Some Like It Hot, Some Like It Warm: Phenotyping To Explore Thermotolerance Diversity

Plants have evolved overlapping but distinct cellular responses to different aspects of high temperature stress. These responses include basal thermotolerance, short- and long-term acquired thermotolerance, and thermotolerance to moderately high temperatures. This ‘thermotolerance diversity’ means that multiple phenotypic assays are essential for fully describing the functions of genes involved in heat stress responses. A large number of genes with potential roles in heat stress responses have been identified using genetic screens and genome wide expression studies. We examine the range of phenotypic assays that have been used to characterize thermotolerance phenotypes in both Arabidopsis and crop plants. Three major variables differentiate thermotolerance assays: (1) the heat stress regime used, (2) the developmental stage of the plants being studied, and (3) the actual phenotype which is scored. Consideration of these variables will be essential for deepening our understanding of the molecular genetics of plant thermotolerance

Puzzles in BB physics

I discuss some puzzles observed in exclusive $B$ meson decays, concentrating on the large difference between the direct CP asymmetries in the $B^0\to \pi^\mp K^\pm$ and $B^\pm\to \pi^0 K^\pm$ modes, the large $B^0\to\pi^0\pi^0$ branching ratio, and the large deviation of the mixing-induced CP asymmetries in the $b\to sq\bar q$ penguins from those in the $b\to c\bar c s$ trees.Comment: 6 pages, 1 figure, talk presented at the 9th Workshop on High Energy Physics Phenomenology, Bhubaneswar, Orissa, India, Jan. 3-14, 2006; reference adde

Sixteen years post radiotherapy of nasopharyngeal carcinoma elicited multi-dysfunction along PTX and chronic kidney disease with microcytic anemia

BACKGROUND: The hypothalamic–pituitary (h-p) unit is a particularly radiosensitive region in the central nervous system. As a consequence, radiation-induced irreversible, progressively chronic onset hypopituitarism (RIH) commonly develops after radiation treatments and can result in variably impaired pituitary function, which is frequently associated with increased morbidity and mortality. CASE PRESENTATION: A 38-year-old male subject, previously having received radiotherapy for treatment of nasopharygeal carcinoma (NPCA) 16 years ago, appeared at OPD complaining about his failure in penile erection, loss of pubic hair, atrophy of external genitalia: testicles reduced to 2×1.5 cm; penile size shrunk to only 4 cm long. Characteristically, he showed extremely lowered human growth hormone, (HGH, 0.115 ng/mL), testosterone (<0.1 ng/mL), total thyroxine (tT4: 4.740 g/mL), free T4 (fT4, 0.410 ng/mL), cortisol (2.34 g/dL); lowered LH (1.37 mIU/mL) and estradiol (22 pg/mL); highly elevated TSH (7.12 IU/mL). As contrast, he had low end normal ACTH, FSH, total T3, free T3, and estriol; high end normal prolactin (11.71 ng/mL), distinctly implicating hypopituitarism-induced hypothyroidism and hypogonadism. serologically, he showed severely lowered Hb (10.6 g/dL), HCT (32.7%), MCV (77.6 fL), MCH (25.3 pg), MCHC (32.6 g/dL), and platelet count (139×103/L) with extraordinarily elevated RDW (18.2%), together with severely lowered ferritin (23.6 ng/mL) and serum iron levels; highly elevated total iron binding capacity (TIBC, 509 g/dL) and transferrin (363.4 mg/dL), suggesting microcytic anemia. Severely reduced estimated glomerular filtration rate (e-GFR) (89 mL/mim/1.73 m2) pointed to CKD2. Hypocortisolemia with hyponatremia indicated secondary adrenal insufficiency. Replacement therapy using androgen, cortisol, and Ringer’s solution has shown beneficial in improving life quality. CONCLUSIONS: To our believe, we are the first group who report such complicate PTX dysfunction with adrenal cortisol insufficiency concomitantly occurring in a single patient

Nonperturbative bound on high multiplicity cross sections in phi^4_3 from lattice simulation

We have looked for evidence of large cross sections at large multiplicities in weakly coupled scalar field theory in three dimensions. We use spectral function sum rules to derive bounds on total cross sections where the sum can be expresed in terms of a quantity which can be measured by Monte Carlo simulation in Euclidean space. We find that high multiplicity cross sections remain small for energies and multiplicities for which large effects had been suggested.Comment: 23 pages, revtex, seven eps figures revised version: typos corrected, some rewriting of discusion, same resul

Inflation and nonequilibrium renormalization group

We study de spectrum of primordial fluctuations and the scale dependence of the inflaton spectral index due to self-interactions of the field. We compute the spectrum of fluctuations by applying nonequilibrium renormalization group techniques.Comment: 6 pages, 1 figure, submitted to J. Phys.

Soft end-point and mass corrections to the eta' g*g* vertex function

Power-suppressed corrections arising from end-point integration regions to the space-like vertex function of the massive eta'-meson virtual gluon transition eta' - g*g* are computed. Calculations are performed within the standard hard-scattering approach (HSA) and the running coupling method supplemented by the infrared renormalon calculus. Contributions to the vertex function from the quark and gluon contents of the eta' -meson are taken into account and the Borel resummed expressions for F_{eta' g*g*}(Q2,\omega ,\eta), as well as for F_{eta' g g*}}(Q^{2},\omega =\pm 1,\eta) and F_{eta' g*g*}(Q^{2},\omega =0,\eta) are obtained. It is demonstrated that the power-suppressed corrections \sim (\Lambda ^{2}/Q^{2})^{n}, in the explored range of the total gluon virtuality 1 <Q2 < 25 GeV2, considerably enhance the vertex function relative to the results found in the framework of the standard HSA with a fixed coupling. Modifications generated by the eta ' -meson mass effects are discussed

Reconstructing large running-index inflaton potentials

Recent fits of cosmological parameters by the first year Wilkinson Microwave Anisotropy Probe (WMAP) measurement seem to favor a primordial scalar spectrum with a large varying index from blue to red. We use the inflationary flow equations to reconstruct large running-index inflaton potentials and comment on current status on the inflationary flow. We find previous negligence of higher order slow rolling contributions when using the flow equations would lead to unprecise results.Comment: Final version to appear in Class. Quant. Grav. References adde

Wolff-Parkinson-White Syndrome: De Novo Variants and Evidence for Mutational Burden in Genes Associated with Atrial Fibrillation

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population. METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, candidate gene approach, and burden testing to explore the genetic contributions to WPW. RESULTS: A heterozygous deleterious variant in PRKAG2 was identified in one subject, accounting for 0.6% (1/151) of the genetic basis of WPW in this study. Another individual with WPW and left ventricular hypertrophy carried a known pathogenic variant in MYH7. We found rare de novo variants in genes associated with arrhythmia and cardiomyopathy (ANK2, NEBL, PITX2, and PRDM16) in this cohort. There was an increased burden of rare deleterious variants (MAF ≤ 0.005) with CADD score ≥ 25 in genes linked to AF in cases compared to controls (P = .0023). CONCLUSIONS: Our findings show an increased burden of rare deleterious variants in genes linked to AF in WPW syndrome, suggesting that genetic factors that determine the development of accessory pathways may be linked to an increased susceptibility of atrial muscle to AF in a subset of patients

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Regulation of CEACAM1 transcription in human breast epithelial cells

<p>Abstract</p> <p>Background</p> <p>Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a transmembrane protein with multiple functions in different cell types. CEACAM1 expression is frequently mis-regulated in cancer, with down-regulation reported in several tumors of epithelial origin and <it>de novo </it>expression of CEACAM1 in lung cancer and malignant melanoma. In this report we analyzed the regulation of CEACAM1 expression in three breast cancer cell lines that varied in CEACAM1 expression from none (MCF7) to moderate (MDA-MB-468) to high (MCF10A, comparable to normal breast).</p> <p>Results</p> <p>Using <it>in vivo </it>footprinting and chromatin immunoprecipitation experiments we show that the <it>CEACAM1 </it>proximal promoter in breast cells is bound in its active state by SP1, USF1/USF2, and IRF1/2. When down-regulated the <it>CEACAM1 </it>promoter remains accessible to USF2 and partially accessible to USF1. Interferon-γ up-regulates CEACAM1 mRNA by a mechanism involving further induction of IRF-1 and USF1 binding at the promoter. As predicted by this analysis, silencing of IRF1 and USF1 but not USF2 by RNAi resulted in a significant decrease in CEACAM1 protein expression in MDA-MB-468 cells. The inactive <it>CEACAM1 </it>promoter in MCF7 cells exhibits decreased histone acetylation at the promoter region, with no evidence of H3K9 or H3K27 trimethylation, histone modifications often linked to condensed chromatin structure.</p> <p>Conclusions</p> <p>Our data suggest that transcription activators USF1 and IRF1 interact to modulate CEACAM1 expression and that the chromatin structure of the promoter is likely maintained in a poised state that can promote rapid induction under appropriate conditions.</p