Structural basis for a six nucleotide genetic alphabet

Expanded genetic systems are most likely to work with natural enzymes if the added nucleotides pair with geometries that are similar to those displayed by standard duplex DNA. Here, we present crystal structures of 16-mer duplexes showing this to be the case with two nonstandard nucleobases (Z, 6-amino-5-nitro-2(1H)-pyridone and P, 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one) that were designed to form a Z:P pair with a standard “edge on” Watson–Crick geometry, but joined by rearranged hydrogen bond donor and acceptor groups. One duplex, with four Z:P pairs, was crystallized with a reverse transcriptase host and adopts primarily a B-form. Another contained six consecutive Z:P pairs; it crystallized without a host in an A-form. In both structures, Z:P pairs fit canonical nucleobase hydrogen-bonding parameters and known DNA helical forms. Unique features include stacking of the nitro group on Z with the adjacent nucleobase ring in the A-form duplex. In both B- and A-duplexes, major groove widths for the Z:P pairs are approximately 1 Å wider than those of comparable G:C pairs, perhaps to accommodate the large nitro group on Z. Otherwise, ZP-rich DNA had many of the same properties as CG-rich DNA, a conclusion supported by circular dichroism studies in solution. The ability of standard duplexes to accommodate multiple and consecutive Z:P pairs is consistent with the ability of natural polymerases to biosynthesize those pairs. This, in turn, implies that the GACTZP synthetic genetic system can explore the entire expanded sequence space that additional nucleotides create, a major step forward in this area of synthetic biology

Evaluation of the efficacy of Alpron disinfectant for dental unit water lines

AIMS: To assess the efficacy of a disinfectant, Alpron, for controlling microbial contamination within dental unit water lines. METHODS: The microbiological quality of water emerging from the triple syringe, high speed handpiece, cup filler and surgery hand wash basin from six dental units was assessed for microbiological total viable counts at 22 degrees C and 37 degrees C before and after treatment with Alpron solutions. RESULTS: The study found that the use of Alpron disinfectant solutions could reduce microbial counts in dental unit water lines to similar levels for drinking water. This effect was maintained in all units for up to six weeks following one course of treatment. In four out of six units the low microbial counts were maintained for 13 weeks. CONCLUSIONS: Disinfectants may have a short term role to play in controlling microbial contamination of dental unit water lines to drinking water quality. However, in the longer term attention must be paid to redesigning dental units to discourage the build up of microbial biofilms

Outcrop Groundwater Prospecting, Drilling, and Well Construction in Hard Rocks in Semi-arid Regions

This chapter presents some recommendations for prospecting, drilling and well construction in hard rocks in semi-arid regions. Considering that these conditions are present in many countries where technology is not always available, the chapter concentrates on the most basic and simple methods to plan where best to drill and maximize success through the direct observation of rock types, weathering and fracturing. The advantage for the geologist and hydrogeologist in an arid or semi-arid environment is that vegetation is normally scarce and the weathering layer thin, allowing a direct view of the rock in circumstances impossible in other climate regions of the world. The close observation of the weathering material, and especially of the fracture network, mainly the fracture density, dip, extension and interconnection, can provide important information for a field hydrogeologist who can then plan the best place for drilling. The most appropriate drilling technique, if available in the area, is rotary percussion, also designated as down-the-hole drilling, with drilling rates that can achieve 100 m per day in normal circumstances. This allows a well to be constructed in about two days, essential in the case of disaster relief. Finally, some information is given about well construction, careful planning of the work, protection to preserve the water quality, avoiding problems of partial or total collapse of the hole during construction or of the well and after completion, and how to avoid direct contact between the surface or sub-surface waters with the aquifer along the walls of the well to protect the well and the aquifer against contamination

Comorbidities in Chilean patients with psoriasis: a Global Healthcare Study on Psoriasis

Background: Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. Aim: To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. Methods: This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. Results: In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. Conclusions: We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting

Maser radiation from collisionless shocks

Funding: UK Engineering and Physical Sciences Research Council (grant Nos. EP/N014472/1, EP/R004773/1 and EP/N013298/1) and the Science and Technologies Facilities Council of the United Kingdom. F.C. and L.O.S. acknowledge support from the European Research Council (InPairs ERC-2015-AdG 695088) and FCT Portugal (grant No. PD/BD/114307/2016).This paper describes a model of electron energization and cyclotron-maser emission applicable to astrophysical magnetized collisionless shocks. It is motivated by the work of Begelman, Ergun and Rees [Astrophys. J. 625 , 51 (2005)] who argued that the cyclotron-maser instability occurs in localized magnetized collisionless shocks such as those expected in blazar jets. We report on recent research carried out to investigate electron acceleration at collisionless shocks and maser radiation associated with the accelerated electrons. We describe how electrons accelerated by lower-hybrid,waves at collisionless shocks generate cyclotron-maser radiation when the accelerated electrons move into regions of stronger magnetic fields. The electrons are accelerated along the magnetic field and magnetically compressed leading to the formation of an electron velocity distribution having a horseshoe shape due to conservation of the electron magnetic moment. Under certain conditions the horseshoe electron velocity distribution function is unstable to the cyclotron-maser instability [Bingham and Cairns, Phys. Plasmas 7, 3089 (2000); Melrose, Rev. Mod. Plasma Phys. 1 , 5 (2017)].Publisher PDFPeer reviewe

T2K ECAL Test–beam Proposal

The T2K experiment will search for the last unknown element of the neutrino mixing matrix. An crucial component of the near detector for this experiment is the electromagnetic calorimeter which is being built in the UK. Testbeam time is requested to test the full ECAL system, validate calibration techniques, and determine the hadronic and electromagnetic energy scale of the calorimeter

Dyadic adjustment, family coping, body image, quality of life and psychological morbidity in patients with psoriasis and their partners

Background Psoriasis is an incurable and chronic disease that includes unpredictable periods of remission and relapse requiring long-term therapy. Purpose This paper focuses on the relationship among family coping, psychological morbidity, body image, dyadic adjustment and quality of life in psoriatic patients and their partners. Method One hundred and one patients with psoriasis and 78 partners comprised the sample. They were regular users of the Dermatology Service of a Central Northern hospital in Portugal and a private dermatology clinic. Patients with psoriasis were assessed on anxiety, depression, body image, quality of life, dyadic adjustment and family coping. Partners were assessed on the same measures except body image and quality of life. Results A positive relationship among dyadic adjustment, psychological morbidity and family coping in patients and their partners was found. Also, patients with lower levels of quality of life had partners with higher levels of depressive and anxious symptoms. Better dyadic adjustment predicted family coping in the psoriatic patient. High levels of dyadic adjustment in patients and low partners’ trait anxiety predicted better dyadic adjustment in partners. Conclusion The results highlight the importance of incorporating family variables in psychological interventions in psoriasis’ care, particularly family coping and dyadic adjustment as well as the need for psychological intervention to focus both on patients and partners

Autistic Development, Trauma and Personhood: Beyond the Frame of the Neoliberal Individual

This chapter critically explores notions of childhood development, particularly in regard to autism, reactions to traumatic events and the meaning of ‘personhood’. The construction of the neoliberal individual is contrasted with that of personhood as experienced by an autistic person. Person-centred methods of engagement as outlined in this chapter can give opportunities for opening up a respectful discursive space where autistic development is not framed from the outset as ‘disordered’