The Gediz River fluvial archive: A benchmark for Quaternary research in Western Anatolia

The Gediz River, one of the principal rivers of Western Anatolia, has an extensive Pleistocene fluvial archive that potentially offers a unique window into fluvial system behaviour on the western margins of Asia during the Quaternary. In this paper we review our work on the Quaternary Gediz River Project (2001–2010) and present new data which leads to a revised stratigraphical model for the Early Pleistocene development of this fluvial system. In previous work we confirmed the preservation of eleven buried Early Pleistocene fluvial terraces of the Gediz River (designated GT11, the oldest and highest, to GT1, the youngest and lowest) which lie beneath the basalt-covered plateaux of the Kula Volcanic Province. Deciphering the information locked in this fluvial archive requires the construction of a robust geochronology. Fortunately, the Gediz archive provides ample opportunity for age-constraint based upon age estimates derived from basaltic lava flows that repeatedly entered the palaeo-Gediz valley floors. In this paper we present, for the first time, our complete dataset of 40Ar/39Ar age estimates and associated palaeomagnetic measurements. These data, which can be directly related to the underlying fluvial deposits, provide age constraints critical to our understanding of this sequence. The new chronology establishes the onset of Quaternary volcanism at ∼1320ka (MIS42). This volcanism, which is associated with GT6, confirms a pre-MIS42 age for terraces GT11-GT7. Evidence from the colluvial sequences directly overlying these early terraces suggests that they formed in response to hydrological and sediment budget changes forced by climate-driven vegetation change. The cyclic formation of terraces and their timing suggests they represent the obliquity-driven climate changes of the Early Pleistocene. By way of contrast the GT5-GT1 terrace sequence, constrained by a lava flow with an age estimate of ∼1247ka, span the time-interval MIS42 – MIS38 and therefore do not match the frequency of climate change as previously suggested. The onset of volcanism breaks the simple linkage of terracing to climate-driven change. These younger terraces more likely reflect a localized terracing process triggered by base level changes forced by volcanic eruptions and associated reactivation of pre-existing faults, lava dam construction, landsliding and subsequent lava-dammed lake drainage. Establishing a firm stratigraphy and geochronology for the Early Pleistocene archive provides a secure framework for future exploitation of this part of the archive and sets the standard as we begin our work on the Middle-Late Pleistocene sequence. We believe this work forms a benchmark study for detailed Quaternary research in Turkey

Drosophila Neurotrophins Reveal a Common Mechanism for Nervous System Formation

Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects.By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spa¨ tzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases

Imaging Findings Associated with Space-Occupying Edema in Patients with Large Middle Cerebral Artery Infarcts

on behalf of the DUST investigators ABSTRACT BACKGROUND AND PURPOSE: Prominent space-occupying cerebral edema is a devastating complication occurring in some but not all patients with large MCA infarcts. It is unclear why differences in the extent of edema exist. Better knowledge of factors related to prominent edema formation could aid treatment strategies. This study aimed to identify variables associated with the development of prominent edema in patients with large MCA infarcts

Mastermind Mutations Generate a Unique Constellation of Midline Cells within the Drosophila CNS

Background: The Notch pathway functions repeatedly during the development of the central nervous system in metazoan organisms to control cell fate and regulate cell proliferation and asymmetric cell divisions. Within the Drosophila midline cell lineage, which bisects the two symmetrical halves of the central nervous system, Notch is required for initial cell specification and subsequent differentiation of many midline lineages. Methodology/Principal Findings: Here, we provide the first description of the role of the Notch co-factor, mastermind, in the central nervous system midline of Drosophila. Overall, zygotic mastermind mutations cause an increase in midline cell number and decrease in midline cell diversity. Compared to mutations in other components of the Notch signaling pathway, such as Notch itself and Delta, zygotic mutations in mastermind cause the production of a unique constellation of midline cell types. The major difference is that midline glia form normally in zygotic mastermind mutants, but not in Notch and Delta mutants. Moreover, during late embryogenesis, extra anterior midline glia survive in zygotic mastermind mutants compared to wild type embryos. Conclusions/Significance: This is an example of a mutation in a signaling pathway cofactor producing a distinct centra

A Gain-of-Function Germline Mutation in Drosophila ras1 Affects Apoptosis and Cell Fate during Development

The RAS/MAPK signal transduction pathway is an intracellular signaling cascade that transmits environmental signals from activated receptor tyrosine kinases (RTKs) on the cell surface and other endomembranes to transcription factors in the nucleus, thereby linking extracellular stimuli to changes in gene expression. Largely as a consequence of its role in oncogenesis, RAS signaling has been the subject of intense research efforts for many years. More recently, it has been shown that milder perturbations in Ras signaling during embryogenesis also contribute to the etiology of a group of human diseases. Here we report the identification and characterization of the first gain-of-function germline mutation in Drosophila ras1 (ras85D), the Drosophila homolog of human K-ras, N-ras and H-ras. A single amino acid substitution (R68Q) in the highly conserved switch II region of Ras causes a defective protein with reduced intrinsic GTPase activity, but with normal sensitivity to GAP stimulation. The ras1R68Q mutant is homozygous viable but causes various developmental defects associated with elevated Ras signaling, including cell fate changes and ectopic survival of cells in the nervous system. These biochemical and functional properties are reminiscent of germline Ras mutants found in patients afflicted with Noonan, Costello or cardio-facio-cutaneous syndromes. Finally, we used ras1R68Q to identify novel genes that interact with Ras and suppress cell death

Pre-attentive processing in children with early and continuously-treated PKU. Effects of concurrent Phe level and lifetime dietary control

Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual’s responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure