Modern humans in Sarawak, Malaysian Borneo, during Oxygen Isotope Stage 3: palaeoenvironmental evidence from the Great Cave of Niah

During recent reinvestigations in the Great Cave of Niah in Borneo, the ‘Hell Trench’ sedimentary sequence seen by earlier excavators was re-exposed. Early excavations here yielded the earliest anatomically-modern human remains in island Southeast Asia. Calibrated radiocarbon dates, pollen, algal microfossils, palynofacies, granulometry and geochemistry of the ‘Hell Trench’ sequence provide information about environmental and vegetational changes, elements of geomorphic history and information about human activity. The ‘Hell’ sediments were laid down episodically in an ephemeral stream or pool. The pollen suggests cyclically changing vegetation with forest habitats alternating with more open environments; indicating that phases with both temperatures and precipitation reduced compared with the present. These events can be correlated with global climate change sequences to produce a provisional dating framework. During some forest phases, high counts of Justicia, a plant which today colonises recently burnt forest areas, point to fire in the landscape. This may be evidence for biomass burning by humans, presumably to maintain forest-edge habitats. There is evidence from palynofacies for fire on the cave floor in the ‘Hell’ area. Since the area sampled is beyond the limit of plant growth, this is evidence for human activity. The first such evidence is during an episode with significant grassland indicators, suggesting that people may have reached the site during a climatic phase characterised by relatively open habitats ~50 ka. Thereafter, people were able to maintain a relatively consistent presence at Niah. The human use of the ‘Hell’ area seems to have intensified through time, probably because changes in the local hydrological regime made the area dryer and more suitable for human use.

Enrichment and analysis of nonenzymatically glycated peptides: Boronate affinity chromatography coupled with electron-transfer dissociation mass spectrometry

Nonenzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the development of diabetic complications. However, no effective high-throughput methods exist for identifying proteins containing this low-abundance posttranslational modification in bottom-up proteomic studies. In this report, phenylboronate affinity chromatography was used in a two-step enrichment scheme to selectively isolate first glycated proteins and then glycated, tryptic peptides from human serum glycated in vitro. Enriched peptides were subsequently analyzed by alternating electron-transfer dissociation (ETD) and collision induced dissociation ( CID) tandem mass spectrometry. ETD fragmentation mode permitted identification of a significantly higher number of glycated peptides (87.6% of all identified peptides) versus CID mode (17.0% of all identified peptides), when utilizing enrichment on first the protein and then the peptide level. This study illustrates that phenylboronate affinity chromatography coupled with LC-MS/MS and using ETD as the fragmentation mode is an efficient approach for analysis of glycated proteins and may have broad application in studies of diabetes mellitus.

Responses to interactive playback predict future pairing success in nightingales

Birdsong is a sexually selected trait that serves in territory defence and mate choice. Individual song traits can be affected by the body condition of the male and thus may reflect his quality. Such relations between male quality and general singing performance raise the question whether differences in male quality also affect response strategies used in dyadic interactions. To address this question, we studied the relation between pairing success of male common nightingales, Luscinia megarhynchos, and their responses to rivals posing different levels of threat. Using interactive playback, we exposed males prior to mating to either aggressively or moderately singing rivals (by song overlapping and song alternating, respectively). Males that remained unpaired throughout the season (bachelors) interrupted their singing significantly more often after being overlapped than after alternating playback, whereas subsequently mated males kept the number of singing interruptions more constant across playback treatment. This suggests that subsequently paired males are less discriminative than are bachelors when challenged by rivals varying in aggressiveness. Regardless of playback treatment, males that later became paired responded significantly more strongly than did bachelor males. Thus, an increase in singing after a vocal interaction prior to mating predicted future mating success. (c) 2006 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Land-use patterns and cultural change in the Middle to Late Bronze Age in Ireland: inferences from pollen records

In Ireland, the Middle to Late Bronze Age (1500-600 cal. B.C.) is characterised by alternating phases of prolific metalwork production (the Bishopsland and Dowris Phases) and apparent recessions (the Roscommon Phase and the Late Bronze Age-Iron Age transition). In this paper, these changes in material culture are placed in a socio-economic context by examining contemporary settlement and land-use patterns interpreted from the pollen record. The vegetation histories of six tephrochronologically-linked sites are presented that provide high-resolution and chronologically well-resolved insights into changes in landscape use over the Middle to Late Bronze Age. The records are compared with published pollen records in an attempt to discern if there are any trends of woodland clearance and abandonment from which changes in settlement patterns can be inferred. The results suggest that prolific metalworking industries correlate chronologically with expansive farming activity, which indicates that they were supported by a productive subsistence economy. Conversely, declines in metalwork production occur during periods when farming activity is generally less extensive and perhaps more centralised, and it is proposed that disparate socio-economic or –political factors, rather than a collapse of the subsistence economy, lies behind the demise of metalworking industries.

Dual adaptation to two opposing visuomotor rotations when each is associated with different regions of workspace

Studies examining dual adaptation to opposing novel environments have yielded contradictory results, with previous evidence supporting both successful dual adaptation and interference leading to poorer adaptive performance. Whether or not interference is observed during dual adaptation appears to be dependent on the method used to allow the performer of the task to distinguish between two novel environments. This experiment tested if colour cues, a separation in workspace, and presentation schedule, could be used to distinguish between two opposing visuomotor rotations and enable dual adaptation. Through the use of a purpose designed manipulandum, each visuomotor rotation was either presented in the same region of workspace and associated with colour cues (Group 1), different regions of workspace in addition to colour cues (Groups 2 and 3) or different regions of workspace only (Groups 4 and 5). We also assessed the effectiveness of the workspace separation with both randomised and alternating presentation schedules (Groups 4 and 5). The results indicated that colour cues were not effective at enabling dual adaptation when each of the visuomotor rotations was associated with the same region of workspace. When associated with different regions of workspace, however, dual adaptation to the opposing rotations was successful regardless of whether colour cues were present or the type of presentation schedule.

Bimanual coordination: constraints imposed by the relative timing of homologous muscle activation

It has often been supposed that patterns of rhythmic bimanual coordination in which homologous muscles are engaged simultaneously, are performed in a more stable manner than those in which the same muscles are activated in an alternating fashion. In order to assess the efficacy of this constraint, the present study investigated the effect of forearm posture (prone or supine) on bimanual abduction-adduction movements of the wrist in isodirectional and non-isodirectional modes of coordination. Irrespective of forearm posture, non-isodirectional coordination was observed to be more stable than isodirectional coordination. In the latter condition, there was a more severe deterioration of coordination accuracy/stability as a function of cycling frequency than in the former condition. With elevations in cycling frequency, the performers recruited extra mechanical degrees of freedom, principally via flexion-extension of the wrist, which gave rise to increasing motion in the vertical plane. The increases in movement amplitude in the vertical plane were accompanied by decreasing amplitude in the horizontal plane. In agreement with previous studies, the present findings confirm that the relative timing of homologous muscle activation acts as a principal constraint upon the stability of interlimb coordination. Furthermore, it is argued that the use of manipulations of limb posture to investigate the role of other classes of constraint (e.g. perceptual) should be approached with caution because such manipulations affect the mapping between muscle activation patterns, movement dynamics and kinematics.

Changes in muscle recruitment patterns during skill acquisition

The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, ill which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMC) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. Tn the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. Tn contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination.

DNA and chromosomal damage in response to intermittent extremely low-frequency magnetic fields.

Considerable controversy still exists as to whether electric and magnetic fields (MF) at extremely low frequencies are genotoxic to humans. The aim of this study was to test the ability of alternating magnetic fields to induce DNA and chromosomal damage in primary human fibroblasts. Single- and double-strand breaks were quantified using the alkaline comet assay and the gammaH2AX-foci assay, respectively. Chromosomal damage was assayed for unstable aberrations, sister chromatid exchange and micronuclei. Cells were exposed to switching fields - 5min on, 10min off - for 15h over the range 50-1000microT. Exposure to ionizing radiation was used as a positive-effect calibration. In this study two separate MF exposure systems were used. One was based on a custom-built solenoid coil system and the other on a commercial system almost identical to that used in previous studies by the EU REFLEX programme. With neither system could DNA damage or chromosomal damage be detected as a result of exposure of fibroblasts to switching MF. The sensitive gammaH2AX assay could also not detect significant DNA damage in the MF-exposed fibroblasts, although the minimum threshold for this assay was equivalent to an X-ray dose of 0.025Gy. Therefore, with comparable MF parameters employed, this study could not confirm previous studies reporting significant effects for both the alkaline and neutral comet assays and chromosomal aberration induction.

Dramatic solvent effects on ring-opening metathesis polymerization of cycloalkenes

A series of metathesis polymers and copolymers have been formed and their structures were analysed by C-13 NMR spectroscopy. Noble metal and non-noble metal salt catalysts are distinguished by their behaviour in various solvents. Thus, in phenolic solvents, the former class produce alternating copolymers from cyclopentene and norbornene, while the latter are unaffected and produce random copolymers. In contrast, ether solvents have the effect of markedly increasing the cis content of polymers from the latter catalysts while the former are unaffected.

Effects of intrahippocampal NAC(61-95) injections on memory in the rat and attenuation with vitamin E

Parkinson's disease (PD)-related dementia affects approximately 40% of PD patients and the severity of this dementia correlates significantly with the density of Lewy body (LB) deposition in the PD brain. Aggregated alpha-synuclein protein is the major component of LB's and the non-amyloid component (NAC) region of alpha-synuclein, residues 61-95, is essential for the aggregation and toxicity of this protein. The current study evaluated the effect of pre-aggregated NAC(61-95) injected into the CA3 area of the dorsal hippocampus of the brain on memory in the rat. Previous research has suggested that oxidative stress processes may play a role in the neuropathology of PD, therefore the effect of treatment with vitamin E, an antioxidant, was also evaluated. Male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, subjects were divided into four groups. Two groups were injected bilaterally into the dorsal hippocampus with aggregated NAC(61-95) (5 mu l suspension), and two groups were injected bilaterally into the dorsal hippocampus with sterile water (5 mu l). Subgroups were treated with either vitamin E (150 mg/kg in Soya oil) or vehicle (Soya oil) daily. Injection of NAC(61-95) induced memory deficits and vitamin E treatment alleviated these. In addition, NAC(61-95) injections induced activated astrocytes and chronic treatment with vitamin E reduced the numbers of activated astrocytes. These results suggest that aggregated NAC(61-95) and associated oxidative stress, may play a role in the pathogenesis of cognitive deficits seen in PD-induced dementia. (C) 2009 Elsevier Inc. All rights reserved.

Rapid ecosystem response to abrupt climate changes during the last glacial period in western Europe, 40-16 ka

We present a high-resolution and independently dated multiproxy lake sediment record from the paleolake at Les Echets in southeastern France that displays synchronous changes in independent limnic and terrestrial ecosystem proxies, in concert with millennial-scale climate oscillations during the last glacial period. Distinct lake-level fluctuations, low lake organic productivity, and open, treeless vegetation indicate cold and dry conditions in response to Heinrich events. Alternating phases of higher and low lake organic productivity, stratified surface waters and long-lasting lake ice cover, decreased or increased catchment erosion, and tree-dominated or herb-dominated vegetation resemble Dansgaard-Oeschger interstadial-stadial variability. Transitions between different ecological states occurred in as little as 40-230 yr and seem to have been controlled by the position of the Polar Front. Ecosystem response after 30 ka suggests that local climate conditions became more important. Our results demonstrate that all parts of the terrestrial system responded to the abrupt and dramatic climatic changes associated with Dansgaard-Oeschger and Heinrich events, and that regional factors modulated ecosystem response.

HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase

Alternative NADH dehydrogenases (NADH:ubiquinone oxidoreductases) are single subunit respiratory chain enzymes found in plant and fungal mitochondria and in many bacteria. It is unclear how these peripheral membrane proteins interact with their hydrophobic substrate ubiquinone. Known inhibitors of alternative NADH dehydrogenases bind with rather low affinities. We have identified 1-hydroxy-2-dodecyl-4(1H)quinolone as a high affinity inhibitor of alternative NADH dehydrogenase from Yarrowia lipolytica. Using this compound, we have analyzed the bisubstrate and inhibition kinetics for NADH and decylubiquinone. We found that the kinetics of alternative NADH dehydrogenase follow a ping-pong mechanism. This suggests that NADH and the ubiquinone headgroup interact with the same binding pocket in an alternating fashion.

Late Holocene linkages between decade-century scale climate variability and productivity at Lake Tanganyika, Africa

Microlaminated sediment cores from the Kalya slope region of Lake Tanganyika provide a near-annually resolved paleoclimate record between similar to 2,840 and 1,420 cal. yr B.P. demonstrating strong linkages between climate variability and lacustrine productivity. Laminae couplets comprise dark, terrigenous-dominated half couplets, interpreted as low density underflows deposited from riverine sources during the rainy season, alternating with light, planktonic diatomaceous ooze, with little terrigenous component, interpreted as windy/dry season deposits. Laminated portions of the studied cores consist of conspicuous dark and light colored bundles of laminae couplets. Light and dark bundles alternate at decadal time scales. Within dark bundles, both light and dark half couplets are significantly thinner than within light bundles, implying slower sediment accumulation rates during both seasons over those intervals.

RS-0406 arrests amyloid-B oligomer-induced behavioural deterioration in vivo

Clinically accessible compounds that arrest or reverse the effects of amyloid-ß (Aß) on progressively developing behavioural symptomatology and neuropathology in Alzheimer's disease (AD) have yet to become available. However, a viable strategy may be to target and neutralise soluble Aß oligomers, which have been shown to mediate synaptic dysfunction and to produce cognitive deficits in the intact organism. Inhibiting the aggregation of Aß is therapeutically attractive, as Aß aggregation is a pathological event and pharmacological interventions targeting this are likely to have a non-toxic profile. A behavioural assay, the alternating-lever cyclic-ratio schedule, was used to assess the effect of Aß oligomers and the non-peptide small molecule RS-0406 in male Sprague-Dawley rats. RS-0406 has been shown to inhibit Aß1-42 fibrillogenesis and protect against Aß1-42–induced cytotoxicity in primary hippocampal neurons. In the current study, RS-0406 ameliorated the adverse effects of secreted oligomers of human Aß on behaviour and dose dependently reduced the behavioural effects of Aß oligomers, with the highest dose, 10 µM, maintaining behaviour approximately at control levels. This effect appeared to be central; peripheral confounds having been extensively investigated. This is the first published report on the effects of RS-0406 in vivo and indicates that RS-0406 has potential as a pharmacotherapeutic intervention for behavioural deficits seen in the early stages of AD, and possibly as an intervention in the development of AD neuropathology. Indeed, an analogue of RS-0406 that could be administered peripherally might be a realistic candidate for the clinical treatment of AD.