Candidate gene analysis of watermelon stripe pattern locus ClSP ongoing recombination suppression

Abstract Stripe pattern is an important commodity trait in watermelon, displaying diverse types. In this study, two segregating populations were generated for genetic mapping the single dominant locus ClSP, which was finally delimited to a 611.78 Kb interval with suppression of recombination. According to polymorphism sites detected among genotypes, four discrete haploblocks were characterized in this target region. Based on reference genomes, 81 predicted genes were annotated in the ClSP interval, including seven transcription factors namely as candidate No1-No7. Meanwhile, the ortholog gene of cucumber ist responsible for the irregular stripes was considered as candidate No8. Strikingly, gene structures of No1-No5 completely varied from their reference descriptions and subsequently re-annotated. Notably, the adjacent distribution candidates No2 and No3, as well as No4 and No5, were confirmed to derive from longer transcripts designated as No2_3 and No4_5, respectively. Sequence analysis demonstrated the third polymorphism in CDS of re-annotated No4_5 resulting in truncated proteins in non-stripe plants. Furthermore, only No4_5 was down-regulated in non-stripes relative to stripes contrast to other candidates. Transcriptome analysis identified 356 DEGs between striped and non-striped peels, with genes involved in photosynthesis and chloroplast development down-regulated in non-stripes but calcium ion binding related genes up-regulated. Additionally, 38 DEGs were annotated as transcription factors, with the majority up-regulated in non-stripes, such as ERFs and WRKYs. This study not only contributes to a better understanding of the molecular mechanisms underlying watermelon stripe development, but also provides new insight into the genomic structure of ClSP locus and valuable candidates.

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Getting the message across, STAT! Design principles of a molecular signaling circuit

The Journal of Cell Biology ◽

10.1083/jcb.200407163 ◽

2004 ◽

Vol 167 (2) ◽

pp. 197-201 ◽

Cited By ~ 77

Author(s):

Uwe Vinkemeier

Keyword(s):

Signal Processing ◽

Transcription Factors ◽

Molecular Mechanisms ◽

Dynamic Properties ◽

Cytokine Signaling ◽

Molecular Signaling ◽

Cytoplasmic Proteins ◽

Cellular Signal ◽

Insight Into ◽

Signaling Circuit

The STAT transcription factors, usually referred to as “latent cytoplasmic proteins,” have experienced a fundamental reevaluation of their dynamic properties. This review focuses on recent studies that have identified continuous transport factor–independent nucleocytoplasmic cycling of STAT1, STAT3, and STAT5 as a basic principle of cytokine signaling. In addition, molecular mechanisms that modulate flux rates or cause retention were recognized, and together these findings have provided novel insight into the rules of cellular signal processing.

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Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽

10.3390/cancers13040795 ◽

2021 ◽

Vol 13 (4) ◽

pp. 795

Author(s):

Lukas Gorecki ◽

Martin Andrs ◽

Jan Korabecny

Keyword(s):

Cell Cycle ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Patient Survival ◽

Current Status ◽

Future Perspectives ◽

Phase Ii Trials ◽

Anticancer Treatment ◽

Positive Outlook ◽

Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

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Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽

10.3390/genes12081150 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1150

Author(s):

Jana Tomc ◽

Nataša Debeljak

Keyword(s):

Signal Transduction ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Oxygen Affinity ◽

Molecular Pathways ◽

Disease Development ◽

Post Translational Modifications ◽

Hemoglobin Oxygen Affinity ◽

Insight Into ◽

Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

International Journal of Molecular Sciences ◽

10.3390/ijms22084209 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4209

Author(s):

Karolina Kot ◽

Natalia Łanocha-Arendarczyk ◽

Michał Ptak ◽

Aleksandra Łanocha ◽

Elżbieta Kalisińska ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Molecular Mechanisms ◽

Kidney Injury ◽

Therapeutic Interventions ◽

Parasitic Infections ◽

Injury Mechanisms ◽

Kidney Involvement ◽

Leishmania Spp ◽

Apoptosis Process ◽

Insight Into

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.

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The apple C2H2-type zinc finger transcription factor MdZAT10 positively regulates JA-induced leaf senescence by interacting with MdBT2

Horticulture Research ◽

10.1038/s41438-021-00593-0 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Kuo Yang ◽

Jian-Ping An ◽

Chong-Yang Li ◽

Xue-Na Shen ◽

Ya-Jing Liu ◽

...

Keyword(s):

Mass Spectrometry ◽

Transcription Factor ◽

Liquid Chromatography ◽

Zinc Finger ◽

Leaf Senescence ◽

Transcriptional Activity ◽

Molecular Mechanisms ◽

Liquid Chromatography Mass Spectrometry ◽

Zinc Finger Transcription Factor ◽

Insight Into

AbstractJasmonic acid (JA) plays an important role in regulating leaf senescence. However, the molecular mechanisms of leaf senescence in apple (Malus domestica) remain elusive. In this study, we found that MdZAT10, a C2H2-type zinc finger transcription factor (TF) in apple, markedly accelerates leaf senescence and increases the expression of senescence-related genes. To explore how MdZAT10 promotes leaf senescence, we carried out liquid chromatography/mass spectrometry screening. We found that MdABI5 physically interacts with MdZAT10. MdABI5, an important positive regulator of leaf senescence, significantly accelerated leaf senescence in apple. MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1, thus accelerating leaf senescence. In addition, we found that MdZAT10 expression was induced by methyl jasmonate (MeJA), which accelerated JA-induced leaf senescence. We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation, thereby delaying MdZAT10-mediated leaf senescence. Taken together, our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.

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Cold-Active β-Galactosidases: Insight into Cold Adaption Mechanisms and Biotechnological Exploitation

Marine Drugs ◽

10.3390/md19010043 ◽

2021 ◽

Vol 19 (1) ◽

pp. 43

Author(s):

Marco Mangiagalli ◽

Marina Lotti

Keyword(s):

Low Temperature ◽

Molecular Mechanisms ◽

Building Blocks ◽

Cold Active ◽

Cold Adaption ◽

Glycosyl Donor ◽

Pharmaceutical Industries ◽

Biotechnological Processes ◽

Hydrolysis Of ◽

Insight Into

β-galactosidases (EC 3.2.1.23) catalyze the hydrolysis of β-galactosidic bonds in oligosaccharides and, under certain conditions, transfer a sugar moiety from a glycosyl donor to an acceptor. Cold-active β-galactosidases are identified in microorganisms endemic to permanently low-temperature environments. While mesophilic β-galactosidases are broadly studied and employed for biotechnological purposes, the cold-active enzymes are still scarcely explored, although they may prove very useful in biotechnological processes at low temperature. This review covers several issues related to cold-active β-galactosidases, including their classification, structure and molecular mechanisms of cold adaptation. Moreover, their applications are discussed, focusing on the production of lactose-free dairy products as well as on the valorization of cheese whey and the synthesis of glycosyl building blocks for the food, cosmetic and pharmaceutical industries.

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Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00422-1 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zi Wang ◽

Pan Wang ◽

Yanan Li ◽

Hongling Peng ◽

Yu Zhu ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Hematological Malignancies ◽

Current Knowledge ◽

Regulation Of Gene Expression ◽

Hematologic Disorders ◽

Cell Lineages ◽

Stage Of Development ◽

Transcription Complexes ◽

Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

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Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs

International Journal of Molecular Sciences ◽

10.3390/ijms22126644 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6644

Author(s):

Xupeng Zang ◽

Ting Gu ◽

Wenjing Wang ◽

Chen Zhou ◽

Yue Ding ◽

...

Keyword(s):

Immune Response ◽

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Gene Set ◽

Cerna Network ◽

Major Interest ◽

End Stage ◽

Insight Into

Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.

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High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes

Biomedicines ◽

10.3390/biomedicines7040076 ◽

2019 ◽

Vol 7 (4) ◽

pp. 76 ◽

Cited By ~ 3

Author(s):

Suresh P. Khadke ◽

Aniket A. Kuvalekar ◽

Abhay M. Harsulkar ◽

Nitin Mantri

Keyword(s):

Type 2 Diabetes ◽

Transcription Factors ◽

Glucose Tolerance ◽

Molecular Mechanisms ◽

Target Genes ◽

High Energy ◽

Tolerance Test ◽

Diabetic Control ◽

Ppar Γ

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκβ, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.

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