Linkage studies of catechol-O-methyltransferase (COMT) and dopamine-beta-hydroxylase (DBH) cDNA expression levels

The COMT and DBH genes are physically located at chromosomes 22q11 and 9q34, respectively, and both COMT and DBH are involved in catecholamine metabolism and are strong candidates for certain psychiatric and neurological disorders. Although the genetic determinants for both enzymes' activities have been widely studied, their genetic involvement on gene mRNA expression levels remains unclear. In this study we performed quantitative linkage analysis of COMT and DBH cDNA expression levels, identifying transcriptional regulatory regions for both genes. Multiple Haseman-Elston regression was used to detect both additive and interactive effects between two loci. We found that the master transcriptional regulatory region 20q13 had an additive effect on the COMT expression level. We also found that chromosome 19p13 showed both additive and interactive effects with 9q34 on DBH expression level. Furthermore, a potential interaction between COMT and DBH was indicated

A case of reactive granulomatous dermatitis associated with neonatal lupus erythematosus

Neonatal lupus erythematosus (NLE) is an uncommon disorder affecting approximately one out of 20 000 live births in the United States. Common manifestations of NLE include cutaneous eruptions and cardiac involvement. The typical rash of NLE most closely resembles the rash of subacute cutaneous lupus erythematosus both clinically and histopathologically. We present a case of reactive granulomatous dermatitis (RGD) associated with NLE in a 3-month-old male in whom the initial histopathology and immunohistochemistry were concerning for hematologic malignancy. RGD is a unifying term used to describe cutaneous granulomatous eruptions that occur in response to a variety of stimuli, including autoimmune connective tissue diseases. Our case demonstrates the range of histopathological findings that may be present in the setting of NLE

Lectotypication of Acroporium hyalinum (Reinw. ex Schwägr.) Mitt. (Hypnales: Sematophyllaceae).

Acroporium hyalinum (Reinw. ex Schwägr.) Mitt., an older name for Acroporium stramineum (Reinw. & Hornsch.) M.Fleisch., is applied here in accordance with the principle of nomenclatural priority. Acroporium hyalinum is broadly circumscribed by its erect-spreading, ovate-lanceolate leaves with short acuminate tips. Its infra-speci¬c delimitation, however, has not been clearly resolved. Based on careful examination of nearly 200 specimens, including 35 types associated with A. hyalinum and its synonyms, all the three varieties proposed by Tan (1994) are accepted here as Acroporium hyalinum (Reinw. ex Schwägr.) Mitt. var. hyalinum,A. hyalinum var. hamulatum (M.Fleisch.) M.S.Chua & B.C.Ho, and A. hyalinum var. turgidum (M.Fleisch.) M.S.Chua & B.C.Ho, the latter two names being new combinations. Descriptions and an identi¬cation key of these three varieties are provided, along with taxonomic notes and illustrations. Lectotypi¬cation of Hypnum hyalinum Reinw. & Hornsch. is proposed

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581. PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables. RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk. CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis

Differential Signal Transduction of Progesterone and Medroxyprogesterone Acetate in Human Endothelial Cells

AbstractThe conjugated equine estrogens-only arm of the Women's Health Initiative trial, showing a trend toward protection from heart disease as opposed to women receiving also medroxyprogesterone acetate (MPA), strengthens the debate on the cardiovascular effects of progestins. We compared the effects of progesterone (P) or MPA on the synthesis of nitric oxide and on the expression of leukocyte adhesion molecules, characterizing the signaling events recruited by these compounds. Although P significantly increases nitric oxide synthesis via transcriptional and nontranscriptional mechanisms, MPA is devoid of such effects. Moreover, when used together with physiological estradiol (E2) concentrations, P potentiates E2 effects, whereas MPA impairs E2 signaling. These findings are observed both in isolated human endothelial cells as well as in vivo, in ovariectomized rat aortas. A marked difference in the recruitment of MAPK and phosphatidylinositol-3 kinase explains the divergent effects of the two gestagens. In addition, both P and MPA decrease the adhesiveness of endothelial cells for leukocytes when given alone or with estrogen. MPA is more potent than P in inhibiting the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. However, when administered together with physiological amounts of glucocorticoids, MPA (which also binds glucocorticoid receptor) markedly interferes with the hydrocortisone-dependent stabilization of the transcription factor nuclear factor κB and with the expression of adhesion molecules, acting as a partial glucocorticoid receptor antagonist. Our findings show significant differences in the signal transduction pathways recruited by P and MPA in endothelial cells, which may have relevant clinical implications

Identifying Highly Conserved and Highly Differentiated Gene Ontology Categories in Human Populations

Detecting and interpreting certain system-level characteristics associated with human population genetic differences is a challenge for human geneticists. In this study, we conducted a population genetic study using the HapMap genotype data to identify certain special Gene Ontology (GO) categories associated with high/low genetic difference among 11 Hapmap populations. Initially, the genetic differences in each gene region among these populations were measured using allele frequency, linkage disequilibrium (LD) pattern, and transferability of tagSNPs. The associations between each GO term and these genetic differences were then identified. The results showed that cellular process, catalytic activity, binding, and some of their sub-terms were associated with high levels of genetic difference, and genes involved in these functional categories displayed, on average, high genetic diversity among different populations. By contrast, multicellular organismal processes, molecular transducer activity, and some of their sub-terms were associated with low levels of genetic difference. In particular, the neurological system process under the multicellular organismal process category had low levels of genetic difference; the neurological function also showed high evolutionary conservation between species in some previous studies. These results may provide a new insight into the understanding of human evolutionary history at the system-level

Interactions of the Apolipoprotein A5 Gene Polymorphisms and Alcohol Consumption on Serum Lipid Levels

Little is known about the interactions of apolipoprotein (Apo) A5 gene polymorphisms and alcohol consumption on serum lipid profiles. The present study was undertaken to detect the interactions of ApoA5-1131T>C, c.553G>T and c.457G>A polymorphisms and alcohol consumption on serum lipid levels.A total of 516 nondrinkers and 514 drinkers were randomly selected from our previous stratified randomized cluster samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P<0.05-0.001). The genotypic and allelic frequencies of three loci were not different between the two groups. The interactions between -1131T>C genotypes and alcohol consumption on ApoB levels (P<0.05) and the ApoA1/ApoB ratio (P<0.01), between c.553G>T genotypes and alcohol consumption on low-density lipoprotein cholesterol (LDL-C) levels (P<0.05) and the ApoA1/ApoB ratio (P<0.05), and between c.457G>A genotypes and alcohol consumption on TG levels (P<0.001) were detected by factorial regression analysis after controlling for potential confounders. Four haplotypes (T-G-G, C-G-G, T-A-G and C-G-T) had frequencies ranging from 0.06 to 0.87. Three haplotypes (C-G-G, T-A-G, and C-G-T) were significantly associated with serum lipid parameters. The -1131T>C genotypes were correlated with TG, and c.553G>T and c.457G>A genotypes were associated with HDL-C levels in nondrinkers (P<0.05 for all). For drinkers, the -1131T>C genotypes were correlated with TC, TG, LDL-C, ApoB levels and the ApoA1/ApoB ratio (P<0.01 for all); c.553G>T genotypes were correlated with TC, TG, HDL-C and LDL-C levels (P<0.05-0.01); and c.457G>A genotypes were associated with TG, LDL-C, ApoA1 and ApoB levels (P<0.05-0.01).The differences in some serum lipid parameters between the drinkers and nondrinkers might partly result from different interactions of the ApoA5 gene polymorphisms and alcohol consumption

Diverse Applications of Nanomedicine

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic. \ua9 2017 American Chemical Society

Measurement-induced entanglement and teleportation on a noisy quantum processor

Measurement has a special role in quantum theory: by collapsing the wavefunction it can enable phenomena such as teleportation and thereby alter the "arrow of time" that constrains unitary evolution. When integrated in many-body dynamics, measurements can lead to emergent patterns of quantum information in space-time that go beyond established paradigms for characterizing phases, either in or out of equilibrium. On present-day NISQ processors, the experimental realization of this physics is challenging due to noise, hardware limitations, and the stochastic nature of quantum measurement. Here we address each of these experimental challenges and investigate measurement-induced quantum information phases on up to 70 superconducting qubits. By leveraging the interchangeability of space and time, we use a duality mapping, to avoid mid-circuit measurement and access different manifestations of the underlying phases -- from entanglement scaling to measurement-induced teleportation -- in a unified way. We obtain finite-size signatures of a phase transition with a decoding protocol that correlates the experimental measurement record with classical simulation data. The phases display sharply different sensitivity to noise, which we exploit to turn an inherent hardware limitation into a useful diagnostic. Our work demonstrates an approach to realize measurement-induced physics at scales that are at the limits of current NISQ processors

Non-Abelian braiding of graph vertices in a superconducting processor

Indistinguishability of particles is a fundamental principle of quantum mechanics. For all elementary and quasiparticles observed to date - including fermions, bosons, and Abelian anyons - this principle guarantees that the braiding of identical particles leaves the system unchanged. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well developed mathematical description of non-Abelian anyons and numerous theoretical proposals, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. While efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasi-particles, superconducting quantum processors allow for directly manipulating the many-body wavefunction via unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons, we implement a generalized stabilizer code and unitary protocol to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of employing the anyons for quantum computation and utilize braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and - through the future inclusion of error correction to achieve topological protection - could open a path toward fault-tolerant quantum computing