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121.
Stephanie L. Gantt Caleb G. Joseph Carol A. Fierke 《The Journal of biological chemistry》2010,285(9):6036-6043
The metal-dependent histone deacetylases (HDACs) catalyze hydrolysis of acetyl groups from acetyllysine side chains and are targets of cancer therapeutics. Two bound monovalent cations (MVCs) of unknown function have been previously observed in crystal structures of HDAC8; site 1 is near the active site, whereas site 2 is located >20 Å from the catalytic metal ion. Here we demonstrate that one bound MVC activates catalytic activity (K1/2 = 3.4 mm for K+), whereas the second, weaker-binding MVC (K1/2 = 26 mm for K+) decreases catalytic activity by 11-fold. The weaker binding MVC also enhances the affinity of the HDAC inhibitor suberoylanilide hydroxamic acid by 5-fold. The site 1 MVC is coordinated by the side chain of Asp-176 that also forms a hydrogen bond with His-142, one of two histidines important for catalytic activity. The D176A and H142A mutants each increase the K1/2 for potassium inhibition by ≥40-fold, demonstrating that the inhibitory cation binds to site 1. Furthermore, the MVC inhibition is mediated by His-142, suggesting that this residue is protonated for maximal HDAC8 activity. Therefore, His-142 functions either as an electrostatic catalyst or a general acid. The activating MVC binds in the distal site and causes a time-dependent increase in activity, suggesting that the site 2 MVC stabilizes an active conformation of the enzyme. Sodium binds more weakly to both sites and activates HDAC8 to a lesser extent than potassium. Therefore, it is likely that potassium is the predominant MVC bound to HDAC8 in vivo. 相似文献
122.
Stephen A. Murray Judith L. Morgan Coleen Kane Yashoda Sharma Caleb S. Heffner Jeffrey Lake Leah Rae Donahue 《PloS one》2010,5(8)
Background
Preterm birth is an enormous public health problem, affecting over 12% of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined.Methodology/Principal Findings
To further develop the mouse as a genetic model of preterm birth, we developed a high-throughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr#A/J/NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length.Conclusions/Significance
Together, these data support the role of genetics in regulating gestation length and present the mouse as an important tool for the discovery of genes governing preterm birth. 相似文献123.
124.
The noun tsara'at appears about two dozen times in the Hebrew Bible, almost exclusively in Leviticus, where it is used to describe a state of ritual defilement manifested as a scaly condition of the skin, a condition of cloth, leather, and the walls of houses. In the Septuagint, the Greek translation of the Hebrew Bible, negac tsara'at was translated as aphe lepras; in the Latin Vulgate, this became plega leprae. These words in Greek and Latin implied a condition that spread over the body, not a term of ritual impurity. Tsara'at has continued to be translated as "leprosy," even though this term is not appropriate, as there was no leprosy as we know it in the Middle East during the time period the Hebrew Bible was written. Others have suggested that the proper translation of tsara'at is "mold." The recent identification of a specific mold (Stachybotrys sp.) that contaminates buildings and causes respiratory distress, memory loss, and rash, and the fact that mold has been present for millennia, lend support to the translation of tsara'at as "mold." 相似文献
125.
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127.
Brett A. DeGregorio Connor Gale Ellery V. Lassiter Andrhea Massey Caleb P. Roberts John T. Veon 《Ecology and evolution》2021,11(22):15874
As the human footprint upon the landscape expands, wildlife seeking to avoid human contact are losing the option of altering their spatial distribution and instead are shifting their daily activity patterns to be active at different times than humans. In this study, we used game cameras to evaluate how human development and activity were related to the daily activity patterns of the nine‐banded armadillo (Dasypus novemcinctus) along an urban to rural gradient in Arkansas, USA during the winter of 2020–2021. We found that armadillos had substantial behavioral plasticity in regard to the timing of their activity patterns; >95% of armadillo activity was nocturnal at six of the study sites, whereas between 30% and 60% of activity occurred during the day at three other sites. The likelihood of diurnal armadillo activity was best explained by the distance to downtown Fayetteville (the nearest population center) and estimated ambient sound level (both indices of human activity) with armadillos being most active during the day at quiet sites far from Fayetteville. Furthermore, armadillo activity occurred later during the night period (minutes after sunset) at sites near downtown and with higher anthropogenic sound. Anecdotal evidence suggests that the observed activity shift may be in response to not only human activity but also the presence of domestic dogs. Our results provide further evidence that human activity has subtle nonlethal impacts on even common, widespread wildlife species. Because armadillos have low body temperatures and basal metabolism, being active during cold winter nights likely has measurable fitness costs. Nature reserves near human population centers may not serve as safe harbors for wildlife as we intend, and managers could benefit from considering these nonlethal responses in how they manage recreation and visitation in these natural areas. 相似文献
128.
Christopher M. Murray Caleb D. McMahan Allison R. Litmer Jeffrey M. Goessling Dustin Siegel 《Ecology and evolution》2021,11(23):17519
Biological patterns across latitudinal gradients elucidate a number of striking natural clines from which numerous processes can be further explored. The trade‐off between reproduction and somatic maintenance and growth represents a suite of life‐history traits with variable energy allocation and potential latitudinal patterns. Specifically, male sexually dimorphic traits in female choice systems represent one such reproductive investment constrained by resource acquisition and subsequent allocation. Latitudinal variation in sexual dimorphism has been suggested although the relationship between dimorphic traits and latitude are conflicting. Here, we test alternative hypotheses regarding this pattern using two broadly distributed vertebrates exhibiting sexually dimorphic traits. We hypothesized that the exaggeration of dimorphic traits correlates with latitude, with males having exaggerated sexually dimorphic traits at either higher or lower latitudes. Results indicate that male sexually dimorphic traits are exaggerated at lower latitudes while relative gonopodium size in Poecilia latipinna was larger at higher latitudes. This pattern may be a result of lower latitude populations experiencing greater population densities and longer access to resources that could manifest in females more intensively selecting for higher quality males in lower latitudes. Experimental work should address this pattern and investigate mechanistic processes. 相似文献
129.
Rebecca L. Vincelette Caleb C. Roth Maureen P. McConnell Jason A. Payne Hope T. Beier Bennett L. Ibey 《PloS one》2013,8(4)
High-amplitude, MV/m, nanosecond pulsed electric fields (nsPEF) have been hypothesized to cause nanoporation of the plasma membrane. Phosphatidylserine (PS) externalization has been observed on the outer leaflet of the membrane shortly after nsPEF exposure, suggesting local structural changes in the membrane. In this study, we utilized fluorescently-tagged Annexin V to observe the externalization of PS on the plasma membrane of isolated Chinese Hamster Ovary (CHO) cells following exposure to nsPEF. A series of experiments were performed to determine the dosimetric trends of PS expression caused by nsPEF as a function of pulse duration, τ, delivered field strength, ED, and pulse number, n. To accurately estimate dose thresholds for cellular response, data were reduced to a set of binary responses and ED50s were estimated using Probit analysis. Probit analysis results revealed that PS externalization followed the non-linear trend of (τ*ED
2)−1 for high amplitudes, but failed to predict low amplitude responses. A second set of experiments was performed to determine the nsPEF parameters necessary to cause observable calcium uptake, using cells preloaded with calcium green (CaGr), and membrane permeability, using FM1-43 dye. Calcium influx and FM1-43 uptake were found to always be observed at lower nsPEF exposure parameters compared to PS externalization. These findings suggest that multiple, higher amplitude and longer pulse exposures may generate pores of larger diameter enabling lateral diffusion of PS; whereas, smaller pores induced by fewer, lower amplitude and short pulse width exposures may only allow extracellular calcium and FM1-43 uptake. 相似文献
130.
Felipe Brice?o Adrian Joseph Linnane Juan Carlos Quiroz Caleb Gardner Gretta Tatyana Pecl 《PloS one》2015,10(10)
Depredation of southern rock lobster (Jasus edwardsii) within fishing gear by the Maori octopus (Pinnoctopus cordiformis) has economic and ecological impacts on valuable fisheries in South Australia. In addition, depredation rates can be highly variable resulting in uncertainties for the fishery. We examined how in-pot lobster predation was influenced by factors such as lobster size and sex, season, fishing zone, and catch rate. Using mixed modelling techniques, we found that in-pot predation risk increased with lobster size and was higher for male lobsters. In addition, the effect of catch rate of lobsters on predation risk by octopus differed among fishing zones. There was both a seasonal and a spatial component to octopus predation, with an increased risk within discrete fishing grounds in South Australia at certain times of the year. Information about predation within lobster gear can assist fishery management decision-making, potentially leading to significant reduction in economic losses to the fishery. 相似文献