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排序方式: 共有74条查询结果,搜索用时 15 毫秒
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McShea A Samuel T Eppel JT Galloway DA Funk JO 《The Journal of biological chemistry》2000,275(30):23181-23186
The cyclin-dependent kinase inhibitor p21(cip1) regulates cell cycle progression, DNA replication, and DNA repair by binding to specific cellular proteins through distinct amino- and carboxyl-terminal protein binding motifs. We have identified a novel human gene, CARB (CIP-1-associated regulator of cyclin B), whose product interacts with the p21 carboxyl terminus. Immunocytochemical analysis demonstrates that the CARB protein is perinuclear and predominantly associated with the centrosome and mitotic spindle poles. In addition, CARB is also able to associate with cyclin B1, a key regulator of mitosis. However, cyclin B1-CARB complex formation occurs preferentially in the absence of p21. Unexpectedly, overexpression of CARB is associated with a growth-inhibitory and ultimately lethal phenotype in p21(-/-) cells but not in p21(+/+) cells. These data identify a novel mechanism that may underlie the effects of p21 in the G(2)/M phases of the cell cycle. 相似文献
3.
Current status of antisense DNA methods in behavioral studies 总被引:4,自引:0,他引:4
The antisense DNA method has been used successfully to block the expression
of specific genes in vivo in neuronal systems. An increasing number of
studies in the last few years have shown that antisense DNA administered
directly into the brain can modify various kinds of behaviors. These
findings strongly suggest that the antisense DNA method can be used as a
powerful tool to study causal relationships between molecular processes in
the brain and behavior. In this article we review the current status of the
antisense method in behavioral studies and discuss its potentials and
problems by focusing on the following four aspects; (i) optimal application
paradigms of antisense DNA methods in behavioral studies; (ii) efficiencies
of different administration methods of antisense DNA used in behavioral
studies; (iii) determination of specificity of behavioral effects of
antisense DNA; and (iv) discrepancies between antisense DNA effects on
behaviors and those on protein levels of the targeted gene.
相似文献
4.
Benjamin Udoka Nwosu Louise Maranda Karen Cullen Lisa Greenman Jody Fleshman Nancy McShea Bruce A. Barton Mary M. Lee 《PloS one》2015,10(9)
Context
Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.Objective
To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.Hypothesis
Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.Design, Setting, and Participants
A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90–120 mg/dL (5.0–6.7 mmol/L). Pubertal maturation was determined by Tanner stage.Results
Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups.Conclusions
This 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.Trial Registration
ClinicalTrial.gov NCT01334125 相似文献5.
Paul DW Kirk Aviva Witkover Alan Courtney Alexandra M Lewin Robin Wait Michael PH Stumpf Sylvia Richardson Graham P Taylor Charles RM Bangham 《Retrovirology》2011,8(1):1-9
Background
A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a cross-species transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain anti-tetherin activity for efficient spread in the human population. Thus far, three SIV/HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans.Results
Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression.Conclusions
Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than non-pandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population. 相似文献6.
7.
Anthropogenic effects on wildlife are typically assessed at the local level, but it is often difficult to extrapolate to larger spatial extents. Macro-level occupancy studies are one way to assess impacts of multiple disturbance factors that might vary over different geographic extents. Here we assess anthropogenic effects on occupancy and distribution for several mammal species within the Appalachian Trail (AT), a forest corridor that extends across a broad section of the eastern United States. Utilizing camera traps and a large volunteer network of citizen scientists, we were able to sample 447 sites along a 1024 km section of the AT to assess the effects of available habitat, hunting, recreation, and roads on eight mammal species. Occupancy modeling revealed the importance of available forest to all species except opossums (Didelphis virginiana) and coyotes (Canis latrans). Hunting on adjoining lands was the second strongest predictor of occupancy for three mammal species, negatively influencing black bears (Ursus americanus) and bobcats (Lynx rufus), while positively influencing raccoons (Procyon lotor). Modeling also indicated an avoidance of high trail use areas by bears and proclivity towards high use areas by red fox (Vulpes vulpes). Roads had the lowest predictive power on species occupancy within the corridor and were only significant for deer. The occupancy models stress the importance of compounding direct and indirect anthropogenic influences operating at the regional level. Scientists and managers should consider these human impacts and their potential combined influence on wildlife persistence when assessing optimal habitat or considering management actions. 相似文献
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10.
L-Lactate dehydrogenase (L-LDH, E.C. 1.1.1.27) is encoded by two or three
loci in all vertebrates examined, with the exception of lampreys, which
have a single LDH locus. Biochemical characterizations of LDH proteins have
suggested that a gene duplication early in vertebrate evolution gave rise
to Ldh-A and Ldh-B and that an additional locus, Ldh-C arose in a number of
lineages more recently. Although some phylogenetic studies of LDH protein
sequences have supported this pattern of gene duplication, others have
contradicted it. In particular, a number of studies have suggested that
Ldh-C represents the earliest divergence among vertebrate LDHs and that it
may have diverged from the other loci well before the origin of
vertebrates. Such hypotheses make explicit statements about the
relationship of vertebrate and invertebrate LDHs, but to date, no closely
related invertebrate LDH sequences have been available for comparison. We
have attempted to provide further data on the timing of gene duplications
leading to multiple vertebrate LDHs by determining the cDNA sequence of the
LDH of the tunicate Styela plicata. Phylogenetic analyses of this and other
LDH sequences provide strong support for the duplications giving rise to
multiple vertebrate LDHs having occurred after vertebrates diverged from
tunicates. The timing of these LDH duplications is consistent with data
from a number of other gene families suggesting widespread gene duplication
near the origin of vertebrates. With respect to the relationships among
vertebrate LDHs, our data are not consistent with previous claims that
Ldh-C represented the earliest divergence. However, the precise
relationships among some of the main lineages of vertebrate LDHs were not
resolved in our analyses.
相似文献