High Expression of hTERT and Stemness Genes in BORIS/CTCFL Positive Cells Isolated from Embryonic Cancer Cells.

BORIS/CTCFL is a member of cancer testis antigen family normally expressed in germ cells. In tumors, it is aberrantly expressed although its functions are not completely well-defined. To better understand the functions of BORIS in cancer, we selected the embryonic cancer cells as a model. Using a molecular beacon, which specifically targets BORIS mRNA, we demonstrated that BORIS positive cells are a small subpopulation of tumor cells (3-5% of total). The BORIS-positive cells isolated using BORIS-molecular beacon, expressed higher telomerase hTERT, stem cell (NANOG, OCT4, SOX2) and cancer stem cell marker genes (CD44 and ALDH1) compared to the BORIS-negative tumor cells. In order to define the functional role of BORIS, stable BORIS-depleted embryonic cancer cells were generated. BORIS silencing strongly down-regulated the expression of hTERT, stem cell and cancer stem cell marker genes. Moreover, the BORIS knockdown increased cellular senescence in embryonic cancer cells, revealing a putative role of BORIS in the senescence biological program. Our data indicate an association of BORIS expressing cells subpopulation with the expression of stemness genes, highlighting the critical role played by BORIS in embryonic neoplastic disease

Unraveling the mechanism to form MoS2 lubricant layers from MoDTC by ab initio simulations

The morphology of molybdenum disulfide (MoS2) is a crucial aspect to ensure the functionality of this remarkable 2D-material both in electronic and tribological applications. Indeed, molybdenum dithiocarbamates (MoDTCs) can be tribochemically transformed into MoS2, which is able to reduce the friction coefficient of metallic moving parts. However, this transformation is influenced by temperature, sulfur/oxygen ratio, normal and shear stresses, making the mechanism of this process particularly challenging to explain. Ab initio simulations based on density functional theory (DFT), including a quantum mechanics/molecular mechanics (QM/MM) approach, are used here to shed light on the crystallization of MoS2 promoted by mechanical stresses. Chemistry plays an important role during the reorganization of the units of MoSx obtained from MoDTC, because sulfur and oxygen atoms tend to move outside of the amorphous layer, surrounding the molybdenum atoms and creating a structure that can crystallize into MoS2. Normal load and sliding have a synergistic effect in rearranging the amorphous units into a crystalline structure, as the former helps overcoming the energy barriers associated to bonds breaking and forming, while the latter allows misplaced atoms to be pulled towards the crystalline sites. A crystalline MoS2 was obtained by ab initio calculations below 1000 K

New Rheumatoid Arthritis Treatments for ‘Old’ Patients : Results of a Systematic Review

Introduction: In the last 20 years, biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have become available for treating rheumatoid arthritis (RA), and a treat-to-target strategy has been introduced. We hypothesise that these advances should have resulted in changes to the characteristics of patients with RA participating in clinical trials of the newest therapies. This study determined whether the baseline characteristics of patients with RA enrolled in clinical trials have changed in the past decade versus patients participating in earlier RA studies. Methods: This secondary analysis was based on randomised controlled trials (RCTs) identified in a systematic literature review. Baseline characteristics of patients with RA with inadequate response to conventional synthetic DMARDs were compared between RCTs published in 1999\u20132009 and those published in 2010\u20132017 using random-effects meta-analyses. Results: Forty RCTs were analysed: 22 from 1999\u20132009 and 18 from 2010\u20132017. No significant difference between the two timeframes and no obvious trend over time were observed for age, gender, disease duration, rheumatoid factor status, tender and swollen joint counts, physician and patient global assessments of disease activity, and pain scores. Variability between RCTs was high. Similar results were observed for Disease Activity Scores and Health Assessment Questionnaire-Disability Index scores, but with low variability between RCTs. Conclusion: The baseline characteristics of patients with RA participating in RCTs do not appear to have changed in the last decade despite the availability of new treatments and a different treatment approach. Further research should determine the impact of baseline patient characteristics on patients\u2019 response to RA treatments

Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma.

TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype

The dark recovery rate in the photocycle of the bacterial photoreceptor YtvA is affected by the cellular environment and by hydration

We report thermal recovery kinetics of the lit state into the parental dark state, measured for the blue light-sensing photoreceptor YtvA inside overexpressing E. coli and B. subtilis bacterial cells, performed for the wild type and several mutated proteins. Recovery was followed as a recovery of the fluorescence, as this property is only found for the parental but not for the photochemically generated lit state. When cells were deposited onto a microscope glass plate, the observed thermal recovery rate in the photocycle was found ca. ten times faster in comparison to purified YtvA in solution. When the E. coli or B. subtilis colonies were soaked in an isotonic buffer, the dark relaxation became again much slower and was very similar to that observed for YtvA in solution. The observed effects show that rate constants can be tuned by the cellular environment through factors such as hydration. Copyright

role of evaluating tumor infiltrating lymphocytes programmed death ligand 1 and mismatch repair proteins expression in malignant mesothelioma

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Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence

Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence

Stable and Solution-Processable Cumulenic sp-Carbon Wires: A New Paradigm for Organic Electronics

open12siAcknowledgements. E.G.F. acknowledges the support through the EU Horizon 2020 research and innovation program, H2020-FETOPEN-01-2018-2020 (FET-Open Challenging Current Thinking), “LION-HEARTED”, grant agreement no. 828984. C.S.C. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program ERC-Consolidator Grant (ERC CoG 2016 EspLORE grant agreement no. 724610, website: www.esplore.polimi.it). R.R.T. acknowledges funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Foundation for Innovation (CFI). This work was partially supported by the European Union's H2020-EU.4.b. – Twinning of research institutions “GREENELIT”, grant agreement number 951747. GIWAXS experiments were performed at BL11 NCD-SWEET beamline at ALBA Synchrotron (Spain) with the collaboration of ALBA staff. This work was in part carried out at Polifab, the micro- and nanotechnology centre of the Politecnico di Milano. Open access funding provided by Istituto Italiano di Tecnologia within the CRUI-CARE Agreement.Solution-processed, large-area, and flexible electronics largely relies on the excellent electronic properties of sp2-hybridized carbon molecules, either in the form of π-conjugated small molecules and polymers or graphene and carbon nanotubes. Carbon with sp-hybridization, the foundation of the elusive allotrope carbyne, offers vast opportunities for functionalized molecules in the form of linear carbon atomic wires (CAWs), with intriguing and even superior predicted electronic properties. While CAWs represent a vibrant field of research, to date, they have only been applied sparingly to molecular devices. The recent observation of the field-effect in microcrystalline cumulenes suggests their potential applications in solution-processed thin-film transistors but concerns surrounding the stability and electronic performance have precluded developments in this direction. In the present study, ideal field-effect characteristics are demonstrated for solution-processed thin films of tetraphenyl[3]cumulene, the shortest semiconducting CAW. Films are deposited through a scalable, large-area, meniscus-coating technique, providing transistors with hole mobilities in excess of 0.1 cm2V−1s−1, as well as promising operational stability under dark conditions. These results offer a solid foundation for the exploitation of a vast class of molecular semiconductors for organic electronics based on sp-hybridized carbon systems and create a previously unexplored paradigm.openPecorario S.; Scaccabarozzi A.D.; Fazzi D.; Gutierrez-Fernandez E.; Vurro V.; Maserati L.; Jiang M.; Losi T.; Sun B.; Tykwinski R.R.; Casari C.S.; Caironi M.Pecorario S.; Scaccabarozzi A.D.; Fazzi D.; Gutierrez-Fernandez E.; Vurro V.; Maserati L.; Jiang M.; Losi T.; Sun B.; Tykwinski R.R.; Casari C.S.; Caironi M

BLUF Domain Function Does Not Require a Metastable Radical Intermediate State

BLUF (blue light using flavin) domain proteins are an important family of blue light-sensing proteins which control a wide variety of functions in cells. The primary light-activated step in the BLUF domain is not yet established. A number of experimental and theoretical studies points to a role for photoinduced electron transfer (PET) between a highly conserved tyrosine and the flavin chromophore to form a radical intermediate state. Here we investigate the role of PET in three different BLUF proteins, using ultrafast broadband transient infrared spectroscopy. We characterize and identify infrared active marker modes for excited and ground state species and use them to record photochemical dynamics in the proteins. We also generate mutants which unambiguously show PET and, through isotope labeling of the protein and the chromophore, are able to assign modes characteristic of both flavin and protein radical states. We find that these radical intermediates are not observed in two of the three BLUF domains studied, casting doubt on the importance of the formation of a population of radical intermediates in the BLUF photocycle. Further, unnatural amino acid mutagenesis is used to replace the conserved tyrosine with fluorotyrosines, thus modifying the driving force for the proposed electron transfer reaction; the rate changes observed are also not consistent with a PET mechanism. Thus, while intermediates of PET reactions can be observed in BLUF proteins they are not correlated with photoactivity, suggesting that radical intermediates are not central to their operation. Alternative nonradical pathways including a keto–enol tautomerization induced by electronic excitation of the flavin ring are considered