Nuclear morphologies: their diversity and functional relevance.

Studies of chromosome and genome biology often focus on condensed chromatin in the form of chromosomes and neglect the non-dividing cells. Even when interphase nuclei are considered, they are often then treated as interchangeable round objects. However, different cell types can have very different nuclear shapes, and these shapes have impacts on cellular function; indeed, many pathologies are linked with alterations to nuclear shape. In this review, we describe some of the nuclear morphologies beyond the spherical and ovoid. Many of the leukocytes of the immune system have lobed nuclei, which aid their flexibility and migration; smooth muscle cells have a spindle shaped nucleus, which must deform during muscle contractions; spermatozoa have highly condensed nuclei which adopt varied shapes, potentially associated with swimming efficiency. Nuclei are not passive passengers within the cell. There are clear effects of nuclear shape on the transcriptional activity of the cell. Recent work has shown that regulation of gene expression can be influenced by nuclear morphology, and that cells can drastically remodel their chromatin during differentiation. The link between the nucleoskeleton and the cytoskeleton at the nuclear envelope provides a mechanism for transmission of mechanical forces into the nucleus, directly affecting chromatin compaction and organisation.Leverhulme Trust (Grant ID: RPG337), Biotechnology and Biological Sciences Research Council (Grant IDs: BB/N000129/1, BB/L502443/1)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00412-016-0614-

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

Lower Use of Hospice by Cancer Patients who Live in Minority Versus White Areas

BACKGROUND: Although hospice care can alleviate suffering at the end of life for patients with cancer, it remains underutilized, particularly by African Americans and Hispanics. OBJECTIVE: To examine whether the racial composition of the census tract where an individual resides is associated with hospice use. DESIGN: Retrospective analysis of the Surveillance, Epidemiology, and End Results–Medicare file for individuals dying from breast, colorectal, lung, or prostate cancer (n = 70,669). MEASUREMENTS: Hospice use during the 12 months before death. RESULTS: Hospice was most commonly used by individuals who lived in areas with fewer African-American and Hispanic residents (47%), and was least commonly used by individuals who lived in areas with a high percentage of African-American and Hispanic residents (35%). Hispanics (odds ratio 0.51, 95% confidence interval 0.29–0.91) and African Americans (0.56, 0.44–0.71) were less likely to use hospice if they lived in a census tract with a high percentage of both African Americans and Hispanics than if they lived in a low minority tract. African Americans and whites were less likely to receive hospice care if they lived in a census tract with a high percentage of Hispanics than if they lived in a low minority area. CONCLUSIONS: Increasing hospice use may require interventions to improve the delivery of hospice care in minority communities

An integrated model of care to counter high incidence of HIV and sexually transmitted diseases in men who have sex with men – initial analysis of service utilizers in Zurich

BACKGROUND: As other countries, Switzerland experiences a high or even rising incidence of HIV and sexually transmitted infections (STI) among men who have sex with men (MSM). An outpatient clinic for gay men ("Checkpoint") was opened in 2006 in Zurich (Switzerland) in order to provide sexual health services. The clinic provides counselling, testing, medical treatment and follow-up at one location under an "open-door-policy" and with a high level of personal continuity. We describe first experiences with the new service and report the characteristics of the population that utilized it. METHODS: During the 6-month evaluation period, individuals who requested counselling, testing or treatment were asked to participate in a survey at their first visit prior to the consultation. The instrument includes questions regarding personal data, reasons for presenting, sexual behaviour, and risk situations. Number and results of HIV/STI tests and treatments for STI were also recorded. RESULTS: During the evaluation period, 632 consultations were conducted and 247 patients were seen by the physician. 406 HIV tests were performed (3.4% positive). 402 men completed the entry survey (64% of all consultations). The majority of respondents had 4 and more partners during the last 12 months and engaged in either receptive, insertive or both forms of anal intercourse. More than half of the responders used drugs or alcohol to get to know other men or in conjunction with sexual activity (42% infrequently, 10% frequently and 0.5% used drugs always). The main reasons for requesting testing were a prior risk situation (46.3%), followed by routine screening without a prior risk situation (24.1%) and clarification of HIV/STI status due to a new relationship (29.6%). A fifth of men that consulted the service had no history of prior tests for HIV or other STIs. CONCLUSION: Since its first months of activity, the service achieved high levels of recognition, acceptance and demand in the MSM community. Contrary to common concepts of "testing clinics", the Checkpoint service provides post-exposure prophylaxis, HIV and STI treatment, psychological support and counselling and general medical care. It thus follows a holistic approach to health in the MSM community with the particular aim to serve as a "door opener" between the established system of care and those men that have no access to, or for any reason hesitate to utilize traditional health care

A Conserved Requirement for fbxo7 during Male Germ Cell Cytoplasmic Remodelling

Fbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here, we show that in addition to the previously known Parkinsonian and hematopoietic phenotypes, male mice with reduced Fbxo7 expression are sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the spermatids undergo cytoplasmic remodeling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7 mutant males. Mutation of the Drosophila Fbxo7 ortholog, nutcracker (ntc) also leads to sterility with germ cell death during cytoplasmic remodeling, indicating that the requirement for Fbxo7 at this stage is conserved. The ntc phenotype was attributed to decreased levels of the proteasome regulator, DmPI31 and reduced proteasome activity. Consistent with the fly model, we observe a reduction in PI31 levels in mutant mice; however, there is no alteration in proteasome activity in whole mouse testes. Our results are consistent with findings that Fbxo7 regulates PI31 protein levels, and indicates that a defect at the late stages of spermiogenesis, possibly due to faulty spatial dynamics of proteasomes during cytoplasmic remodeling, may underlie the fertility phenotype in mice

Parma consensus statement on metabolic disruptors

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16–18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as “metabolic disruptors”, in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome

Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer

BACKGROUND: Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients. METHODS: SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied. RESULTS: SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT\u2013PCR\ubc162 vs 2.21; P\ubc0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (mgml 1) had a median (95% CIs) of 6.0 (4.0\u20138.9) in normal healthy females and 6.0 (4.2\u20138.1) in patients with benign disease (P\ubc0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2\u201356.2), significantly higher than those in the healthy group (P\ubc0.0005) and benign group (P\ubc0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P\ubc0.0024). CONCLUSION: SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy