Molecular evidence of an African Phiomorpha-South American Caviomorpha clade and support for Hystricognathi based on the complete mitochondrial genome of the cane rat (Thryonomys swinderianus)

The complete mitochondrial genome of an African cane rat, Thryonomys swinderianus (Rodentia, Hystricognathi), was included in a phylogenetic analysis along with 4 rodents, 14 additional eutherians, and 3 noneutherian outgroups. Monophyly of the suborder Hystricognathi, represented by the cane rat and the South American guinea pig, Cavia porcellus, was strongly supported by maximum-parsimony, neighbor-joining, and maximum-likelihood methods. The molecular-based estimate of the divergence time of Old and New World Hystricognathi (approximately 85 million years before present, MYBP) is consistent with an hypothesis of vicariance divergence due to the rifting of the African and South American continents 86-100 MYBP. Monophyly of Rodentia or the superordinal clade Glires (Rodentia and Lagomorpha) were not supported.     

Exploring the Potential Use of Seismic Waves as a Communication Channel by Elephants and Other Large Mammals

Bioseismic studies have previously documented the use of seismicstimuli as a method of communication in arthropods and smallmammals. Seismic signals are used to communicate intraspecificallyin many capacities such as mate finding, spacing, warning, resourceassessing, and in group cohesion. Seismic signals are also usedin interspecific mutualism and as a deterrent to predators.Although bioseismics is a significant mode of communicationthat is well documented for relatively small vertebrates, thepotential for seismic communication has been all but ignoredin large mammals. In this paper, we describe two modes of producingseismic waves with the potential for long distance transmission:1) locomotion by animals causing percussion on the ground and2) acoustic, seismic-evoking sounds that couple with the ground.We present recordings of several mammals, including lions, rhinoceroses,and elephants, showing that they generate similar acoustic andseismic vibrations. These large animals that produce high amplitudevocalizations are the most likely to produce seismic vibrationsthat propagate long distances. The elephant seems to be themost likely candidate to engage in long distance seismic communicationdue to its size and its high amplitude, low frequency, relativelymonotonic vocalizations that propagate in the ground and havethe potential to travel long distances. We review particularanatomical features of the elephant that would facilitate thedetection of seismic waves. We also assess low frequency soundsin the environment such as thunder and the likelihood of seismictransmission. In addition, we present the potential role ofseismic stimuli in human communication as well as the impactof modern anthropogenic effects on the seismic environment.     

The mitochondrial genome of the pufferfish,Fugu rubripes,and ordinal teleostean relationships

The small nuclear genome of the pufferfish, Fugu rubripes (order Tetraodontiformes), makes this species highly interesting for genome research. In order to establish the phylogenetic position of the Tetraodontiformes relative to other teleostean orders that might also have a reduced nuclear genome size, we have sequenced the mitochondrial (mt) genome of the pufferfish. The gene order, nucleotide composition and evolutionary rate of the mt genome of the fugu correspond to those of other teleosts. This suggests that the evolution of this genome has not been affected by the processes that led to the dramatic reduction of the size of the nuclear genome of the fugu. The phylogenetic analyses, which were based on the concatenated amino acid sequences of twelve protein-coding mt genes, placed the fugu among the percomorphs. The affinities between the Tetraodontiformes and either the Perciformes or the Zeiformes were limited, however. The common notion of a separate euteleostean clade remained unsupported. The analyses did not support the traditional systematic understanding that the Clupeiformes constitute a basal teleostean lineage. In addition the findings strongly suggest that three teleostean orders, the Perciformes, Zeiformes and Scorpaeniformes, are paraphyletic.     

Aldosterone suppresses expression of an avian colonic sodium-glucose cotransporter

Transport in the colon of the domestic fowl switches from sodium-linked hexose and amino acid cotransport on high-salt intake to amiloride-sensitive sodium channel expression on low-salt (LS) diets. The present experiments were designed to investigate the role of aldosterone in suppression of the colonic sodium-glucose luminal cotransporter (SGLT). LS-adapted hens were resalinated with or without simultaneous aldosterone treatment. Changes in the electrophysiological responses and SGLT protein expression levels were examined at 1, 3, and 7 days of treatment. Serum aldosterone levels fell from approximately 400 pmol/l in LS-adapted hens to values below the detection limit (<44 pmol/l) after 1 day of resalination. At the same time, glucose-stimulated short circuit current (I(SC)) increased from 20.9 +/- 8.7 to 56.3 +/- 15.5 microA/cm(2), whereas amiloride-sensitive I(SC) decreased from -68.9 +/- 12.7 microA/cm(2) on LS to +0.6 +/- 12.0 microA/cm(2). Glucose-stimulated I(SC) increased further at 3 and 7 days of resalination, whereas amiloride-sensitive I(SC) remained suppressed. When resalinated birds were simultaneously treated with aldosterone, the LS pattern of high amiloride-sensitive I(SC) and low glucose-stimulated I(SC) was maintained. Immunoblotting results from the same tissues demonstrated that SGLT-like protein expression increased following resalination. Aldosterone treatment completely blocked this effect. These results demonstrate that aldosterone suppresses both activity and protein expression of hen colonic SGLT. Resalination either through decreased aldosterone or other factors may be able to activate SGLT activity independently of increases in protein expression.     

The Laptev Sea walrus Odobenus rosmarus laptevi: an enigma revisited

The walrus ( Odobenus rosmarus ) is in some current systematic schemes divided into three subspecies: O. r. rosmarus in the North Atlantic, O.   r. divergens in the North Pacific and O.   r. laptevi in the Laptev Sea. These three subspecies have been described as differing in body size, but the taxonomic status of O.   r. laptevi is disputed. The current study applies molecular and morphometric methods to assess the taxonomic status of O.   r. laptevi and to analyse the systematic and phylogeographic relationships between the three purported walrus subspecies. Tusk length and tusk circumference were measured from the few skulls available of O.   r. laptevi , and the obtained values were within the ranges reported for Pacific walruses. Thus, morphologically, subspecies status for O.   r. laptevi is not supported according to the Amadon–Mayr '75% rule'. Phylogenetic analyses and haplotype networks based on mitochondrial nucleotide sequence data of NADH dehydrogenase 1, 16S rRNA, cytochrome oxidase I and the d -loop of the control region of the historic O.   r. laptevi bone material and contemporary O.   r. rosmarus and O.   r. divergens showed that the Laptev Sea walrus groups with individuals from the North Pacific. Thus, the mitochondrial sequence data do not support the recognition of three walrus subspecies as reciprocally monophyletic evolutionary units with independent evolutionary histories. Only O.   r. rosmarus and O.   r. divergens meet this criterion with the present sampling. Accordingly, we recommend that Odobenus r. laptevi be abandoned and the Laptev walrus instead be recognized as the westernmost population of the Pacific walrus, Odobenus r. divergens. However, further research is recommended to assess whether the Laptev walrus could be considered as a significant unit in terms of conservation and management, since it is unique in several ecological parameters.     

A Genome Scale Screen for Mutants with Delayed Exit from Mitosis: Ire1-Independent Induction of Autophagy Integrates ER Homeostasis into Mitotic Lifespan

Proliferating eukaryotic cells undergo a finite number of cell divisions before irreversibly exiting mitosis. Yet pathways that normally limit the number of cell divisions remain poorly characterized. Here we describe a screen of a collection of 3762 single gene mutants in the yeast Saccharomyces cerevisiae, accounting for 2/3 of annotated yeast ORFs, to search for mutants that undergo an atypically high number of cell divisions. Many of the potential longevity genes map to cellular processes not previously implicated in mitotic senescence, suggesting that regulatory mechanisms governing mitotic exit may be broader than currently anticipated. We focused on an ER-Golgi gene cluster isolated in this screen to determine how these ubiquitous organelles integrate into mitotic longevity. We report that a chronic increase in ER protein load signals an expansion in the assembly of autophagosomes in an Ire1-independent manner, accelerates trafficking of high molecular weight protein aggregates from the cytoplasm to the vacuoles, and leads to a profound enhancement of daughter cell production. We demonstrate that this catabolic network is evolutionarily conserved, as it also extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data provide evidence that catabolism of protein aggregates, a natural byproduct of high protein synthesis and turn over in dividing cells, is among the drivers of mitotic longevity in eukaryotes.     

Tumor-Targeted Human T Cells Expressing CD28-Based Chimeric Antigen Receptors Circumvent CTLA-4 Inhibition

Adoptive T cell therapy represents a promising treatment for cancer. Human T cells engineered to express a chimeric antigen receptor (CAR) recognize and kill tumor cells in a MHC-unrestricted manner and persist in vivo when the CAR includes a CD28 costimulatory domain. However, the intensity of the CAR-mediated CD28 activation signal and its regulation by the CTLA-4 checkpoint are unknown. We investigated whether T cells expressing an anti-CD19, CD3 zeta and CD28-based CAR (19-28z) displayed the same proliferation and anti-tumor abilities than T cells expressing a CD3 zeta-based CAR (19z1) costimulated through the CD80/CD28, ligand/receptor pathway. Repeated in vitro antigen-specific stimulations indicated that 19-28z⁺ T cells secreted higher levels of Th1 cytokines and showed enhanced proliferation compared to those of 19z1⁺ or 19z1-CD80⁺ T cells. In an aggressive pre-B cell leukemia model, mice treated with 19-28z⁺ T cells had 10-fold reduced tumor progression compared to those treated with 19z1⁺ or 19z1-CD80⁺ T cells. shRNA-mediated CTLA-4 down-regulation in 19z1-CD80⁺ T cells significantly increased their in vivo expansion and anti-tumor properties, but had no effect in 19-28z⁺ T cells. Our results establish that CTLA-4 down-regulation may benefit human adoptive T cell therapy and demonstrate that CAR design can elude negative checkpoints to better sustain T cell function.     

Resolving the root of the avian mitogenomic tree by breaking up long branches

Incomplete taxon sampling has been a major problem in resolving the early divergences in birds. Five new mitochondrial genomes are reported here (brush-turkey, lyrebird, suboscine flycatcher, turkey vulture, and a gull) and three break up long branches that tended to attract the distant reptilian outgroup. These long branches were to galliforms, and to oscine and suboscine passeriformes. Breaking these long branches leaves the root, as inferred by maximum likelihood and Bayesian phylogenetic analyses, between paleognaths and neognaths. This means that morphological, nuclear, and mitochondrial data are now in agreement on the position of the root of the avian tree and we can, move on to other questions. An overview is then given of the deepest divisions in the mitogenomic tree inferred from complete mitochondrial genomes. The strict monophyly of both the galloanseres and the passerines is strongly supported, leaving the deep six-way split within Neoaves as the next major question for which resolution is still lacking. Incomplete taxon sampling was also a problem for Neoaves, and although some resolution is now available there are still problems because current phylogenetic methods still fail to account for real features of DNA sequence evolution.     

Mitogenomic Analyses Place the Gharial (Gavialis gangeticus) on the Crocodile Tree and Provide Pre-K/T Divergence Times for Most Crocodilians

Based on morphological analyses, extant members of the order Crocodylia are divided into three families, Alligatoridae, Crocodylidae, and Gavialidae. Gavialidae includes one species, the gharial, Gavialis gangeticus. In this study we have examined crocodilian relationships in phylogenetic analyses of seven mitochondrial genomes that have been sequenced in their entirety. The analyses did not support the morphologically acknowledged separate position of the gharial in the crocodilian tree. Instead the gharial joined the false gharial (Tomistoma schlegelii) on a common branch that was shown to constitute a sister group to traditional Crocodylidae (less Tomistoma). Thus, the analyses suggest the recognition of only two Crocodylia families, Alligatoridae and Crocodylidae, with the latter encompassing traditional Crocodylidae plus Gavialis/Tomistoma. A molecular dating of the divergence between Alligatoridae and Crocodylidae suggests that this basal split among recent crocodilians took place ≈140 million years before present, at the Jurassic/Cretaceous boundary. The results suggest that at least five crocodilian lineages survived the mass extinction at the KT boundary. [Reviewing Editor: Dr. Nicolas Galtier]