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Author: Grafiati

Published: 25 July 2024

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1

Sun, Xueqin, Xinghua Diao, Xiaolin Zhu, Xuexue Yin, and Guangying Cheng. "Nanog-mediated stem cell properties are critical for MBNL3-associated paclitaxel resistance of ovarian cancer." Journal of Biochemistry 169, no. 6 (February 18, 2021): 747–56. http://dx.doi.org/10.1093/jb/mvab021.

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Abstract Paclitaxel (PTX) is the standard first-line treatment of ovarian cancer, but its efficacy is limited by multidrug resistance. Therefore, it is crucial to identify effective drug targets to facilitate PTX sensitivity for ovarian cancer treatment. Seventy PTX-administrated ovarian cancer patients were recruited in this study for gene expression and survival rate analyses. Muscleblind-like-3 (MBNL3) gain-of-function and loss-of-function experiments were carried out in ovarian cancer cells (parental and PTX-resistant) and xenograft model. Cancer cell viability, apoptosis, spheroids formation, Nanog gene silencing were examined and conducted to dissect the underlying mechanism of MBNL3-mediated PTX resistance. High expression of MBNL3 was positively correlated with PTX resistance and poor prognosis of ovarian cancer. MBNL3 increased cell viability and decreased apoptosis in ovarian stem-like cells, through upregulating Nanog. This study suggests the MBNL3-Nanog axis is a therapeutic target for the treatment of PTX resistance in ovarian cancer management.

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2

Holm, Frida, Eva Hellqvist, Cayla N. Mason, Shawn A. Ali, Nathaniel Delos-Santos, Christian L. Barrett, Hye-Jung Chun, et al. "Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal." Proceedings of the National Academy of Sciences 112, no. 50 (November 30, 2015): 15444–49. http://dx.doi.org/10.1073/pnas.1506943112.

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Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse model studies demonstrated that malignant reprogramming of progenitors into self-renewing blast crisis chronic myeloid leukemia stem cells (BC LSCs) was partially driven by decreased MBNL3. Lentiviral knockdown of MBNL3 resulted in reversion to an embryonic alternative splice isoform program typified by overexpression of CD44 transcript variant 3, containing variant exons 8–10, and BC LSC proliferation. Although isoform-specific lentiviral CD44v3 overexpression enhanced chronic phase chronic myeloid leukemia (CML) progenitor replating capacity, lentiviral shRNA knockdown abrogated these effects. Combined treatment with a humanized pan-CD44 monoclonal antibody and a breakpoint cluster region - ABL proto-oncogene 1, nonreceptor tyrosine kinase (BCR-ABL1) antagonist inhibited LSC maintenance in a niche-dependent manner. In summary, MBNL3 down-regulation–related reversion to an embryonic alternative splicing program, typified by CD44v3 overexpression, represents a previously unidentified mechanism governing malignant progenitor reprogramming in malignant microenvironments and provides a pivotal opportunity for selective BC LSC detection and therapeutic elimination.

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3

Guendouz, Dj, Z. Charifi, H. Baaziz, T. Ghellab, N. Arikan, Ş. Uğur, and G. Uğur. "Electronic structure, optical and thermodynamic properties of ternary hydrides MBeH3 (M = Li, Na, and K)." Canadian Journal of Physics 94, no. 9 (September 2016): 865–76. http://dx.doi.org/10.1139/cjp-2016-0299.

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Electronic band structure, optical and thermodynamic properties of ternary hydrides MBeH3 (M = Li, Na, and K) were studied using ab initio density functional theory (DFT). The effect of the adopted approximation to the exchange-correlation functional of the DFT is explicitly investigated by considering four different expressions of two different classes (local-density approximation and generalized-gradient approximation). The calculated magnitude of B classifies MBeH3 (M = Li, Na, and K) as easily compressible materials. The bonding interaction in these compounds is quite complicated. The interaction between M and BeH6 is ionic and that between Be and H comprises both ionic and covalent characters. The electronic structure of the complex hydride was investigated by calculating the partial and total densities of states, and electron charge density distribution. Large gaps in the density of states appear at the Fermi energy of LiBeH3, NaBeH3, and KBeH3 indicating that these classes of hydrides are insulators. Optical properties, including the dielectric function, reflectivity, and absorption coefficient, each as a function of photon energy, are calculated and show an optical anisotropy for LiBeH3 and KBeH3. Through the quasi-harmonic Debye model, in which the phononic effects are considered, temperature dependence of volume V(T), bulk modulus B(T), and thermal expansion coefficient α(T), constant-volume and constant-pressure specific heat (Cv and Cp) and Debye temperature ΘD, the entropy S, and the Grüneisen parameter γ were calculated at wide pressure and temperature ranges. The principal aspect of the obtained results is the close similarity of MBeH3 (M = Li, Na, and K) compounds.

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4

Manesis, Anastasia C., Richard J. Jodts, Brian M. Hoffman, and Amy C. Rosenzweig. "Copper binding by a unique family of metalloproteins is dependent on kynurenine formation." Proceedings of the National Academy of Sciences 118, no. 23 (June 1, 2021): e2100680118. http://dx.doi.org/10.1073/pnas.2100680118.

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Some methane-oxidizing bacteria use the ribosomally synthesized, posttranslationally modified natural product methanobactin (Mbn) to acquire copper for their primary metabolic enzyme, particulate methane monooxygenase. The operons encoding the machinery to biosynthesize and transport Mbns typically include genes for two proteins, MbnH and MbnP, which are also found as a pair in other genomic contexts related to copper homeostasis. While the MbnH protein, a member of the bacterial diheme cytochrome c peroxidase (bCcP)/MauG superfamily, has been characterized, the structure and function of MbnP, the relationship between the two proteins, and their role in copper homeostasis remain unclear. Biochemical characterization of MbnP from the methanotroph Methylosinus trichosporium OB3b now reveals that MbnP binds a single copper ion, present in the +1 oxidation state, with high affinity. Copper binding to MbnP in vivo is dependent on oxidation of the first tryptophan in a conserved WxW motif to a kynurenine, a transformation that occurs through an interaction of MbnH with MbnP. The 2.04-Å-resolution crystal structure of MbnP reveals a unique fold and an unusual copper-binding site involving a histidine, a methionine, a solvent ligand, and the kynurenine. Although the kynurenine residue may not serve as a CuI primary-sphere ligand, being positioned ∼2.9 Å away from the CuI ion, its presence is required for copper binding. Genomic neighborhood analysis indicates that MbnP proteins, and by extension kynurenine-containing copper sites, are widespread and may play diverse roles in microbial copper homeostasis.

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5

Wang, Xianxian, Yanchao Cai, Xiucheng Liu, and Cunfu He. "Quantitative Prediction of Surface Hardness in Cr12MoV Steel and S136 Steel with Two Magnetic Barkhausen Noise Feature Extraction Methods." Sensors 24, no. 7 (March 23, 2024): 2051. http://dx.doi.org/10.3390/s24072051.

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The correlation between magnetic Barkhausen noise (MBN) features and the surface hardness of two types of die steels (Cr12MoV steel and S136 steel in Chinese standards) was investigated in this study. Back-propagation neural network (BP-NN) models were established with MBN magnetic features extracted by different methods as the input nodes to realize the quantitative prediction of surface hardness. The accuracy of the BP-NN model largely depended on the quality of the input features. In the extraction process of magnetic features, simplifying parameter settings and reducing manual intervention could significantly improve the stability of magnetic features. In this study, we proposed a method similar to the magnetic Barkhausen noise hysteresis loop (MBNHL) and extracted features. Compared with traditional MBN feature extraction methods, this method simplifies the steps of parameter setting in the feature extraction process and improves the stability of the features. Finally, a BP-NN model of surface hardness was established and compared with the traditional MBN feature extraction methods. The proposed MBNHL method achieved the advantages of simple parameter setting, less manual intervention, and stability of the extracted parameters at the cost of small accuracy reduction.

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6

Holm, Frida Linnea, Eva Hellqvist, Cayla N. Mason, Shawn Ali, Nathaniel Delos Santos, Christian Barrett, Hye-Jung Chun, et al. "Reversion to an Embryonic Alternative Splicing Program Enhances Leukemia Stem Cell Self-Renewal." Blood 126, no. 23 (December 3, 2015): 1227. http://dx.doi.org/10.1182/blood.v126.23.1227.1227.

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Abstract Background Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. However, its role in malignant reprogramming of progenitors into self-renewing leukemia stem cells (LSCs) had not been established. Methods Whole transcriptome RNA sequencing (RNA-seq) was performed on FACS purified progenitors from normal, chronic phase and blast crisis chronic myeloid leukemia samples and analyzed using Cuff-links, GSEA and IPA software. Splice isoform specific qRT-PCR, confocal microscopy, lentiviral overexpression and shRNA knockdown experiments were performed according to published methods (Jamieson NEJM 2004; Geron et al Cancer Cell 2008; Goff et al Cell Stem Cell 2013). Results We performed LSC RNA-seq, lentiviral overexpression and knockdown and discovered that decreased expression of MBNL3, a repressor of an embryonic alternative splicing program and reprogramming, activated a pluripotency network and increased expression of a pro-survival isoform of CD44v3, which is more commonly expressed in human embryonic stem cells. This resulted in malignant reprogramming of progenitors in blast crisis CML endowing them with unbridled survival and self-renewal capacity. This is the first description of MBNL3 downregulation as a mechanism of reversion to an embryonic alternative splicing program, which elicits malignant progenitor reprogramming of progenitors into self-renewing leukemia stem cells. While isoform specific lentiviral CD44v3 overexpression enhanced chronic phase CML progenitor replating capacity, lentiviral shRNA knockdown abrogated these effects. In keeping with activation of a stem cell reprogramming network, CD44v3 upregulation was associated with increased expression of pluripotency transcription factors, including OCT4, SOX2 and b-catenin in addition to the pro-survival long isoforms of MCL1 and BCLX resulting in increased self-renewal and apoptosis resistance. Conclusion In summary, MBNL3 downregulation activates an embryonic alternative splicing program, typified by CD44v3 overexpression, and represents a novel mechanism governing LSC generation in malignant microenvironments. Reversal of malignant reprogramming by epigenetic modulation of embryonic alternative splicing or via monoclonal antibody targeting of CD44v3 splice isoform may represent a pivotal opportunity for selective BC LSC eradication. Disclosures Jamieson: Johnson & Johnson: Research Funding; GlaxoSmithKline: Research Funding.

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Kanadia, Rahul N., Carl R. Urbinati, Valerie J. Crusselle, Defang Luo, Young-Jae Lee, Jeffrey K. Harrison, S. Paul Oh, and Maurice S. Swanson. "Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3." Gene Expression Patterns 3, no. 4 (August 2003): 459–62. http://dx.doi.org/10.1016/s1567-133x(03)00064-4.

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8

Lee, Kyung-Soon, Kimberly Smith, Paul S. Amieux, and Edith H. Wang. "MBNL3/CHCR prevents myogenic differentiation by inhibiting MyoD-dependent gene transcription." Differentiation 76, no. 3 (March 2008): 299–309. http://dx.doi.org/10.1111/j.1432-0436.2007.00209.x.

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9

Grammatikakis, Ioannis, Young-Hwa Goo, Gloria V. Echeverria, and Thomas A. Cooper. "Identification of MBNL1 and MBNL3 domains required for splicing activation and repression." Nucleic Acids Research 39, no. 7 (November 24, 2010): 2769–80. http://dx.doi.org/10.1093/nar/gkq1155.

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10

Helbing, Jan. "Spin state transitions upon visible and infrared excitation of ferric MbN3." Chemical Physics 396 (March 2012): 17–22. http://dx.doi.org/10.1016/j.chemphys.2011.04.001.

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Kenney, Grace E., Laura M. K. Dassama, Anastasia C. Manesis, Matthew O. Ross, Siyu Chen, Brian M. Hoffman, and Amy C. Rosenzweig. "MbnH is a diheme MauG-like protein associated with microbial copper homeostasis." Journal of Biological Chemistry 294, no. 44 (September 11, 2019): 16141–51. http://dx.doi.org/10.1074/jbc.ra119.010202.

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Lin, Jian, Ya T. Chen, Jing Xia, and Qian Yang. "MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3." Oncotarget 7, no. 31 (June 6, 2016): 48978–94. http://dx.doi.org/10.18632/oncotarget.9832.

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Wulsin, Lawson R., Lesley M. Arnold, and J. Randolph Hillard. "Axis I Disorders in Er Patients with Atypical Chest Pain." International Journal of Psychiatry in Medicine 21, no. 1 (March 1991): 37–46. http://dx.doi.org/10.2190/hfq4-j41n-6m1e-mbn3.

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14

Vajeeston, P., P. Ravindran, and H. Fjellvåg. "Structural Phase Stability Studies on MBeH3(M = Li, Na, K, Rb, Cs) from Density Functional Calculations." Inorganic Chemistry 47, no. 2 (January 2008): 508–14. http://dx.doi.org/10.1021/ic7015897.

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15

Lee, Kyung-Soon, Yi Cao, Hanna E. Witwicka, Susan Tom, Stephen J. Tapscott, and Edith H. Wang. "RNA-binding Protein Muscleblind-like 3 (MBNL3) Disrupts Myocyte Enhancer Factor 2 (Mef2) β-Exon Splicing." Journal of Biological Chemistry 285, no. 44 (August 13, 2010): 33779–87. http://dx.doi.org/10.1074/jbc.m110.124255.

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16

Bhutani, Namita, Rajat Maheshwari, Monika Negi, and Pooja Suneja. "Optimization of IAA production by endophytic Bacillus spp. from Vigna radiata for their potential use as plant growth promoters." Israel Journal of Plant Sciences 65, no. 1-2 (July 16, 2018): 83–96. http://dx.doi.org/10.1163/22238980-00001025.

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Endophytic bacteria isolated from nodules of Vigna radiata were screened for indole acetic acid (IAA) production. Three isolates MBN3, MJHN1 and MJHN10, molecularly identified as Bacillus aryabhattai (MF693121.1), B. megaterium (MF693120.1) and B. cereus (MF693119.1) were producing significantly high amount of IAA. Production parameters viz. L-tryptophan concentration, incubation time, carbon and nitrogen sources were optimized. The study revealed the presence of trp-dependent pathway for IAA production in the isolates. All of them gave maximum production with yeast extract as nitrogen source but variation in preference for carbon sources was observed. The invitro application of bacterial isolates on plant roots resulted in increase in root length as well as number of lateral roots. These results confirm the occurrence of Bacillus as predominant non-rhizobial endophytic genera in summer season crop and its potential as plant root growth promoter.

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Yu, Zhanwu, Gebang Wang, Chenlei Zhang, Yu Liu, Wei Chen, Haoyou Wang, and Hongxu Liu. "LncRNA SBF2-AS1 affects the radiosensitivity of non-small cell lung cancer via modulating microRNA-302a/MBNL3 axis." Cell Cycle 19, no. 3 (January 13, 2020): 300–316. http://dx.doi.org/10.1080/15384101.2019.1708016.

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18

Yuan, Ji-hang, Xiao-ning Liu, Tian-tian Wang, Wei Pan, Qi-fei Tao, Wei-ping Zhou, Fang Wang, and Shu-han Sun. "The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1." Nature Cell Biology 19, no. 7 (May 29, 2017): 820–32. http://dx.doi.org/10.1038/ncb3538.

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19

Maasalu, Katre, Ott Laius, Lidiia Zhytnik, Sulev Kõks, Ele Prans, Ene Reimann, and Aare Märtson. "Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis." Experimental Biology and Medicine 242, no. 2 (November 20, 2016): 203–13. http://dx.doi.org/10.1177/1535370216679899.

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Osteoporosis is a disorder associated with bone tissue reorganization, bone mass, and mineral density. Osteoporosis can severely affect postmenopausal women, causing bone fragility and osteoporotic fractures. The aim of the current study was to compare blood mRNA profiles of postmenopausal women with and without osteoporosis, with the aim of finding different gene expressions and thus targets for future osteoporosis biomarker studies. Our study consisted of transcriptome analysis of whole blood serum from 12 elderly female osteoporotic patients and 12 non-osteoporotic elderly female controls. The transcriptome analysis was performed with RNA sequencing technology. For data analysis, the edgeR package of R Bioconductor was used. Two hundred and fourteen genes were expressed differently in osteoporotic compared with non-osteoporotic patients. Statistical analysis revealed 20 differently expressed genes with a false discovery rate of less than 1.47 × 10−4 among osteoporotic patients. The expression of 10 genes were up-regulated and 10 down-regulated. Further statistical analysis identified a potential osteoporosis mRNA biomarker pattern consisting of six genes: CACNA1G, ALG13, SBK1, GGT7, MBNL3, and RIOK3. Functional ingenuity pathway analysis identified the strongest candidate genes with regard to potential involvement in a follicle-stimulating hormone activated network of increased osteoclast activity and hypogonadal bone loss. The differentially expressed genes identified in this study may contribute to future research of postmenopausal osteoporosis blood biomarkers.

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Balsara, Rashna D., and Vasudha P. Joshi. "Molecular Basis of UV-Sensitive Mutant Strain MBH3 of Haemophilus Influenzae Rd: Identification of Mutation in the uvrA Gene." Journal of Environmental Pathology, Toxicology and Oncology 20, no. 1 (2001): 6. http://dx.doi.org/10.1615/jenvironpatholtoxicoloncol.v20.i1.50.

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Negrón-Pérez, Verónica M., Yanping Zhang, and Peter J. Hansen. "Single-cell gene expression of the bovine blastocyst." Reproduction 154, no. 5 (November 2017): 627–44. http://dx.doi.org/10.1530/rep-17-0345.

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The first two differentiation events in the embryo result in three cell types – epiblast, trophectoderm (TE) and hypoblast. The purpose here was to identify molecular markers for each cell type in the bovine and evaluate the differences in gene expression among individual cells of each lineage. The cDNA from 67 individual cells of dissociated blastocysts was used to determine transcript abundance for 93 genes implicated as cell lineage markers in other species or potentially involved in developmental processes. Clustering analysis indicated that the cells belonged to two major populations (clades A and B) with two subpopulations of clade A and four of clade B. Use of lineage-specific markers from other species indicated that the two subpopulations of clade A represented epiblast and hypoblast respectively while the four subpopulations of clade B were TE. Among the genes upregulated in epiblast were AJAP1, DNMT3A, FGF4, H2AFZ, KDM2B, NANOG, POU5F1, SAV1 and SLIT2. Genes overexpressed in hypoblast included ALPL, FGFR2, FN1, GATA6, GJA1, HDAC1, MBNL3, PDGFRA and SOX17, while genes overexpressed in all four TE populations were ACTA2, CDX2, CYP11A1, GATA2, GATA3, IFNT, KRT8, RAC1 and SFN. The subpopulations of TE varied among each other for multiple genes including the prototypical TE marker IFNT. New markers for each cell type in the bovine blastocyst were identified. Results also indicate heterogeneity in gene expression among TE cells. Further studies are needed to confirm whether subpopulations of TE cells represent different stages in the development of a committed TE phenotype.

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Geng, Qiaohong, and Peifu Jiao. "Anti-PD-L1-Based Bispecific Antibodies Targeting Co-Inhibitory and Co-Stimulatory Molecules for Cancer Immunotherapy." Molecules 29, no. 2 (January 17, 2024): 454. http://dx.doi.org/10.3390/molecules29020454.

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Targeting PD-L1 via monospecific antibodies has shown durable clinical benefits and long-term remissions where patients exhibit no clinical cancer signs for many years after treatment. However, the durable clinical benefits and long-term remissions by anti-PD-L1 monotherapy have been limited to a small fraction of patients with certain cancer types. Targeting PD-L1 via bispecific antibodies (referred to as anti-PD-L1-based bsAbs) which can simultaneously bind to both co-inhibitory and co-stimulatory molecules may increase the durable antitumor responses in patients who would not benefit from PD-L1 monotherapy. A growing number of anti-PD-L1-based bsAbs have been developed to fight against this deadly disease. This review summarizes recent advances of anti-PD-L1-based bsAbs for cancer immunotherapy in patents and literatures, and discusses their anti-tumor efficacies in vitro and in vivo. Over 50 anti-PD-L1-based bsAbs targeting both co-inhibitory and co-stimulatory molecules have been investigated in biological testing or in clinical trials since 2017. At least eleven proteins, such as CTLA-4, LAG-3, PD-1, PD-L2, TIM-3, TIGIT, CD28, CD27, OX40, CD137, and ICOS, are involved in these investigations. Twenty-two anti-PD-L1-based bsAbs are being evaluated to treat various advanced cancers in clinical trials, wherein the indications include NSCLC, SNSCLC, SCLC, PDA, MBNHL, SCCHN, UC, EC, TNBC, CC, and some other malignancies. The released data from clinical trials indicated that most of the anti-PD-L1-based bsAbs were well-tolerated and showed promising antitumor efficacy in patients with advanced solid tumors. However, since the approved and investigational bsAbs have shown much more significant adverse reactions compared to PD-L1 monospecific antibodies, anti-PD-L1-based bsAbs may be further optimized via molecular structure modification to avoid or reduce these adverse reactions.

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Gao, Xiaoling, Wenhao Zhang, Yanjuan Jia, Hui Xu, Yuchen Zhu, and Xiong Pei. "Identification of a prognosis-related ceRNA network in cholangiocarcinoma and potentially therapeutic molecules using a bioinformatic approach and molecular docking." Scientific Reports 12, no. 1 (September 28, 2022). http://dx.doi.org/10.1038/s41598-022-20362-w.

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AbstractCholangiocarcinoma (CCA) is a highly malignant disease with a poor prognosis, and mechanisms of initiation and development are not well characterized. It is long noncoding RNAs (lncRNAs) acting as miRNA decoys to regulate cancer-related RNAs in competing endogenous RNA (ceRNA) networks that suggest a possible molecular mechanism in CCA. The current study aims to find potential prognosis biomarkers and small molecule therapeutic targets based on the construction of a CCA prognosis-related ceRNA network. A transcriptome dataset for CCA was downloaded from the TCGA database. Differentially expressed lncRNAs (DElncRNAs), DEmiRNAs and DEmRNAs were identified based on the differential expression and a DEceRNA network was constructed using predicted miRNA-lncRNA and miRNA-mRNA interactions. Heat maps, PCA analysis, and Pathway enrichment analysis and GO enrichment analysis were conducted. The prognostic risk model and molecular docking were constructed based on identified key ceRNA networks. A DElncRNA-miRNA-mRNAs network consisting of 434 lncRNA-miRNA pairs and 284 miRNA-mRNA pairs with 200 lncRNAs, 21 miRNAs, and 245 mRNAs was constructed. There were three lncRNAs (AC090772.1, LINC00519, and THAP7-AS1) and their downstream mRNAs (MECOM, MBNL3, RCN2) screened out as prognostic factors in CAA. Three key networks (LINC00519/ hsa-mir-22/ MECOM, THAP7-AS1/hsa-mir-155/MBNL3, and THAP7-AS1/hsa-mir-155/RCN2) were identified based on binding sites prediction and survival analysis. A prognostic risk model was established with a good predictive ability (AUC = 0.66–0.83). Four anticancer small molecules, MECOM and 17-alpha-estradiol (−7.1 kcal/mol), RCN2 and emodin (−8.3 kcal/mol), RCN2 and alpha-tocopherol (−5.6 kcal/mol), and MBNL3 and 17-beta-estradiol (−7.1 kcal/mol) were identified. Based on the DEceRNA network and Kaplan–Meier survival analysis, we identified three important ceRNA networks associated with the poor prognosis of CCA. Four anti-cancer small molecules were screened out by computer-assisted drug screening as potential small molecules for the treatment of CCA. This study provides theoretical support for the development of ceRNA network-based drugs to improve the prognosis of CCA.

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Park, Seongchul, Jooyoung Kim, and Manho Lim. "Photoexcitation dynamics of azide ion bound ferric myoglobin probed by femtosecond infrared spectroscopy." Bulletin of the Korean Chemical Society, November 29, 2023. http://dx.doi.org/10.1002/bkcs.12803.

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AbstractThe photoexcitation dynamics of N3−‐bound ferric myoglobin (MbN3) were investigated after exciting MbN3 in D2O at 283 K with a 575 nm pulse by probing the anti‐symmetric stretching mode of the azide. Global fitting of the overall time‐resolved spectra revealed that thermal relaxation of two stretching bands proceeded with a time constant of 6 ps, and that a new absorption band formed and decayed with time constants of 0.6 and 23 ps, respectively. The new absorption near 2040 cm−1 was attributed to the high‐spin species 2.4 kJ/mol above the low‐spin species, as the excited low‐spin relaxes thermally via the high‐spin species. However, this absorption could also arise from deligated N3̄ remaining within the protein. The decay of this absorption can be interpreted as either spin transition of the high‐spin species into the low‐spin species or geminate recombination of the dissociated N3̄. The implications of both interpretations are discussed.

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Oladimeji, Peter O., Jesse Bakke, William C. Wright, and Taosheng Chen. "KANSL2 and MBNL3 are regulators of pancreatic ductal adenocarcinoma invasion." Scientific Reports 10, no. 1 (January 30, 2020). http://dx.doi.org/10.1038/s41598-020-58448-y.

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Manesis, Anastasia C., Jeffrey W. Slater, Kenny Cantave, J. Martin Bollinger, Carsten Krebs, and Amy C. Rosenzweig. "Capturing a bis-Fe(IV) State in Methylosinus trichosporium OB3b MbnH." Biochemistry, February 22, 2023. http://dx.doi.org/10.1021/acs.biochem.3c00021.

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Vajeeston, P., P. Ravindran, and H. Fjellvaag. "ChemInform Abstract: Structural Phase Stability Studies on MBeH3(M: Li, Na, K, Rb, Cs) from Density Functional Calculations." ChemInform 39, no. 12 (March 18, 2008). http://dx.doi.org/10.1002/chin.200812003.

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Hinman, Melissa N., Jared I. Richardson, Rose A. Sockol, Eliza D. Aronson, Sarah J. Stednitz, Katrina N. Murray, J. Andrew Berglund, and Karen Guillemin. "Zebrafish mbnl mutants model physical and molecular phenotypes of myotonic dystrophy." Disease Models & Mechanisms 14, no. 6 (June 1, 2021). http://dx.doi.org/10.1242/dmm.045773.

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ABSTRACT The muscleblind RNA-binding proteins (MBNL1, MBNL2 and MBNL3) are highly conserved across vertebrates and are important regulators of RNA alternative splicing. Loss of MBNL protein function through sequestration by CUG or CCUG RNA repeats is largely responsible for the phenotypes of the human genetic disorder myotonic dystrophy (DM). We generated the first stable zebrafish (Danio rerio) models of DM-associated MBNL loss of function through mutation of the three zebrafish mbnl genes. In contrast to mouse models, zebrafish double and triple homozygous mbnl mutants were viable to adulthood. Zebrafish mbnl mutants displayed disease-relevant physical phenotypes including decreased body size and impaired movement. They also exhibited widespread alternative splicing changes, including the misregulation of many DM-relevant exons. Physical and molecular phenotypes were more severe in compound mbnl mutants than in single mbnl mutants, suggesting partially redundant functions of Mbnl proteins. The high fecundity and larval optical transparency of this complete series of zebrafish mbnl mutants will make them useful for studying DM-related phenotypes and how individual Mbnl proteins contribute to them, and for testing potential therapeutics. This article has an associated First Person interview with the first author of the paper.

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Zhou, Jixiang, Tuoen Liu, Hongjuan Xu, Yong Wang, and Ling Liu. "LncRNA FIRRE promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the expression of PXN through interacting with MBNL3." Biochemical and Biophysical Research Communications, July 2022. http://dx.doi.org/10.1016/j.bbrc.2022.07.099.

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Tang, Weiping, Can Huang, Bing Jiang, Junjun Lin, and Yecai Lu. "MBNL3 Acts as a Target of miR-302e to Facilitate Cell Proliferation, Invasion and Angiogenesis of Gastric Adenocarcinoma via AKT/VEGFA Pathway." Journal of Microbiology and Biotechnology, May 30, 2024. http://dx.doi.org/10.4014/jmb.2401.01027.

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Sanchez, Marie-Pierre, Clémentine Escouflaire, Aurélia Baur, Fiona Bottin, Chris Hozé, Mekki Boussaha, Sébastien Fritz, Aurélien Capitan, and Didier Boichard. "X-linked genes influence various complex traits in dairy cattle." BMC Genomics 24, no. 1 (June 19, 2023). http://dx.doi.org/10.1186/s12864-023-09438-7.

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Abstract Background The search for quantitative trait loci (QTL) affecting traits of interest in mammals is frequently limited to autosomes, with the X chromosome excluded because of its hemizygosity in males. This study aimed to assess the importance of the X chromosome in the genetic determinism of 11 complex traits related to milk production, milk composition, mastitis resistance, fertility, and stature in 236,496 cows from three major French dairy breeds (Holstein, Montbéliarde, and Normande) and three breeds of regional importance (Abondance, Tarentaise, and Vosgienne). Results Estimates of the proportions of heritability due to autosomes and X chromosome (h²X) were consistent among breeds. On average over the 11 traits, h²X=0.008 and the X chromosome explained ~ 3.5% of total genetic variance. GWAS was performed within-breed at the sequence level (~ 200,000 genetic variants) and then combined in a meta-analysis. QTL were identified for most breeds and traits analyzed, with the exception of Tarentaise and Vosgienne and two fertility traits. Overall, 3, 74, 59, and 71 QTL were identified in Abondance, Montbéliarde, Normande, and Holstein, respectively, and most were associated with the most-heritable traits (milk traits and stature). The meta-analyses, which assessed a total of 157 QTL for the different traits, highlighted new QTL and refined the positions of some QTL found in the within-breed analyses. Altogether, our analyses identified a number of functional candidate genes, with the most notable being GPC3, MBNL3, HS6ST2, and DMD for dairy traits; TMEM164, ACSL4, ENOX2, HTR2C, AMOT, and IRAK1 for udder health; MAMLD1 and COL4A6 for fertility; and NRK, ESX1, GPR50, GPC3, and GPC4 for stature. Conclusions This study demonstrates the importance of the X chromosome in the genetic determinism of complex traits in dairy cattle and highlights new functional candidate genes and variants for these traits. These results could potentially be extended to other species as many X-linked genes are shared among mammals.

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Smitchger, Jamin A., J. Bret Taylor, Michelle R. Mousel, Daniel Schaub, Jacob W. Thorne, Gabrielle M. Becker, and Brenda M. Murdoch. "Genome-wide associations with longevity and reproductive traits in U.S. rangeland ewes." Frontiers in Genetics 15 (May 27, 2024). http://dx.doi.org/10.3389/fgene.2024.1398123.

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Introduction: Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait. Characterizing genetic factors underpinning ewe longevity and related traits could result in the development of genomic selection strategies to improve the stayability of sheep through early, informed selection of replacement ewes.Methods: Towards this aim, a genome-wide association study (GWAS) was performed to identify genetic markers associated with ewe longevity, reproductive, and production traits. Traits evaluated included longevity (i.e., length of time in the flock), parity and the lifetime number of lambs born, lambs born alive, lambs weaned, and weight of lambs weaned. Ewe records from previous studies were used. Specifically, Rambouillet (n = 480), Polypay (n = 404), Suffolk (n = 182), and Columbia (n = 64) breed ewes (N = 1,130) were analyzed against 503,617 SNPs in across-breed and within-breed GWAS conducted with the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model in R.Results: The across-breed GWAS identified 25 significant SNPs and the within-breed GWAS for Rambouillet, Polypay, and Suffolk ewes identified an additional 19 significant SNPs. The most significant markers were rs411309094 (13:22,467,143) associated with longevity in across-breed GWAS (p-value = 8.3E-13) and rs429525276 (2:148,398,336) associated with both longevity (p-value = 6.4E-15) and parity (p-value = 4.8E-15) in Rambouillet GWAS. Significant SNPs were identified within or in proximity (±50 kb) of genes with known or proposed roles in reproduction, dentition, and the immune system. These genes include ALPL, ANOS1, ARHGEF26, ASIC2, ASTN2, ATP8A2, CAMK2D, CEP89, DISC1, ITGB6, KCNH8, MBNL3, MINDY4, MTSS1, PLEKHA7, PRIM2, RNF43, ROBO2, SLCO1A2, TMEM266, TNFRSF21, and ZNF804B.Discussion: This study proposes multiple SNPs as candidates for use in selection indices and suggests genes for further research towards improving understanding of the genetic factors contributing to longevity, reproductive, and production traits of ewes.

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