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41.
Positive selection and sequence rearrangements generate extensive polymorphism in the gamete recognition protein bindin 总被引:27,自引:12,他引:15
Bindin is a gamete recognition protein of sea urchins that mediates
species-specific attachment of sperm to an egg-surface receptor during
fertilization. Sequences of bindin from closely related urchins show fixed
species-specific differences. Within species, highly polymorphic bindin
alleles result from point substitution, insertion/deletion, and
recombination. Since speciation, positive selection favoring allelic
variants has generated diversity in bindin polypeptides. Intraspecific
bindin variation can be tolerated by the egg receptor, which suggests
functional parallels between this system and other flexible recognition
systems, including immune recognition. These results show that polymorphism
in mate recognition loci required for rapid evolution of sexual isolation
can arise within natural populations.
相似文献
42.
43.
Stem cells in adult tissues 总被引:7,自引:0,他引:7
In recent years the concept of a stem cell has evolved to encompass the hypotheses that stem cells exist within many adult tissues, and that a common 'interchangeable' progenitor cell may exist within the bone marrow capable of regenerating and repairing tissues throughout the body. As more knowledge is gained about stem cells, their potential roles in disease processes, including the development and progression of cancer, have moved to the forefront. The underlying hypothesis of this review is that cell fate is determined by a combination of intrinsic and extrinsic factors; growth and differentiation are regulated through intracellular integration of a multitude of signals initiated by internal and external stimuli. The development of successful stem cell based therapies may depend on experimental approaches that consider both the intrinsic and extrinsic factors that control cell fate. 相似文献
44.
Danillo S Silva Susana SR Milhomem Julio C Pieczarka Cleusa Y Nagamachi 《BMC genetics》2009,10(1):1-8
Background
Previous studies suggested that multiple domestication events in South and South-East Asia (Yunnan and surrounding areas) and India have led to the genesis of modern domestic chickens. Ha Giang province is a northern Vietnamese region, where local chickens, such as the H'mong breed, and wild junglefowl coexist. The assumption was made that hybridisation between wild junglefowl and Ha Giang chickens may have occurred and led to the high genetic diversity previously observed. The objectives of this study were i) to clarify the genetic structure of the chicken population within the Ha Giang province and ii) to give evidence of admixture with G. gallus. A large survey of the molecular polymorphism for 18 microsatellite markers was conducted on 1082 chickens from 30 communes of the Ha Giang province (HG chickens). This dataset was combined with a previous dataset of Asian breeds, commercial lines and samples of Red junglefowl from Thailand and Vietnam (Ha Noï). Measurements of genetic diversity were estimated both within-population and between populations, and a step-by-step Bayesian approach was performed on the global data set.Results
The highest value for expected heterozygosity (> 0.60) was found in HG chickens and in the wild junglefowl populations from Thailand. HG chickens exhibited the highest allelic richness (mean A = 2.9). No significant genetic subdivisions of the chicken population within the Ha Giang province were found. As compared to other breeds, HG chickens clustered with wild populations. Furthermore, the neighbornet tree and the Bayesian clustering analysis showed that chickens from 4 communes were closely related to the wild ones and showed an admixture pattern.Conclusion
In the absence of any population structuring within the province, the H'mong chicken, identified from its black phenotype, shared a common gene pool with other chickens from the Ha Giang population. The large number of alleles shared exclusively between Ha Giang chickens and junglefowl, as well as the results of a Bayesian clustering analysis, suggest that gene flow has been taking place from junglefowl to Ha Giang chickens. 相似文献45.
Robert Mabry Debra G Gilbertson Amanda Frank Tuyen Vu Dan Ardourel Craig Ostrander Brenda Stevens Susan Julien Secil Franke Brent Meengs Jennifer Brody Scott Presnell Nels B Hamacher Megan Lantry Anitra Wolf Tom Bukowski Robert Rosler Cindy Yen Monica Anderson-Haley Kenneth Brasel Qi Pan Hank Franklin Penny Thompson Mike Dodds Sara Underwood Scott Peterson Pallavur V Sivakumar Mark Snavely 《MABS-AUSTIN》2010,2(1):20-34
Targeting angiogenesis is a promising approach to the treatment of solid tumors and age-related macular degeneration (AMD). Inhibition of vascularization has been validated by the successful marketing of monoclonal antibodies (mAbs) that target specific growth factors or their receptors, but there is considerable room for improvement in existing therapies. Combination of mAbs targeting both the VeGF and pDGF pathways has the potential to increase the efficacy of anti-angiogenic therapy without the accompanying toxicities of tyrosine kinase inhibitors and the inability to combine efficiently with traditional chemotherapeutics. However, development costs and regulatory issues have limited the use of combinatorial approaches for the generation of more efficacious treatments.The concept of mediating disease pathology by targeting two antigens with one therapeutic was proposed over two decades ago. While mAbs are particularly suitable candidates for a dual-targeting approach, engineering bispecificity into one molecule can be difficult due to issues with expression and stability, which play a significant role in manufacturability. Here, we address these issues upstream in the process of developing a bispecific antibody (bsAb). Single-chain antibody fragments (scFvs) targeting pDGFRβ and VeGF-A were selected for superior stability. the scFvs were fused to both termini of human Fc to generate a bispecific, tetravalent molecule. resulting molecule displays potent activity, binds both targets simultaneously, and is stable in serum. assembly of a bsAb using stable monomeric units allowed development of an anti-pDGFRB/VeGF-A antibody capable of attenuating angiogenesis through two distinct pathways and represents an efficient method for rapid engineering of dual-targeting molecules.Key words: bispecific, antibody, PDGFRβ, VEGF-A, stability, angiogenesis 相似文献
46.
47.
A novel fluorescence assay to study propeptide interaction with gamma-glutamyl carboxylase 总被引:2,自引:0,他引:2
The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the posttranslational modification of select glutamate residues of its vitamin K-dependent substrates to gamma-carboxyglutamate. In this report, we describe a new fluorescence assay that is sensitive and specific for the propeptide binding site of active carboxylase. We employed the assay to make three important observations: (1) A tight binding fluorescein-labeled consensus propeptide can be used to quantify the active fraction of the enzyme. (2) The off-rate for a fluorescein-labeled factor IX propeptide was 3000-fold slower than the rate of carboxylation, a difference that may explain how carboxylase can carry out multiple carboxylations of a substrate during the same binding event. (3) We show evidence that substrate binding to the active site modifies the propeptide binding site of carboxylase. The significant (9-fold) differences in off-rates for the propeptide in the presence and absence of its co-substrates may represent a release mechanism for macromolecular substrates from the enzyme. Additionally, sedimentation velocity and equilibrium experiments indicate a monomeric association of enzyme with propeptide. Furthermore, the carboxylase preparation is monodisperse in the buffer used for our studies. 相似文献
48.
Ellen M. Langer Brittany L. Allen-Petersen Shelby M. King Nicholas D. Kendsersky Megan A. Turnidge Genevra M. Kuziel Rachelle Riggers Ravi Samatham Taylor S. Amery Steven L. Jacques Brett C. Sheppard James E. Korkola John L. Muschler Guillaume Thibault Young Hwan Chang Joe W. Gray Sharon C. Presnell Deborah G. Nguyen Rosalie C. Sears 《Cell reports》2019,26(3):608-623.e6
49.
50.
Laura E. Dike Haiyan Xia Richard D. Guarino Sharon C. Presnell Mark R. Timmins 《Cytotechnology》2005,49(2-3):133-141
Recently we described a method for estimating the oxygen consumption rate (OCR) of cells in static culture from equilibrium
measurements of dissolved oxygen concentration (dO2), using an oxygen-sensing microplate and the steady-state solution to Fick's Law (Guarino et al. 2004). Here we describe
a complementary method for estimating OCR from the transient-state rate of change of measured dO2. Although the system is open to the atmosphere and subject to a significant lag in sensor response, the rate of change of
the measured dO2 immediately after seeding correlated directly with both cell number and steady-state OCR. This transient-state method is
linear with cell number to a much higher density than is possible with the steady-state method because it derives from measurements
made before diffusion limitations can be established. For a given sensor thickness, the same correlation line between the
transient and non-diffusion-limited steady-state estimates of OCR was found to apply for various preparations of rat hepatocytes.
The correlation slope varied predictably with sensor thickness. Thus, despite the non-idealities of this system, the initial
rate measurement offers a rapid method to obtain an estimate of absolute OCR. To demonstrate the utility of this method, we
purposefully treated rat hepatocytes in ways expected to change OCR. Cells deprived of oxygen by storage under several centimeters
of medium showed decreases in both OCR and viability with time. Likewise, the OCR of hepatocytes exposed to the oxidative
phosphorylation inhibitor rotenone decreased, whereas those exposed to the uncoupler dinoseb increased. 相似文献