Catalytic transformations of syngas (a mixture of H2 and CO), which is one of the most important C1-chemistry platforms, and CO2, a greenhouse gas released from human industrial activities but also a candidate of abundant carbon feedstock, into chemicals and fuels have attracted much attention in recent years. Fischer-Tropsch (FT) synthesis is a classic route of syngas chemistry, but the product selectivity of FT synthesis is limited by the Anderson-Schulz-Flory (ASF) distribution. The hydrogenation of CO2 into C2+ hydrocarbons involving C-C bond formation encounters similar selectivity limitation. The present article focuses on recent advances in breaking the selectivity limitation by using a reaction coupling strategy for hydrogenation of both CO and CO2 into C2+ hydrocarbons, which include key building-block chemicals, such as lower (C2-C4) olefins and aromatics, and liquid fuels, such as gasoline (C5-C11 hydrocarbons), jet fuel (C8-C16 hydrocarbons) and diesel fuel (C10-C20 hydrocarbons). The design and development of novel bifunctional or multifunctional catalysts, which are composed of metal, metal carbide or metal oxide nanoparticles and zeolites, for hydrogenation of CO and CO2 to C2+ hydrocarbons beyond FT synthesis will be reviewed. The key factors in controlling catalytic performances, such as the catalyst component, the acidity and mesoporosity of the zeolite and the proximity between the metal/metal carbide/metal oxide and zeolite, will be analysed to provide insights for designing efficient bifunctional or multifunctional catalysts. The reaction mechanism, in particular the activation of CO and CO2, the reaction pathway and the reaction intermediate, will be discussed to provide a deep understanding of the chemistry of the new C1 chemistry routes beyond FT synthesis.

Control of African swine fever (ASF) in countries in Eastern, Central and Southern Africa (ECSA) is particularly complex owing to the presence of all three known epidemiological cycles of maintenance of the virus, namely an ancient sylvatic cycle involving the natural hosts and vectors of the disease as well as domestic cycles with and without involvement of natural vectors. While the situation is well documented in some of the countries, for others very little information is available. In spite of the unfavourable ASF situation, the pig population in the sub-region has grown exponentially in recent decades and is likely to continue to grow in response to rapid urban growth resulting in increasing demand for animal protein by populations that are no longer engaged in livestock production. Better management of ASF will be essential to permit the pig sector to reach its full potential as a supplier of high quality protein and a source of income to improve livelihoods and create wealth. No vaccine is currently available and it is likely that, in the near future, the sub-region will continue to rely on the implementation of preventive measures, based on the epidemiology of the disease, to avoid both the devastating losses that outbreaks can cause and the risk the sub-region poses to other parts of Africa and the world. The current situation in the ECSA sub-region is reviewed and gaps in knowledge are identified in order to support ongoing strategy development for managing ASF in endemic areas.

Pig production and pork consumption are very important to the People's Republic of China for both economic and cultural reasons. The incursion and spread of a disease such as African swine fever (ASF), which emerged in Eastern Europe in 2007, could have devastating socioeconomic consequences for both the Chinese and the global pig industry. The Chinese government consequently attributes a very high priority to ASF and is actively seeking to improve its preparedness. This paper discusses different drivers and pathways of potential emergence of ASF in China in light of the country's specificities, including international movements of people, pigs and pig products, swill feeding practices and wild boar populations. It suggests that effective ASF risk management in China will require a comprehensive and integrated approach linking science and policy and will need to involve all relevant stakeholders to develop realistic policies.

Understanding how assemblages of species responded to past climate change is a central goal of comparative phylogeography and comparative population genomics, an endeavour that has increasing potential to integrate with community ecology. New sequencing technology now provides the potential to perform complex demographic inference at unprecedented resolution across assemblages of nonmodel species. To this end, we introduce the aggregate site frequency spectrum (aSFS), an expansion of the site frequency spectrum to use single nucleotide polymorphism (SNP) data sets collected from multiple, co-distributed species for assemblage-level demographic inference. We describe how the aSFS is constructed over an arbitrary number of independent population samples and then demonstrate how the aSFS can differentiate various multispecies demographic histories under a wide range of sampling configurations while allowing effective population sizes and expansion magnitudes to vary independently. We subsequently couple the aSFS with a hierarchical approximate Bayesian computation (hABC) framework to estimate degree of temporal synchronicity in expansion times across taxa, including an empirical demonstration with a data set consisting of five populations of the threespine stickleback (Gasterosteus aculeatus). Corroborating what is generally understood about the recent postglacial origins of these populations, the joint aSFS/hABC analysis strongly suggests that the stickleback data are most consistent with synchronous expansion after the Last Glacial Maximum (posterior probability = 0.99). The aSFS will have general application for multilevel statistical frameworks to test models involving assemblages and/or communities, and as large-scale SNP data from nonmodel species become routine, the aSFS expands the potential for powerful next-generation comparative population genomic inference.

In this paper, we develop a theoretical expression for the signal-to-noise ratio (SNR) of shear strain elastograms. The previously-developed ideas for the axial strain filter (ASF) and lateral strain filter (LSF) are extended to define the concept of the shear strain filter (SSF). Some of our theoretical results are verified using simulations and phantom experiments. The results indicate that the signal-to-noise ratio of shear-strain elastograms (SNRsse) improves with increasing shear strain and with improvements in system parameters such as the sonographic signal-to-noise ratio (SNRs) beamwidth, center frequency and fractional bandwidth. The results also indicate that the amount of axial strain present along with the shear strain is an important parameter that determines the upper bound on SNRsse. The SNRsse will be higher in the absence of additional deformation due to axial strain.

BACKGROUND

Patients undergoing immune modulatory therapies for the treatment of autoimmune diseases such as multiple sclerosis, and individuals with an impaired-immune system, most notably AIDS patients, are in the high risk group of developing progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the white matter caused by human neurotropic polyomavirus, JC virus. It is now widely accepted that pathologic strains of JCV shows unique rearrangements consist of deletions and insertions within viral NCCR. While these kinds of rearrangements are related to viral tropism and pathology of the disease, their roles in molecular regulation of JCV gene expression and replication are unclear. We have previously identified SF2/ASF as a negative regulator of JCV gene expression in glial cells. This negative impact of SF2/ASF was dependent on its ability to bind a specific region mapped to the tandem repeat within viral promoter. In this report, functional role of SF2/ASF binding region in viral gene expression and replication was investigated by using deletion mutants of viral regulatory sequences.

RESULTS

The second 98-base-pair tandem repeat on Mad1 strain was first mutated by deletion and named Mad1-(1X98). In addition to this mutant, the CR3 region which served the binding side for SF2/ASF was also mutated and named Mad1-ΔCR3 (1X73). Both mutations were tested for SF2/ASF binding by ChIP assay. While SF2/ASF was associated with Mad1-WT and Mad1-(1X98), its interaction was completely abolished on Mad1-ΔCR3 (1X73) construct as expected. Surprisingly, reporter gene analysis of Mad1-(1X98) and Mad1-ΔCR3 (1X73) early promoter sequences showed two and three fold increase in promoter activities, respectively. The impact of "CR3" region on JCV propagation was also tested on the viral background. While replication of Mad1-(1X98) strain in glial cells was similar to Mad1-WT strain, propagation of Mad1-ΔCR3 (1X73) was less productive. Further analysis of the transcription mediated by Mad1-ΔCR3 (1X73) NCCR revealed that late gene expression was significantly affected.

CONCLUSIONS

The results of this study reveal a differential role of CR3 region within JCV NCCR in expression of JCV early and late genes.

We constructed a novel chicken (Gallus gallus) lung cDNA library fused inside yeast acting domain vector (pGADT7). Using yeast two-hybrid screening with highly pathogenic avian influenza (HPAI) nucleoprotein (NP) from the strain (A/chicken/Malaysia/5858/2004(H5N1)) as bait, and the Gallus gallus lung cDNA library as prey, a novel interaction between the Gallus gallus cellular RNA export adaptor protein Aly/REF and the viral NP was identified. This interaction was confirmed and validated with mammalian two hybrid studies and co-immunoprecipitation assay. Cellular localization studies using confocal microscopy showed that NP and Aly/REF co-localize primarily in the nucleus. Further investigations by mammalian two hybrid studies into the binding of NP of other subtypes of influenza virus such as the swine A/New Jersey/1976/H1N1 and pandemic A/Malaysia/854/2009(H1N1) to human Aly/REF, also showed that the NP of these viruses interacts with human Aly/REF. Our findings are also supported by docking studies which showed tight and favorable binding between H5N1 NP and human Aly/REF, using crystal structures from Protein Data Bank. siRNA knockdown of Aly/REF had little effect on the export of HPAI NP and other viral RNA as it showed no significant reduction in virus titer. However, UAP56, another component of the TREX complex, which recruits Aly/REF to mRNA was found to interact even better with H5N1 NP through molecular docking studies. Both these proteins also co-localizes in the nucleus at early infection similar to Aly/REF. Intriguingly, knockdown of UAP56 in A549 infected cells shows significant reduction in viral titer (close to 10 fold reduction). Conclusively, our study have opened new avenues for research of other cellular RNA export adaptors crucial in aiding viral RNA export such as the SRSF3, 9G8 and ASF/SF2 that may play role in influenza virus RNA nucleocytoplasmic transport.

With the increased number of identified nucleotide sequence variations in genes, the current challenge is to classify them as disease causing or neutral. These variants of unknown clinical significance can alter multiple processes, from gene transcription to RNA splicing or protein function. Using an approach combining several in silico tools, we identified some exons presenting weaker splicing motifs than other exons in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. These exons exhibit higher rates of basal skipping than exons harboring no identifiable weak splicing signals using minigene assays. We then screened 19 described mutations in three different exons, and identified exon-skipping substitutions. These substitutions induced higher skipping levels in exons having one or more weak splicing motifs. Indeed, this level remained under 2% for exons with strong splicing motifs and could reach 40% for exons having at least one weak motif. Further analysis revealed a functional exon splicing enhancer within exon 3 that was associated with the SR protein SF2/ASF and whose disruption induced exon skipping. Exon skipping was confirmed in vivo in two nasal epithelial cell brushing samples. Our approach, which point out exons with some splicing signals weaknesses, will help spot splicing mutations of clinical relevance.

To determine whether drying and hypertonicity of the airway surface fluid (ASF) are involved in thermally induced asthma, nine subjects performed isocapnic hyperventilation (HV) (minute ventilation 62.2 +/- 8.3 l/min) of frigid air (-8.9 +/- 3.3 degrees C) while periciliary fluid was collected endoscopically from the trachea. Osmolality was measured by freezing-point depression. The baseline 1-s forced expiratory volume was 73 +/- 4% of predicted and fell 26.4% 10 min postchallenge (P>> 0.0001). The volume of ASF collected was 11.0 +/- 2.2 microl at rest and remained constant during and after HV as the airways narrowed (HV 10.6 +/- 1.9, recovery 6.5 +/- 1.7 microl; P = 0.18). The osmolality also remained stable throughout (rest 336 +/- 16, HV 339 +/- 16, and recovery 352 +/- 19 mosmol/kgH(2)O, P = 0.76). These data demonstrate that airway desiccation and hypertonicity of the ASF do not develop during hyperpnea in asthma; therefore, other mechanisms must cause exercise- and hyperventilation-induced airflow limitation.

OBJECTIVE

To compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children.

METHODS

We calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models.

METHODS

Bucaramanga, Colombia.

METHODS

Children (n 1261) aged 6-10 years in Tanner stage 1 from a population-based study.

RESULTS

A total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01).

CONCLUSIONS

ASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children.

Geographic coordinates of selected pig farms with confirmed African swine fever (ASF) outbreaks in Ekiti, Lagos, Ogun, Ondo and Oyo States were used to create spatial models of pig farms and ASF outbreaks in south-western Nigeria between 1997 and 2005. The probability of ASF virus-free pigs remaining in a non-infected state when located at various distances from ASF virus infected pigs was estimated. Movement of infected stock was the most important means of spreading the virus. The estimated mean duration of clinical signs prior to death was 3.4 +/- 1.1 days (mean +/- standard deviation); the mean convalescent period was 16.3 +/- 2.3 days and the mean period of survival after full recovery was 1 084 +/- 145.1 days. The continuous presence of recovered pigs in the population enables virus spread through trade and breeding. There is an urgent need for the implementation of an ASF eradication programme in Nigeria.

The gene encoding protein p37, one of the major structural proteins of African swine fever (ASF) virus has been mapped and sequenced. Protein p37 was obtained from purified virions and the first 27 amino acids from its NH2-terminal end were identified by automatic Edman degradation. To map the gene encoding protein p37, a mixture of 20-mer deoxyoligonucleotides based upon a part of this amino acid sequence was hybridized to cloned ASF virus restriction fragments. This allowed localization of the gene in fragment KpnI F/HindIII G1 of the African swine fever virus genome. An analysis of the DNA sequence from this region revealed an open reading frame encoding 418 amino acids. In this sequence, the 27 NH2-terminal amino acids determined by sequence analysis of protein p37 are preceded by a stretch of 132 amino acids residues, indicating that protein p37 is synthesized as a polypeptide of higher molecular weight and then post-translationally processed by cleavage of a Gly-Ala bond. This processing event accounts for the antigenic relationship of protein p37 to a virus-induced, nonstructural protein with a relative molecular weight of 60 kD.

We have detected 86 African swine fever (ASF) virus-induced proteins in infected pig macrophages by two-dimensional electrophoresis. No differences among protein patterns of wild-type viruses could be observed by this methodology. However, during cell culture adaptation and propagation we have characterized changes in the molecular weight of the ASF virus specified protein p54, which show direct correlation with both size and number of viral subpopulation variants generated during cell culture propagation. Passages in culture appear to select for viral subpopulations that specify p54 proteins with higher molecular weights than the wild-type virus. The virus propagation in cell culture also affected its replication phenotype in pig macrophages decreasing the viral titers in these cells between passage 44 and 81. Nevertheless, the changes observed in p54 did not imply differences in biological properties, such as infectivity, virulence or host cell range among viral clones isolated, each one specifying for only one p54 form with different molecular weight. This protein becomes then a valuable quantification marker to follow evolution and generation of ASF virus diversity in vitro.

In this work we report the identification of a strong SF2/ASF binding site within exon 7 of the human fibrinogen Bbeta-chain gene (FGB). Its disruption in the wild-type context has no effect on exon recognition. However, when the mutation IVS7 + 1G>T--initially described in a patient suffering from congenital afibrinogenemia--is present, this SF2/ASF binding site is critical for cryptic 5'ss (splice site) definition. These findings, besides confirming and extending previous results regarding the effect of SF2/ASF on cryptic splice site activation, identify for the first time an enhancer sequence in the FGB gene specific for cryptic splice site usage. Taken together, they suggest the existence of a splicing-regulatory network that is normally silent in the FGB natural splicing environment but which can nonetheless influence splicing decisions when local contexts allow. On a more general note, our conclusions have implications for the evolution of alternative splicing processes and for the development of methods to control aberrant splicing in the context of disease-causing mutations.

In view of the fact that African swine fever (ASF) was recently introduced into the wild boar population of the European Union and that classical swine fever (CSF) keeps reoccurring, targeted surveillance is of utmost importance for early detection. Introduction of both diseases is usually accompanied by an increased occurrence of animals found dead. Thus, fallen wild boar are the main target for passive surveillance. However, encouraging reporting by hunters and sampling of these animals is difficult. Partly, these problems could be solved by providing a pragmatic sampling approach. For this reason, we assessed the applicability of three different dry/semi-dry blood swabs, namely a cotton swab, a flocked swab, and a forensic livestock swab, for molecular swine fever diagnosis. After nucleic acid extraction using manual and automated systems, routine quantitative real-time polymerase chain reactions (qPCR) were carried out. Results obtained from swabs or their fragments were compared to results generated from EDTA blood. It was shown that reliable detection of both pathogens was possible by qPCR. Shifts in genome copy numbers were observed, but they did not change the qualitative results. In general, all swabs were suitable, but the forensic swab showed slight advantages, especially in terms of cutting and further storage. Robustness of the method was confirmed by the fact that different extraction methods and protocols as well as storage at room temperature did not have an influence on the final outcome. Taken together, swab samples could be recommended as a pragmatic approach to sample fallen wild boar.

To alleviate poverty in developing countries, economies must grow. Without the necessary investments in human capital, national economic growth may not lead to poverty alleviation and socioeconomic development, nor be sustainable. Economic growth that leads to poverty alleviation is fueled by the creative and physical capacities of people. The impact of micronutrient malnutrition is established early in life, leading to growth stunting, lower cognitive abilities, lethargy and poor attention, and greater severity and rates of infection. These effects limit educational progress, physical work capacity and life expectancy, thereby reducing individual lifetime productivity and the aggregate ability of the population to enhance its well-being and participate in national and global markets. The diets of the poor are largely cereal-based, monotonous and lacking in diversity and micronutrients. Animal source foods (ASF) have been an important factor in human evolution, a component of what was an historically diverse diet and an important source of micronutrients. Poverty and micronutrient malnutrition positively influence each other. This poverty micronutrient malnutrition (PMM) trap requires outside inputs to change the state of development in developing countries. Nutrition interventions have been excellent investments in development. More productive interaction between agricultural scientists and nutritionists, supported by a strong federal agenda for development, is needed to break the PMM trap. In the end, food is the means by which nutrients are delivered. Food-based approaches will require long-term commitments, but are more likely to be sustainable because they are part of a development process that leads to long-term economic growth.

Extracellular African swine fever (ASF) virus particles were specifically agglutinated by several lectins, suggesting the presence of surface glycosylated component(s) containing at least glucose, mannose, or both; galactose, N-acetylgalactosamine, or both; N-acetylneuraminic acid and N-acetylglucosamine, but not fucose. When virions were purified from infected Vero cells labeled with [14C]glucosamine, [14C]galactose and analyzed by polyacrylamide gel electrophoresis, no major structural glycoproteins were detected. However, several species of glycolipids were found when virions were extracted with organic solvents and analyzed by thin layer chromatography. These, plus two minor glycosylated structural components, of apparent mol wt 230K and 95K, could account for the agglutination of ASF virions with concanavalin A.

METHODS

Four separate studies on the role of Amicar in decreasing perioperative blood loss in idiopathic scoliosis.

OBJECTIVE

To assess the efficacy and possible mechanisms of action for Amicar.

BACKGROUND

Preliminary prospective, randomized double-blind and analysis of same-day anterior spinal fusion (ASF), fibrinogen, and posterior spinal fusion (PSF) studies have demonstrated Amicar to be effective in idiopathic scoliosis surgery. Increased fibrinogen secretion is a possible explanation.

METHODS

Amicar is administered at 100 mg/kg over 15 minutes not to exceed 5 g at anesthesia induction. Maintenance is 10 mg/kg per hour until wound closure.

RESULTS

Preliminary study: Amicar (N = 28) was effective compared with a control group (N = 31). Perioperative blood loss and transfusion following PSF were 1,604 +/- 517 mL and 1.1 +/- 1.0 U in the Amicar group compared with 2,312 +/- 994 mL and 2.1 +/- 1.1 U in the control group (P < 0.003). Prospective, randomized double-blind study confirmed this efficacy, although primarily in postoperative suction drainage: 1,391 +/- 212 mL and 1.1 +/- 1.0 U compared with 1,716 +/- 513 mL and 2.1 +/- 1.3 U (P < 0.002). A fibrinogen study (N = 21) demonstrated steady and excessive increase following PSF: before surgery it was 266 +/- 63 mg/dL and on the fifth postoperative day 699 +/- 94 mg/dL. In same-day anterior and posterior spinal surgery, Amicar was again effective, but primarily in decreasing chest tube drainage and during PSF. Group 1 (N = 15, no Amicar) 3,807 +/- 105 mL and 3.1 +/- 1.5 U; Group 2 (N = 27, Amicar for PSF only) 2,080 +/- 659 mL and 1.9 +/- 0.9 U; and Group 3 (N = 16, both ASF and PSF) 2,183 +/- 851 mL and 1.0 +/- 0.8 U.

CONCLUSIONS

Amicar appears highly effective in decreasing perioperative blood loss. This results in less autologous blood donation, blood transfusion, costs, and complications. Its mechanism of action is uncertain but may be related to increased fibrinogen secretion.

Protection against intestinal secretion induced by cholera toxin (CT) was studied in adult and suckling rats. Peroral CT treatment of lactating females protected their suckling offspring against diarrhea. This milk contained a protective antisecretory factor (ASF) as shown by passive peroral or intravenous transfer of the milk to adult, nontreated recipients in which the cholera response was tested in ligated jejunal loops. Bile from CT-treated rats also contained ASF, which was still present 100 days after the last treatment. Although milk and bile from untreated rats contained no ASF, bile from very old untreated rats did. Chemical characterization showed that ASF in bile and milk both had isoelectric points of about 5.0 and molecular weights of about 25,000. These data are similar to those previously obtained for ASF isolated from porcine pituitary glands, and show that the antisecretory activity is unrelated to immunoglobulins.

The alternative splicing of the last intron (intron D) of bovine growth hormone (bGH) pre-mRNA requires a down-stream exonic splicing enhancer (FP/ESE). The presence of at least one SR protein has been shown to be essential for FP/ESE function and splicing of intron D in in vitro splicing assays. However, in vitro reconstitution of splicing using individual purified SR proteins may not accurately reflect the true complexity of alternative splicing in an intact nucleus, where multiple SR proteins in varying amounts are likely to be available simultaneously. Here, a panel of recombinant baculovirus-expressed SR proteins was produced and tested for the ability to activate FP/ESE-dependent splicing. Individual recombinant SR proteins differed significantly in their activity in promoting intron D splicing. Among the recombinant SR proteins tested, SRp55 was the most active, SC35 showed very little activity, and ASF/SF2 and 9G8 individually had intermediate activity. At least one SR protein (ASF/SF2) bound to the FP/ESE with characteristics of a cooperative interaction. Most interestingly, low concentrations of ASF/SF2 and 9G8 acted synergistically to activate intron D splicing. This was due in part to synergistic binding to the FP/ESE. Splicing of bGH intron D is inherently complex, and is likely controlled by an interaction of the FP/ESE with several trans-acting protein factors acting both independently and cooperatively. This level of complexity may be required for precise control of alternative splicing by an exon sequence, which simultaneously is constrained to maintain translational integrity of the mature mRNA.

METHODS

A retrospective cohort study was conducted.

OBJECTIVE

To evaluate the results of anterior spinal fusion with anterior instrumentation alone in selected patients with neuromuscular scoliosis.

BACKGROUND

Traditionally posterior spinal fusion with instrumentation has been done, usually to the pelvis, to achieve correction of neuromuscular scoliosis. However, certain selected patients might benefit from shorter fusion segment to preserve some motion and yet still achieve good correction of the curve. This may serve to improve or preserve various functional abilities that might be adversely affected by a long fusion.

METHODS

Patients who had anterior spinal fusion (ASF) with anterior instrumentation (AI) alone were selected from an entire group of patients with neuromuscular spinal deformity who had surgery at Shriners Hospital for Children-Chicago since January of 1988. The charts and radiographs of these patients were examined and various radiographic parameters were measured pre- and after surgery and at final follow-up. Additionally, functional level of the patients included, ambulatory status was obtained from the medical records.

RESULTS

In these 21 patients excellent results were obtained with regard to primary and secondary curve correction as well as the pelvic obliquity without significant deterioration at final follow-up. Ambulatory status was not changed after surgery. This cohort of patients had various neuromuscular diseases. However, the majority of them had myelomeningocele. Few complications occurred which resulted in the reoperation of several patients who had progression of the curve around the instrumented segment which itself remained unchanged when the complication was recognized. One infection occurred requiring irrigation and debridement.

CONCLUSIONS

In selected patients with neuromuscular scoliosis, even that associated with pelvic obliquity, excellent correction and maintenance correction can be obtained fusing a relatively short segment of the spine with ASF and AI rather than a long construct posteriorly to the pelvis. Maintenance of the correction of the primary curve as well as the pelvic obliquity was maintained over the period of follow-up. This approach for selected patients should be offered as a way of limiting the extend of the surgery, preserving motion segments and maintaining orenhancing functions such as activities of daily living.

African swine fever (ASF) has recently made its appearance in Madagascar. Ticks of the Ornithodoros moubata group, considered to be O. porcinus Walton, 1962 were formerly known to occur in western Madagascar, but seem to have disappeared from that region. However, three new sites where they occur were found in the humid and cool central highlands of Anatananarivo province. These ticks are known to be efficient reservoirs and vectors of ASF and constitute a considerable complication to the control of the disease. The authors also discuss another potentially complicating factor, the presence of a species of African bushpig, Potamochoerus larvatus.

In about 20-30% of phenylketonuria (PKU) patients, phenylalanine (Phe) levels can be controlled by cofactor 6R-tetrahydrobiopterin (BH(4)) administration. The phenylalanine hydroxylase (PAH) genotype has a predictive value concerning BH(4)-response and therefore a correct assessment of the mutation molecular pathology is important. Mutations that disturb the splicing of exons (e.g. interplay between splice site strength and regulatory sequences like exon splicing enhancers (ESEs)/exon splicing silencers (ESSs)) may cause different severity of PKU. In this study, we identified PAH exon 11 as a vulnerable exon and used patient derived lymphoblast cell lines and PAH minigenes to study the molecular defect that impacted pre-mRNA processing. We showed that the c.1144T>C and c.1066-3C>T mutations cause exon 11 skipping, while the c.1139C>T mutation is neutral or slightly beneficial. The c.1144T>C mutation resides in a putative splicing enhancer motif and binding by splicing factors SF2/ASF, SRp20 and SRp40 is disturbed. Additional mutations in potential splicing factor binding sites contributed to elucidate the pathogenesis of mutations in PAH exon 11. We suggest that PAH exon 11 is vulnerable due to a weak 3' splice site and that this makes exon 11 inclusion dependent on an ESE spanning position c.1144. Importantly, this implies that other mutations in exon 11 may affect splicing, since splicing is often determined by a fine balance between several positive and negative splicing regulatory elements distributed throughout the exon. Finally, we identified a pseudoexon in intron 11, which would have pathogenic consequences if activated by mutations or improved splicing conditions. Exonic mutations that disrupt splicing are unlikely to facilitate response to BH(4) and may lead to inconsistent genotype-phenotype correlations. Therefore, recognizing such mutations enhances our ability to predict the BH(4)-response.

The mammalian serine-arginine (SR) protein, ASF/SF2, contains multiple contiguous RS dipeptides at the C terminus, and approximately 12 of these serines are processively phosphorylated by the SR protein kinase 1 (SRPK1). We have recently shown that a docking motif in ASF/SF2 specifically interacts with a groove in SRPK1, and this interaction is necessary for processive phosphorylation. We previously showed that SRPK1 and its yeast ortholog Sky1p maintain their active conformations using diverse structural strategies. Here we tested if the mechanism of ASF/SF2 phosphorylation by SRPK is evolutionarily conserved. We show that Sky1p forms a stable complex with its heterologous mammalian substrate ASF/SF2 and processively phosphorylates the same sites as SRPK1. We further show that Sky1p utilizes the same docking groove to bind yeast SR-like protein Gbp2p and phosphorylates all three serines present in a contiguous RS dipeptide stretch. However, the mechanism of Gbp2p phosphorylation appears to be non-processive. Thus, there are physical attributes of SR and SR-like substrates that dictate the mechanism of phosphorylation, whereas the ability to processively phosphorylate substrates is inherent to SR protein kinases.