Inter-laboratory comparison of numerical dosimetry for human exposure to 60 Hz electric and magnetic fields

In recent years, with the availability of high resolution models of the human body, numerical computations of induced electric fields and currents have been made in more than one laboratory for various exposure conditions. Despite the verification of computational methods, questions are often asked about the reliability of these data. In this paper, computational results from two laboratories that presented data in compatible formats are compared, supplemented with additional data from the third laboratory. Two exposures to uniform fields at 60 Hz are evaluated. The human body models used in the computations are different and so are the computation al methods and codes. There are some differences in the conductivity values used for some of the tissues, as well. The results of the comparison confirm that these data are reliable, as the overall agreement is reasonably good and the differences can be rationally explained. This comparison also underscores the importance of accurate data on the dielectric properties of tissues.     

Reconstructing voltage sensor-pore interaction from a fluorescence scan of a voltage-gated K+ channel

X-ray crystallography has made considerable recent progress in providing static structures of ion channels. Here we describe a complementary method-systematic fluorescence scanning-that reveals the structural dynamics of a channel. Local protein motion was measured from changes in the fluorescent intensity of a fluorophore attached at one of 37 positions in the pore domain and in the S4 voltage sensor of the Shaker K+ channel. The local rearrangements that accompany activation and slow inactivation were mapped onto the homologous structure of the KcsA channel and onto models of S4. The results place clear constraints on S4 location, voltage-dependent movement, and the mechanism of coupling of S4 motion to the operation of the slow inactivation gate in the pore domain.     

Molecular characterization of the interaction of crotamine-derived nucleolar targeting peptides with lipid membranes

A novel class of cell-penetrating, nucleolar-targeting peptides (NrTPs), was recently developed from the rattlesnake venom toxin crotamine. Based on the intrinsic fluorescence of tyrosine or tryptophan residues, the partition of NrTPs and crotamine to membranes with variable lipid compositions was studied. Partition coefficient values (in the 10(2)-10(5) range) followed essentially the compositional trend POPC:POPG≤POPG相似文献   

Nitratireductor lucknowense sp. nov., a novel bacterium isolated from a pesticide contaminated soil

A straw-yellow pigmented bacterium, strain IITR-21^T was isolated from a pesticide contaminated site and characterized by using a polyphasic taxonomic approach. The organism had morphological and chemotaxonomic properties consistent with its classification in the genus Nitratireductor. Phylogenetic analysis of the 16S rRNA gene sequence showed that the strain IITR-21^T belongs to the genus Nitratireductor and was moderately related to Nitratireductor indicus C115^T (97.7%) and Nitratireductor pacificus pht-3B^T (97.4%), whereas sequence similarity value with the other species including the type species of the genus Nitratireductor, Nitratireductor aquibiodomus showed less than 97.0% similarity. However, the DNA–DNA relatedness values between strain IITR-21^T and the moderately related taxa N. indicus (59.1%) and N. pacificus (40.4%) were well below the 70% threshold value recommended for the delineation of bacterial species. The G+C content of the DNA was 62.4 mol%. Based on physiological, biochemical tests and genotypic differences between the strain IITR-21^T and the other two validly published species of the genus Nitratireductor, it is proposed that the strain be classified as a new species of Nitratireductor as Nitratireductor lucknowense sp. nov. The type strain is IITR-21^T (=MTCC 8354^T = DSM 24322^T).     

Do Bites of Kissing Bugs Cause Unexplained Allergies? Results from a Survey in Triatomine-Exposed and Unexposed Areas in Southern California

Background

The bite of Triatominae can cause cutaneous allergic reactions and even anaphylaxis. Since the early 1980s, no population-based surveys have been done in Southern California, and none was ever carried out in inland Los Angeles or Riverside Counties.

Objectives

To measure the frequency of insect sightings, bites and allergic reactions in a suburban area of eastern Los Angeles County and along with rural and urban sites in Riverside County.

Methods

A door-to-door survey was done in triatomine exposed and unexposed areas. Logistic regression modeling was used for the analysis, and study participants were asked to collect insects.

Results

Out of the 221 study participants in the exposed areas, 46 (20%) knew about the presence of Triatominae in their neighborhood. Fifteen (7%) persons reported triatomine sightings in their house during the month preceding the interview. Also, 15 (7%) participants reported ever being bitten by a triatomine. Ten (5%) participants collected either a Triatoma protracta Uhler and/or Paratriatoma hirsuta Barber in and around their house. Twenty-nine (13%) persons in the rural Riverside County reported symptoms compatible with allergy to triatomine bites. This was 4 times higher than in the urban control area where only 4 (3%) of 115 persons reported these symptoms. The association between living in a triatomine-exposed area and self-reported symptoms suggestive of allergies increased slightly when adjusted for the participant’s sex and the age of their house (adjusted odds ratio: 5.1, 95% confidence interval: 1.2 to 22.0). Reporting these symptoms was associated with seeing Triatominae in the neighborhood and having been bitten.

Conclusion

Allergies to triatomine bites could be a significant problem in inland Southern California. Further investigations, a diagnostic test and better information of persons living in triatomine-exposed areas are needed.     

Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and Tuberculosis Co-Infected Adults in South Africa

Background

In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine – in routine practice – the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.

Methodology/Principle Findings

We conducted a retrospective review of HIV-infected patients who receiving second-line ART with a LPV/r-containing regimen who required concomitant TB treatment. We identified 29 patients; the median age was 36 years (IQR 29–40), 22 (76%) were female, the median CD4 cell count and viral load at first-line ART failure was 86 cells/mm³ (IQR 21–159) and 39,457 copies/mL (IQR 6,025–157,500), respectively. According to physician preference, 15 (52%) of 29 patients received super-boosted LPV/r (400 mg/400 mg) every 12 hours during TB treatment and 14 (48%) of 29 patients received standard dose LPV/r (400 mg/100 mg) twice daily during TB treatment. Among patients who received super-boosted LPV/r there was a trend towards a higher rate of symptomatic transaminitis (27% vs. 7%; p = 0.3), gastrointestinal toxicity (20% vs. 0%; p = 0.2) and a significantly increased need for treatment discontinuation (47% vs. 7%; p = 0.035. The durability of coadministered treatment was significantly shorter in patients who received super-boosted lopinavir/ritonavir with TB treatment compared to patients who received standard lopinavir/ritonavir dosing (log rank, P = 0.036). The rate of virologic failure was not higher in patients with unadjusted LPV/r dosing.

Conclusions/Significance

We observed a high rate of toxicity and need for treatment discontinuation among patients on standard rifampicin-based TB treatment who received super-boosted LPV/r.     

Blink Perturbation Effects on Saccades Evoked by Microstimulation of the Superior Colliculus

Current knowledge of saccade-blink interactions suggests that blinks have paradoxical effects on saccade generation. Blinks suppress saccade generation by attenuating the oculomotor drive command in structures like the superior colliculus (SC), but they also disinhibit the saccadic system by removing the potent inhibition of pontine omnipause neurons (OPNs). To better characterize these effects, we evoked the trigeminal blink reflex by delivering an air puff to one eye as saccades were evoked by sub-optimal stimulation of the SC. For every stimulation site, the peak and average velocities of stimulation with blink movements (SwBMs) were lower than stimulation-only saccades (SoMs), supporting the notion that the oculomotor drive is weakened in the presence of a blink. In contrast, the duration of the SwBMs was longer, consistent with the hypothesis that the blink-induced inhibition of the OPNs could prolong the window of time available for oculomotor commands to drive an eye movement. The amplitude of the SwBM could also be larger than the SoM amplitude obtained from the same site, particularly for cases in which blink-associated eye movements exhibited the slowest kinematics. The results are interpreted in terms of neural signatures of saccade-blink interactions.     

Reverse engineering systems models of regulation: discovery, prediction and mechanisms

Biological systems can now be understood in comprehensive and quantitative detail using systems biology approaches. Putative genome-scale models can be built rapidly based upon biological inventories and strategic system-wide molecular measurements. Current models combine statistical associations, causative abstractions, and known molecular mechanisms to explain and predict quantitative and complex phenotypes. This top-down 'reverse engineering' approach generates useful organism-scale models despite noise and incompleteness in data and knowledge. Here we review and discuss the reverse engineering of biological systems using top-down data-driven approaches, in order to improve discovery, hypothesis generation, and the inference of biological properties.