Pattern of mortality in sickle cell disease: an autopsy study

Background: Sickle haemoglobin is highly prevalent in western India. Sickle cell disease (SCD) is the generic term for the group of haemoglobinopathies caused by the occurrence of haemoglobin S (Hbs) in the homozygous form –sickle cell anaemia (Hbss) or as the heterozygous combination of Hbs with another abnormal haemoglobin such as Hbsc or beta –thalassaemias (Hbs b-thal). While doing autopsy in case of death with no apparent cause, the possibility of death may be due to vaso-occlusive crisis in sickle cell disease should be kept in mind. The findings at autopsy are variation of features which may or may not be directly connected to death. The goal is to draw awareness among physicians and relatives on need of autopsy as to minimize future unexpected death from complication or crisis and to enhance knowledge on both parties.Methods: This was a study of autopsy specimens received between January 2015 to December 2015 at tertiary care hospital.Results: Total of 679 autopsy cases were received, out of which sickled erythrocytes were detected in 25 cases. The mean age at death was 30 years, a male/female ratio of 1.5:1 and peak mortality was in the 2nd to 4th decades of life. The commonest presentation was sudden death. The cause of death in middle aged patients were vaso occlusive crisis, in paediatric patients were infection and in older patients were chronic organ damage.Conclusions: Early diagnosis, prompt treatment and extended screening programme are necessary in prevalent tribal belt of western India to reduce morbidity and mortality. we should also introduce awareness programmes in tribal belt of western India

Re-entrant ferroelectricity in liquid crystals

The ferroelectric (Sm C$^*$) -- antiferroelectric (Sm C$^*_A$) -- reentrant ferroelectric (re Sm C$^*$) phase temperature sequence was observed for system with competing synclinic - anticlinic interactions. The basic properties of this system are as follows (1) the Sm C$^*$ phase is metastable in temperature range of the Sm C$^*_A$ stability (2) the double inversions of the helix handedness at Sm C$^*$ -- Sm C$^*_A$ and Sm C$^*_A$% -- re-Sm C$^*$ phase transitions were found (3) the threshold electric field that is necessary to induce synclinic ordering in the Sm C$^*_A$ phase decreases near both Sm C$^*_A$ -- Sm C$^*$ and Sm C$^*_A$ -- re-Sm C$^*$ phase boundaries, and it has maximum in the middle of the Sm C$^*_A$ stability region. All these properties are properly described by simple Landau model that accounts for nearest neighboring layer steric interactions and quadrupolar ordering only.Comment: 10 pages, 5 figures, submitted to PR

Genetic effects of oxidative DNA damages: comparative mutagenesis of the imidazole ring-opened formamidopyrimidines (Fapy lesions) and 8-oxo-purines in simian kidney cells

Fapy·dG and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) are formed in DNA by hydroxyl radical damage. In order to study replication past these lesions in cells, we constructed a single-stranded shuttle vector containing the lesion in 5′-TGT and 5′-TGA sequence contexts. Replication of the modified vector in simian kidney (COS-7) cells showed that Fapy·dG is mutagenic inducing primarily targeted Fapy·G→T transversions. In the 5′-TGT sequence mutational frequency of Fapy·dG was ∼30%, whereas in the 5′-TGA sequence it was ∼8%. In parallel studies 8-oxo-dG was found to be slightly less mutagenic than Fapy·dG, though it also exhibited a similar context effect: 4-fold G→T transversions (24% versus 6%) occurred in the 5′-TGT sequence relative to 5′-TGA. To investigate a possible structural basis for the higher G→T mutations induced by both lesions when their 3′ neighbor was T, we carried out a molecular modeling investigation in the active site of DNA polymerase β, which is known to incorporate both dCTP (no mutation) and dATP (G→T substitution) opposite 8-oxo-G. In pol β, the syn-8-oxo-G:dATP pair showed greater stacking with the 3′-T:A base pair in the 5′-TGT sequence compared with the 3′-A:T in the 5′-TGA sequence, whereas stacking for the anti-8-oxo-G:dCTP pair was similar in both 5′-TGT and 5′-TGA sequences. Similarly, syn-Fapy·G:dATP pairing showed greater stacking in the 5′-TGT sequence compared with the 5′-TGA sequence, while stacking for anti-Fapy·G:dCTP pairs was similar in the two sequences. Thus, for both lesions less efficient base stacking between the lesion:dATP pair and the 3′-A:T base pair in the 5′-TGA sequence might cause lower G→T mutational frequencies in the 5′-TGA sequence compared to 5′-TGT. The corresponding lesions derived from 2′-deoxyadenosine, Fapy·dA and 8-oxo-dA, were not detectably mutagenic in the 5′-TAT sequence, and were only weakly mutagenic (<1%) in the 5′-TAA sequence context, where both lesions induced targeted A→C transversions. To our knowledge this is the first investigation using extrachromosomal probes containing a Fapy·dG or Fapy·dA site-specifically incorporated, which showed unequivocally that in simian kidney cells Fapy·G→T substitutions occur at a higher frequency than 8-oxo-G→T and that Fapy·dA is very weakly mutagenic, as is 8-oxo-dA

Genetic effects of oxidative DNA damages: comparative mutagenesis of the imidazole ring-opened formamidopyrimidines (Fapy lesions) and 8-oxo-purines in simian kidney cells

Fapy·dG and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) are formed in DNA by hydroxyl radical damage. In order to study replication past these lesions in cells, we constructed a single-stranded shuttle vector containing the lesion in 5′-TGT and 5′-TGA sequence contexts. Replication of the modified vector in simian kidney (COS-7) cells showed that Fapy·dG is mutagenic inducing primarily targeted Fapy·G→T transversions. In the 5′-TGT sequence mutational frequency of Fapy·dG was ∼30%, whereas in the 5′-TGA sequence it was ∼8%. In parallel studies 8-oxo-dG was found to be slightly less mutagenic than Fapy·dG, though it also exhibited a similar context effect: 4-fold G→T transversions (24% versus 6%) occurred in the 5′-TGT sequence relative to 5′-TGA. To investigate a possible structural basis for the higher G→T mutations induced by both lesions when their 3′ neighbor was T, we carried out a molecular modeling investigation in the active site of DNA polymerase β, which is known to incorporate both dCTP (no mutation) and dATP (G→T substitution) opposite 8-oxo-G. In pol β, the syn-8-oxo-G:dATP pair showed greater stacking with the 3′-T:A base pair in the 5′-TGT sequence compared with the 3′-A:T in the 5′-TGA sequence, whereas stacking for the anti-8-oxo-G:dCTP pair was similar in both 5′-TGT and 5′-TGA sequences. Similarly, syn-Fapy·G:dATP pairing showed greater stacking in the 5′-TGT sequence compared with the 5′-TGA sequence, while stacking for anti-Fapy·G:dCTP pairs was similar in the two sequences. Thus, for both lesions less efficient base stacking between the lesion:dATP pair and the 3′-A:T base pair in the 5′-TGA sequence might cause lower G→T mutational frequencies in the 5′-TGA sequence compared to 5′-TGT. The corresponding lesions derived from 2′-deoxyadenosine, Fapy·dA and 8-oxo-dA, were not detectably mutagenic in the 5′-TAT sequence, and were only weakly mutagenic (<1%) in the 5′-TAA sequence context, where both lesions induced targeted A→C transversions. To our knowledge this is the first investigation using extrachromosomal probes containing a Fapy·dG or Fapy·dA site-specifically incorporated, which showed unequivocally that in simian kidney cells Fapy·G→T substitutions occur at a higher frequency than 8-oxo-G→T and that Fapy·dA is very weakly mutagenic, as is 8-oxo-dA

Flexoelectricity and piezoelectricity - reason for rich variety of phases in antiferroelectric liquid crystals

The free energy of antiferroelectric liquid crystal which takes into account polar order explicitly is presented. Steric, van der Waals, piezoelectric and flexoelectric interactions to the nearest layers and dipolar electrostatic interactions to the nearest and to the next nearest layers induce indirect tilt interactions with chiral and achiral properties, which extend to the third and to the fourth nearest layers. Chiral indirect interactions between tilts can be large and induce helicoidal modulations even in systems with negligible chiral van der Waals interactions. If indirect chiral interactions compete with chiral van der Waals interactions, the helix unwinding is possible. Although strength of microscopic interactions change monotonically with decreasing temperature, effective interlayer interactions change nonmonotonically and give rise to nonmonotouous change of modulation period through various phases. Increased enatiomeric excess i.e. increased chirality changes the phase sequence.Comment: 4 pages, 1 figur

Osteological description of Indian Skipper Frog Euphlyctis cyanophlyctis (Anura: Dicroglossidae) from the Western Ghats of India

The present study provides description of the osteology of Skipper Frog Euphlyctis cyanophlyctis. Seven adult specimens of E. cyanophlyctis from northern Western Ghats of India were cleared and double stained for studying osteological characteristics. The baseline description of osteological characters of cranial and post-cranial elements (paired nasals, tubular sphenethmoid, well-developed vomerine teeth, arciferal pectoral girdle, fan-shaped omosternum, cartilaginous W-shaped xiphisternum, hind limb with longest cylindrical humerus, V-shaped pectoral girdle and phalangeal appendages) provided in present study will help in further taxonomic investigations of the genus Euphlyctis. Further, the baseline information on osteology of Skipper frog will serve as a reference material for investigations related to malformations, either in this or related species. We also provide first observation on sacro-pelvic malformation in one of the studied specimens

Evidence for the Role of Proton Shell Closure in Quasifission Reactions from X-Ray Fluorescence of Mass-Identified Fragments

The atomic numbers and the masses of fragments formed in quasifission reactions are simultaneously measured at scission in Ti48+U238 reactions at a laboratory energy of 286 MeV. The atomic numbers are determined from measured characteristic fluorescence x rays, whereas the masses are obtained from the emission angles and times of flight of the two emerging fragments. For the first time, thanks to this full identification of the quasifission fragments on a broad angular range, the important role of the proton shell closure at Z=82 is evidenced by the associated maximum production yield, a maximum predicted by time-dependent Hartree-Fock calculations. This new experimental approach gives now access to precise studies of the time dependence of the N/Z (neutron over proton ratios of the fragments) evolution in quasifission reactions.The authors acknowledge support from the Australian Research Council through Discovery Grants No. FL110100098, No. FT120100760, No. DP130101569, No. DE140100784, No. DP160 101254, and No. DP170102318. Support for accelerator operations through the NCRIS program is acknowledged. Two of us (C. S. and M. A.) acknowledge support from the Scientific Mobility Program of the Embassy of France in Australia. This research was undertaken with the assistance of resources from the National Computational Infrastructure (NCI), which is supported by the Australian Government

SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells

Cellular senescence irreversibly arrests cell proliferation, accompanied by a multi-component senescence-associated secretory phenotype (SASP) that participates in several age-related diseases. Using stable isotope labeling with amino acids (SILACs) and cultured cells, we identify 343 SASP proteins that senescent human fibroblasts secrete at 2-fold or higher levels compared with quiescent cell counterparts. Bioinformatic analysis reveals that 44 of these proteins participate in hemostasis, a process not previously linked with cellular senescence. We validated the expression of some of these SASP factors in cultured cells and in vivo. Mice treated with the chemotherapeutic agent doxorubicin, which induces widespread cellular senescence in vivo, show increased blood clotting. Conversely, selective removal of senescent cells using transgenic p16-3MR mice showed that clearing senescent cells attenuates the increased clotting caused by doxorubicin. Our study provides an in-depth, unbiased analysis of the SASP and unveils a function for cellular senescence in hemostasis