New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

RI-04 Interpretation of Lake Washington Magnetic Anomaly, Meeker County, Minnesota

A magnetic anomaly centered at Lake Washington, in southeastern Meeker County, has been outlined by a ground magnetometer survey. The anomaly is arcuate in outline, about 8.5 miles long and a maximum of 5 miles wide, and has a maximum amplitude greater than 3,000 gammas. A gravity traverse was made across the anomaly to aid in interpretation. Combined magnetic and gravity data are interpreted to indicate that the source is a basin-shaped body having a substantially greater density than the adjacent rocks that lies at a shallow depth. The lithology of the source is not known because of a lack of subsurface data, but is inferred to be either Precambrian iron-formation or mafic igneous rock. The anomaly warrants further investigation

Geologic map of Minnesota, Hibbing sheet, bedrock geology

Scale 1:250,00

M-005 Preliminary geologic map of the Vermilion district and adjacent areas, northern Minnesota

Scale 1:125,000; this map was printed with the wrong scale (1:250,000)indicated on the sheet, an error corrected on most of the distributed copies

Frequency, geographical distribution and potential risk factors associated with a papillomatosis and carcinomatosis syndrome in the endangered western barred bandicoot (Perameles bougainville)

Once widespread across western and southern Australia, wild populations of the western barred bandicoot (Perameles bougainville) are currently only found on Bernier and Dorre Islands, Shark Bay, Western Australia. A debilitating skin disease is hindering conservation efforts to prevent the extinction of this endangered Australian marsupial

Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville)

A progressive wart-like syndrome in both captive and wild populations of the Western barred bandicoot (WBB) is hindering conservation efforts to prevent the extinction of this endangered marsupial. In this study, 42 WBBs exhibiting the papillomatosis and carcinomatosis syndrome were examined. The disease was characterized by multicentric proliferative lesions involving cutaneous and mucosal surfaces, which were seen clinically to increase in size with time. Grossly and histologically the smaller skin lesions resembled papillomas, whereas the larger lesions were most commonly observed to be squamous cell carcinomas. Large amphophilic intranuclear inclusion bodies were observed in hyperplastic conjunctival lesions of 8 WBBs under light microscopy. Conjunctival lesions from 2 WBBs examined using transmission electron microscopy contained a crystalline array of spherical electrondense particles of 45-nm diameter, within the nucleus of conjunctival epithelial cells, consistent with a papillomavirus or polyomavirus. Conjunctival samples from 3 bandicoots that contained intranuclear inclusion bodies also demonstrated a positive immunohistochemical reaction after indirect immunohistochemistry for papillomavirus structural antigens. Ultrastructural and/or immunohistochemical evidence of an etiologic agent was not identified in the nonconjunctival lesions examined. Here we describe the gross, histopathologic, ultrastructural, and immunohistochemical findings of a papillomatosis and carcinomatosis syndrome recently identified in the WBB

Analysing partitioning of recently fixed and of reserve carbon in reproductive Phaseolus vulgaris L. plants

Partitioning of recently-fixed carbon among plant organs and subsequent distribution of reserve carbon were studied by supplying whole shoots of bean plants (Phaseolus vulgaris L.) with 14C-labelled CO2 of constant specific radioactivity throughout a photoperiod. The gain of tracer carbon in each part revealed net accumulation of recently-fixed carbon from direct fixation, import or both. Growth rate coefficients describing the present pattern of plant growth were calculated from ratios of tracer carbon to total carbon present in plant organs and were used to project future plant form. The period 10–20 d after the start of flowering was marked by a major increase in partitioning of recently-fixed carbon to reproductive growth. Growth rates for the plant and its parts during this period were projected on the basis of growth rate coefficients and were found to be similar to rates measured by gravimetric growth analysis. Changes in tracer carbon recovered in individual organs after chase periods of various lengths revealed net Dec.reases for leaves and stems. About 9% of the carbon distributed to fruits came from reserves even in the absence of obvious stress. Respiratory loss during the chase period was determined from the progressive drop in recovery of the original tracer carbon. The methods are being applied to measure current net accumulation rates in studies of sink organ physiology, and to compare partitioning of recently-fixed and of stored carbon in several plant species under defined growth conditions