The Amoroso Lecture. The human spermatozoon--a cell in crisis?

A great deal of evidence has accumulated in recent years to suggest that there has been a gradual increase in male reproductive pathology over the past 30-40 years, as evidenced by increased rates of testicular cancer and declining semen quality. The hypothesis is advanced that this phenomenon is causally related to the ability of male germ cells to generate reactive oxygen metabolites. When produced in low levels, such metabolites are thought to enhance sperm function by stimulating DNA compaction and promoting a redox-regulated cAMP-mediated pathway that is central to the induction of sperm capacitation. When produced in excessive amounts, the same metabolites stimulate DNA fragmentation and a loss of sperm function associated with peroxidative damage to the sperm plasma membrane. Free radical-induced mutations in the male germ line may also be involved in the aetiology of childhood cancer and recent increases in the incidence of seminoma. In light of these considerations, establishing the mechanisms for free radical generation by the male germ line and determining the factors that influence this activity are important objectives for future research in this area.     

Prior expectations evoke stimulus-specific activity in the deep layers of the primary visual cortex

The way we perceive the world is strongly influenced by our expectations. In line with this, much recent research has revealed that prior expectations strongly modulate sensory processing. However, the neural circuitry through which the brain integrates external sensory inputs with internal expectation signals remains unknown. In order to understand the computational architecture of the cortex, we need to investigate the way these signals flow through the cortical layers. This is crucial because the different cortical layers have distinct intra- and interregional connectivity patterns, and therefore determining which layers are involved in a cortical computation can inform us on the sources and targets of these signals. Here, we used ultra-high field (7T) functional magnetic resonance imaging (fMRI) to reveal that prior expectations evoke stimulus-specific activity selectively in the deep layers of the primary visual cortex (V1). These findings are in line with predictive processing theories proposing that neurons in the deep cortical layers represent perceptual hypotheses and thereby shed light on the computational architecture of cortex.

The way we perceive the world is strongly influenced by our expectations, but the neural circuitry through which the brain achieves this remains unknown. A study using ultra-high field fMRI reveals that prior expectations evoke stimulus-specific signals in the deep layers of the primary visual cortex.     

Physical and functional characterisation of monomeric and dimeric eukaryotic cytochrome c oxidases

Cytochrome c oxidases were isolated from heart tissue of beef (Bos tauros), sheep (Ovis aries), horse (Equus caballus), pig (Sus scrofa) (native dimers) and hammerhead shark (Sphyrna lewinii) (native monomer). Limited proteolysis of dimeric enzymes selectively depleted subunit III, resulting in monomerisation and a blue shift (2nm) of the reduced α band to the same wavelength maximum (603nm) as that of the hammerhead shark enzyme. Monomeric enzymes retain the ability to accept electrons rapidly from cytochrome c, and the second-order rate constants for electron transfer between cytochromes c and a are reported. The steady-state kinetics of both native and subunit III-depleted cytochrome c oxidases were biphasic, thus ruling out any explanation for this behaviour that depends on cooperation between functional units (monomers) within a dimer. Functional integrity of the subunit III-depleted enzyme prepared by proteolysis was maintained during multiple turnover, in contrast to reports elsewhere of loss of activity caused by subunit III removal by other means. A model is proposed to explain this difference, in which removal of a hydrophobic membrane-spanning segment of subunit III leads to monomerisation but a residual extra-membrane segment is retained, preserving the functional integrity of the enzyme.