bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the role of TolC in multidrug efflux: the function and assembly of AcrAB–TolC tolerate significant depletion of intracellular TolC protein
Authors: Krishnamoorthy Ganesh , Tikhonova Elena B. , Dhamdhere Girija , Zgurskaya Helen I. 
Published: January 2013

SummaryTolC channel provides a route for the expelled drugs and toxins to cross the outer membrane of Escherichia coli. The puzzling feature of TolC structure is that the periplasmic entrance of the channel is closed by dense packing of 12 α‐helices. Efflux pumps exemplified by AcrAB are proposed to drive the opening of TolC channel. How interactions with AcrAB promote the close‐to‐open transition in TolC remains unclear. In this study, we investigated in vivo the functional and physical interactions of AcrAB with the closed TolC and its conformer opened by mutations in the periplasmic entrance. We found that the two conformers of TolC are readily distinguishable in vivo by characteristic drug susceptibility, thiol modification and proteolytic profiles. However, these profiles of TolC variants respond neither to the in vivo stoichiometry of AcrAB:TolC nor to the presence of vancomycin, which is used often to assess the permeability of TolC channel. We further found that the activity and assembly of AcrAB–TolC tolerates significant changes in amounts of TolC and that only a small fraction of intracellular TolC is likely used to support efflux needs of E. coli. Our findings explain why TolC is not a good target for inhibition of multidrug efflux.
Reduction and the intracellular translocation of EphB2 in Tg2576 mice and the effects of β‐amyloid
Authors: Qu M. , Jiang J. , Liu X‐P. , Tian Q. , Chen L‐M. , Yin G. , Liu D. , Wang J‐Z. , Zhu L‐Q. 
Published: January 2013

AimsEphB2 is a member of receptor tyrosine kinases (RTKs) family that is essential for the cell adhesion, neural crest migration, axon guidance and synaptogenesis in the nervous system. Recent studies show that preservation of EphB2 in a transgenic mouse model of Alzheimer's disease (AD) rescues the cognitive deficit, suggesting a crucial role of EphB2 in AD. However, the expression and distribution profiles of EphB2 in the early stage of AD have not been reported.MethodsImmunohistochemistry, immunoblot and immunofluorescence were used to analyse the level of EphB2 in Tg2576 mice at different ages and in cultured neurones with Aβ treatment at different times.ResultsEphB2 was reduced in an age‐dependent manner in the olfactory bulb and the hippocampus of Tg2576 mice. The decrease of EphB2 appeared earlier in the olfactory bulb than the hippocampus, and reduction of EphB2 appeared earlier than that of MAP2, a dendritic cytoskeleton marker. In the cortex, EphB2 displayed a significant translocation from the neuronal processes to the cell bodies with ageing. In primary hippocampal neuronal cultures, Aβ42 treatment also induced the decrement of EphB2 that was prior to the decline of MAP2.ConclusionsOur findings provide the first evidence for an age‐ and region‐dependent reduction and intracellular translocation of EphB2 in Tg2576 mice, and the foremost decrement of EphB2 in the olfactory bulb may represent an early sign of AD.
Food‐related impulsivity in obesity and Binge Eating Disorder – a systematic review
Authors: Schag K. , Schönleber J. , Teufel M. , Zipfel S. , Giel K. E. 
Published: January 2013

SummaryImpulsivity towards food has been recognized as a potential factor leading to increased food intake in obesity. Patients suffering from binge eating disorder (BED) form a specific subgroup of obese people that might be characterized by increased impulsivity. These assumptions, although, have yet to be verified. Therefore, this review evaluates evidence for food‐related impulsivity in obese people with and without BED and examines possible differences between both populations. More precisely, evidence for the two components of impulsivity is analyzed separately: evidence for reward sensitivity, specifically, the urge for appetitive stimuli and evidence for rash‐spontaneous behaviour such as acting disinhibited with no regard for the consequences. Our search resulted in 51 articles demonstrating generally increased food‐related impulsivity. We found particular emphasis on increased reward sensitivity in obese people, which appeared to be more pronounced in people with BED. There was little and conflicting evidence, however, concerning increased rash‐spontaneous behaviour in obese people without BED, but consistent evidence of an increase in obese people with BED. All in all, the evidence supports the view that BED represents a specific phenotype of obesity with increased food‐related impulsivity. Taking these specific deficits into account can enhance the effectiveness of weight reduction programmes and psychotherapy.
Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure
Authors: Bukvic Blazenka Kljaic , Blekic Mario , Simpson Angela , Marinho Susana , Curtin John A. , Hankinson Jenny , Aberle Neda , Custovic Adnan 
Published: January 2013

AbstractBackgroundWe investigated the association between genetic variation in chromosomal region 20p13‐p12 (ADAM33 and flanking genes ATRN, GFRA4, SIGLEC1 and HSPA12B) and asthma. Amongst asthmatics, we then investigated the association between genetic variants and asthma severity. We evaluated the effect of environmental tobacco smoke (ETS) exposure in the context of genetic variants.MethodsIn a case–control study, we recruited 423 asthmatic children and 414 non‐asthmatic controls (age 5–18 yr). Amongst asthmatics, we measured lung function and extracted data on hospitalisation for asthma exacerbation from medical records. Early‐life ETS exposure was assessed by questionnaire. We included 85 single‐nucleotide polymorphisms (SNPs) in the analysis.ResultsSeventeen SNPs were significantly associated with asthma; one (rs41534847 in ADAM33) remained significant after correction for multiple testing. Thirty‐six SNPs were significantly associated with lung function, of which 15 (six ARTN, three ADAM33, five SIGLEC1 and one HSPA12B) remained significant after correction. We observed a significant interaction between 23 SNPs and early‐life ETS exposure in relation to lung function measures. For example, for rs512625 in ADAM33, there was significant interaction with ETS exposure in relation to hospitalisations (pint = 0.02) and lung function (pint = 0.03); G‐allele homozygotes had a 9.15‐fold [95% CI 2.28–36.89] higher risk of being hospitalized and had significantly poorer lung function if exposed to ETS, with no effect of ETS exposure amongst A‐allele carriers.ConclusionWe demonstrated several novel significant interactions between polymorphisms in 20p13‐p12 and early‐life ETS exposure with asthma presence and, amongst asthmatics, a significant association with the severity of their disease.
Subcutaneous immunoglobulin: rapid push vs. infusion pump in pediatrics
Authors: Shapiro Ralph S. 
Published: January 2013

BackgroundSubcutaneous immunoglobulin (SCIG) therapy is gaining favor for the management of primary immunodeficiency disease (PIDD) in adults and children.MethodsA retrospective chart review captured data on 96 pediatric patients with PIDD using SCIG (16% or 20%) delivered by infusion pump or SC rapid push over 620 clinic visits. Patients previously using intravenous immunoglobulin (IVIG) were converted to SCIG dosing on a 1:1 basis. Patients/caregivers voluntarily chose an administration technique.ResultsAlthough mean SCIG dosing was lower on a g/kg/month basis compared with prior IVIG dosing, mean steady‐state serum IgG levels during SCIG administration were about 100–200 mg/dl higher than IVIG trough values. On average, much more rapid infusion was achieved with the SC rapid push method, with 49% of patients reporting infusion times of 9 min or less; median duration of infusion pump administration was 45 min. The use of 20% SCIG increased dosing efficiency compared with 16% SCIG, allowing for a smaller weekly mean SCIG volume and fewer dosing days per week. Adverse event (AE) rates were lower in the pediatric subgroup compared with adults (15.8% vs. 18.8% of visits), and the majority of AEs were local. SC rapid push was reported most frequently for patients under age 2; its use decreased between ages 2 and <10 yr and then increased in adolescence and into adulthood. Only one of the pediatric patients returned to IVIG use.ConclusionsAdministration of replacement Ig via SC rapid push is a safe and viable option in pediatric patients with PIDD.
Herpesvirus infections and allergic sensitization in children of families with anthroposophic and non‐anthroposophic lifestyle – the ALADDIN birth cohort
Authors: Hesla Helena Marell , Gutzeit Cindy , Stenius Fredrik , Scheynius Annika , Dahl Helena , Linde Annika , Alm Johan 
Published: January 2013

BackgroundGrowing up in families with an anthroposophic lifestyle has been associated with reduced risk of allergic disease in children. The aim of this report was to assess whether children with this lifestyle are infected earlier with Epstein–Barr virus (EBV), which has been associated with reduced risk of allergic disease, and three other herpesviruses potentially involved in allergy development, namely Human herpesvirus 6 (HHV6), Human herpesvirus 7 (HHV7) and cytomegalovirus (CMV).MethodsWithin the ALADDIN (Assessment of Lifestyle and Allergic Disease During Infancy), birth cohort study 157 children were categorized according to lifestyle into anthroposophic and non‐anthroposophic. IgG‐levels for EBV, HHV6, HHV7 and CMV were determined in plasma samples collected at ages 12 and 24 months and from parents. IgE levels against seven common allergens were analyzed at 24 months.ResultsNo significant differences in seroprevalence of EBV, HHV7 or CMV were detected at any age between the two lifestyle groups. The seroprevalence of HHV6 was significantly lower in the anthroposophic group at 24 months of age (74.6% vs. 87.5%, p‐value 0.048). Further, no significant associations between allergic sensitization and seropositivity to any of the viruses were detected; however, an interaction effect of lifestyle could not be ruled out.ConclusionsOur results indicate that there is no strong influence of exposure to the anthroposophic lifestyle on the time for infection with EBV, HHV6, HHV7 or CMV. These infections can therefore not be assumed to be important factors in the allergy‐protective effect of this lifestyle.
Safety of mometasone furoate nasal spray in the treatment of nasal polyps in children
Authors: Chur Victor , Small Catherine B. , Stryszak Paul , Teper Ariel 
Published: January 2013

AbstractBackgroundMometasone furoate nasal spray (MFNS) improves nasal symptoms and reduces polyp size in adults with nasal polyposis. This 4‐month, multinational, randomized, double‐blind study was conducted to assess the safety of MFNS in pediatric subjects aged 6–17 yr.MethodsSubjects aged 6–11 yr with bilateral nasal polyps received MFNS 100 μg once or twice daily or placebo; those aged 12–17 yr received MFNS 200 μg once or twice daily or placebo. End‐points included change in 24‐h urinary free cortisol (primary), change in 24‐h urinary free cortisol corrected for creatinine (key secondary), and adverse events. Efficacy parameters included polyp size, nasal symptoms, and investigator‐evaluated therapeutic response, although the study was not powered for statistical analysis of efficacy.ResultsLeast squares baseline mean urinary free cortisol level (nmol/24 h) for both age groups combined (N = 127) was 49.5 in the MFNS once‐daily group, 39.6 in the MFNS twice‐daily group, and 49.8 in the placebo group. Change in 24‐h urinary free cortisol did not significantly differ among MFNS‐ and placebo‐treated subjects. Least squares mean 24‐h urinary free cortisol levels corrected for creatinine also showed no significant differences among MFNS‐ and placebo‐treated subjects. No safety issues emerged.ConclusionsResults of this study confirm the safety profile of MFNS in pediatric patients with bilateral nasal polyps over 4 months, even at double the recommended pediatric dosage for allergic rhinitis.
Maternal drug use during pregnancy and asthma risk among children
Authors: Källén Bengt , Finnström Orvar , Nygren Karl‐Gösta , Otterblad Olausson Petra 
Published: January 2013

AbstractBackgroundMaternal use of some drugs, notably paracetamol and drugs for gastroesophageal reflux, has been associated with an increased risk of childhood asthma in the child. We wanted to analyze these associations with consideration to the confounding of maternal asthma.MethodsChildhood asthma was identified from the Swedish National Prescription Register and maternal drug use during the latter part of pregnancy from antenatal records, computerized in the Swedish Medical Birth Register. Risks were estimated as odds ratios (OR) with 95% confidence intervals, using Mantel–Haenszel technique with adjustment for year of birth, maternal age, parity, smoking habits, and BMI.ResultsA statistical association between maternal use of many different drugs, including paracetamol, and childhood asthma existed but was mainly due to concomitant drug use, related to maternal asthma. The only associations that appeared to be true were with drugs for gastroesophageal reflux (adjusted (OR) = 1.32, 95% CI, 1.18–1.54) and with opiates (adjusted OR = 1.56 (96% CI, 1.05–2.34).ConclusionsMaternal use of paracetamol did not seem to increase the risk of childhood asthma, but the previously described association with drugs for gastroesophageal reflux was supported. The analysis is complicated by the confounding from maternal asthma.
Dynamic secretion changes in the salt glands of the mangrove tree speciesAvicennia officinalisin response to a changing saline environment
Authors: TAN WEE‐KEE , LIN QINGSONG , LIM TIT‐MENG , KUMAR PRAKASH , LOH CHIANG‐SHIONG 
Published: January 2013

AbstractThe specialized salt glands on the epidermis of halophytic plants secrete excess salts from tissues by a mechanism that is poorly understood. We examined the salt glands as putative salt and water bi‐regulatory units that can respond swiftly to altering environmental cues. The tropical mangrove tree species (Avicennia officinalis) is able to grow under fluctuating salinities (0.7–50.0 dS m−1) at intertidal zones, and its salt glands offer an excellent platform to investigate their dynamic responses under rapidly changing salinities. Utilizing a novel epidermal peel system, secretion profiles of hundreds of individual salt glands examined revealed that these glands could secrete when exposed to varying salinities. Notably, rhythmic fluctuations observed in secretion rates were reversibly inhibited by water channel (aquaporin) blocker, and two aquaporin genes (PIPandTIP) preferentially expressed in the salt gland cells were rapidly induced in response to increasing salt concentration. We propose that aquaporins are involved and contribute to the re‐absorption of water during salt removal inAvicennia officinalissalt glands. This constitutes an adaptive feature that contributes to salt balance of trees growing in saline environments where freshwater availability is limited.
Broader autistic phenotype in parents of children with autism: Autism Spectrum Quotient–Turkish version
Authors: Kose Sezen , Bora Emre , Erermiş Serpil , Özbaran Burcu , Bildik Tezan , Aydın Cahide 
Published: January 2013

AimsThe Autism Spectrum Quotient (AQ) is a self‐assessment screening instrument for measuring the degree to which an individual of normal intelligence shows autistic traits. Genetic factors could be responsible for the relatives of individuals with autism exhibiting higher than normal rates of autism‐related impairments, referred to as the ‘broader autism phenotype’ (BAP). The aim of this study was to test whether there is a difference between the parents of autistic and those of typically developing children (TDC) on AQ scores in a Turkish sample.MethodThe AQ total and subscale scores of the 100 parents (47 fathers, 53 mothers) of children with autistic disorder (AD) were compared with the 100 parents (48 fathers, 52 mothers) of TDC.ResultsThe parents of AD children scored significantly higher than the TDC parents on total AQ score, and two of five subscale scores; social skills, and communication. The other three subscales (attention to detail, attention switching, imagination) did not differentiate groups. There was no significant difference between mothers and fathers on any AQ scores, neither in the AD nor TDC group. The group × gender interaction was not significant on the total or the five subscale scores of AQ.ConclusionSocial skill and communication subscales differentiate AD parents more successfully, and are more sensitive, as reported in other studies. The present findings confirm that social skill and communication impairments in parents of children with autism spectrum disorders are indicators of BAP.
Colluvial sedimentation in a hyperarid setting (Atacama Desert, northern Chile): Geomorphic controls and stratigraphic facies variability
Authors: Ventra Dario , Dìaz Guillermo Chong , De boer Poppe l. 
Published: January 2013

AbstractResearch on colluvial depositional systems has recently emphasized periglacial and high‐altitude settings, and the relations between Quaternary slope stratigraphy and climate change. This article examines the role of variable slope morphology, surface hydrology and microclimate in controlling colluvial sedimentation along a coastal tract of the hyperarid Atacama Desert in northern Chile. Direct accessibility of active surfaces is accompanied by uninterrupted stratigraphic exposures along the base of slopes, allowing direct comparisons between surface processes and the resulting sedimentary record. Four slope sectors are identified, based on differences in morphology and processes over active surfaces. Colluvial sedimentation is controlled by complex interactions of slope gradients and profiles, exposure to dominant winds, and potential runoff pathways, which vary considerably between different sectors. Major differences are evident between these hyperarid deposits and slope sedimentation in periglacial and temperate settings, including the complete absence of pedogenic activity and clay minerals; the volume of aeolian deposits and their role in controlling processes which redistribute sediment downslope, extending colluvial aprons; and the occurrence of runoff processes only where favoured by particular topographic configurations. Depositional surfaces range from steep talus cones, to debris‐flow‐dominated and aeolian‐dominated colluvial aprons, to an aeolian ramp subject to reworking by mass flows and flash floods. Consequently, facies associations and architectures at outcrop are highly variable and highlight the importance of spatial variations in slope morphology and processes in producing distinct, coeval colluvial stratigraphies within a single environmental context. Discrepancies between active processes and the corresponding stratigraphic signatures are also evident in some sectors; for example, preservation of alluvial and aeolian facies in stratigraphic sections does not always reflect the dominant processes over active slopes. Together with the spatial variability in processes and deposits along these slopes, this suggests that caution is required when extracting palaeoenvironmental information from analyses of colluvial successions.
Novel factors interfering with human immunodeficiency virus‐type 1 replication in vivo and in vitro
Authors: Vicenzi E. , Poli G. 
Published: January 2013

AbstractThe strategy of all retroviral infections is based on establishing an equilibrium between virus replication and proviral latency in the infected host. The human immunodeficiency virus‐type 1 (HIV‐1), belonging to the subfamily of lentiviridae, adds an additional level of sophistication to this general rule by encoding two regulatory genes (tat and rev) and four accessory genes (nef, vif, vpr and vpu); HIV‐2, structurally similar to HIV‐1 but characterized by lower pathogenicity in vivo, encodes another accessory gene, vpx. The function of these accessory genes has become clear in recent years: they serve as countermeasures to host‐cell restriction factors that prevent or curtail the capacity of HIV to productively infect its target cells (typically, CD4+ T lymphocytes, macrophages and dendritic cells). Some of the best characterized restriction factors for HIV‐1 are Tripartite Motif‐5α (TRIM5α), preventing infection of nonhuman primates, although not being effective in humans, and apolipoprotein B mRNA‐editing, enzyme‐catalytic, polypeptide‐like 3G (APOBEC 3G), counteracted by the viral accessory protein Vif. In addition, several other molecules are under scrutiny for their mechanism of action and potential exploitation as novel anti‐HIV agents. This review will summarize the recently emerging knowledge on these novel factors and their potential relevance for the discovery of new anti‐HIV agents targeting not only the replicative, but also the latent state of HIV infection.
Sum of parts is greater than the whole: inference of common genetic history of populations
Authors: Utro Filippo , Pybus Marc , Parida Laxmi 
Published: January 2013

Abstract

Background
Reconstructability of population history, from genetic information of extant individuals, is studied under a simulation setting. We do not address the issue of accuracy of the reconstruction algorithms: we assume the availability of the theoretical best algorithm. On the other hand, we focus on the fraction (1 - f) of the common genetic history that is irreconstructible or impenetrable. Thus the fraction, f, gives an upper bound on the extent of estimability. In other words, there exists no method that can reconstruct a fraction larger than f of the entire common genetic history. For the realization of such a study, we first define a natural measure of the amount of genetic history. Next, we use a population simulator (from literature) that has at least two features. Firstly, it has the capability of providing samples from different demographies, to effectively reflect reality. Secondly, it also provides the underlying relevant genetic history, captured in its entirety, where such a measure is applicable. Finally, to compute f, we use an information content measure of the relevant genetic history. The simulator of choice provided the following demographies: Africans, Europeans, Asians and Afro-Americans.

Results
We observe that higher the rate of recombination, lower the value of f, while f is invariant over varying mutation rates, in each of the demographies. The value of f increases with the number of samples, reaching a plateau and suggesting that in all the demographies at least about one-third of the relevant genetic history is impenetrable. The most surprising observation is that the the sum of the reconstructible history of the subsegments is indeed larger than the reconstructible history of the whole segment. In particular, longer the chromosomal segment, smaller the value of f, in all the demographies.

Conclusions
We present the very first framework for measuring the fraction of the relevant genetic history of a population that is mathematically elusive. Our observed results on the tested demographies suggest that it may be better to aggregate the analysis of smaller chunks of chromosomal segments than fewer large chunks. Also, no matter the richness of samples in a population, at least one-third of the population genetic history is impenetrable. The framework also opens up possible new lines of investigation along the following. Given the characteristics of a population, possibly derived from observed extant individuals, to estimate the (1) optimal sample size and (2) optimal sequence length for the most informative analysis.