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991.
Debbie C. Thurmond Anna B. Tang Manabu T. Nakamura Judith S. Stern Stephen D. Phinney 《Obesity (Silver Spring, Md.)》1993,1(2):118-125
Obese Zucker rats (fa/fa) have low levels of arachidonic acid (AA) in liver phospholipids (PL). We have previously shown that a 70% gamma-linolenate concentrate (GLA; an AA intermediate) fed at a fixed dose (0.07 g/day) normalized hepatic PL AA and reduced weight gain selectively in the obese animals. In a follow-up study, 16 obese (fa/fa) and 16 lean (Fa/Fa) 4-week-old male rats were randomized into 4 groups of 8 each and gavaged daily with soybean oil (SOY) containing 55% 18:2ω6 (an AA precursor) or GLA, using a progressive dose (≤ 5% of total calories) based on body weight. A defined diet with 11% of energy as SOY was fed ad libitum for 60 days. GLA obese had lower body weight (p<0.0001) and 60-day cumulative food intake (p<0.05) compared to SOY obese, but neither parameter differed between the lean groups. For the last twenty days cumulative food intake was identical for GLA obese and SOY lean, whereas SOY obese consumed 18% more (p<0.05). Thus the progressive dose of GLA selectively suppressed hyperphagia in obese Zucker rats. Erythrocytes collected at 15-day intervals showed parallel increases in AA in both genotypes over time, suggesting normal AA availability during rapid growth. Thus, the reduced PL AA in the livers from the obese rats probably reflects impaired distribution in selected tissues rather than reduced hepatic production. Due to the potential health risks of enriching tissue lipids with AA, great caution is advised in considering GLA as therapy for human obesity. 相似文献
992.
Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis 下载免费PDF全文
Jens Ingwersen Lorenzo De Santi Britta Wingerath Jonas Graf Barbara Koop Reiner Schneider Christina Hecker Friederike Schröter Mary Bayer Anna Dorothee Engelke Michael Dietrich Philipp Albrecht Hans‐Peter Hartung Pasquale Annunziata Orhan Aktas Tim Prozorovski 《Journal of neurochemistry》2018,146(1):86-98
993.
Conjugative transposition of the vancomycin resistance carrying Tn1549: enzymatic requirements and target site preferences 下载免费PDF全文
Lotte Lambertsen Anna Rubio‐Cosials Kiran Raosaheb Patil Orsolya Barabas 《Molecular microbiology》2018,107(5):639-658
Rapid spread of resistance to vancomycin has generated difficult to treat bacterial pathogens worldwide. Though vancomycin resistance is often conferred by the conjugative transposon Tn1549, it is yet unclear whether Tn1549 moves actively between bacteria. Here we demonstrate, through development of an in vivo assay system, that a mini‐Tn1549 can transpose in E. coli away from its natural Gram‐positive host. We find the transposon‐encoded INT enzyme and its catalytic tyrosine Y380 to be essential for transposition. A second Tn1549 protein, XIS is important for efficient and accurate transposition. We further show that DNA flanking the left transposon end is critical for excision, with changes to nucleotides 7 and 9 impairing movement. These mutations could be partially compensated for by changing the final nucleotide of the right transposon end, implying concerted excision of the two ends. With changes in these essential DNA sequences, or without XIS, a large amount of flanking DNA transposes with Tn1549. This rescues mobility and allows the transposon to capture and transfer flanking genomic DNA. We further identify the transposon integration target sites as TTTT‐N6‐AAAA. Overall, our results provide molecular insights into conjugative transposition and the adaptability of Tn1549 for efficient antibiotic resistance transfer. 相似文献
994.
Anna E. Goodroe Casey Fitz Michael L. Power Ricki J. Colman Saverio Capuano III Toni E. Ziegler 《American journal of primatology》2020,82(6):e23131
Vitamin D3 (cholecalciferol) is endogenously produced in the skin of primates when exposed to the appropriate wavelengths of ultraviolet light (UV-B). Common marmosets (Callithrix jacchus) maintained indoors require dietary provision of vitamin D3 due to lack of sunlight exposure. The minimum dietary vitamin D3 requirement and the maximum amount of vitamin D3 that can be metabolized by marmosets is unknown. Observations of metabolic bone disease and gastrointestinal malabsorption have led to wide variation in dietary vitamin D3 provision amongst research institutions, with resulting variation in circulating 25-hydroxyvitamin D3 (25(OH)D3), the accepted marker for vitamin D sufficiency/deficiency. Multiple studies have reported serum 25(OH)D3 in captive marmosets, but 25(OH)D3 is not the final product of vitamin D3 metabolism. In addition to serum 25(OH)D3, we measured the most physiologically active metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and the less well understood metabolite, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) to characterize the marmoset's ability to metabolize dietary vitamin D3. We present vitamin D3 metabolite and related serum chemistry value colony reference ranges in marmosets provided diets with 26,367 (Colony A, N = 113) or 8,888 (Colony B, N = 52) international units (IU) of dietary vitamin D3 per kilogram of dry matter. Colony A marmosets had higher serum 25(OH)D3 (426 ng/ml [SD 200] vs. 215 ng/ml [SD 113]) and 24,25(OH)2D3 (53 ng/ml [SD 35] vs. 7 ng/ml [SD 5]). There was no difference in serum 1,25(OH)2D3 between the colonies. Serum 1,25(OH)2D3 increased and 25(OH)D3 decreased with age, but the effect was weak. Marmosets tightly regulate metabolism of dietary vitamin D3 into the active metabolite 1,25(OH)2D3; excess 25(OH)D3 is metabolized into 24,25(OH)2D3. This ability explains the tolerance of high levels of dietary vitamin D3 by marmosets, however, our data suggest that these high dietary levels are not required. 相似文献
995.
Anna C. Ortega Samantha P. Dwinnell Tayler N. Lasharr Rhiannon P. Jakopak Kristin Denryter Katey S. Huggler Matthew M. Hayes Ellen O. Aikens Tana L. Verzuh Alexander B. May Matthew J. Kauffman Kevin L. Monteith 《The Journal of wildlife management》2020,84(8):1445-1456
Information garnered from the capture and handling of free-ranging animals helps advance understanding of wildlife ecology and can aid in decisions on wildlife management. Unfortunately, animals may experience increased levels of stress, injuries, and death resulting from captures (e.g., exertional myopathy, trauma). Partial sedation is a technique proposed to alleviate stress in animals during capture, yet efficacy of partial sedation for reducing stress and promoting survival post-capture remains unclear. We evaluated the effects of partial sedation on physiological, biochemical, and behavioral indicators of acute stress and probability of survival post-capture for mule deer (Odocoileus hemionus) that were captured via helicopter net-gunning in the eastern Greater Yellowstone Ecosystem, Wyoming, USA. We administered 10–30 mg of midazolam and 15 mg of azaperone intramuscularly (IM) to 32 mule deer in 2016 and 53 mule deer in 2017, and maintained a control group (captured but not sedated) of 38 mule deer in 2016 and 54 mule deer in 2017. To evaluate indicators of acute stress, we measured heart rate, blood-oxygen saturation, body temperature, respiration rate, and levels of serum cortisol. We recorded number of kicks and vocalizations of deer during handling and evaluated behavior during release. We also measured levels of fecal glucocorticoids as an indicator of baseline stress. Midazolam and azaperone did not reduce physiological, biochemical, or behavioral indicators of acute stress or influence probability of survival post-capture. Mule deer that were administered midazolam and azaperone, however, were more likely to hesitate, stumble or fall, and walk during release compared with individuals in the control group, which were more likely to trot, stot, or run without stumbling or falling. Our findings suggest that midazolam (10–30 mg IM) and azaperone (15 mg IM) may not yield physiological or demographic benefits for captured mule deer as previously assumed and may pose adverse effects that can complicate safety for captured animals, including drug-induced lethargy. Although we failed to find efficacy of midazolam and azaperone as a method for reducing stress in captured mule deer, the efficacy of midazolam and azaperone or other combinations of partial sedatives in reducing stress may depend on the dose of tranquilizer, study animal, capture setting, and how stress is defined. © 2020 The Wildlife Society. 相似文献
996.
Patryk Czortek Anna Delimat Marcin K. Dyderski Antoni Zięba Andrzej M. Jagodziński Bogdan Jaroszewicz 《Nordic Journal of Botany》2020,38(5)
The ability for vegetative growth and development of generative organs often reflects an adaptation to the environment and may be a suitable proxy for understanding population dynamics of rare relict species. An example of such a plant is Carex lachenalii Schkuhr, an arctic-alpine species, in the temperate zone of Europe only occurring in isolated localities of high-elevation mountain ranges. We aimed to assess whether there were relationships between flower production and clonal growth of C. lachenalii, both at the tuft and plot level, and how co-occurring vegetation could modify this relationship. In the study we focused on population-level traits of C. lachenalii, vegetation traits and components of functional diversity. At the tuft level we found that the proportion of flowering ramets of C. lachenalii decreased with increasing diameter of the tuft. At the plot level, in snowbed vegetation C. lachenalii produced more flowering ramets. We suggest this is due to higher environmental stress, expressed by high importance of habitat filtering (low functional dispersion) in shaping species composition of co-occurring vegetation. In granite grasslands and milder environment (expressed by higher functional dispersion), C. lachenalii produced more vegetative ramets, which we suggest is a result of a more competitive environment. While in snowbeds investment in flowering ramets could promote successful persistence of C. lachenalii, survival of subpopulations occurring in the highly competitive conditions of granite grasslands may be uncertain due to potentially weak adaptation to competition with graminoids and dwarf shrubs. 相似文献
997.
Michael Krützen Sina Kreicker Colin D. MacLeod Jennifer Learmonth Anna M. Kopps Pamela Walsham Simon J. Allen 《Proceedings. Biological sciences / The Royal Society》2014,281(1784)
Culturally transmitted tool use has important ecological and evolutionary consequences and has been proposed as a significant driver of human evolution. Such evidence is still scarce in other animals. In cetaceans, tool use has been inferred using indirect evidence in one population of Indo-Pacific bottlenose dolphins (Tursiops sp.), where particular dolphins (‘spongers’) use marine sponges during foraging. To date, evidence of whether this foraging tactic actually provides access to novel food items is lacking. We used fatty acid (FA) signature analysis to identify dietary differences between spongers and non-spongers, analysing data from 11 spongers and 27 non-spongers from two different study sites. Both univariate and multivariate analyses revealed significant differences in FA profiles between spongers and non-spongers between and within study sites. Moreover, FA profiles differed significantly between spongers and non-spongers foraging within the same deep channel habitat, whereas the profiles of non-spongers from deep channel and shallow habitats at this site could not be distinguished. Our results indicate that sponge use by bottlenose dolphins is linked to significant differences in diet. It appears that cultural transmission of tool use in dolphins, as in humans, allows the exploitation of an otherwise unused niche. 相似文献
998.
Sarah J. Morgan Deepak A. Deshpande Brian C. Tiegs Anna M. Misior Huandong Yan Alena V. Hershfeld Thomas C. Rich Reynold A. Panettieri Steven S. An Raymond B. Penn 《The Journal of biological chemistry》2014,289(33):23065-23074
Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. 相似文献
999.
Andrey Poleshko Andrew V Kossenkov Natalia Shalginskikh Anna Pecherskaya Anna Pecherskaya Margret B Einarson Margret B Einarson Anna Marie Skalka Anna Marie Skalka Richard A Katz Richard A Katz 《Epigenetics》2014,9(9):1280-1289
Cellular identity in both normal and disease processes is determined by programmed epigenetic activation or silencing of specific gene subsets. Here, we have used human cells harboring epigenetically silent GFP-reporter genes to perform a genome-wide siRNA knockdown screen for the identification of cellular factors that are required to maintain epigenetic gene silencing. This unbiased screen interrogated 21,121 genes, and we identified and validated a set of 128 protein factors. This set showed enrichment for functional categories, and protein-protein interactions. Among this set were known epigenetic silencing factors, factors with no previously identified role in epigenetic gene silencing, as well as unstudied factors. The set included non-nuclear factors, for example, components of the integrin-adhesome. A key finding was that the E1 and E2 enzymes of the small ubiquitin-like modifier (SUMO) pathway (SAE1, SAE2/UBA2, UBC9/UBE2I) are essential for maintenance of epigenetic silencing. This work provides the first genome-wide functional view of human factors that mediate epigenetic gene silencing. The screen output identifies novel epigenetic factors, networks, and mechanisms, and provides a set of candidate targets for epigenetic therapy and cellular reprogramming. 相似文献
1000.
Anna L. Xavier Jo?o R. L. Menezes Steven A. Goldman Maiken Nedergaard 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1654)
Microglia constitute as much as 10–15% of all cells in the mammalian central nervous system (CNS) and are the only glial cells that do not arise from the neuroectoderm. As the principal CNS immune cells, microglial cells represent the first line of defence in response to exogenous threats. Past studies have largely been dedicated to defining the complex immune functions of microglial cells. However, our understanding of the roles of microglia has expanded radically over the past years. It is now clear that microglia are critically involved in shaping neural circuits in both the developing and adult CNS, and in modulating synaptic transmission in the adult brain. Intriguingly, microglial cells appear to use the same sets of tools, including cytokine and chemokine release as well as phagocytosis, whether modulating neural function or mediating the brain''s innate immune responses. This review will discuss recent developments that have broadened our views of neuro-glial signalling to include the contribution of microglial cells. 相似文献