Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

This article has been made available through the Brunel Open Access Publishing Fund.Background: Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited. Results: By investigating the positioning of all human chromosomes in primary fibroblasts that have left the proliferative cell cycle, we have demonstrated that in cells made quiescent by reversible growth arrest, chromosome positioning is altered considerably. We found that with the removal of serum from the culture medium, chromosome repositioning took less than 15 minutes, required energy and was inhibited by drugs affecting the polymerization of myosin and actin. We also observed that when cells became quiescent, the nuclear distribution of nuclear myosin 1ß was dramatically different from that in proliferating cells. If we suppressed the expression of nuclear myosin 1ß by using RNA-interference procedures, the movement of chromosomes after 15 minutes in low serum was inhibited. When high serum was restored to the serum-starved cultures, chromosome repositioning was evident only after 24 to 36 hours, and this coincided with a return to a proliferating distribution of nuclear myosin 1ß. Conclusions: These findings demonstrate that genome organization in interphase nuclei is altered considerably when cells leave the proliferative cell cycle and that repositioning of chromosomes relies on efficient functioning of an active nuclear motor complex that contains nuclear myosin 1ß.Brunel Open Access Publishing Fun

Self-Similar Propagation and Amplification of Parabolic Pulses in Optical Fibers

Ultrashort pulse propagation in high gain optical fiber amplifiers with normal dispersion is studied by self-similarity analysis of the nonlinear Schrödinger equation with gain. An exact asymptotic solution is found, corresponding to a linearly chirped parabolic pulse which propagates self-similarly subject to simple scaling rules. The solution has been confirmed by numerical simulations and experiments studying propagation in a Yb-doped fiber amplifier. Additional experiments show that the pulses remain parabolic after propagation through standard single mode fiber with normal dispersion

HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

This article has been made available through the Brunel Open Access Publishing Fund.PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a proportion of hypoxic PTK6 subsequently re-localized to the cell membrane. We observed that the rapid stabilization of PTK6 is associated with a decrease in PTK6 ubiquitylation and we have identified c-Cbl as a putative PTK6 E3 ligase in normoxia. The consequences of hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential. This could have particular significance for breast cancer patients with triple negative disease.A Breast Cancer Campaign pilot grant awarded to E.M.H. supported this study. I.M.P. is supported by University of Hull HEFCE funding, and Royal Society and Breast Cancer Campaign pilot grants. S.A.E. is supported by ICR HEFCE funding and Cancer Research UK program grant C309/A11566. A.H. is supported by Brunel University HEFCE funding. E.M.H. is supported by a Cancer Research UK grant

Low-cost, multispectral imaging mini-microscope for longitudinal oximetry in small animals

We present a multispectral imaging mini-microscope for longitudinal oximetry in small animals. By replacing expensive and complex imaging systems using a low-cost imaging system

Key issues in clinic functioning - a case study of two clinics

Objective. The aim of this research was to understand key issues in the functioning of two different primary care clinics serving the same community, in order to learn more about clinic management.Design. An in-depth case study was conducted. A range of qualitative information was collected at both clinics. Data collected in the two clinics were compared, to gain an understanding of the important issues.Setting. Data were collected in a government and an NGO clinic in North West province.Subjects. This report presents the findings from patient and staff  satisfaction surveys and in-depth individual interviews with senior staff.Results. Key findings included the following: (i) there are attitudinal  differences between the staff at the two clinics; (ii) the patients appreciate the services of both clinics, though they view them differently; (iii) clinic A provides a wider range of services to more people more often; (iv) clinic B presents a picture of quality of care, related to the environment and  approach of staff; (v) waiting time is not as important as how patients are treated; (vi) medications are a crucial factor, in the minds of staff and patients; and (vii) a supportive, empowering organisational culture is  needed to encourage staff to deliver better care to their patients. The management of the clinic is part of this culture.Conclusions. This research provides lessons regarding key issues in clinic functioning which can make a major difference to the way services are experienced. Arespectfuland caring approach to patients, and an  organisational culture which supports and enables staff, can achieve much of this without any additional resources

Use of Remote Camera Traps to Evaluate Animal-Based Welfare Indicators in Individual Free-Roaming Wild Horses

We previously developed a Ten-Stage Protocol for scientifically assessing the welfare of individual free-roaming wild animals using the Five Domains Model. The protocol includes developing methods for measuring or observing welfare indices. In this study, we assessed the use of remote camera traps to evaluate an extensive range of welfare indicators in individual free-roaming wild horses. Still images and videos were collected and analysed to assess whether horses could be detected and identified individually, which welfare indicators could be reliably evaluated, and whether behaviour could be quantitatively assessed. Remote camera trapping was successful in detecting and identifying horses (75% on still images and 72% on video observation events), across a range of habitats including woodlands where horses could not be directly observed. Twelve indicators of welfare across the Five Domains were assessed with equal frequency on both still images and video, with those most frequently assessable being body condition score (73% and 79% of observation events, respectively), body posture (76% for both), coat condition (42% and 52%, respectively), and whether or not the horse was sweating excessively (42% and 45%, respectively). An additional five indicators could only be assessed on video; those most frequently observable being presence or absence of weakness (66%), qualitative behavioural assessment (60%), presence or absence of shivering (51%), and gait at walk (50%). Specific behaviours were identified in 93% of still images and 84% of video events, and proportions of time different behaviours were captured could be calculated. Most social behaviours were rarely observed, but close spatial proximity to other horses, as an indicator of social bonds, was recorded in 36% of still images, and 29% of video observation events. This is the first study that describes detailed methodology for these purposes. The results of this study can also form the basis of application to other species, which could contribute significantly to advancing the field of wild animal welfare