Nutritional ecology and diachronic trends in Paleolithic diet and health

Modern nutritional studies have found that diverse diets are linked to lower infant mortality rates and longer life expectancies in humans. This is primarily because humans require more than fifty essential nutrients for growth and cell maintenance and repair; most of these essential nutrients must come from outside food sources rather than being manufactured by the body itself; and a diversity of food types is required to consume the full suite of essential nutrients necessary for optimal human health. These principles and their related affects on human adaptations and demography are the hallmarks of a theoretical paradigm defined as nutritional ecology. This essay applies concepts derived from nutritional ecology to the study of human evolution. Principles of nutritional ecology are applied to the study of the Middle‐to‐Upper Paleolithic transition in order to broadly illustrate the interpretive ramifications of this approach. At any stage in human evolution, those hominid populations that chose to diversify their subsistence base may have had a selective advantage over competitors who restricted their diet principally to one food type, such as terrestrial mammals.     

Codon usage in the vertebrate hemoglobins and its implications

A study of codon usage in vertebrate hemoglobins revealed an evolutionary trend toward elevated numbers of CpG codon boundary pairs in mammalian hemoglobin alpha genes. Selection for CpG codon boundaries countering the generally observed CpG suppression is strongly suggested by these data. These observations parallel recently published experimental results that indicate that constitutive expression of the human alpha-globin gene appears to be determined by regulatory information encoded within the structural gene. The possibility is raised that, in the absence of selection, CpG decay can be used to date the evolutionary origin of a mammalian alpha pseudogene from its active alpha gene.      

Developmental regulation of mechanosensitive calcium channels in skeletal muscle from normal and mdx mice.

Single-channel activity was recorded from cell-attached membrane patches on flexor digitorum brevis fibres acutely isolated from normal and mdx mice at different stages of postnatal development. Recordings from cell-attached patches on both normal and mdx fibres were dominated by the activity of mechanosensitive ion channels with a conductance of approximately 17 pS with 110 mM Ba2+ in the patch electrode. In a small fraction of the patches on mdx fibres from young mice, channels showed very high levels of activity. Channel activity recorded from mdx fibres from older mice was higher than in age-matched normal fibres and the level of activity decreased during development. Channel density decreased in normal fibres, whereas it remained relatively constant in mdx fibres, as if channels are down-regulated in normal, but not mdx, fibres during postnatal development. An early step in the dystrophic process may be an alteration of the mechanisms that regulate the expression of functional channels.     

Evidence for GABA-mediated control of putative nociceptive modulating neurons in the rostral ventromedial medulla: iontophoresis of bicuculline eliminates the off-cell pause.

This study was undertaken to test the hypothesis that gamma-aminobutyric acid (GABA) is an endogeneous neurotransmitter regulating the activity of a class of putative nociceptive modulatory neurons (termed "off-cells") in the rostral ventromedial medulla (RVM) of the barbiturate-anesthetized rat. Off-cells, which are believed to correspond to the RVM output neuron that inhibits nociceptive processing at the level of the spinal cord, exhibit an abrupt pause in firing that begins immediately prior to the occurrence of the tail flick response (TF), a nocifensive reflex evoked by application of noxious heat to the tail. Single-unit recording and iontophoretic techniques were used to examine the ability of the GABAA receptor antagonist bicuculline methiodide (BIC) to antagonize selectively the characteristic off-cell pause. Iontophoretic application of BIC (5-30 nA) blocked the TF-related pause in each of the off-cells tested. This effect of BIC was generally slow in onset, and outlasted the period of application by several minutes. BIC iontophoresis also eliminated the cyclic alternation between active and silent periods that is often displayed by off-cells in lightly anesthetized rats. BIC application did not have a consistent effect on the firing of two other classes of RVM neurons ("on-cells" and "neutral cells"). Iontophoretically applied BIC antagonized the inhibitory effect of iontophoretically applied GABA, but not that produced by glycine. The glycine receptor antagonist strychnine did not mimic the action of BIC on off-cell activity. These data demonstrate antagonism of a synaptically evoked response using iontophoretic application of BIC, and provide strong evidence that the inhibitory neurotransmitter GABA mediates the TF-related off-cell pause. Taken together with behavioral experiments demonstrating that a GABA-mediated inhibitory process within RVM is crucial in permitting execution of the TF response, the present observations point to the significant functional relevance of GABA transmission within RVM in modulation of nociception.     

Variable-Selection Emerges on Top in Empirical Comparison of Whole-Genome Complex-Trait Prediction Methods

Accurate prediction of complex traits based on whole-genome data is a computational problem of paramount importance, particularly to plant and animal breeders. However, the number of genetic markers is typically orders of magnitude larger than the number of samples (p >> n), amongst other challenges. We assessed the effectiveness of a diverse set of state-of-the-art methods on publicly accessible real data. The most surprising finding was that approaches with feature selection performed better than others on average, in contrast to the expectation in the community that variable selection is mostly ineffective, i.e. that it does not improve accuracy of prediction, in spite of p >> n. We observed superior performance despite a somewhat simplistic approach to variable selection, possibly suggesting an inherent robustness. This bodes well in general since the variable selection methods usually improve interpretability without loss of prediction power. Apart from identifying a set of benchmark data sets (including one simulated data), we also discuss the performance analysis for each data set in terms of the input characteristics.     

A support vector machine based test for incongruence between sets of trees in tree space

ABSTRACT: BACKGROUND: The increased use of multi-locus data sets for phylogenetic reconstruction has increased the need to determine whether a set of gene trees significantly deviate from the phylogenetic patterns of other genes. Such unusual gene trees may have been influenced by other evolutionary processes such as selection, gene duplication, or horizontal gene transfer. RESULTS: Motivated by this problem we propose a nonparametric goodness-of-fit test for two empirical distributions of gene trees, and we developed the software GeneOut to estimate a p-value for the test. Our approach maps trees into a multi-dimensional vector space and then applies support vector machines (SVMs) to measure the separation between two sets of pre-defined trees. We use a permutation test to assess the significance of the SVM separation. To demonstrate the performance of GeneOut, we applied it to the comparison of gene trees simulated within different species trees across a range of species tree depths. Applied directly to sets of simulated gene trees with large sample sizes, GeneOut was able to detect very small differences between two set of gene trees generated under different species trees. Our statistical test can also include tree reconstruction into its test framework through a variety of phylogenetic optimality criteria. When applied to DNA sequence data simulated from different sets of gene trees, results in the form of receiver operating characteristic (ROC) curves indicated that GeneOut performed well in the detection of differences between sets of trees with different distributions in a multi-dimensional space. Furthermore, it controlled false positive and false negative rates very well, indicating a high degree of accuracy. CONCLUSIONS: The non-parametric nature of our statistical test provides fast and efficient analyses, and makes it an applicable test for any scenario where evolutionary or other factors can lead to trees with different multi-dimensional distributions. The software GeneOut is freely available under the GNU public license.     

Unexpected ratio of allozyme expression in diploid and triploid individuals of the clonal hybrid fish Phoxinus eos-neogaeus.

Phoxinus eos-neogaeus, a North American freshwater fish, was formed by hybridization between P. neogaeus and P. eos. Individuals of P. eos-neogaeus express one allozyme of P. eos and one allozyme of P. neogaeus for enzymes for which the parental allozymes are distinctive. We performed densitometry on phosphoglucomutase (PGM) and one glucose-6-phosphate isomerase locus (GPI-A) separated by cellulose acetate electrophoresis to determine if the parental species' allozymes are expressed in proportion to the number of genomes present in diploid and triploid individuals, and if these enzymes are regulated separately in different tissues. In diploids, activity of the P. eos allozyme was greater than the P. neogaeus allozyme in eye, liver, and muscle but not in heart (one sample t-test, P = 0.05) for PGM. The activity of the P. eos GPI-A allozyme was significantly greater than the P. neogaeus allozyme in heart, eye and muscle but not in liver (one sample t-test, P = 0.05). The expected ratio of eos:neogaeus expression in triploid P. eos-neogaeus x eos individuals is 2:1. For PGM, the observed ratio of eos:neogaeus expression was not significantly different from 2:1 in all four tissues. The P. eos allozyme for GPI was expressed less than expected in all four tissues (one-sample t-test, P = 0.05). Thus, greater than expected expression of the P. eos allozyme was not observed in triploid individuals as it was in the diploids. These data show that PGM and GPI are regulated separately, and that regulation differs by tissue, and in fish of distinct ploidy levels. J. Exp. Zool. 284:663-674, 1999.     

Nerve decompression at the wrist in patients with Charcot-Marie-Tooth disease

Studies evaluating the effects of nerve release in patients with Charcot-Marie-Tooth disease have been extremely limited to date. This series attempts to evaluate the clinical and electrophysiologic effect of nerve release at the wrist in a series of patients with this disease. Five patients with documented Charcot-Marie-Tooth disease of the upper extremity were followed clinically and had nerve conduction testing both before and after surgery. This study shows that there was an improvement in both sensory and motor testing after release in a significant proportion of patients (p < 0.05). All patients documented improvement in their sensory latency response postoperatively (100 percent) and most showed improvement in motor latency responses (87 percent). More importantly, however, there seems to be an even greater clinical improvement in preoperative complaints (e.g., paresthesia and pain) in the majority of the extremities that underwent surgery with all patients experiencing initial relief and the majority showing no recurrence (63 percent) at last follow-up. From these results, this relief can be variable, but has lasted for a significant duration postoperatively in the majority, necessitating careful consideration for surgery as a legitimate option for patients with Charcot-Marie-Tooth.     

Proliferating cell nuclear antigen (PCNA) as a proliferative marker during embryonic and adult zebrafish hematopoiesis

We investigated the expression of proliferative cell nuclear antigen (PCNA) in zebrafish to delineate the proliferative hematopoietic component during adult and embryonic hematopoiesis. Immunostaining for PCNA and enhanced green fluorescence protein (eGFP) was performed in wild-type and fli1-eGFP (endothelial marker) and gata1-eGFP (erythroid cell marker) transgenic fish. Expression of PCNA mRNA was examined in wild-type and chordin morphant embryos. In adult zebrafish kidney, the renal tubules are surrounded by endothelial cells and it is separated into hematopoietic and excretory compartments. PCNA was expressed in hematopoietic progenitor cells but not in mature neutrophils, eosinophils or erythroid cells. Some PCNA+ cells are scattered in the hematopoietic compartment of the kidney while others are closely associated with renal tubular cells. PCNA was also expressed in spermatogonial stem cells and intestine crypts, consistent with its role in cell proliferation and DNA synthesis. In embryos, PCNA is expressed in the brain, spinal cord and intermediate cell mass (ICM) at 24 h-post fertilization. In chordin morphants, PCNA is significantly upregulated in the expanded ICM. Therefore, PCNA can be used to mark cell proliferation in zebrafish hematopoietic tissues and to identify a population of progenitor cells whose significance would have to be further investigated.