What caused extinction of the Pleistocene megafauna of Sahul?

During the Pleistocene, Australia and New Guinea supported a rich assemblage of large vertebrates. Why these animals disappeared has been debated for more than a century and remains controversial. Previous synthetic reviews of this problem have typically focused heavily on particular types of evidence, such as the dating of extinction and human arrival, and have frequently ignored uncertainties and biases that can lead to misinterpretation of this evidence. Here, we review diverse evidence bearing on this issue and conclude that, although many knowledge gaps remain, multiple independent lines of evidence point to direct human impact as the most likely cause of extinction.

Generativity, hierarchical action and recursion in the technology of the Acheulean to Middle Palaeolithic transition: a perspective from Patpara, the Son Valley, India.

The Acheulean to Middle Palaeolithic transition is one of the most important technological changes that occurs over the course of human evolution. Here we examine stone artefact assemblages from Patpara and two other excavated sites in the Middle Son Valley, India, which show a mosaic of attributes associated with Acheulean and Middle Palaeolithic industries. The bifaces from these sites are very refined and generally small, but also highly variable in size. A strong relationship between flake scar density and biface size indicates extensive differential resharpening. There are relatively low proportions of bifaces at these sites, with more emphasis on small flake tools struck from recurrent Levallois cores. The eventual demise of large bifaces may be attributed to the curation of small prepared cores from which sharper, or more task-specific flakes were struck. Levallois technology appears to have arisen out of adapting aspects of handaxe knapping, including shaping of surfaces, the utilization of two inter-dependent surfaces, and the striking of invasive thinning flakes. The generativity, hierarchical organization of action, and recursion evident in recurrent Levallois technology may be attributed to improvements in working memory.

GABAergic neuron distribution in the pedunculopontine nucleus defines functional subterritories.

gamma-Aminobutyric acid (GABA)ergic neurons are widely distributed in brainstem structures involved in the regulation of the sleep-wake cycle, locomotion, and attention. These brainstem structures include the pedunculopontine nucleus (PPN), which is traditionally characterized by its population of cholinergic neurons that have local and wide-ranging connections. The functional heterogeneity of the PPN is partially explained by the topographic distribution of cholinergic neurons, but such heterogeneity might also arise from the organization of other neuronal populations within the PPN. To understand whether a topographical organization is also maintained by GABAergic neurons, we labeled these neurons by in situ hybridization for glutamic acid decarboxylase mRNA combined with immunohistochemistry for choline acetyltransferase to reveal cholinergic neurons. We analyzed their distribution within the PPN by using a method to quantify regional differences based on stereological cell counts. We show that GABAergic neurons of the rat PPN have a rostrocaudal gradient that is opposite to that of cholinergic neurons. Indeed, GABAergic neurons are predominantly concentrated in the rostral PPN; in addition, they form, along with cholinergic neurons, a small, high-density cluster in the most caudal portion of the nucleus. Thus, we provide evidence of heterogeneity in the distribution of different neuronal populations in the PPN and show that GABAergic and cholinergic neurons define neurochemically distinct areas. Our data suggest that the PPN is neurochemically segregated, and such differences define functional territories.

The evolving landscape and climate of western Flores: an environmental context for the archaeological site of Liang Bua.

The rapidly changing landscape of the eastern Indonesian archipelago has evolved at a pace dictated by its tropical climate and its geological and tectonic history. This has produced accelerated karstification, flights of alluvial terraces, and complex, multi-level cave systems. These cave systems sometimes contain a wealth of archaeological evidence, such as the almost complete skeleton of Homo floresiensis found at the site of Liang Bua in western Flores, but this information can only be understood in the context of the geomorphic history of the cave, and the more general geological, tectonic, and environmental histories of the river valley and region. Thus, a reconstruction of the landscape history of the Wae Racang valley using speleothems, geological structure, tectonic uplift, karst, cave, and terrace development, provides the necessary evidence to determine the formation, age, evolution, and influences on the site. This evidence suggests that Liang Bua was formed as two subterranean chambers approximately 600ka, but could not be occupied until approximately 190ka when the Wae Racang wandered to the southern side of the valley, exposing the chamber and depositing alluvial deposits containing artifacts. During the next approximately 190k.yr., the chambers coalesced and evolved into a multi-level and interconnected cave that was subjected to channel erosion and pooling events by the development of sinkholes. The domed morphology of the front chamber accumulated deep sediments containing well stratified archaeological and faunal remains, but ponded water in the chamber further prevented hominin use of the cave until approximately 100ka. These chambers were periodically influenced by river inundation and volcanic activity, whereas the area outside the cave was greatly influenced by glacial phases, which changed humid forest environments into grassland environments. This combined evidence has important implications for the archaeological interpretation of the site.

Geochronology of cave deposits at Liang Bua and of adjacent river terraces in the Wae Racang valley, western Flores, Indonesia: a synthesis of age estimates for the type locality of Homo floresiensis.

A robust timeframe for the extant cave deposits at Liang Bua, and for the river terraces in the adjoining Wae Racang valley, is essential to constrain the period of existence and time of extinction of Homo floresiensis and other biota that have been excavated at this hominin type locality. Reliable age control is also required for the variety of artifacts excavated from these deposits, and to assist in environmental reconstructions for this river valley and for the region more broadly. In this paper, we summarize the available geochronological information for Liang Bua and its immediate environs, obtained using seven numerical-age methods: radiocarbon, thermoluminescence, optically- and infrared-stimulated luminescence (collectively known as optical dating), uranium-series, electron spin resonance, and coupled electron spin resonance/uranium-series. We synthesize the large number of numerical age determinations reported previously and present additional age estimates germane to questions of hominin evolution and extinction.

Reconstructing the geomorphic history of Liang Bua, Flores, Indonesia: a stratigraphic interpretation of the occupational environment.

Liang Bua, in Flores, Indonesia, was formed as a subterranean chamber over 600ka. From this time to the present, a series of geomorphic events influenced the structure of the cave and cave deposits, creating a complex stratigraphy. Within these deposits, nine main sedimentary units have been identified. The stratigraphic relationships between these units provide the evidence needed to reconstruct the geomorphic history of the cave. This history was dominated by water action, including slope wash processes, channel formation, pooling of water, and flowstone precipitation, which created waterfalls, cut-and-fill stratigraphy, large pools of water, and extensive flowstone cappings. The reconstructed sequence of events over the last 190k.yr. has been summarized by a series of time slices that demonstrate the nature of the occupational environment in Liang Bua. The earliest artifacts at the site, dated to approximately 190ka, testify to hominin presence in the area, but the reconstructions suggest that occupation of the cave itself may not have been possible until after approximately 100ka. At approximately 95ka, channel erosion of a basal unit, which displays evidence of deposition in a pond environment, created a greater relief on the cave floor, and formed remanent areas of higher ground that later became a focus for hominin occupation from 74-61ka by the west wall and in the center of the cave, and from approximately 18-17ka by the east wall. These zones have been identified according to the sloping nature of the stratigraphy and the distribution of artifacts, and their locations have implications for the archaeological interpretation of the site.

Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat.

Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. Although dopamine neurons have been intensively studied and quantified, there is little quantitative information regarding the GABAergic and glutamatergic neurons. We therefore used unbiased stereological methods to estimate the number of dopaminergic, GABAergic and glutamatergic cells in these regions in the rat. Neurons were identified using a combination of immunohistochemistry (tyrosine hydroxylase) and in situ hybridization (glutamic acid decarboxylase mRNA and vesicular glutamate transporter 2 mRNA). In substantia nigra pars compacta 29% of cells were glutamic acid decarboxylase mRNA-positive, 58% in the retrorubral field and 35% in the ventral tegmental area. There were further differences in the relative sizes of the GABAergic populations in subnuclei of the ventral tegmental area. Thus, glutamic acid decarboxylase mRNA-positive neurons represented 12% of cells in the interfascicular nucleus, 30% in the parabrachial nucleus, and 45% in the parainterfascicular nucleus. Vesicular glutamate transporter 2 mRNA-positive neurons were present in the ventral tegmental area, but not substantia nigra or retrorubral field. They were mainly confined to the rostro-medial region of the ventral tegmental area, and represented approximately 2-3% of the total neurons counted ( approximately 1600 cells). These results demonstrate that GABAergic and glutamatergic neurons represent large proportions of the neurons in what are traditionally considered as dopamine nuclei and that there are considerable heterogeneities in the proportions of cell types in the different dopaminergic midbrain regions.

Age-dependent and -independent behavioral deficits in Tg2576 mice.

The Tg2576 mouse model of excessive cerebral beta-amyloid deposition is now more than a decade old, yet consensus as to its exact characteristics and utility as a model of Alzheimer's disease is still lacking. Four different cohorts of control and Tg2576 mice, aged approximately 3, 9, 13 and 21 months, were therefore subjected to a battery of tests, principally to assess cognitive and species-typical behaviors. A novel test, the paddling Y-maze, demonstrated an age-dependent deficit in 10 and 14, but not 3 month Tg2576 mice, also in aged (21 month) control mice. However, in many other cognitive tests few Tg2576-related deficits could be shown. This frequently seemed attributable to poor performance of control mice. Tests of species-typical behaviors showed that Tg2576 mice had a deficit in burrowing behavior at all ages. An age-independent deficit was also seen in nest construction, but only when mice were group-housed; most individually housed mice in either group made reasonable nests. Overall, the results suggested that these Tg2576 mice are not a simple, suitable or reliable model for routine screening of treatments for Alzheimer's disease. However, this model might perform better behaviorally on a different genetic background.

Age and biostratigraphic significance of the Punung Rainforest Fauna, East Java, Indonesia, and implications for Pongo and Homo.

The Punung Fauna is a key component in the biostratigraphic sequence of Java. It represents the most significant faunal turnover on the island in the last 1.5 million years, when Stegodon and other archaic mammal species characteristic of earlier Faunal stages were replaced by a fully modern fauna that included rainforest-dependent species such as Pongo pygmaeus (orangutan). Here, we report the first numerical ages for the Punung Fauna obtained by luminescence and uranium-series dating of the fossil-bearing deposits and associated flowstones. The Punung Fauna contained in the dated breccia is of early Last Interglacial age (between 128+/-15 and 118+/-3 ka). This result has implications for the age of the preceding Ngandong Fauna, including Homo erectus remains found in the Ngandong Terrace, and for the timing of Homo sapiens arrival in Southeast Asia, in view of claims for a modern human tooth associated with the Punung breccia.

Further evidence for small-bodied hominins from the Late Pleistocene of Flores, Indonesia.

Homo floresiensis was recovered from Late Pleistocene deposits on the island of Flores in eastern Indonesia, but has the stature, limb proportions and endocranial volume of African Pliocene Australopithecus. The holotype of the species (LB1), excavated in 2003 from Liang Bua, consisted of a partial skeleton minus the arms. Here we describe additional H. floresiensis remains excavated from the cave in 2004. These include arm bones belonging to the holotype skeleton, a second adult mandible, and postcranial material from other individuals. We can now reconstruct the body proportions of H. floresiensis with some certainty. The finds further demonstrate that LB1 is not just an aberrant or pathological individual, but is representative of a long-term population that was present during the interval 95-74 to 12 thousand years ago. The excavation also yielded more evidence for the depositional history of the cave and for the behavioural capabilities of H. floresiensis, including the butchery of Stegodon and use of fire.

Archaeology and age of a new hominin from Flores in eastern Indonesia.

Excavations at Liang Bua, a large limestone cave on the island of Flores in eastern Indonesia, have yielded evidence for a population of tiny hominins, sufficiently distinct anatomically to be assigned to a new species, Homo floresiensis. The finds comprise the cranial and some post-cranial remains of one individual, as well as a premolar from another individual in older deposits. Here we describe their context, implications and the remaining archaeological uncertainties. Dating by radiocarbon (14C), luminescence, uranium-series and electron spin resonance (ESR) methods indicates that H. floresiensis existed from before 38,000 years ago (kyr) until at least 18 kyr. Associated deposits contain stone artefacts and animal remains, including Komodo dragon and an endemic, dwarfed species of Stegodon. H. floresiensis originated from an early dispersal of Homo erectus (including specimens referred to as Homo ergaster and Homo georgicus) that reached Flores, and then survived on this island refuge until relatively recently. It overlapped significantly in time with Homo sapiens in the region, but we do not know if or how the two species interacted.

Effect of insulin upon protein degradation in cultured human myocytes.

BACKGROUND: The anabolic effects of insulin are well recognized but the mechanism by which insulin decreases muscle protein degradation in human is unclear. However, in a variety of catabolic conditions it is believed to be changes in the activity of the ATP-dependent ubiquitin proteolytic pathway that are responsible for changes in protein degradation in skeletal muscle. The aim of this study was to test the hypothesis that insulin regulates the ATP-dependent ubiquitin proteolytic pathway in human muscle. MATERIAL AND METHODS: The effects of insulin and acidosis on protein degradation were measured in human myocytes using L-[14C]phenylalanine. The effect of insulin on the activity of the ATP-dependent ubiquitin pathway was assessed from the mRNA expression of ubiquitin and the ubiquitin-conjugating enzyme E214k in human myocytes. RESULTS AND CONCLUSIONS: Coincubation of human myocytes with 100 nM of insulin was associated with a significant reduction in protein degradation. Metabolic acidosis is known to increase skeletal muscle protein degradation rates, and in our experiments protein degradation at a pH of 7.0 was significantly higher than pH 7.35. Eight-hour exposure to 100 nM of insulin resulted in a significant reduction in the expression of E214k but no change in the expression of ubiquitin. CONCLUSIONS: In human muscle we have demonstrated regulation by insulin of the ATP-dependent ubiquitin pathway at the level of ubiquitin conjugation.

Relation between measurements of cough severity.

BACKGROUND: In asthma, measurements of airway inflammation correlate poorly with clinical markers and airway hyperresponsiveness. While the relation between determinants of asthma severity is known, that for cough is unknown. We hypothesised that cough sensitivity changes relate to changes in cough scores and objectively measured cough frequency. AIMS: To examine the relation between commonly used outcome measurements of cough severity in children. METHODS: The concentration of capsaicin causing two and five or more coughs (C2 and C5 respectively), cough frequency objectively measured using an ambulatory cough meter, and parent and child recorded subjective cough scores were determined in 40 children with recurrent cough on two occasions. RESULTS: On occasion one, log cough frequency significantly correlated with parent and child recorded log cough score (r(s) = 0.32, p = 0.05; and r(s) = 0.32, p = 0.046 respectively) and significantly negatively correlated with log C2 (r(s)= -0.5, p = 0.005). Subjective cough scores did not relate to either C2 or C5. On occasion two, the relation between cough frequency and C2 and C5 measures was lost, but C2 had a weak but significant relation to parent recorded cough score (r(s) = -0.38, p = 0.047). When the changes in the log values were determined, C5 but not C2 significantly related to cough frequency. CONCLUSION: In children, measures of cough sensitivity have a weak relation with cough frequency. Subjective cough scores have a stronger and consistent relation with cough frequency. These cough severity indices measure different aspects of cough. The choice of indices depends on the reason for performing the measurement.

Sodium bicarbonate treatment and ubiquitin gene expression in acidotic human subjects with chronic renal failure.

BACKGROUND: In chronic renal failure, metabolic acidosis is associated with increased whole body protein degradation. In rats this effect of acidosis occurs in skeletal muscle and is associated with increased ubiquitin mRNA expression. This has not been demonstrated in humans. MATERIALS AND METHODS: Six patients with chronic renal failure and acidosis underwent muscle biopsy before and after 1 month's treatment with sodium bicarbonate. RNA was extracted from the biopsy, and the expression of the genes for ubiquitin and the proteasome component, C2, were measured by Northern blotting. RESULTS AND CONCLUSIONS: There was no significant difference in the expression of ubiquitin or C2 after bicarbonate treatment. This is contrast with results from animal models of acidosis and some other catabolic conditions in humans. This may reflect the complexity of the ubiquitin-dependent pathway, and it may be that changes in ubiquitin expression are only seen with more severe and/or acute changes in pH.