Evolutionary theory and the ultimate-proximate distinction in the human behavioral sciences

To properly understand behavior, we must obtain both ultimate and proximate explanations. Put briefly, ultimate explanations are concerned with why a behavior exists, and proximate explanations are concerned with how it works. These two types of explanation are complementary and the distinction is critical to evolutionary explanation. We are concerned that they have become conflated in some areas of the evolutionary literature on human behavior. This article brings attention to these issues. We focus on three specific areas: the evolution of cooperation, transmitted culture, and epigenetics. We do this to avoid confusion and wasted effort—dangers that are particularly acute in interdisciplinary research. Throughout this article, we suggest ways in which misunderstanding may be avoided in the future

Automatic Extraction of Quranic Lexis Representing Two Different Notions of Linguistic Salience: Keyness and Prosodic Prominence

This paper presents two sets of lexical items automatically extracted from the Arabic Qur’ān, and denoting two different notions of linguistic salience: keyness and prosodic prominence. Our novel hypothesis investigates a possible correlation between them. Our novel findings discover distributionally significant keywords that also occur strategically in phrase‐final position so as to maximise their prominence, and thus meaningfulness, for reader, reciter, and aural recipient. Our methodology first computes Quranic keywords via the Corpus Linguistics technique of Keyword Extraction, and maps them to major Quranic themes in Islamic scholarship. Next, we implement a bespoke algorithm for rule-based capture of words annotated with madd or prolongation, a specific type of prosodic highlighting in Quranic recitation rules or tajwīd. We find it especially interesting that the concept of final syllable lengthening (madd before pause) is encoded in tajwīid and effectively demarcates phrase boundaries in the Qur’ān. We concentrate on nominal keywords (i.e. nouns and adjectives) since these are more likely to be aligned with phrase edges and to bear the hallmarks of pre-boundary lengthening. This correlation between keyness and prominence occurs 43.29% of the time in our data, since 526 keywords appear in our extracted subset of nominal types tagged with madd before pause: ((526/1215)*100). Finally, we identify which Quranic keywords are most likely to be annotated with enhanced prolongation in the final syllable before pause, using an easy-to-interpret, single value metric: the Laplace Point Estimate. Keywords that emerge as semantically weighted in terms of both distributional and prosodic significance are most likely to reflect the Quranic themes of God, Nature, and Eschatology

In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression

April 1, 2010Mouse models have markedly improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss-of-function screening to mouse models of cancer. Specifically, we have been able to introduce a library of shRNAs into individual mice using transplantable Eμ-myc lymphoma cells. This approach has allowed us to screen nearly 1,000 genetic alterations in the context of a single tumor-bearing mouse. These experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo. Validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of two of these targets, Rac2 and twinfilin, potentiated the action of the front-line chemotherapeutic vincristine, suggesting a critical relationship between cell motility and tumor relapse in hematopoietic malignancies.National Institutes of Health (U.S.) (RO1 CA128803-01)Massachusetts Institute of Technology. Dept. of Biology (Training Grant)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramNational Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967

A new bivalve fauna from the Permian-Triassic boundary section of southwestern China

A new marine bivalve fauna from the continuous Upper Permian Longtan Formation to Lower Triassic Yelang Formation of the Zhongzai section in southwestern China is documented. Four bivalve assemblages spanning the Permian–Triassic boundary are recognized and regionally correlated in South China. The bivalve assemblages changed from elements dominated by Palaeozoic types to those dominated by Mesozoic types. Three new species, Claraia zhongzaiensis sp. nov., Claraia sp. nov. 1 and Claraia sp. nov. 2, are described

A novel piggybac transposon inducible expression system identifies a role for akt signalling in primordial germ cell migration

In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development

A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress

Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs. We show that oxaliplatin, unlike cisplatin and carboplatin, does not kill cells through the DNA-damage response. Rather, oxaliplatin kills cells by inducing ribosome biogenesis stress. This difference in drug mechanism explains the distinct clinical implementation of oxaliplatin relative to cisplatin, and it might enable mechanistically informed selection of distinct platinum drugs for distinct malignancies. These data highlight the functional diversity of core components of front-line cancer therapy and the potential benefits of applying a mechanism-based rationale to the use of our current arsenal of anti-cancer drugs

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible ‘knockdown’ mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3–4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin−5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder

Sex and sexuality: An evolutionary view

In this article, I first offer a summary of Darwin’s main ideas, especially relating to sex, and explain how these have been elaborated by more recent evolutionary scholars. I then give an account of the historical divergence between psychoanalysis and classical Darwinian thought, and describe how the early psychoanalyst Sabina Spielrein tried to counter this by addressing some biological themes in her work. Following a review of some contemporary attempts to bring psychoanalysis and evolutionary thought into alignment with each other, I make some suggestions regarding a view of sex and sexuality that would be sound in evolutionary terms while also being helpful in psychoanalytic ones

Suppression of Lung Adenocarcinoma Progression by Nkx2-1

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limitsmetastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

Correction: AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community