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Melinda Bonnie Fagan 《Biology & philosophy》2012,27(2):179-213
Stem cell biology and systems biology are two prominent new approaches to studying cell development. In stem cell biology,
the predominant method is experimental manipulation of concrete cells and tissues. Systems biology, in contrast, emphasizes
mathematical modeling of cellular systems. For scientists and philosophers interested in development, an important question
arises: how should the two approaches relate? This essay proposes an answer, using the model of Waddington’s landscape to
triangulate between stem cell and systems approaches. This simple abstract model represents development as an undulating surface
of hills and valleys. Originally constructed by C. H. Waddington to visually explicate an integrated theory of genetics, development
and evolution, the landscape model can play an updated unificatory role. I examine this model’s structure, representational
assumptions, and uses in all three contexts, and argue that explanations of cell development require both mathematical models
and concrete experiments. On this view, the two approaches are interdependent, with mathematical models playing a crucial
but circumscribed role in explanations of cell development. 相似文献
4.
Bovine adrenal chromaffin cells were incubated with inorganic thiophosphate, using a protocol similar to experiments with inorganic phosphate, in order to determine the source of previously observed thiophosphoproteins. Incubation of cultured cells with [35S]thiophosphate resulted in its incorporation into cell constituents within 2 min. SDS PAGE of the treated cells showed incorporation of label into a broad 97–121 kDa band that was evident after 5 min of treatment and increased progressively to the 40 min exposure limit. Monolayers of chronically treated cells were fractionated into subcellular constituents. The only particulate fraction containing radiolabelled proteins was the chromaffin vesicle fraction. Two-dimensional electrophoresis of the treated cells and isolated chromaffin vesicles showed a majority of proteins in the acidic region of the first dimension gel. A fluorogram of the gel revealed two regions of radiolabelled proteins at acidic and neutral regions of the 2-D gel. These were within the boundaries of the 97–121 kDa band. The thiophosphorylated proteins were released as soluble proteins upon osmotic or freeze-thaw lysis of the vesicles. Chromaffin vesicles isolated from either cultured cells or adrenal medulla tissue were energized by 2 mM ATP but not by the analog adenosine 5′-O-(3-thiotriphosphate). The 97–121 kDa proteins in intact or lysed vesicles prepared from adrenal medulla tissue were not thiophosphorylated by either inorganic thiophosphate or adenosine 5′-O-(3-thiotriphosphate) in the presence or absence of energization by ATP. Nearly complete loss of radiolabel from matrix proteins treated with chondroitinase ABC suggests that it is a component of vesicle proteoglycans.
The results demonstrate that chromaffin vesicle matrix proteins are rapidly and intensely thiophosphorylated in cultured chromaffin cells but not in isolated vesicles. The data suggest that phosphorylation must play an important role in the normal function of these vesicle proteins. 相似文献
5.
Patricia A. Martin-DeLeon Melinda L. Boice 《Molecular reproduction and development》1985,12(2):151-163
The chromosome complement was studied in first-cleavage metaphases of mouse zygotes resulting from sperm aged in the male physiologically, after sexual rest. Females were inseminated by control males mating at 3-day intervals while experimentals mated to males that had had a sexual rest of 14 or more days. A total of 1954 eggs were collected 33–35 h post-HCG from 101 superovulated females mated to 42 controls and 43 experimental males. The fertilization rate was similar in both groups, being 84% and 85%, respectively. G-banded or Q-banded chromosomes were analyzed in 301 (68.3%) controls and 392 (49%) experimental first-cleavage metaphases. The overall rate of chromosome anomalies in controls was 4.45% as compared to 10.94% in experimentals, a highly significant difference. In the experimental group compared to controls, the frequency of trisomy, triploidy, structural rearrangements, and tetraploidy increased from 3.9% to 6.9%, 0% to 1.6%, 0.8% to 2.8%, and 0% to 1.3%, respectively. The genomic source of origin of the abnormalities was determined on the basis of differential condensation of the genomes. In the experimentals, grossly unbalanced sperm (diploids, disomics, double disomics, and those with large fragments) fertilized significantly more oocytes compared to controls. Our results implicate an advantage either in numbers or fertilizing capability for chromosomally abnormal sperm in a physiologically aged population. 相似文献
6.
Joseph G. Major Jr. Melinda E. Wales John E. Houghton Julie A. Maley Jeffrey N. Davidson James R. Wild 《Journal of molecular evolution》1989,28(5):442-450
Summary Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) is the first unique enzyme common to de novo pyrimidine biosynthesis and
is involved in a variety of structural patterns in different organisms. InEscherichia coli, ATCase is a functionally independent, oligomeric enzyme; in hamster, it is part of a trifunctional protein complex, designated
CAD, that includes the preceding and subsequent enzymes of the biosynthetic pathway (carbamoyl phosphate synthetase and dihydroorotase).
The complete complementary DNA (cDNA) nucleotide sequence of the ATCase-encoding portion of the hamster CAD gene is reported
here. A comparison of the deduced amino acid sequences of the hamster andE. coli catalytic peptides revealed an overall 44% amino acid similarity, substantial conservation of predicted secondary structure,
and complete conservation of all the amino acids implicated in the active site of theE. coli enzyme. These observations led to the construction of a functional hybrid ATCase formed by intragenic fusion based on the
known tertiary structure of the bacterial enzyme. In this fusion, the amino terminal half (the “polar domain”) of the fusion
protein was provided by a hamster ATCase cDNA subclone, and the carboxyl terminal portion (the “equatorial domain”) was derived
from a clonedpyrBI operon ofE. coli K-12. The recombinant plasmid bearing the hybrid ATCase was shown to satisfy growth requirements of transformedE. coli pyrB
− cells. The functionality of thisE. coli-hamster hybrid enzyme confirms conservation of essential structure-function relationships between evolutionarily distant
and structurally divergent ATCases. 相似文献
7.
John M. C. Gutteridge Melinda West Kent Eneff Robert A. Floyd 《Free radical research》1990,10(3):159-165
Bleomycin, in the presence of ferric salts, oxygen and a suitable reductant, degrades DNA with the release of base propenals, detected as thiobarbituric acid (TBA) reactivity, and the formation of 8-hydroxydeo-xyguanosine (80HdG) detected by HPLC. When xanthine oxidase is added to the incubated mixture of DNA degradation products, TBA-reactivity is destroyed but 80HdG formation is increased. EPR Spin trapping experiments show that hydroxyl radicals (OH) are formed in the reaction mixture and can be inhibited by the inclusion of either superoxide dismutase or catalase. These findings suggest that the base propenals and possibly malondialdehyde, formed from them, are aldehydic substrates for xanthine oxidase and, the product of this reaction is superoxide (O2-) and hydrogen peroxide (H2O2). Thus, TBA reactivity is destroyed in the formation of O2- and H2O2 which stimulate further oxidative damage to DNA resulting in increased 8OHdG formation. 相似文献
8.
We have earlier isolated a glucocorticoid-resistant, dedifferentiated rat hepatoma variant, the clone 2, which exhibited deficient stress activation of the major stress-inducible heat-shock protein hsp68.Multidrug-resistant variants were isolated from clone 2 cells using increasing concentrations of colchicine. The induction deficiency of hsp68 was maintained in the colchicine-resistant clone 2 cells grown for several months in the presence of 1 g/ml colchicine (termed ashighly multidrug-resistant variant) indicating that this heat-shock protein is not involved in the multidrug resistance. No alteration of the protein synthesis pattern was observed except the strong increase of the P-glycoprotein, which correlated with high level of corresponding mRNA. Stableheat-resistant variants of clone 2 were also isolated, which showed increaseddrug resistance to several drugs, i.e. they becamemoderately multidrug-resistant. This moderate multidrug resistance of the heat-resistant variants was further increased by stepwise selection with colchicine (highly multidrug-resistant heat-resistant variants). The levels of P-glycoprotein mRNA and protein were elevated both in the heat-resistant, non drug selected, moderately drug-resistant and in heatresistant, colchicine selected, highly drug-resistant variants. Decreased retention of antitumor drugs was observed in all multidrug-resistant variants indicating that P-glycoprotein was functional. Verapamil increased doxorubicin retention and cytotoxicity significantly. Our results showing that severely stressed hepatoma cells overexpressed the multidrug resistance gene(s) raise the possibility that the P-glycoprotein may participate in protection against enviromental stress such as heat.Abbreviations hsp
heat-shock protein
- MDR
multidrug resistance
- P-gp
P-glycoprotein 相似文献
9.
Melinda A. Novak Amy Musante Heather Munroe Peggy L. O'Neill Cristofer Price Stephen J. Suomi 《Zoo biology》1993,12(3):285-298
Recent research has indicated that old, individually housed monkeys show little interest in novel objects. Yet unanswered is whether this effect is caused primarily by age or housing condition. The purpose of this study was to assess the role of social living in promoting responsiveness to objects. We measured the rates of object manipulation in older animals, assessed responsiveness over time to particular objects as a measure of habituation, and examined social influences on object use. Several social groups of rhesus monkeys that contained older adults were studied. These groups were housed in indoor pens or in an outdoor enclosure, and all monkeys had continuous access to a variety of objects in their home environment. In contrast to previous studies of individually housed monkeys, our group-housed monkeys showed sustained interest in objects. Old monkeys manipulated objects extensively, and this response was all the more significant, given that the objects were not novel. Monkeys housed in an outdoor enclosure showed object manipulation patterns that were not different from monkeys housed in indoor pens. However, females exhibited much higher object-related responses than males. Social facilitation played a role in the reactions of some monkeys to objects. Patterns of social facilitation as well as avoidance were present in two of the three indoor groups that were observed. Failure to manipulate objects in rhesus macaques appears to be more a function of individual housing than of old age. Factors such as environmental complexity, social needs, and early experience should be considered in order to understand why individually housed rhesus monkeys are unresponsive to objects. © 1993 Wiley-Liss, Inc. 相似文献
10.
Rosalie J. Harris Callum Bryant Melinda A. Coleman Andrea Leigh Verónica F. Briceño Pieter A. Arnold Adrienne B. Nicotra 《Journal of phycology》2023,59(1):179-192
Foundation seaweed species are experiencing widespread declines and localized extinctions due to increased instability of sea surface temperature. Characterizing temperature thresholds are useful for predicting patterns of change and identifying species most vulnerable to extremes. Existing methods for characterizing seaweed thermal tolerance produce diverse metrics and are often time-consuming, making comparisons between species and techniques difficult, hindering insight into global patterns of change. Using three kelp species, we adapted a high-throughput method – previously used in terrestrial plant thermal biology – for use on kelps. This method employs temperature-dependent fluorescence (T–F0) curves under heating or cooling regimes to determine the critical temperature (Tcrit) of photosystem II (PSII), i.e., the breakpoint between slow and fast rise fluorescence response to changing temperature, enabling rapid assays of photosynthetic thermal tolerance using a standardized metric. This method enables characterization of Tcrit for up to 48 samples per two-hour assay, demonstrating the capacity of T–F0 curves for high-throughput assays of thermal tolerance. Temperature-dependent fluorescence curves and their derived metric, Tcrit, may offer a timely and powerful new method for the field of phycology, enabling characterization and comparison of photosynthetic thermal tolerance of seaweeds across many populations, species, and biomes. 相似文献