bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonality of carotenoid‐based plumage coloration: modelling wavelength‐specific change through spectral reconstruction
Authors: Evans Simon R. , Summers Alex G. R. , Sheldon Ben C.
Published: May 2012

Plumage coloration has provided important model systems for research on signal expression. Whilst it had previously been assumed that moulting provided the only mechanism to change plumage coloration, recent studies have shown plumage colours to be seasonally dynamic, with implications both for the quantification of expression and for any signalling role. However, the mechanistic processes underlying such change remain uncertain. Here, we describe within‐moult shifts in expression of a carotenoid‐based colour trait – the yellow ventral plumage of the great tit Parus major – over a nine‐month timespan. We report that plumage chromaticity (‘colour’) – but not achromaticity (‘brightness’) – exhibits a marked seasonal decline, independent of sex, age or body condition, and at a constant rate across twelve environmentally heterogeneous plots within our study site. To gain a greater understanding of the mechanisms underlying this change we employed a spectral reconstruction approach, that generates predicted spectra for any timepoint within the sampling period. By comparing spectra for both early and late in the moult we show that the seasonal decline in chromaticity is driven by both a marked reduction in ultraviolet (UV) reflectance and, to a lesser extent, loss of active carotenoid pigments. Thus, our study shows that seasonal loss of chromaticity in the great tit is driven by altered reflectance primarily in the UV section of the spectrum, a finding made possible by the use of spectral compartmentalisation and multi‐parallel modelling to produce reconstructed spectra. Whether change in plumage coloration influences signal function will depend on the dynamics of the signalling system but it could clearly inflate patterns such as assortative mating and should be considered in studies of colour expression.
Feather mites (Acari: Astigmata) and body condition of their avian hosts: a large correlative study
Authors: Galván Ismael , Aguilera Eduardo , Atiénzar Francisco , Barba Emilio , Blanco Guillermo , Cantó José L. , Cortés Verónica , Frías Óscar , Kovács István , Meléndez Leandro , Møller Anders P. , Monrós Juan S. , Pap Péter L. , Piculo Rubén , Senar Juan C. , Serrano David , Tella José L. , Vágási Csongor I. , Vögeli Matthias , Jovani Roger
Published: May 2012

Feather mites are arthropods that live on or in the feathers of birds, and are among the commonest avian ectosymbionts. However, the nature of the ecological interaction between feather mites and birds remains unclear, some studies reporting negative effects of feather mites on their hosts and others reporting positive or no effects. Here we use a large dataset comprising 20 189 measurements taken from 83 species of birds collected during 22 yr in 151 localities from seven countries in Europe and North Africa to explore the correlation between feather mite abundance and body condition of their hosts. We predicted that, if wing‐dwelling feather mites are parasites, a negative correlation with host body condition should be found, while a mutualistic interaction should yield positive correlation. Although negative relationships between feather mite abundance and host body condition were found in a few species of birds, the sign of the correlation was positive in most bird species (69%). The overall effect size was only slightly positive (r =0.066). The effect of feather mite abundance explained <10% of variance in body condition in most species (87%). Results suggest that feather mites are not parasites of birds, but rather that they hold a commensalistic relationship where feather mites may benefit from feeding on uropygial gland secretions of their hosts and birds do not seem to obtain a great benefit from the presence of feather mites.
Distribution of dust around galaxies: an analytic model
Authors: Masaki Shogo , Yoshida Naoki
Published: May 2012

We develop an analytic halo model for the distribution of dust around galaxies. The model results are compared with the observed surface dust density profile measured through reddening of background quasars in the Sloan Digital Sky Survey (SDSS) reported by Ménard et al. We assume that the dust distribution around a galaxy is described by a simple power law, similar to the mass distribution, but with a sharp cut-off at αRvir, where Rvir is the galaxy's virial radius and α is a model parameter. Our model reproduces the observed dust distribution profile very well over a wide range of radial distance of 10–104h−1 kpc. For the characteristic galaxy halo mass of 2 × 1012h−1 M⊙ estimated for the SDSS galaxies, the best-fitting model is obtained if α is greater than unity, which suggests that dust is distributed to over a few hundred kiloparsecs from the galaxies. The observed large-scale dust distribution profile is reproduced if we assume the total amount of dust is equal to that estimated from the integrated stellar evolution over the cosmic time.
Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting
Authors: Laurie Karen L. , Huston Patricia , Riley Steven , Katz Jacqueline M. , Willison Donald J. , Tam John S. , Mounts Anthony W. , Hoschler Katja , Miller Elizabeth , Vandemaele Kaat , Broberg Eeva , Van Kerkhove Maria D. , Nicoll Angus
Published: May 2012

Please cite this paper as: Laurie et al. (2013) Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting. Influenza and Other Respiratory Viruses 7(2) 211–224.

Background  Serological studies can detect infection with a novel influenza virus in the absence of symptoms or positive virology, providing useful information on infection that goes beyond the estimates from epidemiological, clinical and virological data. During the 2009 A(H1N1) pandemic, an impressive number of detailed serological studies were performed, yet the majority of serological data were available only after the first wave of infection. This limited the ability to estimate the transmissibility and severity of this novel infection, and the variability in methodology and reporting limited the ability to compare and combine the serological data.

Objectives  To identify best practices for conduct and standardisation of serological studies on outbreak and pandemic influenza to inform public policy.

Methods/Setting  An international meeting was held in February 2011 in Ottawa, Canada, to foster the consensus for greater standardisation of influenza serological studies.

Results  Best practices for serological investigations of influenza epidemiology include the following: classification of studies as pre‐pandemic, outbreak, pandemic or inter‐pandemic with a clearly identified objective; use of international serum standards for laboratory assays; cohort and cross‐sectional study designs with common standards for data collection; use of serum banks to improve sampling capacity; and potential for linkage of serological, clinical and epidemiological data. Advance planning for outbreak studies would enable a rapid and coordinated response; inclusion of serological studies in pandemic plans should be considered.

Conclusions  Optimising the quality, comparability and combinability of influenza serological studies will provide important data upon emergence of a novel or variant influenza virus to inform public health action.
CHARACTERIZATION OF A TREE BY MEANS OF COEFFICIENTS OF THE CHROMATIC POLYNOMIAL*
Authors: Eisenberg Bernard
Published: May 2012

Abstract

Let

be the chromatic polynomials of a graph G on n nodes in standard and factorial forms where Λ(r) = Λ(Λ − 1)(Λ − 2) … (Λ ‐ r + 1). It is shown that G is a tree if, and only if (iff), a1 0 and

ar = for some one r in the range 1 ≤ r < n. In particular, G is a tree iff a1 = 1. Likewise, a connected graph G is a tree iff br = S(n − 1, r − 1) for some r in the range 3 ≤ r < n where S(n − 1, r − 1) is a Stirling number of the second kind.
A PHYSIOLOGICAL STUDY OF BYSSINOSIS IN COLONIAL AMERICA*
Authors: Bouhuys Arend , Mitchell Charles A. , Schilling R. S. F. , Zuskin Eugenija
Published: May 2012

Abstract

We assessed the acute effects of inhalation of flax dust, produced during processing of flax fibers under conditions similar to those in colonial America. Exposure to this dust, for about 5 hours, caused minor symptoms of chest tightness in five healthy persons, accompanied by decreases of maximum expiratory flow rates, indicating acute small airway obstruction. Measurements of flow rates on partial expiratory flow‐volume (PEFV) curves were more sensitive than flow rates on MEFV curves and FEV1.0 in assessing constrictor effects of flax dust, even though flow rates on flow‐volume curves are more variable under control conditions than the FEV1.0. Thus, acute symptoms of byssinosis may have been prevalent among early settlers in America who processed flax in their barns. Since these barns were used for many other purposes as well, children and other farm workers were probably also at risk.

Ramazzini's observations on the flax and hemp workers of Northern Italy were, for obvious reasons, not accompanied by objective evidence concerning the effects of flax and hemp dust on the lungs. Since 17th‐century working conditions are being recreated in historical restoration projects, and modern function tests are available, such objective evidence can now be obtained. With the revival of primitive crafts in our times, this is of some practical importance.

The primitive methods used for fiber processing in Ramazzini's time are demonstrated every day at Philipsburg Manor, North Tarrytown, New York. Philipsburg Manor is a restoration project, dedicated to a historical interpretation of life among early Dutch settlers in the Hudson Valley. A recent field study on this site provided an opportunity to assess the acute effects of flax dust on the lungs of people who process flax fibers with primitive methods and on the lungs of others who are exposed to flax dust in the same environment.
SELECTIVE INDUCTION OF ANERGY TO COCCIDIOIDIN OR TUBERCULIN WITH ANTILYMPHOCYTE SERUM†
Authors: Ibrahim Ali Bin
Published: May 2012

Abstract

Specific anergy to coccidioidin or tuberculin was affected in coccidioidin‐ and tuberculin‐sensitive guinea pigs by repeated skin‐testing the animals with either antigen followed by antilymphocyte serum administration at six‐hour intervals. This anergic state to either antigen was lost in about ten days. Further skin‐testing of these animals with either antigen followed by ALS injection resulted in a temporary unresponsiveness to the respective antigen lasting for about ten days.
CHEMOSTERILANT ACTIVITY OF ANTINEOPLASTIC AGENTS
Authors: Chang S. C. , Bořkovec A. B. , Braun B. H.
Published: May 2012

Abstract

Thirty‐five antineoplastic agents were administered to adult house flies, Musca domestica L., by feeding or injection, and effects of the treatment on the flies' reproductive capacity were determined. For both sexes of the insect the most effective sterilants were alkylating agents; none of the hormonal drugs were active, but one antimetabolite sterilized females only. The category of miscellaneous antineoplastic agents contained several chemosterilants including l‐asparaginase, the only known enzyme with insect‐sterilizing effects.
BUCKLING AND INITIAL POSTBUCKLING OF OVAL CYLINDRICAL SHELLS UNDER COMBINED AXIAL COMPRESSION AND BENDING*
Authors: Kempner Joseph , Chen Youl‐Nan
Published: May 2012

Abstract

Buckling and initial postbuckling of an oval cylindrical shell under pure bending and under combined uniform axial compression and bending is investigated. The first‐ and second‐order stability equations are developed from the Donnell‐type equations that are shown to be appropriate. The solution of these two sets of equations determines, respectively, the buckling characteristics and a “sensitivity parameter.” The buckling loads are found to be in good agreement with the engineering approximation based on the assumption that buckling occurs when the local axial stress equals that corresponding to the classical buckling stress of a locally equivalent circular cylindrical shell under uniform axial compression. Results also show that an oval cylinder can be stronger or weaker than the equivalent circular cylinder, depending on the orientation of the couples. However, in any case the oval shell is always found to be sensitive to imperfections; the greater the load‐carrying capacity, the greater the sensitivity.

Furthermore, in contrast to the behavior of the circular and weak oval cylinders, buckling of the strong oval cylinder need not initiate at the position of maximum compressive stress.
MEANING AND FORM*
Authors: Bolinger Dwight
Published: May 2012

Abstract

Recent work in linguistics has assumed that “surface” differences in syntax do not necessarily reflect differences in “deep” structure, i.e., there are differences in form without differences in meaning. But in many, perhaps in all, instances where the assumption has been adopted in practice, an unsuspected difference in meaning can be found. It is a safer working hypothesis that linguistic economy requires all differences in form to be correlated with differences in meaning.
ON THE INDEPENDENCE NUMBERS OF COMPLEMENTARY GRAPHS
Authors: Chartrand Gary , Schuster Seymour
Published: May 2012

Abstract

A set of vertices (edges) is called independent if no two vertices (edges) in the set are adjacent. The independence number β(G) (edge independence number β1(G)) is the maximum number of elements in an independent set of vertices (edges) of G. It is shown for any graph G of order p ≥ 3, having complement Ḡ, that [p/2] ≤ β1(G) + β1(Ḡ) ≤ 2[p/2]. From this, upper and lower bounds for β1(G) · β1(Ḡ) are determined. All four bounds are shown to be best possible. It is verified that for every graph G of order p, the bounds β(G) + β(Ḡ) ≤ p + 1 and β(G) · β(Ḡ) ≤ [(p + 1)/2] · {(p + 1)/2} hold and are best possible. Lower bounds for β(G) + β(Ḡ) and β(G) · β(Ḡ) are considered and are shown to be related to Ramsey numbers.
BACTERIOPHAGE INTERACTIONS WITH HIGHER ORGANISMS
Authors: Merril Carl R.
Published: May 2012

Abstract

Bacteriophages were discovered 59 years ago. Despite the widespread distribution of these viruses, the extent of their interaction with higher organisms, including man, is still largely unknown. Recently, it has been shown that some phages carry genes that code for toxins, as in the case of phage β, which codes for diphtheria toxin. There have also been reports of phage genome transcription and translation in in vitro eukaryotic systems. The word bacteriophage conveys the historical nature of the discovery of this class of viruses, it does not define the limits of the viruses effects or host range. The recent discoveries of bacteriophage in commercial fetal calf serum and human vaccines should stimulate efforts to learn of phage interactions with eukaryotic systems.
UNSOLVED PROBLEMS IN POLYMER PROCESSING*
Authors: Chung Chan I.
Published: May 2012

Abstract

Polymer processing consists of basically three functional steps: plasticization of a solid polymer, forming of the plasticized polymer into a desired shape, and solidification of the formed polymer. Polymer processing requires a good knowledge in the melt rheology, morphology, mechanochemistry, melting and crystallization behavior of the polymer as well as engineering knowledge in heating, cooling and deformation processes. Thus, it presents an unusual challenge to polymer engineers and scientists. The gap between theory and practice is extremely large in polymer processing. In spite of extensive fundamental knowledge, many problems in the procedure still remains “practically” unsolved. In this paper, three important examples of the unsolved problems in polymer processing—namely, screw extrusion process, weld‐line (self‐diffusion) behavior of polymer melt, and temperature build‐up in capillary flow—are discussed in detail.
ETHANOL PREFERENCE IN THE RAT FOLLOWING INHIBITION OF LIVER ALCOHOL DEHYDROGENASE AND S‐ADENOSYL METHIONINE*
Authors: Geller Irving
Published: May 2012

Abstract

A preference for alcohol was established in laboratory rats offered a choice of water or an alcohol solution and kept in constant darkness. They were administered pyrazole, an inhibitor of liver alcohol dehydrogenase (LADH) or homocysteine or homoserine, inhibitors of S‐adenosyl methionine (SAM). These agents reduced alcohol intake in varying degrees. Similarly, a reduction of alcohol drinking occurred following simultaneous administration of ineffective doses of pyrazole with homocysteine or homoserine.
SOME CULTURAL, IMMUNOLOGICAL, AND BIOCHEMICAL PROPERTIES OF PROGENITOR CRYPTOCIDES*
Authors: Livingston Virginia Wuerthele‐Caspe , Livingston Afton Munk
Published: May 2012

Abstract

Guinea pigs became skin‐positive to test doses of PPD (purified protein derivative‐Seibert) and to other related PPD preparations in various degrees following immunization with phenolized cultures of Progenitor cryptocides, an intermittently acid‐fast pleomorphic filterable Actinomycete isolated from human cancer patients. This reactivity, indicative of the relationship to M. tuberculosis as well as to several other related microbes, may account for the effective treatment of some types of human cancer with BCG (Bacillus Calmette Guérin). Another property of P. cryptocides is the production in vitro of a parahormone immunologically and biologically related to human chorionic gonadotropin. Since the cancer patient often exhibits various types of hormonal imbalance, the microbic exogenous production of this hormone may explain the neoplastic parahormone syndrome in man. There are some biological differences in experimental animals between the microbic and human chorionic gonadotropin, but the in vitro and radioimmunological tests are identical. The microbic hormone appears to play an important role in human cancer, since it not only is present in tumors, body tissues, and fluids but may be excreted in large amounts in the urine. The amount excreted is variable, depending upon the rate of microbic production of the hormone in vivo and the resistance of the host as expressed through immunological and metabolic degradation systems.
REGULATION BY SALT OF ACTIVITY OF CITRATE SYNTHASES FROM OSMOREGULATORS AND OSMOCONFORMERS*
Authors: Sarkissian Igor V.
Published: May 2012

Abstract

Citrate synthases from an osmoregulator and 2 osmoconforming animals were purified and studied with respect to interaction with salt levels. Catalytic activity of the shrimp (osmoregulator) citrate synthase was markedly affected by buffer concentrations, and its apparent Km with respect to acetyl coenzyme A was increased almost 60‐fold by increased concentration of salt. The osmoconformer citrate synthases showed slight effects of concentration of salt: the apparent Km of the sea anemone citrate synthase was increased fractionally by salt and about 6‐fold for citrate synthase of the oyster.

Citrate synthase from the osmoregulator shrimp had the conventional hyperbolic kinetics of saturation by acetyl coenzyme A in the presence of moderate concentrations of any salt, but the sea anemone and oyster citrate synthases had sigmoid kinetics in the same saline environment. The oyster was shown to regulate the levels of magnesium, potassium, and chloride in its tissues.

The ecoadaptive significance of these findings is discussed and the generally standing concern of investigators is supported that biologically and physiologically realistic interpretations of enzyme regulation by ionic strength and any other factors can be derived only from studies of enzyme activities in situ.
A GEOMETRIC CONSTRUCTION OF THE DIRICHLET KERNEL*
Authors: Levi Howard
Published: May 2012

If sin (x/2) ≠ 0 then 1/2 + cos x + cos 2x + … + cos nx = sin (n + ½)x/2 sin (x/2). This relation is fundamental in the theory of Fourier series. We define a geometric construction in the euclidean plane whose analysis leads to this and related trigonometric identities.
COMPOSITE MATERIAL MECHANICS: THERMOELASTIC MICROMECHANICS*
Authors: Bert Charles W. , Francis Philip H.
Published: May 2012

This paper is a survey of the principal analytical and experimental developments in the field of composite material mechanics. Emphasis is placed on filamentary‐type composite materials. Topics covered are (1) elastic micromechanics, including a great variety of analytical approaches to the problem, and (2) thermal and other transport phenomena, including a number of useful analogies for such phenomena. The survey concludes with a brief discussion of future trends in the field.
Plasticity of spatial hearing: behavioural effects of cortical inactivation
Authors: Nodal Fernando R. , Bajo Victoria M. , King Andrew J.
Published: May 2012

Key points

The cerebral cortex plays a critical role in perception and in learning‐induced plasticity.

We show that reversibly silencing any of the main regions of auditory cortex impairs the ability of adult ferrets to localize sound, with the largest deficit seen after deactivating the primary fields.

Although these animals had no trouble localizing longer sound bursts, their performance dropped considerably when auditory spatial cues were altered by occluding one ear with an earplug.

In contrast to control ferrets, which recovered their localization abilities with intensive training, adaptation to an earplug was impaired following cortical inactivation, with the greatest disruption in plasticity observed after silencing higher‐level cortical areas.

These findings imply regional differences in the processing of spatial information across the auditory cortex.

Abstract  The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol‐Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach‐to‐target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach‐to‐target responses to brief sounds (40 ms noise bursts) was reduced by muscimol‐Elvax but not by drug‐free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience‐induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach‐to‐target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher‐level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex.
Human phase response curve to a 1 h pulse of bright white light
Authors: St Hilaire Melissa A. , Gooley Joshua J. , Khalsa Sat Bir S. , Kronauer Richard E. , Czeisler Charles A. , Lockley Steven W.
Published: May 2012

Key points

The human circadian pacemaker generates near‐24‐h rhythms that set the timing of many physiological, metabolic and behavioural body rhythms, and is synchronized to environmental time primarily by the 24 h light–dark cycle.

The magnitude and direction of the resetting response of the pacemaker to light depends on the time of day of exposure, and the change in responses over the day is summarized in a phase response curve (PRC).

A previous PRC showed that a 6.7 h bright white light exposure maximally shifted the circadian pacemaker by over 3 h.

We show that a PRC to a 1 h bright white light pulse maximally shifted the circadian pacemaker by ∼2 h, despite representing only ∼15% of the exposure duration.

This study demonstrates that the circadian pacemaker is sensitive to short‐duration light pulses with a non‐linear relationship between light duration and the amount of resetting.

Abstract  The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a <15 lux dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n= 18) or <3 lux dim background light (n= 18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (<3 lux) before and after the light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre‐ and post‐stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak‐to‐trough amplitude of 2.20 h. No discernible PRC was observed in the <3 lux dim background light PRC. The fitted peak‐to‐trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non‐linear duration–response function for the effects of light on circadian resetting.
TACE Activation by MAPK-Mediated Regulation of Cell Surface Dimerization and TIMP3 Association
Authors: Xu Pinglong , Liu Jianming , Sakaki-Yumoto Masayo , Derynck Rik
Published: May 2012

A metalloproteinase implicated in inflammation and cancer is inactive as dimers and active as monomers.
Genomic Survey of Premetazoans Shows Deep Conservation of Cytoplasmic Tyrosine Kinases and Multiple Radiations of Receptor Tyrosine Kinases
Authors: Suga Hiroshi , Dacre Michael , de Mendoza Alex , Shalchian-Tabrizi Kamran , Manning Gerard , Ruiz-Trillo Iñaki
Published: May 2012

A genomic survey suggests that cytoplasmic tyrosine kinases diversified before the establishment of multicellular organisms.
Phosphoinositides as Regulators of Protein-Chromatin Interactions
Authors: Viiri Keijo , Mäki Markku , Lohi Olli
Published: May 2012

Phosphoinositides can promote or reduce the binding of proteins with roles in transcription to chromatin.
Generating Inflammasomes
Authors: Mueller Kristen
Published: May 2012

A human protein activates the assembly of a cellular complex that detects signs of infection.
Systematic Analysis of Metallo-β-Lactamases Using an Automated Database
Authors: Widmann Michael , Pleiss Jürgen , Oelschlaeger Peter
Published: May 2012

Metallo-β-lactamases (MBLs) are enzymes that hydrolyze β-lactam antibiotics, resulting in bacterial resistance to these drugs. These proteins have caused concerns due to their facile transference, broad substrate spectra, and the absence of clinically useful inhibitors. To facilitate the classification, nomenclature, and analysis of MBLs, an automated database system was developed, the Metallo-β-Lactamase Engineering Database (MBLED) (
http://www.mbled.uni-stuttgart.de
). It contains information on MBLs retrieved from the NCBI peptide database while strictly following the nomenclature by Jacoby and Bush (
http://www.lahey.org/Studies/
) and the generally accepted class B β-lactamase (BBL) standard numbering scheme for MBLs. The database comprises 597 MBL protein sequences and enables systematic analyses of these sequences. A systematic analysis employing the database resulted in the generation of mutation profiles of assigned IMP- and VIM-type MBLs, the identification of five MBL protein entries from the NCBI peptide database that were inconsistent with the Jacoby and Bush nomenclature, and the identification of 15 new IMP candidates and 9 new VIM candidates. Furthermore, the database was used to identify residues with high mutation frequencies and variability (mutation hot spots) that were unexpectedly distant from the active site located in the ββ sandwich: positions 208 and 266 in the IMP family and positions 215 and 258 in the VIM family. We expect that the MBLED will be a valuable tool for systematically cataloguing and analyzing the increasing number of MBLs being reported.
HDQ, a Potent Inhibitor of Plasmodium falciparum Proliferation, Binds to the Quinone Reduction Site of the Cytochrome
bc
1
Complex
Authors: Vallières Cindy , Fisher Nicholas , Antoine Thomas , Al-Helal Mohammed , Stocks Paul , Berry Neil G. , Lawrenson Alexandre S. , Ward Stephen A. , O'Neill Paul M. , Biagini Giancarlo A. , Meunier Brigitte
Published: May 2012

The mitochondrial
bc
1
complex is a multisubunit enzyme that catalyzes the transfer of electrons from ubiquinol to cytochrome
c
coupled to the vectorial translocation of protons across the inner mitochondrial membrane. The complex contains two distinct quinone-binding sites, the quinol oxidation site of the
bc
1
complex (Q
o
) and the quinone reduction site (Q
i
), located on opposite sides of the membrane within cytochrome
b
. Inhibitors of the Q
o
site such as atovaquone, active against the
bc
1
complex of
Plasmodium falciparum
, have been developed and formulated as antimalarial drugs. Unfortunately, single point mutations in the Q
o
site can rapidly render atovaquone ineffective. The development of drugs that could circumvent cross-resistance with atovaquone is needed. Here, we report on the mode of action of a potent inhibitor of
P. falciparum
proliferation, 1-hydroxy-2-dodecyl-4(1
H
)quinolone (HDQ). We show that the parasite
bc
1
complex—from both control and atovaquone-resistant strains—is inhibited by submicromolar concentrations of HDQ, indicating that the two drugs have different targets within the complex. The binding site of HDQ was then determined by using a yeast model. Introduction of point mutations into the Q
i
site, namely, G33A, H204Y, M221Q, and K228M, markedly decreased HDQ inhibition. In contrast, known inhibitor resistance mutations at the Q
o
site did not cause HDQ resistance. This study, using HDQ as a proof-of-principle inhibitor, indicates that the Q
i
site of the
bc
1
complex is a viable target for antimalarial drug development.
Decline and Rise of the Antimicrobial Susceptibility of Streptococcus pneumoniae Isolated from Middle Ear Fluid in Children: Influence of Changes in Circulating Serotypes
Authors: Pérez-Trallero Emilio , Marimón José M. , Alonso Marta , Ercibengoa María , García-Arenzana José M.
Published: May 2012

Changes in the antimicrobial susceptibility of
Streptococcus pneumoniae
causing otitis media were studied in 916 isolates from children <5 years old between 1999 and 2010 in a region of northern Spain. The rate of antimicrobial resistance decreased between the period before the introduction of the heptavalent pneumococcal conjugate vaccine (from 1999 to 2001) and the period from 2005 to 2007. However, in 2008 to 2010, resistance rates increased again due to the spread of serotype 19A, especially the multidrug-resistant ST320 and ST276 clones.
Heme Protein and Hydroxyarginase Necessary for Biosynthesis of
d
-Cycloserine
Authors: Kumagai Takanori , Takagi Kisho , Koyama Yusuke , Matoba Yasuyuki , Oda Kosuke , Noda Masafumi , Sugiyama Masanori
Published: May 2012

We have recently cloned a
d
-cycloserine (DCS) biosynthetic gene cluster that consists of 10 genes, designated
dcsA
∼
dcsJ
, from
Streptomyces lavendulae
ATCC 11924 (16). In the predicted pathway of hydroxyurea (HU) formation in DCS biosynthesis,
l
-arginine (L-Arg) must first be hydroxylated, prior to the hydrolysis of
N
ω
-hydroxy-
l
-arginine (NHA) by DcsB, an arginase homolog. The hydroxylation of L-Arg is known to be catalyzed by nitric oxide synthase (NOS). In this study, to verify the supply route of HU, we created a
dcsB
-disrupted mutant, Δ
dcsB
. While the mutant lost DCS productivity, its productivity was restored by complementation of
dcsB
, and also by the addition of HU but not NHA, suggesting that HU is supplied by DcsB. A NOS-encoding gene,
nos
, from
S. lavendulae
chromosome was cloned, to create a
nos
-disrupted mutant. However, the mutant maintained the DCS productivity, suggesting that NOS is not necessary for DCS biosynthesis. To clarify the identity of an enzyme necessary for NHA formation, a
dcsA
-disrupted mutant, designated Δ
dcsA
, was also created. The mutant lost DCS productivity, whereas the DCS productivity was restored by complementation of
dcsA
. The addition of NHA to the culture medium of Δ
dcsA
mutant was also effective to restore DCS production. These results indicate that the
dcsA
gene product, DcsA, is an enzyme essential to generate NHA as a precursor in the DCS biosynthetic pathway. Spectroscopic analyses of the recombinant DcsA revealed that it is a heme protein, supporting an idea that DcsA is an enzyme catalyzing hydroxylation.
Function of Cytochrome P450 Enzymes MycCI and MycG in Micromonospora griseorubida, a Producer of the Macrolide Antibiotic Mycinamicin
Authors: Anzai Yojiro , Tsukada Shu-ichi , Sakai Ayami , Masuda Ryohei , Harada Chie , Domeki Ayaka , Li Shengying , Kinoshita Kenji , Sherman David H. , Kato Fumio
Published: May 2012

The cytochrome P450 enzymes MycCI and MycG are encoded within the mycinamicin biosynthetic gene cluster and are involved in the biosynthesis of mycinamicin II (a 16-membered macrolide antibiotic produced by
Micromonospora griseorubida
). Based on recent enzymatic studies, MycCI is characterized as the C-21 methyl hydroxylase of mycinamicin VIII, while MycG is designated multifunctional P450, which catalyzes hydroxylation and also epoxidation at C-14 and C-12/13 on the macrolactone ring of mycinamicin. Here, we confirm the functions of MycCI and MycG in
M. griseorubida
. Protomycinolide IV and mycinamicin VIII accumulated in the culture broth of the
mycCI
disruption mutant; moreover, the
mycCI
gene fragment complemented the production of mycinamicin I and mycinamicin II, which are produced as major mycinamicins by the wild strain
M. griseorubida
A11725. The
mycG
disruption mutant did not produce mycinamicin I and mycinamicin II; however, mycinamicin IV accumulated in the culture broth. The
mycG
gene was located immediately downstream of the self-resistance gene
myrB
. The
mycG
gene under the control of
mycGp
complemented the production of mycinamicin I and mycinamicin II. Furthermore, the amount of mycinamicin II produced by the strain complemented with the
mycG
gene under the control of
myrBp
was approximately 2-fold higher than that produced by the wild strain. In
M. griseorubida
, MycG recognized mycinamicin IV, mycinamicin V, and also mycinamicin III as the substrates. Moreover, it catalyzed hydroxylation and also epoxidation at C-14 and C-12/13 on these intermediates. However, C-14 on mycinamicin I was not hydroxylated.
Validation of the Rapid Fluorescent Focus Inhibition Test for Rabies Virus-Neutralizing Antibodies in Clinical Samples
Authors: Kostense Stefan , Moore Susan , Companjen Arjen , Bakker Alexander B. H. , Marissen Wilfred E. , von Eyben Rie , Weverling Gerrit Jan , Hanlon Cathleen , Goudsmit Jaap
Published: May 2012

Monoclonal antibodies are successful biologics in treating a variety of diseases, including the prevention or treatment of viral infections. CL184 is a 1:1 combination of two human monoclonal IgG1 antibodies (CR57 and CR4098) against rabies virus, produced in the PER.C6 human cell line. The two antibodies are developed as replacements of human rabies immune globulin (HRIG) and equine rabies immune globulin (ERIG) in postexposure prophylaxis (PEP). The rapid fluorescent focus inhibition test (RFFIT) is a cell-based virus neutralization assay which is usually performed to determine the biological potency of a vaccine and to measure the levels of protection against rabies in humans and animals. In order to confirm the suitability of this assay as a pharmacodynamic assay, we conducted a validation using both HRIG- and CL184-spiked serum samples and sera from vaccinated donors. The validation results met all analytical acceptance criteria and showed that HRIG and CL184 serum concentrations can be compared. Stability experiments showed that serum samples were stable in various suboptimal conditions but that rabies virus should be handled swiftly once thawed. We concluded that the assay is suitable for the measurement of polyclonal and monoclonal rabies neutralizing antibodies in clinical serum samples.
Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation
Authors: Scian Romina , Barrionuevo Paula , Fossati Carlos A. , Giambartolomei Guillermo H. , Delpino M. Victoria
Published: May 2012

Osteoarticular brucellosis is the most common presentation of the active disease in humans. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled. Osteoblasts are responsible for the deposition of bone matrix and are thought to facilitate the calcification and mineralization of the bone matrix, and their function could be altered under infectious conditions. In this article, we describe immune mechanisms wherebyBrucella abortusmay invade and replicate within osteoblasts, inducing apoptosis, inhibiting mineral and organic matrix deposition, and inducing upregulation of RANKL expression. Additionally, all of these mechanisms contributed in different ways to bone loss. These processes implicate the activation of signaling pathways (mitogen-activated protein kinases [MAPK] and caspases) involved in cytokine secretion, expression of activating molecules, and cell death of osteoblasts. In addition, considering the relevance of macrophages in intracellularBrucellasurvival and proinflammatory cytokine secretion in response to infection, we also investigated the role of these cells as modulators of osteoblast survival, differentiation, and function. We demonstrated that supernatants fromB. abortus-infected macrophages may also mediate osteoblast apoptosis and inhibit osteoblast function in a process that is dependent on the presence of tumor necrosis factor alpha (TNF-α). These results indicate thatB. abortusmay directly and indirectly harm osteoblast function, contributing to the bone and joint destruction observed in patients with osteoarticular complications of brucellosis.
Surfactant Protein D Facilitates Cryptococcus neoformans Infection
Authors: Geunes-Boyer Scarlett , Beers Michael F. , Perfect John R. , Heitman Joseph , Wright Jo Rae
Published: May 2012

Concurrent with the global escalation of the AIDS pandemic, cryptococcal infections are increasing and are of significant medical importance. Furthermore,
Cryptococcus neoformans
has become a primary human pathogen, causing infection in seemingly healthy individuals. Although numerous studies have elucidated the virulence properties of
C. neoformans
, less is understood regarding lung host immune factors during early stages of fungal infection. Based on our previous studies documenting that pulmonary surfactant protein D (SP-D) protects
C. neoformans
cells against macrophage-mediated defense mechanisms
in vitro
(S. Geunes-Boyer et al., Infect. Immun. 77:2783–2794, 2009), we postulated that SP-D would facilitate fungal infection
in vivo
. To test this hypothesis, we examined the role of SP-D in response to
C. neoformans
using SP-D
−/−
mice. Here, we demonstrate that mice lacking SP-D were partially protected during
C. neoformans
infection; they displayed a longer mean time to death and decreased fungal burden at several time points postinfection than wild-type mice. This effect was reversed by the administration of exogenous SP-D. Furthermore, we show that SP-D bound to the surface of the yeast cells and protected the pathogenic microbes against macrophage-mediated defense mechanisms and hydrogen peroxide (H
2
O
2
)-induced oxidative stress
in vitro
and
in vivo
. These findings indicate that
C. neoformans
is capable of coopting host SP-D to increase host susceptibility to the yeast. This study establishes a new paradigm for the role played by SP-D during host responses to
C. neoformans
and consequently imparts insight into potential future preventive and/or treatment strategies for cryptococcosis.
NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection
Authors: Theivanthiran Balamayooran , Batra Sanjay , Balamayooran Gayathriy , Cai Shanshan , Kobayashi Koichi , Flavell Richard A. , Jeyaseelan Samithamby
Published: May 2012

Bacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs against
Escherichia coli
, the individual roles of NOD1 and NOD2 in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen,
E. coli
. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2
−/−
mice following
E. coli
infection. Furthermore, we observed reduced activation of NF-κB and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2
−/−
mice upon
E. coli
challenge. Moreover, NOD2
−/−
neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2
−/−
mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2
−/−
mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2
−/−
mice demonstrate a reduction in activation of NF-κB and MAPKs similar to that seen with NOD2
−/−
mice in response to
E. coli
. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation.
Fusobacterium nucleatum and Tannerella forsythia Induce Synergistic Alveolar Bone Loss in a Mouse Periodontitis Model
Authors: Settem Rajendra P. , El-Hassan Ahmed Taher , Honma Kiyonobu , Stafford Graham P. , Sharma Ashu
Published: May 2012

Tannerella forsythia
is strongly associated with chronic periodontitis, an inflammatory disease of the tooth-supporting tissues, leading to tooth loss.
Fusobacterium nucleatum
, an opportunistic pathogen, is thought to promote dental plaque formation by serving as a bridge bacterium between early- and late-colonizing species of the oral cavity. Previous studies have shown that
F. nucleatum
species synergize with
T. forsythia
during biofilm formation and pathogenesis. In the present study, we showed that coinfection of
F. nucleatum
and
T. forsythia
is more potent than infection with either species alone in inducing NF-κB activity and proinflammatory cytokine secretion in monocytic cells and primary murine macrophages. Moreover, in a murine model of periodontitis, mixed infection with the two species induces synergistic alveolar bone loss, characterized by bone loss which is greater than the additive alveolar bone losses induced by each species alone. Further, in comparison to the single-species infection, mixed infection caused significantly increased inflammatory cell infiltration in the gingivae and osteoclastic activity in the jaw bones. These data show that
F. nucleatum
subspecies and
T. forsythia
synergistically stimulate the host immune response and induce alveolar bone loss in a murine experimental periodontitis model.
Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice
Authors: Rosas-Taraco Adrian G. , Perez-Liñan Amira R. , Bocanegra-Ibarias Paola , Perez-Rivera Luz I. , Salinas-Carmona Mario C.
Published: May 2012

Nocardia brasiliensisis an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+Foxp3+regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whetherN. brasiliensismodulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship betweenN. brasiliensisimmunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P< 0.05) in footpad tissue and spleen. Treg subpopulations peaked at days 7 and 15 (P< 0.01) in the footpad and spleen, respectively. Transforming growth factor β1 (TGF-β1) and interleuki-10 (IL-10) are cytokines known for their immunosuppressive effects. During early and chronic infections, these cytokines were elevated with increased TGF-β1 levels from days 3 to 30 (P< 0.01) and sustained IL-10 expression throughout infection compared to uninfected mice. IL-6 production was increased at day 3 (P< 0.01), whereas gamma interferon (IFN-γ), IL-17A, and IL-23 levels were highest at day 15 postinfection (P< 0.01) when a decrease in the bacterial load (>1 log) was also observed (P< 0.05). After these changes, at 30 to 60 days postinfection, IFN-γ production was decreased, whereas the expression of anti-inflammatory cytokines and the bacterial load again increased (P< 0.05). The increment in Treg cells and the related cytokine profile correlated with reduced inflammation at day 15 (P< 0.05) in the footpad. We conclude thatN. brasiliensismodulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.
Vacciniumspecies of sectionHemimyrtillus: their value to cultivated blueberry and approaches to utilization1This article is part of a Special Issue entitled “A tribute to Sam Vander Kloet FLS: Pure and applied research from blueberries to heathland ecology”.
Authors: Ehlenfeldt M.K. , Ballington J.R.
Published: May 2012

The primary gene pool of Vaccinium species used by breeders has traditionally been the North American Vaccinium species in section Cyanococcus. Blueberries in commercial production represent several Vaccinium species and ploidies. Moreover, significant use has been made of the secondary gene pool of Vaccinium, especially in the development of southern highbush cultivars. Section Hemimyrtillus represents species that are part of the tertiary gene pool of Vaccinium. Two species of section Hemimyrtillus, native to the Portuguese islands of Madeira (Vaccinium padifolium Smith) and the Azores (Vaccinium cylindraceum Smith), have features of notable value to conventional blueberry development such as upright structure, strong growth, abundant flowering and fruiting, good self-fertility, acceptable fruit quality, inflorescence structure suited to mechanical harvesting, and repeat flowering. Vaccinium cylindraceum is deciduous, whereas V. padifolium is evergreen. Vaccinium arctostaphylos L., a native of the Caucasus region, is closely allied to V. padifolium, hybridizes freely with it, and has many similar characters, but with the valuable addition of greater cold hardiness. Initial progress has been made at incorporating these species into forms compatible with Vaccinium corymbosum L. based blueberry cultivars, and further evaluations are being made of both parental material and the derived hybrids.