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31.
32.
Bhaskar Ponugoti Fanxing Xu Chenying Zhang Chen Tian Sandra Pacios Dana T. Graves 《The Journal of cell biology》2013,203(2):327-343
Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor β1 (TGF-β1) and its downstream targets, integrin-α3 and -β6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-β1–independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-β1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis. 相似文献
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Pfefferle D Heistermann M Pirow R Hodges JK Fischer J 《International journal of primatology》2011,32(4):992-1006
Females of many Old World primates produce conspicuous vocalizations in combination with copulations. Indirect evidence exists
that in Barbary macaques (Macaca sylvanus), the structure of these copulation calls is related to changes in reproductive hormone levels. However, the structure of
these calls does not vary significantly around the timing of ovulation when estrogen and progestogen levels show marked changes.
We here aimed to clarify this paradox by investigating how the steroid hormones estrogen and progesterone are related to changes
in the acoustic structure of copulation calls. We collected data on semi-free-ranging Barbary macaques in Gibraltar and at
La Forêt des Singes in Rocamadour, France. We determined estrogen and progestogen concentrations from fecal samples and combined
them with a fine-grained structural analysis of female copulation calls (N = 775 calls of 11 females). Our analysis indicates a time lag of 3 d between changes in fecal hormone levels, adjusted for
the excretion lag time, and in the acoustic structure of copulation calls. Specifically, we found that estrogen increased
the duration and frequency of the calls, whereas progestogen had an antagonistic effect. Importantly, however, variation in
acoustic variables did not track short-term changes such as the peak in estrogen occurring around the timing of ovulation.
Taken together, our results help to explain why female Barbary macaque copulation calls are related to changes in hormone
levels but fail to indicate the fertile phase. 相似文献
35.
Le Zhang Sun-Ok Fernandez-Kim Tina L. Beckett Dana M. Niedowicz Katharina Kohler Kalavathi Dasuri Annadora J. Bruce-Keller M. Paul Murphy Jeffrey N. Keller 《生物化学与生物物理学报:疾病的分子基础》2019,1865(9):2157-2167
Alzheimer's disease (AD) is the most common age-related neurodegenerative disease, while obesity is a major global public health problem associated with the metabolic disorder type 2 diabetes mellitus (T2DM). Chronic obesity and T2DM have been identified as invariant risk factors for dementia and late-onset AD, while their impacts on the occurrence and development of AD remain unclear. As shown in our previous study, the diabetic mutation (db, Leprdb/db) induces mixed or vascular dementia in mature to middle-aged APPΔNL/ΔNL x PS1P264L/P264L knock-in mice (db/AD). In the present study, the impacts of the db mutation on young AD mice at 10 weeks of age were evaluated. The db mutation not only conferred young AD mice with severe obesity, impaired glucose regulation and activated mammalian target of rapamycin (mTOR) signaling pathway in the mouse cortex, but lead to a surprising improvement in memory. At this young age, mice also had decreased cerebral Aβ content, which we have not observed at older ages. This was unlikely to be related to altered Aβ synthesis, as both β- and γ-secretase were unchanged. The db mutation also reduced the cortical IL-1β mRNA level and IBA1 protein level in young AD mice, with no significant effect on the activation of microglia and astrocytes. We conclude that the db mutation could transitorily improve the memory of young AD mice, a finding that may be partially explained by the relatively improved glucose homeostasis in the brains of db/AD mice compared to their counterpart AD mice, suggesting that glucose regulation could be a strategy for prevention and treatment of neurodegenerative diseases like AD. 相似文献
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Bilateral lesions of the ventromedial nucleus of the hypothalamus interfered with the estrogenic induction of sexual receptivity in the female rat, but seemingly did not affect the ability of female rats to show lordosis following combined stimulation with estrogen and progesterone. In addition, ventromedial hypothalamic lesions did not affect the ability of females to show male-like sexual activity in response to exogenous androgenic stimulation. 相似文献
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Sarah R. Elkin Nathaniel W. Oswald Dana K. Reed Marcel Mettlen John B. MacMillan Sandra L. Schmid 《Traffic (Copenhagen, Denmark)》2016,17(10):1139-1149
Ikarugamycin (IKA) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low‐density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin‐mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We show that IKA has an IC50 of 2.7 μm in H1299 cells and acutely inhibits CME, but not other endocytic pathways, in a panel of cell lines. Although long‐term incubation with IKA has cytotoxic effects, the short‐term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking. 相似文献
38.
Transposition of the kanamycin-resistance transposon Tn903 总被引:6,自引:0,他引:6
Ry Young Dana Smith Grillo Ralph Isberg Jeffrey Way Michael Syvanen 《Molecular & general genetics : MGG》1980,178(3):681-689
Summary The insertion of the kanamycin-resistance transposon, Tn903, into the Escherichia coli chromosome was studied. Tn903 is similar in structure to the well known transposons Tn5 and Tn10 in that it has a unique central sequence flanked by inverted repeat sequences extending more than a thousand base pairs. However, the central region of Tn903 has enough single-frame coding capacity only for the drug modifying enzyme, whereas Tn5 and Tn10 carry multigenic unique sequences. In this paper we demonstrate that two different classes of insertion event occur: (1) the first class is a complex event in which all or part of the genome of the bacteriophage lambda vector is co-inserted near the purE locus on the E. coli chromosome (11.7 min); (2) the second class appears to be a simple transposition event in which the transposon alone is inserted at relatively nonspecific sites in the chromosome, as has been described for Tn5 and Tn10. Furthermore both classes show dependency on homology-requiring recombination systems. We suggest that Tn903 transposes infrequently because it must utilize a recA-controlled host function, whereas Tn5 and Tn10 are recA-independent and encode similar but more active functions on the transposon DNA. 相似文献
39.
We assessed the influence of ice-storm-derived debris dams on aquatic macroinvertebrates and stream substrates in a high-gradient
watershed in the eastern Adirondack Mountains of New York State. Using a modification of electrofishing techniques, invertebrates
were collected once before (June 2000) and once after (June 2001) wood removal from the downstream reach in each of six pairs
of reaches (second and third-order streams). Stream substrates were also mapped in 2000 and 2001 to evaluate shifts in dominant
substrates within a reach following wood removal. The following metrics were used to compare the invertebrate communities
before and after wood removal: genera similarity, Shannon–Weiner equitability, taxa richness, dominant taxon, percent dominance
and functional feeding group relative abundance. The changes in removal reaches were evaluated relative to changes in upstream
reference reaches using a Before-After Control-Impact (BACI) design and analysis. Stream substrates did not change significantly
in response to wood removal, although a trend toward coarser substrates was observed following removal. Following wood removal,
the relative proportion of grazers increased upstream and downstream from removed dams in all streams; however, comparisons
of other metrics indicated no significant response to removal. Invertebrate responses to wood removal were lower than expected,
perhaps due to the presence of abundant boulder-formed pools in this high gradient system.
Electronic supplementary material Electronic supplementary material is available for this article at
and accessible for authorised users. 相似文献
40.