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The sex determination system of largemouth bass (Micropterus salmoides, LMB) is XX/XY; however, the underlying molecular mechanisms involved in early sex differentiation, gonadal development, and exogenous hormone-induced sex reversal remain unknown. In this study, LMB at 15 days post-hatching (dph) were fed diets containing 20 mg/kg of 17a-methyltestosterone (17a-MT) or 30 mg/kg of 17ß-estradiol (17ß-E2) for 60 days, respectively. Serum steroid levels, histological observations of the gonads, and identification of sex-specific markers were employed to screen the gonads of 60-day-old normal female fish (XX-F), normal male fish (XY-M), 17ß-E2 induced pseudo-female fish (XY-F), and 17a-MT-induced pseudo-male fish (XX-M) for transcriptome sequencing in order to uncover genes and pathway involved in the process of sexual reversal. The results from histology and serum sex steroid hormone analysis showed that both 17a-MT and 17ß-E2 were capable of inducing sex reversal of LMB at 15 dph. Transcriptome results revealed a total of 2,753 genes exhibiting differential expression, and the expression pattern of these genes in the gonads of XX-M or XY-F resembled that of normal females or males. The male sex-biased genes that are upregulated in XX-M and downregulated in XY-F are referred to as key genes for male reversal, while the female sex-biased genes that are upregulated in XY-F and downregulated in XX-M are referred to as key genes for female reversal. Finally, 12 differentially expressed genes (DEGs) related to male sex reversal were screened, including star2, cyp17a, cyp11b1, dmrt1, amh, sox9a, katnal1, spata4, spata6l, spata7, spata18 and foxl3. 2DEGs (foxl2a and cyp19a1b) were found to be associated with female sex reversal. The changes in these genes collectively influence the direction of sex differentiation of LMB. Among them, star2, dmrt1 and cyp19a1b with significantly altered expression levels may play potentially crucial role in the process of gender reversal. The expression patterns of 21 randomly selected genes were verified using qRT-PCR which confirmed the reliability and accuracy of the RNA-seq results. These findings not only enhance our understanding of the molecular basis underlying sex reversal but also provide crucial data support for future breeding research on unisexual LMB. [ABSTRACT FROM AUTHOR]

Purpose of Review: Burkitt's lymphoma and its leukemic form (Burkitt cell acute lymphoblastic leukemia) are a highly aggressive disease. We review the classification, clinical presentation, histology, cytogenetics, and the treatment of the disease. Recent Findings: Burkitt's lymphoma might be associated with tumor lysis syndrome which is a potentially fatal complication that occurs spontaneously or upon initiation of chemotherapy. Major improvements were made in the treatment of pediatric and adults population using short-course dose-intensive chemotherapy regimens, usually 1 week after a prephase induction. Addition of Rituximab to chemotherapy has become a standard of care. Relapsed/refractory disease has a very poor prognosis and the benefit from autologous/allogeneic hematopoietic stem cell transplant remains uncertain. Summary: Rituximab-based short-course dose-intensive chemotherapy is the standard of care of Burkitt's lymphoma even in the immunodeficiency-related form. [ABSTRACT FROM AUTHOR]

Dissolved oxygen (DO) in the overlying water is important in influencing internal phosphorus (P) release. However, the potentially associative effect of DO on the P adsorption and immobilization by La-modified bentonite (LMB) has not been quantified. This 80-day incubation experiment showed the synergistic effect of DO and LMB in the overlying water, which caused the reduction of dissolved inorganic phosphorus (DIP) by 51% (DO = 5 mg L−1) and 77% (DO = 7 mg L−1) on average, respectively, compared with the DO of 3 mg L−1. In addition, the DIP in the pore water decreased from 1.12 mg P L−1 (control) to 0.014 mg P L−1 (5 mg L−1) and 0.004 mg P L−1 (7 mg L−1). Besides, the Fe2+ and NH4+ concentrations were also reduced significantly in the pore water, suggesting the rise in the redox potential in the sediment, which helped P immobilization. Chemical P-fractionation experiments indicate that the Fe-P reduction in sediment was the most significant, reduced by 14%, followed by NH4Cl-P (12%), causing a reduction by 13% (3 mg L−1), 23% (5 mg L−1) and 27% (7 mg L−1) of mobile P in the surface 7-cm sediment, respectively. However, the released P ions were rapidly adsorbed by the Al ions and Ca ions, as well as their compounds, thereby leading to the obvious rise in inert P in the sediment. Accordingly, it was suggested that DO and LMB had a synergistic effect on external P adsorption and immobilization. [ABSTRACT FROM AUTHOR]

In this paper, we propose a technique for the joint tracking and labeling of multiple extended targets. To achieve multiple extended target tracking using this technique, models for the target measurement rate, kinematic component, and target extension are defined and jointly propagated in time under the generalized labeled multi-Bernoulli filter framework. In particular, we developed a Poisson mixture variational Bayesian model to simultaneously estimate the measurement rate of multiple extended targets and extended target extension was modeled using B-splines. We evaluated our proposed method with various performance metrics. Results demonstrate the effectiveness of our approach. [ABSTRACT FROM AUTHOR]

Reactive astrogliosis is a prominent and ubiquitous reaction of astrocytes to many types of brain injury. Up-regulation of glial fibrillary acidic protein (GFAP) expression and astroglial proliferation are hallmarks of reactive astrogliosis. However, the mechanisms that regulate reactive astrogliosis remain elusive. In the present study, status epilepticus (SE, a prolonged seizure activity) led to reactive astrogliosis showing the increases in GFAP expression and the number of proliferating astrocytes with prolonged extracellular signal receptor-activated kinases 1/2 (ERK1/2) activation and reduced nuclear p27Kip1 level. U0126, an ERK1/2 inhibitor, showed opposite effects. Leptomycin B (LMB), an inhibitor of chromosomal maintenance 1 (CRM1), attenuated nucleocytoplasmic p27Kip1 export and astroglial proliferation, although it up-regulated ERK1/2 phosphorylation and GFAP expression. Roscovitine ameliorated the reduced nuclear p27Kip1 level and astroglial proliferation without changing GFAP expression and ERK1/2 phosphorylation. U0126 aggravated SE-induced astroglial apoptosis in the molecular layer of the dentate gyrus that was unaffected by LMB and roscovitine. In addition, U0126 exacerbated SE-induced neuronal death, while LMB mitigated it. Roscovitine did not affect SE-induced neuronal death. The present data elucidate for the first time the roles of nucleocytoplasmic p27Kip1 transport in ERK1/2-mediated reactive astrogliosis independent of SE-induced neuronal death and astroglial apoptosis. Therefore, our findings suggest that nucleocytoplasmic p27Kip1 export may be required for ERK1/2- mediated astroglial proliferation during reactive astrogliosis, and that nuclear p27Kip1 entrapment may be a potential therapeutic strategy for anti-proliferation in reactive astrocytes. [ABSTRACT FROM AUTHOR]

Trafficking of proteins between the cytoplasm and nucleus occurs exclusively across the nuclear pore complex of eucaryotic cells. Fundamental aspects of this process affect temporal and spatial parameters, the latter carried out by specific import [nuclear localization sequence (NLS)] and export [nuclear export sequence (NES)] sequences. In this study, we focused on the adaptation of a protein heterodimerization assay to kinetically measure Crm1-mediated nuclear export in living cells using the rapalog AP21967, a heterodimerizing agent and NLS- and NES-containing fusion proteins equipped with distinct AP21967-specific binding motifs. In HeLa cells, we observed rapid nuclear export of the NLS-containing fusion protein in the presence of AP21967, with the extent of this process being a function of the number of AP21967-binding motifs. AP21967-induced nuclear export was specifically inhibited by the Crm1-binding molecule leptomycin B. Half maximal export was achieved after ∼ 10 min. We further applied protein heterodimerization in HeLa cells to study induced NLS-mediated nuclear import. Only in the presence of heterodimerizer AP21967 nuclear import of a cytoplasmically localizing fusion protein was observed. Induced protein heterodimerization is thus a valuable tool to quantitatively study nucleocytoplasmic protein trafficking in cultured cells, in a non-invasive, time-saving manner. [ABSTRACT FROM AUTHOR]

Fluorescent protein biosensors are powerful cellular systems biology tools for dissecting the complexity of cellular processes with high spatial and temporal resolution. As regulated nucleo-cytoplasmic transport is crucial for the modulation of numerous (patho)physiological cellular responses, a detailed understanding of its molecular mechanism would open up novel options for a rational manipulation of the cell. In contrast to genetic approaches, we here established and employed high-content cellular translocation biosensors applicable for dissecting nuclear export by chemicogenomics. A431 cell lines, stably expressing a translocation biosensor composed of glutathione Stransferase, GFP and a rational combination of nuclear import and export signals, were engineered by antibiotic selection and flow cytometry sorting. Using an optimized nuclear translocation algorithm, the translocation response could be robustly quantified on the Cellomics Arrayscan® VTI platform. Subsequent to assay optimization, the assay was developed into a higher density 384-well format high-content assay and employed for the screening of the 17K ChemBioNet compound collection. This library was selected on the basis of a genetic algorithm used to identify maximum common chemical substructures in a database of annotated bioactive molecules and hence, is well-placed in the chemical space covered by bioactive compounds. Automated multiparameter data analysis combined with visual inspection allowed us to identify and to rationally discriminate true export inhibitors from false positives, which included fluorescent compounds or cytotoxic substances that dramatically affected the cellular morphology. A total of 120 potential hit compounds were selected for Cellomics Arrayscan® VTI based rescreening. The export inhibitory activity of 20 compounds effective at concentrations < 25 μM were confirmed by fluorescence microscopy in several cell lines. Interestingly, kinetic analysis allowed the identification of inhibitors capable to interfere with the export receptor CRM1-mediated nuclear export not only in an irreversible, but also in a reversible fashion. In sum, exploitation of biosensor based screening allows the identification of chemicogenomic tools applicable for dissecting nucleo-cytoplasmic transport in living cells. [ABSTRACT FROM AUTHOR]

Survivin appears to function as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Here we report the molecular characterization of the nucleocytoplasmic transport of survivin mid its potential implications for tumorigenesis. We identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. In dividing cells, the NES is essential for tethering survivin and the survivin/Aurora-B kinase complex to the mitotic machinery, which in turn appears to be essential for proper cell division. In addition, export seems to be required for the cytoprotective activity of survivin, as export-deficient survivin fails to protect tumor cells against chemo- and radiotherapy-induced apoptosis. These findings appear to be clinically relevant since preferential nuclear localization of survivin correlated with enhanced survival in colorectal cancer patients. Targeting survivin's nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We demonstrate that nuclear export is essential for the biological activity of survivin and promote the identification of molecular decoys to specifically interfere with survivin's nuclear export as potential anticancer therapeutics. [ABSTRACT FROM AUTHOR]

Survivin appears to function as a regulator of cell division and as an apoptosis inhibitor in many species. Here, we characterized the nucleocytoplasmic transport of mouse survivin140, and its splice variants survivin121 and survivin40. We show that the dynamic intracellular localization of survivin140 is mediated by a Crm1-dependent nuclear export signal (NES) present also in survivin121, but absent in survivin40. In contrast, neither survivin nor survivin splice variants contain an active nuclear import signal and seem to enter the nucleus by passive diffusion. The activity of the NES is required for survivin-mediated protection against cell death inducing stimuli and influences protein degradation. During mitosis, NES-deficient survivin variants fail to correctly localize to the mitotic machinery and promote proper cell division. In vivo and in vitro protein interaction assays show that survivin140 and survivin121 as well as their export-deficient mutants are able to form homo- as well as heterodimers. The trans-dominant negative phenotype observed upon expression of export-deficient survivin appears, therefore, to be mediated by the formation of inactive survivin heterodimers. The survivin–Crm1 axis is essential for the biological activities of murine survivin, and mouse models will allow investigating its functional implications during development and tumorigenesis. [ABSTRACT FROM AUTHOR]

The purpose of this study is to promote a new way of application composite materials to restore eutrophic waters. A new sustainable way of application is based on the "teabag" method, in which materials were placed in water-permeable bags and immersed in the water column in order to sorb phosphate—one of the main contributory element for the eutrophication problem. Particularly, the two composites materials of Phoslock™ (lanthanum-modified bentonite, LMB) and Bephos™ (Fe-modified bentonite, f-MB) were tested and bench-scale batch experiments were employed to investigate their sorption efficiency in the forms of slurry and teabag. The adsorption kinetics and the relevant adsorption isotherms were deployed, while the effect of the materials on turbidity and their aging were also investigated. Experimental results showed that Phoslock™ and Bephos™ (as teabag), being applied at initial concentration range: 0.05–5 mg/L, they sustained a maximum adsorption capacity of 7.80 mg/g and 25.1 mg/g, respectively, which are considered sufficient rates for P concentrations reported at natural aquatic ecosystems. At the same time this new method did not cause turbidity in the water column, since the material was not released into the water, thus, preventing potential harmful consequences for the living organisms. Moreover, the "teabag" method prevents the material to cover the lake bottom, avoiding the phenomenon of smothering of benthos. Βy teabag method, the materials can be collected for further applicability as soil improver or crops fertilizer. Finally, it was argued that the possibility to recycle LMB and f-MB materials for agricultural use is of paramount importance, sustaining also positive impacts on sustainable ecology and on the routes of circular economy (CE). [ABSTRACT FROM AUTHOR]