Identification of hydroxyapatite spherules provides new insight into sub-retinal pigment epithelial deposit formation in the aging eye

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye. Proc Natl Acad Sci U S A , 112 Keywords: Hydroxyapatite, calcium, drusen, macula, retinal pigment epithelium, RPE, age-related macular degeneration, AMD, cholesterol, complement factor H, CFH, amyloid-beta, vitronectin Significance Statement Proteins and lipids accumulating in deposits external to the RPE represent a barrier to metabolic exchange between the retina and the choroidal capillaries. With time, these deposits can lead to age-related macular degeneration (AMD), the most common cause of blindness in the elderly in the developed world. It remains unclear how sub-RPE deposits are initiated and grow to clinically relevant features. Using a combination of high resolution analytical techniques we found that tiny hydroxyapatite (bone mineral) spherules with cholesterol-containing cores are present in all examined sub-RPE deposits, providing a scaffold to which proteins adhere. If the spherules are important in initiating sub-RPE deposit formation this may provide attractive new approaches for early identification and treatment of AMD

Multiple Statistical Analysis Techniques Corroborate Intratumor Heterogeneity in Imaging Mass Spectrometry Datasets of Myxofibrosarcoma

MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups) and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of all patient tissue samples. To aid the further development of imaging MS based molecular histology as a complementary histological tool the Matlab code of the agreement analysis, instructions and a reduced dataset are included as supporting information

International Factors and the 1964 Election

International issues are not usually seen as having been significant to the 1964 general election result. Harold Wilson made only limited references to foreign policy and defence during the campaign, while opinion polls showed that voters saw domestic questions as being far more important. Traditionally, international issues have had only a limited impact upon British general elections. But the 1964 election was one of the most closely run in history and this article argues that, interpreted broadly, international questions did have a real effect on the contest. The sitting prime minister Sir Alec Douglas-Home focused on the future of the nuclear deterrent for much of the campaign, while considerations about the country's relative decline in the world, reflected in chronic balance of payment problems, helped Labour's case that it was ‘time for a change’ at the top. Besides, the mid-1960s was a significant point for the country's global position: the post-war policy of ‘three circles’—in which Britain played a major role in Europe, maintained a global empire and influenced US policy via the ‘special relationship’—was being called into question. The question deserves to be asked, therefore, why there was not a more intense debate between the political leaders about Britain's international role

Results From the (1) Data Collection Workshop, (2) Modeling Workshop and (3) Drilling and Coring Methods Workshop as Part of the Joint Industry Participation (JIP) Project to Characterize Natural Gas Hydrates in the Deepwater Gulf of Mexico

In 2000, Chevron began a project to learn how to characterize the natural gas hydrate deposits in the deepwater portions of the Gulf of Mexico. A Joint Industry Participation (JIP) group was formed in 2001, and a project partially funded by the U.S. Department of Energy (DOE) began in October 2001. The primary objective of this project is to develop technology and data to assist in the characterization of naturally occurring gas hydrates in the deepwater Gulf of Mexico. These naturally occurring gas hydrates can cause problems relating to drilling and production of oil and gas, as well as building and operating pipelines. Other objectives of this project are to better understand how natural gas hydrates can affect seafloor stability, to gather data that can be used to study climate change, and to determine how the results of this project can be used to assess if and how gas hydrates act as a trapping mechanism for shallow oil or gas reservoirs. As part of the project, three workshops were held. The first was a data collection workshop, held in Houston during March 14-15, 2002. The purpose of this workshop was to find out what data exist on gas hydrates and to begin making that data available to the JIP. The second and third workshop, on Geoscience and Reservoir Modeling, and Drilling and Coring Methods, respectively, were held simultaneously in Houston during May 9-10, 2002. The Modeling Workshop was conducted to find out what data the various engineers, scientists and geoscientists want the JIP to collect in both the field and the laboratory. The Drilling and Coring workshop was to begin making plans on how we can collect the data required by the project's principal investigators

Mass spectrometry imaging shows major derangements in neurogranin and in purine metabolism in the triple-knockout 3×Tg Alzheimer mouse model

Proteomic