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Slice preparations are typically used to study the effects of pharmacological manipulations on the electrophysiological activity of mature neurons. However, the severing of afferent inputs is known to significantly change the natural membrane activity of the neuron. To study the effects of local pharmacological manipulations on neurons in the intact brain, we combined the methods of microdialysis and intracellular recording in vivo. After implantation of a microdialysis probe into the prefrontal cortex (PFC) or striatum, intracellular recordings were conducted within approximately 500 microm of the active surface of the probe. The spontaneous membrane activity, passive membrane properties, and intracellularly and synaptically evoked responses of striatal and cortical neurons recorded during perfusion of artificial cerebral spinal fluid were not different from that of neurons recorded in intact animals. Moreover, in the PFC, local perfusion with glutamate or N-methyl-D-aspartate depolarized neurons and increased spike activity. Conversely, local perfusion of tetrodotoxin hyperpolarized neurons while markedly reducing spontaneous membrane depolarizations and eliminating spike activity. In the striatum, local perfusion of the gamma-aminobutyric acid(A) receptor antagonist bicuculline rapidly depolarized neurons and increased spontaneous spike activity. Given that striatal and PFC neurons recorded in animals undergoing microdialysis in the current study exhibited electrophysiological properties similar to those recorded in intact controls, it is likely that the effects of local microdialysis on ongoing synaptic activity, neuronal excitability, and endogenous neurotransmitter levels are minimal. We conclude that the use of local microdialysis with intracellular recording is a powerful method for studying local receptor regulation of synaptic activity in vivo.

Proper mitotic chromosome segregation requires dynamic interactions between spindle microtubules and kinetochores. Here we demonstrate that two related fission yeast kinesins, klp5(+) and klp6(+), are required for normal chromosome segregation in mitosis. Null mutants frequently lack a normal metaphase chromosome alignment. Chromosome pairs move back and forth along the spindle for an extended period prior to sister chromatid separation, a phenotype reminiscent of the loss of CENP-E in metazoans. Ultimately, sister chromatids segregate, regardless of chromosome position along the spindle, and viable daughter cells are usually produced. The initiation of anaphase B is sometimes delayed, but the rate of spindle elongation is similar to wildtype. Despite a delay, anaphase B often begins before anaphase A is completed. The klp5Delta and klp6Delta null mutants are synthetically lethal with a deletion of the spindle assembly checkpoint gene, bub1(+), several mutants in components of the anaphase promoting complex, and a cold sensitive allele of the kinetochore and microtubule-binding protein, Dis1p. Klp5p-GFP and Klp6p-GFP localize to kinetochores from prophase to the onset of anaphase A, but relocalize to the spindle midzone during anaphase B. These data indicate that Klp5p and Klp6p are kinetochore kinesins required for normal chromosome movement in prometaphase.

The kinesin superfamily of microtubule motor proteins is important in many cellular processes, including mitosis and meiosis, vesicle transport, and the establishment and maintenance of cell polarity. We have characterized two related kinesins in fission yeast, klp5+ and klp6+,, that are amino-terminal motors of the KIP3 subfamily. Analysis of null mutants demonstrates that neither klp5+ nor klp6+, individually or together, is essential for vegetative growth, although these mutants have altered microtubule behavior. klp5Delta and klp6Delta are resistant to high concentrations of the microtubule poison thiabendazole and have abnormally long cytoplasmic microtubules that can curl around the ends of the cell. This phenotype is greatly enhanced in the cell cycle mutant cdc25-22, leading to a bent, asymmetric cell morphology as cells elongate during cell cycle arrest. Klp5p-GFP and Klp6p-GFP both localize to cytoplasmic microtubules throughout the cell cycle and to spindles in mitosis, but their localizations are not interdependent. During the meiotic phase of the life cycle, both of these kinesins are essential. Spore viability is low in homozygous crosses of either null mutant. Heterozygous crosses of klp5Delta with klp6Delta have an intermediate viability, suggesting cooperation between these proteins in meiosis.

We have identified Klp2p, a new kinesin-like protein (KLP) of the KAR3 subfamily in fission yeast. The motor domain of this protein is 61% identical and 71% similar to Pkl1p, another fission yeast KAR3 protein, yet the two enzymes are different in behavior and function. Pkl1p is nuclear throughout the cell cycle, whereas Klp2p is cytoplasmic during interphase. During mitosis Klp2p enters the nucleus where it forms about six chromatin-associated dots. In metaphase-arrested cells these migrate back and forth across the nucleus. During early anaphase they segregate with the chromosomes into two sets of about three, fade, and are replaced by other dots that form on the spindle interzone. Neither klp2(+) nor pkl1(+) is essential, and the double deletion is also wild type for both vegetative and sexual reproduction. Each deletion rescues different alleles of cut7(ts), a KLP that contributes to spindle formation and elongation. When either or both deletions are combined with a dynein deletion, vegetative growth is normal, but sexual reproduction fails: klp2 Delta,dhc1-d1 in karyogamy, pkl1 Delta,dhc1-d1 in multiple phases of meiosis, and the triple deletion in both. Deletion of Klp2p elongates a metaphase-arrested spindle, but pkl1 Delta shortens it. The anaphase spindle of klp2 Delta becomes longer than the cell, leading it to curl around the cell's ends. Apparently, Klp2p promotes spindle disassembly and contributes to the behavior of mitotic chromosomes.

OBJECTIVE: To provide an overview of the role of social support in smoking cessation and to critically review evidence regarding the use of "buddy systems" (where smokers are specifically provided with someone to support them) to aid smoking cessation. DATA SOURCES: Studies were located by searching Medline and Psyclit using the key words "smoking", "smoking cessation", "social support", and "buddy". Additional studies were identified through reference lists. Only studies reported in English and published since 1980 were included. STUDY SELECTION: Studies were selected on four criteria: publication in a peer reviewed journal; randomised controlled trial using smokers who wanted to stop; the use of a social support intervention, including a "buddy"; dependent variable of smoking abstinence. Most research in this area does not use a randomised design so only a small proportion of the originally identified studies were included. DATA SYNTHESIS: In view of the diverse nature of the studies, a meta-analysis was not attempted. Ten studies were identified: nine were clinic based smoking trials, eight used a group format, and nine used buddies from among smokers' existing relationships. Support training varied from role play and rehearsal to a simple instruction to call each other regularly. Intervention and follow up periods varied between studies. Two studies showed a significant benefit of the intervention in the short term. CONCLUSIONS: Research methodology in many cases was poor. The evidence would suggest that in the context of a smokers clinic the use of buddies may be of some benefit. There is a lack of evidence regarding the efficacy of the use of buddies in community interventions. This is an important area for future research.

An extensive range of orthorhombic perovskites with the GdFeO3 structure, variable B-cation content and variable oxygen content form according to the formula Ca2Mn2–xNbxOγ: 0

The phase ‘NdMnO3’ has been synthesised and characterised by a combination of electron probe microanalysis, X-ray and neutron diffraction and H2-reduction thermogravimetry. NdMnO3 forms, at ≈1400 °C, over the range Nd1.00(1)Mn0.95(1)O2.92(1) to Nd0.88(1)Mn1.00(1)O2.72(1). Oxygen contents vary in air over the range 700 to 1400 °C and can be varied further, either by high pressure O2 treatment or by reduction in H2. The structure of ‘NdMnO3’ is based on the GdFeO3 structure with a Jahn-Teller distortion associated with the high proportion of Mn3+ ions present. However, it also shows a very varied defect structure; depending on composition and heat treatment, vacancies can form on any one or any two of the three sublattices, Nd, Mn and O and the overall Mn oxidation state can include 2+, 3+ and 4+ contributions. Data on compositional range and defect crystal structure are presented in the form of a novel phase diagram-defect structure map.

The cycle of spindle pole body (SPB) duplication, differentiation, and segregation in Schizosaccharomyces pombe is different from that in some other yeasts. Like the centrosome of vertebrate cells, the SPB of S. pombe spends most of interphase in the cytoplasm, immediately next to the nuclear envelope. Some gamma-tubulin is localized on the SPB, suggesting that it plays a role in the organization of interphase microtubules (MTs), and serial sections demonstrate that some interphase MTs end on or very near to the SPB. gamma-Tubulin is also found on osmiophilic material that lies near the inner surface of the nuclear envelope, immediately adjacent to the SPB, even though there are no MTs in the interphase nucleus. Apparently, the MT initiation activities of gamma-tubulin in S. pombe are regulated. The SPB duplicates in the cytoplasm during late G2 phase, and the two resulting structures are connected by a darkly staining bridge until the mitotic spindle forms. As the cell enters mitosis, the nuclear envelope invaginates beside the SPB, forming a pocket of cytoplasm that accumulates dark amorphous material. The nuclear envelope then opens to form a fenestra, and the duplicated SPB settles into it. Each part of the SPB initiates intranuclear MTs, and then the two structures separate to lie in distinct fenestrae as a bipolar spindle forms. Through metaphase, the SPBs remain in their fenestrae, bound to the polar ends of spindle MTs; at about this time, a small bundle of cytoplasmic MTs forms in association with each SPB. These MTs are situated with one end near to, but not on, the SPBs, and they project into the cytoplasm at an orientation that is oblique to the simple axis. As anaphase proceeds, the nuclear fenestrae close, and the SPBs are extruded back into the cytoplasm. These observations define new fields of enquiry about the control of SPB duplication and the dynamics of the nuclear envelope.

Single crystals of Ba2Li2/3Ti16/3O13 have been isolated and its crystal structure solved from X-ray diffraction data. The structure is similar to that of Ba2Ti6O13and Na2Ti6O13 [monoclinic, space group C2/m (no.12), a=15.171(13), b=3.8992(18), c=9.106(4) Å, β=98.64(6)°, Z=2], but one of the three independent octahedral sites contains partial substitution of Ti by Li, whereas the others are uniquely occupied by Ti. This phase contains only Ti4+ , in contrast to Ba2Ti6O13 , which has a mixture of Ti3+ and Ti4+. The structure is described in terms of both an octahedral framework and a cubic close-packing model of [Ba2 □O13 ] layers (□: vacancy).

OBJECTIVE: To evaluate rehabilitation after myocardial infarction. DESIGN: Randomised controlled trial of rehabilitation in unselected myocardial infarction patients in six centres, baseline data being collected on admission and by structured interview (of patients and spouses) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months. SETTING: Six district general hospitals. SUBJECTS: All 2328 eligible patients admitted over two years with confirmed myocardial infarction and discharged home within 28 days. INTERVENTIONS: Rehabilitation programmes comprising psychological therapy, counselling, relaxation training, and stress management training over seven weekly group outpatient sessions for patients and spouses. MAIN OUTCOME MEASURES: Anxiety, depression, quality of life, morbidity, use of medication, and mortality. RESULTS: At six months there were no significant differences between rehabilitation patients and controls in reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients reported a lower frequency of angina (median three versus four episodes a week), medication, and physical activity. At 12 months there were no differences in clinical complications, clinical sequelae, or mortality. CONCLUSIONS: Rehabilitation programmes based on psychological therapy, counselling, relaxation training, and stress management seem to offer little objective benefit to patients who have experienced myocardial infarction compared with previous reports of smaller trials.

The "cut" mutants of Schizosaccharomyces pombe are defective in spindle formation and/or chromosome segregation, but they proceed through the cell cycle, resulting in lethality. Analysis of temperature-sensitive alleles of cut11(+) suggests that this gene is required for the formation of a functional bipolar spindle. Defective spindle structure was revealed with fluorescent probes for tubulin and DNA. Three-dimensional reconstruction of mutant spindles by serial sectioning and electron microscopy showed that the spindle pole bodies (SPBs) either failed to complete normal duplication or were free floating in the nucleoplasm. Localization of Cut11p tagged with the green fluorescent protein showed punctate nuclear envelope staining throughout the cell cycle and SPBs staining from early prophase to mid anaphase. This SPB localization correlates with the time in the cell cycle when SPBs are inserted into the nuclear envelope. Immunoelectron microscopy confirmed the localization of Cut11p to mitotic SPBs and nuclear pore complexes. Cloning and sequencing showed that cut11(+) encodes a novel protein with seven putative membrane-spanning domains and homology to the Saccharomyces cerevisiae gene NDC1. These data suggest that Cut11p associates with nuclear pore complexes and mitotic SPBs as an anchor in the nuclear envelope; this role is essential for mitosis.

The new phase Ca2MnNbOγ has an orthorhombic, GdFeO3 structure with B site disorder of Mn and Nb. The oxygen content γ varies from 5.86 to 6.00 depending on heat treatment conditions. Treatment in high pressure O2 required for full oxidation. Magnetic susceptibility measurements indicate mixed valence (2+, 3+) of Mn for γ=5.87 and Curie-Weiss paramagnetism at high temperatures. SQUID measurements indicate spin glass-like behaviour below 15 K. Ac impedance shows semiconducting behaviour, E=0.31(2) eV. On heating in O2-poor atmospheres, resistive surface layers and grain boundary effects are seen, which point to a p-type conduction mechanism.

The spinels Li2MM′3O8 (MM′=MgTi, CoTi, CoGe, NiGe and ZnGe) are cubic with space group P4332 . Simple crystal field theory qualitatively explains the distribution of M over tetrahedral and octahedral sites: Ni occupies only octahedral sites, whereas Zn, Mg and Co show strong preference for tetrahedral sites. 1:3 cation ordering of Li/M and M′ occurs on the octahedral sites. The titanates undergo an order–disorder phase transition involving the octahedral cations at high temperatures, whereas the ordered phase is maintained until melting for the germanates. Solid solutions Li2–2XM1+3XM′3–XO8 form at both sides of the Li2MM′3O8 stoichiometry for the titanates; but there is no substantial range of solid solution for Li2ZnGe3O8 and Li2NiGe3O8 . The occurrence of order–disorder phenomena and solid solutions in the titanates is attributed to the similarity in size of Li, M and Ti, whereas the smaller Ge is less able to disorder with Li/M. M is shown to be divalent from magnetic susceptibility measurements (for Co and Ni) with the support of conductivity data. The samples containing Co and Ni are paramagnetic down to 5 K. From impedance measurements on pellets with blocking electrodes, the main conductive species is deduced to be Li+ : the activation energies for conduction are high, 0.55<ΔH/eV<2.14. Cyclic voltammograms show a set of reversible peaks at ca. 1.5 V vs. Li/Li+ for the titanates, attributed to the Ti3+/4+ couple, but no Li could be electrochemically extracted from either titanates or germanates up to 5 V vs. Li/Li+ .

The spinel phase, Li2CoMn3O8 , can be used as a cathode in secondary lithium batteries, Li/LiPF6 ,propylene carbonate/Li2CoMn3O8 , with a discharge capacity of ca. 40 mAh g–1 at 5.0 V increasing to ca. 130 mAh g–1 at 3.8 V. This appears to be the first single cell system to operate reversibly over 5 volts.