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1.  Encephalocraniocutaneous lipomatosis with calvarial exostosis - Case report and review of literature 
Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a rare syndrome with unknown etiology. The syndrome is characterized by a triad of unique cutaneous, ocular, and central nervous system (CNS) manifestations. The cutaneous hallmark, nevus psiloliparus (NP), along with overlying alopecia is a constant feature. Choristoma of the eyelid is the most common ocular manifestation, while intracranial lipoma is the predominant CNS finding. Genetic counseling is required to emphasize that the disorder, although congenital, is not inheritable. We present a 21-year-old female with cutaneous, ocular, and CNS features satisfying the diagnostic criteria for ECCL. To our knowledge, this is the first case of ECCL having a large temporal exostosis. The objective of this article is to better understand the phenotypic spectrum of this syndrome whose molecular basis is still unknown.
doi:10.4103/0971-3026.125607
PMCID: PMC3932575  PMID: 24604937
Choristoma; encephalocraniocutaneous lipomatosis; exostosis; neurocutaneous; nevus psiloliparus
2.  Production of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\pi ^0}$$\end{document}π0 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta $$\end{document}η mesons up to high transverse momentum in pp collisions at 2.76 TeV 
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P. | Sugitate, T. | Suire, C. | Suleymanov, M. | Suljic, M. | Sultanov, R. | Šumbera, M. | Sumowidagdo, S. | Suzuki, K. | Swain, S. | Szabo, A. | Szarka, I. | Szczepankiewicz, A. | Szymanski, M. | Tabassam, U. | Takahashi, J. | Tambave, G. J. | Tanaka, N. | Tarhini, M. | Tariq, M. | Tarzila, M. G. | Tauro, A. | Muñoz, G. Tejeda | Telesca, A. | Terasaki, K. | Terrevoli, C. | Teyssier, B. | Thakur, D. | Thakur, S. | Thomas, D. | Tieulent, R. | Tikhonov, A. | Timmins, A. R. | Toia, A. | Tripathy, S. | Trogolo, S. | Trombetta, G. | Trubnikov, V. | Trzaska, W. H. | Trzeciak, B. A. | Tsuji, T. | Tumkin, A. | Turrisi, R. | Tveter, T. S. | Ullaland, K. | Umaka, E. N. | Uras, A. | Usai, G. L. | Utrobicic, A. | Vala, M. | Van Der Maarel, J. | Van Hoorne, J. W. | van Leeuwen, M. | Vanat, T. | Vyvre, P. Vande | Varga, D. | Vargas, A. | Vargyas, M. | Varma, R. | Vasileiou, M. | Vasiliev, A. | Vauthier, A. | Doce, O. Vázquez | Vechernin, V. | Veen, A. M. | Velure, A. | Vercellin, E. | Limón, S. 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doi:10.1140/epjc/s10052-017-4890-x
PMCID: PMC5586361
doi:10.4103/ijmr.IJMR_1888_15
PMCID: PMC5644306  PMID: 28948962
Indian Journal of Microbiology  2015;56(1):88-98.
Xanthine oxidase is an important enzyme of purine metabolism that catalyzes the hydroxylation of hypoxanthine to xanthine and then xanthine to uric acid. A thermostable xanthine oxidase is being reported from a thermophilic organism RL-2d isolated from the Manikaran (Kullu) hot spring of Himachal Pradesh (India). Based on the morphology, physiological tests, and 16S rDNA gene sequence, RL-2d was identified as Bacillus pumilus. Optimization of physiochemical parameters resulted into 4.1-fold increase in the xanthine oxidase activity from 0.051 U/mg dcw (dry cell weight) to 0.209 U/mg dcw. The xanthine oxidase of B. pumilus RL-2d has exhibited very good thermostability and its t1/2 at 70 and 80 °C were 5 and 1 h, respectively. Activity of this enzyme was strongly inhibited by Hg2+, Ag+ and allopurinol. The investigation showed that B. pumilus RL-2d exhibited highest xanthine oxidase activity and remarkable thermostability among the other xanthine oxidases reported so far.
doi:10.1007/s12088-015-0547-3
PMCID: PMC4729748  PMID: 26843701
Bacillus pumilus; Xanthine oxidase; Thermophilic microorganisms; Thermostability
3 Biotech  2016;6(2):180.
Proteases are a class of enzymes that catalyze hydrolysis of peptide bonds of proteins. In this study, 221 proteolytic bacterial isolates were obtained by enrichment culture method from soils of various regions of Himachal Pradesh, India. From these a hyper producer of protease was screened and identified by morphological and physiological testing and by 16S rDNA sequence as Serratia marcescens PPB-26. Statistical optimization of physiochemical parameters enhanced the protease production by 75 %. Protease of S. marcescens PPB-26 was classified as a metalloprotease. It showed optimal activity at 30 °C, pH 7.5 (0.15 M Tris–HCl buffer) and with 0.8 % substrate concentration. It had K m = 0.3 %, V max = 34.5 μmol min−1 mg−1 protein and a half life of 2 days at 30 °C. The enzyme was stable in most metal ions but showed increased activity with Fe2+ and Cu2+ while strong inhibition with Co2+ and Zn2+. Further investigation showed that the enzyme could not only retain its activity in various organic solvents but also showed increased activity with methanol and ethanol. The reported metalloprotease is thus a potential candidate for carrying out industrial peptide synthesis.
doi:10.1007/s13205-016-0500-0
PMCID: PMC4999571
Serratia marcescens; Organic solvent tolerant protease; Metalloprotease; 16S rDNA sequencing; Response surface methodology
Genome Announcements  2015;3(5):e00943-15.
The complete genome sequence of 6.45 Mb is reported here for Pseudomonas trivialis strain IHBB745 (MTCC 5336), which is an efficient, stress-tolerant, and broad-spectrum plant growth-promoting rhizobacterium. The gene-coding clusters predicted the genes for phosphate solubilization, siderophore production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, indole-3-acetic acid (IAA) production, and stress response.
doi:10.1128/genomeA.00943-15
PMCID: PMC4559727  PMID: 26337878
Industrial Psychiatry Journal  2015;24(2):140-143.
Background:
Adolescent suicide is an important public health issue. Suicidal ideations are often the precursor of suicide and can be targeted by appropriate and timely interventions.
Aims and Objectives:
To determine the prevalence of suicide ideation and to study its predictive factors among school going adolescents.
Materials and Methods:
This cross-sectional study was carried out in selected senior secondary schools in Shimla district of Himachal Pradesh, India. A pre-validated, self-administered questionnaire was used for data collection. Both descriptive and inferential statistics were applied using Epi info software for windows (CDC Atlanta) software for windows.
Results:
A total of 218 study subjects (30.9%; confidence interval = 27.6–34.5%) had suicide ideation. Discussing problems with parents (adjusted odds ratio [AOR] =0.5), having good relations with school teachers (AOR = 0.6) and helpful classmates (AOR = 0.6) lowered the odds of having suicidal ideations. On the contrary, adolescents having worrying issues in family (AOR = 2.5), verbally or physically abused (AOR = 2.8) and body image conscious (AOR = 1.8) had increased odds of suicidal ideations.
Conclusions:
Suicidal ideation is a common experience among adolescents residing in Shimla district of North India. The supportive environment at home and in school decrease its vulnerability.
doi:10.4103/0972-6748.181719
PMCID: PMC4866340  PMID: 27212817
Adolescents; predictors; suicidal ideation
ABSTRACT
Aim: To evaluate the effects of postbleaching antioxidant application fluoridation treatment on the surface morphology and microhardness of human enamel.
Materials and methods: Ten freshly extracted human maxillary central incisors were cut at cementoenamel junction. Crown portion was sectioned into six slabs which were divided into five groups: group A – untreated controls; group B – 35% carbamide peroxide (CP); group C – 35% CP and catalase; group D – treatment with 35% CP and 5% sodium fluoride; group E – 35% CP, catalase and 5% sodium fluoride. Thirty-five percent carbamide peroxide application included two applications of 30 minutes each at a 5-day interval. After treatment, the slabs were thoroughly washed with water for 10 seconds and stored in artificial saliva at 37°C until the next treatment. Two percent sodium fluoride included application for 5 minutes. Three catalase included application for 3 minutes.
Results: After 5 days, groups B and C showed significantly decreased enamel microhardness compared to control. Group D specimens showed relatively less reduction in enamel micro-hardness than group C specimens. There is a marked increase in enamel microhardness in group E specimens.
Conclusions: Fluoride take up was comparatively enhanced after catalase application resulting in less demineralization and increased microhardness.
How to cite this article: Thakur R, Shigli AL, Sharma DS, Thakur G. Effect of Catalase and Sodium Fluoride on Human
Enamel bleached with 35% Carbamide Peroxide. Int J Clin Pediatr Dent 2015;8(1):12-17.
doi:10.5005/jp-journals-10005-1276
PMCID: PMC4472865  PMID: 26124575
In-office bleaching; Carbamide peroxide; Catalase; Sodium fluoride.
Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host–virus interactions and pathogenesis of viral diseases. Lately, miRNAs have also shown potential as important targets for the development of novel antiviral therapeutics. Although several miRNA and their target repositories are available for human and other organisms in literature, but a dedicated resource on viral miRNAs and their targets are lacking. Therefore, we have developed a comprehensive viral miRNA resource harboring information of 9133 entries in three subdatabases. This includes 1308 experimentally validated miRNA sequences with their isomiRs encoded by 44 viruses in viral miRNA ‘VIRmiRNA’ and 7283 of their target genes in ‘VIRmiRtar’. Additionally, there is information of 542 antiviral miRNAs encoded by the host against 24 viruses in antiviral miRNA ‘AVIRmir’. The web interface was developed using Linux-Apache-MySQL-PHP (LAMP) software bundle. User-friendly browse, search, advanced search and useful analysis tools are also provided on the web interface. VIRmiRNA is the first specialized resource of experimentally proven virus-encoded miRNAs and their associated targets. This database would enhance the understanding of viral/host gene regulation and may also prove beneficial in the development of antiviral therapeutics.
Database URL: http://crdd.osdd.net/servers/virmirna
doi:10.1093/database/bau103
PMCID: PMC4224276  PMID: 25380780
South Asian Journal of Cancer  2014;3(4):193-195.
Background:
Cigarettes smoking is a common mode of consuming tobacco in India. This habit usually starts in adolescence and tracks across the life course. Interventions like building decision making skills and resisting negative influences are effective in reducing the initiation and level of tobacco use.
Aims and Objectives:
The purpose of this study was to assess the prevalence of adolescent current cigarette smoking behavior and to investigate the individual and social factors, which influence them both to and not to smoke.
Methodology:
A cross-sectional study was carried out among school going adolescents in Shimla town of North India. After obtaining their written informed consent, a questionnaire was administered.
Results:
The overall prevalence of current cigarette smoking was 11.8%. The binary logistic regression model revealed that parents’ and peers’ smoking behavior influence adolescent smoking behavior. Individual self-harm tendency also significantly predicted cigarette smoking behavior. Parental active participation in keeping a track of their children's free time activities predicted to protect adolescents from taking this habit.
Conclusion:
Our research lends support to the need for intervention on restricting adolescents from taking up this habit and becoming another tobacco industries’ addicted customer. Parents who smoke should quit this habit, which will not only restore their own health, but also protect their children. All parents should be counseled to carefully observe their children's free time activities.
doi:10.4103/2278-330X.142946
PMCID: PMC4236693  PMID: 25422801
Adolescent; smoking; social environment
The morphogenesis of the pancreas is a complex process having a very low frequency of anatomic variation. The congenital anomalies are rare. Complete pancreatic and ventral pancreatic agenesis are incompatible with life. Dorsal pancreatic agenesis is exceedingly rare with less than 100 cases reported in the world literature. Patients with this anomaly may be asymptomatic or may present with abdominal pain, hyperglycemia, diabetes mellitus, and acute or chronic pancreatitis. Such anomalies are rarely reported; therefore, clinical awareness of agenesis of the dorsal pancreas as a cause of these symptoms can expand the differential diagnosis and improve patient management.
doi:10.4103/0971-3026.134401
PMCID: PMC4094968  PMID: 25024525
Dorsal pancreatic agenesis; embryogenesis; hyperglycemia
Genes & Nutrition  2013;9(1):369.
Folic acid is the key one-carbon donor required for de novo nucleotide and methionine synthesis. Its deficiency is associated with megaloblastic anemia, cancer and various complications of pregnancy. However, its supplementation results in reduction of neural tube defects and prevention of several types of cancer. The intake of folic acid from fortified food together with the use of nutritional supplements creates a state of folate oversupplementation. Fortification of foods is occurring worldwide with little knowledge of the potential safety and physiologic consequences of intake of such high doses of folic acid. So, we planned to examine the effects of acute and chronic folate oversupplementation on the physiology of renal folate transport in rats. Male Wistar rats were procured and divided into two groups. Rats in group I were given semisynthetic diets containing 2 mg folic acid/kg diet (control) and those in group II were given folate-oversupplemented rat diet, i.e., 20 mg folic acid/kg diet (oversupplemented). Six animals from group I and group II received the treatment for 10 days (acute treatment) and remaining six for 60 days (chronic treatment). In acute folate-oversupplemented rats, 5-[14C]-methyltetrahydrofolate uptake was found to be significantly reduced, as compared to chronic folate-oversupplemented and control rats. This reduction in uptake was associated with a significant decrease in the mRNA and protein levels of the folate transporters. Results of the present investigation showed that acute oversupplementation led to a specific and significant down-regulation of renal folate uptake process mediated via transcriptional and translational regulatory mechanism(s).
doi:10.1007/s12263-013-0369-z
PMCID: PMC3896635  PMID: 24306960
Folate; Folate transport; FBP; PCFT; RFC; Folate oversupplementation
Dens invaginatus occurs as a result of the invagination of the enamel organ. These cases may present difficulties with respect to its diagnosis and treatment because of canal morphology. It frequently leads to caries, pulpal, and periodontal involvement with necrosis and loss of attachment. The knowledge of classification and anatomical variations of teeth with dens invaginatus are of great importance for correct treatment. This article presents two case reports of two different types of dens invaginatus along with profound review of the literature regarding etiology, epidemiology, and histology. It discusses clinical appearance and diagnosis, and it provides guidelines for decision-making and treatment of invaginated teeth.
doi:10.4103/0976-9668.127341
PMCID: PMC3961942  PMID: 24678234
Case reports; classification; dens invaginatus; Etiology
Dental Research Journal  2014;11(1):129-132.
This report presents a case of severe intrusive luxation of multiple anterior teeth in an 11-year-old girl. The teeth were repositioned successfully by endodontic and orthodontic management. The case was monitored for 7 years. Depending on the severity of the injury, different clinical approaches for treatment of intrusive luxation may be used. Despite the variety of treatment modalities, rehabilitation of intruded teeth is always a challenge and a multidisciplinary approach is important to achieve a successful result. In this case, intruded teeth were endodontically treated with multiple calcium hydroxide dressings and repositioned orthodontically. The follow-up of such cases is very important as the repair process after intrusion is complex. After 7 years, no clinical or radiographic pathology was detected.
PMCID: PMC3955308  PMID: 24688573
Intrusion; management; seven year follow-up
Craniosynostosis means premature closure of calvarial sutures. It may be primary or secondary. The patient presents with unexplained neuropsychological impairment and radiological imaging clinches the diagnosis. We present a case of 31-year-old female having primary isolated craniosynostosis who survived into adulthood without any surgical intervention. The imaging findings of such a case are rarely described in the literature.
doi:10.4103/0972-2327.128563
PMCID: PMC3992780  PMID: 24753669
Craniosynostosis; convolutional; imaging; sutures; syndrome
Chinese Journal of Cancer  2013;32(8):434-440.
Radiotherapy plays a major role in the treatment of cervical cancer. A successful radiotherapy program integrates both external beam and brachytherapy components. The principles of radiotherapy are strongly based on the anatomy of the organ and patterns of local and nodal spread. However, in patients with distorted anatomy, several practical issues arise in the delivery of optimal radiotherapy, especially with brachytherapy. Müllerian duct anomalies result in congenital malformations of the female genital tract. Though being very commonly studied for their deleterious effects on fertility and pregnancy, they have not been recognized for their potential to interfere with the delivery of radiotherapy among patients with cervical cancer. Here, we discuss the management of cervical cancer among patients with Müllerian duct anomalies and review the very sparse amount of published literature on this topic.
doi:10.5732/cjc.012.10222
PMCID: PMC3845580  PMID: 23419195
Cancer of the cervix; cervical carcinoma; uterocervical anomalies; Müllerian duct anomalies
To study the prevalence of metabolic syndrome (MS) among newly diagnosed hypertensive patients in a tertiary care hospital in the northern hilly state of Himachal Pradesh, India, located in western Himalayas at a moderate altitude of 2200 m above mean sea level. One hundred and eighteen newly diagnosed hypertensive patients above the age of 20 years were studied in a hospital-based cross-sectional study. MS prevalence was estimated by International Diabetes Federation (IDF) criteria and modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Student's t-test was used to compare the mean of the continuous variables. Chi-square test was used to compare discrete variables. The prevalence of MS in hypertensive patients was 68.6% (modified NCEP-ATP III) and 63.6% (IDF criteria). The most common phenotype of MS with the component of hypertension was the coexistence of waist circumference (90.1%), low high-density lipoprotein (HDL; 70.4%), and high triglycerides (67.9%) as per the modified NCEP-ATP III criteria, and low HDL (76.2%) and high triglycerides (66.4%) as per the IDF criteria. Fasting blood glucose (33.2% as per the modified NCEP-ATP III criteria and 32.6% as per the IDF criteria) was the least significant factor having an association with MS. The prevalence of MS among hypertensive patients was high and indicates the need for metabolic screening in all hypertensive patients at the first diagnosis.
doi:10.4103/2230-8210.113768
PMCID: PMC3743377  PMID: 23961493
Hypertension; India; metabolic syndrome; moderate altitude; western Himalayas
Iranian Journal of Neurology  2013;12(4):169-171.
Intracranial lipomas are congenital malformations. These uncommon lesions have an incidence of 0.1 to 1.7% of all intracranial tumors. Most cases are located at midline and 5% are along the sylvian fissures. If symptomatic, seizures are the most common symptom. These tumors are slow growing and have favorable outcome. We report a case of a 25-year-old man whose CT and MRI revealed a lesion in right sylvian fissure suggesting a lipoma with abnormal vasculature and overlying cortical dysplasia.
PMCID: PMC3829310  PMID: 24250928
Sylvian Fissure; Angiomatous; Lipoma; Cortical Dysplasia
Tuberculosis of parotid is a rare clinical entity, and cases of bilateral tubercular parotitis are even rarer. We present a case of bilateral primary parotid tuberculosis in a 49-year-old female. The patient received anti-tuberculosis treatment for six months, resulting in complete resolution of the disease. We also review the theories related to the pathogenesis of tubercular parotitis, and propose a novel hypothesis about greater involvement of parotid gland as compared to other salivary glands in primary tuberculosis.
doi:10.4103/0974-777X.83543
PMCID: PMC3162820  PMID: 21887065
Mycobacteria; Parotid; Pathogenesis; Tuberculosis
Background:
Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy.
Materials and Methods:
Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD50 and CD99 values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100–300 mg/kg), lamotrigine (3–12 mg/kg) and flunarizine (5–20 mg/kg), and then each group of mice was injected with CD99 dose of PTZ (65mg/kg i.p.). Another group of mice received single ED50 dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal–Wallis ANOVA on Ranks test.
Results:
As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection.
Conclusion:
As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish flunarizine as add-on therapy in refractory epilepsy.
doi:10.4103/0975-7406.80782
PMCID: PMC3103921  PMID: 21687355
Flunarizine; lamotrigine; PTZ; seizure; sodium valproate
Background
Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from other urban areas offers the opportunity to study clinical pathogenesis of ALI in a search for potential prevention targets.
Methods/Design
In this population-based observational cohort study, the investigators identify patients at high risk of ALI using the prediction model applied within the first six hours of hospital admission. Using a validated system-wide electronic surveillance, Olmsted County patients at risk are followed until ALI, death or hospital discharge. Detailed in-hospital (second hit) exposures and meaningful short and long term outcomes (quality-adjusted survival) are compared between ALI cases and high risk controls matched by age, gender and probability of developing ALI. Time sensitive biospecimens are collected for collaborative research studies. Nested case control comparison of 500 patients who developed ALI with 500 matched controls will provide an adequate power to determine significant differences in common hospital exposures and outcomes between the two groups.
Discussion
This population-based observational cohort study will identify patients at high risk early in the course of disease, the burden of ALI in the community, and the potential targets for future prevention trials.
doi:10.1186/1471-227X-10-8
PMCID: PMC2873575  PMID: 20420711
Venturia inaequalis is the causal agent of apple scab, a devastating disease of apple. We outline several unique features of this pathogen which are useful for molecular genetics studies intended to understand plant-pathogen interactions. The pathogenicity mechanisms of the pathogen and overview of apple defense responses, monogenic and polygenic resistance, and their utilization in scab resistance breeding programs are also reviewed.
doi:10.1155/2009/680160
PMCID: PMC2817808  PMID: 20150969
Background
The benign tumors of nasopharynx are least encountered tumors in otolaryngology, as nasopharynx is considered one of notorious anatomical site for the malignant tumors. Pleomorphic adenoma of the minor salivary gland of nasopharynx and parapharyngeal space is rare. We present a pleomorphic adenoma of minor salivary gland which was mismanaged.
Case presentation
An adult male presented with left nostril obstruction for five months. The examination found big mass extending from nasopharynx to oropharynx. On CT scan, this tumor was quite big and extending to the parapharyngeal space. The FNAB found it a carcinoma but it did not respond to radiotherapy. The excision biopsy of tumor revealed it as pleomorphic adenoma. We found only five published reports on this tumor arising from nasopharynx.
Discussion and conclusion
Although, in this case report exact origin of the tumor could not be ascertained as it also appeared to be a parapharyngeal tumor but we kept the possibility of a nasopharyngeal tumor on the basis of clinical features. The pleomorphic adenoma of nasopharynx is rare. It can be misdiagnosed as malignant epithelial tumor on histopathology. The differentiation from its malignant variant is also difficult. A possibility of benign tumor should always be kept in nasopharyngeal growth with no evidence of metastasis, and histopathological diagnosis of growth should be available before any definitive treatment.
doi:10.1186/1472-6815-10-2
PMCID: PMC2821363  PMID: 20157428
Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17 amino acid flanking sequence (httNT) N-terminal to the polyQ in the toxic huntingtin exon1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation the httNT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in httNT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with httNT cores and exposed polyQ. In a second step, a new, amyloid-like aggregate is formed with a core composed of both httNT and polyQ. The results indicate unprecedented complexity in how primary sequence controls aggregation within a substantially disordered peptide, and have implications for the molecular mechanism of Huntington's disease.
doi:10.1038/nsmb.1570
PMCID: PMC2706102  PMID: 19270701

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