bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continued evolution of highly pathogenic avian influenza A (H5N1): updated nomenclature
Authors:   WHO/OIE/FAO H5N1 Evolution Working Group
Published: October 2011

Please cite this paper as: WHO/OIE/FAO. (2012) Continued evolution of highly pathogenic avian influenza A(H5N1): Updated nomenclature. Influenza and Other Respiratory Viruses 6(1), 1–5.Background  Continued evolution of highly pathogenic avian influenza A (H5N1) throughout many regions of the eastern hemisphere has led to the emergence of new phylogenetic groups. A total of 1637 new H5N1 hemagglutinin (HA) sequences have become available since the previous nomenclature recommendations described in 2009 by the WHO/OIE/FAO H5N1 Evolution Working Group. A comprehensive analysis including all the new data is needed to update HA clade nomenclature.Methods  Phylogenetic trees were constructed from data sets of all available H5N1 HA sequences. New clades were designated on the basis of phylogeny and p‐distance using the pre‐established nomenclature system (Emerg Infec Dis 2008; 14:e1). Each circulating H5N1 clade was subjected to further phylogenetic analysis and nucleotide sequence divergence calculations.Results  All recently circulating clades (clade 1 in the Mekong River Delta, 2.1.3 in Indonesia, 2.2 in India/Bangladesh, 2.2.1 in Egypt, 2.3.2, 2.3.4 and 7 in Asia) required assignment of divergent HA genes to new second‐, third‐, and/or fourth‐order clades. At the same time, clades 0, 3, 4, 5, 6, 8, 9, and several second‐ and third‐order groups from clade 2 have not been detected since 2008 or earlier.Conclusions  New designations are recommended for 12 HA clades, named according to previously defined criteria. In addition, viruses from 13 clades have not been detected since 2008 or earlier. The periodic updating of this dynamic classification system allows continued use of a unified nomenclature in all H5N1 studies.
Collaborative Watershed Groups in Three Pacific Northwest States: A Regional Evaluation of Group Metrics and Perceived Success1
Authors: Chaffin B.C. , Mahler R.L. , Wulfhorst J.D. , Shafii B. 
Published: October 2011

Chaffin, B.C., R.L. Mahler, J.D. Wulfhorst, and B. Shafii, 2011. Collaborative Watershed Groups in Three Pacific Northwest States: A Regional Evaluation of Group Metrics and Perceived Success. Journal of the American Water Resources Association (JAWRA) 48(1): 113‐122. DOI: 10.1111/j.1752‐1688.2011.00599.xAbstract:  Watershed management through collaborative groups has become important throughout the United States over the past two decades. Although several studies of Oregon and Washington watershed groups exist, a definitive regional analysis of Pacific Northwest (PNW) watershed groups’ success is lacking. This paper uses data collected from a single survey instrument to determine the status, structure, and success of watershed groups in Idaho, Oregon, and Washington, respectively. Results indicate that watershed group member satisfaction with elements of group structure correlates with levels of perceived group success. Strong leadership within a group and a clear mission statement also indicate higher levels of perceived success. Contrasting realized successes among PNW watershed groups with metrics of perceived success constructed from survey data define watershed groups’ missions and goals and is validated by analysis of the Washington State planning groups’ responses. Overall, PNW watershed groups identified themselves as largely successful. Therefore, the structure, function, and operation identified as characteristic of PNW watershed groups could be used as a model for developing watershed group programming in regions with similar conditions.
Treatment of a patient with large keratocystic odontogenic tumour in the mandible: case report with literature review
Authors: Mojsa I. , Stypulkowska J. , Kaczmarzyk T. , Okon K. , Zaleska M. 
Published: October 2011

AbstractPresented heretofore is the case of a 26‐year‐old male suffering from a keratocystic odontogenic tumour that exhibits progressive development in the mandible. During our evaluation, the patient underwent numerous diagnostic and therapeutic procedures to restore his normal appearance and function.
Effects of incretins on blood pressure: A promising therapy for type 2 diabetes mellitus with hypertension
Authors: WANG Bin , NI Yinxing , ZHONG Jian , SUN Fang 
Published: October 2011

AbstractThe prevalence of type 2 diabetes mellitus (T2DM) has increased markedly worldwide. A recent epidemiological study reported that approximately 63% of T2DM patients also have high blood pressure (>130/80 mmHg), which doubles their risk of cardiac events. Of the medications used to treat T2DM, the incretins are a group of peptides that not only regulate blood glucose effectively and moderately, but also protect patients against cardiovascular events and improve several cardiovascular parameters. Here were review data from preclinical and short‐ and long‐term clinical studies investigating the antihypertensive effects of incretins. We also elucidate four possible mechanisms underlying the antihypertensive effects of incretins. We conclude that incretins can lower blood pressure of T2DM patients, independent of weight loss, and will surely improve the prognosis of these patients.
Sleepwalking, Subjectivity and the Nervous Body in Eighteenth‐Century Britain
Authors: HANDLEY SASHA 
Published: October 2011

AbstractThis article offers an in‐depth study of sleepwalking in the long eighteenth century. It explores how and why the physical condition of sleepwalking was conceptually transformed into a modish nervous disorder that was central to explorations of the human mind, imagination and personal identity in the final decades of the century. This cultural revaluation of sleepwalking, or ‘somnambulism’ as it was increasingly termed, is situated within the context of late seventeenth‐ and eighteenth‐century medical and philosophical thought surrounding the physical act of sleep and its disorders, and within the cults of sensibility and Romanticism.
Nitrous oxide production in soil isolates of nitrate‐ammonifying bacteria
Authors: Stremińska Marta A. , Felgate Heather , Rowley Gary , Richardson David J. , Baggs Elizabeth M. 
Published: October 2011

SummaryHere we provide the first demonstration of the potential for N2O production by soil‐isolated nitrate‐ammonifying bacteria under different C and N availabilities, building on characterizations informed from model strains. The potential for soil‐isolated Bacillus sp. and Citrobacter sp. to reduce NO3‐, and produce NH4+, NO2‐ and N2O was examined in batch and continuous (chemostat) cultures under different C‐to‐NO3‐ ratios, NO3‐‐limiting (5 mM) and NO3‐‐sufficient (22 mM) conditions. C‐to‐NO3‐ ratio had a major influence on the products of nitrate ammonification, with NO2‐, rather than NH4+, being the major product at low C‐to‐NO3‐ ratios in batch cultures. N2O production was maximum and accompanied by high NO2‐ production under C‐limitation/NO3‐sufficiency conditions in chemostat cultures. In media with lower C‐to‐NO3‐N ratios (5‐ and 10‐to‐1) up to 2.7% or 5.0% of NO3‐ was reduced to N2O by Bacillus sp. and Citrobacter sp., respectively, but these reduction efficiencies were only 0.1% or 0.7% at higher C‐to‐NO3‐ ratios (25‐ and 50‐to‐1). As the highest N2O production did not occur under the same C‐to‐NO3‐ conditions as highest NH4+ production we suggest that a re‐evaluation may be necessary of the environmental conditions under which nitrate ammonification contributes to N2O emission from soil.
Automatic 3D registration of dynamic stress and rest 82Rb and flurpiridaz F 18 myocardial perfusion PET data for patient motion detection and correction
Authors: Woo Jonghye , Tamarappoo Balaji , Dey Damini , Nakazato Ryo , Le Meunier Ludovic , Ramesh Amit , Lazewatsky Joel , Germano Guido , Berman Daniel S. , Slomka Piotr J. 
Published: October 2011

Purpose:The authors aimed to develop an image‐based registration scheme to detect and correct patient motion in stress and rest cardiac positron emission tomography (PET)/CT images. The patient motion correction was of primary interest and the effects of patient motion with the use of flurpiridaz F 18 and82Rb were demonstrated.Methods:The authors evaluated stress/rest PET myocardial perfusion imaging datasets in 30 patients (60 datasets in total, 21 male and 9 female) using a new perfusion agent (flurpiridaz F 18) (n = 16) and 82Rb (n = 14), acquired on a Siemens Biograph‐64 scanner in list mode. Stress and rest images were reconstructed into 4 (82Rb) or 10 (flurpiridaz F 18) dynamic frames (60 s each) using standard reconstruction (2D attenuation weighted ordered subsets expectation maximization). Patient motion correction was achieved by an image‐based registration scheme optimizing a cost function using modified normalized cross‐correlation that combined global and local features. For comparison, visual scoring of motion was performed on the scale of 0 to 2 (no motion, moderate motion, and large motion) by two experienced observers.Results:The proposed registration technique had a 93% success rate in removing left ventricular motion, as visually assessed. The maximum detected motion extent for stress and rest were 5.2 mm and 4.9 mm for flurpiridaz F 18 perfusion and 3.0 mm and 4.3 mm for82Rb perfusion studies, respectively. Motion extent (maximum frame‐to‐frame displacement) obtained for stress and rest were (2.2 ± 1.1, 1.4 ± 0.7, 1.9 ± 1.3) mm and (2.0 ± 1.1, 1.2 ±0 .9, 1.9 ± 0.9) mm for flurpiridaz F 18 perfusion studies and (1.9 ± 0.7, 0.7 ± 0.6, 1.3 ± 0.6) mm and (2.0 ± 0.9, 0.6 ± 0.4, 1.2 ± 1.2) mm for 82Rb perfusion studies, respectively. A visually detectable patient motion threshold was established to be ≥2.2 mm, corresponding to visual user scores of 1 and 2. After motion correction, the average increases in contrast‐to‐noise ratio (CNR) from all frames for larger than the motion threshold were 16.2% in stress flurpiridaz F 18 and 12.2% in rest flurpiridaz F 18 studies. The average increases in CNR were 4.6% in stress 82Rb studies and 4.3% in rest 82Rb studies.Conclusions:Fully automatic motion correction of dynamic PET frames can be performed accurately, potentially allowing improved image quantification of cardiac PET data.
Antibiotic Modulation of the Plasminogen Binding Ability of Viridans Group Streptococci
Authors: Teles Cristina , Smith Andrew , Lang Sue 
Published: October 2011

ABSTRACT

The ability of viridans group streptococci to bind human plasminogen and its subsequent activation into plasmin may contribute to the pathogenesis of infective endocarditis (IE) by leading to a decreased stability of the streptococcal vegetation and facilitating dehiscence of emboli. At levels greater than or equal to their MICs, penicillin, vancomycin, and linezolid are efficacious in the treatment of streptococcal endocarditis. However, at sub-MICs, antibiotics can modulate the expression of bacterial genes, including virulence-associated genes, which can have counterproductive effects on the treatment of endocarditis. The effects of 1/8× and 1/4× MICs of penicillin, vancomycin, and linezolid on the plasminogen binding ability of IE isolates
Streptococcus mitis
881/956,
Streptococcus oralis
12601, and
Streptococcus sanguinis
12403 were assessed phenotypically and the expression of plasminogen receptors α-enolase and glyceraldehyde 3-phosphate dehydrogenase of
S. oralis
12601 when exposed to 1/4× MIC of penicillin, was analyzed through quantitative reverse transcription (qRT)-PCR. The plasminogen binding ability of
S. mitis
881/956 and
S. sanguinis
12403 remained unaffected by exposure to sub-MICs of all of the antibiotics tested, while that of
S. oralis
12601 was significantly enhanced by all of the antibiotics tested at sub-MICs. qRT-PCR analysis of
S. oralis
12601 demonstrated an upregulation of the
eno
and
gapdh
genes, indicating an overexpression of plasminogen receptors. These findings suggest that for some endocarditis isolates, the effect of antibiotic sub-MICs, in addition to a reduced antibacterial effect, may influence the clinical response to nonsurgical therapy. It remains difficult to accurately predict isolate responses to sub-MIC antimicrobials since there appears to be interspecies variation.
Pharmacokinetic-Pharmacodynamic Model for Gentamicin and Its Adaptive Resistance with Predictions of Dosing Schedules in Newborn Infants
Authors: Mohamed Ami F. , Nielsen Elisabet I. , Cars Otto , Friberg Lena E. 
Published: October 2011

ABSTRACT

Gentamicin is commonly used in the management of neonatal infections. Development of adaptive resistance is typical for aminoglycosides and reduces the antibacterial effect. There is, however, a lack of understanding of how this phenomenon influences the effect of different dosing schedules. The aim was to develop a pharmacokinetic-pharmacodynamic (PKPD) model that describes the time course of the bactericidal activity of gentamicin and its adaptive resistance and to investigate different dosing schedules in preterm and term newborn infants based on the developed model.
In vitro
time-kill curve experiments were conducted on a strain of
Escherichia coli
(MIC of 2 mg/liter). The gentamicin exposure was either constant (0.125 to 16 mg/liter) or dynamic (simulated concentration-time profiles in a kinetic system with peak concentrations of 2.0, 3.9, 7.8, and 16 mg/liter given as single doses or as repeated doses every 6, 12, or 24 h). Semimechanistic PKPD models were fitted to the bacterial counts in the NONMEM (nonlinear mixed effects modeling) program. A model with compartments for growing and resting bacteria, with a function allowing the maximal bacterial killing of gentamicin to reduce with exposure, characterized both the fast bactericidal effect and the adaptive resistance. Despite a lower peak concentration, preterm neonates were predicted to have a higher bacterial killing effect than term neonates for the same per-kg dose because of gentamicin's longer half-life. The model supported an extended dosing interval of gentamicin in preterm neonates, and for all neonates, dosing intervals of 36 to 48 h were as effective as a 24-h dosing interval for the same total dose.
Activation of Benznidazole by Trypanosomal Type I Nitroreductases Results in Glyoxal Formation
Authors: Hall Belinda S. , Wilkinson Shane R. 
Published: October 2011

ABSTRACT

Benznidazole, a 2-nitroimidazole, is the front-line treatment used against American trypanosomiasis, a parasitic infection caused by
Trypanosoma cruzi
. Despite nearly 40 years of use, the trypanocidal activity of this prodrug is not fully understood. It has been proposed that benznidazole activation leads to the formation of reductive metabolites that can cause a series of deleterious effects, including DNA damage and thiol depletion. Here, we show that the key step in benznidazole activation involves an NADH-dependent trypanosomal type I nitroreductase. This catalyzes an oxygen-insensitive reaction with the interaction of enzyme, reductant, and prodrug occurring through a ping-pong mechanism. Liquid chromatography/mass spectrometry (LC/MS) analysis of the resultant metabolites identified 4,5-dihydro-4,5-dihydroxyimidazole as the major product of a reductive pathway proceeding through hydroxylamine and hydroxy intermediates. The breakdown of this product released the reactive dialdehyde glyoxal, which, in the presence of guanosine, generated guanosine-glyoxal adducts. These experiments indicate that the reduction of benznidazole by type I nitroreductase activity leads to the formation of highly reactive metabolites and that the expression of this enzyme is key to the trypanocidal properties displayed by the prodrug.
An Enlarged, Adaptable Active Site in CYP164 Family P450 Enzymes, the Sole P450 in Mycobacterium leprae
Authors: Agnew Christopher R. J. , Warrilow Andrew G. S. , Burton Nicholas M. , Lamb David C. , Kelly Steven L. , Brady R. Leo 
Published: October 2011

ABSTRACT

CYP164 family P450 enzymes are found in only a subset of mycobacteria and include CYP164A1, which is the sole P450 found in
Mycobacterium leprae
, the causative agent of leprosy. This has previously led to interest in this enzyme as a potential drug target. Here we describe the first crystal structure of a CYP164 enzyme, CYP164A2 from
Mycobacterium smegmatis
. CYP164A2 has a distinctive, enlarged hydrophobic active site that extends above the porphyrin ring toward the access channels. Unusually, we find that CYP164A2 can simultaneously bind two econazole molecules in different regions of the enlarged active site and is accompanied by the rearrangement and ordering of the BC loop. The primary location is through a classic interaction of the azole group with the porphyrin iron. The second econazole molecule is bound to a unique site and is linked to a tetracoordinated metal ion complexed to one of the heme carboxylates and to the side chains of His 105 and His 364. All of these features are preserved in the closely homologous
M. leprae
CYP164A1. The computational docking of azole compounds to a homology model of CYP164A1 suggests that these compounds will form effective inhibitors and is supported by the correlation of parallel docking with experimental binding studies of CYP164A2. The binding of econazole to CYP164A2 occurs primarily through the high-spin “open” conformation of the enzyme (

K
d

[dissociation constant] of 0.1 μM), with binding to the low-spin “closed” form being significantly hindered (

K
d

of 338 μM). These studies support previous suggestions that azole derivatives may provide an effective strategy to improve the treatment of leprosy.
Molecular Dynamics Approaches Estimate the Binding Energy of HIV-1 Integrase Inhibitors and Correlate with
In Vitro
Activity
Authors: Johnson Barry C. , Métifiot Mathieu , Pommier Yves , Hughes Stephen H. 
Published: October 2011

ABSTRACT

The design of novel integrase (IN) inhibitors has been aided by recent crystal structures revealing the binding mode of these compounds with a full-length prototype foamy virus (PFV) IN and synthetic viral DNA ends. Earlier docking studies relied on incomplete structures and did not include the contribution of the viral DNA to inhibitor binding. Using the structure of PFV IN as the starting point, we generated a model of the corresponding HIV-1 complex and developed a molecular dynamics (MD)-based approach that correlates with the
in vitro
activities of novel compounds. Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their
in vitro
activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data. Three additional compounds were docked into the IN-DNA complex model and subjected to MD simulations. All three gave interaction potentials within 1 standard deviation of values estimated from the training set, and the most active compound was identified. Additional MD analysis of the raltegravir- and dolutegravir-bound complexes gave internal and interaction energy values that closely match the experimental binding energy of a compound related to raltegravir that has similar activity. These approaches can be used to gain a deeper understanding of the interactions of the inhibitors with the HIV-1 intasome and to identify promising scaffolds for novel integrase inhibitors, in particular, compounds that retain activity against a range of drug-resistant mutants, making it possible to streamline synthesis and testing.
In Vitro
and
In Vivo
Trypanocidal Synergistic Activity of
N
-Butyl-1-(4-Dimethylamino)Phenyl-1,2,3,4-Tetrahydro-β-Carboline-3-Carboxamide Associated with Benznidazole
Authors: Valdez Rodrigo Hinojosa , Tonin Lilian Tatiani Düsman , Ueda-Nakamura Tânia , Silva Sueli Oliveira , Dias Filho Benedito Prado , Kaneshima Edilson Nobuyoshi , Yamada-Ogatta Sueli Fumie , Yamauchi Lucy Megumi , Sarragiotto Maria Helena , Nakamura Celso Vataru 
Published: October 2011

ABSTRACT

American trypanosomiasis, or Chagas' disease, is caused by
Trypanosoma cruzi
and affects around 15 million people throughout the American continent. The available treatment is based on two nitroheterocyclic drugs, nifurtimox and benznidazole, both only partially effective and toxic. In this context, new drugs must be found. In our previous work, the tetrahydro-β-carboline compound
N
-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide, named C4, showed a potent
in vitro
trypanocidal effect. The goal of this study was to evaluate the
in vitro
and
in vivo
trypanocidal effects of the compound C4 associated with other drugs (benznidazole, ketoconazole, and amphotericin B). For this, we used the checkerboard technique to analyze the effect of combinations of C4 reference drugs. C4 was assayed in a murine model alone as well as in association with benznidazole. We also evaluated the parasitemia, mortality, weight, and presence of amastigote nests in cardiac tissue. A synergic effect of C4 plus benznidazole against epimastigote and trypomastigote forms was observed
in vitro
, and in the murine model, we observed a substantial reduction in parasitemia levels and lowered mortality rates. These findings encourage supplementary investigations of carboline compounds as potential new trypanocidal drugs.
Bacteriocin Production: a Probiotic Trait?
Authors: Dobson Alleson , Cotter Paul D. , Ross R. Paul , Hill Colin 
Published: October 2011

ABSTRACT
Bacteriocins are an abundant and diverse group of ribosomally synthesized antimicrobial peptides produced by bacteria and archaea. Traditionally, bacteriocin production has been considered an important trait in the selection of probiotic strains, but until recently, few studies have definitively demonstrated the impact of bacteriocin production on the ability of a strain to compete within complex microbial communities and/or positively influence the health of the host. Although research in this area is still in its infancy, there is intriguing evidence to suggest that bacteriocins may function in a number of ways within the gastrointestinal tract. Bacteriocins may facilitate the introduction of a producer into an established niche, directly inhibit the invasion of competing strains or pathogens, or modulate the composition of the microbiota and influence the host immune system. Here we review the role of bacteriocin production in complex microbial communities and their potential to enhance human health.
Genome Sequences and Characterization of the Related Gordonia Phages GTE5 and GRU1 and Their Use as Potential Biocontrol Agents
Authors: Petrovski Steve , Tillett Daniel , Seviour Robert J. 
Published: October 2011

ABSTRACT

Activated sludge plants suffer frequently from the operational problem of stable foam formation on aerobic reactor surfaces, which can be difficult to prevent. Many foams are stabilized by mycolic acid-containing
Actinobacteria
, the mycolata. The
in situ
biocontrol of foaming using phages is an attractive strategy. We describe two polyvalent phages, GTE5 and GRU1, targeting
Gordonia terrae
and
Gordonia rubrupertincta
, respectively, isolated from activated sludge. Phage GRU1 also propagates on
Nocardia nova
. Both phages belong to the family
Siphoviridae
and have similar-size icosahedral heads that encapsulate double-stranded DNA genomes (∼65 kb). Their genome sequences are similar to each other but markedly different from those of other sequenced phages. Both are arranged in a modular fashion. These phages can reduce or eliminate foam formation by their host cells under laboratory conditions.