Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion.

HECT-E3 ligases play an essential role in catalyzing the transfer of ubiquitin to protein substrates. The noncatalytic roles of HECT-E3 ligases in cells are unknown. Here, we report that a HECT-E3 ligase, HACE1, functions as an adaptor independent of its E3 ligase activity. We identified Spindlin-1, a histone reader, as a new HACE1-associated protein. Interestingly, we found that HACE1 promotes Spindlin-1 degradation via the proteasome in an ubiquitination-independent manner. Functionally, we demonstrated that the loss of HACE1 results in weak cell-cell adhesion due to Spindlin-1-mediated accumulation of GDNF, a negative regulator of cell adhesion. Together, our data suggest that HACE1 acts as a molecular adaptor and plays an important noncatalytic role in presenting selected substrates directly to the proteasome for degradation.

Evaluation of Impact of Tinea Capitis on Quality of Life in Pediatric Patients Using Children's Dermatology Life Quality Index and Its Correlation with Disease Duration.

INTRODUCTION: The superficial fungal infection of the scalp caused by dermatophytes is called tinea capitis. It has a predilection for the pediatric age group. In developing countries like India factors such as overcrowding, inadequate hygiene, and low literacy rate contribute to its high incidence. AIMS AND OBJECTIVE: This study aimed at identifying and grading the psychosocial impact of tinea capitis in children and correlating it with disease duration and socioeconomic status of patient's family. MATERIALS AND METHODS: This was a cross-sectional study conducted in our skin outpatient department involving children aged 6-16 years with clinical diagnosis of tinea capitis. We used the children's dermatology life quality index (CDLQI) instrument to observe the psychological implications in these children. RESULTS: The study included 134 patients, with a mean CDLQI score of 6.01 ± 4.17. There was a male preponderance in our study with 112 (68.3%) male patients and 52 (31.7%) female patients. The age group affected most commonly was 6-8 years (37.8%). The domains affected most severely were symptoms and feelings (Q1 and Q2) followed by sleep (Q 9). The psychological implications were higher in patients suffering from kerion, older children, and female patients. There was a statistically significant correlation between the impact on quality of life (QOL) and disease duration as well as disease severity; however, no correlation could be made between QOL and socioeconomic strata of family. CONCLUSION: The study brings into question the overlooked psychological implications of tinea capitis which are often overlooked by the dermatologist and parents as a mere dermatological disease. Instead a holistic approach including a complete psychological evaluation of children and appropriate counseling of both patients and their parents must be done.

Enhancement of contralateral ptosis on passively holding an eyelid in mitochondrial myopathy resembling myasthenia gravis.

Ptosis has long been recognized as a presenting sign of myasthenia gravis, and the appearance of ptosis or increasing ptosis with passive lid elevation of opposite eye is a useful bedside diagnostic test for this disease. We describe a patient whose ptosis worsened in either eye when the examiner passively held the opposite eyelid. She was initially thought to have myasthenia gravis, but ultimately it was discovered her ocular findings were caused by a mitochondrial myopathy.

Dropped head presentation of mitochondrial myopathy.

Dropped head secondary to weakness of the neck extensors has been reported in a wide assortment of neuromuscular disorders. Infrequently, dropped head can be the first sign of disease. We describe two patients with dropped head as the presenting manifestation of mitochondrial myopathy. In both patients, serum lactate was elevated and muscle biopsy showed mitochondrial proliferation. Mitochondrial myopathy should be considered in the differential diagnosis of dropped head syndrome, particularly when other, more common causes such as myasthenia gravis, polymyositis, and amyotrophic lateral sclerosis have been excluded by appropriate laboratory and electrophysiological studies.