Radiographic closure time of appendicular growth plates in the Icelandic horse

<p>Abstract</p> <p>Background</p> <p>The Icelandic horse is a pristine breed of horse which has a pure gene pool established more than a thousand years ago, and is approximately the same size as living and extinct wild breeds of horses. This study was performed to compare the length of the skeletal growth period of the "primitive" Icelandic horse relative to that reported for large horse breeds developed over the recent centuries. This information would provide practical guidance to owners and veterinarians as to when the skeleton is mature enough to commence training, and would be potentially interesting to those scientists investigating the pathogenesis of osteochondrosis. Interestingly, osteochondrosis has not been documented in the Icelandic horse.</p> <p>Methods</p> <p>The radiographic closure time of the appendicular growth plates was studied in 64 young Icelandic horses. The results were compared with previously published closure times reported for other, larger horse breeds. The radiographs were also examined for any signs of developmental orthopaedic diseases. In order to describe further the growth pattern of the Icelandic horse, the total serum alkaline phosphatase (ALP) activity was determined and the height at the withers was measured.</p> <p>Results</p> <p>Most of the examined growth plates were fully closed at the age of approximately three years. The horses reached adult height at this age; however ALP activity was still mildly increased over baseline values. The growth plates in the digits were the first to close at 8.1 to 8.5 months of age, and those in the regions of the distal radius (27.4 to 32.0 months), tuber olecrani (31.5 to 32.2 months), and the stifle (27.0 to 40.1 months) were the last to close. No horse was found to have osteochondrosis type lesions in the neighbouring joints of the evaluated growth plates.</p> <p>Conclusion</p> <p>The Icelandic horse appears to have similar radiographic closure times for most of the growth plates of its limbs as reported for large new breeds of horses developed during the past few centuries. It thus appears that different breeding goals and the intensity of breeding have not altered the length of the growth period in horses. Instead, it can be assumed that the pristine and relatively small Icelandic horse has a slower rate of growth. The appendicular skeleton of Icelandic horses has completed its bone growth in length at approximately 3 years of age, and therefore may be able to enter training at this time.</p

A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder

Effectiveness of an HIV Prevention Program for Women Visiting Their Incarcerated Partners: The HOME Project

Having an incarcerated partner presents a unique HIV risk for women, particularly low-income women of color. We developed a population-specific risk reduction intervention for women visiting men in prison that was peer educator-based and included individual and community-level intervention components. Women who were assessed prior to the intervention period had a positive association between the number of unprotected penetrative intercourse (UPI) episodes prior to their partners’ incarceration and the number of UPI episodes following partners’ release from prison. However, this association was negated among women assessed during the intervention. Intervention participants also were more likely to be tested for HIV, to have partners who got tested, and to talk with their partners about significantly more HIV-related topics. Conducting intervention and evaluation activities with women visiting incarcerated men is feasible and is a useful model for reaching more at-risk women

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts