Primary Succession on a Hawaiian Dryland Chronosequence

We used measurements from airborne imaging spectroscopy and LiDAR to quantify the biophysical structure and composition of vegetation on a dryland substrate age gradient in Hawaii. Both vertical stature and species composition changed during primary succession, and reveal a progressive increase in vertical stature on younger substrates followed by a collapse on Pleistocene-aged flows. Tall-stature Metrosideros polymorpha woodlands dominated on the youngest substrates (hundreds of years), and were replaced by the tall-stature endemic tree species Myoporum sandwicense and Sophora chrysophylla on intermediate-aged flows (thousands of years). The oldest substrates (tens of thousands of years) were dominated by the short-stature native shrub Dodonaea viscosa and endemic grass Eragrostis atropioides. We excavated 18 macroscopic charcoal fragments from Pleistocene-aged substrates. Mean radiocarbon age was 2,002 years and ranged from < 200 to 7,730. Genus identities from four fragments indicate that Osteomeles spp. or M. polymorpha once occupied the Pleistocene-aged substrates, but neither of these species is found there today. These findings indicate the existence of fires before humans are known to have occupied the Hawaiian archipelago, and demonstrate that a collapse in vertical stature is prevalent on the oldest substrates. This work contributes to our understanding of prehistoric fires in shaping the trajectory of primary succession in Hawaiian drylands.     

Regulation of Escherichia coli secA mRNA translation by a secretion-responsive element.

The Escherichia coli secA gene, whose translation is responsive to the proficiency of protein export within the cell, is the second gene in a three-gene operon and is flanked by gene X and mutT. By using gene fusion and oligonucleotide-directed mutagenesis techniques, we have localized this translationally regulated site to a region at the end of gene X and the beginning of secA. This region has been shown to bind SecA protein in vitro. These studies open the way for a direct investigation of the mechanism of secA regulation and its coupling to the protein secretion capability of the cell.     

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.     

Expression of a pepT homologue from Bacillus subtilis

Abstract We isolated pepT from Bacillus subtilis , a gene with homology to various tripeptidases from different bacterial sources, pepT is preceded by genes encoding a two component regulatory system. Its expression is activated during stationary phase. In minimal medium this activation is boosted in the presence of phosphate. The response regulator is preceded by putative promoter consensus sequences recognized by the stationary phase specific sigma factors σ ^H, σ ^F, and σ ^G. This is in accordance with the initiation of expression at the beginning of stationary phase. Inactivation of pepT causes no obvious phenotype.     

The Biophysical Properties of Basal Lamina Gels Depend on the Biochemical Composition of the Gel

The migration of cells within a three-dimensional extracellular matrix (ECM) depends sensitively on the biochemical and biophysical properties of the matrix. An example for a biological ECM is given by reconstituted basal lamina gels purified from the Engelbreth-Holm-Swarm sarcoma of mice. Here, we compare four different commercial variants of this ECM, which have all been purified according to the same protocol. Nevertheless, in those gels, we detect strong differences in the migration behavior of leukocyte cells as well as in the Brownian motion of nanoparticles. We show that these differences correlate with the mechanical properties and the microarchitecture of the gels which in turn arise from small variations in their biochemical composition.     

Automatic Detection of Attention Shifts in Infancy: Eye Tracking in the Fixation Shift Paradigm

This study measured changes in switches of attention between 1 and 9 months of age in 67 typically developing infants. Remote eye-tracking (Tobii X120) was used to measure saccadic latencies, related to switches of fixation, as a measure of shifts of attention, from a central stimulus to a peripheral visual target, measured in the Fixation Shift Paradigm. Fixation shifts occur later if the central fixation stimulus stays visible when the peripheral target appears (competition condition), than if the central stimulus disappears as the peripheral target appears (non-competition condition). This difference decreases with age. Our results show significantly faster disengagement in infants over 4 months than in the younger group, and provide more precise measures of fixation shifts, than behavioural observation with the same paradigm. Reduced saccadic latencies in the course of a test session indicate a novel learning effect. The Fixation Shift Paradigm combined with remote eye-tracking measures showed improved temporal and spatial accuracy compared to direct observation by a trained observer, and allowed an increased number of trials in a short testing time. This makes it an infant-friendly non-invasive procedure, involving minimal observational training, suitable for use in future studies of clinical populations to detect early attentional abnormalities in the first few months of life.     

SecA proteins of Bacillus subtilis and Escherichia coli possess homologous amino-terminal ATP-binding domains regulating integration into the plasma membrane.

The Bacillus subtilis secA homolog, div, was cloned and expressed at a variety of different levels in wild-type and secA mutant strains of Escherichia coli. Analysis of Div function showed that it could not substitute for SecA despite being present at a wide range of concentrations at or above the physiological level. Location of regions of functional similarity between the two proteins using div-secA chimeras revealed that only the amino-terminal ATP-binding domain of Div could functionally substitute for the corresponding region of SecA. The role of this domain was revealed by subcellular localization experiments that demonstrated that in both B. subtilis and E. coli Div had cytoplasmic, peripheral, and integral membrane distributions similar to those of its SecA homolog and that an intact ATP-binding domain was essential for regulating integration of this protein into the plasma membrane. These results suggest strongly that the previously observed cycle of membrane binding, insertion, and deinsertion of SecA protein (A. Economou and W. Wickner, Cell 78:835-843, 1994) is common to these two bacteria, and they demonstrate the importance of the conserved ATP-binding domain in promoting this cycle.     

Neuronal Basis of Innate Olfactory Attraction to Ethanol in Drosophila

The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine – the invertebrate analogue of noradrenaline – in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b). Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse), the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.     

Stabilizing ER Ca2+ Channel Function as an Early Preventative Strategy for Alzheimer’s Disease

Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca²⁺ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca²⁺ signaling, predominantly through the ER-localized inositol triphosphate (IP₃) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca²⁺ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca²⁺ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca²⁺ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca²⁺ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients.