Simulated ecology-driven sympatric speciation

We introduce a multi-locus genetically acquired phenotype, submitted to mutations and with selective value, in an age-structured model for biological aging. This phenotype describes a single-trait effect of the environment on an individual, and we study the resulting distribution of this trait among the population. In particular, our simulations show that the appearance of a double phenotypic attractor in the ecology induces the emergence of a stable polymorphism, as observed in the Galapagos finches. In the presence of this polymorphism, the simulations generate short-term speciation, when mating preferences are also allowed to suffer mutations and acquire selective value.Comment: 11 pages, 5 figures, 1 table, uses package RevTe

Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids

ABSTRACT: BACKGROUND AND OBJECTIVE: With prolonged use of anabolic androgenic steroids (AAS), occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17) gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS. PRESENTATION OF THE HYPOTHESIS: The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate. TESTING THE HYPOTHESIS: In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body. IMPLICATIONS OF THE HYPOTHESIS: If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be exposed to an increased risk of developing renal disorders. In the current detecting - sanctioning anti-doping system, athletes motivated by the potential to evade detection owing to their unique genetic make-up could subject themselves to a serious health consequence. More research on AAS metabolism in the presence of UGT2B17 gene deletion is required. Benefit - harm evaluations in therapeutic use of anabolic steroids should also consider this potential link between UGT2B17 gene deletion polymorphism and renal disorders

Forgetting Exceptions is Harmful in Language Learning

We show that in language learning, contrary to received wisdom, keeping exceptional training instances in memory can be beneficial for generalization accuracy. We investigate this phenomenon empirically on a selection of benchmark natural language processing tasks: grapheme-to-phoneme conversion, part-of-speech tagging, prepositional-phrase attachment, and base noun phrase chunking. In a first series of experiments we combine memory-based learning with training set editing techniques, in which instances are edited based on their typicality and class prediction strength. Results show that editing exceptional instances (with low typicality or low class prediction strength) tends to harm generalization accuracy. In a second series of experiments we compare memory-based learning and decision-tree learning methods on the same selection of tasks, and find that decision-tree learning often performs worse than memory-based learning. Moreover, the decrease in performance can be linked to the degree of abstraction from exceptions (i.e., pruning or eagerness). We provide explanations for both results in terms of the properties of the natural language processing tasks and the learning algorithms.Comment: 31 pages, 7 figures, 10 tables. uses 11pt, fullname, a4wide tex styles. Pre-print version of article to appear in Machine Learning 11:1-3, Special Issue on Natural Language Learning. Figures on page 22 slightly compressed to avoid page overloa

Concepts of Drift and Selection in “The Great Snail Debate” of the 1950s and Early 1960s

Recently, much philosophical discussion has centered on the best way to characterize the concepts of random drift and natural selection, and, in particular, on the question of whether selection and drift can be conceptually distinguished (Beatty 1984; Brandon 2005; Hodge 1983, 1987; Millstein 2002, 2005; Pfeifer 2005; Shanahan 1992; Stephens 2004). These authors all contend, to a greater or lesser degree, that their concepts make sense of biological practice. So, it should be instructive to see how the concepts of drift and selection were distinguished by the disputants in a high-profile debate; debates such as these often force biologists to take a more philosophical turn, discussing the concepts at issue in greater detail than usual. A prime candidate for just such a case study is what William Provine (1986) has termed “The Great Snail Debate,” that is, the debate over the highly polymorphic land snails Cepaea nemoralis and Cepaea hortensis in the 1950s and early 1960s. This study will reveal that much of the present-day confusion over the concepts of drift and selection is rooted in confusions of the past. Nonetheless, there are lessons that can be learned about nonadaptiveness, indiscriminate sampling, and causality with respect to these two concepts. In particular, this paper will shed light on the following questions: 1) What is “drift”? Is “drift” a purely mathematical construct, a physical process analogous to the indiscriminate sampling of balls from an urn, or the outcome of a sampling process? 2) What is “nonadaptiveness,” and is a proponent of drift committed to claims that organisms’ traits are nonadaptive? 3) Can disputes concerning selection and drift be settled by statistics alone, or is causal information essential? If causal information is essential, what does that say about the concepts of “drift” and “selection” themselves

Bad Nature, Bad Nurture, and Testimony Regarding MAOA and SLC6A4 Genotyping in Murder Trials

Recent research—in which subjects were studied longitudinally from childhood until adulthood—has started to clarify how a child’s environment and genetic makeup interact to create a violent adolescent or adult. For example, male subjects who were born with a particular allele of the monoamine oxidase A gene and also were maltreated as children had a much greater likelihood of manifesting violent antisocial behavior as adolescents and adults. Also, individuals who were born with particular alleles of the serotonin transporter gene and also experienced multiple stressful life events were more likely to manifest serious depression and suicidality. This research raises the question of whether testimony regarding a defendant’s genotype, exposure to child maltreatment, and experience of unusual stress is appropriate to present during the guilt or penalty phases of criminal trials, especially when capital punishment is a consideration. The authors present their experience in genotyping criminal defendants and presenting genetic information at criminal trials

Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing and Analysis Consortium published in late 2005. Neuroevolutionary insights relevant to fear circuitry symptoms that primarily emerge overconsolidationally (especially Combat related Posttraumatic Stress Disorder) are presented. Also introduced is a human-evolution-based principle for clustering innate fear traits. The "Neuroevolutionary Time-depth Principle" of innate fears proposed in this article may be useful in the development of a neuroevolution-based taxonomic re-clustering of stress-triggered and fear-circuitry disorders in DSM-V. Four broad clusters of evolved fear circuits are proposed based on their time-depths: 1) Mesozoic (mammalian-wide) circuits hardwired by wild-type alleles driven to fixation by Mesozoic selective sweeps; 2) Cenozoic (simian-wide) circuits relevant to many specific phobias; 3) mid Paleolithic and upper Paleolithic (Homo sapiens-specific) circuits (arguably resulting mostly from mate-choice-driven stabilizing selection); 4) Neolithic circuits (arguably mostly related to stabilizing selection driven by gene-culture co-evolution). More importantly, the author presents evolutionary perspectives on warzone-related PTSD, Combat-Stress Reaction, Combat-related Stress, Operational-Stress, and other deployment-stress-induced symptoms. The Neuroevolutionary Time-depth Principle presented in this article may help explain the dissimilar stress-resilience levels following different types of acute threat to survival of oneself or one's progency (aka DSM-III and DSM-V PTSD Criterion-A events). PTSD rates following exposure to lethal inter-group violence (combat, warzone exposure or intentionally caused disasters such as terrorism) are usually 5-10 times higher than rates following large-scale natural disasters such as forest fires, floods, hurricanes, volcanic eruptions, and earthquakes. The author predicts that both intentionally-caused large-scale bioevent-disasters, as well as natural bioevents such as SARS and avian flu pandemics will be an exception and are likely to be followed by PTSD rates approaching those that follow warzone exposure. During bioevents, Amygdala-driven and locus-coeruleus-driven epidemic pseudosomatic symptoms may be an order of magnitude more common than infection-caused cytokine-driven symptoms. Implications for the red cross and FEMA are discussed. It is also argued that hospital phobia as well as dog phobia, bird phobia and bat phobia require re-taxonomization in DSM-V in a new "overconsolidational disorders" category anchored around PTSD. The overconsolidational spectrum category may be conceptualized as straddling the fear circuitry spectrum disorders and the affective spectrum disorders categories, and may be a category for which Pitman's secondary prevention propranolol regimen may be specifically indicated as a "morning after pill" intervention. Predictions are presented regarding obsessive-compulsive disorder (OCD) (e.g., female-pattern hoarding vs. male-pattern hoarding) and "culture-bound" acute anxiety symptoms (taijin-kyofusho, koro, shuk yang, shook yong, suo yang, rok-joo, jinjinia-bemar, karoshi, gwarosa, Voodoo death). Also discussed are insights relevant to pseudoneurological symptoms and to the forthcoming Dissociative-Conversive disorders category in DSM-V, including what the author terms fright-triggered acute pseudo-localized symptoms (i.e., pseudoparalysis, pseudocerebellar imbalance, psychogenic blindness, pseudoseizures, and epidemic sociogenic illness). Speculations based on studies of the human abnormal-spindle-like, microcephaly-associated (ASPM) gene, the microcephaly primary autosomal recessive (MCPH) gene, and the forkhead box p2 (FOXP2) gene are made and incorporated into what is termed "The pre-FOXP2 Hypothesis of Blood-Injection-Injury Phobia." Finally, the author argues for a non-reductionistic fusion of "distal (evolutionary) neurobiology" with clinical "proximal neurobiology," utilizing neurological heuristics. It is noted that the value of re-clustering fear traits based on behavioral ethology, human-phylogenomics-derived endophenotypes and on ontogenomics (gene-environment interactions) can be confirmed or disconfirmed using epidemiological or twin studies and psychiatric genomics

Increased NFκ-B Activity in HCT116 Colorectal Cancer Cell Line Harboring TLR4 Asp299Gly Variant

Toll-Like Receptor 4 (TLR4), considered one of the most important TLR, recognizes lipopolysaccharide of gram-negative bacteria. Recognition of ligands by TLRs induces signaling pathways resulting in activation of transcriptional factors such as NF-κB which are involved in the expression of inflammatory cytokines and chemokines. To prevent an inappropriate immune response, a complex network of molecules negatively regulates TLRs and their associated signaling pathways. Two cosegregating single nucleotide polymorphisms of the human TLR4 gene, namely Asp299Gly and Thr399Ile, have been associated with hyporesponsiveness to inhaled LPS. The purpose of this study was to determine the impact of TLR4 gene variant on NF-κB activity in colorectal cancer cell line. HCT116 cells were transfected with wild-type and mutants Flag-CMV1-TLR4 expression vectors. Western blot analysis was performed to evaluate selected molecules involved in TLR4 signaling. NF-κB activity was assessed by dualluciferase reporter assay and cytokine profiles were evaluated by ELISA and Cytometric Bead Array method. Results showed that the activity of pNF-κB was higher in cells harboring TLR4 D299G compared to the other cells. However, the activity of pAKT, pERK1 and pIRAK was higher in wild-type. The results of cytokine measurements showed about four fold higher level of IL-8 in cells with wild-type TLR4. This study suggest that TLR4 Asp299Gly gene variant has an impact on TLR4 signaling and potentially on intestinal homeostasis due to impaired control signals at the epithelial cell level which may lead to chronic intestinal inflammation and interrupted intestinal homeostasis and may eventually lead to colorectal cancer. Copyright© 2012, Iranian Journal of Allergy, Asthma and Immunology. All rights reserved