Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells.

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations.

Junior doctors need training in sickness certification.

BACKGROUND: A recent report highlights the need for clear standards of practice regarding working-age health. Despite this, little is known about training or performance of sickness certification by junior doctors in secondary care. AIMS: To see what sickness certification training had been received by practising hospital postgraduate trainees and establish how confident and knowledgeable they were in this area. We also evaluated the feasibility and face validity of a paper-based educational module. METHODS: We surveyed 51 junior doctors in a variety of specialties, at all grades. Questions concerned training and practice of sickness certification and assessing capacity for work. A knowledge test regarding formal guidelines, use of forms and self-certification was undertaken, before participants evaluated a 10 min training module. RESULTS: Seventy-nine per cent of participants lacked knowledge in sickness certification, and 55% were not confident to assess capacity for work; 66% had received no training at all and 71% participants followed no guideline. Many could not identify or explain the use of certificates: MED-3 (50 or 71%, respectively), MED-5 (42 or 38%, respectively), MED-10 (0 or 17%, respectively), RM-7 (2 or 6%, respectively) and DS-1500 (6 or 8%, respectively). Majority of participants thought that an educational module could increase knowledge and skill in sickness certification (96%) and in assessing work capacity (74%). CONCLUSIONS: Junior doctors are involved in sickness certification, but there is a lack of training at undergraduate and postgraduate level, and many are unaware of formal guidance. The majority of junior doctors are concerned about lack of knowledge in this area and to a lesser extent in assessing patients' capacity to work. A simple educational module could improve confidence, knowledge and skills in sickness certification.

Gene regulation in Aspergillus: From genetics to genomics.

A fundamental aspect of any organism's success is the ability to monitor and respond effectively to its environment, a process which is largely achieved through the appropriate regulation of gene expression. There are few better examples than fungi, which inhabit diverse and often hostile environments, ranging from leaf litter to the human body. Regulation can occur at many levels, and as we investigate specific genes in detail, the paradigm is one of increasing complexity. We will briefly review the different levels at which regulation is known to occur in Aspergillus and the insights gained from the available genome sequences.