ACONITASE 3 is part of theANAC017 transcription factor-dependent mitochondrial dysfunction response.

Mitochondria are tightly embedded within metabolic and regulatory networks that optimize plant performance in response to environmental challenges. The best-known mitochondrial retrograde signaling pathway involves stress-induced activation of the transcription factor NAC DOMAIN CONTAINING PROTEIN 17 (ANAC017), which initiates protective responses to stress-induced mitochondrial dysfunction in Arabidopsis (Arabidopsis thaliana). Posttranslational control of the elicited responses, however, remains poorly understood. Previous studies linked protein phosphatase 2A subunit PP2A-B'γ, a key negative regulator of stress responses, with reversible phosphorylation of ACONITASE 3 (ACO3). Here we report on ACO3 and its phosphorylation at Ser91 as key components of stress regulation that are induced by mitochondrial dysfunction. Targeted mass spectrometry-based proteomics revealed that the abundance and phosphorylation of ACO3 increased under stress, which required signaling through ANAC017. Phosphomimetic mutation at ACO3-Ser91 and accumulation of ACO3S91D-YFP promoted the expression of genes related to mitochondrial dysfunction. Furthermore, ACO3 contributed to plant tolerance against ultraviolet B (UV-B) or antimycin A-induced mitochondrial dysfunction. These findings demonstrate that ACO3 is both a target and mediator of mitochondrial dysfunction signaling, and critical for achieving stress tolerance in Arabidopsis leaves.

Red- and green-emitting nano-clay materials doped with Eu3+ and/or Tb3.

Trivalent europium (Eu3+ ) and terbium (Tb3+ ) ions are important activator centers used in different host lattices to produce red and green emitting materials. The current work shows the design of new clay minerals to act as host lattices for rare earth (RE) ions. Based on the hectorite structure, nano-chlorohectorites and nano-fluorohectorites were developed by replacing the OH- present in the hectorite structure with Cl- or F- , thus avoiding the luminescence quenching expected due to the OH- groups. The produced matrices were characterized through X-ray powder diffraction (XPD), transmission electron microscopy (TEM), FT-IR, 29 Si MAS (magic angle spinning) NMR, nitrogen sorption, thermogravimetry-differential scanning calorimetry (TGA-DSC) and luminescence measurements, indicating all good features expected from a host lattice for RE ions. The nano-clay materials were successfully doped with Eu3+ and/or Tb3+ to yield materials preserving the hectorite crystal structure and showing the related luminescence emissions. Thus, the present work shows that efficient RE3+ luminescence can be obtained from clays without the use of organic 'antenna' molecules.

Parental Risk Factors among Children with Reactive Attachment Disorder Referred to Specialized Services: A Nationwide Population-Based Study.

This nationwide population-based register study examined the family and parental risk factors associated with offspring reactive attachment disorder (RAD). We identified 614 children diagnosed with RAD from the Finnish Care Register for Health Care and each case was matched with four controls. Univariate and multivariate models examined the associations between risk factors and RAD. In the multivariate model, offspring RAD was associated with only mother, only father and both parents having psychiatric diagnoses. Increased odds were observed for maternal smoking during pregnancy, single motherhood and paternal age ≥ 45 years. This study provides information on several parental adversities and offspring RAD that have important implications for public health, when planning early prevention and interventions in infant mental health.

21Ne and 131Xe NMR study of electric field gradients and multinuclear NMR study of the composition of a ferroelectric liquid crystal.

This study has two goals. First, the electric field gradient (EFG) present in the liquid-crystalline phases of ferroelectric FELIX-R&D is determined using NMR spectroscopy of noble gases 21Ne and 131Xe. The 21Ne and 131Xe NMR spectra were recorded over a temperature range, which covers all the mesophases of FELIX-R&D: nematic N*, smectic A, and smectic C*. The spin quantum number of both 21Ne and 131Xe is 3/2. Their electric quadrupole moment interacts with the EFG at the nuclear site, which in liquid-crystalline phases results in the NMR spectra of the triplet structure, instead of a singlet detectable in the isotropic phase. The total EFG experienced by the noble gas nuclei consists of two contributions; one arises from the quadrupole moments of the liquid crystal molecules (external contribution) and the other one from the deformation of the electron distribution of the atoms (deformational contribution). The total EFGs determined from the 131Xe and 21Ne quadrupole splittings are very similar in the nematic and smectic A phases but differ in the smectic C* phase, being about twice larger in the 21Ne case which stems from the larger deformation of the xenon electron cloud than that of neon. For the first time, EFG was determined also in the smectic C* phase applying noble gas NMR spectroscopy. Second, the structure of molecules which, as a mixture, compose the used ferroelectric liquid crystal, FELIX-R&D, is determined by applying a number of various NMR methods and sophisticated spectral analysis. In this part, NMR spectra were recorded from FELIX-R&D/CDCl3 solution. The NMR spectral analysis was divided into four subsystems with over 13 000 000 nonzero intensity transitions. It appeared that FELIX-R&D is composed of three phenyl pyrimidine derivatives and a chiral dopant with fluorine in the asymmetric carbon atom.

Child and family-related predictors of psychological outcomes in children adopted from abroad; what is the role of caregiver time?

International adoptees need to cope with stressful transitions and to develop secure attachment with their caregivers at the same time. Although most children adopted from abroad adjust fine, they are at increased risk of psychological problems. We investigated whether both child and family-related factors are associated with later psychological problems and whether the length of time spent at home after adoption before daycare moderates these associations among internationally adopted children in Finland (FinAdo, Finnish Adoption Study). The sample consisted of 1,265 children (708 girls, 557 boys) who arrived in Finland before they started school (mean age 2 years at arrival). Later behavioral problems were measured using the Child Behavior Check List (CBCL). According to our results, male gender, older age, child's early clinical symptoms (problems of sensory processing) and single parenthood were associated with later behavioral problems measured by CBCL scores. Longer stay at home before the start of daycare or school modified these results. Longer stay at home was associated with less later behavioral externalizing problems in girls but not in boys compared to those who spent a shorter time at home.

Design, discovery, modelling, synthesis, and biological evaluation of novel and small, low toxicity s-triazine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors.

A set of top-ranked compounds from a multi-objective in silico screen was experimentally tested for toxicity and the ability to inhibit the activity of HIV-1 reverse transcriptase (RT) in cell-free assay and in cell-based assay using HIV-1 based virus-like particles. Detailed analysis of a commercial sample that indicated specific inhibition of HIV-1 reverse transcription revealed that a minor component that was structurally similar to that of the main compound was responsible for the strongest inhibition. As a result, novel s-triazine derivatives were proposed, modelled, discovered, and synthesised, and their antiviral activity and cellular toxicity were tested. Compounds 18a and 18b were found to be efficient HIV-1 RT inhibitors, with an IC50 of 5.6±1.1µM and 0.16±0.05µM in a cell-based assay using infectious HIV-1, respectively. Compound 18b also had no detectable toxicity for different human cell lines. Their binding mode and interactions with the RT suggest that there was strong and adaptable binding in a tight (NNRTI) hydrophobic pocket. In summary, this iterative study produced structural clues and led to a group of non-toxic, novel compounds to inhibit HIV-RT with up to nanomolar potency.

Persistent Luminescence of Tenebrescent Na8Al6Si6O24(Cl,S)2: Multifunctional Optical Markers.

Na8Al6Si6O24(Cl,S)2 materials were prepared with a solid state reaction. The products were studied using X-ray powder diffraction, reflectance measurements as well as X-ray fluorescence, conventional and persistent luminescence, nuclear magnetic resonance, and electron paramagnetic resonance spectroscopies. All materials containing sulfur showed purple tenebrescence, which persisted 2 days in a lit room at room temperature. Considerable blue persistent luminescence peaking at 460 nm and lasting for 1 h was obtained, as well. Persistent luminescence was obtained with irradiation at 365 nm, while tenebrescence required 254 nm. The materials show great promise as low-cost multifunctional optical markers.

Biosynthetic pathway toward carbohydrate-like moieties of alnumycins contains unusual steps for C-C bond formation and cleavage.

Carbohydrate moieties are important components of natural products, which are often imperative for the solubility and biological activity of the compounds. The aromatic polyketide alnumycin A contains an extraordinary sugar-like 4'-hydroxy-5'-hydroxymethyl-2',7'-dioxane moiety attached via a carbon-carbon bond to the aglycone. Here we have extensively investigated the biosynthesis of the dioxane unit through (13)C labeling studies, gene inactivation experiments and enzymatic synthesis. We show that AlnA and AlnB, members of the pseudouridine glycosidase and haloacid dehalogenase enzyme families, respectively, catalyze C-ribosylation conceivably through Michael-type addition of d-ribose-5-phosphate and dephosphorylation. The ribose moiety may be attached both in furanose (alnumycin C) and pyranose (alnumycin D) forms. The C(1')-C(2') bond of alnumycin C is subsequently cleaved and the ribose unit is rearranged into an unprecedented dioxolane (cis-bicyclo[3.3.0]-2',4',6'-trioxaoctan-3'ß-ol) structure present in alnumycin B. The reaction is catalyzed by Aln6, which belongs to a previously uncharacterized enzyme family. The conversion was accompanied with consumption of O(2) and formation of H(2)O(2), which allowed us to propose that the reaction may proceed via hydroxylation of C1' followed by retro-aldol cleavage and acetal formation. Interestingly, no cofactors could be detected and the reaction was also conducted in the presence of metal chelating agents. The last step is the conversion of alnumycin B into the final end-product alnumycin A catalyzed by Aln4, an NADPH-dependent aldo-keto reductase. This characterization of the dioxane biosynthetic pathway sets the basis for the utilization of C-C bound ribose, dioxolane and dioxane moieties in the generation of improved biologically active compounds.

Protective role of polyphenols from Bauhinia hookeri against carbon tetrachloride-induced hepato- and nephrotoxicity in mice.

The hepatoprotective and nephroprotective activity of a polyphenol-rich fraction (BHPF) obtained from Bauhinia hookeri was investigated against CCl4-induced acute hepatorenal toxicity in mice. BHPF was administered (100, 200 and 400 mg/kg/day) for 5 days, then CCl4 was administered. BHPF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT, AST, ALP, LDH, total bilirubin, cholesterol, creatinine, uric acid, urea and malondialdehyde in a dose-dependent manner. In contrast, BHPF pretreatment markedly increased the contents of glutathione and superoxide dismutase in the liver and kidney tissues, indicating the strong in vivo antioxidant activity of BHPF. Pretreatment with BHPF preserved the hepatic architecture and conferred marked protection against necrosis and ballooning degeneration. Pretreatment with BHPF reduced the inflammatory cell aggregation and degenerative changes in the lining epithelium of the kidney tubules. It can be concluded that BHPF has a remarkable hepato- and nephroprotective activity by enhancing the antioxidant defense status, reducing lipid peroxidation and protecting against the histopathological changes induced by CCl4 in the liver and kidney tissues.

Associations between attachment-related symptoms and later psychological problems among international adoptees: results from the FinAdo study.

We examined the associations between attachment-related symptoms (symptoms of reactive attachment disorder (RAD), symptoms of disinhibited social engagement disorder (DSED), and clinging) and later psychological problems among international adoptees. The study population comprised internationally adopted children (591 boys and 768 girls, 6-15 years) from the ongoing Finnish Adoption (FinAdo) study. Data were gathered with self-administered questionnaires both from adoptive parents and from adoptees aged over 9 years. Attachment-related symptoms were measured using of a short (8-item) questionnaire and later behavioral/emotional problems were assessed using the Child Behavior Checklist (CBCL) and the Five to Fifteen (FTF) scale for attention-deficit/hyperactivity disorder (ADHD) symptoms. RAD and DSED symptom subscales were associated with an increased risk of emotional and behavioral problems and ADHD. Especially the mixed type of attachment-related symptoms was strongly associated with later emotional and behavioral problems.

Secondary metabolite from Nostoc XPORK14A inhibits photosynthesis and growth of Synechocystis PCC 6803.

Screening of 55 different cyanobacterial strains revealed that an extract from Nostoc XPORK14A drastically modifies the amplitude and kinetics of chlorophyll a fluorescence induction of Synechocystis PCC6803 cells.After 2 d exposure to the Nostoc XPORK14A extract, Synechocystis PCC 6803 cells displayed reduced net photosynthetic activity and significantly modified electron transport properties of photosystem II under both light and dark conditions. However, the maximum oxidizable amount of P700 was not strongly affected. The extract also induced strong oxidative stress in Synechocystis PCC 6803 cells in both light and darkness. We identified the secondary metabolite of Nostoc XPORK14A causing these pronounced effects on Synechocystis cells. Mass spectrometry and nuclear magnetic resonance analyses revealed that this compound, designated as M22, has a non-peptide structure. We propose that M22 possesses a dualaction mechanism: firstly, by photogeneration of reactive oxygen species in the presence of light, which in turn affects the photosynthetic machinery of Synechocystis PCC 6803; and secondly, by altering the in vivo redox status of cells, possibly through inhibition of protein kinases.

Structural studies, homology modeling and molecular docking of novel non-competitive antagonists of GluK1/GluK2 receptors.

Non-competitive ligands of kainate receptors have focused significant attention as medicinal compounds because they seem to be better tolerated than competitive antagonists and uncompetitive blocker of these receptors. Here we present structural studies (X-ray structure determination, NMR and MS spectra) of novel indole-derived non-competitive antagonists of GluK1/GluK2 receptors, homology models of GluK1 and GluK2 receptors based on novel AMPA receptor template as well as molecular docking of ligands to their molecular targets. We find that the allosteric site is in the receptor transduction domain, in one receptor subunit, not between the two subunits as it was indicated by our earlier studies.

Phenolic compounds of the inner bark of Betula pendula: seasonal and genetic variation and induction by wounding.

The contents of individual phenolic compounds in the inner bark of silver birch (Betula pendula Roth) were analyzed by HPLC-DAD. Samples from 21 mature trees originating from three micropropagated parent trees were collected six times over a 1-year period. Significant seasonal variation in the quantities of ten compounds and four chromatographically unresolved compound pairs was found. A majority of the compounds also exhibited significant quantitative variation among birch clones. There were no qualitative differences associated with the season or among the clones. However, wounding of the bark induced the production of new types of bark phenolics: several ellagitannins were detected in the callus tissues of birch for the first time.

Moluccensins R-Y, limonoids from the seeds of a mangrove, Xylocarpus moluccensis.

Eight limonoids, named moluccensins R-Y (1, 2, 5-10), and six known compounds, including 6-hydroxymexicanolide (3), were isolated from the seeds of an Indian mangrove, Xylocarpus moluccensis, collected in the estuaries of Andhra Pradesh. The absolute configuration of moluccensin V (7) was confirmed by means of single-crystal X-ray diffraction analysis. The (1)H and (13)C NMR data for 6-hydroxymexicanolide (3) was assigned for the first time, and the 6R absolute configuration established by single-crystal X-ray diffraction analysis. Moluccensin R (1), 6R-hydroxymexicanolide (3), and 2-hydroxyfissinolide (4) exhibited marked antifeedant activity against the third-instar larvae of Brontispa longissima at a concentration of 1 mg/mL. The most potent compound tested was 2-hydroxyfissinolide (4), with an AFC(50) (concentration for 50% antifeedant activity) value of 94 µg/mL at 24 h.

Experiences of school bullying among internationally adopted children: results from the Finnish Adoption (FINADO) Study.

This study investigated the prevalence of and factors associated with school bullying and victimization among Finnish international adoptees. The Olweus bully/victim questionnaire was sent to all 9-15-year-old children adopted in Finland between 1985 and 2007 through the mediating organizations officially approved by the Ministry of Social Affairs and Health. The children were identified through official adoption organizations. The response rate in the target sample was 49.4%: the study sample consisted of 364 children (190 girls, 52.2%). The children's background factors and symptoms of reactive attachment disorder (RAD) were evaluated using a FINADO questionnaire. Their learning difficulties and social and language skills were assessed using a standardized parental questionnaire (Five to Fifteen). Of the participants, 19.8% reported victimization by peers while 8% had bullied others. Both victimization and bullying were associated with severe symptoms of RAD at the time of adoption (RR 2.68, 95%CI 1.50-4.77 and RR 2.08, 95%CI 1.17-3.69 for victimization and bullying, respectively). Lack of social skills was associated with victimization (RR 1.74, 95%CI 1.06-2.85) but not independently with being a bully (RR 1.50, 95%CI 0.91-2.45). In a multivariate analysis the child's learning difficulties and language difficulties were not associated with either bullying others or victimization.

SUBSTANCE-ABUSING MOTHERS IN RESIDENTIAL TREATMENT WITH THEIR BABIES: IMPORTANCE OF PRE- AND POSTNATAL MATERNAL REFLECTIVE FUNCTIONING.

A residential treatment program has been developed specifically for substance-abusing pregnant and parenting women in Finland, focusing on simultaneously supporting maternal abstinence from substances and the mother-baby relationship. The aims of the study are to explore maternal pre- and postnatal reflective functioning and its association with background factors, maternal exposure to trauma, and psychiatric symptoms, postnatal interaction, child development, and later child foster care placement. Participants were 34 mother-baby pairs living in three residential program units during the pre- to postnatal period. We employed self-report questionnaires on background, trauma history, and psychiatric symptoms (Brief Symptom Inventory: L.R. Derogatis, 1993; Edinburgh Postnatal Depression Scale: J.L. Cox, J.M. Holden, & R. Sagovsky, 1987; Traumatic Antecedents Questionnaire: B. Van der Kolk, 2003), videotaped mother-child interactions coded for sensitivity, control, and unresponsiveness (Care Index for Infants and Toddlers: P. Crittenden, 2003); a standardized test of child development (Bayley Scales of Infant Development-II: N. Bayley, 1993); and semistructured interviews for maternal reflective functioning (Pregnancy Interview: A. Slade, E. Bernbach, J. Grienenberger, D.W. Levy, & A. Locker, 2002; Parent Development Interview: A. Slade et al., 2005). Pre- and postnatal maternal reflective functioning (RF) was on average low, but varied considerably across participants. Average RF increased significantly during the intervention. Increase in RF level was found to be associated with type of abused substance and maternal trauma history. Mothers who showed lower postnatal RF levels relapsed to substance use more often after completing a residential treatment period, and their children were more likely to be placed in foster care. The intensive focus on maternal RF is an important direction in the development of efficacious treatment for this very high risk population.

Chemical ecology of tannins: recent developments in tannin chemistry reveal new structures and structure-activity patterns.

Tannins are chemically complex plant polyphenols and only little is known of their true molecule-specific anti-herbivore activities. Here we will show that modern tannin chemistry is able to reveal fully new types of tannins in plants together with new types of biological activities for the tannins. Most of these new findings relate to ellagitannins, one of the least studied and underestimated classes of bioactive plant polyphenols.

Birch inner bark procyanidins can be resolved with enhanced sensitivity by hydrophilic interaction HPLC-MS.

A complex mixture of procyanidin aglycones was isolated by Sephadex LH-20 column chromatography from the silver birch inner bark, which is a polyphenol-rich source of natural antioxidants. Procyanidins were studied by using hydrophilic interaction liquid chromatography combined with high-resolution ESI-TOF-MS. A good chromatographic separation was achieved and procyanidins eluted according to their increasing degree of polymerization. Individual procyanidins were detected from dimers up to the degree of polymerization of 22 by their negative-ion mass spectra. The results showed that hydrophilic interaction liquid chromatography can be successfully applied for the analysis of high-molecular-weight procyanidins with enhanced sensitivity in electrospray mass spectrometry.

1-Oxo-1,3-dithiolanes--synthesis and stereochemistry.

1-Oxo-1,3-dithiolane (4) and its cis- and trans-2-methyl (5,6), -4-methyl (7,8) and -5-methyl (9,10) derivatives were prepared by oxidizing the corresponding 1,3-dithiolanes (1-3) with NaIO(4) in water. The oxides were purified and their isomers separated using thin layer chromatography. The structural characterization was carried out with (1)H and (13)C NMR spectroscopy and molecular modelling. The sulfoxides 4-6 and 8-10 attain two S(1) type envelopes (sometimes slightly distorted) the S=O(ax) envelope greatly dominating. Cis-4-methyl-1-oxo-1,3-dithiolane is a special case exhibiting both two closely related S=O(ax) (30 and 27%) as well as S=O(eq) (21 and 22%) forms [S(1) and C(4) envelopes, respectively]. The relative energies of these conformations, the values of (1)H-(1)H coupling constants and (1)H and (13)C chemical shifts were estimated by computational methods and they support well the conclusions based on the experimental data.

Substance abusing mothers in residential treatment with their babies: postnatal psychiatric symptomatology and its association with mother-child relationship and later need for child protection actions.

BACKGROUND: A residential treatment model has been developed in Finland, which is specifically designed for substance abusing pregnant and parenting women, and has its focus on supporting both maternal abstinence from substances and mother-baby relationship. AIMS: Among mother-baby pairs in this residential treatment, to explore amount and type of maternal postnatal psychiatric symptoms, relationship with the baby, and their association with later need for child substitution care placements. METHODS: Participants were 34 mother-baby pairs from three units during pre- to postnatal period. Methods included self-report questionnaires for substance abuse and background data (pregnancy and perinatal period), experienced difficulties with the baby (1 month postnatally); maternal psychiatric symptoms (Brief Symptom Inventory, Edinburgh Pre-postnatal Depression Screen, Inventory of Interpersonal Problems; (pregnancy and 3 months) postnatally; videotaped mother-child interaction measure (Care Index for infants and toddlers) and standardized test of child development (Bayley Scales of Infant Development) (4 months postnatally); questionnaire for follow-up information (2 years of child's age). RESULTS: Mothers showed high levels of different types of psychiatric symptomatology. Maternal interaction with the baby was on average weak, as 53% were within the high-risk range regarding sensitivity. Experiencing more difficulties in early care-giving of the baby was associated with higher amount of postnatal psychiatric symptomatology. Specific psychiatric symptoms were associated with later need for child substitution care. CONCLUSIONS: In designing treatment and follow-up of these mother-baby pairs, careful attention should be paid to pre- and perinatal identification and type of maternal psychiatric symptoms, and mothers' expressions of subjectively experienced difficulties in early care-giving of the baby.