Clausulas de los mayorazgos que fundaron D. Gutierrez de Cardenas, comendador mayor de Leon..., y Doña Teresa Enriquez su muger, en virtud de facultad de los... Reyes Catolicos, en 28 de Enero de 1503, de las villas de Maqueda, Torrijos, Elche y otras

Tit. tomado de encabezamiento de texto

Epistolae D. Hieronymi... et ; Libri contra haereticos

Colofón

Señor el doctor Don Vicente Perler... alcalde mayor de Alicante de cuyo empleo se halla despojado e ignominiosamente depuesto a... instancia del Marques de Vila-Real Governador interino de aquella ciudad...

Tít. tomado del principio del texto

Copia de la carta, que escriuio el doctor D. Joseph Salinas a un amigo suyo, sobre la aprobacion del doctor D. Blas Antonio Nasarre y Ferriz ... [a la obra del doctor Ferreras]

Adicion al tit. consta en preliminares

Addicion al papel en derecho que se escriuió en fauor del que assiste al ... señor Don Antonio Ponce de Leon, &c. Duque de Arcos ... Marquès de Elche en el pleyto que sigue en grado de reuista con el Concejo, Justicia y Regimiento de dicha su villa de Elche, sobre el dominio, y propiedad del terreno de saladares

Precede al tít.: "Jesus, Maria, Joseph y S. Antonio de Padua"

Homilia dicha al pueblo

Sign.: [A]-D4, E3

Reconuencion que hace al cura de Parla un amigo suyo [Texto impreso] : sobre el papel precursor respuesta al manifiesto del Doct. Collados...

Al final de texto consta : Madrid, 13 de agosto de 1731

Carta que sobre la vida y virtudes del P. Vicente Juan [Texto impreso]

El texto aparece fechado en : "Valencia y Julio 5 de 1747"

Sermon que en la... dedicacion del nuevo templo de la Merced de la villa de Elche celebrada el 29 de febrero del... año 1796 [Texto impreso]

Sign. : []4, B-D4, E3

Oratio funebris in obitu... Theodosii lusitanorum Principis, Ioannis IV Portugaliae Regis... primogeniti... [Texto impreso]

Sign. : []4, B-D4, E3

Instruccion para los que han de tomar el Estado del santo matrimonio [Texto impreso] : leyes o Reglas que deven guardar los casados : con un pasmoso prodigio del Inclito protho-martir San Estevan

Según Palau, el autor es Francisco Mira

Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway

The rapid loss of muscle mass that accompanies many disease states, such as cancer or sepsis, is primarily a result of increased protein breakdown in muscle, and several observations have suggested an activation of the ubiquitin–proteasome system. Accordingly, in extracts of atrophying muscles from tumor-bearing or septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were found to be higher than in control extracts. On the other hand, in extracts of muscles from hypothyroid rats, where overall proteolysis is reduced below normal, the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and treatment with triiodothyronine (T3) restored ubiquitination to control levels. Surprisingly, the N-end rule pathway, which selectively degrades proteins with basic or large hydrophobic N-terminal residues, was found to be responsible for most of these changes in ubiquitin conjugation. Competitive inhibitors of this pathway that specifically block the ubiquitin ligase, E3α, suppressed most of the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and septic rats. These inhibitors also suppressed ubiquitination in normal extracts toward levels in hypothyroid extracts, which showed little E3α-dependent ubiquitination. Thus, the inhibitors eliminated most of the differences in ubiquitination under these different pathological conditions. Moreover, 125I-lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in extracts from tumor-bearing and septic rats, and more slowly in those from hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation increases in atrophying muscles, and these hormone- and cytokine-dependent responses are in large part due to activation of the N-end rule pathway.

Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression

Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host–tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules. To examine the antitumor effect of direct in vivo gene transfer of murine interleukin 12 (IL-12) and B7-1 into tumors, we developed an adenovirus (Ad) vector, AdIL12–B7-1, that encodes the two IL-12 subunits in early region 1 (E1) and the B7-1 gene in E3 under control of the murine cytomegalovirus promoter. This vector expressed high levels of IL-12 and B7-1 in infected murine and human cell lines and in primary murine tumor cells. In mice bearing tumors derived from a transgenic mouse mammary adenocarcinoma, a single intratumoral injection with a low dose (2.5 × 107 pfu/mouse) of AdIL12–B7-1 mediated complete regression in 70% of treated animals. By contrast, administration of a similar dose of recombinant virus encoding IL-12 or B7-1 alone resulted in only a delay in tumor growth. Interestingly, coinjection of two different viruses expressing either IL-12 or B7-1 induced complete tumor regression in only 30% of animals treated at this dose. Significantly, cured animals remained tumor free after rechallenge with fresh tumor cells, suggesting that protective immunity had been induced by treatment with AdIL12–B7-1. These results support the use of Ad vectors as a highly efficient delivery system for synergistically acting molecules and show that the combination of IL-12 and B7-1 within a single Ad vector might be a promising approach for in vivo cancer therapy.

A single amino acid substitution converts a carboxylesterase to an organophosphorus hydrolase and confers insecticide resistance on a blowfly

Resistance to organophosphorus (OP) insecticides is associated with decreased carboxylesterase activity in several insect species. It has been proposed that the resistance may be the result of a mutation in a carboxylesterase that simultaneously reduces its carboxylesterase activity and confers an OP hydrolase activity (the “mutant ali-esterase hypothesis”). In the sheep blowfly, Lucilia cuprina, the association is due to a change in a specific esterase isozyme, E3, which, in resistant flies, has a null phenotype on gels stained using standard carboxylesterase substrates. Here we show that an OP-resistant allele of the gene that encodes E3 differs at five amino acid replacement sites from a previously described OP-susceptible allele. Knowledge of the structure of a related enzyme (acetylcholinesterase) suggests that one of these substitutions (Gly137 → Asp) lies within the active site of the enzyme. The occurrence of this substitution is completely correlated with resistance across 15 isogenic strains. In vitro expression of two natural and two synthetic chimeric alleles shows that the Asp137 substitution alone is responsible for both the loss of E3’s carboxylesterase activity and the acquisition of a novel OP hydrolase activity. Modeling of Asp137 in the homologous position in acetylcholinesterase suggests that Asp137 may act as a base to orientate a water molecule in the appropriate position for hydrolysis of the phosphorylated enzyme intermediate.