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In recent years, intrinsically disordered proteins (IDPs) and disordered domains have attracted great attention. Many of them contain linear motifs that mediate interactions with other factors during formation of multicomponent protein complexes. NMR spectrometry is a valuable tool for characterizing this type of interactions on both amino acid (aa) and atomic levels. Alphaviruses encode a nonstructural protein nsP3, which drives viral replication complex assembly. Selleckchem Plumbagin nsP3 proteins contain over 200-aa-long hypervariable domains (HVDs), which exhibits no homology between different alphavirus species, are predicted to be intrinsically disordered and appear to be critical for alphavirus adaptation to different cells. Previously, we have shown that nsP3 HVD of chikungunya virus (CHIKV) is completely disordered with low tendency to form secondary structures in free form. In this new study, we used novel NMR approaches to assign the spectra for the nsP3 HVD of Venezuelan equine encephalitis virus (VEEV). The HVDs of CHIKV and VEEV have no homology but are both involved in replication complex assembly and function. We have found that VEEV nsP3 HVD is also mostly disordered but contains a short stable α-helix in its C-terminal fragment, which mediates interaction with the members of cellular Fragile X syndrome protein family. Our NMR data also suggest that VEEV HVD has several regions with tendency to form secondary structures.Nearly 100 years after the first report of tick-borne tularemia, questions remain about the tick vector(s) that pose the greatest risk for transmitting Francisella tularensis (Ft), the causative agent of tularemia. Additionally, few studies have identified genes/proteins required for Ft to infect, persist, and replicate in ticks. To answer questions about vector competence and Ft transmission by ticks, we infected Dermacentor variabilis (Dv),Amblyomma americanum (Aa), and Haemaphysalis longicornis (Hl; invasive species from Asia) ticks with Ft, finding that although Aa ticks initially become infected with 1 order of magnitude higher Ft, Ft replicated more robustly in Dv ticks, and did not persist in Hl ticks. In transmission studies, both Dv and Aa ticks efficiently transmitted Ft to naïve mice, causing disease in 57% and 46% of mice, respectively. Of four putative Ft chitinases, FTL1793 is the most conserved among Francisella sp. We generated a ΔFTL1793 mutant and found that ΔFTL1793 was deficient for infection, persistence, and replication in ticks. Recombinant FTL1793 exhibited chitinase activity in vitro, suggesting that FTL1793 may provide an alternative energy source for Ft in ticks. Taken together, Dv ticks appear to pose a greater risk for harboring and transmitting tularemia and FTL1793 plays a major role in promoting tick infections by Ft.Metastasis remains a clinically unsolved issue in cancer that is initiated by the acquisition of collective migratory properties of cancer cells. Phenotypic and functional heterogeneity that arise among cancer cells within the same tumor increase cellular plasticity and promote metastasis, however, their impact on collective cell migration is incompletely understood. Here, we show that in vitro collective cancer cell migration depends on FAK and MMP-2 and on the presence of cancer-associated fibroblasts (CAFs). The absence of functional FAK rendered cancer cells incapable of invading the surrounding stroma. However, CAFs and cancer cells over-expressing MMP-2 released FAK-deficient cells from this constraint by taking the leader positions in the invasive tracks, pushing FAK-deficient squamous cell carcinoma (SCC) cells towards the stroma and leading to the transformation of non-invasive cells into invasive cells. Our cell-based studies and the RNAseq data from the TCGA cohort of patients with head and neck squamous cell carcinomas reveal that, although both FAK and MMP-2 over-expression are associated with epithelial-mesenchymal transition, it is only MMP-2, not FAK, that functions as an independent prognostic factor. Given the significant role of MMP-2 in cancer dissemination, targeting of this molecule, better than FAK, presents a more promising opportunity to block metastasis.The removal of organic dyes in aquatic media is, nowadays, a very pressing environmental problem. These dyes usually come from industries, such as textiles, food, and pharmaceuticals, among others, and their harm is produced by preventing the penetration of solar radiation in the aquatic medium, which leads to a great reduction in the process of photosynthesis, therefore damaging the aquatic ecosystems. The feasibility of implementing a process of nanofiltration in the purification treatment of an aqueous stream with small size dyes has been studied. Six dyes were chosen Acid Brown-83, Allura Red, Basic Fuchsin, Crystal Violet, Methyl Orange and Sunset Yellow, with similar molecular volume (from 250 to 380 Å). The nanofiltration membrane NF99 was selected. Five of these molecules with different sizes, shapes and charges were employed in order to study the behavior of the membrane for two system characteristic parameters permeate flux and rejection coefficient. Furthermore, a microscopy study and a behavior analysis of the membrane were carried out after using the largest molecule. Finally, the Spiegler-Kedem-Katchalsky model was applied to simulate the behavior of the membrane on the elimination of this group of dyes.Compensatory movements at the trunk are commonly utilized during reaching by persons with motor impairments due to neurological injury such as stroke. Recent low-cost motion sensors may be able to measure trunk compensation, but their validity and reliability for this application are unknown. The purpose of this study was to compare the first (K1) and second (K2) generations of the Microsoft Kinect to a video motion capture system (VMC) for measuring trunk compensation during reaching. Healthy participants (n = 5) performed reaching movements designed to simulate trunk compensation in three different directions and on two different days while being measured by all three sensors simultaneously. Kinematic variables related to reaching range of motion (ROM), planar reach distance, trunk flexion and lateral flexion, shoulder flexion and lateral flexion, and elbow flexion were calculated. Validity and reliability were analyzed using repeated-measures ANOVA, paired t-tests, Pearson's correlations, and Bland-Altman limits of agreement. Results show that the K2 was closer in magnitude to the VMC, more valid, and more reliable for measuring trunk flexion and lateral flexion during extended reaches than the K1. Both sensors were highly valid and reliable for reaching ROM, planar reach distance, and elbow flexion for all conditions. Results for shoulder flexion and abduction were mixed. The K2 was more valid and reliable for measuring trunk compensation during reaching and therefore might be prioritized for future development applications. Future analyses should include a more heterogeneous clinical population such as persons with chronic hemiparetic stroke.As part of the optimization of assisted reproductive technology programs, the aim of the study was to identify key small noncoding RNA (sncRNA) molecules that participate in maternal-to-zygotic transition and determine development potential and competence to form a healthy fetus. Small RNA deep sequencing followed by quantitative real-time RT-PCR was used to profile sncRNAs in 50 samples of spent culture medium from morula with different development potentials (no potential (degradation/developmental arrest), low potential (poor-quality blastocyst), and high potential (good/excellent quality blastocyst capable of implanting and leading to live birth)) obtained from 27 subfertile couples who underwent in vitro fertilization. We have shown that the quality of embryos at the morula stage is determined by secretion/uptake rates of certain sets of piRNAs and miRNAs, namely hsa_piR_011291, hsa_piR_019122, hsa_piR_001311, hsa_piR_015026, hsa_piR_015462, hsa_piR_016735, hsa_piR_019675, hsa_piR_020381, hsa_piR_020485, hsa_piR_004880, hsa_piR_000807, hsa-let-7b-5p, and hsa-let-7i-5p. Predicted gene targets of these sncRNAs included those globally decreased at the 8-cell-morula-blastocyst stage and critical to early embryo development. We show new original data on sncRNA profiling in spent culture medium from morula with different development potential. Our findings provide a view of a more complex network that controls human embryogenesis at the pre-implantation stage. Further research is required using reporter analysis to experimentally confirm interactions between identified sncRNA/gene target pairs.The term ionone is derived from "iona" (Greek for violet) which refers to the violet scent and "ketone" due to its structure. Ionones can either be chemically synthesized or endogenously produced via asymmetric cleavage of β-carotene by β-carotene oxygenase 2 (BCO2). We recently proposed a possible metabolic pathway for the conversion of α-and β-pinene into α-and β-ionone. The differences between BCO1 and BCO2 suggest a unique physiological role of BCO2; implying that β-ionone (one of BCO2 products) is involved in a prospective biological function. This review focuses on the effects of ionones and the postulated mechanisms or signaling cascades involved mediating these effects. β-Ionone, whether of an endogenous or exogenous origin possesses a range of pharmacological effects including anticancer, chemopreventive, cancer promoting, melanogenesis, anti-inflammatory and antimicrobial actions. β-Ionone mediates these effects via activation of olfactory receptor (OR51E2) and regulation of the activity or expression of cell cycle regulatory proteins, pro-apoptotic and anti-apoptotic proteins, HMG-CoA reductase and pro-inflammatory mediators. α-Ionone and β-ionone derivatives exhibit anti-inflammatory, antimicrobial and anticancer effects, however the corresponding structure activity relationships are still inconclusive. Overall, data demonstrates that ionone is a promising scaffold for cancer, inflammation and infectious disease research and thus is more than simply a violet's fragrance.Cercarial dermatitis, or Swimmer's itch, is one of the emerging diseases caused by the cercariae of water-borne schistosomes, mainly Trichobilharzia spp. Since the zoonotic potential of Allobilharzia visceralis is still unknown, studies on this schistosome would be helpful to add knowledge on its possible role in causing human infections. In the present study, 54 whooper swans (Cygnus cygnus) from rescue/rehabilitation centers in Honshu, Japan, were necropsied to identify the cause of death. Grossly, 33 (61.11%) swans were severely emaciated and 23 (42.59%) had multiple reddened areas throughout the length of the intestine with no worms detected in the internal organs. Microscopically, adult schistosomes were found in the lumen of the mesenteric, serosal, portal, and testicular veins, in the capillaries of the intestinal lamina propria, and in the sinusoids of the adrenal gland, spleen, and liver of 23 (42.59%) swans. Hypertrophy of veins containing adult worms was identified in 15 (27.77%) swans, and vascular lumen obliteration was observed in 8 (14.
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