Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1

REV1 is central to the DNA damage response of eukaryotes through an as yet poorly understood role in translesion synthesis. REV1 is a member of the Y-type DNA polymerase family and is capable of in vitro deoxycytidyl transferase activity opposite a range of damaged bases. However, non-catalytic roles for REV1 have been suggested by the Saccharomyces cerevisiae rev1-1 mutant, which carries a point mutation in the N-terminal BRCT domain, and the recently demonstrated ability of the mammalian protein to interact with each of the other translesion polymerases via its extreme C-terminus. Here, we show that a region adjacent to this polymerase interacting domain mediates an interaction with PCNA. These C-terminal domains of REV1 are necessary, although not sufficient, for effective tolerance of DNA damage in the avian cell line DT40, while the BRCT domain and transferase activity are not directly required. Together these data provide strong support for REV1 playing an important non-catalytic role in coordinating translesion synthesis. Further, unlike in budding yeast, rad18 is not epistatic to rev1 for DNA damage tolerance suggesting that REV1 and RAD18 play largely independent roles in the control of vertebrate translesion synthesis

Biventricular Assist Device Terminates Polymorphic Ventricular Tachycardia in Giant Cell Myocarditis

We present the case of a 55-year-old woman with giant cell myocarditis who experienced a rapid deterioration in her condition. As her heart failure progressed, she developed more ventricular ectopic beats, which culminated in a polymorphic ventricular tachycardia that did not improve despite immunosuppressive and antiarrhythmic therapy. Emergent biventricular assist device placement, however, did eliminate her arrhythmia

Measuring Redshift-Space Distortions using Photometric Surveys

We outline how redshift-space distortions (RSD) can be measured from the angular correlation function w({\theta}), of galaxies selected from photometric surveys. The natural degeneracy between RSD and galaxy bias can be minimized by comparing results from bins with top-hat galaxy selection in redshift, and bins based on the radial position of galaxy pair centres. This comparison can also be used to test the accuracy of the photometric redshifts. The presence of RSD will be clearly detectable with the next generation of photometric redshift surveys. We show that the Dark Energy Survey (DES) will be able to measure f(z){\sigma}_8(z) to a 1{\sigma} accuracy of (17 {\times} b)%, using galaxies drawn from a single narrow redshift slice centered at z = 1. Here b is the linear bias, and f is the logarithmic rate of change of the linear growth rate with respect to the scale factor. Extending to measurements of w({\theta}) for a series of bins of width 0.02(1 + z) over 0.5 < z < 1.4 will measure {\gamma} to a 1{\sigma} accuracy of 25%, given the model f = {\Omega}_m(z)^{\gamma}, and assuming a linear bias model that evolves such that b = 0.5 + z (and fixing other cosmological parameters). The accuracy of our analytic predictions is confirmed using mock catalogs drawn from simulations conducted by the MICE collaboration.Comment: Accepted by MNRAS, revisions include fixing of typos and clarification of the tex

Changes in the capacity of visual working memory in 5- to 10-year-olds

Using the Luck and Vogel change detection paradigm, we sought to investigate the capacity of visual working memory in 5-, 7-, and 10-year-olds. We found that performance on the task improved significantly with age and also obtained evidence that the capacity of visual working memory approximately doubles between 5 and 10 years of age, where it reaches adult levels of approximately three to four items

Structure and metallicity of phase V of hydrogen

A new phase V of hydrogen was recently claimed in experiments above 325 GPa and 300 K. Due to the extremely small sample size at such record pressures the measurements were limited to Raman spectroscopy. The experimental data on increase of pressure shows decreasing Raman activity and darkening of the sample, which suggests band-gap closure and impending molecular dissociation, but no definite conclusions could be reached. Furthermore, the available data is insufficient to determine the structure of phase V, which remains unknown. Introducing saddle-point ab initio random structure searching (sp-AIRSS), we find several new structural candidates of hydrogen which could describe the observed properties of phase V. We investigate hydrogen metallisation in the proposed candidate structures, and demonstrate that smaller band gaps are associated with longer bond lengths. We conclude that phase V is a stepping stone towards metallisation

Phage therapy: Awareness and demand among clinicians in the United Kingdom.

Bacterial resistance or tolerance to antibiotics is costly to patients and healthcare providers. With the impact of antibiotic resistance forecast to grow, alternative antimicrobial approaches are needed to help treat patients with antibiotic refractory infections and reduce reliance upon existing antibiotics. There is renewed interest in bacteriophage (phage) therapy as a promising antimicrobial strategy. We therefore performed the first multi-specialty survey about phage therapy and the first such survey among clinicians in the United Kingdom. An anonymous 10-question survey of clinicians from medical and surgical specialties in two Scottish Health Boards was performed. The 90 respondents spanned 26 specialties and were predominantly consultants (73.3%). The respondents were concerned about antibiotic resistance in their clinical practice; 83 respondents estimated having seen 711 patients in the last 12 months whose infections were refractory to antibiotics (delaying or preventing resolution). Over half (58.8%) of the respondents had previously heard of phage therapy. Staphylococci, Pseudomonas and E. coli were identified as the highest cross-specialty priorities for the development of phage therapy. Together, 77 respondents estimated seeing 300 patients in the last 12 months for whom phage therapy may have been appropriate (an average of 3.9 patients per clinician). Most respondents (71.1%, n = 90) were already willing to consider using phage therapy in appropriate cases. Additional comments from the respondents affirmed the potential utility of phage therapy and highlighted a need for more information. The results of this survey demonstrate substantial demand for and willingness to use phage therapy in appropriate cases, both from individual clinicians and across specialties. Demand from a wide range of specialties illustrates the broad clinical utility of phage therapy and potential scope of impact. Widening access to phage therapy could deliver substantial clinical and financial benefits for patients and health authorities alike