Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation

Background: Coats plus syndrome is an autosomal recessive, pleiotropic, multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is caused by compound heterozygous mutations in the CTC1 gene. Case presentation: We encountered a case of an eight-year old boy from an Indian family with manifestations of Coats plus syndrome along with an unusual occurrence of dextrocardia and situs inversus. Targeted resequencing of the CTC1 gene as well as whole exome sequencing (WES) were conducted in this family to identify the causal variations. The identified candidate variations were screened in ethnicity matched healthy controls. The effect of CTC1 variation on telomere length was assessed using Southern blot. A novel homozygous missense mutation c.1451A > C (p.H484P) in exon 9 of the CTC1 gene and a rare 3'UTR known dbSNP variation (c.*556 T > C) in HES7 were identified as the plausible candidates associated with this complex phenotype of Coats plus and dextrocardia. This CTC1 variation was absent in the controls and we also observed a reduced telomere length in the affected individual's DNA, suggesting its likely pathogenic nature. The reported p.H484P mutation is located in the N-terminal 700 amino acid regionthat is important for the binding of CTC1 to ssDNA through its two OB domains. WES data also showed a rare homozygous missense variation in the TEK gene in the affected individual. Both HES7 and TEK are targets of the Notch signaling pathway. Conclusions: This is the first report of a genetically confirmed case of Coats plus syndrome from India. By means of WES, the genetic variations in this family with unique and rare complex phenotype could be traced effectively. We speculate the important role of Notch signaling in this complex phenotypic presentation of Coats plus syndrome and dextrocardia. The present finding will be useful for genetic diagnosis and carrier detection in the family and for other patients with similar disease manifestations.

High Proton Mobility, Solvent Induced Single Crystal to Single Crystal Structural Transformation, and Related Studies on a Family of Compounds Formed from Mn-3 Oxo-Clusters

The reaction between 4,4'-sulfonyldibenzoic acid (H(2)SDBA) and manganese under mild conditions resulted in the isolation of two new three-dimensional compounds, Mn-4(C14H8O6S)(4)(DMA)(2)]center dot 3DMA, I, and Mn-3(C14H8O6S)(3)(DMA)(2)(MeOH)]center dot DMA, IIa. Both structures have Mn-3 trimer oxo cluster units. While the Mn-3 oxoclusters are connected through octahedral manganese forming one-dimensional Mn-O-Mn chains in I, the Mn-3 units are isolated in IIa. The SDBA units connect the Mn-O-Mn chains and the Mn-3 clusters giving rise to the three-dimensional structure. Both compounds have coordinated and free solvent molecules. In IIa, two different solvent molecules are coordinated, of which one solvent can be reversibly exchanged by a variety of other similar solvents via a solvent-mediated single crystal to single crystal (SCSC) transformation. The free lattice DMA solvent molecules in I can be exchanged by water molecules resulting in hydrophilic channels. Proton conductivity studies on I reveals a high proton mobility with conductivity values of similar to 0.87 x 10(-3) Omega(-1) cm(-1) at 34 degrees C and 98% RH, which is comparable to some of the good proton conductivity values observed in inorganic coordination polymers. We have also shown structural transformation of I to IIa through a possible dissolution and recrystallization pathway. In addition, both I and IIa appear to transform to two other manganese compounds H3O]Mn-3(mu(3)-OH)(C14H8O6S)(3)(H2O)](DMF)(5) and H3O](2)Mn-7(mu 3-OH)(4)(C14H8O6S)(6)(H2O)(4)](H2O)(2)(DMF)(8) under suitable reaction conditions. We have partially substituted Co in place of Mn in the Mn-3 trimer clusters forming CoMn2(C14H8O6S)(3)(DMA)(2)(EtOH)]center dot DMA, III, a structure that is closely related to IIa. All the compounds reveal antiferromagnetic behavior. On heating, the cobalt substituted phase (compound III) forms a CoMn2O4 spinel phase with particle sizes in the nanometer range.

A Family of Domains Associated with mu-Synthesis

We introduce a family of domains-which we call the -quotients-associated with an aspect of -synthesis. We show that the natural association that the symmetrized polydisc has with the corresponding spectral unit ball is also exhibited by the -quotient and its associated unit `` -ball''. Here, is the structured singular value for the case Specifically: we show that, for such an E, the Nevanlinna-Pick interpolation problem with matricial data in a unit `` -ball'', and in general position in a precise sense, is equivalent to a Nevanlinna-Pick interpolation problem for the associated -quotient. Along the way, we present some characterizations for the -quotients.

Molecular and Functional Characterization of RecD, a Novel Member of the SF1 Family of Helicases, from Mycobacterium tuberculosis

Background: The heterotrimeric M. tuberculosis RecBCD complex, or each of its individual subunits, remains uncharacterized. Results: MtRecD exists as a homodimer in solution, catalyzes ssDNA-dependent ATP hydrolysis, unwinding of DNA replication/recombination intermediates, and interacts with RecA. Conclusion: MtRecD possesses strong 5 3- and weak 3 5-helicase activities. Significance: These findings provide insights into the mechanism underlying DSB repair and homologous recombination in mycobacteria. The annotated whole-genome sequence of Mycobacterium tuberculosis revealed the presence of a putative recD gene; however, the biochemical characteristics of its encoded protein product (MtRecD) remain largely unknown. Here, we show that MtRecD exists in solution as a stable homodimer. Protein-DNA binding assays revealed that MtRecD binds efficiently to single-stranded DNA and linear duplexes containing 5 overhangs relative to the 3 overhangs but not to blunt-ended duplex. Furthermore, MtRecD bound more robustly to a variety of Y-shaped DNA structures having 18-nucleotide overhangs but not to a similar substrate containing 5-nucleotide overhangs. MtRecD formed more salt-tolerant complexes with Y-shaped structures compared with linear duplex having 3 overhangs. The intrinsic ATPase activity of MtRecD was stimulated by single-stranded DNA. Site-specific mutagenesis of Lys-179 in motif I abolished the ATPase activity of MtRecD. Interestingly, although MtRecD-catalyzed unwinding showed a markedly higher preference for duplex substrates with 5 overhangs, it could also catalyze significant unwinding of substrates containing 3 overhangs. These results support the notion that MtRecD is a bipolar helicase with strong 5 3 and weak 3 5 unwinding activities. The extent of unwinding of Y-shaped DNA structures was approximate to 3-fold lower compared with duplexes with 5 overhangs. Notably, direct interaction between MtRecD and its cognate RecA led to inhibition of DNA strand exchange promoted by RecA. Altogether, these studies provide the first detailed characterization of MtRecD and present important insights into the type of DNA structure the enzyme is likely to act upon during the processes of DNA repair or homologous recombination.

Lithium metal borate (LiMBO3) family of insertion materials for Li-ion batteries: a sneak peak

Rechargeable lithium-ion battery remains the leading electrochemical energy-storage device, albeit demanding steady effort of design and development of superior cathode materials. Polyanionic framework compounds are widely explored in search for such cathode contenders. Here, lithium metal borate (LiMBO3) forms a unique class of insertion materials having the lowest weight polyanion (i. e., BO33-), thus offering the highest possible theoretical capacity (ca. 220 mAh/g). Since the first report in 2001, LiMBO3 has rather slow progress in comparison to other polyanionic cathode systems based on PO4, SO4, and SiO4. The current review gives a sneak peak to the progress on LiMBO3 cathode systems in the last 15 years highlighting their salient features and impediments in cathode implementation. The synthesis and structural aspects of borate family are described along with the critical analysis of the electrochemical performance of borate family of insertion materials.

Effects of Patterned Substrate on Thin Films Simulated by Family Model

Patterned substrate growth has been a subject of much interest. In this work, characteristics of some statistical properties of a film grown on triangular and vicinal substrates using the Family model are studied. Substrate size and tilt angle are varied. It is found that the interface width and the correlation function increase as the roughness of the pattern is increased. The new scaling exponents are calculated and anomalous scaling is obtained. The transient persistence probability does not show a power law relation when the initial surface is sufficiently rough. The initial rough surface also causes multifractal behavior in the model.

Na2.44Mn1.79(SO4)(3): a new member of the alluaudite family of insertion compounds for sodium ion batteries

Sodium-ion batteries have been extensively pursued as economic alternatives to lithium-ion batteries. Investigating the polyanion chemistry, alluaudite structured Na2Fe2II(SO4)(3) has been recently discovered as a 3.8 V positive electrode material (Barpanda et al., Nature Commun., 5: 4358, 2014). Registering the highest ever Fe-III/Fe-II redox potential (vs. Na/Na+) and formidable energy density, it has opened up a new polyanion family for sodium batteries. Exploring the alluaudite family, here we report isotypical Na2+2xMn2-xII(SO4)(3) (x = 0.22) as a novel high-voltage cathode material for the first time. Following low-temperature (ca. 350 degrees C) solid-state synthesis, the structure of this new alluaudite compound has been solved adopting a monoclinic framework (s.g. C2/c) showing antiferromagnetic ordering at 3.4 K. Synergising experimental and ab initio DFT investigation, Na2+2xMn2-xII(SO4)(3) has been found to be a potential high-voltage (ca. 4.4 V) cathode material for sodium batteries.

Robust Glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI Family Member Protein, Is Critical for Oxidative Stress Resistance in Saccharomyces cerevisiae

Methylglyoxal (MG) is a reactive metabolic intermediate generated during various cellular biochemical reactions, including glycolysis. The accumulation of MG indiscriminately modifies proteins, including important cellular antioxidant machinery, leading to severe oxidative stress, which is implicated in multiple neurodegenerative disorders, aging, and cardiac disorders. Although cells possess efficient glyoxalase systems for detoxification, their functions are largely dependent on the glutathione cofactor, the availability of which is self-limiting under oxidative stress. Thus, higher organisms require alternate modes of reducing the MG-mediated toxicity and maintaining redox balance. In this report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpI family in Saccharomyces cerevisiae, plays an indispensable role in regulating redox homeostasis. Our results show that Hsp31 possesses robust glutathione-independent methylglyoxalase activity and suppresses MG-mediated toxicity and ROS levels as compared with another paralog, Hsp34. On the other hand, glyoxalase-defective mutants of Hsp31 were found highly compromised in regulating the ROS levels. Additionally, Hsp31 maintains cellular glutathione and NADPH levels, thus conferring protection against oxidative stress, and Hsp31 relocalizes to mitochondria to provide cytoprotection to the organelle under oxidative stress conditions. Importantly, human DJ-1, which is implicated in the familial form of Parkinson disease, complements the function of Hsp31 by suppressing methylglyoxal and oxidative stress, thus signifying the importance of these proteins in the maintenance of ROS homeostasis across phylogeny.

Cyclic Cationic Peptides Containing Sugar Amino Acids Selectively Distinguishes and Inhibits Maturation of Pre-miRNAs of the Same Family

The discovery of microRNAs (miRNAs) has added a new dimension to the gene regulatory networks, making aberrantly expressed miRNAs as therapeutically important targets. Small molecules that can selectively target and modulate miRNA levels can thus serve as lead structures. Cationic cyclic peptides containing sugar amino acids represent a new class of small molecules that can target miRNA selectively. Upon treatment of these small molecules in breast cancer cell line, we profiled 96 therapeutically important miRNAs associated with cancer and observed that these peptides can selectively target paralogous miRNAs of the same seed family. This selective inhibition is of prime significance in cases when miRNAs of the same family have tissue-specific expression and perform different functions. During these conditions, targeting an entire miRNA family could lead to undesired adverse effects. The selective targeting is attributable to the difference in the three-dimensional structures of precursor miRNAs. Hence, the core structure of these peptides can be used as a scaffold for designing more potent inhibitors of miRNA maturation and hence function.

Air-pollution and economics: diesel bus versus electric bus

The Bangalore Metropolitan Transport Corporation (BMTC) took an initiative to check the overall benefits of introducing electric buses as a suitable replacement for the diesel buses to tackle the burgeoning pollution in the city of Bengaluru, India. For a trial run of three months, an electric bus was procured from a Chinese company `Build Your Dreams' (BYD). Data were collected by BMTC on the operation and maintenance of the bus. This new initiative, if rightly guided, could have a direct impact on the lives of those in the city. An economic analysis of the running as well as maintenance of the electric buses within the city limits was performed. For comparison, the same analysis was performed for the data from the existing diesel bus operating on the same route. On the basis of the study, it can be concluded that the introduction of electric buses as a means of public transport in the city would be beneficial both economically as well as environmentally. The electric bus also makes much less noise, thereby helping reduce noise pollution and makes less vibration when compared to the diesel bus. This results in a more comfortable journey for the passengers.

A family of interesting exact solutions of the sine-Gordon equation

By using AKNS [Phys. Rev. Lett. 31 (1973) 125] system and introducing the wave function, a family of interesting exact solutions of the sine-Gordon equation are constructed. These solutions seem to be some soliton, kink, and anti-kink ones respectively for the different choice of the spectrum, whereas due to the interaction between two traveling-waves they have some properties different from usual soliton, kink, and anti-kink solutions.

Economic measurement in public welfare economics : practical experiences on the regional level in Germany

Resumen: ¿Cuál es el precio justo para la asistencia social? Este artículo muestra que la medición económica efectuada en mercados basados en el valor de los servicios prestados podría responder esta pregunta. La medición económica puede hacer lo mismo en distintos campos del trabajo social aplicando diferentes métodos, tales como ofertas públicas o negociaciones calificadas. Después de dar un breve panorama teórico, se presentan y analizan en detalle dos proyectos alemanes. El artículo muestra cómo la introducción de mecanismos de negociación en la asistencia social expresados en términos de resultados pueden traer efectos positivos para las finanzas públicas, así como también para el bien común.

Reseña bibliográfica : poor economics. A radical rethinking of the way to fight global poverty

El libro recientemente publicado Poor Economics -y la técnica de evaluaciones aleatorias que dan sustento a sus conclusionestienen el potencial para cambiar radicalmente la manera de diseñar políticas para combatir la pobreza en el mundo. El libro fue escrito por Abhijit Banerjee y Esther Duflo, dos jóvenes reconocidos economistas del MIT (Massachusetts Institute of Technology). Duflo, nacida en Francia y educada en el École Normale Supérieure de Paris y MIT, fue ganadora en 2010 del premio John Bates Clark al mejor economista menor de 40 años y considerada por la revista Foreign Policy como una de los 100 intelectuales más influyentes del mundo. Abhijit Banerjee educado en la Universidad de Calcuta (su ciudad de origen) y la Universidad de Harvard también es ganador de numerosos premios.