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Background: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all newborns. DDH increases the risk of osteoarthritis and is the cause of 30% of all total hip arthroplasties in adults < 40 years of age. We aim to explore the genetic background of DDH in order to improve diagnosis and personalize treatment., Methods: We conducted a structured literature review using PRISMA guidelines searching the Medline, Embase and Cochrane databases. We included 31 case control studies examining single nucleotide polymorphisms (SNPs) in non-syndromic DDH., Results: A total of 73 papers were included for full text review, of which 31 were single nucleotide polymorphism (SNP) case/control association studies. The literature review revealed that the majority of published papers on the genetics of DDH were mostly underpowered for detection of any significant association. One large genome wide association study has been published (N = 9,915), establishing GDF5 as a plausible risk factor., Conclusions: DDH is known to be congenital and heritable, with family occurrence of DDH already included as a risk factor in most screening programs. Despite this, high quality genetic research is scarce and no genetic risk factors have been soundly established, prompting the need for more research., (© 2024. The Author(s).)

Spore-forming bacteria are the most complex group of microbes to eliminate from the dairy production line due to their ability to withstand heat treatment usually used in dairy processing. These ubiquitous microorganisms have ample opportunity for multiple points of entry into the milk chain, creating issues for food quality and safety. Certain spore-formers, namely bacilli and clostridia, are more problematic to the dairy industry due to their possible pathogenicity, growth, and production of metabolites and spoilage enzymes. This research investigated the spore-forming population from raw milk reception at two Norwegian dairy plants through the cheesemaking stages until ripening. Samples were collected over two years and examined by amplicon sequencing in a culture independent manner and after an anaerobic spore-former enrichment step. In addition, a total of 608 isolates from the enriched samples were identified at the genus or species level using MALDI-TOF analysis. Most spore-forming isolates belong to the genera Bacillus or Clostridium, with the latter dominating the enriched MPN tubes of raw milk and bactofugate. Results showed a great variation among the clostridia and bacilli detected in the enriched MPN tubes. However, B. licheniformis and C. tyrobutyricum were identified in all sample types from both plants throughout the 2-year study. In conclusion, our results shed light on the fate of different spore-formers at different processing stages in the cheese production chain, which could facilitate targeted actions to reduce quality problems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 ​% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome., Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01, R 2 ≥ 0.8 and Hardy-Weinberg equilibrium (HWE) P -value ≥ 0.0001. Significance level was set at p ​< ​5 ​× ​10 -8 . Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee., Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 ( β  ​= ​-0.43, SE ​= ​0.07, p ​= ​8.4 ​× ​10 -9 ) and rs6577334 ( β  ​= ​-0.43, SE ​= ​0.08, p ​= ​8.9 ​× ​10 -9 ). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis., Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed., Competing Interests: All authors report no competing interests., (© 2023 The Author(s).)

Anaerobic spore-forming bacteria are a continuous threat to the dairy industry due to their ability to withstand processing conditions, such as those during heat treatment. These ubiquitous microorganisms have ample opportunity for multiple entry points into the milk chain, creating food quality and safety issues. Certain spore-formers, namely bacilli and clostridia, are more problematic due to their ability to spoil dairy products and pathogenicity. In this study, we investigated how milk treatment and milk powder production influenced the composition and survival of anaerobic spore-formers. Samples were obtained on three different days (replicate blocks) during the production of dairy powders and examined in a culture-dependent manner using the most probable number method coupled with 16S rRNA amplicon sequencing and metagenomic analysis of the enriched samples. Results revealed that the milk separation greatly affected the spore-former presence and composition which were detected along the entire production line from raw material to milk powders. Throughout the various points of the production line, the occurrence of species belonging to the Bacillus cereus sensu lato was higher than that of clostridia. Sequence variants (SVs) belonging to the anaerobic spore-forming genus Clostridium were taxonomically assigned to two SVs groups and were detected in all three replicate blocks. A total of 19 metagenome-assembled genomes were recovered from nine enrichments. Four near-complete and two medium-quality genomes were found in raw milk/milk powder samples and further assigned as Clostridium tyrobutyricum and Clostridium diolis, which may constitute a problem in the finished dairy product. In conclusion, our findings highlight spore-formers' importance on dairy quality and may aid in their intervention and control in the dairy production line., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Osmotic gradient ektacytometry is an important method for diagnosis of red blood cell membrane disorders. For interpretation of the osmoscan parameters on the ektacytomety, an age-matched control sample drawn at the same time is recommended for direct comparison. However, this can be challenging for laboratories to fulfil, especially when ektacytometry is performed in children. Therefore, the aim of this study was to evaluate the influence of age and sex on the osmoscan parameters., Materials and Methods: Blood samples from 231 subjects were analyses on a LoRRca MaxSIS. Data were investigated for need of partitioning by age and sex. After outlier detection, reference intervals (RIs) for osmoscan parameters were estimated., Results: For all parameters except EImin, lower values were observed in infants < 3 month (N = 50) than in all other age group. Hence, RIs were calculated separately for this age group. For EImin, a unified RI was calculated. No difference between sexes was observed for any of the parameters., Conclusion: Lower RIs and a left shift in the osmoscan curves were observed in infants < 3 months compared with older subjects. Hence, age-matched controls are necessary when evaluating ektacytometry in newborns, but can be ignored in older children and adults. This will ease the laboratory workflow when performing ektacytometry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In organic electronics, thermal management is a challenge, as most organic materials conduct heat poorly. As these devices become smaller, thermal transport is increasingly limited by organic-inorganic interfaces, for example that between a metal and a polymer. However, the mechanisms of heat transport at these interfaces are not well understood. In this work, we compare three types of metal-polymer interfaces. Polymethyl methacrylate (PMMA) films of different thicknesses (1-15 nm) were spin-coated on silicon substrates and covered with an 80 nm gold film either directly, or over an interface layer of 2 nm of an adhesion promoting metal-either titanium or nickel. We use the frequency-domain thermoreflectance (FDTR) technique to measure the effective thermal conductivity of the polymer film and then extract the metal-polymer thermal boundary conductance (TBC) with a thermal resistance circuit model. We found that the titanium layer increased the TBC by a factor of 2, from 59 × 10 6 W·m -2 ·K -1 to 115 × 10 6 W·m -2 ·K -1 , while the nickel layer increased TBC to 139 × 10 6 W·m -2 ·K -1 . These results shed light on possible strategies to improve heat transport in organic electronic systems.

Background: Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 may be transmitted and cause morbidity and mortality in hospitals. The economic cost of stopping hospital transmission of LA-MRSA CC398 is poorly described. Early detection of transmission may limit the extent of the intervention., Aim: To evaluate core genome multi-locus sequence typing (cgMLST) for detecting transmission chains and to estimate the costs for interventions to prevent further spread after discovery of hospital transmission of LA-MRSA CC398., Methods: Five patients were involved in two episodes of transmission of LA-MRSA CC398 in a hospital. Standard interventions including MRSA screening of patients and healthcare workers were initiated. Whole genome sequences of the five isolates and 17 epidemiologically unrelated MRSA CC398 isolates from other hospitalized patients were analysed by single nucleotide polymorphism (SNP) comparisons and cgMLST. The economic costs of constraining transmission were calculated from relevant sources., Findings: The five isolates suspected to be involved in hospital transmission clustered with ≤2 SNPs in the draft genome sequences with some distance to other isolates. cgMLST allocated the five isolates to the same type, which was different from all but two of the sporadic isolates. Furthermore, cgMLST separated the five transmission isolates from all other isolates. The economic costs of the outbreak interventions exceeded €11,000 per patient., Conclusion: LA-MRSA CC398 is transmittable in hospitals, and intervention against transmission may reach considerable costs. cgMLST is useful in surveillance of hospital transmission of LA-MRSA., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Aim: To study how sociodemographic factors and family structure associate with baseline BMI z-scores (BMIz) and BMIz change in 767 Norwegian children aged 6-15 years., Methods: Baseline BMIz and 1-year BMIz increments in children from the Bergen Growth Study were analysed with linear and logistic regression, according to sociodemographic factors and family structure. A blended family was defined as including a step-parent and/or half-sibling., Results: In a fully adjusted regression model, baseline BMIz were only significantly associated with maternal BMI (b = 0.087, 95%CI 0.067, 0.107). Body Mass Index z-scores increments were larger in children living in a blended family (b = 0.060, 95%CI 0.006, 0.115), with a lower parental education (b = 0.127, 95%CI 0.029, 0.226) and with a higher maternal BMI (b = 0.008, 95%CI 0.001, 0.014). The odds for a large BMIz increment (>1 SD) were higher in children living in blended families (OR 1.82, 95%CI 1.16, 2.88) and with higher maternal BMI (OR 1.07, 95%CI 1.01, 1.13) and lower in 9-11-year-old children (OR 0.44, 95%CI 0.26, 0.77) compared with 12-15-year-olds., Conclusion: Body Mass Index z-scores increments were more strongly associated with sociodemographic factors and living in a blended family than baseline BMIz values. BMI z-scores increments could be useful for identifying children at risk of becoming overweight or obese., (© 2019 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objectives: The purpose of this study was to investigate the association between weight-related anthropometric measures and children's eating habits, physical activity and sedentary lifestyle at a population level., Methods: Data from the Bergen Growth Study were used to study the association of z-scores of waist circumference (WC), weight-to-height ratio (WHtR), subscapularis (SSF) and triceps (TSF) skinfolds and BMI, with lifestyle factors in 3063 Norwegian children (1543 boys) aged 4-15 years, using linear regression analysis. Each sex was analyzed separately., Results: In a fully adjusted model with additional correction for BMI z-scores, the consumption of vegetables was associated with higher WC (b = 0.03) and TSF (b = 0.05) z-scores in girls. Sedentary behavior was not associated with any of the anthropometric measures. Physical activity was negatively associated with SSF (b = -0.07) and TSF (b = -0.07) z-scores in boys, while a significant negative association was observed with WC (b = -0.02), WHtR (b = -0.03), SSF (b = -0.04) and TSF (b = -0.06) in girls., Conclusion: Physical activity was negatively associated with skinfolds in both sexes. The BMI was not related to the level of physical activity, and should be complemented with direct measures of fat tissue, like skinfolds, when studying the effect of physical activity on body composition in children., (© 2018 Wiley Periodicals, Inc.)

Background and Objectives: Growth reference charts are usually based on measurements of children free from a medical condition that affects growth. However, samples collected during the past decades often contain a large proportion of overweight or obese children. Because obesity increases linear growth, the question arises to what extent the percentiles curves for length/height are affected by the presence of children with overweight or obesity., Methods: Data from two cross-sectional samples of 2-year-old to 18-year-old children were analysed: 12,252 Belgian children, measured in 2002-2004, and 6159 Norwegian children, measured in 2003-2006. The LMS method was used to estimate height-for-age curves with and without children considered overweight or obese according to the International Obesity Task Force thresholds., Results: The prevalence of overweight (including obesity) and obesity was 13.0% and 2.8% in the Belgian and 13.8% and 2.3% in the Norwegian sample. Children were taller when overweight (+0.49 and 0.43 SD, in the Belgian and Norwegian sample, respectively) or obese (+0.73 and 0.72 SD in the Belgian and Norwegian sample, respectively). Effect sizes were smaller in younger and older children, which points to an advanced age of maturation as a possible cause. Excluding overweight and obese children had only a minor impact on the growth curves with largest difference in mean height SD scores -0.09 in the Belgian and -0.12 in the Norwegian sample with a corresponding increase of up to 0.5% and 1.2% in number of children >+2 SD., Conclusions: Current Belgian and Norwegian growth references for length/height were found to be largely unaffected by the current proportion of overweight and obese children. There is, therefore, no need for revised height charts that exclude overweight or obese children., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins that mediate antiviral activity through the synthesis of 2'-5'-linked oligoadenylates and subsequent activation of the endoribonuclease RNase L. However, we have recently demonstrated that exogenous recombinant OAS1 is taken up by cells and reduces viral replication both in cell culture and in vivo, independent of RNase L. These results demonstrate a novel paracrine antiviral activity of OAS working in parallel with the classical RNase L pathway. In this study, we investigate the uptake kinetics of recombinant porcine OAS1 and show that it is rapidly and efficiently internalized in a manner that can be blocked by heparin. Heparin, furthermore, abolishes the antiviral activity of OAS1, demonstrating the requirement of the intracellular localization of OAS1 to inhibit the virus. In addition, we demonstrate that exogenous OAS1 affects an early step of the viral replication cycle.

Two forms, α and β, are known for the racemic amino acid dl-me-thio-nine, C5H11NO2S. The phase transition between them, taking place around 326 K, is associated with sliding at the central inter-faces of the hydro-phobic regions in the crystal, leaving the hydrogen-bonding pattern unperturbed. For the high-temperature α phase, only a structure of rather low quality has been available [R factor = 0.118, no H-atom coordinates; Taniguchi et al. (1980 ▶). Bull. Chem. Soc. Jpn, 53, 803-804]. We here present accurate structural data for this polymorph [R(F) = 0.049], which are compared with other related amino acid structures with similar properties. We report for the first time that the side chain of this phase has a minor disorder component [occupancy 0.0491 (18)] with a gauche+ rather than a gauche- conformation for the N-C-C-C group. In the crystal of the title compound, N-H⋯O hydrogen bonds link the mol-ecules into (100) sheets.

Anisotropic conductive adhesives (ACAs) are promising materials used for producing ultra-thin liquid-crystal displays. Because the mechanical response of polymer particles can have a significant impact in the performance of ACAs, understanding of this apparent size effect is of fundamental importance in the electronics industry. The objective of this research is to use a coarse-grained molecular dynamics model to verify and gain physical insight into the observed size dependence effect in polymer particles. In agreement with experimental studies, the results of this study clearly indicate that there is a strong size effect in spherical polymer particles with diameters approaching the nanometer length scale. The results of the simulations also clearly indicate that the source for the increases in modulus is the increase in relative surface energy for decreasing particle sizes. Finally, the actual contact conditions at the surface of the polymer nanoparticles are shown to be similar to those predicted using Hertz and perfectly plastic contact theory. As ACA thicknesses are reduced in response to reductions in polymer particle size, it is expected that the overall compressive stiffness of the ACA will increase, thus influencing the manufacturing process.

Aim: To analyse the effect of lifestyle factors on the prevalence of overweight and obesity in 6-15-year-old Norwegian children., Methods: Questionnaire data on lifestyle factors (sedentary behaviour, activity and eating habits) and prevalence numbers of overweight and obesity based on measured height and weight were analysed using multinomial logistic regression in a sample of 2281 children included in the Bergen Growth Study., Results: More screen time increased the risk of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02) as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR: 1.81 (obese); p = 0.04). The obese children reported less sugar intake than the not overweight children (OR: 0.58; p = 0.01). Higher parental education was associated with less screen time (p = 0.02), lower frequency of TV in the child's bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and vegetables, less sweets, soft drinks and fast food, and more regular meals (for all, p < 0.03)., Conclusion: Indicators of sedentary lifestyle, such as screen time and the presence of a TV in the child's bedroom, were associated with overweight and obesity in Norwegian schoolchildren. Higher parental education was generally associated with less obesogenic lifestyle., (©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.)

Aims: To investigate the influence of left ventricular (LV) lead position on LV dyssynchrony in cardiac resynchronization therapy (CRT)., Methods and Results: The LV lead was prospectively targeted to the latest activated LV segment (concordant) evaluated by two-dimensional speckle tracking radial strain (ST-RS) echocardiography in 103 CRT recipients (67 ± 12 years). Mechanical dyssynchrony was assessed by anteroseptal-to-posterior (AS-P) delay and interventricular mechanical delay (IVMD). Concordant LV leads were obtained in 72 (70%) patients. Superior LV reverse remodelling (LV-RR; ≥ 15% LV end-systolic volume reduction at 6-month follow-up) was observed in the concordant LV leads compared with the discordant LV leads [51 (76%) vs. 13 (45%); P = 0.003]. Mechanical resynchronization responders (≥ 50% AS-P delay reduction at 6-month follow-up) obtained in the concordant LV leads [44 (66%)] was greater than in the discordant LV leads [10 (34%); P = 0.005]. The discordant LV leads located adjacent to the concordant LV leads (+1 segment; n = 22) and 2 segments apart (+2 segments; n = 9) were evaluated in a subgroup analysis. Mechanical resynchronization responders 6 months after CRT were as follows: in +1 segment [n = 10 (48%)] and in +2 segments (n = 0; P = 0.001). The concordant LV lead was the only independent predictor of LV-RR at 6-month follow-up (odds ratio, 4.177; P = 0.004). Independent predictors of mechanical resynchronization responders were AS-P delay (odds ratio, 1.007; P = 0.032), IVMD (odds ratio, 1.024; P = 0.038), and concordant LV lead (odds ratio, 4.691; P = 0.004)., Conclusion: Concordant LV leads in CRT provided more responders according to both LV reverse remodelling and mechanical resynchronization.

Aims: The effect on left ventricular (LV) systolic function and LV dyssynchrony by alternative right ventricular (RV) lead position in cardiac resynchronization therapy (CRT) is unclear. In the present study, RV apical (RV-A) was compared with RV high posterior septal (RV-HS) lead position in CRT., Methods and Results: In 85 consecutive CRT patients (mean age 66 ±11 years) the RV lead placement was randomized to RV-A (n = 43) or RV-HS (n = 42). The LV lead was targeted to the latest activated LV segment (concordant LV lead), identified by two-dimensional speckle tracking radial strain (ST-RS) echocardiography. Concordant LV leads were obtained in 72%, similar in RV-A and RV-HS (79% vs. 64%; P = 0.13). Six months after CRT, no difference was found in LV reverse remodelling (reduction of LV end-systolic volume ≥15%) according to RV-A and RV-HS leads [26 (65%) vs. 25 (64%); P = 0.93]. Superior LV reverse remodelling was observed in concordant LV leads compared with discordant LV leads [41 (73%) vs. 10 (43%); P = 0.01]. At 6-month follow-up, LV reverse dyssynchrony (reduction of anteroseptal to posterior delay ≥50%) using ST-RS imaging was similar in RV-A and RV-HS [25 (63%) vs. 24 (62%); P = 0.93]. More LV reverse dyssynchrony was found in concordant LV leads vs. discordant LV leads [39 (70%) vs. 10 (43%); P = 0.03]. A concordant LV lead was an independent predictor of LV reverse remodelling (odds ratio, 3.65; P = 0.01) and LV reverse dyssynchrony (odds ratio, 4.22; P = 0.02) 6 months after CRT., Conclusion: RV-A and RV-HS in CRT demonstrated similar LV reverse remodelling and LV reverse dyssynchrony at 6-month follow-up. Concordant LV leads provided superior LV reverse remodelling and LV reverse dyssynchrony.

Background: The conventional right ventricular (RV) lead position in cardiac resynchronization therapy pacemakers (CRT-P) is the RV apex (RV-A). Little is known about electrophysiological stability and associated complications of pacing leads in RV high posterior septal (RV-HS) position in CRT-P., Methods: Two hundred and thirty-five consecutive CRT-P patients were included from 1999-2010. Pacing thresholds at 0.5ms and 2.5V, sensing electrograms and lead impedances were measured at implant and repeated 1,3,6,12,18 and 24 months after CRT-P. Electrophysiological measurements of leads located in RV-A and RV-HS were analyzed retrospectively. Bipolar RV leads were used, including high impedance leads, passive fixation and active fixation., Results: RV pacing leads were implanted in RV-A (n=79) and RV-HS (n=156). Average RV pacing thresholds from CRT implant procedure to 24-month follow-up at 0.5ms were 0.77±0.69V in RV-A and 0.71±0.35V in RV-HS (P=0.31), and at 2.5V were 0.06±0.08ms in RV-A and 0.07±0.05ms in RV-HS (P=0.12). Average RV electrogram amplitudes from baseline to 24 months after CRT were 15.3±6.9mV in RV-A and 12.1±6.0mV in RV-HS (P=0.55). Average RV impedances during follow-up were 850±286Ω in RV-A and 618±147Ω in RV-HS (P=0.57). Similar RV lead revisions between RV-A and RV-HS were observed after 2-year follow-up (P=0.55)., Conclusion: The RV-HS lead position demonstrated stable and acceptable long-term pacing and sensing function, with rates of complications comparable to conventional RV-A lead position in CRT. The RV-HS lead position is feasible in CRT-P.

The 2'-5' oligoadenylate synthetases (OAS) are interferon-induced antiviral enzymes that recognize virally produced dsRNA and initiate RNA destabilization through activation of RNase L within infected cells. However, recent evidence points toward several RNase L-independent pathways, through which members of the OAS family can exert antiviral activity. The crystal structure of OAS led to a novel insight into the catalytic mechanism, and revealed a remarkable similarity between OAS, Polyadenosine polymerase, and the class I CCA-adding enzyme from Archeoglobus fulgidus. This, combined with a variety of bioinformatic data, leads to the definition of a superfamily of template independent polymerases and proved that the OAS family are ancient proteins, which probably arose as early as the beginning of metazoan evolution.

Low energy antiprotons have been used previously to give benchmark data for theories of atomic collisions. Here we present measurements of the cross section for single, nondissociative ionization of molecular hydrogen for impact of antiprotons with kinetic energies in the range 2-11 keV, i.e., in the velocity interval of 0.3-0.65 a.u. We find a cross section which is proportional to the projectile velocity, which is quite unlike the behavior of corresponding atomic cross sections, and which has never previously been observed experimentally.

The 2'-5' oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins. However, several studies demonstrate a correlation between the concentration of freely circulating OAS protein in sera from hepatitis C patients and their clinical prognosis. Here we demonstrate that extracellular OAS1 enters into cells and possesses a strong antiviral activity, both in vitro and in vivo, which is independent of RNase L. The OAS protein directly inhibits viral proliferation and does not require the activation of known antiviral signaling pathways. We propose that OAS produced by cells infected with viruses is released to the extracellular space, where it acts as a paracrine antiviral agent. Thus, the OAS protein represents the first direct antiviral compound released by virus-infected cells.

The size effect on mechanical properties of glassy polyethylene (PE) nanoscale particles has been investigated by extensive coarse-grained molecular dynamics simulations. The diameter of the PE particles varies in the range of 5-40 nm, we confirm that the particle's behaviour under compressive stress strongly depends on its size-the smaller the particle diameter is, the stiffer the particle behaves. The present mechanical responses of compressed particles are in good agreement with our previous experimental phenomena of micron-sized polymer particles measured by a nanoindentation-based flat punch method. Possible reasons for the size effect are discussed.

The 2'-5' oligoadenylate synthetase (OAS) family consist of three genes encoding active OAS enzymes (OAS1-3) and an OAS-Like (OASL) gene encoding an inactive protein. The transcription of all four members of this family is actively induced by interferon (IFN), but so far no attempt to systematically analyze the expression of these genes during viral infection has been made. We analyzed the expression of the human OAS1 and OASL genes in response to infection with Sendai virus or Influenza A virus. Surprisingly, we found a marked difference in the expression pattern of these genes. Our data showed that the OASL gene is rapidly induced in response to viral infection and that this induction is mediated by IFN regulatory factor 3 (IRF-3). In contrast to the OASL gene, the induction of the OAS1 gene by virus infection was lower, and did require a functional type I IFN response. The pronounced difference in gene regulation between the OAS1 and OASL genes agrees with a functional difference between these genes, which must exist as a consequence of the lack of the 2-5A synthetase activity of the OASL protein. Furthermore, the behavior of the OASL gene is consistent with the behavior of an antiviral gene.

The total cross sections for single ionization of helium and single and double ionization of argon by antiproton impact have been measured in the kinetic energy range from 3 to 25 keV using a new technique for the creation of intense slow antiproton beams. The new data provide benchmark results for the development of advanced descriptions of atomic collisions and we show that they can be used to judge, for the first time, the validity of the many recent theories.

Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We describe that NPY promotes SVZ neurogenesis. NPY (1 microM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ, as shown by functional autoradiography. Moreover, short exposure to NPY increased immunoreactivity for the phosphorylated form of extracellular signal-regulated kinase 1/2 in the nucleus, compatible with a trigger for proliferation, whereas 6 hours of treatment amplified the phosphorylated form of c-Jun-NH(2)-terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell-based brain therapy. Disclosure of potential conflicts of interest is found at the end of this article.

The unbalanced excitatory/inhibitory neurotransmitter function in the neuronal network afflicted by seizures is the main biochemical and biophysical hallmark of epilepsy. The aim of this work was to identify changes in the signaling mechanisms associated with neuropeptide Y (NPY)-mediated inhibition of glutamate release that may contribute to hyperexcitability. Using isolated rat hippocampal nerve terminals, we showed that the KCl-evoked glutamate release is inhibited by NPY Y2 receptor activation and is potentiated by the stimulation of protein kinase C (PKC). Moreover, we observed that immediately after status epilepticus (6 h postinjection with kainate, 10 mg/kg), the functional inhibition of glutamate release by NPY Y2 receptors was transiently blocked concomitantly with PKC hyperactivation. The pharmacological blockade of seizure-activated PKC revealed again the Y2 receptor-mediated inhibition of glutamate release. The functional activity of PKC immediately after status epilepticus was assessed by evaluating phosphorylation of the AMPA receptor subunit GluR1 (Ser-831), a substrate for PKC. Moreover, NPY-stimulated [35S]GTPgammaS autoradiographic binding studies indicated that the common target for Y2 receptor and PKC on the inhibition/potentiation of glutamate release was located downstream of the Y2 receptor, or its interacting G-protein, and involves voltage-gated calcium channels.

Although electroconvulsive seizures (ECS) are widely used as a treatment for severe depression, the working mechanism of ECS remains unclear. Repeated ECS causes anticonvulsant effects that have been proposed to underlie the therapeutic effect of ECS, and neuropeptide Y (NPY) is a potential candidate for mediating this anticonvulsant effect. Repeated ECS results in prominent increases in NPY synthesis. In contrast, NPY-sensitive receptor binding is decreased, so it is unclear whether ECS causes a net increase in NPY signalling. Agonist-stimulated [35S]GTPgammaS binding is a method for detecting functional activation of G-protein-coupled receptors. The present study in mice examined the effects of daily ECS for 14 days on NPY-stimulated [35S]GTPgammaS functional binding and compared this with gene expression of NPY and NPY receptors as well as [125I]peptide YY (PYY) binding in hippocampus of the same animals. Significant increases in NPY mRNA and concomitant reductions in NPY-sensitive binding were found in the dentate gyrus, hippocampal CA1, and neocortex of ECS treated mice, which is consistent with previous rat data. These changes remained significant 1 week after repeated ECS. Significant increases in NPY Y1, Y2, and Y5 mRNA were found in the dentate gyrus after ECS. Surprisingly, unaltered levels of functional NPY receptor binding accompanied the decreased NPY-sensitive binding. This suggests that mechanisms coupling NPY receptor stimulation to G-protein activation could be augmented after repeated ECS. Thus increased synthesis of NPY after repeated ECS should result in a net increase in NPY signalling in spite of reduced levels of NPY-sensitive binding., (Copyright 2006 Wiley-Liss, Inc.)

To study the 5-HT(2A) receptors in the living human brain, using positron emission tomography (PET), two selective radiotracers are currently in use: [(18)F]altanserin and [(11)C]MDL 100907. It is, however, currently unknown to what extent data obtained with either tracer are directly comparable. The aim of this study was to compare binding characteristics of these two radiotracers in rat brain with respect to affinity (K(d)), receptor binding density (B(max)), binding potential (BP), and nonspecific binding. Further, binding kinetics, sensitivity towards competition with the endogenous transmitter serotonin, and the competitive/noncompetitive interaction between the two radioligands were evaluated. In addition, the selectivity of [(18)F]altanserin for the 5-HT(2A) receptor was assessed. The K(d) value of [(18)F]altanserin and [(3)H]MDL 100907 was in the order of 0.3 nM. B(max) in frontal cortex was 523 and 527 fmol/mg protein, respectively. The binding of [(18)F]altanserin was not influenced by blocking either the 5-HT(2B/2C) or the alpha(1)-adrenergic receptors. At 37 degrees C the association t(1/2) was 2.8 and 2.7 min and the dissociation t(1/2) was 11 and 13.5 min for [(18)F]altanserin and [(3)H]MDL 100907, respectively. Both radioligands were displaced by 5-HT, only at high concentrations; the K(i) value of 5-HT ranging between 650 and 3,300 nM. This indicates that binding of both radioligands in PET studies is not directly influenced by changes in endogenous 5-HT.Overall, the binding of [(18)F]altanserin and [(3)H]MDL 100907 to the 5-HT(2A) receptor was very comparable, showing selective high affinity binding in the subnanomolar range., (Copyright 2005 Wiley-Liss, Inc.)

The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [18F]altanserin. [18F]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [18F]altanserin administration. Three hours after commencement of radiotracer administration, 0.25 mg/kg of the selective serotonin reuptake inhibitor, citalopram (Lundbeck, Valby, Denmark), was administered to all subjects as a constant infusion for 20 minutes. To reduce 5-HT1A-mediated autoinhibition of cortical 5-HT release, four of the seven subjects were pretreated with the partial 5-HT1A agonist pindolol for 3 days at an increasing oral dose (25 mg on the day of scanning). In each subject, the baseline condition (120 to 180 minutes) was compared with the stimulated condition (195 to 300 minutes). Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT-induced adverse effect, cortical [18F]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment. The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [18F]altanserin are discussed.

Several major bacterial pathogens and related commensal species colonizing the human mucosa express phosphocholine (PC) at their cell surfaces. PC appears to impact host-microbe biology by serving as a ligand for both C-reactive protein and the receptor for platelet-activating factor. Type IV pili of Neisseria gonorrhoeae (Ng) and Neisseria meningitidis, filamentous protein structures critical to the colonization of their human hosts, are known to react variably with monoclonal antibodies recognizing a PC epitope. However, the structural basis for this reactivity has remained elusive. To address this matter, we exploited the finding that the PilE pilin subunit in Ng mutants lacking the PilV protein acquired the PC epitope independent of changes in pilin primary structure. Specifically, we show by using mass spectrometry that PilE derived from the pilV background is composed of a mixture of subunits bearing O-linked forms of either phosphoethanolamine (PE) or PC at the same residue, whereas the wild-type background carries only PE at that same site. Therefore, PilV can influence pilin structure and antigenicity by modulating the incorporation of these alternative modifications. The disaccharide covalently linked to Ng pilin was also characterized because it is present on the same peptides bearing the PE and PC modifications and, contrary to previous reports, was found to be linked by means of 2,4-diacetamido-2,4,6-trideoxyhexose. Taken together, these findings provide new insights into Ng type IV pilus structure and antigenicity and resolve long-standing issues regarding the nature of both the PC epitope and the pilin glycan.

In order to determine the prevalence of Cryptosporidium and other intestinal parasites, a household sample survey of children under 5 years old was carried out during the late dry season in 8 rural villages in southern Guinea-Bissau, West Africa. Cryptosporidium oocysts were found in 10 of 270 stool samples (3.7%), using a safranin-methylene blue staining method. Of these 10 children (age range 5-16 months), all non-Muslims, 6 had diarrhoea, giving a prevalence of 12.5% in 48 children with diarrhoea, compared with 1.8% in children without diarrhoea (P less than 0.001). The ethnic group with the highest prevalence (9.2%) also kept most domestic animals, and was the only group to keep cattle. Giardia lamblia was found in 16 children, and the overall prevalences of other enteric parasites were: hookworm, 21.7%; Strongyloides stercoralis, 7.4%; Ascaris lumbricoides, 6.9%; Trichuris trichiura, 4.4%; Entamoeba histolytica, 1.5%; and Taenia sp., 0.5%. The prevalence of cryptosporidiosis was highest in the age group 7-12 months, while for the other parasites it was highest in the oldest children. The prevalence of hookworm was highest (c. 50%) in the southernmost villages. No significant relationship was found between hookworm infection and anaemia.

In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine.