Continuous-flow NMR culture system for mammalian cells

A continuous-flow NMR culture system for mammalian cells has been developed on which ³¹P-NMR experiments under complete and strictly physiologic conditions have been performed. Observations on the response of the cellular metabolism to stresses such as starvation, low temperature and changes in environmental pH monitored by ³¹P-NMR are reported. The response of the intracellular pH relative to the external pH of the growth medium is studied. We find that under the experimental conditions used there exists a ΔpH varying between less than 0.2 and more than 0.6 pH units. These results are compatible with those obtained using other techniques.     

A programmable environmental system for maintenance and observation of individually housed ticks

This paper describes an inexpensive, space-saving, and labor-efficient method for housing and making repeated observations of individual ticks held under specific photoperiodic, temperature, and humidity conditions. Using 96-well assay plates to house ticks, various developmental parameters, sex, survival, etc., of several thousand individual ticks can be recorded routinely in less than 1 hr. This design also permits more than 3,500 individual ticks to be maintained in 1 small (18.9-L) aquarium that serves as a humidity chamber. A small, unilluminated constant temperature incubator was converted inexpensively into a light and temperature programmable unit to contain the aquarium by adding a timing system, light fixture, and a second thermostat.     

Design and optimization of selective serotonin re-uptake inhibitors with high synthetic accessibility Part 1

The reported selective serotonin Re-uptake Inhibitor Litoxetine was used as the starting point in the design of a range of potential SSRIs with high ease of synthetic accessibility. Preparation and subsequent optimization yielded a range of potent and highly selective SSRIs.     

Nutrition and inflammatory events: highly unsaturated fatty acids (omega-3 vs omega-6) in surgical injury.

Given the poor prognosis and high cost of care for patients with acute inflammatory responses (often leading to organ failure and/or allograft rejection), immunomodulation of this hyperresponse represents an important priority for research in nutritional medicine. The primary goal of nutritional support in inflammatory disease is to provide adequate energy, particularly through use of novel lipids (to alter eicosanoid pathway toward a more regulated inflammatory state), and protein to meet endogenous requirements for tissue repair IL-1 production, and restored cellular function, thus preventing secondary infection (52). Manipulation of macrophage eicosanoid production by use of omega-3 PUFA may reduce the cellular immune response (by competing with arachidonic acid, which produces inflammatory eicosanoids of the 2- and 4-series), whereas inclusion of MCT found in coconut oil may lower the arachidonic acid content of membrane phospholipids. As more data are obtained on the use of such tailored therapies in critically ill patients, a new generation of parenteral and enteral diets will be developed to reduce inflammation and immune dysfunction.     

The Articulation of Indigenous and Exogenous Orders in Highland New Guinea and Beyond

One of the leading challenges for contemporary anthropology is to try to contribute to an understanding of the interaction between indigenous and exogenous socio‐cultural orders, especially at the frontiers of globalisation. Here I review three recent attempts to do so: (1) a model of structural transformation as developed by Marshall Sahlins; (2) a model of articulation as developed by James Clifford; (3) a model of ‘adoption’ proposed by Joel Robbins. As a test case for these models, I consider them in relation to some recent developments in local segmentary politics and verbal art in the Ku Waru region of Highland New Guinea. I show that all three models are in certain respects inadequate for understanding those developments, and offer some proposals as to what kinds of theory might be more adequate to the task.     

In vivo suppression of phytochrome aggregation by the GroE chaperonins in Escherichia coli

When expressed in Escherichia coli, a truncated form of phytochrome (oat PHYA AP3 residues 464-1129) self associates to form a series of products ranging in size from monomers to aggregates of greater than 20 subunits. When these same phytochrome sequences are coexpressed with the chaperonins GroEL and GroES, the truncated phytochrome migrates as a native-like dimer in size exclusion chromatography and no higher-order aggregates were detected. GroEL and GroES inhibition of phytochrome aggregation in E. coli presumably occurs via the suppression of folding pathways leading to incorrectly folded phytochrome.     

Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE--To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN--Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING--Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS--1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES--Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS--There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS--Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.     

Solvent cage effects: the influence of radical mass and volume on the recombination dynamics of radical cage pairs generated by photolysis of [CpCH2CH2N(CH3)C(O)(CH2)nCH3Mo(CO)3]2 (n = 3, 8, 13, 18) (Cp = eta 5-C5H4) complexes

The photochemistry of the [(CpR)Mo(CO)(3)](2) molecules, where CpR = eta(5)-C(5)H(4)(CH(2))(2)C(O)NCH(3)(CH(2))(n)CH(3) (n = 3, 8, 13, and 18), was examined using femtosecond pump-probe transient absorption spectroscopy. The goal of this study was to investigate the importance of radical size and mass on the dynamics and efficiency of geminate radical-radical recombination. The femtosecond results demonstrated the lack of any size/mass dependence of the recombination efficiency. This finding contrasts with results from a prior study that did find a size/mass dependence using a steady-state photochemical technique. To explain these conflicting results, it is proposed that the femtosecond pump-probe results are a measurement of the efficiency of primary geminate recombination whereas the steady-state method results are a measurement of the sum of primary and secondary geminate recombination efficiencies. The size/mass dependence is evident in the latter because secondary geminate recombination is a slower diffusive recombination process and therefore depends on the steric properties of the radicals. Although the existence of primary and secondary recombination channels is often taken for granted, experimental differentiation of primary and secondary caging has proven to be difficult because it is not possible for a single experimental technique to span the entire timescale for recombination of a radical cage pair and adequately resolve these recombination pathways.     

Isolation and characterization of a type II restriction endonuclease from Streptococcus thermophilus

The alpha-toxin (phospholipase C) of Clostridium perfringens has been reported to contain catalytically essential zinc ions. We report here that histidine residues are essential for the co-ordination of these ion(s). Incubation of alpha toxin with diethylpyrocarbonate, a histidine modifying reagent, did not result in the loss of phospholipase C activity unless the protein was first incubated with EDTA, suggesting that zinc ions normally protect the susceptible histidine residues. When the amino acid sequences of three phospholipase C's were aligned, essential zinc binding histidine residues in the non-toxic B. cereus phospholipase C were found in similar positions in the toxic C. perfringens enzyme and the weakly toxic C. bifermentans phospholipase C.