Signaling through retinoic acid receptors is essential for mammalian uterine receptivity and decidualization

Retinoic acid (RA) signaling has long been speculated to regulate embryo implantation, because many enzymes and proteins responsible for maintaining RA homeostasis and transducing RA signals are tightly regulated in the endometrium during this critical period. However, due to a lack of genetic data, it was unclear whether RA signaling is truly required for implantation and which specific RA signaling cascades are at play. Herein we utilize a genetic murine model that expresses a dominant-negative form of RA receptor (RAR) specifically in female reproductive organs to show that functional RA signaling is fundamental to female fertility, particularly implantation and decidualization. Reduction in RA signaling activity severely affects the ability of the uterus to achieve receptive status and decidualize, partially through dampening follistatin expression and downstream activin B/bone morphogenetic protein 2 signaling. To confirm translational relevance of these findings to humans, human endometrial stromal cells (hESCs) were treated with a pan-RAR antagonist to show that in vitro decidualization is impaired. RNA interference perturbation of individual RAR transcripts in hESCs revealed that RARα in particular was essential for proper decidualization. These data provide direct functional evidence that uterine RAR-mediated RA signaling was crucial for mammalian embryo implantation, and its disruption led to failure of uterine receptivity and decidualization, resulting in severely compromised fertility

Sensitivity of tile drainage flow and crop yield on measured and calibrated soil hydraulic properties

Process-based agricultural system models require detailed description of soil hydraulic properties that are usually not available. The objectives of this study were to evaluate the sensitivity of model simulation results to variability in measured soil hydraulic properties and to compare simulation results using measured and default soil parameters. To do so, we measured soil water retention curves and saturated soil hydraulic conductivity (Ksat) from intact soil cores taken from a long-term experimental field near Nashua, Iowa for the Kenyon–Clyde–Floyd–Readlyn soil association. The soil water retention curves could be well described using the pore size distribution index (λ). Measured λ values from undisturbed soil cores ranged from 0.04 to 0.12 and the measured Ksat values ranged from 1.8 to 14.5 cm/h. These hydraulic properties were then used to calibrate the Root Zone Water Quality Model (RZWQM) for simulating soil water content, water table, tile drain flow, and crop yield (corn and soybean) by optimizing the lateral Ksat(LKsat) and hydraulic gradient (HG) for subsurface lateral flow. The measured soil parameters provided better simulations of soil water storage, water table, and N loss in tile flow than using the default soil parameters based on soil texture classes in RZWQM. Sensitivity analyses were conducted for λ, Ksat, saturated soil water content (θs) or drainable porosity, LKsat, and HG using the Latin Hypercubic Sampling (LHS) and for LKsat and HG also using a single variable analysis. Results of sensitivity analyses showed that RZWQM-simulated yield and biomass were not sensitive to soil hydraulic properties. Simulated tile flow and N losses in tile flow were not sensitive to λ and Ksat either, but they were sensitive to LKsat and HG. Further sensitivity analyses using a single variable showed that LKsat in the tile layer was a more sensitive parameter compared to LKsat in other soil layers, and HG was the most sensitive parameter for tile flow under the experimental soil and weather conditions

Empirical analysis and prediction of nitrate loading and crop yield for corn–soybean rotations

Nitrate nitrogen losses through subsurface drainage and crop yield are determined by multiple climatic and management variables. The combined and interactive effects of these variables, however, are poorly understood. Our objective is to predict crop yield, nitrate concentration, drainage volume, and nitrate loss in subsurface drainage from a corn (Zea mays L.) and soybean (Glycine max (L.) Merr.) rotation as a function of rainfall amount, soybean yield for the year before the corn–soybean sequence being evaluated, N source, N rate, and timing of N application in northeastern Iowa, U.S.A. Ten years of data (1994–2003) from a long-term study near Nashua, Iowa were used to develop multivariate polynomial regression equations describing these variables. The regression equations described over 87, 85, 94, 76, and 95% of variation in soybean yield, corn yield, subsurface drainage, nitrate concentration, and nitrate loss in subsurface drainage, respectively. A two-year rotation under average soil, average climatic conditions, and 125 kg N/ha application was predicted to loose 29, 37, 36, and 30 kg N/ha in subsurface drainage for early-spring swine manure, fall-applied swine manure, early-spring UAN fertilizer, and late-spring split UAN fertilizer (urea ammonium nitrate), respectively. Predicted corn yields were 10.0 and 9.7 Mg/ha for the swine manure and UAN sources applied at 125 kg N/ha. Timing of application (i.e., fall or spring) did not significantly affect corn yield. These results confirm other research suggesting that manure application can result in less nitrate leaching than UAN (e.g., 29 vs. 36 kg N/ha), and that spring application reduces nitrate leaching compared to fall application (e.g., 29 vs. 37 kg N/ha). The regression equations improve our understanding of nitrate leaching; offer a simple method to quantify potential N losses from Midwestern corn–soybean rotations under the climate, soil, and management conditions of the Nashua field experiment; and are a step toward development of easy to use N management tools

Evaluating and predicting agricultural management effects under tile drainage using modified APSIM

An accurate and management sensitive simulation model for tile-drained Midwestern soils is needed to optimize the use of agricultural management practices (e.g., winter cover crops) to reduce nitrate leaching without adversely affecting corn yield. Our objectives were to enhance the Agricultural Production Systems Simulator (APSIM) for tile drainage, test the modified model for several management scenarios, and then predict nitrate leaching with and without winter wheat cover crop. Twelve years of data (1990–2001) from northeast Iowa were used for model testing. Management scenarios included continuous corn and corn–soybean rotations with single or split N applications. For 38 of 44 observations, yearly drain flow was simulated within 50 mm of observed for low drainage (\u3c 100 mm) or within 30% of observed for high drain flow. Corn yield was simulated within 1500 kg/ha for 12 of 24 observations. For 30 of 45 observations yearly nitrate-N loss in tile drains was simulated within 10 kg N/ha for low nitrate-N loss (\u3c 20 kg N/ha) or within 30% of observed for high nitrate-N loss. Several of the poor yield and nitrate-N loss predictions appear related to poor N-uptake simulations. The model accurately predicted greater corn yield under split application (140–190 kg N/ha) compared to single 110 kg N/ha application and higher drainage and nitrate-N loss under continuous corn compared to corn/soybean rotations. A winter wheat cover crop was predicted to reduce nitrate-N loss 38% (341 vs. 537 kg N/ha with and without cover) under 41-years of corn-soybean rotations and 150 kg N/ha applied to corn. These results suggest that the modified APSIM model is a promising tool to help estimate the relative effect of alternative management practices under fluctuating high water tables

Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model.

The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a heavily mutated spike protein capable of escaping preexisting immunity identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-4482 against the earlier Alpha, Beta and Delta VOCs and Omicron in the hamster COVID-19 model. Omicron replication and associated lung disease in vehicle treated hamsters was reduced compared to the earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of Alpha, Beta and Delta VOC infected hamsters. Importantly, MK-4482 profoundly inhibited virus replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC. Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory effect on infectious titers compared to viral RNA genome load. Histopathologic analysis showed that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral antigen load in infected hamsters across all VOCs examined. Together, our data indicate the potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially Omicron, and likely future SARS-CoV-2 variants

Direct and Indirect Detection of Dark Matter in D6 Flavor Symmetric Model

We study a fermionic dark matter in a non-supersymmetric extension of the standard model with a family symmetry based on D6xZ2xZ2. In our model, the final state of the dark matter annihilation is determined to be e+ e- by the flavor symmetry, which is consistent with the PAMELA result. At first, we show that our dark matter mass should be within the range of 230 GeV - 750 GeV in the WMAP analysis combined with mu to e gamma constraint. Moreover we simultaneously explain the experiments of direct and indirect detection, by simply adding a gauge and D6 singlet real scalar field. In the direct detection experiments, we show that the lighter dark matter mass ~ 230 GeV and the lighter standard model Higgs boson ~ 115 GeV is in favor of the observed bounds reported by CDMS II and XENON100. In the indirect detection experiments, we explain the positron excess reported by PAMELA through the Breit-Wigner enhancement mechanism. We also show that our model is consistent with no antiproton excess suggested by PAMELA.Comment: 20 pages, 9 figures, 2 tables, accepted version for publication in European Physical Journal

Applying the Coulomb Failure Function with an optimally oriented plane to the 2008 Mw 7.9 Wenchuan earthquake triggering

The Coulomb failure function (CFF) quantitatively describes static stress changes in secondary faults near the source fault of an earthquake. CFF can be employed to monitor how static stress transfers and then shed some light on the probability of successive events occurring around a source fault. In this paper we focus on the CFF and particularly on optimally oriented planes. We present a unified model to determine an optimally oriented plane and its corresponding Coulomb stress, then apply the model to the 2003 Mw 6.6 Bam (Iran) earthquake and the 2008 Mw 7.9 Wenchuan (China) earthquake, thereby checking its effectiveness. Our results show that spatial correlation between positive Coulomb stress changes and aftershocks are, for the 2003 Bam earthquake, 47.06% when elastic Coulomb stress changes are resolved on uniform planes and 87.53% when these are resolved on optimally oriented planes at depth; for the 2008 Wenchuan earthquake the correlations are 45.68% and 58.20%, respectively. It is recommended that account be taken of optimally oriented planes when drawing a Coulomb stress map for analyzing earthquake triggering effects

Searching for Secluded Dark Matter via Direct Detection of Recoiling Nuclei as well as Low Energy Electrons

Motivated by recent cosmic ray experimental results there has been a proposition for a scenario where a secluded dark matter particle annihilates, primarily, into Standard Model leptons through a low mass mediator particle. We consider several varieties of this scenario depending on the type of mixing among gauge bosons and we study the implications in novel direct dark matter experiments for detecting low energy recoiling electrons. We find significant event rates and time modulation effects, especially in the case where the mediator is massless, that may be complementary to those from recoiling nuclei.Comment: 27 pages, references added, published versio

Single production of the top partners at high energy colliders

The left-right twin $Higgs$ ($LRTH$) model is a concrete realization of the twin $Higgs$ mechanism, which predicts the existence of the top partner $T$. In this paper, we consider production of $T$ associated with the top quark $t$ at the high energy linear $e^{+}e^{-}$ collider ($ILC$) and the $LHC$ experiments, and its single production in future linac-ring type $ep$ collider experiment. To compare our results with those of the littlest $Higgs$ model with $T$-parity, we also estimate production of the $T$-even top partner $T_{+}$ via the corresponding processes in these high energy collider experiments. A simply phenomenological analysis is also given.Comment: 21 pages, 10 figures; to be published in Nucl. Phys.

Phenomenological Aspects of Gauge Mediation with Sequestered Supersymmetry Breaking in light of Dark Matter Detection

In a recent work, a model of gauge mediation with sequestered supersymmetry (SUSY) breaking was proposed. In this model, the mass of the gravitino is O(100) GeV without causing the flavor-changing neutral-current problem. In contrast to traditional gauge mediation, the gravitino is not the lightest SUSY particle and the neutralino is the candidate of the dark matter. In this paper, we investigate phenomenological aspects of this model and discuss the possibility of the direct detection of the dark matter. In particular, we focus on the light neutralino case and find that the light-Higgsino scenario such as the focus point is interesting, taking account of the recent CDMS result.Comment: 17 pages, 8 figures; v2:references added, some corrections; v3:version accepted for publication in JHE