Pancreatic cancer diagnosis and management: Has the time come to prick the bubble?

Pancreatic cancer (PC) is associated with poor prognosis and very dismal survival rates. The most effective possibility of cure is tumor resection, which is only possible in about 15% of patients diagnosed at early stages of disease progression. Recent whole-genome sequencing studies pointed genetic alterations in 12 core signaling pathways in PC. These observations hint at the possibility that the initial mutation in PC might appear nearly 20 years before any symptoms occur, suggesting that a large window of opportunity may exist for early detection. Biomarkers with the potential to identify pre-neoplastic disease or very early stages of cancer are of great promise to improve patient survival. The concept of liquid biopsy refers to a minimally invasive sampling and analysis of liquid biomarkers that can be isolated from body fluids, primarily blood, urine and saliva. A myriad of circulating molecules may be useful as tumor markers, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating tumor cells (CTC), circulating tumor proteins, and extracellular vesicles, more specifically exosomes. In this review, we discuss with more detail the potential role of exosomes in several aspects related to PC, from initiation to tumor progression and its applicability in early detection and treatment. Exosomes are small circulating extracellular vesicles of 50-150 nm in diameter released from the plasma membrane by almost all cells and exhibit some advantages over other biomarkers. Exosomes are central players of intercellular communication and they have been implicated in a series of biological process, including tumorigenesis, migration and metastasis. Several exosomal microRNAs and proteins have been observed to distinguish PC from benign pancreatic diseases and healthy controls. Besides their possible role in diagnosis, understanding exosomes functions in cancer has clarified the importance of microenvironment in PC progression as well as its influence in proliferation, metastasis and resistance to chemotherapy. Increasing knowledge on cancer exosomes provides valuable insights on new therapeutic targets and can potentially open new strategies to treat this disease. Continuous research is needed to ascertain the reliability of using exosomes and their content as potential biomarkers, so that, hopefully, in the near future, they will provide the opportunity for early diagnosis, treatment intervention and increase survival of PC patients.The Melo team is supported by the project NORTE-01-0145-FEDER-000029, Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and national funds through FCT—Foundation for Science and Technology IF/00543/2013/CP1184/CT0004, PTDC/BIM-ONC/2754/2014, POCI-01-0145-FEDER-32189 and Astrazeneca Foundation, FAZ Ciencia Award

Influence of nitrogen content on the structural, mechanical and electrical properties of TiN thin films

This paper reports on the preparation of TiNx thin films by d.c. reactive magnetron sputtering. The coating thickness ranged from 1.7 to 4.2 Am and the nitrogen content varied between 0 and 55 at.%. X-Ray diffraction showed the development of the hexagonal a-Ti phase, with strong [002] orientation for low nitrogen contents, where the N atoms fit into octahedral sites in the Ti lattice as the amount of nitrogen is increased. For nitrogen contents of 20 and 30 at.%, the q-Ti2N phase appears with [200] orientation. With further increasing the nitrogen content, the y-TiN phase becomes dominant. The electrical resistivity of the different compositions reproduces this phase behavior. The hardness of the samples varied from approximately 8 GPa for pure titanium up to 27 GPa for a nitrogen content of 30 at.%, followed by a slight decrease at the highest contents. A similar increase of stresses with nitrogen is observed. Structure and composition with the consequent changes in crystalline phases and the lattice distortion were found to be crucial in the evolution of the mechanical properties

Total antioxidant activity and trace elements in human milk: the first 4 months of breast-feeding

The content of many nutrients in breast milk are dependent on the nutritional status of the lactating woman. This is particularly true for fat and water-soluble vitamins, some of which have antioxidant properties. The aim of the study entertained herein was to evaluate the changes in total antioxidant status of human milk during the first 4 months of lactation, and to correlate such changes with the contents in specific antioxidant oligoelements (Cu, Zn, Mn and Se). Milk samples were collected from (31) lactating women recruited at the Service of Obstetrics of the Hospital de São João in Porto, after 1, 4, 8, 12 and 16 weeks after birth. The total antioxidant status (TAS) of human milk was measured by the Randox® commercial kit and trace metals by ICP-MS (inductively coupled plasma-mass spectrometry). The results found for TAS and oligoelements under study show a decrease in the concentration of these parameters from 7 days to 4 months of breast-feeding and significant correlations (p < 0.05) were found between TAS and Cu, Zn and Se (not Mn). The decreases of Cu, Zn and Se were also correlated, but not proportional between them, suggesting diverse excretion mechanisms for all. Between primipara and multipara women, a significant difference was found only for Cu and Zn concentrations at 7 days of lactation, but not for the other metals or TAS. With respect to the mother’s age, no correlation was found, either for trace metal concentrations or TAS

THREE OMNI-DIRECTIONAL WHEELS CONTROL ON A MOBILE ROBOT

Keywords: Omni-directional wheels, motor control. Traditional two wheels differential drive normally used on mobile robots have manoeuvrability limitations and take time to sort out. Most teams use two driving wheels (with one or two cast wheels), four driving wheels and even three driving wheels. A three wheel drive with omni-directional wheel has been tried with success, and was implemented on fast moving autonomous mobile robots. This paper deals with the mathematical kinematics description of such mobile platform, it describes the advantages and also the type of control used.

Amyloid pathology reduces ELP3 expression and tRNA modifications leading to impaired proteostasis

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by accumulation of β-amyloid aggregates and loss of proteostasis. Transfer RNA (tRNA) modifications play a crucial role in maintaining proteostasis, but their impact in AD remains unclear. Here, we report that expression of the tRNA modifying enzyme ELP3 is reduced in the brain of AD patients and amyloid mouse models and negatively correlates with amyloid plaque mean density. We further show that SH-SY5Y neuronal cells carrying the amyloidogenic Swedish familial AD mutation (SH-SWE) display reduced ELP3 levels, tRNA hypomodifications and proteostasis impairments when compared to cells not carrying the mutation (SH-WT). Additionally, exposing SH-WT cells to the secretome of SH-SWE cells led to reduced ELP3 expression, wobble uridine tRNA hypomodification, and increased protein aggregation. Importantly, correcting tRNA deficits due to ELP3 reduction reverted proteostasis impairments. These findings suggest that amyloid pathology dysregulates proteostasis by reducing ELP3 expression and tRNA modification levels, and that targeting tRNA modifications may be a potential therapeutic avenue to restore neuronal proteostasis in AD and preserve neuronal function.publishe

Intralayer and interlayer electron–phonon interactions in twisted graphene heterostructures

Electron–phonon interactions in van der Waals layered materials can occur either within the same layer (intralayer) or in different layers (interlayer). Here, the authors use multi-wavelength Raman spectroscopy to probe intra- and inter-layer electron–phonon interactions in twisted graphene heterostructures