Effect of Commonly Prescribed Liquid Medications on Streptococcus mutans Biofilm. An in vitro study

Objective: This study addressed the effect of pediatric liquid antibiotic medications on Streptococcus mutans UA159. These suspensions commonly contain sugars such as sucrose to make them more palatable for children. The study was designed to evaluate the effects of oral liquid antibiotics on Streptococcus mutans growth and biofilm formation. Study Design: A 24 hour culture of S. mutans was treated with various concentrations of liquid medications commonly prescribed to children for odontogenic or fungal infections– amoxicillin, penicillin VK, clindamycin, and nystatin. The study was conducted in sterile 96-well flat bottom microtiter plates. The minimum inhibitory and biofilm inhibitory concentrations (MIC/MBIC) of S. mutans were determined for each medication. S. mutans was cultured with and without the test drugs, the amount of total growth measured, the biofilms washed, fixed, and stained with crystal violet. The absorbance was determined to evaluate biofilm formation. Results: Higher concentrations of amoxicillin, penicillin VK and clindamycin had decreased biofilm and overall growth than the control. The MICs were 1:2,560 (1.95 ug/ml), 1:2,560 (1.95 ug/ml) and 1:40 (9.375 ug/ml), while the MBIC were 1:640 (7.8 ug/ml), 1:1,280 (3.9 ug/ml) and 1:20 (18.75 ug/ml), respectively. Lower concentrations provided increased biofilm and overall growth. Nystatin induced significantly more biofilm and overall growth than the control at all concentrations. Conclusion: At high concentrations, approximately at the levels expected to be present in the oral cavity of children, amoxicillin, penicillin, and clindamycin inhibited S. mutans biofilm and overall growth due to their antibiotic activity, while at lower concentrations the three antibiotics demonstrated an increase in biofilm and growth. The increase in S. mutans biofilm and overall growth is most likely attributed to the sugar content in the medications. Nystatin provided an increase in biofilm and growth at each concentration tested

The debris disk around gamma Doradus resolved with Herschel

We present observations of the debris disk around gamma Doradus, an F1V star, from the Herschel Key Programme DEBRIS (Disc Emission via Bias-free Reconnaissance in the Infrared/Submillimetre). The disk is well-resolved at 70, 100 and 160 micron, resolved along its major axis at 250 micron, detected but not resolved at 350 micron, and confused with a background source at 500 micron. It is one of our best resolved targets and we find it to have a radially broad dust distribution. The modelling of the resolved images cannot distinguish between two configurations: an arrangement of a warm inner ring at several AU (best-fit 4 AU) and a cool outer belt extending from ~55 to 400 AU or an arrangement of two cool, narrow rings at ~70 AU and ~190 AU. This suggests that any configuration between these two is also possible. Both models have a total fractional luminosity of ~10^{-5} and are consistent with the disk being aligned with the stellar equator. The inner edge of either possible configuration suggests that the most likely region to find planets in this system would be within ~55 AU of the star. A transient event is not needed to explain the warm dust's fractional luminosity.Comment: 12 pages, 6 figures, accepted for publication in Ap

Effect of developmental stage of HSC and recipient on transplant outcomes

The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aorta-gonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage, there is a discrepancy between the apparent frequency of HSCs depicted with imaging and their rarity when measured with limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates, whereas developmentally mature, definitive HSCs from E14.5 fetal liver or adult bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived HSCs preferentially homed to the liver in neonatal mice yet showed balanced homing to the liver and spleen in adults. These findings emphasize the functional differences between nascent and mature definitive HSCs

A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation

The KRAS GTPase plays a critical role in the control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also post-translational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role of this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, because mutations at this position impaired GEF-mediated nucleotide exchange. Because the KRAS K104Q mutant has recently been employed as an acetylation mimetic, we conducted a series of studies to evaluate its in vitro and cell-based properties. Herein, we found that KRAS K104Q exhibited defects in both GEF-mediated exchange and GAP-mediated GTP hydrolysis, consistent with NMR-detected structural perturbations in localized regions of KRAS important for recognition of these regulatory proteins. Despite the partial defect in both GEF and GAP regulation, KRAS K104Q did not alter steady-state GTP-bound levels or the ability of the oncogenic KRAS G12V mutant to cause morphologic transformation of NIH 3T3 mouse fibroblasts and of WT KRAS to rescue the growth defect of mouse embryonic fibroblasts deficient in all Ras genes. We conclude that the KRAS K104Q mutant retains both WT and mutant KRAS function, probably due to offsetting defects in recognition of factors that up-regulate (GEF) and down-regulate (GAP) RAS activity

Transforming Environmental Water Management to Adapt to a Changing Climate

Environmental water management has become a global imperative in response to environmental degradation and the growing recognition that human well-being and livelihoods are critically dependent on freshwater ecosystems and the ecological functions and services they provide. Although a wide range of techniques and strategies for planning and implementing environmental flows has developed, many remain based on assumptions of hydrologic stationarity, typically focusing on restoring freshwater ecosystems to pre-development or “natural” conditions. Climate change raises major challenges to this conventional approach, in part because of increasing uncertainties in patterns of water supply and demand. In such a rapidly changing world, the implementation of, and capacity of water managers to deliver flow regimes resembling historical hydrological patterns may be both unfeasible and undesirable. Additionally, as emphasis shifts from species-focused water allocation plans toward a greater appreciation of freshwater ecological functions and services, many of which will be influenced by climate change, a thorough re-evaluation of the conventional objectives, planning, delivery and monitoring of environmental water, including its role in the broader context of water and environmental management, is essential. Here, we identify the major challenges posed by climate change to environmental water management and discuss key adaptations and research needed to meet these challenges to achieve environmental and societal benefits and avoid maladaptation

The BDNF p.Val66Met polymorphism, childhood trauma, and brain volumes in adolescents with alcohol abuse

Background: Previous studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents. However, data on the interactive effects of early life adversity, genetic factors (e.g. p.Met66 allele of BDNF), and alcohol dependence, on brain structure in adolescents is limited. We examined whether the BDNF p.Val66Met polymorphism interacts with childhood trauma to predict alterations in brain volume in adolescents with alcohol use disorders (AUDs). Methods: We examined 160 participants (80 adolescents with DSM-IV AUD and 80 age- and gender-matched controls) who were assessed for trauma using the Childhood Trauma Questionnaire (CTQ). Magnetic resonance images were acquired for a subset of the cohort (58 AUD and 58 controls) and volumes of global and regional structures were estimated using voxel-based morphometry (VBM). Samples were genotyped for the p.Val66Met polymorphism using the TaqMan® Assay. Analysis of covariance (ANCOVA) and post-hoc t-tests were conducted using SPM8 VBM. Results: No significant associations, corrected for multiple comparisons, were found between the BDNF p.Val66Met polymorphism, brain volumes and AUD in adolescents with childhood trauma. Conclusions: These preliminary findings suggest that the BDNF p.Met66 allele and childhood trauma may not be associated with reduced structural volumes in AUD. Other genetic contributors should be investigated in future studies