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  • Lokki, A I; Järvelä, Irma; Israelsson, Elisabeth; Maiga, Bakary; Troye-Blomberg, Marita; Dolo, Amagana; Doumbo, Ogobara K; Meri, Seppo; Holmberg, Ville (BioMed Central Ltd, 2011)
    Abstract Background Fulani are a widely spread African ethnic group characterized by lower susceptibility to Plasmodium falciparum, clinical malaria morbidity and higher rate of lactase persistence compared to sympatric tribes. Lactase non-persistence, often called lactose intolerance, is the normal condition where lactase activity in the intestinal wall declines after weaning. Lactase persistence, common in Europe, and in certain African people with traditions of raising cattle, is caused by polymorphisms in the enhancer region approximately 14 kb upstream of the lactase gene. Methods To evaluate the relationship between malaria and lactase persistence genotypes, a 400 bp region surrounding the main European C/T-13910 polymorphism upstream of the lactase gene was sequenced. DNA samples used in the study originated from 162 Fulani and 79 Dogon individuals from Mali. Results Among 79 Dogon only one heterozygote of the lactase enhancer polymorphism was detected, whereas all others were homozygous for the ancestral C allele. Among the Fulani, the main European polymorphism at locus C/T-13910 was by far the most common polymorphism, with an allele frequency of 37%. Three other single-nucleotide polymorphisms were found with allele frequencies of 3.7%, 1.9% and 0.6% each. The novel DNA polymorphism T/C-13906 was seen in six heterozygous Fulani. Among the Fulani with lactase non-persistence CC genotypes at the C/T-13910 locus, 24% had malaria parasites detectable by microscopy compared to 18% for lactase persistent genotypes (P = 0.29). Pooling the lactase enhancer polymorphisms to a common presumptive genotype gave 28% microscopy positives for non-persistent and 17% for others (P = 0.11). Conclusions Plasmodium falciparum parasitaemia in asymptomatic Fulani is more common in individuals with lactase non-persistence genotypes, but this difference is not statistically significant. The potential immunoprotective properties of dietary cow milk as a reason for the partial malaria resistance of Fulani warrant further investigation.
  • Weitschek, Emanuel; Cunial, Fabio; Felici, Giovanni (BioMed Central, 2015)
    Abstract Alignment-free algorithms can be used to estimate the similarity of biological sequences and hence are often applied to the phylogenetic reconstruction of genomes. Most of these algorithms rely on comparing the frequency of all the distinct substrings of fixed length (k-mers) that occur in the analyzed sequences. In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa. This method searches for a minimal subset of k-mers whose relative frequencies are used to build classification models as disjunctive-normal-form logic formulas (if-then rules). We apply LAF successfully to the classification of bacterial genomes to their corresponding taxonomy. In particular, we succeed in obtaining reliable classification at different taxonomic levels by extracting a handful of rules, each one based on the frequency of just few k-mers. State of the art methods to adjust the frequency of k-mers to the character distribution of the underlying genomes have negligible impact on classification performance, suggesting that the signal of each class is strong and that LAF is effective in identifying it.
  • Tanislav, Christian; Grittner, Ulrike; Misselwitz, Bjoern; Jungehuelsing, Gerhard Jan; Enzinger, Christian; von Sarnowski, Bettina; Putaala, Jukka; Kaps, Manfred; Kropp, Peter; Rolfs, Arndt; Tatlisumak, Turgut; Fazekas, Franz; Kolodny, Edwin; Norrving, Bo (BioMed Central Ltd, 2014)
    Abstract Background Translating knowledge derived from medical research into the clinical setting is dependent on the representativeness of included patients. Therefore we compared baseline data of patients included in a recent large study addressing young stroke in comparison to a large representative stroke registry. Methods We analysed baseline data of 5023 patients (age 18-55 years) with an acute cerebrovascular event included in the sifap1 (Stroke in Young Fabry Patients) study. For comparison 17007 stroke patients (age 18-55 years) documented (2004-2010) in a statutory stroke registry of the Institute of Quality Assurance Hesse of the Federal State of Hesse (GQH), Germany. Results Among 17007 juvenile (18-55 years) patients identified in the GQH registry 15997 had an ischaemic stroke or TIA (91%) or an intracranial haemorrhage (9%). In sifap1 5023 subjects were included. Sex distribution was comparable (men: 59% sifap1 versus 60.5% GQH) whereas age differed between the groups: median age was 46 years in sifap1 versus 49 years in GQH. Slightly higher percentages for diabetes mellitus and hypertension in the GQH registry were noted. There were no differences in stroke severity as assessed by NIHSS (median 3) and mRS (median 2). In patients with ischaemic stroke or TIA (n = 4467 sifap1; n = 14522 GQH) higher rates of strokes due to small artery occlusion and atherosclerosis occurred in older age groups; cardioembolism and strokes of other determined cause occurred more frequently in younger patients. Conclusions The comparison of baseline characteristics between the sifap1 study and the GQH registry revealed differences mainly determined by age.
  • Kuuskeri, Jaana; Mäkelä, Miia R; Isotalo, Jarkko; Oksanen, Ilona; Lundell, Taina (BioMed Central, 2015)
    Abstract Background The fungal genus Phlebia consists of a number of species that are significant in wood decay. Biotechnological potential of a few species for enzyme production and degradation of lignin and pollutants has been previously studied, when most of the species of this genus are unknown. Therefore, we carried out a wider study on biochemistry and systematics of Phlebia species. Methods Isolates belonging to the genus Phlebia were subjected to four-gene sequence analysis in order to clarify their phylogenetic placement at species level and evolutionary relationships of the genus among phlebioid Polyporales. rRNA-encoding (5.8S, partial LSU) and two protein-encoding gene (gapdh, rpb2) sequences were adopted for the evolutionary analysis, and ITS sequences (ITS1 + 5.8S + ITS2) were aligned for in-depth species-level phylogeny. The 49 fungal isolates were cultivated on semi-solid milled spruce wood medium for 21 days in order to follow their production of extracellular lignocellulose-converting oxidoreductases and carbohydrate active enzymes. Results Four-gene phylogenetic analysis confirmed the polyphyletic nature of the genus Phlebia. Ten species-level subgroups were formed, and their lignocellulose-converting enzyme activity profiles coincided with the phylogenetic grouping. The highest enzyme activities for lignin modification (manganese peroxidase activity) were obtained for Phlebia radiata group, which supports our previous studies on the enzymology and gene expression of this species on lignocellulosic substrates. Conclusions Our study implies that there is a species-level connection of molecular systematics (genotype) to the efficiency in production of both lignocellulose-converting carbohydrate active enzymes and oxidoreductases (enzyme phenotype) on spruce wood. Thus, we may propose a similar phylogrouping approach for prediction of lignocellulose-converting enzyme phenotypes in new fungal species or genetically and biochemically less-studied isolates of the wood-decay Polyporales.
  • Kuuskeri, Jaana; Mäkelä, Miia R; Isotalo, Jarkko; Oksanen, Ilona; Lundell, Taina (BioMed Central, 2015)
    Abstract Background The fungal genus Phlebia consists of a number of species that are significant in wood decay. Biotechnological potential of a few species for enzyme production and degradation of lignin and pollutants has been previously studied, when most of the species of this genus are unknown. Therefore, we carried out a wider study on biochemistry and systematics of Phlebia species. Methods Isolates belonging to the genus Phlebia were subjected to four-gene sequence analysis in order to clarify their phylogenetic placement at species level and evolutionary relationships of the genus among phlebioid Polyporales. rRNA-encoding (5.8S, partial LSU) and two protein-encoding gene (gapdh, rpb2) sequences were adopted for the evolutionary analysis, and ITS sequences (ITS1 + 5.8S + ITS2) were aligned for in-depth species-level phylogeny. The 49 fungal isolates were cultivated on semi-solid milled spruce wood medium for 21 days in order to follow their production of extracellular lignocellulose-converting oxidoreductases and carbohydrate active enzymes. Results Four-gene phylogenetic analysis confirmed the polyphyletic nature of the genus Phlebia. Ten species-level subgroups were formed, and their lignocellulose-converting enzyme activity profiles coincided with the phylogenetic grouping. The highest enzyme activities for lignin modification (manganese peroxidase activity) were obtained for Phlebia radiata group, which supports our previous studies on the enzymology and gene expression of this species on lignocellulosic substrates. Conclusions Our study implies that there is a species-level connection of molecular systematics (genotype) to the efficiency in production of both lignocellulose-converting carbohydrate active enzymes and oxidoreductases (enzyme phenotype) on spruce wood. Thus, we may propose a similar phylogrouping approach for prediction of lignocellulose-converting enzyme phenotypes in new fungal species or genetically and biochemically less-studied isolates of the wood-decay Polyporales.
  • Tommiska, Johanna; Sorensen, Kaspar; Aksglaede, Lise; Koivu, Rosanna; Puhakka, Lea; Juul, Anders; Raivio, Taneli (BioMed Central Ltd, 2011)
    Abstract Background Pubertal timing is a strongly heritable trait, but no single puberty gene has been identified. Thus, the genetic background of idiopathic central precocious puberty (ICPP) is poorly understood. Overall, the genetic modulation of pubertal onset most likely arises from the additive effect of multiple genes, but also monogenic causes of ICPP probably exist, as cases of familial ICPP have been reported. Mutations in KISS1 and KISSR, coding for kisspeptin and its receptor, involved in GnRH secretion and puberty onset, have been suggested causative for monogenic ICPP. Variation in LIN28B was associated with timing of puberty in genome-wide association (GWA) studies. LIN28B is a human ortholog of the gene that controls, through microRNAs, developmental timing in C. elegans. In addition, Lin28a transgenic mice manifest the puberty phenotypes identified in the human GWAS. Thus, both LIN28B and LIN28A may have a role in pubertal development and are good candidate genes for monogenic ICPP. Methods Thirty girls with ICPP were included in the study. ICPP was defined by pubertal onset before 8 yrs of age, and a pubertal LH response to GnRH testing. The coding regions of LIN28B, LIN28A, KISS1, and KISS1R were sequenced. The missense change in LIN28B was also screened in 132 control subjects. Results No rare variants were detected in KISS1 or KISS1R in the 30 subjects with ICPP. In LIN28B, one missense change, His199Arg, was found in one subject with ICPP. However, this variant was also detected in one of the 132 controls. No variation in LIN28A was found. Conclusions We did not find any evidence that mutations in LIN28B or LIN28A would underlie ICPP. In addition, we confirmed that mutations in KISS1 and KISS1R are not a common cause for ICPP.
  • Haapala, Sini; Niemitalo-Haapola, Elina; Raappana, Antti; Kujala, Tiia; Suominen, Kalervo; Jansson-Verkasalo, Eira; Kujala, Teija (BioMed Central, 2016)
    Abstract Background A large group of young children are exposed to repetitive middle ear infections but the effects of the fluctuating hearing sensations on immature central auditory system are not fully understood. The present study investigated the consequences of early childhood recurrent acute otitis media (RAOM) on involuntary auditory attention switching. Methods By utilizing auditory event-related potentials, neural mechanisms of involuntary attention were studied in 22–26 month-old children (N = 18) who had had an early childhood RAOM and healthy controls (N = 19). The earlier and later phase of the P3a (eP3a and lP3a) and the late negativity (LN) were measured for embedded novel sounds in the passive multi-feature paradigm with repeating standard and deviant syllable stimuli. The children with RAOM had tympanostomy tubes inserted and all the children in both study groups had to have clinically healthy ears at the time of the measurement assessed by an otolaryngologist. Results The results showed that lP3a amplitude diminished less from frontal to central and parietal areas in the children with RAOM than the controls. This might reflect an immature control of involuntary attention switch. Furthermore, the LN latency was longer in children with RAOM than in the controls, which suggests delayed reorientation of attention in RAOM. Conclusions The lP3a and LN responses are affected in toddlers who have had a RAOM even when their ears are healthy. This suggests detrimental long-term effects of RAOM on the neural mechanisms of involuntary attention.
  • Raj, R; Kivisaari, R; Siironen, J; SkrifVars, M (BioMed Central Ltd, 2014)
  • Rodger, Marc A; Langlois, Nicole J; de Vries, Johanna IP; Rey, Évelyne; Gris, Jean-Christophe; Martinelli, Ida; Schleussner, Ekkehard; Ramsay, Timothy; Mallick, Ranjeeta; Skidmore, Becky; Middeldorp, Saskia; Bates, Shannon; Petroff, David; Bezemer, Dick; van Hoorn, Marion E; Abheiden, Carolien NH; Perna, Annalisa; de Jong, Paulien; Kaaja, Risto (BioMed Central Ltd, 2014)
    Abstract Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249
  • Laurenne, Nina; Tuominen, Jouni; Saarenmaa, Hannu; Hyvönen, Eero (BioMed Central, 2014)
    Abstract Background The scientific names of plants and animals play a major role in Life Sciences as information is indexed, integrated, and searched using scientific names. The main problem with names is their ambiguous nature, because more than one name may point to the same taxon and multiple taxa may share the same name. In addition, scientific names change over time, which makes them open to various interpretations. Applying machine-understandable semantics to these names enables efficient processing of biological content in information systems. The first step is to use unique persistent identifiers instead of name strings when referring to taxa. The most commonly used identifiers are Life Science Identifiers (LSID), which are traditionally used in relational databases, and more recently HTTP URIs, which are applied on the Semantic Web by Linked Data applications. Results We introduce two models for expressing taxonomic information in the form of species checklists. First, we show how species checklists are presented in a relational database system using LSIDs. Then, in order to gain a more detailed representation of taxonomic information, we introduce meta-ontology TaxMeOn to model the same content as Semantic Web ontologies where taxa are identified using HTTP URIs. We also explore how changes in scientific names can be managed over time. Conclusions The use of HTTP URIs is preferable for presenting the taxonomic information of species checklists. An HTTP URI identifies a taxon and operates as a web address from which additional information about the taxon can be located, unlike LSID. This enables the integration of biological data from different sources on the web using Linked Data principles and prevents the formation of information silos. The Linked Data approach allows a user to assemble information and evaluate the complexity of taxonomical data based on conflicting views of taxonomic classifications. Using HTTP URIs and Semantic Web technologies also facilitate the representation of the semantics of biological data, and in this way, the creation of more “intelligent” biological applications and services.
  • Lee, Jamie; Prokopec, Stephenie D; Watson, John D; Sun, Ren X; Pohjanvirta, Raimo; Boutros, Paul C (BioMed Central, 2015)
    Abstract Background 2,3,7,8–tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 μg/kg) in adult male and female C57BL/6Kuo mice. Results Several key findings were revealed by our study. 1) Hepatic transcriptomes varied significantly between the sexes at all doses examined. 2) The liver transcriptome of males was more dysregulated by TCDD than that of females. 3) The alteration of “AHR-core” genes was consistent in magnitude, regardless of sex. 4) A subset of genes demonstrated sex-dependent TCDD-induced transcriptional changes, including Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In addition, a meta-analysis was performed to contrast transcriptomic profiles of various organisms and tissues following exposure to equitoxic doses of TCDD. Minimal overlap was observed in the differences between TCDD-sensitive or TCDD-resistant models. Conclusions Sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes. In addition, complex interactions between the aryl hydrocarbon and sex hormone receptors may affect the observable differences in sensitivity phenotypes between the sexes. Further work is necessary to better understand the roles of those genes altered by TCDD in a sex-dependent manner, and their association with changes to sex hormones and receptors.
  • Lee, Jamie; Prokopec, Stephenie D; Watson, John D; Sun, Ren X; Pohjanvirta, Raimo; Boutros, Paul C (BioMed Central, 2015)
    Abstract Background 2,3,7,8–tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 μg/kg) in adult male and female C57BL/6Kuo mice. Results Several key findings were revealed by our study. 1) Hepatic transcriptomes varied significantly between the sexes at all doses examined. 2) The liver transcriptome of males was more dysregulated by TCDD than that of females. 3) The alteration of “AHR-core” genes was consistent in magnitude, regardless of sex. 4) A subset of genes demonstrated sex-dependent TCDD-induced transcriptional changes, including Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In addition, a meta-analysis was performed to contrast transcriptomic profiles of various organisms and tissues following exposure to equitoxic doses of TCDD. Minimal overlap was observed in the differences between TCDD-sensitive or TCDD-resistant models. Conclusions Sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes. In addition, complex interactions between the aryl hydrocarbon and sex hormone receptors may affect the observable differences in sensitivity phenotypes between the sexes. Further work is necessary to better understand the roles of those genes altered by TCDD in a sex-dependent manner, and their association with changes to sex hormones and receptors.
  • Kruit, Heidi; Heikinheimo, Oskari; Ulander, Veli-Matti; Aitokallio-Tallberg, Ansa; Nupponen, Irmeli; Paavonen, Jorma; Rahkonen, Leena (BioMed Central, 2015)
    Abstract Background Induction of labour is associated with increased risk for caesarean delivery among nulliparous women. The aims of this study were to evaluate the risk factors for caesarean delivery and to investigate the risk of maternal and neonatal infections in nulliparous women undergoing induction of labour by Foley catheter. Methods This clinical retrospective study of 432 nulliparous women with singleton pregnancy and intact amniotic membranes at or beyond 37 gestational weeks scheduled for induction of labour by Foley catheter was conducted over the course of one year, between January 2012 and January 2013, in Helsinki University Hospital. The main outcome measures were caesarean section rate and maternal and neonatal infections. Univariate and multivariate logistic regressions were used to estimate relative risks by odds ratios with 95 % confidence intervals. Results The caesarean section rate was 39.1 % (n = 169). In multivariate regression analysis, the factors associated with caesarean section were the need for oxytocin for labour induction [OR 2.9 (95 % CI 1.8-4.5) p < 0.001] and early epidural analgesia [OR 9.9 (95 % CI 2.1-47.5), p = 0.004]. The maternal intrapartum infection rate was 6.3 %, and the clinical neonatal infection rate was 2.8 %. In multivariate analysis, gestational diabetes was associated with maternal intrapartum infection [OR 4.3 (95 % CI 1.7-11.0, p = 0.002] and early epidural analgesia with neonatal clinical sepsis [OR 10.5 (95 % CI 1.4-76), p = 0.02]. Conclusions Oxytocin induction and early epidural analgesia were associated with caesarean delivery. Gestational diabetes and early epidural analgesia were associated with infectious morbidity. Since the first caesarean delivery has a major impact on subsequent pregnancies, optimising labour induction among nulliparous women is important.
  • Valros, Anna; Munsterhjelm, Camilla; Hänninen, Laura; Kauppinen, Tiina; Heinonen, Mari (BioMed Central, 2016)
    Abstract Background Tail biting is a common and serious welfare problem in pig production, causing large economical losses. Tail docking is performed routinely in most EU countries to reduce the tail biting risk. However, tail docking is painful, and does not prevent tail biting totally. The risk factors behind tail docking are multifactorial and most analyses are based on studies using biological or epidemiological approaches. There is very little information available on how producers deal with tail biting on-farm. There are also no studies on the attitude of producers towards tail docking and tail biting in systems with long-tailed pigs. We aimed to study how farmers rate the efficiency of different measures for preventing and intervening with tail biting, when tail docking is not allowed. Furthermore, we investigated the attitudes of Finnish farmers to tail docking and tail biting. Results Respondents scored feeding-related issues to be most important for prevention of tail biting, identifying and removing the biting pig as most important intervention measures, and straw as the most important manipulable material when preventing tail biting. Tail biting was not perceived as a very serious problem by over 70 % of the respondents, even though docking is not allowed, and was reported to occur close to a level which was also considered acceptable by the respondents. Most respondents did not think it is probable they would raise tail docked pigs if it were possible, but about 21 % probably would. Conclusions In comparison with other authors’ findings, the ranking of importance of risk factors for tail biting differs between scientists and farmers, and between farmers in different cultures of pig production. In addition, the attitude towards tail biting and tail docking appears to be very different in producers with different experiences of tail docking. These results indicate that a scientist-farmer dialogue, as well as international communication is important when trying to reduce the risk of tail biting, and subsequently the need for tail docking.
  • Moilanen, Ulla; Kellock, Miriam; Várnai, Anikó; Andberg, Martina; Viikari, Liisa (BioMed Central Ltd, 2014)
    Abstract Background The recalcitrance of softwood to enzymatic hydrolysis is one of the major bottlenecks hindering its profitable use as a raw material for platform sugars. In softwood, the guaiacyl-type lignin is especially problematic, since it is known to bind hydrolytic enzymes non-specifically, rendering them inactive towards cellulose. One approach to improve hydrolysis yields is the modification of lignin and of cellulose structures by laccase-mediator treatments (LMTs). Results LMTs were studied to improve the hydrolysis of steam pre-treated spruce (SPS). Three mediators with three distinct reaction mechanisms (ABTS, HBT, and TEMPO) and one natural mediator (AS, that is, acetosyringone) were tested. Of the studied LMTs, laccase-ABTS treatment improved the degree of hydrolysis by 54%, while acetosyringone and TEMPO increased the hydrolysis yield by 49% and 36%, respectively. On the other hand, laccase-HBT treatment improved the degree of hydrolysis only by 22%, which was in the same order of magnitude as the increase induced by laccase treatment without added mediators (19%). The improvements were due to lignin modification that led to reduced adsorption of endoglucanase Cel5A and cellobiohydrolase Cel7A on lignin. TEMPO was the only mediator that modified cellulose structure by oxidizing hydroxyls at the C6 position to carbonyls and partially further to carboxyls. Oxidation of the reducing end C1 carbonyls was also observed. In contrast to lignin modification, oxidation of cellulose impaired enzymatic hydrolysis. Conclusions LMTs, in general, improved the enzymatic hydrolysis of SPS. The mechanism of the improvement was shown to be based on reduced adsorption of the main cellulases on SPS lignin rather than cellulose oxidation. In fact, at higher mediator concentrations the advantage of lignin modification in enzymatic saccharification was overcome by the negative effect of cellulose oxidation. For future applications, it would be beneficial to be able to understand and modify the binding properties of lignin in order to decrease unspecific enzyme binding and thus to increase the mobility, action, and recyclability of the hydrolytic enzymes.
  • Krogius-Kurikka, Lotta; Lyra, Anna; Malinen, Erja; Aarnikunnas, Johannes; Tuimala, Jarno; Paulin, Lars; Mäkivuokko, Harri; Kajander, Kajsa; Palva, Airi (BioMed Central Ltd, 2009)
    Abstract Background A growing amount of scientific evidence suggests that microbes are involved in the aetiology of irritable bowel syndrome (IBS), and the gastrointestinal (GI) microbiota of individuals suffering from diarrhoea-predominant IBS (IBS-D) is distinguishable from other IBS-subtypes. In our study, the GI microbiota of IBS-D patients was evaluated and compared with healthy controls (HC) by using a high-resolution sequencing method. The method allowed microbial community analysis on all levels of microbial genomic guanine plus cytosine (G+C) content, including high G+C bacteria. Methods The collective faecal microbiota composition of ten IBS-D patients was analysed by examining sequences obtained using percent G+C (%G+C) -based profiling and fractioning combined with 16S rRNA gene clone library sequencing of 3267 clones. The IBS-D library was compared with an analogous healthy-control library of 23 subjects. Real-time PCR analysis was used to identify phylotypes belonging to the class Gammaproteobacteria and the order Coriobacteriales. Results Significant differences were found between clone libraries of IBS-D patients and controls. The microbial communities of IBS-D patients were enriched in Proteobacteria and Firmicutes, but reduced in the number of Actinobacteria and Bacteroidetes compared to control. In particular, 16S rDNA sequences belonging to the family Lachnospiraceae within the phylum Firmicutes were in greater abundance in the IBS-D clone library. Conclusions In the microbiota of IBS-D sufferers, notable differences were detected among the prominent bacterial phyla (Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria) localized within the GI tract.
  • Wang, Yilin; Hedman, Lea; Perdomo, Maria F; Elfaitouri, Amal; Bölin-Wiener, Agnes; Kumar, Arun; Lappalainen, Maija; Söderlund-Venermo, Maria; Blomberg, Jonas; Hedman, Klaus (BioMed Central, 2016)
    Abstract Background Human parvovirus B19 (B19V), cytomegalovirus (CMV) and Toxoplasma gondii (T. gondii) may cause intrauterine infections with potentially severe consequences to the fetus. Current serodiagnosis of these infections is based on detection of antibodies most often by EIA and individually for each pathogen. We developed singleplex and multiplex microsphere-based Suspension Immuno Assays (SIAs) for the simultaneous detection of IgG antibodies against B19V, CMV and T. gondii. Methods We tested the performances of SIAs as compared to in-house and commercial reference assays using serum samples from well-characterized cohorts. Results The IgG SIAs for CMV and T. gondii showed good concordance with the corresponding Vidas serodiagnostics. The B19V IgG SIA detected IgG in all samples collected >10 days after onset of symptoms and showed high concordance with EIAs (in-house and Biotrin). The serodiagnostics for these three pathogens performed well in multiplex format. Conclusions We developed singleplex and multiplex IgG SIAs for the detection of anti-B19V,-CMV and -T. gondii antibodies. The SIAs were highly sensitive and specific, and had a wide dynamic range. These components thus should be suitable for construction of a multiplex test for antibody screening during pregnancy.
  • Karhu, Lasse; Turku, Ainoleena; Xhaard, Henri (BioMed Central, 2015)
    Abstract Background Interactions between the orexin peptides and their cognate OX1 and OX2 receptors remain poorly characterized. Site-directed mutagenesis studies on orexin peptides and receptors have indicated amino acids important for ligand binding and receptor activation. However, a better understanding of specific pairwise interactions would benefit small molecule discovery. Results We constructed a set of three-dimensional models of the orexin 1 receptor based on the 3D-structures of the orexin 2 receptor (released while this manuscript was under review), neurotensin receptor 1 and chemokine receptor CXCR4, conducted an exhaustive docking of orexin-A16–33 peptide fragment with ZDOCK and RDOCK, and analyzed a total of 4301 complexes through multidimensional scaling and clustering. The best docking poses reveal two alternative binding modes, where the C-terminus of the peptide lies deep in the binding pocket, on average about 5–6 Å above Tyr6.48 and close to Gln3.32. The binding modes differ in the about 100° rotation of the peptide; the peptide His26 faces either the receptor’s fifth transmembrane helix or the seventh helix. Both binding modes are well in line with previous mutation studies and partake in hydrogen bonding similar to suvorexant. Conclusions We present two binding modes for orexin-A into orexin 1 receptor, which help rationalize previous results from site-directed mutagenesis studies. The binding modes should serve small molecule discovery, and offer insights into the mechanism of receptor activation.
  • Karhu, Lasse; Turku, Ainoleena; Xhaard, Henri (BioMed Central, 2015)
    Abstract Background Interactions between the orexin peptides and their cognate OX1 and OX2 receptors remain poorly characterized. Site-directed mutagenesis studies on orexin peptides and receptors have indicated amino acids important for ligand binding and receptor activation. However, a better understanding of specific pairwise interactions would benefit small molecule discovery. Results We constructed a set of three-dimensional models of the orexin 1 receptor based on the 3D-structures of the orexin 2 receptor (released while this manuscript was under review), neurotensin receptor 1 and chemokine receptor CXCR4, conducted an exhaustive docking of orexin-A16–33 peptide fragment with ZDOCK and RDOCK, and analyzed a total of 4301 complexes through multidimensional scaling and clustering. The best docking poses reveal two alternative binding modes, where the C-terminus of the peptide lies deep in the binding pocket, on average about 5–6 Å above Tyr6.48 and close to Gln3.32. The binding modes differ in the about 100° rotation of the peptide; the peptide His26 faces either the receptor’s fifth transmembrane helix or the seventh helix. Both binding modes are well in line with previous mutation studies and partake in hydrogen bonding similar to suvorexant. Conclusions We present two binding modes for orexin-A into orexin 1 receptor, which help rationalize previous results from site-directed mutagenesis studies. The binding modes should serve small molecule discovery, and offer insights into the mechanism of receptor activation.
  • Maliniemi, Pilvi; Hahtola, Sonja; Ovaska, Kristian; Jeskanen, Leila; Väkevä, Liisa; Jäntti, Kirsi; Stadler, Rudolf; Michonneau, David; Fraitag, Sylvie; Hautaniemi, Sampsa; Ranki, Annamari (BioMed Central, 2014)
    Abstract Background Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. SPTL affects predominantly young adults and presents with multifocal subcutaneous nodules and frequently associated autoimmune features. The pathogenesis of SPTL is not completely understood. Methods The aim of this study was to unravel molecular pathways critical to the SPTL pathogenesis. Therefore, we analyzed 23 skin samples from 20 newly diagnosed SPTL patients and relevant control samples of adipose and non-malignant panniculitis tissue by using gene expression microarray, quantitative PCR, and two-colour immunohistochemistry. Results Interestingly, indoleamine 2,3-dioxygenase (IDO-1), an immunotolerance-inducing enzyme, was among the most highly overexpressed genes in all comparisons. The expression of Th1-specific cytokines, known to be associated with autoimmune inflammation (i.e. IFNG, CXCR3, CXCL9, CXCL10, CXCL11, and CCL5), were also significantly increased. Confirmed using immunohistochemistry, the morphologically malignant lymphocytes expressed CXCR3 and CXCL9. IDO-1 expression was found both in some morphologically malignant lymphocytes rimming the adipocytes and in surrounding CD11c− CD68− cells but not in CD11c+ dendritic cells in the microenvironment. The proportion of FoxP3+ cells in SPTL exceeded that in the benign panniculitis samples. Conclusions Our results indicate that the up regulation of the tolerogenic IDO-1 together with the up regulation of IFNG, CXCR3 ligands, and CCL5 are features of SPTL lesions. We anticipate that the IFNG-inducible IDO-1 expression contributes to the formation of an immunosuppressive microenvironment, favorable for the malignant T cells. This study provides a relevant molecular basis for further studies exploring novel therapeutic means for subcutaneous T cell lymphoma.