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Howard, L.

Publications and source records attributed to Howard, L..

2 recordsLinked to original sources
bioRxiv2018

Endothelial Cells Filopodia Participation In The Anastomosis Of CNS Capillaries

By combining the classic Golgi method and the electron microscope, we have gained a better understanding of the anastomosis of CNS blood capillaries. The participation of growing capillary leading endothelial cells filopodia in the anastomotic process is described. The two approaching capillaries leading endothelial cells filopodia intermingle and interact forming complex conglomerates with narrow spaces filled with proteinaceous material (possibly basal lamina) secreted by them. The presence of tight junctions among the filopodia corroborates their vascular nature. Their presence also suggests a different endothelial cells origin as will those from the two approaching capillaries. The original narrow spaces coalesce into larger ones leading to the eventual formation of a single one that will interconnect (anastomose) the two capillaries. The newly formed post-anastomotic CNS capillaries are rather small with irregular and narrow lumina that might permit the passage of fluid but not yet of blood cells. Eventually, the new capillaries lumina will enlarge permitting the passage of blood cells.\n\nFunding informationThe M. M-P. Golgi studies were supported by a \"Jacob Javits Neurosciences Investigator Award\". NIH Grant NS-22897. And the L. H. EM studies were supported by the Gilman Fund/Class of 1978 Life Sciences Center. M. M-P. is Emeritus Professor of Pathology and Pediatrics and L. H. is a Consulting Electron Microscopists. Both from the Geisel School of Medicine at Dartmouth. Hanover, NH 03755, USA

neuroscience↗
bioRxiv2017

Novel causative genes for heritable pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-{beta} pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlie most heritable forms of PAH. Since the missing heritability likely involves genetic variation confined to small numbers of cases, we performed whole genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses revealed significant overrepresentation of rare variants in novel genes, namely ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. We provide evidence for familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, led to reduced secretion from transfected cells. In addition, we identified pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings provide new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.

genetics↗