Biology subjects

Rosenbaum, M.

Publications and source records attributed to Rosenbaum, M..

4 recordsLinked to original sources

bioRxiv2026

Antimicrobial and Cytotoxic Lysolipins I-M Isolated from Streptomyces sp. P8-2B18

Lysolipin I (1) is a highly bioactive xanthone with strong antibacterial and cytotoxic properties. Given the limited number of lysolipin analogues, discovery of new natural lysolipin derivatives is important for understanding their structure-activity relationships. A soil-derived Streptomyces sp. P8-2B18 harbors a putative lysolipin biosynthetic gene cluster and LC-MS based metabolomic analysis revealed the production of lysolipin I along with unreported analogues. Large-scale fermentation followed by isolation led to the discovery of four new analogues, lysolipins J-M (2- 5), the structures of which were elucidated by mass spectrometric and NMR spectroscopic data analyses. Lysolipin L features a five-membered lactam F ring, which was unprecedented in reported lysolipins. Lysolipin M has a novel skeleton, with an extra methyl (Me-36) and a glycosyl group replacing a 1,3-oxane ring in lysolipin I. While lysolipins I, J and K displayed strong activity against Staphylococcus aureus and Aspergillus flavus with MIC values ranging from 0.25 to 4 g/mL and lysolipin L showed only moderate activities, lysolipin M was inactive (>50 g/mL). Lysolipins I-K showed potent cytotoxic activity against prostate cancer cell lines LNCaP and C4-2B, with IC50 values in the submicromolar range. In contrast, lysolipin L exhibited no cytotoxicity and lysolipin M exhibited substantially reduced potency. Their broad, non-selective bioactivities restricted their applicability as therapeutic agents.

microbiology↗

bioRxiv2022

Streptomyces alleviate abiotic stress in plant by producing pteridic acids

Soil microbiota can confer fitness advantages to plants and increase crop resilience to drought and other abiotic stressors. However, there is little evidence on the mechanisms correlating a microbial trait with plant abiotic stress tolerance. Here, we report that Streptomyces effectively alleviates the drought and salinity stress by producing spiroketal polyketide pteridic acid H (1) and its isomer F (2), both of which promote root growth in Arabidopsis at a concentration of 1.3 nM under abiotic stress. Pteridic acids induce stress response genes expression in salinity-stressed Arabidopsis seedlings. The bifunctional biosynthetic gene cluster of pteridic acids and antimicrobial elaiophylin is confirmed in vivo and mainly disseminated by vertical transmission which is geographically distributed in various environments. This discovery reveals a perspective for understanding plant-Streptomyces interactions and provides a promising approach for utilising beneficial Streptomyces and their secondary metabolites in agriculture to mitigate the detrimental effects of climate change.

microbiology↗

bioRxiv2018

Clinical and Functional Characterization of Melanocortin 4 Receptor genetic variants in African American and/or Hispanic children with severe early onset obesity.

ContextMutations in melanocortin receptor (MC4R) are the most frequent cause of monogenic obesity in children of European ancestry, but little is known about their prevalence in children from minority populations in the United States.\n\nObjectiveThis study aims to identify the prevalence of MC4R mutations in children with severe early onset obesity of African-American and/or Latina ancestry.\n\nDesign and SettingIndividuals were recruited from the weight management clinics at two hospitals and from the institutional biobank at a third hospital. Sequencing of the MC4R gene was performed by whole exome and/or Sanger sequencing. Functional testing was performed to establish the surface expression of the receptor and cAMP response to its cognate ligand -melanocyte stimulating hormone.\n\nParticipantsThree hundred and twelve children (1-18 years, 50% girls) with body mass index (BMI) > 120% of 95th percentile of CDC 2000 growth charts at an age < 6 years, with no known pathological cause of obesity were enrolled.\n\nResultsEight rare MC4R mutations (2.6%) were identified in this study (R7S, F202L (n=2), M215I, G252D, V253I, I269N, F284I), three of which have not been previously reported (M215I, G252D, F284I). The pathogenicity of the variants was confirmed either by prior literature reports, or by functional testing. There was no significant difference in the BMI or height trajectories of children with or without MC4R mutations in this cohort.\n\nConclusionsWhile the prevalence of MC4R mutations in this cohort was similar to that reported in obese children of European ancestry, some of the variants were novel.

genetics↗

bioRxiv2018

Potential Bias of Doubly Labeled Water for Measuring Energy Expenditure Differences Between Diets Varying in Carbohydrate

BackgroundVery low-carbohydrate diets have been reported to substantially increase human energy expenditure as measured by doubly labeled water (DLW) but not by respiratory chambers. Do the DLW data reflect true physiological differences that are undetected by respiratory chambers? Alternatively, are the apparent DLW energy expenditure a consequence of failure to fully account for respiratory quotient (RQ) differences between diets?\n\nObjectiveTo examine energy expenditure differences between diets varying drastically in carbohydrate and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework.\n\nDesignDLW measurements were obtained during the final two weeks of month-long baseline (BD; 50% carbohydrate, 35% fat, 15% protein) and isocaloric ketogenic diets (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with BMI 25-35 kg/m2. Subjects resided 2d/week in respiratory chambers to measure energy expenditure (EEchamber). DLW expenditure was calculated using chamber-determined respiratory quotients (RQ) either unadjusted (EEDLW) or adjusted (EEDLW{Delta}RQ) for net energy imbalance using diet-specific coefficients. Accelerometers measured physical activity. Body composition changes were measured by dual-energy X-ray absorptiometry which were combined with energy intake measurements to calculate energy expenditure by balance (EEbal).\n\nResultsAfter transitioning from BD to KD, neither EEchamber nor EEbal were significantly changed ({triangleup}EEchamber=24{+/-}30 kcal/d; p=0.43 and {triangleup}EEbal=-141{+/-}118 kcal/d; p=0.25). Similarly, physical activity (-5.1{+/-}4.8%; p=0.3) and exercise efficiency (-1.6{+/-}2.4%; p=0.52) were not significantly changed. However, EEDLW was 209{+/-}83 kcal/d higher during the KD (p=0.023) but was not significantly increased when adjusted for energy balance (EEDLW{Delta}RQ =139{+/-}89 kcal/d; p=0.14). After removing 2 outliers whose EEDLW were incompatible with other data, EEDLW and EEDLW{triangleup}RQ were marginally increased during the KD by 126{+/-}62 kcal/d (p=0.063) and 46{+/-}65 kcal/d (p=0.49), respectively.\n\nConclusionsDLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that very low carbohydrate diets substantially increase energy expenditure.

physiology↗