Coordination properties of vic-isonitrosoimines in their copper (II) and palladium (II) complexes

Preparation and structural characterization of palladium (II) complexes of ligands III-V and copper (II) complexes of III are reported. The elemental analyses of the complexes show that the metal: ligand ratio is 1 : 2. The electrical conductance in acetone shows the non-electrolytic nature of the complexes. The diamagnetic character suggests a gross square-planar geometry for the palladium (II) complexes. Copper (II) complexes are paramagnetic with/~eff.~l'90 B.M. Spectral data suggest that in all the complexes the ligand coordinates to the metal (II) symmetrically through isonitroso-nitrogen and imine-nitrogen, forming a ¡ membered chelate ring. Amine-exchange reactions of the complexes are discussed and compared on the basis of their structures.

Lanthanide coordination in dimethyl sulphoxide and antipyrine complexes of rare earth nitrates

Abstract is not available.

Synthesis of a one-dimensional coordination polymer containing pendant hydrosulfide groups

In view of the recent interest in compounds containing M-SH units, an organotin hydrosulfide compound, Me2Sn(SH)(O2CMe) (1) was prepared by controlled hydrolysis of the diorganotin thioacetate. Under similar mild hydrolytic conditions the corresponding benzoate could not be isolated. Instead, the thiobenzoate complex, Me2Sn(SOCPh)(2) (3) was obtained in excellent yields indicating that there was no hydrolysis. Both 1 and 3 were characterized by X-ray crystallography. Some properties of the polymeric compound 1, such as spectral, electrical conductivity and NLO response were also studied. The reactivity and properties were explained using density functional calculations.

Molecular genetics of Meckel syndrome : Ciliary genes are defective in MKS

Meckel syndrome (MKS, MIM 249000) is a severe developmental disorder that leads to death already in utero or shortly after birth. MKS diagnosis can be established by a careful ultrasound examination already at 11-14 weeks of gestation. The main features of MKS are occipital meningoencephalocele, cystic kidney dysplasia and fibrotic changes of the liver. In addition, polydactyly is frequently reported in the cases. The aim of the study was to characterize the molecular and functional defects in MKS. In this study we were able to identify two major MKS mutations in Finnish population, which cover over 90% of the cases. The first mutation is a 29 bp intronic deletion in the MKS1 gene (c.1483-7_35del) that is found in 70% of the families and the second is a C>T substitution in the coding region of CC2D2A (c.1762C>T), that is found in 20% of the MKS families. Both of these mutations result in abnormal splicing. The discovery of the disease genes has revealed that MKS is caused by primary cilia dysfunction. MKS1 gene has a conserved B9 domain, and it is found in the predicted ciliary proteome. CC2D2A protein is also found in the predicted ciliary proteome and it has a Ca2+ binding domain. The number of genes behind MKS has increased rapidly in the past years and to date, mutations have been identified in five genes (MKS1, TMEM67/MKS3, CEP290/MKS4, RPGRIP1L/MKS5 and CC2D2A/MKS6). Identification of the disease genes mutations has also revealed that MKS is an allelic disorder with other syndromes with overlapping phenotypes. Disorders that are caused by primary cilia dysfunction are collectively known as ciliopathies. Sequence analysis of all the known MKS genes in Finnish and non-Finnish families available to us, where the mutation was still unknown, revealed mutations in 14 out of the 30 families included in the study. When we collected all the reported mutations in MKS genes in different syndromes we could see that there was clearly a genotype-syndrome correlation between the mutations and the syndromes, since the same pair of mutations has never been reported in different syndromes. The basic molecular events behind MKS will not only give us information of this syndrome, but also significant novel information on early fetal development in general.

Nuclear quadrupole resonance in coordination compounds

Abstract is not available.

Time to rest : Signals in shoot apex developmental transitions underlying dormancy

Vuodenajat rytmittävät monivuotisten kasvien elämää pohjoisella pallonpuoliskolla, jolla varmin merkki lähestyvästä talvikaudesta on asteittain lyhenevä päivänpituus. Kun päivänpituus on lyhentynyt tiettyyn raja-arvoon saakka, kasvu hiipuu ja kasvin kehityksessä tapahtuu suuria muutoksia. Väitöskirjatyössäni tutkittiin mekanismeja, jotka liittyvät pituuskasvun päättymiseen, silmujen lepotilan kehittymiseen ja kärkisilmun muodostumiseen hybridihaavan ja koivuntaimilla lyhyen päivänpituuden seurauksena kasvihuoneolosuhteissa. Vain lepotilaiset silmut selviytyvät luonnossa ankaran talvikauden yli, joten etenkin lepotilan kehittymisen tutkiminen on keskeistä pyrittäessä selvittämään monivuotisille kasveille tyypillisen kasvutavan mekanismeja. Jo pitkään on tiedetty, että täysikasvuiset lehdet vastaanottavat tiedon päivänpituudesta ja lähettävät signaaleja varren johtojänteissä ylöspäin kohti kasvin kärkiosaa. Sen sijaan varren kärjen ja kärkikasvupisteen roolia lepotilan kehittymisessä on selvitetty vain vähän. Kuitenkin juuri kärkikasvupisteen selviytyminen vuodesta toiseen on tärkeää, koska sen jakautumiskykyiset solukot tuottavat kasvin maanpäälliset osat. Tässä työssä tehdyissä varttamiskokeissa osoitettiin, että varren kärki ei ainoastaan vastaanota signaaleja lehdistä ja ajoita toimintaansa niiden mukaan, vaan myös kärjellä itsellään on aktiivinen rooli lepotilan kehittymisessä. Erityisesti kiinnitettiin huomiota kärkikasvupisteen eri alueiden, ns. apikaalimeristeemin ja rib-meristeemin erilaisiin tehtäviin ja pääteltiin, että molemmat vaikuttavat lepotilan kehittymiseen. Kokeissa käytettiin normaalien hybridihaapojen lisäksi siirtogeenisiä hybridihaapoja, jotka eivät lopeta kasvuaan lyhyt päivä –olosuhteissa. Siirtogeeniset hybridihaavat ilmensivät voimakkaasti fytokromi A -nimistä valon vastaanottajamolekyyliä rib-meristeemin alueella, mikä saattoi osaltaan vaikuttaa poikkeavaan pituuskasvukäyttäytymiseen. Myös useiden lepotilan kehittymiseen liittyvien geenien ilmenemisessä havaittiin poikkeavuuksia verrattuna ei-siirtogeenisiin kontrolleihin, joiden silmuissa kehittyi lepotila lyhyt päivä –altistuksen seurauksena. Väitöskirjatyössäni havaittiin, että myös kaasumainen kasvihormoni etyleeni toimii viestinvälittäjänä silmujen lepotilan kehittymisessä ja vaikuttaa etenkin lepotilan oikeaan ajoittumiseen. Etyleenillä huomattiin olevan määräävä rooli päätesilmun muodostumisessa: siirtogeeniset koivut, jotka eivät aisti etyleeniä, eivät muodostaneet päätesilmua. Silti siirtogeeniset koivut vaipuivat lepotilaan, joskin myöhemmin kuin ei-siirtogeeniset kontrollit. Tämän perusteella todettiin, että lepotilan ja päätesilmun kehittyminen ovat erillisiä kehitystapahtumia, vaikka ne saattavatkin ajoittua osaksi päällekkäin.

CADASIL: molecular studies on the most common hereditary vascular dementing disorder

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common hereditary vascular dementia. CADASIL is a systemic disease of small and medium-sized arteries although the symptoms are almost exclusively neurological, including migraineous headache, recurrent ischemic episodes, cognitive impairment and, finally, subcortical dementia. CADASIL is caused by over 170 different mutations in the NOTCH3 gene, which encodes a receptor expressed in adults predominantly in the vascular smooth muscle cells. The function of NOTCH3 is not crucial for embryonic development but is needed after birth. NOTCH3 directs postnatal arterial maturation and helps to maintain arterial integrity. It is involved in regulation of vascular tone and in the wound healing of a vascular injury. In addition, NOTCH3 promotes cell survival by inducing expression of anti-apoptotic proteins. NOTCH3 is a membrane-spanning protein with a large extracellular domain (N3ECD) containing 34 epidermal growth factor-like (EGF) repeats and a smaller intracellular domain with six ankyrin repeats. All CADASIL mutations are located in the EGF repeats and the majority of the mutations cause gain or loss of one cysteine residue in one of these repeats leading to an odd number of cysteine residues, which in turn leads to misfolding of N3ECD. This misfolding most likely alters the maturation, targetting, degradation and/or function of the NOTCH3 receptor. CADASIL mutations do not seem to affect the canonical NOTCH3 signalling pathway. The main pathological findings are the accumulation of the NOTCH3 extracellular domain on degenerating vascular smooth muscle cells (VSMCs), accumulation of granular osmiophilic material (GOM) in the close vicinity of VSMCs as well as fibrosis and thickening of arterial walls. Narrowing of the arterial lumen and local thrombosis cause insufficient blood flow, mainly in small arteries of the cerebral white matter, resulting in tissue damage and lacunar infarcts. CADASIL is suspected in patients with a suggestive family history and clinical picture as well as characteristic white matter alterations in magnetic resonance imaging. A definitive verification of the diagnosis can be achieved by identifying a pathogenic mutation in the NOTCH3 gene or through the detection of GOM by electron microscopy. To understand the pathology underlying CADASIL, we have generated a unique set of cultured vascular smooth muscle cell (VSMC) lines from umbilical cord, placental, systemic and cerebral arteries of CADASIL patients and controls. Analyses of these VSMCs suggest that mutated NOTCH3 is misfolded, thus causing endoplasmic reticulum stress, activation of the unfolded protein response and increased production of reactive oxygen species. In addition, mutation in NOTCH3 causes alterations in actin cytoskeletal structures and protein expression, increased branching and abnormal node formation. These changes correlate with NOTCH3 expression levels within different VSMCs lines, suggesting that the phenotypic differences of SMCs may affect the vulnerability of the VSMCs and, therefore, the pathogenic impact of mutated NOTCH3 appears to vary in the arteries of different locations. Furthermore, we identified PDGFR- as an immediate downstream target gene of NOTCH3 signalling. Activation of NOTCH induces up-regulation of the PDGFR- expression in control VSMCs, whereas this up-regulation is impaired in CADASIL VSMCs and might thus serve as an alternative molecular mechanism that contributes to CADASIL pathology. In addition, we have established the congruence between NOTCH3 mutations and electron microscopic detection of GOM with a view to constructing a strategy for CADASIL diagnostics. In cases where the genetic analysis is not available or the mutation is difficult to identify, a skin biopsy is an easy-to-perform and highly reliable diagnostic method. Importantly, it is invaluable in setting guidelines concerning how far one should proceed with the genetic analyses.

X-ray crystal structure of a ternary copper(II) vitamin B6 complex, hydroxo(2,2'-bipyridyl)(pyridoxinato) copper(II) monohydrate. A rare example of monodentate coordination of copper(II) by the hydroxyl ion

A ternary metal complex involving Vitamin B6 with the formula [Cu(bipy)(pn) (OH)]H2O (bipy = 2,2'²-bipyridine, PN = anionic pyridoxine) has been synthesized and studied in the solid state by means of spectroscopy and X-ray crystallography. The geometry around copper(II) is distorted square pyramidal, two oxygens from phenolic and 4-(hydroxymethyl) groups of pn, two nitrogens from bipy and an axial OH- ion forming the coordination sphere. In this structure pn exists in a new anionic form with deprotonation of the phenolic group. The structure also provides a rare example of monodentate hydroxyl coordination to copper.

A study of the nature of coordination in metal monothiocarbamates based on infrared spectroscopy and the HSAB concept

The nature of coordination in metal monothiocarbamates is shown to depend on the hardness or softness of the metal ton. Thus, the monothiocarbamate ion acts as a monodentate ligand with metal-sulphur bending when the metal ion is a soft acid while it acts as a bidentate ligand when the metal ion is a hard acid; it can exhibit either behaviour when the metal ion is a borderline acid. In dialkyltin and dialkylmonocholorotin complexes, the monothiocarbamate ion acts as a bidentate ligand with strong Sn-S bonding while in trialkyl-or triaryl-tin complexes it acts essentially as a monodentate ligand. Thus, R3Sn(I) seems to be a soft or borderline acid while R2Sn(II) is a hard acid.

Stress and developmental responses in Arabidopsis thaliana: regulation through the transcription factor-interacting protein RCD1

Plants constantly face adverse environmental conditions, such as drought or extreme temperatures that threaten their survival. They demonstrate astonishing metabolic flexibility in overcoming these challenges and one of the key responses to stresses is changes in gene expression leading to alterations in cellular functions. This is brought about by an intricate network of transcription factors and associated regulatory proteins. Protein-protein interactions and post-translational modifications are important steps in this control system along with carefully regulated degradation of signaling proteins. This work concentrates on the RADICAL-INDUCED CELL DEATH1 (RCD1) protein which is an important regulator of abiotic stress-related and developmental responses in Arabidopsis thaliana. Plants lacking this protein function display pleiotropic phenotypes including sensitivity to apoplastic reactive oxygen species (ROS) and salt, ultraviolet B (UV-B) and paraquat tolerance, early flowering and senescence. Additionally, the mutant plants overproduce nitric oxide, have alterations in their responses to several plant hormones and perturbations in gene expression profiles. The RCD1 gene is transcriptionally unresponsive to environmental signals and the regulation of the protein function is likely to happen post-translationally. RCD1 belongs to a small protein family and, together with its closest homolog SRO1, contains three distinguishable domains: In the N-terminus, there is a WWE domain followed by a poly(ADP-ribose) polymerase-like domain which, despite sequence conservation, does not seem to be functional. The C-terminus of RCD1 contains a novel domain called RST. It is present in RCD1-like proteins throughout the plant kingdom and is able to mediate physical interactions with multiple transcription factors. In conclusion, RCD1 is a key point of signal integration that links ROS-mediated cues to transcriptional regulation by yet unidentified means, which are likely to include post-translational mechanisms. The identification of RCD1-interacting transcription factors, most of whose functions are still unknown, opens new avenues for studies on plant stress as well as developmental responses.

The trishanku gene and terminal morphogenesis in Dictyostelium discoideum

P>Multicellular development in the social amoeba Dictyostelium discoideum is triggered by starvation. It involves a series of morphogenetic movements, among them being the rising of the spore mass to the tip of the stalk. The process requires precise coordination between two distinct cell types-presumptive (pre-) spore cells and presumptive (pre-) stalk cells. Trishanku (triA) is a gene expressed in prespore cells that is required for normal morphogenesis. The triA- mutant shows pleiotropic effects that include an inability of the spore mass to go all the way to the top. We have examined the cellular behavior required for the normal ascent of the spore mass. Grafting and mixing experiments carried out with tissue fragments and cells show that the upper cup, a tissue that derives from prestalk cells and anterior-like cells (ALCs), does not develop properly in a triA- background. A mutant upper cup is unable to lift the spore mass to the top of the fruiting body, likely due to defective intercellular adhesion. If wild-type upper cup function is provided by prestalk and ALCs, trishanku spores ascend all the way. Conversely, Ax2 spores fail to do so in chimeras in which the upper cup is largely made up of mutant cells. Besides proving that under these conditions the wild-type phenotype of the upper cup is necessary and sufficient for terminal morphogenesis in D. discoideum, this study provides novel insights into developmental and evolutionary aspects of morphogenesis in general. Genes that are active exclusively in one cell type can elicit behavior in a second cell type that enhances the reproductive fitness of the first cell type, thereby showing that morphogenesis is a cooperative process.

Deciphering the Distinct Role for the Metal Coordination Motif in the Catalytic Activity of Mycobacterium smegmatis Topoisomerase I

Mycobacterium smegmatis topoisomerase I (Mstopol) is distinct from typical type IA topoisomerases. The enzyme binds to both single- and double-stranded DNA with high affinity, making specific contacts. The enzyme comprises conserved regions similar to type IA topoisomerases from Escherichia coli and other eubacteria but lacks the typically found zinc fingers in the carboxy-terminal domain. The enzyme can perform DNA cleavage m the absence of Mg2+ but religation needs exogenously added Mg2+. One molecule of Mg2+ tightly bound to the enzyme has no role in DNA cleavage but is needed only for the religation reaction. The toprim. (topoisomerase-primase) domain in MstopoI comprising the Mg2+ binding pocket, conserved in both type IA and type II topoisomerases, was subjected to mutagenesis to understand the role of Mg2+, in different steps of the reaction. The residues D108, D110, and E112 of the enzyme, which form the acidic triad in the DXDXE motif, were changed to alanines. D108A mutation resulted in an enzyme that is Mg2+ dependent for DNA cleavage unlike Mstopol and exhibited enhanced DNA cleavage property and reduced religation activity. The mutant was toxic for cell growth, most likely due to the imbalance in cleavage-religation equilibrium. In contrast, the E112A mutant behaved like wild-type enzyme, cleaving DNA in a Mg2+-independent fashion, albeit to a reduced extent. Intra- and intermolecular religation assays indicated specific roles for D108 and E112 residues during the reaction. Together, these results indicate that the D108 residue has a major role during cleavage and religation, while E112 is important for enhancing the efficiency of cleavage. Thus, although architecturally and mechanistically similar to topoisomerase I from E. coli, the metal coordination pattern of the mycobacterial enzyme is distinct, opening up avenues to exploit the enzyme to develop inhibitors.

Next-generation sequencing: A frameshift in skeletal dysplasia gene discovery

In the last decade, huge breakthroughs in genetics - driven by new technology and different statistical approaches - have resulted in a plethora of new disease genes identified for both common and rare diseases. Massive parallel sequencing, commonly known as next-generation sequencing, is the latest advance in genetics, and has already facilitated the discovery of the molecular cause of many monogenic disorders. This article describes this new technology and reviews how this approach has been used successfully in patients with skeletal dysplasias. Moreover, this article illustrates how the study of rare diseases can inform understanding and therapeutic developments for common diseases such as osteoporosis. © International Osteoporosis Foundation and National Osteoporosis Foundation 2013.