Miracle-dz/UniFAR-FTUs huggingface dataset:
Rolling-Circle Replication of an Animal Circovirus Genome in a Theta-Replicating Bacterial Plasmid in Escherichia coli

ABSTRACT A bacterial plasmid containing 1.75 copies of double-stranded porcine circovirus (PCV) DNA in tandem (0.8 copy of PCV type 1 [PCV1], 0.95 copy of PCV2) with two origins of DNA replication (Ori) yielded three different DNA species when transformed into Escherichia coli: the input construct, a unit-length chimeric PCV1Rep/PCV2Cap genome with a composite Ori but lacking the plasmid vector, and a molecule consisting of the remaining 0.75 copy PCV1Cap/PCV2Rep genome with a different composite Ori together with the bacterial plasmid. Replication of the input construct was presumably via the theta replication mechanism utilizing the ColE1 Ori, while characteristics of the other two DNA species, including a requirement of two PCV Oris and the virus-encoded replication initiator Rep protein, suggest they were generated via the rolling-circle copy-release mechanism. Interestingly, the PCV-encoded Rep′ protein essential for PCV DNA replication in mammalian cells was not required in bacteria. The fact that the Rep′ protein function(s) can be compensated by the bacterial replication machinery to support the PCV DNA replication process echoes previous suggestions that circular single-stranded DNA animal circoviruses, plant geminiviruses, and nanoviruses may have evolved from prokaryotic episomal replicons.
Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials

Mitochondria are the cellular center of energy production and of several important metabolic processes. Mitochondrion health is maintained with a substantial intervention of mitophagy, a process of macroautophagy that degrades selectively dysfunctional and irreversibly damaged organelles. Because of its crucial duty, alteration in mitophagy can cause functional and structural adjustment in the mitochondria, changes in energy production, loss of cellular adaptation, and cell death. In this review, we discuss the dual role that mitophagy plays in cancer and age-related pathologies, as a consequence of oxidative stress, evidencing the triggering stimuli and mechanisms and suggesting the molecular targets for its therapeutic control. Finally, a section has been dedicated to the interplay between mitophagy and therapies using nanoparticles that are the new frontier for a direct and less invasive strategy.
SCANNING ELECTRON MICROSCOPIC AND X RAY MICRODIFFRACTOMETERIC STUDIES ON SIALOLITH‐CRYSTALS IN HUMAN SUBMANDIBULAR GLANDS

The crsytalline structures of 18 submandibular gland calculi were studied by radiomicrography, scanning electron microscope, and X ray microdiffractometeric techniques. The following observations were made by SEM: Granular or globular structure was seen on the surface of all cases and pyramidal crystal in one case. In the inside, all showed lamellar pattern with amorphous nucleus in the center, and granular, plate‐like and rhombohedral structures were also observed. X‐ray microdiffractometeric analyses: Apatite was frequently observed in both outside and inside of the calculi. Whitlockite was next frequently detected and was seen more often in the inisde. Brushite and weddellite were noted in the outside of calculi in one case each. Thus, it is suggested that brushite and weddellite were present in the front portion of calculus formation and then transformed into the more stable form e.g. apatite.
Association Between Serosorting and Bacterial Sexually Transmitted Infection Among HIV-Negative Men Who Have Sex With Men at an Urban Lesbian, Gay, Bisexual, and Transgender Health Center

Background Serosorting, selecting sex partners of the same HIV status, may be associated with increased risk of sexually transmitted infection (STI). We examined the association between unprotected anal intercourse (UAI) with a seroconcordant partner and STIs among HIV-negative men who have sex with men (MSM) at an urban lesbian, gay, bisexual, and transgender STI clinic. Methods Subjects reported how they assessed their most recent sex partner’s HIV status. Those who reported getting tested together or asking were classified as known concordant; those who determined their partner’s serostatus based on appearance, age, or social aspects were classified as assumed concordant. Generalized estimating equations generated prevalence ratios for associations between seroconcordance and STIs. Results From May 2010 through October 2011, 961 HIV-negative MSM were screened for gonorrhea, chlamydia, and syphilis at 1110 visits. Sexually transmitted infection prevalence was 20.1%: 20.2% at visits with known seroconcordant UAI, 35.3% at visits with assumed seroconcordant UAI, 29.5% at visits where UAI with an unknown status partner was reported, 34.8% at visits with serodiscordant UAI, and 16.1% at visits with no reported UAI. Assumed serodiscordant UAI (adjusted prevalence ratio [aPR], 2.51; 95% confidence interval [CI], 1.79–3.51), unknown status partner (aPR, 1.76; 95% CI, 1.31–2.38), and serodiscordant UAI (aPR, 2.57; 95% CI, 1.76–3.75) were significant predictors of STI after controlling for age and race/ethnicity, STI history, alcohol use, substance use, and multiple sex partners. Known seroconcordant UAI was not associated with STI. Conclusions Assumed seroconcordant UAI was associated with increased STI prevalence, although known seroconcordant UAI was not. The risk associated with UAI with a partner of assumed seroconcordance should be emphasized for HIV-negative MSM.
Gag Cytotoxic T Lymphocyte Escape Mutations Can Increase Sensitivity of HIV-1 to Human TRIM5α, Linking Intrinsic and Acquired Immunity

ABSTRACT Although laboratory-adapted HIV-1 strains are largely resistant to the human restriction factor TRIM5α (hTRIM5α), we have recently shown that some viruses carrying capsid (CA) sequences from clinical isolates can be more sensitive to this restriction factor. In this study we evaluated the contribution to this phenotype of CA mutations known to be associated with escape from cytotoxic T lymphocyte (CTL) responses. Recombinant viruses carrying HIV-1 CA sequences from NL4-3 and three different clinical isolates were prepared, along with variants in which mutations associated with CTL resistance were modified by site-directed mutagenesis, and the infectivities of these viruses in target cells expressing hTRIM5α and cells in which TRIM5α activity had been inhibited by overexpression of TRIM5γ were compared. For both hTRIM5α-sensitive viruses studied, CTL-associated mutations were found to be responsible for this phenotype. Both CTL resistance mutations occurring within HLA-restricted CA epitopes and compensatory mutations occurring outside CTL epitopes influenced hTRIM5α sensitivity, and mutations associated with CTL resistance selected in prior hosts can contribute to this effect. The impact of CTL resistance mutations on hTRIM5α sensitivity was context dependent, because mutations shown to be responsible for the TRIM5α-sensitive phenotype in viruses from one patient could have little or no impact on this parameter when introduced into another virus. No fixed relationship between changes in hTRIM5α sensitivity and infectivity was discernible in our studies. Taken together, these findings suggest that CTL mutations may influence HIV-1 replication by modifying both viral infectivity and sensitivity to TRIM5α.
Antibiotics Sensitivity and Resistance Patterns of Uropathogens to Quinolones in Patients with Urinary Tract Infections in a Nigerian Community.

Urinary tract infection is one of the most common bacterial infections in humans. Urine samples from one hundred patients within the age range of 20 to 50 years were collected and examined for the presence of urinary tract infections. The significant growth was observed in 9% of the population. A majority of the isolates in this study were totally sensitive to levofloxacin, and showed various degrees of sensitivity to nalidixic acid, ciprofloxacin and ofloxacin; while some of the isolates were totally resistant to cotrimoxazole and amoxicillin.
Interaction of the Antarctic Circumpolar Current With Seamounts Fuels Moderate Blooms but Vast Foraging Grounds for Multiple Marine Predators

In the Antarctic Circumpolar Current region of the Southern Ocean, the massive phytoplankton blooms stemming from islands support large trophic chains. Contrary to islands, open ocean seamounts appear to sustain blooms of lesser intensity and, consequently, are expected to play a negligible role in the productivity of this area. Here we revisit this assumption by focusing on a region of the Antarctic Circumpolar Current zone which is massively targeted by marine predators, even if no island fertilizes this area. By combining high resolution bathymetric data, Lagrangian analyses of altimetry-derived velocities and chlorophyll a observations derived from BGC-Argo floats and ocean color images, we reveal that the oligotrophic nature of the study region considered in low chlorophyll a climatological maps hides in reality a much more complex environment. Significant (chlorophyll a in excess of 0.6 mg/m3) phytoplankton blooms spread over thousands of kilometers and have bio-optical signatures similar to the ones stemming from island systems. By adopting a Lagrangian approach, we demonstrate that these moderate blooms (i) originate at specific sites where the Antarctic Circumpolar Current interacts with seamounts, and (ii) coincide with foraging areas of five megafauna species. These findings underline the ecological importance of the open ocean subantarctic waters and advocate for a connected vision of future conservation actions along the Antarctic Circumpolar Current.
Tumor-Infiltrating Lymphocytes Expressing the Tissue Resident Memory Marker CD103 Are Associated with Increased Survival in High-Grade Serous Ovarian Cancer

Background: The presence of CD8+ tumor-infiltrating lymphocytes (TIL) is associated with prolonged survival in high-grade serous ovarian cancer (HGSC) and other epithelial cancers. Survival is most strongly associated with intraepithelial versus intrastromal CD8+ TILs; however, the mechanisms that promote the intraepithelial localization of TILs remain poorly understood. We hypothesized that intraepithelial CD8+ TILs, like normal mucosal intraepithelial lymphocytes, might express CD103, a subunit of αE/β7 integrin, which binds E-cadherin on epithelial cells. Methods: A large collection of primary ovarian tumors (HGSC, endometrioid, mucinous, and clear cell) was analyzed by immunohistochemistry for the presence of TIL-expressing CD103. The activation and differentiation status of CD103+ TILs were assessed by flow cytometry. The prognostic significance of TIL subsets was evaluated by Kaplan–Meier analysis. Results: CD103+ TILs were present in all major ovarian cancer subtypes and were most abundant in HGSC. CD103+ TILs were preferentially localized to epithelial regions of tumors and were comprised predominantly of CD8+ T cells expressing activation (HLA-DR, Ki-67, PD-1) and cytolytic (TIA-1) markers, as well as CD56+ NK cells. Tumor infiltration by CD103+ TILs was strongly associated with patient survival in HGSC. Tumors containing CD8+ TILs that were CD103− showed poor prognosis equivalent to tumors lacking CD8+ TILs altogether. Conclusions: CD103+ TILs comprise intraepithelial, activated CD8+ T cells, and NK cells and are strongly associated with patient survival in HGSC. CD103 may serve as a useful marker for enriching the most beneficial subsets of TILs for immunotherapy. Clin Cancer Res; 20(2); 434–44. ©2013 AACR.
Protein tyrosine phosphatases: structure–function relationships

Structural analysis of protein tyrosine phosphatases (PTPs) has expanded considerably in the last several years, producing more than 200 structures in this class of enzymes (from 35 different proteins and their complexes with ligands). The small–medium size of the catalytic domain of ∼280 residues plus a very compact fold makes it amenable to cloning and overexpression in bacterial systems thus facilitating crystallographic analysis. The low molecular weight PTPs being even smaller, ∼150 residues, are also perfect targets for NMR analysis. The availability of different structures and complexes of PTPs with substrates and inhibitors has provided a wealth of information with profound effects in the way we understand their biological functions. Developments in mammalian expression technology recently led to the first crystal structure of a receptor‐like PTP extracellular region. Altogether, the PTP structural work significantly advanced our knowledge regarding the architecture, regulation and substrate specificity of these enzymes. In this review, we compile the most prominent structural traits that characterize PTPs and their complexes with ligands. We discuss how the data can be used to design further functional experiments and as a basis for drug design given that many PTPs are now considered strategic therapeutic targets for human diseases such as diabetes and cancer.
Effect of GCI perturbation on speech quality in Indian languages

Harmonic plus noise model (HNM) divides the speech spectrum into two bands: harmonic and noise. One is modeled with harmonics of the fundamental and the other is simulated using random noise. As HNM analysis/synthesis is performed at each glottal closure instant (GCI), errors in estimation of GCIs affect the quality of the synthesized speech. The objective of this paper is to investigate the effect of the perturbation in GCIs on the synthesized speech quality. Childers and Hu's algorithm is used for GCIs calculations. Investigations show that the speech quality is very sensitive to positions of the GCIs. A small perturbation with maximum of 4 % of the local pitch period considerably degrades the synthesized speech. Perturbations above 8 % severely affect quality of the output speech.
A comparison of the effects of new technology on searching habits in industrial and academic institutions

This article is based mainly upon the findings of three surveys on the effects of new technology on searching habits in industrial and academic institutions. conducted in Autumn 1988 and Autumn 1990. It is appreciated that this two-year time gap between the two sets of surveys must be taken into account, as should more recent advances in the technology and services available, in that they have an influ ence on the findings. These are investigated, and conclusions drawn as to the overall differences, similarities and changes in searching in industrial and academic institutions. In particu lar, the effects of new technology on information personnel and end-users with regard to their searching are rewewed and compared, and changes in the roles of the various players in the field considered.
RELAÇÃO ENTRE FATORES ASSOCIADOS ÀS PARASITOSES GASTROINTESTINAIS, DESEMPENHO E ESTADO FISIOLÓGICO DE OVELHAS SANTA INÊS

O objetivo foi de verificar a correlacao entre os escores de Famacha©, contagem de ovos por grama de fezes (OPG), volume globular (VG) e variaveis de desempenho, de ovelhas em diferentes estados fisiologicos (vazias, gestantes e lactantes), criadas no municipio de Quissama, estado de Rio de Janeiro. O estudo foi realizado durante um ano, utilizando 60 femeas adultas da raca Santa Ines, criadas em sistema semi extensivo. A cada 14 dias foram coletadas, de cada animal, amostras de fezes e de sangue. Os animais tambem foram pesados (PV) e avaliados quanto ao escore de condicao corporal (EC). Houve diferenca significativa entre as caracteristicas avaliadas devido ao estado fisiologico (P<0,05), durante a fase de lactacao, as ovelhas apresentam maiores valores de OPG e Famacha© e menores medias para PV, EC e VG. As correlacoes de maior magnitude foram entre OPG e VG (-0,40) nos tres estados fisiologicos. As correlacoes entre PV, EC e OPG foram baixas (0,12 e -0,17), proximas de zero no final da gestacao e na lactacao. Em geral, a magnitude das correlacoes entre as caracteristicas foi similar nos tres estados fisiologicos. As correlacoes entre EC mostraram-se mais associadas as demais caracteristicas, do que o peso do animal. Por apresentar uma correlacao negativa media com o volume globular, o metodo Famacha© pode ser indicado como uma forma pratica e sustentavel de avaliar o grau de anemia dos ovinos e, consequentemente, as infecoes por Haemonchus contortus.
Strong backscattering enhancement for partially convex targets in random media

Abstract Earlier work pointed out that the radar cross section (RCS), owing to the double-passage effect on waves propagating through random media, is enhanced by a factor ranging from one up to three. However, our study has manifested numerically a strong enhancement in RCS of targets with concave-convex surfaces in continuous random media, by taking account of boundary conditions of waves on targets. We have found that when a plane wave illuminates a convex portion of the concave–convex conducting target in a random medium, the factor of enhancement oscillates about two with target size. Moreover, this enhancement becomes quite large at certain target shapes and also under a specific condition of target size and spatial coherence length of the incident H-wave. The large enhancement is considered as an anomalous feature in the behaviour of backscattered waves in random media. By analysing the scattering problem for beam-wave incidence on the same target in free space, we manifest the mechanism of such anomalous enhancement.
Competition, Signaling and Non-Walking Through the Book: Effects on Order Choice

We investigate the effects of competition and signaling in a pure order driven market and examine the trading patterns of agents when walking through the book is not allowed. Our results suggest that the variables capturing the cost of a large market order are not informative for an impatient trader under this market mechanism. We also document that the competition effect is not present only at the top of the book but persistent beyond the best quotes. Moreover, it dominates the signaling effect for both a limit order and a market order trader. Finally, we show that institutional investors’ order submission strategies are characterized by only a few pieces of the limit order book information. This is consistent with informed traders placing orders based on their own private valuations rather than the state of the book.
Identification of a murine locus conveying susceptibility to cadmium-induced forelimb malformations.

The heavy metal cadmium (Cd), an environmentally ubiquitous contaminant, is a potent teratogen in mice. When administered parenterally, it induces an array of malformations that vary in scope and severity with the route, dose, time of administration, and the strain of the animal. When administered intraperitoneally on day 9.0 of gestation, 4 mg/kg cadmium chloride produces forelimb defects (predominantly ectrodactyly) in over 80% of fetuses of the C57BL/6 mouse strain, while no limb defects are observed in the identically treated SWV strain. Like other examples of strain-specific teratogenic activity, the underlying nature of the differential susceptibility remains unknown. The present study investigates the segregation of sensitivity to Cd-induced forelimb defects in crosses between C57BL/6 and SWV mice and provides evidence for the involvement of both maternal and fetal factors in the determination of defect expression. In addition, quantitative trait loci (QTL) analysis of the fetal genetic component was performed among 198 backcross progeny, utilizing a genomic linkage map of 149 informative microsatellite markers. One QTL demonstrating significant linkage to expression of the defect, designated Cadfar (cadmium-induced forelimb autopod reduction), was mapped to the distal end of chromosome 6 with a lod score of 3.1.
Phytochrome‐mediated development in land plants: red light sensing evolves to meet the challenges of changing light environments

Phytochromes are photoreceptors that provide plants with circadian, seasonal, and positional information critical for the control of germination, seedling development, shade avoidance, reproduction, dormancy, and sleep movements. Phytochromes are unique among photoreceptors in their capacity to interconvert between a red‐absorbing form (absorption maximum of ∼660 nm) and a far‐red absorbing form (absorption maximum of ∼730 nm), which occur in a dynamic equilibrium within plant cells, corresponding to the proportions of red and far‐red energy in ambient light. Because pigments in stems and leaves absorb wavelengths below about 700 nm, this provides plants with an elegant system for detecting their position relative to other plants, with which the plants compete for light. Certain aspects of phytochrome‐mediated development outside of flowering plants are strikingly similar to those that have been characterized in Arabidopsis thaliana and other angiosperms. However, early diverging land plants have fewer distinct phytochrome gene lineages, suggesting that both diversification and subfunctionalization have been important in the evolution of the phytochrome gene family. There is evidence that subfunctionalization proceeded by the partitioning among paralogues of photosensory specificity, physiological response modes, and light‐regulated gene expression and protein stability. Parallel events of duplication and functional divergence may have coincided with the evolution of canopy shade and the increasing complexity of the light environment. Within angiosperms, patterns of functional divergence are clade‐specific and the roles of phytochromes in A. thaliana change across environments, attesting to the evolutionary flexibility and contemporaneous plasticity of phytochrome signalling in the control of development.
E1B-55 kDa-Defective Adenoviruses Activate p53 in Mesothelioma and Enhance Cytotoxicity of Anticancer Agents

Introduction: Genetic characterization of malignant mesothelioma shows a homozygous deletion of the INK4A/ARF locus, which results in inactivation of the p53 pathways. Methods: We examined possible antitumor effects of adenoviruses with a deletion of the E1B-55kD gene (Ad-delE1B55) on mesothelioma and investigated combinatory actions with the first-line chemotherapeutic agents. Results: Ad-delE1B55 produced cytotoxicity on mesothelioma cells, which was associated with p53 phosphorylation, pRb dephosphorylation, and cleavage of caspases. Ad-delE1B55–infected cells displayed hyperploidy at the cell-cycle analysis and showed enlarged nuclear configurations. Combination of Ad-delE1B55 plus cisplatin or pemetrexed produced antitumor effects in vitro. Furthermore, Ad-delE1B55 and cisplatin showed combinatory effects in an orthotopic animal model. Conclusions: Cell death caused by Ad-delE1B55 is attributable to cell-cycle arrest at M-phase checkpoint followed by activated apoptotic pathways, and combination of the first-line chemotherapeutic agents and the oncolytic adenovirus is a potential therapeutic for mesothelioma.