Autoinhibition of c-Abl

AbstractDespite years of investigation, the molecular mechanism responsible for regulation of the c-Abl tyrosine kinase has remained elusive. We now report inhibition of the catalytic activity of purified c-Abl in vitro, demonstrating that regulation is an intrinsic property of the molecule. We show that the interaction of the N-terminal 80 residues with the rest of the protein mediates autoregulation. This N-terminal “cap” is required to achieve and maintain inhibition, and its loss turns c-Abl into an oncogenic protein and contributes to deregulation of BCR-Abl

Effect of reducing dietary crude protein in hog finisher barrows and gilts on technical performance

The objective of this study was to determine the effect of reducing dietary crude protein (CP) levels in hog finisher barrows and gilts on animal performance. Diets were formulated to meet the requirements of the first six essential amino acids. It was hypothesised that lowest dietary CP levels without negative effects on technical performance would be close to treatments D (barrows) and J (gilts). From those CP level onwards, isoleucine (and histidine) likely became limiting factors.The most important conclusions are mentioned below. Performance30-55 kg BW:- The response to CP level was different in barrows compared to gilts (P interaction0.05).- A quadratic response to CP level was observed for ADG and efficiency (both P0.05).- Performance increased with increasing CP level and cost per kg gain decreased with increasing CP level (all P linear0.05). Quadratic responses were observed for final bodyweight, slaughter weight and carcass weight (all

Creatine Kinase–Mediated ATP Supply Fuels Actin-Based Events in Phagocytosis

Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type creatine kinase (CK-B), an enzyme involved in high-energy phosphoryl transfer. We demonstrate that endogenous CK-B in macrophages is mobilized from the cytosolic pool and coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP-tagged CK-B and β-actin revealed the transient and specific nature of this partitioning process. Overexpression of a catalytic dead CK-B or CK-specific cyclocreatine inhibition caused a significant reduction of actin accumulation in the phagocytic cup area, and reduced complement receptor–mediated, but not Fc-γR–mediated, ingestion capacity of macrophages. Finally, we found that inhibition of CK-B affected phagocytosis already at the stage of particle adhesion, most likely via effects on actin polymerization behavior. We propose that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply

Stray-field calculations on a shielded planar actuator using 3-D hybrid analytical modeling

ABSTRACT This paper applies a hybrid analytical modeling technique to calculate the magnetic stray-field of a shielded planar motor. The magnetic stray-field of the planar magnet array is accurately predicted by the presented modeling method. The inclusion of the magnetic shield is visible as a clear reduction of the magnetic field as will be confirmed by measurements

Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia.

POP1 is a large protein common to the RNase-MRP and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8 s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals demonstrate the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development

Sensor data classification for the indication of lameness in sheep

Lameness is a vital welfare issue in most sheep farming countries, including the UK. The pre-detection at the farm level could prevent the disease from becoming chronic. The development of wearable sensor technologies enables the idea of remotely monitoring the changes in animal movements which relate to lameness. In this study, 3D-acceleration, 3D-orientation, and 3D-linear acceleration sensor data were recorded at ten samples per second via the sensor attached to sheep neck collar. This research aimed to determine the best accuracy among various supervised machine learning techniques which can predict the early signs of lameness while the sheep are walking on a flat field. The most influencing predictors for lameness indication were also addressed here. The experimental results revealed that the Decision Tree classifier has the highest accuracy of 75.46%, and the orientation sensor data (angles) around the neck are the strongest predictors to differentiate among severely lame, mildly lame and sound classes of sheep