Gender-specific reproductive tissue in ratites and Tyrannosaurus rex

Unambiguous indicators of gender in dinosaurs are usually lost during fossilization, along with other aspects of soft tissue anatomy. We report the presence of endosteally derived bone tissues lining the interior marrow cavities of portions of Tyrannosaurus rex (Museum of the Rockies specimen number 1125) hindlimb elements, and we hypothesize that these tissues are homologous to specialized avian tissues known as medullary bone. Because medullary bone is unique to female birds, its discovery in extinct dinosaurs solidifies the link between dinosaurs and birds, suggests similar reproductive strategies, and provides an objective means of gender differentiation in dinosaurs.     

APOBEC-mediated editing of viral RNA

Retroviral DNA can be subjected to cytosine-to-uracil editing through the action of members of the APOBEC family of cytidine deaminases. Here we demonstrate that APOBEC-mediated cytidine deamination of human immunodeficiency virus (HIV) virion RNA can also occur. We speculate that the natural substrates of the APOBEC enzymes may extend to RNA viruses that do not replicate through DNA intermediates. Thus, cytosine-to-uracil editing may contribute to the sequence diversification of many viruses.     

Pyogenic bacterial infections in humans with MyD88 deficiency

MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.     

The shaping of modern human immune systems by multiregional admixture with archaic humans

Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.     

Foundering lithosphere imaged beneath the southern Sierra Nevada, California, USA

Seismic tomography reveals garnet-rich crust and mantle lithosphere descending into the upper mantle beneath the southeastern Sierra Nevada. The descending lithosphere consists of two layers: an iron-rich eclogite above a magnesium-rich garnet peridotite. These results place descending eclogite above and east of high P wave speed material previously imaged beneath the southern Great Valley, suggesting a previously unsuspected coherence in the lithospheric removal process.     

Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin

Environmental temperature is thought to be directly sensed by neurons through their projections in the skin. A subset of the mammalian transient receptor potential (TRP) family of ion channels has been implicated in this process. These "thermoTRPs" are activated at distinct temperature thresholds and are typically expressed in sensory neurons. TRPV3 is activated by heat (>33 degrees C) and, unlike most thermoTRPs, is expressed in mouse keratinocytes. We found that TRPV3 null mice have strong deficits in responses to innocuous and noxious heat but not in other sensory modalities; hence, TRPV3 has a specific role in thermosensation. The natural compound camphor, which modulates sensations of warmth in humans, proved to be a specific activator of TRPV3. Camphor activated cultured primary keratinocytes but not sensory neurons, and this activity was abolished in TRPV3 null mice. Therefore, heat-activated receptors in keratinocytes are important for mammalian thermosensation.