bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole-Genome Analysis: Small-Scale Italian Scenario within a Single Hospital
Authors: Onori Raffaella , Gaiarsa Stefano , Comandatore Francesco , Pongolini Stefano , Brisse Sylvain , Colombo Alberto , Cassani Gianluca , Marone Piero , Grossi Paolo , Minoja Giulio , Bandi Claudio , Sassera Davide , Toniolo Antonio
Published: July 2015

Multidrug-resistant (MDR)
Klebsiella pneumoniae
is one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistant
K. pneumoniae
strains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the “Italian scenario.” We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistant
K. pneumoniae
isolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity of
K. pneumoniae
strains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens.
Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia
Authors: Fabeni Lavinia , Berno Giulia , Svicher Valentina , Ceccherini-Silberstein Francesca , Gori Caterina , Bertoli Ada , Mussini Cristina , Lichtner Miriam , Zaccarelli Mauro , Ammassari Adriana , Pinnetti Carmela , Cicalini Stefania , Mastroianni Claudio Maria , Andreoni Massimo , Antinori Andrea , Perno Carlo Federico , Santoro Maria Mercedes
Published: July 2015

The possibility of performing genotypic tropism testing (GTT) with proviral DNA (pvDNA) even during suppressed viremia would facilitate the use of CCR5 inhibitors as part of switching, simplification, or intensification strategies. Thus, we aimed to evaluate the tropism concordance between plasma RNA and pvDNA samples and to assess which factors could affect possible discrepancies between the two compartments. GTT was performed using both plasma RNA and pvDNA from 55 sample pairs from drug-experienced patients. Potential differences between the two compartments were evaluated by analyzing coreceptor usage and genetic variability. Paired samples were also stratified in three levels of viremia (<50, 51 to 500, and >500 copies/ml). Overall, Geno2Pheno comparisons of false-positive rates in the two compartments showed good correlation (
r
= 0.72). A high level of concordance in tropism predictions for the two compartments was found (46/55 sample pairs [83.6%]). Among the 9 sample pairs with discordant tropisms, a larger proportion of pvDNA samples harboring CXCR4/dual-mixed-tropic viruses was found, in comparison with plasma RNA samples (88.9% versus 11.1%;
P
= 0.0034). Discordant samples were characterized by greater genetic variability than were concordant samples. With stratification of the paired samples according to viremia levels, the prevalence of discordant samples decreased with increasing viremia (<50 copies/ml, 21.4%; 51 to 500 copies/ml, 15.4%; >500 copies/ml, 6.7%;
P
= 0.2). Our findings confirm that prediction of viral tropism using pvDNA is feasible even in low-level viremia and provides useful information for therapy optimization for patients with low or suppressed viremia.
Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements
Authors: Kramer Rolf , Sauer-Heilborn Annette , Welte Tobias , Guzman Carlos A. , Abraham Wolf-Rainer , Höfle Manfred G.
Published: July 2015

The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF.
Phaeohyphomycosis Caused by a Novel Species, Pseudochaetosphaeronema martinelli
Authors: Ahmed Sarah A. , Desbois Nicole , Quist D. , Miossec C. , Atoche Carlos , Bonifaz Alexandro , de Hoog G. Sybren
Published: July 2015

Among the opportunistic mycoses that are emerging in patients with immunosuppression or severe underlying illness, many isolates lack of characteristic sporulation and until recently could not be identified. Clinical signs are mostly nonspecific and therefore such infections have often been disregarded. In the present paper we describe a novel, nonsporulating fungal species causing subcutaneous phaeohyphomycosis in two patients of different origin. One is a 73-year-old female from Martinique who suffered from rheumatoid arthritis, while the other case concerns a 72-year-old male from Mexico who had a history of type 2 diabetes mellitus. Sequencing of the partial ribosomal operon revealed that in both cases a member of the order
Pleosporales
was concerned which could not be affiliated to any family within this order. Multilocus analysis revealed that the fungus was related to another, unaffiliated agent of human mycetoma,
Pseudochaetosphaeronema larense
, and therefore the name
Pseudochaetosphaeronema martinelli
was introduced.
Disseminated Balamuthia mandrillaris Infection
Authors: Schafer Katherine R. , Shah Neil , Almira-Suarez M. I. , Reese Jennifer M. , Hoke George M. , Mandell James W. , Roy Sharon L. , Visvesvara Govinda
Published: July 2015

Balamuthia mandrillarisis a rare cause of human infection, but when infections do occur, they result in high rates of morbidity and mortality. A case of disseminatedBalamuthiainfection is presented. Early diagnosis and initiation of recommended therapy are essential for increased chances of successful outcomes.
HIV-1 Cell-Free and Cell-to-Cell Infections Are Differentially Regulated by Distinct Determinants in the Env gp41 Cytoplasmic Tail
Authors: Durham Natasha D. , Chen Benjamin K.
Published: July 2015

The HIV-1 envelope (Env) glycoprotein mediates viral entry during both cell-free and cell-to-cell infection of CD4
+
T cells. The highly conserved long cytoplasmic tail (CT) of Env is required in a cell type-dependent manner for optimal infectivity of cell-free virus. To probe the role of the CT in cell-to-cell infection, we tested a panel of mutations in the CT region that maintain or attenuate cell-free infection to investigate whether the functions of the CT are conserved during cell-free and cell-to-cell infection. The mutations tested included truncations of structural motifs in the gp41 CT and two point mutations in lentiviral lytic peptide 3 (LLP-3) previously described as disrupting the infectivity of cell-free virus. We found that small truncations of 28 to 43 amino acids (aa) or two LLP-3 point mutations, YW_SL and LL_RQ, severely impaired single-round cell-free infectivity 10-fold or more relative to wild-type full-length CT. These mutants showed a modest 2-fold reduction in cell-to-cell infection assays. Conversely, large truncations of 93 to 124 aa severely impaired cell-to-cell infectivity 20-fold or more while resulting in a 50% increase in infectivity of cell-free viral particles when produced in 293T cells. Intermediate truncations of 46 to 90 aa showed profound impairment of both modes of infection. Our results show that the abilities of Env to support cell-free and cell-to-cell infection are genetically distinct. These differences are cell type dependent for large-CT-truncation mutants. Additionally, point mutants in LLP-3 can maintain multiround propagation from cell-to-cell in primary CD4
+
T cells.

IMPORTANCE
The functions of HIV Env gp41 CT remain poorly understood despite being widely studied in the context of cell-free infection. We have identified domains of the gp41 CT responsible for striking selective deficiencies in either cell-free or cell-to-cell infectivity. These differences may reflect a different intrinsic regulatory influence of the CT on cell-associated versus particle-associated Env or differential interaction with host or viral proteins. Our findings provide novel insight into the key regulatory potential of the gp41 CT in cell-free and cell-to-cell HIV-1 infection, particularly for short-truncation mutants of ≤43 amino acids or mutants with point mutations in the LLP-3 helical domain of the CT, which are able to propagate via cell-to-cell infection in the absence of infectious cell-free virus production. These mutants may also serve as tools to further define the contributions of cell-free and cell-to-cell infection
in vitro
and
in vivo
.
Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae
Authors: Gjessing Mona C. , Yutin Natalya , Tengs Torstein , Senkevich Tania , Koonin Eugene , Rønning Hans Petter , Alarcon Marta , Ylving Sonja , Lie Kai-Inge , Saure Britt , Tran Linh , Moss Bernard , Dale Ole Bendik
Published: July 2015

Poxviruses are large DNA viruses of vertebrates and insects causing disease in many animal species, including reptiles, birds, and mammals. Although poxvirus-like particles were detected in diseased farmed koi carp, ayu, and Atlantic salmon, their genetic relationships to poxviruses were not established. Here, we provide the first genome sequence of a fish poxvirus, which was isolated from farmed Atlantic salmon. In the present study, we used quantitative PCR and immunohistochemistry to determine aspects of salmon gill poxvirus disease, which are described here. The gill was the main target organ where immature and mature poxvirus particles were detected. The particles were detected in detaching, apoptotic respiratory epithelial cells preceding clinical disease in the form of lethargy, respiratory distress, and mortality. In moribund salmon, blocking of gas exchange would likely be caused by the adherence of respiratory lamellae and epithelial proliferation obstructing respiratory surfaces. The virus was not found in healthy salmon or in control fish with gill disease without apoptotic cells, although transmission remains to be demonstrated. PCR of archival tissue confirmed virus infection in 14 cases with gill apoptosis in Norway starting from 1995. Phylogenomic analyses showed that the fish poxvirus is the deepest available branch of chordopoxviruses. The virus genome encompasses most key chordopoxvirus genes that are required for genome replication and expression, although the gene order is substantially different from that in other chordopoxviruses. Nevertheless, many highly conserved chordopoxvirus genes involved in viral membrane biogenesis or virus-host interactions are missing. Instead, the salmon poxvirus carries numerous genes encoding unknown proteins, many of which have low sequence complexity and contain simple repeats suggestive of intrinsic disorder or distinct protein structures.

IMPORTANCE
Aquaculture is an increasingly important global source of high-quality food. To sustain the growth in aquaculture, disease control in fish farming is essential. Moreover, the spread of disease from farmed fish to wildlife is a concern. Serious poxviral diseases are emerging in aquaculture, but very little is known about the viruses and the diseases that they cause. There is a possibility that viruses with enhanced virulence may spread to new species, as has occurred with the myxoma poxvirus in rabbits. Provision of the first fish poxvirus genome sequence and specific diagnostics for the salmon gill poxvirus in Atlantic salmon may help curb this disease and provide comparative knowledge. Furthermore, because salmon gill poxvirus represents the deepest branch of chordopoxvirus so far discovered, the genome analysis provided substantial insight into the evolution of different functional modules in this important group of viruses.
Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis
Authors: Butchi Niranjan , Kapil Parul , Puntambekar Shweta , Stohlman Stephen A. , Hinton David R. , Bergmann Cornelia C.
Published: July 2015

Myd88 signaling is critical to the control of numerous central nervous system (CNS) infections by promoting both innate and adaptive immune responses. Nevertheless, the extent to which Myd88 regulates type I interferon (IFN) versus proinflammatory factors and T cell function, as well as the anatomical site of action, varies extensively with the pathogen. CNS infection by neurotropic coronavirus with replication confined to the brain and spinal cord induces protective IFN-α/β via Myd88-independent activation of melanoma differentiation-associated gene 5 (MDA5). However, a contribution of Myd88-dependent signals to CNS pathogenesis has not been assessed. Infected Myd88−/−mice failed to control virus, exhibited enhanced clinical disease coincident with increased demyelination, and succumbed to infection within 3 weeks. The induction of IFN-α/β, as well as of proinflammatory cytokines and chemokines, was impaired early during infection. However, defects in both IFN-α/β and select proinflammatory factors were rapidly overcome prior to T cell recruitment. Myd88 deficiency also specifically blunted myeloid and CD4 T cell recruitment into the CNS without affecting CD8 T cells. Moreover, CD4 T cells but not CD8 T cells were impaired in IFN-γ production. Ineffective virus control indeed correlated most prominently with reduced antiviral IFN-γ in the CNS of Myd88−/−mice. The results demonstrate a crucial role for Myd88 both in early induction of innate immune responses during coronavirus-induced encephalomyelitis and in specifically promoting protective CD4 T cell activation. In the absence of these responses, functional CD8 T cells are insufficient to control viral spread within the CNS, resulting in severe demyelination.

IMPORTANCEDuring central nervous system (CNS) infections, signaling through the adaptor protein Myd88 promotes both innate and adaptive immune responses. The extent to which Myd88 regulates antiviral type I IFN, proinflammatory factors, adaptive immunity, and pathology is pathogen dependent. These results reveal that Myd88 protects from lethal neurotropic coronavirus-induced encephalomyelitis by accelerating but not enhancing the induction of IFN-α/β, as well as by promoting peripheral activation and CNS accumulation of virus-specific CD4 T cells secreting IFN-γ. By controlling both early innate immune responses and CD4 T cell-mediated antiviral IFN-γ, Myd88 signaling limits the initial viral dissemination and is vital for T cell-mediated control of viral loads. Uncontrolled viral replication in the absence of Myd88 leads to severe demyelination and pathology despite overall reduced inflammatory responses. These data support a vital role of Myd88 signaling in protective antimicrobial functions in the CNS by promoting proinflammatory mediators and T cell-mediated IFN-γ production.
Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses
Authors: Son Kyung-No , Liang Zhiguo , Lipton Howard L.
Published: July 2015

Early biochemical studies of viral replication suggested that most viruses produce double-stranded RNA (dsRNA), which is essential for the induction of the host immune response. However, it was reported in 2006 that dsRNA could be detected by immunofluorescence antibody staining in double-stranded DNA and positive-strand RNA virus infections but not in negative-strand RNA virus infections. Other reports in the literature seemed to support these observations. This suggested that negative-strand RNA viruses produce little, if any, dsRNA or that more efficient viral countermeasures to mask dsRNA are mounted. Because of our interest in the use of dsRNA antibodies for virus discovery, particularly in pathological specimens, we wanted to determine how universal immunostaining for dsRNA might be in animal virus infections. We have detected the
in situ
formation of dsRNA in cells infected with vesicular stomatitis virus, measles virus, influenza A virus, and Nyamanini virus, which represent viruses from different negative-strand RNA virus families. dsRNA was also detected in cells infected with lymphocytic choriomeningitis virus, an ambisense RNA virus, and minute virus of mice (MVM), a single-stranded DNA (ssDNA) parvovirus, but not hepatitis B virus. Although dsRNA staining was primarily observed in the cytoplasm, it was also seen in the nucleus of cells infected with influenza A virus, Nyamanini virus, and MVM. Thus, it is likely that most animal virus infections produce dsRNA species that can be detected by immunofluorescence staining. The apoptosis induced in several uninfected cell lines failed to upregulate dsRNA formation.

IMPORTANCE
An effective antiviral host immune response depends on recognition of viral invasion and an intact innate immune system as a first line of defense. Double-stranded RNA (dsRNA) is a viral product essential for the induction of innate immunity, leading to the production of type I interferons (IFNs) and the activation of hundreds of IFN-stimulated genes. The present study demonstrates that infections, including those by ssDNA viruses and positive- and negative-strand RNA viruses, produce dsRNAs detectable by standard immunofluorescence staining. While dsRNA staining was primarily observed in the cytoplasm, nuclear staining was also present in some RNA and DNA virus infections. The nucleus is unlikely to have pathogen-associated molecular pattern (PAMP) receptors for dsRNA because of the presence of host dsRNA molecules. Thus, it is likely that most animal virus infections produce dsRNA species detectable by immunofluorescence staining, which may prove useful in viral discovery as well.
Role of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors for Herpes Simplex Virus 1 on Primary Murine Dermal Fibroblasts
Authors: Petermann Philipp , Rahn Elena , Thier Katharina , Hsu Mei-Ju , Rixon Frazer J. , Kopp Sarah J. , Knebel-Mörsdorf Dagmar
Published: July 2015

The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) can both mediate the entry of herpes simplex virus 1 (HSV-1). We have recently shown how these receptors contribute to infection of skin by investigating HSV-1 entry into murine epidermis.
Ex vivo
infection studies reveal nectin-1 as the primary receptor in epidermis, whereas HVEM has a more limited role. Although the epidermis represents the outermost layer of skin, the contribution of nectin-1 and HVEM in the underlying dermis is still open. Here, we analyzed the role of each receptor during HSV-1 entry in murine dermal fibroblasts that were deficient in expression of either nectin-1 or HVEM or both receptors. Because infection was not prevented by the absence of either nectin-1 or HVEM, we conclude that they can act as alternative receptors. Although HVEM was found to be highly expressed on fibroblasts, entry was delayed in nectin-1-deficient cells, suggesting that nectin-1 acts as the more efficient receptor. In the absence of both receptors, entry was strongly delayed leading to a much reduced viral spread and virus production. These results suggest an unidentified cellular component that acts as alternate but inefficient receptor for HSV-1 on dermal fibroblasts. Characterization of the cellular entry mechanism suggests that HSV-1 can enter dermal fibroblasts both by direct fusion with the plasma membrane and via endocytic vesicles and that this is not dependent on the presence or absence of nectin-1. Entry was also shown to require dynamin and cholesterol, suggesting comparable entry pathways in keratinocytes and dermal fibroblasts.

IMPORTANCE
Herpes simplex virus (HSV) is a human pathogen which infects its host via mucosal surfaces or abraded skin. To understand how HSV-1 overcomes the protective barrier of mucosa or skin and reaches its receptors in tissue, it is essential to know which receptors contribute to the entry into individual skin cells. Previously, we have explored the contribution of nectin-1 and herpesvirus entry mediator (HVEM) as receptors for HSV-1 entry into murine epidermis, where keratinocytes form the major cell type. Since the underlying dermis consists primarily of fibroblasts, we have now extended our study of HSV-1 entry to dermal fibroblasts isolated from nectin-1- or HVEM-deficient mice or from mice deficient in both receptors. Our results demonstrate a role for both nectin-1 and HVEM as receptors and suggest a further receptor which appears much less efficient.
Blockage of CD59 Function Restores Activities of Neutralizing and Nonneutralizing Antibodies in Triggering Antibody-Dependent Complement-Mediated Lysis of HIV-1 Virions and Provirus-Activated Latently Infected Cells
Authors: Yang Kai , Lan Jie , Shepherd Nicole , Hu Ningjie , Xing Yanyan , Byrd Daniel , Amet Tohti , Jewell Corlin , Gupta Samir , Kounga Carole , Gao Jimin , Yu Qigui
Published: July 2015

Both HIV-1 virions and infected cells use their surface regulators of complement activation (RCA) to resist antibody-dependent complement-mediated lysis (ADCML). Blockage of the biological function of RCA members, particularly CD59 (a key RCA member that controls formation of the membrane attack complex at the terminal stage of the complement activation cascades via all three activation pathways), has rendered both HIV-1 virions and infected cells sensitive to ADCML mediated by anti-Env antibodies (Abs) or sera/plasma from patients at different stages of viral infection. In the current study, we used the well-characterized anti-HIV-1 neutralizing Abs (nAbs), including 2G12, 2F5, and 4E10, and non-nAbs, including 2.2C, A32, N5-i5, and N12-i15, to investigate whether the enhancement of ADCML by blockage of CD59 function is mediated by nAbs, non-nAbs, or both. We found that all nAbs and two non-nAbs (N5-i5 and A32) strongly reacted to three HIV-1 laboratory strains (R5, X4, and R5/X4), six primary isolates, and provirus-activated ACH-2 cells examined. In contrast, two non-nAbs, 2.2C and N12-i15, reacted weakly and did not react to these targets, respectively. After blockage of CD59 function, the reactive Abs, regardless of their neutralizing activities, significantly enhanced specific ADCML of HIV-1 virions (both laboratory strains and primary isolates) and provirus-activated latently infected cells. The ADMCL efficacy positively correlated with the enzyme-linked immunosorbent assay-reactive intensity of those Abs with their targets. Thus, blockage of RCA function represents a novel approach to restore activities of both nAbs and non-nAbs in triggering ADCML of HIV-1 virions and provirus-activated latently infected cells.

IMPORTANCEThere is a renewed interest in the potential role of non-nAbs in the control of HIV-1 infection. Our data, for the first time, demonstrated that blockage of the biological function of RCA members rendered both HIV-1 virions and infected cells sensitive to ADCML mediated by not only nAbs but also non-nAbs. Our results are significant in developing novel immune-based approaches to restore the functions of nAbs and non-nAbs in the circulation of HIV-1-infected individuals to specifically target and clear HIV-1 virions and infected cells. Our data also provide new insights into the mechanisms by which HIV-1 virions and infected cells escape Ab-mediated immunity and could aid in the design and/or development of therapeutic HIV-1 vaccines. In addition, a combination of antiretroviral therapy with RCA blockage, provirus activators, and therapeutic vaccines may represent a novel approach to eliminate HIV-1 reservoirs, i.e., the infected cells harboring replication-competent proviruses and residual viremia.
Impact of Nucleoporin-Mediated Chromatin Localization and Nuclear Architecture on HIV Integration Site Selection
Authors: Wong Richard W. , Mamede João I. , Hope Thomas J.
Published: July 2015

It has been known for a number of years that integration sites of human immunodeficiency virus type 1 (HIV-1) DNA show a preference for actively expressed chromosomal locations. A number of viral and cellular proteins are implicated in this process, but the underlying mechanism is not clear. Two recent breakthrough publications advance our understanding of HIV integration site selection by focusing on the localization of the preferred target genes of integration. These studies reveal that knockdown of certain nucleoporins and components of nucleocytoplasmic trafficking alter integration site preference, not by altering the trafficking of the viral genome but by altering the chromatin subtype localization relative to the structure of the nucleus. Here, we describe the link between the nuclear basket nucleoporins (Tpr and Nup153) and chromatin organization and how altering the host environment by manipulating nuclear structure may have important implications for the preferential integration of HIV into actively transcribed genes, facilitating efficient viral replication.
The Plasmid Mobilome of the Model Plant-SymbiontSinorhizobium meliloti: Coming up with New Questions and Answers
Authors: Lagares Antonio , Sanjuán Juan , Pistorio Mariano
Published: July 2015

Rhizobia are Gram-negative Alpha- and Betaproteobacteria living in the underground which have the ability to associate with legumes for the establishment of nitrogen-fixing symbioses.Sinorhizobium melilotiin particular—the symbiont ofMedicago,Melilotus, andTrigonellaspp.—has for the past decades served as a model organism for investigating, at the molecular level, the biology, biochemistry, and genetics of a free-living and symbiotic soil bacterium of agricultural relevance. To date, the genomes of seven differentS. melilotistrains have been fully sequenced and annotated, and several other draft genomic sequences are also available. The vast amount of plasmid DNA thatS. melilotifrequently bears (up to 45% of its total genome), the conjugative ability of some of those plasmids, and the extent of the plasmid diversity has provided researchers with an extraordinary system to investigate functional and structural plasmid molecular biology within the evolutionary context surrounding a plant-associated model bacterium. Current evidence indicates that the plasmid mobilome inS. melilotiis composed of replicons varying greatly in size and having diverse conjugative systems and properties along with different evolutionary stabilities and biological roles. While plasmids carrying symbiotic functions (pSyms) are known to have high structural stability (approaching that of chromosomes), the remaining plasmid mobilome (referred to as the non-pSym,functionally cryptic, oraccessorycompartment) has been shown to possess remarkable diversity and to be highly active in conjugation. In light of the modern genomic and current biochemical data on the plasmids ofS. meliloti, the current article revises their main structural components, their transfer and regulatory mechanisms, and their potential as vehicles in shaping the evolution of the rhizobial genome.
The
Agrobacterium
Ti Plasmids
Authors: Gordon Jay E. , Christie Peter J.
Published: July 2015

Agrobacterium tumefaciens
is a plant pathogen with the capacity to deliver a segment of oncogenic DNA carried on a large plasmid called the tumor-inducing or Ti plasmid to susceptible plant cells.
A. tumefaciens
belongs to the class
Alphaproteobacteria
, whose members include other plant pathogens (
Agrobacterium rhizogenes
), plant and insect symbionts (
Rhizobium
spp. and
Wolbachia
spp., respectively), human pathogens (
Brucella
spp.,
Bartonella
spp.,
Rickettsia
spp.), and nonpathogens (
Caulobacter crescentus, Rhodobacter sphaeroides
). Many species of
Alphaproteobacteria
carry large plasmids ranging in size from ∼100 kb to nearly 2 Mb. These large replicons typically code for functions essential for cell physiology, pathogenesis, or symbiosis. Most of these elements rely on a conserved gene cassette termed
repABC
for replication and partitioning, and maintenance at only one or a few copies per cell (
1
). The subject of this review is the ∼200-kb Ti plasmids carried by infectious strains of
A. tumefaciens
. We will summarize the features of this plasmid as a representative of the
repABC
family of megaplasmids. We will also describe novel features of this plasmid that enable
A. tumefaciens
cells to incite tumor formation in plants, sense and respond to an array of plant host and bacterial signal molecules, and maintain and disseminate the plasmid among populations of agrobacteria. At the end of this review, we will describe how this natural genetic engineer has been adapted to spawn an entire industry of plant biotechnology and review its potential for use in future therapeutic applications of plant and nonplant species.
Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-Negatives: the
Klebsiella pneumoniae
Paradigm
Authors: Ramirez Maria S. , Traglia German M. , Lin David L. , Tran Tung , Tolmasky Marcelo E.
Published: July 2015

Plasmids harbor genes coding for specific functions including virulence factors and antibiotic resistance that permit bacteria to survive the hostile environment found in the host and resist treatment. Together with other genetic elements such as integrons and transposons, and using a variety of mechanisms, plasmids participate in the dissemination of these traits, resulting in the virtual elimination of barriers among different kinds of bacteria. In this article we review the current information about the physiology of plasmids and their role in virulence and antibiotic resistance from the Gram-negative opportunistic pathogen
Klebsiella pneumoniae
. This bacterium has acquired multidrug resistance and is the causative agent of serious community- and hospital-acquired infections. It is also included in the recently defined ESKAPE group of bacteria that cause most U.S. hospital infections.
Iteron Plasmids
Authors: Konieczny Igor , Bury Katarzyna , Wawrzycka Aleksandra , Wegrzyn Katarzyna
Published: July 2015

Iteron-containing plasmids are model systems for studying the metabolism of extrachromosomal genetic elements in bacterial cells. Here we describe the current knowledge and understanding of the structure of iteron-containing replicons, the structure of the iteron plasmid encoded replication initiation proteins, and the molecular mechanisms for iteron plasmid DNA replication initiation. We also discuss the current understanding of control mechanisms affecting the plasmid copy number and how host chaperone proteins and proteases can affect plasmid maintenance in bacterial cells.
Plasmid Diversity and Adaptation Analyzed by Massive Sequencing of
Escherichia coli
Plasmids
Authors: de Toro María , Garcilláon-Barcia M. Pilar , De La Cruz Fernando
Published: July 2015

Whole-genome sequencing is revolutionizing the analysis of bacterial genomes. It leads to a massive increase in the amount of available data to be analyzed. Bacterial genomes are usually composed of one main chromosome and a number of accessory chromosomes, called plasmids. A recently developed methodology called PLACNET (for
pla
smid
c
onstellation
net
works) allows the reconstruction of the plasmids of a given genome. Thus, it opens an avenue for plasmidome analysis on a global scale. This work reviews our knowledge of the genetic determinants for plasmid propagation (conjugation and related functions), their diversity, and their prevalence in the variety of plasmids found by whole-genome sequencing. It focuses on the results obtained from a collection of 255
Escherichia coli
plasmids reconstructed by PLACNET. The plasmids found in
E. coli
represent a nonaleatory subset of the plasmids found in proteobacteria. Potential reasons for the prevalence of some specific plasmid groups will be discussed and, more importantly, additional questions will be posed.
An adolescent with hereditary spherocytosis who presented with splenic infarction
Authors: Jones Lara , Refai Zafer , Linney Mike
Published: July 2015

A 16-year-old male patient with known hereditary spherocytosis presented with a 4-day history of chest pain and lethargy. On admission, he had a low-grade fever and was grossly anaemic; examination revealed splenomegaly. An ultrasound scan confirmed splenomegaly with areas of splenic infarction. Subsequent tests suggested possible Epstein-Barr virus infection. The patient recovered well and had a functional spleen on discharge. This case report presents an unusual complication of isolated hereditary spherocytosis.
Postnatal acute renal failure after fetal exposure to angiotensin receptor blockers
Authors: Marchetto Luca , Sordino Desiree , De Bernardo Giuseppe , Trevisanuto Daniele
Published: July 2015

Maternal hypertensive treatment with angiotensin receptor blockers (ARBs) during the second and third trimester of pregnancy is associated with several fetal and neonatal complications, and potential adverse outcomes. We report a neonate presenting with transient renal acute failure during the first days of life after maternal treatment with ARBs. Women who became pregnant while taking one of these drugs must modify antihypertensive therapy with a different class drug as soon as pregnancy is recognised.
Clinical use of low haemoglobin density, transferrin saturation, bone marrow morphology, Perl's stain and other plasma markers in the identification of treatable anaemia presenting for cardiac surgery in a prospective cohort study
Authors: Martin-Cabrera Pedro , Hung Matthew , Ortmann Erik , Richards Toby , Ghosh Marcus , Bottrill Fiona , Collier Timothy , Klein Andrew A , Besser Martin W
Published: July 2015

Objectives

The differential diagnosis between iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) with or without associated iron deficiency can be challenging. We assessed the use of different parameters, both classical like ferritin, transferrin saturation and stainable bone marrow iron stores, and novel markers such as low haemoglobin density (LHD) and hepcidin to help discriminate between the three entities. This would allow the detection of patients with ACD with associated iron deficiency, which could benefit from iron supplementation that would have otherwise remained undetected.

Materials and methods

Prospective and observational cohort study from 2012 to 2013 where 200 anaemic cardiac surgical patients were recruited and 165 were studied. Detailed blood and bone marrow analyses were performed to establish the aetiology of anaemia.

Results

Seventy-four patients (44.8%) had ACD and 29 (39%) of these had an elevated LHD indicating concomitant iron deficiency. Hepcidin was inappropriately normal or increased in the IDA and ACD group. Mean hepcidin was however lower in the group with IDA (4.8 ng/mL) than in the ACD group (15.0 ng/mL; p=0.002). Median hepcidin was lower in patients with ACD and iron restriction as indicated by LHD >4% (17.5 ng/mL) than on those with no iron restriction (25.9 ng/mL; p=0.045). In patients with ACD there was no concordance between Perl's stain and LHD.

Conclusions

LHD was superior to hepcidin and bone marrow iron stores in identifying patients with ACD and associated iron deficiency, which would potentially benefit from parenteral iron therapy.
Mycobacterium avium subspecies hominissuis infection in a dog from Germany with multifocal alopecia, exfoliative dermatitis, hypercalcaemia and subsequent sebaceous atrophy
Authors: Hobi Stefan , Bettenay Sonya , Majzoub Monir , Mueller Ralf , Moser Irmgard
Published: July 2015

Mycobacterium avium subspecies hominissuis belongs to the M avium complex and infections with this agent are reported rarely in the dog. A nine‐year‐old intact female Elo dog was presented with widespread hypotrichosis, erythema and exfoliation. Other clinical signs were polyuria/polydipsia and severe weight loss. No other animals or humans in the household showed any dermatological abnormalities. Multiple skin biopsies identified a pyogranulomatous dermatitis but no causative agent could be detected. Skin tissue culture and PCR revealed M avium subspecies hominissuis. Hypercalcaemia (ionised calcium) was initially present. All other serum biochemistry parameters, chest radiographs, abdominal ultrasound, parathyroid hormone and parathyroid hormone‐related protein were within the reference interval. Subsequent to therapy with rifampicin, pradofloxacin and oral fatty acids the pyogranulomatous dermatitis resolved and mycobacteria could not be detected but sebaceous glands were lost histopathologically. This is the first report describing a dog infected with M avium subspecies hominissuis successfully treated with antibiotic therapy and with no zoonotic transmission.
Effect of rare earth substitution on the structural and electrical properties of Cu–Mg ferrite
Authors: Ateia E. , Ahmed M. A. , Ghouniem R. M.
Published: July 2015

The samples of Cu 0.9 Mg 0.1 R y Fe 2-y O 4, where y = 0.01 and R = Sm , Dy , Ho and Hf , were prepared by standard ceramic method. All investigated samples were sintered at 1150°C with a heating rate of 4°C/min and sintering time of 8 h. X-ray diffraction study of the compositions revealed the formation of cubic spinel structure with the appearance of small peaks indicating the presence of secondary phases. Seebeck coefficient was obtained from thermo-electromotive force (emf) measurements. The alternation of the Seebeck coefficient sign between (+)ve and (-)ve means that the two conduction mechanisms take place simultaneously. The dielectric parameters such as dielectric constant, quality factor were determined as a function of temperature and at different frequencies. The decrease in Fe 3+ ions on the octahedral site decreased the polarization of the system, through the dielectric transition point.
Influence of quantum energy equation on electronic plasma oscillations
Authors: Ivanov A. Yu. , Kuz'menkov L. S.
Published: July 2015

Five-moment approximation in hydrodynamics includes not only a continuity equation and a momentum balance equation, but also an energy equation. A set of hydrodynamic equations in this approximation is presented for a system of nonrelativistic quantum particles with the Coulomb interaction. This set of equations is linearized, and dispersion relation for Langmuir waves in quasi-neutral system of electrons and immobile ions is obtained. The plasma waves suffer damping in this case, and also there is another damping branch.
A Synthesis Method of Quantum Reversible Logic Circuit Based on Elementary Qutrit Quantum Logic Gates
Authors: Fan Fuyou , Yang Guowu , Yang Gang , Hung William N. N.
Published: July 2015

Because ternary computer has more superiority than other d-ary number systems, we focus on the investigation of ternary elementary quantum gates and the synthesis algorithm of ternary quantum logic circuits. Above all, Pauli operators and their matrices on qutrit are introduced. Then eight qutrit operators are selected as elementary operators and eight qutrit quantum logic gates are defined. Permutation groups are introduced to characterize the quantum gates and quantum logic circuits. Some important qutrit quantum logic gates are defined also, such as QNOT, QKCXi, EQKCXi, QSwap, QCNOT and EQCNOT. Based on these elementary gates, we prove two very important theorems: (1) all qutrit quantum reversible logic circuit can be generated by Xi gate and QKCXi gate; (2) all qutrit quantum reversible logic circuits can be generated by Xi gate and QCNOT gate. The two theorems indicate that any complicated qutrit quantum reversible circuit can be constructed by the simplest ternary quantum gate. This will greatly simplify the implementation difficulty of quantum circuit. Subsequently, we propose a synthesis algorithm for qutrit quantum reversible logic circuit, which is verified through simulation experiment by the computer program we have designed.
Performance Analysis of Reversible Finite Field Arithmetic Architectures Over GF(p) and GF(2m) in Elliptic Curve Cryptography
Authors: Saravanan P. , Kalpana P.
Published: July 2015

Elliptic curve cryptosystems (ECC) are becoming more and more popular and are included in many standards, as they offer high security strength when compared with other conventional public-key cryptosystems, for the same key length. But the security strength of hardware implementations of ECC is challenged by side channel attacks (SCA) such as power analysis. Reversible logic circuits ideally consume zero energy, which serves as the motivation to implement cryptographic algorithms against power analysis attacks. This paper proposes two new hardware architectures for performing montgomery multiplication in GF(p) and GF(2m), as they are the power consuming operations in ECC. The two architectures are optimized to reduce the hardware cost and they are then implemented in reversible logic with reduced number of quantum cost. In this work, the reversible logic synthesis is performed with Toffoli family of reversible gates. The performance metrics of all the multipliers are analyzed and properly tabulated. Scalar multiplication on elliptic curve points, which is the core operation used in every elliptic curve cryptosystem, has been implemented in reversible logic by using the proposed reversible montgomery multipliers.
A Routing Aggregation for Load Balancing Network-on-Chip
Authors: Zhou Xiaofeng , Liu Lu , Zhu Zhangming , Zhou Duan
Published: July 2015

A routing aggregation (RA) is proposed for load balancing network-on-chip (NoC). The computing nodes with dense traffic and long distance in network are gathered into the same routing node to form a super router. A load balancing routing algorithm for super router is presented to improve the overall performance of NoC. A simulation platform using System C is presented to confirm the feasibility of the proposed design in 2D mesh. The simulation results show that the proposed RA design can reduce the average packet latency and the standard deviation of host link utilization 8% and 33%, respectively compared with the reported routing methods. The area cost and power consumption compared with the reported schemes are 22% and 12% less, respectively.
Plebański–Demiański solution of general relativity and its expressions quadratic and cubic in curvature: Analogies to electromagnetism
Authors: Boos Jens
Published: July 2015

Analogies between gravitation and electromagnetism have been known since the 1950s. Here, we examine a fairly general type D solution — the exact seven parameter solution of Plebański–Demiański (PD) — to demonstrate these analogies for a physically meaningful spacetime.

The two quadratic curvature invariants B2 - E2 and E⋅B are evaluated analytically. In the asymptotically flat case, the leading terms of E and B can be interpreted as gravitoelectric mass and gravitoelectric current of the PD solution, respectively, if there are no gravitomagnetic monopoles present.

Furthermore, the square of the Bel–Robinson tensor reads (B2 + E2)2 for the PD solution, reminiscent of the square of the energy density in electrodynamics. By analogy to the energy–momentum 3-form of the electromagnetic field, we provide an alternative way to derive the recently introduced Bel–Robinson 3-form, from which the Bel–Robinson tensor can be calculated.

We also determine the Kummer tensor, a tensor cubic in curvature, for a general type D solution for the first time, and calculate the pieces of its irreducible decomposition.

The calculations are carried out in two coordinate systems: In the original polynomial PD coordinates and in a modified Boyer–Lindquist-like version introduced by Griffiths and Podolský (GP) allowing for a more straightforward physical interpretation of the free parameters.
Systematics of band moment of inertia of yrast and excited SD bands of even–even nuclei in A~150 mass region
Authors: Sharma Neha , Mittal H. M.
Published: July 2015

A four parameter formula has been applied to all the yrast and excited superdeformed (SD) bands of even–even nuclei in the A~150 mass region to obtain band moment of inertia J0. In even–even nuclei, totally three yrast SD bands and 16 excited SD bands have been fitted. The measured Qt values and hence the axes ratios have been used to calculate the rigid body J0 values and compared with the fitted values of J0. It is interesting to look at the yrast SD band 152 Dy (1), the doubly magic SD nucleus and the first one to be discovered that the J0 values are quite larger than that extracted from Qt measurement. We found that all the excited SD bands in even–even nuclei are signature partner SD bands because the J0 value of each signature partner SD band is almost identical. Among all these excited SD bands, 150 Gd (4) is found to be super-rigid in nature having J0 value larger than that observed from the measured Qt value.
Optimization of Curvilinearly Stiffened Panels with Single Cutout Concerning the Collapse Load
Authors: Hao Peng , Wang Bo , Tian Kuo , Li Gang , Zhang Xi
Published: July 2015

The motivation of this study is to meet the requirement of cutout reinforcements in aerospace industry by using the design flexibility of curvilinearly stiffened panels. The reason is that the load path and tension field caused by curvilinear stiffeners can increase the load-carrying capacity of stiffened panels. The inherent superiority of such structures was examined in detail by comparison with those having straight stiffeners. Due to the large computational burden caused by post-buckling analysis, the optimum design of curvilinearly stiffened panels with single cutout was obtained based on surrogate model. On this basis, variable symmetrization and reduction methods were developed for different design cases, aimed at reducing the number of dependent variables in the optimization. Illustrative examples show the superiority of curvilinearly stiffened panels for cutout reinforcement, and demonstrate the effectiveness of the proposed optimization framework.