Magnetic fields in early-type stars

For several decades we have been cognizant of the presence of magnetic fields in early-type stars, but our understanding of their magnetic properties has recently (over the last decade) expanded due to the new generation of high-resolution spectropolarimeters (ESPaDOnS at CFHT, Narval at TBL, HARPSpol at ESO). The most detailed surface magnetic field maps of intermediate-mass stars have been obtained through Doppler imaging techniques, allowing us to probe the small-scale structure of these stars. Thanks to the effort of large programmes (e.g. the MiMeS project), we have, for the first time, addressed key issues regarding our understanding of the magnetic properties of massive (M > 8 M_sun) stars, whose magnetic fields were only first detected about fifteen years ago. In this proceedings article we review the spectropolarimetric observations and statistics derived in recent years that have formed our general understanding of stellar magnetism in early-type stars. We also discuss how these observations have furthered our understanding of the interactions between the magnetic field and stellar wind, as well as the consequences and connections of this interaction with other observed phenomena.Comment: 8 pages, 2 figures. To appear in the proceedings of the IAUS 305 - Polarimetry: From the sun to stars and stellar environment

Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy.

Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity in the nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates cardiac transcription by directly binding to chromatin and regulating the phosphorylation of histone H3 at serine-10. These specific activities are demonstrated both in vitro and in primary neonatal rat cardiomyocytes. Activation of CaMKII signaling by hypertrophic agonists increases H3 phosphorylation in primary cardiac cells and is accompanied by concomitant cellular hypertrophy. Conversely, specific silencing of nuclear CaMKII using RNA interference reduces both H3 phosphorylation and cellular hypertrophy. The hyper-phosphorylation of H3 associated with increased chromatin binding of CaMKII occurs at specific gene loci reactivated during cardiac hypertrophy. Importantly, H3 Ser-10 phosphorylation and CaMKII recruitment are associated with increased chromatin accessibility and are required for chromatin-mediated transcription of the Mef2 transcription factor. Unlike phosphorylation of H3 by other kinases, which regulates cellular proliferation and immediate early gene activation, CaMKII-mediated signaling to H3 is associated with hypertrophic growth. These observations reveal a previously unrecognized function of CaMKII as a kinase signaling to histone H3 and remodeling chromatin. They suggest a new epigenetic mechanism controlling cardiac hypertrophy

Tissue-type plasminogen activator-primed human iPSC-derived neural progenitor cells promote motor recovery after severe spinal cord injury.

The goal of stem cell therapy for spinal cord injury (SCI) is to restore motor function without exacerbating pain. Induced pluripotent stem cells (iPSC) may be administered by autologous transplantation, avoiding immunologic challenges. Identifying strategies to optimize iPSC-derived neural progenitor cells (hiNPC) for cell transplantation is an important objective. Herein, we report a method that takes advantage of the growth factor-like and anti-inflammatory activities of the fibrinolysis protease, tissue plasminogen activator tPA, without effects on hemostasis. We demonstrate that conditioning hiNPC with enzymatically-inactive tissue-type plasminogen activator (EI-tPA), prior to grafting into a T3 lesion site in a clinically relevant severe SCI model, significantly improves motor outcomes. EI-tPA-primed hiNPC grafted into lesion sites survived, differentiated, acquired markers of motor neuron maturation, and extended βIII-tubulin-positive axons several spinal segments below the lesion. Importantly, only SCI rats that received EI-tPA primed hiNPC demonstrated significantly improved motor function, without exacerbating pain. When hiNPC were treated with EI-tPA in culture, NMDA-R-dependent cell signaling was initiated, expression of genes associated with stemness (Nestin, Sox2) was regulated, and thrombin-induced cell death was prevented. EI-tPA emerges as a novel agent capable of improving the efficacy of stem cell therapy in SCI

Effects of radio-frequency fields on bacterial cell membranes and nematode temperature-sensitive mutants

Membrane-related bioeffects have been reported in response to both radio-frequency (RF) and extremely low-frequency (ELF) electromagnetic fields (EMFs), particularly in neural cells. We have tested whether RF fields might cause inner membrane leakage in ML35 E. coli cells, which express β-galactosidase (lacZ) constitutively, but lack the lacY permease required for substrate entry. The activity of lacZ (indicating substrate leakage through the inner cell membrane) was increased only slightly by RF exposure (1 GHz, 0.5 W) over 45 min. Since lacZ activity showed no further increase with a longer exposure time of 90 min, this suggests that membrane permeability per se is not significantly affected by RF fields, and that slight heating (≤ 0.1°C) could account for this small difference. Temperature-sensitive (ts) mutants of the nematode, Caenorhabditis elegans, are wild-type at 15°C but develop the mutant phenotype at 25°C; an intermediate temperature of 21°C results in a reproducible mixture of both phenotypes. For two ts mutants affecting transmembrane receptors (TRA-2 and GLP-1), RF exposure for 24 h during the thermocritical phase strongly shifts the phenotype mix at 21°C towards the mutant end of the spectrum. For ts mutants affecting nuclear proteins, such phenotype shifts appear smaller (PHA-1) or non-significant (LIN-39), apparently confirming suggestions that RF power is dissipated mainly in the plasma membrane of cells. However, these phenotype shifts are no longer seen when microwave treatment is applied at 21°C in a modified exposure apparatus that minimises the temperature difference between sham and exposed conditions. Like other biological effects attributed to microwaves in the C. elegans system, phenotype shifts in ts mutants appear to be an artefact caused by very slight heating

Interventions for reducing sedentary behaviour in people with stroke

BACKGROUND: Stroke survivors are often physically inactive as well as sedentary,and may sit for long periods of time each day. This increases cardiometabolic risk and has impacts on physical and other functions. Interventions to reduce or interrupt periods of sedentary time, as well as to increase physical activity after stroke, could reduce the risk of secondary cardiovascular events and mortality during life after stroke. OBJECTIVES: To determine whether interventions designed to reduce sedentary behaviour after stroke, or interventions with the potential to do so, can reduce the risk of death or secondary vascular events, modify cardiovascular risk, and reduce sedentary behaviour. SEARCH METHODS: In December 2019, we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, Conference Proceedings Citation Index, and PEDro. We also searched registers of ongoing trials, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing interventions to reduce sedentary time with usual care, no intervention, or waiting‐list control, attention control, sham intervention or adjunct intervention. We also included interventions intended to fragment or interrupt periods of sedentary behaviour. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and performed 'Risk of bias' assessments. We analyzed data using random‐effects meta‐analyses and assessed the certainty of the evidence with the GRADE approach. MAIN RESULTS: We included 10 studies with 753 people with stroke. Five studies used physical activity interventions, four studies used a multicomponent lifestyle intervention, and one study used an intervention to reduce and interrupt sedentary behaviour. In all studies, the risk of bias was high or unclear in two or more domains. Nine studies had high risk of bias in at least one domain. The interventions did not increase or reduce deaths (risk difference (RD) 0.00, 95% confidence interval (CI) ‐0.02 to 0.03; 10 studies, 753 participants; low‐certainty evidence), the incidence of recurrent cardiovascular or cerebrovascular events (RD ‐0.01, 95% CI ‐0.04 to 0.01; 10 studies, 753 participants; low‐certainty evidence), the incidence of falls (and injuries) (RD 0.00, 95% CI ‐0.02 to 0.02; 10 studies, 753 participants; low‐certainty evidence), or incidence of other adverse events (moderate‐certainty evidence). Interventions did not increase or reduce the amount of sedentary behaviour time (mean difference (MD) +0.13 hours/day, 95% CI ‐0.42 to 0.68; 7 studies, 300 participants; very low‐certainty evidence). There were too few data to examine effects on patterns of sedentary behaviour. The effect of interventions on cardiometabolic risk factors allowed very limited meta‐analysis. AUTHORS' CONCLUSIONS: Sedentary behaviour research in stroke seems important, yet the evidence is currently incomplete, and we found no evidence for beneficial effects. Current World Health Organization (WHO) guidelines recommend reducing the amount of sedentary time in people with disabilities, in general. The evidence is currently not strong enough to guide practice on how best to reduce sedentariness specifically in people with stroke. More high‐quality randomised trials are needed, particularly involving participants with mobility limitations. Trials should include longer‐term interventions specifically targeted at reducing time spent sedentary, risk factor outcomes, objective measures of sedentary behaviour (and physical activity), and long‐term follow‐up

Immunization with L. sigmodontis Microfilariae Reduces Peripheral Microfilaraemia after Challenge Infection by Inhibition of Filarial Embryogenesis

Lymphatic filariasis is caused by parasitic filarial worms that are transmitted by mosquitoes, requiring uptake of larvae and distribution into the blood of the host. More than 120 million people are infected and about 30% of these individuals suffer from clinical symptoms. Reduction in transmission currently depends on mass drug administration, which has significantly reduced transmission rates over the past years. However, despite repetitive rounds of administration, transmission has not been eliminated completely from endemic areas. In some infected individuals the immune system can partially control the parasite, such that a proportion of infected individuals remain microfilaria-negative, despite the presence of adult worms. Therefore mechanisms must exist that are able to combat microfilaraemia. Identifying such mechanisms would help to design vaccines against disease transmitting microfilarial stages. Using the Litomosoides sigmodontis murine model of filariasis research we show a successful immunization against the blood-circulating larval stage that is responsible for arthropod-dependent transmission of the disease. Reduced microfilaraemia was associated with impairment of worm embryogenesis, with systemic and local microfilarial-specific host IgG and with IFN-γ secretion by host cells at the site of infection. These results raise hope for developing a microfilariae-based vaccine, being a pivotal step towards eradicating filariasis

Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

<p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p

In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP-PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention

HNF1B Genetic Testing In a Turkish Cypriot Population with a High Incidence of Familial Kidney Disease

This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published

Impact of the use of cryobank samples in a selected cattle breed: a simulation study

<p>Abstract</p> <p>Background</p> <p>High selection pressure on domestic cattle has led to an undesirable increase in inbreeding, as well as to the deterioration of some functional traits which are indirectly selected. Semen stored in a cryobank may be a useful way to redirect selection or limit the loss of genetic diversity in a selected breed. The purpose of this study was to analyse the efficiency of current cryobank sampling methods, by investigating the benefits of using cryopreserved semen in a selection scheme several generations after the semen was collected.</p> <p>Methods</p> <p>The theoretical impact of using cryopreserved semen in a selection scheme of a dairy cattle breed was investigated by simulating various scenarios involving two negatively correlated traits and a change in genetic variability of the breed.</p> <p>Results</p> <p>Our results indicate that using cryopreserved semen to redirect selection will have an impact on negatively selected traits only if it is combined with major changes in selection objectives or practices. If the purpose is to increase genetic diversity in the breed, it can be a viable option.</p> <p>Conclusions</p> <p>Using cryopreserved semen to redirect selection or to improve genetic diversity should be carried out with caution, by considering the pros and cons of prospective changes in genetic diversity and the value of the selected traits. However, the use of genomic information should lead to more interesting perspectives to choose which animals to store in a cryobank and to increase the value of cryobank collections for selected breeds.</p