Receptor signaling: when dimerization is not enough.

Activation of receptors that signal via tyrosine kinase domains has been thought to involve receptor dimerization and transphosphorylation of juxtaposed catalytic domains. Recent results suggest things might be more complex - specific intersubunit conformational changes within a dimer can also be important.     

Assigning pathogenicity to mitochondrial tRNA mutations: when "definitely maybe" is not good enough

Some mutations in mitochondrial tRNA (mt-tRNA) genes cause devastating disease, whereas others have no clinical consequences. We understand little of the factors determining the pathogenicity of specific mt-tRNA mutations, making prediction of clinical outcome extremely difficult. Using extensive sequence databases, we compared the characteristics of neutral variations with those of pathogenic mutations. We recommend that the location of the proposed mutation within the secondary structure of the mt-tRNA molecule and the disruption it causes to Watson-Crick base pairing should be considered when assessing the pathological significance of a novel mt-tRNA mutation.     

Oogenesis: when most is good enough

In male meiosis an unaligned chromosome blocks meiotic progression. However, oocytes with one or more misaligned chromosomes can complete meiosis. This difference reflects a more permissive role of the spindle assembly checkpoint, rather than solely reflecting the ability of some univalents to adopt a meiosis II-like orientation on the spindle.     

When enough is not enough: shorebirds and shellfishing

In a number of extensive coastal areas in northwest Europe, large numbers of long-lived migrant birds eat shellfish that are also commercially harvested. Competition between birds and people for this resource often leads to conflicts between commercial and conservation interests. One policy to prevent shellfishing from harming birds is to ensure that enough food remains after harvesting to meet most or all of their energy demands. Using simulations with behaviour-based models of five areas, we show here that even leaving enough shellfish to meet 100% of the birds' demands may fail to ensure that birds survive in good condition. Up to almost eight times this amount is needed to protect them from being harmed by the shellfishery, even when the birds can consume other kinds of non-harvested prey.     

Combining multiple fluorescence imaging techniques in biology: when one microscope is not enough

While fluorescence microscopy has proven to be an exceedingly useful tool in bioscience, it is difficult to offer simultaneous high resolution, fast speed, large volume, and good biocompatibility in a single imaging technique. Thus, when determining the image data required to quantitatively test a complex biological hypothesis, it often becomes evident that multiple imaging techniques are necessary. Recent years have seen an explosion in development of novel fluorescence microscopy techniques, each of which features a unique suite of capabilities. In this Technical Perspective, we highlight recent studies to illustrate the benefits, and often the necessity, of combining multiple fluorescence microscopy modalities. We provide guidance in choosing optimal technique combinations to effectively address a biological question. Ultimately, we aim to promote a more well-rounded approach in designing fluorescence microscopy experiments, leading to more robust quantitative insight.     

Medical audit data: counting is not enough.

OBJECTIVE--To assess the meaningfulness of a year''s worth of audit data relating to all the inpatients of one consultant general surgeon and to question the usefulness of certain outcome measures. DESIGN--Analysis of records entered on to audit computer (Dunnfile) and relating to inpatient episodes for one consultant general surgeon over one year. Data obtained were compared with ward records and the patient administration system to check their accuracy. SETTING--The three hospitals and 12 wards in Brighton health district where the surgeon admitted patients. SUBJECTS--859 Records relating to inpatient episodes from 1 January to 31 December 1988. These covered 655 main procedures and 79 secondary procedures performed at the same time. MAIN OUTCOME MEASURES--Procedures were analysed by complexity of operation (BUPA code) and grade of surgeon; complications were counted and rates constructed by surgeon and by BUPA code: returns to theatre were analysed. RESULTS--Simple counts revealed some data, such as the fact that one registrar performed more major operations (32) than the senior registrars (22 and 14), and an analysis of complications showed that he had a lower complication rate (11.4% v 20.0% and 19.4%). But the simple complication rate disclosed nothing about whether the complication was avoidable. Likewise, the number of returns to theatre needed further qualification. Analysis of data collection for February to April 1988 showed a 30% deficit of information on the audit system compared with ward records and prompted a re-examination of everyone''s role in collecting data. After the year''s audit there was still a 17% shortfall compared with the district''s patient administration system, though some of this was accounted for by a backlog of work. CONCLUSIONS--It is difficult to ensure adequate data collection and entails everyone in an unfamiliar discipline. Connecting the audit system to the patient administration system would help. Despite the limitations of crude analyses of workload and complications rates, the audit data helped to measure activity and in the management of the firm. Nevertheless, time and care have to be taken in presenting and interpreting audit data carefully. IMPLICATIONS--Counting is not enough.