Chromosome territory repositioning induced by PHA-activation of lymphocytes: A 2D and 3D appraisal

BACKGROUND: Genomes and by extension chromosome territories (CTs) in a variety of organisms exhibit nonrandom organization within interphase nuclei. CTs are susceptible to movement upon induction by a variety of stimuli, including: cell differentiation, growth factors, genotoxic agents, proliferating status, and stimulants that induce novel transcription profiles. These findings suggest nuclear architecture can undergo reorganization, providing support for a functional significance of CT organization. The effect of the initiation of transcription on global scale chromatin architecture has been underexplored. This study investigates the organization of all 24 human chromosomes in lymphocytes from two individuals in resting and phytohaemagglutinin activated lymphocytes using 2D and 3D approaches. RESULTS: The radial organization of CTs in lymphocytes in both resting and activated lymphocytes follows a gene-density pattern. However, CT organization in activated nuclei appears less constrained exhibiting a more random organization. We report differences in the spatial relationship between homologous and heterologous CTs in activated nuclei. In addition, a reproducible radial hierarchy of CTs was identified and evidence of a CT repositioning was observed in activated nuclei using both 2D and 3D approaches. CONCLUSIONS: Alterations between resting and activated lymphocytes could be adaptation of CTs to the new transcription profile and possibly the formation of new neighborhoods of interest or interaction of CTs with nuclear landmarks. The increased distances between homologous and heterologous CTs in activated lymphocytes could be a reflection of a defensive mechanism to reduce potential interaction to prevent any structural chromosome abnormalities (e.g. translocations) as a result of DNA damage that increases during lymphocyte activation

Predicting the early therapeutic alliance in the treatment of drug misuse

Aims - To predict the early therapeutic alliance from a range of potentially relevant factors, including clients' social relationships, motivation and psychological resources, and counsellors' professional experience and ex-user status. Design - The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Counsellor and client information was assessed at intake, and client and counsellor ratings of the alliance were obtained during weeks 1, 2 and 3. Measurements - The intake assessment battery included scales on psychological wellbeing, treatment motivation, coping strategies and attachment style. Client and counsellor versions of the Working Alliance Inventory (WAI-S) were used for weekly alliance measurement. Hierarchical linear models were used to examine the relationship between alliance and predictor variables. Findings - Clients who had better motivation, coping strategies, social support and a secure attachment style were more likely to develop good alliances. Findings with regard to counsellor characteristics were not clear cut: clients rated their relationships with ex-user counsellors, experienced counsellors and male counsellors as better, but more experienced counsellors rated their alliances as worse. Conclusions - The findings offer important leads as to what interventions might improve the therapeutic alliance. Further work will need to establish whether the therapeutic alliance and ultimately treatment outcomes can be enhanced by working on improving clients' motivation and psychosocial resources

First birth following spindle transfer for mitochondrial replacement therapy: hope and trepidation

In this issue, Zhang et al. (2017) report the birth of a healthy boy after mitochondrial replacement therapy (MRT) by spindle transfer to prevent transmission of mitochondrial disease from mother to child. The case was first publicized in the lay press (Hamzelou, 2016; see also editorial by Johnson, 2016) and then presented during the 2016 Annual Meeting of the American Society for Assisted Reproduction (ASRM) in October 2016 (Zhang et al., 2016a). It followed an earlier report of an unsuccessful attempt at MRT by pronuclear transfer by the same group (Zhang et al., 2016b). This world-first birth represents an achievement and a steppingstone, and it has played a role in encouraging the Human Fertilization and Embryology Authority (HFEA) in the UK to issue a final recommendation that the technique ‘be approved for cautious use in specific circumstances’. (http://www.hfea.gov.uk/10559.html) We, the editors, were unanimous in deciding that this paper should be published in RBMO, based on our conviction that the scientific community must be informed of the details of the work in full in order to evaluate it critically and discuss it openly. We decided this despite the fact that the work has weaknesses and limitations in a number of areas. Moreover, although we were able to encourage the authors to include more details of their work in the submission, some uncertainties concerning methodologies and results still remain. Here we outline our concerns regarding the approach and the treatment process described by Zhang and colleagues

Novel NR5A1 Missense Mutation in Premature Ovarian Failure: Detection in Han Chinese Indicates Causation in Different Ethnic Groups

Background The etiology of most premature ovarian failure (POF) cases is usually elusive. Although genetic causes clearly exist and a likely susceptible region of 8q22.3 has been discovered, no predominant explanation exists for POF. More recently, evidences have indicated that mutations in NR5A1 gene could be causative for POF. We therefore screened for mutations in the NR5A1 gene in a large cohort of Chinese women with non-syndromic POF. Methods Mutation screening of NR5A1 gene was performed in 400 Han Chinese women with well-defined 46,XX idiopathic non-syndromic POF and 400 controls. Subsequently, functional characterization of the novel mutation identified was evaluated in vitro. Results A novel heterozygous missense mutation [c.13T\u3eG (p.Tyr5Asp)] in NR5A1 was identified in 1 of 384 patients (0.26%). This mutation impaired transcriptional activation on Amh, Inhibin-a, Cyp11a1and Cyp19a1 gene, as shown by transactivation assays. However, no dominant negative effect was observed, nor was there impact on protein expression and nuclear localization. Conclusions This novel mutation p.Tyr5Asp, in a novel non-domain region, is presumed to result in haploinsufficiency. Irrespectively, perturbation in NR5A1 is not a common explanation for POF in Chinese

The biology of five scale insects (Homoptera : Coccoidea) in Tennessee

The biologies of two soft scales, Coccus hesperidum Linnaeus and Toumeyella liriodendri (Gmelin) (Homoptera: Coccidae),and three armoured scales, Chionaspis kosztarabi Takagi and Kawai, Pinnaspis aspidistrae (Signoret), and Quadraspidiotus juglansregiae (Comstock) (Homoptera: Dia-spididae), were investigated at the University of Tennessee, Agricul-ture Campus using populations in Tennessee. All studies were conducted from 1975 to 1976 except those for T. liriodendri were from 1973 to 1976. The brown soft scale, C. hesperidum, was a multivoltine parthenogenetic species on spider plant, Chlorophytum comosum Wood. There were seven to eight generations per year. One mite species was collected in close association with the brown soft scale with no parasites or predators found. Biological studies revealed the tuliptree scale, T. liriodendri, to be univoltine and ovoviparous on yellow-popular, Liriodendron tulipifera L. overwintering as first and second instars. Four Formi-cids, one Dipteran and one Hymenopterous wasp were found collecting honeydew produced by the tuliptree scale. The tuliptree scale was parasitized by three Hymenopterous species and one Dipteran and preyed upon by one Lepidopteran and four Coccinellid species. Two other Hjnnenopterous parasites and one mite were collected in close associ-ation with this species. Chionaspis kosztarabi was bivoltine and oviparous on white ash, Fraxinus americana L., overwintering as fertilized adult females. One Hymenopterous parasite was found parasitizing C. kosztarabi second instar females and one scavenger mite was found in close association with adult females. Studies revealed the fern scale, P. aspidistrae, to be a multivoltine parthenogenetic species on lilly turf, Liriope spicata, over-wintering as adult females. One Hymenopterous parasite was found parasitizing second instar females. The walnut scale, Q juglansregiae, was bivoltine and oviparous on flowering dogwood, Cornus florida L.,overwintering as second instar males and females. One Hymenopterous parasite was found parasitizing second instar females. Three mite species were found in close associ-ation with this species. Seasonal history tables of the four latter species are included along with photographs of each biological study and mounting methods. All nymphal instars and adults are discussed. Selected chemical insecticides were evaluated in greenhouse studies in 1975 to compare their efficiency in controlling brown soft scale on C. comosum and fern scale on L. spicata. Insecticides tested were orthene 75W, two rates of carbaryl 50W, and dimethoate 2E. All chemi-cal treatments gave effective control of both species

Enabling precision medicine in neonatology, an integrated repository for preterm birth research.

Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of 'omics' data, which together with integrative computational approaches, can help refine the current knowledge about disease mechanisms, diagnostics, and therapeutics. Here we describe the March of Dimes' Database for Preterm Birth Research (http://www.immport.org/resources/mod), a unique resource that contains a variety of 'omics' datasets related to preterm birth. The database is open publicly, and as of January 2018, links 13 molecular studies with data across tens of thousands of patients from 6 measurement modalities. The data in the repository are highly diverse and include genomic, transcriptomic, immunological, and microbiome data. Relevant datasets are augmented with additional molecular characterizations of almost 25,000 biological samples from public databases. We believe our data-sharing efforts will lead to enhanced research collaborations and coordination accelerating the overall pace of discovery in preterm birth research

Charging Ahead:Unlocking Business Opportunities in the UK's Transition to Electric Vehicles

The purpose of this paper is to examine the current state of electric vehicles (EVs) in the UK, with a focus on the challenges and opportunities for businesses as they transition from internal combustion engine vehicles (ICEVs) in line with the government's Net Zero roadmap. The plan to phase out ICEVs by 2035, with a ban on new sales by 2030, is driven not only by regulatory mandates but also by increasing pressure from partners and customers for more sustainable practices, particularly through the adoption of EVs

Charging Ahead:Unlocking Business Opportunities in the UK's Transition to Electric Vehicles

The purpose of this paper is to examine the current state of electric vehicles (EVs) in the UK, with a focus on the challenges and opportunities for businesses as they transition from internal combustion engine vehicles (ICEVs) in line with the government's Net Zero roadmap. The plan to phase out ICEVs by 2035, with a ban on new sales by 2030, is driven not only by regulatory mandates but also by increasing pressure from partners and customers for more sustainable practices, particularly through the adoption of EVs

Protocol investigating the clinical outcomes and cost-effectiveness of cognitive–behavioural therapy delivered remotely for unscheduled care users with health anxiety: randomised controlled trial

Background Health anxiety and medically unexplained symptoms cost the National Health Service (NHS) an estimated £3 billion per year in unnecessary costs with little evidence of patient benefit. Effective treatment is rarely taken up due to issues such as stigma or previous negative experiences with mental health services. An approach to overcome this might be to offer remotely delivered psychological therapy, which can be just as effective as face-to-face therapy and may be more accessible and suitable. Aims To investigate the clinical outcomes and cost-effectiveness of remotely delivered cognitive–behavioural therapy (CBT) to people with high health anxiety repeatedly accessing unscheduled care (trial registration: NCT02298036). Method A multicentre randomised controlled trial (RCT) will be undertaken in primary and secondary care providers of unscheduled care across the East Midlands. One hundred and forty-four eligible participants will be equally randomised to receive either remote CBT (6–12 sessions) or treatment as usual (TAU). Two doctoral research studies will investigate the barriers and facilitators to delivering the intervention and the factors contributing to the optimisation of therapeutic outcome. Results This trial will be the first to test the clinical outcomes and costeffectiveness of remotely delivered CBT for the treatment of high health anxiety. Conclusions The findings will enable an understanding as to how this intervention might fit into a wider care pathway to enhance patient experience of care