A Publish-Subscribe Model of Genetic Networks

We present a simple model of genetic regulatory networks in which regulatory connections among genes are mediated by a limited number of signaling molecules. Each gene in our model produces (publishes) a single gene product, which regulates the expression of other genes by binding to regulatory regions that correspond (subscribe) to that product. We explore the consequences of this publish-subscribe model of regulation for the properties of single networks and for the evolution of populations of networks. Degree distributions of randomly constructed networks, particularly multimodal in-degree distributions, which depend on the length of the regulatory sequences and the number of possible gene products, differed from simpler Boolean NK models. In simulated evolution of populations of networks, single mutations in regulatory or coding regions resulted in multiple changes in regulatory connections among genes, or alternatively in neutral change that had no effect on phenotype. This resulted in remarkable evolvability in both number and length of attractors, leading to evolved networks far beyond the expectation of these measures based on random distributions. Surprisingly, this rapid evolution was not accompanied by changes in degree distribution; degree distribution in the evolved networks was not substantially different from that of randomly generated networks. The publish-subscribe model also allows exogenous gene products to create an environment, which may be noisy or stable, in which dynamic behavior occurs. In simulations, networks were able to evolve moderate levels of both mutational and environmental robustness

Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aβ1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure

Automated liquid-handling operations for robust, resilient, and efficient bio-based laboratory practices

Increase in the adoption of liquid handling devices (LHD) can facilitate experimental activities. Initially adopted by businesses and industry-based laboratories, the practice has also moved to academic environments, where a wide range of non-standard/non-typical experiments can be performed. Current protocols or laboratory analyses require researchers to transfer liquids for the purpose of dilution, mixing, or inoculation, among other operations. LHD can render laboratories more efficient by performing more experiments per unit of time, by making operations robust and resilient against external factors and unforeseen events such as the COVID-19 pandemic, and by remote operation. The present work reviews literature that reported the adoption and utilisation of LHD available in the market and presents examples of their practical use. Applications demonstrate the critical role of automation in research development and its ability to reduce human intervention in the experimental workflow. Ultimately, this work will provide guidance to academic researchers to determine which LHD can fulfil their needs and how to exploit their use in both conventional and non-conventional applications. Furthermore, the breadth of applications and the scarcity of academic institutions involved in research and development that utilise these devices highlights an important area of opportunity for shift in technology to maximize research outcomes

Bird taxonomic and functional responses to land abandonment in wood-pastures

Wood-pastures are socio-ecological systems covering vast areas in Europe. Although used for grazing and production of various forest goods, wood-pastures harbour a rich biodiversity and are usually considered as High Nature Value Farmlands. However, socio-economic pressures are driving the transformation of these valuable landscapes from multi-functional, heterogeneous habitats to homogeneous areas through either intensification or land abandonment. We investigated how changes in management intensity influence the taxonomic diversity, functional diversity and functional composition of birds in these landscapes using generalized linear models. In contrast to taxonomic diversity, functional diversity decreased significantly towards shrub-dominated and less heterogeneous areas related to the abandonment of grazing and/or understory management practices. Grassland and generalist species, and associated guilds such as granivores, ground-nesters and ground-foragers are almost absent less managed areas. On the other hand, shrub-dominated areas favour forest species, particularly understory/canopy foragers and arboreal nesters, although the forest guild is still well-represented in actively managed, heterogeneous areas. Our results indicate the abandonment of wood-pasture management affects the prevalence of grassland and generalist species, leading to functional diversity loss and potentially reduced ecosystem functioning. We suggest non-intensive, active management is needed to maintain habitat heterogeneity and canopy openness, enhancing trait diversity in wood-pastures.Peer reviewe

ANALYSIS OF SHORT TRACK SPEED SKATERS COURAGE LEVELS FROM DIFFERENT VARIABLES

The object of this work is to analyze the courage levels of short track speed skaters from different variables. The study has been carried out on a total of 20 individuals, including 6 women and 14 men, who performed as short track speed skaters in Erzurum province of Turkey in 2017. DBA courage scale developed by (Imamoğlu, 1998) has been applied to skaters in the study9. SPSS 21 package program has been used for the analysis of the data. In the analysis of the data, frequency distribution for the demographic characteristics, T test to examine the relationship between two independent variables and courage level and ANOVA Variance analysis tests have been used to examine the relationship between more than two variables and courage level. The difference between the variables has been interpreted based on p 0.05 relevance level. According to the findings, it is determined that there is a significant difference between the level of courage of the athletes and being a national athlete. It is also determined that there is no significant difference between gender, education level, age, type of school they attended, educational background of mother and father and mother and father’s occupations. It is observed that, courage levels of national athletes are higher than that of non-national athletes. It is proposed that, it is important to determine the variables that will positively influence the level of courage for the athletes to be successful in sports and daily life.  Article visualizations

Computational inference of a genomic pluripotency signature in human and mouse stem cells

Distribution of distance to TSS for selected features (A) human and (B) mouse. (PDF 376 kb

Effects of Delayed Finishing/Polishing on Surface Roughness, Hardness and Gloss of Tooth-Coloured Restorative Materials

Objectives: The aim of this study was to investigate the effect of delayed finishing/polishing on the surface roughness, hardness and gloss of tooth-coloured restorative materials. Methods: Four different tooth-coloured restoratives: a flowable resin composite- Tetric Flow, a hybrid resin composite- Venus, a nanohybrid resin composite- Grandio, and a polyacid modified resin composite- Dyract Extra were used. 30 specimens were made for each material and randomly assigned into three groups. The first group was finished/polished immediately and the second group was finished/polished after 24 hours. The remaining 10 specimens served as control. The surface roughness of each sample was recorded using a laser profilometer. Gloss measurements were performed using a small-area glossmeter. Vickers microhardness measurements were performed from three locations on each specimen surface under 100g load and 10s dwell time. Data for surface roughness and hardness were analyzed by Kruskal Wallis test and data for gloss were subjected to one-way ANOVA and Tukey test (P .05). The lowest hardness values were found under Mylar strip. Delayed finishing/polishing significantly increased the hardness of all materials. Conclusions: The effect of delayed finishing/polishing on surface roughness, gloss and hardness appears to be material dependent.PubMe

Nature of the spin resonance mode in CeCoIn5_5

Spin-fluctuation-mediated unconventional superconductivity can emerge at the border of magnetism, featuring a superconducting order parameter that changes sign in momentum space. Detection of such a sign-change is experimentally challenging, since most probes are not phase-sensitive. The observation of a spin resonance mode (SRM) from inelastic neutron scattering is often seen as strong phase-sensitive evidence for a sign-changing superconducting order parameter, by assuming the SRM is a spin-excitonic bound state. Here, we show that for the heavy fermion superconductor CeCoIn$_5$, its SRM defies expectations for a spin-excitonic bound state, and is not a manifestation of sign-changing superconductivity. Instead, the SRM in CeCoIn$_5$ likely arises from a reduction of damping to a magnon-like mode in the superconducting state, due to its proximity to magnetic quantum criticality. Our findings emphasize the need for more stringent tests of whether SRMs are spin-excitonic, when using their presence to evidence sign-changing superconductivity.Comment: accepted for publication in Communications Physic

Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones

Background: In inherited retinal disorders such as retinitis pigmentosa (RP), rod photoreceptor-specific mutations cause primary rod degeneration that is followed by secondary cone death and loss of high-acuity vision. Mechanistic studies of retinal degeneration are challenging because of retinal heterogeneity. Moreover, the detection of early cone responses to rod death is especially difficult due to the paucity of cones in the retina. To resolve heterogeneity in the degenerating retina and investigate events in both types of photoreceptors during primary rod degeneration, we utilized droplet-based single-cell RNA sequencing in an RP mouse model, rd10. Results: Using trajectory analysis, we defined two consecutive phases of rod degeneration at P21, characterized by the early transient upregulation of Egr1 and the later induction of Cebpd. EGR1 was the transcription factor most significantly associated with the promoters of differentially regulated genes in Egr1-positive rods in silico. Silencing Egr1 affected the expression levels of two of these genes in vitro. Degenerating rods exhibited changes associated with metabolism, neuroprotection, and modifications to synapses and microtubules. Egr1 was also the most strongly upregulated transcript in cones. Its upregulation in cones accompanied potential early respiratory dysfunction and changes in signaling pathways. The expression pattern of EGR1 in the retina was dynamic during degeneration, with a transient increase of EGR1 immunoreactivity in both rods and cones during the early stages of their degenerative processes. Conclusion: Our results identify early and late changes in degenerating rd10 rod photoreceptors and reveal early responses to rod degeneration in cones not expressing the disease-causing mutation, pointing to mechanisms relevant for secondary cone degeneration. In addition, our data implicate EGR1 as a potential key regulator of early degenerative events in rods and cones, providing a potential broad target for modulating photoreceptor degeneration