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Biomedical subjects

J R Rojas

Publications and source records attributed to J R Rojas.

13 recordsLinked to original sources

[Taxonomic review of species of the Epinephelinae and Serraninae (Pisces: Serranidae) subfamilies of Chile].

A revision of epinepheline (Epinephelinae) and serranine (Serraninae) fishes from the Eastern Chilean South Pacific is presented, based on collections housed in Chile, Peru and the USA. Four species are recognized: Pseudogramma australis pasquensis; Diplectrum conceptione; Paralabrax humeralis and Serranus huacarii. According to literature Paralabrax semifasciatus, Serranus semifasciatus and Prionodes huascarii are relegated to the synonymy of Paralabrax humeralis and Serranus huascarii respectively. Keys for the identification of genera and species are presented, and for each species we provide a diagnosis, remarks on colors, distribution, number of species in each genus and illustration. The keys use easily observed characters for differentiating the four species of the Eastern South Pacific epinepheline and serranine fishes of Chile.

Animals↗

Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis.

OBJECTIVES: We sought to describe characteristics and outcome in adults with isolated ventricular noncompaction (IVNC). BACKGROUND: Isolated ventricular noncompaction is an unclassified cardiomyopathy due to intrauterine arrest of compaction of the loose interwoven meshwork. Knowledge regarding diagnosis, morbidity and prognosis is limited. METHODS: Echocardiographic criteria for IVNC include-in the absence of significant heart lesions-segmental thickening of the left ventricular myocardial wall consisting of two layers: a thin, compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep recesses. Thirty-four adults (age >16 years, 25 men) fulfilled the diagnostic criteria and were followed prospectively. RESULTS: At diagnosis, mean age was 42 + 17 years, and 12 patients (35%) were in New York Heart Association class III/IV. Left ventricular end-diastolic diameter was 65 + 12 mm and ejection fraction 33 + 13%. Apex and/or midventricular segments of both the inferior and lateral wall were involved in >80% of patients. Follow-up was 44 + 40 months. Major complications were heart failure in 18 patients (53%), thromboembolic events in 8 patients (24%) and ventricular tachycardias in 14 patients (41%). There were 12 deaths: sudden in six, end-stage heart failure in four and other causes in two patients. Four patients underwent heart transplantation. Automated cardioverter/defibrillators were implanted in four patients. CONCLUSIONS: Diagnosis of IVNC by echocardiography using strict criteria is feasible. Its mortality and morbidity are high, including heart failure, thrombo-embolic events and ventricular arrhythmias. Risk stratification includes heart failure therapy, oral anticoagulation, heart transplantation and implantation of an automated defibrillator/cardioverter. As IVNC is a distinct entity, its classification as a specific cardiomyopathy seems to be more appropriate.

Adolescent↗

Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14.

Multiple covalent modifications exist in the amino-terminal tails of core histones, but whether a relationship exists between them is unknown. We examined the relationship between serine 10 phosphorylation and lysine 14 acetylation in histone H3 and have found that, in vitro, several HAT enzymes displayed increased activity on H3 peptides bearing phospho-Ser-10. This augmenting effect of Ser-10 phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the ternary tGcn5/CoA/histone H3 complex. Gcn5(R164A) had reduced activity in vivo at a subset of Gcn5-dependent promoters, and, strikingly, transcription of this same subset of genes was also impaired by substitution of serine 10 to alanine in the histone H3 tail. These observations suggest that transcriptional regulation occurs by multiple mechanistically linked covalent modifications of histones.

Acetylation↗

Structure of Tetrahymena GCN5 bound to coenzyme A and a histone H3 peptide.

Gene activation is a highly regulated process that requires the coordinated action of proteins to relieve chromatin repression and to promote transcriptional activation. Nuclear histone acetyltransferase (HAT) enzymes provide a mechanistic link between chromatin destabilization and gene activation by acetylating the epsilon-amino group of specific lysine residues within the aminoterminal tails of core histones to facilitate access to DNA by transcriptional activators. Here we report the high-resolution crystal structure of the HAT domain of Tetrahymena GCN5 (tGCN5) bound with both its physiologically relevant ligands, coenzyme A (CoA) and a histone H3 peptide, and the structures of nascent tGCN5 and a tGCN5/acetyl-CoA complex. Our structural data reveal histone-binding specificity for a random-coil structure containing a G-K-X-P recognition sequence, and show that CoA is essential for reorienting the enzyme for histone binding. Catalysis appears to involve water-mediated proton extraction from the substrate lysine by a glutamic acid general base and a backbone amide that stabilizes the transition-state reaction intermediate. Comparison with related N-acetyltransferases indicates a conserved structural framework for CoA binding and catalysis, and structural variability in regions associated with substrate-specific binding.

Acetyltransferases↗

Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator.

The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Here, we present the high resolution crystal structure of the HAT domain of yGCN5 and probe the functional importance of a conserved glutamate residue. The structure reveals a central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-N-acetyltransferase. A pronounced cleft lying above this core, and flanked by N- and C-terminal regions that show no sequence conservation within N-acetyltransferase enzymes, is implicated by cross-species conservation and mutagenesis studies to be a site for histone substrate binding and catalysis. Located at the bottom of this cleft is a conserved glutamate residue (E173) that is in position to play an important catalytic role in histone acetylation. Functional analysis of an E173Q mutant yGCN5 protein implicates glutamate 173 to function as a general base for catalysis. Together, a correlation of the yGCN5 structure with functionally debilitating yGCN5 mutations provides a paradigm for understanding the structure/function relationships of the growing number of transcriptional regulators that function as histone acetyltransferase enzymes.

Acetylation↗

Crystal structure of the histone acetyltransferase domain of the human PCAF transcriptional regulator bound to coenzyme A.

The human p300/CBP-associating factor, PCAF, mediates transcriptional activation through its ability to acetylate nucleosomal histone substrates as well as transcriptional activators such as p53. We have determined the 2.3 A crystal structure of the histone acetyltransferase (HAT) domain of PCAF bound to coenzyme A. The structure reveals a central protein core associated with coenzyme A binding and a pronounced cleft that sits over the protein core and is flanked on opposite sides by the N- and C-terminal protein segments. A correlation of the structure with the extensive mutagenesis data for PCAF and the homologous yeast GCN5 protein implicates the cleft and the N- and C-terminal protein segments as playing an important role in histone substrate binding, and a glutamate residue in the protein core as playing an essential catalytic role. A structural comparison with the coenzyme-bound forms of the related N-acetyltransferases, HAT1 (yeast histone acetyltransferase 1) and SmAAT (Serratia marcescens aminoglycoside 3-N-acetyltransferase), suggests the mode of substrate binding and catalysis by these enzymes and establishes a paradigm for understanding the structure-function relationships of other enzymes that acetylate histones and transcriptional regulators to promote activated transcription.

Acetylation↗

Acanthocolpid metacercariae in the sea bass from Alejandro Selkirk Island, Chile.

Morphological characteristics of a metacercaria from muscle of 15 sea bass Caprodon longimanus (Serranidae) collected near Alejandro Selkirk Island (Chile) in the south-eastern Pacific Ocean indicate that it belongs to the genus Manteria (Acanthocolpidae). All metacercarie were encapsulated with connective tissue. The prevalence of infection was 100%, with 64% of metacercariae were located between dorsal pterygiophores and dorsal fin base. Mean intensities of metacercariae did not differ significantly with respect to sex of the fish. There was no significant correlation with intensities of infection and condition in the host.

Animals↗

[Embryonic mortality and hatching rate of Trachemys scripta (Testudines: Emydidae) eggs artificially grown in a protected natural area].

In the northeast of Costa Rica, illegal collecting, habitat destruction and heavy predation on adult females, young and eggs of Trachemys scripta produced a population decline in recent years. The slider turtle has a high reproductive potential and nests were relocated. Between January and March 1991, 179 nests (3220 eggs) were collected from natural areas of Caño Negro National Wildlife Refuge, Costa Rica and relocated for incubation under natural conditions in a protected site. The mean of number of eggs per clutch was 19.5 +/- 4.5 (range 8 to 31) and the mean incubation period was 77.4 +/- 11.4 days (range 50 to 110 days). The mean hatching success was 89.6 +/- 3.4% (range 60.0 to 100%). The mean early and mid embryonic mortality was 5.5 +/- 4.3%, the average late embryonic mortality was 8.5 +/- 3.5% and infertility 1.8 +/- 1.0%.

Animals↗

Childhood blindness in Peru.

A survey of childhood blindness in Peruvian children was done. Although most causes of blindness were due to congenital and hereditary conditions, measles accounted for almost 10% of blindness. With widespread measles immunization, this preventable cause of blindness in children can be eliminated or dramatically reduced.

Adolescent↗

Pterygium in Lima, Peru.

A survey of the prevalence of pterygium was performed, and a random proportional sampling was taken of 367 patients in four hospitals in Lima, Peru. An overall incidence of 31.06% was found, with a statistically significant increase in prevalence with regard to age. No statistically significant differences with regard to sex or occupation were found. Although incidence of pterygium was higher in men and in outdoor workers, these factors were not statistically significant.

Adolescent↗