Diagnostic utility of α-methylacyl CoA racemase (P504S) & HMWCK in morphologically difficult prostate cancer

The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%). After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004). This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.     

A neural mechanism of synergy formation for whole body reaching

The present study proposes a computational model for the formation of whole body reaching synergy, i.e., coordinated movements of lower and upper limbs, characterized by a focal component (the hand must reach a target) and a postural component (the center of mass must remain inside the support base). The model is based on an extension of the equilibrium point hypothesis that has been called Passive Motion Paradigm (PMP), modified in order to achieve terminal attractor features and allow the integration of multiple constraints. The model is a network with terminal attractor dynamics. By simulating it in various conditions it was possible to show that it exhibits many of the spatio-temporal features found in experimental data. In particular, the motion of the center of mass appears to be synchronized with the motion of the hand and with proportional amplitude. Moreover, the joint rotation patterns can be accounted for by a single functional degree of freedom, as shown by principal component analysis. It is also suggested that recent findings in motor imagery support the idea that the PMP network may represent the motor cognitive part of synergy formation, uncontaminated by the effect of execution.     

Exophiala dermatitidis as a cause of central line associated bloodstream infection in an infant: Case report and literature review

BackgroundExophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described.Case reportClinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06 mg/l), voriconazole (0.03 mg/l) and itraconazole (0.03 mg/l) showed very low MICs when compared to fluconazole (4 mg/l)ConclusionsAs we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment.     

Germinal Center B-Cells Resist Transformation by Kras Independently of Tumor Suppressor Arf

Activating mutations in Ras (N- and K-) are the most common point mutations found in patients with multiple myeloma (MM) and are associated with poor clinical outcome. We sought to directly examine the role of Ras activation in MM pathogenesis and used two different tissue-specific Cre recombinase mouse lines (Cγ1-Cre and AID-Cre), to generate mice with mutant Kras (Kras^G12D) activated specifically in germinal center B-cells. We also generated mice with activation of the Kras^G12D allele in a tumor-prone Arf-null genetic background. Surprisingly, we observed no significant disruption in B-cell homeostasis in any of these models by serum immunoglobulin ELISA, SPEP, flow cytometry and histological examination. We observed development of non-overlapping tumor types due to off-target Cre expression, but despite successful recombination in germinal center and later B-cell populations, we observed no B-cell phenotype. Together, these data demonstrate that Ras activation is not sufficient to transform primary germinal center B-cells, even in an Arf-null context, and that the temporal order of mutation acquisition may be critical for myeloma development. Specific pathways, yet to be identified, are required before Kras can contribute to the development of MM.     

A novel minimally invasive method for monitoring oxygen in microbial fuel cells

Oxygen availability is a potential rate-limiting step in the bioelectrochemical process catalyzed by microbes in microbial fuel cells (MFC). Determination of oxygen availability using a minimally invasive oxygen sensor is advantageous in terms of ease of usage, maintenance and cost-effectiveness as compared to using conventional probe-type oxygen sensors. The utility of this method is substantiated by using this sensor to demonstrate the relationship between oxygen availability and current density. 10 % drop in oxygen concentration resulted in a concomitant drop in current density by about 36 %, further establishing the criticality of monitoring oxygen levels in the MFC. The detachable sensor membrane of the minimally invasive sensor confers multiple advantages. The novel method would enable real-time monitoring of oxygen in MFCs, simplify process optimization and validation and more importantly, provide an impetus for development of more efficient MFC designs.     

Development,cross-species/genera transferability of novel EST-SSR markers and their utility in revealing population structure and genetic diversity in sugarcane

Sugarcane (Saccharum spp. hybrid) with complex polyploid genome requires a large number of informative DNA markers for various applications in genetics and breeding. Despite the great advances in genomic technology, it is observed in several crop species, especially in sugarcane, the availability of molecular tools such as microsatellite markers are limited. Now-a-days EST-SSR markers are preferred to genomic SSR (gSSR) as they represent only the functional part of the genome, which can be easily associated with desired trait. The present study was taken up with a new set of 351 EST-SSRs developed from the 4085 non redundant EST sequences of two Indian sugarcane cultivars. Among these EST-SSRs, TNR containing motifs were predominant with a frequency of 51.6%. Thirty percent EST-SSRs showed homology with annotated protein. A high frequency of SSRs was found in the 5′UTR and in the ORF (about 27%) and a low frequency was observed in the 3′UTR (about 8%). Two hundred twenty-seven EST-SSRs were evaluated, in sugarcane, allied genera of sugarcane and cereals, and 134 of these have revealed polymorphism with a range of PIC value 0.12 to 0.99. The cross transferability rate ranged from 87.0% to 93.4% in Saccharum complex, 80.0% to 87.0% in allied genera, and 76.0% to 80.0% in cereals. Cloning and sequencing of EST-SSR size variant amplicons revealed that the variation in the number of repeat-units was the main source of EST-SSR fragment polymorphism. When 124 sugarcane accessions were analyzed for population structure using model-based approach, seven genetically distinct groups or admixtures thereof were observed in sugarcane. Results of principal coordinate analysis or UPGMA to evaluate genetic relationships delineated also the 124 accessions into seven groups. Thus, a high level of polymorphism adequate genetic diversity and population structure assayed with the EST-SSR markers not only suggested their utility in various applications in genetics and genomics in sugarcane but also enriched the microsatellite marker resources in sugarcane.     

The organisational structure of protein networks: revisiting the centrality–lethality hypothesis

Protein networks, describing physical interactions as well as functional associations between proteins, have been unravelled for many organisms in the recent past. Databases such as the STRING provide excellent resources for the analysis of such networks. In this contribution, we revisit the organisation of protein networks, particularly the centrality–lethality hypothesis, which hypothesises that nodes with higher centrality in a network are more likely to produce lethal phenotypes on removal, compared to nodes with lower centrality. We consider the protein networks of a diverse set of 20 organisms, with essentiality information available in the Database of Essential Genes and assess the relationship between centrality measures and lethality. For each of these organisms, we obtained networks of high-confidence interactions from the STRING database, and computed network parameters such as degree, betweenness centrality, closeness centrality and pairwise disconnectivity indices. We observe that the networks considered here are predominantly disassortative. Further, we observe that essential nodes in a network have a significantly higher average degree and betweenness centrality, compared to the network average. Most previous studies have evaluated the centrality–lethality hypothesis for Saccharomyces cerevisiae and Escherichia coli; we here observe that the centrality–lethality hypothesis hold goods for a large number of organisms, with certain limitations. Betweenness centrality may also be a useful measure to identify essential nodes, but measures like closeness centrality and pairwise disconnectivity are not significantly higher for essential nodes.