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Elias Lopez
Elias Lopez

Hmm Lea Set 14 Part 1 135

In the first of the onychomycosis trials (26), 60% of patients treated with TTO and 61% of patients treated with 1% clotrimazole had full or partial resolution. There were no statistically significant differences between the two treatment groups for any parameter. The second onychomycosis trial (143) compared two creams, one containing 5% TTO alone and the other containing 5% TTO and 2% butenafine, both applied three times daily for 8 weeks. The overall cure rate was 0% for patients treated with 5% TTO alone, compared to 80% for patients treated with both butenafine and TTO. Unfortunately, butenafine alone was not evaluated. The observation that TTO may be useful adjunct therapy for onychomycosis has been made by Klimmek et al. (95). However, onychomycosis is considered to be largely unresponsive to topical treatment of any kind, and a high rate of cure should therefore not be expected.

Hmm Lea Set 14 Part 1 135

Some of the movies do not fall under any of the aforementioned groups. The following list consists of television films and miniseries produced for or by Hallmark Entertainment that did not premiere on either Hallmark Channel, its sister channels, or as part of the Hallmark Hall of Fame anthology series.

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Late embryogenesis abundant (LEA) proteins are widespread in multiple types of tissues of living organisms [1, 2]. These proteins have been observed in bacteria, cyanobacteria [3], fungi and animals [1, 3] but were first discovered in mature cotton seed by researchers in 1981 [4]. As the name implies, this protein accumulates during the late stage of seed maturation. Subsequent discoveries identified the protein in other plants, such as rice, Arabidopsis thaliana, maize [1, 5, 6], etc. [7,8,9]. In plants, LEA genes express in many different tissues, such as seeds, roots, stems, and buds [10], so their potential functions are not limited to the process of seed development. Scientists have identified that LEA proteins can be induced to express and function as protectants of proteins and membranes in unique ways when cells are under stress, in particular drought and desiccation. Most LEA proteins are low-weight molecules ranging in size from 10 to 30 kD.

Seed development, a crucial part of the angiosperm life cycle, is regulated by a large intricate network involving multiple factors, including transcription, epigenes, hormones, peptides and sugar signaling regulators [16]. In general, seed development can be roughly divided into two phases, morphogenesis and maturation [17]. Of the latter phase, strong expression of LEA proteins is regarded as a clear indication of seed maturation [18, 19]. Previous studies indicate that LEA proteins might be related to seed longevity, desiccation tolerance, and viability [20,21,22,23]. A subset of LEA proteins are regulated by a network of transcription factors containing ABI3, ABI4, ABI5, EEL and DOG1, as evidenced by the down-regulation of LEA transcripts in abi3, abi5, leafy cotyledon1 and fusca3 mutants [18, 24]. The transcription factors LEC1, FUSCA3, and ABI3 are involved in fatty acid biosynthesis and lipid storage in seeds [25]. However, little evidence demonstrates that LEA proteins control seed traits directly or indirectly. This may be because most research has been focused on the contributions of LEA proteins to the tolerance of drought, heat, cold and other abiotic stresses [19, 26]. To our knowledge, only Liang et al. (2019) demonstrated that overexpression of LEA3 in Arabidopsis and Brassica napus enhanced seed, seed weight, and oil content [27]. Overall, our knowledge on how LEA proteins are involved in seed development and the lipid-regulated network still have many gaps to fill. Moreover, LEA proteins in every subfamily exhibit different functions, thus these potential functions are additional gaps of knowledge that need to be filled.

The 50 LEA genes in flax were divided into eight subfamilies. Among the subfamilies, the dehydrin subfamily has the greatest number of genes, 10, in the LuLEA family, while the LuLEA_6 subfamily has the least with 2. The distributions of the LEA_6 and dehydrin genes in flax are similar to those in A. thaliana. From multiple plant species comparisons, although some are largely occupied with LEA_4 subfamily or LEA_2 subfamilies, such as A. thaliana, B. napus, cotton (Gossypium hirsutum), tea (Camellia sinensis), dehydrin subfamily tends to share considerably part, which means dehydrin is relatively conserved and likely to provide more stable protection for cells during the evolution. Evidence shows that the LEA_6 subfamily is not found in algal and rice genomes [6, 22], which suggests LEA_6 was extended from other ancient LEA genes, and probably makes contribution to struggling with the water loss.

In flax, LEA_2 genes may only be present in chloroplasts and mitochondria, which indicates that LEA_2 may function in protecting proteins in these particular cellular organelles. There were also some LuLEA proteins in the nucleus and cytoplasm as well as cytoplasmic membranes. These results indicate that LEA proteins are widely distributed within cells, so these proteins having an important role such as protection of cellular compartments during stressful conditions is not without support. Moreover, most of our identified LuLEA proteins are hydrophilic according to their GRAVY values, which is quite similar to characterizations determined of LEA proteins in other higher plants [5, 9, 29]. Many studies have shown that the trait of high hydrophilicity is attributable to the presence of IDPs in LEA proteins, and high hydrophilicity facilitates their potential functions as protein and membrane protectants and molecular chaperones to ensure cellular survival in a variety of adverse environments.

Past studies have shown that LEA genes participate in the regulatory network of seed development [18], thus we investigated the phenotypes of seeds produced from LuLEA1-overexpressing transgenic Arabidopsis. The traits of seed weight, area and circumference were all reduced. Furthermore, fatty acid contents in seeds also declined. Based on those results, we conclude that the LEA_1 subfamily of genes negatively regulate seed size and fatty acid contents. Interestingly, Liang et al. [27] showed the opposite result: overexpression of a gene belonging to the LEA_4 subfamily, BnLEA3, could increase seed size and seed oil content in Arabidopsis. However, there is no evidence indicating the direct involvement of LEA genes in the regulatory mechanism of seed size and oil synthesis. Based on existing findings, LEA proteins are regulated by transcription factors ABI3, ABI4, ABI5 [18], and these factors have also been shown to affect seed size and lipid biosynthesis [23, 41, 42]. Thus, LEA proteins likely have a feedback relationship with these transcription factors, and different LEA families may have contrasting functions conferred by their different subfamilies to maintain a balance among functions in collectively protecting a plant.

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Somatic point mutations play a key role in tumorigenesis and the development of cancer60. Recent studies on somatic mutation evolution in cancer have identified cancer driver genes61 and mutational cancer signatures62,63,64. However, the analysis of somatic mutations has focused mainly on the protein-coding genes of the genome, and their potential impact on the non-coding RNA genes has been far less studied. ncRNAs have long been considered a non-functional part of the human genome65. However, these non-coding elements (majority lncRNAs) have recently opened a new insight into the study of breast cancer, acting as indispensable contributors to cellular activities, including the proliferation, apoptosis, survival, differentiation, and breast cancer metastasis66. In addition, ncRNAs have been used as biomarkers in many cancers, including breast cancer, through various mechanisms, including regulating the expression of protein-coding genes and functions at transcriptional, translational, and post-translational levels21,22,23,24,25. This indicates that ncRNAs may have the potential for diagnosis, prognosis, and therapeutics of cancers. This study identified ncRNAs that were mutated explicitly in breast cancer patients and then uncovered the connection between somatic point mutations in BC-associated ncRNAs and ncRNA regulatory properties in breast cancer.

This work was funded by the UNSW Scientia Program Fellowship and the Australian Research Council Discovery Early Career Researcher Award (DECRA) under grant DE220101210 to H.A.R. We kindly acknowledge the Government of Western Australia, Department of Health, Clinical Excellence, for their kind support on this project through the MERIT award to H.A.R. H.A.R is also supported by UNSW Scientia Program Fellowship. Analysis was made possible with computational resources provided by the BioMedical Machine Learning Bioinformatics Server with funding from the Australian Government and the UNSW SYDNEY. H.R.R is supported by IRN National Science Foundation (INSF) Grant No. 96006077.


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