AP-1 and Mitf interact with NFATc1 to stimulate cathepsin K promoter activity in osteoclast precursors.

Cathepsin K (CTSK) is a secreted protease that plays an essential role in osteoclastic bone resorption and osteoporotic bone loss. We have previously shown that activator protein 1 (AP-1) stimulates CTSK promoter activity and that proximal nuclear factor of activated T cells cytoplasmic 1 (NFATc1)-binding sites play a major role in the stimulation of CTSK gene expression by receptor activator of NFκB ligand (RANKL). In the present study, we have extended these observations and further dissected the effects of transcription factors involved in the regulation of CTSK gene expression. Our aim was to investigate the cooperative interplay among transcription factors AP-1, microphthalmia-associated transcription factor (Mitf), and NFATc1, and the consequent regulatory effects on CTSK transcription. Experiments were carried out in RAW 264.7 cells, which can be readily differentiated to osteoclasts upon RANKL stimulation. Our data show that AP-1, Mitf, and NFATc1 are capable of independently stimulating CTSK promoter activity. A combination of any two factors further enhances CTSK promoter activity, with the combination of AP-1 (c-fos/c-jun) and NFATc1 inducing the largest increase. We further identify a synergistic effect when all three factors cooperate intimately at the proximal promoter region, yielding maximal transcriptional upregulation of the CTSK promoter. RANKL induces temporal localization of AP-1 and NFATc1 to the CTSK promoter. These results suggest that the interaction of multiple transcription factors mediate a maximal response to RANKL-induced CTSK gene expression.

Frecuencia de signos y síntomas clínicos extraorales en los estudiantes con trastornos temporomandibulares de la Facultad de Odontología de la Universidad de El Salvador / Frequency of extra oral clinical signs and symptoms in students with temporomandibular disorders of the School of Dentistry of the University of El Salvador

En la presente investigación se estudio la frecuencia de signos y síntomas clínicos extraorales de los Trastornos Temporomandibulares en los estudiantes de 17 a 25 años de la Facultad de Odontología de la Universidad de El Salvador, con el objetivo de determinar la percepción de dolor en músculos masticatorios, cuello, cabeza y ATM, tonicidad muscular, detectando ruidos articulares, desviación mandibular a la apertura/cierre, apertura normal y máxima de cada estudiante. Dicho estudio se llevó a cabo en las instalaciones de la Facultad de Odontología, contando con una población total de 119 estudiantes, que presentaron signos y síntomas característicos de Trastornos Temporomandibulares. De la población total, la investigadora A evaluó clínicamente a los estudiantes mientras la investigadora B realizaba las respectivas anotaciones en la Guía de Observación; posteriormente invirtieron sus funciones. Se realizó durante este examen clínico la palpación, auscultación de músculos, articulación, medición de apertura normal - máxima y observación de movimientos de apertura y cierre en cada estudiante. En base a la investigación realizada se obtuvieron los siguientes resultados: Mayor prevalencia de signos y síntomas en mujeres que en hombres, presencia de dolor en ATM en un 18% de los estudiantes. El signo más frecuente fue ruido articular con un 66%, al realizar la evaluación clínica presentaron un 87% de desviación mandibular; el 68% desviación durante la apertura y un 79% desviación durante el cierre. El síntoma más frecuente en los estudiantes fue dolor en el músculo masetero con un 47% y el de menor frecuencia el músculo temporal con un 24%. Con respecto a la hipertonicidad, el músculo masetero presentó un 58%, seguido del músculo temporal con un 41%, el músculo trapecio presentó un 32% y el 29% el músculo Esternocleidomastoideo.

In the present investigation, the frequency of extraoral clinical signs and symptoms of Temporomandibular Disorders in students aged 17 to 25 years of the Faculty of Dentistry of the University of El Salvador was studied, with the aim of determining the perception of pain in masticatory muscles , neck, head and TMJ, muscle tonicity, detecting joint noises, mandibular deviation when opening / closing, normal and maximum opening of each student. This study was carried out in the facilities of the Faculty of Dentistry, with a total population of 119 students, who presented signs and symptoms characteristic of Temporomandibular Disorders. From the total population, researcher A clinically evaluated the students while researcher B made the respective annotations in the Observation Guide; they later reversed their functions. During this clinical examination, palpation, auscultation of muscles, articulation, measurement of normal opening - maximum and observation of opening and closing movements were performed in each student. Based on the research carried out, the following results were obtained: Greater prevalence of signs and symptoms in women than in men, presence of TMJ pain in 18% of the students. The most frequent sign was joint noise with 66%, when performing the clinical evaluation they presented 87% of mandibular deviation; 68% deviation during opening and 79% deviation during closing. The most frequent symptom in the students was pain in the masseter muscle with 47% and the least frequent the temporal muscle with 24%. Regarding hypertonicity, the masseter muscle presented 58%, followed by the temporal muscle with 41%, the trapezius muscle presented 32% and the sternocleidomastoid muscle 29%.

Number, position, and significance of the pseudouridines in the large subunit ribosomal RNA of Haloarcula marismortui and Deinococcus radiodurans.

The number and position of the pseudouridines of Haloarcula marismortui and Deinococcus radiodurans large subunit RNA have been determined by a combination of total nucleoside analysis by HPLC-mass spectrometry and pseudouridine sequencing by the reverse transcriptase method and by LC/MS/MS. Three pseudouridines were found in H. marismortui, located at positions 1956, 1958, and 2621 corresponding to Escherichia coli positions 1915, 1917, and 2586, respectively. The three pseudouridines are all in locations found in other organisms. Previous reports of a larger number of pseudouridines in this organism were incorrect. Three pseudouridines and one 3-methyl pseudouridine (m3Psi) were found in D. radiodurans 23S RNA at positions 1894, 1898 (m3Psi), 1900, and 2584, the m3Psi site being determined by a novel application of mass spectrometry. These positions correspond to E. coli positions 1911, 1915, 1917, and 2605, which are also pseudouridines in E. coli (1915 is m3Psi). The pseudouridines in the helix 69 loop, residues 1911, 1915, and 1917, are in positions highly conserved among all phyla. Pseudouridine 2584 in D. radiodurans is conserved in eubacteria and a chloroplast but is not found in archaea or eukaryotes, whereas pseudouridine 2621 in H. marismortui is more conserved in eukaryotes and is not found in eubacteria. All the pseudoridines are near, but not exactly at, nucleotides directly involved in various aspects of ribosome function. In addition, two D. radiodurans Psi synthases responsible for the four Psi were identified.

WW or WoW: the WW domains in a union of bliss.

WW domains are small protein modules that recognize proline-rich peptide motifs or phosphorylated-serine/threonine proline sites in cognate proteins. Within host proteins these modules are joined to other protein domains or to a variety of catalytic domains acting together as adaptors or targeting anchors of enzymes. An important aspect of signaling by WW domains is their ability to recognize their cognate ligands in tandem. Tandem WW domains not only act in a synergistic manner but also appear to chaperone the function of each other. In this review, we focus on structure, function, and mechanism of the tandem WW domains co-operativity as well as independent actions. We emphasize here the implications of tandem arrangement and cooperative function of the domains for signaling pathways.