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The liver stem cell niche is a specialized and dynamic microenvironment with biomechanical and biochemical characteristics that regulate stem cell behavior. This is feasible due to the coordination of a complex network of secreted factors, small molecules, neural, blood inputs and extracellular matrix (ECM) components involved in the regulation of stem cell fate (self-renewal, survival, and differentiation into more mature phenotypes like hepatocytes and cholangiocytes). In this review, we describe and summarize all the major components that play essential roles in the liver stem cell niche, in particular, growth factor signaling and the biomechanical properties of the ECM., (Copyright © 2019 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

This paper analyses Libor interest rates for seven different maturities and referred to operations in British pounds, euros, Swiss francs and Japanese yen, during the period 2001-2015. The analysis is performed by means of two quantifiers derived from information theory: the permutation Shannon entropy and the permutation Fisher information measure. An anomalous behaviour in the Libor is detected in all currencies except euros during the years 2006-2012. The stochastic switch is more severe in one, two and three months maturities. Given the special mechanism of Libor setting, we conjecture that the behaviour could have been produced by the manipulation that was uncovered by financial authorities. We argue that our methodology is pertinent as a market overseeing instrument., (© 2015 The Author(s).)

Nutrient-rich, turbid river plumes that are common to large lakes and coastal marine ecosystems have been hypothesized to benefit survival of fish during early life stages by increasing food availability and (or) reducing vulnerability to visual predators. However, evidence that river plumes truly benefit the recruitment process remains meager for both freshwater and marine fishes. Here, we use genotype assignment between juvenile and larval yellow perch (Perca flavescens) from western Lake Erie to estimate and compare recruitment to the age-0 juvenile stage for larvae residing inside the highly turbid, south-shore Maumee River plume versus those occupying the less turbid, more northerly Detroit River plume. Bayesian genotype assignment of a mixed assemblage of juvenile (age-0) yellow perch to putative larval source populations established that recruitment of larvae was higher from the turbid Maumee River plume than for the less turbid Detroit River plume during 2006 and 2007, but not in 2008. Our findings add to the growing evidence that turbid river plumes can indeed enhance survival of fish larvae to recruited life stages, and also demonstrate how novel population genetic analyses of early life stages can contribute to determining critical early life stage processes in the fish recruitment process.

Turbidity associated with river plumes is known to affect the search ability of visual predators and thus can drive 'top-down' impacts on prey populations in complex ecosystems; however, traditional quantification of predator-prey relationships (i.e. stomach content analysis) often fails with larval fish due to rapid digestion rates. Herein, we use novel molecular genetic methods to quantify larval yellow perch (YP) in predator stomachs in western Lake Erie to test the hypothesis that turbidity drives variation in larval predation. We characterize predator stomach content DNA to first identify YP DNA (single nucleotide polymorphism) and then quantify larval YP predation (microsatellite allele counting) in two river plumes differing in turbidity. Our results showed elevated larval YP predation in the less turbid river plume, consistent with a top-down impact of turbidity on larval survival. Our analyses highlight novel ecological hypothesis testing using the power of innovative molecular genetic approaches., (© 2014 John Wiley & Sons Ltd.)

OTK18 is a C2H2 type zinc finger protein involved in the regulation of HIV-1 replication in human mononuclear phagocytes. Previously, we reported OTK18 expression in brain perivascular macrophages but not in microglia in HIV encephalitis brain. We have cloned the OTK18 promoter region proximal to the transcriptional start site and determined the region responsible (-884/+1) for the basal transcriptional activity in a microglia cell line. Sequential deletion mutation analyses reveal three important response elements: Yingyang-1 (YY1; -805/-777), an HIV-1 response element for promoter activation; FoxD3 (-743/-725), a negative regulatory element; and Ets response element (-725/-707), a basal transcriptional activity response element. HIV-1 infection-induced upregulation of YY1 and c-Ets-1 protein, binding to the promoter region as determined by immunoblotting and chromatin immunoprecipitation and polymerase chain reaction (PCR) assays, and induction of YY1 was also observed in virus-infected monocyte-derived macrophages. Silencing of FoxD3 and YY1 in the cell line by small interfering RNA duplexes specific to these molecules significantly up- and downregulated basal OTK18 promoter activity in FoxD3 and YY1 response element-dependent manners, respectively. On the other hand, infection of primary cultured human microglia significantly reduced YY1 expression and induced FoxD3 as determined by immunoblotting and reverse transcription real-time PCR. These data suggest that HIV-1 induces OTK18 expression through a YY1-mediated manner in human macrophages, although its gene expression is suppressed by FoxD3 upregulation and YY1 downregulation in human microglia. This mechanism may explain the perivascular macrophage-specific expression of OTK18 in HIV encephalitis brains.

As part of the innate immune defense against HIV infection, OTK18, a zinc finger protein, is upregulated in human macrophages and reduces viral replication through suppression of viral long-terminal repeat promoter activity. Although we know that the processing products of OTK18 accumulate in the cytoplasm of brain perivascular macrophages in advanced HIV encephalitis cases, the molecular mechanisms behind its post-translational processing are still poorly understood. To characterize OTK18 processing, we assessed a panel of protease inhibitors to identify the candidates involved in the OTK18 processing using human monocyte-derived macrophages (MDM) overexpressing OTK18 by recombinant adenoviral gene transfer. Viral infection of MDM strongly increased the processing of OTK18 into its N-terminal fragment. Treatment of OTK18-expressing MDM with calpain and proteasome inhibitors significantly accumulated either full-length or processed OTK18 fragments in time- and dose-dependent manners. A series of OTK18 truncation mutants and synthetic peptides were tested to locate the calpain cleavage sites after arginine 359. Finally, we developed an enhanced cyan and yellow fluorescent protein (ECFP and EYFP)-based intramolecular fluorescent resonance energy transfer (intramolecular FRET) system to monitor the OTK18 endoproteolysis in human microglia cell line. Inhibition of proteasome activity significantly increased the intramolecular FRET signal in the nucleus. These data suggest that calpain and proteasome are involved in OTK18 endoproteolysis and degradation. Additionally, intramolecular FRET has proven to be a useful tool for monitoring the processing in live cells.

Tau-tubulin kinase-1 (TTBK1) is involved in phosphorylation of tau protein at specific Serine/Threonine residues found in paired helical filaments, suggesting its role in tauopathy pathogenesis. We found that TTBK1 levels were upregulated in brains of human Alzheimer' disease (AD) patients compared with age-matched non-AD controls. To understand the effects of TTBK1 activation in vivo, we developed transgenic mice harboring human full-length TTBK1 genomic DNA (TTBK1-Tg). Transgenic TTBK1 is highly expressed in subiculum and cortical pyramidal layers, and induces phosphorylated neurofilament aggregation. TTBK1-Tg mice show significant age-dependent memory impairment as determined by radial arm water maze test, which is associated with enhancement of tau and neurofilament phosphorylation, increased levels of p25 and p35, both activators of cyclin-dependent protein kinase 5 (CDK5), enhanced calpain I activity, and reduced levels of hippocampal NMDA receptor types 2B (NR2B) and D. Enhanced CDK5/p35 complex formation is strongly correlated with dissociation of F-actin from p35, suggesting the inhibitory mechanism of CDK5/p35 complex formation by F-actin. Expression of recombinant TTBK1 in primary mouse cortical neurons significantly downregulated NR2B in a CDK5- and calpain-dependent manner. These data suggest that TTBK1 in AD brain may be one of the underlying mechanisms inducing CDK5 and calpain activation, NR2B downregulation, and subsequent memory dysfunction.

It has previously been shown by our laboratory that OTK18, a human immunodeficiency virus (HIV)-inducible zinc-finger protein, reduces progeny-virion production in infected human macrophages. OTK18 antiviral activity is mediated through suppression of Tat-induced HIV-1 long terminal repeat (LTR) promoter activity. Through the use of LTR-scanning mutant vectors, the specific regions responsible for OTK18-mediated LTR suppression have been defined. Two different LTR regions were identified as potential OTK18-binding sites by an enhanced DNA-transcription factor ELISA system; the negative-regulatory element (NRE) at -255/-238 and the Ets-binding site (EBS) at -150/-139 in the LTR. In addition, deletion of the EBS in the LTR blocked OTK18-mediated LTR suppression. These data indicate that OTK18 suppresses LTR activity through two distinct regulatory elements. Spontaneous mutations in these regions might enable HIV-1 to escape from OTK18 antiretroviral activity in human macrophages.

Background: Augmented serum prolactin (PRL) levels have been implicated as a cause for infertility in patients with endometriosis. However, it has not been established whether this lactogenic hormone or its receptor (PRLR) have specific effects on the development of human endometriosis. In the present study we assessed PRLR expression in human endometriotic and normal tissue., Methods: Fourteen patients with laparoscopically proven endometriosis were recruited and the negative or positive expression of the PRLR in normal endometrial and endometriotic tissues obtained during the mid-late proliferative phase of the menstrual cycle was evaluated by RT-PCR. Evaluation of serum prolactin, and peritoneal fluid estradiol content were carried out by specific radioimmunoassays (RIA)., Results: In endometriotic tissue samples the corresponding 1048 bp PRLR transcript was negative in 12/14 of the samples (86%) and positive in two samples (14%). The opposite was seen in normal tissue, since PRLR expression was positive in 11/14 samples (79%) and negative in the remaining three samples (21%). There was an association between serum prolactin concentrations and PRLR expression in normal tissue but not in endometriotic tissue., Conclusions: The PRLR is expressed in normal endometrium, while cells of the endometriotic tissues did not express the PRLR, at least during the mid-late proliferative phase of the menstrual cycle. The absence of the PRLR in the endometriotic tissues could not be correlated with the serum prolactin levels. These results suggest the existence of differential regulation of PRLR expression between normal and endometriotic tissue.

Pollen grains of Lolium perenne (rye grass) were prepared for transmission electron microscopy by rapid freezing in liquid propane, substitution in acetone, methanol or diethyl ether, and embedment in the acrylic resin London Resin gold. These were compared to pollen chemically fixed (CF) in aldehyde/osmium tetroxide and embedded in the epoxy resin Quetol 651. Ultrastructural preservation was superior in freeze-substituted (FS) pollen, particularly with the use of acetone or methanol. Optimally preserved FS pollen displayed a homogeneous aspect of the cytoplasm and nucleoplasm, and smooth, uninterrupted contour or organelles. A striking difference was also seen in the preservation of inclusions in the intine. Varied forms and sizes of intine inclusions were evident in FS pollen but these were not discernible in the CF image. The FS scheme studied here presents enormous potential for both ultrastructural and immunolabelling studies in rye grass pollen. Problems discussed include artifacts associated with each of the substitution solvents used, and a gradient of freezing damage observed within the pollen grain.

Myasthenia gravis developed in a 51-year-old woman in 1956; she was found to have a thymoma. Complete remission of the myasthenia gravis occurred within 18 months of thymomectomy. In 1975, myasthenia gravis recurred in association with recurrence of the thymoma. Remission of the myasthenic state once more followed the thymomectomy. The asymptomatic period of 18 years is, to our knowledge, the longest reported interval for recurrence of a thymoma-associated myasthenia gravis; 15 years is the longest reported interval for recurrence of a thymoma.