identify the fliO promoter. Our results indicate that this promoter is recognized by the factor ς54. Additionally, 5′-end mapping of the flgB andfliK transcripts suggests that these mRNAs are also transcribed from ς54 promoters. Finally, we showed evidence that suggests that fliC transcription is not entirely dependent on the presence of a complete basal body-hook structure. Our results are discussed in the context of a possible regulatory hierarchy controlling flagellar gene expression in R. sphaer...
European Biophysics Journal, 2011
The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, wa... more The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, was studied in mice small intestinal transit. Its mechanism was evaluated in the presence of several adrenergic and cholinergic antagonist drugs and one opioid antagonist. Docking of dehydroleucodine into the homology model of the α2-adrenergic receptor allowed us to analyze the structural basis of their interactions. The experiments showed that dehydroleucodine delayed intestinal transit. The docking of dehydroleucodine showed a unique binding site, equivalent to the binding site of carozolol in the β-adrenergic receptor. The results suggested that dehydroleucodine produced an inhibitory effect on intestinal transit. Its action could be mediated, at least in part, through the α2-adrenergic receptor.
Cell Reports, 2020
During aging, there is a progressive loss of volume and function in skeletal muscle that impacts ... more During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [MuSCs]), but in aging, MuSCs decrease in numbers
SUMMARYThroughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a p... more SUMMARYThroughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission and muscle contraction have been well characterized, little is known on the reciprocal crosstalk between neural cells and MuSCs within the muscle microenvironment. Here, we report that mild peripheral nerve injury enhances MuSC myogenic function and muscle regeneration by synergistically augmenting MuSC mitochondrial bioenergetics and upregulating anabolic protein synthesis pathways. We also demonstrate that chronic disruption or degeneration of neuromuscular synapses, such as in muscular dystrophy and biological aging, abolishes MuSC and motor neuron interactions, causing s...
Reproductive Toxicology, 2015
Protein Expression and Purification, 2001
and folded TcP0, a very hydrophobic protein with a The P0 protein is part of the ribosomal eukary... more and folded TcP0, a very hydrophobic protein with a The P0 protein is part of the ribosomal eukaryotic high tendency to aggregation. ᭧ 2001 Academic Press stalk, which is an elongated lateral protuberance of the large ribosomal subunit involved in the translocation step of protein synthesis. P0 is the minimal portion The ribosomal stalk is a structural feature present of the stalk that is able to support accurate protein in the large subunit of eukaryotic and prokaryotic ribosynthesis. The P0 C-terminal peptide is highly antisomes that is involved in the interaction of elongation genic and a major target of the antibody response in factors with the ribosome. Although the structure of patients with systemic lupus erythematosus and the large ribosomal subunit has been described for bacpatients suffering chronic heart disease produced by teria at atomic resolution (1) there is not clear electronic the Trypanosoma cruzi parasite. The T. cruzi P0 (TcP0) density for the ribosomal stalk proteins. Electron miprotein was cloned into the pRSET A vector and croscopy and low-resolution X-ray studies have sugexpressed in Escherichia coli fused to a His-tag. The gested that the ribosomal stalk is an elongated and identity of the protein was confirmed by immunoblothighly flexible lateral protuberance on the large riboting. Due to the formation of inclusion bodies the prosomal subunit (2). The prokaryotic stalk is made up of tein was purified using the following steps: (i) two dimers of the 12-kDa acidic ribosomal proteins L7/ differential centrifugation to separate the inclusion L12, forming a very stable complex with protein L10 bodies from soluble proteins and (ii) affinity chroma-(3). In eukaryotes this pentamer is formed by the family tography under denaturing conditions. TcP0 showed of ribosomal P proteins, P0, P1, and P2, which show no high tendency to aggregation during refolding assays. significant sequence identity with the analogous bacte-However, TcP0 could be efficiently folded in the presrial proteins L10 and L7/L12. ence of a low concentration of SDS. The folding of the The ribosomal stalk has been proposed to play a role protein was confirmed using urea gradient electrophoin the translocation step of protein synthesis (2, 4). resis, limited proteolysis, circular dichroism, and tryp-Moreover, it has been shown to be involved in the activtophan fluorescence. Native electrophoresis showed ity of the elongation factors in both bacteria (5) and that the folded TcP0 (and not a folding intermediate) eukaryotes (6, 7). A direct interaction between the ribowas the cause of aggregation in the absence of SDS. somal stalk and EF-Tu and EF-G has been recently The protocol described here permitted us to obtain confirmed by electron microscopy (8, 9). large amounts (up to 30 mg per culture liter) of pure The small P proteins (P1 and P2) interact via their N-terminal domains with a region close to the C-terminus of P0 (10, 11). The C-terminal domains of P1 and
Neuron, 2010
Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradi... more Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradiance) for the circadian clock, the pupillomotor system, and other influential behavioral/physiological responses. mRGCs are activated both by their intrinsic phototransduction cascade and by the rods and cones. However, the individual contribution of each photoreceptor class to irradiance responses remains unclear. We address this deficit using mice expressing human red cone opsin, in which rod-, cone-, and melanopsin-dependent responses can be identified by their distinct spectral sensitivity. Our data reveal an unexpectedly important role for rods. These photoreceptors define circadian responses at very dim ''scotopic'' light levels but also at irradiances at which pattern vision relies heavily on cones. By contrast, cone input to irradiance responses dissipates following light adaptation to the extent that these receptors make a very limited contribution to circadian and pupillary light responses under these conditions. Our data provide new insight into retinal circuitry upstream of mRGCs and optimal stimuli for eliciting irradiance responses.
Journal of Molecular Biology, 1992
Dinucleotides containing guanine, when soaked into crystals of bovine pancreatic ribonuclease, ha... more Dinucleotides containing guanine, when soaked into crystals of bovine pancreatic ribonuclease, have been found to bind in an unexpected manner, quite unlike interpretations of earlier X-ray diffraction studies. This finding has prompted a reexamination of three mononucleotide-RNase complexes from this laboratory resulting in a re-interpretation of the complex that involved a guanine mononucleotide.
Journal of Bacteriology, 2000
Gene expression of the flagellar system is tightly controlled by external stimuli or intracellula... more Gene expression of the flagellar system is tightly controlled by external stimuli or intracellular signals. A general picture of this regulation has been obtained from studies of Salmonella enterica serovar Typhimurium. However, these regulatory mechanisms do not apply to all bacterial groups. In this study, we have investigated regulation of the flagellar genetic system inRhodobacter sphaeroides. Deletion analysis, site-directed mutagenesis, and 5′-end mapping were conducted in order to identify the fliO promoter. Our results indicate that this promoter is recognized by the factor ς54. Additionally, 5′-end mapping of the flgB andfliK transcripts suggests that these mRNAs are also transcribed from ς54 promoters. Finally, we showed evidence that suggests that fliC transcription is not entirely dependent on the presence of a complete basal body-hook structure. Our results are discussed in the context of a possible regulatory hierarchy controlling flagellar gene expression in R. sphaer...
European Biophysics Journal, 2011
The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, wa... more The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, was studied in mice small intestinal transit. Its mechanism was evaluated in the presence of several adrenergic and cholinergic antagonist drugs and one opioid antagonist. Docking of dehydroleucodine into the homology model of the α2-adrenergic receptor allowed us to analyze the structural basis of their interactions. The experiments showed that dehydroleucodine delayed intestinal transit. The docking of dehydroleucodine showed a unique binding site, equivalent to the binding site of carozolol in the β-adrenergic receptor. The results suggested that dehydroleucodine produced an inhibitory effect on intestinal transit. Its action could be mediated, at least in part, through the α2-adrenergic receptor.