A Unified Approach to Linking Experimental,Statistical and Computational Analysis of Spike Train Data

A fundamental issue in neuroscience is how to identify the multiple biophysical mechanisms through which neurons generate observed patterns of spiking activity. In previous work, we proposed a method for linking observed patterns of spiking activity to specific biophysical mechanisms based on a state space modeling framework and a sequential Monte Carlo, or particle filter, estimation algorithm. We have shown, in simulation, that this approach is able to identify a space of simple biophysical models that were consistent with observed spiking data (and included the model that generated the data), but have yet to demonstrate the application of the method to identify realistic currents from real spike train data. Here, we apply the particle filter to spiking data recorded from rat layer V cortical neurons, and correctly identify the dynamics of an slow, intrinsic current. The underlying intrinsic current is successfully identified in four distinct neurons, even though the cells exhibit two distinct classes of spiking activity: regular spiking and bursting. This approach – linking statistical, computational, and experimental neuroscience – provides an effective technique to constrain detailed biophysical models to specific mechanisms consistent with observed spike train data.     

Impact fact-or fiction?

The Journal Impact Factor dominates research assessment in many disciplines and in many countries. While research assessment will always have to rely to some extent on quantitative, standardized metrics, the focus on this single measure has gone so far as to hamper and distort scientific research. The Declaration on Research Assessment (DORA), signed by influential journals, funders, academic institutions and individuals across the natural sciences, aims to raise awareness and to redress the use of non‐objective research assessment practices.     

Interindividual variability and intraindividual reaction stability of bioelectric muscular tension of the long finger flexor in model exercise]

Twelve untrained subjects had to perform opening and closing movements of the hand (2 mm-sec(-1) on a hand ergometer. The load was 2kp for woman and 5 kp for man. Two sequences of the test were carried out, one after the other. The EMG was derived unipolarly from the belly of the Mm. flex. digit, and the mean bioelectrical muscle activity was measured. The following factors were tested in each subject by means of an analysis of variance. Factor A -- phase of exercise, Factor B --repetition of exercise and Factor C -- type of sequence. The analysis of the stability of individual reactions was made through serial correlations. Factor A influenced the mean bioelectrical muscle activity in all subjects while Factors B and C had an influence only in some cases. A significant interaction effect between pairs of factors occurred only in a few subjects. The serial correlation coefficients for Factor A of the same composition is between 0.40 and 0.80. The values of the mean correlation functions for the two sequences of Factor C, C(I) and C(II), are 0.69 and 0.68 respectively. In each subject the range of the cross correlation coefficients of the sequences C(I) and C(II) was between 0.70 and 0.92. Possible causes for the varying experimental results were discussed.     

Renal microvasculature in the adult pipid frog,Xenopus laevis: A scanning electron microscope study of vascular corrosion casts

We studied the opisthonephric (mesonephric) kidneys of adult male and female Xenopus laevis using scanning electron microscopy (SEM) of vascular corrosion casts and light microscopy of paraplast embedded tissue sections. Both techniques displayed glomeruli from ventral to mid-dorsal regions of the kidneys with single glomeruli located dorsally close beneath the renal capsule. Glomeruli in general were fed by a single afferent arteriole and drained via a single thinner efferent arteriole into peritubular vessels. Light microscopy and SEM of vascular corrosion casts revealed sphincters at the origins of afferent arterioles, which arose closely, spaced from their parent renal arteries. The second source of renal blood supply via renal portal veins varied interindividually in branching patterns with vessels showing up to five branching orders before they became peritubular vessels. Main trunks and their first- and second-order branches revealed clear longish endothelial cell nuclei imprint patterns oriented parallel to the vessels longitudinal axis, a pattern characteristic for arteries. Peritubular vessels had irregular contours and were never seen as clear cylindrical structures. They ran rather parallel, anastomosed with neighbors and changed into renal venules and veins, which finally emptied into the ventrally located posterior caval vein. A third source of blood supply of the peritubular vessels by straight terminal portions of renal arteries (vasa recta) was not found.     

When is a native species invasive? Incursion of a novel predatory marsupial detected using molecular and historical data

Aim

Range expansions facilitated by humans or in response to local biotic or abiotic stressors provide the opportunity for species to occupy novel environments. Classifying the status of newly expanded populations can be difficult, particularly when the timing and nature of the range expansion are unclear. Should native species in new habitats be considered invasive pests or actively conserved? Here, we present an analytical framework applied to an Australian marsupial, the sugar glider (Petaurus breviceps), a species that preys upon on an endangered parrot in Tasmania, and whose provenance was uncertain.

Location

Tasmania, Australia.

Methods

We conducted an extensive search of historical records for sugar glider occurrences in Tasmania. Source material included museum collection data, early European expedition logs, community observation records, and peer‐reviewed and grey literature. To determine the provenance of the Tasmanian population, we sequenced two mitochondrial genes and one nuclear gene in Tasmanian animals (n = 27) and in individuals across the species' native range. We then estimated divergence times between Tasmania and southern Australian populations using phylogenetic and Bayesian analyses.

Results

We found no historical evidence of sugar gliders occurring in Tasmania prior to 1835. All Tasmanian individuals (n = 27) were genetically identical at the three genes surveyed here with those individuals being 0.125% divergent from individuals from a population in Victoria. Bayesian analysis of divergence between Tasmanian individuals and southern Australian individuals suggested a recent introduction of sugar gliders into Tasmania from southern Australia.

Main conclusions

Molecular and historical data demonstrate that Tasmanian sugar gliders are a recent, post‐European, anthropogenic introduction from mainland Victoria. This result has implications for the management of the species in relation to their impact on an endangered parrot. The analytical framework outlined here can assist environmental managers with the complex task of assessing the status of recently expanded or introduced native species.

     

A proposal to use plant demographic data to assess potential weed biological control agents impacts on non-target plant populations

Weed biocontrol programs aim to reduce the spread and population growth rate of the target plant while stabilizing or increasing populations of those native species considered under threat by invasive plants. This goal is not unique to weed biocontrol but applies to all other invasive plant management techniques, though such information is rarely collected. Without this information, success of management interventions can be ambiguous, and regulatory agencies, the public, policy makers, funders and land managers cannot be held accountable for chosen treatments. A fundamental reform, including use of demographic studies and long-term assessments, are essential to guide weed biocontrol programs. We propose to add use of plant demography (an assessment of how environmental factors and ecological interactions, for example competition, disease or herbivory, may affect plant populations by altering survival, growth, development and reproductive rates of plant individuals) during host specificity risk assessments of potential biological control agents. Demographic models can refine assessments of potential impacts for those plant species that experience some feeding or larval development during host specificity testing. Our proposed approach to focus on impact on plant demography instead of attack on plant individuals is useful in appropriately gauging threats potential weed biocontrol agents may pose to non-target species after field release.     

Cardiolipin synthases of Escherichia coli have phospholipid class specific phospholipase D activity dependent on endogenous and foreign phospholipids

E. coli has three Cls-isoenzymes for cardiolipin (CL) synthesis but the differences between these three enzymes remain unresolved. All three Cls enzymes contain the phospholipase D (PLD) characteristic HKD motive and synthesize CL using PLD activity. Here, using LC-MS we show the effect of overexpressing or deletion of the three individual Cls enzymes on the lipidome, which included changes in lipid class distribution and CL species profiles. We demonstrate, for the first time, that overexpression of only ClsB resulted in the appreciable synthesis of a variety of phosphatidylalcohols, thereby establishing a ‘classic’ PLD activity for this enzyme: phospholipid headgroup exchange. Endogenous E. coli lipids and primary alcohols were substrates for this trans-phosphatidylation reaction. Furthermore, we show that endogenous levels of ClsA mediated a similar trans-phosphatidylation reaction to form phosphatidylalcohols, however this reaction was dependent on the presence of the foreign phospholipid class phosphatidylcholine (PC). This allows us to clarify the different specificities of the cardiolipin synthases.     

Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis

1. Download high-res image (160KB)
2. Download full-size image

     

Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses

Introduction

Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations.

Objectives

To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker’s yeast Saccharomyces cerevisiae were isolated and subjected to metabolic profiling.

Methods

Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography–mass spectrometry (GC–MS) based metabolic profiling.

Results

Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the F_OF₁-ATP-synthase (complex V) can be discriminated in both compartments by principal component analysis from wild-type and each other. These mitochondrial oxidative phosphorylation machinery mutants altered not only citric acid cycle related metabolites but also amino acids, fatty acids, purine and pyrimidine intermediates and others.

Conclusion

By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism.