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.     

Assessing overmedication: biology,philosophy and common sense

Overmedication is nowadays a serious problem in health care due to influences from the pharmaceutical industry and agencies responsible for regulation. The situation has indeed become appalling in psychiatry, where both theories and treatments have deteriorated under the impact of the industry. The overmedication problem is associated with biased biology in medicine. Adequate biological approaches would indicate that drug therapies must yield to diet therapies, particularly treatments involving omega-3 fatty acids, in many cases. To the extent that philosophy of science adapts to mainstream medicine in analyses of the current situation, it may reinforce the existing bias. To redress imbalances in health care, we ultimately have to rely on common sense.     

Inbreeding depression and haplodiploidy: experimental measures in a parasitoid and comparisons across diploid and haplodiploid insect taxa

Abstract. It has long been assumed that inbreeding depression in haplodiploid organisms is low due to their ability to purge genetic load in haploid males. It has been suggested that this low genetic load could facilitate the evolution of inbreeding behaviors driven by local mate competition in hymenopteran parasitoids. I have examined inbreeding depression in haplodiploids in two ways. First I show that an outbreeding haplodiploid wasp Uscana semifumipennis (Hymenoptera: Trichogrammatidae) suffers substantial inbreeding depression. Longevity was 38% shorter, fecundity was 32% lower, and sex ratio was 5% more male for experimentally inbred wasps when compared to outbred controls. There were interactions between size and both fecundity and sex ratio for inbred wasps that were not seen for outbred individuals. Second, an analysis of data from the literature suggests that when inbreeding is experimentally imposed on populations, haplodiploid insects and mites as a group do suffer less from inbreeding depression than diploid insects, although substantial inbreeding depression in haplodiploid taxa does exist. The meta-analysis revealed no difference in inbreeding depression between gregarious haplodiploid wasps, which are likely to have a history of inbreeding, and solitary haplodiploid species, which are assumed to be primarily outbred.     

Viability selection at three early life stages of the tropical tree,Platypodium elegans (Fabaceae,Papilionoideae)

Given the enormous number and high mortality of fertilized ovules in plants, it is possible that selection during the earliest stages of the life cycle plays an important role in shaping the genetic composition of plant populations. Previous research involving selection component analyses found strong evidence for viability selection in annual plant species. Yet despite this evidence, few attempts have been made to identify the magnitude and timing of viability selection as well as the mechanisms responsible for mortality among genotypes. Platypodium elegans, a Neotropical tree with high rates of early fruit mortality, represents an opportunity to study viability selection at a level of discernment not previously possible. Microsatellite markers were used to analyze the genetic composition of aborted embryos, as well as mature seeds and seedlings of the same cohort. While selection resulted in an overall decrease in self-fertilized progeny across each life stage, the greatest change in the genetic composition of progeny occurred between mature seeds and established seedlings. This suggested that inbreeding depression, and not late-acting self-incompatibility, was responsible for early selection. An investigation of the mature seed stage revealed that self-fertilized seeds weigh significantly less than outcrossed seeds. The result of this early selection conceals the mixed-mating system and high levels of inbreeding depression in Platypodium elegans, resulting in an apparently outcrossed adult population that does not differ significantly from Hardy-Weinberg expectations.     

Breeding system in the dichogamous hermaphrodite Silene acutifolia (Caryophyllaceae)

The breeding system of the dichogamous hermaphrodite species Silene acutifolia, endemic to north-west Spain and north and central Portugal, is examined. Pollen germinability and style-stigma receptivity were analysed to determine whether protandry is a barrier to self-fertilization. By 48 h after anthesis, pollen germinability had declined to approx. 10 %. The short straight styles are not receptive when flowers first open. They gradually elongate and curve outwards, develop stigma papillae and become receptive. There is no clear separation between stigma and style: the stigma papillae appear in a line along the length of the style. Fruit set is high regardless of pollen source; however, seed set is significantly reduced after both spontaneous and facilitated autogamy. Seed set following spontaneous autogamy was 30 % (86 % in controls) in 1998 and 33 % (87 % in controls) in 1999. Seed set following facilitated autogamy was 62 % (86 % in controls) in 1998 and 67 % (89 % in controls) in 1999. Thus, separation of the male and female phases does not prevent production of seeds by self-pollination, although it does reduce the likelihood of this. Furthermore, results of the present experiments indicate that this species has no self-incompatibility mechanisms (self-compatibility index = 0.98). The selfing rate in the study population was 0.41, which is supported by the lack of self-incompatibility systems and by the incomplete protandry.     

Spike-based synaptic plasticity and the emergence of direction selective simple cells: mathematical analysis

In the companion paper we presented extended simulations showing that the recently observed spike-timing dependent synaptic plasticity can explain the development of simple cell direction selectivity (DS) when simultaneously modifying the synaptic strength and the degree of synaptic depression. Here we estimate the spatial shift of the simple cell receptive field (RF) induced by the long-term synaptic plasticity, and the temporal phase advance caused by the short-term synaptic depression in response to drifting grating stimuli. The analytical expressions for this spatial shift and temporal phase advance lead to a qualitative reproduction of the frequency tuning curves of non-directional and directional simple cells. In agreement with in vivo recordings, the acquired DS is strongest for test gratings with a temporal frequency around 1–4 Hz. In our model this best frequency is determined by the width of the learning function and the time course of depression, but not by the temporal frequency of the training stimuli. The analysis further reveals the instability of the initially symmetric RF, and formally explains why direction selectivity develops from a non-directional cell in a natural, directionally unbiased stimulation scenario.     

Presynaptic Frequency- and Pattern-Dependent Filtering

Dual intracellular recordings from pairs of synaptically connected neurones have demonstrated that the frequency-dependent pattern of transmitter release varies dramatically between different classes of connections. Somewhat surprisingly, these patterns are not determined by the class of neurone supplying the axon alone, but to a large degree by the class of postsynaptic neurone. A wide range of presynaptic mechanisms, some that depress the release of transmitter and others that enhance release have been identified. It is the selective expression of these different mechanisms that determines the unique frequency- and pattern-dependent properties of each class of connection. Although the molecular interactions underlying these several mechanisms have yet to be fully identified, the wealth and complexity of the protein-protein and protein-lipid interactions that have been shown to control the release of transmitter suggest many ways in which the properties of a synapse may be tuned to respond to particular patterns and frequencies.