The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues

Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, leading to reduced expression of frataxin protein. Evidence suggests that the mutation may induce epigenetic changes and heterochromatin formation, thereby impeding gene transcription. In particular, studies using FRDA patient blood and lymphoblastoid cell lines have detected increased DNA methylation of specific CpG sites upstream of the GAA repeat and histone modifications in regions flanking the GAA repeat. In this report we show that such epigenetic changes are also present in FRDA patient brain, cerebellum and heart tissues, the primary affected systems of the disorder. Bisulfite sequence analysis of the FXN flanking GAA regions reveals a shift in the FRDA DNA methylation profile, with upstream CpG sites becoming consistently hypermethylated and downstream CpG sites becoming consistently hypomethylated. We also identify differential DNA methylation at three specific CpG sites within the FXN promoter and one CpG site within exon 1. Furthermore, we show by chromatin immunoprecipitation (ChIP) analysis that there is overall decreased histone H3K9 acetylation together with increased H3K9 methylation of FRDA brain tissue. Further studies of brain, cerebellum and heart tissues from our GAA repeat expansion-containing FRDA YAC transgenic mice reveal comparable epigenetic changes to those detected in FRDA patient tissue. We have thus developed a mouse model that will be a valuable resource for future therapeutic studies targeting epigenetic modifications of the FXN gene to increase frataxin expression

Liposomes mediated drug delivery in infectious diseases

Liposome-mediated drug delivery systems along with other newer approaches of drug targeting have revolutionized the measures of controlling parasitic infections, including, malaria, leishmania, fungal infections, besides providing a new approach to control several bacterial infections, including Mycobacterial, Salmonella, Pseudomonas, etc. some of which have acquired resistance. These approaches provide definite reduction in drug toxicity, specially in leishmaniasis and control of candidiasis and other pathogenic fungi. Liposomal drugs, like amphotericin B, would have extensive use in the management of fungal diseases. Liposome mediated drug delivery has an exceptional advantage of biocompatibility, biodegradability, non-immunogenicity and can be used in clinical cases without any side effects

Organization and copy number of initiator tRNA genes in slow- and fast- growing mycobacteria

We have previously reported the isolation and characterization of a functional initiator tRNA gene, metA, and a second initiator tRNA-like sequence, metB, from Mycobacterium tuberculosis. Here we describe the fine mapping of the initiator tRNA gene locus of the avirulent (H37Ra) and virulent (H37Rv) strains ofM. tuberculosis. The genomic blot analyses show that the 1.7 kb (harbouring metE) and the 6.0 kb BamHI (harbouring metA) fragments are linked. Further, sequencing of a portion of the 6.0kb fragment, in conjunction with the sequence of the 1.7 kb fragment confirmed the presence of an IS6110 element in the vicinity ofmetB. The IS element is flanked by inverted (28 bp, with 3 contiguous mismatches in the middle) and direct (3 bp) repeats considered to be the hallmarks of IS6110 integration sites. The organization of the initiator tRNA gene locus is identical in both the H37Ra and H37Rv strains and they carry a single copy of the functional initiator tRNA gene. Interestingly, the fast growing Mycobacterium smegmatis also bears a single initiator tRNA gene. This finding is significant in view of the qualitative differences in total tRNA pools and the copy number of rRNA genes in the fast- and slow-growing mycobacteria. Finally, we discuss hypotheses related to the origin of metB in M. tuberculosis

High frequency induction of somatic embryos and plantlet regeneration from nodal explants of Hygrophila spinosa T. Anders

An efficient protocol is described for the rapid in vitro plant regeneration of a medicinally important plant, Hygrophila spinosa through direct somatic embryogenesis from nodal explants excised from 4 week old aseptic seedlings. Somatic embryos differentiated directly from nodal explants on Murashige and Skoog (MS) medium supplemented with 1.0 ìM 6- benzyladenine (BA) after 1 week of culture. The highest number (110.40 ± 3.55) of somatic embryos were recorded on MS medium supplemented with 1.0 ìM BA and 0.5 ìM NAA, growth regulator free half strength MS medium was found suitable for maturation and conversion of somatic embryos into complete plantlets. The well developed in vitro regenerated plantlets were successfully established in pots containing garden soil and grown in agreenhouse with 85% survival rate. The regenerants present an appearance similar to the seedlings obtained from normal seeds. The described method can be successfully employed for large scale multiplication and long term in vitro conservation of H. spinosa

Possible manifestation of spin fluctuations in the temperature behavior of resistivity in Sm_{1.85}Ce_{0.15}CuO_4 thin films

A pronounced step-like (kink) behavior in the temperature dependence of resistivity $\rho (T)$ is observed in the optimally-doped $Sm_{1.85}Ce_{0.15}CuO_4$ thin films around $T_{sf}=87K$ and attributed to manifestation of strong spin fluctuations induced by $Sm^{3+}$ moments with the energy $\hbar \omega_{sf}=k_BT_{sf}\simeq 7meV$. In addition to fluctuation induced contribution $\rho_{sf}(T)$ due to thermal broadening effects (of the width $\omega_{sf}$), the experimental data are found to be well fitted accounting for residual (zero-temperature) $\rho_{res}$, electron-phonon $\rho _{e-ph}(T)=AT$ and electron-electron $\rho_{e-e}(T)=BT^2$ contributions. The best fits produced $\omega_p=2.1meV$, $\tau_0^{-1}=9.5\times 10^{-14}s^{-1}$, $\lambda =1.2$, and $E_F=0.2eV$ for estimates of the plasmon frequency, the impurity scattering rate, electron-phonon coupling constant, and the Fermi energy, respectively.Comment: 6 pages (REVTEX4), 2 EPS figures; accepted for publication in JETP Letter

Evaluation of Power Quality Issues in grid Connected PV Systems

This paper deals with the evaluation of power quality issues in grid connected PV systems. This paper also presents  complete simulation, modeling and control of three phase grid connected solar PV module with Maximum Power Point Tracking. Perturb and Observe (P&O) method has been used for Maximum Power Point Tracking. In the proposed model DC bus voltage control , harmonic mitigation and power factor control are discussed as power quality issues. The simulation results are shown in the graphical waveforms and simulation is performed in MATLAB using SIMULINK environment and PSB toolboxes.

The Humoral Immune Response to Various Domains of Protective Antigen of Bacillus anthracis in Cutaneous Anthrax Cases in India

Anthrax, caused by Bacillus anthracis is known to occur globally since antiquity. Besides being an important biothreat agent, it is an important public health importance pathogen also in countries like India. B. anthracis secretes three distinct toxins, namely protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is the central moiety of the anthrax toxin complex and therefore has been a molecule of choice for vaccine development. PA has four different domains with different functions. In this study, the major domains of PA were cloned and expressed in bacterial system. The purified recombinant proteins were used to determine the humoral immune response by ELISA using 43 human cutaneous anthrax serum samples. The maximum immunoreactivity was observed with the whole PA protein followed by domain 2, 4 and 1. The study corroborated that in addition to full PA, individual domain 2 and 4 can also be good target for vaccine development as well as for serodiagnostic assays for cutaneous anthra