Study of short range correlations and two-fold spin reorientation in NdFe0.5Mn0.5O3.

Detailed powder neutron diffraction studies as a function of temperature is performed on NdFe0.5Mn0.5O3 in the temperature range 400-1.5 K. Diffused magnetic scattering is observed due to three dimensional short range ordering (SRO), between Fe3+/Mn3+ spins, over the whole temperature range 400-1.5 K. The presence of SRO is independent of long range ordering (LRO) in this compound which has never been observed in any Fe3+/Mn3+ based compounds. Further, in this compound two-fold spin reorientation is discussed in the temperature range 300-1.5 K. Development of long range ordering at 300 K is due to the mixture of Γ4 and Γ1 magnetic structure, not like other orthoferrites which have Γ4 structure at 300 K. This occurs due to the presence of large single ion anisotropy of Mn3+ ions. Volume fraction of Γ4 decreases with temperature leading to pure Γ1 magnetic structure in the temperature range 150-90 K. Another spin reorientation of Fe3+/Mn3+ spins occurs from Γ1 to Γ2 in the temperature range 70-25 K.

Human muscle pathology is associated with altered phosphoprotein profile of mitochondrial proteins in the skeletal muscle.

Analysis of human muscle diseases highlights the role of mitochondrial dysfunction in the skeletal muscle. Our previous work revealed that diverse upstream events correlated with altered mitochondrial proteome in human muscle biopsies. However, several proteins showed relatively unchanged expression suggesting that post-translational modifications, mainly protein phosphorylation could influence their activity and regulate mitochondrial processes. We conducted mitochondrial phosphoprotein profiling, by proteomics approach, of healthy human skeletal muscle (n = 10) and three muscle diseases (n = 10 each): Dysferlinopathy, Polymyositis and Distal Myopathy with Rimmed Vacuoles. Healthy human muscle mitochondrial proteins displayed 253 phosphorylation sites (phosphosites), which contributed to metabolic and redox processes and mitochondrial organization etc. Electron transport chain complexes accounted for 84 phosphosites. Muscle pathologies displayed 33 hyperphosphorylated and 14 hypophorphorylated sites with only 5 common proteins, indicating varied phosphorylation profile across muscle pathologies. Molecular modelling revealed altered local structure in the phosphorylated sites of Voltage-Dependent Anion Channel 1 and complex V subunit ATP5B1. Molecular dynamics simulations in complex I subunits NDUFV1, NDUFS1 and NDUFV2 revealed that phosphorylation induced structural alterations thereby influencing electron transfer and potentially altering enzyme activity. We propose that altered phosphorylation at specific sites could regulate mitochondrial protein function in the skeletal muscle during physiological and pathological processes.

Tryptophan Oxidation in the UQCRC1 Subunit of Mitochondrial Complex III (Ubiquinol-Cytochrome C Reductase) in a Mouse Model of Myodegeneration Causes Large Structural Changes in the Complex: A Molecular Dynamics Simulation Study.

Muscle diseases display mitochondrial dysfunction and oxidative damage. Our previous study in a cardiotoxin model of myodegeneration correlated muscle damage with mitochondrial dysfunction, which in turn entailed altered mitochondrial proteome and oxidative damage of mitochondrial proteins. Proteomic identification of oxidized proteins in muscle biopsies from muscular dystrophy patients and cardiotoxin model revealed specific mitochondrial proteins to be targeted for oxidation. These included respiratory complexes which displayed oxidative modification of Trp residues in different subunits. Among these, Ubiquinol-Cytochrome C Reductase Core protein 1 (UQCRC1), a subunit of Ubiquinol-Cytochrome C Reductase Complex or Cytochrome b-c1 Complex or Respiratory Complex III displayed oxidation of Trp395, which could be correlated with the lowered activity of Complex III. We hypothesized that Trp395 oxidation might contribute to altered local conformation and overall structure of Complex III, thereby potentially leading to altered protein activity. To address this, we performed molecular dynamics simulation of Complex III (oxidized at Trp395 of UQCRC1 vs. non-oxidized control). Molecular dynamic simulation analyses revealed local structural changes in the Trp395 site. Intriguingly, oxidized Trp395 contributed to decreased plasticity of Complex III due to significant cross-talk among the subunits in the matrix-facing region and subunits in the intermembrane space, thereby leading to impaired electron flow from cytochrome C.

Mapping the protein phosphorylation sites in human mitochondrial complex I (NADH: Ubiquinone oxidoreductase): A bioinformatics study with implications for brain aging and neurodegeneration.

In eukaryotes, mitochondrial complex I (NADH: ubiquinone oxidoreductase; CI) is central to oxidative phosphorylation (OXPHOS). Mammalian CI is a 45 subunit complex that forms supercomplexes with other OXPHOS complexes. Since CI defects are associated with aging and neurodegeneration, it is pertinent to understand its structure-function relationship. Although genetic mutations could lower CI activity causing mitochondrial dysfunction in several pathologies, post-translational modifications (PTMs) have emerged as a key mechanism contributing to altered CI activity. Among non-oxidative PTMs, protein phosphorylation is the most intricate regulatory mechanism controlling CI structure and function during normal physiology, aging and neurodegeneration. To comprehend this, we carried out a comprehensive bioinformatics analysis of protein phosphorylation of human CI subunits using software-based prediction of phosphorylation (phospho) sites and associated kinases. Phosphorylation was higher among core subunits and active domains of the complex. Among the subunits, NDUFS1 displayed significantly higher number as well as percent phospho sites compared to others. Analysis of the subunits containing iron-sulfur (Fe-S) cluster, NADH and FMN binding sites and quinone binding sites indicated the presence of phospho sites in close proximity to the binding sites of these cofactors with potential functional implications. Phosphoproteomics experiment in rat and human muscle mitochondria identified specific phospho sites in CI subunits, thereby validating the bioinformatic analysis. Molecular modeling of CI subunits indicated structural implications following phosphorylation. We surmise that protein phosphorylation, a transient and regulatory event could influence the structure-function relationship of CI thereby impinging on bioenergetics and ultimately contributing to aging and neurodegeneration.

An experimental and theoretical study of magnetocaloric effect in Nd0.5Dy0.5FeO3.

A significant magnetocaloric effect (MCE) has been revealed in our investigation on polycrystalline Nd0.5Dy0.5FeO3 below 30 K. Observed magnetization of the system at low temperature is 32% higher than the expected average magnetization of NdFeO3 and DyFeO3. Such an enhancement in the magnetization led to a large change in magnetic entropy (10.4 Jkg-1 K-1) at 4 K. The observed entropy change is remarkable considering the higher natural abundance of Nd compared to that of Dy and negligible MCE seen in case of NdFeO3. Theoretical calculations performed using mean-field approximation and Monte Carlo simulations on an Ising type spin model indicate that the high magnetocaloric effect is caused primarily by the ordering of rare-earth ions in C-type antiferromagnetic state in presence of molecular exchange field created by Fe ions.

Coupled superconducting and magnetic order in CeCoIn5.

Strong magnetic fluctuations can provide a coupling mechanism for electrons that leads to unconventional superconductivity. Magnetic order and superconductivity have been found to coexist in a number of magnetically mediated superconductors, but these order parameters generally compete. We report that close to the upper critical field, CeCoIn5 adopts a multicomponent ground state that simultaneously carries cooperating magnetic and superconducting orders. Suppressing superconductivity in a first-order transition at the upper critical field leads to the simultaneous collapse of the magnetic order, showing that superconductivity is necessary for the magnetic order. A symmetry analysis of the coupling between the magnetic order and the superconducting gap function suggests a form of superconductivity that is associated with a nonvanishing momentum.

Conflicts and child survival.

PIP: An overview is provided of the gravity of the problems of trauma from conflicts and effects on the health and survival of children and the relevance for India. Article 39 of the convention of the Rights of the Child adopted by the UN General Assembly is an agreement "to promote physical and psychological recovery and social reintegration of a child victim of any form of neglect, exploitation, abuse, inhuman treatment, or armed conflicts." The World Summit expanded the provision to include protecting women and children from the effects of war and to work toward preventing future conflicts. Safe corridors must be secured in order to protect children and families from surrounding war or violence. Concern for children was first indicated in the formation of UNICEF in the aftermath of World War II. Since that time, civilians, mostly women and children, have been the dominant population suffering from the effects of war. By 1991, 80% of the 20 million killed and the 80 million wounded were women and children involved in 150 conflicts. In the recent past, the Gulf War had a disastrous impact on children. Infant mortality increased from 39/1000 to 111/1000 and low birth weight rose from 5% to 12%. Child mortality of these under 5 years increased from 48/1000 to 143/1000. Another impact of armed conflicts on children is psychological trauma and detachment from emotional ties and enjoyment, and sleeplessness. Other symptoms are described. Recent action to counteract children's trauma has been taken in Kuwait, Mozambique, and Sri Lanka. Community-based programs help to identify needy children through parent and teacher education and to offer counseling. Several manuals are available on how to help children affected by war. One strategy is the establishment of a trauma center. In the Philippines, programs have been developed to involve children in therapy through drama, painting, and dance. India has experienced severe rioting, which has left many women and children orphaned. Programs need to be developed to deal with the effects on women and children.^ieng

Child survival and development.

PIP: November 14 is Children's Day in India. The designation of such a day along with the government's National Policy for Children and the signing of the World Declaration and Action Plan for the survival, protection, and development of children are a few indications of the government's recognition that the future of India depends upon the general well-being and education of its children. India is making fairly good progress in improving child health according to UNICEF measurement criteria in infant and maternal mortality, immunization against measles, children reaching grade 5 in schools, and the rate of total fertility. The government is failing, however, in the area of nutrition. India has 72 million malnourished children under 5 years of age or 38% of such children worldwide. Protein energy malnutrition affects 52.5% of children under the age of 6 years, of whom 10% suffer severe malnutrition. Vitamin A deficiency is also widespread. The government of India acknowledges the shortcomings of its efforts thus far and has developed a draft National Nutrition Policy which envisions a 50% reduction in the 1990 level of malnutrition by the year 2000. Reducing the extent of child labor, increasing the proportion of children enrolled in schools, and caring for orphans are also concerns on the agenda to be addressed.^ieng

Design of peptides: crystal and molecular structure of a 3(10)-helical peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val-OCH3.

Highly specific peptide structures can be designed by inserting dehydro residues into peptide sequences. The peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val- OCH3, synthesized by conventional procedures, crystallizes from methanol-water mixtures at 4 degrees C in the tetragonal space group P4(3) with cell parameters a = b = 13.829 +/- 0.003 A, c = 27.587 +/- 0.008 A, V = 5275.5 +/- 0.2 A3, Z = 4, dm = 1.152 +/- 0.005 g cm-3, dcal = 1.150 +/- 0.005 g cm-3. The overall residual factor R = 0.084 for 2342 reflections, with 2 theta max = 140 degrees using CuK alpha radiation. The backbone torsion angles are theta 1 = -171(1) degrees, omega 0 = 168(1) degrees, phi 1 = 77(2) degrees, psi 1 = 41(2) degrees, omega 1 = 169(1) degrees, phi 2 = -46(2) degrees, psi 2 = -24(2) degrees, omega 2 = 179(1) degrees, phi 3 = -63(2) degrees, psi 3 = 19(2) degrees, omega 3 = 171(1) degrees, phi 4 = -67(2) degrees, psi 4 = -8(1) degrees, omega 4 = 169(1) degrees, phi 5 = -61(1) degrees, psi 5 = -26(1) degrees, omega 5 = 177(1) degrees, phi 6 = -122(1) degrees, psi 6T = 26(2) degrees. The peptide adopts a 3(10)-helical conformation with three intramolecular hydrogen bonds (i + 3-->i) involving carbonyl oxygen atoms of Phe1, dehydro-Phe2, Val3, and the NH groups of Phe4, dehydro-Phe5, and Val6 with distances of 3.01(1), 2.82(1), and 3.09(2) A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Purification, crystallization and preliminary X-ray crystallographic analysis of human CCG1-interacting factor B.

A novel human factor CIB (CCG1-interacting factor B) has been isolated using the yeast two-hybrid system. The 22 kDa CIB protein has been expressed in Escherichia coli, purified to homogeneity and crystallized in a form suitable for crystallographic studies. The protein was crystallized in the orthogonal space group P2(1)2(1)2(1), with unit-cell parameters a = 43.60 (2), b = 44.45 (1), c = 110.70 (5) A and one molecule in the asymmetric unit. The crystal diffracted beyond 2.2 A resolution using synchrotron radiation.

Design of peptides: synthesis, crystal structure, molecular conformation, and conformational calculations of N-Boc-L-Phe-Dehydro-Ala-OCH3.

It is noteworthy that the dehydro-Ala residue adopts an extended conformation that is different than those observed in dehydro-Phe, dehydro-Leu, and dehydro-Abu. The peptide N-Boc-L-Phe-dehydro-Ala-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc-L-Phe-dehydro-Ala- OCH3. It was crystallized from its solution in a methanol-water mixture at room temperature. The crystals belong to the monoclonic space group P2(1), with a = 9.577(1) A, b = 5.195(3) A, c = 19.563(3) A, beta = 94.67(5) degrees, V = 970.1(6) A3, Z = 2, dm = 1.201(5) Mg m-3, dc = 1.197(5) Mg m-3. The structure was determined using direct method procedures. It was refined by a full-matrix least-squares procedure to an R value of 0.048 for 1370 observed reflections. The C2 alpha-C2 beta distance is 1.327(8) A, while the bond angles N2-C2 alpha-C2' and C1'-N2-C2 alpha are 109.8(5) degrees and 127.8(5) degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta 1 = 175.2(4) degrees, omega 0 = 170.2(4) degrees, phi 1 = 135.8(5) degrees, psi 1 = -22.6(6) degrees, omega 1 = 168.5(5) degrees, phi 2 = -170.3(5) degrees, psi 2T = -178.6(5) degrees, theta T = 178.4(7) degrees. The rigid planar and trans conformation of dehydro-Ala forces Phe to adopt a strained conformation. The Boc group has a trans-trans conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Descriptive epidemiology of lymphoid and haemopoietic malignancies in Bangalore, India.

Lymphoid and haemopoietic malignancies as a group constitute one of the important cancers in India, as elsewhere in the world. While information on incidence and mortality of these cancers, and that on survival, are available from most developed countries, there are very few reports describing this experience in developing ones. Population-based cancer registration commenced in Bangalore, India, in January 1982, under the auspices of the Indian Council of Medical Research. This source provides fairly complete and reliable incidence data, but, in order to obtain mortality and survival information, active follow-up involving visits of homes of patients was undertaken. Between 1982 and 1989, 1397 cases of lymphoid and haemopoietic malignancies were registered in the Bangalore cancer registry, giving an age-adjusted incidence rate of 7.7 and 4.8 per 100,000 in males and females respectively. Active follow-up provided mortality/survival information in 1267 or 90.7% of these cases. The overall observed 5-year survival for these cancers combined (both sexes) was 26%, and relative survival 28.4%. The 5-year survival rate was lower in all the individual lymphomas and leukaemias as compared with similar reports from the developed countries. Survival in Hodgkin's disease was influenced by clinical stage and age at presentation.

Crystallization and preliminary X-ray diffraction studies of HutP protein: an RNA-binding protein that regulates the transcription of hut operon in Bacillus subtilis.

HutP is an RNA-binding protein and regulates the expression of the histidine utilization (hut) operon in Bacillus subtilis by binding to cis-acting regulatory sequences on hut mRNA. HutP and its mutant, which has increased affinity for the regulatory sequences, were purified and crystallized by the hanging-drop vapor diffusion method. The space group was P2(1)3 with unit cell dimensions a=b=c=95.6A for HutP and a=b=c=96.8A for the mutant. Complete data sets of 3.0-A resolution for wild-type HutP and of 2.70-A resolution for the mutant HutP were collected.