bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnaporthe oryzae conidia on basal wheat leaves as a potential source of wheat blast inoculum
Authors: Cruz C. D. , Kiyuna J. , Bockus W. W. , Todd T. C. , Stack J. P. , Valent B.
Published: May 2015

Wheat blast caused by Magnaporthe oryzae Triticum causes significant losses on wheat during outbreak years in several South American countries. Despite reports of wheat blast leaf lesions on some wheat cultivars, the importance of inoculum originating from leaves in severely affected commercial fields is disputed. It is generally considered that leaf lesions and/or sporulation on leaves do not usually appear before the occurrence of spike blast in wheat. The purpose of this study was to (i) determine the occurrence of wheat blast on basal leaves, (ii) estimate the number of conidia produced on these leaves, and (iii) determine the impact of current fungicide application practices on inoculum produced from sporulating lesions on basal wheat leaves. Inoculations at the three‐leaf stage showed that certain cultivar and isolate combinations caused more disease on old wheat leaves than young expanding leaves. Under optimum conditions, M. oryzae had the potential to produce tens to hundreds of thousands of conidia on small amounts of wheat basal leaves. A mean of 1 669 000 conidia were produced on 1 g dry basal leaves of a highly susceptible cultivar under optimum conditions for sporulation. Conidia production on leaves coincided with spike emergence under both greenhouse and field conditions. When field studies were conducted under natural epidemic conditions, foliar fungicide applications reduced the amount of M. oryzae conidia on basal leaves by 62–77% compared to non‐sprayed controls. An earlier application of foliar fungicides might reduce inoculum if conidia from basal leaves contribute to wheat spike blast development.
Circulation of water through a mussel raft: clearance area vs. idealized linear flows
Authors: Aguiar Eva , Piedracoba Silvia , Álvarez‐Salgado Xosé Antón , Labarta Uxío
Published: May 2015

This study suggests revision of ecological concepts as food depletions and/or water flow reductions based on idealized linear flows through mussel rafts. We offer an alternative based on the extension of the clearance area, defined as the area affected by the nonlinear effects produced by each raft and surroundings ones. These conclusions are supported by our results, which indicate that (i) the preferential entry of water through a mussel raft does not occur through the bow, contrary to previously thought, and (ii) the intraraft circulation is strongly influenced by the orientation of the raft relative to the background current direction and does not follow a defined pattern. Intraraft circulation is assessed by means of four current metres installed at each side of the raft and the dimensions of the clearance area using long‐term data provided by GPS and compass. While both intraraft circulation and clearance area dimensions are mainly controlled by tide, the net water exchange through the raft is reasonably explained by wind (velocity and direction) and river discharges.
A Synthetical Two‐Component Model with Peakon Solutions
Authors: Xia Baoqiang , Qiao Zhijun , Zhou Ruguang
Published: May 2015

A generalized two‐component model with peakon solutions is proposed in this paper. It allows an arbitrary function to be involved in as well as including some existing integrable peakon equations as special reductions. The generalized two‐component system is shown to possess Lax pair and infinitely many conservation laws. Bi‐Hamiltonian structures and peakon interactions are discussed in detail for typical representative equations of the generalized system. In particular, a new type of N‐peakon solution, which is not in the traveling wave type, is obtained from the generalized system.
How we provide thawed plasma for trauma patients
Authors: Stubbs James R. , Zielinski Martin D. , Berns Kathleen S. , Badjie Karafa S. , Tauscher Craig D. , Hammel Scott A. , Zietlow Scott P. , Jenkins Donald
Published: May 2015

Almost 50% of trauma‐related fatalities within the first 24 hours of injury are related to hemorrhage. Improved survival in severely injured patients has been demonstrated when massive transfusion protocols are rapidly invoked as part of a therapeutic approach known as damage control resuscitation (DCR). DCR incorporates the early use of plasma to prevent or correct trauma‐induced coagulopathy. DCR often requires the transfusion of plasma before determination of the recipient's ABO group. Historically, group AB plasma has been considered the “universal donor” plasma product. At our facility, the number of AB plasma products produced on an annual basis was found to be inadequate to support the trauma service's DCR program. A joint decision was made by the transfusion medicine and trauma services to provide group A thawed plasma (TP) for in‐hospital and prehospital DCR protocols. A description of the implementation of group A TP into the DCR program is provided as well as outcome data pertaining to the use of TP in trauma patients.
Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples
Authors: Laperche Syria , Nübling C. Micha , Stramer Susan L. , Brojer Ewa , Grabarczyk Piotr , Yoshizawa Hiroshi , Kalibatas Vytenis , El Elkyabi Magdy , Moftah Faten , Girault Annie , van Drimmelen Harry , Busch Michael P. , Lelie Nico
Published: May 2015

BACKGROUND

Hepatitis C virus (HCV) antigen and antibody combination assays have been launched as a cost‐effective alternative to nucleic acid testing (NAT) for reducing the antibody‐negative window period (WP). Later, a HCV antigen chemiluminescence immunoassay (CLIA) became available.

STUDY DESIGN AND METHODS

A panel composed of 337 HCV NAT–yield samples that were characterized for viral load (VL) and genotype was used to compare the sensitivity of two combination enzyme‐linked immunosorbent assays (Monolisa, Bio‐Rad; and Murex, formerly Abbott) and a HCV antigen CLIA (Abbott). Analytic sensitivity was compared with HCV RNA detection using Ultrio (Grifols) by testing serial dilutions of 10 genotype (gt)1 to gt4 samples.

RESULTS

HCV antigen CLIA detected 92.4% of samples, whereas Monolisa and Murex detected 38.3 and 47.5%, respectively. In the HCV RNA VL range of 105 to 107 IU/mL, Monolisa and Murex detected 38% to 56% of gt1, 85% to 78% of gt2, and 21% to 37% of gt3. The overall geometric mean 50% limit of detection (range) of Ultrio on gt1 to gt4 dilution series was 3.5 (1.2‐7.7) copies/mL, compared to 3.3 × 106 (4.4 × 105‐2.7 × 107), 3.4 × 106 (2.2 × 105‐4.2 × 107), and 2728 (415‐7243) copies/mL for Monolisa, Murex, and HCV antigen CLIA, respectively.

CONCLUSION

Analytical sensitivity of NAT was on average 1 million‐ and 780‐fold higher than combination assays and HCV antigen CLIA, respectively. Relative sensitivities of combination assays differed for genotypes with Murex being more sensitive for gt1 and gt3 and Monolisa more sensitive for gt2. Although being less sensitive than NAT, combination assays could be considered in resource‐limited settings since they detect 38% to 47% of seronegative WP donations.
Nicotine and the adolescent brain
Authors: Yuan Menglu , Cross Sarah J. , Loughlin Sandra E. , Leslie Frances M.
Published: May 2015

Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e‐cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e‐cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi‐chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e‐cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.
Applied Sport Psychology: A Profession?
Authors: Winter Stacy , Collins David J.
Published: May 2015

Although the field of applied sport psychology has developed, it faces further challenges on its way toward gaining greater professional status. The following principal criteria of professionalism are proposed as a test of such status: (a) provides an important public service, (b) has a knowledge-base underpinning, (c) has organizational regulation, (d) has a distinct ethical dimension, and (e) has professional autonomy. This article undertakes to explore the nature of implications for practice and the extent to which the suggested principal criteria justify a distinctive applied sport psychology profession. In doing so, we hope to stimulate debate on these and other issues in order that an even greater professionalization of our applied discipline may emerge.
In Vitro
Triple Combination of Antifungal Drugs against Clinical Scopulariopsis and Microascus Species
Authors: Yao Limin , Wan Zhe , Li Ruoyu , Yu Jin
Published: May 2015

Broth microdilution checkerboard techniques based on the methodology of the Clinical and Laboratory Standards Institute (CLSI) were employed to study the triple antifungal combination of caspofungin, posaconazole, and terbinafine against 27 clinical isolates of
Scopulariopsis
and
Microascus
species. Synergy was observed for 26 isolates, whereas antagonism was observed for
Scopulariopsis
candida
in this study.
Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria
Authors: Rocha Paulo Novis , Kobayashi Carla Dinamérica , de Carvalho Almeida Luna , de Oliveira dos Reis Camilla , Santos Barbara Mendes , Glesby Marshall Jay
Published: May 2015

Studies on amphotericin B (AmB) nephrotoxicity use diverse definitions of acute kidney injury (AKI). Here, we used the new Kidney Disease Improving Global Outcome (KDIGO) system to describe the incidence, predictors, and impact of AmB-induced AKI on hospital mortality in 162 patients treated with AmB (120 with deoxycholate preparation and 42 with liposomal preparation). KDIGO stage 1 requires an absolute increase of ≥0.3 mg/dl or ≥1.5× over baseline serum creatinine (SCr), while stage 2 requires ≥2×, and stage 3 requires ≥3×. A binary KDIGO definition (KDIGObin) corresponds to stage ≥1. For comparison, we included two definitions of AKI traditionally utilized in nephrotoxicity studies: ≥0.5 mg/dl (NT0.5) and ≥2× (NT2×) increase in baseline SCr. The overall incidence of AmB-induced AKI by KDIGObin was 58.6% (stage 1, 30.9%; stage 2, 18.5%; stage 3, 9.3%). Predictors of AKI by KDIGObin were older age and use of furosemide and angiotensin-converting enzyme inhibitor (ACE-I). Traditional criteria detected lower incidences of AKI, at 45.1% (NT0.5) and 27.8% (NT2×). Predictors of AKI by traditional criteria were older age and use of vancomycin (NT0.5) and use of vancomycin and vasopressors (NT2×). KDIGObin detected AKI 2 days earlier than the most sensitive traditional criterion. However, only traditional criteria were associated with intensive care unit (ICU) admission, mechanical ventilation, and mortality. In conclusion, the increase in sensitivity of KDIGObin is accompanied by a loss of specificity and ability to predict outcomes. Prospective studies are required to weigh the potential gain from early AKI detection against the potential loss from undue changes in management in patients with subtle elevations in SCr.
In Vivo
Selection of Paromomycin and Miltefosine Resistance in Leishmania donovani and L. infantum in a Syrian Hamster Model
Authors: Hendrickx S. , Mondelaers A. , Eberhardt E. , Delputte P. , Cos P. , Maes L.
Published: May 2015

In 2002 and 2006, respectively, miltefosine (MIL) and paromomycin (PMM) were licensed in the Indian subcontinent for treatment of visceral leishmaniasis; however, their future routine use might become jeopardized by the development of drug resistance. Although experimental selection of resistant strains
in vitro
has repeatedly been reported using the less relevant promastigote vector stage, the outcome of resistance selection on intracellular amastigotes was reported to be protocol and species dependent. To corroborate these
in vitro
findings, selection of resistance in
Leishmania donovani
and
Leishmania infantum
was achieved by successive treatment/relapse cycles in infected Syrian golden hamsters. For PMM, resistant amastigotes were already obtained within 3 treatment/relapse cycles, while their promastigotes retained full susceptibility, thereby sharing the same phenotypic characteristics as
in vitro
-generated PMM-resistant strains. For MIL, even five treatment/relapse cycles failed to induce significant susceptibility changes in either species, which also corresponds with the
in vitro
observations where selection of an MIL-resistant phenotype proved to be quite challenging. In conclusion, these results argue for cautious use of PMM in the field to avoid rapid emergence of primary resistance and highlight the need for additional research on the mechanisms and dynamics of MIL resistance selection.
Hsp70 and the Cochaperone StiA (Hop) Orchestrate Hsp90-Mediated Caspofungin Tolerance in Aspergillus fumigatus
Authors: Lamoth Frédéric , Juvvadi Praveen R. , Soderblom Erik J. , Moseley M. Arthur , Steinbach William J.
Published: May 2015

Aspergillus fumigatus
is the primary etiologic agent of invasive aspergillosis (IA), a major cause of death among immunosuppressed patients. Echinocandins (e.g., caspofungin) are increasingly used as second-line therapy for IA, but their activity is only fungistatic. Heat shock protein 90 (Hsp90) was previously shown to trigger tolerance to caspofungin and the paradoxical effect (i.e., decreased efficacy of caspofungin at higher concentrations). Here, we demonstrate the key role of another molecular chaperone, Hsp70, in governing the stress response to caspofungin via Hsp90 and their cochaperone Hop/Sti1 (StiA in
A. fumigatus
). Mutation of the StiA-interacting domain of Hsp70 (C-terminal EELD motif) impaired thermal adaptation and caspofungin tolerance with loss of the caspofungin paradoxical effect. Impaired Hsp90 function and increased susceptibility to caspofungin were also observed following pharmacologic inhibition of the C-terminal domain of Hsp70 by pifithrin-μ or after
stiA
deletion, further supporting the links among Hsp70, StiA, and Hsp90 in governing caspofungin tolerance. StiA was not required for the physical interaction between Hsp70 and Hsp90 but had distinct roles in the regulation of their function in caspofungin and heat stress responses. In conclusion, this study deciphering the physical and functional interactions of the Hsp70-StiA-Hsp90 complex provided new insights into the mechanisms of tolerance to caspofungin in
A. fumigatus
and revealed a key C-terminal motif of Hsp70, which can be targeted by specific inhibitors, such as pifithrin-μ, to enhance the antifungal activity of caspofungin against
A. fumigatus
.
Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease
Authors: Moretti Nilmar Silvio , da Silva Augusto Leonardo , Clemente Tatiana Mordente , Antunes Raysa Paes Pinto , Yoshida Nobuko , Torrecilhas Ana Claudia , Cano Maria Isabel Nogueira , Schenkman Sergio
Published: May 2015

Acetylation of lysine is a major posttranslational modification of proteins and is catalyzed by lysine acetyltransferases, while lysine deacetylases remove acetyl groups. Among the deacetylases, the sirtuins are NAD
+
-dependent enzymes, which modulate gene silencing, DNA damage repair, and several metabolic processes. As sirtuin-specific inhibitors have been proposed as drugs for inhibiting the proliferation of tumor cells, in this study, we investigated the role of these inhibitors in the growth and differentiation of
Trypanosoma cruzi
, the agent of Chagas disease. We found that the use of salermide during parasite infection prevented growth and initial multiplication after mammalian cell invasion by
T. cruzi
at concentrations that did not affect host cell viability. In addition,
in vivo
infection was partially controlled upon administration of salermide. There are two sirtuins in
T. cruzi
, TcSir2rp1 and TcSir2rp3. By using specific antibodies and cell lines overexpressing the tagged versions of these enzymes, we found that TcSir2rp1 is localized in the cytosol and TcSir2rp3 in the mitochondrion. TcSir2rp1 overexpression acts to impair parasite growth and differentiation, whereas the wild-type version of TcSir2rp3 and not an enzyme mutated in the active site improves both. The effects observed with TcSir2rp3 were fully reverted by adding salermide, which inhibited TcSir2rp3 expressed in
Escherichia coli
with a 50% inhibitory concentration (IC
50
) ± standard error of 1 ± 0.5 μM. We concluded that sirtuin inhibitors targeting TcSir2rp3 could be used in Chagas disease chemotherapy.
A Short-Term Borrelia burgdorferi Infection Model Identifies Tissue Tropisms and Bloodstream Survival Conferred by Adhesion Proteins
Authors: Caine Jennifer A. , Coburn Jenifer
Published: May 2015

Borrelia burgdorferi
, the causative agent of Lyme disease in the United States, is able to persist in the joint, heart, skin, and central nervous system for the lifetime of its mammalian host.
Borrelia
species achieve dissemination to distal sites in part by entry into and travel within the bloodstream. Much work has been performed
in vitro
describing the roles of many
B. burgdorferi
outer surface proteins in adhesion to host cell surface proteins and extracellular matrix components, although the biological relevance of these interactions is only beginning to be explored
in vivo
. A need exists in the field for an
in vivo
model to define the biological roles of
B. burgdorferi
adhesins in tissue-specific vascular interactions. We have developed an
in vivo
model of vascular interaction of
B. burgdorferi
in which the bacteria are injected intravenously and allowed to circulate for 1 h. This model has shown that the fibronectin binding protein BB0347 has a tropism for joint tissue. We also have shown an importance of the integrin binding protein, P66, in binding to vasculature of the ear and heart. This model also revealed unexpected roles for
Borrelia
adhesins BBK32 and OspC in bacterial burdens in the bloodstream. The intravenous inoculation model of short-term infection provides new insights into critical
B. burgdorferi
interactions with the host required for initial survival and tissue colonization.
Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B
Authors: Rajaram Krithika , Nelson David E.
Published: May 2015

The ability of certain species ofChlamydiato inhibit the biogenesis of phagolysosomes permits their survival and replication within macrophages. The survival of macrophage-adapted chlamydiae correlates with the multiplicity of infection (MOI), and optimal chlamydial growth occurs in macrophages infected at an MOI of ≤1. In this study, we examined the replicative capacity ofChlamydia muridarumin the RAW 264.7 murine macrophage cell line at different MOIs.C. muridarumproductively infected these macrophages at low MOIs but yielded few viable elementary bodies (EBs) when macrophages were infected at a moderate (10) or high (100) MOI. While high MOIs caused cytotoxicity and irreversible host cell death, macrophages infected at a moderate MOI did not show signs of cytotoxicity until late in the infectious cycle. Inhibition of host protein synthesis rescuedC. muridarumin macrophages infected at a moderate MOI, implying that chlamydial growth was blocked by activated defense mechanisms. Conditioned medium from these macrophages was antichlamydial and contained elevated levels of interleukin 1β (IL-1β), IL-6, IL-10, and beta interferon (IFN-β). Macrophage activation depended on Toll-like receptor 2 (TLR2) signaling, and cytokine production required live, transcriptionally active chlamydiae. A hydroxyl radical scavenger and inhibitors of inducible nitric oxide synthase (iNOS) and cathepsin B also reversed chlamydial killing. High levels of reactive oxygen species (ROS) led to an increase in cathepsin B activity, and pharmacological inhibition of ROS and cathepsin B reduced iNOS expression. Our data demonstrate that MOI-dependent TLR2 activation of macrophages results in iNOS induction via a novel ROS- and cathepsin-dependent mechanism to facilitateC. muridarumclearance.
Observations on the Role of TcdE Isoforms in Clostridium difficile Toxin Secretion
Authors: Govind Revathi , Fitzwater Leah , Nichols Rebekah
Published: May 2015

Clostridium difficile
is a major nosocomial pathogen and the principal causative agent of antibiotic-associated diarrhea. The toxigenic
C. difficile
strains that cause disease secrete virulence factors, toxin A and toxin B, that cause colonic injury and inflammation.
C. difficile
toxins have no export signature and are secreted by an unusual mechanism that involves TcdE, a holin-like protein. We isolated a TcdE mutant of the epidemic R20291 strain with impaired toxin secretion, which was restored by complementation with functional TcdE. In the TcdE open reading frame (ORF), we identified three possible translation start sites; each translated isoform may play a specific role in TcdE-controlled toxin release. We created plasmid constructs that express only one of the three TcdE isoforms and complemented the TcdE mutant with these isoforms. Western blot analysis of the complemented strains demonstrated that TcdE is translated efficiently from the start codon at the 25th and 27th positions in the predicted ORF, producing proteins with 142 amino acids (TcdE
142
) and 140 amino acids (TcdE
140
), respectively. TcdE
166
was not detected when expressed from its own ribosomal binding site (RBS). The effects of all three TcdE isoforms on
C. difficile
cell viability and toxin release were determined. Among the three isoforms, overexpression of TcdE
166
and TcdE
142
had a profound effect on cell viability compared to the TcdE
140
isoform. Similarly, TcdE
166
and TcdE
142
facilitated toxin release more efficiently than did TcdE
140
. The importance of these variations among TcdE isoforms and their role in toxin release are discussed.

IMPORTANCE
C. difficile
is a nosocomial pathogen that has become the most prevalent cause of antibiotic-associated diarrhea in North America and in several countries in Europe. Most strains of
C. difficile
produce two high-molecular-weight toxins that are regarded as the primary virulence factors. The mechanism by which these large toxins are secreted from bacterial cells is not yet clear but involves TcdE, a holin-like protein. In this work, we show that TcdE could be translated from three different start codons, resulting in the production of three TcdE isoforms. Furthermore, we investigated the role of these isoforms in toxin release and cell lysis in
C. difficile
. An understanding of TcdE-dependent toxin secretion may be helpful for the development of strategies for preventing and treating
C. difficile
infections.
Functional Analysis of Porphyromonas gingivalis W83 CRISPR-Cas Systems
Authors: Burmistrz Michał , Dudek Bartosz , Staniec Dominika , Rodriguez Martinez Jose Ignacio , Bochtler Matthias , Potempa Jan , Pyrc Krzysztof
Published: May 2015

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) system provides prokaryotic cells with an adaptive and heritable immune response to foreign genetic elements, such as viruses, plasmids, and transposons. It is present in the majority of
Archaea
and almost half of species of
Bacteria
.
Porphyromonas gingivalis
is an important human pathogen that has been proven to be an etiological agent of periodontitis and has been linked to systemic conditions, such as rheumatoid arthritis and cardiovascular disease. At least 95% of clinical strains of
P. gingivalis
carry CRISPR arrays, suggesting that these arrays play an important function
in vivo
. Here we show that all four CRISPR arrays present in the
P. gingivalis
W83 genome are transcribed. For one of the arrays, we demonstrate
in vivo
activity against double-stranded DNA constructs containing protospacer sequences accompanied at the 3′ end by an NGG protospacer-adjacent motif (PAM). Most of the 44 spacers present in the genome of
P. gingivalis
W83 share no significant similarity with any known sequences, although 4 spacers are similar to sequences from bacteria found in the oral cavity and the gastrointestinal tract. Four spacers match genomic sequences of the host; however, none of these is flanked at its 3′ terminus by the appropriate PAM element.

IMPORTANCE
The CRISPR-Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) system is a unique system that provides prokaryotic cells with an adaptive and heritable immunity. In this report, we show that the CRISPR-Cas system of
P. gingivalis
, an important human pathogen associated with periodontitis and possibly also other conditions, such as rheumatoid arthritis and cardiovascular disease, is active and provides protection from foreign genetic elements. Importantly, the data presented here may be useful for better understanding the communication between cells in larger bacterial communities and, consequently, the process of disease development and progression.
Complete Bypass of Restriction Systems for Major Staphylococcus aureus Lineages
Authors: Monk Ian R. , Tree Jai J. , Howden Benjamin P. , Stinear Timothy P. , Foster Timothy J.
Published: May 2015

Staphylococcus aureus
is a prominent global nosocomial and community-acquired bacterial pathogen. A strong restriction barrier presents a major hurdle for the introduction of recombinant DNA into clinical isolates of
S. aureus
. Here, we describe the construction and characterization of the IMXXB series of
Escherichia coli
strains that mimic the type I adenine methylation profiles of
S. aureus
clonal complexes 1, 8, 30, and ST93. The IMXXB strains enable direct, high-efficiency transformation and streamlined genetic manipulation of major
S. aureus
lineages.

IMPORTANCE
The genetic manipulation of clinical
S. aureus
isolates has been hampered due to the presence of restriction modification barriers that detect and subsequently degrade inappropriately methylated DNA. Current methods allow the introduction of plasmid DNA into a limited subset of
S. aureus
strains at high efficiency after passage of plasmid DNA through the restriction-negative, modification-proficient strain RN4220. Here, we have constructed and validated a suite of
E. coli
strains that mimic the adenine methylation profiles of different clonal complexes and show high-efficiency plasmid DNA transfer. The ability to bypass RN4220 will reduce the cost and time involved for plasmid transfer into
S. aureus
. The IMXXB series of
E. coli
strains should expedite the process of mutant construction in diverse genetic backgrounds and allow the application of new techniques to the genetic manipulation of
S. aureus
.
Barrier-to-Autointegration Factor 1 (BAF/BANF1) Promotes Association of the SETD1A Histone Methyltransferase with Herpes Simplex Virus Immediate-Early Gene Promoters
Authors: Oh Hyung Suk , Traktman Paula , Knipe David M.
Published: May 2015

We have shown previously that A-type lamins and intranuclear localization of the herpes simplex virus (HSV) genome are critical for the formation of the VP16 activator complex on HSV immediate-early (IE) gene promoters in murine cells, which implies a critical role for lamin A and its associated proteins in HSV gene expression. Because barrier-to-autointegration factor 1 (BAF/BANF1) has been thought to bridge chromosomes to the nuclear lamina, we hypothesized that BAF might mediate viral genome targeting to the nuclear lamina. We found that overexpression of BAF enhances HSV-1 replication and knockdown of BAF decreases HSV gene expression, delays the kinetics of viral early replication compartment formation, and reduces viral yield compared to those in control small interfering RNA-transfected cells. However, BAF depletion did not affect genome complex targeting to the nuclear periphery. Instead, we found that the levels of a histone-modifying enzyme, SETD1A methyltransferase, and histone H3 lysine 4 trimethylation were reduced on IE and early (E) gene promoters in BAF-depleted cells during HSV lytic infection. Our results demonstrate a novel function of BAF as an epigenetic regulator of HSV lytic infection. We hypothesize that BAF facilitates IE and E gene expression by recruiting the SETD1A methyltransferase to viral IE and E gene promoters.

IMPORTANCE
The nuclear lamina is composed of lamin proteins and numerous lamina-associated proteins. Previously, the chromatin structure of DNA localized proximally to the lamina was thought to be characterized by heterochromatin marks associated with silenced genes. However, recent studies indicate that both heterochromatin- and euchromatin-rich areas coexist on the lamina. This paradigm suggests that lamins and lamina-associated proteins dynamically regulate epigenetic modifications of specific genes in different locations. Our goal is to understand how the lamina and its associated proteins regulate the epigenetics of genes through the study of HSV infection of human cells. We have shown previously that A-type lamins are critical for HSV genome targeting to the nuclear lamina and epigenetic regulation in viral replication. In this study, we found that another lamina-associated protein, BAF, regulates HSV gene expression through an epigenetic mechanism, which provides basic insights into the nuclear lamina and its associated proteins’ roles in epigenetic regulation.
Staphylococcus aureus Fibronectin-Binding Protein A Mediates Cell-Cell Adhesion through Low-Affinity Homophilic Bonds
Authors: Herman-Bausier Philippe , El-Kirat-Chatel Sofiane , Foster Timothy J. , Geoghegan Joan A. , Dufrêne Yves F.
Published: May 2015

Staphylococcus aureus
is an important opportunistic pathogen which is a leading cause of biofilm-associated infections on indwelling medical devices. The cell surface-located fibronectin-binding protein A (FnBPA) plays an important role in the accumulation phase of biofilm formation by methicillin-resistant
S. aureus
(MRSA), but the underlying molecular interactions are not yet established. Here, we use single-cell and single-molecule atomic force microscopy to unravel the mechanism by which FnBPA mediates intercellular adhesion. We show that FnBPA is responsible for specific cell-cell interactions that involve the FnBPA A domain and cause microscale cell aggregation. We demonstrate that the strength of FnBPA-mediated adhesion originates from multiple low-affinity homophilic interactions between FnBPA A domains on neighboring cells. Low-affinity binding by means of FnBPA may be important for biofilm dynamics. These results provide a molecular basis for the ability of FnBPA to promote cell accumulation during
S. aureus
biofilm formation. We speculate that homophilic interactions may represent a generic strategy among staphylococcal cell surface proteins for guiding intercellular adhesion. As biofilm formation by MRSA strains depends on proteins rather than polysaccharides, our approach offers exciting prospects for the design of drugs or vaccines to inhibit protein-dependent intercellular interactions in MRSA biofilms.

IMPORTANCE
Staphylococcus aureus
is a human pathogen that forms biofilms on indwelling medical devices, such as central venous catheters and prosthetic joints. This leads to biofilm infections that are difficult to treat with antibiotics because many cells within the biofilm matrix are dormant. The fibronectin-binding proteins (FnBPs) FnBPA and FnBPB promote biofilm formation by clinically relevant methicillin-resistant
S. aureus
(MRSA) strains, but the molecular mechanisms involved remain poorly understood. We used atomic force microscopy techniques to demonstrate that FnBPA mediates cell-cell adhesion via multiple, low-affinity homophilic bonds between FnBPA A domains on adjacent cells. Therefore, FnBP-mediated homophilic interactions represent an interesting target to prevent MRSA biofilms. We propose that such homophilic mechanisms may be widespread among staphylococcal cell surface proteins, providing a means to guide intercellular adhesion and biofilm accumulation.
The Enterococcus faecalis EbpA Pilus Protein: Attenuation of Expression, Biofilm Formation, and Adherence to Fibrinogen Start with the Rare Initiation Codon ATT
Authors: Montealegre Maria Camila , La Rosa Sabina Leanti , Roh Jung Hyeob , Harvey Barrett R. , Murray Barbara E.
Published: May 2015

The endocarditis and biofilm-associated pili (Ebp) are important in
Enterococcus faecalis
pathogenesis, and the pilus tip, EbpA, has been shown to play a major role in pilus biogenesis, biofilm formation, and experimental infections. Based on
in silico
analyses, we previously predicted that ATT is the EbpA translational start codon, not the ATG codon, 120 bp downstream of ATT, which is annotated as the translational start. ATT is rarely used to initiate protein synthesis, leading to our hypothesis that this codon participates in translational regulation of Ebp production. To investigate this possibility, site-directed mutagenesis was used to introduce consecutive stop codons in place of two lysines at positions 5 and 6 from the ATT, to replace the ATT codon
in situ
with ATG, and then to revert this ATG to ATT; translational fusions of
ebpA
to
lacZ
were also constructed to investigate the effect of these start codons on translation. Our results showed that the annotated ATG does not start translation of EbpA, implicating ATT as the start codon; moreover, the presence of ATT, compared to the engineered ATG, resulted in significantly decreased EbpA surface display, attenuated biofilm, and reduced adherence to fibrinogen. Corroborating these findings, the translational fusion with the native ATT as the initiation codon showed significantly decreased expression of β-galactosidase compared to the construct with ATG in place of ATT. Thus, these results demonstrate that the rare initiation codon of EbpA negatively regulates EbpA surface display and negatively affects Ebp-associated functions, including biofilm and adherence to fibrinogen.

IMPORTANCE
Enterococcus faecalis
is among the leading causes of serious infections in the hospital setting, and the endocarditis and biofilm-associated pili (Ebp) have been shown to play significant roles in
E. faecalis
pathogenesis. Understanding the regulation of virulence is important for the development of new approaches to counteract multidrug-resistant pathogens. We previously predicted that ATT, which has been reported to start protein synthesis only in rare instances, is the most likely translational start codon of EbpA in
E. faecalis
. Here, we demonstrate that ATT is the initiation codon of EbpA and, relative to a constructed ATG start codon, results in smaller amounts of EbpA on the surface of the cells, attenuating biofilm formation and fibrinogen adherence, phenotypes associated with the ability of
E. faecalis
to cause infections. This provides the first example of pilus regulation through the use of an ATT initiation codon.
Escape of Actively Secreting Shigella flexneri from ATG8/LC3-Positive Vacuoles Formed during Cell-To-Cell Spread Is Facilitated by IcsB and VirA
Authors: Campbell-Valois François-Xavier , Sachse Martin , Sansonetti Philippe J. , Parsot Claude
Published: May 2015

The enteropathogenic bacterium
Shigella flexneri
uses a type 3 secretion apparatus (T3SA) to transfer proteins dubbed translocators and effectors inside host cells, inducing bacterial uptake and subsequent lysis of the entry vacuole. Once in the cytoplasm, the outer membrane protein IcsA induces actin polymerization, enabling cytoplasmic movement and cell-to-cell spread of bacteria. During this infectious process,
S. flexneri
is targeted by ATG8/LC3. The effector IcsB was proposed to inhibit LC3 recruitment by masking a region of IcsA recognized by the autophagy pathway component ATG5. The effector VirA, a GTPase-activating protein (GAP) for Rab1, was also shown to prevent LC3 recruitment. However, the context of LC3 recruitment around
S. flexneri
is not fully understood. Here, we show that LC3 is recruited specifically around secreting bacteria that are still present in vacuoles formed during entry and cell-to-cell spread. While LC3 recruitment occurs around a small proportion of intracellular wild-type bacteria, the
icsB
,
virA
, and
icsB virA
mutants display incremental defaults in escape from LC3-positive vacuoles formed during cell-to-cell spread. Our results indicate that IcsB and VirA act synergistically to allow bacteria to escape from LC3-positive vacuoles by acting at or in the immediate vicinity of the vacuole membrane(s). We also demonstrate that LC3 is recruited around bacteria still present in the single-membrane entry vacuole, in a manner akin to that seen with LC3-associated phagocytosis. Our results indicate that LC3 recruitment occurs around bacteria still, or already, in membrane compartments formed during entry and cell-to-cell spread, and not around bacteria free in the cytoplasm.

IMPORTANCE
The targeting of
S. flexneri
by LC3 is a classic example of the targeting of foreign cytoplasmic particles by autophagy (so-called “xenoautophagy”). It is often assumed that LC3 is recruited around bacteria present in the cytoplasm through the formation of canonical double-membrane autophagosomes. Our results indicate that LC3 is recruited around the entry vacuole composed of a single membrane as in the case of LC3-associated phagocytosis. Effectors IcsB and VirA had been implicated in the blocking of LC3 recruitment, but it was not known if they acted on the same or distinct LC3-recruiting pathways. Our results indicate that LC3 is recruited exclusively around bacteria present in vacuoles formed during entry and cell-to-cell spread and that both IcsB and VirA intervene at the latter stage to facilitate bacterial escape. Our report reconciles several findings and may have broad implications for our understanding of the specific targeting of bacterial pathogens by LC3.
Comparative study of DFT/B3LYP, B3PW91, and HSEH1PBE methods applied to molecular structures and spectroscopic and electronic properties of flufenpyr and amipizone
Authors: Avcı D. , Bahçeli S. , Tamer Ö. , Atalay Y.
Published: May 2015

The optimized molecular structures, conformational analyses, vibrational (IR) frequencies and their assignments, maximum electronic absorption wavelengths (gas phase and in ethanol solvent),1H and13C NMR chemical shift values (gas phase and in CDCl3solvent), HOMO−LUMO analysis, molecular electrostatic potential surfaces, and nonlinear optical properties of flufenpyr (C14H9ClF4N2O4) and amipizone (C14H16ClN3O) compounds that have many biological activities have been calculated using the DFT/B3LYP, B3PW91, and HSEH1PBE methods with the 6-311G(d,p) basis set in the ground state. A comparison among the results calculated at the mentioned levels indicates that the HSEH1PBE calculations give usually greater values compared with the others in terms of vibrational frequencies, the maximum electronic absorption wavelengths, and HOMO−LUMO energy gaps of the title compounds.
Chaotic attractors based on unstable dissipative systems via third-order differential equation
Authors: Campos-Cantón E.
Published: May 2015

In this paper, we present an approach how to yield 1D, 2D and 3D-grid multi-scroll chaotic systems in [Formula: see text] based on unstable dissipative systems via third-order differential equation. This class of systems is constructed by a switching control law(SCL) changing the equilibrium point of an unstable dissipative system. The switching control law that governs the position of the equilibrium point varies according to the number of scrolls displayed in the attractor.
Adaptive impulsive cluster synchronization in community network with nonidentical nodes
Authors: Gong Xiaoli , Gan Luyining , Wu Zhaoyan
Published: May 2015

In this paper, cluster synchronization in community network with nonidentical nodes is investigated. Through introducing proper adaptive strategy into impulsive control scheme, adaptive impulsive controllers are designed for achieving the cluster synchronization. In this adaptive impulsive control scheme, for any given networks, the impulsive gains can adjust themselves to proper values according to the proposed adaptive strategy when the impulsive intervals are fixed. The impulsive instants can be estimated by solving a sequence of maximum value problems when the impulsive gains are fixed. Both community networks without and with coupling delay are considered. Based on the Lyapunov function method and mathematical analysis technique, two synchronization criteria are derived. Several numerical examples are performed to verify the effectiveness of the derived theoretical results.
Ultrafast and Distinct Spin Dynamics in Magnetic Alloys
Authors: Radu I. , Stamm C. , Eschenlohr A. , Radu F. , Abrudan R. , Vahaplar K. , Kachel T. , Pontius N. , Mitzner R. , Holldack K. , Föhlisch A. , Ostler T. A. , Mentink J. H. , Evans R. F. L. , Chantrell R. W. , Tsukamoto A. , Itoh A. , Kirilyuk A. , Kimel A. V. , Rasing Th.
Published: May 2015

Controlling magnetic order on ultrashort timescales is crucial for engineering the next-generation magnetic devices that combine ultrafast data processing with ultrahigh-density data storage. An appealing scenario in this context is the use of femtosecond (fs) laser pulses as an ultrafast, external stimulus to fully set the orientation and the magnetization magnitude of a spin ensemble. Achieving such control on ultrashort timescales, e.g., comparable to the excitation event itself, remains however a challenge due to the lack of understanding the dynamical behavior of the key parameters governing magnetism: The elemental magnetic moments and the exchange interaction. Here, we investigate the fs laser-induced spin dynamics in a variety of multi-component alloys and reveal a dissimilar dynamics of the constituent magnetic moments on ultrashort timescales. Moreover, we show that such distinct dynamics is a general phenomenon that can be exploited to engineer new magnetic media with tailor-made, optimized dynamic properties. Using phenomenological considerations, atomistic modeling and time-resolved X-ray magnetic circular dichroism (XMCD), we demonstrate demagnetization of the constituent sub-lattices on significantly different timescales that depend on their magnetic moments and the sign of the exchange interaction. These results can be used as a “recipe” for manipulation and control of magnetization dynamics in a large class of magnetic materials.
Lower Carboniferous ramp sedimentation of the Central Alborz Basin, northern Iran: integrated sedimentological and rock–magnetic studies
Authors: Sardar Abadi Mehrdad , Da Silva Anne-Christine , Mossadegh Hossein , Spassov Simo , Boulvain Frédéric
Published: May 2015

The Lower Carboniferous Mobarak Formation in the Alborz Basin (northern Iran) was deposited along the northeastern margin of Gondwana in a carbonate ramp setting. This paper focuses on the Tournaisian stratigraphic interval of this formation that crops out at the Jaban section in the southwestern Central Alborz Basin. The following facies associations, representing different ramp palaeoenvironments, have been identified: (1) mudstone–wackestone outer-ramp facies; (2) crinoidal to skeletal grainstone–packstone mid-ramp facies; (3) peloidal to crinoidal grainstone–packstone inner-ramp facies; and (4) coastal facies, which include a variety of microbial laminated to oncoidal grainstones and mudstones with evaporitic pseudomorphs. This ramp profile was affected by frequent storms that were responsible for the formation of several skeletal to non-skeletal shoals in the distal mid-ramp to the most proximal inner-ramp areas. The development of the skeletal to non-skeletal shoals along the sea side of the ramp formed a semi-enclosed lagoon sensitive to the influence of both high tides and storm surges. The magnetic susceptibility (χ
in
) of all the samples was measured and compared with that of the facies from which the sample was taken. There is a clear link between χ
in
and the facies; the average χ
in
values were higher for the distal facies than for the proximal facies. The χ
in
profile of this Lower Carboniferous carbonate sequence reflects stratigraphic variations in response to relative changes in sea level and the input of detrital materials. In the context of the sequence stratigraphic framework, the average χ
in
values for lowstand and transgressive systems tract deposits are higher than for the highstand systems tract deposits. The clear link between χ
in
and facies indicates at least a partly preserved primary χ
in
signal related to the detrital inputs. However, to obtain a better understanding of the nature and origin of the minerals carrying the χ
in
, we performed hysteresis measurements on selected samples. It appears that the χ
in
signal is mainly carried by low-coercivity ferromagnetic minerals such as magnetite, with a mixture of relatively coarse grains (detrital fraction) and ultra-fine grains (probably formed during diagenesis).
A Survey of Interactive Remote Rendering Systems
Authors: Shi Shu , Hsu Cheng-Hsin
Published: May 2015

Remote rendering means rendering 3D graphics on a computing device and displaying the results on another computing device connected through a network. The concept was originally developed for sharing computing resources remotely. It has been receiving increasing attention from researchers in both academia and industry in recent years due to the proliferation of cloud computing and mobile devices. In this article, we survey the interactive remote rendering systems proposed in the literature, analyze how to improve the state of the art, and summarize the related technologies. The readers of this article will understand the history of remote rendering systems and obtain some inspirations of the future research directions in this area.