Ab initio studies on the tri- and diphosphate fragments of adenosine triphosphate

Pyrophosphate prototypes such as methyl triphosphate and methyl diphosphate molecules in their different protonation states have been investigated at high levels of quantum chemical calculations. The optimized geometries, the thermochemistry of the hydrolysis and the molecular orbitals contributing to the high energy of these compounds have been analyzed. These investigations provide insights into the "high energy" character of ATP molecule. Further, the dependence of vibrational frequencies on the number of phosphate groups and the charged states has also been presented. These results can aid the interpretation of spectra obtained by experiments on complexes containing pyrophosphate prototypes.     

Anatomic Guidance For Ablation: Atrial Flutter,Fibrillation, and Outflow Tract Ventricular Tachycardia

After initial documentation of excellent efficacy with radiofrequency ablation, this procedure is being performed increasingly in more complex situations and for more difficult arrhythmia. In these circumstances, an accurate knowledge of the anatomic basis for the ablation procedure will help maintain this efficacy and improve safety. In this review, we discuss the relevant anatomy for electrophysiology interventions for typical right atrial flutter, atrial fibrillation, and outflow tract ventricular tachycardia. In the pediatric population, maintaining safety is a greater challenge, and here again, knowing the neighboring and regional anatomy of the arrhythmogenic substrate for these arrhythmias may go a long way in preventing complications.     

Protein Kinase C�� Mediates Cigarette Smoke/Aldehyde- and Lipopolysaccharide-induced Lung Inflammation and Histone Modifications

Atypical protein kinase C (PKC) ζ is an important regulator of inflammation through activation of the nuclear factor-κB (NF-κB) pathway. Chromatin remodeling on pro-inflammatory genes plays a pivotal role in cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced abnormal lung inflammation. However, the signaling mechanism whereby chromatin remodeling occurs in CS- and LPS-induced lung inflammation is not known. We hypothesized that PKCζ is an important regulator of chromatin remodeling, and down-regulation of PKCζ ameliorates lung inflammation by CS and LPS exposures. We determined the role and molecular mechanism of PKCζ in abnormal lung inflammatory response to CS and LPS exposures in PKCζ-deficient (PKCζ^−/−) and wild-type mice. Lung inflammatory response was decreased in PKCζ^−/− mice compared with WT mice exposed to CS and LPS. Moreover, inhibition of PKCζ by a specific pharmacological PKCζ inhibitor attenuated CS extract-, reactive aldehydes (present in CS)-, and LPS-mediated pro-inflammatory mediator release from macrophages. The mechanism underlying these findings is associated with decreased RelA/p65 phosphorylation (Ser³¹¹) and translocation of the RelA/p65 subunit of NF-κB into the nucleus. Furthermore, CS/reactive aldehydes and LPS exposures led to activation and translocation of PKCζ into the nucleus where it forms a complex with CREB-binding protein (CBP) and acetylated RelA/p65 causing histone phosphorylation and acetylation on promoters of pro-inflammatory genes. Taken together, these data suggest that PKCζ plays an important role in CS/aldehyde- and LPS-induced lung inflammation through acetylation of RelA/p65 and histone modifications via CBP. These data provide new insights into the molecular mechanisms underlying the pathogenesis of chronic inflammatory lung diseases.     

Combined effects of temperature,food (<Emphasis Type="Italic">Chlorella vulgaris</Emphasis>) concentration and predation (<Emphasis Type="Italic">Asplanchna girodi</Emphasis>) on the morphology of <Emphasis Type="Italic">Brachionus havanaensis</Emphasis> (Rotifera)

The combined effect of temperature, food level and the presence of an invertebrate predator on the body size of the rotifer Brachionus havanaensis were tested in this study. B. havanaensis was cultured at 15, 20, and 25°C under three different Chlorella vulgaris levels (0.5 × 10⁶, 1.0 × 10⁶ and 2.0 × 10⁶ cells ml⁻¹) in the presence and in the absence of Asplanchna girodi. For each treatment we maintained three replicates and constant (0.4 ind ml⁻¹) population density of B. havanaensis. In treatments containing A. girodi, the predator was separated from the prey by a mesh (pore size 50 μm). On the last day of the experiment, a portion of the B. havanaensis population was sampled for several morphometric measurements (adult lorica length, width, posterior spine length, body volume, and the egg volume). Size measurements were done by drawing the specimens using a calibrated camera lucida. Statistically significant impact of temperature as well as the predator’s presence was observed on the lorica length, posterior spine, and egg volume of B. havanaensis. The interactions of food × temperature, or predator′s presence × food × temperature were non-significant (P > 0.05) for lorica length, spine length, body volume, and egg volume. Regardless of the type of treatment, there was a direct positive correlation between lorica length and width. Egg volume was linearly related to the adult size. Notably long posterior spines were observed in treatments containing the presence of A. girodi. Guest editors: S. S. S. Sarma, R. D. Gulati, R. L. Wallace, S. Nandini, H. J. Dumont & R. Rico-Martínez. Advances in Rotifer Research     

The efficacy of Scenedesmus morphology as a defense mechanism against grazing by selected species of rotifers and cladocerans

Phytoplankton often develop various defense mechanisms in response to zooplankton grazing, such as spines and colonies. While it is now known that increased spine length and cells in a colony of members of the genus Scenedesmus, when zooplankton grazing is intense, helps in reducing zooplankton filtering rates, the effect of these defense mechanisms at the population level has been observed in few studies. Here we present data on the growth rates of four zooplankton species, Brachionus calyciflorus, B. patulus, Ceriodaphnia dubia and Daphnia pulex at two food levels using two species of colony-forming Scenedesmus spp.: S. acutus (cell length = 18.2 ± 0.4 µm; width = 4.2 ± 0.1 µm; average colony length = 90 µm; width: 21 µm) and S. quadricauda (cell length: 21 ± 0.5 width 7.5 ± 0.3 µm; average colony length: 84 µm; width: 30 µm). Whereas S. acutus had no spines, S. quadricauda had spines of 6–10 µm. Population growth experiments of the test rotifers and cladocerans were conducted in 100 ml containers with 50 ml of the medium with test algae. Algae concentrations used were: 13 and 52 mg dw l^–1 of each of the two algal species offered in colonial forms. We used an initial inoculation zooplankter density of 1 ind. ml^–1 for either of the rotifer species and 0.2 ind. ml^–1 for either of the cladoceran species. In all, we had 64 test containers (4 test species of zooplankton × 2 test species of algae × 2 algal densities × 4 replicates). We found a significant effect of algal size on the growth rates of all the four tested species of zooplankton. The population growth rates of zooplankton ranged from –0.58 to 0.66 and were significantly higher on diet of S. acutus than of S. quadricauda. Thus, our study confirms that the larger colony size and the formation of spines in S. quadricauda were effective defenses against grazing by both rotifers and smaller sized cladoceran Ceriodaphnia dubia but that larger-bodied Daphnia pulex could exploit both the algal populations equally.     

Dissecting the Molecular Mechanisms of the Tropism of Varicella-Zoster Virus for Human T Cells

Studies of varicella-zoster virus (VZV) tropism for T cells support their role in viral transport to the skin during primary infection. Multiparametric single-cell mass cytometry demonstrates that, instead of preferentially infecting skin-homing T cells, VZV alters cell signaling and remodels surface proteins to enhance T cell skin trafficking. Viral proteins dispensable in skin, such as that encoded by open reading frame 66, are necessary in T cells. Interference with VZV T cell tropism may offer novel strategies for drug and vaccine design.     

Critical reanalysis of the methods that discriminate the activity of CDK2 from CDK1

Cyclin dependent kinases 1 and 2 (CDK1 and CDK2) play crucial roles in regulating cell cycle progression from G1 to S, through S, and G2 to M phase. Both inhibition and aberrant activation of CDK1/2 can be detrimental to cancer cell growth. However, the tools routinely employed to discriminate between the activities of these 2 kinases do not have the selectivity commonly attributed to them. Activation of these kinases is often assayed as a decrease of the inhibitory tyrosine-15 phosphorylation, yet the antibodies used cannot discriminate between phosphorylated CDK1 and CDK2. Inhibitors of these kinases, while partially selective against purified kinases, may lack selectivity when applied to intact cells. High levels of cyclin E are often considered a marker of increased CDK2 activity, yet active CDK2 targets cyclin E for degradation, hence high levels usually reflect inactive CDK2. Finally, inhibition of CDK2 does not arrest cells in S phase suggesting CDK2 is not required for S phase progression. Furthermore, activation of CDK2 in S phase can rapidly induce DNA double-strand breaks in some cell lines. The misunderstandings associated with the use of these tools has led to misinterpretation of results. In this review, we highlight these challenges in the field.