RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans

Introduction of exogenous double-stranded RNA (dsRNA) into Caenorhabditis elegans has been shown to specifically and potently disrupt the activity of genes containing homologous sequences. In this study we present evidence that the primary interference effects of dsRNA are post-transcriptional. First, we examined the primary DNA sequence after dsRNA-mediated interference and found no evidence for alterations. Second, we found that dsRNA-mediated interference with the upstream gene in a polar operon had no effect on the activity of the downstream gene; this finding argues against an effect on initiation or elongation of transcription. Third, we observed by in situ hybridization that dsRNA-mediated interference produced a substantial, although not complete, reduction in accumulation of nascent transcripts in the nucleus, while cytoplasmic accumulation of transcripts was virtually eliminated. These results indicate that the endogenous mRNA is the target for interference and suggest a mechanism that degrades the targeted RNA before translation can occur. This mechanism is not dependent on the SMG system, an mRNA surveillance system in C. elegans responsible for targeting and destroying aberrant messages. We suggest a model of how dsRNA might function in a catalytic mechanism to target homologous mRNAs for degradation.

ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma

DPC4 is known to mediate signals initiated by type β transforming growth factor (TGFβ) as well as by other TGFβ superfamily ligands such as activin and BMP (bone morphogenic proteins), but mutational surveys of such non-TGFβ receptors have been negative to date. Here we describe the gene structure and novel somatic mutations of the activin type I receptor, ACVR1B, in pancreatic cancer. ACVR1B has not been described previously as a mutated tumor-suppressor gene.

An evaluation of the performance of cDNA microarrays for detecting changes in global mRNA expression

The cDNA microarray is one technological approach that has the potential to accurately measure changes in global mRNA expression levels. We report an assessment of an optimized cDNA microarray platform to generate accurate, precise and reliable data consistent with the objective of using microarrays as an acquisition platform to populate gene expression databases. The study design consisted of two independent evaluations with 70 arrays from two different manufactured lots and used three human tissue sources as samples: placenta, brain and heart. Overall signal response was linear over three orders of magnitude and the sensitivity for any element was estimated to be 2 pg mRNA. The calculated coefficient of variation for differential expression for all non-differentiated elements was 12–14% across the entire signal range and did not vary with array batch or tissue source. The minimum detectable fold change for differential expression was 1.4. Accuracy, in terms of bias (observed minus expected differential expression ratio), was less than 1 part in 10 000 for all non-differentiated elements. The results presented in this report demonstrate the reproducible performance of the cDNA microarray technology platform and the methods provide a useful framework for evaluating other technologies that monitor changes in global mRNA expression.

Do cyanobacteria swim using traveling surface waves?

Bacteria that swim without the benefit of flagella might do so by generating longitudinal or transverse surface waves. For example, swimming speeds of order 25 microns/s are expected for a spherical cell propagating longitudinal waves of 0.2 micron length, 0.02 micron amplitude, and 160 microns/s speed. This problem was solved earlier by mathematicians who were interested in the locomotion of ciliates and who considered the undulations of the envelope swept out by ciliary tips. A new solution is given for spheres propagating sinusoidal waveforms rather than Legendre polynomials. The earlier work is reviewed and possible experimental tests are suggested.

A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and the development of scales and crusts. The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders. Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J)F1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as few as one), in addition to CD18, determine susceptibility to the disorder. This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta2 integrins in inflammatory processes.

Prolactin-immunoglobulin G complexes from human serum act as costimulatory ligands causing proliferation of malignant B lymphocytes.

Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-prolactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of prolactin with IgG was purified from serum by anti-human prolactin affinity chromatography and was shown to contain close to 1 mole of N epsilon-(gamma-glutamyl)lysine crosslinks per mole of complex, a characteristic feature in structures crosslinked by transglutaminase. Interestingly, the complex caused a proliferation of cells from a subset of patients with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimulated the proliferation of cells in the bioassay but had no effect on the complex-responsive cells from the patients. Competition studies with prolactin and free Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and the immunoglobulin receptors for proliferation. More importantly, competition for the growth response by free prolactin and IgG suggests both possible reasons for the slow growth of this neoplasm as well as avenues for control of the disease.

Developing Autonomous Microgrids: A Theoretical Case Study

Microgrids are autonomously operated, geographically clustered electricity generation and distribution systems that supply power in closed system settings; they are highly compatible with renewable energy sources and distributed generation technologies. Mocrogrids are currently a serially underutilized and underappreciated commodity in the energy infrastructure portfolio worldwide. To demonstrate feasibility under poor conditions (little renewable energy potential and high demand) this capstone project develops a theoretical case study in which a renewable microgrid is employed to power rural communities of southern Montgomery County, Arkansas. Utilizing commercially manufactured 1.5-megawatt wind turbines and a 1-megawatt solar panel generation system, 4-megawatts of lithium ion battery storage, and demand response technology, a microgrid is designed that supplies 235 households with reliable electricity supply.

Poolesville, Maryland and vicinity, 1862 (Raster Image)

This layer is a georeferenced raster image of the untitled historic paper manuscript map: [Map of Poolesville, Maryland and vicinity showing the position of Union brigades]. It was sketched by Union General George Stoneman, Oct. 24th, 1862. Scale not given. Covers a portion of Montgomery County, Maryland from Poolesville to the Potomac River. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Maryland State Plane Coordinate System (in Meters) (Fipszone 1900). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, towns and villages, drainage, troop location, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps of the Civil War from the Harvard Map Collection. Many items from this selection are from a collection of maps deposited by the Military Order of the Loyal Legion of the United States Commandery of the State of Massachusetts (MOLLUS) in the Harvard Map Collection in 1938. These maps typically portray both natural and manmade features, in particular showing places of military importance. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Susquehanna and Delaware Rivers headwaters, New York, 1790 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the head waters of the rivers Susquehanna & Delaware embracing the early patents on the south side of the Mohawk River : from the original, drawn about the year 1790, by Simeon DeWitt, Esq. ... ; with the date of each patent now appended from the rec. in surveyr. genls. office, by E.B. O'C. It was published by Weed, Parsons & Co. in 1849. Scale [ca. 1:260,000]. Covers portion of Central New York including Oneida, Herkimer, Montgomery, Schenectady, Schoharie, Otsego, Delaware, and Greene Counties. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD83 projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This is a cadastral map showing property boundaries, names of property owners, dates of patent, drainage, and more. Includes ill. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania and vicinity, Landowners, 1681 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Fac-simile of a portion of Holme's map of the Province of Pennsylvania : with names of original purchasers from William Penn 1681. It was published by L. H. Everts & co. ca. 1884. Scale not given. Facsimile of a map published in 1681. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. Cadastral map showing townships, landowner names, property boundaries, drainage, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania (East), and vicinity, 1955 (Raster Image) (Image 1 of 2)

This layer is a georeferenced raster image of the United States Geological Survey sheet map set entitled: Philadelphia and vicinity, east, 1955 (and west, 1956) (Pennsylvania - New Jersey) by the Geological Survey. It was published in 1958. Scale 1:24,000. Covers Philadelphia and portions of adjacent counties. Mapped by the Geological Survey, U.S. Coast and Geodetic Survey and Army Map Service. Compiled from 1:24,000 scale maps of Langhorne 1953, Hatboro 1952, Ambler 1952, Germantown 1952, Frankford 1950, Beverly 1955, Moorestown 1953, Camden 1949, Philadelphia 1949, Woodbury 1949, Rennemede 1952, and Clementon 1953 7.5 minute quadrangles. This layer is image 1 of 2 total images of the two sheet source map set representing the eastern portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD27 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. USGS maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works of humans, such as roads, railroads, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 10 and 20 feet. Please pay close attention to map collar information on projections, spheroid, sources, dates, and keys to grid numbering and other numbers which appear inside the neatline. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania and vicinity, Roads, 1897 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the country around Philadelphia : with the good roads specially marked. It was published by J. L. Smith in 1897. Scale [1:63,360]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads ("Good roads" are shown in red), railroads, drainage, canals, selected buildings, towns, county and state boundies, and more. Includes explanation of signs. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.