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71.
Non-selective effects, like genetic drift, are an important factor in modern conceptions of evolution, and have been extensively studied for constant population sizes (Kimura, 1955; Otto and Whitlock, 1997). Here, we consider non-selective evolution in the case of growing populations that are of small size and have varying trait compositions (e.g. after a population bottleneck). We find that, in these conditions, populations never fixate to a trait, but tend to a random limit composition, and that the distribution of compositions “freezes” to a steady state. This final state is crucially influenced by the initial conditions. We obtain these findings from a combined theoretical and experimental approach, using multiple mixed subpopulations of two Pseudomonas putida strains in non-selective growth conditions (Matthijs et al, 2009) as model system. The experimental results for the population dynamics match the theoretical predictions based on the Pólya urn model (Eggenberger and Pólya, 1923) for all analyzed parameter regimes. In summary, we show that exponential growth stops genetic drift. This result contrasts with previous theoretical analyses of non-selective evolution (e.g. genetic drift), which investigated how traits spread and eventually take over populations (fixate) (Kimura, 1955; Otto and Whitlock, 1997). Moreover, our work highlights how deeply growth influences non-selective evolution, and how it plays a key role in maintaining genetic variability. Consequently, it is of particular importance in life-cycles models (Melbinger et al, 2010; Cremer et al, 2011; Cremer et al, 2012) of periodically shrinking and expanding populations. 相似文献
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Marina Fugmann Olaf Uhl Christian Hellmuth Holger Hetterich Nora N. Kammer Uta Ferrari Klaus G. Parhofer Berthold Koletzko Jochen Seissler Andreas Lechner 《PloS one》2015,10(5)
BackgroundNonesterified fatty acids (NEFA) play pathophysiological roles in metabolic syndrome and type 2 diabetes (T2D). In this study, we analyzed the fasting NEFA profiles of normoglycemic individuals at risk for T2D (women with a recent history of gestational diabetes (GDM)) in comparison to controls (women after a normoglycemic pregnancy). We also examined the associations of NEFA species with overweight/obesity, body fat distribution and insulin sensitivity.ResultsWomen after GDM had a lower molar percentage of total saturated fatty acids (SFA; 38.55% vs. 40.32%, p = 0.0002) than controls. At an explorative level of significance several NEFA species were associated with post-GDM status (with and without adjustment for body mass index (BMI) and HbA1c): The molar percentages of 14:0, 16:0, 18:0 and 18:4 were reduced, whereas those of 18:1, 18:2, 20:2, 24:4, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and total n-6 NEFA were increased. BMI and the amount of body fat correlated inversely with several SFA and MUFA and positively with various PUFA species over the whole study cohort (abs(ρ)≥0.3 for all). 14:0 was inversely and BMI-independently associated with abdominal visceral adiposity. We saw no correlations of NEFA species with insulin sensitivity and the total NEFA concentration was similar in the post-GDM and the control group.ConclusionIn conclusion, we found alterations in the fasting NEFA profile associated with a recent history of gestational diabetes, a risk marker for T2D. NEFA composition also varied with overweight/obesity and with body fat distribution, but not with insulin sensitivity. 相似文献
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This article serves as a brief history and review of EBM—how EBM developed, its strengths and limitations, and the need for constant improvements. Hopefully, this review will have enhanced your understanding of EBM and its importance and stimulated you to apply EBM to your own practice. As more data and therapies become available, and as clinical guidelines continue to evolve based on EBM, we should expect patient outcomes to improve. 相似文献
75.
Background: A preponderance of evidence indicates that when treatment of hyperglycemia with insulin is provided for certain hospitalized populations, the attainment of appropriate glycemic targets improves nonglycemic outcomes such as mortality rates, morbidities (eg, wound infection, critical illness polyneuropathy, bacteremia, new renal insufficiency), duration of ventilator dependency, transfusion requirements, and length of hospital stay. Nevertheless, randomized controlled trials (RCTs) of intensive insulin therapy and studies of outcomes before and after implementation of tight glycemic control have consistently recognized an increased incidence of hypoglycemia as a complication associated with the use of lower glycemic targets and higher doses of insulin.Objectives: This commentary compares the quality of the available evidence on the clinical impact of iatrogenic hypoglycemia. We present treatment strategies designed to prevent iatrogenic hypoglycemia in the hospital setting.Methods: The PubMed database and online citations of articles tracked subsequent to publication were searched for articles on the epidemiology, clinical impact, and mechanism of harm of hypoglycemia published since 1986. In addition, we searched the literature for RCTs conducted since 2001 concerning intensive insulin therapy in the hospital critical care setting, including meta-analyses; letters to the editor were excluded. The retrieved studies were scanned and chosen selectively for full-text review based on the study size and design, novelty of findings, and evidence related to the possible clinical impact of hypoglycemia. Reference lists from the retrieved studies were searched for additional studies. Reports were summarized for the purpose of comparing and contrasting the qualitative nature of information about iatrogenic hypoglycemia in the hospital.Results: Eight RCTs of intensive glycemic management, 16 observational studies of hospitalized patients with hypoglycemia (including studies of outcomes before and after implementation of tight glycemic control), and 4 case reports on patients with hypoglycemia were selected for discussion of the incidence of hypoglycemia, significance of hypoglycemia as a marker or cause of poor prognosis, and clinical harm of hypoglycemia. Hypoglycemia was identified in clinical trials as either a category of adverse events or a complication of intensified insulin treatment. For example, a recent meta-analysis found that the incidence of severe hypoglycemia was higher among critically ill patients treated with intensive insulin therapy than among control patients, with a pooled relative risk of 6.0 (95% CI, 4.5–8.0). In the largest multisite RCT on glycemic control among patients in intensive care units (ICUs) conducted to date, deaths were reported for 27.5% (829/3010 patients) in the intensive-treatment group and 24.9% (751/3012 patients) in the conventional-treatment group (odds ratio, 1.14; 95% CI, 1.02–1.28; P = 0.02). In another multisite ICU study, although the intensive and control groups had similar mortality rates, the mortality rate was higher among hypoglycemic participants than among nonhypoglycemic participants (32.2% vs 13.6%, respectively; P < 0.01). Pooled data from 2 singlesite studies in medical and surgical ICUs revealed an increased risk of hypoglycemia in the intensive-treatment group compared with the conventional-treatment group (11.3% [154/1360] and 1.8% [25/1388], respectively; P < 0.001), but the hospital mortality rate was similar for the 2 groups (50.6% [78/154] and 52.0% [13/25], respectively). Specific sequelae of hypoglycemia affecting individual patients were described in the RCTs as well as in the observational studies. New guidelines for glycemic control have recently been issued, but results of the studies using the new targets are not yet available. We propose treatment strategies designed to prevent iatrogenic hypoglycemia in the hospital setting.Conclusions: In response to the growing evidence on the risk of hypoglycemia during intensified glycemic management of hospitalized patients, professional organizations recently revised targets for glycemic control. It is appropriate for institutions to reevaluate hospital protocols for glycemic management with intravenous insulin and, on general wards, to implement standardized order sets for use of subcutaneous insulin to achieve beneficial targets using safe strategies. 相似文献
76.
The yeast centrosome translates the positional information of the anaphase spindle into a cell cycle signal 总被引:3,自引:0,他引:3
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The spindle orientation checkpoint (SPOC) of budding yeast delays mitotic exit when cytoplasmic microtubules (MTs) are defective, causing the spindle to become misaligned. Delay is achieved by maintaining the activity of the Bfa1-Bub2 guanosine triphosphatase-activating protein complex, an inhibitor of mitotic exit. In this study, we show that the spindle pole body (SPB) component Spc72, a transforming acidic coiled coil-like molecule that interacts with the gamma-tubulin complex, recruits Kin4 kinase to both SPBs when cytoplasmic MTs are defective. This allows Kin4 to phosphorylate the SPB-associated Bfa1, rendering it resistant to inactivation by Cdc5 polo kinase. Consistently, forced targeting of Kin4 to both SPBs delays mitotic exit even when the anaphase spindle is correctly aligned. Moreover, we present evidence that Spc72 has an additional function in SPOC regulation that is independent of the recruitment of Kin4. Thus, Spc72 provides a missing link between cytoplasmic MT function and components of the SPOC. 相似文献
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Lechner SG Markworth S Poole K Smith ES Lapatsina L Frahm S May M Pischke S Suzuki M Ibañez-Tallon I Luft FC Jordan J Lewin GR 《Neuron》2011,69(2):332-344
In mammals, the osmolality of the extracellular fluid (ECF) is highly stable despite radical changes in salt/water intake and excretion. Afferent systems are required to detect hypo- or hyperosmotic shifts in the ECF to trigger homeostatic control of osmolality. In humans, a pressor reflex is triggered by simply drinking water which may be mediated by peripheral osmoreceptors. Here, we identified afferent neurons in the thoracic dorsal root ganglia (DRG) of mice that innervate hepatic blood vessels and detect physiological hypo-osmotic shifts in blood osmolality. Hepatic sensory neurons are equipped with an inward current that faithfully transduces graded changes in osmolality within the physiological range (~15 mOsm). In mice lacking the osmotically activated ion channel, TRPV4, hepatic sensory neurons no longer exhibit osmosensitive inward currents and activation of peripheral osmoreceptors in vivo is abolished. We have thus identified a new population of sensory neurons that transduce ongoing changes in hepatic osmolality. 相似文献
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