Molecular characterisation of ABC transporter type FtsE and FtsX proteins of Mycobacterium tuberculosis.

Elicitation of drug resistance and various survival strategies inside host macrophages have been the hallmarks of Mycobacterium tuberculosis as a successful pathogen. ATP Binding Cassette (ABC) transporter type proteins are known to be involved in the efflux of drugs in bacterial and mammalian systems. FtsE, an ABC transporter type protein, in association with the integral membrane protein FtsX, is involved in the assembly of potassium ion transport proteins and probably of cell division proteins as well, both of which being relevant to tubercle bacillus. In this study, we cloned ftsE gene of M. tuberculosis, overexpressed and purified. The recombinant MtFtsE-6xHis protein and the native MtFtsE protein were found localized on the membrane of E. coli and M. tuberculosis cells, respectively. MtFtsE-6xHis protein showed ATP binding in vitro, for which the K42 residue in the Walker A motif was found essential. While MtFtsE-6xHis protein could partially complement growth defect of E. coli ftsE temperature-sensitive strain MFT1181, co-expression of MtFtsE and MtFtsX efficiently complemented the growth defect, indicating that the MtFtsE and MtFtsX proteins might be performing an associated function. MtFtsE and MtFtsX-6xHis proteins were found to exist as a complex on the membrane of E. coli cells co-expressing the two proteins.

Prognostic tumour markers in pancreatic cancer

Background. Pancreatic cancer is one of the major causes of cancer death in the industrialised world. The overall survival of patients with ductal pancreatic adenocarcinoma is poor: 5-year survival is only 0.2 to 4%. Tumour stage and histological grade are used as prognostic markers in pancreatic cancer. However, there are differences in survival within stages and histological grades. New, additional and more accurate prognostic tools are needed. Aims. The purpose of this study was to investigate whether the tissue expression of potential and promising tumour markers p27, tenascin C, syndecan-1, COX-2 and MMP-2 are associated with clinicopathological parameters in pancreatic cancer. The expression of p27, tenascin C and syndecan-1 was also evaluated in acute and chronic pancreatitis. The main purpose in the study was to find new prognostic markers for pancreatic adenocarcinoma. Patients. The study included 147 patients with histologically verified pancreatic adenocarcinoma treated at Helsinki University Central Hospital from 1974 to1998. Methods. The expression of tumour marker antigens was demonstrated by immunohistochemistry using monoclonal antibodies against p27, syndecan-1, tenascin C, COX-2 and MMP-2. The results were compared with clinicopathological variables, i.e. age, sex, TNM stage and histological grade. Survival analyses were performed with univariate Kaplan-Meier life-tables and the log-rank test, while multivariate analyses were performed using Cox regression. Results. Pancreatic adenocarcinomas expressed p27, syndecan-1, tenascin C, COX-2 and MMP-2 in 30, 94, 92, 36 and 50% of the samples, respectively. Loss of p27 expression was associated with poor prognosis in stage I and II pancreatic cancer. Stromal syndecan-1 expression was an independent prognostic marker in pancreatic cancer, whereas epithelial syndecan-1 expression predicted better prognosis only in stage I and II disease. Tenascin C expression did not correlate with survival but was associated with differentiation. COX-2 expression was associated with poor outcome and was an independent prognostic factor. Epithelial MMP-2 correlated with poor prognosis in pancreatic cancer. Conclusion: p27 and epithelial syndecan-1 are prognostic markers in early (stage I and II) pancreatic cancer. Stromal syndecan-1, COX-2 and epithelial MMP-2 are prognostic factors in ductal pancreatic adenocarcinoma.

Structural and electrical transport of carbon nanofibers derived from dihydro-2,5-furandione

Carbon nanofibers of 50–500 nm diameter and several micrometer length were synthesized by high-temperature pyrolysis of dihydro-2,5-furandione (C4H4O3) in the temperature range of 600–980 °C. The formation of both graphitic and non-graphitic structured carbon fibers was observed in high-resolution transmission electron microscope. The Raman spectra of the samples showed the presence of both the D and G bands of varying intensity and sharpness. The low-temperature electrical transport studies on the samples have shown interesting metal–insulator transitions. The films showed variable range hopping conduction in the insulating regime and power law behavior in the critical regime at low temperatures.

Lung cancer stem cells: The root of resistance

In the absence of specific treatable mutations, platinum-based chemotherapy remains the gold standard of treatment for lung cancer patients. However, 5-year survival rates remain poor due to the development of resistance and eventual relapse. Resistance to conventional cytotoxic therapies presents a significant clinical challenge in the treatment of this disease. The cancer stem cell (CSC) hypothesis suggests that tumors are arranged in a hierarchical structure, with the presence of a small subset of stem-like cells that are responsible for tumor initiation and growth. This CSC population has a number of key properties such as the ability to asymmetrically divide, differentiate and self-renew, in addition to having increased intrinsic resistance to therapy. While cytotoxic chemotherapy kills the bulk of tumor cells, CSCs are spared and have the ability to recapitulate the heterogenic tumor mass. The identification of lung CSCs and their role in tumor biology and treatment resistance may lead to innovative targeted therapies that may ultimately improve clinical outcomes in lung cancer patients. This review will focus on lung CSC markers, their role in resistance and their relevance as targets for future therapies.

Conformations of disulfide bridges in proteins

The conformational characteristics of disulfide bridges in proteins have been analyzed using a dataset of 22 protein structures, available at a resolution of 2.0 Å, containing a total of 72 disulfide crosslinks. The parameters used in the analysis include (φ, Ψ) values at Cys residues, bridge dihedral angles χss, χ1i, χ1j, χ2i and χ2j the distances Cαi-Cαj and Cβi-Cβj between the Cα and Cβ atoms of Cys(i) and Cys(j). Eight families of bridge conformations with three or more occurrences have been identified on the basis of these stereochemical parameters. The most populated family corresponds to the "left handed spiral" identified earlier by Richardson ((1981) Adv. Protein Chem. 34, 167–330). Disulfide bridging across antiparallel extended strands is observed in α-lytic protease, crambin, and β-trypsin and this structure is shown to be very similar to those obtained in small cystine peptides. Solvent accessible surface area calculations show that the overwhelming majority of disulfide bridges are inaccessible to solvent.

Analysis of the binding of polymyxin B to endotoxic lipid A and core glycolipid using a fluorescent displacement probe

Dansylcadaverine, a cationic fluorescent probe binds to bacterial lipopolysaccharide and lipid A, and is displaced competitively by other compounds which possess affinity toward endotoxins. The binding parameters of dansylcadaverine for lipid A were determined by Scatchard analysis to be two apparently equivalent sites with apparent dissociation constants (Kd) ranging between 16 μM to 26 μM, while that obtained for core glycolipid from Salmonella minnesota Re595 yielded a Kd of 22 μM to 28 μM with three binding sites. The Kd of polymyxin B for lipid A was computed from dansylcadaverine displacement by the method of Horovitz and Levitzki (Horovitz, A., and Levitzki, A. (1987) Proc. Natl. Acad. Sci. USA 84, 6654–6658). The applicability of this method for analyzing fluorescence data was validated by comparing the Kds of melittin for lipid A obtained by direct Scatchard analysis, and by the Horovitz-Levitzki method. The displacement of dansylcadaverine from lipid A by polymyxin B was distinctly biphasic with Kds for polymyxin B-lipid A interactions corresponding to 0.4 μM and 1.5 μM, probably resulting as a consequence of lipid A being a mixture of mono- and di-phosphoryl species. This was not observed with core glycolipid, for which the Kd for polymyxin was estimated to range from 1.1 μM to 5.8 μM. The use of dansylcadaverine as a displacement probe offers a novel and convenient method of quantitating the interactions of a wide variety of substances with lipid A.

Effect of dietary cholesterol and ubiquinone on isoprene synthesis in rat liver

The effect of dietary cholesterol and ubiquinone on the synthesis of isoprene compounds in the liver, as tested by the incorporation of acetate-1-14C and mevalonate-2-14C, was studied in rats. In cholesterol feeding, there appears to be a second site of inhibition after squalene in addition to the previously known primary site of inhibition at the β-hydroxy-β-methyl glutaryl-CoA reductase. Feeding ubiquinone inhibited at some common step between acetate and mevalonate in the synthesis of both cholesterol and ubiquinone, without affecting the acetate activation or fatty acid synthesis, and also at a step in the synthesis of ubiquinone not common with the synthesis of cholesterol. These results are suggestive of a role for ubiquinone in the regulation of isoprene synthesis.

Isobaric vapor-liquid equilibrium of n-heptane-n-butanol system

Vapor-liquid equilibrium data for the system n-heptane-n-butanol have been reported. The thermodynamic consistency of the data was tested with Chao's modified Redlich-Kister equation and Tao's method.

Studies on iron metabolism in Neurospora crassa

Neurospora crassa Em 5297a secretes an ironbinding compound (X) when grown under conditions of iron deficiency. Decreasing the concentration of iron in the medium results in an increase of X and a corresponding fall in catalase activity. Under iron-deficient conditions the production of X precedes the fall in catalase activity. The iron complex of the iron-binding compound (XFe) can act as a good iron source to the organism to maintain normal growth and catalase activity, even though the iron is held very firmly in the chemical sense. While ferrichrome is as potent as XFe, as an iron source to N. crassa, ferrichrome A and ferric acethydroxamate are only partially beneficial. XFe, when provided as the sole iron source, also influences nonheme iron enzyme activities like succinic dehydrogenase and aconitase. XFe is permeable to N. crassa mycelia and is incorporated at a much faster rate compared with that from a simple chelate such as ferric citrate.

Power Optimal Network-on-Chip Interconnect Design

A large part of today's multi-core chips is interconnect. Increasing communication complexity has made essential new strategies for interconnects, such as Network on Chip. Power dissipation in interconnects has become a substantial part of the total power dissipation. Techniques to reduce interconnect power have thus become a necessity. In this paper, we present a design methodology that gives values of bus width for interconnect links, frequency of operation for routers, in Network on Chip scenario that satisfy required throughput and dissipate minimal switching power. We develop closed form analytical expressions for the power dissipation, with bus width and frequency as variables and then use Lagrange multiplier method to arrive at the optimal values. We present a 4 port router in 90 nm technology library as case study. The results obtained from analysis are discussed.

Accumulation of point mutations and reassortment of genomic RNA segments are involved in the microevolution of Puumala hantavirus in a bank vole (Myodes glareolus) population

"The genetic diversity of Puumala hantavirus (PUUV) was studied in a local population of its natural host, the bank vole (Myodes glareolus). The trapping area (2.5x2.5 km) at Konnevesi, Central Finland, included 14 trapping sites, at least 500 m apart; altogether, 147 voles were captured during May and October 2005. Partial sequences of the S, M and L viral genome segments were recovered from 40 animals. Seven, 12 and 17 variants were detected for the S, M and L sequences, respectively; these represent new wild-type PUUV strains that belong to the Finnish genetic lineage. The genetic diversity of PUUV strains from Konnevesi was 0.2-4.9% for the S segment, 0.2-4.8% for the M segment and 0.2-9.7% for the L segment. Most nucleotide substitutions were synonymous and most deduced amino acid substitutions were conservative, probably due to strong stabilizing selection operating at the protein level. Based on both sequence markers and phylogenetic clustering, the S, M and L sequences could be assigned to two groups, 'A' and 'B'. Notably, not all bank voles carried S, M and L sequences belonging to the same group, i.e. SAMALA or SBMBLB.. A substantial proportion (8/40, 20%) of the newly characterized PUUV strains possessed reassortant genomes such as SBMALA, SAMBLB or SBMALB. These results suggest that at least some of the PUUV reassortants are viable and can survive in the presence of their parental strains."

Pajala–Kolarin ja Soklin kaivoshankkeisiin liittyvien rautatie- ja tieinvestointien ja Kemin satamainvestointien aluetaloudelliset vaikutukset

Lappiin suunnitteilla olevat Pajala–Kolarin rauta- ja Soklin fosforikaivos ovat megaluokan hankkeita. Kaivosten rakentaminen ei voi kuitenkaan toteutua jos niiden tarvitsemia rautatie-, satama- ja tieinvestointeja ei voida toteuttaa. Tutkimuksen tavoitteena oli arvioida näiden väyläinvestointien aluetaloudellisia vaikutuksia. Tutkimus on jatkoa Ruraliassa juuri valmistuneelle yhdeksää Pohjois- ja Itä-Suomen kaivoshanketta koskevalle tutkimukselle, jossa keskitytään itse kaivosinvestointien vaikutuksiin. Tutkimuksen on rahoittanut Liikenne- ja viestintäministeriö yhdessä Työ- ja elinkeinoministeriön kanssa. Työvälineenä oli Ruraliassa kehitetty RegFinDyn-aluemalli. Simuloinnit suoritettiin vuosille 2008–2030 ja raportoitiin Lapin seutukuntien tasolla. Tulosten mukaan kaikki, mutta erityisesti mittavat rautatieinvestoinnit olisivat merkittäviä seutukuntien taloudelliselle kasvulle. Äkäsjoki–Ajos radan rakentaminen auttaisi Tunturi-Lapin, Torniolaakson ja Kemi–Tornion seutukuntia taantuman yli. Taloudellinen kasvu voisi lisääntyä läntisen Lapin seutukunnissa yhteensä 0,6–2,2% vuoteen 2011 ja yhteensä 1,3–4,3% vuoteen 2016 mennessä. Tämä olisi keskimäärin 0,1–0,5% vuodessa. Soklin kaivoksen tapauksessa Kemijärvi–Kelloselkä–Sokli rautatien vaikutukset Itä- ja Pohjois-Lapin seutukuntiin olisivat merkittäviä. Investointien edetessä Itä-Lapin seutukunnan taloudellinen kasvu voisi vahvistua kumulatiivisesti tarkasteltuna 8,3% vuoteen 2013 mennessä. Vuosikeskiarvona tämä olisi 2,8%. Radan vaikutus Pohjois-Lapin taloudelliseen kasvuun olisi pienempi, vuoteen 2014 mennessä yhteensä 3% eli keskimäärin 0,8% vuodessa. Väyläinvestointien työllisyysvaikutukset olisivat myönteisiä. Pajala–Kolarin kaivoksen rautatieinvestoinnit toisivat läntiseen Lappiin uusia työpaikkoja vuoteen 2015 mennessä yhteensä 418. Tästä Tunturi-Lapin osuus olisi 147, Torniolaakson 114 ja Kemi–Tornion seutukunnan 157. Vastaavat vuosikeskiarvot olisivat 52, 18, 14 ja 20. Soklin kaivoksen rautatieinvestoinnit toisivat jonkun verran enemmän uusia työpaikkoja Pajala–Kolariin verrattuna koska investoinnit olisivat suuremmat. Radan rakentaminen voisi tuoda Itä-Lappiin yhteensä 506 uutta työpaikkaa vuoden 2013 loppuun mennessä. Pohjois-Lapin työllisyys voisi lisääntyä 153 uudella työpaikalla. Yhteensä voisi siten syntyä 660 uutta työpaikkaa. Vastaavat vuosikeskiarvot olisivat 169, 51, 220 uutta työpaikkaa. Kun kaivoksia tarkastellaan yhdessä, työllisyysvaikutukset olisivat suurimmat vuonna 2015, jonka loppuun mennessä väyläinvestoinnit voisivat luoda yhteensä 1288 uutta työpaikkaa. Vastaava vuosikeskiarvo olisi 161. Taloudellisen kasvun ohella työllisyystulokset korostavat analysoitujen väyläinvestointien myönteistä aluetaloudellista merkitystä. Ruralia-instituutin arvioinnin perusteella molempien kaivosten rautatie-, satama- ja tieinvestoinnit olisivat toteuttamiskelpoisia aluetaloudellisin perustein. Ne lisäisivät tuotantoa, työllisyyttä, tuloja, kulutusta ja verotuloja useissa Lapin seutukunnissa.

Benchmarking Scientific Journals from the Submitting Author’s Viewpoint

Authors of scholarly papers to a large extent base the decision on where to submit their manuscripts on the prestige of journals, taking little account of other possible factors. Information concerning such factors is in fact often not available. This paper argues for the establishment of methods for benchmarking scientific journals, taking into account a wider range of journal performance parameters than is currently available. A model for how prospective authors determine the value of submitting to a particular journal is presented. The model includes eight factors that influence an author’s decision and 21 other underlying factors. The model is a qualitative one. The method proposes to benchmark groups of journals by application of the factors. Initial testing of the method has been undertaken in one discipline.