Unraveling the Molecular Basis of Temperature-Dependent Genetic Regulation in Penicillium marneffei

Penicillium marneffei is an opportunistic fungal pathogen endemic in Southeast Asia, causing lethal systemic infections in immunocompromised patients. P. marneffei grows in a mycelial form at the ambient temperature of 25°C and transitions to a yeast form at 37°C. The ability to alternate between the mycelial and yeast forms at different temperatures, namely, thermal dimorphism, has long been considered critical for the pathogenicity of P. marneffei, yet the underlying genetic mechanisms remain elusive. Here we employed high-throughput sequencing to unravel global transcriptional profiles of P. marneffei PM1 grown at 25 and 37°C. Among ∼11,000 protein-coding genes, 1,447 were overexpressed and 1,414 were underexpressed at 37°C. Counterintuitively, heat-responsive genes, predicted in P. marneffei through sequence comparison, did not tend to be overexpressed at 37°C. These results suggest that P. marneffei may take a distinct strategy of genetic regulation at the elevated temperature; the current knowledge concerning fungal heat response, based on studies of model fungal organisms, may not be applicable to P. marneffei. Our results further showed that the tandem repeat sequences (TRSs) are overrepresented in coding regions of P. marneffei genes, and TRS-containing genes tend to be overexpressed at 37°C. Furthermore, genomic sequences and expression data were integrated to characterize gene clusters, multigene families, and species-specific genes of P. marneffei. In sum, we present an integrated analysis and a comprehensive resource toward a better understanding of temperature-dependent genetic regulation in P. marneffei

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

Genetic Dissection of Epidermal Growth Factor Receptor Signaling during Luteinizing Hormone-Induced Oocyte Maturation

Recent evidence that luteinizing hormone (LH) stimulation of ovulatory follicles causes transactivation of the epidermal growth factor receptor (EGFR) has provided insights into the mechanisms of ovulation. However, the complete array of signals that promote oocyte reentry into the meiotic cell cycle in the follicle are still incompletely understood. To elucidate the signaling downstream of EGFR involved in oocyte maturation, we have investigated the LH responses in granulosa cells with targeted ablation of EGFR. Oocyte maturation and ovulation is disrupted when EGFR expression is progressively reduced. In granulosa cells from mice with either global or granulosa cell-specific disruption of EGFR signaling, LH-induced phosphorylation of MAPK3/1, p38MAPK, and connexin-43 is impaired. Although the LH-induced decrease in cGMP is EGFR-dependent in wild type follicles, LH still induces a decrease in cGMP in Egfrdelta/f Cyp19-Cre follicles. Thus compensatory mechanisms appear activated in the mutant. Spatial propagation of the LH signal in the follicle also is dependent on the EGF network, and likely is important for the control of signaling to the oocyte. Thus, multiple signals and redundant pathways contribute to regulating oocyte reentry into the cell cycle

Initial Visible and Mid-IR Characterization of P/2019 LD₂ (ATLAS), an Active Transitioning Centaur Among the Trojans, with Hubble, Spitzer, ZTF, Keck, APO and GROWTH Imaging and Spectroscopy

We present visible and mid-infrared imagery and photometry of Jovian co-orbital comet P/2019 LD₂ (ATLAS) taken with Hubble Space Telescope/WFC3 on 2020 April 1, Spitzer Space Telescope/IRAC on 2020 January 25, Zwicky Transient Facility between 2019 April 9 and 2019 Nov 8 and the GROWTH telescope network from 2020 May to July, as well as visible spectroscopy from Keck/LRIS on 2020 August 19. Our observations indicate that LD₂ has a nucleus with radius 0.2-1.8 km assuming a 0.08 albedo and that the coma is dominated by ∼100 μ m-scale dust ejected at ∼1 m/s speeds with a ∼1" jet pointing in the SW direction. LD₂ experienced a total dust mass loss of ∼10⁸ kg and dust mass loss rate of ∼6 kg/s with Afρ/cross-section varying between ∼85 cm/125 km² and ∼200 cm/310 km² between 2019 April 9 and 2019 Nov 8. If the Afρ/cross-section increase remained constant, it implies that LD₂ has remained active since ∼2018 November when it came within 4.8 au of the Sun, a typical distance for comets to begin sublimation of H₂O. From our 4.5 μm Spitzer observations, we set a limit on CO/CO₂ gas production of ∼10²⁷/∼10²⁶ mol/s. Multiple bandpass photometry of LD₂ taken by the GROWTH network measured in a 10,000 km aperture provide color measurements of g-r = 0.59±0.03, r-i = 0.18±0.05, and i-z = 0.01±0.07, colors typical of comets. We set a spectroscopic upper limit to the production of H₂O gas of ∼80 kg/s. Improving the orbital solution for LD₂ with our observations, we determine that the long-term orbit of LD₂ is that of a typical Jupiter Family Comet having close encounters with Jupiter coming within ∼0.5 Hill radius in the last ∼3 y to within 0.8 Hill radius in ∼9 y and has a 95% chance of being ejected from the Solar System in < 10 Myr

Regioselective synthesis of plant (iso)flavone glycosides in Escherichia coli

The flavonoids genistein, biochanin A, luteolin, quercetin, and kaempferol are plant natural products with potentially useful pharmacological and nutraceutical activities. These natural products usually exist in plants as glycosides, and their glycosylation has a remarkable influence on their pharmacokinetic properties. The glycosyltransferases UGT71G1 and UGT73C8 from Medicago truncatula are excellent reagents for the regioselective glycosylation of (iso)flavonoids in Escherichia coli grown in Terrific broth. Ten to 20 mg/L of either genistein or biochanin A 7-O-glucoside was produced after feeding genistein or biochanin A to E. coli expressing UGT71G1, and similar levels of luteolin 4’-O- and 7-O-glucosides were produced after feeding luteolin to cultures expressing UGT73C8. For the production of kaempferol 3-O-glucoside or quercetin 3-O-glucoside, the Phe148Val or Tyr202Ala mutants of UGT71G1 were employed. Ten to 16 mg/L of either kaempferol 3-O- or quercetin 3-O-glucosides were produced on feeding kaempferol or quercetin to E. coli expressing these enzymes. More than 90% of the glucoside products were released to the medium, facilitating their isolation

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Predicting the seasonal evolution of southern African summer precipitation in the DePreSys3 prediction system

We assess the ability of the DePreSys3 prediction system to predict austral summer precipitation (DJF) over southern Africa, defined as the African continent south of 15°S. DePresys3 is a high resolution prediction system (at a horizontal resolution of ~ 60 km in the atmosphere in mid-latitudes and of the quarter degree in the Ocean) and spans the long period 1959–2016. We find skill in predicting interannual precipitation variability, relative to a long-term trend; the anomaly correlation skill score over southern Africa is greater than 0.45 for the first summer (i.e. lead month 2–4), and 0.37 over Mozambique, Zimbabwe and Zambia for the second summer (i.e. lead month 14–16). The skill is related to the successful prediction of the El-Nino Southern Oscillation (ENSO), and the successful simulation of ENSO teleconnections to southern Africa. However, overall skill is sensitive to the inclusion of strong La-Nina events and also appears to change with forecast epoch. For example, the skill in predicting precipitation over Mozambique is significantly larger for the first summer in the 1990–2016 period, compared to the 1959–1985 period. The difference in skill in predicting interannual precipitation variability over southern Africa in different epochs is consistent with a change in the strength of the observed teleconnections of ENSO. After 1990, and consistent with the increased skill, the observed impact of ENSO appears to strengthen over west Mozambique, in association with changes in ENSO related atmospheric convergence anomalies. However, these apparent changes in teleconnections are not captured by the ensemble-mean predictions using DePreSys3. The changes in the ENSO teleconnection are consistent with a warming over the Indian Ocean and modulation of ENSO properties between the different epochs, but may also be associated with unpredictable atmospheric variability

Performance of the CMS High Granularity Calorimeter prototype to charged pion beams of 20−-300 GeV/c

The upgrade of the CMS experiment for the high luminosity operation of the LHC comprises the replacement of the current endcap calorimeter by a high granularity sampling calorimeter (HGCAL). The electromagnetic section of the HGCAL is based on silicon sensors interspersed between lead and copper (or copper tungsten) absorbers. The hadronic section uses layers of stainless steel as an absorbing medium and silicon sensors as an active medium in the regions of high radiation exposure, and scintillator tiles directly readout by silicon photomultipliers in the remaining regions. As part of the development of the detector and its readout electronic components, a section of a silicon-based HGCAL prototype detector along with a section of the CALICE AHCAL prototype was exposed to muons, electrons and charged pions in beam test experiments at the H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology as foreseen for the HGCAL but with much finer longitudinal segmentation. The performance of the calorimeters in terms of energy response and resolution, longitudinal and transverse shower profiles is studied using negatively charged pions, and is compared to GEANT4 predictions. This is the first report summarizing results of hadronic showers measured by the HGCAL prototype using beam test data.Comment: To be submitted to JINS

The Zwicky Transient Facility: System Overview, Performance, and First Results

The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg 2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF’s public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope