A murine model for developmental dysplasia of the hip: ablation of CX3CR1 affects acetabular morphology and gait.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a debilitating condition whose distinguishing signs include incomplete formation of the acetabulum leading to dislocation of the femur, accelerated wear of the articular cartilage and joint laxity resulting in osteoarthritis. It is a complex disorder having environmental and genetic causes. Existing techniques fail to detect milder forms of DDH in newborns leading to hip osteoarthritis in young adults. A sensitive, specific and cost effective test would allow identification of newborns that could be non-invasively corrected by the use of a Pavlik harness. Previously, we identified a 2.5 MB candidate region on human chromosome 3 by using linkage analysis of a 4 generation, 72 member family. Whole exome sequencing of the DNA of 4 severely affected members revealed a single nucleotide polymorphism variant, rs3732378 co-inherited by all 11 affected family members. This variant causes a threonine to methionine amino acid change in the coding sequence of the CX3CR1 chemokine receptor and is predicted to be harmful to the function of the protein To gain further insight into the function of this mutation we examined the effect of CX3CR1 ablation on the architecture of the mouse acetabulum and on the murine gait. METHODS: The hips of 5 and 8 weeks old wild type and CX3CR1 KO mice were analyzed using micro-CT to measure acetabular diameter and ten additional dimensional parameters. Eight week old mice were gait tested using an inclined treadmill with and without load and then underwent micro-CT analysis. RESULTS: (1) KO mice showed larger a 5-17% larger diameter left acetabula than WT mice at both ages. (2) At 8 weeks the normalized area of space (i.e. size discrepancy) between the femur head and acetabulum is significantly larger [38% (p = 0.001)-21% (p = 0.037)] in the KO mice. (3) At 8 weeks gait analysis of these same mice shows several metrics that are consistent with impairment in the KO but not the WT mice. These deficits are often seen in mice and humans who develop hip OA. CONCLUSION: The effect of CX3CR1 deletion on murine acetabular development provides suggestive evidence of a susceptibility inducing role of the CX3CR1 gene on DDH

Economic Outlook for Representative Cotton Farms Given the August 2005 FAPRI/AFPC Baseline

The Agricultural and Food Policy Center (AFPC) at Texas A&M University develops and maintains data to simulate eighteen representative cotton operations in major production areas of seven states. The chief purpose of this analysis is to project those farms’ economic viability for 2005 through 2009. The data necessary to simulate the economic activity of these operations is developed through ongoing cooperation with panels of agricultural producers in each of these states. The Food and Agricultural Policy Research Institute (FAPRI) provided projected prices, policy variables, and input inflation rates in their August 2005 Baseline. Under the August 2005 Baseline, only the moderately sized Tennessee cotton farm (TNC1900) and Louisiana cotton farm (LAC2640) are considered in good liquidity condition (less than a 25 percent chance of negative ending cash during 2005-2009). Five cotton farms (TXSP3745, TXRP2500, TXMC3500, TXCB1850, and TNC4050) have between a 25 percent and a 50 percent likelihood of negative ending cash. The remaining eleven cotton farms have greater than a 50 percent chance of negative ending cash. Additionally, TNC1900 is the only farm in the set considered in good equity position (less than a 25 percent chance of decreasing real net worth during 2005-2009). Three cotton farms (TXRP2500, TXMC3500, and TXCB1850) have between a 25 percent and 50 percent likelihood of losing real net worth, and the remaining fourteen cotton farms have greater than a 50 percent probability of decreasing real net worth.Agribusiness, Agricultural and Food Policy, Crop Production/Industries,

Representative Farms Economic Outlook for the December 2005 FAPRI/AFPC Baseline

The Agricultural and Food Policy Center (AFPC) at Texas A&M University develops and maintains data to simulate 102 representative crop and livestock operations in major production areas in 28 states. The chief purpose of this analysis is to project those farms’ economic viability for 2005 through 2011. The data necessary to simulate the economic activity of these operations is developed through ongoing cooperation with panels of agricultural producers in each of these states. The Food and Agricultural Policy Research Institute (FAPRI) provided projected prices, policy variables, and input inflation rates in their December 2005 Baseline. Under the December 2005 Baseline, 12 of the 66 crop farms are considered in good liquidity condition (less than a 25 percent chance of negative ending cash during 2005-2011). Five crop farms have between a 25 percent and a 50 percent likelihood of negative ending cash. The remaining 49 crop farms have greater than a 50 percent of negative ending cash. Additionally, 22 of the 66 crop farms are considered in good equity position (less than a 25 percent chance of decreasing real net worth during 2005-2011). Ten crop farms have between a 25 percent and 50 percent likelihood of losing real net worth, and 34 crop farms have greater than a 50 percent probability of decreasing real net worth.Agribusiness, Agricultural and Food Policy, Crop Production/Industries, Livestock Production/Industries,

Developmental dysplasia of the hip: Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in all affected members of a large multi-generation family.

Developmental Dysplasia of the Hip (DDH) is a debilitating condition characterized by incomplete formation of the acetabulum leading to dislocation of the femur, suboptimal joint function, and accelerated wear of the articular cartilage resulting in arthritis. DDH affects 1 in 1000 newborns in the United States with well defined pockets of high prevalence in Japan, Italy and other Mediterranean countries. Although reasonably accurate for detecting gross forms of hip dysplasia, existing techniques fail to find milder forms of dysplasia. Undetected hip dysplasia is the leading cause of osteoarthritis of the hip in young individuals causing over 40% of cases in this age group. A sensitive and specific test for DDH has remained a desirable yet elusive goal in orthopaedics for a long time. A 72 member, four generation affected family has been recruited, and DNA from its members retrieved. Genome-wide linkage analysis revealed a 2.61 Mb candidate region (38.7-41.31 Mb from the p term of chromosome 3) co-inherited by all affected members with a maximum LOD score of 3.31. Whole exome sequencing and analysis of this candidate region in four severely affected family members revealed one shared variant, rs3732378, that causes a threonine (polar) to methionine (non-polar) alteration at position 280 in the trans-membrane domain of CX3CR1. This mutation is predicted to have a deleterious effect on its encoded protein which functions as a receptor for the ligand fractalkine. By Sanger sequencing this variant was found to be present in the DNA of all affected individuals and obligate heterozygotes. CX3CR1 mediates cellular adhesive and migratory functions and is known to be expressed in mesenchymal stem cells destined to become chondrocytes. A genetic risk factor that might to be among the etiologic factors for the family in this study has been identified, along with other possible aggravating mutations shared by 4 severely affected family members. These findings might illuminate the molecular pathways affecting chondrocyte maturation and bone formation

Representative Farms Economic Outlook for the January 2005 FAPRI/AFPC Baseline

The farm level economic impacts of the Farm Security and Rural Investment Act of 2002 on representative crop and livestock operations are projected in this report. The analysis was conducted over the 2002-2009 planning horizon using FLIPSIM, AFPC’s whole farm simulation model. Data to simulate farming operations in the nation’s major production regions came from two sources:•Producer panel cooperation to develop economic information to describe and simulate representative crop, livestock, and dairy farms, and•Projected prices, policy variables, and input inflation rates from the Food and Agricultural Policy Research Institute (FAPRI) January 2005 Baseline. The FLIPSIM policy simulation model incorporates the historical risk faced by farmers for prices and production. This report presents the results of the January 2005 Baseline in a risk context using selected simulated probabilities and ranges for annual net cash farm income values. The probability of a farm experiencing negative ending cash reserves and the probability of a farm losing real net worth are included as indicators of the cash flow and equity risks facing farms through the year 2009.Agribusiness, Agricultural and Food Policy, Crop Production/Industries, Livestock Production/Industries,

Representative Farms Economic Outlook for the August 2005 FAPRI/AFPC Baseline

The farm level economic impacts of the Farm Security and Rural Investment Act of 2002 on representative crop and livestock operations are projected in this report. The analysis was conducted over the 2002-2009 planning horizon using FLIPSIM, AFPC’s whole farm simulation model. Data to simulate farming operations in the nation’s major production regions came from two sources: • Producer panel cooperation to develop economic information to describe and simulate representative crop, livestock, and dairy farms, and • Projected prices, policy variables, and input inflation rates from the Food and Agricultural Policy Research Institute (FAPRI) August 2005 Baseline. The FLIPSIM policy simulation model incorporates the historical risk faced by farmers for prices and production. This report presents the results of the August 2005 Baseline in a risk context using selected simulated probabilities and ranges for annual net cash farm income values. The probability of a farm experiencing negative ending cash reserves and the probability of a farm losing real net worth are included as indicators of the cash flow and equity risks facing farms through the year 2009.Agribusiness, Agricultural and Food Policy, Crop Production/Industries, Livestock Production/Industries,

Routine dynamics in action: replication and transformation

Contains an Open Access chapter.This book explores central themes in the enactment and coordination of organizational routines, including replication and transfer, ecologies and interdependence, action and the generation of novelty and technology and sociomateriality.