New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Rapid quantification of microRNAs in plasma using a fast real time PCR system

The ability to rapidly detect circulating small RNAs, in particular microRNAs (miRNAs), would further increase their already established potential as biomarkers in a range of conditions. One rate-limiting factor is the time taken to perform quantitative real time PCR amplification. We therefore evaluated the ability of a novel thermal cycler to perform this step in less than 10 minutes. Quantitative PCR was performed on an xxpress® thermal cycler (BJS Biotechnologies, Perivale, UK), which employs a resistive heating system and forced air cooling to achieve thermal ramp rates of 10 °C/s, and a conventional peltier-controlled LightCycler 480 system (Roche, Basel, Switzerland) ramping at 4.8 °C/s. The threshold cycle (Ct) for detection of 18S rDNA from a standard genomic DNA sample was significantly more variable across the block (F-test, p=2.4x10-25) for the xxpress (20.01±0.47SD) than the LightCycler (19.87±0.04SD). RNA was extracted from human plasma, reverse transcribed and a panel of miRNAs amplified and detected using SYBR green (Kapa Biosystems, Wilmington, Ma, USA). The sensitivity of both systems was broadly comparable and both detected a panel of miRNAs reliably and indicated similar relative abundances. The xxpress thermal cycler facilitates rapid qPCR detection of small RNAs and brings point-of care diagnostics based upon circulating miRNAs a step closer to reality.

Development of a combined RT-PCR: NGS assay for microRNA biomarkers

The ability of miRNAs to act as diagnostic biomarkers could be expanded by availability of improved methodologies to detect and analyse these molecules. We have therefore developed an assay with the ability to selectively analyse pools of miRNAs, using the specificity of PCR to select targets and the power of NGS to reveal isomiRs of the chosen targets in a total assay time of two days.

The Cyrenaican Prehistory Project 2011: Late-Holocene environments and human activity from a cave fill in Cyrenaica, Libya

Little is known about late Holocene environmental change in Cyrenaica. The late Holocene sequence in the Haua Fteah, the key regional site, is highly discontinuous and characterised by stable-burning deposits. The geoarchaeology of the late-Holocene cave fill of a small cave, CP1565, located close to the Haua Fteah, is described. The well-stratified sequence, dating from the fourth century AD to the present day, provides a glimpse of life at the bottom of the settlement hierarchy and of changing environments over the last 1600 years, with degraded vegetation and aridity in the ‘Little Ice Age’.

Stable standard essential for prosperity. Speech in the Senate of the United States, February 4, 1878

This speech was given when the United States Senate was considering a bill to authorize the free coinage of the standard silver dollar and to restore its legal tender character. Mr. Bayard argues against the bill in this speech. He is interrupted during his speech multiple times and questioned about his points.

Second Welland Canal - Book 2, Survey Map 8 - Little Deep Cut in Thorold

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in Thorold South. Identified structures associated with the Canal include the Little Deep Cut and the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Road to Beaverdams and Road to Allanburgh), two unnamed bridges, the Spoil Bank, a pond, and the Back Water. Properties and property owners of note are: Lots 29 and 30, Jacob Keefer, John Brown, William Bouck, C. Gisso, and a property reserved for Bridge Tender.

Second Welland Canal - Book 2, Survey Map 10 - Through Thorold

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in Thorold Township. Identified structures associated with the Canal include the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Road to Allanburgh), an unnamed bridege, several barns, a structure labelled Bridge Tender, and a dwelling. Properties and property owners of note are: Lots 30, 31, 32, 48, 49, and 50, Robert Booth, Hiram Marlatt, George Keefer, John Kelly, Isaac Kelly, John Brown, Thomas Lee, and the Board of Works.

Second Welland Canal - Book 3, Survey Map 2 - Canal to Chippewa Creek with Port Robinson

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal as it passes through Port Robinson. Identified structures associated with the Canal include the Guard Lock, Collector Toll Office, towing path, and the New Cut of the canal. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Island Street, Bridge Street, John Street, and Cross Street), bridges (Swing Bridge, and several unnamed bridges), Welland Railroad, Canal to Chippewa Creek (and two old locks and one new lock associated with the canal), Chippewa Creek, Back Water, an unnamed Island, Dry Dock leased to McFarland and Abbey, Abbey's Office, D. McFarland and Co. Saw Mill (Burnt), G. Jordan Tavern, Robert Elliot Store House and Wharf, Isaac Pew's Shop, Colemans Hotel, R. Band and Co. Girst Mill, Donaldson and Co. Grist Mill, H. Marlatt Dwelling House and barn, Henry W. Timms Hotel, Methodist Church, Post Office, Blacksmith Shop, a church, a structure labeled B. Patch, and a number of other structures that are not named. Properties and property owners of note are: Lots 202 and 203, S. Hill, D. McFarland, Church Society, G. Jordan, D. Coleman, John Brown, Rob Coulter, Robert Elliot, Isaac Pew, James McCoppen, William Bell, Charles Stuart, Andrew Elliot, Robert Band, Ed. Feney, John Betty, F. Sharp, William B. Hendershot, A. Brownson, H. Marlatt, J. S. Powell, and the School Trustees. Two reserved properties are labeled in red.The current spelling of Chippewa Creek is Chippawa. Although it not possible to make out the entire name of the H. W. Timms hotel located at Front and Bridge Street on the map itself, it was discovered to belong to Henry W. Timms after consulting the 1851-52 Canada Directory.

Second Welland Canal - Book 3, Survey Map 16 - Through Humberstone

Survey map of the Second Welland Canal created by the Welland Canal Company showing the border area of the townships of Crowland and Humberstone. Identified structures associated with the Canal include back ditches, towing path and spoil banks. Surveyor measurements and notes can be seen in red and black ink and pencil. Local area landmarks include line between the 7th Concession of Crowland and the Gore, Town Line between the Townhips of Crowland and Humberstone and the Highane and Company Store. Roads parallel to Canal include southern Road Allowance and the Road to Port Colborne. Roads perpendicular to Canal include Road Allowance between the 4th and 5th Concession. Properties and property owners are noted as Thomas Merrit, John Betty, John Brown, Charles French, James McCoppen, and S.D. Woodruff. Lots noted are: Lots Number 22, 23, 24, 5th Concession."Humberstone" - Scale: 4 Chs. per Inch "Gore"

Chart of estimate for work done on the Port Dalhousie and Thorold Railway

Chart of estimate for work done on the Port Dalhousie and Thorold Railway by John Brown, contractor regarding the section between Geneva Street and the Thorold Station for the month of Dec. 1855. This document is burned on the right hand side. This affects the text slightly. It is signed by S.D. Woodruff, Jan. 1856.

Letter from Francis Lalor to S.D. Woodruff

Letter which gives an addition to the estimate for work done by John Brown for Dec. 1855. This is made out to S.D. Woodruff from Francis Lalor. The request is for money for extra ties, fence posts, stone and labour. The letter is slightly singed at the bottom. This does not affect the text, Jan. 3, 1856.

Letter to S.D. Woodruff from F. Lalor, assistant engineer

Letter to S.D. Woodruff from F. Lalor, assistant engineer. This is an estimate of work done by John Brown between Grantham and Thorold, Mar. 4, 1856.

Chart of estimate of work done on Port Dalhousie and Thorold Railway in the section between Geneva Street and Thorold Station of the Grantham Railway

Chart of estimate of work done on Port Dalhousie and Thorold Railway in the section between Geneva Street and Thorold Station of the Grantham Railway by John Brown for February, 1856. This is signed by S.D. Woodruff, engineer, March 1856.

Chart of estimate of work done on Port Dalhousie and Thorold Railway in the section between Geneva Street and Thorold Station of the Grantham Railway

Chart of estimate of work done on Port Dalhousie and Thorold Railway in the section between Geneva Street and Thorold Station of the Grantham Railway by John Brown for March, April and May 1856.

Chart of estimate of work done on Port Dalhousie and Thorold Railway in the section between Geneva Street and Thorold Station of the Grantham Railway

Chart of estimate of work done on Port Dalhousie and Thorold Railway in the section between Geneva Street and Thorold Station of the Grantham Railway by John Brown for May, 1856. This is signed by S.D. Woodruff, engineer, June 3, 1856.