The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and ...histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.
We present a new release of the galform semi-analytical model of galaxy formation and evolution, which exploits a Millennium Simulation-class N-body run performed with the Wilkinson Microwave ...Anisotropy Probe 7 cosmology. We use this new model to study the impact of the choice of stellar population synthesis (SPS) model on the predicted evolution of the galaxy luminosity function. The semi-analytical model is run using seven different SPS models. In each case, we obtain the rest-frame luminosity function in the far-ultraviolet, optical and near-infrared (NIR) wavelength ranges. We find that both the predicted rest-frame ultraviolet and optical luminosity function are insensitive to the choice of SPS model. However, we find that the predicted evolution of the rest-frame NIR luminosity function depends strongly on the treatment of the thermally pulsating asymptotic giant branch (TP-AGB) stellar phase in the SPS models, with differences larger than a factor of 2 for model galaxies brighter than M
AB(K) − 5 log h < −22 (∼L
* for 0 ≤ z ≤ 1.5). We have also explored the predicted number counts of galaxies, finding remarkable agreement between the results with different choices of SPS model, except when selecting galaxies with very red optical-NIR colours. The predicted number counts of these extremely red galaxies appear to be more affected by the treatment of star formation in discs than by the treatment of TP-AGB stars in the SPS models.
The neutron-rich nucleus Ba-144 (t(1/2) = 11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for ...such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV Ba-144 beam on a 1.0-mg/cm(2) Pb-208 target. The measured value of the matrix element, < 3(1)(-)parallel to M(E3)parallel to 0(1)(+)> = 0.65((+17)(-23)) eb(3/2,) corresponds to a reduced Bd(E3) transition probability of 48((+25)(-34)) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.
Background
Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism ...linking obesity to chronic diseases is an alteration in adipose‐derived adiponectin and leptin levels. We investigated the effects of 12‐month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations.
Methods
Overweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight‐loss diet (diet; N = 118), (ii) moderate‐to‐vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight‐loss diet and moderate‐to‐vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight‐loss goal. The exercise intervention consisted of 45 min of moderate‐to‐vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay.
Results
Adiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, −40.1%, P < 0.0001; diet, −27.1%, P < 0.0001; exercise, −12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P‐trend = 0.0002; diet + exercise, P‐trend = 0.0005) and directly associated with leptin (diet, P‐trend < 0.0001; diet + exercise, P‐trend < 0.0001).
Conclusion
Weight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.
Morphological analyses of Utopia Planitia, Mars, have led to the hypothesis that the region contains a substantial amount of near‐surface ice. This paper tests this hypothesis using ...ground‐penetrating radar techniques. We have identified an expansive radar reflective region spanning approximately 375,000 km2 in SHAllow RADar (SHARAD) data over western Utopia Planitia. The SHARAD reflective regions coincides with high densities of scalloped depressions and polygonal terrain. The reflectors are associated with layered mesas ∼80–170 m thick. We find a value of 2.8 ± 0.8 for the dielectric constant of the material overlying the reflectors. This work finds that the dielectric constant is consistent with a mixture of ice, air, and dust, containing a water ice volume up to 14,300 km3 in this unit.
Key Points
Layered mesas up to 170 m high in western Utopia Planitia, Mars, exhibit periglacial morphologies
SHARAD data were used to map a regional subsurface reflector associated with the layered mesas
The dielectric constant is consistent with a 50‐85% water ice composition, with an ice volume of up to 14,300 km3
Abstract
Woody breast meat has recently become prevalent in the broiler industry in both the United States and European Union. Recent publications have described the meat quality characteristics of ...woody breast meat as having hardened areas and pale ridge-like bulges at both the caudal and cranial regions of the breast. The present study investigated the meat quality (pH, color, cooking loss, and shear force) and protein quality characteristics (protein and salt-soluble protein content) in woody breast meat as compared to normal breast meat. In addition, the differences in the muscle proteome profiles of woody and normal breast meat were characterized. Results indicated that woody breast meat had a greater average pH (P < 0.0001) and cooking loss (P = 0.001) than normal breast meat, but woody breast meat did not differ in shear force (P > 0.05) in comparison to normal breast meat samples. The L*, a*, and b* values of woody breast fillets were greater than normal breast fillets (P < 0.0001 to L*; P = 0.002 to a*; P = 0.016 to b*). The woody breast meat had more fat (P < 0.0001) and moisture (P < 0.021) and less protein (P < 0.0001) and salt-soluble protein (P < 0.0001) when compared with normal breast fillets. Whole muscle proteome analysis indicated 8 proteins that were differentially expressed (P < 0.05) between normal and woody breast meat samples. The differences in muscle proteome between normal and woody breast meat indicated an increased oxidative stress in woody breast meat when compared to normal meat. In addition, the abundance of some glycolytic enzymes, which are critical to the regeneration of adenosine triphosphate (ATP) in postmortem muscles, was lower in woody breast meat than in normal breast meat. Proteomic differences provide additional information on the biochemical pathways and genetic variations that lead to woody breast meat. Further research should be conducted to elucidate the genetic and nutritional contributions to the proliferation of woody breast meat in the United States.
The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological ...knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology.
Single nucleotide polymorphisms (SNPs) are appealing genetic markers due to several beneficial attributes, but uncertainty remains about how many of these bi-allelic markers are necessary to have ...sufficient power to differentiate populations, a task now generally accomplished with highly polymorphic microsatellite markers. In this study, we tested the utility of 37 SNPs and 13 microsatellites for differentiating 29 broadly distributed populations of Chinook salmon (n = 2783). Information content of all loci was determined by In and graphic removed , and the top 12 markers ranked by In were microsatellites, but the 6 highest, and 7 of the top 10 graphic removed ranked markers, were SNPs. The mean ratio of random SNPs to random microsatellites ranged from 3.9 to 4.1, but this ratio was consistently reduced when only the most informative loci were included. Individual assignment test accuracy was higher for microsatellites (73.1%) than SNPs (66.6%), and pooling all 50 markers provided the highest accuracy (83.2%). When marker types were combined, as few as 15 of the top ranked loci provided higher assignment accuracy than either microsatellites or SNPs alone. Neighbour-joining dendrograms revealed similar clustering patterns and pairwise tests of population differentiation had nearly identical results with each suite of markers. Statistical tests and simulations indicated that closely related populations were better differentiated by microsatellites than SNPs. Our results indicate that both types of markers are likely to be useful in population genetics studies and that, in some cases, a combination of SNPs and microsatellites may be the most effective suite of loci.
Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific ...nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs
, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref.
) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca
handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.
We introduce a superconducting qubit architecture that combines high-coherence qubits and tunable qubit-qubit coupling. With the ability to set the coupling to zero, we demonstrate that this ...architecture is protected from the frequency crowding problems that arise from fixed coupling. More importantly, the coupling can be tuned dynamically with nanosecond resolution, making this architecture a versatile platform with applications ranging from quantum logic gates to quantum simulation. We illustrate the advantages of dynamical coupling by implementing a novel adiabatic controlled-z gate, with a speed approaching that of single-qubit gates. Integrating coherence and scalable control, the introduced qubit architecture provides a promising path towards large-scale quantum computation and simulation.
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