Publications by authors named "Michael Millman"

5 Publications

  • Page 1 of 1

Small extracellular vesicles ameliorate peripheral neuropathy and enhance chemotherapy of oxaliplatin on ovarian cancer.

J Extracell Vesicles 2021 Mar 4;10(5):e12073. Epub 2021 Mar 4.

Department of Neurology Henry Ford Health System Detroit Michigan USA.

There are no effective treatments for chemotherapy induced peripheral neuropathy (CIPN). Small extracellular vesicles (sEVs) facilitate intercellular communication and mediate nerve function and tumour progression. We found that the treatment of mice bearing ovarian tumour with sEVs derived from cerebral endothelial cells (CEC-sEVs) in combination with a chemo-drug, oxaliplatin, robustly reduced oxaliplatin-induced CIPN by decreasing oxaliplatin-damaged myelination and nerve fibres of the sciatic nerve and significantly amplified chemotherapy of oxaliplatin by reducing tumour size. The combination therapy substantially increased a set of sEV cargo-enriched miRNAs, but significantly reduced oxaliplatin-increased proteins in the sciatic nerve and tumour tissues. Bioinformatics analysis revealed the altered miRNAs and proteins formed two distinct networks that regulate neuropathy and tumour growth, respectively. Intravenously administered CEC-sEVs were internalized by axons of the sciatic nerve and cancer cells. Reduction of CEC-sEV cargo miRNAs abolished the effects of CEC-sEVs on oxaliplatin-inhibited axonal growth and on amplification of the anti-cancer effect in ovarian cancer cells, suggesting that alterations in the networks of miRNAs and proteins in recipient cells contribute to the therapeutic effect of CEC-sEVs on CIPN. Together, the present study demonstrates that CEC-sEVs suppressed CIPN and enhanced chemotherapy of oxaliplatin in the mouse bearing ovarian tumour.
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http://dx.doi.org/10.1002/jev2.12073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931803PMC
March 2021

The Pentatricopeptide Repeat Protein MEF100 Is Required for the Editing of Four Mitochondrial Editing Sites in .

Cells 2021 Feb 22;10(2). Epub 2021 Feb 22.

Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia.

In there are more than 600 C-to-U RNA editing events in the mitochondria and at least 44 in the chloroplasts. Pentatricopeptide repeat (PPR) proteins provide the specificity for these reactions. They recognize RNA sequences in a partially predictable fashion via key amino acids at the fifth and last position in each PPR motif that bind to individual ribonucleotides. A combined approach of RNA-Seq, mutant complementation, electrophoresis of mitochondrial protein complexes and Western blotting allowed us to show that MEF100, a PPR protein identified in a genetic screen for mutants resistant to an inhibitor of γ -glutamylcysteine synthetase, is required for the editing of -493, -403, -698 and -356 sites in Arabidopsis mitochondria. The absence of editing in leads to a decrease in mitochondrial Complex I activity, which probably explains the physiological phenotype. Some plants have lost the requirement for MEF100 at one or more of these sites through mutations in the mitochondrial genome. We show that loss of the requirement for MEF100 editing leads to divergence in the MEF100 binding site.
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http://dx.doi.org/10.3390/cells10020468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926422PMC
February 2021

Six centuries of geomagnetic intensity variations recorded by royal Judean stamped jar handles.

Proc Natl Acad Sci U S A 2017 02 13;114(9):2160-2165. Epub 2017 Feb 13.

Department of Archaeology and Ancient Near Eastern Cultures, Tel Aviv University, Tel Aviv 69978, Israel.

Earth's magnetic field, one of the most enigmatic physical phenomena of the planet, is constantly changing on various time scales, from decades to millennia and longer. The reconstruction of geomagnetic field behavior in periods predating direct observations with modern instrumentation is based on geological and archaeological materials and has the twin challenges of () the accuracy of ancient paleomagnetic estimates and () the dating of the archaeological material. Here we address the latter by using a set of storage jar handles (fired clay) stamped by royal seals as part of the ancient administrative system in Judah (Jerusalem and its vicinity). The typology of the stamp impressions, which corresponds to changes in the political entities ruling this area, provides excellent age constraints for the firing event of these artifacts. Together with rigorous paleomagnetic experimental procedures, this study yielded an unparalleled record of the geomagnetic field intensity during the eighth to second centuries BCE. The new record constitutes a substantial advance in our knowledge of past geomagnetic field variations in the southern Levant. Although it demonstrates a relatively stable and gradually declining field during the sixth to second centuries BCE, the new record provides further support for a short interval of extreme high values during the late eighth century BCE. The rate of change during this "geomagnetic spike" [defined as virtual axial dipole moment > 160 ZAm (10 Am)] is further constrained by the new data, which indicate an extremely rapid weakening of the field (losing ∼27% of its strength over 30 y).
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http://dx.doi.org/10.1073/pnas.1615797114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338537PMC
February 2017

A Comparison of Disease Burden Between Twins and Control Pairs in Medicare: Quantification of Heredity's Role in Human Health.

Popul Health Manag 2015 Oct 6;18(5):383-91. Epub 2015 Feb 6.

3 Centers for Medicare & Medicaid Services , Washington, D.C.

To quantify heredity's effects on the burden of illness in the Medicare population, this study linked information between participants in a research twin registry to a comprehensive set of Medicare claims. To calculate disease categories, the authors used the Centers for Medicare & Medicaid Services Hierarchical Conditions Categories (HCC) model that was developed to risk adjust Medicare's capitation payments to private health care plans based on the health expenditure risk of their enrollees. Using the Medicare database, 2 sets of unrelated but demographically matched control pairs (MCPs) were generated, one specific for the monozygotic twin population and the second specific for the dizygotic twin population. The concordance and correlation rates of the 70 HCC categories for the 2 twin populations, in comparison to their corresponding MCP, was then calculated using Medicare claims data from 1991 through 2011. When indicated, HCCs for which there was a statistically significant difference between the twin and corresponding MCP control group were analyzed by calculating concordance and correlation rates of the International Classification of Diseases, Ninth Revision codes that compose the HCC. Findings reveal that monozygotic twins share 6.5% more HCC disease categories than their MCP while dizygotic twins share 3.8% more HCC disease categories than their MCP. Atrial fibrillation is a highly heritable disease category, a finding consistent with prior literature describing the heritability of the cardiac arrhythmias. These findings are consistent with qualitative assessments of heredity's role found in previous models of population health, and provide both novel methods and quantitative evidence to support future model development.
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http://dx.doi.org/10.1089/pop.2014.0145DOI Listing
October 2015

Temporal variation in patterns of comorbidities in the medicare population.

Popul Health Manag 2013 Apr 31;16(2):120-4. Epub 2012 Oct 31.

Office of Science and Data Policy, Washington, District of Columbia 20201, USA.

It is widely accepted that Medicare beneficiaries with multiple comorbidities (ie, patients with combinations of more than 1 disease) account for a disproportionate amount of mortality and expenditures. The authors previously studied this phenomenon by analyzing Medicare claims data from 2008 to determine the pattern of disease combinations (DCs) for 32,220,634 beneficiaries. Their findings indicated that 22% of these individuals mapped to a long-tailed distribution of approximately 1 million DCs. The presence of so many DCs, each populated by a small number of individuals, raises the possibility that the DC distribution varies over time. Measuring this variability is important because it indicates the rate at which the health care system must adapt to the needs of new patients. This article analyzes Medicare claims data for 3 consecutive calendar years, using 2 algorithms based on the Centers for Medicare & Medicaid Services (CMS)-Hierarchical Conditions Categories (HCC) claims model. These algorithms make different assumptions regarding the degree to which the CMS-HCC model could be disaggregated into its underlying International Classification of Diseases, Ninth Revision, Clinical Modification codes. The authors find that, although a large number of beneficiaries belong to a set of DCs that are nationally stable across the 3 study years, the number of DCs in this set is large (in the range of several hundred thousand). Furthermore, the small number of beneficiaries associated with the larger number of variable DCs (ie, DCs that were not constantly populated in all 3 study years) represents a disproportionally high level of expenditures and death.
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http://dx.doi.org/10.1089/pop.2012.0045DOI Listing
April 2013