Polyploidy and mTOR signaling: a possible molecular link.

Polyploidy is typically described as the condition wherein a cell or organism has more than two complete sets of chromosomes. Occurrence of polyploidy is a naturally occurring phenomenon in the body's development and differentiation processes under normal physiological conditions. However, in pathological conditions, the occurrence of polyploidy is documented in numerous disorders, including cancer, aging and diabetes. Due to the frequent association that the polyploidy has with these pathologies and physiological process, understanding the cause and consequences of polyploidy would be beneficial to develop potential therapeutic applications. Many of the genetic and epigenetic alterations leading to cancer, diabetes and aging are linked to signaling pathways. Nonetheless, the specific signaling pathway associated with the cause and consequences of polyploidy still remains largely unknown. Mammalian/mechanistic target of rapamycin (mTOR) plays a key role in the coordination between eukaryotic cell growth and metabolism, thereby simultaneously respond to various environmental inputs including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in the regulation of many fundamental cellular processes that range from protein synthesis to autophagy. Dysregulated mTOR signaling has been found to be implicated in various disease progressions. Importantly, there is a strong correlation between the hallmarks of polyploidy and dysregulated mTOR signaling. In this review, we explore and discuss the molecular connection between mTOR signaling and polyploidy along with its association with cancer, diabetes and aging. Additionally, we address some unanswered questions and provide recommendations to further advance our understanding of the intricate relationship between mTOR signaling and polyploidy.

Co- and distinct existence of Tris-NTA and biotin functionalities on individual and adjacent micropatterned surfaces generated by photo-destruction.

Micropatterned surfaces with Tris-NTA and biotin functionalities both in the same micropattern as well as individually in adjacent micropatterns are generated by UV light illumination through photo-masks. These surfaces are extremely useful for the immobilization of oligohistidine and biotin tagged multiple biomolecules/proteins.

Characterization of polyploidy in cancer: Current status and future perspectives.

Various cancers frequently exhibit polyploidy, observed in a condition where a cell possesses more than two sets of chromosomes, which is considered a hallmark of the disease. The state of polyploidy often leads to aneuploidy, where cells possess an abnormal number or structure of chromosomes. Recent studies suggest that oncogenes contribute to aneuploidy. This finding significantly underscores its impact on cancer. Cancer cells exposed to certain chemotherapeutic drugs tend to exhibit an increased incidence of polyploidy. This occurrence is strongly associated with several challenges in cancer treatment, including metastasis, resistance to chemotherapy and the recurrence of malignant tumors. Indeed, it poses a significant hurdle to achieve complete tumor eradication and effective cancer therapy. Recently, there has been a growing interest in the field of polyploidy related to cancer for developing effective anti-cancer therapies. Polyploid cancer cells confer both advantages and disadvantages to tumor pathogenicity. This review delineates the diverse characteristics of polyploid cells, elucidates the pivotal role of polyploidy in cancer, and explores the advantages and disadvantages it imparts to cancer cells, along with the current approaches tried in lab settings to target polyploid cells. Additionally, it considers experimental strategies aimed at addressing the outstanding questions within the realm of polyploidy in relation to cancer.

Long-term, non-invasive FTIR detection of low-dose ionizing radiation exposure.

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.

An infrared spectral biomarker accurately predicts neurodegenerative disease class in the absence of overt symptoms.

Although some neurodegenerative diseases can be identified by behavioral characteristics relatively late in disease progression, we currently lack methods to predict who has developed disease before the onset of symptoms, when onset will occur, or the outcome of therapeutics. New biomarkers are needed. Here we describe spectral phenotyping, a new kind of biomarker that makes disease predictions based on chemical rather than biological endpoints in cells. Spectral phenotyping uses Fourier Transform Infrared (FTIR) spectromicroscopy to produce an absorbance signature as a rapid physiological indicator of disease state. FTIR spectromicroscopy has over the past been used in differential diagnoses of manifest disease. Here, we report that the unique FTIR chemical signature accurately predicts disease class in mouse with high probability in the absence of brain pathology. In human cells, the FTIR biomarker accurately predicts neurodegenerative disease class using fibroblasts as surrogate cells.