Yielding and irreversible deformation below the microscale: Surface effects and non-mean-field plastic avalanches

Nanoindentation techniques recently developed to measure the mechanical response of crystals under external loading conditions reveal new phenomena upon decreasing sample size below the microscale. At small length scales, material resistance to irreversible deformation depends on sample morphology. Here we study the mechanisms of yield and plastic flow in inherently small crystals under uniaxial compression. Discrete structural rearrangements emerge as series of abrupt discontinuities in stress-strain curves. We obtain the theoretical dependence of the yield stress on system size and geometry and elucidate the statistical properties of plastic deformation at such scales. Our results show that the absence of dislocation storage leads to crucial effects on the statistics of plastic events, ultimately affecting the universal scaling behavior observed at larger scales.Comment: Supporting Videos available at http://dx.plos.org/10.1371/journal.pone.002041

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

AMPK:a nutrient and energy sensor that maintains energy homeostasis

AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability

Diet during pregnancy and infancy, and risk of allergic or autoimmune disease: a systematic review and meta-analysis

Background: There is uncertainty about the influence of diet during pregnancy and infancy on a child’s immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease. Methods and findings: Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease. We identified 260 original studies (964,143 participants) of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies (542,672 participants) of other maternal or infant dietary exposures, including 80 trials of maternal (n = 26), infant (n = 32), or combined (n = 22) interventions. Risk of bias was high in 125 (48%) milk feeding studies and 44 (25%) studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68–0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20–64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53–0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10–47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow’s milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures—including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake—influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy. Conclusions: Our findings support a relationship between maternal diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitisation to food, respectively

Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior

Two genome duplications early in the vertebrate lineage expanded gene families, including GluN2 subunits of the NMDA receptor. Diversification between the four mammalian GluN2 proteins occurred primarily at their intracellular C−terminal domains (CTDs). To identify shared ancestral functions and diversified subunit−specific functions, we exchanged the exons encoding the GluN2A (also known as Grin2a) and GluN2B (also known as Grin2b) CTDs in two knock−in mice and analyzed the mice's biochemistry, synaptic physiology, and multiple learned and innate behaviors. The eight behaviors were genetically separated into four groups, including one group comprising three types of learning linked to conserved GluN2A/B regions. In contrast, the remaining five behaviors exhibited subunit−specific regulation. GluN2A/B CTD diversification conferred differential binding to cytoplasmic MAGUK proteins and differential forms of long−term potentiation. These data indicate that vertebrate behavior and synaptic signaling acquired increased complexity from the duplication and diversification of ancestral GluN2 gene

Cast aluminium single crystals cross the threshold from bulk to size-dependent stochastic plasticity

Metals are known to exhibit mechanical behaviour at the nanoscale different to bulk samples. This transition typically initiates at the micrometre scale, yet existing techniques to produce micrometre-sized samples often introduce artefacts that can influence deformation mechanisms. Here, we demonstrate the casting of micrometre-scale aluminium single-crystal wires by infiltration of a salt mould. Samples have millimetre lengths, smooth surfaces, a range of crystallographic orientations, and a diameter D as small as 6 μm. The wires deform in bursts, at a stress that increases with decreasing D. Bursts greater than 200 nm account for roughly 50% of wire deformation and have exponentially distributed intensities. Dislocation dynamics simulations show that single-arm sources that produce large displacement bursts halted by stochastic cross-slip and lock formation explain microcast wire behaviour. This microcasting technique may be extended to several other metals or alloys and offers the possibility of exploring mechanical behaviour spanning the micrometre scale

Neurobiology of rodent self-grooming and its value for translational neuroscience

Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders-including models of autism spectrum disorder and obsessive compulsive disorder-that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.National Institutes of Health (U.S.) (Grant NS025529)National Institutes of Health (U.S.) (Grant HD028341)National Institutes of Health (U.S.) (Grant MH060379

Highly variable use of diagnostic methods for sexually transmitted infections-results of a nationwide survey, Germany 2005

Background: Sexual transmitted infections (STIs) have increased in Germany and other countries in Europe since the mid-nineties. To obtain a better picture of diagnostic methods used in STI testing institutions in Germany, we performed a nationwide survey amongst STI specialists in order to evaluate the quality of STI reports and provide recommendations to harmonize and possibly improve STI diagnostics in Germany. Methods: We asked sentinel physicians and randomly chosen gynaecologists, urologists and dermato-venerologists, about the diagnostic methods used in 2005 to diagnose HIV, chlamydia (CT), gonorrhoea (GO) and syphilis (SY) in a national cross-sectional survey in order to recognize potential problems and provide recommendations. Results: A total of 739/2287 (32%) physicians participated. Of all participants, 80% offered tests for HIV, 84% for CT, 83% for GO and 83% for SY. Of all participants who performed HIV testing, 90% requested an antibody test, 3% a rapid test and 1% a nucleic acid amplification test (NAAT). For CT testing, NAAT was used in 33% and rapid tests in 34% of participants. GO resistance testing was performed by 31% of the participants. SY testing was performed in 98% by serology. Conclusions: Diagnostic methods for STI vary highly among the participants. Diagnostic guidelines should be reviewed and harmonised to ensure consistent use of the optimal STI diagnostic methods