The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo

© 2008 Hutt et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Developmental Biology 8 (2008): 1, doi:10.1186/1471-213X-8-1.Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation. We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts. We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.This research was supported by NIH/NIEHS-012916 (BKP), ESHE Fund (DFA), Hall Family Foundation (DFA and KJH) and Biomedical Research Training Grant KUMC (KJH)

Stimulus statistics shape oscillations in nonlinear recurrent neural networks.

Rhythmic activity plays a central role in neural computations and brain functions ranging from homeostasis to attention, as well as in neurological and neuropsychiatric disorders. Despite this pervasiveness, little is known about the mechanisms whereby the frequency and power of oscillatory activity are modulated, and how they reflect the inputs received by neurons. Numerous studies have reported input-dependent fluctuations in peak frequency and power (as well as couplings across these features). However, it remains unresolved what mediates these spectral shifts among neural populations. Extending previous findings regarding stochastic nonlinear systems and experimental observations, we provide analytical insights regarding oscillatory responses of neural populations to stimulation from either endogenous or exogenous origins. Using a deceptively simple yet sparse and randomly connected network of neurons, we show how spiking inputs can reliably modulate the peak frequency and power expressed by synchronous neural populations without any changes in circuitry. Our results reveal that a generic, non-nonlinear and input-induced mechanism can robustly mediate these spectral fluctuations, and thus provide a framework in which inputs to the neurons bidirectionally regulate both the frequency and power expressed by synchronous populations. Theoretical and computational analysis of the ensuing spectral fluctuations was found to reflect the underlying dynamics of the input stimuli driving the neurons. Our results provide insights regarding a generic mechanism supporting spectral transitions observed across cortical networks and spanning multiple frequency bands

An evaluation of Thiomicrospira, Hydrogenovibrio and Thioalkalimicrobium: reclassification of 4 species of Thiomicrospira to each Thiomicrorhabdus gen. nov. and Hydrogenovibrio, and reclassification of all 4 species of Thioalkalimicrobium to Thiomicrospira.

Thiomicrospira spp. are small sulfur-oxidising chemolithoautotrophic members of the Gammaproteobacteria. Whilst the type species Tms. pelophila and closely related Tms. thyasirae exhibit canonical spiral morphology under sub-optimal growth conditions, most species are vibrios or rods. The 16S rRNA gene diversity is vast, with identities as low as 91.6 % to Tms. pelophila versus Tms. frisia, for example. Thiomicrospira was examined with closely related genera Hydrogenovibrio and Thioalkalimicrobium and, to rationalise organisms on the basis of the 16S rRNA gene phylogeny, physiology and morphology, we reclassify Tms. kuenenii, Tms. crunogena, Tms. thermophila and Tms. halophila to Hydrogenovibrio kuenenii comb. nov., H. crunogenus corrig. comb. nov., H. thermophilus corrig. comb. nov., and H. halophilus corrig. comb. nov. We reclassify Tms. frisia, Tms. arctica, Tms. psychrophila and Tms. chilensis to Thiomicrorhabdus gen. nov., as Tmr. frisia comb. nov., Tmr. arctica comb. nov., Tmr. psychrophila comb. nov. and Tmr. chilensis comb. nov. – the type species of Thiomicrorhabdus is Tmr. frisia. We demonstrate Thioalkalimicrobium spp. fall in the genus Thiomicrospira sensu stricto, thus reclassifying them to Tms. aerophila corrig. comb. nov., Tms. microaerophila corrig. comb. nov., Tms. cyclica corrig. comb. nov.and Tms. sibirica corrig. comb. nov. We provide emended descriptions of the genera Thiomicrospira and Hydrogenovibrio and of Tms. thyasirae

Deaths in people from Black, Asian and minority ethnic communities from both COVID-19 and non-COVID causes in the first weeks of the pandemic in London: a hospital case note review

Objective To undertake a case review of deaths in a 6-week period during the COVID-19 pandemic commencing with the first death in the hospital from COVID-19 on 12th of March 2020 and contrast this with the same period in 2019. Setting A large London teaching hospital. Participants Three groups were compared: group 1—COVID-19-associated deaths in the 6-week period (n=243), group 2—non-COVID deaths in the same period (n=136) and group 3—all deaths in a comparison period of the same 6 weeks in 2019 (n=194). Primary and secondary outcome measures This was a descriptive analysis of death case series review and as such no primary or secondary outcomes were pre-stipulated. Results Deaths in patients from the Black, Asian and minority ethnic (BAME) communities in the pandemic period significantly increased both in the COVID-19 group (OR=2.43, 95% CI=1.60–3.68, p<0.001) and the non-COVID group (OR=1.76, 95% CI=1.09–2.83, p=0.02) during this time period and the increase was independent of differences in comorbidities, sex, age or deprivation. While the absolute number of deaths increased in 2020 compared with 2019, across all three groups the distribution of deaths by age was very similar. Our analyses confirm major risk factors for COVID-19 mortality including male sex, diabetes, having multiple comorbidities and background from the BAME communities. Conclusions There was no evidence of COVID-19 deaths occurring disproportionately in the elderly compared with non-COVID deaths in this period in 2020 and 2019. Deaths in the BAME communities were over-represented in both COVID-19 and non-COVID groups, highlighting the need for detailed research in order to fully understand the influence of ethnicity on susceptibility to illness, mortality and health-seeking behaviour during the pandemic

Clinical applications and limitations of current ovarian stem cell research: a review

The publication of a report in Nature in 2004 by the Tilly group suggesting that mouse ovaries are capable of generating oocytes de novo post-natally, has sparked interest in a problem long thought to have been resolved from classical studies in a variety of mammalian species. Within a nearly two year time period, laboratories around the world have taken up the challenge to dogma raised by this initial report, either to test this concept in an experimental basic science setting or give direction to clinical applications that could result, were the original premises of this work in the mouse valid for extrapolation to humans. This review provides a status report for this promising area of research, (1) to summarize recent findings in the literature with respect to the validity of the original hypothesis proffered by the Tilly group, and, (2) to gauge the potential utility of ovarian stem cells as a treatment for certain forms of human infertility

Contextualising and challenging under-representation in research in light of cultural trauma: a qualitative focus group and interview study

Background Although underserved populations— including those from ethnic minority communities and those living in poverty—have worse health and poorer healthcare experiences, most primary care research does not fairly reflect these groups. Patient and public involvement (PPI) is usually embedded within research studies in the United Kingdom (UK), but often fails to represent underserved populations. This study worked with patient and public contributors and local community leaders, situated in a socio-economically deprived and ethnically diverse urban area, to explore under-representation in primary healthcare research. Methods We undertook a focus group with a purposive sample of 6 members of a Patient and Public Involvement Group (PPIG), and interviews with 4 community leaders (representing Black, South Asian, Roma and socio-economically deprived communities). An iterative analysis process based on template analysis was used. Focus group 1 was rapidly analysed, and a template created. Findings were presented in focus group 2, and the template further developed. The Cultural Trauma concept was than applied to the template to give a wider theoretical lens. In-depth analysis of focus groups and interviews was then performed based on the template. Results Wider societal and historical influences have degraded trust in academic and healthcare institutions within underserved populations. Along with more practical considerations, trust underpins personal motivations to engage with research. Researchers need to invest time and resources in prolonged, mutually beneficial engagement with communities of importance to their research, including sharing power and influence over research priorities. Researcher reflexivity regarding differential power and cultural competencies are crucial. Utilising participatory methodologies including co-production demonstrates a commitment to inclusive study design. Conclusions Re-framing evidence-based medicine to be more useful and relevant to underserved populations with the highest burden of ill health is urgently needed. Lack of representation in primary healthcare research reflects wider societal inequalities, to which Cultural Trauma provides a useful lens. However, there are actions that researchers can take to widen representation. This will ultimately help achieve the goal of increased health equity by enhancing scientific rigour and research generalizability

Fabrication of Polymer Waveguides by Laser Ablation Using a 355 nm Wavelength Nd:YAG Laser

The demand for optical waveguides integrated into Printed Circuit Boards (PCBs) is increasing as the limitations of copper interconnects for greater than 10 Gb/s data rates are being reached. Optical polymer materials offer a good solution due to their relatively low cost and compatibility with traditional PCB manufacturing processes. Laser ablation is one method of manufacture, for which excimer lasers have been used, but UV Nd:YAG (Neodymium-doped Yttrium Aluminium Garnet) lasers are an attractive alternative due to their widespread use within the PCB industry for drilling vias. In this paper, 355 nm, 60 ns pulse length UV Nd:YAG laser ablation of Truemode™ acrylate-based optical polymer was investigated. The UV Nd:YAG laser was found to be able to ablate the polymer efficiently and the effects of laser ablation power and pulse repetition frequency (PRF) on depth of ablation were studied and used to determine preferred settings. 45 μm × 45 μm multimode optical waveguides were fabricated to demonstrate the process and optical loss measurements were carried out. These measurements demonstrated that the structures were able to transmit light at the data communications wavelength of 850 nm (NIR), but further work is required to reduce the level of loss. The use of UV Nd:YAG as a possible alternative to excimer for laser micromachining would facilitate the rapid deployment of the optical technology within the PCB industry

Experimental and numerical study of micropitting initiation in real rough surfaces in a micro-elastohydrodynamic lubrication regime

Micropitting is a form of surface fatigue damage that happens at the surface roughness scale in lubricated contacts in commonly used machine elements, such as gears and bearings. It occurs where the specific film thickness (ratio of smooth surface film thickness to composite surface roughness) is sufficiently low for the contacts to operate in the mixed lubrication regime, where the load is in part carried by direct asperity contacts. Micropitting is currently seen as a greater issue for gear designers than is regular pitting fatigue failure as the latter can be avoided by control of steel cleanliness. This paper describes the results of both theoretical and experimental studies of the onset of micropitting in test disks operated in the mixed lubrication regime. A series of twin disk mixed-lubrication experiments were performed in order to examine the evolution of micropitting damage during repeated cyclic loading of surface roughness asperities as they pass through the contact. Representative measurements of the surfaces used in the experimental work were then evaluated using a numerical model which combines a transient line contact micro-elastohydrodynamic lubrication (micro-EHL) simulation with a calculation of elastic sub-surface stresses. This model generated time-history of stresses within a block of material as it passes through the contact, based on the instantaneous surface contact pressure and traction at each point in the computing mesh at each timestep. This stress time-history was then used within a shear-strain-based fatigue model to calculate the cumulative damage experienced by the surface due to the loading sequence experienced during the experiments. The proposed micro-EHL model results and the experimental study were shown to agree well in terms of predicting the number of loading cycles that are required for the initial micropitting to occur