F-box Protein βTrCP1 Is a Substrate of Extracellular Signal-regulated Kinase 2

F-box proteins, consisting of 69 members which are organized into the three subclasses FBXW, FBXL, and FBXO, are the substrate specific recognition subunits of the SKP1-Cullin 1-F-box protein E3 ligase complex. Although βTrCP 1 and 2, members of the FBXW subfamily, are known to regulate some protein stability, molecular mechanisms by which these proteins can recognize proper substrates are unknown. In this study, it was found that βTrCP1 showed strong interaction with members of mitogen-activated protein kinases. Although extracellular signal-regulated kinase (ERK) 3, p38β, and p38δ showed weak interactions, ERK2 specifically interacted with βTrCP1 as assessed by immunoprecipitation. In interaction domain determination experiments, we found that ERK2 interacted with two independent ERK docking sites located in the F-box domain and linker domain, but not the WD40 domain, of βTrCP1. Notably, mutations of βTrCP1 at the ERK docking sites abolished the interaction with ERK2. βTrCP1 underwent phosphorylation by EGF stimulation, while the presence of the mitogen-activated protein kinase kinases inhibitor U0126, genetic silencing by sh-ERK2, and mutation of the ERK docking site of βTrCP1 inhibited phosphorylation. This inhibition of βTrCP1 phosphorylation resulted in a shortened half-life and low protein levels. These results suggest that ERK2-mediated βTrCP1 phosphorylation may induce the destabilization of βTrCP1.

F-box Protein βTrCP1 Is a Substrate of Extracellular Signal-regulated Kinase 2

F-box proteins, consisting of 69 members which are organized into the three subclasses FBXW, FBXL, and FBXO, are the substrate specific recognition subunits of the SKP1-Cullin 1-F-box protein E3 ligase complex. Although βTrCP 1 and 2, members of the FBXW subfamily, are known to regulate some protein stability, molecular mechanisms by which these proteins can recognize proper substrates are unknown. In this study, it was found that βTrCP1 showed strong interaction with members of mitogen-activated protein kinases. Although extracellular signal-regulated kinase (ERK) 3, p38β, and p38δ showed weak interactions, ERK2 specifically interacted with βTrCP1 as assessed by immunoprecipitation. In interaction domain determination experiments, we found that ERK2 interacted with two independent ERK docking sites located in the F-box domain and linker domain, but not the WD40 domain, of βTrCP1. Notably, mutations of βTrCP1 at the ERK docking sites abolished the interaction with ERK2. βTrCP1 underwent phosphorylation by EGF stimulation, while the presence of the mitogen-activated protein kinase kinases inhibitor U0126, genetic silencing by sh-ERK2, and mutation of the ERK docking site of βTrCP1 inhibited phosphorylation. This inhibition of βTrCP1 phosphorylation resulted in a shortened half-life and low protein levels. These results suggest that ERK2-mediated βTrCP1 phosphorylation may induce the destabilization of βTrCP1.

Investigation of Water Safety in Non-treated Drinking Water with Trace Toxic Metals

The trace toxic metal copper was assayed using mercury immobilized on a carbon nanotube electrode (MCW), with a graphite counter and a reference electrode. In this study, a macro-scale convection motor was interfaced with a MCW three-electrode system, in which a handmade MCW was optimized using cyclic-and square-wave stripping voltammetry. An analytical electrolyte for tap water was used instead of an expensive acid or base ionic solution. Under these conditions, optimum parameters were 0.09 V amplitude, 40 Hz frequency, 0.01 V incremental potential, and a 60-s accumulation time. A diagnostic working curve was obtained from 50.0 to 350 microg/L. At a constant Cu(II) concentration of 10.0 microg/L, the statistical relative standard deviation was 1.78% (RSD, n = 15), the analytical accumulation time was only 60 s, and the analytical detection limit approached 4.6 microg/L (signal/noise = 3). The results were applied to non-treated drinking water. The content of the analyzed copper using 9.0 and 4.0 microg/L standards were 8.68 microg/L and 3.96 microg/L; statistical values R2 = 0.9987 and R2 = 0.9534, respectively. This method is applicable to biological diagnostics or food surveys.

Femoral Neuropathy and Meralgia Paresthetica Secondary to an Iliacus Hematoma

Compressive femoral and lateral femoral cutaneous neuropathies from an iliacus hematoma are unusual presentation. We report a case of a 16-year-old boy who developed right femoral and lateral femoral cutaneous neuropathies as a complication of traumatic ipsilateral iliacus hematoma formation. The patient complained of numbness in the right thigh and calf as well as right leg weakness, and pain in the right inguinal area. Nerve conduction study and needle electromyography identified the neuropathies. After the electrodiagnostic studies, the pelvic bone MRI revealed a large, 9x5x4.5 cm right iliacus hematoma. As a result, diagnosis of a right iliacus hematoma compressing the femoral and lateral femoral cutaneous nerves was made, and the patient underwent an operation to remove the hematoma. Symptoms and neurological signs showed notable improvement after surgical decompression. Subsequent follow-up electrodiagnostic studies after 11 weeks demonstrated regeneration evidence.

Factors that Influence Quiet Standing Balance of Patients with Incomplete Cervical Spinal Cord Injuries

OBJECTIVE: To investigate the factors influencing the quiet standing balance of patients with incomplete cervical spinal cord injuries. Also to find the correlations between posturographic parameters and clinical balance tests as well as to find the correlation between posturographic parameters and functional independence. METHOD: We conducted a tetra-ataxiometric posturography, lower extremity motor score (LEMS), Korean version of the Berg Balance Scale (K-BBS), Timed Up and Go test (TUG), and Korean Version of the Modified Barthel Index (K-MBI) of 10 patients. 10 healthy adults carried out the posturography. We checked stability, weight distribution, Fourier and synchronization indices of eight positions, and the fall index of the posturography. RESULTS: The patient group showed significantly higher stability and weight distribution indices in all eight positions. Stability indices significantly increased with eyes closed or standing on pillows. Weight distribution indices were significantly higher with eyes closed or the head bent backwards. The patient group showed significantly higher Fourier indices of low, low-medium, and high frequency in eight positions. The Fourier indices at high-medium frequency were significantly higher with eyes closed on pillows or in variable head positions. There were no significant differences of synchronization indices between the patient and the control group. The falling index of the patient group significantly correlated with K-BBS, TUG, and K-MBI. LEMS had significant correlation with some synchronization indices, but not with the falling index. CONCLUSION: The quiet standing balance of the patients was influenced by somatosensory limitations or insufficient visual compensation. We should try to improve the postural balance and functional independence of patients through proper proprioceptive and lower extremity strength training for better postural and pedal control, and to make efforts to minimize environmental hazards.

Nutritional Status of Children with Cerebral Palsy

OBJECTIVE: To determine the nutritional status of children with cerebral palsy (CP) and to compare their anthropometric and functional indices. METHOD: Seventy children with cerebral palsy, were at class I (12), II (17), III (18), IV (9) and V (14) on Gross Motor Function Classification System (GMFCS). They varied by age from 25 to 130 months with a mean of 48 months, and consisted of spastic diplegic cerebral palsy (30), quadriplegia (28), triplegia (3), hemiplegia (4), athetoid (4) and hypotonia (1). Evaluation of weight, height, subcutaneous fat thickness, brachial circumference, Body Mass Index (BMI), level of albumin, lymphocyte and blood ferritn were conducted. To identify the factors affecting nutritional status, dietary status and symptoms of dysphagia were investigated. RESULTS: Low BMI percentile was in 23 children (32.9%) and obese condition in 3 children (4.3%). Low BMI percentile tends to frequently observed in groups III, IV, V of GMFCS. BMI percentile with subcutaneous fat thickness, Gross Motor Function Measure (GMFM) score were significantly related (p<0.05). Seen from the symptom of dysphagia, low BMI percentile was correlated with decreased tongue motion (p<0.05). CONCLUSION: Cerebral palsy children with lower GMFM score, decreased tongue motion were significantly related with low BMI percentile. Subcutaneous fat thickness can be useful tool for evaluation of malnutrition of cerebral palsy children.

Clinical Characteristics of the Causes of Plantar Heel Pain

OBJECTIVE: The objectives of this study were to investigate the causes of plantar heel pain and find differences in the clinical features of plantar fasciitis (PF) and fat pad atrophy (FPA), which are common causes of plantar heel pain, for use in differential diagnosis. METHOD: This retrospective study analyzed the medical records of 250 patients with plantar heel pain at the Foot Clinic of Rehabilitation Medicine at Bundang Jesaeng General Hospital from January to September, 2008. RESULTS: The subjects used in this study were 114 men and 136 women patients with a mean age of 43.8 years and mean heel pain duration of 13.3 months. Causes of plantar heel pain were PF (53.2%), FPA (14.8%), pes cavus (10.4%), PF with FPA (9.2%), pes planus (4.8%), plantar fibromatosis (4.4%), plantar fascia rupture (1.6%), neuropathy (0.8%), and small shoe syndrome (0.8%). PF and FPA were most frequently diagnosed. First-step pain in the morning, and tenderness on medial calcaneal tuberosity correlated with PF. FPA mainly involved bilateral pain, pain at night, and pain that was aggravated by standing. Heel cord tightness was the most common biomechanical abnormality of the foot. Heel spur was frequently seen in X-rays of patients with PF. CONCLUSION: Plantar heel pain can be provoked by PF, FPA, and other causes. Patients with PF or FPA typically show different characteristics in clinical features. Plantar heel pain requires differential diagnosis for appropriate treatment.