Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear preservation and cytoplasmic degradation of human immunodeficiency virus type 1 Rev protein

Rev, a major regulatory protein of human immunodeficiency virus type 1, has been demonstrated to shuttle between the nucleus and cytoplasm of infected cells. The fate of the Rev protein in living cells was evaluated by pulse-chase experiments using a transient Rev expression system. Sixteen hours after chasing with unlabelled amino acids, 45% of the labelled Rev was still present, which clearly indicates a long half-life of Rev in living cells. A Rev mutant which is deficient in the ability to migrate from the nucleus to the cytoplasm was degraded more slowly than the wild-type Rev protein. As well, another Rev mutant protein, which lacks a functional nucleolar targeting signal (NOS) and is unable to enter the cell nucleus, was rapidly degraded and undetectable 16 h after chasing. Nuclear-nucleolar targeting properties provided by a divergent NOS from a related retrovirus, which was used to substitute for the NOS of Rev, increased the intracellular half-life of this Rev mutant. Moreover, coexpression of an intracellular anti-Rev single-chain antibody (SFv), which has been shown to interfere with the nuclear translocation of Rev, accelerated the degradation of the wild-type Rev protein. Differential degradation of Rev in the nucleus and cytoplasm may play a critical role in determining and maintaining different stages of human immunodeficiency virus type 1 infection, in conjunction with the shuttling properties of the Rev protein.
Increase of vascular endothelial growth factor mRNA expression by 1,25‐dihydroxyvitamin D3 in human osteoblast‐like cells

Vascular endothelial growth factor (VEGF), a secreted endothelial cell‐specific mitogen, is produced in endocrine organs and regulated by trophic hormones. Because angiogenesis and osteogenesis are closely regulated, we studied whether human osteoblast‐like cells produce VEGF, and if so, what factors regulate VEGF mRNA expression. Human osteoblast‐like cells (HObLC) derived from trabecular bone explants were cultured in α‐MEM supplemented with 10% fetal calf serum. Northern blot analysis revealed that HObLC expressed VEGF mRNA, as did several human osteosarcoma cells. 1,25‐(OH)2D3 increased the steady‐state levels of VEGF mRNA in a time‐ and concentration‐dependent manner in HObLC and one of the osteosarcoma cell lines, SaOS‐2, accompanied by an increase in the concentration of immunoreactive VEGF in the conditioned medium. PTH and IGF‐I also increased the level of VEGF mRNA in HObLC and SaOS‐2 cells. Furthermore, 12‐O‐tetradecanoylphorbol ester stimulated VEGF mRNA in a time‐and concentration‐dependent manner. The VEGF mRNA expression induced by 1,25‐(OH)2D3 was completely inhibited by H‐7, but only partially by staurosporine. We have demonstrated that PTH, IGF‐I, and most potently 1,25‐(OH)2D3 stimulate the mRNA expression and secretion of VEGF in human osteoblast‐like cells, suggesting that one of the anabolic effects of 1,25‐(OH)2D3 on skeletal tissue may be mediated by VEGF produced by osteoblasts.
Hyaluronidase Induction of a WW Domain-containing Oxidoreductase That Enhances Tumor Necrosis Factor Cytotoxicity*

To determine how hyaluronidase increases certain cancer cell sensitivity to tumor necrosis factor (TNF) cytotoxicity, we report here the isolation and characterization of a hyaluronidase-induced murine WW domain-containing oxidoreductase (WOX1). WOX1 is composed of two N-terminal WW domains, a nuclear localization sequence, and a C-terminal alcohol dehydrogenase (ADH) domain. WOX1 is mainly located in the mitochondria, and the mitochondrial targeting sequence was mapped within the ADH domain. Induction of mitochondrial permeability transition by TNF, staurosporine, and atractyloside resulted in WOX1 release from mitochondria and subsequent nuclear translocation. TNF-mediated WOX1 nuclear translocation occurred shortly after that of nuclear factor-κB nuclear translocation, whereas both were independent events. WOX1 enhanced TNF cytotoxicity in L929 cells via its WW and ADH domains as determined using stable cell transfectants. In parallel with this observation, WOX1 also enhanced TRADD (TNFreceptor-associated deathdomain protein)-mediated cell death in transient expression experiments. Antisense expression of WOX1 raised TNF resistance in L929 cells. Enhancement of TNF cytotoxicity by WOX1 is due, in part, to its significant down-regulation of the apoptosis inhibitors Bcl-2 and Bcl-xL (>85%), but up-regulation of pro-apoptotic p53 (∼200%) by the ADH domain. When overexpressed, the ADH domain mediated apoptosis, probably due to modulation of expression of these proteins. The WW domains failed to modulate the expression of these proteins, but sensitized COS-7 cells to TNF killing and mediated apoptosis in various cancer cells independently of caspases. Transient cotransfection of cells with both p53 and WOX1 induced apoptosis in a synergistic manner. WOX1 colocalizes with p53 in the cytosol and binds to the proline-rich region of p53 via its WW domains. Blocking of WOX1 expression by antisense mRNA abolished p53 apoptosis. Thus, WOX1 is a mitochondrial apoptogenic protein and an essential partner of p53 in cell death.
Community-Onset Escherichia coli Infection Resistant to Expanded-Spectrum Cephalosporins in Low-Prevalence Countries

ABSTRACT By global standards, the prevalence of community-onset expanded-spectrum-cephalosporin-resistant (ESC-R) Escherichia coli remains low in Australia and New Zealand. Of concern, our countries are in a unique position, with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbors with high ESC-R E. coli rates. We aimed to characterize the risks and dynamics of community-onset ESC-R E. coli infection in our low-prevalence region. A case-control methodology was used. Patients with ESC-R E. coli or ESC-susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary care hospitals in Australia and New Zealand. Epidemiological data were prospectively collected, and bacteria were retained for analysis. In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R among E. coli strains, including birth on the Indian subcontinent (odds ratio [OR] = 11.13, 95% confidence interval [95% CI] = 2.17 to 56.98, P = 0.003), urinary tract infection in the past year (per-infection OR = 1.430, 95% CI = 1.13 to 1.82, P = 0.003), travel to southeast Asia, China, the Indian subcontinent, Africa, and the Middle East (OR = 3.089, 95% CI = 1.29 to 7.38, P = 0.011), prior exposure to trimethoprim with or without sulfamethoxazole and with or without an expanded-spectrum cephalosporin (OR = 3.665, 95% CI = 1.30 to 10.35, P = 0.014), and health care exposure in the previous 6 months (OR = 3.16, 95% CI = 1.54 to 6.46, P = 0.02). Among our ESC-R E. coli strains, the blaCTX-M ESBLs were dominant (83% of ESC-R E. coli strains), and the worldwide pandemic ST-131 clone was frequent (45% of ESC-R E. coli strains). In our low-prevalence setting, ESC-R among community-onset E. coli strains may be associated with both “export” from health care facilities into the community and direct “import” into the community from high-prevalence regions.
Understanding the Macro-Financial Effects of Household Debt: A Global Perspective

We confirm the negative relationship between household debt and future GDP growth documented in Mian, Sufi, and Verner (2017) for a wider set of countries over the period 1950â2016. Three mutually reinforcing mechanisms help explain this relationship. First, debt overhang impairs household consumption when negative shocks hit. Second, increases in household debt heighten the probability of future banking crises, which significantly disrupts financial intermediation. Third, crash risk may be systematically neglected due to investorsâ overoptimistic expectations associated with household debt booms. In addition, several institutional factors such as flexible exchange rates, higher financial development and inclusion are found to mitigate this impact. Finally, the tradeoff between financial inclusion and stability nuances downside risks to growth.
Disentangling Investor Sentiment: Mood and Household Attitudes Towards the Economy

In this paper, we disentangle investor sentiment into two components: mood and household attitudes towards the economy. We apply acoustical analysis to the daily top ten of music downloads in iTunes for Germany to derive a novel and direct measure for mood. We match this novel mood index with trading data of German individual investors. We find that when mood is positive, investors purchase more, particularly trading into risky and out of less-risky securities. To proxy for household attitudes towards the economy, we use an already existing index (FEARS), which bases on Google search volumes of negative economic terms. We find that FEARS drives trading in the same fashion as in previous studies and that these effects significantly depend on mood. We conclude that there are two sources of sentiment driving individual investors, which significantly interact.
Severe acute respiratory syndrome: global initiatives for disease diagnosis

Abstract We present a retrospective analysis of the available articles on severe acute respiratory syndrome (SARS) published since the outbreak of the disease. SARS is a new infectious disease caused by a novel coronavirus. Originating in Guangdong, Southern China, at the end of 2002, it has spread to regions all over the world, affecting more than 8000 people. With high morbidity and mortality, SARS is an important respiratory disease which may be encountered world-wide. The causative virus was identified by a WHO-led network of laboratories, which identified the genome sequence and developed the first molecular assays for diagnosis. For the respiratory physician, detecting SARS in its earliest stages, identifying pathways of transmission, and implementing preventive and therapeutic strategies are all important. The WHO and the CDC have published helpful definitions of ‘suspected’ and ‘probable’ cases. However, the symptoms of the disease may change, and laboratory tests and definitions are still limited. Even in a situation of no new cases of infection, SARS remains a major respiratory health hazard. As with influenza virus outbreaks, new epidemics may arise at the end of each year.
Diagnose der kaninen Parvovirus-Infektion

Zusammenfassung Die kanine Parvovirus-Infektion stellt die weltweit häufigste Viruserkrankung beim Hund dar und weist noch immer eine sehr hohe Mortalitätsrate auf. Sie betrifft vor allem Welpen, wenn deren Titer an maternalen Antikörpern abgesunken ist und sich impfinduzierte Antikörper noch nicht entwickelt haben. Eine schnelle und sichere Diagnose ist aus zwei Gründen essenziell, einerseits, um erkrankte Welpen schnell zu erkennen und sie einer intensiven Therapie zu unterziehen, andererseits, um Ausscheider zu identifizieren und eine Verbreitung des Virus zu vermeiden. Zur Diagnosestellung gibt es viele verschiedene Möglichkeiten. Während sich der Nachweis von Antikörpern gegen kanine Parvoviren für die Diagnose nicht eignet, ist der Nachweis der Viren oder ihrer Bestandteile (Antigen, DNA) beweisend. Für diesen direkten Erregernachweis können verschiedene Tests aus kommerziellen Labors wie auch auf ELISA basierende praxistaugliche Schnelltests verwendet werden. Letztgenannte verfügen über eine durchweg exzellente Spezifität, doch liegt die Anzahl falsch negativer Testergebnisse in der Regel sehr hoch, woraus sich Fehldiagnosen ergeben können. Die Polymerasekettenreaktion ist eine sehr sensitive und spezifische Nachweismethode. Sie bietet den weiteren Vorteil, dass durch eine sich anschließende Sequenzierung eine Differenzierung zwischen Impf- und Feldstämmen vorgenommen werden kann.
A Budget-Impact and Cost-Effectiveness Model for Second-Line Treatment of Major Depression

BACKGROUND: Depressed patients who initially fail to achieve remission when placed on a selective serotonin reuptake inhibitor (SSRI) may require a second treatment. OBJECTIVES: The purpose of this study was to evaluate the effectiveness, cost, cost-effectiveness, and budget impact of second-line pharmacologic treatment for major depressive disorder (MDD). METHODS: A cost-effectiveness analysis was conducted to evaluate second line therapies (citalopram, escitalopram, fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, and venlafaxine extended release [XR]) for the treatment of depression. Effectiveness data were obtained from published clinical studies. The primary outcome was remission defined as a score of 7 or less on the Hamilton Rating Scale for Depression (HAM-D) or a score of 10 or less on the Montgomery-Asberg Depression Rating Scale (MADRS) depression rating scales. The wholesale acquisition cost (WAC) for medications and medical treatment costs for depression were included. The perspective was derived from a managed care organization (MCO) with 500,000 members, a 1.9% annual incidence of depression, and treatment duration of 6 months. Assumptions included: second-line treatment is not as effective as first-line treatment, WAC price reflects MCO costs, and side effects were identical. Sensitivity analyses were conducted to determine variables that influenced the results. RESULTS: Second-line remission rates were 20.4% for venlafaxine XR, 16.9% for sertraline, 16.4% for escitalopram, 15.1% for generic SSRIs (weighted average), and 13.6% for paroxetine CR. Pharmacy costs ranged from $163 for generic SSRIs to $319 for venlafaxine XR. Total cost per patient achieving remission was $14,275 for venlafaxine XR, followed by $16,100 for escitalopram. The incremental cost-effectiveness ratio (ICER) for venlafaxine XR compared with generic SSRIs was $2,073 per patient achieving remission, followed by escitalopram with an ICER of $3,566. The model was most sensitive to nonpharmacy costs. CONCLUSIONS: This analysis suggests that second-line treatment of depression with venlafaxine XR may result in more patients achieving remission, with an ICER that is favorable to other therapies.
Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction

Ca-activated Cl channels are an important component of olfactory transduction. Odor binding to olfactory receptors in the cilia of olfactory sensory neurons (OSNs) leads to an increase of intraciliary Ca concentration by Ca entry through cyclic nucleotide-gated (CNG) channels. Ca activates a Cl channel that leads to an efflux of Cl from the cilia, contributing to the amplification of the OSN depolarization. The molecular identity of this Cl channel remains elusive. Recent evidence has indicated that bestrophins are able to form Ca-activated Cl channels in heterologous systems. Here we have analyzed the expression of bestrophins in the mouse olfactory epithelium and demonstrated that only mouse bestrophin-2 (mBest2) was expressed. Single-cell RT-PCR showed that mBest2 was expressed in OSNs but not in supporting cells. Immunohistochemistry revealed that mBest2 was expressed on the cilia of OSNs, the site of olfactory transduction, and colocalized with the main CNGA2 channel subunit. Electrophysiological properties of Ca-activated Cl currents from native channels in dendritic knob/cilia of mouse OSNs were compared with those induced by the expression of mBest2 in HEK-293 cells. We found the same anion permeability sequence, small estimated single-channel conductances, a Ca sensitivity difference of one order of magnitude, and the same side-specific blockage of the two Cl channel blockers commonly used to inhibit the odorant-induced Ca-activated Cl current in OSNs, niflumic acid, and 4-acetamido-4′-isothiocyanato-stilben-2,2′-disulfonate (SITS). Therefore, our data suggest that mBest2 is a good candidate for being a molecular component of the olfactory Ca-activated Cl channel.
Politics of the pantry: housewives, food, and consumer protest in twentieth-century America

Michelle Glowa’s chapter—"Urban agriculture, food justice, and neoliberal urbanisation: rebuilding the institution of property”—focuses on how community groups and urban agriculture programs can work around or within existing land ownership rights. Glowa examines different programs where participants are growing gardens in their backyards (with permission from their landlords), how public–private partnerships allow gardeners to make use of underutilized city space, like parks, and the use of “mobile community gardens” that allow the garden to move if the land it is based on comes under development. This is not, Glowa argues, simply a neoliberal case of private gardeners moving in to create space or access when the city cannot. Rather, this is about empowering residents to pressure the city for a voice when it comes to decision-making (p. 244). Within these different approaches to land-use—mobile, interim, temporary, or long-term—there are conflicts. Activists disagree on which methods might work best. Food workers have often been a blind spot in the work of alternative food activists, and this book goes a way to redress this, featuring three separate chapters specifically chronicling food and farm workers. Joshua Sbicca discusses some of these “labor–food justice alliances” (p. 108) in his chapter, “Resetting the ‘Good Food’ Table. ” Sbicca’s focus is Los Angeles, and the labor– food worker alliances that have developed in the city, showing how alliances between labor movements and food workers can mean a better outcome in all divisions of the food system. This book made me contemplate how we frame problems and their potential solutions. The authors in this volume do not shy away from the complexity of addressing food issues, often drawing the reader’s attention to the conflicts that exist within particular campaigns or programs. The book provides examples of how people can focus on a shared goal and set aside disputes for a period. This book is a compelling read for students and academics studying and researching food system activism, and food justice. It is also an important book for activists and others at the frontline of these campaigns and programs, who might take heart from the examples discussed in this book.
The Epithelial‐to‐Mesenchymal Transition‐Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation

Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer due to its highly invasive nature that impedes the surgical removal of all tumor cells, making relapse inevitable. However, the mechanisms used by glioma cells to invade the surrounding tissue are still unclear. In this context, epithelial‐to‐mesenchymal transition (EMT) has emerged as a key regulator of this invasive state and although the real relevance of this program in malignant glioma is still controversial, it has been strongly associated with GBM malignancy. EMT is a very complex process regulated by several families of transcriptional factors through many signaling pathways that form a network that allows cancer cells to acquire invasive properties and penetrate the neighboring stroma, resulting in the formation of an advantageous microenvironment for cancer progression and metastasis. In this systematic review, we focus on the molecular mechanisms of EMT including EMT‐factors, drug resistance, miRNA, and new therapeutic strategies. In addition, we address controversial questions about mesenchymal shift in GBMs with a bioinformatics analysis to show that in terms of epithelial and mesenchymal phenotype, the majority of GBMs samples analyzed have a profile more mesenchymal than epithelial. If induced, this phenotype can be shifted toward an even more mesenchymal phenotype in an EMT‐like process in glioma cells. A better understanding of the molecular regulation of the EMT during tumor spreading will help to provide potential therapeutic interventions to target this program when treating GBM.
Translation Control of Swarming Proficiency in Bacillus subtilis by 5-Amino-pentanolylated Elongation Factor P*

Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram-negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys32 of B. subtilis EF-P that is required for swarming motility. A fluorescent in vivo B. subtilis reporter system identified peptide motifs whose efficient synthesis was most dependent on 5-aminopentanol EF-P. Examination of the B. subtilis genome sequence showed that these EF-P-dependent peptide motifs were represented in flagellar genes. Taken together, these data show that, in B. subtilis, a previously uncharacterized posttranslational modification of EF-P can modulate the synthesis of specific diprolyl motifs present in proteins required for swarming motility.
Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head‐and‐neck cancer xenografts

The CD44 protein family consists of isoforms with tissue‐specific expression, which are encoded by standard exons and up to 9 alternatively spliced variant exons (v2–v10) of the same gene. The murine MAbs U36 and BIWA‐1, directed against overlapping epitopes within the v6 region of CD44, have previously been shown to efficiently target HNSCC. We herein report on the construction of 1 chimeric (BIWA‐2) and 2 humanized (BIWA‐4 and BIWA‐8) derivatives of BIWA‐1. Together with U36 and BIWA‐1, these new antibodies were evaluated for affinity to the antigen in vitro as well as for biodistribution and efficacy in RIT using nude mice bearing the HNSCC xenograft line HNX‐OE. As determined by surface plasmon resonance, the MAbs bound to CD44v6 with an up to 46‐fold difference in affinity (Kd ranging from 1.1 × 10−8 to 2.4 × 10−10 M) with the following ranking: mMAb U36 < hMAb BIWA‐4 < hMAb BIWA‐8 < mMAb BIWA‐1 ∼ cMAb BIWA‐2. To evaluate their in vivo tumor‐targeting properties, 2 MAbs with identical murine or human isotype were labeled with either 131I or 125I and administered simultaneously (50 μg/10 μCi each) as pairs showing a stepwise decrease in the difference in affinity: U36 vs. BIWA‐1 (35.0‐fold difference), BIWA‐4 vs. BIWA‐2 (14.0‐fold) and BIWA‐4 vs. BIWA‐8 (4.0‐fold). Biodistribution was assessed at 1, 2, 3 or 4 and 7 days after injection. Remarkably, for all 3 MAb pairs tested, the lower‐affinity MAb showed a higher degree and specificity of tumor localization. The difference in tumor localization was more pronounced when the difference in affinity was larger. For example, 3 days after injection, the lower‐affinity mMAb U36 showed a 50% higher tumor uptake than the higher‐affinity mMAb BIWA‐1, while blood levels and uptake in organs were similar. After labeling with 186Re (300 or 400 μCi), the same MAb pairs showed RIT efficacy consistent with the biodistribution data: 186Re‐U36 was more effective than 186Re‐BIWA‐1, 186Re‐BIWA‐4 was slightly more effective than 186Re‐BIWA‐2 and 186Re‐BIWA‐4 and 186Re‐BIWA‐8 demonstrated similar efficacy. Based on these data, we conclude that antibodies with markedly lower affinity to a given target antigen (e.g., U36, BIWA‐4) may show superior tumor targeting in comparison with higher‐affinity versions of these antibodies. © 2002 Wiley‐Liss, Inc.