Steroid Hormone Actions on the Brain: When Is the Genome Involved?

It has become customary to distinguish between so-called "genomic" actions of steroid hormones involving intracellular receptors and "non-genomic" effects of steroids that involve putative cell surface receptors. Whereas there is no doubt that this distinction has considerable validity, it does not go far enough in addressing the variety of mechanisms that steroid hormones use to produce their effects on cells. This is because cell surface receptors may signal changes in gene expression, while genomic actions sometimes affect neuronal excitability, often doing so quite rapidly. Moreover, steroid hormones and neurotransmitters may operate together to produce effects, and sometimes these effects involve collaborations between groups of neurons. As illustrations. evidence is reviewed in this article that a number of steroid actions in the hippocampus involves the co-participation of excitatory amino acids. These interactions are evident for the regulation of synaptogenesis by estradiol in the CA1 pyramidal neurons or hippocampus and for the induction of dendritic atrophy of CA3 neurons by repeated stress as well as by glucocorticoid injections. In addition, neurogenesis in the adult and developing dentate gyrus is "contained" by adrenal steroids as well as by excitatory amino acids. In each of these three examples, NMDA receptors are involved. These results not only point to a high degree of interdependency between certain neurotransmitters and the actions of steroid hormones but also emphasize the degree to which structural plasticity is an important aspect of steroid hormone action in the adult as well as developing nervous system.     

Sympatric Speciation: When Is It Possible in Bacteria?

According to theory, sympatric speciation in sexual eukaryotes is favored when relatively few loci in the genome are sufficient for reproductive isolation and adaptation to different niches. Here we show a similar result for clonally reproducing bacteria, but which comes about for different reasons. In simulated microbial populations, there is an evolutionary tradeoff between early and late stages of niche adaptation, which is resolved when relatively few loci are required for adaptation. At early stages, recombination accelerates adaptation to new niches (ecological speciation) by combining multiple adaptive alleles into a single genome. Later on, without assortative mating or other barriers to gene flow, recombination generates unfit intermediate genotypes and homogenizes incipient species. The solution to this tradeoff may be simply to reduce the number of loci required for speciation, or to reduce recombination between species over time. Both solutions appear to be relevant in natural microbial populations, allowing them to diverge into ecological species under similar constraints as sexual eukaryotes, despite differences in their life histories.     

Peak Waste: When Is It Likely to Occur?

Population and per capita gross domestic product (GDP) projections are used to estimate total global municipal solid waste (MSW) generation over the twenty‐first century. Some projections for global population suggest that it will peak this century. Waste generation rates per capita generally increase with affluence, although in the most affluent countries there is also a trend toward dematerialization. The confluence of these factors means that at some point in the future total global waste generation could possibly peak. To determine when peak waste might occur, we used the shared‐socioeconomic pathway scenarios (used in Intergovernmental Panel on Climate Change [IPCC] studies) combined with estimates of municipal solid waste (MSW) generation rates, extrapolated from our work for the World Bank. Despite the expectation that total MSW generation in Organisation for Economic Co‐operation and Development (OECD) and high‐income countries will peak mid‐century, with current trajectories global peak waste is not expected before 2100. The peak could be moved forward to around 2075 and reduced in intensity by some 30% if a more aggressive sustainability growth scenario were followed, rather than the current business‐as‐usual scenario. Further, the magnitude of peak waste is sensitive to the intensity of waste generation; it could vary from 7.3 to 10.9 megatonnes per day under the sustainability scenario. The timing of peak waste will substantially depend on the development of cities in Sub‐Saharan Africa, where population growth rates are more than double the rest of the world.     

What Is the Minimum Number of Residues to Determine the Secondary Structural State?

The failure of protein secondary structural prediction is commonly attributed to the neglect of long-range interactions. The question is, what is the minimum length of subsequence required to determine the central secondary structural state, stabilized only by local interactions? In the present work, the 20 amino acids were classified into eight groups to analyze systematically the relationship between the length and secondary structural state of subsequences in the PDB database. It was found that the fraction of subsequences with a unique central secondary structural state increases with increasing length, and the minimum length of subsequence required to determine the central secondary structural state is about 14–17 residues. The low accuracy of secondary structure prediction does not result from the neglect of long-range interactions, but may result from the limitation of the available protein database size or prediction algorithm.     

Cerebellar Motor Learning: When Is Cortical Plasticity Not Enough?

Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo–ocular reflex (VOR) have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This “cortex-first” learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed “brainstem-first” mechanism that operates when ocular tracking mechanisms are effective. These results (i) describe a process whereby information originally learnt in one area of the brain (cerebellar cortex) can be transferred and expressed in another (brainstem), and (ii) indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay.     

Brain Evolution: When Is a Group Not a Group?

In testing the 'social brain hypothesis' with comparative data, most research has used group size as an index of cognitive challenge. Recent work suggests that this measure is too crude to apply to a wide range of species, and biologists may need to develop other ways of extending these analyses.     

Language Acquisition: When Does the Learning Begin?

Language acquisition is quite sophisticated by four months of age. Two cues that babies use to discriminate their language from another are the stress patterns of words and visual cues inherent in language production.