bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of tree genotypic diversity and species diversity effects on different guilds of insect herbivores
Authors: Abdala‐Roberts Luis , Mooney Kailen A. , Quijano‐Medina Teresa , Campos‐Navarrete María José , González‐Moreno Alejandra , Parra‐Tabla Víctor
Published: February 2015

Although the effects of plant diversity on herbivores are contingent upon herbivore traits and the source of plant diversity (e.g. intra‐ and interspecific), most studies have analyzed these effects separately. We compared the effects of genotypic diversity of big‐leaf mahoganySwietenia macrophyllawith that of tree species diversity on two specialist caterpillars(Hypsipyla grandellastem borers andPhyllocnistis meliacellaleaf miners) and three generalist leafhoppers (Cicadellidae) feeding on mahogany in a large‐scale (7.2 ha) forest diversity experiment in southern Mexico. The experiment consisted of fifty‐nine 21 × 21‐m plots, with 64 tree saplings each (3‐m spacing between plants). Plots were either mahogany monocultures or species polycultures of four species (including mahogany) and – within each of these two plot types – mahogany was represented by either one or four genotypes. Throughout a five‐month period, beginning six months after planting, we measured mahogany growth and monitored herbivore and predator (spider) abundance. We found no effect of mahogany genotypic diversity on either specialist caterpillars or generalist leafhoppers, and this result was consistent across levels of tree species diversity. In contrast, species diversity had significant effects on both specialists but neither of the generalist herbivores. Specifically, species diversity loweredH. grandellaattack at the middle of the sampling season, but increased attack at the end of the season, whereasP. meliacellaabundance was consistently reduced. Such effects were not mediated by effects of species diversity on plant growth (of which there were none), but rather through resource heterogeneity. Diversity did not influence spider abundance. This study is one of few to directly compare sources of plant diversity, and uniquely compares such effects among herbivores with contrasting life histories (e.g. diet breadths). Overall, we demonstrate that plant species diversity effects outweigh those of genotypes, and our results suggest that such effects are stronger on specialist than generalist herbivores.
Multi‐scale habitat modification by coexisting ecosystem engineers drives spatial separation of macrobenthic functional groups
Authors: Donadi Serena , van der Heide Tjisse , Piersma Theunis , van der Zee Els M. , Weerman Ellen J. , van de Koppel Johan , Olff Han , Devine Clare , Hernawan Udhi E. , Boers Myra , Planthof Linda , Klemens Eriksson Britas
Published: February 2015

By changing habitat conditions, ecosystem engineers increase niche diversity and have profound effects on the distribution and abundances of other organisms. Although many ecosystems contain several engineering species, it is still unclear how the coexistence of multiple engineers affects the physical habitat and the structure of the community on a landscape scale. Here, we investigated through a large‐scale field manipulation how three coexisting engineers on intertidal flats (cockles Cerastoderma edule; lugworms Arenicola marina; blue mussels Mytilus edulis) influence the functional composition of the local macrobenthic community and what the consequences are at the landscape level. By using biological trait analysis (BTA), we show that on the local scale biogenic changes in sediment accumulation and organic matter content translated into specific shifts in the distribution of functional traits within the community. At a landscape scale, the co‐occurrence of multiple ecosystem engineers resulted in the spatial separation of different functional groups, i.e. different functional groups dominated unique complementary habitats. Our results emphasize the role of co‐occurring multiple engineers in shaping natural communities, thus contributing to a better knowledge of community assembly rules. This understanding can profitably be used to improve ecosystem‐based management and conservation actions.
Cyclosporin Treatment Improves Skin Findings in Omenn Syndrome
Authors: Caglayan Sozmen Sule , Isik Sakine , Arikan Ayyildiz Zeynep , Yildiz Kaan , Cakır Yasemin , Ozer Erdener , Asilsoy Suna , Uzuner Nevin , Karaman Ozkan , Anal Ozden
Published: February 2015

Omenn syndrome is a combined immunodeficiency characterized by a generalized erythematous skin rash, enlarged lymph nodes, hepatosplenomegaly, severe susceptibility to infections, eosinophilia, and hyperimmunoglobulinemia E. A 3‐month‐old girl was admitted to our hospital with a history of recurrent sepsis. Physical examination revealed severe erythroderma, hepatosplenomegaly, lymphadenopathy, and failure to thrive. Laboratory findings revealed leukocytosis, lymphocytosis with high CD3 T‐cells, a high CD4:CD8 ratio, absence of CD19 B‐cells, high eosinophil count, and low immunoglobulin levels. A heterozygote RAG1 gene mutation was found. She had itchy, scaling, ichthyosiform erythroderma and protracted diarrhea. Cyclosporin treatment up to 10 mg/kg effectively resolved erythroderma and lowered total eosinophil counts, and she gained weight during treatment. Since extensive erythroderma with generalized itching causes patient discomfort in Omenn syndrome, cyclosporin treatment can be considered while waiting for treatment with hematopoietic stem cell transplantation.
Putting the Public Back into Governance: The Challenges of Citizen Participation and Its Future
Authors: Fung Archon
Published: February 2015

The past two decades have seen a proliferation of large‐ and small‐scale experiments in participatory governance. This article takes stock of claims about the potential of citizen participation to advance three values of democratic governance: effectiveness, legitimacy, and social justice. Increasing constraints on the public sector in many societies, combined with increasing demand for individual engagement and the affordances of digital technology, have paved the way for participatory innovations aimed at effective governance. Deepening legitimation deficits of representative government create opportunities for legitimacy‐enhancing forms of citizen participation, but so far, the effect of participation on legitimacy is unclear. Efforts to increase social justice through citizen participation face the greatest obstacles. The article concludes by highlighting three challenges to creating successful participatory governance: the absence of systematic leadership, the lack of popular or elite consensus on the place of direct citizen participation, and the limited scope and powers of participatory innovations.
Currency Exposure to Downside Risk: Which Fundamentals Matter?
Authors: Dobrynskaya Victoria
Published: February 2015

I study whether or not countries' macroeconomic characteristics are systematically related to their currencies' exposure to the downside market risk. I find that the currency downside risk is strongly associated with the local inflation rate, real interest rate and net foreign asset position. Currencies of countries with high inflation and real interest rates and negative net foreign asset position (debtor countries) are more exposed to the downside risk whereas currencies of countries with low inflation and real interest rates and positive net foreign asset position (creditor countries) exhibit “safe haven” properties. The local real interest rate has the highest explanatory power in accounting for the cross‐section of currency exposure to the downside risk. This suggests that the high currency exposure to the downside risk is a consequence of investments in high‐yield risky countries and flight from them in “hard times”.
IL‐33 Receptor (ST2) Signalling is Important for Regulation of Th2‐Mediated Airway Inflammation in a Murine Model of Acute Respiratory Syncytial Virus Infection
Authors: Zeng S. , Wu J. , Liu J. , Qi F. , Liu B.
Published: February 2015

T1/ST2, an orphan receptor with homology with the interleukin (IL)‐1 receptor family, is the ligand‐binding component of the receptor for the cytokine IL‐33, a newly identified cytokine known to amplify the Th2 cell‐dominant immune responses. The function of IL‐33/ST2 signalling during respiratory syncytial virus (RSV) infection is not fully known. In this study, following intranasal infection with RSV, BALB/c mice showed a marked increase in the production of IL‐33, with an elevated expression of ST2 mRNA as well as a massive infiltration of CD45+ST2+ cells in the lungs, suggesting that during the early phase of RSV infection, IL‐33 target cells which express ST2 on cell surface, may play a critical role for the development of RSV‐induced airway inflammation. Indeed, blocking ST2 signalling using anti‐ST2 monoclonal antibody diminished not only RSV‐induced eosinophil recruitment, but also the amounts of Th2‐associated cytokines, particularly IL‐13, and Th17‐type cytokine IL‐17A in the lungs of infected mice. However, anti‐ST2 antibody treatment did not affect the production of Th1‐type cytokine IFN‐γ as well as pulmonary viral growth and clearance. These results indicate that IL‐33/ST2 signalling is involved in RSV‐induced, Th2‐associated airway inflammation but not protective immunity.
Autoimmune Response to IGF2 mRNA‐Binding Protein 2 (IMP2/p62) in Breast Cancer
Authors: Liu W. , Li Y. , Wang B. , Dai L. , Qian W. , Zhang J.‐Y.
Published: February 2015

The purpose of this study was to understand the autoimmune response and immunogenicity of a tumour‐associated antigen IMP2/p62 in breast cancer. Autoantibody responses to IMP2/p62 were evaluated by enzyme‐linked immunosorbent assay (ELISA), Western blotting and indirect immunofluorescence assay in sera from patients with breast cancer, benign breast tumour and normal human individuals. Immunohistochemistry (IHC) study with breast cancer tissues was also performed to analyse protein expression of IMP2/p62. The results have demonstrated that IMP2/p62 can induce a relatively higher frequency of autoantibody response in breast cancer (14.3%, 7/49) compared to patients with benign breast tumour (5.6%, 2/36) and normal individuals (2.2%, 1/44). The frequency of IMP2/p62 expression in breast cancer tissues was significantly higher than that in normal tissues (P < 0.01). The data suggest that autoantibody against IMP2/p62 may be a useful serum biomarker for early‐stage breast cancer screening and diagnosis.
The Asian Development Bank and the production of poverty: Neoliberalism, technocratic modernization and land dispossession in the Greater Mekong Subregion
Authors: Sims Kearrin
Published: February 2015

In 1992 the Asian Development Bank coordinated a meeting between government representatives from China, Cambodia, Laos, Myanmar, Thailand and Vietnam to discuss regional economic integration. From that meeting the Greater Mekong Subregion was formed to promote peace and prosperity within the Mekong countries. Yet, despite more than more than USD 14 billion being spent on facilitating trade, development and infrastructural ties between these nations, poverty remains widespread. This article provides a critical analysis of the Asian Development Bank and its approach to development and poverty alleviation within the Greater Mekong Subregion. It suggests that the institution's technocratic neoliberal development ideology provides a discursive legitimation to processes of displacement and dispossession that has seen the production of new forms of poverty. To make this argument, the article draws on an ethnographic study of the local‐scale implications of forced resettlement at the Luang Prabang Airport. It conducts an analysis of how the Asian Development Bank defines and measures poverty, and critiques the institution's resettlement guidelines for the airport project.
Autoimmune risk loci of IL12RB2, IKZF1, XKR6, TMEM39A and CSK in Chinese patients with systemic lupus erythematosus
Authors: You Y. , Zhai Z. F. , Chen F. R. , Chen W. , Hao F.
Published: February 2015

Recent genome‐wide or follow‐up studies conducted in European or Caucasian populations have identified single nucleotide polymorphisms (SNPs) conferring increased risk to autoimmune diseases. It is unclear whether these observations can apply to systemic lupus erythematosus (SLE) in China. An association study was performed on 395 SLE patients and 378 healthy controls recruited from the Chinese population, in which the IL12RB2 rs3790567, IKZF1 rs2366293, XKR6 rs4240671, TMEM39A rs1132200 and CSK rs34933034 polymorphisms were examined by Matrix Assisted Laser Desorption Time of Flight Mass Spectrometry. The frequency of the A allele of IL12RB2 rs3790567 was lower in the cases compared with the controls (24.8% vs 30.2%, P = 0.018) and significant difference among the AA, AG and GG genotypes of rs3790567 was detected between the SLE patients and healthy controls (P = 0.020). We also found a statistically significant difference in the dominant model (GG+AG vs AA, P = 0.008). There was no correlation between the genotypes and specific sub‐phenotypes in the current cohort. Associations with IKZF1 rs2366293, XKR6 rs4240671, TMEM39A rs1132200 and CSK rs34933034 were also lacking (P > 0.05). The results supported the theory that IL12RB2 is associated with SLE in the Chinese population.
Metagenomic profiling of the viromes of plasma collected from blood donors with elevated serum alanine aminotransferase levels
Authors: Furuta Rika A. , Sakamoto Hirotaka , Kuroishi Ayumu , Yasiui Kazuta , Matsukura Harumichi , Hirayama Fumiya
Published: February 2015

BACKGROUND

In Japanese Red Cross (JRC) blood centers, blood collected from donors with serum alanine aminotransferase (ALT) levels of more than 60 U/L are disqualified even if serologically negative for transfusion‐transmitted infections (TTIs). To assess potential risks of TTIs in plasma with elevated serum ALT levels in the current donor screening program of the JRC, we conducted a metagenomic analysis (MGA) of virome profiles in the plasma of blood donors with or without elevated serum ALT levels.

STUDY DESIGN AND METHODS

Based on serum ALT levels, donors were classified into three groups: “high,” more than 79 U/L; “middle,” 61 to 79 U/L; and “low,” less than 61 U/L. We individually analyzed 100 plasma samples from each group by MGA, employing shotgun sequencing. Viral sequences detected using MGA were partly confirmed using real‐time polymerase chain reaction (PCR).

RESULTS

Donors with high and middle ALT levels were significantly younger than those with low ALT levels, and more than 90% were males.Herpesviridae,Anelloviridae,Picornaviridae, andFlaviviridaesequences were identified in plasma samples, and their distribution and frequency were not significantly different among the three groups.

CONCLUSION

The serum ALT test may be unsuitable for monitoring for additional risks of TTIs in blood donors who were negative for typical TTIs using serologic and nucleic acid tests. Although MGA is less sensitive than PCR, it remains the best technology to detect known viruses in these donors.
Comparing multiplier ideals to test ideals on numerically ℚ‐Gorenstein varieties
Authors: de Fernex Tommaso , Docampo Roi , Takagi Shunsuke , Tucker Kevin
Published: February 2015

We show that the reduction to positive characteristic of the multiplier ideal in the sense of de Fernex and Hacon agrees with the test ideal for infinitely many primes, assuming that the variety is numerically ‐Gorenstein. It follows, in particular, that this reduction property holds in dimension 2 for all normal surfaces.
Fabrication of a platform to isolate the influences of surface nanotopography from chemistry on bacterial attachment and growth
Authors: Pegalajar-Jurado Adoracion , Easton Christopher D. , Crawford Russell J. , McArthur Sally L.
Published: February 2015

Billions of dollars are spent annually worldwide to combat the adverse effects of bacterial attachment and biofilm formation in industries as varied as maritime, food, and health. While advances in the fabrication of antifouling surfaces have been reported recently, a number of the essential aspects responsible for the formation of biofilms remain unresolved, including the important initial stages of bacterial attachment to a substrate surface. The reduction of bacterial attachment to surfaces is a key concept in the prevention or minimization of biofilm formation. The chemical and physical characteristics of both the substrate and bacteria are important in understanding the attachment process, but substrate modification is likely the most practical route to enable the extent of bacterial attachment taking place to be effectively controlled. The microtopography and chemistry of the surface are known to influence bacterial attachment. The role of surface chemistry versus nanotopography and their interplay, however, remain unclear. Most methods used for imparting nanotopographical patterns onto a surface also induce changes in the surface chemistry and vice versa. In this study, the authors combine colloidal lithography and plasma polymerization to fabricate homogeneous, reproducible, and periodic nanotopographies with a controllable surface chemistry. The attachment of Escherichia coli bacteria onto carboxyl (plasma polymerized acrylic acid, ppAAc) and hydrocarbon (plasma polymerized octadiene, ppOct) rich plasma polymer films on either flat or colloidal array surfaces revealed that the surface chemistry plays a critical role in bacterial attachment, whereas the effect of surface nanotopography on the bacterial attachment appears to be more difficult to define. This platform represents a promising approach to allow a greater understanding of the role that surface chemistry and nanotopography play on bacterial attachment and the subsequent biofouling of the surface.
Optothermal profile of an ablation catheter with integrated microcoil for MR‐thermometry during Nd:YAG laser interstitial thermal therapies of the liver—An in‐vitro experimental and theoretical study
Authors: Kardoulaki Evdokia M. , Syms Richard R. A. , Young Ian R. , Choonee Kaushal , Rea Marc , Gedroyc Wladyslaw M. W.
Published: February 2015

Purpose:

Flexible microcoils integrated with ablation catheters can improve the temperature accuracy during local MR‐thermometry in Nd:YAG laser interstitial thermal therapies. Here, the authors are concerned with obtaining a preliminary confirmation of the clinical utility of the modified catheter. They investigate whether the thin‐film substrate and copper tracks of the printed coil inductor affect the symmetry of the thermal profile, and hence of the lesion produced.

Methods:

Transmission spectroscopy in the near infrared was performed to test for the attenuation at 1064 nm through the 25 μm thick Kapton substrate of the microcoil. The radial transmission profile of an infrared high‐power, light emitting diode with >80% normalized power at 1064 nm was measured through a cross section of the modified applicator to assess the impact of the copper inductor on the optical profile. The measurements were performed in air, as well as with the applicator surrounded by two types of scattering media; crystals of NaCl and a layer of liver‐mimicking gel phantom. A numerical model based on Huygens–Fresnel principle and finite element simulations, using a commercially available package (COMSOL Multiphysics), were employed to compare with the optical measurements. The impact of the modified optical profile on the thermal symmetry was assessed by examining the high resolution microcoil derived thermal maps from a Nd:YAG laser ablation performed on a liver‐mimicking gel phantom.

Results:

Less than 30% attenuation through the Kapton film was verified. Shadowing behind the copper tracks was observed in air and the measured radial irradiation correlated well with the diffraction pattern calculated numerically using the Huygens–Fresnel principle. Both optical experiments and simulations, demonstrate that shadowing is mitigated by the scattering properties of a turbid medium. The microcoil derived thermal maps at the end of a Nd:YAG laser ablation performed on a gel phantom in a 3 T scanner confirm that the modified irradiation pattern does not disrupt the thermal symmetry, even though, unlike tissue, the gel is minimally scattering.

Conclusions:

The results from this initial assessment indicate that microcoils can be safely integrated with ablation catheters and ensure that the complete necrosis of the liver tumor can still be achieved.
Media Industries and Sport Scandals: Deadspin, Sports Illustrated, ESPN, and the Manti Te’o Hoax
Authors: Burroughs Benjamin , Vogan Travis
Published: February 2015

The growing body of scholarship on sport scandals focuses on how media cover these incidents, how scandalized parties disrupt expectations and repair their images, and the circumstances under which punishment and forgiveness are issued. This article uses Deadspin, Sports Illustrated, and ESPN’s coverage of the 2013 Manti Te’o hoax to suggest that sport scandals also compose instruments through which media outlets fashion their brands, critique competitors, and compete for market share. It demonstrates how these outlets used the Te’o incident to negotiate their positions in the sport-media industry and, more broadly, how sport scandals and coverage of them can reshape that increasingly digital industry’s established hierarchies.
Recruitment of the adaptor protein Nck to PECAM-1 couples oxidative stress to canonical NF-κB signaling and inflammation
Authors: Chen Jie , Leskov Igor L. , Yurdagul Arif , Thiel Bonnie , Kevil Christopher G. , Stokes Karen Y. , Orr A. Wayne
Published: February 2015

Targeting an endothelial cell adaptor protein may prevent reperfusion injury after episodes of ischemia.
Evolution of dynamics affects function
Authors: Vinson Valda
Published: February 2015

Characterization of ancestors of the kinases Src and Abl reveals why they respond differently to the cancer drug Gleevec.
Too hungry to eat, too hungry not to eat
Authors: Hurtley Stella M.
Published: February 2015

Newly formed insulin granules are degraded by lysosomes to prevent insulin release upon fasting.
A network approach to finding disease modules
Authors: Jasny Barbara R.
Published: February 2015

Incomplete networks of protein-protein interactions help explain disease relationships, even in the absence of shared genes.
MAGE takes down a tumor suppressor
Authors: Ferrarelli Leslie K.
Published: February 2015

Cancer cells overcome the growth-restrictive activity of the kinase AMPK by reactivating a testis-specific protein that promotes AMPK degradation.
Autism heritability: A new twist on familial genetics?
Authors: Lemaire Mathieu
Published: February 2015

Analysis of whole-genome sequencing data suggests that a substantial proportion of presumed pathogenic mutations are not shared by autistic siblings.
Neurons cool off
Authors: Schaefer Anne
Published: February 2015

The cold shock–induced protein RBM3 controls synapse regeneration and protects mice with neurodegenerative disease.
Azithromycin Resistance and Its Mechanism in Neisseria gonorrhoeae Strains in Hyogo, Japan
Authors: Shigemura Katsumi , Osawa Kayo , Miura Makiko , Tanaka Kazushi , Arakawa Soichi , Shirakawa Toshiro , Fujisawa Masato
Published: February 2015

Therapeutic options are limited for
Neisseria gonorrhoeae
infection, especially for oral drugs. The purpose of this study was to investigate the susceptibility of
N. gonorrhoeae
to oral azithromycin (AZM) and the correlation between AZM resistance-related gene mutations and MIC. We examined the AZM MICs of clinical strains of
N. gonorrhoeae
, sequenced the peptidyltransferase loop in domain V of 23S rRNA, and investigated the statistical correlation between AZM MIC and the presence and number of the mutations. Among 59
N. gonorrhoeae
strains, our statistical data showed that a deletion mutation was seen significantly more often in the higher-MIC group (0.5 μg/ml or higher) (35/37; 94.6%) than in the lower-MIC group (0.25 μg/ml or less) (4/22; 18.2%) (
P
< 0.0001). However, a mutation of codon 40 (Ala→Asp) in the
mtrR
gene (helix-turn-helix) was seen significantly more often in the lower-MIC group (12/22; 54.5%) (
P
< 0.0001). In
N. gonorrhoeae
multiantigen sequence typing (NG-MAST) analyses, ST4777 was representative of the lower-MIC group and ST1407, ST6798, and ST6800 were representative of the higher-MIC group. NG-MAST type 1407 was detected as the most prevalent type in AZM-resistant or -intermediate strains, as previously described. In conclusion, a deletion mutation in the
mtrR
promoter region may be a significant indicator for higher MIC (0.5 μg/ml or higher). ST4777 was often seen in the lower-MIC group, and ST1407, ST6798, and ST6800 were characteristic of the higher-MIC group. Further research with a greater number of strains would help elucidate the mechanism of AZM resistance in
N. gonorrhoeae
infection.
C/N Ratio Drives Soil Actinobacterial Cellobiohydrolase Gene Diversity
Authors: de Menezes Alexandre B. , Prendergast-Miller Miranda T. , Poonpatana Pabhon , Farrell Mark , Bissett Andrew , Macdonald Lynne M. , Toscas Peter , Richardson Alan E. , Thrall Peter H.
Published: February 2015

Cellulose accounts for approximately half of photosynthesis-fixed carbon; however, the ecology of its degradation in soil is still relatively poorly understood. The role of actinobacteria in cellulose degradation has not been extensively investigated despite their abundance in soil and known cellulose degradation capability. Here, the diversity and abundance of the actinobacterial glycoside hydrolase family 48 (cellobiohydrolase) gene in soils from three paired pasture-woodland sites were determined by using terminal restriction fragment length polymorphism (T-RFLP) analysis and clone libraries with gene-specific primers. For comparison, the diversity and abundance of general bacteria and fungi were also assessed. Phylogenetic analysis of the nucleotide sequences of 80 clones revealed significant new diversity of actinobacterial GH48 genes, and analysis of translated protein sequences showed that these enzymes are likely to represent functional cellobiohydrolases. The soil C/N ratio was the primary environmental driver of GH48 community compositions across sites and land uses, demonstrating the importance of substrate quality in their ecology. Furthermore, mid-infrared (MIR) spectrometry-predicted humic organic carbon was distinctly more important to GH48 diversity than to total bacterial and fungal diversity. This suggests a link between the actinobacterial GH48 community and soil organic carbon dynamics and highlights the potential importance of actinobacteria in the terrestrial carbon cycle.
An Inexpensive, Accurate, and Precise Wet-Mount Method for Enumerating Aquatic Viruses
Authors: Cunningham Brady R. , Brum Jennifer R. , Schwenck Sarah M. , Sullivan Matthew B. , John Seth G.
Published: February 2015

Viruses affect biogeochemical cycling, microbial mortality, gene flow, and metabolic functions in diverse environments through infection and lysis of microorganisms. Fundamental to quantitatively investigating these roles is the determination of viral abundance in both field and laboratory samples. One current, widely used method to accomplish this with aquatic samples is the “filter mount” method, in which samples are filtered onto costly 0.02-μm-pore-size ceramic filters for enumeration of viruses by epifluorescence microscopy. Here we describe a cost-effective (ca. 500-fold-lower materials cost) alternative virus enumeration method in which fluorescently stained samples are wet mounted directly onto slides, after optional chemical flocculation of viruses in samples with viral concentrations of <5 × 10
7
viruses ml
−1
. The concentration of viruses in the sample is then determined from the ratio of viruses to a known concentration of added microsphere beads via epifluorescence microscopy. Virus concentrations obtained by using this wet-mount method, with and without chemical flocculation, were significantly correlated with, and had precision equivalent to, those obtained by the filter mount method across concentrations ranging from 2.17 × 10
6
to 1.37 × 10
8
viruses ml
−1
when tested by using cultivated viral isolates and natural samples from marine and freshwater environments. In summary, the wet-mount method is significantly less expensive than the filter mount method and is appropriate for rapid, precise, and accurate enumeration of aquatic viruses over a wide range of viral concentrations (≥1 × 10
6
viruses ml
−1
) encountered in field and laboratory samples.
Preferential Association of Endophytic Bradyrhizobia with Different Rice Cultivars and Its Implications for Rice Endophyte Evolution
Authors: Piromyou Pongdet , Greetatorn Teerana , Teamtisong Kamonluck , Okubo Takashi , Shinoda Ryo , Nuntakij Achara , Tittabutr Panlada , Boonkerd Nantakorn , Minamisawa Kiwamu , Teaumroong Neung
Published: February 2015

Plant colonization by bradyrhizobia is found not only in leguminous plants but also in nonleguminous species such as rice. To understand the evolution of the endophytic symbiosis of bradyrhizobia, the effect of the ecosystems of rice plantations on their associations was investigated. Samples were collected from various rice (
Oryza sativa
) tissues and crop rotational systems. The rice endophytic bradyrhizobia were isolated on the basis of oligotrophic properties, selective medium, and nodulation on siratro (
Macroptilium atropurpureum
). Six bradyrhizobial strains were obtained exclusively from rice grown in a crop rotational system. The isolates were separated into photosynthetic bradyrhizobia (PB) and nonphotosynthetic bradyrhizobia (non-PB). Thai bradyrhizobial strains promoted rice growth of Thai rice cultivars better than the Japanese bradyrhizobial strains. This implies that the rice cultivars possess characteristics that govern rice-bacterium associations. To examine whether leguminous plants in a rice plantation system support the persistence of rice endophytic bradyrhizobia, isolates were tested for legume nodulation. All PB strains formed symbioses with
Aeschynomene indica
and
Aeschynomene evenia
. On the other hand, non-PB strains were able to nodulate
Aeschynomene americana
,
Vigna radiata
, and
M. atropurpureum
but unable to nodulate either
A. indica
or
A. evenia
. Interestingly, the
nodABC
genes of all of these bradyrhizobial strains seem to exhibit low levels of similarity to those of
Bradyrhizobium diazoefficiens
USDA110 and
Bradyrhizobium
sp. strain ORS285. From these results, we discuss the evolution of the plant-bradyrhizobium association, including nonlegumes, in terms of photosynthetic lifestyle and
nod
-independent interactions.
Monitoring F165
1
P-Like Fimbria Expression at the Single-Cell Level Reveals a Highly Heterogeneous Phenotype
Authors: Graveline Richard , Lavoie Rémi , Garneau Philippe , Daigle France , Sénéchal Serge , Martin Christine , Harel Josée
Published: February 2015

F165
1
and the pyelonephritis-associated pili (Pap) are two members of the type P family of adhesive factors. They play a key role in establishing disease caused by extraintestinal pathogenic
Escherichia coli
(ExPEC) strains in animals and humans. Both F165
1
and Pap are under the control of an epigenetic and reversible switch that defines the number of fimbriated (ON) and afimbriated (OFF) cells within a clonal population. Using the Gfp reporter system, we monitored
in vitro
the level of fluorescence intensity corresponding to the F165
1
and Pap fimbrial synthesis. Monitoring individual
Escherichia coli
cells by flow cytometry and by real-time fluorescence microscopy, we identified cells associated with a low or high level of fluorescence intensity and a large amount of cells with partial levels of fluorescence, mostly present in the F165
1
system. This mixed population identified through fluorescence intensity could be attributed to the high switching rate previously observed in F165
1
-positive bacteria. The fimbrial heterogeneous phenotype for these ExPEC could represent increased fitness in unpredictable environments. Our study illustrates that within the large repertoire of fimbrial variants such as the well-characterized Pap, F165
1
is an exquisite example of regulatory expression that arms the bacterium with strategies for surviving in more than one particular environment.
In Vitro
Passage Selects for Chlamydia muridarum with Enhanced Infectivity in Cultured Cells but Attenuated Pathogenicity in Mouse Upper Genital Tract
Authors: Chen Chaoqun , Zhou Zhou , Conrad Turner , Yang Zhangsheng , Dai Jin , Li Zhongyu , Wu Yimou , Zhong Guangming
Published: February 2015

Although modern
Chlamydia muridarum
has been passaged for decades, there are no reports on the consequences of serial passage with strong selection pressure on its fitness. In order to explore the potential for Pasteurian selection to induce genomic and phenotypic perturbations to
C. muridarum
, a starter population was passaged in cultured cells for 28 generations without standard infection assistance. The resultant population, designated CMG28, displays markedly reduced
in vitro
dependence on centrifugation for infection and low incidence and severity of upper genital tract pathology following intravaginal inoculation into mice compared to the parental
C. muridarum
population, CMG0. Deep sequencing of CMG0 and CMG28 revealed novel protein variants in the hypothetical genes TC0237 (Q117E) and TC0668 (G322R).
In vitro
attachment assays of isogenic plaque clone pairs with mutations in either TC0237 and TC0668 or only TC0237 reveal that TC0237(Q117E) is solely responsible for enhanced adherence to host cells. Paradoxically, double mutants, but not TC0237(Q117E) single mutants, display severely attenuated
in vivo
pathogenicity. These findings implicate TC0237 and TC0668 as novel genetic factors involved in chlamydial attachment and pathogenicity, respectively, and show that serial passage under selection pressure remains an effective tool for studying
Chlamydia
pathogenicity.
High-Throughput Analysis of Gene Essentiality and Sporulation in Clostridium difficile
Authors: Dembek Marcin , Barquist Lars , Boinett Christine J. , Cain Amy K. , Mayho Matthew , Lawley Trevor D. , Fairweather Neil F. , Fagan Robert P.
Published: February 2015

Clostridium difficile
is the most common cause of antibiotic-associated intestinal infections and a significant cause of morbidity and mortality. Infection with C. difficile requires disruption of the intestinal microbiota, most commonly by antibiotic usage. Therapeutic intervention largely relies on a small number of broad-spectrum antibiotics, which further exacerbate intestinal dysbiosis and leave the patient acutely sensitive to reinfection. Development of novel targeted therapeutic interventions will require a detailed knowledge of essential cellular processes, which represent attractive targets, and species-specific processes, such as bacterial sporulation. Our knowledge of the genetic basis of C. difficile infection has been hampered by a lack of genetic tools, although recent developments have made some headway in addressing this limitation. Here we describe the development of a method for rapidly generating large numbers of transposon mutants in clinically important strains of C. difficile. We validated our transposon mutagenesis approach in a model strain of C. difficile and then generated a comprehensive transposon library in the highly virulent epidemic strain R20291 (027/BI/NAP1) containing more than 70,000 unique mutants. Using transposon-directed insertion site sequencing (TraDIS), we have identified a core set of 404 essential genes, required for growth
in vitro
. We then applied this technique to the process of sporulation, an absolute requirement for C. difficile transmission and pathogenesis, identifying 798 genes that are likely to impact spore production. The data generated in this study will form a valuable resource for the community and inform future research on this important human pathogen.

IMPORTANCE
Clostridium difficile
is a common cause of potentially fatal intestinal infections in hospital patients, particularly those who have been treated with antibiotics. Our knowledge of this bacterium has been hampered by a lack of tools for dissecting the organism. We have developed a method to study the function of every gene in the bacterium simultaneously. Using this tool, we have identified a set of 404 genes that are required for growth of the bacteria in the laboratory. C. difficile also produces a highly resistant spore that can survive in the environment for a long time and is a requirement for transmission of the bacteria between patients. We have applied our genetic tool to identify all of the genes required for production of a spore. All of these genes represent attractive targets for new drugs to treat infection.
Toxin Synthesis by Clostridium difficile Is Regulated through Quorum Signaling
Authors: Darkoh Charles , DuPont Herbert L. , Norris Steven J. , Kaplan Heidi B.
Published: February 2015

Clostridium difficile
infection (CDI) is dramatically increasing as a cause of antibiotic- and hospital-associated diarrhea worldwide. C. difficile, a multidrug-resistant pathogen, flourishes in the colon after the gut microbiota has been altered by antibiotic therapy. Consequently, it produces toxins A and B that directly cause disease. Despite the enormous public health problem posed by this pathogen, the molecular mechanisms that regulate production of the toxins, which are directly responsible for disease, remained largely unknown until now. Here, we show that C. difficile toxin synthesis is regulated by an accessory gene regulator quorum-signaling system, which is mediated through a small (<1,000-Da) thiolactone that can be detected directly in stools of CDI patients. These findings provide direct evidence of the mechanism of regulation of C. difficile toxin synthesis and offer exciting new avenues both for rapid detection of C. difficile infection and development of quorum-signaling-based non-antibiotic therapies to combat this life-threatening emerging pathogen.

IMPORTANCE
Clostridium difficile
infection (CDI) is the most common definable cause of hospital-acquired and antibiotic-associated diarrhea in the United States, with the total cost of treatment estimated between 1 and 4.8 billion U.S. dollars annually. C. difficile, a Gram-positive, spore-forming anaerobe, flourishes in the colon after the gut microbiota has been altered by antibiotic therapy. As a result, there is an urgent need for non-antibiotic CDI treatments that preserve the colonic microbiota. C. difficile produces toxins A and B, which are directly responsible for disease. Here, we report that C. difficile regulates its toxin synthesis by quorum signaling, in which a novel signaling peptide activates transcription of the disease-causing toxin genes. This finding provides new therapeutic targets to be harnessed for novel nonantibiotic therapy for C. difficile infections.
Peritoneal lymphomatosis: a rare presentation of follicular lymphoma mimicking peritoneal carcinomatosis
Authors: Cunningham Niamh , Ffrench-Constant Sara , Planche Katie , Gillmore Roopinder
Published: February 2015

Patients presenting with ascites associated with peritoneal disease have a wide differential diagnosis including both malignant and non-malignant related causes. We present the unusual case of a patient, clinically deteriorating, whose malignant peritoneal disease was due to an underlying follicular lymphoma. An urgent staging CT scan followed by a peritoneal biopsy allowed the patient to start chemotherapy within days of acute presentation to the hospital. This case emphasises the importance of obtaining tissue diagnosisurgentlyin these patients to ensure that the correct treatment can be started in a timely manner.
Prolapse of all cardiac valves in Noonan syndrome
Authors: Otikunta Adikesava Naidu , Subbareddy Y V , Polamuri Praneeth , Thakkar Ashok
Published: February 2015

Noonan syndrome is an autosomal dominant disorder with genetically heterogeneous inheritance. The incidence of cardiac abnormalities is higher in patients with Noonan syndrome and approximately 80% patients with Noonan syndrome are reported to have cardiac abnormalities during their lifetimes. However, polyvalvular disease in Noonan syndrome is rare. In this case-report, we describe a case of a young man whose features were strongly suggestive of Noonan syndrome and who was diagnosed with prolapse of all four cardiac valves after 22 years of uneventful survival.
Use of a medication passport in a disabled child seen across many care settings
Authors: Jubraj Barry , Blair Mitchel
Published: February 2015

Written information for patients about their medicines has demonstrable benefits for their understanding and adherence. In the UK, no single, complete record of medications for individual patients can be guaranteed. Therefore, patients and carers are often relied on to recall the complete medication list, which can be a challenge given multiple and potentially stressful appointments. Wide-ranging feedback suggests that a medication ‘passport’ developed by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care North West London (NIHR CLAHRC NWL) has benefited elderly patients, who often attend many appointments where the current medication list may not be available. We describe the use of this passport (known as ‘My Medication Passport’—MMP) in a child with multiple disabilities. The practical advantages are explored, including the potential for a paediatric version to facilitate discussions around the administration of medicines. MMP is an early example of a useful tool to help children and young people, parents and carers to manage medicines more effectively.
Acute scrotal pain and priapism: an early sign of progression in metastatic renal cell carcinoma?
Authors: Patel Kunal , Lamb Benjamin W , Hawkesford Kathryn , Peters John L
Published: February 2015

A 43 -year-old man was treated with pazopanib for metastatic renal cell carcinoma (RCC) with imaging studies suggesting a partial response to treatment. However, the patient presented numerous times with severe testicular pain and gradually increasing priapism. He underwent an inguinal orchidectomy for symptom control. Histopathology confirmed invasion of the cord and tunica vaginalis with metastatic RCC. Further CT of the abdomen and pelvis suggested non-progression of the disease. The patient continued to develop priapism for several weeks before imaging studies confirmed disease progression; a month later the patient died. Genital involvement in metastatic RCC is unusual but should alert clinicians to the possibility of disease progression.
Spontaneous regression and recurrence of stage III Merkel cell carcinoma
Authors: Jansen Sandra Catharina Petronella , Groeneveld-Haenen Christine P M , Klinkhamer Paul J J M , Roumen Rudi M H
Published: February 2015

Merkel cell carcinoma (MCC) is a malignant neuroendocrine carcinoma originating in the skin. It is typically aggressive with a tendency to recur locally and metastasise. There have been several case reports about spontaneous regression of MCC over the past years, but to the best of our knowledge this is the first case of a regional lymph node metastasised MCC with complete spontaneous regression and recurrence. In addition, the primary tumour has an unusual localisation on the foot.
The ‘Best Practice Guide to Conservative Management of Patellofemoral Pain’: incorporating level 1 evidence with expert clinical reasoning
Authors: Barton Christian John , Lack Simon , Hemmings Steph , Tufail Saad , Morrissey Dylan
Published: February 2015

Importance

Patellofemoral pain (PFP) is both chronic and prevalent; it has complex aetiology and many conservative treatment options.

Objective

Develop a comprehensive contemporary guide to conservative management of PFP outlining key considerations for clinicians to follow.

Design

Mixed methods.

Methods

We synthesised the findings from sixhigh-qualitysystematic reviews to September 2013 with the opinions of 17 experts obtained via semistructured interviews. Experts had at least 5 years clinical experience with PFP as a specialist focus, were actively involved in PFP research and contributed to specialist international meetings. The interviews covered clinical reasoning, perception of current evidence and research priorities.

Results

Multimodal intervention including exercise to strengthen the gluteal and quadriceps musculature, manual therapy and taping possessed the strongest evidence. Evidence also supports use of foot orthoses and acupuncture. Interview transcript analysis identified 23 themes and 58 subthemes. Four key over-arching principles to ensure effective management included—(1) PFP is a multifactorial condition requiring an individually tailored multimodal approach. (2) Immediate pain relief should be a priority to gain patient trust. (3) Patient empowerment by emphasising active over passive interventions is important. (4) Good patient education and activity modification is essential. Future research priorities include identifying risk factors, testing effective prevention, developing education strategies, evaluating the influence of psychosocial factors on treatment outcomes and how to address them, evaluating the efficacy of movement pattern retraining and improving clinicians’ assessment skills to facilitate optimal individual prescription.

Conclusions and relevance

Effective management of PFP requires consideration of a number of proven conservative interventions. An individually tailored multimodal intervention programme including gluteal and quadriceps strengthening, patellar taping and an emphasis on education and activity modification should be prescribed for patients with PFP. We provide a ‘Best Practice Guide to Conservative Management of Patellofemoral Pain’ outlining key considerations.
Abortion legislation, maternal healthcare, fertility, female literacy, sanitation, violence against women and maternal deaths: a natural experiment in 32 Mexican states
Authors: Koch Elard , Chireau Monique , Pliego Fernando , Stanford Joseph , Haddad Sebastian , Calhoun Byron , Aracena Paula , Bravo Miguel , Gatica Sebastián , Thorp John
Published: February 2015

Objective

To test whether there is an association between abortion legislation and maternal mortality outcomes after controlling for other factors thought to influence maternal health.

Design

Population-based natural experiment.

Setting and data sources

Official maternal mortality data from 32 federal states of Mexico between 2002 and 2011.

Main outcomes

Maternal mortality ratio (MMR), MMR with any abortive outcome (MMRAO) and induced abortion mortality ratio (iAMR).

Independent variables

Abortion legislation grouped as less (n=18) or more permissive (n=14); constitutional amendment protecting the unborn (n=17); skilled attendance at birth; all-abortion hospitalisation ratio; low birth weight rate; contraceptive use; total fertility rates (TFR); clean water; sanitation; female literacy rate and intimate-partner violence.

Main results

Over the 10-year period, states with less permissive abortion legislation exhibited lower MMR (38.3 vs 49.6; p<0.001), MMRAO(2.7 vs 3.7; p<0.001) and iAMR (0.9 vs 1.7; p<0.001) than more permissive states. Multivariate regression models estimating effect sizes (β-coefficients) for mortality outcomes showed independent associations (p values between 0.001 and 0.055) with female literacy (β=−0.061 to −1.100), skilled attendance at birth (β=−0.032 to −0.427), low birth weight (β=0.149 to 2.166), all-abortion hospitalisation ratio (β=−0.566 to −0.962), clean water (β=−0.048 to −0.730), sanitation (β=−0.052 to −0.758) and intimate-partner violence (β=0.085 to 0.755). TFR showed an inverse association with MMR (β=−14.329) and MMRAO(β=−1.750) and a direct association with iAMR (β=1.383). Altogether, these factors accounted for (R2) 51–88% of the variance among states in overall mortality rates. No statistically independent effect was observed for abortion legislation, constitutional amendment or other covariates.

Conclusions

Although less permissive states exhibited consistently lower maternal mortality rates, this finding was not explained by abortion legislation itself. Rather, these differences were explained by other independent factors, which appeared to have a more favourable distribution in these states.