The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition.

Charybdotoxin (CTX) is a peptide of known structure that inhibits Shaker K+ channels by a pore-blocking mechanism. Point mutagenesis of all 30 solvent-exposed residues identified the part of the CTX molecular surface making contact with the receptor in the K+ channel. All close-contact residues are clustered in a well-defined interaction surface; the shape of this surface implies that the outer opening of the Shaker channel conduction pore abruptly widens to a 25 x 35 A plateau. A mutagenic scan of the S5-S6 linker sequence of the Shaker K+ channel identified those channel residues influencing CTX binding affinity. The Shaker residues making the strongest contribution to toxin binding are located close to the pore-lining sequence, and more distant residues on both sides of this region influence CTX binding weakly, probably by an electrostatic mechanism. Complementary mutagenesis of both CTX and Shaker suggests that Shaker-F425 contacts a specific area near T8 and T9 on the CTX molecular surface. This contact point constrains Shaker-F425 to be located at a 20 A radial distance from the pore axis and 10-15 A above the "floor" of the CTX receptor

Impaired clearance of ceftizoxime and cefotaxime after orthotopic liver transplantation.

The pharmacokinetics of ceftizoxime (CZX) and of cefotaxime (CTX) were studied in five children and five adults after orthotopic liver transplantation (OLT). Delayed clearance of CZX (clearance of 0.21 to 1.26 ml/min per kg [body weight]) and CTX (clearance of 0.40 to 1.49 ml/min per kg) occurred in 7 of the 10 OLT patients. We conclude that abnormal CZX and CTX clearance is common after OLT and may be associated with minimal change in serum creatinine

Characterization of extended-spectrum β-lactamases produced by Escherichia coli isolated from hospitalized and nonhospitalized patients : emergence of CTX-M-15-producing strains causing urinary tract infections

Extended-spectrum β-lactamase-producing Escherichia coli isolates were obtained from hospitalised and non-hospitalised patients in Belgium between August 2006 and November 2007. The antimicrobial susceptibility of these isolates was determined and their ESBL genes were characterized. Clonal relationships between the CTX-M-producing E. coli isolates causing urinary tract infections were also studied. A total of 90 hospital- and 45 community-acquired cephalosporin-resistant E. coli isolates were obtained. Tetracycline, enrofloxacine, gentamicin and trimethoprim-sulfamethaxozole resistance rates were significantly different between the community-onset and hospital-acquired isolates. A high diversity of different ESBLs was observed among the hospital-acquired E. coli isolates whereas CTX-M-15 was dominating among the community-acquired E. coli isolates (n=28). Thirtheen different PFGE profiles were observed in the community-acquired CTX-M-15-producing E. coli indicating that multiple clones have acquired the blaCTX-M-15 gene. All community-acquired CTX-M-15-producing E. coli isolates of phylogroups B2 and D were assigned to the sequence type ST131. The hospital-acquired CTX-M-15-producing E. coli isolates of phylogroups B2, B1, A and D corresponded to ST131, ST617, ST48 and ST405, respectively. In conclusion, CTX-M-type ESBLs have emerged as the predominant class of ESBLs produced by E. coli isolates in the hospital and community in Belgium. Of particular concern is the predominant presence of the CTX-M-15 enzyme in ST131 community-acquired E. coli

Ito channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2.

Mammalian voltage-gated K+ channels are assemblies of pore-forming alpha-subunits and modulating beta-subunits. To operate correctly, Kv4 alpha-subunits in the heart and central nervous system require recently identified beta-subunits of the neuronal calcium sensing protein family called K+ channel-interacting proteins (KChIPs). Here, Kv4.2.KChIP2 channels are purified, integrity of isolated complexes confirmed, molar ratio of the subunits determined, and subunit valence established. A complex has 4 subunits of each type, a stoichiometry expected for other channels employing neuronal calcium sensing beta-subunits

Antibiotic susceptibility and high prevalence of extended spectrum beta-lactamase producing Escherichia coli in iranian broilers

Extended-spectrum β-lactamase (ESBL) producing Escherichia coli have rapidly spread worldwide and cause serious threats for public health. The study was conducted to determine the antibiotic resistance and characterization of ESBL producing E. coli strains isolated from broilers in Northern Iran. Antibiotic susceptibility test was done for a total of 100 isolates of E. coli, recovered from 240 broiler fecal samples at the slaughterhouse stage. ESBL production was screened using double-disc synergy test (DDST) and presence of four ESBL genes including blaPER, blaVEB, blaTEM and blaCTX-M was tested using PCR. Among 100 strains isolated from broilers, 53 were identified as ESBL-producing E. coli. All (100) ESBL positive isolates were typed according to the presence of one or two ESBL-associated genes. The most prevalent gene among ESBLs was CTX-M (60.3) and the PER gene was not present among isolates. All isolates in this study were resistant to colistin and nalidixic acid but were 100 sensitive to cefalexin and furazolidone. The results demonstrated the high prevalence of antibiotic resistant and ESBL producing E. coli among broilers which representing the risk of increasing these strains in human infections associated with food animals

High Serum Concentration of Interleukine-6 and Rank-ligand as Risk Factors for Osteoporosis in Estrogen Deficiency Post-menopausal Women

Osteoporosis in post-menopausal women is not merely due to deficient estrogenhormone production. The development of osteoporosis is due to increased boneresorption by osteoclasts. The osteoclast\u27s number and activity is controlled by activatingfactors such as IL-6 and RANK-L. The objective of this study was to determine that highIL-6 and RANK-L serum concentrations are risks for osteoporosis in estrogen deficientpost-menopausal women. The serum concentration of ß-CrossLaps (CTx) was measuredto determine bone resorption rate. This is an observational analytical study using case andcontrol design conducted at Sanglah General Hospital of Denpasar. The sample size wascalculated using the paired case-control study formula. There were 41 osteoporotic and41 non-osteoporotic (control) estrogen deficient post-menopausal women involved in thestudy.Data were analyzed by using the t-paired and McNemar tests. Mean serumconcentration of IL-6 among the osteoporotic women was significantly higher ascompared to that of the controls (3.47±1.75 pg/ml vs 2.51±1.13 pg/ml, p = 0.001). Meanserum concentration of RANK-L among the osteoporotic women was also significantlyhigher as compared to that of the controls (320.66±122.44ng/ml vs 249.94±82.41 ng/ml,p = 0.002). To qualify as risk factors for osteoporosis, the cut-off point for IL-6 was 2.17pg/ml (OR = 4, CI 95%: 1.23-14.24; p = 0.032); the cut-off point for RANK-L was275.165 ng/ml (OR = 8, CI 95%: 1.84-34.79; p = 0.001). Analysis of both high serumconcentration of IL-6 and RANK-L was associated with an odd ratio of 9 (CI 95%: 4,27-18,96, p=0,000). CTx concentration in the osteoporotic women was significantly higherthan in the controls (0.60±0.22ng/ml vs 0.46±0.16ng/ml, p = 0.004).We found that the high IL-6 and RANK-L serum concentrations were risk factorsin estrogen deficient post-menopausal women. CTx being a marker for osteoclastic boneresorption activity, increased in concentration higher in osteoporotic than in nonosteoporoticwomen. The high serum concentrations of IL-6 and RANK-L could be usedas predictors for osteoporosis in estrogen deficient post-menopausal women

Order Statistics Based List Decoding Techniques for Linear Binary Block Codes

The order statistics based list decoding techniques for linear binary block codes of small to medium block length are investigated. The construction of the list of the test error patterns is considered. The original order statistics decoding is generalized by assuming segmentation of the most reliable independent positions of the received bits. The segmentation is shown to overcome several drawbacks of the original order statistics decoding. The complexity of the order statistics based decoding is further reduced by assuming a partial ordering of the received bits in order to avoid the complex Gauss elimination. The probability of the test error patterns in the decoding list is derived. The bit error rate performance and the decoding complexity trade-off of the proposed decoding algorithms is studied by computer simulations. Numerical examples show that, in some cases, the proposed decoding schemes are superior to the original order statistics decoding in terms of both the bit error rate performance as well as the decoding complexity.Comment: 17 pages, 2 tables, 6 figures, submitted to IEEE Transactions on Information Theor

Seasonal Variation in 25(OH)D at Aberdeen (57°N) and Bone Health Indicators- Could Holidays in the Sun and Cod Liver Oil Supplements Alleviate Deficiency?

Vitamin D has been linked with many health outcomes. The aim of this longitudinal study, was to assess predictors of seasonal variation of 25-hydroxy-vitamin D (25(OH)D) (including use of supplements and holidays in sunny destinations) at a northerly latitude in the UK (57°N) in relation to bone health indicators. 365 healthy postmenopausal women (mean age 62.0 y (SD 1.4)) had 25(OH)D measurements by immunoassay, serum C-telopeptide (CTX), estimates of sunlight exposure (badges of polysulphone film), information regarding holidays in sunny destinations, and diet (from food diaries, including use of supplements such as cod liver oil (CLO)) at fixed 3-monthly intervals over 15 months (subject retention 88%) with an additional 25(OH)D assessment in spring 2008. Bone mineral density (BMD) at the lumbar spine (LS) and dual hip was measured in autumn 2006 and spring 2007 (Lunar I-DXA). Deficiency prevalence (25(OH)

Step-Indexed Logical Relations for Probability (long version)

It is well-known that constructing models of higher-order probabilistic programming languages is challenging. We show how to construct step-indexed logical relations for a probabilistic extension of a higher-order programming language with impredicative polymorphism and recursive types. We show that the resulting logical relation is sound and complete with respect to the contextual preorder and, moreover, that it is convenient for reasoning about concrete program equivalences. Finally, we extend the language with dynamically allocated first-order references and show how to extend the logical relation to this language. We show that the resulting relation remains useful for reasoning about examples involving both state and probabilistic choice.Comment: Extended version with appendix of a FoSSaCS'15 pape