Crystallographic Analyses of Ion Channels: Lessons and Challenges

Membrane proteins fascinate at many levels, from their central functional roles in transport, energy transduction, and signal transduction processes to structural questions concerning how they fold and operate in the exotic environments of the membrane bilayer and the water-bilayer interface and to methodological issues associated with studying membrane proteins either in situ or extracted from the membrane. This interplay is beautifully exemplified by ion channels, a collection of integral membrane proteins that mediate the transmembrane passage of ions down their electrochemical potential gradient (for general reviews, see Refs. 1 and 2). Ion channels are key elements of signaling and sensing pathways, including nerve cell conduction, hormone response, and mechanosensation. The characteristic properties of ion channels reflect their conductance, ion selectivity, and gating. Ion channels are often specific for a particular type of ion (such as potassium or chloride) or a class of ions (such as anions) and are typically regulated by conformational switching of the protein structure between "open" and "closed" states. This conformational switching may be gated in response to changes in membrane potential, ligand binding, or application of mechanical forces. Detailed functional characterizations of channels and their gating mechanisms have been achieved, reflecting exquisite methodological advances such as patch clamp methods that can monitor the activities of individual channels (3). Until recently, corresponding information about the three-dimensional structures of channels was not available, reflecting difficulties in obtaining sufficient quantities of membrane proteins for crystallization trials. Happily, this situation has started to change with the structure determinations of the Streptomyces lividans K+ channel (KcsA (4)) and the Mycobacterium tuberculosis mechanosensitive channel (MscL (5)). A variety of reviews (6-12) have appeared recently that discuss functional implications of these channel structures. This review discusses these developments from a complementary perspective, by considering the implications of these structures from within the larger framework of membrane protein structure and function. Because of space restrictions, this review necessarily emphasizes membrane proteins that are composed primarily of alpha-helical bundles, such as KcsA and MscL, rather than beta-barrel proteins, such as porins, typically found in bacterial outer membranes

Nitrogen fixation and soil nitrogen in organic ley arable rotations

This report was presented at the UK Organic Research 2002 Conference. Nitrogen (N) fixation in a white clover/ryegrass mixture was measured in 1,2,3 and 4-year-old organically managed leys during 2000. N fixation varied between 73.7 in 1-year-old leys and 33.5 kg ha-1 in 4-year-old leys. Soil nitrate-N, grass N yield and N content of grass and clover were all lowest in 2-year-old leys and highest in 3-year-old leys. The proportion of clover nitrogen derived from the atmosphere (pNdfa) was significantly lower in 3-year-old leys

The Politics of Sovereignty

Volume 4 Number 3

Facilitating Emotional Self-Regulation in Preschool Children: Efficacy of the Early HeartSmarts Program in Promoting Social, Emotional and Cognitive Development

Developed by the Institute of HeartMath (IHM), the Early HeartSmarts (EHS) program is designed to train teachers to guide and support young children (3 -- 6 years old) in learning emotional self-regulation and key age-appropriate socioemotional competencies, with the goal of facilitating their emotional, social and cognitive development. This work reports the results of an evaluation study conducted to assess the efficacy of the EHS program in a pilot implementation of the program carried out during the 2006 -- 2007 academic year in schools of the Salt Lake City School District. The study was conducted using a quasi-experimental longitudinal field research design with three measurement moments (baseline and pre- and post-intervention panels) using The Creative Curriculum Assessment (TCCA) instrument, a teacher-scored, 50-item instrument measuring student growth in four areas of development -- social/emotional, physical, cognitive and language development. Children in nineteen preschool classrooms were divided into intervention and control group samples (N = 66 and 309, respectively; mean age = 3.6 years), in which classes in the former were specifically selected to target children of lower socioeconomic and ethnic minority family backgrounds. Overall, there is compelling evidence of the efficacy of the EHS program in increasing total psychosocial development and each of the four development areas measured by the TCCA: the results of a series of ANCOVAs found a strong, consistent pattern of significant differences on the development measures favoring preschool children who received the EHS program over those in the control group who did not

The synthesis of novel porphyrin macrocycles for their use as potential non-linear optical materials

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The potential organic molecular compounds exhibit for the use as nonlinear optical materials, has received a lot of attention recently. Aromatic compounds containing extensive delocalised π-electronic systems are of particular interest. Porphyrins and metalloporphyrins contain an extensive delocalised 7t-electron system and are amongst those compounds of interest. The ability to manipulate the porphyrins peripheral substitution pattern has led to the synthesis of a range of novel porphyrin macrocycles. A series of meso- substituted porphyrin macrocycles ha been synthesised and the non-linear optical properties of these compounds screened. The synthesis of a series of symmetrical meso- substituted porphyrins was achieved by the reactions of various aldehydes with pyrrole or a dipyrromethane. The synthesis of a series of unsymmetrical porphyrins was achieved by the mixed condensation of two benzaldehydes and pyrrole and also by reactions at the periphery of the symmetrical porphyrins. The Reverse Saturable Absorption properties of the synthesised porphyrins was tested and was exhibited by a number of these compounds. The RSA properties of the compounds were enhanced on the introduction of an unsymmetrical nature to the macrocycle. Also, the effect is enhanced when the ethynyl moiety was introduced to the porphyrins periphery. This is due to the greater overlap between the macrocycle and the peripheral substituents.DERA Malver

A Survey of digital and offset print quality issues

Using an Internet-based industry survey, the differences and similarities of offset and digital print demerits within the print industry are examined. Running parallel to this examination is a look at the extent to which demerit-based quality assurance procedures exist within the printing industry. The survey findings indicate that offset and digital printing processes share common color-related print demerits. What differentiates offset print demerits from digital print demerits can be attributed to two factors: (1) technology differences and (2) printing standards. Offset printing, given the multitude of material choices, produces more frequent print demerits, relating to non-conforming materials. Digital print demerits more likely result from technical constraints such as addressability and resolution. The other factor associated is a lack of printing standards for digital printers. While both processes show a high frequency of color-related problems, offset print providers have more tools and standards available for addressing these problems. Digital print providers, on the other hand, have few color standards or tools for solving similar problems. When examining procedures for defect prevention, the general lack of digital printing standards makes the use of formal quality assurance procedures difficult. Offset print providers are more likely to have formal quality assurance procedures for dealing with frequent and severe print demerits and formal procedures for how customer quality requirements are communicated