Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

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Now showing 1 - 10 of 26
  • Article
    Citation - WoS: 28
    Citation - Scopus: 30
    Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner
    (Springer, 2023) Warde, Kate M.; Smith, Lorenzo J.; Liu, Lihua; Stubben, Chris J.; Lohman, Brian K.; Willett, Parker W.; Ammer, Julia L.; Castaneda Hernandez, Guadalupe; Imodoye, Sikiru O.; Zhang, Chenge; Jones, Kara D.; Converso Baran, Kimber; Ekiz, H. Atakan
    The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens. Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and increased susceptibility to metastatic cancer. Senescence-recruited myeloid cells become depleted as tumors progress, which is recapitulated in patients in whom a low myeloid signature is associated with worse outcomes. Our study uncovers a role for myeloid cells in restraining adrenal cancer with substantial prognostic value and provides a model for interrogating pleiotropic effects of cellular senescence in cancer.
  • Article
    Assessment of Undergraduate Health Students' Perception and Satisfaction on Training and Participation in Community Health Outreach
    (Springer, 2023) Adegbore, Abidemi Kafayat; Adedokun, Amudatu Ambali; Adegoke, Juliet Ifeoluwa; Lawal, Maruf Ayobami; Oke, Muse
    AimThe need to improve training of health professionals has increased in recent years due to increasing frequencies of public health events. Consequently, a descriptive cross-sectional survey was carried out to determine the level of satisfaction and knowledge acquired by undergraduate students in the health sciences during a community health outreach program.Subject and methodsStudents were invited to complete an online-administered questionnaire (consisting of both open- and closed-ended questions) to assess their perceptions and experiences on the community health outreach program. Additionally, the survey was carried out to assess the quality of training provided and obtain suggestions for further improvements. Responses were collected and analysed using Microsoft Excel.ResultsMost respondents (>83%) reported satisfaction with the community diagnosis and community intervention briefing and training sessions. All respondents reported familiarity with standard community health outreach instruments and were capable of identifying environmental health risk factors that may contribute to the spread of communicable diseases. Interestingly, respondents reported greater appreciation of health challenges faced by rural communities. However, respondents expressed dissatisfaction with the duration of the outreach program (24%) and funding (15%).ConclusionAlthough respondents reported overall satisfaction with the organization and execution of the health outreach program, certain aspects of the program were deemed unsatisfactory. Despite the shortcomings, we believe that our student-centred learning strategy is readily adaptable for training future healthcare professionals and improving health literacy of rural communities, particularly in sub-Saharan Africa.
  • Article
    Citation - WoS: 4
    Citation - Scopus: 4
    Mapping of Quantitative Trait Loci for the Nutritional Value of Fresh Market Tomato
    (Springer, 2023) Gürbüz Çolak, Nergiz; Tek Eken, Neslihan; Ülger, Mehmet; Frary, Anne; Doğanlar, Sami
    The incidence of many diseases, such as cancer, cardiovascular diseases, and diabetes, is associated with malnutrition and an unbalanced daily diet. Vegetables are an important source of vitamins and essential compounds for human health. As a result, such metabolites have increasingly become the focus of breeding programs. Tomato is one of the most popular components of our daily diet. Therefore, the improvement of tomato's nutritional quality is an important goal. In the present study, we performed targeted metabolic profiling of an interspecific Solanum pimpinellifolium x S. lycopersicum inbred backcross line (IBL) population and identified quantitative trait loci responsible for the nutritional value of tomato. Transgressive segregation was apparent for many of the nutritional compounds such that some IBLs had extremely high levels of various amino acids and vitamins compared to their parents. A total of 117 QTLs for nutritional traits including 62 QTLs for amino acids, 18 QTLs for fatty acids, 12 QTLs for water-soluble vitamins, and 25 QTLs for fat-soluble vitamins were identified. Moreover, almost 24% of identified QTLs were confirmed in previous studies, and 40 possible gene candidates were found for 18 identified QTLs. These findings can help breeders to improve the nutritional value of tomato.
  • Article
    Citation - WoS: 7
    Citation - Scopus: 8
    High-Fat Diet Feeding Triggers a Regenerative Response in the Adult Zebrafish Brain
    (Springer, 2023) Azbazdar, Yağmur; Poyraz, Yusuf Kaan; Özalp, Özgün; Nazlı, Dilek; İpekgil, Doğaç; Cucun, GÖkhan; Özhan, Güneş
    Non-alcoholic fatty liver disease (NAFLD) includes a range of liver conditions ranging from excess fat accumulation to liver failure. NAFLD is strongly associated with high-fat diet (HFD) consumption that constitutes a metabolic risk factor. While HFD has been elucidated concerning its several systemic effects, there is little information about its influence on the brain at the molecular level. Here, by using a high-fat diet (HFD)-feeding of adult zebrafish, we first reveal that excess fat uptake results in weight gain and fatty liver. Prolonged exposure to HFD induces a significant increase in the expression of pro-inflammation, apoptosis, and proliferation markers in the liver and brain tissues. Immunofluorescence analyses of the brain tissues disclose stimulation of apoptosis and widespread activation of glial cell response. Moreover, glial activation is accompanied by an initial decrease in the number of neurons and their subsequent replacement in the olfactory bulb and the telencephalon. Long-term consumption of HFD causes activation of Wnt/β-catenin signaling in the brain tissues. Finally, fish fed an HFD induces anxiety, and aggressiveness and increases locomotor activity. Thus, HFD feeding leads to a non-traumatic brain injury and stimulates a regenerative response. The activation mechanisms of a regeneration response in the brain can be exploited to fight obesity and recover from non-traumatic injuries.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Gras-Di Snp-Based Molecular Characterization and Fingerprinting of a Turkish Corylus Avellana Core Set Provide Insights Into the Cultivation and Breeding of Hazelnut in Turkey
    (Springer, 2023) Yanar, Ertuğrul Gazi; Doğanlar, Sami; Frary, Anne
    Hazelnut (Corylus avellana L.) is an economically and socially important product for Turkey, the country that leads global production of this crop. The preservation of Turkish hazelnut genetic diversity and informed breeding of new cultivars are crucial for maintaining quality and crop yield stability. In this study, genotyping by random amplicon sequencing (GRAS-Di) was used to identify single-nucleotide polymorphisms (SNPs) in a panel of 96 individuals representing the Turkish national hazelnut collection. The resulting 7609 high-quality SNPs were physically mapped to the Tombul cultivar reference genome and used for population structure and diversity analyses. These analyses revealed that cultivars are not less diverse than wild accessions and that 44% of the panel had admixed ancestry. The results also indicated that recently released Turkish cultivars are highly similar to each other, suggesting that diversity analysis is an important tool that should be employed to prevent future genetic bottlenecks in this crop. A minimal marker algorithm was used to select a set of seven SNP markers that were capable of differentiating the panel accessions. These fingerprinting markers should be useful for the propagation of true-to-type elite cultivars that can be used to renew Turkey's aging hazelnut orchards.
  • Book Part
    Citation - Scopus: 5
    Epitranscriptomics Changes the Play: M6a Rna Modifications in Apoptosis
    (Springer, 2022) Akçaöz, Azime; Akgül, Bünyamin
    Apoptosis is a form of programmed cell death that is essential for cellular and organismal homeostasis. Any irregularities that disturb the balance between apoptosis and cell survival have severe implications, such as improper development or life-threatening diseases. Thus, it is highly critical to maintain a proper rate of apoptosis throughout development. In fact, several complex transcriptional and posttranscriptional mechanisms exist in eukaryotes to critically regulate the rate of apoptotic processes. Recent studies suggest that not only RNA sequences but also their modifications, such as m6A methylation, play a fundamental role in these transcriptional and posttranscriptional processes. A specific set of proteins, called writer, eraser, and reader of m6A marks, modulate the rate of apoptosis by determining the m6A repertoire and the fate of certain transcripts associated with apoptosis. In this Review, we will cover the dynamic m6A RNA modifications and their impact on modulation of apoptosis.
  • Article
    Citation - WoS: 6
    Citation - Scopus: 6
    An Integrative-Omics Analysis of an Industrial Clavulanic Acid-Overproducing Streptomyces Clavuligerus
    (Springer, 2022) Kurt Kızıldoğan, Aslıhan; Çelik, Gözde; Ünsaldı, Eser; Özcan, Servet; Ayaz Güner, Şerife; Özcengiz, Gülay
    Clavulanic acid (CA) is a clinically important secondary metabolite used to treat infectious diseases. We aimed to decipher complex regulatory mechanisms acting in CA biosynthesis by analyzing transcriptome- and proteome-wide alterations in an industrial CA overproducer Streptomyces clavuligerus strain, namely DEPA and its wild-type counterpart NRRL3585. A total of 924 differentially expressed genes (DEGs) and 271 differentially produced proteins (DPPs) were obtained by RNA-seq and nanoLC-MS/MS analyses, respectively. In particular, CA biosynthetic genes, namely, car (cad), cas2, oat2, pah, bls, ceas2, orf12, and claR, a cluster situated regulatory (CSR) gene, were significantly upregulated as shown by RNA-seq. Enzymes of clavam biosynthesis were downregulated considerably in the DEPA strain, while the genes involved in the arginine biosynthesis, one of the precursors of CA pathway, were overexpressed. However, the biosynthesis of the other CA precursor, glyceraldehyde-3-phosphate (G3P), was not affected. CA overproduction in the DEPA strain was correlated with BldD, BldG, BldM, and BldN (AdsA) overrepresentation. In addition, TetR, WhiB, and Xre family transcriptional regulators were shown to be significantly overrepresented. Several uncharacterized/unknown proteins differentially expressed in the DEPA strain await further studies for functional characterization. Correlation analysis indicated an acceptable degree of consistency between the transcriptome and proteome data. The study represents the first integrative-omics analysis in a CA overproducer S. clavuligerus strain, providing insights into the critical control points and potential rational engineering targets for a purposeful increase of CA yields in strain improvement.
  • Article
    Citation - WoS: 5
    Citation - Scopus: 5
    The Designing of a Gel Formulation With Chitosan Polymer Using Liposomes as Nanocarriers of Amphotericin B for a Non-Invasive Treatment Model of Cutaneous Leishmaniasis
    (Springer, 2022) Gürbüz, Nergiz; Çetin Uyanıkgil, Emel Öykü; Özbel, Yusuf; Töz, Seray
    Purpose Leishmaniasis is a disease caused by different Leishmania spp., which are transmitted to humans by a bite of infected female sand flies. Cutaneous leishmaniasis (CL, oriental sore), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) are three main clinical forms, however, only CL and VL are seen in Turkey. Cutaneous leishmaniasis is characterized by skin lesion(s) and is one of the most important vector-borne diseases in Turkey with over 2000 cases reported annually in 40 out of 81 provinces. The treatment is usually made invasively and painfully by intralesional injection of pentavalent antimony compounds. Non-invasive and innovative treatment methods are needed as aimed in this study. Methods In the present study, one of the classical antileishmanial drugs, amphotericin B (AmB), encapsulated in liposomes was evaluated using non-invasive design based on chitosan, which is a nontoxic, biocompatible and biodegradable polymer. To avoid the invasive effect of conventional intralesional needle application, the drug was encapsulated in liposomes and incorporated into a chitosan gel for applying topically on the skin lesion. The efficacy of encapsulation of amphotericin B into liposomes and the drug release from liposomes were studied. The chitosan gel was evaluated for viscosity, flowability, appearance and pH. The efficacy of the drug embedded into chitosan gel, liposomal AmB alone and chitosan gel alone in four different concentrations was also tested using Leishmania spp. promastigotes in vitro. Results The findings have shown that AmB was encapsulated into the liposomes with high efficiency (86.6%) and long-term physical and chemical stability. Therefore, designed liposomal formulation was suitable for sustained release. The appearance of the drug-embedded chitosan gel was transparent and appropriate. Chitosan gels showed non- Newtonian behavior and plastic flow. The liposomal AmB also showed higher efficacy with no parasites in all concentrations while drug embedded into chitosan gel and chitosan gel alone were effective in two higher concentrations. The lower efficacy of the drug-embedded chitosan gel in 24 h in in-vitro study was probably due to slow release of the drug. Conclusion The gel design created in this study will provide ease of use for the lesions of CL patients that do not have a specific number, size, and shape. Follow-up studies by the ex-vivo macrophage infection model with Leishmania intracellular amastigote forms and Leishmania-infected animal models are needed to understand the present design's efficacy better.
  • Article
    Citation - WoS: 7
    Citation - Scopus: 7
    Connexin 32 Overexpression Increases Proliferation, Reduces Gap Junctional Intercellular Communication, Motility and Epithelial-To Transition in Hs578t Breast Cancer Cells
    (Springer, 2022) Uğur, Deniz; Güngül, Taha Buğra; Yücel, Simge; Özçivici, Engin; Yalçın Özuysal, Özden; Meşe Özçivici, Gülistan
    Connexins (Cx) are primary components of gap junctions that selectively allow molecules to be exchanged between adjacent cells, regulating multiple cellular functions. Along with their channel forming functions, connexins play a variety of roles in different stages of tumorigenesis and their roles in tumor initiation and progression is isoform- and tissue-specific. While Cx26 and Cx43 were downregulated during breast tumorigenesis, Cx32 was accumulated in the cytoplasm of the cells in lymph node metastasis of breast cancers and Cx32 was further upregulated in metastasis. Cx32's effect on cell proliferation, gap junctional communication, hemichannel activity, cellular motility and epithelial-to-mesenchymal transition (EMT) were investigated by overexpressing Cx32 in Hs578T and MCF7 breast cancer cells. Additionally, the expression and localization of Cx26 and Cx43 upon Cx32 overexpression were examined by Western blot and immunostaining experiments, respectively. We observed that MCF7 cells had endogenous Cx32 while Hs578T cells did not and when Cx32 was overexpressed in these cells, it caused a significant increase in the percentages of Hs578T cells at the S phase in addition to increasing their proliferation. Further, while Cx32 overexpression did not induce hemichannel activity in either cell, it decreased gap junctional communication between Hs578T cells. Additionally, Cx32 was mainly observed in the cytoplasm in both cells, where it did not form gap junction plaques but Cx32 overexpression reduced Cx43 levels without affecting Cx26. Moreover, migration and invasion potentials of Hs578T and migration in MCF7 were reduced upon Cx32 overexpression. Finally, the protein level of mesenchymal marker N-cadherin decreased while epithelial marker ZO-1 and E-cadherin increased in Hs578T cells. We observed that Cx32 overexpression altered cell proliferation, communication, migration and EMT in Hs578T, suggesting a tumor suppressor role in these cells while it had minor effects on MCF7 cells.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    Frequency-Specific Sensitivity of 3t3-L1 Preadipocytes To Low-Intensity Vibratory Stimulus During Adipogenesis
    (Springer, 2022) Baskan, Öznur; Sarıgil, Öykü; Meşe Özçivici, Gülistan; Özçivici, Engin
    Adipocyte accumulation in the bone marrow is a severe complication leading to bone defects and reduced regenerative capacity. Application of external mechanical signals to bone marrow cellular niche is a non-invasive and non-pharmaceutical methodology to improve osteogenesis and suppress adipogenesis. However, in the literature, the specific parameters related to the nature of low-intensity vibratory (LIV) signals appear to be arbitrarily selected for amplitude, bouts, and applied frequency. In this study, we performed a LIV frequency sweep ranging from 30 to 120 Hz with increments of 15 Hz applied onto preadipocytes during adipogenesis for 10 d. We addressed the effect of LIV with different frequencies on single-cell density, adipogenic gene expression, lipid morphology, and triglycerides content. Results showed that LIV signals with 75-Hz frequency had the most significant suppressive effect during adipogenesis. Our results support the premise that mechanical-based interventions for suppressing adipogenesis may benefit from optimizing input parameters.