RESUMO
Maintaining genetic diversity and variation in livestock populations is critical for natural and artificial selection promoting genetic improvement while avoiding problems due to inbreeding. In Laos, there are concerns that there has been a decline in genetic diversity and a rise in inbreeding among native goats in their village-based smallholder system. In this study, we investigated the genetic diversity of Lao native goats in Phin, Songkhone and Sepon districts in Central Laos for the first time using Illumina's Goat SNP50 BeadChip. We also explored the genetic relationships between Lao goats with 163 global goat populations from 36 countries. Our results revealled a close genetic relationship between Lao native goats and Chinese, Mongolian and Pakistani goats, sharing ancestries with Guangfen, Jining Grey and Luoping Yellow breeds (China) and Teddi goats (Pakistan). The observed (Ho) and expected (He) heterozygosity were 0.292 and 0.303 (Laos), 0.288 and 0.288 (Sepon), 0.299 and 0.308 (Phin) and 0.289 and 0.305 (Songkhone), respectively. There was low to moderate genetic differentiation (FST: 0.011-0.043) and negligible inbreeding coefficients (FIS: -0.001 to 0.052) between goat districts. The runs of homozygosity (ROH) had an average length of 5.92-6.85 Mb, with short ROH segments (1-5 Mb length) being the most prevalent (66.34%). Longer ROH segments (20-40 and >40 Mb length categories) were less common, comprising only 4.81% and 1.01%, respectively. Lao goats exhibit moderate genetic diversity, low-inbreeding levels and adequate effective population size. Some genetic distinctions between Lao goats may be explained by geographic and cultural features.
Assuntos
Variação Genética , Cabras , Animais , Cabras/genética , Cabras/classificação , Laos , Genética Populacional , Endogamia , Polimorfismo de Nucleotídeo Único , CruzamentoRESUMO
BACKGROUND: Glenoid resurfacing can be a challenging component of total shoulder arthroplasty when significant glenoid retroversion or deformity is present. The purpose of this study was to determine whether a newly designed glenoid-targeting guide using the parallel relationship between glenoid version and an anatomic fulcrum axis could accurately estimate the central axis of the scapula. MATERIALS AND METHODS: Three orthopaedic surgeons used a newly designed glenoid-targeting guide to place a guide pin into 6 normal Sawbones scapulae (Pacific Research Laboratories, Vashon Island, WA, USA), 6 retroverted Sawbones scapulae, 8 cadaveric scapular specimens, and 5 cadaveric shoulder specimens. Angles of deviation from the central scapular axis and from perpendicular to the fulcrum axis were measured. RESULTS: The mean pin deviation angle from the central scapular axis and the mean fulcrum deviation angle for the normal Sawbones scapulae were 1.7° (SD, 1.2°) and 2.1° (SD, 1.5°), respectively. For altered retroverted Sawbones scapulae, the mean deviation angles were 1.8° (SD, 1.2°) and 2.8° (SD, 1.6°), respectively. The combined mean pin deviation angle and mean fulcrum deviation angle for cadaveric shoulder specimens were 2.8° (SD, 3.3°) and 2.3° (SD, 2.3°), respectively. The surgeons' results did not differ significantly whether using Sawbones models, cadaveric scapular specimens, or cadaveric shoulder specimens. CONCLUSION: A glenoid-targeting guide based on the relationship of the fulcrum axis and glenoid version can be used to accurately estimate the central scapular axis. Such a tool can be accurate and reliable intraoperatively, aiding in glenoid component placement to within 5° of ideal version, irrespective of glenoid deformity.
Assuntos
Artroplastia de Substituição , Escápula/diagnóstico por imagem , Escápula/cirurgia , Artroplastia de Substituição/instrumentação , Artroplastia de Substituição/métodos , Cadáver , Fluoroscopia , Humanos , Modelos Anatômicos , Escápula/fisiopatologia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgiaRESUMO
PAC1 is a recently cloned and characterized heptahelical, G protein-coupled receptor with high affinity to PACAP-27 and PACAP-38 and is differentially coupled to activate intracellular Ca2+ and cAMP. PAC1 is expressed as four major splice variants, each possessing differential coupling to inositol phosphates and intracellular Ca2+. PAC1 has been shown previously to be expressed and regulate the growth and proliferation of nonsquamous cell lung cancer cells, as well as breast cancer cell lines. PAC1 is expressed on the HCT8 human colon cancer cell line and is coupled to the activation of both intracellular cAMP and Ca2+ with consequent stimulation of growth. In the current study, we contrast the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the HCT8 colon cancer cell lines to the HCT116 and FET cell lines wherein PAC1 is expressed as the SV1 or HIP splice variant and is coupled to the activation only of cAMP but not of intracellular Ca2+. These data indicate that human colon tumor cells express PAC1 and are differentially coupled to intracellular signal transduction molecules. The ability to activate both cAMP and Ca2+ appears to be a prerequisite for activation of tumor proliferation, indicating a potentially important factor in how PACAP potentiates the growth of certain tumors.
Assuntos
Sinalização do Cálcio/fisiologia , Carcinoma/genética , Neoplasias do Colo/genética , AMP Cíclico/metabolismo , Neuropeptídeos/metabolismo , Receptores do Hormônio Hipofisário/genética , Adenilil Ciclases/metabolismo , Processamento Alternativo/genética , Cálcio/metabolismo , Carcinoma/metabolismo , Carcinoma/fisiopatologia , Divisão Celular/genética , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Humanos , Líquido Intracelular/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/fisiopatologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores do Hormônio Hipofisário/metabolismoRESUMO
The pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1) is a heptahelical, G protein-coupled receptor that has been shown to be expressed by non-squamous lung cancer and breast cancer cell lines, and to be coupled to the growth of these tumors. We have previously shown that PACAP and its receptor, PAC1, are expressed in rat colonic tissue. In this study, we used polyclonal antibodies directed against the COOH terminal of PAC1, as well as fluorescently labeled PACAP, Fluor-PACAP, to demonstrate the expression of PAC1 on HCT8 human colonic tumor cells, using FACS analysis and confocal laser scanning microscopy. Similarly, anti-PACAP polyclonal antibodies were used to confirm the expression of PACAP hormone by this cell line. We then investigated the signal transduction properties of PAC1 in these tumor cells. PACAP-38 elevated intracellular cAMP levels in a dose-dependent manner, with a half-maximal (EC(50)) stimulation of approximately 3 nM. In addition, PACAP-38 stimulation caused an increase in cytosolic Ca(2+) concentration [Ca(2+)](i), which was partially inhibited by the PACAP antagonist, PACAP-(6-38). Finally, we studied the potential role of PACAP upon the growth of these tumor cells. We found that PACAP-38, but not VIP, increased the number of viable HCT8 cells, as measured by MTT activity. We also demonstrated that HCT8 cells expressed the Fas receptor (Fas-R/CD95), which was subsequently down-regulated upon activation with PACAP-38, further suggesting a possible role for PACAP in the growth and survival of these tumor cells. These data indicate that HCT8 human colon tumor cells express PAC1 and produce PACAP hormone. Furthermore, PAC1 activation is coupled to adenylate cyclase, increase cytosolic [Ca(2+)](i), and cellular proliferation. Therefore, PACAP is capable of increasing the number of viable cells and regulating Fas-R expression in a human colonic cancer cell line, suggesting that PACAP might play a role in the regulation of colon cancer growth and modulation of T lymphocyte anti-tumoral response via the Fas-R/Fas-L apoptotic pathway.