Structural Aspects and Prediction of Calmodulin-Binding Proteins

Calmodulin (CaM) is an important intracellular protein that binds Ca²⁺ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca²⁺ concentration through interactions with CaM.     

Similarities in normal and binocularly rivalrous viewing

We report here a series of observations-most of which the reader can experience directly-showing that distinct components of patterned visual stimuli (orthogonal lines of a different hue) vary in perception as sets. Although less frequent and often less complete, these perceptual fluctuations in normal viewing are otherwise similar to the binocular rivalry experienced when incompatible scenes are presented dichoptically.     

Homonucleotide tracts, short repeats and CpG/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene

Glutamatergic synaptic potentials induced by micromolar concentrations of the potassium conductance blocker 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in the presence of 10 microM bicuculline (BIC). These synaptic potentials originate from neostriatal cortical and thalamic afferents and were completely blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 100 microM D-2-amino-5-phosphonovaleric acid (2-APV). Their inter-event time intervals could be fitted to exponential distributions, suggesting that they are induced randomly. Their amplitude distributions had most counts around 1 mV and fewer counts with values up to 5 mV. Since input resistance of the recorded neurons is about 40 M omega, the amplitudes agree to quantal size measurements in mammalian central neurons. The action of a D2 agonist, quinpirole, was studied on the frequency of these events. Mean amplitude of synaptic potentials was preserved in the presence of 2-10 microM quinpirole, but the frequency of 4-AP-induced glutamatergic synaptic potentials was reduced in 35% of cases. The effect was blocked by the D2 antagonist sulpiride (10 microM). Input resistance, membrane potential, or firing threshold did not change during quinpirole effect, suggesting a presynaptic site of action for quinpirole in some but not all glutamatergic afferents that make contact on a single cell. The present experiments show that dopaminergic presynaptic modulation of glutamatergic transmission in the neostriatum does not affect all stimulated afferents, suggesting that it is selective towards some of them. This may control the quality and quantity of afferent flow upon neostriatal neurons.     

StAR protein is expressed in both medulla and cortex of the bovine and rat adrenal gland

We have employed polyclonal antibodies to a peptide sequence of bovine steroidogenic acute regulatory (StAR) protein and human placental 3beta-hydroxysteroid dehydrogenase (3beta-HSD) to determine the localisation and distribution of these proteins in rat and bovine adrenal glands. Immunohistochemical staining demonstrated the presence of StAR protein in the zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis (ZR) and in the medulla of both species. For 3beta-HSD, immunostaining was observed in the ZG, ZF and ZR of the rat adrenal and was absent in the medulla. Immunoblotting experiments showed intense bands for StAR protein (30 kDa, 37 kDa) in the mitochondria of bovine ZG, ZF and medulla and a less intense band (30 kDa) in the microsomes. In rat ZG and ZF/R mitochondria only the 30 kDa protein was present. For 3beta-HSD, an intense band (42 kDa) was found in microsomes and mitochondria of rat and bovine ZG and ZFR. A very faint signal for 3beta-HSD was seen in adrenal medulla. In conclusion, StAR (or a closely related) protein is present throughout the adrenal gland in rat and bovine species in contrast to 3beta-HSD which is confined to the steroidogenic zones. The possible function of StAR protein in the adrenal medulla merits investigation.     

Excited-state-absorption cross sections and amplifier modeling inthe 1300-nm region for Nd-doped glasses

The performance of Nd³⁺-doped fibre amplifiers is limited by strong excited-state absorption (ESA) of the signal, and, even for fluorozirconate glasses, ESA prevents the important region below 1320 nm from being used. To quantify this limitation and explore alternative host materials, ESA and stimulated-emission cross sections have been measured for a representative group of glass compositions. These parameters have been used in an accurate fiber-amplifier model to provide the first quantitative comparisons of performance for Nd³⁺ -doped glasses in the 1300-nm band as a function of host     

Actions of cisplatin on the electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats

In this study we have employed the whole cell patch clamp technique to investigate the effects of an anti-cancer drug cisplatin on basic electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats. The results show that within the clinical concentration range, cisplatin (0.1 to 10 microM) caused a decrease in input conductance, and complex changes in resting membrane potential in these cultured sensory neurones. The dominant effects of cisplatin on input conductance may be due to inhibition of leak conductances. Transplatin (5 microM) was significantly less effective than cisplatin at reducing input conductance which suggests a degree of stereoselectivity. Cisplatin (1 to 5 microM) transiently increased excitability of the cultured neurones as reflected by a reduction in the threshold for activation of action potentials by 8 mV. The rise time, peak amplitude and duration of action potentials were not changed by acute application of 5 microM cisplatin. Long term treatment of neurones with cisplatin (5 microM), for up to 1 week reduced the viability of the cultures, and attenuated neurone excitability, although input conductance of the cells was significantly increased to 322 +/- 49 M omega (n = 9) compared with controls of 210 +/- 20 M omega (n = 30; P < 0.05). Acute and chronic treatment of cultured neurones with cisplatin therefore produced contrasting actions.     

The Effects of Scaling and Bias Configuration on Operating-Voltage Constraints in SiGe HBTs for Mixed-Signal Circuits

This paper presents a comprehensive picture of operating-voltage constraints in SiGe heterojunction bipolar transistors, addressing breakdown-related issues as they relate to technology generation, bias configuration, and operating-current density. New definitions for breakdown voltage, adopted from standard measurements, are presented. Practical design implications and physical origins of breakdown are explored using calibrated 2-D simulations and quasi-3-D compact models. Device-level analysis of ac instabilities and power performance, which is relevant to mixed-signal circuit design, is presented, and implications of the relaxed voltage constraints for common-base operation are explored.     

Developing competency-based methods for near-real-time air combat problem solving assessment

Air combat scenarios present unique problems where the solution is not obvious. An advanced networked simulation environment can be used to train high-level cognitive air combat skills such as problem solving. A problem in the development of principled and construct oriented assessment is related to determining the level of specificity of the assessment. We present a detailed discussion of the definition of critical competencies associated with combat mission problem solving performance, and we describe our approach to develop and implement an embedded performance assessment system that maps outcomes to these competencies. Finally, we discuss the implications for our approach for comprehensive assessment and discuss our goals for an evaluation of the competency-based approach to assessment.