Identifying control ensembles for information processing within the cortico-basal ganglia-thalamic circuit

In situations featuring uncertainty about action-reward contingencies, mammals can flexibly adopt strategies for decision-making that are tuned in response to environmental changes. Although the cortico-basal ganglia thalamic (CBGT) network has been identified as contributing to the decision-making process, it features a complex synaptic architecture, comprised of multiple feed-forward, reciprocal, and feedback pathways, that complicate efforts to elucidate the roles of specific CBGT populations in the process by which evidence is accumulated and influences behavior. In this paper we apply a strategic sampling approach, based on Latin hypercube sampling, to explore how variations in CBGT network properties, including subpopulation firing rates and synaptic weights, map to variability of parameters in a normative drift diffusion model (DDM), representing algorithmic aspects of information processing during decision-making. Through the application of canonical correlation analysis, we find that this relationship can be characterized in terms of three low-dimensional control ensembles within the CBGT network that impact specific qualities of the emergent decision policy: responsiveness (a measure of how quickly evidence evaluation gets underway, associated with overall activity in corticothalamic and direct pathways), pliancy (a measure of the standard of evidence needed to commit to a decision, associated largely with overall activity in components of the indirect pathway of the basal ganglia), and choice (a measure of commitment toward one available option, associated with differences in direct and indirect pathways across action channels). These analyses provide mechanistic predictions about the roles of specific CBGT network elements in tuning the way that information is accumulated and translated into decision-related behavior.     

Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity

FMRFamide (Phe-Met-Arg-Phe-amide, FMRFa) and similar neuropeptides are important physiological modulators in most invertebrates, but the molecular basis of FMRFa activity at its receptors is unknown. We therefore sought to identify the molecular determinants of FMRFa potency against one of its native targets, the excitatory FMRFa-gated sodium channel (FaNaC) from gastropod mollusks. Using molecular phylogenetics and electrophysiological measurement of neuropeptide activity, we identified a broad FaNaC family that includes mollusk and annelid channels gated by FMRFa, FVRIamides, and/or Wamides (or myoinhibitory peptides). A comparative analysis of this broader FaNaC family and other channels from the overarching degenerin (DEG)/epithelial sodium channel (ENaC) superfamily, incorporating mutagenesis and experimental dissection of channel function, identified a pocket of amino acid residues that determines activation of FaNaCs by neuropeptides. Although this pocket has diverged in distantly related DEG/ENaC channels that are activated by other ligands but enhanced by FMRFa, such as mammalian acid-sensing ion channels, we show that it nonetheless contains residues that determine enhancement of those channels by similar peptides. This study thus identifies amino acid residues that determine FMRFa neuropeptide activity at FaNaC receptor channels and illuminates the evolution of ligand recognition in one branch of the DEG/ENaC superfamily of ion channels.     

Modulation of inducible nitric oxide synthase (iNOS) expression and cardiovascular responses during static exercise following iNOS antagonism within the ventrolateral medulla

Previous reports indicate that inducible nitric oxide synthase (iNOS) blockade within the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) differentially modulated cardiovascular responses, medullary glutamate, and GABA concentrations during static skeletal muscle contraction. In the current study, we determined the role of iNOS antagonism within the RVLM and CVLM on cardiovascular responses and iNOS protein expression during the exercise pressor reflex in anesthetized rats. Following 120 min of bilateral microdialysis of a selective iNOS antagonist, aminoguanidine (AGN; 10 µM), into the RVLM, the pressor responses were attenuated by 72 % and changes in heart rate were reduced by 38 % during a static muscle contraction. Furthermore, western blot analysis of iNOS protein abundance within the RVLM revealed a significant attenuation when compared to control animals. In contrast, bilateral administration of AGN (10 µM) into the CVLM augmented the increases in mean arterial pressure by 60 % and potentiated changes in heart rate by 61 % during muscle contractions, but did not alter expression of the iNOS protein within the CVLM. These results demonstrate that iNOS protein expression within the ventrolateral medulla is differentially regulated by iNOS blockade that may, in part, contribute to the modulation of cardiovascular responses during static exercise.     

Organic matter and nitrogen accumulation and nitrogen fixation during early ecosystem development in Hawaii

We used a chronosequence comprised of 10 y, 52 y and 142 yold `a'a lava flows on Mauna Loa, Hawaii, to determine theaccumulation of organic matter and nitrogen and rates of nitrogenfixation through time. The mass of organic matter (live and deadbiomass and soil organic matter) on the 1984, 1942 and 1852 lavaflows was 0.6, 2.2 and 7.6 kg m^{– 2}, respectively, while total N was 4.8, 10.9 and 85.7 g m^{– 2}.We estimated the total rates of nitrogen fixation for thethree different aged ecosystems using an acetylene reduction assaycalibrated with ¹⁵N incubations. While mean rates of total N fixation remained largely constant across the three sites – between2.0 and 3.1 kg ha^{– 1} y^{– 1} – the most important sources of N fixation changed. On the 10 y flow, the most important fixer was the pioneering cyanolichen, Stereocaulon vulcani. After 52 years ofecosystem development, the most important N fixer was a cyanoalga,while after 142 years, the predominant N fixers were heterotrophicbacteria associated with leaf litter, twigs and detritus. The totalamount of N accumulated after 52 years of ecosystem development wasequivalent to cumulative inputs through biological N fixation. After 142 years, however, cumulative inputs from N fixation couldonly account for between 27–59% of the total nitrogen accrued.We used fertilizer additions of all essential nutrients otherthan N to test whether the availability of lithophilic nutrientsregulated rates of N fixation in early ecosystem development. Ratesof nitrogen fixation by the lichen, S. vulcani, approximately doubled when fertilized on the 1984 and 1942 flows. Rates of N-fixation by heterotrophic nitrogen fixing bacteria on leaf litter ofMetrosideros polymorpha also increased significantly when fertilized with lithophilic nutrients. These findings suggest that weathering rates of lava in part regulate rates of nitrogen fixation in these young ecosystems.     

Scale‐dependent spatial patterns in benthic communities around a tropical island seascape

Understanding and predicting patterns of spatial organization across ecological communities is central to the field of landscape ecology, and a similar line of inquiry has begun to evolve sub‐tidally among seascape ecologists. Much of our current understanding of the processes driving marine community patterns, particularly in the tropics, has come from small‐scale, spatially‐discrete data that are often not representative of the broader seascape. Here we expand the spatial extent of seascape ecology studies and combine spatially‐expansive in situ digital imagery, oceanographic measurements, spatial statistics, and predictive modeling to test whether predictable patterns emerge between coral reef benthic competitors across scales in response to intra‐island gradients in physical drivers. We do this around the entire circumference of a remote, uninhabited island in the central Pacific (Jarvis Island) that lacks the confounding effects of direct human impacts. We show, for the first time, that competing benthic groups demonstrate predictable scaling patterns of organization, with positive autocorrelation in the cover of each group at scales < ~1 km. Moreover, we show how gradients in subsurface temperature and surface wave power drive spatially‐abrupt transition points in group dominance, explaining 48–84% of the overall variation in benthic cover around the island. Along the western coast, we documented ten times more sub‐surface cooling‐hours than any other part of the coastline, with events typically resulting in a drop of 1–4°C over a period of < 5 h. These high frequency temperature fluctuations are indicative of upwelling induced by internal waves and here result in localized nitrogen enrichment (NO₂ + NO₃) that promotes hard coral dominance around 44% of the island's perimeter. Our findings show that, in the absence of confounding direct human impacts, the spatial organization of coral reef benthic competitors are predictable and somewhat bounded across the seascape by concurrent gradients in physical drivers.     

The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2

Using an interspecies backcross, we have mapped the HOX-5 and surfeit (surf) gene clusters within the proximal portion of mouse chromosome 2. While the HOX-5 cluster of homeobox-containing genes has been localized to chromosome 2, bands C3-E1, by in situ hybridization, its more precise position relative to the genes and cloned markers of chromosome 2 was not known. Surfeit, a tight cluster of at least six highly conserved “housekeeping” genes, has not been previously mapped in mouse, but has been localized to human chromosome 9q, a region of the human genome with strong homology to proximal mouse chromosome 2. The data presented here place HOX-5 in the vicinity of the closely linked set of developmental mutations rachiterata, lethargic, and fidget and place surf close to the proto-oncogene Abl, near the centromere of chromosome 2.     

Knockdown of a laccase in Populus deltoides confers altered cell wall chemistry and increased sugar release

Plant laccases are thought to function in the oxidation of monolignols which leads to higher order lignin formation. Only a hand‐full of laccases in plants have been functionally evaluated, and as such little is known about the breadth of their impact on cell wall chemistry or structure. Here, we describe a previously uncharacterized laccase from Populus, encoded by locus Potri.008G064000, whose reduced expression resulted in transgenic Populus trees with changes in syringyl/guaiacyl ratios as well as altered sugar release phenotypes. These phenotypes are consistent with plant biomass exhibiting reduced recalcitrance. Interestingly, the transgene effect on recalcitrance is dependent on a mild pretreatment prior to chemical extraction of sugars. Metabolite profiling suggests the transgene modulates phenolics that are associated with the cell wall structure. We propose that this particular laccase has a range of functions related to oxidation of phenolics and conjugation of flavonoids that interact with lignin in the cell wall.     

Selective antibacterial activity of the cationic peptide PaDBS1R6 against Gram-negative bacteria

Infections caused by Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa foremost among them, constitute a major worldwide health problem. Bioinformatics methodologies are being used to rationally design new antimicrobial peptides, a potential alternative for treating these infections. One of the algorithms used to develop antimicrobial peptides is the Joker, which was used to design the peptide PaDBS1R6. This study evaluates the antibacterial activities of PaDBS1R6 in vitro and in vivo, characterizes the peptide interaction to target membranes, and investigates the PaDBS1R6 structure in contact with mimetic vesicles. Moreover, we demonstrate that PaDBS1R6 exhibits selective antimicrobial activity against Gram-negative bacteria. In the presence of negatively charged and zwitterionic lipids the structural arrangement of PaDBS1R6 transits from random coil to α-helix, as characterized by circular dichroism. The tertiary structure of PaDBS1R6 was determined by NMR in zwitterionic dodecylphosphocholine (DPC) micelles. In conclusion, PaDBS1R6 is a candidate for the treatment of nosocomial infections caused by Gram-negative bacteria, as template for producing other antimicrobial agents.     

Xylem cavitation vulnerability influences tree species’ habitat preferences in miombo woodlands

Although precipitation plays a central role in structuring Africa’s miombo woodlands, remarkably little is known about plant-water relations in this seasonally dry tropical forest. Therefore, in this study, we investigated xylem vulnerability to cavitation for nine principal tree species of miombo woodlands, which differ in habitat preference and leaf phenology. We measured cavitation vulnerability (Ψ₅₀), stem-area specific hydraulic conductivity (K _S), leaf specific conductivity (K _L), seasonal variation in predawn water potential (Ψ_PD) and xylem anatomical properties [mean vessel diameter, mean hydraulic diameter, mean hydraulic diameter accounting for 95 % flow, and maximum vessel length (V _L)]. Results show that tree species with a narrow habitat range (mesic specialists) were more vulnerable to cavitation than species with a wide habitat range (generalists). Ψ₅₀ for mesic specialists ranged between ?1.5 and ?2.2 MPa and that for generalists between ?2.5 and ?3.6 MPa. While mesic specialists exhibited the lowest seasonal variation in Ψ_PD, generalists displayed significant seasonal variations in Ψ_PD suggesting that the two miombo habitat groups differ in their rooting depth. We observed a strong trade-off between K _S and Ψ₅₀ suggesting that tree hydraulic architecture is one of the decisive factors setting ecological boundaries for principal miombo species. While vessel diameters correlated weakly (P > 0.05) with Ψ₅₀, V _L was positively and significantly correlated with Ψ₅₀. Ψ_PD was significantly correlated with Ψ₅₀ further reinforcing the conclusion that tree hydraulic architecture plays a significant role in species’ habitat preference in miombo woodlands.