Polysaccharide co-polymerases:the enigmatic conductors of the O-antigen assembly orchestra

The O-antigen lipopolysaccharides on bacterial surface contain variable number of oligosaccharide repeat units with their length having a modal distribution specific to the bacterial strain. The polysaccharide length distribution is controlled by the proteins called polysaccharide co-polymerases (PCPs), which are embedded in the inner membrane in Gram-negative bacteria and form homo oligomers. The 3D structures of periplasmic domains of several PCPs have been determined and provided the first insights into the possible mechanism of polysaccharide length determination mechanism. Here we review the current knowledge of structure and function of these polysaccharide length regulators.

Anthelmintic resistance in Northern Ireland (II): Variations in nematode control practices between lowland and upland sheep flocks

A questionnaire to obtain information on nematode control practices and sheep management was sent to over 1000 farmers in Northern Ireland. Replies were received from 305 flock owners, and data from 252 of them were analysed. Farms were divided into lowland and upland areas. Sizes of pasture and stocking rates on lowland and upland farms were 59.5 hectares, 6.99 sheep/hectare and 62.9 hectares and 10.01 sheep/hectare, respectively. Mean drenching rates for lambs and adults were 2.33 and 2.44, respectively, in lowland flocks and 2.73 and 2.71, respectively, in upland flocks. Between 2008 and 2011, the most frequently identified compounds in use were benzimidazoles and moxidectin in lowland flocks, and benzimidazoles and avermectins in upland flocks. Over the same period the most frequently identified commercial formulations were Tramazole (R), Panacur (R) and Allverm (R) (white drench), Levacide (R) (yellow drench), Oramec (R) (clear drench; avermectin), Cydectin (R) (clear drench; moxidectin) and Monepantel (R) (orange drench).

Most respondents (56.35%) treated their lambs at weaning and the most common time to treat ewes was identified to be pre-mating (67.86% of respondents).

The results of the questionnaire survey revealed that lowland annual drench frequency was 233 and 2.44 in lambs and ewes, respectively, although drench frequencies were higher in upland flocks: 2.73 and 2.71 for lambs and ewes, respectively.

Annual drench rotation was practiced by 43.96% of flock owners, but whether this was true rotation or pseudo-rotation (i.e., substitution of one anthelmintic product by another product belonging to the same chemical group of anthelmintics) could not be explicitly determined. (C) 2012 Elsevier B.V. All rights reserved.

The anatomy of Last Glacial Maximum climate variations in south Westland, New Zealand, derived from pollen records

We present pollen records from three sites in south Westland, New Zealand, that document past vegetation and inferred climate change between approximately 30,000 and 15,000 cal. yr BP. Detailed radiocarbon dating of the enclosing sediments at one of those sites, Galway tarn, provides a more robust chronology for the structure and timing of climate-induced vegetation change than has previously been possible in this region. The Kawakawa/Oruanui tephra, a key isochronous marker, affords a precise stratigraphic link across all three pollen records, while other tie points are provided by key pollen-stratigraphic changes which appear to be synchronous across all three sites. Collectively, the records show three episodes in which grassland, interpreted as indicating mostly cold subalpine to alpine conditions, was prevalent in lowland south Westland, separated by phases dominated by subalpine shrubs and montane-lowland trees, indicating milder interstadial conditions. Dating, expressed as a Bayesian-estimated single 'best' age followed in parentheses by younger/older bounds of the 95% confidence modelled age range, indicates that a cold stadial episode, whose onset was marked by replacement of woodland by grassland, occurred between 28,730 (29,390-28,500) and 25,470 (26,090-25,270) cal. yr BP (years before AD, 1950), prior to the deposition of the Kawakawa/Oruanui tephra. Milder interstadial conditions prevailed between 25,470 (26,090-25,270) and 24,400 (24,840-24,120) cal. yr BP and between 22,630 (22,930-22,340) and 21,980 (22,210-21,580) cal. yr BP, separated by a return to cold stadial conditions between 24,400 and 22,630 cal. yr BP. A final episode of grass-dominated vegetation, indicating cold stadial conditions, occurred from 21,980 (22,210-21,580) to 18,490 (18,670-17,950) cal. yr BP. The decline in grass pollen, indicating progressive climate amelioration, was well advanced by 17,370 (17,730-17,110) cal. yr BP, indicating that the onset of the termination in south Westland occurred sometime between ca 18,490 and ca 17,370 cal. yr BP. A similar general pattern of stadials and interstadials is seen, to varying degrees of resolution but generally with lesser chronological control, in many other paleoclimate proxy records from the New Zealand region. This highly resolved chronology of vegetation changes from southwestern New Zealand contributes to the examination of past climate variations in the southwest Pacific region. The stadial and interstadial episodes defined by south Westland pollen records represent notable climate variability during the latter part of the Last Glaciation. Similar climatic patterns recorded farther afield, for example from Antarctica and the Southern Ocean, imply that climate variations during the latter part of the Last Glaciation and the transition to the Holocene interglacial were inter-regionally extensive in the Southern Hemisphere and thus important to understand in detail and to place into a global context. © 2013 Elsevier Ltd. All rights reserved.

Impact of geometric variations on delivered dose in highly focused single vocal cord IMRT

Purpose. To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. Material and methods. Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. Results. Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by -0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and -1.0 ± 9.6%, respectively. Conclusions. On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol. 

BRCA1--conductor of the breast stem cell orchestra:the role of BRCA1 in mammary gland development and identification of cell of origin of BRCA1 mutant breast cancer

Breast cancer treatment has been increasingly successful over the last 20 years due in large part to targeted therapies directed against different subtypes. However, basal-like breast cancers still represent a considerable challenge to clinicians and scientists alike since the pathogenesis underlying the disease and the target cell for transformation of this subtype is still undetermined. The considerable similarities between basal-like and BRCA1 mutant breast cancers led to the hypothesis that these cancers arise from transformation of a basal cell within the normal breast epithelium through BRCA1 dysfunction. Recently, however, a number of studies have called this hypothesis into question. This review summarises the initial findings which implicated the basal cell as the cell of origin of BRCA1 related basal-like breast cancers, as well as the more recent data which identifies the luminal progenitor cells as the likely target of transformation. We compare a number of key studies in this area and identify the differences that could explain some of the contradictory findings. In addition, we highlight the role of BRCA1 in breast cell differentiation and lineage determination by reviewing recent findings in the field and our own observations suggesting a role for BRCA1 in stem cell regulation through activation of the p63 and Notch pathways. We hope that through an increased understanding of the BRCA1 role in breast differentiation and the identification of the cell(s) of origin we can improve treatment options for both BRCA1 mutant and basal-like breast cancer subgroups.

Zinc Phosphate Cement: Variations in proportioning affects dimetral tensile strength

Objectives: To quantify variability in hand proportioning of zinc phosphate cement among a cohort of dental undergraduates and to determine the effect of any such variability on the diametral tensile strength (DTS) of the set cement. The null hypothesis was that such variability has no effect on DTS. 
Methods: Thirty-four operators dispensed a zinc phosphate cement [Fleck's® Cement] according to the manufacturers' instructions. The mass of powder and liquid dispensed was recorded. Cylindrical specimens (n = 2 x 34) of dimensions 6mm x 3mm were prepared using a stainless steel split mould. The maximum mass of powder and the minimum volume of liquid were used as one extreme ratio and the minimum mass of powder and the maximum volume of liquid used on the other extreme. The manufacturers' recommended ratio was also tested (n=34).The samples were left to set for one hour before being transferred into distilled water for 48 hours. Compression across a diameter was carried out using a universal testing machine, H10KS [Tinius Olsen], at a constant crosshead speed of 0.75 ±0.25 mm/min. Statistical analyses (α = 0.05) were by Student's t-test for the powder/liquid ratio and one-way ANOVA and Tukey HSD for for pair-wise comparisons of mean DTS. Tests were carried out for normality and constant variability. 
Results: The mean (range) amount of powder dispensed was 0.863g (0.531-1.216)g. The mean (range) amount of liquid dispensed was 0.341ml (0.265-0.394)ml. The manufacturer's recommended amounts were 0.8g of powder and 0.3ml of liquid. The mean powder/liquid ratio was not significantly different from the manufacturer's recommended value (p=0.64). Mean (SD) DTS were (MPa) max: 7.19(1.50), min: 2.65(1.01), manufacturer: 6.01(1.30). All pair-wise comparisons were significantly different (p<0.001). 
Conclusions: Variability exists in the hand proportioning powder and liquid components of zinc phosphate cement. This variability can affect the DTS of zinc phosphate cement.

Transit timing variations in WASP-10b induced by stellar activity

The hot-JupiterWASP-10bwas reported by Maciejewski et al. to showtransit timing variations (TTVs) with an amplitude of ~3.5 min. These authors proposed that the observed TTVs were caused by a 0.1M_Jup perturbing companion with an orbital period of ~5.23 d, and hence, close to the outer 5:3 mean-motion resonance with WASP-10b. To test this scenario, we present eight new transit light curves of WASP-10b obtained with the Faulkes Telescope North and the Liverpool Telescope. The new light curves, together with 22 previously published ones, were modelled with a Markov Chain Monte Carlo transit fitting code. Transit depth differences reported forWASP-10b are thought to be due to starspot-induced brightness modulation of the host star. Assuming the star is brighter at the activity minimum, we favour a small planetary radius. We find Rp = 1.039^+0.043 _-0.049R_Jup in agreement with Johnson et al. and Maciejewski et al. Recent studies find no evidence for a significant eccentricity in this system. We present consistent system parameters for a circular orbit and refine the orbital ephemeris ofWASP-10b. Our homogeneously derived transit times do not support the previous claimed TTV signal, which was strongly dependent on two previously published transits that have been incorrectly normalized. Nevertheless, a linear ephemeris is not a statistically good fit to the transit times of WASP-10b. We show that the observed transit time variations are due to spot occultation features or systematics. We discuss and exemplify the effects of occultation spot features in the measured transit times and show that despite spot occultation during egress and ingress being difficult to distinguish in the transit light curves, they have a significant effect in the measured transit times. We conclude that if we account for spot features, the transit times of WASP-10b are consistent with a linear ephemeris with the exception of one transit (epoch 143) which is a partial transit. Therefore, there is currently no evidence for the existence of a companion to WASP-10b. Our results support the lack of TTVs of hot-Jupiters reported for the Kepler sample.