Nematode chemosensory GPCRs in Caenorhabditis elegans (NemChRs) are classified into 19 gene families, and are initially thought to have split from the ancestral Rhodopsin family of GPCRs. However, earlier studies have shown that among all 19 NemChR gene families, only the srw family has a clear sequence relationship to the ancestral Rhodopsin GPCR family. Yet, the phylogenetic relationships between the srw family of NemChRs and the Rhodopsin subfamilies are not fully understood. Also, a widespread search was not previously performed to check for the presence of putative srw family-like sequences or the other 18 NemChR families in several new protostome species outside the nematode lineage. In this study, we have investigated for the presence of 19 NemChR families across 26 eukaryotic species, covering basal eukaryotic branches and provide the first evidence that the srw family of NemChRs is indeed present across several phyla of protostomes. We could identify 29 putative orthologs of the srw family in insects (15 genes), molluscs (11 genes) and Schistosoma mansoni (3 genes). Furthermore, using HMM-HMM profile based comparisons and phylogenetic analysis we show that among all Rhodopsin subfamilies, the peptide and SOG (somatostatin/opioid/galanin) subfamilies are phylogenetically the closest relatives to the srw family of NemChRs. Taken together, we demonstrate that the srw family split from the large Rhodopsin family, possibly from the peptide and/or SOG subfamilies, well before the split of the nematode lineage, somewhere close to the divergence of the common ancestor of protostomes. Our analysis also suggests that the srsx family of NemChRs shares a clear sequence homology with the Rhodopsin subfamilies, as well as with few of the vertebrate olfactory receptors. Overall, this study provides further insights into the evolutionary events that shaped the GPCR chemosensory system in protostome species.
Acinetobacter baumannii has emerged as one of the most common nosocomial pathogens and is considered to be a significant threat to public health worldwide. Here, we present the draft genome sequence of a multidrug-resistant clinical strain of A. baumannii PKAB07 isolated from a wound infection in India during 2011 to 2012.
Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility.
To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed.
Bioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells.
These data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock.
Breast cancer; Hyperthermia; Heat shock; Microarray; Genomics; Gene expression
Relapsing polychondritis is an acute, recurrent and progressive inflammation and degeneration of cartilage and connective tissue including that within the tracheobronchial tree affecting men and women equally and usually in the middle age. Serious airway manifestations occur in at least half of these patients. We present to you an interesting case report of a 20-year-old female who presented with exertional breathlessness. Imaging revealed diffuse calcification of pinna and tracheobronchial tree. Based on the characteristic clinical features and imaging studies a diagnosis of relapsing polychondritis was attained.
Auricular; Chondritis; Laryngotracheal; Polychondritis; Stenosis
The UAB-ITREOH program has initiated a skill-based MPH program at Manipal University (MU), India, in 2009, to address the critical need for trained public health professionals and build institutional public health training capacity in the country.
Funds from Fogarty have supported the curriculum development and specialized training of MU faculty to teach in the MPH program.
The program has been successfully launched and is gaining momentum. The lessons learned from our experiences as well as several challenges faced from the initialization to execution of the program are described in the paper.
Government support is crucial for raising the profile of this program by accreditation, creating job opportunities and by recognizing these professionals as leaders in the public health sector.
MPH; Manipal; UAB; Inter-professional practice; skill-based; ITREOH; Public Health training; curriculum
Health science students (HSS) are at increased risk of contracting and transmitting viral disease such as measles, mumps, rubella and varicella (chickenpox). This study was undertaken to determine the prevalence of susceptibility of HSS to these infections.
Using a cross-sectional design, 790 HSS of Manipal University, Manipal, India, answered a questionnaire and provided a blood sample which was tested for specific IgG antibodies to measles, mumps, rubella and varicella by ELISA (Enzygnost®).
The study group was comprised of medical (53.9%), nursing (16.6%) and allied health (29.5%) students. Among the overall group (n=790), the prevalence of serological susceptibility to measles, mumps, rubella and varicella were 9.5%, 32.0%, 16.6%, and 25.8%, respectively. Among the subgroup of vaccinated subjects, susceptibility to measles, mumps, rubella and varicella were 7.9%, 34.7%, 10.7% and 35.2%, respectively.
HSS susceptible to measles, mumps, rubella and/or varicella are at risk of acquiring these diseases during their training period. In addition, they may be a potential source for nosocomial transmission posing a risk to immunocompromised patients. Hence, in the Indian setting, HSS should be immunized against measles, mumps, rubella and varicella at the time of joining the medical school.
Susceptibility; Measles; Mumps; Rubella; Varicella
Toll-like receptor 9 (TLR9) recognizes microbial DNA containing unmethylated cytosyl guanosyl (CpG) sequences, induces innate immune responses, and facilitates antigen-specific adaptive immunity. Recent studies reported that in addition to stimulating innate immunity, TLR9 ligands induce apoptosis in TLR9 expressing cancer cells. To understand the mechanism of TLR9-induced apoptosis, we compared the effects of CpG containing oligodeoxynucleotides (CpG ODN) on a mouse lymphoma B cell line CH27 with mouse splenic B cells. CpG ODN inhibited constitutive proliferation and induced apoptosis of CH27 lymphoma B cells, in contrast to CpG ODN-treated primary B cells that were stimulated to proliferate and rescued from spontaneous apoptosis. The induction of apoptosis required CpG motif in ODNs and expression of TLR9 in lymphoma B cells. Accompanying the apoptosis of the lymphoma B cells, there was a decrease in Bcl-xl and an increase in the expression of Fas and Fas ligand. The treatment of Fas ligand neutralizing antibody inhibited CpG ODN-induced apoptosis. CpG ODN triggered a transient activation of NF-κB in the lymphoma B cells that constitutively expressed a high level of c-Myc, while it induced sustained increases in NF-κB activation and c-Myc expression in the primary B cells. Furthermore, NF-κB inhibitor inhibited the proliferation of CH27 lymphoma B cells. Our data suggest that the differential responses of lymphoma and primary B cells to CpG ODN are the result of differences in NF-κB activation. The impaired NF-κB activation in CpG ODN-treated lymphoma B cells alters the balance between NF-κB and c-Myc, inducing Fas/Fas ligand-dependent apoptosis.
Apoptosis; lymphoma B cells; TLR 9; NF-κB
Aims and objectives: The aim of this study was to identify the organisms responsible and to determine the antibiotic susceptibility pattern of the bacterial isolates from conjunctiva and nasal mucosa in cases of chronic dacryocystitis and comparing with lacrimal sac specimen.
Design: Prospective longitudinal study.
Methods: A prospective analysis of 44 lacrimal sac contents of patients with chronic dacryocystitis conducted during the period from April 2012 to March 2013. Material was obtained directly from the lacrimal sac while making sac flap during external dacryocystorhinostomy for chronic dacryocystitis. Samples were also collected from ipsilateral conjunctiva and inferior meatus of nose. The specimens were cultured and results analyzed.
Statistical Analysis: The results were analyzed by using Chi-square (χ2) test.
Results: All the patients were in age group of 30 and above. Gram positive bacteria i.e., Coagulase negative staphylococci and Staphylococcus aureus were the most common isolates (71% and 14% respectively). Vancomycin, amikacin, 3rd generation cephalosporins and amoxyclav were most sensitive antibiotics (100%, 89%, 83%, and 78% respectively). Comparison between lacrimal and nasal/conjunctival isolates showed high degree of identicalness between the isolates of two sites (p< 0.05).
Conclusion: Majority of the chronic dacryocystitis cases are caused by Coagulase negative Staphylococci and Staphylococcus aureus. Amoxyclav and 3rd generation cephalosporins can be used to treat chronic dacryocystitis. Commensal flora of nose and conjunctiva have a direct role in pathogenesis of chronic dacryocystitis.
Cephalosporins; Chronic dacryocystitis; Coagulase negative Staphylococcus; Nasolacrimal duct
This study evaluated whether genotypically different clinical isolates of S. aureus have similar susceptibilities to individual antibiotics. It further aims to check the impact of biofilm on the in vitro activity of vancomycin, daptomycin, linezolid, and tigecycline against S. aureus clones. The study used a total of 60 different clinical MSSA and MRSA isolates. Susceptibilities were performed in planktonic cultures by macrobroth dilution and epsilon-test (E test) system. Biofilm production was determined using an adherent plate assay. The efficacy of antimicrobial activities against biofilms formation was checked using confocal laser scanning microscopy (CLSM). The study found that similar and different spa, MLST, and SCCmec types displayed high variation in their susceptibilities to antibiotics with tigecycline and daptomycin being the most effective. The biofilms were found resistant to high concentrations of most antibiotics tested with daptomycin being the most effective drug used in adhesive biofilms. A considerable difference exists among similar and various clone types against antibiotics tested. This variation could have contributed to the degree of virulence even within the same clonal genotype and enhanced heterogeneity in the infection potential. Thus, the development of a rapid and precise identification profile for each clone in human infections is important.
Obesity and diabetes are associated with increased breast cancer risk and worse disease progression once cancer is diagnosed; however, the exact etiology behind these observations remains to be fully elucidated. Due to the global obesity/diabetes pandemic, it is imperative to understand how these diseases promote and enhance breast cancer and other common cancers. In this study we demonstrate that hyperglycemia promotes breast cancer by altering leptin/IGF1R and AKT/mTOR signaling. To our knowledge, we show for the first time that in breast epithelial cells, hyperglycemia alone directly impacts leptin signaling. Hyperglycemia increased proliferation of both non-tumorigenic and malignant mammary epithelial cells. These observations coincided with increased leptin receptor and IGF1R receptor, as well as, increased levels of GRB2, pJAK2, pSTAT3, pIRS1/2, pAKT, and p-mTOR. Moreover, pJAK2 was almost completely colocalized with leptin receptor under high glucose conditions. These results demonstrate how hyperglycemia can potentially increase the risk of breast cancer in premalignant lesions and enhance cancer progression in malignant cells.
In the title compound, C15H14ClNO2S2, the 2H-chromene ring system is essentially planar, with a maximum deviation of 0.0133 (10) Å. Three C atoms and their attached H atoms of the pyrrolidine ring are disordered [occupany ratio 0.874 (7):0.126 (7)] with both disorder components adopting a twisted conformation. The dihedral angle between the 2H-chromene ring system and the major occupancy component of the pyrrolidine ring is 89.45 (7)°. In the crystal, inversion dimers linked by pairs of C—H⋯S and C—H⋯O interactions generate R
2(24) and R
2(10) loops, respectively. Further C—H⋯O hydrogen bonds link the dimers into  chains. C—H⋯π interactions also occur and there is very weak π–π stacking [interplanar spacing = 3.650 (5) Å; centroid–centroid distance = 4.095 (7) Å] between inversion-related chlorobenzene rings.
Plant-based medicines are useful in the treatment of cancer. Many breast cancer patients use complementary and alternative medicine in parallel with conventional treatments. Neem is historically well known in Asia and Africa as a versatile medicinal plant with a wide spectrum of biological activities. The experiments reported herein determined whether the administration of an ethanolic fraction of Neem leaf (EFNL) inhibits progression of chemical carcinogen-induced mammary tumorigenesis in rat models. Seven-week-old female Sprague Dawley rats were given a single intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Upon the appearance of palpable mammary tumors, the rats were divided into vehicle-treated control groups and EFNL-treated groups. Treatment with EFNL inhibited MNU-induced mammary tumor progression. EFNL treatment was also highly effective in reducing mammary tumor burden and in suppressing mammary tumor progression even after the cessation of treatment. Further, we found that EFNL treatment effectively upregulated proapoptotic genes and proteins such as p53, B cell lymphoma-2 protein (Bcl-2)-associated X protein (Bax), Bcl-2-associated death promoter protein (Bad) caspases, phosphatase and tensin homolog gene (PTEN), and c-Jun N-terminal kinase (JNK). In contrast, EFNL treatment caused downregulation of anti-apoptotic (Bcl-2), angiogenic proteins (angiopoietin and vascular endothelial growth factor A [VEGF-A]), cell cycle regulatory proteins (cyclin D1, cyclin-dependent kinase 2 [Cdk2], and Cdk4), and pro-survival signals such as NFκB, mitogen-activated protein kinase 1 (MAPK1). The data obtained in this study demonstrate that EFNL exert a potent anticancer effect against mammary tumorigenesis by altering key signaling pathways.
Neem; breast cancer; apoptosis; cell cycle; angiogenesis
Gallbladder cancer is common in north India. It is also a well established fact that gall bladder cancer is frequently associated with gallstone disease in north India, similar to reports from the West. The magnitude of the problem of gallbladder cancer in south India and its link to gallstone disease is not clearly established. The aim of the study was to determine retrospectively, the characteristics of individuals with GBC in south India and to determine its association with gallstone disease. Retrospective data was obtained from records of proven cases of gallbladder cancer and patients undergoing cholecystectomy for gallstone disease between Jan 2001 and Dec 2010. Data retrieved included age, gender, and clinical presentation, findings on imaging, histology and details of management. The number of proven cases of gallbladder cancer each year ranged from 8 to 17. There were 38 men and 23 women. Male female ratio was 1.6:1. There were more men in the successive decades. Right upper quadrant pain (42 %) followed by jaundice (27 %) and a presence of a palpable mass (12 %) were the common clinical presentation. Pre-operative diagnosis of gall bladder cancer was possible in 80 %. Twelve patients had co-existing gallstones (19.6 %). Forty patients (50 %) had stage IV disease; only 6 patients had Stage I operable disease (9.8 %). During the same time 758 patients had cholecystectomy for gallstone disease. Only one patient had an incidental gall bladder cancer, who had an extended cholecystectomy. Gallbladder cancer is uncommon in south India and its association with gallstone is also low.
Gall bladder; Gallstones; Carcinoma
The establishment of a complete genomic sequence of silkworm, the model species of Lepidoptera, laid a foundation for its functional genomics. A more complete annotation of the genome will benefit functional and comparative studies and accelerate extensive industrial applications for this insect. To realize these goals, we embarked upon a large-scale full-length cDNA collection from 21 full-length cDNA libraries derived from 14 tissues of the domesticated silkworm and performed full sequencing by primer walking for 11,104 full-length cDNAs. The large average intron size was 1904 bp, resulting from a high accumulation of transposons. Using gene models predicted by GLEAN and published mRNAs, we identified 16,823 gene loci on the silkworm genome assembly. Orthology analysis of 153 species, including 11 insects, revealed that among three Lepidoptera including Monarch and Heliconius butterflies, the 403 largest silkworm-specific genes were composed mainly of protective immunity, hormone-related, and characteristic structural proteins. Analysis of testis-/ovary-specific genes revealed distinctive features of sexual dimorphism, including depletion of ovary-specific genes on the Z chromosome in contrast to an enrichment of testis-specific genes. More than 40% of genes expressed in specific tissues mapped in tissue-specific chromosomal clusters. The newly obtained FL-cDNA sequences enabled us to annotate the genome of this lepidopteran model insect more accurately, enhancing genomic and functional studies of Lepidoptera and comparative analyses with other insect orders, and yielding new insights into the evolution and organization of lepidopteran-specific genes.
Bombyx mori; large-scale full-length cDNA collection; tissue-specific genes; sexual dimorphism; gene cluster; silkworm
A 19-year-old male presented with recurrent episodes of pericardial effusion. On evaluation, he was diagnosed to have idiopathic chylous effusion. As there was persistent pericardial collection, chemical pericardiodesis was done. Following pericardiodesis, there was no recurrence of pericardial effusion. Chemical pericardiodesis may be an effective treatment option for recurrent, idiopathic chylopericardium.
In a previous study, Chung, Legge & Cheung (2004) showed that training using repeated presentation of trigrams (sequences of three random letters) resulted in an increase in the size of the visual span (number of letters recognized in a glance) and reading speed in the normal periphery. In this study, we asked whether we could optimize the benefit of trigram training on reading speed by using trigrams more specific to the reading task (i.e. trigrams frequently used in the English language) and presenting them according to their frequencies of occurrence in normal English usage and observers’ performance. Averaged across seven observers, our training paradigm (four days of training) increased the size of the visual span by 6.44 bits, with an accompanied 63.6% increase in the maximum reading speed, compared with the values before training. However, these benefits were not statistically different from those of Chung et al (2004) using a random-trigram training paradigm. Our findings confirm the possibility of increasing the size of the visual span and reading speed in the normal periphery with perceptual learning, and suggest that the benefits of training on letter recognition and maximum reading speed may not be linked to the types of letter strings presented during training.
A 45-year-old female known to suffer from rheumatic heart disease (RHD), presented with breathlessness of 1 year duration. Two-dimensional echocardiography revealed significant mitral and aortic valve disease mandating double valve replacement. In addition, an unusual finding in the form of a well-defined, densely calcified intramyocardial left ventricular mass was noted on echocardiography. The nature and extent of the mass was assessed by additional imaging modalities. Patient underwent excision of the mass followed by double valve replacement. Histopathology was consistent with cardiac calcific amorphous tumour (CAT). An unusual occurrence of CAT in a patient with RHD is presented herein. This rare tumour has not been previously described in patients with RHD.
Introduction: India is on the verge of being the diabetic capital of the world, owing to the increasing prevalence of diabetes in India. The aim of this study was to find the association between anthropometry and dyslipidaemia, with a particular reference to the triacylglycerol levels, besides suggesting a better anthropometric variable.
Method: A group of eighty diabetic patients took part in the study. The Waist Circumference (WC), the waist to hip ratio, the serum triacylglycerol (TAG) levels and the glycated haemoglobin (HbA1c) levels were measured and studied.
Results: We found out that there was a significant association between the WC and the TAG levels (p-value = 0.030), between high TAG levels and high HbA1c values (p-value = 0.038) with greater accuracy, in favour of the waist circumference.
Conclusion: This depicted the fact that a simple measuring tape which is used in measuring the WC, could prove to be a useful and a cost-effective diagnostic approach for monitoring the metabolic complications of type 2 DM.
Diabetes mellitus; Waist circumference; Dyslipidaemia; Waist to hip ratio; Triacylglycerol; HbA1c
Liposarcomas are common tumors arising in the retroperitoneum. However, a primary mesenteric liposarcoma is a rare entity and less than 50 cases have been reported so far. Further, a liposarcoma arising in the transverse mesocolon is very unusual, and cases of multiple primary tumors arising from the transverse mesocolon are extremely rare. We want to report a case of a multiple primary mesenteric liposarcoma arising from the transverse mesocolon in a 63-year-old female who was successfully treated by surgery. Because a primary mesenteric liposarcoma is a rare entity, it should be considered with the differential diagnosis of an abdominal mesenchymal tumor. It can be diagnosed preoperatively by using contrast enhanced computed tomography and magnetic resonance imaging. The treatment for such a liposarcoma is surgical resection with sufficient surgical margin; the role of adjuvant therapy has yet to be defined.
Liposarcoma; Mesentric; Transverse magacolon; Diagnosis
Production of tannase by Aspergillus flavus (MTCC 3783) using tamarind seed powder as substrate was studied in submerged fermentation. Plackett–Burman design was applied for the screening of 12 medium nutrients. From the results, the significant nutrients were identified as tannic acid, magnesium sulfate, ferrous sulfate and ammonium sulfate. Further the optimization of process parameters was carried out using response surface methodology (RSM). RSM has been applied for designing of experiments to evaluate the interactive effects through a full 31 factorial design. The optimum conditions were tannic acid concentration, 3.22 %; fermentation period, 96 h; temperature, 35.1 °C; and pH 5.4. Higher value of the regression coefficient (R2 = 0.9638) indicates excellent evaluation of experimental data by second-order polynomial regression model. The RSM revealed that a maximum tannase production of 139.3 U/ml was obtained at the optimum conditions.
Tannase; Response surface methodology; Plackett–Burman design; Submerged fermentation
The success of any genomic study depends primarily on the quality of the starting material, like genomic DNA (gDNA). The integrity of the extracted gDNA affects the downstream applications like microarray hybridization and next generation sequencing library construction. Since these are expensive and time consuming applications, a quality control (QC) of the genomic DNA has become highly recommended. The integrity of gDNA has traditionally been analyzed using agarose gel electrophoresis, which is manual, cumbersome and can involve exposure to hazardous chemicals like ethidium bromide. The new Agilent gDNA ScreenTape has been developed for the electrophoretic separation, sizing and quantification of large DNA samples (up to >60000 bp). This ready-to-use device, which runs on the Agilent 2200 TapeStation instrument, provides a reproducible QC method for analyzing the integrity and quantity of genomic DNA combined with the convenience of an automated system. With minimal sample preparation, automated loading and a variable throughput system, digital results can be presented as gel image, data table and in an electropherogram view. The ability to overlap and compare electropherograms within the software enables the discrimination of sample quality across different degradation states, sample types and concentrations. We present data that shows the Genomic DNA ScreenTape can easily verify the integrity of gDNA starting material with high sensitivity, precision and accuracy.