Alkaline Gels Research Articles

Quantitative analysis of preferential utilization of AAV ITR as the packaging terminal signal.

Genetic engineering advances have led to recombinant adeno-associated virus (rAAV) becoming an invaluable tool for the development of effective gene therapies. The production of rAAV is susceptible to off-target heterogeneous packaging, the effects of which are still being understood. Here, rAAV vectors with four-genome lengths were produced using both adherent and suspension HEK293 cells to understand the 5'ITR termination. AAV8 vectors were produced from the human FVIII plasmid for a full-length cargo of 4,707 nucleotides with specific truncations, creating smaller genomes. Conventionally, rAAV is characterized by differentiating empty capsids from full capsids, but for this work, that description is incomplete. The small genomes in this study were characterized by charge detection-mass spectrometry (CD-MS). Using CD-MS, packaged genomes in the range conventionally attributed to partials were resolved and quantified. In addition, alkaline gels and qPCR were used to assess the identity of the packaged genomes. Together, these results showed a propensity for unit-length genomes to be encapsidated. Packaged genomes occurred as replication intermediates emanating from the 5'ITR, indicating that HEK293 cells prefer unit-length genomes as opposed to the 5'ITR termination and heterogeneous DNA packaging observed previously from Sf9 cell systems. As both manufacturing processes are used and continually assessed to produce clinical material, such an understanding will benefit rAAV design for basic research and gene therapy.

Partial genome content within rAAVs impacts performance in a cell assay-dependent manner

Recombinant adeno-associated viruses (rAAVs) deliver DNA to numerous cell types. However, packaging of partial genomes into the rAAV capsid is of concern. Although empty rAAV capsids are studied, there is little information regarding the impact of partial DNA content on rAAV performance in controlled studies. To address this, we tested vectors containing varying levels of partial, self-complementary EGFP genomes. Density gradient cesium chloride ultracentrifugation was used to isolate three distinct rAAV populations: (1) a lighter fraction, (2) a moderate fraction, and (3) a heavy fraction. Alkaline gels, Illumina Mi-Seq, size exclusion chromatography with multi-angle light scattering (SEC-MALS), and charge detection mass spectrometry (CD-MS) were used to characterize the genome of each population and ddPCR to quantify residual DNA molecules. Live-cell imaging and EGFP ELISA assays demonstrated reduced expression following transduction with the light fraction compared with the moderate and heavy fractions. However, PCR-based assays showed that the light density delivered EGFP DNA to cells as efficiently as the moderate and heavy fractions. Mi-Seq data revealed an underrepresentation of the promoter region for EGFP, suggesting that expression of EGFP was reduced because of lack of regulatory control. This work demonstrates that rAAVs containing partial genomes contribute to the DNA signal but have reduced vector performance.

Determination of the Ribonucleotide Content of mtDNA Using Alkaline Gels.

Impaired mitochondrial DNA (mtDNA) maintenance, due to, e.g., defects in the replication machinery or an insufficient dNTP supply, underlies a number of mitochondrial disorders. The normal process of mtDNA replication leads to the incorporation of multiple single ribonucleotides (rNMPs) per mtDNA molecule. Given that embedded rNMPs alter the stability and properties of the DNA, they may have consequences for mtDNA maintenance and thereby for mitochondrial disease. They also serve as a readout of the intramitochondrial NTP/dNTP ratios. In this chapter, we describe a method for the determination of mtDNA rNMP content using alkaline gel electrophoresis and Southern blotting. This procedure is suited for the analysis of mtDNA in total genomic DNA preparations as well as in purified form. Moreover, it can be performed using equipment found in most biomedical laboratories, allows the simultaneous analysis of 10-20 samples depending on the gel system employed, and can be modified for the analysis of other mtDNA modifications.

Hydrolytic Stability of Crosslinked, Highly Alkaline Diallyldimethylammonium Hydroxide Hydrogels.

The aim of this study was to evaluate the persistence of alkaline hydrogels based on a common (N,N′-methylenebisacrylamide, BIS) and three recently published tetraallyl crosslinkers. Such hydrogels have been shown to be suitable materials for the rehabilitation of cementitious materials. Of the four crosslinkers under investigation, N,N,N′,N′-tetraallylpiperazinium dibromide decomposed quickly in 1 m KOH solution and was not considered further. BIS showed the first signs of a decomposition after several days, while tetraallylammonium bromide and N,N,N′,N′-tetraallyltrimethylene dipiperidine dibromide remained unaffected. In contrast to BIS, which suffers from low solubility in water, the two tetraallyl crosslinkers show unlimited miscibility with diallyldimethylammonium hydroxide solutions. For the study, gels with up to 50 wt % crosslinker were prepared. Of these, gels containing tetraallylammonium bromide always show the highest degrees of swelling, with a peak value of 397 g/g at a content of 2 wt %. Under accelerated ageing at 60 °C for 28 d, gels crosslinked with BIS ultimately turned liquid, while the storage modulus and the degree of swelling of the two tetraallyl-crosslinked gels remained unchanged. This indicates that alkaline gels can be suitable for long application periods, which are common for rehabilitation measures in the construction industry.

Controlled treatment of a high velocity anisotropic aquifer model contaminated by hexachlorocyclohexanes.

Xanthan gels were assessed to control the reductive dechlorination of hexachlorocyclohexanes (HCHs) and trichlorobenzenes (TCBs) in a strong permeability contrast and high velocity sedimentary aquifer. An alkaline degradation was selected because of the low cost of NaOH and Ca(OH)2. The rheology of alkaline xanthan gels and their ability to deliver alkalinity homogeneously, while maintaining the latter, were studied. Whereas the xanthan gels behaved like non-Newtonian shear-thinning fluids, alkalinity and Ca(OH)2 microparticles had detrimental effects, yet, the latter decreased with the shear-rate. Breakthrough curves for the NaOH and Ca(OH)2 in xanthan solutions, carried out in the lowest permeability soil (9.9μm2), demonstrated the excellent transmission of alkalinity, while moderate pressure gradients were applied. Injection velocities ranging from 1.8 to 3.8mh-1 are anticipated in the field, given the permeability range from 9.9 to 848.7μm2. Despite a permeability contrast of 8.7 in an anisotropic aquifer model, the NaOH and the Ca(OH)2 both in xanthan gels spread only 5- and 7-times faster in the higher permeability zone, demonstrating that the delivery was enhanced. Moreover, the alkaline gels which were injected into a high permeability layer under lateral water flow, showed a persistent blocking effect and longevity (timescale of weeks), in contrast to the alkaline solution in absence of xanthan. Kinetics of alkaline dechlorination carried out on the historically contaminated soil, using the Ca(OH)2 suspension in xanthan solution, showed that HCHs were converted in TCBs by dehydrodechlorination, whereas the latter were then degraded by reductive hydrogenolysis. Degradation kinetics were achieved within 30h for the major and most reactive fraction of HCHs.

Physically cross-linked xanthan hydrogels as solid electrolytes for Al/air batteries

This paper presents the results of an experimental study aimed at preparing high-conductivity solid electrolytes for Al-air primary cells, starting from an eco-friendly polysaccharide (xanthan) and KOH or HCl concentrated solutions (up to 11 M). Xanthan permits all-solid-state Al-air cells to be prepared with both KOH and HCl solutions but, differently from the already acquired knowledge, the best performance are obtained with acid electrolytes. The results evidence that different formation mechanisms can explain the ionic conductivities of acid and alkaline gels, and then the cell discharge performance. However, the cell capacities at higher current density are enhanced with acid hydrogels, thanks to the capability of xanthan to inhibit the anodic self-corrosion in an acid medium. In particular, a solid electrolyte prepared with 5 M HCl solution and a xanthan/liquid ratio of 0.7 g/ml provides a cell capacity higher than 70 mAh cm−2 at discharge current density of 10 mA cm−2, corresponding to 2.2 Ah gAl−1 consumed (or 1430 Wh kg−1).

In-office bleaching with a commercial 40% hydrogen peroxide gel modified to have different pHs: Color change, surface morphology, and penetration of hydrogen peroxide into the pulp chamber.

In-office bleaching gels are usually marketed in different pHs. This study is aimed at evaluating the efficacy, enamel surface morphology and concentration of hydrogen peroxide (HP) in the pulp chamber of teeth bleached with 40% HP with different pHs. Forty premolars were randomly divided according to bleaching gel pH: 5.1, 6.3, 7.0, and control (no bleaching). Teeth were prepared, an acetate buffer was placed in the pulp chamber and teeth were bleached with two 20-minutes applications. The amount of HP was determined on a UV-VIS spectrophotometer. Color change was assessed by using a digital spectrophotometer before and 1 week after bleaching treatment. Five additional premolars were divided into four parts, assigned to the same groups above for analysis under scanning electron microscope. Data were subjected to anova and Tukey's tests (alpha =0.05). The group pH5.1 showed the highest HP diffusion in the pulp chamber (P< .001). No significant difference was detected in color change (P= .51). All groups presented the same pattern of enamel demineralization. The bleaching agent with pH5.1 presented the highest HP amounts in the pulp chamber, but color change and enamel morphology were similar among groups. Regardless of the pH, the bleaching effect can be observed in teeth submitted to high concentrations of HP, but a higher permeability of HP was found in the pulp chamber of teeth bleached with more acidic bleaching agents. Based on that, we suggest the use of alkaline gels for in-office bleaching to minimize damage to the pulpal tissue.

How It All Began: A Personal History of Gel Electrophoresis.

Arne Tiselius' moving boundary electrophoresis method was still in general use in 1951 when this personal history begins, although zonal electrophoresis with a variety of supporting media (e.g., filter paper or starch grains) was beginning to replace it. This chapter is an account of 10years of experiments carried out by the author during which molecular sieving gel electrophoresis was developed and common genetic variants of two proteins, haptoglobin and transferrin, were discovered in normal individuals. Most of the figures are images of pages from the author's laboratory notebooks, which are still available, so that some of the excitement of the time and the humorous moments are perhaps apparent. Alkaline gels, acidic gels with and without denaturants, vertical gels, two-dimensional gels and gels with differences in starch concentration are presented. The subtle details that can be discerned in these various gels played an indispensable role in determining the nature of the change in the haptoglobin gene (Hp) that leads to the polymeric series characteristic of Hp 2/Hp 2 homozygotes. Where possible the names of scientific friends who made this saga of gel electrophoresis so memorable and enjoyable are gratefully included.

Simultaneous Mapping and Quantitation of Ribonucleotides in Human Mitochondrial DNA.

Established approaches to estimate the number of ribonucleotides present in a genome are limited to the quantitation of incorporated ribonucleotides using short synthetic DNA fragments or plasmids as templates and then extrapolating the results to the whole genome. Alternatively, the number of ribonucleotides present in a genome may be estimated using alkaline gels or Southern blots. More recent in vivo approaches employ Next-generation sequencing allowing genome-wide mapping of ribonucleotides, providing the position and identity of embedded ribonucleotides. However, they do not allow quantitation of the number of ribonucleotides which are incorporated into a genome. Here we describe how to simultaneously map and quantitate the number of ribonucleotides which are incorporated into human mitochondrial DNA in vivo by Next-generation sequencing. We use highly intact DNA and introduce sequence specific double strand breaks by digesting it with an endonuclease, subsequently hydrolyzing incorporated ribonucleotides with alkali. The generated ends are ligated with adapters and these ends are sequenced on a Next-generation sequencing machine. The absolute number of ribonucleotides can be calculated as the number of reads outside the recognition site per average number of reads at the recognition site for the sequence specific endonuclease. This protocol may also be utilized to map and quantitate free nicks in DNA and allows adaption to map other DNA lesions that can be processed to 5´-OH ends or 5´-phosphate ends. Furthermore, this method can be applied to any organism, given that a suitable reference genome is available. This protocol therefore provides an important tool to study DNA replication, 5´-end processing, DNA damage, and DNA repair.

Simultaneous Mapping and Quantitation of Ribonucleotides in Human Mitochondrial DNA

Established approaches to estimate the number of ribonucleotides present in a genome are limited to the quantitation of incorporated ribonucleotides using short synthetic DNA fragments or plasmids as templates and then extrapolating the results to the whole genome. Alternatively, the number of ribonucleotides present in a genome may be estimated using alkaline gels or Southern blots. More recent in vivo approaches employ Next-generation sequencing allowing genome-wide mapping of ribonucleotides, providing the position and identity of embedded ribonucleotides. However, they do not allow quantitation of the number of ribonucleotides which are incorporated into a genome. Here we describe how to simultaneously map and quantitate the number of ribonucleotides which are incorporated into human mitochondrial DNA in vivo by Next-generation sequencing. We use highly intact DNA and introduce sequence specific double strand breaks by digesting it with an endonuclease, subsequently hydrolyzing incorporated ribonucleotides with alkali. The generated ends are ligated with adapters and these ends are sequenced on a Next-generation sequencing machine. The absolute number of ribonucleotides can be calculated as the number of reads outside the recognition site per average number of reads at the recognition site for the sequence specific endonuclease. This protocol may also be utilized to map and quantitate free nicks in DNA and allows adaption to map other DNA lesions that can be processed to 5´-OH ends or 5´-phosphate ends. Furthermore, this method can be applied to any organism, given that a suitable reference genome is available. This protocol therefore provides an important tool to study DNA replication, 5´-end processing, DNA damage, and DNA repair.

Synthesis of highly dispersed cobalt oxide clusters encapsulated within LTA zeolites

Small Co3O4 nanoparticles uniformly distributed in size were encapsulated within LTA zeolite crystals in a one-step process through hydrothermal self-assembly of crystalline frameworks around ligated Co2+ precursors. The use of bifunctional ligands containing a chelating bidentate amine functionality and an alkoxysilane moiety prevented the precipitation of Co2+ species as colloidal hydroxides in the highly alkaline synthesis gels, while also allowing the formation of linkages between precursors and the framework during the nucleation and growth of LTA crystals. Oxidative treatments of ligated compounds occluded within zeolite crystals removed ligand residues and formed small Co3O4 nanoparticles visible in transmission electron micrographs. These nanoparticles retained their small size (average diameter 1.5 nm) after oxidative treatment at 620–870 K, a reflection of their stabilization by confinement within zeolite voids. The infrared spectra of adsorbed CO on Co-LTA samples confirmed the absence of Co2+ as exchanged cations or aluminosilicates, indicating the presence of Co oxide clusters, with dynamics and stoichiometry of reduction in H2 corresponding to small Co3O4 clusters. Ethanol oxidation rates on Co-LTA samples, exchanged with K+ or Ca2+ cations to vary the diffusive properties of LTA crystals, indicated that more than 97% of the active surfaces on these Co3O4 clusters resided within zeolite crystals, where ethanol and O2 concentrations depend on the diffusive properties of the LTA framework. The Co3O4 clusters prepared by these methods, in contrast with Co2+ in exchanged or aluminosilicate forms, exhibit reactivity in CO and NO oxidation. Their turnover rates (per exposed Co atom), however, were lower than on bulk Co3O4 powders, because of the combined effects of diffusional constraints imposed by the confining framework and the small size of these clusters, which leads to lower intrinsic reactivities as a result of their more difficult reduction during catalytic redox cycles. These clusters would be attractive in catalytic applications requiring stability against sintering during reaction or regeneration, reactant or product shape selectivity, or protection from contact with large molecules that block active surfaces. Such oxide clusters cannot be formed by sequential ion exchange, detachment by reduction to Co0, and re-oxidation because the extremely high temperatures required for reduction destroy the aluminosilicate frameworks. The synthesis protocols and their mechanistic interpretations described herein represent a conceptual and practical platform for the encapsulation of nanoparticles of base elements within a broad range of confining crystalline environments through one-step hydrothermal self-assembly.

Investigations on the ion exchange process of Cs+ and Sr2+ cations by ETS materials

Ion exchange experiments were carried out for evaluation the removal capability of cesium and strontium ions by the microporous Engelhard Titanium Silicates – 4 and 10 (ETS-4 and ETS-10, respectively) synthesized from alkaline gels. Ionic selectivities were estimated from the ion exchange isotherms, Kielland and Langmuir plots. It is shown that both microporous titanosilicates perform under a similar ion exchange profile against Cs+ cations and the selectivity of ETS-4 for Sr2+ is highly depended on temperature. ETS-10 is unselective for Sr2+ over a wide range of equivalent ionic fraction of strontium in solution. The Langmuir isotherms indicate that in the absence of ionic competition both titanosilicates retain Cs+ and Sr2+ cations, as much as their ion exchange capacities. These positive results promote ETS materials as very good candidates for the removal of both cesium and strontium from nuclear waste solutions.

Band smearing of PCR amplified bacterial 16S rRNA genes: Dependence on initial PCR target diversity

Band smearing in agarose gels of PCR amplified bacterial 16S rRNA genes is understood to comprise amplicons of varying sizes arising from PCR errors, and requires elimination. We consider that with amplified heterogeneous DNA, delayed electro-migration is caused not by PCR errors but by dsDNA structures that arise from imperfect strand pairing. The extent of band smearing was found to be proportional to the sequence heterogeneity in 16S rRNA variable regions. Denaturing alkaline gels showed that all amplified DNA was of the correct size. A novel bioinformatic approach was used to reveal that band smearing occurred due to imperfectly paired strands of the amplified DNA. Since the smear is a structural fraction of the correct size PCR product, it carries important information on richness and diversity of the target DNA. For accurate analysis, the origin of the smear must first be identified before it is eliminated by examining the amplified DNA in denaturing alkaline gels.

Assessment of Different Methods for Cleaning the Limestone Façades of the Former Workers Hospital of Madrid, Spain

Five different methods for cleaning the limestone façades on what was originally the Workers Hospital in Madrid are analyzed in this paper. Due to the pollution in the surrounding air, just 20 years after a prior cleaning operation, sulfate crusts had developed on the entire stone surface of the building. The gypsum mortar used in the original masonry constituted an additional source of sulfur. Limestone is a traditional building material in Madrid and its surroundings. The petrography, mineralogy and petrophysical properties of the biomicrite, pelmicrite and biopelmicrite varieties of limestone identified in the hospital walls were determined. Analysis of a black layer on the stone surface showed that it consisted primarily of sulfate crusts. The cleaning methods tested were alkaline gels (sodium hydroxide and potassium hydroxide), pressurized hot water, glass bead blasting and latex peeling. The criteria for assessing the effectiveness and potential risks of the various cleaning systems included changes in the chromatic parameters of the stone, the formation of alteration products (i.e. salts) and modification of the stone surface. The stones cleaned with the three most effective methods, together with a rain-washed stone as a reference, were washed with water to generate an artificial runoff. The collected drain water was analyzed to determine the presence of any by-products from the cleaning process. The method found to be most effective and which caused the least alteration to the stone surface was glass bead blasting, particularly after adjustment of the bead size and pressure conditions used for the test.

Low-level infrared laser effect on plasmid DNA

Low-level laser therapy is used in the treatment of many diseases based on its biostimulative effect. However, the photobiological basis for its mechanism of action and adverse effects are not well understood. The aim of this study, using experimental models, was to evaluate the effects of laser on bacterial plasmids in alkaline agarose gel electrophoresis and Escherichia coli cultures. The electrophoretic profile of bacterial plasmids in alkaline agarose gels were used for studying lesions in DNA exposed to infrared laser. Transformation efficiency and survival of Escherichia coli AB1157 (wild-type), BH20 (fpg/mutM(-)), BW9091 (xth(-)), and DH5αF'Iq (recA(-)) cells harboring pBSK plasmids were used as experimental models to assess the effect of laser on plasmid DNA outside and inside of cells. Data indicate low-level laser: (1) altered the electrophoretic profile of plasmids in alkaline gels at 2,500-Hz pulsed-emission mode but did not alter at continuous wave, 2.5- and 250-Hz pulsed-emission mode; (2) altered the transformation efficiency of plasmids in wild-type and fpg/mutM(-) E. coli cells; (3) altered the survival fpg/mutM(-), xthA(-) and recA(-) E. coli cultures harboring pBSK plasmids. Low-level infrared laser with therapeutic fluencies at high frequency in pulsed-emission modes have effects on bacterial plasmids. Infrared laser action can differently affect the survival of plasmids in E. coli cells proficient and deficient in DNA repair mechanisms, therefore, laser therapy protocol should take into account fluencies, frequencies and wavelength of laser, as well as tissue conditions and genetic characteristics of cells before beginning treatment.

The effect of ageing on the rheological properties of gelatin gels

The effect of ageing at 4 degrees on the viscoelastic properties of 1-5 and 2-0% acid and alkaline processed gelatin gels has been investigated. Viscoelastic properties were not markedly affected by ageing time although evidence of a decrease in gel structure with increasing ageing time was apparent. This has been tentatively attributed to hydrolysis of amide links. 1-5% alkaline gels were shown to be more rigid than the corresponding acid gels and this has been discussed in terms of differences in molecular weight, polydispersity, charge and charge distribution.

The influence of Si/Al and Si/Ti molar ratios of different [Ti, Al]-beta catalysts in the partial oxidation of cyclohexene with hydrogen peroxide

The catalytic activity, epoxide selectivity and hydrogen peroxide conversion and efficiency using [Ti, Al]-beta catalysts with different Ti and Al contents have been evaluated in the epoxidation of cyclohexene at 70 °C with hydrogen peroxide and acetonitrile as the oxidant and the solvent, respectively. The catalysts tested were obtained by two methods: (1) varying the alkalinity in the initial gel (Method I), and (2) substituting part of the template agent with equivalent quantities of fluoride ions in the mother gel (Method II). Characterizations were used to examine the chemical composition, crystallinity, framework Ti and Brønsted acidity in the catalysts. The catalysts crystallized by Method II hold both less Ti and Al and showed better performances in the cyclohexene epoxidation. Catalysts obtained from more alkaline gels and crystallized for shorter times by Method I contained less Ti but more Al. These catalysts showed both lower epoxide selectivity and hydrogen peroxide efficiency. For catalysts with similar Al, but different Ti contents, those richer in Ti showed higher activity and epoxide selectivity. Catalysts with both higher Ti (Si/Ti: 50–60) and Al (Si/Al: 36–56) contents, obtained from more alkaline gels for more prolonged crystallization times by Method I showed the lowest activities, epoxide selectivities and peroxide efficiencies. The dramatic influence of the Al and Ti contents in catalysts on the epoxide yields and peroxide efficiencies were explained through the intrinsic properties of the Ti-hydroperoxo complex formed, responsible for the oxygen transfer to olefin on Ti centers having different Lewis acid strengths.

Evaluación de la reactividad árido-álcali en diversos áridos silicatados. Alternativas para minimizar esta reacción

Siliceous aggregates are characterized for presenting certain chemical reactivity opposite to the calcium hydroxide liberated in the hydration of the Portland cement. The consequence of this reaction between the aggregate and the components of the intermediate concrete phase is the formation of gels very eager for water that can generate important disruptive pressures in the deeper structure of concrete. We have assessed the potential reactivity of several siliceous aggregates (granites, gneiss, hornfels, granites, quartzite and serpentine) by means of the accelerated method in concrete bars (normalized method) and the superficial reactivity method, observing by scanning electron microscopy (SEM) the formation of silica calcium alkaline gels. On the other hand, we explore the way of minimizing this disruptive reaction employing ground clay bricks and cement type CEM IV UNE-EN 197-1.

An evaluation of the SPIFE® 3000 semi‐automated gel electrophoresis system for the identification of hemoglobin variants and comparison of relative electrophoretic mobilities with manual gel electrophoresis methods

Laboratory identification of hemoglobin (Hb) variants can involve multiple techniques. The use of semi-automated instruments that perform gel electrophoresis and staining, such as the SPIFE 3000 electrophoresis system, can greatly reduce the labor required for these commonly used techniques. We performed a comparison of the method involved in SPIFE 3000 system with those of manual gel electrophoresis. A total of 22 540 samples were analyzed using the SPIFE 3000, and compared with mobilities on cellulose acetate and citrate agar gels using standard manual methods. The results were compared using relative electrophoretic mobilities (REM). Of the 191 Hb variants identified, only 13 had REM that differed from manual electrophoresis when analyzed using the SPIFE 3000 system. One variant (Hb O-Indonesia) showed different mobility on both acid and alkaline gels, two (Hb E, Hb Sunshine Seth) on alkaline gel only, and 10 (Hbs N-Baltimore, N-Seattle, O-Arab, Shelby, Summer Hill, Tak, Hasharon, M-Iwate, Q-Iran, and Setif) on acid gels only. The SPIFE 3000 semi-automated electrophoresis system produces similar results when compared with those of standard manual electrophoresis methods.

Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression

Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients’ brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients’ brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients’ brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here.