Biomedical subjects

Michael T Montgomery

Publications and source records attributed to Michael T Montgomery.

4 recordsLinked to original sources

PubMed2025

Enhancer activation from transposable elements in extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) drives oncogene amplification and intratumoral heterogeneity in aggressive cancers. While transposable element (TE) reactivation is common in cancer, its role on ecDNA remains unexplored. Here, we map the 3D architecture of MYC-amplified ecDNA in colorectal cancer cells and identify 68 ecDNA-interacting elements (EIEs)-genomic loci enriched for TEs that are frequently integrated onto ecDNA. We focus on an L1M4a1#LINE/L1 fragment co-amplified with MYC, which functions only in the ecDNA amplified context. Using CRISPR-CATCH, CRISPR interference, and reporter assays, we confirm its presence on ecDNA, enhancer activity, and essentiality for cancer cell fitness. These findings reveal that repetitive elements can be reactivated and co-opted as functional rather than inactive sequences on ecDNA, potentially driving oncogene expression and tumor evolution. Our study uncovers a mechanism by which ecDNA harnesses repetitive elements to shape cancer phenotypes, with implications for diagnosis and therapy.

Journal Article↗

PubMed2006

Effects of naphthalene on microbial community composition in the Delaware estuary.

The effects of naphthalene on microbial communities in the bottom boundary layer of the Delaware Bay estuary were investigated in microcosms using denaturing gradient gel electrophoresis (DGGE) and fluorescent in situ hybridization (FISH) with oligonucleotide probes. Three days after the addition of naphthalene, rates of bacterial production and naphthalene mineralization were higher than in no-addition controls and than in cases where glucose was added. Analyses using both DGGE and FISH indicated that the bacterial community changed in response to the addition of naphthalene. FISH data indicated that a few major phylogenetic groups increased in response to the glucose addition and especially to the naphthalene addition. DGGE also demonstrated differences in community composition among treatments, with four phylotypes being unique to naphthalene-amended treatments and three of these having 16S rRNA genes similar to known hydrocarbon degraders. The bacterial community in the naphthalene-amended treatment was distinct from the communities in the glucose-amended treatment and in the no-addition control. These data suggest that polycyclic aromatic hydrocarbons may have large effects on microbial community structure in estuaries and probably on microbially mediated biogeochemical processes.

Acinetobacter↗

PubMed2005

Reduction of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine by zerovalent iron: product distribution.

RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) are cyclic nitramines ((CH2NNO2)n; n = 3 or 4, respectively) widely used as energetic chemicals. Their extensive use led to wide environmental contamination. In contrast to RDX, HMX tends to accumulate in soils due to its unique recalcitrance. In the present study, we investigated the potential of zerovalent iron (ZVI) to transform HMX under anoxic conditions. HMX underwent a rapid transformation when added in well-mixed anoxic ZVI-H2O batch systems to ultimately produce formaldehyde (HCHO), ammonium (NH4+), hydrazine (NH2NH2), and nitrous oxide (N2O). Time course experiments showed that the mechanism of HMX transformation occurred through at least two initial reactions. One reaction involved the sequential reduction of N-NO2 groups to the five nitroso products (1NO-HMX, cis-2NO-HMX, trans-2NO-HMX, 3NO-HMX, and 4NO-HMX). Another implied ring cleavage from either HMX or 1NO-HMX as demonstrated by the observation of methylenedinitramine (NH(NO2)CH2NH(NO2)) and another intermediate that was tentatively identified as (NH(NO2)CH2N(NO)CH2NH-(NO2)) or its isomer (NH(NO)CH2N(NO2)CH2NH(NO2)). This is the first study that demonstrates transformation of HMX by ZVI to significant amounts of NH2NH2 and HCHO. Both toxic products seemed to persist under reductive conditions, thereby suggesting that the ultimate fate of these chemicals, particularly hydrazine, should be understood prior to using zerovalent iron to remediate cyclic nitramines.

Anaerobiosis↗

PubMed2002

Transport, deposition and biodegradation of particle bound polycyclic aromatic hydrocarbons in a tidal basin of an industrial watershed.

Polycylic aromatic hydrocarbons (PAHs) are common contaminants in industrial watersheds. Their origin, transport and fate are important to scientists, environmental managers and citizens. The Philadelphia Naval Reserve Basin (RB) is a small semi-enclosed embayment near the confluence of the Schuylkill and Delaware Rivers in Pennsylvania (USA). We conducted a study at this site to determine the tidal flux of particles and particle-bound contaminants associated with the RB. Particle traps were placed at the mouth and inside the RB and in the Schuylkill and Delaware Rivers. There was net particle deposition into the RB, which was determined for three seasons. Spring and fall depositions were highest (1740 and 1230 kg of particles, respectively) while winter deposition was insignificant. PAH concentrations on settling particles indicated a net deposition of 12.7 g PAH in fall and 2.1 g PAH in spring over one tidal cycle. There was no significant PAH deposition in the winter. Biodegradation rates, calculated from 14C-labeled PAH substrate mineralization, could attenuate only about 0.25% of the PAH deposited during a tidal cycle in fall. However, in the spring, biodegradation could be responsible for degrading 50% of the settling PAHs. The RB appears to be a sink for PAHs in this watershed.

Biodegradation, Environmental↗