Modified hippocampal long-term potentiation in PKC gamma-mutant mice

Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.     

The need for repeat angiography in subarachnoid haemorrhage

OBJECTIVE: To determine the actual use of 'statin' therapy for primary and secondary prevention and the potential effect of using the Sheffield Table for primary prevention of coronary heart disease upon 'statin' use in a consultant-run Hypertension and Cardiovascular Risk Clinic. DESIGN: Prospective audit of the current use of cholesterol-lowering therapy and the effect of implementing the criteria used in the Sheffield Table and the Scandinavian Simvastatin Study for cholesterol lowering in 'at risk' patients upon statin use in a consultant-led cardiovascular risk clinic. SETTING: The Aberdeen Hypertension Clinic. RESULTS: A total of 1500 patients were reviewed of which 416 (27.7%) had experienced at least one clinical manifestation of atherosclerotic cardiovascular disease (CVD) and 392 (94%) of these had a total cholesterol measured of whom 298 (76%) had a total cholesterol >5.5 mmol/l. Only 11.2% of eligible patients were actually receiving lipid-lowering treatment for secondary prevention. A total of 1084 patients with no prior cardiovascular disease were identified, 97 (8.9%) were excluded because of age. Using the Sheffield Table, 92 (9.4%) of these patients were eligible for statin therapy and only six of the 92 patients were actually receiving treatment. CONCLUSIONS: The results of this study reveal that even in a consultant-led cardiovascular prevention clinic there is a significant discrepancy between optimal evidence-based management and the actual delivery of clinical care. Seventy-two per cent and 9.3% of patients attending the clinic were eligible for statin treatment for secondary and primary prevention, respectively. However, only 11.2% of patients suitable for secondary prevention and 6.5% of patients suitable for primary prevention were actually receiving appropriate lipid-lowering therapy. Considering the proven benefit of this form of medical intervention the results of this study are of real importance to practising clinicians and patients alike.     

Scientific co-operation in Europe and the citation of multinationally authored papers

Under the sponsorship of the U.S. National Science Foundation, CHI Research, Inc. developed the bibliometric indicators for the U.S. National Science Board'sScience Indicators Reports starting withScience Indicators 1972. In the work reported here, for the Commission of the European Communities, CHI has extended the Science Indicators techniques and database to a study of publication, coauthorship and citation within 28 scientific fields related to various European Community programs.Perhaps the most important finding of the research was that internationally coauthored papers — papers authored by scientists affiliated with institutions in more than one EC country — were cited two times as highly as papers authored by scientists working at a single institution within a single country. These EC-EC internationally coauthored papers were cited as highly as EC-Non EC and Non-EC papers. This indicates that the internationally linked European science is of as high impact as any other science in the world.A second key finding was that, after compensating for national scientific size, the degree of international coauthorship did not appear to be particularly dependent upon size. However, linguistic and cultural factors were found to be very strong. The patterns of coauthorship amongst the European countries are far from homogeneous, and are quite heavily affected by linguistic, historical, and cultural factors.Finally, it was found that international coauthorship is increasing steadily, both within and outside of the Community, with some evidence that international cooperation is increasing more rapidly in scientific fields that have been targeted by the Commission.This work has been sponsored by the MONITOR programme of the Commission of the European Communities.     

Integrating trust into the CyberCraft Initiative via the Trust Vectors model [Application Notes]

This research supports the hypothesis that the Trust Vector model can be modified to fit the CyberCraft Initiative, and that there are limits to the utility of historical data. This research proposed some modifications and expansions to the Trust Model Vector, and identified areas for future research.     

Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases

Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure.     

Normality and impairment following profound early institutional deprivation: A longitudinal follow-up into early adolescence.

Longitudinal analyses on normal versus impaired functioning across 7 domains were conducted in children who had experienced profound institutional deprivation up to the age of 42 months and were adopted from Romania into U.K. families. Comparisons were made with noninstitutionalized children adopted from Romania and with nondeprived within-U.K. adoptees placed before the age of 6 months. Specifically, the validity of the assessment, the degree of continuity and change in levels of functioning from 6 to 11 years, and the factors in the pre- and postadoption environment accounting for heterogeneity in outcome were examined. Pervasive impairment was significantly raised in children experiencing institutional deprivation for ≥6 months of life, with a minority within this group showing no impairment. There was no additional significant effect of duration of deprivation beyond the 6-month cutoff, and few other predictors explained outcome. The pattern of normality/impairment was mainly established by 6 years of age, with considerable continuity at the individual level between 6 and 11 years. The findings are discussed in terms of the possibility of a sensitive period for development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Good clinical laboratory practice (GCLP): the need for a hybrid of good laboratory practice and good clinical practice guidelines/standards for medical testing laboratories conducting clinical trials in developing countries.

There has been a significant increase in the number of clinical drug trials (particularly phase III) being conducted in developing countries for infectious diseases such as HIV, malaria, and tuberculosis. Laboratory results provided by medical testing laboratories in the region are critical to ensuring the safety of patients and the generation of good quality data. A number of well accepted Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) guidelines govern the conduct of clinical trials internationally. Good Clinical Practice guidelines remain too vague with respect to sample analysis to ensure practical implementation in these laboratories. In their strictest sense, Good Laboratory Practice guidelines refer to the analysis of samples from non-clinical studies. A specific set of minimum standards or requirements for practical implementation of clinical trial requirements in medical testing laboratories in the developing world is urgently required.