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Biology subjects

Ebrahimi, E.

Publications and source records attributed to Ebrahimi, E..

5 recordsLinked to original sources

Trends in stomatal density and size in maize hybrids representing 100 years of long-term breeding for yield

Maize hybrid breeding started over 100 years ago, has increased yield and vigor through improved genetics in conjunction with increased fertilizer and pesticide use, planting density, and agricultural mechanization. Stomata are expected to change in response to rising atmospheric CO2 concentration and average temperature anomalies ({degrees}C). Yet, the impact of long-term maize breeding over the past century on stomatal traits and their responses to climate factors remains poorly understood. We evaluated stomatal traits at the seedling stage in 27 maize hybrids released from 1920 to 2022, grown under controlled conditions. Modern hybrids (2013 - 2022) had a smaller total stomatal pore area (9.17 x 108 m2) than (1920 - 2012) historical ERA hybrids (9.94 x 108 m2; p[≤] 0.001), a higher stomatal density (47.2 per mm-2) vs. historical ERA hybrids (44.5), and a smaller leaf area (17.9 cm2 vs. 20.5 cm2). No significant differences were found in the size (m2), length (m), or width (m) of stomata between the two groups. Stomatal density increased, while all other traits decreased in modern hybrids. Stomatal density was negatively correlated with stomatal size (r = -0.62), length (r = -0.57), width (r = - 0.54), and leaf area (r = -0.54). Stomatal size had a negative correlation with atmospheric CO2 concentration (r = -0.22) and average temperature anomalies ({degrees}C) (r = -0.35) in the hybrids year of release and climate proxies. In contrast, stomatal density had a positive correlation with both atmospheric CO2 concentration and average temperature anomalies ({degrees}C) (r = 0.44) in year of release. Total stomatal pore area negatively correlated with atmospheric CO2 concentration (r = -0.45) and average temperature anomalies ({degrees}C) (r = -0.36). Our study indicates that maize stomatal traits suggest inadvertent selection for key stomatal traits (density and size), total stomatal pore area (per year decline of about 0.02%) associated with yield stability and environmental adaptation. HighlightsMaize stomatal traits changed through environmental (CO2 and {degrees}C) adaptation but total stomatal pore area, effects indirectly by decreased leaf area in maize hybrids representing 100 years of long-term breeding for yield. A negative correlation was observed across 27 ERA hybrids between stomatal density and stomatal size, length, width and leaf area. Stomatal density increases while stomata size, length width and leaf area decrease per se. Over the past 100 years, the total stomatal pore area on leaves decreased, while stomatal density increased as leaf area declined, revealing a connection between these two patterns. A negative correlation was found between total stomatal pore area and atmospheric CO2 concentrations, and temperature over the past century.

genetics↗

P3 site-directed mutagenesis: An efficient method based on primer pairs with 3-prime overhangs

Site-directed mutagenesis is a fundamental tool indispensable for protein and plasmid engineering. An important technological question is how to achieve the efficiency at the ideal level of 100%. Based on complementary primer pairs, the QuickChange method has been widely used, but it requires significant improvements due to its low efficiency and frequent unwanted mutations. An alternative and innovative strategy is to utilize primer pairs with 3-prime overhangs, but this approach has not been fully developed. As the first step towards reaching the efficiency of 100%, we have optimized this approach systematically (such as use of newly designed short primers, test of different Pfu DNA polymerases and modification of PCR parameters) and evaluated the resulting method extensively with over 100 mutations on 12 mammalian expression vectors, ranging from 7.0-13.4 kb in size and encoding ten epigenetic regulators with links to cancer and neurodevelopmental disorders. We have also tested the new method with two expression vectors for the SARS-COV-2 spike protein. Compared to the QuickChange method, the success rate has increased substantially, with an average efficiency of [~]50%, with some at or close to 100 percent, and requiring much less time for engineering various mutations. Therefore, we have developed a new site-directed mutagenesis method for efficient and economical generation of various mutations. Notably, the method failed with a human KAT2B expression plasmid that possesses extremely GC-rich sequences. Thus, this study also sheds light on how to improve the method for developing ideal mutagenesis methods with the efficiency at [~]100% for a wide spectrum of plasmids.

molecular biology↗

Protein Language Models in Directed Evolution

The dominant paradigms for integrating machine-learning into protein engineering are de novo protein design and guided directed evolution. Guiding directed evolution requires a model of protein fitness, but most models are only evaluated in silico on datasets comprising few mutations. Due to the limited number of mutations in these datasets, it is unclear how well these models can guide directed evolution efforts. We demonstrate in vitro how zero-shot and few-shot protein language models of fitness can be used to guide two rounds of directed evolution with simulated annealing. Our few-shot simulated annealing approach recommended enzyme variants with 1.62 x improved PET degradation over 72 h period, outperforming the top engineered variant from the literature, which was 1.40 x fitter than wild-type. In the second round, 240 in vitro examples were used for training, 32 homologous sequences were used for evolutionary context and 176 variants were evaluated for improved PET degradation, achieving a hit-rate of 39 % of variants fitter than wild-type.

bioinformatics↗

Cell dichotomous role of STING in pulmonary hypertension

RationalePatients with constitutive activation of DNA sensing pathway through stimulator of interferon genes (STING), such as those with STING-Associated Vasculopathy with onset in Infancy (SAVI), frequently have complications related to pulmonary hypertension (PH). However, the role of STING-signaling in adult PH patients is heretofore undescribed. ObjectiveTo investigate the role of STING in PH development. Methods and ResultsPH was induced in global STING deficient or cell-specific STING deficient mice using either bleomycin or chronic hypoxia exposure. PH development was evaluated with right ventricular systolic pressure, Fulton index, histological and flow cytometric measurements. STING expression in patient lungs were examined using both immunohistochemistry and flow cytometry. Herein, we describe how STING overactivation in a SAVI mouse model results in a baseline elevation in pulmonary pressures, while global STING deficiency protects mice from PH development. Furthermore, STING-associated PH appears to be independent of type I Interferon (IFN) signaling. We further demonstrate a cellular dichotomous role of STING in PH development with STING expression by smooth muscle cells contributing to PH, and its activation on myeloid cells being pivotal in severe disease prevention. Finally, we demonstrate a STING-PD-L1 axis as necessary for disease progression, suggesting future potential therapeutic applications. ConclusionsOverall, these data provide concrete evidence of STING involvement in PH, establishing biologic plausibility for STING-related therapies in PH treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/518422v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@7f5b50org.highwire.dtl.DTLVardef@143e485org.highwire.dtl.DTLVardef@4fe1a4org.highwire.dtl.DTLVardef@66fe26_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Defining the age-dependent and tissue-specific circadian transcriptome in male mice

Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence supports age-associated changes in circadian functions. To define age-dependent changes at the systems level, we profiled the circadian transcriptome in the hypothalamus, lung, heart, kidney, skeletal muscle, and adrenal gland in 3 age groups. We found age-dependent and tissue-specific clock output changes. Aging reduced the number of rhythmically expressed genes (REGs), indicative of weakened circadian control. Many genes gained rhythmicity in old tissues, reflecting an adaptive response. REGs were enriched for the hallmarks of aging, adding a new dimension to our understanding of aging. Differential gene expression analysis found that there were temporally distinct clusters of genes in tissue-specific manner. Increased daily gene expression variability is a common feature of aged tissues. This novel analysis extends the landscape of the understanding of aging and highlights the impact of aging on circadian clock function and temporal changes in gene expression. HIGHLIGHTS- Rhythmically expressed genes (REGs) in Young, but not Old mice, are enriched for the aging hallmarks across all tissues. - The numbers of REGs decline across all tissues with age implicating the circadian clock in altered homeostasis. - Age- and tissue-specific differentially expressed genes (DEGs) cluster at specific times of the day. - Increase in gene expression variability over a day is a common feature of aging tissues.

genomics↗