2-Amino-3-aroyl-4,5-alkylthiophenes: Agonist allosteric enhancers at human A1 adenosine receptors

2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A₁ adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A₁AR (hA₁AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5- dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro 4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino- 3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A₁AR agonist [¹²⁵I]ABA and membranes from CHO-K1 cells stably expressing the hA¹AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist- A₁AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH₂)_n- bridge, n ) 3 < n ) 4 < n ) 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA₁AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.

Cytogenetic analysis in the incertae sedis species Astyanax altiparanae Garutti and Britzki, 2000 and Hyphessobrycon eques Steindachner, 1882 (Characiformes, Characidae) from the upper Parana river basin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative analysis of the testes and spermatogenesis in species of the family Pentatomidae (Heteroptera)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphological patterns of the heteropycnotic chromatin and nucleolar material in meiosis and spermiogenesis of some Pentatomidae (Heteroptera)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MICROBIAL COUNTS of DARK RED LATOSOL SAMPLES STORED AT DIFFERENT TEMPERATURES

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Plasma cortisol levels in captive wild felines after chemical restraint

Eight Panthera onca (Po), 13 Felis concolor (Fc), 7 Felis yagouaroundi (Fy), 7 Felis tigrina (Ft) and 5 Felis pardalis (Fp) specimens from São Paulo State zoos were used. All animals were restrained with darts containing 10 mg/kg ketamine and 1 mg/kg xylazine. Venous blood samples were collected as soon as possible (within 15-20 min) and serum was frozen until the time for cortisol quantification. Cortisol was determined using a solid phase radioimmunoassay with an intra-assay coefficient of 8.51%. Data were analyzed statistically by the Kruskal-Wallis test, followed by Dunn's multiple comparisons test, and the one-sample t-test, with the level of significance set at P<0.05. Data are reported as means ± SEM. Cortisol levels differed among the captive felines: Po = 166 ± 33a, Fc = 670 ± 118b, Fy = 480 ± 83b, Ft = 237 ± 42ab, Fp = 97 ± 12a nmol/l (values followed by different superscript letters were significantly different (P<0.001)). Since most of the veterinary procedures on these species involve chemical restraint, these results show the necessity of preventive measures in order to minimize the effect of restraint stress on more susceptible species

OCCURRENCE OF MACRO-B CHROMOSOMES IN ASTYANAX-SCABRIPINNIS PARANAE (PISCES, CHARACIFORMES, CHARACIDAE)

B chromosomes occur in several Neotropical fish species. Cytogenetic analysis of 27 specimens (15 females and 12 males) of Astyanax scabripinnis paranae from the Araqua river (a small headwater tributary of the Tiete river) shows that this population has 2n = 50 chromosomes (4M + 30 SM + 4ST + 12A), two chromosome pairs with NORs and conspicuous C-band positive blocks in the terminal position of the long arm of four chromosome pairs. In this population, eight females presented 2n = 51 chromosomes and the extra chromosome was a large metacentric similar in size and morphology to the first chromosome pair in the karotype. This accessory chromosome is entirely heterochromatic in C-banded metaphases and shows a late replication pattern evidenced by BrdU incorporation. There was no significant correlation between the presence of B chromosomes and increased NOR activity at the P >0.05 level. Some aspects related to these B chromosomes are discussed.

Study of chromosomal and nucleolar aspects in testes of Nysius californicus (Heteroptera: Lygaeidae)

In Nysius californicus (family Lygaeidae, subfamily Orsillinae), a pest commonly known as the seed bug, the chromosome complement is 2n = 16 (12A + 2m + XY), testes are formed by seven seminiferous tubules covered by an orange-colored membrane, and spermatogenesis is cystic. At prophase, sex chromosomes are heteropycnotic and autosomes usually show a chiasma. At metaphase, sex chromosomes along with microchromosomes may be seen located at the center of a ring formed by the remaining autosomes. A characteristic specific of N. californicus was the presence of nucleolar material observed from the cystic cell to the completely differentiated spermatozoon. Variations in size, shape and location of the nucleolar material occur during this process, denoting a variable degree of activity in the different stages. ©FUNPEC-RP.

Cytogenetical analyses in three Astyanax scabripinnis populations (Pisces, Characidae) from Minas Gerais State, Brazil

Cytogenetical data in 3 populations of characid fish assigned to the complex of Astyanax scabripinnis from São Francisco river basin and Grande river basin, Minas Gerais State, Brazil, are presented for the first time. The same diploid number, 2n=50, was detected in the 3 populations, which has conspicuous differences involving karyotype morphology: 8M, 20SM, 6ST and 16A (Cambeba stream), 6M, 28SM, 6ST and 10A (Machado headwater), 6M, 24SM, 8ST and 12A (Pedra Branca stream). Differences involving amount and/or locations of heterochromatin blocks, number and position of nucleolar organizer regions (NORs) and CMA3 positive signals were also observed. Some aspects related to the chromosome diversification of Astyanax scabripinnis are discussed. © 2007 The Japan Mendel Society.

Evaluacion de la cobertura geografica del censo nacional de poblacion de 1971 de la Republica de Nicaragua

Incluye Bibliografía

Note on Twelfth Meeting of CARICOM Council

Nota sobre la 12a Reunión del Consejo de CARICOM en la cual se tomaron decisiones sobre asuntos que afectan las operaciones del Mercado Común y que se incluyen en el anexo del informe.

Report on attendance at the 12th Annual Caribbean Water Engineers Conference

Informe de asistencia a la 12a conferencia anual de ingenieros hidráulicos del Caribe. Incluye comentarios, recomendaciones dirigidas a la CEPAL y acciones de la Oficina de la CEPAL para el Caribe.

Caracterização citogenética e molecular das espécies pintado (Pseudoplatystoma corruscans), cachara (Pseudoplatystoma reticulatum) e seus híbridos utilizados na piscicultura brasileira

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desempenho, características de carcaça e atributos da carne de bovinos jovens confinados suplementados com vitaminas D e E

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Qualidade da carne maturada de bovinos Nelore terminados em confinamento

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)