A new macrofaunal limit in the deep biosphere revealed by extreme burrow depths in ancient sediments.

Macrofauna is known to inhabit the top few 10s cm of marine sediments, with rare burrows up to two metres below the seabed. Here, we provide evidence from deep-water Permian strata for a previously unrecognised habitat up to at least 8 metres below the sediment-water interface. Infaunal organisms exploited networks of forcibly injected sand below the seabed, forming living traces and reworking sediment. This is the first record that shows sediment injections are responsible for hosting macrofaunal life metres below the contemporaneous seabed. In addition, given the widespread occurrence of thick sandy successions that accumulate in deep-water settings, macrofauna living in the deep biosphere are likely much more prevalent than considered previously. These findings should influence future sampling strategies to better constrain the depth range of infaunal animals living in modern deep-sea sands. One Sentence Summary: The living depth of infaunal macrofauna is shown to reach at least 8 metres in new habitats associated with sand injections.

Unhappiness, health and cognitive ability in old age.

BACKGROUND: To test whether scores on depression inventories on entry to a longitudinal study predict mental ability over the next 4-16 years. METHOD: Associations between scores on the Beck Depression Inventory and on tests of intelligence, vocabulary and memory were analysed in 5070 volunteers aged 49-93 years after differences in prescribed drug consumption, death and drop-out, sex, socio-economic advantage and recruitment cohort effects had also been considered. RESULTS: On all cognitive tasks Beck scores on entry, even in the range 0-7 indicating differences in above average contentment, affected overall levels of cognitive performance but not rates of age-related cognitive decline suggesting effects of differences in life satisfaction rather than in depression. CONCLUSIONS: A new finding is that, in old age, increments in life satisfaction are associated with better cognitive performance. Implications for interpreting associations between depression inventory scores and cognitive performance in elderly samples are discussed.

An inverse agonist selective for alpha5 subunit-containing GABAA receptors enhances cognition.

Alpha5IA is a compound that binds with equivalent subnanomolar affinity to the benzodiazepine (BZ) site of GABA(A) receptors containing an alpha1, alpha2, alpha3, or alpha5 subunit but has inverse agonist efficacy selective for the alpha5 subtype. As a consequence, the in vitro and in vivo effects of this compound are mediated primarily via GABA(A) receptors containing an alpha5 subunit. In a mouse hippocampal slice model, alpha5IA significantly enhanced the burst-induced long-term potentiation of the excitatory postsynaptic potential in the CA1 region but did not cause an increase in the paroxysmal burst discharges that are characteristic of convulsant and proconvulsant drugs. These in vitro data suggesting that alpha5IA may enhance cognition without being proconvulsant were confirmed in in vivo rodent models. Hence, alpha5IA significantly enhanced performance in a rat hippocampal-dependent test of learning and memory, the delayed-matching-to-position version of the Morris water maze, with a minimum effective oral dose of 0.3 mg/kg, which corresponded to a BZ site occupancy of 25%. However, in mice alpha5IA was not convulsant in its own right nor did it potentiate the effects of pentylenetetrazole acutely or produce kindling upon chronic dosing even at doses producing greater than 90% occupancy. Finally, alpha5IA was not anxiogenic-like in the rat elevated plus maze nor did it impair performance in the mouse rotarod assay. Together, these data suggest that the GABA(A) alpha5-subtype provides a novel target for the development of selective inverse agonists with utility in the treatment of disorders associated with a cognitive deficit.

Relationship between self-reported prevalence of diabetes mellitus using the Cornell Medical Index (CMI) and prevalence determined by glycosylated hemoglobin (HbA(1c)) in an elderly community-dwelling population.

Reports of diabetes mellitus samples in community-dwelling unselected populations suggest a prevalence of 6%. A further 3% of unknown diabetes mellitus subjects are suggested when using formal biochemical methods of diagnosis. In this study, we present the prevalence of diabetes mellitus by self-reports using the CMI and concomitant biochemical detection in 436 community-dwelling older adults who have participated in a 20-year-study of age and cognitive performance in Manchester, UK. Twenty-three of the group reported that they had diagnosed diabetes mellitus, three individuals had a raised HbA(1c) of greater than 7.0% on random testing, but no knowledge of having diabetes mellitus. These individuals were re-contacted and three said they subsequently had a diagnosis of diabetes mellitus made within the two years following the questionnaire. We conclude that in an older population of community-dwelling subjects the numbers of undiagnosed cases of diabetes mellitus is lower than anticipated, based on large unselected population samples. The greater opportunity to interact with health care professionals who may consider screening for diabetes mellitus may explain these findings.

Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus-maze: profile comparisons with 8-OH-DPAT, CGS 12066B, TFMPP and mCPP.

It has recently been proposed that the "serenic" (antiaggressive) agents, fluprazine and eltoprazine, may enhance fear/anxiety reactions in laboratory rodents. In the present study, the influence of these compounds (1.25-10.0mg/kg) on anxiety-related behaviour in male mice was examined in the elevated plus-maze test. For comparative purposes, the effects of 8-OH-DPAT (0.01-1.0mg/kg) CGS 12066B (1.25-10mg/kg), TFMPP (0.63-5.0mg/kg) and mCPP (0.5-4.0mg/kg) were also assessed. Behavioural analysis incorporated not only traditional parameters but also several novel measures of defensive behaviour (i.e. "risk assessment"). The selective 5-HT(1A) agonist 8-OH-DPAT produced effects only at 1.0mg/kg, with evidence of an anxiolytic/sedative action at this dose. In the absence of other behavioural changes, CGS 12066B (a selective 5-HT(1B) agonist) caused a preferential and dose-dependent (2.5-10.0mg/kg) stimulation of closed arm entries, an effect also seen with low doses of TFMPP (0.63mg/kg) and the serenics (1.25-2.5mg/kg). In addition, both TFMPP and mCPP (5-HT(1C/1B) agonists) induced dose dependent anxiogenic-like effects over the dose ranges tested, with the most pronounced changes observed on measures of risk assessment. The profiles of fluprazine and eltoprazine on plus-maze behaviour were not only similar to one another but, on most parameters, were also remarkably like those observed with TFMPP and mCPP. These data question the behavioural selectivity of the serenics and further support the proposal that these compounds may potentiate anxiety. Findings are discussed in relation to underlying receptor mechanisms, and the utility of a more ethological approach to the analysis of behaviour on the elevated plus-maze.