Interview of James T. Dever

James T. Dever was born in 1945 in the Kensington section of Philadelphia, Pennsylvania to Walter and Ruth Dever. He attended North Catholic High School in Philadelphia and joined the Order of the Oblates of St. Francis de Sales while still in High School. He majored in Theology and English at Catholic University and Allentown College, then received his Master of Arts in English at Villanova University. He taught English at North Catholic High. Ordained as a priest in 1973, Father Dever has been a parish priest, hospital chaplain, and most recently campus minister of the University Ministry and Service (UMAS) at La Salle University

Conical Bearingless Motor/Generators

Motor/generators based on conical magnetic bearings have been invented as an improved alternative to prior such machines based, variously, on radial and/or axial magnetic bearings. Both the present and prior machines are members of the class of so-called bearingless or self bearing (in the sense of not containing mechanical bearings) rotary machines. Each motor/generator provides both a torque and force allowing it to either function as a motor and magnetic bearing or a generator and magnetic bearing concurrently. Because they are not subject to mechanical bearing wear, these machines have potentially long operational lives and can function without lubrication and over wide ranges of speed and temperature that include conditions under which lubricants would become depleted, degraded, or ineffective and mechanical bearings would fail. The figure shows three typical configurations of conical bearingless motor/generators. The main elements of each motor/generator are concentric rotor and stator portions having conically tapered surfaces facing each other across a gap. Because a conical motor/generator imposes both radial and axial magnetic forces, it acts, in effect, as a combination of an axial and a radial magnetic bearing. Therefore, only two conical motor/generators - one at each end of a rotor - are needed to effect complete magnetic leviation of the rotor, whereas previously, it was necessary to use a combination of an axial and a radial magnetic bearing at each end of the rotor to achieve complete magnetic levitation and a separate motor to provide torque

Organochlorine Pesticides in Chlorioallantoic Membranes of Morelet\u27s Crocodile Eggs from Belize

Recent studies examined the utility of the chorioallantoic membrane (CAM) as a nonlethal, noninvasive indicator of environmental contaminant exposure in oviparous wildlife. The CAM is a highly vascularized extraembryonic membrane that functions as a site for respiration, nutrient transport, and waste storage during embryonic development. After hatching, the CAM is usually discarded with the eggshell and can be used for chemical residue analysis. Chorioallantoic membranes have been used successfully to examine contaminant exposure and predict chemical concentrations in multiple species of birds and reptiles. In this study, we examined organochlorine (OC) pesticide concentrations in CAMs from eggs of Morelet\u27s crocodiles (Crocodylus moreletii) from northern Belize. Multiple OCs were detected in crocodile CAMs, including aldrin, dieldrin, endrin, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethane, dichlorodiphenyldichloroethylene (DDE), heptachlor, lindane, and methoxychlor. Number and concentrations of OC compounds in CAMs were variable. The most prevalent contaminant detected was DDE, which occurred in 69% of CAMs, with concentrations ranging from 0.3 parts per billion (ppb) to 17.0 ppb. The OC burdens in crocodile CAMs confirm contamination of eggs and suggest exposure in embryos and maternal females. These results further support the use of CAMs as qualitative indicators of OC exposure in oviparous wildlife. The efficacy of this sampling technique in the field will depend on the logistics and cost associated with CAM collection and the specific life history traits of the wildlife species

Double-stranded RNA-activated protein kinase PKR of fishes and amphibians: Varying the number of double-stranded RNA binding domains and lineage-specific duplications

BackgroundDouble-stranded (ds) RNA, generated during viral infection, binds and activates the mammalian anti-viral protein kinase PKR, which phosphorylates the translation initiation factor eIF2alpha leading to the general inhibition of protein synthesis. Although PKR-like activity has been described in fish cells, the responsible enzymes eluded molecular characterization until the recent discovery of goldfish and zebrafish PKZ, which contain Z-DNA-binding domains instead of dsRNA-binding domains (dsRBDs). Fish and amphibian PKR genes have not been described so far.ResultsHere we report the cloning and identification of 13 PKR genes from 8 teleost fish and amphibian species, including zebrafish, demonstrating the coexistence of PKR and PKZ in this latter species. Analyses of their genomic organization revealed up to three tandemly arrayed PKR genes, which are arranged in head-to-tail orientation. At least five duplications occurred independently in fish and amphibian lineages. Phylogenetic analyses reveal that the kinase domains of fish PKR genes are more closely related to those of fish PKZ than to the PKR kinase domains of other vertebrate species. The duplication leading to fish PKR and PKZ genes occurred early during teleost fish evolution after the divergence of the tetrapod lineage. While two dsRBDs are found in mammalian and amphibian PKR, one, two or three dsRBDs are present in fish PKR. In zebrafish, both PKR and PKZ were strongly upregulated after immunostimulation with some tissue-specific expression differences. Using genetic and biochemical assays we demonstrate that both zebrafish PKR and PKZ can phosphorylate eIF2alpha in yeast.ConclusionConsidering the important role for PKR in host defense against viruses, the independent duplication and fixation of PKR genes in different lineages probably provided selective advantages by leading to the recognition of an extended spectrum of viral nucleic acid structures, including both dsRNA and Z-DNA/RNA, and perhaps by altering sensitivity to viral PKR inhibitors. Further implications of our findings for the evolution of the PKR family and for studying PKR/PKZ interactions with viral gene products and their roles in viral infections are discussed

Low levels of nucleotide diversity in Crocodylus moreletii and evidence of hybridization with C. acutus

Examinations of both population genetic structure and the processes that lead to such structure in crocodilians have been initiated in several species in response to a call by the IUCN Crocodile Specialist Group. A recent study used microsatellite markers to characterize Morelet\u27s crocodile (Crocodylus moreletii) populations in north-central Belize and presented evidence for isolation by distance. To further investigate this hypothesis, we sequenced a portion of the mitochondrial control region for representative animals after including samples from additional locales in Belize, Guatemala and Mexico. While there is limited evidence of subdivision involving other locales, we found that most of the differentiation among populations of C. moreletii can be attributed to animals collected from a single locale in Belize, Banana Bank Lagoon. Furthermore, mitochondrial DNA sequence analysis showed that animals from this and certain other locales display a haplotype characteristic of the American crocodile, C. acutus, rather than C. moreletii. We interpret this as evidence of hybridization between the two species and comment on how these new data have influenced our interpretation of previous findings. We also find very low levels of nucleotide diversity in C. moreletii haplotypes and provide evidence for a low rate of substitution in the crocodilian mitochondrial control region. Finally, the conservation implications of these findings are discussed

Genetically Engineered Phages: a Review of Advances over the Last Decade

Summary: Soon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.D.P.P. acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT) through grant SFRH/BD/76440/2011. This work was funded by The Center for Microbiome Informatics and Therapeutics and NSF Expeditions in Computing Program award #1522074 as part of the Living Computing Project. This work was further supported by grants from the Defense Threat Reduction Agency (grants HDTRA1-14-1-0007 and HDTRA1-15-1-0050), the National Institutes of Health (grants 1DP2OD008435,1P50GM098792,1R01EB017755, and 1R21AI12166901), and the U.S. Army Research Laboratory and U.S. Army Research Office, through the Institute for Soldier Nanotechnologies, under contract number W911NF-13-D-0001.S.S.is an FCT investigator (IF/01413/2013). D.P.P., S.S., and J.A. also acknowledge financial support from FCT under the scope of the strategic funding of the UID/ BIO/04469/2013 unit and COMPETE 2020 (grant POCI-01-0145FEDER-006684). T.K.L. is a founder of Sample6 Inc. and Eligo Biosciences, two companies developing phage-based technologies

Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy

CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response

Here, we report that genome editing by CRISPR-Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR-Cas9.Peer reviewe