The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial–mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal–epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.

New species Pseudomonas capeferrum TDA1 as a plastic monomer utilizer and a PHA native producer

Over the decades, global plastic production has been exponentially increasing with a significant increase of plastic waste as well. Consequently, our environment has suffered a lot because synthetic plastic is less biodegradable or even not completely biodegradable. On the other hand, the conventional recycling rate and plastic management in the top ten plastic contributors are still low to reduce the contamination and pollution from plastic waste. Particularly, Indonesia, one of the world’s most outstanding emerging market economies and has the most contribution on plastic waste in ASEAN, should consider breakthrough and novel technology to fight global plastic waste. Polyhydroxyalkanoates (PHA) might have the closest relation to plastic waste upcycling because this compound can be used as the primary material to synthesize bioplastic, so-called plastic, to the bioplastic process. Many Pseudomonads can natively produce PHA as their extracellular product. This study qualitatively shows that the new strain Pseudomonas capeferrum TDA 1 natively produces PHA from various sole carbon sources, including plastic monomers. This finding gives significant insight for many improvements to the “plastic to bio-plastic” process on an industrial scale.

Surface construction for orthrotropic perfectly elastic-plastic Murnaghan material

The problem of constructing a yield surface is described. The magnitude of the stress velocity potential is explained graphically. The parameters of an elastic-plastic process are introduced: a modified R. Schmidt parameter and an analogue of the Lode parameter, the sign of which changes only when the singular point of the plasticity curve passes. The formal work area of the Murnaghan law is calculated, the real area will be much smaller. An effect similar to the Bauschinger effect for the deviator of the stress tensor is assumed to be fair. In the basic experiments of uniaxial and biaxial tension, compression and shear, a piecewise-linear generator with vertices at the corresponding singular points of the plasticity curves is determined. The magnitude of the effect is approximated by a quadratic dependence in the place parameter and piecewise-linear one in the hardening parameter. According to the magnitude of the effect, at the point of the active process there is a singular point of the curve, into which the basic generator moves. The yield surface is constructed by ductility curves drawn through the generator. Determination of the magnitude of the effect under repeated loading after unloading is considered.

Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells

Tumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not fully understood. Syndecan-1 (SDC1) is the major cell surface proteoglycan in epithelial cells and has been shown to regulate carcinoma progression and EMT. Recently, it was discovered that SDC1 translocates into the cell nucleus in certain tumor cells. Nuclear SDC1 inhibits cell proliferation, but whether nuclear SDC1 contributes to the regulation of EMT is not clear. Here, we report that loss of nuclear SDC1 is associated with cellular elongation and an E-cadherin-to-N-cadherin switch during TGF-β1-induced EMT in human A549 lung adenocarcinoma cells. Further studies showed that nuclear translocation of SDC1 contributed to the repression of mesenchymal and invasive properties of human B6FS fibrosarcoma cells. The results demonstrate that nuclear translocation contributes to the capacity of SDC1 to regulate epithelial-mesenchymal plasticity in human tumor cells and opens up to mechanistic studies to elucidate the mechanisms involved.

Myometrial myxoidosis in a patient with systemic lupus erythematosus

Myometrium myxoidosis is new terminology to describe a non-neo-plastic process of extracellular mucinous accumulation in the myometrium wall of the uterus. We report a rare association of myometrial myxoidosis with lupus erythematosus in a 35-year old woman with a history of leiomyoma. At presentation, this case was diagnosed as a pelvic abscess and treated with specific antibiotherapy, and then discharged after clinical improvement. One week later, after recurrence of the symptoms, the patient underwent hysterectomy with bilateral salpingo-oophorectomy and appendectomy with anterior abdominal soft tissue part resection. Pathological analysis revealed diffuse hypo-cellular myxoid areas intersecting the smooth muscle layer of the uterus and cervix in addition to a focal area in the interstitium of smooth muscles of the appendix and soft tissue of the anterior abdominal wall. This case emphasizes the importance of distinguishing between myxoid neoplastic and non-neoplastic lesions with myxoid changes. SIMILAR CASES PUBLISHED: To our knowledge, there are only two similar cases reported.

Adult-born neurons immature during learning are necessary for remote memory reconsolidation in rats

Memory reconsolidation, the process by which memories are again stabilized after being reactivated, has strengthened the idea that memory stabilization is a highly plastic process. To date, the molecular and cellular bases of reconsolidation have been extensively investigated particularly within the hippocampus. However, the role of adult neurogenesis in memory reconsolidation is unclear. Here, we combined functional imaging, retroviral and chemogenetic approaches in rats to tag and manipulate different populations of rat adult-born neurons. We find that both mature and immature adult-born neurons are activated by remote memory retrieval. However, only specific silencing of the adult-born neurons immature during learning impairs remote memory retrieval-induced reconsolidation. Hence, our findings show that adult-born neurons immature during learning are required for the maintenance and update of remote memory reconsolidation.

Title: Prematurity, the Diagnosis of Bronchopulmonary Dysplasia, and Maturation of Ventilatory Control Abbreviated Title: Control of Breathing and the Diagnosis of BPD

Infants born before 32 weeks post-menstrual age (PMA) and receiving respiratory support at 36 weeks PMA are diagnosed with bronchopulmonary dysplasia. This label suggests that their need for supplemental oxygen is primarily due to acquired dysplasia of airways and airspaces, and that the supplemental oxygen (O2) is treating residual parenchymal lung disease. However, current approaches to ventilatory support in the first days of life, including artificial surfactant use and lower ventilating pressures have changed the pathology of chronic lung disease, and emerging evidence suggests that immature ventilatory control may also contribute to the need for supplemental oxygen at 36 weeks PMA. In all newborns, maturation of ventilatory control continues ex utero and is a plastic process. Supplemental O2 mitigates the hypoxemic effects of delayed maturation of ventilatory control, as well as reduces the duration and frequency of periodic breathing events. Prematurity is associated with altered and occasionally aberrant maturation of ventilatory control. Infants born prematurely, with or without a diagnosis of BPD, are more prone to long-lasting effects of dysfunctional ventilatory control. Awareness of the interaction between parenchymal lung disease and delayed maturation of ventilatory control is essential to understanding why a given premature infant requires and is benefitting from supplemental O2 at 36 weeks PMA.

Changes in the Fracture Toughness under Mode II Loading of Low Calcium Fly Ash (LCFA) Concrete Depending on Ages

This study investigated the influence of the curing time on the fracture toughness of concrete produced with different content of low calcium fly ash (LCFA). During the study, the amounts of 20% and 30% of pozzolanic additive were used. In order to observe the effect of the applied pozzolanic additive on the analyzed concrete properties, the obtained results were compared with the values obtained for the reference concrete. Compressive strength—fcm and fracture toughness, by using mode II loading—KIIc (shearing), were determined between the 3rd and 365th days of curing. In the course of experiments, changes in the development of cracks in individual series of concrete were also analyzed. In addition, the microstructures of all composites and the nature of macroscopic crack propagation in mature concretes were assessed. It was observed that the greatest increase in fracture toughness at shear was in the case of reference concrete during the first 28 days, whereas, in the case of concretes containing LCFA, in the period of time above 4 weeks. Furthermore, concrete without the LCFA additives were characterized by a brittle fracture. In contrast to it, concretes with LCFA additives are mainly characterized by a quasi-plastic process of failure. Moreover, most of the samples showed a typical pattern of the destruction that occurs as a result of shearing. The presented test results may be helpful in selecting the composition of concrete mixtures containing LCFA to be used in concrete and reinforced concrete structures subjected to shear loads.

H3.1 Eviction Marks Female Germline Precursors in Arabidopsis

In flowering plants, germline precursors are differentiated from somatic cells. The female germline precursor of Arabidopsis thaliana is located in the internal (nucellar) tissue of the ovule, and is known as the Megaspore Mother Cell (MMC). MMC differentiation in Arabidopsis occurs when a cell in the subepidermal layer of the nucellar apex enters the meiotic program. Increasing evidence has demonstrated that MMC specification is a plastic process where the number and developmental outcome of MMCs are variable. During its differentiation, the MMC displays specific chromatin hallmarks that distinguish it from other cells within the primordium. To date, these signatures have been only analyzed at developmental stages where the MMC is morphologically conspicuous, and their role in reproductive fate acquisition remains to be elucidated. Here, we show that the histone 3 variant H3.1 HISTONE THREE RELATED 13 (HTR13) can be evicted in multiple subepidermal cells of the nucellus, but that H3.1 eviction persists only in the MMC. This pattern is established very early in ovule development and is reminiscent of the specific eviction of H3.1 that marks cell cycle exit in other somatic cell types, such as the root quiescent center (QC) of Arabidopsis. Our findings suggest that cell cycle progression in the subepidermal region of the ovule apex is modified very early in development and is associated with plasticity of reproductive fate acquisition.

Altered T cell plasticity favours Th17 cells in early arthritis

Objectives The predominance of differentiated Th17 cells has been implied as a key driver of autoimmune arthritis, including early RA. Because accumulating evidence suggests that Th cell differentiation is a plastic process, we investigated plasticity and underlying molecular mechanisms to address the shift towards the Th17 phenotype in early RA. Methods A cohort of 61 patients with early, active, untreated RA and 45 age- and sex-matched healthy controls were studied. Viable in vitro- and in vivo-generated Th1, Th2 and Th17 cells were FACS-sorted and transdifferentiated under Th1-, Th2- or Th17-inducing conditions. The cytokine Th profile of the transdifferentiated cells was assessed by flow cytometry. Th cell-associated cytokine and transcription factor gene loci were analysed by chromatin immunoprecipitation assay and their expression by quantitative real-time PCR. Results In vitro-generated Th cells showed substantial plasticity, which was similar between RA and healthy controls, whereas in vivo-derived Th1 and Th2 cells from RA patients demonstrated an enhanced plasticity towards IL-17-expressing phenotypes compared with healthy controls. Further, in vivo-generated Th17 cells from RA patients showed a resistance to transdifferentiate into Th1 or Th2 cells. The serum/glucocorticoid-regulated kinase 1–forkhead box protein O1–IL-23 receptor (SGK1–FOXO1–IL-23R) axis together with increased RORC expression was associated with the predominant Th17 phenotype in early RA. Conclusions Our data indicate that in vivo-originated Th subsets are prone to Th17 cell transdifferentiation in early RA, while Th17 cells are resistant to changes in their phenotype. Together, the data imply that an altered plasticity contributes to the Th17 shift in early RA.