Small-molecule targeting of translation initiation for cancer therapy

Translation initiation plays a critical role in the regulation of cell growth and tumorigenesis. We report here that inhibiting translation initiation through induction of eIF2α phosphorylation by small-molecular-weight compounds restricts the availability of the eIF2·GTP·Met-tRNAi ternary complex and abrogates the proliferation of cancer cells in vitro and tumor growth in vivo. Restricting the availability of the ternary complex preferentially down-regulates the expression of growth-promoting proteins and up-regulates the expression of ER stress response genes in cancer cells as well as in tumors excised from either animal models of human cancer or cancer patients. These findings provide the first direct evidence for translational control of gene-specific expression by small molecules in vivo and indicate that translation initiation factors are bona fide targets for development of mechanism-specific anti-cancer agents

The monitoring of feather mites (Acari, Astigmata) of the Warbler (Aves: Sylviidae) species in the Kizilirmak delta, Samsun, Turkey

Feather mites (Astigmata) arc among the most common ectosymbionts that live on birds. The present research was conducted between 2010 and 2013 in the Kizilirmak delta Cernek Bird Ringing Station in Samsun, Turkey. Assessments of the taxonomy, collection methods, and the periodic host-species relationships of the mites collected were conducted for 591 individuals of 10 bird species belonging to the family Sylviidae captured using mist nets during the bird migration periods. Ten feather mite species were identified from the families Proctophyllodidae, Analgidae, and Trouesartidae. These species are Strelkoviacarus quadratus (Haller, 1882); Dolichodectes edwardsi (Trouessart, 1885); Proctophyllodes cetti Badek, Mironov, and Dabert, 2008; Proctophyllodes clavatus Fritsch, 1961; Proctophyllodes doleophyes Gaud, 1957; Proctophyllodes sylvia Gaud, 1957; Trouessartia bifurcata (Trouessart) 1884; Trouessartia inexpectata Gaud, 1957; and Trouessartia trouessarti Oudemans, 1904. Among these species, Trouessartia bifurcata (Trouessart) 1884 is a new record for Turkey. New host records were reported from Turkey for 7 feather mite species. The least damaging method for the birds is to collect mites directly by using a stereomicroscope and forceps. The maximum number of feather mite species (7) was detected on Sylvia atricapilla and the minimum (1) on Phylloscopus trochilus. Proctophyllodes clavatus and Proctophyllodes sylvia were the most commonly recorded feather mite species

Glucocorticoid use in psoriatic arthritis and treatment outcomes: does the gender have a role?

Abstract Background Systemic glucocorticoids are commonly used in practice in the treatment of psoriatic arthritis. However, authorities advise against prescribing it, primarily because of the risk of psoriasis flare-ups. The authors aimed to assess the glucocorticoid use in psoriatic arthritis (PsA), factors associated with the use of glucocorticoids and to uncover whether gender has an impact on glucocorticoid use and treatment responses. Disease-modifying antirheumatic drug (DMARD)-naive PsA patients were included in this cross-sectional study. Baseline clinical and demographic characteristics were recorded. After starting DMARD treatment, patients were followed for 2 years. The number of patients who started glucocorticoids, the clinical demographics of these patients, the duration of glucocorticoid administration, and the dose for administration were recorded. Patient outcomes and gender differences were analyzed. Disease activity was measured using the Disease Activity Scale 28 (DAS28-CRP) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Results Fifty-five of the 141 patients (39%) received glucocorticoids at the 2-year follow-up. There was no difference between the sexes who are in remission-low disease activity (LDA) on cDMARD monotherapy (p = 0.300). Glucocorticoid usage (p = 0.660), dose (p = 0.054), and duration (p = 0.159) did not differ between male and female patients. Higher glucocorticoid doses were associated with dactylitis, higher CRP levels, higher DAS-28 and DAPSA scores, and longer (> 3 months) glucocorticoid administration. Glucocorticoid duration was longer in patients with higher TJS, SJS, serum CRP, higher DAS-28 and DAPSA scores, and higher glucocorticoid doses. Sustained remission-LDA was achieved in 16 of 55 patients after cessation of glucocorticoids and no sex difference was observed. Conclusion Systemic glucocorticoids are commonly prescribed in PsA, and when added to treatment even for short periods and in low doses, they help achieve significant disease control. Except for axial involvement, there is no difference in treatment responses between male and female patients, making it unnecessary to make a gender distinction in the treatment algorithm. Given these findings, prospective studies are needed to evaluate glucocorticoids as a bridging treatment in PsA, such as rheumatoid arthritis

Bot Detection on Social Networks Using Persistent Homology

The growth of social media in recent years has contributed to an ever-increasing network of user data in every aspect of life. This volume of generated data is becoming a vital asset for the growth of companies and organizations as a powerful tool to gain insights and make crucial decisions. However, data is not always reliable, since primarily, it can be manipulated and disseminated from unreliable sources. In the field of social network analysis, this problem can be tackled by implementing machine learning models that can learn to classify between humans and bots, which are mostly harmful computer programs exploited to shape public opinions and circulate false information on social media. In this paper, we propose a novel topological feature extraction method for bot detection on social networks. We first create weighted ego networks of each user. We then encode the higher-order topological features of ego networks using persistent homology. Finally, we use these extracted features to train a machine learning model and use that model to classify users as bot vs. human. Our experimental results suggest that using the higher-order topological features coming from persistent homology is promising in bot detection and more effective than using classical graph-theoretic structural features

Oxidation and peroxidation of phenols at carbon paste and peroxidase: immobilized carbon paste electrodes

info:eu-repo/semantics/publishe