Biology subjects

Sanders, J. N.

Publications and source records attributed to Sanders, J. N..

3 recordsLinked to original sources

bioRxiv2018

Bleeding, Cramping, and Satisfaction Among New Copper IUD Users: A Prospective Study

ObjectiveWe assess change in bleeding, cramping, and satisfaction among new copper (Cu) IUD users during the first six months of use, and evaluate the impact of bleeding and cramping on method satisfaction.\n\nMethodsWe recruited 77 women ages 18-45 for this prospective longitudinal observational cohort study. Eligible women reported regular menses, had no exposure to hormonal contraception in the last three months, and desired a Cu IUD for contraception. We collected data prospectively for 180 days following IUD insertion. Monthly, Participants reported bleeding scores using the validated pictorial blood loss assessment chart (PBAC), IUD satisfaction using a five-point Likert scale, and cramping using a seven-level ordinal scale. We used multiple imputation to address nonrandom attrition. Structural equation models for count and ordered outcomes modeled bleeding, cramping, and satisfaction growth curves over the six monthly repeated assessments.\n\nResultsBleeding significantly decreased (approximately 25%) over the course of the study from an estimated PBAC=195 at one month post-insertion to PBAC=151 at six months (t=-2.38, p<0.05). Additionally, IUD satisfaction improved over time (t=2.65, p<0.01), increasing from between \"Neutral\" and \"Satisfied\" to \"Satisfied\", over the six month study. Cramping decreased sharply over the six-month study from between biweekly and weekly, to once or twice a month (t=-4.38, p<0.001). Finally, bleeding, but not cramping, was associated with IUD satisfaction (study mean: t=-2.31, p<0.05; study end: t=-2.81, p<0.01).\n\nConclusionsNew Cu IUD users reported decreasing bleeding and cramping, and increasing IUD satisfaction, over the first six months. Method satisfaction was negatively associated with bleeding.

epidemiology↗

bioRxiv2018

The thermodynamic landscape of carbon redox biochemistry

Redox biochemistry plays a key role in the transduction of chemical energy in living systems. However, the compounds observed in metabolic redox reactions are a minuscule fraction of chemical space. It is not clear whether compounds that ended up being selected as metabolites display specific properties that distinguish them from non-biological compounds. Here we introduce a systematic approach for comparing the chemical space of all possible redox states of linear-chain carbon molecules to the corresponding metabolites that appear in biology. Using cheminformatics and quantum chemistry, we analyze the physicochemical and thermodynamic properties of the biological and non-biological compounds. We find that, among all compounds, aldose sugars have the highest possible number of redox connections to other molecules. Metabolites are enriched in carboxylic acid functional groups and depleted of carbonyls, and have higher solubility than non-biological compounds. Upon constructing the energy landscape for the full chemical space as a function of pH and electron donor potential, we find that over a large range of conditions metabolites tend to have lower Gibbs energies than non-biological molecules. Finally, we generate Pourbaix phase diagrams that serve as a thermodynamic atlas to indicate which compounds are local and global energy minima in redox chemical space across a set of pH values and electron donor potentials. Our work yields insight into the physicochemical principles governing redox metabolism, and suggests that thermodynamic stability in aqueous environments may have played an important role in early metabolic processes.

systems biology↗

bioRxiv2017

Structural basis of the Cope rearrangement and C-C bond-forming cascade in hapalindole/fischerindole biogenesis

STRUCTURESThe atomic coordinates and structure factors for:\n\nHpiC1 W73M/K132M SeMet (P212121) -1.7 [A]\n\nHpiC1 native (C2) -1.5 [A]\n\nHpiC1 native (P42) -2.1 [A]\n\nHpiC1 Y101F (C2) -1.4 [A]\n\nHpiC1 Y101S (C2) -1.4 [A]\n\nHpiC1 F138S (P21) -1.7 [A]\n\nHpiC1 Y101F/F138S (P21 -1.65 [A] have been deposited with the Research Collaboratory for Structural Bioinformatics as Protein Data Bank entries 5WPP, 5WPR, 6AL6, 5WPR, 5WPU, 6AL7, and 6AL8 (www.rcsb.org).\n\nGRANTSThis work was supported by: The authors thank the National Science Foundation under the CCI Center for Selective C-H Functionalization (CHE-1205646), the National Institutes of Health (CA70375 to RMW and DHS), R35 GM118101, R01 GM076477 and the Hans W. Vahlteich Professorship (to DHS) for financial support. M.G-B. thanks the Ramon Areces Foundation for a postdoctoral fellowship. J.N.S. acknowledges the support of the National Institute of General Medical Sciences of the National Institutes of Health under Award Number F32GM122218. Computational resources were provided by the UCLA Institute for Digital Research and Education (IDRE) and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI-1053575). The content does not necessarily represent the official views of the National Institutes of Health.\n\nABSTRACTHapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These polycyclic scaffolds are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps, including a rare Cope-rearrangement, 6-exo-trig cyclization, and electrophilic aromatic substitution. Here we report the structure of HpiC1, a Stig cyclase that catalyzes the formation of 12-epi-hapalindole U in vitro. The 1.5 [A] structure reveals a dimeric assembly with two calcium ions per monomer and the active sites located at the distal ends of the protein dimer. Mutational analysis and computational methods uncovered key residues for an acid catalyzed [3,3]-sigmatropic rearrangement and specific determinants that control the position of terminal electrophilic aromatic substitution leading to a switch from hapalindole to fischerindole alkaloids.

biochemistry↗