A global phosphosite-correlated network map of Thousand And One Kinase 1 (TAOK1).

Thousand and one amino acid kinase 1 (TAOK1) is a sterile 20 family Serine/Threonine kinase linked to microtubule dynamics, checkpoint signaling, DNA damage response, and neurological functions. Molecular-level alterations of TAOK1 have been associated with neurodevelopment disorders and cancers. Despite their known involvement in physiological and pathophysiological processes, and as a core member of the hippo signaling pathway, the phosphoregulatory network of TAOK1 has not been visualized. Aimed to explore this network, we first analyzed the predominantly detected and differentially regulated TAOK1 phosphosites in global phosphoproteome datasets across diverse experimental conditions. Based on 709 qualitative and 210 quantitative differential cellular phosphoproteome datasets that were systematically assembled, we identified that phosphorylation at Ser421, Ser9, Ser965, and Ser445 predominantly represented TAOK1 in almost 75% of these datasets. Surprisingly, the functional role of all these phosphosites in TAOK1 remains unexplored. Hence, we employed a robust strategy to extract the phosphosites in proteins that significantly correlated in expression with predominant TAOK1 phosphosites. This led to the first categorization of the phosphosites including those in the currently known and predicted interactors, kinases, and substrates, that positively/negatively correlated with the expression status of each predominant TAOK1 phosphosites. Subsequently, we also analyzed the phosphosites in core proteins of the hippo signaling pathway. Based on the TAOK1 phosphoregulatory network analysis, we inferred the potential role of the predominant TAOK1 phosphosites. Especially, we propose pSer9 as an autophosphorylation and TAOK1 kinase activity-associated phosphosite and pS421, the most frequently detected phosphosite in TAOK1, as a significant regulatory phosphosite involved in the maintenance of genome integrity. Considering that the impact of all phosphosites that predominantly represent each kinase is essential for the efficient interpretation of global phosphoproteome datasets, we believe that the approach undertaken in this study is suitable to be extended to other kinases for accelerated research.

Adrenal morphology and cortical function in patients with extrapulmonary tuberculosis: response to antituberculosis treatment

ABSTRACT Objective: Enlargement of the adrenal glands and variable adrenocortical function have been reported in patients with pulmonary tuberculosis and, in a few studies, in patients with extrapulmonary tuberculosis (EPTB). However, none of the studies have evaluated the course of the adrenal morphology in these patients. Subjects and methods: Prospective study including 37 patients with EPTB and 37 healthy age- and sex-matched controls. The adrenal function was evaluated by measurement of cortisol levels at baseline and after stimulation with ACTH (Acton Prolongatum) before and 6 months after antituberculosis treatment. The size of both adrenal glands was evaluated using 64-slice computed tomography (CT) scanning before and 6 months after treatment. The findings were compared with those in a group of healthy matched controls. Results: Clinical and biochemical parameters were comparable between groups. The mean baseline serum cortisol level was significantly lower in the EPTB group (397.1 ± 184.9 nmol/L) compared with the control group (696.3 ± 101.8 nmol/L). Compared with controls, patients with EPTB had significantly lower mean cortisol levels at baseline and 1 hour after ACTH, both before (397 ± 184.9 nmol/L and 750.7 ± 176.8 nmol/L, respectively) and after (529.7 ± 100.4 nmol/L and 1017.2 ± 119.7 nmol/L, respectively) antituberculosis treatment. Both the length and thickness of the right and left adrenal glands were greater in patients with EPTB than in controls but became comparable to those in controls after treatment completion. Conclusions: Patients with EPTB have an enlarged adrenal size and low baseline and stimulated serum cortisol levels. After treatment completion, cortisol levels increased significantly, and the adrenal size normalized in these patients.

Biological activities, therapeutic potential, and pharmacological aspects of blackcurrants (Ribes nigrum L): A comprehensive review.

Blackcurrant possesses various health-endorsing attributes owing to its polyphenol profile. Recent studies have demonstrated its therapeutic potential against various health disorders. Various bioactives present in blackcurrants have different functional and pharmacological aspects including anti-inflammatory, antioxidant, and antimicrobial properties. The most dominant and important bioactive include anthocyanins, flavonols, phenolic acids, and polyunsaturated fatty acids. Food formats derived from blackcurrants comprise pomace, juice, powder, and extracts. All these food formats have industrial, prebiotic, and pharmacological benefits. In the current article, the nutritional composition, industrial applications, and therapeutic potential are discussed in the recent literature. Moreover, novel extraction techniques for the extraction of bioactive compounds present in blackcurrants and their safety concerns have been elaborated.

Developmental association of palatal dimensions and palatal rugae characteristics in Angle´s classes I, II and III of malocclusion / Asociación de desarrollo de las dimensiones palatinas y las características de las rugas palatinas en las clases I, II y III de maloclusión de Angle

During development, bony changes in the palate are reflected in the palatal rugae. Therefore, we hypothesized that the palatal dimensions (PD) influence the shape and number of palatal rugae (PR). The objectives were to record the palatal rugae characteristics (PRC) and palatal dimensions (intercanine distance (ICD), intermolar distance (IMD), palatal height (PH) and palatal area (PA) in Classes I, II and III malocclusion patients and investigate their interrelationship, and statistically examine the possibility of predicting PRC with the PD. Four hundred eighty-one pre-orthodontic study casts of healthy patients with normal palate anatomy were grouped as Classes I, II and III and scanned using 3D cast scanner. The PRC, ICD, IMD, PH, and PA were recorded digitally using 3D enabled software. The data was statistically analyzed. A strong statistically significant difference was observed between PA and number of straight and wavy rugae. ICD and the number of straight rugae were also related. A weak correlation exists between malocclusion classes and PA. The remaining rugae characteristics did not exhibit any relation with palatal dimensions. PA is positively related to the number of straight rugae and negatively related to the number of wavy rugae. Bigger palates have more straight rugae and less number of wavy rugae. A weak correlation between PA and Angle's class I malocclusion exists. We also propose that PA has a developmental association with the number and shape of PR.

Durante el desarrollo, los cambios óseos en el paladar se reflejan en las rugas palatinas. Por lo tanto, planteamos la hipótesis de que las dimensiones palatinas influyen en la forma y el número de las rugas palatinas. Los objetivos fueron registrar las características de las rugas palatinas y las dimensiones palatales (distancia intercanina, distancia intermolar, altura palatina y área palatina) en pacientes con maloclusión de clases I, II y III e investigar su interrelación, y examinar estadísticamente la posibilidad de predecir las características de las rugas palatinas con las dimensiones palatinas. Cuatrocientos ochenta y un estudios pre-ortodónticos de pacientes sanos con anatomía normal del paladar se agruparon como Clases I, II y III y se escanearon con un escáner de emisión 3D. La distancia intercanina, distancia inter molar, altura palatina y área palatina se registraron digitalmente utilizando el software 3D. Los datos se analizaron estadísticamente. Se observó una diferencia estadísticamente significativa entre la altura palatina y el número de rugas rectas y onduladas. Se registró también la distancia intercanina y el número de rugas rectas. Existe una correlación débil entre las clases de maloclusión y la altura palatina. Las características restantes de las rugas palatinas no mostraron ninguna relación con las dimensiones palatinas. El área palatina está relacionada positivamente con el número de rugas rectas y negativamente relacionada con el número de rugas onduladas. Los paladares más grandes tienen más rugas rectas y menor cantidad de rugas onduladas. Existe una correlación débil entre el área palatina y la clase I de maloclusión de Angle. También proponemos que el área palatina tiene una asociación de desarrollo con el número y la forma de rugas palatinas.

A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one candidate gene that has been studied. OBJECTIVE: Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India. MATERIALS AND METHODS: This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years) without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2, and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/non-parametric tests. RESULTS: The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p = 0.177 and 0.43, respectively). CONCLUSION: Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India.

Tubercular osteomyelitis of the mandible in a young female.

A 16-year-old female presented with a 6-month history of a gradually increasing swelling of the left side of her face. A panoramic radiographic view of the mandible showed diffuse radiolucency in the ramus of the mandible with a loss of cortication on the superior and anterior portion of the condyle. The computed tomography (CT) scan revealed destruction of the mandibular bone and a large retromandibular and inferior temporal fossa mass with areas of breakdown. The biopsy was consistent with tubercular osteomyelitis. Antitubercular therapy resulted in a marked reduction of the size of the swelling over a 9-month period.

Radiation risk assessment in professionals working in dental radiology area using buccal micronucleus cytome assay.

OBJECTIVE: The aim of this study was to assess the incidence of micronuclei (MN) in buccal mucosal cells of professionals working in radiology area to determine the risk of stochastic effects of radiation. MATERIALS AND METHODS: All the professionals and students working in King Khalid University - College of Dentistry radiology area were included in the Risk Group (RG = 27). The Control Group (CG = 27) comprised of healthy individual matching the gender and age of the RG. Buccal mucosal scraping from all the 54 subjects of RG and CG were stained with Papanicolaou stain and observed under oil immersion lens (×100) for the presence of micronuclei (MN) in the exfoliated epithelial cells. RESULTS: There was no significant difference between the incidence of MN in RG and CG (p = >0.05) using t-test. CONCLUSION: Routine radiation protection protocol does minimize the risk of radiation induced cytotoxicity, however, screening of professionals should be carried out at regular intervals.