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1. Construction and applications of a B vitamin genetic resource for investigation of vitamin‐dependent metabolism in maize

   https://doi.org/10.1111/tpj.14535  

   Suzuki, Masaharu; Wu, Shan; Mimura, Manaki; Alseekh, Saleh; Fernie, Alisdair R.; Hanson, Andrew D.; McCarty, Donald R. (November 2019, The Plant Journal)

   Summary The B vitamins provide essential co‐factors for central metabolism in all organisms. In plants, B vitamins have surprising emerging roles in development, stress tolerance and pathogen resistance. Hence, there is a paramount interest in understanding the regulation of vitamin biosynthesis as well as the consequences of vitamin deficiency in crop species. To facilitate genetic analysis of B vitamin biosynthesis and functions in maize, we have mined the UniformMu transposon resource to identify insertional mutations in vitamin pathway genes. A screen of 190 insertion lines for seed and seedling phenotypes identified mutations in biotin, pyridoxine and niacin biosynthetic pathways. Importantly, isolation of independent insertion alleles enabled genetic confirmation of genotype‐to‐phenotype associations. Because B vitamins are essential for survival, null mutations often have embryo lethal phenotypes that prevent elucidation of subtle, but physiologically important, metabolic consequences of sub‐optimal (functional) vitamin status. To circumvent this barrier, we demonstrate a strategy for refined genetic manipulation of vitamin status based on construction of heterozygotes that combine strong and hypomorphic mutant alleles. Dosage analysis ofpdx2alleles in endosperm revealed that endosperm supplies pyridoxine to the developing embryo. Similarly, a hypomorphicbio1allele enabled analysis of transcriptome and metabolome responses to incipient biotin deficiency in seedling leaves. We show that systemic pipecolic acid accumulation is an early metabolic response to sub‐optimal biotin status highlighting an intriguing connection between biotin, lysine metabolism and systemic disease resistance signaling. Seed‐stocks carrying insertions for vitamin pathway genes are available for free, public distribution via the Maize Genetics Cooperation Stock Center. 

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2. Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1

   https://doi.org/10.3390/cancers15133432  

   Khazan, Negar; Quarato, Emily R.; Singh, Niloy A.; Snyder, Cameron W.; Moore, Taylor; Miller, John P.; Yasui, Masato; Teramoto, Yuki; Goto, Takuro; Reshi, Sabeeha; et al (July 2023, Cancers)

   Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential. 

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3. Understanding the Retention of Vaping Additives in the Lungs: Model Lung Surfactant Membrane Perturbation by Vitamin E and Vitamin E Acetate

   https://doi.org/10.1021/acs.langmuir.3c02952  

   Taktikakis, Panagiota; Côté, Mathieu; Subramaniam, Nivetha; Kroeger, Kailen; Youssef, Hala; Badia, Antonella; DeWolf, Christine (March 2024, Langmuir)
4. Cross-kingdom vitamin B5 biosynthesis and cyst nematode susceptibility

   https://doi.org/10.1016/j.pt.2022.11.004  

   Li, Min; Guo, Baodian; Liu, Fengquan; Fu, Zheng Qing (January 2023, Trends in Parasitology)
5. Influence of vitamin B12 availability on oceanic dimethylsulfide and dimethylsulfoniopropionate

   https://doi.org/10.1071/EN15043  

   Lee, Peter A.; Bertrand, Erin M.; Saito, Mak A.; DiTullio, Giacomo R. (January 2016, Environmental Chemistry)

   Environmental contextCobalamin, or vitamin B12, is receiving increased attention as a critical trace nutrient in the growth and metabolic processes of oceanic phytoplankton and bacterial communities. We present evidence that indicates B12 has a more significant role in the biogeochemical cycling of the climatically important compounds dimethylsulfide and dimethylsulfoniopropionate than previously understood. Several possible mechanisms are examined that link cellular-level processes involving B12 to global-scale biogeochemical processes involving the oceanic cycling of dimethylsulfoniopropionate and dimethylsulfide.AbstractEvidence is presented showing that dissolved dimethylsulfoniopropionate (DMSPd) and dimethylsulfide (DMS) concentrations are influenced by the availability of vitamin B12 in two oceanographically distinct regions with different DMS production capacities, the central equatorial Pacific Ocean and the Ross Sea, Antarctica. In both locations, addition of B12 to incubation experiments resulted in decreases in DMS and, in some cases, DMSPd concentrations relative to unamended controls. In no case did increasing iron availability significantly (α=0.1) alter DMS concentrations relative to controls. The relative decreases in DMS between B12 addition and control experiments were significant (α=0.1) in five of seven experiments conducted at ambient iron levels. Overall, DMS concentrations were on average 33.4% (±15.1%; 1 standard deviation) lower, relative to unamended controls, by the end of incubation experiments when B12 was added. Declines in DMSPd were observed in three of five experiments. Similar trends were observed when B12 was added to iron-supplemented bottle incubation experiments (30.4±10.4% lower final DMS concentrations in +B12Fe treatments relative to +Fe treatments). Several possible molecular-level explanations exist for this link between B12 and DMS production, including potential B12 dependence of methyltransferase enzymes involved in both DMS and DMSP degradation. Although the enzymology of these reactions remains unclear, the relationships described here provide evidence for plausible mechanisms behind the microbial modulation of oceanic DMS. 

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