Testing single aliquot regenerative dose (SAR) protocols for violet stimulated luminescence

Basic assumptions of the single aliquot regenerative dose (SAR) protocol are tested using the violet stimulated luminescence (VSL) signal from quartz. The VSL signal is shown to be reduced to a sufficiently low background level between SAR steps, and the SAR protocol appears to adequately correct for sensitivity changes during measurement. The VSL SAR protocol can recover a large (405 Gy) laboratory beta dose within uncertainties, however the mean value for the dose recovery ratio is commonly 0.8 or less. This poor behaviour is echoed in the measurements of equivalent dose (De) for a sample with an expected De of ∼354 Gy, which underestimates De by 50–70%. Further investigations are required to understand the mechanisms underlying these underestimations in VSL SAR De values

Design of (ω-N-(O-acyl)hydroxy amid) aminodicarboxylic acid pyrrolidides as potent inhibitors of proline-specific peptidases

AbstractA novel class of competitive, acylating inhibitors for the proline-specific peptidases: dipeptidyl peptidase IV, dipeptidyl peptidase II and prolyl endopeptidase, has been developed. The inhibitor molecules combine the efficacy of aminoacyl pyrrolidides and the potential transacylating capability of diacyl hydroxyl amines. The N-terminal deblocked inhibitors are potent reversible inhibitors of porcine kidney dipeptidyl peptidase IV, human placenta dipeptidyl peptidase II exhibiting K1 values in the μM range. Boc-protected (ω-N-hydroxy acyl amid) aminodiacarboxylic acid pyrrolidides inhibit substrate hydrolysis by prolyl endopeptidases from different sources competitively reaching K, values of 30 nM to 60 μM. Additionally, α-N-BOC-(ω-N-hydroxy acetyl) glutaminyl pyrrolidide modifies human placenta prolyl endopeptidase in a time-dependent reaction

Using multiple chronometers to establish a long, directly-dated lacustrine record:Constraining >600,000 years of environmental change at Chew Bahir, Ethiopia

Despite eastern Africa being a key location in the emergence of Homo sapiens and their subsequent dispersal out of Africa, there is a paucity of long, well-dated climate records in the region to contextualize this history. To address this issue, we dated a ∼293 m long composite sediment core from Chew Bahir, south Ethiopia, using three independent chronometers (radiocarbon, 40Ar/39Ar, and optically stimulated luminescence) combined with geochemical correlation to a known-age tephra. The site is located in a climatically sensitive region, and is close to Omo Kibish, the earliest documented Homo sapiens fossil site in eastern Africa, and to the proposed dispersal routes for H. sapiens out of Africa. The 30 ages generated by the various techniques are internally consistent, stratigraphically coherent, and span the full range of the core depth. A Bayesian age-depth model developed using these ages results in a chronology that forms one of the longest independently dated, high-resolution lacustrine sediment records from eastern Africa. The chronology illustrates that any record of environmental change preserved in the composite sediment core from Chew Bahir would span the entire timescale of modern human evolution and dispersal, encompassing the time period of the transition from Acheulean to Middle Stone Age (MSA), and subsequently to Later Stone Age (LSA) technology, making the core well-placed to address questions regarding environmental change and hominin evolutionary adaptation. The benefits to such studies of direct dating and the use of multiple independent chronometers are discussed. Highlights • Four independent dating methods applied to ∼293 m lake core from southern Ethiopia. • Reveals 620 ka high-resolution sedimentary record near key fossil hominin sites. • Mean accumulation rate of 0.47 mm/a comparable to other African lacustrine sediments. • Accumulation rate fell to 0.1 mm/a during MIS 2, likely due to reduced sediment supply. • Use of multiple independent chronometers is a powerful approach in lake settings

Hydroclimate changes in eastern Africa over the past 200,000 years may have influenced early human dispersal

Abstract: Reconstructions of climatic and environmental conditions can contribute to current debates about the factors that influenced early human dispersal within and beyond Africa. Here we analyse a 200,000-year multi-proxy paleoclimate record from Chew Bahir, a tectonic lake basin in the southern Ethiopian rift. Our record reveals two modes of climate change, both associated temporally and regionally with a specific type of human behavior. The first is a long-term trend towards greater aridity between 200,000 and 60,000 years ago, modulated by precession-driven wet-dry cycles. Here, more favorable wetter environmental conditions may have facilitated long-range human expansion into new territory, while less favorable dry periods may have led to spatial constriction and isolation of local human populations. The second mode of climate change observed since 60,000 years ago mimics millennial to centennial-scale Dansgaard-Oeschger cycles and Heinrich events. We hypothesize that human populations may have responded to these shorter climate fluctuations with local dispersal between montane and lowland habitats

Pleistocene climate variability in eastern Africa influenced hominin evolution

AbstractDespite more than half a century of hominin fossil discoveries in eastern Africa, the regional environmental context of hominin evolution and dispersal is not well established due to the lack of continuous palaeoenvironmental records from one of the proven habitats of early human populations, particularly for the Pleistocene epoch. Here we present a 620,000-year environmental record from Chew Bahir, southern Ethiopia, which is proximal to key fossil sites. Our record documents the potential influence of different episodes of climatic variability on hominin biological and cultural transformation. The appearance of high anatomical diversity in hominin groups coincides with long-lasting and relatively stable humid conditions from ~620,000 to 275,000 years bp (episodes 1–6), interrupted by several abrupt and extreme hydroclimate perturbations. A pattern of pronounced climatic cyclicity transformed habitats during episodes 7–9 (~275,000–60,000 years bp), a crucial phase encompassing the gradual transition from Acheulean to Middle Stone Age technologies, the emergence of Homo sapiens in eastern Africa and key human social and cultural innovations. Those accumulative innovations plus the alignment of humid pulses between northeastern Africa and the eastern Mediterranean during high-frequency climate oscillations of episodes 10–12 (~60,000–10,000 years bp) could have facilitated the global dispersal of H. sapiens.</jats:p

Type-specific dendritic integration in mouse retinal ganglion cells

Neural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, it is far from understood how different cell types tune this process to establish cell-type specific computations. Here, using two-photon imaging of dendritic Ca2+ signals, electrical recordings of somatic voltage and biophysical modelling, we demonstrate that four morphologically distinct types of mouse retinal ganglion cells with overlapping excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-mini Off) exhibit type-specific dendritic integration profiles: in contrast to the other types, dendrites of transient Off alpha cells were spatially independent, with little receptive field overlap. The temporal correlation of dendritic signals varied also extensively, with the highest and lowest correlation in transient Off mini and transient Off alpha cells, respectively. We show that differences between cell types can likely be explained by differences in backpropagation efficiency, arising from the specific combinations of dendritic morphology and ion channel densities

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.