Search PubMed⌕ Search

Biomedical subjects

Benjamin Martin

Publications and source records attributed to Benjamin Martin.

7 recordsLinked to original sources
PubMed2025

Core passive and facultative mTOR-mediated mechanisms coordinate mammalian protein synthesis and decay.

The maintenance of cellular homeostasis requires tight regulation of proteome concentration and composition. To achieve this, protein production and elimination must be robustly coordinated. However, the mechanistic basis of this coordination remains unclear. Here, we address this question using quantitative live-cell imaging, computational modeling, transcriptomics, and proteomics approaches. We found that protein decay rates systematically adapt to global alterations of protein synthesis rates. This adaptation is driven by a core passive mechanism supplemented by facultative changes in mechanistic/mammalian target of rapamycin (mTOR) signaling. Passive adaptation hinges on changes in the production rate of the machinery governing protein decay and allows for partial maintenance of the cellular proteome. Sustained changes in mTOR signaling provide an additional layer of adaptation unique to naive pluripotent stem cells, allowing for near-perfect maintenance of proteome composition. Our work unravels the mechanisms protecting the integrity of mammalian proteomes upon variations in protein synthesis rates. A record of this paper's transparent peer review process is included in the supplemental information.

TOR Serine-Threonine Kinases↗
PubMed2006

New method based on 1-(trimethysilyl)alk-1-yne to prepare 1,4-skipped diynes.

[reaction: see text] We have developed a novel reaction between a terminal TMS-alkyne and a propargyl halide in the presence of a fluoride source and a catalytic amount of copper iodide to prepare 1,4-skipped diynes with good yields and in mild conditions. We have shown that this reaction also works very well with germanium and tin derivatives as an alternative to silicon. This new method can be useful for the synthesis of polyunsaturated fatty acids.

Journal Article↗
PubMed2006

A unified approach for inversion problems in intensity-modulated radiation therapy.

We propose and study a unified model for handling dose constraints (physical dose, equivalent uniform dose (EUD), etc) and radiation source constraints in a single mathematical framework based on the split feasibility problem. The model does not impose on the constraints an exogenous objective (merit) function. The optimization algorithm minimizes a weighted proximity function that measures the sum of the squares of the distances to the constraint sets. This guarantees convergence to a feasible solution point if the split feasibility problem is consistent (i.e., has a solution), or, otherwise, convergence to a solution that minimally violates the physical dose constraints and EUD constraints. We present computational results that demonstrate the validity of the model and the power of the proposed algorithmic scheme.

Algorithms↗
PubMed2005

Temporo-spatial IMRT optimization: concepts, implementation and initial results.

With the recent availability of 4D-CT, the accuracy of information on internal organ motion during respiration has improved significantly. We investigate the utility of organ motion information in IMRT treatment planning, using an in-house prototype optimization system. Four approaches are compared: (1) planning with optimized margins, based on motion information; (2) the 'motion kernel' approach, in which a more accurate description of the dose deposit from a pencil beam to a moving target is achieved either through time-weighted averaging of influence matrices, calculated for different instances of anatomy (subsets of 4D-CT data, corresponding to various phases of motion) or through convolution of the pencil beam kernel with the probability density function describing the target motion; (3) optimal gating, or tracking with beam intensity maps optimized independently for each instance of anatomy; and (4) optimal tracking with beam intensity maps optimized simultaneously for all instances of anatomy. The optimization is based on a gradient technique and can handle both physical (dose-volume) and equivalent uniform dose constraints. Optimization requires voxel mapping from phase to phase in order to score the dose in individual voxels as they move. The results show that, compared to the other approaches, margin expansion has a significant disadvantage by substantially increasing the integral dose to patient. While gating or tracking result in the best dose conformation to the target, the former elongates treatment time, and the latter significantly complicates the delivery procedure. The 'motion kernel' approach does not provide a dosimetric advantage, compared to optimal tracking or gating, but might lead to more efficient delivery. A combination of gating with the 'motion kernel' or margin expansion approach will increase the duty cycle and may provide one with the most efficient solution, in terms of complexity of the delivery procedure and dose conformality to the target.

Algorithms↗
PubMed2004

Novel cationic lipids incorporating an acid-sensitive acylhydrazone linker: synthesis and transfection properties.

Cationic lipid-mediated gene transfection involves uptake of the lipid/DNA complexes via endocytosis, a cellular pathway characterized by a significant drop in pH. Thus, in the present study, we aimed to explore the impact on transfection efficiency of the inclusion of an acid-sensitive acylhydrazone function in the cationic lipid structure. We synthesized and evaluated the transfection properties of a series of four cationic steroid derivatives characterized by an acylhydrazone linkage connecting a guanidinium-based headgroup to a saturated cholestanone or an unsaturated cholest-4-enone hydrophobic domain. Acid-catalyzed hydrolysis was confirmed for all lipids, its rate being highest for those with a cholestanone moiety. The compound bis-guanidinium bis(2-aminoethyl)amine hydrazone (BGBH)-cholest-4-enone was found to mediate efficient gene transfection into various mammalian cell lines in vitro and into the mouse airways in vivo. In vitro transfection studies with BGBH-cholest-4-enone formulations also showed that incorporation of a degradable acylhydrazone bond led to low cytotoxicity and impacted the intracellular trafficking of the lipoplexes. Thus, our work allowed us to identify a cationic lipid structure with an acid-cleavable acylhydrazone linker capable of mediating efficient gene transfection in vitro and in vivo and it thereby provides a basis for further development of related acid-sensitive gene delivery systems.

Animals↗
PubMed2003

Similar age-specific PSA, complexed PSA, and percent cPSA levels among African-American and white men of southern Louisiana. Prostate-specific antigen.

OBJECTIVES: To determine the mean and median complexed prostate-specific antigen (cPSA) levels in a predominantly African-American population and to explore whether differences in cPSA exist between the races. Differences in total PSA (tPSA) levels between age-matched African-American and white men have been reported by several groups. Age-specific cPSA levels, however, have not been thoroughly evaluated and reported among African-American populations. METHODS: We prospectively evaluated the serum cPSA, tPSA, and percent cPSA levels by the Bayer Immuno 1 assay as a function of age among 1755 African-American and 630 white men in southern Louisiana presenting to a prostate cancer screening program. All men had a normal digital rectal examination or biopsy-proven benign pathologic findings. The intragroup and intergroup statistical analyses were carried out for each decade of age. RESULTS: The median cPSA level for African-American men aged 40 to 49, 50 to 59, and 60 to 69 years old was 0.45, 0.61, and 0.84 ng/mL, respectively. These did not differ significantly from those of age-matched white men. Also, no difference was found in the mean or median tPSA between the races. The percent cPSA values showed a trend for lower levels in African Americans. CONCLUSIONS: These findings suggest that no significant difference exists between cPSA or tPSA levels in African-American and white men without prostate cancer. Genetic and epigenetic factors distinct to this region may account for this observation and thus need further evaluation.

Adult↗