Recrafting the neighbor-joining method

Background  

The neighbor-joining method by Saitou and Nei is a widely used method for constructing phylogenetic trees. The formulation of the method gives rise to a canonical Θ(n ³) algorithm upon which all existing implementations are based.     

Identification of Bacillus anthracis proteins associated with germination and early outgrowth by proteomic profiling of anthrax spores

The use of anthrax spores as a bioweapon has spurred efforts aimed at identifying key proteins expressed in Bacillus anthracis. Because spore germination and outgrowth occur prior to and are required for disease manifestations, blocking germination and early outgrowth with novel vaccines or inhibitors targeting critical B. anthracis germination and outgrowth-associated factors is a promising strategy in mitigating bioterror. By screening 587 paired protein spots that were isolated from dormant and germinating anthrax spores, respectively, we identified 10 spore proteins with statistically significant germination-associated increases and decreases. It is likely that proteins whose levels change during germination may play key roles in the germination and outgrowth processes, and they should be listed as priority targets for development of prophylactic and therapeutic agents against anthrax. The 31 new proteins identified in this study also complement an emerging proteomic database of B. anthracis.     

Taphonomic analysis of skeletal remains from chimpanzee hunts at Ngogo, Kibale National Park, Uganda

This study provides a taphonomic analysis of the largest known sample of bone fragments collected from chimpanzee hunts. The entire sample consists of 455 bone fragments from 57 chimpanzee hunting episodes of 65 prey individuals at Ngogo, Kibale National Park, Uganda. It has low taxonomic diversity, consisting overwhelmingly of primates, especially red colobus monkeys. The age distribution of the prey remains is skewed towards pre-adults. Cranial bones are the dominant element, followed by long bones. Axial postcranial elements have low survivorship, with a complete absence of pre-caudal vertebrae. Bone is damaged in distinct ways, such as: destruction of long bone ends, typically with intact but chewed shafts; fragmentation and compression cracking of crania; and preservation of only the iliac blades of the innominates. Tooth marks are present but uncommon (4.4% of total NISP). These analyses enable us to: 1) describe and characterize consistent patterns of bone damage inflicted by chimpanzees across a much larger prey sample than has been previously studied; 2) make a preliminary comparison of the generalized chimpanzee taphonomic signature to that of leopard and eagle consumption of primates, as well as modern human consumption of small mammals; and 3) assess the utility of such samples for recognition of early hominin small mammal carnivory. We present a model that may be useful for detecting a pre-technological hominin carnivory and suggest some fossil locales at which close inspection of cercopithecoid remains for the above patterns might reveal traces of hominin hunting, though we caution that a pre-technological hominin hunted "assemblage" is not likely to be archaeologically visible.     

Differential Effect of Nimodipine in Attenuating Iron-Induced Toxicity in Brain- and Blood–Brain Barrier-Associated Cell Types

Metal homeostasis is increasingly being evaluated as a therapeutic target in stroke and neurodegenerative diseases. Metal dysregulation has been shown to lead to protein aggregation, plaque formation and neuronal death. In 2007, we first reported that voltage-gated calcium channels act as a facile conduit for the entry of free ferrous (Fe²⁺) ions into neurons. Herein, we evaluate differential iron toxicity to central nervous system cells and assess the ability of the typical L-type voltage-gated calcium channel blocker nimodipine to attenuate iron-induced toxicity. The data demonstrate that iron sulfate induces a dose-dependent decrease in cell viability in rat brain endothelial cells (RBE4; LC₅₀ = 150 μM), neuronal cells (Neuro-2α neuroblastoma; LC₅₀ = 400 μM), and in astrocytes (DI TNC1; LC₅₀ = 1.1 mM). Pre-treatment with nimodipine prior to iron sulfate exposure provided a significant (P < 0.05) increase in viable cell numbers for RBE4 (2.5-fold), Neuro2-α (~2-fold), and nearly abolished toxicity in primary neurons. Astrocytes were highly resistant to iron toxicity compared to the other cell types tested and nimodipine had no (P > 0.05) protective effect in these cells. The data demonstrate variable susceptibility to iron overload conditions in different cell types of the brain and suggest that typical L-type voltage-gated calcium channel blockers (here represented by nimodipine), may serve as protective agents in conditions involving iron overload, particularly in cell types highly susceptible to iron toxicity.     

A fossil hominoid proximal femur from Kikorongo Crater, southwestern Uganda

The external morphology of a fragmentary right proximal femur from southwestern Uganda is described here. Discovered in the Kikorongo Crater of Queen Elizabeth National Park in 1961, this specimen was informally assigned to Homo sapiens (although never described) and tentatively dated to the late Pleistocene. However, because aspects of the external morphology of the femur align the fossil with the African great apes, we suggest that the Kikorongo femur may be the first postcranial fossil of the genus Pan. Like the African apes, the Kikorongo specimen lacks both an obturator externus groove and an intertrochanteric line. It has a short femoral neck with a circular cross section, and a narrow and deep superior notch. Using resampling statistics and discriminant function analysis, the Kikorongo femur clustered with the genus Pan, as opposed to Gorilla or Homo. However, if the specimen is from Pan, it would be large for this taxon. Furthermore, features that clearly distinguish the external morphology of Plio-Pleistocene hominin proximal femora from African ape femora, such as the shape of the femoral neck in cross section and femoral neck length, have converged in Holocene humans and African apes. Unfortunately, the internal morphology of the femoral neck of the Kikorongo fossil was not discernable. Although we hypothesize that the Kikorongo femur is from the genus Pan, there is such variability in the proximal femora of modern humans that, although it would be an unusual human, it remains possible that this fossil represents H. sapiens.     

Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation

Abstract. Objectives: Mesotheliomas occur in occult serous cavities after chronic exposure of mesothelial cells to asbestos fibres. Molecular events that contribute to the development of this cancer are therefore not readily accessible for study. We have used in vitro culture systems to study and compare induced and spontaneous transformation events in primary mouse mesothelial cells. Materials and methods: Mouse mesothelial cells were cultivated until small populations of proliferating cells emerged from senescing cultures. Spontaneously transformed cultures of cells were characterized and compared to malignantly transformed cells. Results: Human mesothelial cells had a finite lifespan of 10–15 population doublings when cultured in vitro; mouse mesothelial cells typically exhibit this same pattern. Here, we show that mouse mesothelial cells can be cultured for extended periods and that these cells can transform spontaneously. Lines of spontaneously transformed cells generated in this study are immortal and growth factor‐independent. They display the salient characteristic features of transformation, including increased proliferation rate, lack of contact inhibition, aneuploidy and ability to grow in anchorage‐independent conditions. A subset of these cell lines developed into tumours in syngeneic mice. Comparative gene expression analysis demonstrated that spontaneously transformed cell lines were more closely related to neoplastic cells than to primary cells. Conclusion: These findings have implications for interpretation of in vitro transformation studies, demonstrating broad similarity between spontaneous and induced genetic changes.     

CoaSim: A flexible environment for simulating genetic data under coalescent models

Background  

Coalescent simulations are playing a large role in interpreting large scale intra-specific sequence or polymorphism surveys and for planning and evaluating association studies. Coalescent simulations of data sets under different models can be compared to the actual data to test the importance of different evolutionary factors and thus get insight into these.