There must be a prokaryote somewhere: microbiology's search for itself.

While early microbiologists showed considerable interest in the problem of the natural (evolutionary) relationships among prokaryotes, by the middle of this century that problem had largely been discarded as being unsolvable. In other words, the science of microbiology developed without an evolutionary framework, the lack of which kept it a weak discipline, defined largely by external forces. Modern technology has allowed microbiology finally to develop the needed evolutionary framework, and with this comes a sense of coherence, a sense of identity. Not only is this development radically changing microbiology itself, but also it will change microbiology''s relationship to the other biological disciplines. Microbiology of the future will become the primary biological science, the base upon which our future understanding of the living world rests, and the font from which new understanding of it flows.     

Regulated serine proteinase lytic system on mammalian sperm surface: There must be a role

Serine proteases play key roles in many biological processes, regulating surface proteins that are key-points in signaling pathways. Several studies have reported the presence of members of this protease family in sperm from various species. The precise regulation of their activity is thought to be performed by specific endogenous or extrinsic inhibitors. The contribution of the sperm serine to proteases to fertilization has been demonstrated by synthetic inhibitors and several single knock out experiments, but to date, there is no evidence that links a single enzyme to a single step of fertilization. The explanation for the failure in the understanding of the “one-enzyme-one-process” hypothesis may be that sperm have multiple serine proteases as a mechanism to ensure the success of fertilization. In addition to the classical purification and expression studies, we summarized recent advances in proteomics and performed a bioinformatics search of proteases and inhibitors, providing support for the idea of redundancy. This review summarizes current knowledge about serine proteases and their inhibitors in sperm capacitation and maturation, identifies questions that need to be answered, and provides a reference for future research.     

Endpiece: Ideas must be comforting

ObjectivesTo explore general practitioners’ perceptions of effective health care and its application in their own practice; to examine how these perceptions relate to assumptions about clinicians’ values and behaviour implicit in the evidence based medicine approach.DesignA qualitative study using semistructured interviews.SettingEight general practices in North Thames region that were part of the Medical Research Council General Practice Research Framework.Participants24 general practitioners, three from each practice.ResultsThree categories of definitions emerged: clinical, patient related, and resource related. Patient factors were the main reason given for not practising effectively; others were lack of time, doctors’ lack of knowledge and skills, lack of resources, and “human failings.” Main sources of information used in situations of clinical uncertainty were general practitioner partners and hospital doctors. Contact with hospital doctors and observation of hospital practice were just as likely as information from medical and scientific literature to bring about changes in clinical practice.ConclusionsThe findings suggest that the central assumptions of the evidence based medicine paradigm may not be shared by many general practitioners, making its application in general practice problematic. The promotion of effective care in general practice requires a broader vision and a more pragmatic approach which takes account of practitioners’ concerns and is compatible with the complex nature of their work.

Key messages

• Evidence based medicine has emerged as a new paradigm to prevent inappropriate variations in clinical practice
• This study explored the extent to which evidence based medicine’s emphasis on clinical effectiveness, self analysis, and information seeking is congruent with the modes of thinking and behaviour of general practitioners
• General practitioners’ definitions of effective health care fell into three categories of clinical, patient related, and resource related; their main reason for not practising effectively was patient factors, and others were lack of time, lack of knowledge and skills, lack of resources, and “human failings”; and their main sources of information in cases of clinical uncertainty were general practitioner partners and hospital doctors
• The central assumptions of the evidence based medicine paradigm may not be shared by many general practitioners, making its application in general practice problematic
• Promotion of effective care in general practice requires a broader vision and a more pragmatic approach that takes account of practitioners’ concerns and is compatible with the complex nature of their work