Slow Recovery from Inbreeding Depression Generated by the Complex Genetic Architecture of Segregating Deleterious Mutations

The deleterious effects of inbreeding have been of extreme importance to evolutionary biology, but it has been difficult to characterize the complex interactions between genetic constraints and selection that lead to fitness loss and recovery after inbreeding. Haploid organisms and selfing organisms like the nematode Caenorhabditis elegans are capable of rapid recovery from the fixation of novel deleterious mutation; however, the potential for recovery and genomic consequences of inbreeding in diploid, outcrossing organisms are not well understood. We sought to answer two questions: 1) Can a diploid, outcrossing population recover from inbreeding via standing genetic variation and new mutation? and 2) How does allelic diversity change during recovery? We inbred C. remanei, an outcrossing relative of C. elegans, through brother-sister mating for 30 generations followed by recovery at large population size. Inbreeding reduced fitness but, surprisingly, recovery from inbreeding at large populations sizes generated only very moderate fitness recovery after 300 generations. We found that 65% of ancestral single nucleotide polymorphisms (SNPs) were fixed in the inbred population, far fewer than the theoretical expectation of ∼99%. Under recovery, 36 SNPs across 30 genes involved in alimentary, muscular, nervous, and reproductive systems changed reproducibly across replicates, indicating that strong selection for fitness recovery does exist. Our results indicate that recovery from inbreeding depression via standing genetic variation and mutation is likely to be constrained by the large number of segregating deleterious variants present in natural populations, limiting the capacity for recovery of small populations.     

Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause

Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor; thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.     

Evidence that presynaptic changes are involved in the expression of LTP and LTD of NMDA receptor-mediated EPSCs in area CA1 of the hippocampus

Plasticity of NMDA receptor-mediated synaptic transmission was studied in the CA1 region of the hippocampus utilising whole cell patch-clamp recording techniques. LTP was associated with a decrease in CV whereas LTD was accompanied by an increase in CV and a decrease in Pr. These data are consistent with LTP and LTD being an opposite expression of the same fundamental process.     

The evolution of trade-offs: effects of inbreeding on fecundity relationships in the cricket Gryllus firmus

The evolution of traits is modulated by their interrelationships with each other, particularly when those relationships result in a fitness trade-off. In this paper we explore the consequences of genetic architecture on functional relationships between traits. Specifically, we address the consequences of inbreeding on these relationships. We show that the linear regression between two traits will not be affected if there is no dominance genetic variance in either trait, whereas the intercept but not the slope of the regression will change if there is dominance genetic variance in one trait only. We test the latter hypothesis using fecundity relationships in the cricket Gryllus firmus. Data from pedigree analysis and an inbreeding experiment show that there is significant dominance genetic variance in fecundity, but not head width (an index of body size) or dorsal longitudinal muscle (DLM) mass. Fecundity increases with head width, but decreases with DLM mass. As predicted, the intercepts of the regressions of fecundity on these two morphological traits decrease with inbreeding, but there is little or no change in slope. Gryllus firmus is wing dimorphic, with the macropterous (LW) morph having a lower fecundity than the micropterous (SW) morph. We hypothesize that the difference in fecundity arises primarily because of a competition for resources in the LW females between DLM maintenance (i.e., mass) and egg production. As a consequence, we predict that the fecundity within each morph should decline linearly with the inbreeding coefficient at the same rate in both morphs. The result of this will be a change in the relative fitness of the two morphs, that of the SW morph increasing with inbreeding. This prediction is supported. These results indicate that trade-offs will evolve and such changes will affect evolutionary trajectories by altering the pattern of relationships among fitness components.     

Effects of Chronic Administration of Interferon α A/D on Serotonergic Receptors in Rat Brain

The effects of chronic administration of interferon (IFN; recombinant human IFN -A/D) on serotonergic binding sites in rat brain were investigated. IFN was injected daily for 2 weeks at a dose of 100000 I.U./kg, (i.p.) in male Wistar rats. IFN did not alter either [³H]ketanserin binding to 5-HT_2A receptors or [³H]paroxetine binding to 5-HT transporters. Scatchard analysis of [³H]8-hydroxy-dipropylaminotetraline (8-OH-DPAT) binding to 5-HT_1A receptors demonstrated the presence of high- and low-affinity binding sites in both treatment and control groups. IFN significantly increased both Kd and Bmax measures of [³H]8-OH-DPAT binding at low-affinity binding sites, but not at the high-affinity sites. These results suggest that IFN affects the low-affinity 5-HT_1A receptors sites and may be involved in the development of IFN-induced psychiatric disturbances.     

Breeding system in a population of Trigonella balansae (Leguminosae)

BACKGROUND AND AIMS: Although some taxonomic studies in the genus Trigonella have been conducted, there has been no concerted effort to study the breeding system. This paper examines the floral structure and pollination system in a population of T. balansae, an annual pasture legume. METHODS: Floral morphology, hand and vector pollination, stigma receptivity, pollen tube growth, using scanning electron and fluorescence microscopy, were conducted. KEY RESULTS: Measurements of floral structure from before to after anthesis indicates an inability for T. balansae to self-pollinate and a requirement for an external vector to effectively transfer pollen from the anthers onto the stigmas of this species. Seed set can be obtained by hand or honeybee manipulation of T. balansae flowers. CONCLUSIONS: Trigonella balansae is a self-compatible species, but which requires vectors such as honeybees to bring about pollination.     

Stomatal closure induced by high vapor pressure deficit limited midday photosynthesis at the canopy top of <Emphasis Type="Italic">Fagus crenata</Emphasis> Blume on Naeba mountain in Japan

Diurnal changes in gas exchange, chlorophyll fluorescence and leaf water potential (_leaf) were measured to determine the environmental and physiological factors that limit carbon gain in the horizontal leaves of Fagus crenata Blume at the canopy top. Although midday depression of the net CO₂ assimilation rate (A_n) and stomatal conductance (gH₂O) were clearly evident on a fine day, the potential quantum yield of PS II (F_v/F_m) was fairly constant around 0.83 throughout the day. This result indicates that the leaves at the canopy top do not suffer from chronic photoinhibition, and the excess energy is dissipated safely. Large reversible increases in non-photochemical quenching (NPQ) were evident on fine days. Therefore, the non-radiative energy dissipation of excess light energy contributed to avoid chronic photoinhibition. The electron transfer rate (ETR) reached maximum during the midday depression, and thus there was no positive relation between ETR and A_n under high light conditions, indicating a high rate of photorespiration and the absence of non-stomatal effect during midday. The protective mechanisms such as non-radiative energy dissipation and photorespiration play an important role in preventing photoinhibitory damage, and stomatal limitation is the main factor of midday depression of A_n. To separate the effect of air to leaf vapor pressure deficit (ALVPD) and leaf temperature (T_leaf) on gas exchange, the dependencies of A_n and gH₂O on ALVPD and T_leaf were measured using detached branches under controlled conditions. A_n and gH₂O were insensitive to an increase in T_leaf. With the increase in ALVPD, A_n and gH₂O exhibited more than a 50% decrease even though water supply was optimum, suggesting the dominant role of high ALVPD in the midday depression of gH₂O. We conclude that midday depression of A_n results from the midday stomatal closure caused by high ALVPD.     

Major histocompatibility complex variation at three class II loci in the northern elephant seal

Northern elephant seals were hunted to near extinction in the 19th century, yet have recovered remarkably and now number around 175,000. We surveyed 110 seals for single-strand conformation polymorphism (SSCP) and sequence variation at three major histocompatibility (MHC) class II loci (DQA, DQB and DRB) to evaluate the genetic consequences of the population bottleneck at these loci vs. other well-studied genes. We found very few alleles at each MHC locus, significant variation among breeding sites for the DQA locus, and linkage disequilibrium between the DQB and DRB loci. Northern elephant seals are evidently inbred, although there is as yet no evidence of correlative reductions in fitness.     

Astrocytes and stroke: networking for survival?

Astrocytes are now known to be involved in the most integrated functions of the central nervous system. These functions are not only necessary for the normally working brain but are also critically involved in many pathological conditions, including stroke. Astrocytes may contribute to damage by propagating spreading depression or by sending proapoptotic signals to otherwise healthy tissue via gap junction channels. Astrocytes may also inhibit regeneration by participating in formation of the glial scar. On the other hand, astrocytes are important in neuronal antioxidant defense and secrete growth factors, which probably provide neuroprotection in the acute phase, as well as promoting neurogenesis and regeneration in the chronic phase after injury. A detailed understanding of the astrocytic response, as well as the timing and location of the changes, is necessary to develop effective treatment strategies for stroke patients.     

Primary cortical neuronal cultures reduce cellular energy utilization during anoxic energy deprivation

It has been widely hypothesized that neurons reduce cellular energy use in response to periods of energy deprivation. To test this hypothesis, we measured rates of energy use under normoxia and anoxia in immature (6 days in vitro) and mature (13 days in vitro) neuronal cultures. During anoxic incubation immature and mature cultures reduced cellular energy use by 80% and 45%, respectively. Reduced cellular energy use dramatically affected ATP depletion in neuronal cultures under anoxia. Intracellular ATP stores were expected to deplete within 3 min of anoxia. However, ATP was maintained at decreased but stabilized concentrations for at least 3 h. The capacity of neuronal cultures to reduce cellular energy use during anoxia correlated with their sensitivity towards simulated ischemia. Immature cultures, with the largest capacity to reduce cellular energy use, survived simulated ischemia 2.5 times longer than mature cultures. The addition of glutamate receptor antagonists to mature cultures further decreased cellular energy use during anoxia and significantly extended their survival time under simulated ischemia. This study verifies that primary cortical neuronal cultures reduce cellular energy use during energy deprivation. Additionally, we show that maturation of glutamate receptor activity increases non-depressible energy demand in neuronal cultures.