282 research outputs found

    Molecular motors robustly drive active gels to a critically connected state

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    Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

    Splitting or lumping? A conservation dilemma exemplified by the critically endangered Dama Gazelle (Nanger dama)

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    Managers of threatened species often face the dilemma of whether to keep populations separate to conserve local adaptations and minimize the risk of outbreeding, or whether to manage populations jointly to reduce loss of genetic diversity and minimise inbreeding. In this study we examine genetic relatedness and diversity in three of the five last remaining wild populations of dama gazelle and a number of captive populations, using mtDNA control region and cytochrome b data. Despite the sampled populations belonging to the three putative subspecies, which are delineated according to phenotypes and geographical location, we find limited evidence for phylogeographical structure within the data and no genetic support for the putative subspecies. In the light of these data we discuss the relevance of inbreeding depression, outbreeding depression, adaptive variation, genetic drift, and phenotypic variation to the conservation of the dama gazelle and make some recommendations for its future conservation management. The genetic data suggest that the best conservation approach is to view the dama gazelle as a single species without subspecific divisions

    Experiences of the Flint Water Crisis Among Reproductive-Age Michigan Women in Communities Outside of Flint: Differences by Race and Ethnicity

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    We sought to understand how women in Michigan communities outside of Flint experienced the Flint water crisis, an avoidable public health disaster widely attributed to structural racism. Using survey data from 950 Michigan women aged 18–45 from communities outside of Flint, we examined racial and ethnic differences in personal connections to Flint, perceived knowledge about the water crisis, and beliefs about the role of anti-Black racism in the water crisis factors that could contribute to poor health via increased psychological stress. We found that White (OR = 0.32; 95% CI: 0.22, 0.46) and Hispanic (OR = 0.21; 95% CI: 0.09, 0.49) women had lower odds than Black women of having family or friends who lived in Flint during the water crisis. Compared to Black women, White women were less likely to be moderately or very knowledgeable about the water crisis (OR = 0.58; 95% CI: 0.41, 0.80). White women (OR = 0.26; 95% CI: 0.18, 0.37), Hispanic women (OR = 0.38; 95% CI: 0.21, 0.68), and women of other races (OR = 0.28; 95% CI: 0.15, 0.54) were less likely than Black women to agree that the water crisis happened because government officials wanted to hurt Flint residents. Among those who agreed, White women (OR = 0.47; 95% CI: 0.30, 0.74) and women of other races (OR = 0.33; 95% CI: 0.12, 0.90) were less likely than Black women to agree that government officials wanted to hurt people in Flint because most residents are Black. We conclude that the Flint water crisis was a racialized stressor, with potential implications for the health of reproductive-age Black women

    Experiences of acceptance and commitment therapy for people living with motor neuron disease (MND): a qualitative study from the perspective of people living with MND and therapists

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    \ua9 The Author(s), 2024. Published by Cambridge University Press on behalf of British Association for Behavioural and Cognitive Psychotherapies.Background: Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND\u27s experiences of receiving adapted ACT, tailored to their specific needs, and therapists\u27 experiences of delivering it. Method: Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis. Results: Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy. Conclusions: Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND. Key learning aims (1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition. (2) To understand the facilitators of and barriers to ACT for plwMND. (3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population

    Is Emotion Recognition Impaired in Individuals with Autism Spectrum Disorders?

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    Researchers have argued that individuals with autism spectrum disorders (ASDs) use an effortful “systematizing” process to recognize emotion expressions, whereas typically developing (TD) individuals use a more holistic process. If this is the case, individuals with ASDs should show slower and less efficient emotion recognition, particularly for socially complex emotions. We tested this account by assessing the speed and accuracy of emotion recognition while limiting exposure time and response window. Children and adolescents with ASDs showed quick and accurate recognition for most emotions, including pride, a socially complex emotion, and no differences emerged between ASD and TD groups. Furthermore, both groups trended toward higher accuracy when responding quickly, even though systematizing should promote a speed-accuracy trade-off for individuals with ASDs

    A probability-conserving cross-section biasing mechanism for variance reduction in Monte Carlo particle transport calculations

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    In Monte Carlo particle transport codes, it is often important to adjust reaction cross sections to reduce the variance of calculations of relatively rare events, in a technique known as non-analogous Monte Carlo. We present the theory and sample code for a Geant4 process which allows the cross section of a G4VDiscreteProcess to be scaled, while adjusting track weights so as to mitigate the effects of altered primary beam depletion induced by the cross section change. This makes it possible to increase the cross section of nuclear reactions by factors exceeding 10^4 (in appropriate cases), without distorting the results of energy deposition calculations or coincidence rates. The procedure is also valid for bias factors less than unity, which is useful, for example, in problems that involve computation of particle penetration deep into a target, such as occurs in atmospheric showers or in shielding

    Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA

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    Human UNG2 is a multifunctional glycosylase that removes uracil near replication forks and in non-replicating DNA, and is important for affinity maturation of antibodies in B cells. How these diverse functions are regulated remains obscure. Here, we report three new phosphoforms of the non-catalytic domain that confer distinct functional properties to UNG2. These are apparently generated by cyclin-dependent kinases through stepwise phosphorylation of S23, T60 and S64 in the cell cycle. Phosphorylation of S23 in late G1/early S confers increased association with replication protein A (RPA) and replicating chromatin and markedly increases the catalytic turnover of UNG2. Conversely, progressive phosphorylation of T60 and S64 throughout S phase mediates reduced binding to RPA and flag UNG2 for breakdown in G2 by forming a cyclin E/c-myc-like phosphodegron. The enhanced catalytic turnover of UNG2 p-S23 likely optimises the protein to excise uracil along with rapidly moving replication forks. Our findings may aid further studies of how UNG2 initiates mutagenic rather than repair processing of activation-induced deaminase-generated uracil at Ig loci in B cells

    Signaling Role of Fructose Mediated by FINS1/FBP in Arabidopsis thaliana

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    Sugars are evolutionarily conserved signaling molecules that regulate the growth and development of both unicellular and multicellular organisms. As sugar-producing photosynthetic organisms, plants utilize glucose as one of their major signaling molecules. However, the details of other sugar signaling molecules and their regulatory factors have remained elusive, due to the complexity of the metabolite and hormone interactions that control physiological and developmental programs in plants. We combined information from a gain-of-function cell-based screen and a loss-of-function reverse-genetic analysis to demonstrate that fructose acts as a signaling molecule in Arabidopsis thaliana. Fructose signaling induced seedling developmental arrest and interacted with plant stress hormone signaling in a manner similar to that of glucose. For fructose signaling responses, the plant glucose sensor HEXOKINASE1 (HXK1) was dispensable, while FRUCTOSE INSENSITIVE1 (FINS1), a putative FRUCTOSE-1,6-BISPHOSPHATASE, played a crucial role. Interestingly, FINS1 function in fructose signaling appeared to be independent of its catalytic activity in sugar metabolism. Genetic analysis further indicated that FINS1–dependent fructose signaling may act downstream of the abscisic acid pathway, in spite of the fact that HXK1–dependent glucose signaling works upstream of hormone synthesis. Our findings revealed that multiple layers of controls by fructose, glucose, and abscisic acid finely tune the plant autotrophic transition and modulate early seedling establishment after seed germination
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