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The development of an influenza vaccine with broad protection and durability remains an attractive idea due to the high mutation rate of the influenza virus. An extracellular domain of Matrix 2 protein (M2e) is among the most attractive target for the universal influenza vaccine owing to its high conservancy rate. Here, we generated two recombinant live attenuated influenza vaccine (LAIV) candidates encoding four M2e epitopes representing consensus sequences of human, avian and swine influenza viruses, and studied them in a preclinical ferret model. Both LAIV+4M2e viruses induced higher levels of M2e-specific antibodies compared to the control LAIV strain, with the LAIV/HA+4M2e candidate being significantly more immunogenic than the LAIV/NS+4M2e counterpart. A high-dose heterosubtypic influenza virus challenge revealed the highest degree of protection after immunization with LAIV/HA+4M2e strain, followed by the NS-modified LAIV and the classical LAIV virus. Furthermore, only the immune sera from the LAIV/HA+4M2e-immunized ferrets protected mice from a panel of lethal influenza viruses encoding M genes of various origins. These data suggest that the improved cross-protection of the LAIV/HA+4M2e universal influenza vaccine candidate was mediated by the M2e-targeted antibodies. Taking into account the safety profile and improved cross-protective potential, the LAIV/HA+4M2e vaccine warrants its further evaluation in a phase I clinical trial.Muskellunge (Esox masquinongy) is the largest and most prized game fish in North America. However, little is known about Muskellunge genetic diversity in Iowa's propagation program. We used Whole-Genome Sequencing of 12 brooding individuals from Iowa and publicly available RAD-seq of 625 individuals from the St. Lawrence River in Canada to study the genetic differences between populations, analyze signatures of selection, and evaluate the levels of genetic diversity in both populations. Given that there is no reference genome available, reads were aligned to the genome of Pike (Esox lucius). Variant calling produced 7,886,471 biallelic variants for the Iowa population and 16,867 high-quality SNPs that overlap with the Canadian samples. Principal component analysis (PCA) and Admixture analyses showed a large genetic difference between Canadian and Iowan populations. Window-based pooled heterozygosity found 6 highly heterozygous windows in the Iowa population and Fst between populations found 14 windows with fixation statistic (Fst) values larger than 0.9. check details Canadian inbreeding rate (Froh = 0.32) appears to be higher due to the inbreeding of Iowa population (Froh = 0.03), presumably due to isolation of subpopulations. Although inbreeding does not seem to be an immediate concern for Muskellunge in Iowa, the Canadian population seems to have a high rate of inbreeding. Finally, this approach can be used to assess the long-term viability of the current management practices of Muskellunge populations across North America.Polylactic acid (PLA) is one of the most suitable materials for 3D printing. Blending with nanoparticles improves some of its properties, broadening its application possibilities. The article presents a study of composite PLA matrix filaments with added unmodified and lignin/polymerised lignin surface-modified nanofibrillated cellulose (NFC). The influence of untreated and surface-modified NFC on morphological, mechanical, technological, infrared spectroscopic, and dynamic mechanical properties was evaluated for different groups of samples. As determined by the stereo and scanning electron microscopy, the unmodified and surface-modified NFCs with lignin and polymerised lignin were present in the form of plate-shaped agglomerates. The addition of NFC slightly reduced the filaments' tensile strength, stretchability, and ability to absorb energy, while in contrast, the initial modulus slightly improved. By adding NFC to the PLA matrix, the bending storage modulus (E') decreased slightly at lower temperatures, especially in the PLA samples with 3 wt% and 5 wt% NFC. When NFC was modified with lignin and polymerised lignin, an increase in E' was noticed, especially in the glassy state.Decades of research identified genomic similarities among prostate cancer patients and proposed general solutions for diagnostic and treatments. However, each human is a dynamic unique with never repeatable transcriptomic topology and no gene therapy is good for everybody. Therefore, we propose the Genomic Fabric Paradigm (GFP) as a personalized alternative to the biomarkers approach. Here, GFP is applied to three (one primary-"A", and two secondary-"B" & "C") cancer nodules and the surrounding normal tissue ("N") from a surgically removed prostate tumor. GFP proved for the first time that, in addition to the expression levels, cancer alters also the cellular control of the gene expression fluctuations and remodels their networking. Substantial differences among the profiled regions were found in the pathways of P53-signaling, apoptosis, prostate cancer, block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy, and sustained angiogenesis. ENTPD2, AP5M1 BAIAP2L1, and TOR1A were identified as the master regulators of the "A", "B", "C", and "N" regions, and potential consequences of ENTPD2 manipulation were analyzed. The study shows that GFP can fully characterize the transcriptomic complexity of a heterogeneous prostate tumor and identify the most influential genes in each cancer nodule.Through the years, the available psychopharmacological treatments have expanded with numerous new drugs. Besides weight gain, gastro-intestinal problems or Parkinson-like symptoms, ocular adverse effects of psychiatric drugs have been reported. These adverse effects are not common, but can be dangerous for the patient. This review summarises the current knowledge on the risk of raised intraocular pressure and glaucoma entailed by psychopharmacological treatment. Also, it provides updated data for clinicians involved in the treatment of patients with glaucoma or glaucoma risk factors. For this purpose, we performed an extensive literature search in the PubMed database using specific terms. Selective serotonin and noradrenaline reuptake inhibitors are the best evidenced as having no association with glaucoma. Antipsychotics, and especially first generation, seem to have no correlation with an increased intraocular pressure and therefore possibly with a risk of glaucoma, although a special attention should be paid when using ziprasidone.
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