bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cladosporium Species Recovered from Clinical Samples in the United States
Authors: Sandoval-Denis Marcelo , Sutton Deanna A. , Martin-Vicente Adela , Cano-Lira José F. , Wiederhold Nathan , Guarro Josep , Gené Josepa 
Published: July 2015

ABSTRACTCladosporiumspecies are ubiquitous, saprobic, dematiaceous fungi, only infrequently associated with human and animal opportunistic infections. We have studied a large set ofCladosporiumisolates recovered from clinical samples in the United States to ascertain the predominant species there in light of recent taxonomic changes in this genus and to determine whether some could possibly be rare potential pathogens. A total of 92 isolates were identified using phenotypic and molecular methods, which included sequence analysis of the internal transcribed spacer (ITS) region and a fragment of the large subunit (LSU) of the nuclear ribosomal DNA (rDNA), as well as fragments of the translation elongation factor 1 alpha (EF-1α) and actin (Act) genes. The most frequent species wasCladosporium halotolerans(14.8%), followed byC. tenuissimum(10.2%),C. subuliforme(5.7%), andC. pseudocladosporioides(4.5%). However, 39.8% of the isolates did not correspond to any known species and were deemed to comprise at least 17 new lineages forCladosporium. The most frequent anatomic site of isolation was the respiratory tract (54.5%), followed by superficial (28.4%) and deep tissues and fluids (14.7%). Species of the two recently described cladosporiumlike generaToxicocladosporiumandPenidiellaare reported for the first time from clinical samples.In vitrosusceptibility testing of 92 isolates against nine antifungal drugs showed a variety of results but high activity overall for the azoles, echinocandins, and terbinafine.
The Multiplicity of Cellular Infection Changes Depending on the Route of Cell Infection in a Plant Virus
Authors: Gutiérrez Serafín , Pirolles Elodie , Yvon Michel , Baecker Volker , Michalakis Yannis , Blanc Stéphane 
Published: July 2015

ABSTRACT

The multiplicity of cellular infection (MOI) is the number of virus genomes of a given virus species that infect individual cells. This parameter chiefly impacts the severity of within-host population bottlenecks as well as the intensity of genetic exchange, competition, and complementation among viral genotypes. Only a few formal estimations of the MOI currently are available, and most theoretical reports have considered this parameter as constant within the infected host. Nevertheless, the colonization of a multicellular host is a complex process during which the MOI may dramatically change in different organs and at different stages of the infection. We have used both qualitative and quantitative approaches to analyze the MOI during the colonization of turnip plants by
Turnip mosaic virus
. Remarkably, different MOIs were observed at two phases of the systemic infection of a leaf. The MOI was very low in primary infections from virus circulating within the vasculature, generally leading to primary foci founded by a single genome. Each lineage then moved from cell to cell at a very high MOI. Despite this elevated MOI during cell-to-cell progression, coinfection of cells by lineages originating in different primary foci is severely limited by the rapid onset of a mechanism inhibiting secondary infection. Thus, our results unveil an intriguing colonization pattern where individual viral genomes initiate distinct lineages within a leaf. Kin genomes then massively coinfect cells, but coinfection by two distinct lineages is strictly limited.

IMPORTANCE
The MOI is the size of the viral population colonizing cells and defines major phenomena in virus evolution, like the intensity of genetic exchange and the size of within-host population bottlenecks. However, few studies have quantified the MOI, and most consider this parameter as constant during infection. Our results reveal that the MOI can depend largely on the route of cell infection in a systemically infected leaf. The MOI is usually one genome per cell when cells are infected from virus particles moving long distances in the vasculature, whereas it is much higher during subsequent cell-to-cell movement in mesophyll. However, a fast-acting superinfection exclusion prevents cell coinfection by merging populations originating from different primary foci within a leaf. This complex colonization pattern results in a situation where within-cell interactions are occurring almost exclusively among kin and explains the common but uncharacterized phenomenon of genotype spatial segregation in infected plants.
Replication of Tomato Yellow Leaf Curl Virus in Its Whitefly Vector, Bemisia tabaci
Authors: Pakkianathan Britto Cathrin , Kontsedalov Svetlana , Lebedev Galina , Mahadav Assaf , Zeidan Muhammad , Czosnek Henryk , Ghanim Murad 
Published: July 2015

ABSTRACT

Tomato yellow leaf curl virus
(TYLCV) is a begomovirus transmitted exclusively by the whitefly
Bemisia tabaci
in a persistent, circulative manner. Replication of TYLCV in its vector remains controversial, and thus far, the virus has been considered to be nonpropagative. Following 8 h of acquisition on TYLCV-infected tomato plants or purified virions and then transfer to non-TYLCV-host cotton plants, the amounts of virus inside whitefly adults significantly increased (>2-fold) during the first few days and then continuously decreased, as measured by the amounts of genes on both virus DNA strands. Reported alterations in insect immune and defense responses upon virus retention led us to hypothesize a role for the immune response in suppressing virus replication. After virus acquisition, stress conditions were imposed on whiteflies, and the levels of three viral gene sequences were measured over time. When whiteflies were exposed to TYLCV and treatment with two different pesticides, the virus levels continuously increased. Upon exposure to heat stress, the virus levels gradually decreased, without any initial accumulation. Switching of whiteflies between pesticide, heat stress, and control treatments caused fluctuating increases and decreases in virus levels. Fluorescence
in situ
hybridization analysis confirmed these results and showed virus signals inside midgut epithelial cell nuclei. Combining the pesticide and heat treatments with virus acquisition had significant effects on fecundity. Altogether, our results demonstrate for the first time that a single-stranded DNA plant virus can replicate in its hemipteran vector.

IMPORTANCE
Plant viruses in agricultural crops are of great concern worldwide. Many of them are transmitted from infected to healthy plants by insects. Persistently transmitted viruses often have a complex association with their vectors; however, most are believed not to replicate within these vectors. Such replication is important, as it contributes to the virus's spread and can impact vector biology.
Tomato yellow leaf curl virus
(TYLCV) is a devastating begomovirus that infects tomatoes. It is persistently transmitted by the whitefly
Bemisia tabaci
but is believed not to replicate in the insect. To demonstrate that TYLCV is, in fact, propagative (i.e., it replicates in its insect host), we hypothesized that insect defenses play a role in suppressing virus replication. We thus exposed whitefly to pesticide and heat stress conditions to manipulate its physiology, and we showed that under such conditions, the virus is able to replicate and significantly influence the insect's fecundity.
2′-5′-Oligoadenylate Synthetase-Like Protein Inhibits Respiratory Syncytial Virus Replication and Is Targeted by the Viral Nonstructural Protein 1
Authors: Dhar Jayeeta , Cuevas Rolando A. , Goswami Ramansu , Zhu Jianzhong , Sarkar Saumendra N. , Barik Sailen 
Published: July 2015

ABSTRACT
2′-5′-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible antiviral protein. Here we describe differential inhibitory activities of human OASL and the two mouse OASL homologs against respiratory syncytial virus (RSV) replication. Interestingly, nonstructural protein 1 (NS1) of RSV promoted proteasome-dependent degradation of specific OASL isoforms. We conclude that OASL acts as a cellular antiviral protein and that RSV NS1 suppresses this function to evade cellular innate immunity and allow virus growth.
Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model
Authors: Boukhvalova Marina , McKay Jamall , Mbaye Aissatou , Sanford-Crane Hannah , Blanco Jorge C. G. , Huber Ashley , Herold Betsy C. 
Published: July 2015

ABSTRACT

Subunit vaccines based on the herpes simplex virus 2 (HSV-2) glycoprotein D (gD-2) have been the major focus of HSV-2 vaccine development for the past 2 decades. Based on the promising data generated in the guinea pig model, a formulation containing truncated gD-2, aluminum salt, and MPL (gD/AS04) advanced to clinical trials. The results of these trials, however, were unexpected, as the vaccine protected against HSV-1 infection but not against HSV-2. To address this discrepancy, we developed a Depot medroxyprogesterone acetate (DMPA)-treated cotton rat
Sigmodon hispidus
model of HSV-2 and HSV-1 genital infection. The severity of HSV-1 genital herpes was less than that of HSV-2 genital herpes in cotton rats, and yet the model allowed for comparative evaluation of gD/AS04 immunogenicity and efficacy. Cotton rats were intramuscularly vaccinated using a prime boost strategy with gD/AS04 (Simplirix vaccine) or control vaccine formulation (hepatitis B vaccine FENDrix) and subsequently challenged intravaginally with HSV-2 or HSV-1. The gD/AS04 vaccine was immunogenic in cotton rats and induced serum IgG directed against gD-2 and serum HSV-2 neutralizing antibodies but failed to efficiently protect against HSV-2 disease or to decrease the HSV-2 viral load. However, gD/AS04 significantly reduced vaginal titers of HSV-1 and better protected animals against HSV-1 compared to HSV-2 genital disease. The latter finding is generally consistent with the clinical outcome of the Herpevac trial of Simplirix. Passive transfer of serum from gD/AS04-immunized cotton rats conferred stronger protection against HSV-1 genital disease. These findings suggest the need for alternative vaccine strategies and the identification of new correlates of protection.

IMPORTANCE
In spite of the high health burden of genital herpes, there is still no effective intervention against the disease. The significant gap in knowledge on genital herpes pathogenesis has been further highlighted by the recent failure of GSK HSV-2 vaccine Simplirix (gD/AS04) to protect humans against HSV-2 and the surprising finding that the vaccine protected against HSV-1 genital herpes instead. In this study, we report that gD/AS04 has higher efficacy against HSV-1 compared to HSV-2 genital herpes in the novel DMPA-synchronized cotton rat model of HSV-1 and HSV-2 infection. The findings help explain the results of the Simplirix trial.
Distribution and Redistribution of HIV-1 Nucleocapsid Protein in Immature, Mature, and Integrase-Inhibited Virions: a Role for Integrase in Maturation
Authors: Fontana Juan , Jurado Kellie A. , Cheng Naiqian , Ly Ngoc L. , Fuchs James R. , Gorelick Robert J. , Engelman Alan N. , Steven Alasdair C. 
Published: July 2015

ABSTRACT

During virion maturation, HIV-1 capsid protein assembles into a conical core containing the viral ribonucleoprotein (vRNP) complex, thought to be composed mainly of the viral RNA and nucleocapsid protein (NC). After infection, the viral RNA is reverse transcribed into double-stranded DNA, which is then incorporated into host chromosomes by integrase (IN) catalysis. Certain IN mutations (class II) and antiviral drugs (allosteric IN inhibitors [ALLINIs]) adversely affect maturation, resulting in virions that contain “eccentric condensates,” electron-dense aggregates located outside seemingly empty capsids. Here we demonstrate that in addition to this mislocalization of electron density, a class II IN mutation and ALLINIs each increase the fraction of virions with malformed capsids (from ∼12% to ∼53%). Eccentric condensates have a high NC content, as demonstrated by “tomo-bubblegram” imaging, a novel labeling technique that exploits the susceptibility of NC to radiation damage. Tomo-bubblegrams also localized NC inside wild-type cores and lining the spherical Gag shell in immature virions. We conclude that eccentric condensates represent nonpackaged vRNPs and that either genetic or pharmacological inhibition of IN can impair vRNP incorporation into mature cores. Supplying IN in
trans
as part of a Vpr-IN fusion protein partially restored the formation of conical cores with internal electron density and the infectivity of a class II IN deletion mutant virus. Moreover, the ability of ALLINIs to induce eccentric condensate formation required both IN and viral RNA. Based on these observations, we propose a role for IN in initiating core morphogenesis and vRNP incorporation into the mature core during HIV-1 maturation.

IMPORTANCE
Maturation, a process essential for HIV-1 infectivity, involves core assembly, whereby the viral ribonucleoprotein (vRNP, composed of vRNA and nucleocapsid protein [NC]) is packaged into a conical capsid. Allosteric integrase inhibitors (ALLINIs) affect multiple viral processes. We have characterized ALLINIs and integrase mutants that have the same phenotype. First, by comparing the effects of ALLINIs on several steps of the viral cycle, we show that inhibition of maturation accounts for compound potency. Second, by using cryoelectron tomography, we find that ALLINIs impair conical capsid assembly. Third, by developing tomo-bubblegram imaging, which specifically labels NC protein, we find that ALLINIs block vRNP packaging; instead, vRNPs form “eccentric condensates” outside the core. Fourth, malformed cores, typical of integrase-deleted virus, are partially replaced by conical cores when integrase is supplied in
trans
. Fifth, vRNA is necessary for ALLINI-induced eccentric condensate formation. These observations suggest that integrase is involved in capsid morphogenesis and vRNP packaging.
HIV Vpu Interferes with NF-κB Activity but Not with Interferon Regulatory Factor 3
Authors: Manganaro Lara , de Castro Elisa , Maestre Ana M. , Olivieri Kevin , García-Sastre Adolfo , Fernandez-Sesma Ana , Simon Viviana 
Published: July 2015

ABSTRACT

The accessory HIV protein Vpu inhibits a number of cellular pathways that trigger host innate restriction mechanisms. HIV Vpu-mediated degradation of tetherin allows efficient particle release and hampers the activation of the NF-κB pathway thereby limiting the expression of proinflammatory genes. In addition, Vpu reduces cell surface expression of several cellular molecules such as newly synthesized CD4. However, the role of HIV Vpu in regulating the type 1 interferon response to viral infection by degradation of the interferon regulatory factor 3 (IRF3) has been subject of conflicting reports. We therefore systematically investigated the expression of IRF3 in primary CD4
+
T cells and macrophages infected with HIV at different time points. In addition, we also tested the ability of Vpu to interfere with innate immune signaling pathways such as the NF-κB and the IRF3 pathways. We report here that HIV Vpu failed to degrade IRF3 in infected primary cells. Moreover, we observed that HIV NL4.3 Vpu had no effect on IRF3-dependent gene expression in reporter assays. On the other hand, HIV NL4.3 Vpu downmodulated NF-κB-dependent transcription. Mutation of two serines (positions 52 and 56) involved in the binding of NL4.3 Vpu to the βTrCP ubiquitin ligase abolishes its ability to inhibit NF-κB activity. Taken together, these results suggest that HIV Vpu regulates antiviral innate response in primary human cells by acting specifically on the NF-κB pathway.

IMPORTANCE
HIV Vpu plays a pivotal role in enhancing HIV infection by counteraction of Tetherin. However, Vpu also regulates host response to HIV infection by hampering the type 1 interferon response. The molecular mechanism by which Vpu inhibits the interferon response is still controversial. Here we report that Vpu affects interferon expression by inhibiting NF-κB activity without affecting IRF3 levels or activity. These data suggest that Vpu facilitates HIV infection by regulating NF-κB transcription to levels sufficient for viral transcription while limiting cellular responses to infection.
Acylation of Biomolecules in Prokaryotes: a Widespread Strategy for the Control of Biological Function and Metabolic Stress
Authors: Hentchel Kristy L. , Escalante-Semerena Jorge C. 
Published: July 2015

SUMMARY

Acylation of biomolecules (e.g., proteins and small molecules) is a process that occurs in cells of all domains of life and has emerged as a critical mechanism for the control of many aspects of cellular physiology, including chromatin maintenance, transcriptional regulation, primary metabolism, cell structure, and likely other cellular processes. Although this review focuses on the use of acetyl moieties to modify a protein or small molecule, it is clear that cells can use many weak organic acids (e.g., short-, medium-, and long-chain mono- and dicarboxylic aliphatics and aromatics) to modify a large suite of targets. Acetylation of biomolecules has been studied for decades within the context of histone-dependent regulation of gene expression and antibiotic resistance. It was not until the early 2000s that the connection between metabolism, physiology, and protein acetylation was reported. This was the first instance of a metabolic enzyme (acetyl coenzyme A [acetyl-CoA] synthetase) whose activity was controlled by acetylation via a regulatory system responsive to physiological cues. The above-mentioned system was comprised of an acyltransferase and a partner deacylase. Given the reversibility of the acylation process, this system is also referred to as
r
eversible
l
ysine
a
cylation (RLA). A wealth of information has been obtained since the discovery of RLA in prokaryotes, and we are just beginning to visualize the extent of the impact that this regulatory system has on cell function.
Birefringence of Collagen Fibres in Rat Calcaneal Tendons Treated with Acupuncture during Three Phases of Healing
Authors: Almeida Marcos dos Santos , Oliveira Letícia Prado , Vieira Cristiano Pedrozo , Guerra Flávia Da Ré , Pimentel Edson Rosa 
Published: July 2015

Background Birefringence is an optical anisotropy that is investigated by polarisation microscopy, and has been valuable for the study of the oriented organisation of collagen fibres in tendons. However, the application of this technology to evaluate the effect of different acupuncture points during tendon healing has not yet been described. Objectives To evaluate the concentration of non-collagenous proteins (NCP) and birefringence in rat calcaneal tendons following injury during the three different phases of healing: inflammatory (7th day), proliferative (14th day), and remodelling (21st day). Methods Tendons of 120 Wistar rats were tenotomised and left untreated (teno group, n=24), treated with manual acupuncture at ST36 (ST36 group, n=24), BL57 (BL57 group, n=24) or ST36+BL57 (SB group, n=24), or treated with electroacupuncture at ST36+BL57 (EA group, n=24). Tendon samples were collected at 7, 14 and 21 days after injury (n=8 per group). NCP concentrations were measured using the Bradford method (n=4 each) and birefringence was examined using polarisation microscopy and image analysis (n=4 each). Comparison was also made with healthy (non-tenotomised) tendons in a subgroup of rats (n=4 each). Results Manual acupuncture at ST36 and BL57 increased molecular organisation of collagen fibres on day 14 and 21 after injury. Isolated use of BL57 and ST36 also increased collagen fibre organisation when examined on day 14 and 21, respectively. No significant increase in NCP concentration was observed in any of the treated tenotomised groups. Conclusions Acupuncture, through putative anti-inflammatory and mechanotransductor effects, may have a role in strengthening tendons and increasing resistance to re-rupture.
Carcinoid tumours of the lung and the ‘PEPPS’ approach: evaluation of preoperative bronchoscopic tumour debulking as preparation for subsequent parenchyma-sparing surgery
Authors: Neuberger Michael , Hapfelmeier Alexander , Schmidt Michael , Gesierich Wolfgang , Reichenberger Frank , Morresi-Hauf Alicia , Hatz Rudolf A , Lindner Michael 
Published: July 2015

BackgroundPreoperative bronchoscopic tumour ablation has been suggested as a beneficial treatment for bronchopulmonary carcinoid tumours, although data regarding its effects and long-term outcome are lacking.MethodsIn our case-matched cohort study with 208 patients with bronchopulmonary carcinoid tumours we investigated the role of preoperative bronchoscopic interventions before subsequent surgery and analysed the safety of this Procedure of Endobronchial Preparation for Parenchyma-sparing Surgery (PEPPS) based on metastasis and recurrence rates as well as survival data from 1991 to 2010. The subsequent surgery was classified into parenchyma-sparing procedures and classical lobectomies, bilobectomies and pneumonectomies. Data were obtained from the tumour registry and medical reports. Outcomes were the frequency of parenchyma-sparing surgery after bronchoscopic treatment as well as rates of metastasis, recurrence and survival.Results132 of 208 carcinoids were located centrally. Among them, 77 patients could be recanalised preoperatively. After bronchoscopic preparation, the rate of subsequent parenchyma-sparing surgery methods was higher (p=0.021). The effect was measured by the number of segments removed. The 10-year survival rate was 89% (typical carcinoids) and 68% (atypical carcinoids), respectively. After applying PEPPS, long-term survival was slightly higher (p=0.23). Metastasis and recurrence rates showed no relevant differences between the bronchoscopically treated or non-treated groups, or between the two types of surgery classes or between the PEPPS and non-PEPPS groups.ConclusionsAfter preoperative bronchoscopic treatment, parenchyma-sparing surgery techniques can be applied more frequently. Furthermore, we detected no negative effects after PEPPS based on metastasis, recurrence and survival rates.
Recent trends in cyclist fatalities in Australia
Authors: Boufous Soufiane , Olivier Jake 
Published: July 2015

The study examines trends in bicycling fatalities reported to the Australian police between 1991 and 2013. Trends were estimated using Poisson regression modelling. Overall, cycling fatalities decreased by 1.9% annually between 1991 and 2013. However, while deaths following multivehicle crashes decreased at a rate of 2.9% per annum (95% CI −4.0% to −1.8%), deaths from single vehicle crashes increased by 5.8% per annum (95% CI 4.1% to 7.5%). Over the study period, the average age of cyclists who died in single vehicle crashes (45.3 years, 95% CI 41.5 to 49.1) was significantly higher than cyclists who died in multivehicle crashes (36.2 years, 95% CI 34.7 to 37.7). The average age of deceased cyclists increased significantly for both types of crashes. The observed increase in single vehicle crashes need to be closely monitored in Australia and internationally. In-depth studies are needed to investigate the circumstances of fatal single bicycle crashes in order to develop appropriate countermeasures.