Loss and recovery of ecological diversity associated with evolutionary rescue in abruptly and gradually deteriorating environments.

Populations may survive environmental deterioration by evolutionary adaptation. However, such evolutionary rescue events may be associated with ecological costs, such as reduction in growth performance and loss of ecologically important genetic diversity. Those negative ecological consequences may be mitigated by additional adaptive evolution. Both the ecological costs and the opportunities for additional evolution are contingent on the severity of environmental deterioration. Here, we hypothesize that populations evolutionarily rescued from faster, relative to slow, environmental deterioration suffer more severe long-term fitness decline and diversity loss. An experiment with the model adaptive radiation of bacterium Pseudomonas fluorescens exposed to abruptly or gradually increased antibiotic stress supported our hypothesis. The effect of additional adaptive evolution in recovering population size and ecological diversity was far from perfect. Cautions are therefore needed in predicting the role of rapid evolution for mitigating the impacts of environmental changes, in particular very fast environmental deterioration. We also found that bacterial populations rescued from gradually increased antibiotic stress evolved higher levels of antibiotic resistance, lending more support to aggressive chemotherapy in pathogen control.

Fast drug rotation reduces bacterial resistance evolution in a microcosm experiment.

Drug rotation (cycling), in which multiple drugs are administrated alternatively, has the potential for limiting resistance evolution in pathogens. The frequency of drug alternation could be a major factor to determine the effectiveness of drug rotation. Drug rotation practices often have low frequency of drug alternation, with an expectation of resistance reversion. Here we, based on evolutionary rescue and compensatory evolution theories, suggest that fast drug rotation can limit resistance evolution in the first place. This is because fast drug rotation would give little time for the evolutionarily rescued populations to recover in population size and genetic diversity, and thus decrease the chance of future evolutionary rescue under alternate environmental stresses. We experimentally tested this hypothesis using the bacterium Pseudomonas fluorescens and two antibiotics (chloramphenicol and rifampin). Increasing drug rotation frequency reduced the chance of evolutionary rescue, and most of the finally surviving bacterial populations were resistant to both drugs. Drug resistance incurred significant fitness costs, which did not differ among the drug treatment histories. A link between population sizes during the early stages of drug treatment and the end-point fates of populations (extinction vs survival) suggested that population size recovery and compensatory evolution before drug shift increase the chance of population survival. Our results therefore advocate fast drug rotation as a promising approach to reduce bacterial resistance evolution, which in particular could be a substitute for drug combination when the latter has safety risks.

Compensatory adaptation and diversification subsequent to evolutionary rescue in a model adaptive radiation.

Biological populations may survive lethal environmental stress through evolutionary rescue. The rescued populations typically suffer a reduction in growth performance and harbor very low genetic diversity compared with their parental populations. The present study addresses how population size and within-population diversity may recover through compensatory evolution, using the experimental adaptive radiation of bacterium Pseudomonas fluorescens. We exposed bacterial populations to an antibiotic treatment and then imposed a one-individual-size population bottleneck on those surviving the antibiotic stress. During the subsequent compensatory evolution, population size increased and leveled off very rapidly. The increase of diversity was of slower paces and persisted longer. In the very early stage of compensatory evolution, populations of large sizes had a greater chance to diversify; however, this productivity-diversification relationship was not observed in later stages. Population size and diversity from the end of the compensatory evolution was not contingent on initial population growth performance. We discussed the possibility that our results be explained by the emergence of a "holey" fitness landscape under the antibiotic stress.

Cognition, serum BDNF levels, and BDNF Val66Met polymorphism in type 2 diabetes patients and healthy controls.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is associated with cognitive deficits. However, their pathophysiological mechanisms are still unknown. Recent study suggests that brain-derived neurotrophic factor (BDNF) is correlated with cognitive deficits in T2DM patients. This study was to determine whether altered serum BDNF levels and cognitive deficits depended on the BDNF Val66Met polymorphism in T2DM. RESULTS: The BDNF Val66Met polymorphism may not contribute directly to the susceptibility to T2DM. The total and nearly all index scores (all p < 0.01) except for the attention and visuospatial/constructional indexes (both p > 0.05) of RBANS were markedly decreased in T2DM compared with healthy controls. Serum BDNF levels were significantly lower in patients than that in controls (p < 0.001), and BDNF was positively associated with delayed memory in patients (p < 0.05). The Met variant was associated with worse delayed memory performance among T2DM patients but not among normal controls. Moreover, serum BDNF was positively associated with delayed memory among Met homozygote patients (ß = 0.29, t = 2.21, p = 0.033), while serum BDNF was negatively associated the RBANS total score (ß = -0.92, t = -3.40, p = 0.002) and language index (ß = -1.17, t = -3.54, p = 0.001) among Val homozygote T2DM patients. CONCLUSIONS: BDNF gene Val66Met variation may be associated with cognitive deficits in T2DM, especially with delayed memory. The association between lower BDNF serum levels and cognitive impairment in T2DM is dependent on the BDNF Val66Met polymorphism. METHODS: We recruited 311 T2DM patients and 346 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), serum BDNF levels, and the BDNF Val66Met polymorphism.

Sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway: An experimental study.

OBJECTIVE: To study whether sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway. METHODS: H9c2 myocardial cell lines were cultured and divided into control group (C group), hypoxia reoxygenation group (H/R group), sevoflurane pretreatment + hypoxia reoxygenation group (SP group) and sevoflurane combined with Compound C pretreatment + hypoxia reoxygenation group (ComC group), and the cell proliferation activity and apoptosis rate, myocardial enzyme levels in culture medium as well as the expression of apoptosis genes and p-AMPK in cells were determined. RESULTS: p-AMPK expression in cells of H/R group was significantly lower than that of C group, SP group was significantly higher than that of H/R group; cell proliferation activity value and Bcl-2 expression in cells of H/R group were significantly lower than those of C group, SP group were significantly higher than those of H/R group, ComC group were significantly lower than those of SP group; apoptosis rate, LDH, CK and AST levels as well as the Bax and Caspase-3 expression in cells of H/R group were significantly higher than those of C group, SP group were significantly lower than those of H/R group, ComC group were significantly higher than those of SP group. CONCLUSIONS: Sevoflurane pretreatment can activate AMPK signaling pathway to inhibit the myocardial apoptosis caused by hypoxia reoxygenation.

Low BDNF is associated with cognitive deficits in patients with type 2 diabetes.

OBJECTIVE: Studies suggest that brain-derived neurotrophic factor (BDNF) plays an essential role in regulating memory-related neuroplasticity in the hippocampus. Type 2 diabetes (T2DM) is associated with impairment in many domains of cognitive function which may result from reduced BDNF; however, the correlation of BDNF with cognitive impairment in T2DM has not been investigated. MATERIALS AND METHODS: We compared 208 patients with T2DM to 212 normal controls on serum BDNF and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: Serum BDNF levels were significantly decreased in T2DM patients compared to normal controls (p < 0.001). The total score and nearly all indexes (all p < 0.01) except for attention and visuospatial/constructional indexes (all p > 0.05) of RBANS were markedly lower in T2DM than controls. There was a positive relationship between serum BDNF and delayed memory in patients with T2DM. CONCLUSION: Our results suggest that BDNF may play a role in the pathophysiology of cognitive deficits, especially delayed memory in T2DM.

Gender differences in the prevalence of diabetes mellitus in chronic hospitalized patients with schizophrenia on long-term antipsychotics.

Gender-specific relationships between diabetes mellitus (DM) and schizophrenia have previously received little systematic study. The results showed that the overall DM prevalence was 20% with rates of 17% (58/343) in males and 27% (46/172) in females (p<0.01). Furthermore, increased body mass index (BMI), abdominal obesity and antipsychotic types were predictors of diabetes in these chronic schizophrenic patients.

The study of BDNF Val66Met polymorphism in Chinese schizophrenic patients.

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Recent studies have reported that the Val66Met polymorphism of the BDNF gene may be associated with susceptibility for schizophrenia and age of onset of this disease, with mix results. In the present study, the BDNF Val66Met gene polymorphism was examined in 387 inpatients (259 men and 128 women) meeting the DSM-IV criteria for schizophrenia and unrelated 365 healthy controls (255 men and 110 women). The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS). Age of onset was defined as the age at which the psychotic symptoms first appeared. Our results showed that genotype frequency distributions and allelic frequencies did not differ between patients and controls. No interaction was found between sex and genotypes. Analysis of covariance (ANCOVA) showed a significance of the BDNF Val66Met genotypes on the age of onset (F=3.76, p<0.02), after adjusting sex, age and duration of illness. Furthermore, ANCOVA showed that the significance of the BDNFVal66Met genotypes on age of onset was increased comparing the Val66Met heterozygotes with the combination of Val66Val and Met66Met homozygotes (F=5.85, p<0.01). Our results suggest that the BDNF Val66Met polymorphism may not contribute directly to the susceptibility to schizophrenia, but to the onset of the disease. Furthermore, our results show the heterozygous effect of the BDNF Val66Met gene on the clinical variability of schizophrenia phenotype.