The very early evolution of protein translocation across membranes

In this study, we used a computational approach to investigate the early evolutionary history of a system of proteins that, together, embed and translocate other proteins across cell membranes. Cell membranes comprise the basis for cellularity, which is an ancient, fundamental organizing principle shared by all organisms and a key innovation in the evolution of life on Earth. Two related requirements for cellularity are that organisms are able to both embed proteins into membranes and translocate proteins across membranes. One system that accomplishes these tasks is the signal recognition particle (SRP) system, in which the core protein components are the paralogs, FtsY and Ffh. Complementary to the SRP system is the Sec translocation channel, in which the primary channel-forming protein is SecY. We performed phylogenetic analyses that strongly supported prior inferences that FtsY, Ffh, and SecY were all present by the time of the last universal common ancestor of life, the LUCA, and that the ancestor of FtsY and Ffh existed before the LUCA. Further, we combined ancestral sequence reconstruction and protein structure and function prediction to show that the LUCA had an SRP system and Sec translocation channel that were similar to those of extant organisms. We also show that the ancestor of Ffh and FtsY that predated the LUCA was more similar to FtsY than Ffh but could still have comprised a rudimentary protein translocation system on its own. Duplication of the ancestor of FtsY and Ffh facilitated the specialization of FtsY as a membrane bound receptor and Ffh as a cytoplasmic protein that could bind nascent proteins with specific membrane-targeting signal sequences. Finally, we analyzed amino acid frequencies in our ancestral sequence reconstructions to infer that the ancestral Ffh/FtsY protein likely arose prior to or just after the completion of the canonical genetic code. Taken together, our results offer a window into the very early evolutionary history of cellularity.     

Ideological Language in the Transformation of Identity

Christians who have undergone conversion experiences usually claim that the experience has not only strengthened their religious commitment, it has in addition transformed their lives. The idea that a person may be transformed through using a set of symbols (called an "ideology" here) is not limited to Christianity; many ideologies make similar claims. Using the example of the conversion experience, I argue that ideologies may indeed create a sense of self-transformation in the subject. This sense arises out of the fact that the subject is able to use the ideological language to resolve enduring problems of meaning in his or her life. Such problems are not, however, resolved once and for all; rather, the discourse of informants reveals that self-transformation is an ongoing process wherein ideological language is used to express and come to terms with persisting emotional ambivalence.     

Resilience,Restoration, and Riparian Ecosystems: Case Study of a Dryland,Urban River

Resilient systems can absorb disturbance and persist despite variability as long as the capacity of the system to adapt is not exceeded. Riparian plant communities of dryland alluvial rivers are expected to be naturally resilient systems because they persist in the highly variable floodplain. River modification has altered the flow regime on many dryland rivers, in some cases exceeding the adaptive capacity of the riparian vegetation, but these changes may be readily reversible. The Salt River in Phoenix, Arizona has been impounded, dewatered, channelized, but also re‐watered with urban effluent and storm drain runoff. To determine whether riparian vegetation is resilient to these various perturbations, paired comparisons were made in the vegetation and seed bank between a non‐diverted reference reach, a diverted reach, and a re‐watered urban reach. In the diverted reach, composition had shifted to that of a stress tolerant xeroriparian shrubland with low diversity in both the seed bank and extant vegetation. Most surprisingly, few differences were observed in the composition and structure of the vegetation and soil seed banks between the reference reach and the urban reach, particularly in the wet patches, suggesting that hydric riparian plant communities have the capacity to adapt to these modified conditions. These results provide support for a process‐oriented approach to restoration on the Salt River and other urban dryland rivers using patches of persisting vegetation as models for achievable restoration targets.     

Proteomic analysis of endothelial cold-adaptation

Background

Milkweeds (Asclepias L.) have been extensively investigated in diverse areas of evolutionary biology and ecology; however, there are few genetic resources available to facilitate and compliment these studies. This study explored how low coverage genome sequencing of the common milkweed (Asclepias syriaca L.) could be useful in characterizing the genome of a plant without prior genomic information and for development of genomic resources as a step toward further developing A. syriaca as a model in ecology and evolution.

Results

A 0.5× genome of A. syriaca was produced using Illumina sequencing. A virtually complete chloroplast genome of 158,598 bp was assembled, revealing few repeats and loss of three genes: accD, clpP, and ycf1. A nearly complete rDNA cistron (18S-5.8S-26S; 7,541 bp) and 5S rDNA (120 bp) sequence were obtained. Assessment of polymorphism revealed that the rDNA cistron and 5S rDNA had 0.3% and 26.7% polymorphic sites, respectively. A partial mitochondrial genome sequence (130,764 bp), with identical gene content to tobacco, was also assembled. An initial characterization of repeat content indicated that Ty1/copia-like retroelements are the most common repeat type in the milkweed genome. At least one A. syriaca microread hit 88% of Catharanthus roseus (Apocynaceae) unigenes (median coverage of 0.29×) and 66% of single copy orthologs (COSII) in asterids (median coverage of 0.14×). From this partial characterization of the A. syriaca genome, markers for population genetics (microsatellites) and phylogenetics (low-copy nuclear genes) studies were developed.

Conclusions

The results highlight the promise of next generation sequencing for development of genomic resources for any organism. Low coverage genome sequencing allows characterization of the high copy fraction of the genome and exploration of the low copy fraction of the genome, which facilitate the development of molecular tools for further study of a target species and its relatives. This study represents a first step in the development of a community resource for further study of plant-insect co-evolution, anti-herbivore defense, floral developmental genetics, reproductive biology, chemical evolution, population genetics, and comparative genomics using milkweeds, and A. syriaca in particular, as ecological and evolutionary models.     

Trapped in a vicious loop: Toll-like receptors sustain the spontaneous cytokine production by rheumatoid synovium

Synovial tissue of patients with rheumatoid arthritis (RA) spontaneously produces several cytokines, of which a fundamental role in joint inflammation and destruction has been established. However, the factors sustaining this phenomenon remain poorly understood. In a recent report, blockade of Toll-like receptor 2 (TLR2) was found to inhibit the spontaneous release of inflammatory cytokines by intact RA synovial explant cultures. Adding to the recent evidence implicating other TLRs (in particular, TLR4), this observation highlights the potential of TLRs as therapeutic targets to suppress the local production of multiple cytokines and to control the chronic inflammatory loop in RA.     

Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis

The severity and mortality rates of acute pancreatitis (AP) are significantly elevated in the elderly population. However, due to a lack of appropriate animal models, the underlying mechanisms for this age‐dependent vulnerability remain largely unknown. The purpose of this study was to characterize a murine model of AP, which displays age‐associated severity, and to use this model to identify pathophysiologies that are distinctive of the aged with AP. AP was induced in young (4–5 months), middle‐aged (12–13 months), and aged (23–25 months) C57BL/6 mice by repeated injection of caerulein, a homologue of the gastrointestinal hormone cholecystokinin. Approximately 10% of aged mice died during AP, while young and middle‐aged mice showed no mortality. Although both young and aged mice exhibited early signs of edema and inflammation in the pancreas, kidney, and lung, young mice showed signs of recovery within 24 h, while aged mice exhibited increasingly severe tissue damage and cell death. There was a significant age‐dependent increase in pancreatic neutrophil activation and systemic inflammation as assessed by pancreatic myeloperoxidase and plasma interleukin‐6 (IL‐6) concentration, respectively. Importantly, aged but not young mice with AP showed significantly elevated thrombosis in the lung and kidney as well as a marked increase in plasma concentration of plasminogen activator inhibitor‐1 (PAI‐1), a primary inhibitor of the fibrinolytic system. These results demonstrate that aging is associated with increased severity of AP characterized by augmented and prolonged pancreatic inflammation and the presence of multiple extra‐pancreatic sequelae including thrombosis.