The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

Expression of hormone receptors in oropharyngeal squamous cell carcinoma

Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics. AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival. AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.Peer reviewe

Polymorphous adenocarcinoma of the salivary glands : reappraisal and update

Although relatively rare, polymorphous adenocarcinoma (PAC) is likely the second most common malignancy of the minor salivary glands (MiSG). The diagnosis is mainly based on an incisional biopsy. The optimal treatment comprises wide surgical excision, often with adjuvant radiotherapy. In general, PAC has a good prognosis. Previously, PAC was referred to as polymorphous low-grade adenocarcinoma (PLGA), but the new WHO classification of salivary gland tumours has also included under the PAC subheading, the so-called cribriform adenocarcinoma of minor salivary glands (CAMSG). This approach raised controversy, predominantly because of possible differences in clinical behaviour. For example, PLGA (PAC, classical variant) only rarely metastasizes, whereas CAMSG often shows metastases to the neck lymph nodes. Given the controversy, this review reappraises the definition, epidemiology, clinical presentation, diagnostic work-up, genetics, treatment modalities, and prognosis of PAC of the salivary glands with a particular focus on contrasting differences with CAMSG.Peer reviewe

Cellular trans-differentiation and morphogenesis towards the lymphatic lineage in regenerative medicine

Lymphoedema is a medically irresolvable condition. The lack of therapies addressing lymphatic vessel dysfunction suggests that improved understanding of lymphatic cell differentiation and vessel maturation processes is key to the development of novel, regenerative medicine and tissue engineering approaches. In this review we provide an overview of lymphatic characterisation markers and morphology in development. Furthermore, we describe multiple differentiation processes of the lymphatic system during embryonic, post-natal and pathogenic development. Using the example of pathogenic Kaposi Sarcoma-associated Herpes infection we illustrate the involvement of the Notch and PI3K pathways for lymphatic trans-differentiation. We also discuss the plasticity of certain cell types and bio-factors which enable trans-differentiation towards the lymphatic lineage. Here we argue the importance of pathway-associated induction factors for lymphatic trans-differentiation including growth factors such as VEGF-C and interleukins, and the involvement of extracellular matrix characteristics and dynamics for morphological functionality

The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture

BACKGROUND: A wealth of evidences have shown the participation and benefits of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing and skin tissue repair in vivo. However, their role in epidermal development and reconstitution is not clearly investigated. OBJECTIVE: Here we examine the quantitative effect of human BM-MSCs on epidermal regeneration in vitro. METHOD: Human keratinocytes and BM-MSCs are cultured at ratios from 0% to 100% on top of a fibroblast-embedded collagen gel in a three-dimensional organotypic co-culture model at an air-liquid interface up to 20 days and analyzed by histochemical and immunochemical staining of filaggrin, involucrin and keratin 10 on days 14 and 20. Human BM-MSCs were tracked with quantum dots in organotypic co-cultures. RESULTS: It was found that epidermal development is strongly influenced by the percentage of co-cultured BM-MSCs. A strong chemotactic effect between keratinocytes and MSCs was seen in the group with 50% of BM-MSCs, which resulted in an impaired epidermal development, whereas at a low percentage of BM-MSCs (10%), a stratified epidermal structure resembling native skin was established on day 14 of culture. Moreover, the immunostaining studies revealed that BM-MSCs in the low percentage (10%) participated in the basal periphery of reconstructed epidermis and a similar pattern characteristic of native epidermis was demonstrated in this experimental group, which was superior to all other experimental groups in terms of the thickness of stratum corneum and the expression profile of epidermal differentiation markers. CONCLUSION: This study indicates the advantage of using a new skin equivalent model incorporating a small fraction of MSCs to develop biologically useful tissues for maintaining homeostasis during skin regeneration and wound healing process

Differentiation of bone marrow-derived mesenchymal stem cells into multi-layered epidermis-like cells in 3D organotypic coculture

10.1016/j.biomaterials.2009.02.025Biomaterials30193251-3258BIMA

Influencing the Fate of Cardiac and Neural Stem Cell Differentiation Using Small Molecule Inhibitors of ALK5

10.1002/sctm.17-0246Stem Cells Translational Medicine710709-72