Metric variation and species recognition in the fossil record

One of the first and most important tasks of the paleontologist is classifying specimens into species. Species recognition commonly involves sorting specimens on the basis of qualitative and quantitative similarities and differences. Often, however, variation in simple metric characters like tooth size or jaw length plays an important role in debates about whether a sample comprises a single species or more than one morphologically similar species. For example, Simpson, Roe, and Lewontin 1 suggested that a fossil sample showing a coefficient of variation greater than 10.0 was likely to comprise more than one species. Well‐known controversies over species recognition in which metric sample variation has been important have simmered for years, focusing on hominids, hominoids, and other extinct primates. Some of these have been resolved; others have not. For example, Pilbeam and Zwell 2 convincingly demonstrated multiple species among South African hominids by showing that metric tooth size variation was too great to be reasonably interpreted as sexual dimorphism. But metric variation continues to play a role in debates about whether Australopithecus afarensis 3 , 4 and Homo habilis 5 - 9 each comprise a single species or two or more separate species. Similarly, there has been steady debate about the number of species present in African Proconsul. Some favor an interpretation of a single extremely dimorphic species, 10 - 12 while others favor an interpretation of two or more species. 13     

Is horizontal transmission really a problem for phylogenetic comparative methods? A simulation study using continuous cultural traits

Phylogenetic comparative methods (PCMs) provide a potentially powerful toolkit for testing hypotheses about cultural evolution. Here, we build on previous simulation work to assess the effect horizontal transmission between cultures has on the ability of both phylogenetic and non-phylogenetic methods to make inferences about trait evolution. We found that the mode of horizontal transmission of traits has important consequences for both methods. Where traits were horizontally transmitted separately, PCMs accurately reported when trait evolution was not correlated even at the highest levels of horizontal transmission. By contrast, linear regression analyses often incorrectly concluded that traits were correlated. Where simulated trait evolution was not correlated and traits were horizontally transmitted as a pair, both methods inferred increased levels of positive correlation with increasing horizontal transmission. Where simulated trait evolution was correlated, increasing rates of separate horizontal transmission led to decreasing levels of inferred correlation for both methods, but increasing rates of paired horizontal transmission did not. Furthermore, the PCM was also able to make accurate inferences about the ancestral state of traits. These results suggest that under certain conditions, PCMs can be robust to the effects of horizontal transmission. We discuss ways that future work can investigate the mode and tempo of horizontal transmission of cultural traits.     

Social learning and the replication process: an experimental investigation

Human cultural traits typically result from a gradual process that has been described as analogous to biological evolution. This observation has led pioneering scholars to draw inspiration from population genetics to develop a rigorous and successful theoretical framework of cultural evolution. Social learning, the mechanism allowing information to be transmitted between individuals, has thus been described as a simple replication mechanism. Although useful, the extent to which this idealization appropriately describes the actual social learning events has not been carefully assessed. Here, we used a specifically developed computer task to evaluate (i) the extent to which social learning leads to the replication of an observed behaviour and (ii) the consequences it has for fitness landscape exploration. Our results show that social learning does not lead to a dichotomous choice between disregarding and replicating social information. Rather, it appeared that individuals combine and transform information coming from multiple sources to produce new solutions. As a consequence, landscape exploration was promoted by the use of social information. These results invite us to rethink the way social learning is commonly modelled and could question the validity of predictions coming from models considering this process as replicative.     

Microsatellite and major histocompatibility complex variation in an endangered rattlesnake,the Eastern Massasauga (Sistrurus catenatus)

Genetic diversity is fundamental to maintaining the long‐term viability of populations, yet reduced genetic variation is often associated with small, isolated populations. To examine the relationship between demography and genetic variation, variation at hypervariable loci (e.g., microsatellite DNA loci) is often measured. However, these loci are selectively neutral (or near neutral) and may not accurately reflect genomewide variation. Variation at functional trait loci, such as the major histocompatibility complex (MHC), can provide a better assessment of adaptive genetic variation in fragmented populations. We compared patterns of microsatellite and MHC variation across three Eastern Massasauga (Sistrurus catenatus) populations representing a gradient of demographic histories to assess the relative roles of natural selection and genetic drift. Using 454 deep amplicon sequencing, we identified 24 putatively functional MHC IIB exon 2 alleles belonging to a minimum of six loci. Analysis of synonymous and nonsynonymous substitution rates provided evidence of historical positive selection at the nucleotide level, and Tajima's D provided support for balancing selection in each population. As predicted, estimates of microsatellite allelic richness, observed, heterozygosity, and expected heterozygosity varied among populations in a pattern qualitatively consistent with demographic history and abundance. While MHC allelic richness at the population and individual levels revealed similar trends, MHC nucleotide diversity was unexpectedly high in the smallest population. Overall, these results suggest that genetic variation in the Eastern Massasauga populations in Illinois has been shaped by multiple evolutionary mechanisms. Thus, conservation efforts should consider both neutral and functional genetic variation when managing captive and wild Eastern Massasauga populations.     

Hybrid incompatibilities in the parasitic wasp genus Nasonia: negative effects of hemizygosity and the identification of transmission ratio distortion loci

The occurrence of hybrid incompatibilities forms an important stage during the evolution of reproductive isolation. In early stages of speciation, males and females often respond differently to hybridization. Haldane's rule states that the heterogametic sex suffers more from hybridization than the homogametic sex. Although haplodiploid reproduction (haploid males, diploid females) does not involve sex chromosomes, sex-specific incompatibilities are predicted to be prevalent in haplodiploid species. Here, we evaluate the effect of sex/ploidy level on hybrid incompatibilities and locate genomic regions that cause increased mortality rates in hybrid males of the haplodiploid wasps Nasonia vitripennis and Nasonia longicornis. Our data show that diploid F(1) hybrid females suffer less from hybridization than haploid F(2) hybrid males. The latter not only suffer from an increased mortality rate, but also from behavioural and spermatogenic sterility. Genetic mapping in recombinant F(2) male hybrids revealed that the observed hybrid mortality is most likely due to a disruption of cytonuclear interactions. As these sex-specific hybrid incompatibilities follow predictions based on Haldane's rule, our data accentuate the need to broaden the view of Haldane's rule to include species with haplodiploid sex determination, consistent with Haldane's original definition.     

Beyond the sentence given

A central and influential idea among researchers of language is that our language faculty is organized according to Fregean compositionality, which states that the meaning of an utterance is a function of the meaning of its parts and of the syntactic rules by which these parts are combined. Since the domain of syntactic rules is the sentence, the implication of this idea is that language interpretation takes place in a two-step fashion. First, the meaning of a sentence is computed. In a second step, the sentence meaning is integrated with information from prior discourse, world knowledge, information about the speaker and semantic information from extra-linguistic domains such as co-speech gestures or the visual world. Here, we present results from recordings of event-related brain potentials that are inconsistent with this classical two-step model of language interpretation. Our data support a one-step model in which knowledge about the context and the world, concomitant information from other modalities, and the speaker are brought to bear immediately, by the same fast-acting brain system that combines the meanings of individual words into a message-level representation. Underlying the one-step model is the immediacy assumption, according to which all available information will immediately be used to co-determine the interpretation of the speaker's message. Functional magnetic resonance imaging data that we collected indicate that Broca's area plays an important role in semantic unification. Language comprehension involves the rapid incorporation of information in a 'single unification space', coming from a broader range of cognitive domains than presupposed in the standard two-step model of interpretation.     

Dendritic cell populations in colon and mesenteric lymph nodes of patients with Crohn's disease.

Dendritic cells (DCs) are key cells in innate and adaptive immune responses that determine the pathophysiology of Crohn's disease. Intestinal DCs migrate from the mucosa into mesenteric lymph nodes (MLNs). A number of different markers are described to define the DC populations. In this study we have identified the phenotype and localization of intestinal and MLN DCs in patients with Crohn's disease and non-IBD patients based on these markers. We used immunohistochemistry to demonstrate that all markers (S-100, CD83, DC-SIGN, BDCA1-4, and CD1a) showed a different staining pattern varying from localization in T-cell areas of lymph follicles around blood vessels or single cells in the lamina propria and in the MLN in the medullary cords and in the subcapsular sinuses around blood vessels and in the T-cell areas. In conclusion, all different DC markers give variable staining patterns so there is no marker for the DC.     

Discovery of catalytically active orthologues of the Parkinson's disease kinase PINK1: analysis of substrate specificity and impact of mutations

Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is known about the intrinsic catalytic properties of PINK1 since the human enzyme displays such low kinase activity in vitro. We have discovered that, in contrast to mammalian PINK1, insect orthologues of PINK1 we have investigated-namely Drosophila melanogaster (dPINK1), Tribolium castaneum (TcPINK1) and Pediculus humanus corporis (PhcPINK1)-are active as judged by their ability to phosphorylate the generic substrate myelin basic protein. We have exploited the most active orthologue, TcPINK1, to assess its substrate specificity and elaborated a peptide substrate (PINKtide, KKWIpYRRSPRRR) that can be employed to quantify PINK1 kinase activity. Analysis of PINKtide variants reveal that PINK1 phosphorylates serine or threonine, but not tyrosine, and we show that PINK1 exhibits a preference for a proline at the +1 position relative to the phosphorylation site. We have also, for the first time, been able to investigate the effect of Parkinson's disease-associated PINK1 missense mutations, and found that nearly all those located within the kinase domain, as well as the C-terminal non-catalytic region, markedly suppress kinase activity. This emphasizes the crucial importance of PINK1 kinase activity in preventing the development of Parkinson's disease. Our findings will aid future studies aimed at understanding how the activity of PINK1 is regulated and the identification of physiological substrates.     

Antiplatelet antibodies in cases of Glanzmann's thrombasthenia with and without a history of multiple platelet transfusion

Antiplatelet antibodies are known to be present in a wide spectrum of patients, which include chronic Idiopathic Thrombocytopenic Purpura (ITP), infections, etc., including Glanzmann''s thrombasthenia (GT) patients who receive multiple platelet transfusions. The presence of natural antibodies to platelet receptors is not studied in cases of GT. We studied the antiplatelet antibodies in 23 patients with GT, 15 of which had received multiple transfusions and eight that had not received transfusions, along with 50 cases of chronic ITP. The prevalence and specificity of platelet-bound antibodies were detected by inhibition assays using O-group platelets on flow cytometry. The mean antiplatelet antibodies in 15 patients of GT who had not received transfusions and eight patients with multiple transfusions was 8427 + 2131.88 and 9038 + 2856 antibodies/platelet, respectively, while in case of the 50 ITP patients studied, it was 22166 + 5616 antibodies/platelet (Normal Range 1500–3200 antibodies/platelet). We conclude that GT patients who have not received transfusions may develop antiplatelet antibodies to the missing/abnormal receptor. Whether this is due to a molecular mimicry or due to some other mechanism needs to be explored.     

Catheter Ablation of Hemodynamically Unstable Ventricular Tachycardia in a Patient with Dextro - Transposition of the Great Arteries and Mustard's Repair

Introduction

A patient with D-TGA and surgical repair (Mustard''s procedure) presented with appropriate ICD shocks due to monomorphic ventricular tachycardia, refractory to antiarrhythmic medications.

Methods and Results

The patient underwent an electrophysiological study and catheter ablation for the VT. Substrate and pace mapping techniques, with the help of an electroanatomical mapping system, was used to localize and ablate the tachycardia successfully.

Conclusions

In patients with D-TGA and Mustard''s repair, scar tissue resulting from VSD repair can act as a substrate for recurrent VT. Catheter ablation of VT is useful in management of VT that occurs despite antiarrhythmic therapy and/or when it is unstable.     

Effect of Quadrat and Core Sizes on Determining the Spatial Pattern of Criconemella sphaerocephalus

An unmanaged pasture was sampled on four occasions (A, B, C, D) with five different quadrat sizes for Criconemella sphaerocephalus by removing a constant soil core volume of 75 cm³ (A) and 300 cm³ (C) from increasing quadrat areas of 0.5-8 m², and removing soil core volumes of increasing size - 75-1,200 cm³ (B) and 300-4,800 cm³ (D) - proportionally with an increase in quadrat area (0.5-8 m²). Frequency counts of C. sphaerocephalus were fitted to six probability distributions. The index of aggregation (b) for Taylor''s power law and Morisita''s index of dispersion were also calculated where appropriate. Twelve of nineteen of the sampling combinations were best described by negative binomial distribution (P = 0.05). Criconemella sphaerocephalus appeared more highly aggregated when sampled with constant soil core volumes (A and C) than from increasing soil core volumes (B and D) based on Taylor''s index of aggregation (b). Morisita''s index of dispersion indicated aggregation at the smallest quadrat area (0.5 m²) for all sampling occasions (A, B, C, D).     

Lifetime monogamy and the evolution of eusociality

All evidence currently available indicates that obligatory sterile eusocial castes only arose via the association of lifetime monogamous parents and offspring. This is consistent with Hamilton''s rule (br_s > r_oc), but implies that relatedness cancels out of the equation because average relatedness to siblings (r_s) and offspring (r_o) are both predictably 0.5. This equality implies that any infinitesimally small benefit of helping at the maternal nest (b), relative to the cost in personal reproduction (c) that persists throughout the lifespan of entire cohorts of helpers suffices to establish permanent eusociality, so that group benefits can increase gradually during, but mostly after the transition. The monogamy window can be conceptualized as a singularity comparable with the single zygote commitment of gametes in eukaryotes. The increase of colony size in ants, bees, wasps and termites is thus analogous to the evolution of multicellularity. Focusing on lifetime monogamy as a universal precondition for the evolution of obligate eusociality simplifies the theory and may help to resolve controversies about levels of selection and targets of adaptation. The monogamy window underlines that cooperative breeding and eusociality are different domains of social evolution, characterized by different sectors of parameter space for Hamilton''s rule.     

A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein.

It is well established that mutations in the presenilin 1 and 2 genes cause the majority of early onset Alzheimer's disease (AD). However, our understanding of the cellular functions of the proteins they encode remains rudimentary. Knowledge of proteins with which the presenilins interact should lead to a better understanding of presenilin function in normal and disease states. We report here the identification of a calcium-binding protein, calmyrin, that interacts preferentially with presenilin 2 (PS2). Calmyrin is myristoylated, membrane-associated, and colocalizes with PS2 when the two proteins are overexpressed in HeLa cells. Yeast two-hybrid liquid assays, affinity chromatography, and coimmunoprecipitation experiments confirm binding between PS2 and calmyrin. Functionally, calmyrin and PS2 increase cell death when cotransfected into HeLa cells. These results allude to several provocative possibilities for a dynamic role of calmyrin in signaling, cell death, and AD.     

Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL

Parkinson disease (PD)- and cancer-associated protein, DJ-1, mediates cellular protection via many signaling pathways. Deletions or mutations in the DJ-1 gene are directly linked to autosomal recessive early-onset PD. DJ-1 has potential roles in mitochondria. Here, we show that DJ-1 increases its mitochondrial distribution in response to ultraviolet B (UVB) irradiation and binds to Bcl-X(L). The interactions between DJ-1 and Bcl-X(L) are oxidation-dependent. DJ-1(C106A), a mutant form of DJ-1 that is unable to be oxidized, binds Bcl-X(L) much less than DJ-1 does. Moreover, DJ-1 stabilizes Bcl-X(L) protein level by inhibiting its ubiquitination and degradation through ubiquitin proteasome system (UPS) in response to UVB irradiation. Furthermore, under UVB irradiation, knockdown of DJ-1 leads to increases of Bcl-X(L) ubiquitination and degradation upon UVB irradiation, thereby increasing mitochondrial Bax, caspase-3 activation and PARP cleavage. These data suggest that DJ-1 protects cells against UVB-induced cell death dependent on its oxidation and its association with mitochondrial Bcl-X(L).     

Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer's patients with the Swedish APP 670/671 mutation

There is a significant flux of the neurotoxic oxysterol 27-hydroxycholesterol (27OHC) from the circulation across the blood-brain barrier. Because there is a correlation between 27OHC and cholesterol in the circulation and lipoprotein-bound cholesterol does not pass the blood-brain barrier, we have suggested that 27OHC may mediate the effects of hypercholesterolemia on the brain. We previously demonstrated a modest accumulation of 27OHC in brains of patients with sporadic Alzheimer's disease (AD), consistent with a role of 27OHC as a primary pathogenetic factor. We show here that there is a 4-fold accumulation of 27OHC in different regions of the cortexes of patients carrying the Swedish amyloid precursor protein (APPswe) 670/671 mutation. The brain levels of sitosterol and campesterol were not significantly different in the AD patients compared with the controls, suggesting that the blood-brain barrier was intact in the AD patients. We conclude that accumulation of 27OHC is likely to be secondary to neurodegeneration, possibly a result of reduced activity of CYP7B1, the neuronal enzyme responsible for metabolism of 27OHC. We discuss the possibility of a vicious circle in the brains of the patients with familial AD whereby neurodegenerative changes cause an accumulation of 27OHC that further accelerates neurodegeneration.     

What you feel is what you see: inverse dynamics estimation underlies the resistive sensation of a delayed cursor

How our central nervous system (CNS) learns and exploits relationships between force and motion is a fundamental issue in computational neuroscience. While several lines of evidence have suggested that the CNS predicts motion states and signals from motor commands for control and perception (forward dynamics), it remains controversial whether it also performs the ‘inverse’ computation, i.e. the estimation of force from motion (inverse dynamics). Here, we show that the resistive sensation we experience while moving a delayed cursor, perceived purely from the change in visual motion, provides evidence of the inverse computation. To clearly specify the computational process underlying the sensation, we systematically varied the visual feedback and examined its effect on the strength of the sensation. In contrast to the prevailing theory that sensory prediction errors modulate our perception, the sensation did not correlate with errors in cursor motion due to the delay. Instead, it correlated with the amount of exposure to the forward acceleration of the cursor. This indicates that the delayed cursor is interpreted as a mechanical load, and the sensation represents its visually implied reaction force. Namely, the CNS automatically computes inverse dynamics, using visually detected motions, to monitor the dynamic forces involved in our actions.     

Crystal structure of the E2 domain of amyloid precursor protein-like protein 1 in complex with sucrose octasulfate

Missense mutations in the amyloid precursor protein (APP) gene can cause familial Alzheimer disease. It is thought that APP and APP-like proteins (APLPs) may play a role in adhesion and signal transduction because their ectodomains interact with components of the extracellular matrix. Heparin binding induces dimerization of APP and APLPs. To help explain how these proteins interact with heparin, we have determined the crystal structure of the E2 domain of APLP1 in complex with sucrose octasulfate (SOS). A total of three SOS molecules are bound to the E2 dimer. Two SOSs are bound inside a narrow intersubdomain groove, and the third SOS is bound near the two-fold axis of the protein. Mutational analyses show that most residues interacting with SOS also contribute to heparin binding, although in varying degrees; a deep pocket, defined by His-376, Lys-422, and Arg-429, and an interfacial site between Lys-314 and its symmetry mate are most important in the binding of the negatively charged polysaccharide. Comparison with a lower resolution APP structure shows that all key heparin binding residues are conserved and identically positioned, suggesting that APLP1 and APP may bind heparin similarly. In transfected HEK-293 cells, mutating residues responsible for heparin binding causes little change in the proteolysis of APP by the secretases. However, mutating a pair of conserved basic residues (equivalent to Arg-414 and Arg-415 of APLP1) immediately adjacent to the heparin binding site affects both the maturation and the processing of APP.     

Branching habit and the allocation of reproductive resources in conifers

Background and Aims Correlated relationships between branch thickness, branch density, and twig and leaf size have been used extensively to study the evolution of plant canopy architecture, but fewer studies have explored the impact of these relationships on the allocation of reproductive resources. This study quantifies pollen cone production in conifers, which have similar basic reproductive biology but vary dramatically in branching habit, in order to test how differences in branch diameter influence pollen cone size and the density with which they are deployed in the canopy. Methods Measurements of canopy branch density, the number of cones per branch and cone size were used to estimate the amount of pollen cone tissues produced by 16 species in three major conifer clades. The number of pollen grains produced was also estimated using direct counts from individual pollen cones. Key Results The total amount of pollen cone tissues in the conifer canopy varied little among species and clades, although vegetative traits such as branch thickness, branch density and pollen cone size varied over several orders of magnitude. However, branching habit controls the way these tissues are deployed: taxa with small branches produce small pollen cones at a high density, while taxa with large branches produce large cones relatively sparsely. Conclusions Conifers appear to invest similar amounts of energy in pollen production independent of branching habit. However, similar associations between branch thickness, branch density and pollen cone size are seen across conifers, including members of living and extinct groups not directly studied here. This suggests that reproductive features relating to pollen cone size are in large part a function of the evolution of vegetative morphology and branching habit.     

Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain

Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer''s disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer''s, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.