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Abstract: Allele frequencies of the 15 autosomal STR loci: D8S1179, D21S11, D7S820, CSF1PO, D19S433, vWA, TPOX, D18S51, D3S1358, THO1, D13S317, D16S539, D2S1338, D5S818, and FGA were determined in two endogamous Muslim populations (Dawoodi Bohra Muslims from Shiite Muslims and Sunni Muslims) residing in Tamilnadu, India. The Loci D7S820, CSF1PO, D19S433, vWA, TPOX, D13S317, D16S539, D5S818, and FGA in Dawoodi Bohra Muslims from Shiite Muslims, and CSF1PO, D19S433, TPOX, and D16S539 in Sunni Muslims were found to deviate significantly from Hardy–Weinberg equilibrium. The power of discrimination of the analyzed markers was found to be high for the populations, thereby facilitating the validation and efficiency of these STR markers in human identification. [Copyright &y& Elsevier]

Abstract: Background: Direct carotid cavernous fistulae (CCF) are commonly treated by endovascular deployment of a detachable balloon into the cavernous sinus to reconstruct the sidewall of the carotid artery and preserve flow in that vessel. Relatively few reports exist describing revisions using constructive, transarterial approaches when this technique fails. Methods: We describe a novel method using expandable hydrogel-coated platinum coils to revise a failed balloon reconstruction in which the balloon had migrated within the cavernous sinus away from the rent in the carotid wall. Results: This new technique to buttress the balloon back into the desired position using expandable coils proved to be effective, safe, and durable. Conclusions: As endovascular treatments for direct CCF continue to evolve, techniques for revision will likely follow. This report adds a novel approach to our therapeutic armamentarium. [Copyright &y& Elsevier]

We have designed and synthesized anthraquinone containing compounds which have oligopyrrole side chains of varying lengths. These compounds stabilized the G-quadruplex DNA formed in the promoter regions of c-MYC oncogenes selectively over the duplex DNA. These observations were recorded using UV–vis spectroscopic titrations, fluorescence measurements and circular dichroism (CD) spectral titrations. The potency of the compounds to stabilize the G4 DNA has been shown from the thermal denaturation experiments. The compound interacts with c-MYC G-quadruplex DNA through stacking mode as obtained from ethidium bromide displacement assay, cyclic voltammetric titration, and docking experiments. Molecular modeling studies suggested that the stacking of the anthraquinone moiety over the G-tetrad of the G4 structures are responsible for the stability of such quadruplex secondary structure. Furthermore , polymerase stop assay also supported the formation of stable G4 structures in the presence of the above-mentioned compounds. The compounds have shown selective cancer cell (HeLa and HEK293T) cytotoxicity over normal cells (NIH3T3 and HDFa) under in vitro conditions as determined from MTT based cell viability assay. Apoptosis was found to be the mechanistic pathway underlying the cancer cell cytotoxicity as obtained from Annexin V-FITC and PI dual staining assay which was further substantiated by nuclear morphological changes as observed by AO/EB dual staining assay. Cellular morphological changes, as well as nuclear condensation and fragmentation upon treatment with these compounds, were observed under bright field and confocal microscopy. Image 1 • Oligopyrrole carboxamides conjugated anthraquinone derivatives stabilize G-quadruplex DNA over duplex DNA. • Oligopyrrole carboxamides conjugated anthraquinone derivatives stabilize promoter G-quadruplex DNA. • Stacking mode of interaction of the ligand with c-MYC G-quadruplex DNA. • Selective cancer cell cytotoxicity over normal cells was obtained upon treatment of these ligands. • Cellular morphological changes and nuclear condensation observed in the ligand treated cells. [ABSTRACT FROM AUTHOR]

Autonomic Nervous System (ANS) operates to achieve the optimum physiological functioning and maintains homeostasis in a tonic and continuous manner. Evaluation of ANS profile is crucial in assessing autonomic dysfunction. Conventional ANS evaluation procedures fail to capture minute dynamic alterations of ANS activities. The ANS output pattern is appropriately reflected in the fine alteration of the resting heart rate (HR). HR is a non-stationary variable, results from the dynamic interplay between the multiple physiologic mechanisms. The control of cardiac rate or the chronotropic regulation of heart is considered as a coupled network of oscillators, each representing a specific facet of the cardiovascular reflex. The slower vasomotor oscillation via sympathetic system is combined with rapid respiratory oscillation by parasympathetic system to modulate the intrinsic oscillation pattern of the SA Node. Heart Rate Variability (HRV) is used to understand the autonomic influence on cardiovascular system in health and disease. Fourier decomposition of HRV offers us mainly two different frequency components. High frequency (HF) variation indicates parasympathetic variability due to respiration and Low frequency (LF) mainly implicates tonic sympathetic influence, due to slower vasomotor modulation of heart rate. However, different studies show conflicting results and direct recording of sympathetic nerve activity also failed to correlate with LF power in either healthy subjects or in patients with increased cardiac sympathetic drive. A scatter-plot where each R-R interval is plotted against the preceding R-R interval forms a distributed elliptic point cloud in two dimensional plane. The phase space realization of this plot with dimension two and delay one is referred to as Poincaré plot analysis, an emerging quantitative-visual technique where the shape of the plot is categorized into different functional classes. The plot provides summary as well as detailed beat-to-beat information of the heart. This plot can be extended to three dimensions and with multi-lag, offering more insight and information. A mathematical expression was developed by an interventional study by Toichi et al., using pharmacological blockers during different physiological variables that calculated the lengths of transverse and longitudinal axes of the Poincaré plot to derive two quantitative expressions of sympathetic and vagal influence on HRV: 'cardiac sympathetic index' (CSI)) and 'cardiac vagal index' (CVI). In the present study, we emulate Poincaré plot patterns seen in normal range of sympatho-vagal balances and also in Diabetes Mellitus (DM), known to cause autonomic dysfunction. The emerging pattern of R-R interval time series would provide valuable insight into the altered temporal dynamics and also extract crucial features embedded within. DM is a major public health crisis globally and particularly in Indian population. We hypothesize that, CSI and CVI will effectively segregate the two arms of ANS and can be utilized as an effective evaluation tool to explore the disease status in patients of Diabetes Mellitus. We also propose that, the dynamics of fluctuations in physiological rhythms that exhibit long-term correlation and memory, can also be explored and expressed quantitatively by incorporating various degrees of 'lag' in these recurrence plots. [ABSTRACT FROM AUTHOR]

Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington's disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to these structured RNAs. Both Huntington's disease-like 2 (HDL2) and myotonic dystrophy type 1 (DM1) are caused by a r(CUG) repeat expansion, or r(CUG)exp. The RNA folds into a hairpin structure with a periodic array of 1 × 1 nucleotide UU loops (5′C U G/3′G U C; where the underlined nucleotides indicate the Us in the internal loop) that sequester various RNA-binding proteins (RBPs) and hence the source of its gain-of-function. Here, we report nuclear magnetic resonance (NMR)-refined structures of single 5′C U G/3′G U C motifs in complex with three different small molecules, a di-guandinobenzoate (1), a derivative of 1 where the guanidino groups have been exchanged for imidazole (2), and a quinoline with improved drug-like properties (3). These structures were determined using NMR spectroscopy and simulated annealing with restrained molecular dynamics (MD). Compounds 1 , 2 , and 3 formed stacking and hydrogen bonding interactions with the 5′C U G/3′G U C motif. Compound 3 also formed van der Waals interactions with the internal loop. The global structure of each RNA-small molecule complexes retains an A-form conformation, while the internal loops are still dynamic but to a lesser extent compared to the unbound form. These results aid our understanding of ligand-RNA interactions and enable structure-based design of small molecules with improved binding affinity for and biological activity against r(CUG)exp. As the first ever reported structures of a r(CUG) repeat bound to ligands, these structures can enable virtual screening campaigns combined with machine learning assisted de novo design. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effect of mineral chelator addition during skim milk powder (SMP) manufacture on the solubility, turbidity, soluble protein, and heat stability (HS). Three chelators (sodium citrate dihydrate, sodium polyphosphate, and disodium EDTA) at 3 different concentrations (5, 15, and 25 mM) were added to skim milk concentrate (30% total solids), and the pH was adjusted to 6.65 before spray drying to produce SMP. Spray-dried SMP samples were tested for solubility index (SI). Additionally, samples were reconstituted to contain 9% total solids, adjusted to pH 7.0, and tested for turbidity, protein content from supernatants of ultracentrifuged samples, and HS. Lower SI values were observed for samples treated with 5 mM disodium EDTA and sodium polyphosphate than control samples or samples with 5 mM sodium citrate dihydrate. Furthermore, lower SI values were observed with an increased level of chelating agents regardless of chelator type. A decreased turbidity value was found with increasing levels of mineral chelating salt treatment. Low turbidity with increasing levels of added chelators may be associated with the dissociation of caseins from micelles. Furthermore, higher protein content was observed in supernatants of ultracentrifuged samples treated with increased level of chelators as compared with the control sample. Higher HS was observed in samples treated with 5 mM compared with samples treated with 25 mM mineral chelator. The results suggest improved solubility and HS upon addition of mineral chelators to SMP during its manufacture. [ABSTRACT FROM AUTHOR]