bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocyte‐derived fibrocytes induce an inflammatory phenotype in airway smooth muscle cells
Authors: Lin T.‐Y. , Venkatesan N. , Nishioka M. , Kyoh S. , Al‐Alwan L. , Baglole C. J. , Eidelman D. H. , Ludwig M. S. , Hamid Q.
Published: September 2014

Background

Infiltration of fibrocytes (FC) in the airway smooth muscle is a feature of asthma, but the pathological significance is unknown.

Objective

We sought to explore whether FC modulate the phenotype of airway smooth muscle cells (ASMC) in asthmatic vs. control subjects.

Methods

Fibrocytes were isolated from CD14+ monocytes from asthmatic and normal subjects. Proliferation of ASMC of asthmatic or normal subjects was analysed by 3H‐thymidine incorporation, cell number counting and Ki‐67 expression after treatment of ASMC with FC‐conditioned medium (FCCM) or co‐culture with FC. ASMC‐associated cytokines/chemokines implicated in asthma (TGF‐β1, eotaxin, IL‐6 and IL‐8) were measured in co‐culture or transwell culture of ASMC + FC by ELISA. Immunofluorescence staining was performed to localize these cytokines in ASMC. Cytokine secretion was measured in the transwell culture of ASMC + FC, where NF‐κB‐p65 or ERK1/2 in ASMC was silenced by siRNA. Contractile phenotype of ASMC in transwell culture was assessed by immunoblotting of α‐smooth muscle actin (α‐SMA) and myosin light chain kinase (MLCK).

Results

Fibrocytes did not affect ASMC proliferation and expression of TGF‐β1, eotaxin, α‐SMA and MLCK; however, ASMC production of IL‐8 and IL‐6 was increased in the co‐culture and transwell culture by FC. ASMC treated with FCCM were immunopositive for IL‐8/IL‐6 and produced more IL‐8/IL‐6. Furthermore, siRNA silencing of NF‐κB‐p65 or ERK1/2 in transwell cultures of asthmatic ASMC with normal subject FC decreased IL‐8 and IL‐6 production.

Conclusions and Clinical Relevance

Fibrocytes promoted IL‐8 and IL‐6 production by ASMC, demonstrating a proinflammatory role for FC and a possible mechanism of the inflammatory phenotype in asthma.
The social support in kinship foster care: a way to enhance resilience
Authors: Fuentes‐Peláez Nuria , Balsells Mª Àngels , Fernández Josefina , Vaquero Eduard , Amorós Pere
Published: September 2014

This paper analyses how social support enhances family resilience in kinship foster families by involving the families in an educational group programme. Sixty‐two kinship foster families from Spain participated in the research. The data were collected before the programme (interviews) and after the programme (interviews and focus groups), and these were analysed by content analysis with the programme Atlas.ti. The results show that the factors that contribute most to the development of family resilience are as follows: (i) feeling able to look for solutions when facing problems; (ii) an increase of their network of formal support; (iii) being able to offer support to other foster families; and (iv) feeling that the support they give to parents' foster children is socially recognized.
Achieving early molecular response in chronic myeloid leukemia in chronic phase to reduce the risk of progression: clinical relevance of the 3‐ and 6‐month time points
Authors: Lapusan Simona , Yong Agnes , Savani Bipin N. , Mohty Mohamad
Published: September 2014

Patients with chronic myeloid leukemia in chronic phase who achieve early molecular response (EMR; generally defined as BCR‐ABL ≤ 10% on the International Scale at 3 or 6 months) have improved outcomes. However, there is no consensus on whether EMR failure at 3 months requires a change in therapy, and the value of the 6‐month time point remains under debate. Some patients who do not achieve EMR at 3 months achieve significant decreases in BCR‐ABL levels by 6 months, whereas others have progressive disease. For patients who do not achieve EMR at either time point, the risk of disease progression is higher both between 3 and 6 months and over the longer term, underlining the therapeutic relevance of the 3‐ to 6‐month time period. For patients with EMR failure at 3 months, although there is currently no consensus on whether to switch therapy or wait until the 6‐month assessment, some patients may benefit from an early change in treatment. This review synthesizes key clinical data demonstrating improved outcomes associated with the achievement of EMR and discusses the relevance of the 3‐ and 6‐month time points on survival and the risk of disease progression. Several potential clinical situations are also presented to explore when a change in therapy may be considered.
Hybridization facilitates evolutionary rescue
Authors: Stelkens Rike B. , Brockhurst Michael A. , Hurst Gregory D. D. , Greig Duncan
Published: September 2014

The resilience of populations to rapid environmental degradation is a major concern for biodiversity conservation. When environments deteriorate to lethal levels, species must evolve to adapt to the new conditions to avoid extinction. Here, we test the hypothesis that evolutionary rescue may be enabled by hybridization, because hybridization increases genetic variability. Using experimental evolution, we show that interspecific hybrid populations of Saccharomyces yeast adapt to grow in more highly degraded environments than intraspecific and parental crosses, resulting in survival rates far exceeding those of their ancestors. We conclude that hybridization can increase evolutionary responsiveness and that taxa able to exchange genes with distant relatives may better survive rapid environmental change.
Identifying behavioural differences in working donkeys in response to analgesic administration
Authors: Regan F. H. , Hockenhull J. , Pritchard J. C. , Waterman‐Pearson A. E. , Whay H. R.
Published: September 2014

Reasons for performing study

To identify pain‐related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain.

Objectives

To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti‐inflammatory drug meloxicam (Metacam).

Study design

Observer‐blinded, placebo‐controlled trial.

Methods

Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20). Observation of postural and event behaviours was undertaken at 2 pretreatment time points followed by 4 post treatment time points, using scan (instantaneous) and focal sampling.

Results

In comparison to pretreatment baselines, donkeys receiving meloxicam were more alert post treatment than the placebo group. They were observed lying down less frequently (P = 0.007), with their eyes closed less frequently (P = 0.04) and having a high head carriage more frequently (P = 0.02). Dozing behaviour decreased after meloxicam compared with the pretreatment baseline (P = 0.03). Donkeys given meloxicam also showed more interest in their environment, turning to look at environmental stimuli more frequently (P = 0.05) than those in the placebo group post treatment. Neither the meloxicam nor the placebo group showed a significant post treatment improvement in lameness scores.

Conclusions

Working donkeys receiving meloxicam were more active and alert compared with their pretreatment behaviour, confirming the potential value of nonsteroidal anti‐inflammatory drugs in identifying behaviours indicative of pain in working donkeys. Behavioural assessment of pain in working donkeys in field clinic conditions will enable veterinary staff and owners to identify welfare issues promptly and monitor response to analgesia.

The Summary is available in Chinese – see Supporting information.
Changes in the faecal microbiota of mares precede the development of post partum colic
Authors: Weese J. S. , Holcombe S. J. , Embertson R. M , Kurtz K. A. , Roessner H. A. , Jalali M. , Wismer S. E.
Published: September 2014

Reasons for performing study

Disruptions in the gastrointestinal microbiota may trigger development of post partum colic.

Objectives

To determine the effects of the periparturient period on the faecal microbiome and identify associations between the faecal microbiota and post partum colic.

Study design

Longitudinal case–control study.

Methods

Pre‐ and post partum faecal samples were collected from mares on 3 farms in central Kentucky. Next generation sequencing of the V4 region of the 16S rRNA gene was performed on samples from 13 mares that developed colic, 13 mares that did not display colic and 5 nonpregnant controls.

Results

There were 4,523,727 sequences from 85 samples evaluated (mean ± s.d. 53,220 ± 29,160, range 8442–122,535). Twenty‐five phyla were identified, although only Firmicutes, Verrucomicrobia, Actinobacteria and Proteobacteria were present at a relative abundance of 1% or greater. The faecal microbiota of late‐term mares differed from nonpregnant mares, with differences in microbial community membership and structure but not the relative abundance of major phyla. There was limited impact of foaling and the post partum period on the faecal microbiome. Faecal samples obtained from mares prior to episodes of colic had significantly higher relative abundance of Proteobacteria (8.2%, P = 0.0006) compared with samples from mares that did not display colic (3.7%). All samples with a relative abundance of Firmicutes of ≤50% preceded colic, as did 6/7 (86%) samples with >4% Proteobacteria. Differences in microbiota membership and structure were also present between mares that developed large colon volvulus and matched controls that did not have colic. Sixty‐one indicator operational taxon units were identified for the control (vs. volvulus) samples, and these were dominated by Lachnospiraceae (n = 38) and Ruminococcaceae (n = 8).

Conclusions

Foaling had minimal effects on the mares' faecal microbiota. Numerous differences in the faecal microbiota preceded colic. Associations between Firmicutes (particularly Lachnospiraceae and Ruminococcaceae) and Proteobacteria and development of colic could lead to measures to predict and prevent colic.

The Summary is available in Chinese – see Supporting information.
Validation and evaluation of VapA‐specific IgG and IgG subclass enzyme‐linked immunosorbent assays (ELISAs) to identify foals with Rhodococcus equi pneumonia
Authors: Sanz M. G. , Oliveira A. F. , Loynachan A. , Page A. , Svansson V. , Giguère S. , Horohov D. W.
Published: September 2014

Reasons for performing study

Rhodococcus equi (Rhodococcus hoagii/Prescottella equi) is a common cause of foal pneumonia, but its diagnosis remains a challenge for equine veterinarians. While the VapA‐specific (virulence‐associated protein A) immunoglobulin G (IgG) enzyme‐linked immunosorbent assay (ELISA) has low sensitivity and specificity for detecting pneumonic foals, little is known about VapA‐specific IgG subclasses.

Objectives

To evaluate the performance of VapA‐specific ELISA for IgG and its subclasses IgGa, IgGb and IgG(T) in the early diagnosis of pneumonia caused by R. equi.

Study design

Assay validation followed by assessment of diagnostic performance using archived samples from animals of known status.

Methods

Serum samples from exposed (n = 125) and nonexposed adult horses (n = 10) and from experimentally challenged and naturally infected foals were used for ELISA validation. Post mortem and tissue culture records of the last 24 years from the Institute for Experimental Pathology at the University of Iceland in Keldur, Iceland laboratory were evaluated to confirm the absence of R. equi cases in Iceland. The diagnostic performance of VapA‐specific IgG and its subclasses was evaluated using banked serum samples from pneumonic (n = 21) and healthy foals (n = 80). To evaluate each IgG assay, a cut‐off value was selected based on receiver operating characteristic curve analysis and used to calculate sensitivity and specificity. The intra‐ and interassay coefficients of variation were calculated for each ELISA.

Results

Using sera from Iceland, where R. equi infection has not been reported, the VapA‐specific IgG ELISA differentiated exposed from nonexposed horses. When used to identify infected foals, VapA‐specific IgG, IgGa and IgGb had no diagnostic value. In contrast, IgG(T) had high sensitivity and specificity.

Conclusions

Horses from Iceland are not exposed to VapA+ R. equi and can serve as negative controls. VapA‐specific IgG subclasses, with the exception of IgG(T), are poor predictors of disease. Further investigation on the use of IgG(T) as a diagnostic tool in field conditions is needed.
Greenhouse gas deposits in the deep sea
Authors: Bell James B.
Published: September 2014

Gas hydrates are the largest deposits of hydrocarbons in the world. They are distributed throughout marine sediments and their stability depends largely upon temperature and pressure. Typically, ∼99 percent of these hydrocarbon deposits are composed of methane, which is a potent greenhouse gas. Methane release from gas hydrates has been implicated in mass extinction events. Present and future changes in ocean temperature have the potential to increase the rate of methane production from gas hydrates and thus to affect Earth's climate. Whilst the deep sea normally serves as a sink for greenhouse gases, the release of methane from gas hydrates could be a hugely significant source in the future and pose a real threat to our efforts to limit greenhouse gas emissions.
Anti‐inflammatory and anti‐bacterial properties of tetramethylhexadecenyl succinyl cysteine (TSC): a skin‐protecting cosmetic functional ingredient
Authors: Fernandéz J. R. , Rouzard K. , Voronkov M. , Huber K. L. , Stock J. B. , Stock M. , Gordon J. S. , Pérez E.
Published: September 2014

Synopsis

Background

The skin is the first line of defence against exposure to microbial, physical, environmental and chemical insults. In mobilizing a protective response, several different cell types located in our skin release and respond to pro‐inflammatory cytokines ensuring skin homeostasis and health. However, chronic activation of this response eventually causes damage resulting in premature ageing. Diosodium tetramethylhexadecenyl succinyl cysteine (TSC or SIG1273), an isoprenylcysteine small molecule, down modulates these inflammatory signalling pathways in various cell types (keratinocytes, peripheral blood mononuclear cells (PBMCs) and endothelial cells) and possesses anti‐bacterial properties. Thus, TSC represents a novel cosmetic functional ingredient that provides a broad spectrum of benefits for the skin.

Objective

To assess the anti‐inflammatory properties of TSC in several cutaneous cell types and further investigate its anti‐microbial activity.

Methods

Cultured normal human epidermal keratinocytes were exposed to chemical irritant phorbol 12‐myrisate 13‐acetate (TPA) or ultraviolet‐B light (UVB) to induce pro‐inflammatory cytokine (IL‐6, IL‐8 and TNF‐α) production. T‐cell receptor (TCR) activation of PBMCs and nickel (Ni2+) treatments of human dermal microvascular endothelial cells (HDMECs) were performed resulting in IL‐4, IL‐6, IL‐8 and IL‐17 production. Streptococcus pyogenes were cultured to determine minimal inhibitory concentration values.

Results

In vitro studies demonstrate TSC blocks TPA and UVB‐induced cytokine production in cultured keratinocytes. Similarly, TSC inhibits overproduction of IL‐4 and IL‐17 in T‐cell receptor (TCR)‐activated PBMCs as well as nickel induction of IL‐6 and IL‐8 in HDMECs. Lastly, TSC demonstrated anti‐microbial properties, inhibiting cell growth of S. pyogenes.

Conclusions

Tetramethylhexadecenyl succinyl cysteine represents a novel cosmetic functional ingredient that provides a dual modulating benefit of skin protection to individuals by reducing inflammation in keratinocytes, endothelial and mononuclear cell types and S. pyogenes counts.
Transcriptome of a specialized extra‐embryonic cell, teratocyte, and its host immunosuppressive role revealed by ex vivo RNA interference
Authors: Ali M. R. , Lim J. , Kim Y.
Published: September 2014

The specialized wasp cells teratocytes (TCs) are derived from the embryonic serosal membrane of some parasitic hymenopteran insects. As a parasitic factor, TCs are multifunctional in host regulation, such as host nutritional deprivation, immunosuppression and developmental arrest; however, little is understood about their genetic constituents. The present study provides a comprehensive view of the genes expressed by TCs through a transcriptome analysis based on RNA sequencing technology. The assembled 34 686 contigs (>200 base pairs) were annotated into different functional categories, indicating a distinct distribution in gene transcripts compared with those of haemocytes and fat body. The TC transcriptome contained components of insulin signalling and biosyntheses of juvenile hormone and 20‐hydroxyecdysone. TCs also expressed various groups of digestive enzymes, indicating that they have nutritional role for the growing parasitoid larvae in parasitism. Furthermore, through this transcriptome analysis two kinds of immunosuppressive serine protease inhibitors (serpins) and Rho GTPase‐activating proteins (RhoGAPs) were annotated. To determine the biological functions of these factors, we devised ex vivo RNA interference (RNAi) by conducting knockdown of gene expression in in vitro‐cultured TCs followed by injection of the treated TCs to test insects. Ex vivo RNAi revealed that some serpins and RhoGAPs expressed in TCs inhibited host cellular immunity. This study reports a transcriptome of the unique TC animal cell and its immunosuppressive genetic factors using ex vivo RNAi technology.
Food Riots and the Politics of Provisions in World History
Authors: Bohstedt John
Published: September 2014

The food riots of 2007–8 in dozens of developing countries placed food security on the agendas of the global political economy. Material outcomes remain to be assessed. The problematic of the politics of provisions is: Under what circumstances do the common people's necessities create a political necessity for their rulers to act? What combination of ingredients gives them political leverage (or not)? Food riots (crowd violence: usually seizing food, intercepting carts and barges, or setting prices) set in motion political processes that often led to food relief and/or repression. To riot about food, rioters needed much more than motivations of hunger and outrage, or else world history would consist mostly of food riots. In addition rioters needed both sufficient solidarities to be able to act collectively, and sufficient confidence that the benefits (getting food, both immediately and in more sustained supply) would outweigh the risks and costs of repression and punishment. The latter would be based on reciprocal relationships with the rulers. The outcomes of such ‘trials‐by‐ordeal’ were then entered into social memory to be consulted in the next crisis. Of course rulers also had their social memories and political calculations. So the ‘politics of provisions’ – the political economy of food crises and their resolutions – has typically included such components as: political, social, and economic structures; the players' sociopolitical assets, capacities, and relationships; shared ideologies; strategic bargaining in the moment between chief actors; and accidental factors. Those components vary from one time and place to another, so this paper compares the politics of provisions in: pre‐modern England and France; famines in Ireland and India; ‘famine‐proofed’ Ming and Qing China; Mao's Great Leap Forward Famine; the IMF austerity riots of the 1970s and 80s; and the food riots of 2008, particularly in Egypt, West Africa, and Haiti. The point of such comparisons is not to construct a unified theory of provision politics, but to illuminate significant parameters that shape policies and conflicts over food.
Historical biogeography of the lacertid lizard Mesalina in North Africa and the Middle East
Authors: Kapli P. , Lymberakis P. , Crochet P.‐A. , Geniez P. , Brito J. C. , Almutairi M. , Ahmadzadeh F. , Schmitz A. , Wilms T. , Pouyani N. R. , Poulakakis N.
Published: September 2014

Aim

We explored the phylogenetic relationships of species of Mesalina, using one nuclear and two mitochondrial loci. This genus of lacertid lizards is widely distributed in North Africa and the Middle East and our goal was to develop a scenario capable of explaining the current distribution and evolutionary patterns within the genus in the context of the wider historical biogeography of the region.

Location

North Africa and the Middle East.

Methods

The assembled dataset consisted of 193 Mesalina individuals, representing 12 species distributed across the geographical range of the genus. Bayesian and maximum likelihood methods were used to support phylogenetic inferences on two mitochondrial (cytochrome b and 16S ribosomal RNA) and one nuclear (beta‐fibrinogen intron 7) markers. Palaeogeographical and palaeoclimatic data were used to support the inferred phylogeographical patterns.

Results

Mesalina lizards exhibit high genetic diversity and complex phylogenetic patterns, leading to an unsatisfactory systematic hypothesis of one paraphyletic and three polyphyletic traditional species. The estimated divergence times place the origin of the genus in the early Miocene (c. 22 Ma) and the divergence of most currently recognized species in the middle to late Miocene. The inferred ancestral distribution suggests that the genus and most of its species originated somewhere in Arabia or the Middle East, with the exception of the Mesalina olivieri complex, which may be of African origin.

Main conclusions

Phylogenetic reconstruction based on the three loci studied suggests a higher than expected cryptic diversity of Mesalina in North Africa and the Middle East. We suggest that the tectonic movements of the Arabian plate, coupled with the climatic changes occurring since the Miocene, may be responsible for the phylogeographical patterns of North African and Middle Eastern Mesalina.
Cell membrane damage is involved in the impaired survival of bone marrow stem cells by oxidized low‐density lipoprotein
Authors: Li Xin , Xiao Yuan , Cui Yuqi , Tan Tao , Narasimhulu Chandrakala A. , Hao Hong , Liu Lingjuan , Zhang Jia , He Guanglong , Verfaillie Catherine M. , Lei Minxiang , Parthasarathy Sampath , Ma Jianjie , Zhu Hua , Liu Zhenguo
Published: September 2014

Cell therapy with bone marrow stem cells (BMSCs) remains a viable option for tissue repair and regeneration. A major challenge for cell therapy is the limited cell survival after implantation. This study was to investigate the effect of oxidized low‐density lipoprotein (ox‐LDL, naturally present in human blood) on BMSC injury and the effect of MG53, a tissue repair protein, for the improvement of stem cell survival. Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox‐LDL, which caused significant cell death as reflected by the increased LDH release to the media. Exposure of MAPCs to ox‐LDL led to entry of fluorescent dye FM1‐43 measured under confocal microscope, suggesting damage to the plasma membrane. Ox‐LDL also generated reactive oxygen species (ROS) as measured with electron paramagnetic resonance spectroscopy. While antioxidant N‐acetylcysteine completely blocked ROS production from ox‐LDL, it failed to prevent ox‐LDL‐induced cell death. When MAPCs were treated with the recombinant human MG53 protein (rhMG53) ox‐LDL induced LDH release and FM1‐43 dye entry were significantly reduced. In the presence of rhMG53, the MAPCs showed enhanced cell survival and proliferation. Our data suggest that membrane damage induced by ox‐LDL contributed to the impaired survival of MAPCs. rhMG53 treatment protected MAPCs against membrane damage and enhanced their survival which might represent a novel means for improving efficacy for stem cell‐based therapy for treatment of diseases, especially in setting of hyperlipidemia.
Evaluation of association of maternal IL‐10 polymorphisms with risk of preeclampsia by A meta‐analysis
Authors: Yang Wenchao , Zhu Zhenmin , Wang Jin , Ye Wei , Ding Yong
Published: September 2014

Emerging evidence shows that interleukin (IL)‐10 gene polymorphisms can regulate its expression level and thus influence person's susceptibility to preeclampsia. However, various published results were inconsistent. To explore the association between maternal IL‐10 gene polymorphisms and preeclampsia, we performed a meta‐analysis based upon 11 individual studies here. Our meta‐analysis results indicated that IL‐10 ‐819C/T (C versus T, OR = 1.28, 95% CI = 1.08–1.50, P = 0.003) and ‐592C/A (C versus A, OR = 1.28, 95% CI = 1.03–1.59, P = 0.03) polymorphisms were associated with preeclampsia. Although there was no overall association between ‐1082A/G polymorphism and preeclampsia (G versus A, OR = 0.93, 95% CI = 0.77–1.13, P = 0.49), such association existed among Asian (G versus A, OR = 1.29, 95% CI = 1.04–1.60, P = 0.02) and South American (G versus A, OR = 0.72, 95% CI = 0.54–0.94, P = 0.02) populations in the subgroup analysis stratified by continents.
A Threatening Horizon: The Impact of the Welfare State on Support for Europe
Authors: Beaudonnet Laurie
Published: September 2014

From the cradle to the grave, social protection is the major bond between citizen and national authority. European integration challenges the social boundaries of nation‐states and this phenomenon is not without consequences for individual attitudes. Within public debate, there are many discussions about the impact of European integration on the welfare state, but conclusive analysis of the consequences on individual support for Europe is still lacking. This article provides an empirical test of the relationship between support for Europe and attitudes towards the welfare state. The findings show that both welfare regimes and welfare issues have a strong impact on individual support for Europe. When it comes to social protection, the European Union works like a distant, albeit strong, threat for individuals.
Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus‐induced activation
Authors: Oliviero B. , Mantovani S. , Ludovisi S. , Varchetta S. , Mele D. , Paolucci S. , Baldanti F. , Mondelli M. U.
Published: September 2014

Chronic hepatitis C virus (HCV) infection is characterized by persistent B‐cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B‐cell subset distribution, we examined ex vivo frequencies and B‐cell inhibitory receptor expression in 37 chronic HCV‐infected patients and 25 healthy donors (HD). In addition, we determined whether short‐term exposure to culture‐derived HCV (HCVcc) resulted in B‐cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue‐like memory (TLM) B cells in HCV‐infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor‐like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B‐cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell‐free HCVcc in vitro did not result in B‐cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV‐infected patients but not in HD, in whom cell‐associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B‐cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B‐cell subsets does not impair virus‐induced B‐cell activation.
Contribution of glucan‐binding protein A to firm and stable biofilm formation by Streptococcus mutans
Authors: Matsumi Y. , Fujita K. , Takashima Y. , Yanagida K. , Morikawa Y. , Matsumoto‐Nakano M.
Published: September 2014

Glucan‐binding proteins (Gbps) of Streptococcus mutans, a major pathogen of dental caries, mediate the binding of glucans synthesized from sucrose by the action of glucosyltransferases (GTFs) encoded by gtfB, gtfC, and gtfD. Several stress proteins, including DnaK and GroEL encoded by dnaK and groEL, are related to environmental stress tolerance. The contribution of Gbp expression to biofilm formation was analyzed by focusing on the expression levels of genes encoding GTFs and stress proteins. Biofilm‐forming assays were performed using GbpA‐, GbpB‐, and GbpC‐deficient mutant strains and the parental strain MT8148. The expression levels of gtfB, gtfC, gtfD, dnaK, and groEL were evaluated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Furthermore, the structure of biofilms formed by these Gbp‐deficient mutant strains was observed using confocal laser scanning microscopy (CLSM). Biofilm‐forming assay findings demonstrated that the amount formed by the GbpA‐deficient mutant strain (AD1) was nearly the same as that by the parental strain, while the GbpB‐ and GbpC‐deficient mutant strains produced lower amounts than MT8148. Furthermore, RT‐qPCR assay results showed that the expressions of gtfB, dnaK, and groEL in AD1 were elevated compared with MT8148. CLSM also revealed that the structure of biofilm formed by AD1 was prominently different compared with that formed by the parental strain. These results suggest that a defect in GbpA influences the expression of genes controlling biofilm formation, indicating its importance as a protein for firm and stable biofilm formation.
Gestational Age‐Specific Associations between Infantile Acute Bronchiolitis and Asthma after Age Five
Authors: Strickland Matthew J. , Marsh Caitlin A. , Darrow Lyndsey A.
Published: September 2014

Background

Infantile acute bronchiolitis (AB) is a risk factor for the development of paediatric asthma. The associations might differ according to gestational age.

Methods

Data sets of emergency department (ED) visits (January 2002 to June 2010) and livebirth records (January 2002 to December 2004) from the state of Georgia were linked for all children who survived 1 year. Exposure was an ED visit for AB during infancy, and the outcome was an ED visit for asthma after age 5 years. The risk of asthma among children with AB (n = 11 564) was compared with the risk of asthma among children who did not have an ED visit for AB but who utilised the ED for another reason during infancy (n = 131 694). Associations were estimated using log‐binomial regression models that controlled for several plausible confounders. Effect measure modification of the risk ratio by gestational age was investigated.

Results

Unadjusted asthma risks (per 100 children) through June 2010 were 4.5 for children with AB and 2.3 for children without AB. The adjusted risk ratio for the overall association was 1.9 [95% confidence interval 1.7, 2.1]. We did not observe effect modification of the risk ratio by gestational age.

Conclusion

A positive association was observed between ED visits for AB and subsequent asthma ED visits after age 5; associations did not vary meaningfully by gestational age. Sensitivity analyses did not suggest large biases due to differences in ED utilisation across sociodemographic groups or loss to follow‐up from residential migration.
Optimizing Electrical Activation of Porcine Oocytes by Adjusting Pre‐ and Post‐Activation Mannitol Exposure Times
Authors: Kwon D , Saadeldin IM , Kim SJ , Park SJ , Kang JT , Park HJ , Moon JH , Koo OJ , Jang G , Lee BC
Published: September 2014

Contents

Modifying electrical activation conditions have been used to improve in vitro embryo production and development in pigs. However, there is insufficient information about correlations of porcine embryo development with oocyte pre‐ and post‐activation conditions. The purpose of this study was to compare the developmental rates of porcine oocytes subjected to different mannitol exposure times, either pre‐ or post‐electrical activation, and to elucidate the reason for the optimal mannitol exposure time. Mannitol exposure times around activation were adjusted as 0, 1, 2 or 3 min. Blastocyst development were checked on day 7. Exposure of oocytes to mannitol for 1 or 2 min before electrical activation produced significantly higher blastocyst rates than exposure for 0 or 3 min. There was no significant difference in blastocyst rates when activated oocytes were exposed to mannitol for 0, 1, 2 or 3 min after electrical activation. While exposure of oocytes to mannitol for 1 min pre‐ and 3 min post‐activation showed significantly higher blastocyst development than 0 min pre‐ and 0 min post‐activation. It also showed higher maintenance of normal oocyte morphology than exposure for 0 min pre‐ and 0 min post‐activation. In conclusion, exposure of oocytes to mannitol for 1 min pre‐ and 3 min post‐activation seems to be optimal for producing higher in vitro blastocyst development of porcine parthenogenetic embryos. The higher blastocyst development is correlated with higher maintenance of normal morphology in oocytes exposed to mannitol for 1 min pre‐ and 3 min post‐activation.
Local Dependence in Random Graph Models: Characterization, Properties and Statistical Inference
Authors: Schweinberger Michael , Handcock Mark S.
Published: September 2014

Dependent phenomena, such as relational, spatial and temporal phenomena, tend to be characterized by local dependence in the sense that units which are close in a well-defined sense are dependent. In contrast with spatial and temporal phenomena, though, relational phenomena tend to lack a natural neighbourhood structure in the sense that it is unknown which units are close and thus dependent. Owing to the challenge of characterizing local dependence and constructing random graph models with local dependence, many conventional exponential family random graph models induce strong dependence and are not amenable to statistical inference. We take first steps to characterize local dependence in random graph models, inspired by the notion of finite neighbourhoods in spatial statistics and M-dependence in time series, and we show that local dependence endows random graph models with desirable properties which make them amenable to statistical inference. We show that random graph models with local dependence satisfy a natural domain consistency condition which every model should satisfy, but conventional exponential family random graph models do not satisfy. In addition, we establish a central limit theorem for random graph models with local dependence, which suggests that random graph models with local dependence are amenable to statistical inference. We discuss how random graph models with local dependence can be constructed by exploiting either observed or unobserved neighbourhood structure. In the absence of observed neighbourhood structure, we take a Bayesian view and express the uncertainty about the neighbourhood structure by specifying a prior on a set of suitable neighbourhood structures. We present simulation results and applications to two real world networks with ‘ground truth’.
Causal Inference from 2K Factorial Designs by Using Potential Outcomes
Authors: Dasgupta Tirthankar , Pillai Natesh S. , Rubin Donald B.
Published: September 2014

A framework for causal inference from two-level factorial designs is proposed, which uses potential outcomes to define causal effects. The paper explores the effect of non-additivity of unit level treatment effects on Neyman's repeated sampling approach for estimation of causal effects and on Fisher's randomization tests on sharp null hypotheses in these designs. The framework allows for statistical inference from a finite population, permits definition and estimation of estimands other than ‘average factorial effects’ and leads to more flexible inference procedures than those based on ordinary least squares estimation from a linear model.
A report on the conservation status of segetal weeds in Tajikistan
Authors: Nowak A , Nowak S , Nobis M , Nobis A
Published: September 2014

Intensification of agriculture has significantly diminished the populations of segetal weeds worldwide in recent decades. Remarkable changes to the entire flora and vegetation of man‐made habitats are being observed in agroecosystems. The present study analyses, for the first time, the threat status of segetal weeds in Tajikistan. A group of 871 weed species were evaluated against IUCN criteria. The assessment of threat status revealed that 214 weed taxa have to be regarded as threatened in Tajikistan, including 18 endemic and four subendemic plants. Five species have been classified as extinct, 27 as critically endangered, 27 as endangered, 39 as vulnerable, 34 as near threatened and 44 as in the ‘least concern’ category. For 38 species, the threat level was not possible, due to lack of data. The most threatened group of taxa is related to rice paddy fields. Numerous losses and disappearances were also observed in cereal communities. Percentages of threatened species in different chorological groups amounted to 58% in the Irano–Turanian, 17% in the Pluriregional, 11% in the Mediterranean, 9.5% in the Cosmopolitan and 4% in the Euro–Siberian species group. Assessment of the threatened status of the rich segetal flora of Tajikistan affords the opportunity to raise awareness of the value of this group of species in the country and may be useful in the conservation management of arable habitats. The results show that even though agriculture in Tajikistan is still based on traditional management and manual work, weed control causes a serious threat to its segetal flora.
Experimental Validation of Numerically Optimized Short Annular Diffusers
Authors: Cerantola D. J. , Birk A. M.
Published: September 2014

Short annular diffusers with negative wall angles were evaluated numerically and experimentally with up to 40 deg inlet swirl at an inlet Reynolds number of Ret ≈ 1.4 × 105 and Mach number of Mt ≈ 0.16. The 80% experimental effectiveness of the 1.61 and 1.91 area ratio (AR) diffusers with 0–20 deg inlet swirl were on par with unswirled maximums reported in literature and computational fluid dynamics (CFD) predicted reasonable outlet axial velocity profiles and wall pressure distributions. The AR = 2.73 diffuser's effectiveness without swirl was 13% below the maximum for the given AR and larger discrepancies occurred in the CFD results due to the incorrect prediction of the recirculation zone strength. Preference was given to the realizable k–ε model on coarse grids with wall functions that predicted performance of all cases with at least 20 deg inlet swirl to within 20%.
Coordination of progenitor specification and growth in mouse and chick spinal cord
Authors: Kicheva Anna , Bollenbach Tobias , Ribeiro Ana , Valle Helena Pérez , Lovell-Badge Robin , Episkopou Vasso , Briscoe James
Published: September 2014

Differentiation rates regulate pool sizes

Even though a basketball player is bigger than a gymnast, their neural tubes are organized in the same way. Studying chick and mouse embryos, Kicheva
et al.
show that rates of cell differentiation are key (see the Perspective by Pourquie). In a two-phase process, signaling sweeps through the neural tube early on to establish some aspects of cell fate, but later, pools of progenitor cells take on their own regulation. A progenitor that differentiates is no longer a progenitor, and thus the rate of differentiation determines the size of the progenitor pool. The relative sizes of progenitor pools shift as development progresses, to build the spinal cord so that everyone, large or small, has the right proportion of each component.

Science
, this issue p.
10.1126/science.1254927
; see also p.
1565
Detection of a branched alkyl molecule in the interstellar medium:
iso
-propyl cyanide
Authors: Belloche Arnaud , Garrod Robin T. , Müller Holger S. P. , Menten Karl M.
Published: September 2014

Carbon chains branch out on space dust

Meteorites found on Earth contain a wide range of complex constituent molecules, including amino acids. Astrochemists proposed the existence of these molecules in interstellar space in the 1980s, but detections have been elusive. Belloche
et al.
used the ALMA telescope array in Chile to observe the massive star-forming region Sgr B2. There, the vast quantities of gas enabled detection of even sparsely distributed species such as
iso
-propyl cyanide. Despite being difficult to detect, such nonlinear organic molecules may be common. The formation of branched molecules is important, given the analogous structure of familiar amino acids — some of the building blocks for life.

Science
, this issue p.
1584
NOνA's shining moment
Authors: Cho Adrian
Published: September 2014

Despite years of delay, Fermilab's massive new experiment has a chance to take the next big step in neutrino physics.
Characterization and Protective Property of Brucella abortuscydCandlooPMutants
Authors: Truong Quang Lam , Cho Youngjae , Barate Abhijit Kashinath , Kim Suk , Hahn Tae-Wook
Published: September 2014

Brucella abortusreadily multiplies in professional or nonprofessional phagocytesin vitroand is highly virulent in mice. Isogenic mutants ofB. abortusbiovar 1 strain IVKB9007 lacking the ATP/GDP-binding protein motif A (P-loop) (namedlooP; designated here the IVKB9007looP::Tn5mutant) and the ATP-binding/permease protein (cydC; designated here the IVKB9007cydC::Tn5mutant) were identified and characterized by transposon mutagenesis using the mini-Tn5Km2 transposon. Both mutants were found to be virtually incapable of intracellular replication in both murine macrophages (RAW264.7) and the HeLa cell line, and their virulence was significantly impaired in BALB/c mice. Respective complementation of the IVKB9007looP::Tn5and IVKB9007cydC::Tn5mutants restored their ability to survivein vitroandin vivoto a level comparable with that of the wild type. These findings indicate that thecydCandlooPgenes play important roles in the virulence ofB. abortus. In addition, intraperitoneal immunization of mice with a dose of the live IVKB9007looP::Tn5and IVKB9007cydC::Tn5mutants provided a high degree of protection against challenge with pathogenicB. abortusstrain 544. Both mutants should be evaluated further as a live attenuated vaccine against bovine brucellosis for their ability to stimulate a protective immune response.
Inter- and Intralaboratory Comparison of JC Polyomavirus Antibody Testing Using Two Different Virus-Like Particle-Based Assays
Authors: Kardas Piotr , Sadeghi Mohammadreza , Weissbach Fabian H. , Chen Tingting , Hedman Lea , Auvinen Eeva , Hedman Klaus , Hirsch Hans H.
Published: September 2014

JC polyomavirus (JCPyV) can cause progressive multifocal leukoencephalopathy (PML), a debilitating, often fatal brain disease in immunocompromised patients. JCPyV-seropositive multiple sclerosis (MS) patients treated with natalizumab have a 2- to 10-fold increased risk of developing PML. Therefore, JCPyV serology has been recommended for PML risk stratification. However, different antibody tests may not be equivalent. To study intra- and interlaboratory variability, sera from 398 healthy blood donors were compared in 4 independent enzyme-linked immunoassay (ELISA) measurements generating >1,592 data points. Three data sets (Basel1, Basel2, and Basel3) used the same basic protocol but different JCPyV virus-like particle (VLP) preparations and introduced normalization to a reference serum. The data sets were also compared with an independent method using biotinylated VLPs (Helsinki1). VLP preadsorption reducing ≥35% activity was used to identify seropositive sera. The results indicated that Basel1, Basel2, Basel3, and Helsinki1 were similar regarding overall data distribution (
P
= 0.79) and seroprevalence (58.0, 54.5, 54.8, and 53.5%, respectively;
P
= 0.95). However, intra-assay intralaboratory comparison yielded 3.7% to 12% discordant results, most of which were close to the cutoff (0.080 < optical density [OD] < 0.250) according to Bland-Altman analysis. Introduction of normalization improved overall performance and reduced discordance. The interlaboratory interassay comparison between Basel3 and Helsinki1 revealed only 15 discordant results, 14 (93%) of which were close to the cutoff. Preadsorption identified specificities of 99.44% and 97.78% and sensitivities of 99.54% and 95.87% for Basel3 and Helsinki1, respectively. Thus, normalization to a preferably WHO-approved reference serum, duplicate testing, and preadsorption for samples around the cutoff may be necessary for reliable JCPyV serology and PML risk stratification.
Maintenance of Leptospira Species in Leptospira Vanaporn Wuthiekanun Agar
Authors: Wuthiekanun Vanaporn , Amornchai Premjit , Langla Sayan , Oyuchua Malinee , Day Nicholas P. J. , Limmathurotsakul Direk
Published: September 2014

The maintenance of
Leptospira
species in liquid or semisolid medium is time-consuming and at risk of contamination due to the needs of routine subculture and dark field microscopy. Using
Leptospira
Vanaporn Wuthiekanun (LVW) agar, we maintained 100 pathogenic
Leptospira
isolates for 12 months without the need for subculture and confirmed the viability of all isolates by the naked eye.
Evaluation of the Xpert Flu Rapid PCR Assay in High-Risk Emergency Department Patients
Authors: Dugas Andrea F. , Valsamakis Alexandra , Gaydos Charlotte A. , Forman Michael , Hardick Justin , Kidambi Pranav , Amin Sharmeen , Gupta Alisha , Rothman Richard E.
Published: September 2014

We prospectively evaluated the performance of Cepheid's GeneXpert Xpert Flu assay in a target population of 281 adults presenting to the emergency department with an acute respiratory illness who met Centers for Disease Control and Prevention (CDC) criteria for recommended antiviral treatment. Compared with the Prodesse ProFlu+ assay, Xpert Flu had an overall sensitivity of 95.3% and specificity of 99.2%.
Point-Counterpoint: Consolidated Clinical Microbiology Laboratories
Authors: Sautter Robert L. , Thomson Richard B.
Published: September 2014

The manner in which medical care is reimbursed in the United States has resulted in significant consolidation in the U.S. health care system. One of the consequences of this has been the development of centralized clinical microbiology laboratories that provide services to patients receiving care in multiple off-site, often remote, locations. Microbiology specimens are unique among clinical specimens in that optimal analysis may require the maintenance of viable organisms. Centralized laboratories may be located hours from patient care settings, and transport conditions need to be such that organism viability can be maintained under a variety of transport conditions. Further, since the provision of rapid results has been shown to enhance patient care, effective and timely means for generating and then reporting the results of clinical microbiology analyses must be in place. In addition, today, increasing numbers of patients are found to have infection caused by pathogens that were either very uncommon in the past or even completely unrecognized. As a result, infectious disease specialists, in particular, are more dependent than ever on access to high-quality diagnostic information from clinical microbiology laboratories. In this point-counterpoint discussion, Robert Sautter, who directs a Charlotte, NC, clinical microbiology laboratory that provides services for a 40-hospital system spread over 3 states in the southeastern United States explains how an integrated clinical microbiology laboratory service has been established in a multihospital system. Richard (Tom) Thomson of the NorthShore University HealthSystem in Evanston, IL, discusses some of the problems and pitfalls associated with large-scale laboratory consolidation.