REGULATION OF P GRANULES BY THE DISORDERED PROTEIN MEG-3

C. elegans P granules are RNA granules which form in the zygote and are preferentially segregated to the germ cell lineage as the embryo develops. Formation of P granules in the embryo requires the intrinsically disordered protein MEG-3 and its close paralog MEG-4. In the absence of MEG-3/4, many protein and RNA components of the germ plasm are not properly concentrated in the embryonic germ cells. Consequently meg-3 meg-4 worms are approximately 30% sterile. In this study we use genome editing at the endogenous locus as well as in vitro techniques to perform a structure-function analysis of MEG-3. In the course of this work, we have greatly expanded our ability to perform genome editing in C. elegans. We find that the long N-terminal intrinsically disordered region (IDR) of MEG-3 is necessary and sufficient to bind RNA in vitro, while in vivo the IDR is required enrich MEG-3 in the germ lineage. The C-terminus of MEG-3 is required both to form granules in vivo and to bind to PGL-1 and PGL-3, two protein components of P granules. We also identify a region within the C-terminus of MEG-3 with homology to HMG-box domains. By mutating four amino acids within this HMG-like motif, we completely disrupted the MEG-PGL interaction in vivo. Finally, the MEG-3 IDR, C-terminus and HMG-like motif are all required to enrich mRNAs in the germline and protect them from degradation. This study provides evidence for a greater role of globular protein-protein interaction domains in the assembly of RNA granule

The State of the Birds 2011 Report on Public Lands and Waters: United States of America

Foreword Public Lands and Waters Are Essential for Birds Each year, the State of the Birds report provides important scientific data to a broad audience with a call to action to improve the conservation status of birds and the environment. This year’s report brings attention to the tremendous promise of public lands and waters for conserving America’s wildlife and habitats. The United States has a long history of conservation on public lands. More than one-third of U.S. lands and all of our oceans are publicly owned, including some of our nation’s most spectacular natural areas. These habitats support more than 1,000 bird species, one-third of which are endangered, threatened, or of conservation concern. In 1864, President Abraham Lincoln established Yosemite as the first park set aside by the federal government specifically for public use and preservation. As environmental exploitation continued across unprotected lands, the Passenger Pigeon, once the world’s most abundant bird, was driven to extinction in the wild by the turn of the century. Recognizing that this loss meant “mankind was just so much poorer,” President Theodore Roosevelt championed the irreplaceable value of birds and other wildlife, and set aside 80 million acres for public land conservation, including the first National Wildlife Refuge in 1903. Today, more than 850 million acres of land and 3.5 million square miles of ocean are publicly owned, including more than 245 million acres managed by the Bureau of Land Management, 6,000 State Park units, 1,600 Marine Protected Areas, 550 National Wildlife Refuges, 350 military installations, 150 National Forests, and nearly 400 National Park Service units. These areas support our native bird species, many of which are declining, as described in the 2009 and 2010 State of the Birds reports. This year’s report provides the nation’s first assessment of the distribution of birds on public lands and helps public agencies identify which species have significant potential for conservation in each habitat. This assessment used high-performance computing techniques to analyze a massive data set on bird distribution from citizen-science participants across the U.S. (eBird), along with the first comprehensive database of public land ownership (Protected Areas Database of the U.S.). The state of our birds is a measurable indicator of how well we are doing as stewards of our environment. The signal is clear. Greater conservation efforts on public lands and waters are needed to realize the vision of a nation sustained economically and spiritually by abundant natural resources and spectacular wildlife. President Obama’s new initiative, “America’s Great Outdoors,” recognizes that throughout our nation’s history, conservation actions have been grounded in the premise that our natural heritage belongs to the people, and that its protection is shared by all Americans. The call to action for bird conservation in this report goes hand in hand with “America’s Great Outdoors,” which empowers all Americans to share in the responsibility to conserve, restore, and provide better access to our lands and waters in order to leave a healthy, vibrant outdoor legacy for generations yet to come

A new framework for urban ecology: an integration of proximate and ultimate responses to anthropogenic change

As urban areas continue to grow, understanding how species respond and adapt to urban habitats is becoming increasingly important. Knowledge of the mechanisms behind observed phenotypic changes of urban-dwelling animals will enable us to better evaluate the impact of urbanization on current and future generations of wildlife and predict how animals respond to novel environments. Recently, urban ecology has emerged not only as a means of understanding organismal adaptation but also as a framework for exploring mechanisms mediating evolutionary phenomena. Here, we have identified four important research topics that will advance the field of urban ecology and shed light on the proximate and ultimate causes of the phenotypic differences commonly seen among species and populations that vary in their responses to urbanization. First, we address the ecological and socio-economic factors that characterize cities, how they might interact with each other, and how they affect urban species. Second, we ask which are the proximate mechanisms underlying the emergence over time of novel traits in urban organisms, focusing on developmental effects. Third, we emphasize the importance of understanding the ultimate causations that link phenotypic shifts to function. This question highlights the need to quantify the strength and direction of selection that urban individuals are exposed to, and whether the phenotypic shifts associated with life in the city are adaptive. Lastly, we stress the need to translate how individual-level responses scale up to population dynamics. Understanding the mechanistic underpinnings of variation among populations and species in their responses to urbanization will unravel species resilience to environmental perturbation, which will facilitate predictive models for sustainability and development of green cities that maintain or even increase urban biodiversity and wildlife health and wellbeing

Multiphoton microfabrication of conducting polymer-based biomaterials

We report the application of multiphoton microfabrication to prepare conducting polymer (CP)-based biomaterials that were capable of drug delivery and interacting with brain tissue ex vivo, thereby highlighting the potential of multiphoton lithography to prepare electroactive biomaterials which may function as implantable neural biointerfaces (e.g. electrodes)

Medically relevant ElectroNeedle technology development.

ElectroNeedles technology was developed as part of an earlier Grand Challenge effort on Bio-Micro Fuel Cell project. During this earlier work, the fabrication of the ElectroNeedles was accomplished along with proof-of-concept work on several electrochemically active analytes such as glucose, quinone and ferricyanide. Additionally, earlier work demonstrated technology potential in the field of immunosensors by specifically detecting Troponin, a cardiac biomarker. The current work focused upon fabrication process reproducibility of the ElectroNeedles and then using the devices to sensitively detect p-cresol, a biomarker for kidney failure or nephrotoxicity. Valuable lessons were learned regarding fabrication assurance and quality. The detection of p-cresol was accomplished by electrochemistry as well as using fluorescence to benchmark ElectroNeedles performance. Results from these studies will serve as a guide for the future fabrication processes involving ElectroNeedles as well as provide the groundwork necessary to expand technology applications. One paper has been accepted for publication acknowledging LDRD funding (K. E. Achyuthan et al, Comb. Chem. & HTS, 2008). We are exploring the scope for a second paper describing the applications potential of this technology

Novel ultrasonographic Halo Score for giant cell arteritis:assessment of diagnostic accuracy and association with ocular ischaemia

OBJECTIVES: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. METHODS: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. RESULTS: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%). CONCLUSIONS: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA

Evaluation of histological changes after tracheal occlusion at different gestational ages in a fetal rat model

OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model. METHODS: Rat fetuses were divided into two groups: a) External control, composed of non-operated rats, and b) Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days), divided into triads: 1) Tracheal occlusion, 2) Internal control and 3) Sham (manipulated but not operated). Morphological data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day. RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (