Biomedical subjects

William Knight

Publications and source records attributed to William Knight.

7 recordsLinked to original sources

PubMed2006

Deep brain stimulation in the internal capsule and nucleus accumbens region: responses observed during active and sham programming.

BACKGROUND: Recently, anterior limb of the internal capsule and nucleus accumbens deep brain stimulation (DBS) has been used in the treatment of medication-refractory obsessive-compulsive disorder (OCD). This region has been previously explored with lesion therapy, but with the advent of DBS there exists the possibility of monitoring the acute and chronic effects of electrical stimulation. The stimulation-induced benefits and side effects can be reversibly and blindly applied to a variety of locations in this region. OBJECTIVE: To explore the acute effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region. METHODS: Ten total DBS leads in five patients with chronic and severe treatment-refractory OCD were tested. Patients were examined 30 days after DBS placement and received either "sham" testing or actual testing of the acute effects of DBS (the alternative condition tested 30 days later). RESULTS: Pooled responses were reviewed for comparability of distribution using standard descriptive methods, and relationships between the variables of interest were sought using chi2 analysis. A total of 845 stimulation trials across the five patients were recorded and pooled. Of these 16% were elicited from sham stimulation and 17% from placebo (0 V stimulation). A comparison of active to sham trials showed that sham stimulation was not associated with significant side effects or responses from patients. Non-mood-related responses were found to be significantly associated with the ventral lead contacts (0 and 1) (p = 0.001). Responses such as taste, smell and smile were strongly associated with the most ventral lead positions. Similarly, physiological responses--for example, autonomic changes, increased breathing rate, sweating, nausea, cold sensation, heat sensation, fear, panic and panic episodes--were significantly associated with ventral stimulation (p = 0.001). Fear and panic responses appeared clustered around the most ventral electrode (0). Acute stimulation resulted in either improved or worsened mood responses in both the dorsal and ventral regions of the anterior limb of the internal capsule. CONCLUSION: The acute effects of DBS in the region of the anterior limb of the internal capsule and nucleus accumbens, particularly when obtained in a blinded fashion, provide a unique opportunity to localise brain regions and explore circuitry.

Adult↗

PubMed2005

A time-resolved investigation of ribosomal subunit association.

The notion that the ribosome is dynamic has been supported by various biochemical techniques, as well as by differences observed in high-resolution structures of ribosomal complexes frozen in various functional states. Yet, the mechanisms and extent of rRNA dynamics are still largely unknown. We have used a novel, fast chemical-modification technique to provide time-resolved details of 16 S rRNA structural changes that occur as bridges are formed between the ribosomal subunits as they associate. Association of different 16 S rRNA regions was found to be a sequential, multi-step process involving conformational rearrangements within the 30 S subunit. Our results suggest that key regions of 16 S rRNA, necessary for decoding and tRNA A-site binding, are structurally altered in a time-dependent manner by association with the 50 S ribosomal subunits.

Base Pairing↗

PubMed2005

Ribosome builder: a software project to simulate the ribosome.

The Ribosome Builder is a software project that provides tools and techniques to create dynamic models of macromolecular systems from the rapidly growing numbers of atomic structural models. It includes a computer program that allows the user to assemble the multiple molecular components within a 3D space and to define the hypothetical interactions of these components with the initial goal of understanding protein translation at an atomic level of detail. The program employs a simplified molecular dynamics forcefield that can simulate the long time-scale events, such as docking of translation factors and mRNA translocation. An embedded scripting language and Application Programming Interface (API) enable the creation of Steered Molecular Dynamics (SMD) simulations through the programmable application of external forces and torques on atoms and bonds. A graphical interface is provided for displaying and interacting with models, recording movies of molecular dynamics movements, and creating annotated 3D simulations of complex macromolecular events. Initial applications of the project include simulation of tetraloop folding, docking of an mRNA on the 30S subunit and a schematic simulation of the translation elongation cycle. The program is an open source project released under the GNU public license.

Computer Simulation↗

PubMed2003

Compost convective airflow under passive aeration.

For composting, passive aeration can save energy costs while being just as efficient as forced or active aeration. Passive aeration requires the proper design of aeration ducts, and thus, the proper prediction of the convective airflow rates created by the temperature differential between the compost and the ambient air. To establish such relationship, the temperature and convective air flow regimes of composts were investigated using three bulking agents (wood shavings, hay and straw), each at three moisture contents (MC-60%, 65% and 70%) spanning the normal values. All bulking agent and aeration treatments were aerated in duplicate under passive and active regimes. Laboratory vessels of 105 L were used for all treatments. Passive aeration treatments produced temperatures above 57 degrees C, as did the treatments actively aerated at 4 mg of air s(-1) kg(-1) of initial dry compost material. Compost MC had an effect only on the peak compost temperature, occurring between day 2 and 6. After 6 days of composting, MC no longer had any effect on temperature regime because of the loss of moisture by each mixture. A relationship was established between the Grasholf number (Gr-ratio of buoyancy to viscous forces) and the convective airflow rates, to size the aeration ducts for passive aeration. In general, convective airflow rates ranged from 1.5 to 0.7 mg of dry air s(-1) kg(-1) of initial compost dry matter, from day 0 to day 20, respectively, and for all compost treatments. This airflow rate sizes the aeration ducts installed under compost piles for passive aeration. As compared to straw where airflow rate dropped over a given level of Gr, wood shavings and hay were found to be more effective as bulking agents, as their airflow rate increased constantly with Gr.

Air Movements↗

PubMed2003

Predicting mutation frequencies in stem-loop structures of derepressed genes: implications for evolution.

This work provides evidence that, during transcription, the mutability (propensity to mutate) of a base in a DNA secondary structure depends both on the stability of the structure and on the extent to which the base is unpaired. Zuker's DNA folding computer program reveals the most probable stem-loop structures (SLSs) and negative energies of folding (-DeltaG) for any given nucleotide sequence. We developed an interfacing program that calculates (i) the percentage of folds in which each base is unpaired during transcription; and (ii) the mutability index (MI) for each base, expressed as an absolute value and defined as -follows: MI = (% total folds in which the base is unpaired) x (highest -DeltaG of all folds in which it is unpaired). Thus, MIs predict the relative mutation or reversion frequencies of unpaired bases in SLSs. MIs for 16 mutable bases in auxotrophs, selected during starvation in derepressed genes, are compared with 70 background mutations in lacI and ebgR that were not derepressed during mutant selection. All the results are consistent with the location of known mutable bases in SLSs. Specific conclusions are: (i) Of 16 mutable bases in transcribing genes, 87% have higher MIs than the average base of the sequence analysed, compared with 50% for the 70 background mutations. (ii) In 15 of the mutable bases of transcribing genes, the correlation between MIs and relative mutation frequencies determined experimentally is good. There is no correlation for 35 mutable bases in the lacI gene. (iii) In derepressed auxotrophs, 100% of the codons containing the mutable bases are within one codon's length of a stem, compared with 53% for the background mutable bases in lacI. (iv) The data suggest that environmental stressors may cause as well as select mutations in derepressed genes. The implications of these results for evolution are discussed.

Base Composition↗

PubMed2003

Ribosomal localization of translation initiation factor IF2.

Bacterial translation initiation factor IF2 is a GTP-binding protein that catalyzes binding of initiator fMet-tRNA in the ribosomal P site. The topographical localization of IF2 on the ribosomal subunits, a prerequisite for understanding the mechanism of initiation complex formation, has remained elusive. Here, we present a model for the positioning of IF2 in the 70S initiation complex as determined by cleavage of rRNA by the chemical nucleases Cu(II):1,10-orthophenanthroline and Fe(II):EDTA tethered to cysteine residues introduced into IF2. Two specific amino acids in the GII domain of IF2 are in proximity to helices H3, H4, H17, and H18 of 16S rRNA. Furthermore, the junction of the C-1 and C-2 domains is in proximity to H89 and the thiostrepton region of 23S rRNA. The docking is further constrained by the requisite proximity of the C-2 domain with P-site-bound tRNA and by the conserved GI domain of the IF2 with the large subunit's factor-binding center. Comparison of our present findings with previous data further suggests that the IF2 orientation on the 30S subunit changes during the transition from the 30S to 70S initiation complex.

Base Sequence↗

PubMed2002

Effect of carbon source on compost nitrogen and carbon losses.

The effect of C source on N losses by volatilization during composting was measured using four bulking agents, each at three humidity levels and composted in duplicate under passive and active aeration. The bulking agents were pine shavings alone and corrected with soybean, chopped grass hay alone and corrected with urea, long (unchopped) wheat straw and chopped oat straw. The readily available C of each bulking agent was determined by analyzing for BOD5. In 105 l laboratory vessels, the bulking agents were mixed with liquid swine manure and tap water for a C/N of 20 and three humidity levels of 60%, 65% and 70%. While being aerated actively or passively, the mixtures were composted for 21 days. Their initial and final C and N contents were measured to conduct a mass balance analysis and calculate C and N losses. C and N losses were compared to bulking agent BOD5. N losses were compared to C losses. The humidity level and aeration regime had no effect on C and N losses but the N losses were correlated to C losses and only the C losses could be correlated to the BOD5 of the bulking agent. Thus, the N losses are related not only to the availability of C but also to the extent of composting. A relationship established between N and C losses indicated that 85% of the initial total N of the compost was available for microbial degradation and that 70% of the available C was lost as CO2 during the immobilization process.

Air Movements↗