Publications by authors named "Michael Bowler"

21 Publications

  • Page 1 of 1

Berlin Excor Cannulation of Left Atrial Appendage in Left Ventricular Restrictive Physiology: A Novel Bailout Strategy.

ASAIO J 2020 Dec 18;Publish Ahead of Print. Epub 2020 Dec 18.

From the Divisions of Pediatric Cardiovascular Surgery Pediatric Cardiology Pediatric Critical Care, Masonic Children's Hospital, University of Minnesota, Minneapolis, Minnesota.

Ventricular assist device (VAD) management continues to be a challenge in the presence of restrictive physiology. Left atrial (LA) decompression is not satisfactory even with good function and position of the left ventricular cannula. We describe an alternate approach with LA cannulation via the left atrial appendage (LAA) as a rescue strategy in a patient who had restrictive physiology, in our case was secondary to viral myocarditis acute systolic heart failure with subsequent insidious diffuse endomyocardial fibrosis and superimposed massive calcification, causing inadequate emptying of the left ventricle despite optimal VAD apical cannula position.
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http://dx.doi.org/10.1097/MAT.0000000000001330DOI Listing
December 2020

Ensembles of Atoms, Ensembles of Species: Comparative Statistical Mechanics.

Authors:
Michael G Bowler

Entropy (Basel) 2020 May 30;22(6). Epub 2020 May 30.

Department of Physics, University of Oxford, Keble Road, Oxford OX1 3RH, UK.

The methods of statistical physics are exemplified in the classical perfect gas-each atom is a single dynamical entity. Such methods can be applied in ecology to the distribution of cosmopolitan species over many sites. The analogue of an atom is a class of species distinguished by the number of sites at which it occurs, hardly a material entity; yet, the methods of statistical physics nonetheless seem applicable. This paper compares the application of statistical mechanics to the distribution of atoms and to the vastly different problem of distribution of cosmopolitan species. A number of different approaches show that these distributed entities must be in some sense equivalent; the dynamics must be controlled by interaction between species and the global environment rather than between species and many uncorrelated local environments.
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http://dx.doi.org/10.3390/e22060610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517146PMC
May 2020

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model.

Transl Stroke Res 2020 08 6;11(4):776-788. Epub 2019 Dec 6.

Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA.

Magnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale (mRS) and were significantly correlated with 52 measured acute (day 1 post) and chronic (day 84 post) gait and behavior impairments in non-treated stroked animals. These results suggest that MLS may be an important non-invasive biomarker that can be used to predict patient outcomes and prognosis as well as guide therapeutic intervention and rehabilitation in non-treated animals and potentially human patients that do not receive interventional treatments. Neural stem cell-derived extracellular vesicle (NSC EV) was a disruptive therapy because NSC EV administration post-stroke disrupted MLS correlations observed in non-treated stroked animals. MLS was not associated with survival and functional outcomes in NSC EV-treated animals. In contrast to untreated animals, NSC EVs improved stroked animal outcomes regardless of MLS severity.
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http://dx.doi.org/10.1007/s12975-019-00753-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340639PMC
August 2020

Extracellular Vesicles Mediate Neuroprotection and Functional Recovery after Traumatic Brain Injury.

J Neurotrauma 2020 06 10;37(11):1358-1369. Epub 2020 Feb 10.

Regenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.

The lack of effective therapies for moderate-to-severe traumatic brain injuries (TBIs) leaves patients with lifelong disabilities. Neural stem cells (NSCs) have demonstrated great promise for neural repair and regeneration. However, direct evidence to support their use as a cell replacement therapy for neural injuries is currently lacking. We hypothesized that NSC-derived extracellular vesicles (NSC EVs) mediate repair indirectly after TBI by enhancing neuroprotection and therapeutic efficacy of endogenous NSCs. We evaluated the short-term effects of acute intravenous injections of NSC EVs immediately following a rat TBI. Male NSC EV-treated rats demonstrated significantly reduced lesion sizes, enhanced presence of endogenous NSCs, and attenuated motor function impairments 4 weeks post-TBI, when compared with vehicle- and TBI-only male controls. Although statistically not significant, we observed a therapeutic effect of NSC EVs on brain lesion volume, nestin expression, and behavioral recovery in female subjects. Our study demonstrates the neuroprotective and functional benefits of NSC EVs for treating TBI and points to gender-dependent effects on treatment outcomes, which requires further investigation.
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http://dx.doi.org/10.1089/neu.2019.6443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249471PMC
June 2020

Endemics and Cosmopolitans: Application of Statistical Mechanics to the Dry Forests of Mexico.

Entropy (Basel) 2019 Jun 22;21(6). Epub 2019 Jun 22.

Department of Integrative Biology, University of South Florida, Tampa, FL 33620, USA.

Data on the seasonally dry tropical forests of Mexico have been examined in the light of statistical mechanics. The results suggest a division into two classes of species. There are drifting populations of a cosmopolitan class capable of existing in most dry forest sites; these have a statistical distribution previously only observed (globally) for populations of alien species. We infer that a high proportion of species found only at a single site are specialists, endemics, and that these prefer sites comparatively low in species richness.
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http://dx.doi.org/10.3390/e21060616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515108PMC
June 2019

Raoult's law revisited: accurately predicting equilibrium relative humidity points for humidity control experiments.

J Appl Crystallogr 2017 Apr 29;50(Pt 2):631-638. Epub 2017 Mar 29.

European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, CS 90181, Grenoble F-38042, France; Unit for Virus Host Cell Interactions, Université Grenoble Alpes-EMBL-CNRS, 71 avenue des Martyrs, CS 90181, Grenoble F-38042, France.

The humidity surrounding a sample is an important variable in scientific experiments. Biological samples in particular require not just a humid atmosphere but often a relative humidity (RH) that is in equilibrium with a stabilizing solution required to maintain the sample in the same state during measurements. The controlled dehydration of macromolecular crystals can lead to significant increases in crystal order, leading to higher diffraction quality. Devices that can accurately control the humidity surrounding crystals while monitoring diffraction have led to this technique being increasingly adopted, as the experiments become easier and more reproducible. Matching the RH to the mother liquor is the first step in allowing the stable mounting of a crystal. In previous work [Wheeler, Russi, Bowler & Bowler (2012). F, 111-114], the equilibrium RHs were measured for a range of concentrations of the most commonly used precipitants in macromolecular crystallography and it was shown how these related to Raoult's law for the equilibrium vapour pressure of water above a solution. However, a discrepancy between the measured values and those predicted by theory could not be explained. Here, a more precise humidity control device has been used to determine equilibrium RH points. The new results are in agreement with Raoult's law. A simple argument in statistical mechanics is also presented, demonstrating that the equilibrium vapour pressure of a solvent is proportional to its mole fraction in an ideal solution: Raoult's law. The same argument can be extended to the case where the solvent and solute molecules are of different sizes, as is the case with polymers. The results provide a framework for the correct maintenance of the RH surrounding a sample.
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http://dx.doi.org/10.1107/S1600576717003636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377353PMC
April 2017

Genetic etiology of renal agenesis: fine mapping of Renag1 and identification of Kit as the candidate functional gene.

PLoS One 2015 18;10(2):e0118147. Epub 2015 Feb 18.

McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America; Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America; University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America.

Congenital anomalies of the kidney and urogenital tract (CAKUT) occur in approximately 0.5% of live births and represent the most frequent cause of end-stage renal disease in neonates and children. The genetic basis of CAKUT is not well defined. To understand more fully the genetic basis of one type of CAKUT, unilateral renal agenesis (URA), we are studying inbred ACI rats, which spontaneously exhibit URA and associated urogenital anomalies at an incidence of approximately 10%. URA is inherited as an incompletely dominant trait with incomplete penetrance in crosses between ACI and Brown Norway (BN) rats and a single responsible genetic locus, designated Renag1, was previously mapped to rat chromosome 14 (RNO14). The goals of this study were to fine map Renag1, identify the causal genetic variant responsible for URA, confirm that the Renag1 variant is the sole determinant of URA in the ACI rat, and define the embryologic basis of URA in this rat model. Data presented herein localize Renag1 to a 379 kilobase (kb) interval that contains a single protein coding gene, Kit (v-kit Hardy-Zukerman 4 feline sarcoma viral oncogene homolog); identify an endogenous retrovirus-derived long terminal repeat located within Kit intron 1 as the probable causal variant; demonstrate aberrant development of the nephric duct in the anticipated number of ACI rat embryos; and demonstrate expression of Kit and Kit ligand (Kitlg) in the nephric duct. Congenic rats that harbor ACI alleles at Renag1 on the BN genetic background exhibit the same spectrum of urogenital anomalies as ACI rats, indicating that Renag1 is necessary and sufficient to elicit URA and associated urogenital anomalies. These data reveal the first genetic link between Kit and URA and illustrate the value of the ACI rat as a model for defining the mechanisms and cell types in which Kit functions during urogenital development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333340PMC
December 2015

Improved outcomes after alloplastic TMJ replacement: analysis of a multicenter study from Australia and New Zealand.

J Oral Maxillofac Surg 2014 Jul 19;72(7):1251-7. Epub 2014 Feb 19.

Consultant Surgeon, Palmerston North Hospital, and Private Practice, Palmerston North, New Zealand.

Purpose: The aim of the present study was to assess pain, function, diet, and quality of life (QOL) in subjects undergoing alloplastic temporomandibular joint (TMJ) reconstruction.

Materials And Methods: A total of 72 subjects were sent a questionnaire an average of 4 years after undergoing either unilateral or bilateral total joint replacement with a custom TMJ Concepts or stock Biomet total joint replacement device. The changes in pain, function, diet, and quality of life were assessed.

Results: Of the 72 subjects, 52 returned the questionnaire. Pain, function, diet, and QOL were all significantly improved at a mean follow-up of 46.3 months. The complications reported included an altered facial sensation and facial weakness. No implant failures were reported.

Conclusions: The placement of an alloplastic TMJ total joint replacement can provide benefits for patients in the areas of pain, function, diet, and QOL. Additional research is required in this area.
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http://dx.doi.org/10.1016/j.joms.2014.02.019DOI Listing
July 2014

Measurement of the intrinsic variability within protein crystals: implications for sample-evaluation and data-collection strategies.

Acta Crystallogr F Struct Biol Commun 2014 Jan 24;70(Pt 1):127-32. Epub 2013 Dec 24.

European Molecular Biology Laboratory, Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble, France.

The advent of micro-focused X-ray beams has led to the development of a number of advanced methods of sample evaluation and data collection. In particular, multiple-position data-collection and helical oscillation strategies are now becoming commonplace in order to alleviate the problems associated with radiation damage. However, intra-crystal and inter-crystal variation means that it is not always obvious on which crystals or on which region or regions of a crystal these protocols should be performed. For the automation of this process for large-scale screening, and to provide an indication of the best strategy for data collection, a metric of crystal variability could be useful. Here, measures of the intrinsic variability within protein crystals are presented and their implications for optimal data-collection strategies are discussed.
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http://dx.doi.org/10.1107/S2053230X13032007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943112PMC
January 2014

On the statistical mechanics of species abundance distributions.

Theor Popul Biol 2012 Sep 7;82(2):85-91. Epub 2012 Jun 7.

Department of Physics, University of Oxford, Keble Road, Oxford OX1 3RH, UK.

A central issue in ecology is that of the factors determining the relative abundance of species within a natural community. The proper application of the principles of statistical physics to species abundance distributions (SADs) shows that simple ecological properties could account for the near universal features observed. These properties are (i) a limit on the number of individuals in an ecological guild and (ii) per capita birth and death rates. They underpin the neutral theory of Hubbell (2001), the master equation approach of Volkov et al. (2003, 2005) and the idiosyncratic (extreme niche) theory of Pueyo et al. (2007); they result in an underlying log series SAD, regardless of neutral or niche dynamics. The success of statistical mechanics in this application implies that communities are in dynamic equilibrium and hence that niches must be flexible and that temporal fluctuations on all sorts of scales are likely to be important in community structure.
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http://dx.doi.org/10.1016/j.tpb.2012.05.006DOI Listing
September 2012

Measurement of the equilibrium relative humidity for common precipitant concentrations: facilitating controlled dehydration experiments.

Acta Crystallogr Sect F Struct Biol Cryst Commun 2012 Jan 24;68(Pt 1):111-4. Epub 2011 Dec 24.

Structural Biology Group, European Synchrotron Radiation Facility, 6 Rue Jules Horowitz, 38043 Grenoble, France.

The dehydration of crystals of macromolecules has long been known to have the potential to increase their diffraction quality. A number of methods exist to change the relative humidity that surrounds crystals, but for reproducible results, with complete characterization of the changes induced, a precise humidity-control device coupled with an X-ray source is required. The first step in these experiments is to define the relative humidity in equilibrium with the mother liquor of the system under study; this can often be quite time-consuming. In order to reduce the time spent on this stage of the experiment, the equilibrium relative humidity for a range of concentrations of the most commonly used precipitants has been measured. The relationship between the precipitant solution and equilibrium relative humidity is explained by Raoult's law for the equilibrium vapour pressure of water above a solution. The results also have implications for the choice of cryoprotectant and solutions used to dehydrate crystals. For the most commonly used precipitants (10-30% PEG 2000-8000), the starting point will be a relative humidity of 99.5%.
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http://dx.doi.org/10.1107/S1744309111054029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253849PMC
January 2012

The statistical mechanics of community assembly and species distribution.

New Phytol 2011 Aug 27;191(3):819-827. Epub 2011 Apr 27.

Department of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, UK.

• Theoretically, communities at or near their equilibrium species number resist entry of new species. Such 'biotic resistance' recently has been questioned because of successful entry of alien species into diverse natural communities. • Data on 10,409 naturalizations of 5350 plant species over 16 sites dispersed globally show exponential distributions both for species over sites and for sites over number of species shared. These exponentials signal a statistical mechanics of species distribution, assuming two conditions. First, species and sites are equivalent, either identical ('neutral') or so complex that the chance a species is in the right place at the right time is vanishingly small ('idiosyncratic'); the range of species and sites in our data disallows a neutral explanation. Secondly, the total number of naturalizations is fixed in any era by a 'regulator'. • Previous correlation of species naturalization rates with net primary productivity over time suggests that the regulator is related to productivity. • We conclude that biotic resistance is a moving ceiling, with resistance controlled by productivity. The general observation that the majority of species occur naturally at only a few sites, and only a few species occur at many sites, now has a quantitative (exponential) character, offering the study of species' distributions a previously unavailable rigor.
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http://dx.doi.org/10.1111/j.1469-8137.2011.03721.xDOI Listing
August 2011

Casein kinase 1-dependent phosphorylation of familial advanced sleep phase syndrome-associated residues controls PERIOD 2 stability.

J Biol Chem 2011 Apr 15;286(14):12766-74. Epub 2011 Feb 15.

University of Wisconsin School of Medicine and Public Health, the Department of Pharmacology, Madison, WI 53705, USA.

The mammalian circadian clock component PERIOD2 (PER2) plays a critical role in circadian rhythm entrainment. Recently, a missense mutation at a putative phosphorylation site in hPER2, Ser-662, was identified in patients that suffer from familial advanced sleep phase syndrome (FASPS). Patients with FASPS display abnormal sleep-wake patterns characterized by a lifelong pattern of sleep onset in the early evening and offset in the early morning. Although the phosphorylation of PER2 is strongly implied from functional studies, it has not been possible to study the site-specific phosphorylation of PER2 on Ser-662, and the biochemical functions of this residue are unclear. Here, we used phospho-specific antibodies to show that PER2 is phosphorylated on Ser-662 and flanking casein kinase (CK) sites in vivo. The phosphorylation of PER2 was carried out by the combined activities of casein kinase 1δ (CK1 δ) and casein kinase 1ε (CK1ε) and was antagonized by protein phosphatase 1. PER2 phosphorylation was rapidly induced in response to circadian entrainment of mammalian cell lines and occurred in both cytosolic and nuclear compartments. Importantly, we found that the pool of Ser-662-phosphorylated PER2 proteins was more stable than the pool of total PER2 molecules, implying that the FASPS phosphorylation cluster antagonizes PER2 degradation. Consistent with this idea, a Ser-662→Ala mutation that abrogated PER2 phosphorylation significantly reduced its half-life, whereas a phosphomimetic Ser-662→Asp substitution led to an elevation in half-life. Our combined findings provide new insights into PER2 regulation and the biochemical basis of FASPS.
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http://dx.doi.org/10.1074/jbc.M111.224014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069476PMC
April 2011

Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA.

J Biol Chem 2010 Oct 18;285(44):34097-105. Epub 2010 Aug 18.

Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that preferentially targets motor neurons. It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA-binding domain protein) and FUS/TLS (fused in sarcoma/translated in liposarcoma) cause a subset of ALS. The convergent ALS phenotypes associated with TDP-43 and FUS/TLS mutations are suggestive of a functional relationship; however, whether or not TDP-43 and FUS/TLS operate in common biochemical pathways is not known. Here we show that TDP-43 and FUS/TLS directly interact to form a complex at endogenous expression levels in mammalian cells. Binding was mediated by an unstructured TDP-43 C-terminal domain and occurred within the context of a 300-400-kDa complex that also contained C-terminal cleavage products of TDP-43 linked to neuropathology. TDP-43 C-terminal fragments were excluded from large molecular mass TDP-43 ribonucleoprotein complexes but retained FUS/TLS binding activity. The functional significance of TDP-43-FUS/TLS complexes was established by showing that RNAi silencing of either TDP-43 or FUS/TLS reduced the expression of histone deacetylase (HDAC) 6 mRNA. TDP-43 and FUS/TLS associated with HDAC6 mRNA in intact cells and in vitro, and competition experiments suggested that the proteins occupy overlapping binding sites. The combined findings demonstrate that TDP-43 and FUS/TLS form a functional complex in intact cells and suggest that convergent ALS phenotypes associated with TDP-43 and FUS/TLS mutations may reflect their participation in common biochemical processes.
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http://dx.doi.org/10.1074/jbc.M110.154831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962508PMC
October 2010

Investigating the role of enemies in temporal dynamics: Differential sensitivity, competition and stable coexistence.

Theor Popul Biol 2009 Dec 15;76(4):278-84. Epub 2009 Sep 15.

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.

The impact of herbivores and other pests on plants varies greatly from year to year. Here we develop an analytical model of a temporal niche dynamic as a tool to examine how natural fluctuations in pest (enemy) levels may determine coexistence in competing annual plant species when one but not the other is affected by the pest. We show that the probability and speed with which the resistant drives out the sensitive species, coexists with it, or is driven out by its sensitive competitor depends on the cost of pest-resistance to the unaffected species, the frequency of high pest levels in the habitat and the competitive advantage of the sensitive species when the pest is not actively present. The interaction is regulated primarily by pest impact on relative seedling survival of the two, with relative yield per capita of seeds viable into the following season (effective fecundity) the next most vulnerable life-cycle stage.
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http://dx.doi.org/10.1016/j.tpb.2009.09.001DOI Listing
December 2009

Non-specific in vivo inhibition of CK1 by the pyridinyl imidazole p38 inhibitors SB 203580 and SB 202190.

BMB Rep 2009 Mar;42(3):142-7

Molecular and Cellular Pharmacology Program, Department of Pharmacology, The University of Wisconsin-Madison Medical School, WI 53706, Madison, USA.

Small-molecule inhibitors of protein kinases have contributed immensely to our understanding of biological signaling pathways and have been exploited therapeutically for the treatment of cancers and other disease states. The pyridinyl imidazole compounds SB 203580 and SB 202190 were identified as ATP competitive antagonists of the p38 stress-activated protein kinases and have been widely used to elucidate p38-dependent cellular processes. Here, we identify SB 203580 and SB 202190 as potent inhibitors of stress-induced CREB phosphorylation on Serine 111 (Ser-111) in intact cells. Unexpectedly, we found that the inhibitory activity of SB 203580 and SB 202190 on CREB phosphorylation was independent of p38, but instead correlated with inhibition of casein kinase 1 (CK1) in vitro. The inhibition of CK1-mediated CREB phosphorylation by concentrations of pyridinyl imidazoles commonly employed to suppress p38, suggests that in some cases conclusions of p38-dependence derived solely from the use of these inhibitors may be invalid.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412876PMC
http://dx.doi.org/10.5483/bmbrep.2009.42.3.142DOI Listing
March 2009

Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1.

J Biol Chem 2009 Mar 26;284(12):8083-92. Epub 2008 Dec 26.

Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.

TDP-43 (43-kDa TAR DNA-binding domain protein) is a major constituent of ubiquitin-positive cytoplasmic aggregates present in neurons of patients with fronto-temporal lobular dementia and amyotrophic lateral sclerosis (ALS). The pathologic significance of TDP-43 aggregation is not known; however, dominant mutations in TDP-43 cause a subset of ALS cases, suggesting that misfolding and/or altered trafficking of TDP-43 is relevant to the disease process. Here, we show that the presenilin-binding protein ubiquilin 1 (UBQLN) plays a role in TDP-43 aggregation. TDP-43 interacted with UBQLN both in yeast and in vitro, and the carboxyl-terminal ubiquitin-associated domain of UBQLN was both necessary and sufficient for binding to polyubiquitylated forms of TDP-43. Overexpression of UBQLN recruited TDP-43 to detergent-resistant cytoplasmic aggregates that colocalized with the autophagosomal marker, LC3. UBQLN-dependent aggregation required the UBQLN UBA domain, was mediated by non-overlapping regions of TDP-43, and was abrogated by a mutation in UBQLN previously linked to Alzheimer disease. Four ALS-associated alleles of TDP-43 also coaggregated with UBQLN, and the extent of aggregation correlated with in vitro UBQLN binding affinity. Our findings suggest that UBQLN is a polyubiquitin-TDP-43 cochaperone that mediates the autophagosomal delivery and/or proteasome targeting of TDP-43 aggregates.
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http://dx.doi.org/10.1074/jbc.M808064200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658102PMC
March 2009

Phylogeny, niches, and relative abundance in natural communities.

Ecology 2008 Apr;89(4):962-70

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.

Community structure refers to the number of species in a community and the pattern of distribution of individuals among those species. We use a novel way of representing community structure to show that abundance within closely related pairs of co-occurring tree species in a highly diverse Mexican forest is more equitable than is abundance within more distantly related pairs. This observation is at odds with the fundamental assumption of neutral models of community structure, i.e., that species are interchangeable. The observed patterns suggest niche apportionment, in which interaction is focused pairwise between congeners but falls away from the phylogenetic structure above the genus level. Thus niche processes may significantly affect community structure through regulating relative abundance in a substantial proportion of species, which in turn potentially enhances community stability. One such mechanism of stable coexistence has already been shown to be active in this forest.
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http://dx.doi.org/10.1890/07-0322.1DOI Listing
April 2008

An analytical model assessing the potential threat to natural habitats from insect resistance transgenes: continuous transgene input.

Biol Lett 2006 Jun;2(2):293-7

University of Oxford, Department of Zoology, South Parks Road, Oxford OX1 3PS, UK.

The potential effects of 'escape' of genetically modified material (transgenes) into natural communities is a major concern in their use. These effects may be limited in the first instance by limiting the proportion of transgene-carrying plants in the natural community. We previously presented an analytical model of the ecological processes governing the relative abundance and persistence of insect resistance (IR) transgenes in a natural community. In that paper, we illustrated the case in which the transgene is input into the community in a single season using data from oilseed rape (OSR) and its known herbivore, Plutella macropennis. We found that the transgene is unlikely to have a great impact on the natural community. Here, we extend the model for repeated input of crop pollen carrying the transgene. We show the model output, again using OSR, for continuous input of the transgene over 10 years, the projected commercial lifetime of a transgene without associated undesirable agronomic effects. Our results do not change our original conclusion that the IR transgene need not have a large impact on the natural community and our suggestions for assessing and mitigating any threat still stand.
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http://dx.doi.org/10.1098/rsbl.2006.0444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618884PMC
June 2006

An analytical model assessing the potential threat to natural habitats from insect resistance transgenes.

Proc Biol Sci 2005 Sep;272(1574):1759-67

School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.

We examine the role of ecological interactions on effective gene flow from genetically manipulated plants to their wild relatives. We do so by constructing and applying to oilseed rape (OSR) an analytical model for interaction between plants with and without an insect resistance (IR) allele in natural communities, incorporating documented levels of herbivore variability. We find that with reasonable values of advantage to the IR allele, little concomitant disadvantage (physiological costs of the allele) restricts it to low proportions of the natural population for large numbers of generations. We conclude that OSR IR transgenes are unlikely to pose an immediate threat to natural communities. Our model identifies those factors best able to regulate particular transgenes at the population level, the most effective being impaired viability of seeds in the period between production and the following growing season, although other possibilities exist. Because solutions rely on ratios, limiting values of regulating factors are testable under controlled conditions, minimizing risk of release into the environment and offering significant advancement on existing testing programmes. Our model addresses folivory but is easily modified for herbivory damaging the seed or directly affecting seed production by infested plants, or for pathogens altering seed survival in the seedbank.
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http://dx.doi.org/10.1098/rspb.2005.3131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559875PMC
September 2005

Coexistence and relative abundance in forest trees.

Nature 2002 May;417(6887):437-40

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.

Contemporary acceleration of biodiversity loss makes increasingly urgent the need to understand the controls of species coexistence. Tree diversity in particular plays a pivotal role in determining terrestrial biodiversity, through maintaining diversity of its dependent species and with them, their predators and parasites. Most theories of coexistence based on the principle of limiting similarity suggest that coexistence of competing species is inherently unstable; coexistence of competitors must be maintained by external forces such as disturbance, immigration or 'patchiness' of resources in space and time. In contrast, storage theory postulates stable coexistence of competing species through temporal alternation of conditions favouring recruitment of one species over the other. Here we use storage theory to develop explicit predictions for relative differences between competitors that allow us to discriminate between coexistence models. Data on tree species from a primary forest on the Mexican Pacific coast support a general dynamic of storage processes determining coexistence of similar tree species in this community, and allow us to reject all other theories of coexistence.
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http://dx.doi.org/10.1038/417437aDOI Listing
May 2002
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