The consequences of replicating in the wrong orientation: Bacterial chromosome duplication without an active replication origin

Chromosome replication is regulated in all organisms at the assembly stage of the replication machinery at specific origins. In Escherichia coli the DnaA initiator protein regulates the assembly of replication forks at oriC. This regulation can be undermined by defects in nucleic acid meta¬bolism. In cells lacking RNase HI replication initiates indepen¬dently of DnaA and oriC, presumably at persisting R-loops. A similar mechanism was assumed for origin-independent synthesis in cells lacking RecG. However, recently we suggested that this synthesis initiates at intermediates resulting from replication fork fusions. Here we present data suggesting that in cells lacking RecG or RNase HI origin-independent synthesis arises by different mechanisms, indicative of these two proteins having different roles in vivo. Our data support the idea that RNase HI processes R-loops, while RecG is required to process replication fork fusion intermediates. However, regardless of how origin-independent synthesis is initiated, a fraction of forks will proceed in an orientation opposite to normal. We show that the resulting head-on encounters with transcription threaten cell viability, especially if taking place in highly-transcribed areas. Thus, despite their different functions, RecG and RNase HI are both important factors for maintaining replication control and orientation. Their absence causes severe replication problems, highlighting the advantages of the normal chromosome arrangement, which exploits a single origin to control the number of forks and their orientation relative to transcription, and a defined termination area to contain fork fusions. Any changes to this arrangement endanger cell cycle control, chromosome dynamics and, ultimately, cell viability.This work was supported by the Royal Society (RG110414 to C.J.R.) and The Biotechnology and Biological Sciences Research Council (BB/K015729/1 to C.J.R.)

Adopting Minds — a mentalization-based therapy for families in a post-adoption support service: preliminary evaluation and service user experience

Children placed for adoption often face unique challenges and are at higher risk of mental health problems compared to the general population. Yet despite some important clinical developments, there is still a lack of evidence related to effective therapeutic interventions for this population. This study reports on the preliminary evaluation of a mentalization-based family therapy service, Adopting Minds, offered as part of a post-adoption support service. Thirty-six families who had adopted 42 children were referred to the service between September 2015 and December 2016. Demographic information was collected and assessments undertaken on the families at baseline and at the end of therapy, using a range of validated measures. Five families who had completed therapy were also interviewed about their experience of the approach. For those families on which data were available, positive outcomes in mental health and parental self-efficacy were identified, and adoptive parents reported high levels of satisfaction with the mentalization-based family therapy service. Analysis of the interviews revealed that the families found it a containing space that was supportive and non-judgemental. They felt able to express their fears and worries to a therapist who was friendly and knowledgeable and reported that the service helped them to deal with and link struggles they were facing to their own as well as their child's past experiences. However, some adoptive families felt that this short-term, six-session service alone was not enough to address all the difficulties that had brought the family to seek help, and would have preferred a longer-term intervention or therapy in combination with other types of support

Analysis of a continuous-variable quadripartite cluster state from a single optical parametric oscillator

We examine the feasibility of generating continuous-variable multipartite entanglement in an intra-cavity quadruply concurrent downconversion scheme that has been proposed for the generation of cluster states by Menicucci \textit{et al.} [Physical Review Letters \textbf{101}, 130501 (2008)]. By calculating optimized versions of the van Loock-Furusawa correlations we demonstrate genuine quadripartite entanglement and investigate the degree of entanglement present. Above the oscillation threshold the basic cluster state geometry under consideration suffers from phase diffusion. We alleviate this problem by incorporating a small injected signal into our analysis. Finally, we investigate squeezed joint operators. While the squeezed joint operators approach zero in the undepleted regime, we find that this is not the case when we consider the full interaction Hamiltonian and the presence of a cavity. In fact, we find that the decay of these operators is minimal in a cavity, and even depletion alone inhibits cluster state formation.Comment: 26 pages, 12 figure

Identification of Non-unitary triplet pairing in a heavy Fermion superconductor UPt_3

A NMR experiment recently done by Tou et al. on a heavy Fermion superconductor UPt$_3$ is interpreted in terms of a non-unitary spin-triplet pairing state which we have been advocating. The proposed state successfully explains various aspects of the seemingly complicated Knight shift behaviors probed for major orientations, including a remarkable d-vector rotation under weak fields. This entitles UPt$_3$ as the first example that a charged many body system forms a spin-triplet odd-par ity pairing at low temperatures and demonstrates unambiguously that the putative spin-orbit coupling in UPt$_3$ is weak.Comment: 4 pages, 2 eps figures, to be published in J. Phys. Soc. Jpn. 67 (1998) No.

TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres.

Shorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable and may be an intermediate phenotype linked to genetic susceptibility to CRC

Hypoxia mediated release of endothelial microparticles and increased association of S100A12 with circulating neutrophils

Microparticles are released from the endothelium under normal homeostatic conditions and have been shown elevated in disease states, most notably those characterised by endothelial dysfunction. The endothelium is sensitive to oxidative stress/status and vascular cell adhesion molecule-1 (VCAM-1) expression is upregulated upon activated endothelium, furthermore the presence of VCAM-1 on microparticles is known. S100A12, a calcium binding protein part of the S100 family, is shown to be present on circulating leukocytes and is thought a sensitive marker to local inflammatory process, which may be driven by oxidative stress. Eight healthy males were subjected to breathing hypoxic air (15% O2, approximately equivalent to 3000 metres altitude) for 80 minutes in a temperature controlled laboratory and venous blood samples were processed immediately for VCAM-1 microparticles (VCAM-1 MP) and S100A12 association with leukocytes by flow cytometry. A pre-hypoxic blood sample was used for comparison. Both VCAM-1 MP and S100A12 association with neutrophils were significantly elevated post hypoxic breathing later declining to levels observed in the pre-test samples. A similar trend was observed in both cases and a correlation may exist between these two markers in response to hypoxia. These data offer evidence using novel markers of endothelial and circulating blood responses to hypoxia

Evidence for a two component magnetic response in UPt3

The magnetic response of the heavy fermion superconductor UPt_3 has been investigated on a microscopic scale by muon Knight shift studies. Two distinct and isotropic Knight shifts have been found for the field in the basal plane. While the volume fractions associated with the two Knight shifts are approximately equal at low and high temperatures, they show a dramatic and opposite temperature dependence around T_N. Our results are independent on the precise muon localization site. We conclude that UPt_3 is characterized by a two component magnetic response.Comment: 5 pages, 4 figure