Synthesis of a Carboxamide Linked T∗T Dimer with an Acyclic Nucleoside Unit and Its Incorporation in Oligodeoxynucleotides

Abstract

A T?T dimer with ? representing a 2′-OCH₂CH₂NHC(O)-4′ linkage connecting two nucleoside units was prepared by condensation of (S)-1-[2-(2-aminoethoxy)-3-(4,4′-dimethoxytrityloxy)propyl]thymine with 1,2-dideoxy-1-thyminyl-β-D-erythro-pento-furanuronic acid. The T?T dimer was incorporated in oligodeoxynucleotides and investigated for hybridization to DNA.     

Cardiovascular anatomy and cardiac function in the air-breathing swamp eel (Monopterus albus)

Monopterus albus, a swamp eel inhabiting the freshwaters of South East Asia, relies on an extensive vascularisation of the buccal cavity, pharynx and anterior oesophagus for gas exchange, while the gills are much reduced. In the present study we describe the macro-circulation in the cephalic region and the vascularisation of the buccal cavity of M. albus using vascular fillings and micro-computed tomography (μCT). We also show that M. albus has the capacity to use the buccal cavity for aquatic gas exchange, being able to maintain normal arterial blood gas composition, blood pressure, heart rate and cardiac output throughout 10 h of forced submergence. M. albus therefore can be characterised as a facultative air-breather. Because M. albus aestivates for many months in moist mud during the dry season we characterised in vivo cardiovascular function during exposure to anoxia as well as the effects of anoxia on in vitro contractility of strip preparations from atria and ventricle. Both studies revealed a low anoxia tolerance, rendering it unlikely that M. albus can survive prolonged exposure to anoxia.     

The capacity of CD4+ Vγ9Vδ2 T cells to kill cancer cells correlates with co-expression of CD56

Human Vγ9Vδ2 T cells are a unique T-cell type, and data from recent studies of Vγ9Vδ2 T cells emphasize their potential relevance to cancer immunotherapy. Vγ9Vδ2 T cells exhibit dual properties since they are both antigen-presenting cells and cytotoxic toward cancer cells. The majority of Vγ9Vδ2 T cells are double-negative for the co-receptors CD4 and CD8, and only 20–30% express CD8. Even though they are mostly neglected, a small fraction of Vγ9Vδ2 T cells also express the co-receptor CD4. Here the authors show that CD4⁺ Vγ9Vδ2 T cells comprise 0.1–7% of peripheral blood Vγ9Vδ2 T cells. These cells can be expanded in vitro using zoledronic acid, pamidronic acid or CD3 antibodies combined with IL-2 and feeder cells. Unlike most conventional CD4⁺ αβ T cells, CD4⁺ Vγ9Vδ2 T cells are potently cytotoxic and can kill cancer cells, which is here shown by the killing of cancer cell lines of different histological origins, including breast cancer, prostate cancer and melanoma cell lines, upon treatment with zoledronic acid. Notably, the killing capacity of CD4⁺ Vγ9Vδ2 T cells correlates with co-expression of CD56.     

Evaluation of APOE polymorphisms and the risk for age-related macular degeneration in a Southeastern Brazilian population

This study aimed to evaluate the role of APOE polymorphisms (rs429358 and rs7412) in the risk of age-related macular degeneration in a sample of the Southeastern Brazilian population. Seven hundred and five unrelated individuals were analyzed, 334 with age-related macular degeneration (case group), and 371 without the disease (control group). In the case group, patients were further stratified according to disease phenotypes, divided into dry and wet age-related macular degeneration, and non-advanced and advanced age-related macular degeneration. APOE polymorphisms (rs429358 and rs7412) were evaluated through polymerase chain reaction and direct sequencing. In the comparison of cases vs. controls, none of the associations reached statistical significance, considering the Bonferroni-adjusted P-value, although there was a suggestive protection for the E3/E4 genotype (OR = 0.626; P-value = 0.037) and E4 carriers (OR = 0.6515; P-value = 0.047). Statistically significant protection for both the E3/E4 genotype and E4 carriers was observed in the comparisons: advanced age-related macular degeneration vs. controls (OR = 0.3665, P-value = 0.491 × 10⁻³ and OR = 0.4031, P-value = 0.814 × 10⁻³, respectively), advanced age-related macular degeneration vs. non-advanced age-related macular degeneration (OR = 0.2529, P-value = 0.659 × 10⁻⁴ and OR = 0.2692, P-value = 0.631 × 10⁻⁴, respectively). In the comparison of wet age-related macular degeneration vs. control, protection was statistically significant only for E3/E4 (OR = 0.4052, P-value = 0.001). None of the comparisons demonstrated any significant association for E2 genotypes or E2 carriers in age-related macular degeneration risk in this study. Findings suggest a protective role of the E4 haplotype in the APOE gene in the risk for advanced and wet forms of age-related macular degeneration, in a sample of the Brazilian population. To our knowledge, this is the first Brazilian study to show the association between APOE polymorphisms and age-related macular degeneration.     

Reliability of performance velocity for jump squats under feedback and nonfeedback conditions

Randell, AD, Cronin, JB, Keogh, JWL, Gill, ND, and Pedersen, MC. Reliability of performance velocity for jump squats under feedback and nonfeedback conditions. J Strength Cond Res 25(12): 3514-3518, 2011-Advancements in the monitoring of kinematic and kinetic variables during resistance training have resulted in the ability to continuously monitor performance and provide feedback during training. If equipment and software can provide reliable instantaneous feedback related to the variable of interest during training, it is thought that this may result in goal-oriented movement tasks that increase the likelihood of transference to on-field performance or at the very least improve the mechanical variable of interest. The purpose of this study was to determine the reliability of performance velocity for jump squats under feedback and nonfeedback conditions over 3 consecutive training sessions. Twenty subjects were randomly allocated to a feedback or nonfeedback group, and each group performed a total of 3 "jump squat" training sessions with the velocity of each repetition measured using a linear position transducer. There was less change in mean velocities between sessions 1-2 and sessions 2-3 (0.07 and 0.02 vs. 0.13 and -0.04 m·s), less random variation (TE = 0.06 and 0.06 vs. 0.10 and 0.07 m·s) and greater consistency (intraclass correlation coefficient = 0.83 and 0.87 vs. 0.53 and 0.74) between sessions for the feedback condition as compared to the nonfeedback condition. It was concluded that there is approximately a 50-50 probability that the provision of feedback was beneficial to the performance in the squat jump over multiple sessions. It is suggested that this has the potential for increasing transference to on-field performance or at the very least improving the mechanical variable of interest.     

A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps

Plasma membrane ATPases are primary active transporters of cations that maintain steep concentration gradients. The ion gradients and membrane potentials derived from them form the basis for a range of essential cellular processes, in particular Na(+)-dependent and proton-dependent secondary transport systems that are responsible for uptake and extrusion of metabolites and other ions. The ion gradients are also both directly and indirectly used to control pH homeostasis and to regulate cell volume. The plasma membrane H(+)-ATPase maintains a proton gradient in plants and fungi and the Na(+),K(+)-ATPase maintains a Na(+) and K(+) gradient in animal cells. Structural information provides insight into the function of these two distinct but related P-type pumps.     

Climate change in Norway: warm summers limit grouse reproduction

Grouse and vole numbers may peak after peaks in the seed crop of bilberry (Vaccinium myrtillus) because of reduced levels of feeding deterrents in bilberry plants. We predicted that grouse reproduction depends also on summer (June–September) temperatures in the 2 previous years, because bilberry plants will be less exhausted after a high seed crop in or after warm summers, and thus rebuild their chemical defence more quickly. After berry peak years, population indices of capercaillie (Tetrao urogallus) and bank vole (Myodes glareolus) in southern Norway were negatively related to summer temperatures in the previous year or previous 2 years. Willow grouse (Lagopus lagopus) chick production in five areas in Norway was negatively related to summer temperatures in the 2 previous years when controlling for vole density. A similar pattern was found for the bilberry-feeding moth (Eulithis populata), an important prey for grouse chicks. In eastern Norway, autumn densities of capercaillie and black grouse (Tetrao tetrix) were more likely to peak in vole peak years at high altitudes, where summer temperatures are low. We conclude that high summer temperatures may limit grouse reproduction through the effect on bilberry plants and that a warm climate thus adversely affects population levels of grouse.