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Strong winds that accentuated a fire outbreak in the western United States in early September of 2020 resulted from an atmospheric wave train that spanned the Pacific Ocean. Days before the atmospheric waves developed in the United States, three western Pacific tropical cyclones (typhoons) underwent an extratropical transition over Korea within an unprecedentedly short span of 12 days. Using a climate diagnostic approach and historical forecast data, it was found that the amplitude of the atmospheric waves accompanying the western U.S. fire weather would not have been so profound if not for the influence of these typhoons. Together, the recurving typhoons provided a significant source of wave activity flux directed toward North America – amplifying the ridge over the U.S. west coast while deepening the trough in central Canada. This anomalous circulation produced the severe frontal system that caused extreme winds in western Oregon, Washington and California – rapidly spreading fire. Plain Language Summary: The weather pattern that contributed to rapidly spreading fires in Oregon in early September 2020 can be traced back to an unexpected source: Three typhoons in the western Pacific that ran into the Korean Peninsula within two weeks of each other. Together, Typhoon Bavi, Typhoon Maysak, and Typhoon Haishen each contained enough energy to perturb the jet stream – creating an atmospheric wave train that enhanced the hot, dry weather of the western United States. This study uses forecast models and weather observations to show that these typhoons amplified areas of high and low pressure in North America leading to the intense winds which rapidly spread fire in Oregon, Washington, and California. While the impacts of climate change on these events were not evaluated in this study, the implication is that the effect of weather extremes that are known to be exasperated by climate warming are not always limited to the region in which those extremes occur. Key points: Three western Pacific typhoons tracked through the Korean peninsula – with sequential landfall within a two‐week period of timeThe diabatic outflow from these typhoons amplified an atmospheric wave train – increasing the pressure gradient over the western U.S.The heightened pressure gradient resulted in strong winds, a key element in the rapid spread of fires in Oregon and California [ABSTRACT FROM AUTHOR]

The 2013 federal Colorado River Basin Water Supply and Demand Study projected the water imbalance between future supply and demand to increase. The Colorado water supply (WS) exemplifies a pronounced quasi-decadal oscillation (QDO) of 10-20 years throughout its historical record; however, this QDO feature is unaccounted for in the climate models used to project the future WS. Adjacent to the Colorado River, the large watershed of the Great Salt Lake (GSL) in Utah records the hydrologicQDOsignal in its water surface, leading previous studies to explore the cause of decadal fluctuations in the lake elevation and assess predictability. This study reports a remarkable coherence between the Colorado WS and the GSL elevation at the 10-20-yr time scale. Analysis of precipitation and terrestrial water storage anomalies suggests a crossbasin connection in the climate and hydrometeorological variations of the Colorado WS and the GSL. The 160-yr-long and well-kept GSL elevation record makes it an effective indicator for the Colorado WS. [ABSTRACT FROM AUTHOR]

Ongoing (2014-16) drought in the state of California has played a major role in the depletion of groundwater. Within California's Central Valley, home to one of the world's most productive agricultural regions, drought and increased groundwater depletion occurs almost hand in hand, but this relationship appears to have changed over the last decade. Data derived from 497 wells have revealed a continued depletion of groundwater lasting a full year after drought, a phenomenon that was not observed in earlier records before the twenty-first century. Possible causes include 1) lengthening of drought associated with amplification in the 4-6-yr drought and El Niño frequency since the late 1990s and 2) intensification of drought and increased pumping that enhances depletion. Altogether, the implication is that current groundwater storage in the Central Valley will likely continue to diminish even further in 2016, regardless of the drought status. [ABSTRACT FROM AUTHOR]

Tropical cyclones ( TCs) leave a cold wake in the sea surface temperature ( SST). In the northwest Pacific, TC activity and SST have both increased since the 1980s, but the extent to which ocean surface warming is affected by the changing TC activity is unknown. Analysis of the 1981-2014 period indicates that the intensified effect of TC cold wakes has offset the SST warming trend by 37% during the typhoon season, implying that the observed SST warming might be underestimated. This factor could affect long-term climate simulations that are forced with prescribed SST. [ABSTRACT FROM AUTHOR]

Severe flooding occurred in Thailand during the 2011 summer season, which resulted in more than 800 deaths and affected 13.6 million people. The unprecedented nature of this flood in the Chao Phraya River basin (CPRB) was examined and compared with historical flood years. Climate diagnostics were conducted to understand the meteorological conditions and climate forcing that led to the magnitude and duration of this flood. Neither the monsoon rainfall nor the tropical cyclone frequency anomalies alone was sufficient to cause the 2011 flooding event. Instead, a series of abnormal conditions collectively contributed to the intensity of the 2011 flood: anomalously high rainfall in the premonsoon season, especially during March; record-high soil moisture content throughout the year; elevated sea level height in the Gulf of Thailand, which constrained drainage; and other water management factors. In the context of climate change, the substantially increased premonsoon rainfall in CPRB after 1980 and the continual sea level rise in the river outlet have both played a role. The rainfall increase is associated with a strengthening of the premonsoon northeasterly winds that come from East Asia. Attribution analysis using phase 5 of the Coupled Model Intercomparison Project historical experiments pointed to anthropogenic greenhouse gases as the main external climate forcing leading to the rainfall increase. Together, these findings suggest increasing odds for potential flooding of similar intensity to that of the 2011 flood. [ABSTRACT FROM AUTHOR]

Because of the geography of a narrow valley and surrounding tall mountains, Cache Valley (located in northern Utah and southern Idaho) experiences frequent shallow temperature inversions that are both intense and persistent. Such temperature inversions have resulted in the worst air quality in the nation. In this paper, the historical properties of Cache Valley's winter inversions are examined by using two meteorological stations with a difference in elevation of approximately 100 m and a horizontal distance apart of ~4.5 km. Differences in daily maximum air temperature between two stations were used to define the frequency and intensity of inversions. Despite the lack of a long-term trend in inversion intensity from 1956 to present, the inversion frequency increased in the early 1980s and extending into the early 1990s but thereafter decreased by about 30% through 2013. Daily mean air temperatures and inversion intensity were categorized further using a mosaic plot. Of relevance was the discovery that after 1990 there was an increase in the probability of inversions during cold days and that under conditions in which the daily mean air temperature was below −15°C an inversion became a certainty. A regression model was developed to estimate the concentration of past particulate matter of aerodynamic diameter ≤ 2.5 μm (PM2.5). The model indicated past episodes of increased PM2.5 concentrations that went into decline after 1990; this was especially so in the coldest of climate conditions. [ABSTRACT FROM AUTHOR]

Longitude-time evolution of sea surface temperature anomalies (SSTA) reveals a slow southeastward propagation from the western North Pacific (WNP) around 20°N to the Niño-3.4 region in the equatorial Central Pacific. The propagation is manifested as a narrow, southwest-northeast oriented SSTA band across the subtropical North Pacific, and its journey takes about 2-3 years. The propagating SSTA appears to engage the initiation of the El Niño-Southern Oscillation (ENSO). The anomalies of surface winds, sea level pressure, outgoing longwave radiation, and velocity potential all exhibit a concurrent and distinct eastward propagation, one that appears to be circumglobal and is coupled with the predominant 4-5 year frequency of the ENSO cycle. It is suggested that the previously found warming/cooling in the Indian Ocean induced by El Niño/La Niña, the progressive SSTA and wind anomalies across the Indian Ocean towards the WNP, and the predominant 4-5-year frequency of the North Pacific Oscillation collectively contribute to the reported SSTA propagation . The findings implicate that monitoring the SSTA propagation from the WNP towards the tropical central Pacific could be useful in tracking the ENSO development. [ABSTRACT FROM AUTHOR]

The present study examines the current research on how socio-economic factors affect the decision-making process and adoption of agricultural technologies by farmers in crop production scheduling. It reviews existing literature to identify gaps in knowledge and determine the most relevant factors influencing crop production in Northwest India from 2016 to 2021. The study finds that socio-economic factors, such as education, age, awareness and financial limitations, significantly impact farmers' decision-making when it comes to crop planning. Additionally, societal issues like politics and religion also influence crop output. The study suggests that government policies and subsidies can help improve farmers' livelihoods, and effective communication from agricultural scientists can encourage the adoption of affordable and environmentally friendly production technologies. However, the study emphasizes the need for more primary data to address socio-economic constraints in intervention efforts. [ABSTRACT FROM AUTHOR]

After endocytosis, transmembrane cargo reaches endosomes, where it encounters complexes dedicated to opposing functions: recycling and degradation. Microdomains containing endosomal sorting complexes required for transport (ESCRT)-0 component Hrs [hepatocyte growth factor-regulated tyrosine kinase substrate (HGRS-1) in Caenorhabditis elegans]mediate cargo degradation, concentrating ubiquitinated cargo and organizing the activities of ESCRT. At the same time, retromer associated sorting nexin one (SNX-1) and its binding partner, J-domain protein RME-8, sort cargo away from degradation, promoting cargo recycling to the Golgi. Thus, we hypothesized that there could be important regulatory interactions between retromer and ESCRT that balance degradative and recycling functions. Taking advantage of the naturally large endosomes of the C. elegans coelomocyte, we visualized complementary ESCRT-0 and RME-8/SNX-1 microdomains in vivo and assayed the ability of retromer and ESCRT microdomains to regulate one another. We found in snx-1(0) and rme-8(ts) mutants increased endosomal coverage and intensity of HGRS-1-labeled microdomains, as well as increased total levels of HGRS-1 bound to membranes. These effects are specific to SNX-1 and RME-8, as loss of other retromer components SNX-3 and vacuolar protein sorting-associated protein 35 (VPS-35) did not affect HGRS-1 microdomains. Additionally, knockdown of hgrs-1 had little to no effect on SNX-1 and RME-8microdomains, suggesting directionality to the interaction. Separation of the functionally distinct ESCRT-0 and SNX-1/RME-8 microdomains was also compromised in the absence of RME-8 and SNX-1, a phenomenonwe observed to be conserved, as depletion of Snx1 and Snx2 in HeLa cells also led to greater overlap of Rme-8 and Hrs on endosomes. [ABSTRACT FROM AUTHOR]

Summary Predicting lake level fluctuations of the Great Salt Lake (GSL) in Utah – the largest terminal salt-water lake in the Western Hemisphere – is critical from many perspectives. The GSL integrates both climate and hydrological variations within the region and is particularly sensitive to low-frequency climate cycles. Since most hydroclimate variable records cover less than a century, forecasting the predominant yet under-represented decadal variability of the GSL level with such relatively short instrumental records poses a challenge. To overcome data limitations, this study assesses two options: (1) developing a model using the observational GSL elevation record of 137 years to predict itself; (2) incorporating the recently reconstructed GSL elevation that utilized 576 years worth of tree-ring records into the predictive model. It was found that the statistical models that combined the tree-ring reconstructed data with the observed data outperformed those that did not, in terms of reducing the root mean squared errors. Such predictive models can serve as a means toward practical water risk management. [ABSTRACT FROM AUTHOR]

In this study we investigated how different dimensions of service quality might influence the loyalty of customers in the context of online games. By studying the gamers of massively multiplayer online role-playing games (MMORPGs), we tested our hypotheses using structural equation modeling techniques. We found that the service quality dimensions of privacy, effectiveness, and entertainment indirectly influence the loyalty of gamers through satisfaction, whereas interaction has a direct effect on their loyalty. These findings have implications for online game companies to improve customers' loyalty. [ABSTRACT FROM AUTHOR]

Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor β (TGFβ)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector β-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf. [ABSTRACT FROM AUTHOR]

Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents. The hierarchical filters in the pipeline (i.e., similarity search, a pharmacophore model, a shape-based model, and molecular docking) rendered 13 potential hits from Specs chemical library. By using PC12 cells (exposed to rotenone) as a cell model for bioassay, we first identified that AK-918/42829299, AN-465/41520984, and AT-051/43421517 were able to protect PC12 cells from rotenone-induced cell death. Molecular docking suggested these hit compounds were likely to bind to hPgk1 in a similar mode to terazosin. In summary, we not only present a versatile VS pipeline for potential apoptosis inhibitors discovery, but also provide three novel-scaffold hit compounds that are worthy of further development and biological study. [ABSTRACT FROM AUTHOR]

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive "flexible docking", as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way. [ABSTRACT FROM AUTHOR]

Background: A major barrier to effective treatment of glioblastoma multiforme (GBM) is the invasion of glioma cells into the brain parenchyma rendering local therapies such as surgery and radiation therapy ineffective. GBM patients with such highly invasive and infiltrative tumors have poor prognosis with a median survival time of only about a year. However, the mechanisms leading to increased cell migration, invasion and diffused behavior of glioma cells are still poorly understood. Methods: In the current study, we applied quantitative proteomics for the identification of differentially expressed proteins in GBMs as compared to non-malignant brain tissues. Results: Our study led to the identification of 23 proteins showing overexpression in GBM; these include membrane proteins, moesin and CD44. The results were verified using Western blotting and immunohistochemistry in independent set of GBM and non-malignant brain tissues. Both GBM tissues and glioma cell lines (U87 / U373) demonstrated membranous expression of moesin and CD44, as revealed by immunohistochemistry and immunofluorescence, respectively. Notably, glioma cells transfected with moesin siRNA displayed reduced migration and invasion on treatment with hyaluronan (HA), an important component of the extracellular matrix in GBM. CD44, a transmembrane glycoprotein, acts as a major receptor for hyaluronan (HA). Using co-immunoprecipitation assays, we further demonstrated that moesin interacts with CD44 in glioma cells only after treatment with HA; this implicates a novel role of moesin in HA-CD44 signaling in gliomas. Conclusions: Our results suggest that development of inhibitors which interfere with CD44-moesin interactions may open a new avenue in the future to mitigate cellular migration in gliomas. [ABSTRACT FROM AUTHOR]

Structure-based drug design relies on static protein structures despite significant evidence for the need to include protein dynamics as a serious consideration. In practice, dynamic motions are neglected because they are not under- stood well enough to model, a situation resulting from a lack of explicit exprimental examples of dynamic receptor-ligand complexes. Here, we report high-resolution details of pro- nounced -4 ms time scale motions of a receptor-small molecule complex using a combination of NMR and X-ray crystallography. Large conformational dynamics in Escherichia coli dihydrofolatereductase are driven by internal switching motions of the drug-like, nanomolar-aflinity inhibitor. Carr-Purcell-Meiboom-Gill relaxation dispersion experiments and NOEs revealed the crystal structure to contain critical elements of the high energy protein-ligand conformation. The availability of accurate, structurally resolved dynamics in a protein-ligand complex should serve as a valuable benchmark for modeling dynamics in other receptor-ligand complexes and prediction of binding affinities. reductase are driven by internal switching motions of the drug-like, nanomolar-aflinity inhibitor. Carr-Purcell-Meiboom-Gill relaxation dispersion experiments and NOEs revealed the crystal structure to contain critical elements of the high energy protein-ligand conformation. The availability of accurate, structurally resolved dynamics in a protein-ligand complex should serve as a valuable benchmark for modeling dynamics in other receptor-ligand complexes and prediction of binding affinities. [ABSTRACT FROM AUTHOR]