The C9ORF72 mutation brings more answers and more questions.

The clinical, neuropsychiatric and neuroimaging features of patients who carry the important new C9ORF72 mutation are discussed in this special series of Alzheimer's Research & Therapy. First reported in November 2011, the C9ORF72 mutation is the most common mutation associated with both frontotemporal dementia and amyotrophic lateral sclerosis in the Western hemisphere and Europe. It is a gene with strong penetrance, and the vast majority of subjects with the C9ORF72 mutation die from a neurodegenerative condition. The most common clinical manifestation of disease in gene carriers is behavioral variant frontotemporal dementia. An extremely long hexanucleotide repeat (usually greater than 400), appears to lead to ribonucleic acid aggregates within the nucleus and suppression of gene expression. Finding therapies for C9ORF72 will be difficult and require novel therapeutic approaches that involve suppression of the expression of the C9ORF72 repeat

Activation of type II calcium/calmodulin-dependent protein kinase by Ca^(2+)/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain

It is now well established that autophosphorylation of a threonine residue located next to each calmodulin-binding domain in the subunits of type II Ca^(2+)/calmodulin-dependent protein kinase causes the kinase to remain active, although at a reduced rate, after Ca^(2+) is removed from the reaction. This autophosphorylated form of the kinase is still sensitive to Ca2+/calmodulin, which is required for a maximum catalytic rate. After removal of Ca^(2+), new sites are autophosphorylated by the partially active kinase. Autophosphorylation of these sites abolishes sensitivity of the kinase to Ca^(2+)/calmodulin (Hashimoto, Y., Schworer, C. M., Colbran, R. J., and Soderling, T. R. (1987) J. Biol. Chem. 262, 8051-8055). We have identified two pairs of homologous residues, Thr^(305) and Ser^(314) in the alpha subunit and Thr^(306) and Ser^(315) in the beta subunit, that are autophosphorylated only after removal of Ca^(2+) from an autophosphorylation reaction. The sites were identified by direct sequencing of labeled tryptic phosphopeptides isolated by reverse-phase high pressure liquid chromatography. Thr^(305-306) is rapidly dephosphorylated by purified protein phosphatases 1 and 2A, whereas Ser^(314-315) is resistant to dephosphorylation. We have shown by selective dephosphorylation that the presence of phosphate on Thr^(305-306) blocks sensitivity of the kinase to Ca^(2+)/calmodulin. In contrast, the presence of phosphate on Ser^(314-315) is associated with an increase in the Kact for Ca^(2+)/calmodulin of only about 2-fold, producing a relatively small decrease in sensitivity to Ca^(2+)/calmodulin

Evaluation of Three Rations on Growth and Reproductive Performance for Replacement Heifers

Nutrition following weaning of replacement heifers affects their performance as cows. Low levels of energy can delay puberty and reduce conception rates. Excessively high levels can decrease milk production and life span. Previous research indicates that gains should be kept to about 220 pounds from weaning to first breeding. This level of gain precludes high concentrate rations, curtailing flexibility and ability to minimize feed costs when concentrates are a cheaper source of energy. Limiting feed intake to supply desired total energy consumption would allow flexibility and use of higher percentage grain when economical. Limit feeding has been studied with finishing cattle regarding its influence on digestibility of feed stuffs. Limit feeding has been used to produce desired gains in heifers but not studied as a possible feeding program for replacement heifers. This study was conducted to determine if the use of rations containing various energy levels with intake limited could be successfully used to raise replacement heifers

Hypervelocity Impact of Composite Overwrap Pressure Vessels

There is a limited amount of hypervelocity impact (HVI) data on pressurized composite overwrapped pressure vessels (COPV). In recent years, NASA has performed HVI tests to characterize impact conditions resulting in either leak or burst of the COPVs representative of spacecraft hardware. This paper reports on the results of 40 tests that have been conducted on several types of COPV configurations, pressurized by inert gas to near the vessels rated maximum expected operating pressure (MEOP). These tests were used to better understand COPV response under HVI conditions and develop ballistic limit equations (BLE) related to these tests

An Evaluation of Three Feeding Schemes to Winter Replacement Heifers

Many different feeding practices have been used to grow out replacement heifers. The goal for replacement heifers is to overwinter at gains sufficiently high enough that they will be at 60% of mature body weight at breeding. This should be done as efficiently as possible and to meet all nutrient requirements. This study was designed to evaluate three methods of growing replacements as to dollar efficiency and animal performance

An Evaluation of Three Feeding Schemes to Winter Replacement Heifers

Many different feeding practices have been used to grow out replacement heifers. The goal for replacement heifers is to over winter at gains sufficiently high enough that they will be at 60% of mature body weight at breeding. This should be done as efficiently as possible and to meet all nutrient requirements. This study was designed to evaluate three methods of growing replacements as to dollar efficiency and animal performance