Molecular Phylogenetics of Bromus (Poaceae: Pooideae) Based on Chloroplast and Nuclear DNA Sequence Data

We conducted a phylogenetic analysis to characterize relationships among Bromus and test the monophyly of five of the seven morphologically distinct groups within Bromus (Poaceae: Pooideae) that have been treated as sections, subgenera, or genera. We sequenced the chloroplast trnL (UAA) intron, the 3\u27-end of the chloroplast ndhF gene, and the internal transcribed spacers (ITS) of the nuclear ribosomal DNA region for 46 species that represent a large proportion of the morphological and geographical diversity in the genus. Independent analyses of plastid and nuclear ribosomal data identified several lineages in Bromus, but there is some evidence of incongruence between these linkage groups. Nuclear ribosomal trees indicate that two clades comprising some North and South American species of sect. Bromopsis are the successive sister groups of the rest of the genus, and that Old World species of sect. Bromopsis are more closely related to sects. Ceratochloa and Neobromus than they are to the remaining North American species of sect. Bromopsis. In contrast, plastid trees indicate a close relationship between Old World and some North American species of sect. Bromopsis. In the nuclear ribosomal trees, sects. Genea and Bromus (if sect. Triniusia is included within it, as treated by most authors) are monophyletic and not closely related. In the plastid trees, species of these two sections are intermixed, supporting a hybrid origin for B. pectinatus. The monophyly of sect. Ceratochloa is supported in the plastid and nuclear ribosomal trees, and the monophyly of sect. Neobromus is robustly supported in the nuclear ribosomal trees. Current classification schemes do not reflect phylogenetic relationships in Bromus. Tentative evidence of conflict among nuclear and plastid data partitions needs clarification with more robustly supported plastid and nuclear ribosomal gene trees

Recognition of Bromus Richardsonii and B. Ciliatus: Evidence from Morphology, Cytology, and DNA Fingerprinting (Poaceae: Bromeae)

Since our goal was to determine characteristic differences between Bromus richardsonii and B. ciliates, a discriminate analysis (DA), principal components analysis (PCA), multidimensional scaling (MDS), bivariate analysis, and an amplified fragment length polymorphisms (AFLP) analysis were undertaken on 93 herbarium specimens and 31 field-collected populations. A cytological survey of B. ciliates, B. richardsonii, and B. mucroglumis confirm previous reports that the first species is diploid (2n = 14) and the latter two are tetraploid (2n = 28). All taxa were correctly classified in the DA and important characters for each of the species were identified. Bromus richardsonii has lemmas with scattered hairs on the lower half between the mid nerve and margins [glabrous in B. ciliatus], anthers (1.2) 1.6-2.7 (3.4) mm long [(0.9) 1-1.4 (1.6) mm long in B. ciliatus], second glumes (7.8) 8.9 - 11.3 (13.2) mm long [(6.2) 7.1-8.5 (9.5) in B. ciliatus); and basal sheaths with dense, short to medium hairs [glabrous or with long hairs in B. ciliatus]. The PCA easily separated B. ciliatus and B. richardsonii into two well-defined groups and MDS mirrored the principal components analysis but displayed more overlap of individuals between the two groups. The AFLP-derived UPGMA dendrogram separated 154 individuals into two distinct clusters, one consisting entirely of B. ciliatus individuals and the other consisting of B. richardsonii individuals with six individuals of B. mucroglumis embedded within. Our study clearly indicates that there are distinctive morphological, cytological, and genetic differences to distinguish B. richardsonii and B. ciliatus as separate species

Computational prediction of neural progenitor cell fates

Understanding how stem and progenitor cells choose between alternative cell fates is a major challenge in developmental biology. Efforts to tackle this problem have been hampered by the scarcity of markers that can be used to predict cell division outcomes. Here we present a computational method, based on algorithmic information theory, to analyze dynamic features of living cells over time. Using this method, we asked whether rat retinal progenitor cells (RPCs) display characteristic phenotypes before undergoing mitosis that could foretell their fate. We predicted whether RPCs will undergo a self-renewing or terminal division with 99% accuracy, or whether they will produce two photoreceptors or another combination of offspring with 87% accuracy. Our implementation can segment, track and generate predictions for 40 cells simultaneously on a standard computer at 5 min per frame. This method could be used to isolate cell populations with specific developmental potential, enabling previously impossible investigations.The computational aspects of this work were supported by the Center for Subsurface Sensing and Imaging Systems (NSF Grant EEC-9986821), by the Rensselaer Polytechnic Institute and by the University of Wisconsin-Milwaukee. This work was supported by grants from the Canadian Institutes of Health Research and the Foundation Fighting Blindness – Canada (to M.C). M.C. is a CIHR New Investigator and a W.K. Stell Scholar of the Foundation Fighting Blindness – Canada

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Spectral modeling of scintillator for the NEMO-3 and SuperNEMO detectors

We have constructed a GEANT4-based detailed software model of photon transport in plastic scintillator blocks and have used it to study the NEMO-3 and SuperNEMO calorimeters employed in experiments designed to search for neutrinoless double beta decay. We compare our simulations to measurements using conversion electrons from a calibration source of $\rm ^{207}Bi$ and show that the agreement is improved if wavelength-dependent properties of the calorimeter are taken into account. In this article, we briefly describe our modeling approach and results of our studies.Comment: 16 pages, 10 figure

Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness

Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photo-receptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness.Foundation Fighting Blindness CanadaCanadian Institutes of Health ResearchNIHCharles University institutional programmesBIOCEV-Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, from the European Regional Development FundMinistry of Health of the Czech RepublicGraduate School of Life Sciences (University of Wuerzburg)Government of Canada through Genome CanadaOntario Genomics InstituteGenome QuebecGenome British ColumbiaMcLaughlin CentreCharles Univ Prague, Inst Inherited Metab Disorders, Fac Med 1, Prague 12000 2, Czech RepublicMcGill Univ, Dept Human Genet, Fac Med, Montreal, PQ H3A 0G1, CanadaGenome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, CanadaClin Res Inst Montreal, Cellular Neurobiol Res Unit, Montreal, PQ H2W 1R7, CanadaMcGill Univ, Montreal, PQ H3A 0G4, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Paediat Surg, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Human Genet, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Ophthalmol, Montreal, PQ H3H 1P3, CanadaUniv Alberta, Royal Alexandra Hosp, Dept Ophthalmol & Visual Sci, Edmonton, AB T5H 3V9, CanadaCharles Univ Prague, Inst Biol & Med Genet, Fac Med 1, Prague 12000 2, Czech RepublicBaylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USAUniversidade Federal de São Paulo, Dept Neurol, Div Gen Neurol, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, Ataxia Unit, BR-04021001 São Paulo, BrazilNewcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, EnglandUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilSo Gen Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, ScotlandCardiff Univ, Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, WalesHadassah Hebrew Univ Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, IsraelOregon Hlth & Sci Univ, Oregon Inst Occupat Hlth Sci, Portland, OR 97239 USAUniv Wurzburg, Lehrstuhl Neurobiol & Genet, D-97074 Wurzburg, GermanyUniv Montreal, Dept Med, Montreal, PQ H3T 1P1, CanadaMcGill Univ, Dept Anat & Cell Biol, Div Expt Med, Montreal, PQ H3A 2B2, CanadaUniversidade Federal de São Paulo, Dept Neurol, Div Gen Neurol, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, Ataxia Unit, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilNIH: EY022356-01NIH: EY018571-05NIH: NS047663-09Charles University institutional programmes: PRVOUK-P24/LF1/3Charles University institutional programmes: UNCE 204011Charles University institutional programmes: SVV2013/266504BIOCEV-Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, from the European Regional Development Fund: CZ.1.05/1.1.00/02.0109Ministry of Health of the Czech Republic: NT13116-4/2012Ministry of Health of the Czech Republic: NT14015-3/2013Ontario Genomics Institute: OGI-049Web of Scienc

Long-term retinal PEDF overexpression prevents neovascularization in a murine adult model of retinopathy

Neovascularization associated with diabetic retinopathy (DR) and other ocular disorders is a leading cause of visual impairment and adult-onset blindness. Currently available treatments are merely palliative and offer temporary solutions. Here, we tested the efficacy of antiangiogenic gene transfer in an animal model that mimics the chronic progression of human DR. Adeno-associated viral (AAV) vectors of serotype 2 coding for antiangiogenic Pigment Epithelium Derived Factor (PEDF) were injected in the vitreous of a 1.5 month-old transgenic model of retinopathy that develops progressive neovascularization. A single intravitreal injection led to long-term production of PEDF and to a striking inhibition of intravitreal neovascularization, normalization of retinal capillary density, and prevention of retinal detachment. This was parallel to a reduction in the intraocular levels of Vascular Endothelial Growth Factor (VEGF). Normalization of VEGF was consistent with a downregulation of downstream effectors of angiogenesis, such as the activity of Matrix Metalloproteinases (MMP) 2 and 9 and the content of Connective Tissue Growth Factor (CTGF). These results demonstrate long-term efficacy of AAV-mediated PEDF overexpression in counteracting retinal neovascularization in a relevant animal model, and provides evidence towards the use of this strategy to treat angiogenesis in DR and other chronic proliferative retinal disorders