75 research outputs found

    Approximating Mexican highways with slime mould

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    Plasmodium of Physarum polycephalum is a single cell visible by unaided eye. During its foraging behavior the cell spans spatially distributed sources of nutrients with a protoplasmic network. Geometrical structure of the protoplasmic networks allows the plasmodium to optimize transport of nutrients between remote parts of its body. Assuming major Mexican cities are sources of nutrients how much structure of Physarum protoplasmic network correspond to structure of Mexican Federal highway network? To find an answer undertook a series of laboratory experiments with living Physarum polycephalum. We represent geographical locations of major cities by oat flakes, place a piece of plasmodium in Mexico city area, record the plasmodium's foraging behavior and extract topology of nutrient transport networks. Results of our experiments show that the protoplasmic network formed by Physarum is isomorphic, subject to limitations imposed, to a network of principle highways. Ideas and results of the paper may contribute towards future developments in bio-inspired road planning

    Functional redundancy between Apc and Apc2 regulates tissue homeostasis and prevents tumorigenesis in murine mammary epithelium

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    Aberrant Wnt signaling within breast cancer is associated with poor prognosis, but regulation of this pathway in breast tissue remains poorly understood and the consequences of immediate or long-term dysregulation remain elusive. The exact contribution of the Wnt-regulating proteins adenomatous polyposis coli (APC) and APC2 in the pathogenesis of human breast cancer are ill-defined, but our analysis of publically available array data sets indicates that tumors with concomitant low expression of both proteins occurs more frequently in the ‘triple negative’ phenotype, which is a subtype of breast cancer with particularly poor prognosis. We have used mouse transgenics to delete Apc and/or Apc2 from mouse mammary epithelium to elucidate the significance of these proteins in mammary homeostasis and delineate their influences on Wnt signaling and tumorigenesis. Loss of either protein alone failed to affect Wnt signaling levels or tissue homeostasis. Strikingly, concomitant loss led to local disruption of β-catenin status, disruption in epithelial integrity, cohesion and polarity, increased cell division and a distinctive form of ductal hyperplasia with ‘squamoid’ ghost cell nodules in young animals. Upon aging, the development of Wnt activated mammary carcinomas with squamous differentiation was accompanied by a significantly reduced survival. This novel Wnt-driven mammary tumor model highlights the importance of functional redundancies existing between the Apc proteins both in normal homeostasis and in tumorigenesis

    Advances in the role of sacral nerve neuromodulation in lower urinary tract symptoms

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    Sacral neuromodulation has been developed to treat chronic lower urinary tract symptoms, resistant to classical conservative therapy. The suspected mechanisms of action include afferent stimulation of the central nervous system and modulation of activity at the level of the brain. Typical neuromodulation is indicated both in overactivity and in underactivity of the lower urinary tract. In the majority of patients, a unilateral electrode in a sacral foramen and connected to a pulse generator is sufficient to achieve significant clinical results also on long term. In recent years, other urological indications have been explored

    Global urban environmental change drives adaptation in white clover.

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    Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

    Potent amyloidogenicity and pathogenicity of Aβ43.

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    The amyloid-β peptide Aβ42 is known to be a primary amyloidogenic and pathogenic agent in Alzheimer\u27s disease. However, the role of Aβ43, which is found just as frequently in the brains of affected individuals, remains unresolved. We generated knock-in mice containing a pathogenic presenilin-1 R278I mutation that causes overproduction of Aβ43. Homozygosity was embryonic lethal, indicating that the mutation involves a loss of function. Crossing amyloid precursor protein transgenic mice with heterozygous mutant mice resulted in elevated Aβ43, impairment of short-term memory and acceleration of amyloid-β pathology, which accompanied pronounced accumulation of Aβ43 in plaque cores similar in biochemical composition to those observed in the brains of affected individuals. Consistently, Aβ43 showed a higher propensity to aggregate and was more neurotoxic than Aβ42. Other pathogenic presenilin mutations also caused overproduction of Aβ43 in a manner correlating with Aβ42 and with the age of disease onset. These findings indicate that Aβ43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo

    Hidden resilience and adaptive dynamics of the global online hate ecology

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    Online hate and extremist narratives have been linked to abhorrent real-world events, including a current surge in hate crimes and an alarming increase in youth suicides that result from social media vitriol ; inciting mass shootings such as the 2019 attack in Christchurch, stabbings and bombings ; recruitment of extremists , including entrapment and sex-trafficking of girls as fighter brides ; threats against public figures, including the 2019 verbal attack against an anti-Brexit politician, and hybrid (racist-anti-women-anti-immigrant) hate threats against a US member of the British royal family ; and renewed anti-western hate in the 2019 post-ISIS landscape associated with support for Osama Bin Laden's son and Al Qaeda. Social media platforms seem to be losing the battle against online hate and urgently need new insights. Here we show that the key to understanding the resilience of online hate lies in its global network-of-network dynamics. Interconnected hate clusters form global 'hate highways' that-assisted by collective online adaptations-cross social media platforms, sometimes using 'back doors' even after being banned, as well as jumping between countries, continents and languages. Our mathematical model predicts that policing within a single platform (such as Facebook) can make matters worse, and will eventually generate global 'dark pools' in which online hate will flourish. We observe the current hate network rapidly rewiring and self-repairing at the micro level when attacked, in a way that mimics the formation of covalent bonds in chemistry. This understanding enables us to propose a policy matrix that can help to defeat online hate, classified by the preferred (or legally allowed) granularity of the intervention and top-down versus bottom-up nature. We provide quantitative assessments for the effects of each intervention. This policy matrix also offers a tool for tackling a broader class of illicit online behaviours such as financial fraud
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