Tubulin glutamylation regulates ciliary motility by altering inner dynein arm activity.

How microtubule-associated motor proteins are regulated is not well understood. A potential mechanism for spatial regulation of motor proteins is provided by posttranslational modifications of tubulin subunits that form patterns on microtubules. Glutamylation is a conserved tubulin modification [1] that is enriched in axonemes. The enzymes responsible for this posttranslational modification, glutamic acid ligases (E-ligases), belong to a family of proteins with a tubulin tyrosine ligase (TTL) homology domain (TTL-like or TTLL proteins) [2]. We show that in cilia of Tetrahymena, TTLL6 E-ligases generate glutamylation mainly on the B-tubule of outer doublet microtubules, the site of force production by ciliary dynein. Deletion of two TTLL6 paralogs caused severe deficiency in ciliary motility associated with abnormal waveform and reduced beat frequency. In isolated axonemes with a normal dynein arm composition, TTLL6 deficiency did not affect the rate of ATP-induced doublet microtubule sliding. Unexpectedly, the same TTLL6 deficiency increased the velocity of microtubule sliding in axonemes that also lack outer dynein arms, in which forces are generated by inner dynein arms. We conclude that tubulin glutamylation on the B-tubule inhibits the net force imposed on sliding doublet microtubules by inner dynein arms.

Frecuencia y fenomenología de lesiones autoinfligidas en mujeres colombianas con trastornos del comportamiento alimentario / Frequency and Phenomenology of Self-Inflicted Injuries in Colombian Women with Eating Disorders

Para la realización del estudio se evaluaron tanto la frecuencia de las lesiones auto infligidas sin intencionalidad suicida consciente como las variables asociadas con el riesgo de presentar este tipo de conducta, en 362 mujeres con anorexia nerviosa (n = 130), bulimia nerviosa (n = 141) o trastorno por atracones de alimentación (n = 91), atendidas en un programa ambulatorio en la ciudad de Bogotá, entre junio de 1997 y enero de 2005. Se encontraron 82 mujeres (22,6%) que, además de los síntomas anoréxicos o bulímicos, se cortaban o quemaban la piel, se golpeaban la cabeza u otras partes del cuerpo hasta sentir dolor, se mutilaban dedos u otras partes del cuerpo hasta sangrar o presentaban varias conductas simultáneamente. De éstas, 12 eran anoréxicas de tipo restrictivo, 17 tenían anorexia combinada con atracones o purgas, 38 padecían bulimia nerviosa y 17 presentaban un trastorno por atracones de alimentación. La automutilación estuvo asociada de manera significativa con trastorno de estrés postraumático (TEPT), personalidad limítrofe, trastorno afectivo bipolar (TAB) con episodios mixtos e intentos de suicidio previos. El riesgo de TEPT en las pacientes con trastornos del comportamiento alimentario (TCA) que se automutilan es el doble de aquéllas sin comportamientos de autodaño, que se ajustan a TAB con episodios mixtos, personalidad limítrofe e intentos de suicidio (OR = 2,04; IC 95%: 1,1-3,8). Estos hallazgos evidencian la necesidad de realizar una aproximación sistemática y estandarizada del síntoma automutilatorio en pacientes con TCA y muestran la relevancia de otras patologías comórbidas, en las que sobresalen los síntomas disociativos, afectivos o de discontrol de impulsos. Las pacientes con TCA y automutilaciones parecen constituir un subgrupo clínico de mayor gravedad, en las que se necesita una aproximación terapéutica específica.

The frequency of self-inflicted injuries without suicidal intent as well as the variables associated with the risk of displaying this kind of conduct were assessed in 362 women with Anorexia Nervosa (n=130), Bulimia Nervosa (n=141) and Binge-eating disorder (n=91) attending an out-patient program in Bogotá, between June 1997 and January 2005. 82 of the women (22.6%) presented, besides the symptoms of anorexia or bulimia, skin burning or cutting, headbanging, mutilation of fingers or other body parts or several of these conducts simultaneously. 12 of the 82 women had Anorexia Nervosa restricting type and 17 had bingeeating/ purging type, 38 had Bulimia Nervosa and 17 had Binge-eating disorder. Self-injury was associated significantly with Posttraumautic Stress Disorder (PTSD), borderline personality, Bipolar Disorder (BD) with mixed episodes and previous suicide attempts. The risk of PTSD in patients with Eating Disorders (ED) and self-injury is twice of those without self-injury behaviors that comply with BD with mixed episodes, borderline personality and suicide attempts (OR = 2.04; IC 95%: 1.1-3,8). These findings emphasize the need of applying a systematic and standardized evaluation of self-injury in patients with ED and highlight the relevance of comorbid pathology, including dissociative, mood and impulse control symptoms. Patients with ED and self-injury seem to constitute a clinical subgroup of greater severity in need of a specific therapeutic approach.