Miracle-dz/UniFAR-FTUs huggingface dataset:
FTO Genotype and Type 2 Diabetes Mellitus: Spatial Analysis and Meta-Analysis of 62 Case-Control Studies from Different Regions

Type 2 diabetes mellitus (T2DM) is a global health problem that results from the interaction of environmental factors with genetic variants. Although a number of studies have suggested that genetic polymorphisms in the fat mass and obesity-associated (FTO) gene are associated with T2DM risk, the results have been inconsistent. To investigate whether FTO polymorphisms associate with T2DM risk and whether this association is region-related, we performed this spatial analysis and meta-analysis. More than 60,000 T2DM patients and 90,000 controls from 62 case-control studies were included in this study. Odds ratios (ORs), 95% confidence intervals (CIs) and Moran’s I statistic were used to estimate the association between FTO rs9939609, rs8050136, rs1421085, and rs17817499, and T2DM risk in different regions. rs9939609 (OR = 1.15, 95% CI 1.11–1.19) and rs8050136 (OR = 1.14, 95% CI 1.10–1.18) conferred a predisposition to T2DM. After adjustment for body mass index (BMI), the association remained statistically significant for rs9939609 (OR = 1.11, 95% CI 1.05–1.17) and rs8050136 (OR = 1.08, 95% CI 1.03–1.12). In the subgroup analysis of rs9939609 and rs8050136, similar results were observed in East Asia, while no association was found in North America. In South Asia, an association for rs9939609 was revealed but not for rs8050136. In addition, no relationship was found with rs1421085 or rs17817499 regardless of adjustment for BMI. Moran’s I statistic showed that significant positive spatial autocorrelations existed in rs9939609 and rs8050136. Studies on rs9939609 and rs8050136 focused on East Asia and South Asia, whereas studies on rs1421085 and rs17817499 were distributed in North America and North Africa. Our data suggest that the associations between FTO rs9939609, rs8050136 and T2DM are region-related, and the two single-nucleotide polymorphisms contribute to an increased risk of T2DM. Future studies should investigate this issue in more regions.
A comparative study of three finite element-based explicit numerical schemes for solving maxwell's equations

Three finite element-based explicit numerical algorithms, named the dual-field domain decomposition at the element level (DFDD-ELD), the discontinuous Galerkin time-domain method with upwind fluxes (DGTD-Upwind), and the discontinuous Galerkin time-domain method with central fluxes (DGTD-Central), are implemented and compared in terms of accuracy, efficiency, and higher-order convergence. All three algorithms can perform an efficient domain decomposition and avoid the inversion of a global system matrix, yet they differ from each other in terms of accuracy and efficiency.
Performance and Carcass Characteristics of Finishing Steers Fed Low-Fat and Normal-Fat Wet Distillers Grains

Wet distillers grains plus solubles (WDGS) varying in fat content (6.7 vs. 12.9 %) were fed at 35% of the diet DM to compare fat level from WDGS on cattle performance and carcass characteristics. Final BW, hot carcass weight, and ADG were increased for steers fed 12.9% fat WDGS compared to steers fed corn or 6.7% fat WDGS. Steers fed 6.7% fat WDGS or corn control diets had identical DMI, ADG, and F:G.
In Vivo Mechanistic Studies on the Metabolic Activation of 2-Phenylpropionic Acid in Rat

Two alternative metabolic pathways, acyl glucuronidation and acyl-CoA formation, are implicated in the generation of reactive acylating metabolites of carboxylic acids. Here, we describe studies that determine the relative importance of these two pathways in the metabolic activation of a model substrate, 2-phenylpropionic acid (2-PPA), in vivo in rats. Male Sprague-Dawley rats were pretreated with and without (−)-borneol (320 mg/kg i.p.), an inhibitor of acyl glucuronidation, or trimethylacetic acid (TMA, 500 mg/kg i.p.), an inhibitor of acyl-CoA formation, before receiving 2-PPA (racemic, 130 mg/kg). After administration of 2-PPA, livers were collected over a 2-h period and analyzed for 2-PPA acyl glucuronidation and 2-PPA-CoA formation by high-performance liquid chromatography. Covalent binding was measured by scintillation counting of washed liver protein precipitates. Results showed that pretreatment with TMA led to a 49% decrease in covalent binding of 2-PPA to liver proteins, when a 64% decrease in the exposure of 2-PPA-CoA was observed. Conversely, 95% inhibition of acyl glucuronidation by (−)-borneol, led to a 23% decrease in covalent binding to protein. These results suggest that metabolic activation by 2-PPA-CoA formation contributes to covalent adduct formation to protein in vivo to a greater extent than metabolic activation by acyl glucuronidation for this model substrate.
Small Animal X-ray Micro-CT with Zoom-in Imaging Capability

Most of micro-CTs are capable of micron-resolution imaging if a small sample is of interest. Recent micro-CT developments with a flat-panel detector make it possible to scan the whole body of a small animal as large as a medium sized rat. However, the spatial resolution in the whole body imaging should be sacrificed down to the order of 100 mum due to the limitation in the number of X-ray detector pixels and low signal-to-noise ratio. In this study, we introduce an X-ray zoom-in micro tomography system which has localized imaging capability, i.e., high resolution imaging of a local ROI inside a large subject, for small animal imaging studies. In zoom-in micro tomography, two projection data sets, one obtained with a full FOV scan and the other obtained with a limited FOV scan, are acquired with different magnification ratios. To obtain exact images of the ROI, the out-of-FOV projection data are calculated from the full FOV projection data, and then, the calculated projection data are augmented to the limited FOV projection data. The zoom-in micro tomography system consists of a micro focus X-ray source, a CMOS flat-panel detector, a rotating gantry and a parallel data processing system. We have used the zoom-in micro tomography system for in vivo femoral bone imaging in osteoporosis studies with SD rat models in which fine trabecular bone structure imaging is essential.
Long-term effects of manipulated natal brood size on metabolic rate in zebra finches

Long-term effects of developmental conditions on health, longevity and other fitness components in humans are drawing increasing attention. In evolutionary ecology, such effects are of similar importance because of their role in the trade-off between quantity and quality of offspring. The central role of energy consumption is well documented for some long-term health effects in humans (e.g. obesity), but little is known of the long-term effects of rearing conditions on energy requirements later in life. We manipulated the rearing conditions in zebra finches (Taeniopygia guttata) using brood size manipulation and cross-fostering. It has previously been shown in this species that being reared in a large brood has negative fitness consequences, and that such effects are stronger in daughters than in sons. We show that, independent of mass, standard metabolic rate of 1-year-old birds was higher when they had been reared in a large brood, and this is to our knowledge the first demonstration of such an effect. Furthermore, the brood size effect was stronger in daughters than in sons. This suggests that metabolic efficiency may play a role in mediating the long-term fitness consequences of rearing conditions.
Effect of D‐amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency

Background. The D‐Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D‐amino acid oxidase (DAO), which metabolizes D‐serine, a co‐agonist of NMDA‐type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder. Aims. To examine the influence of G72 variation on brain function in the healthy population. Method. Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task‐dependent functional connectivity during word generation was compared between different rs746187 genotypes. Results. G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task‐dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05). Conclusions. Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D‐amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Coherent development of dermomyotome and dermis from the entire mediolateral extent of the dorsal somite

We have previously shown that overall growth of the myotome in the mediolateral direction occurs in a coherent and uniform pattern. We asked whether development of the dermomyotome and resultant dermis follow a similar pattern or are, alternatively, controlled by restricted pools of stem cells driving directional growth. To this end, we studied cellular events that govern dermomyotome development and the regional origin of dermis. Measurements of cell proliferation, nuclear density and cellular rearrangements revealed that the developing dermomyotome can be subdivided in the transverse plane into three distinct and dynamic regions: medial, central and lateral, rather than simply into epaxial and hypaxial domains. To understand how these temporally and spatially restricted changes affect overall dermomyotome growth, lineage tracing with CM-DiI was performed. A proportional pattern of growth was measured along the entire epithelium, suggesting that mediolateral growth of the dermomyotome is coherent. Hence, they contrast with a stem cell view suggesting focal and inversely oriented sources of growth restricted to the medial and lateral edges. Consistent with this uniform mediolateral growth, lineage tracing experiments showed that the dermomyotome-derived dermis originates from progenitors that reside along the medial as well as the lateral halves of somites, and whose contribution to dermis is regionally restricted. Taken together, our results support the view that all derivatives of the dorsal somite (dermomyotome, myotome and dermis) keep a direct topographical relationship with their epithelial ascendants.
Variation in RNA Virus Mutation Rates across Host Cells

It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms. However, their mutation rates vary amply, from 10−6 to 10−4 substitutions per nucleotide per round of copying (s/n/r) and the causes of this variability remain poorly understood. In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors. Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV), which has a broad host range and cell tropism. Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly in baby hamster kidney, murine embryonic fibroblasts, colon cancer, and neuroblastoma cells (approx. 10−5 s/n/r). Cell immortalization through p53 inactivation and oxygen levels (1–21%) did not have a significant impact on viral replication fidelity. This shows that previously published mutation rates can be considered reliable despite being based on a narrow and artificial set of laboratory conditions. Interestingly, we also found that VSV mutated approximately four times more slowly in various insect cells compared with mammalian cells. This may contribute to explaining the relatively slow evolution of VSV and other arthropod-borne viruses in nature.
Curve Shortening and the Rendezvous Problem for Mobile Autonomous Robots

If a smooth, closed, and embedded curve is deformed along its normal vector field at a rate proportional to its curvature, it shrinks to a circular point. This curve evolution is called Euclidean curve shortening and the result is known as the Gage-Hamilton-Grayson theorem. Motivated by the rendezvous problem for mobile autonomous robots, we address the problem of creating a polygon shortening flow. A linear scheme is proposed that exhibits several analogues to Euclidean curve shortening: The polygon shrinks to an elliptical point, convex polygons remain convex, and the perimeter of the polygon is monotonically decreasing.
Perception-Based Visualization of Manifold-Valued Medical Images Using Distance-Preserving Dimensionality Reduction

A method for visualizing manifold-valued medical image data is proposed. The method operates on images in which each pixel is assumed to be sampled from an underlying manifold. For example, each pixel may contain a high dimensional vector, such as the time activity curve (TAC) in a dynamic positron emission tomography (dPET) or a dynamic single photon emission computed tomography (dSPECT) image, or the positive semi-definite tensor in a diffusion tensor magnetic resonance image (DTMRI). A nonlinear mapping reduces the dimensionality of the pixel data to achieve two goals: distance preservation and embedding into a perceptual color space. We use multidimensional scaling distance-preserving mapping to render similar pixels (e.g., DT or TAC pixels) with perceptually similar colors. The 3D CIELAB perceptual color space is adopted as the range of the distance preserving mapping, with a final similarity transform mapping colors to a maximum gamut size. Similarity between pixels is either determined analytically as geodesics on the manifold of pixels or is approximated using manifold learning techniques. In particular, dissimilarity between DTMRI pixels is evaluated via a Log-Euclidean Riemannian metric respecting the manifold of the rank 3, second-order positive semi-definite DTs, whereas the dissimilarity between TACs is approximated via ISOMAP. We demonstrate our approach via artificial high-dimensional, manifold-valued data, as well as case studies of normal and pathological clinical brain and heart DTMRI, dPET, and dSPECT images. Our results demonstrate the effectiveness of our approach in capturing, in a perceptually meaningful way, important features in the data.
The role of scene type and priming in the processing and selection of a spatial frame of reference

The selection and processing of a spatial frame of reference (FOR) in interpreting verbal scene descriptions is of great interest to psycholinguistics. In this study, we focus on the choice between the relative and the intrinsic FOR, addressing two questions: (a) does the presence or absence of a background in the scene influence the selection of a FOR, and (b) what is the effect of a previously selected FOR on the subsequent processing of a different FOR. Our results show that if a scene includes a realistic background, this will make the selection of the relative FOR more likely. We attribute this effect to the facilitation of mental simulation, which enhances the relation between the viewer and the objects. With respect to the response accuracy, we found both a higher (with the same FOR) and a lower accuracy (with a different FOR), while for the response latencies, we only found a delay effect with a different FOR.
Multicenter Evaluation of the New Vitek 2 Neisseria-Haemophilus Identification Card

ABSTRACT The new Neisseria-Haemophilus identification (NH) card for Vitek 2 was compared with 16S rRNA gene sequencing (16S) as the reference method for accurate identification of Neisseria spp. , Haemophilus spp. , and other fastidious gram-negative bacteria. Testing was performed on the Vitek 2 XL system with modified software at three clinical trial laboratories. Reproducibility was determined with nine ATCC quality control strains tested 20 times over a minimum of 10 days at all three sites. A challenge set of 30 strains with known identifications and 371 recent fresh and frozen clinical isolates were also tested. Expected positive and negative biochemical reactions were also evaluated for substrate reproducibility. All microorganisms were tested on the NH card, and all clinical and stock isolates were saved for 16S testing. All reproducibility tests yielded expected results within a 95% confidence interval. For challenge microorganisms, there was 98% overall correct identification, including 8% low discrimination, 2% incorrect identification, and 0% unidentified. For clinical strains, there was 96.5% overall correct identification, including 10.2% low discrimination, 2.7% incorrect identification, and 0.8% unidentified. The 2.7% (10/371) of clinical isolates that gave an incorrect identification consisted of 7 isolates correct to genus and 3 strains incorrect to genus. There were an additional 27 strains (primarily Neisseria species) for which the 16S identification result was different from the NH card result. These were all unclaimed species by the system. The new NH card met all performance criteria within a 95% confidence interval compared to identification of clinical isolates by 16S.
Stable isotopes document the trophic structure of a deep-sea cephalopod assemblage including giant octopod and giant squid

Although deep-sea cephalopods are key marine organims, their feeding ecology remains essentially unknown. Here, we report for the first time the trophic structure of an assemblage of these animals (19 species) by measuring the isotopic signature of wings of their lower beaks, which accumulated in stomachs of stranded sperm whales. Overall, the species encompassed a narrow range in δ13C values (1.7‰), indicating that they lived in closely related and overlapping habitats. δ13C values can be interpreted in terms of distribution with the more 13C-depleted species (e.g. Stigmatoteuthis arcturi, Vampyroteuthis infernalis) having a more pelagic habitat than the more 13C-enriched, bathyal species (e.g. Todarodes sagittatus and the giant squid Architeuthis dux). The cephalopods sampled had δ15N values ranging 4.6‰, which is consistent with the species spanning approximately 1.5 trophic levels. Neither the giant octopod (Haliphron atlanticus) nor the giant squid reached the highest trophic position. Species δ15N was independent of body size, with large squids having both the highest (Taningia danae) and lowest (Lepidoteuthis grimaldii) δ15N values. Their trophic position indicates that some species share the top of the food web, together with other megacarnivores such as the sperm whale.
Helical flow of surface protein required for bacterial gliding motility

Cells of Flavobacterium johnsoniae and of many other members of the phylum Bacteroidetes exhibit rapid gliding motility over surfaces by a unique mechanism. These cells do not have flagella or pili; instead, they rely on a novel motility apparatus composed of Gld and Spr proteins. SprB, a 669-kDa cell-surface adhesin, is required for efficient gliding. SprB was visualized by electron microscopy as thin 150-nm-long filaments extending from the cell surface. Fluorescence microscopy revealed movement of SprB proteins toward the poles of the cell at ∼2 μm/s. The fluorescent signals appeared to migrate around the pole and continue at the same speed toward the opposite pole along an apparent left-handed helical closed loop. Movement of SprB, and of cells, was rapidly and reversibly blocked by the addition of carbonyl cyanide m-chlorophenylhydrazone, which dissipates the proton gradient across the cytoplasmic membrane. In a gliding cell, some of the SprB protein appeared to attach to the substratum. The cell body moved forward and rotated with respect to this point of attachment. Upon reaching the rear of the cell, the attached SprB often was released from the substratum, and apparently recirculated to the front of the cell along a helical path. The results suggest a model for Flavobacterium gliding, supported by mathematical analysis, in which adhesins such as SprB are propelled along a closed helical loop track, generating rotation and translation of the cell body.
Poly(ADP-ribose) Polymerase-1 Is a Positive Regulator of the p53-mediated G1 Arrest Response following Ionizing Radiation*

Poly(ADP-ribose) polymerase-1 (PARP-1) and the p53 tumor suppressor protein are both involved in the cellular response to genotoxic stress. Upon binding to the site of DNA strand breakage, PARP-1 is activated, leading to rapid and transient poly(ADP-ribosyl)ation of nuclear proteins using NAD+ as substrate. To investigate the role of PARP-1 in the p53 response to ionizing radiation in human cells, PARP-1 function was disrupted in wild-type p53 expressing MCF-7 and BJ/TERT cells using two strategies: chemical inhibition with 1,5-dihydroxyisoquinoline, and trans-dominant inhibition by overexpression of the PARP-1 DNA-binding domain. Although a number of proteins can catalyze poly(ADP-ribosyl)ation in addition to PARP-1, we show that PARP-1 is the only detectable active species in BJ/TERT and MCF-7 cells. 1,5-Dihydroxyisoquinoline treatment prior to ionizing radiation delayed and attenuated the induction of two p53-responsive genes, p21 and mdm-2, and led to suppression of the p53-mediated G1-arrest response in MCF-7 and BJ/TERT cells. Trans-dominant inhibition of PARP-1 by overexpression of the PARP-1 DNA-binding domain in MCF-7 cells also led to a delay and attenuation in p21 induction and suppression of the p53-mediated G1 arrest response to ionizing radiation. Hence, inhibition of endogenous PARP-1 function suppresses the transactivation function of p53 in response to ionizing radiation. This study establishes PARP-1 as a critical regulator of the p53 response to DNA damage.
Headache in Cerebrovascular Disease

Two hundred fifteen consecutive patients with cerebrovascular events were evaluated pro- spectively for the incidence and characteristics of headache. Of 163 patients able to communicate, headache occurred in 29% with bland infarcts, 57% with parenchymal hemorrhage, 36% with transient Lschemic attacks and 17% with lacunar infarcts. Patients with a history of recurrent throbbing headache were significantly more likely to have headache, usually throbbing in quality, during the present illness. Women developed headache significantly more often than men. Headache began prior to the vascular event in 60% of patients and at its onset in 25%. The quality, onset and duration of the headache varied widely among patients. Headache in cerebrovascular disease is common, though neither its occurrence nor characteristics predict lesion type or location. Though the pathogenesis of the headache is unknown, its association with prior throbbing headache suggests that similar factors may operate in both. Stroke Vol 15, No 6, 1984