Aims/hypothesis
MicroRNAs regulate a broad range of biological mechanisms. To investigate the relationship between microRNA expression and type 2 diabetes, we compared global microRNA expression in ...insulin target tissues from three inbred rat strains that differ in diabetes susceptibility.
Methods
Using microarrays, we measured the expression of 283 microRNAs in adipose, liver and muscle tissue from hyperglycaemic (Goto–Kakizaki), intermediate glycaemic (Wistar Kyoto) and normoglycaemic (Brown Norway) rats (
n
= 5 for each strain). Expression was compared across strains and validated using quantitative RT-PCR. Furthermore, microRNA expression variation in adipose tissue was investigated in 3T3-L1 adipocytes exposed to hyperglycaemic conditions.
Results
We found 29 significantly differentiated microRNAs (
p
adjusted
< 0.05): nine in adipose tissue, 18 in liver and two in muscle. Of these, five microRNAs had expression patterns that correlated with the strain-specific glycaemic phenotype. MiR-222 (
p
adjusted
= 0.0005) and miR-27a (
p
adjusted
= 0.006) were upregulated in adipose tissue; miR-195 (
p
adjusted
= 0.006) and miR-103 (
p
adjusted
= 0.04) were upregulated in liver; and miR-10b (
p
adjusted
= 0.004) was downregulated in muscle. Exposure of 3T3-L1 adipocytes to increased glucose concentration upregulated the expression of miR-222 (
p
= 0.008), miR-27a (
p
= 0.02) and the previously reported miR-29a (
p
= 0.02). Predicted target genes of these differentially expressed microRNAs are involved in pathways relevant to type 2 diabetes.
Conclusion
The expression patterns of miR-222, miR-27a, miR-195, miR-103 and miR-10b varied with hyperglycaemia, suggesting a role for these microRNAs in the pathophysiology of type 2 diabetes, as modelled by the Gyoto–Kakizaki rat. We observed similar patterns of expression of miR-222, miR-27a and miR-29a in adipocytes as a response to increased glucose levels, which supports our hypothesis that altered expression of microRNAs accompanies primary events related to the pathogenesis of type 2 diabetes.
Although some ecosystem responses to climate change are gradual, many ecosystems react in highly nonlinear ways. They show little response until a threshold or tipping point is reached where even a ...small perturbation may trigger collapse into a state from which recovery is difficult (1). Increasing evidence shows that the critical climate level for such collapse may be altered by conditions that can be managed locally. These synergies between local stressors and climate change provide potential opportunities for proactive management. Although their clarity and scale make such local approaches more conducive to action than global greenhouse gas management, crises in iconic UNESCO World Heritage sites illustrate that such stewardship is at risk of failing.
November 11, 2016/65(44);1234–1237.
What is already known about this topic?
Candida auris is an emerging pathogenic fungus that has been reported from at least a dozen countries on four continents ...during 2009–2015. The organism is difficult to identify using traditional biochemical methods, some isolates have been found to be resistant to all three major classes of antifungal medications, and C. auris has caused health care–associated outbreaks.
What is added by this report?
This is the first description of C. auris cases in the United States. C. auris appears to have emerged in the United States only in the last few years, and U.S. isolates are related to isolates from South America and South Asia. Evidence from U.S. case investigations suggests likely transmission of the organism occurred in health care settings.
What are the implications for public health practice?
It is important that U.S. laboratories accurately identify C. auris and for health care facilities to implement recommended infection control practices to prevent the spread of C. auris. Local and state health departments and CDC should be notified of possible cases of C. auris and of isolates of C. haemulonii and Candida spp. that cannot be identified after routine testing.
This report details the first U.S. cases of a new fungal infection seen primarily in immunocompromised hosts, including stem cell transplant recipients.
•Emotion and motivation are crucial psychological processes.•Typical neural perspectives focus on emotion or motivation not both.•New views of integration emphasize merging functionality and brain ...basis of emotion and motivation.•Key brain regions and circuits of functional integration are explored.•A broad analysis including cognitive, social and cultural influences on these merged or segregated functions is addressed.
As a part of a larger Affectome Project (http://neuroqualia.org/background.php) with an overarching goal of mapping and redefining biological substrates of feelings and emotions, we explored the neural underpinnings for the functions of motivation and emotion. Historically emotion and motivation have been placed into distinct neural circuits and examined separately. We propose a novel view of significant neural convergence of emotion and motivation, in contrast to conventional neural-based frameworks emphasizing segregation. Evidence from diverse research areas in emotion and motivation was reviewed, pinpointing key neural regions of overlap. The findings support important neural sharing between emotion and motivation, suggesting that these two functions are tightly intertwined with one another in the brain. Neural overlap does not necessarily imply continuous functional overlap. Even if identical brain regions/systems are activated for motivation and emotion, this activation may involve distinct and unique patterns of connection and information flow as the network shifts functionality. This review highlights the crucial importance of further research to explicate the patterns and modes of responding of these overlapping systems.
Display omitted
The failure of endovascular treatments of peripheral arterial disease represents a critical clinical issue. Specialized data are required to tailor such procedures to account for the ...mechanical response of the diseased femoral arterial tissue to medical device deployment. The purpose of this study is to characterize the mechanical response of atherosclerotic femoral arterial tissue to large deformation, the conditions typical of angioplasty and stenting, and also to determine the mechanically induced failure properties and to relate this behaviour to biological content and structural composition using uniaxial testing, Fourier transform infrared spectroscopy and scanning electron microscopy. Mechanical and biological characterization of 20 plaque samples obtained from femoral endarterectomy identified three distinct classifications. “Lightly calcified” samples display linear mechanical responses and fail at relatively high stretch. “Moderately calcified” samples undergo an increase in stiffness and ultimate strength coupled with a decrease in ductility. Structural characterization reveals calcified nodules within this group that may be acting to reinforce the tissue matrix, thus increasing the stiffness and ultimate strength. “Heavily calcified” samples account for the majority of samples tested and exhibit significantly reduced ultimate strength and ductility compared to the preceding groups. Structural characterization of this group reveals large areas of calcified tissue dominating the failure cross-sections of the samples. The frequency and structural dominance of these features solely within this group offers an explanation as to the reduced ultimate strength and ductility and highlights the need for modern peripheral endovascular devices to account for this behaviour during novel medical device design.
The extent to which evolution is deterministic is a key question in biology,1,2,3,4,5,6,7,8,9 with intensive debate on how adaptation6,10,11,12,13 and constraints14,15,16 might canalize solutions to ...ecological challenges.4,5,6 Alternatively, unique adaptations1,9,17 and phylogenetic contingency1,3,18 may render evolution fundamentally unpredictable.3 Information from the fossil record is critical to this debate,1,2,11 but performance data for extinct taxa are limited.7 This knowledge gap is significant, as general morphology may be a poor predictor of biomechanical performance.17,19,20 High-fiber herbivory originated multiple times within ornithischian dinosaurs,21 making them an ideal clade for investigating evolutionary responses to similar ecological pressures.22 However, previous biomechanical modeling studies on ornithischian crania17,23,24,25 have not compared early-diverging taxa spanning independent acquisitions of herbivory. Here, we perform finite-element analysis on the skull of five early-diverging members of the major ornithischian clades to characterize morphofunctional pathways to herbivory. Results reveal limited functional convergence among ornithischian clades, with each instead achieving comparable performance, in terms of reconstructed patterns and magnitudes of functionally induced stress, through different adaptations of the feeding apparatus. Thyreophorans compensated for plesiomorphic low performance through increased absolute size, heterodontosaurids expanded jaw adductor muscle volume, ornithopods increased jaw system efficiency, and ceratopsians combined these approaches. These distinct solutions to the challenges of herbivory within Ornithischia underpinned the success of this diverse clade. Furthermore, the resolution of multiple solutions to equivalent problems within a single clade through macroevolutionary time demonstrates that phenotypic evolution is not necessarily predictable, instead arising from the interplay of adaptation, innovation, contingency, and constraints.1,2,3,7,8,9,18
•The performance of the feeding apparatus is compared among key ornithischian taxa•Diverse morphofunctional patterns are observed among early members of major clades•These differences reveal distinct solutions to herbivory in each of these clades•This non-convergence demonstrates that evolution is not necessarily predictable
Button et al. perform biomechanical modeling of the skull of early members of herbivorous ornithischian dinosaur clades. Their results demonstrate performance differences and distinct solutions to herbivory among taxa. These non-convergent responses to common ecological pressures highlight the potential unpredictability of morphological evolution.
Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in ...human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers.
Human carotid plaque segments, obtained from endarterectomy, were incubated in 111InIn-DOTA-butylamino-NorBIRT (111InIn-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology.
On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype.
Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit.
Display omitted
The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral ...vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake.
This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness.
Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330–3035 for location and 140–4560J/m2 for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, p<0.001). SEM reveals the presence of large calcified regions in the toughest sections that are absent from the least tough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a preoperative tool for predicting the fracture response of a target lesion to CBA (R2=0.885, p<0.001).
This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment.
Carotid artery stenting (CAS) in calcified arteries carries a higher peri-operative risk. This study investigates the relationship between the stretching limits of carotid plaque samples and ...calcification in order to determine a stretch tolerance criterion for endovascular intervention.
Seventeen carotid plaque samples were acquired from standard endarterectomy procedures. The maximum stretch capability of the global plaque was determined by circumferentially extending the tissue to complete failure. Quantitative assessment of calcification was performed using high resolution computed tomography, including measures of percent calcification volume fraction (%CVF) and calcification configuration. Maximum stretch properties were then related to calcification measures in order to evaluate the predictive power of calcification for determining plaque stretching limits.
A strong negative correlation was found between %CVF and stretch ratio with respect to specific calcification configuration types. All plaques with < 70% stenosis superseded the minimum required stretch threshold. Severe stenosis (> 70%) warrants a stretch of at least 2.33 during revascularisation and only plaques containing concentric calcifications with < 20% CVF successfully reached this minimum required stretch threshold.
The addition of calcification measures to the stenosis classification may help in guiding endovascular intervention techniques to achieve a balance between an acceptable residual patency level while avoiding plaque rupture in calcified carotid plaques.
Display omitted
To date, a great deal of attention has focused on characterizing the performance of quantum error correcting codes via their thresholds, the maximum correctable physical error rate for a given noise ...model and decoding strategy. Practical quantum computers will necessarily operate below these thresholds meaning that other performance indicators become important. In this work we consider the scaling of the logical error rate of the toric code and demonstrate how, in turn, this may be used to calculate a key performance indicator. We use a perfect matching decoding algorithm to find the scaling of the logical error rate and find two distinct operating regimes. The first regime admits a universal scaling analysis due to a mapping to a statistical physics model. The second regime characterizes the behaviour in the limit of small physical error rate and can be understood by counting the error configurations leading to the failure of the decoder. We present a conjecture for the ranges of validity of these two regimes and use them to quantify the overhead-the total number of physical qubits required to perform error correction.
PDF
