Evolution of Risk Aversion over Five Years after a Major Natural Disaster.

The impact of exposure to a major unanticipated natural disaster on the evolution of survivors' attitudes toward risk is examined, exploiting plausibly exogenous variation in exposure to the 2004 Indian Ocean tsunami in combination with rich population-representative longitudinal survey data spanning the five years after the tsunami. Respondents chose among pairs of hypothetical income streams. Those directly exposed to the tsunami made choices consistent with greater willingness to take on risk relative to those not directly exposed to the tsunami. These differences are short-lived: starting a year later, there is no evidence of differences in willingness to take on risk between the two groups. These conclusions hold for tsunami-related exposures measured at the individual and community level. Apparently, tsunami survivors were inclined to assume greater financial risk in the short-term while rebuilding their lives after the disaster.

The effects of fiscal policy on households during the COVID-19 pandemic: Evidence from Thailand and Vietnam.

The economic crisis created by the COVID-19 pandemic induced many governments to provide financial assistance to households. Using representative consumer surveys conducted during the pandemic in 2020, we examine the effects of this fiscal policy instrument on households in two emerging economies, Thailand and Vietnam. Our paper contributes to the literature by studying how consumer sentiment and durable spending relate to receiving government financial support and the underlying transmission channels for these responses. We find that financial support to households is related to more positive consumer sentiment and increases in actual and planned durable spending, while also being correlated with a more optimistic macroeconomic outlook, higher trust in the government, and higher personal well-being.

Food Consumption and Food Security during the COVID-19 Pandemic in Addis Ababa.

International humanitarian organizations have expressed substantial concern about the potential for increases in food insecurity resulting from the COVID-19 pandemic. We use a unique panel survey of a representative sample households in Addis Ababa to study both food security and food consumption during the pandemic. In contrast to some other countries in the region, Ethiopia never went into a full lockdown severely restricting movement. Despite subjective income measures suggesting a large proportion of households have been exposed to job loss or reduced incomes, we find that relative to a survey conducted in August and September of 2019, food consumption and household dietary diversity are largely unchanged or slightly increased by August 2020. We find some changes in the composition of food consumption, but they are not related to shocks found in previous phone surveys conducted with the same households. The results therefore suggest the types of subjective questions about income typically being asked in COVID-19 phone surveys may not appropriately reflect the magnitude of such shocks. They also imply, at least indirectly, that in the aggregate food value chains have been resilient to the shock associated with the pandemic.

Would A National Sugar-Sweetened Beverage Tax In The United States Be Well Targeted?

Sugar-sweetened beverage (SSB) taxes have been proposed to discourage excessive sugar consumption, but it is unclear how high- vs. low-SSB purchasers respond to such taxes. We first examine heterogeneity in the purchase and financial effects of a national SSB tax across different types of households buying varying amounts of SSBs. We find high-SSB purchasers are less responsive to SSB price changes than low purchasers but make larger absolute reductions in SSB purchases in response to the tax, given their notably greater purchase levels prior to the tax. Nonetheless, the economic burden of the tax falls more heavily on high-SSB purchasers who are more likely comprised of lower-income households. We then investigate whether the income regressivity of the tax will be mitigated if low-income households are targeted by fruit and vegetable (FV) subsidies. We show that depending on the tax pass-through and subsidy rates, FV subsidies can fully offset high-SSB purchasers' tax burdens, and subsidy transfers are distributed relatively uniformly across the SSB purchase distribution of low-income households. Therefore, FV subsidy transfers would be financially more beneficial to low- and moderate-SSB purchasers because they bear smaller shares of the tax burden than high-SSB purchasers.

The transcription factor MML4_D12 regulates fiber development through interplay with the WD40-repeat protein WDR in cotton.

In planta, a vital regulatory complex, MYB-basic helix-loop-helix (bHLH)-WD40 (MBW), is involved in trichome development and synthesis of anthocyanin and proanthocyanin in Arabidopsis. Usually, WD40 proteins provide a scaffold for protein-protein interaction between MYB and bHLH proteins. Members of subgroup 9 of the R2R3 MYB transcription factors, which includes MYBMIXTA-Like (MML) genes important for plant cell differentiation, are unable to interact with bHLH. In this study, we report that a cotton (Gossypium hirsutum) seed trichome or lint fiber-related GhMML factor, GhMML4_D12, interacts with a diverged WD40 protein (GhWDR) in a process similar to but different from that of the MBW ternary complex involved in Arabidopsis trichome development. Amino acids 250-267 of GhMML4_D12 and the first and third WD40 repeat domains of GhWDR determine their interaction. GhWDR could rescue Arabidopsis ttg1 to its wild type, confirming its orthologous function in trichome development. Our findings shed more light towards understanding the key role of the MML and WD40 families in plants and in the improvement of cotton fiber production.

Gant61 ameliorates CCl4-induced liver fibrosis by inhibition of Hedgehog signaling activity.

As an intercellular signaling molecule, Hedgehog (Hh) plays a critical role in liver fibrosis/regeneration. Transcription effectors Gli1 and Gli2 are key components of the Hh signaling pathway. However, whether inhibition of Gli1/2 activity can affect liver fibrogenesis is largely unknown. In the present study, we investigated the effect of Gant61 (a Gli1/2 transcription factor inhibitor) on liver fibrosis and its possible mechanism. Wild-type and Shh-EGFP-Cre male mice were exposed to CCl4, and then treated with or without Gant61 for four weeks. The level of liver injury/fibrosis and expression levels of mRNA and protein related to the Hh ligand/pathway were assessed. In our study, CCl4 treatment induced liver injury/fibrosis and promoted activation of hepatic stellate cells (HSCs). In addition, CCl4 induced the expression of Shh ligands in and around the fibrotic lesion, accompanied by induction of mRNA and protein expression of Hh components (Smo, Gli1 and Gli2). However, administration of Gant61 decreased liver fibrosis by reduction in HSC number, down-regulation of mRNA and protein expression of Hh components (Smo, Gli1 and Gli2), and cell-cycle arrest of HSCs. Our data highlight the importance of the Shh pathway for the development of liver fibrosis, and also suggest Glis as potential therapeutic targets for the treatment of liver fibrosis.

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway.

Microglia-mediated neuroinflammation is a crucial risk factor for neurological disorders. Recently, dopamine receptors have been found to be involved in multiple immunopathological processes and considered as valuable therapeutic targets for inflammation-associated neurologic diseases. In this study we investigated the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound isolated from medicinal plant Murraya exotica. We showed that isosibiricin (10-50 µM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). By using transcriptomics coupled with bioinformatics analysis, we revealed that isosibiricin treatment mainly affect dopamine receptor signalling pathway. We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 µM) or sultopride (1 µM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1ß. Collectively, this study demonstrates a promising therapeutic strategy for neuroinflammation by targeting dopamine D1/2 receptors.

Scanner Data-Based Panel Price Indexes.

We construct panel price indexes using retail scanner data that allow comparisons of consumption cost across space and time. Two types of panel indexes are examined: the rolling-window panel extensions of the multilateral Cave-Christensen-Diewert (CCD) index with the Törnqvist index as its elements, and of the multilateral Gini-Eltetö-Köves-Szulc (GEKS) index using the Fisher ideal index as its elements. The rolling window method maintains the nonrevisability of published index numbers while it allows index numbers for new periods and locations be calculated and the basket of items be updated. Meanwhile, the multilateral structure of price comparison eliminates significant downward drift in standard chained indexes. Using county-level bilateral and panel indexes based on retail beverage scanner data, we experimentally adjust for purchasing parity the portion of Supplemental Nutrition Assistance Program (SNAP) benefits that participants spend on beverages. Accounting for temporal and spatial cost differences causes over 2% of SNAP allotment spent on beverages be reallocated, or approximately a 5% change in allotment on average for a county. About 90% of the relocated SNAP fund is to adjust for spatial differences in food cost. We also compare SNAP allotments implied by the retail scanner data indexes with those implied by indexes based on the USDA Quarterly Food-at-Home Price Database (QFAHPD). The treatment of unit values and product quality may have contributed to the significant differences observed between the retail scanner data indexes and the QFAHPD indexes.

Modeling household energy consumption and adoption of energy efficient technology.

This study develops a model to study household energy use behavior that can impose common preferences for feasible demand estimation with multiple discrete technology choices and multiple continuous energy consumption uses. The model imposes fixed proportions production and additivity of uses for plausible estimation feasibility while adopting a second-order translog flexible functional form to focus on flexibility in identification of consumer preferences that determine interactions among energy uses and between short-run and long-run choices. Using a unique household-level dataset from California, the model is applied to estimate short-run household demand for electricity and natural gas and the long-run technology choices with respect to clothes washing, water heating, space heating, and clothes drying. The estimation results support commonality of underlying preferences except in one case that is explained by an unavailable variable.

One plus one can be greater than two: Evaluating synergies of development programmes in Malawi.

This paper investigates the interplay between the Social Cash Transfer Programme (SCTP) and the Farm Input Subsidy Programme (FISP) in Malawi. We take advantage of data collected from a seventeen-month evaluation of a sample of households eligible to receive SCTP, which also provided information about inclusion into FISP. We estimate two types of synergies: i) the complementarity between SCTP and FISP, i.e. whether the impact of both interventions run together is larger than the sum of the impacts of these interventions when run separately, and ii) the incremental impact of receiving FISP when a household already receives SCTP, as well as the incremental impact of receiving SCTP when a household already receives FISP. The analysis shows that there are synergies between the two policy interventions, mainly in terms of incremental impact of each programme over the other, in increasing expenditure, agricultural production and livestock.

Adaptations to climate-mediated selective pressures in sheep.

Following domestication, sheep (Ovis aries) have become essential farmed animals across the world through adaptation to a diverse range of environments and varied production systems. Climate-mediated selective pressure has shaped phenotypic variation and has left genetic "footprints" in the genome of breeds raised in different agroecological zones. Unlike numerous studies that have searched for evidence of selection using only population genetics data, here, we conducted an integrated coanalysis of environmental data with single nucleotide polymorphism (SNP) variation. By examining 49,034 SNPs from 32 old, autochthonous sheep breeds that are adapted to a spectrum of different regional climates, we identified 230 SNPs with evidence for selection that is likely due to climate-mediated pressure. Among them, 189 (82%) showed significant correlation (P ≤ 0.05) between allele frequency and climatic variables in a larger set of native populations from a worldwide range of geographic areas and climates. Gene ontology analysis of genes colocated with significant SNPs identified 17 candidates related to GTPase regulator and peptide receptor activities in the biological processes of energy metabolism and endocrine and autoimmune regulation. We also observed high linkage disequilibrium and significant extended haplotype homozygosity for the core haplotype TBC1D12-CH1 of TBC1D12. The global frequency distribution of the core haplotype and allele OAR22_18929579-A showed an apparent geographic pattern and significant (P ≤ 0.05) correlations with climatic variation. Our results imply that adaptations to local climates have shaped the spatial distribution of some variants that are candidates to underpin adaptive variation in sheep.

Healthcare Demand in the Presence of Discrete Price Changes.

Deductibles in health insurance generate nonlinear budget sets and dynamic incentives. Using detailed individual health expenditure data from a Swiss health insurer, we estimate the response in healthcare demand to the discrete price increase generated by resetting the deductible at the start of each calendar year. We find that for individuals with high deductibles, healthcare demand drops by 27%. The decrease is most pronounced for inpatient care and prescription drugs. By contrast, for individuals with low deductibles, there is no significant change in healthcare demand (except for prescription drugs). Overall our results suggest that healthy individuals respond much stronger to the price change.

Detailed characterization of Act d 12 and Act d 13 from kiwi seeds: implication in IgE cross-reactivity with peanut and tree nuts.

BACKGROUND: Act d 12 (11S globulin) and Act d 13 (2S albumin) are two novel relevant allergens from kiwi seeds that might be useful to improve the diagnostic sensitivity and the management of kiwifruit-allergic patients. OBJECTIVE: To perform a comprehensive structural and immunological characterization of purified Act d 12 and Act d 13 from kiwi seeds. METHODS: Sera from 55 well-defined kiwifruit-allergic patients were used. Act d 12 and Act d 13 were purified by chromatographic procedures. Circular dichroism, mass spectrometry, concanavalin A detection, immunoblotting, enzyme-linked immunosorbent assays, basophil activation tests, and IgE-inhibition experiments were used. RESULTS: Act d 12 and Act d 13 were purified from kiwi seeds to homogeneity by combining size-exclusion, ion-exchange, and RP-HPLC chromatographies. Both purified allergens preserve the structural integrity and display typical features of their homologous counterparts from the 11S globulin and 2S albumin protein families, respectively. These allergens are released from kiwi seeds after oral and gastric digestion of whole kiwifruit, demonstrating their bioavailability after ingestion. The allergens retain the capacity to bind serum IgE from kiwifruit-allergic patients, induce IgE cross-linking in effector-circulating basophils, and display in vitro IgE cross-reactivity with homologous counterparts from peanut and tree nuts. CONCLUSION: Purified Act d 12 and Act d 13 from kiwi seeds are well-defined molecules involved in in vitro IgE cross-reactivity with peanut and tree nuts. Their inclusion in component-resolved diagnosis of kiwifruit allergy might well contribute to improve the diagnostic sensitivity and the management of kiwifruit-allergic patients.

Can price get the monkey off our back? A meta-analysis of illicit drug demand.

Because of the increased availability of price data over the past 15 years, several studies have estimated the demand for illicit drugs, providing 462 estimates of the price elasticity. Results from estimating several meta-regressions reveal that these price elasticity estimates are influenced by a number of study characteristics. For instance, the price elasticity differs across drugs, with its absolute value being smallest for marijuana, compared with cocaine and heroin. Furthermore, price elasticity estimates are sensitive to whether demand is modeled in the short-run or the long-run, measures of quantity and price, whether or not alcohol and other illicit drugs are included in the specification of demand, and the location of demand. However, a number of other factors, including the functional form of demand, several specification issues, the type of data and method used to estimate demand, and the quality of the publication outlet, have less influence on the price elasticity.

Non-Invasive Delivery of Negatively Charged Nanobodies by Anodal Iontophoresis: When Electroosmosis Dominates Electromigration.

Iontophoresis enables the non-invasive transdermal delivery of moderately-sized proteins and the needle-free cutaneous delivery of antibodies. However, simple descriptors of protein characteristics cannot accurately predict the feasibility of iontophoretic transport. This study investigated the cathodal and anodal iontophoretic transport of the negatively charged M7D12H nanobody and a series of negatively charged variants with single amino acid substitutions. Surprisingly, M7D12H and its variants were only delivered transdermally by anodal iontophoresis. In contrast, transdermal permeation after cathodal iontophoresis and passive diffusion was

A(1) and A(3) adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes.

Adenosine (Ado) exerts neuroprotective and anti-inflammatory functions by acting through four receptor subtypes A1, A2A, A2B and A3. Astrocytes are one of its targets in the central nervous system. Hypoxia-inducible factor-1 (HIF-1), a master regulator of oxygen homeostasis, is induced after hypoxia, ischemia and inflammation and plays an important role in brain injury. HIF-1 is expressed by astrocytes, however the regulatory role played by Ado on HIF-1α modulation induced by inflammatory and hypoxic conditions has not been investigated. Primary murine astrocytes were activated with lipopolysaccharide (LPS) with or without Ado, Ado receptor agonists, antagonists and receptor silencing, before exposure to normoxia or hypoxia. HIF-1α accumulation and downstream genes regulation were determined. Ado inhibited LPS-increased HIF-1α accumulation under both normoxic and hypoxic conditions, through activation of A1 and A3 receptors. In cells incubated with the blockers of p44/42 MAPK and Akt, LPS-induced HIF-1α accumulation was significantly decreased in normoxia and hypoxia, suggesting the involvement of p44/42 MAPK and Akt in this effect and Ado inhibited kinases phosphorylation. A series of angiogenesis and metabolism related genes were modulated by hypoxia in an HIF-1 dependent way, but not further increased by LPS, with the exception of GLUT-1 and hexochinase II that were elevated by LPS only in normoxia and inhibited by Ado receptors. Instead, genes involved in inflammation, like inducible nitric-oxide synthase (iNOS) and A2B receptors, were increased by LPS in normoxia, strongly stimulated by LPS in concert with hypoxia and inhibited by Ado, through A1 and A3 receptor subtypes. In conclusion A1 and A3 receptors reduce the LPS-mediated HIF-1α accumulation in murine astrocytes, resulting in a downregulation of genes involved in inflammation and hypoxic injury, like iNOS and A2B receptors, in both normoxic and hypoxic conditions.

Enhanced binding to and killing of hepatocellular carcinoma cells in vitro by melittin when linked with a novel targeting peptide screened from phage display.

A random phage 12-mer peptide library and a whole-cell subtractive biopanning protocol against HepG2 cells were used to select a novel peptide-specific binding to hepatocellular carcinoma cells. As a result, peptide SLSLITMLKISR (AM-2) was screened as a novel homing peptide to hepatocellular carcinoma cells, tested by immunofluorescence and immunochemistry assays. Subsequently, peptide AM-2 was linked to melittin by A(EAAAK)2A, and the antitumor effect of this ligation product was detected by MTT assay, fluorescence-activated cell sorting, and scanning electron microscopy methods. Results of cell growth inhibition tests confirmed that the affinity of melittin was increased after being incorporated into AM-2, and AM-2-melittin specifically targeted and killed HepG2 cells in vitro. Thus, AM-2 is a valuable ligand for tumor targeting, which leads to increased binding and killing effect of hepatocellular carcinoma cells in vitro when ligated to melittin, and AM-2-melittin has a clinical potential application as target agents for the treatment of human hepatocellular carcinoma.

Green Tea Epigallocatechin Gallate Inhibits Preadipocyte Growth via the microRNA-let-7a/HMGA2 Signaling Pathway.

SCOPE: This study investigates the effect of epigallocatechin gallate (EGCG) on white and beige preadipocyte growth and explores the involvement of the miR-let-7a/HMGA2 pathway. METHODS AND RESULTS: 3T3-L1 and D12 cells are treated with EGCG. The effect of EGCG on cell proliferation and viability is evaluated, as well as microRNA (miRNA)-related signaling pathways. EGCG inhibits 3T3-L1 and D12 preadipocyte growth, upregulates miR-let-7a expression, and downregulates high-mobility group AT-hook 2 (HMGA2) mRNA and protein levels in a time- and dose-dependent manner. In addition, overexpression of miR-let-7a significantly inhibits the growth of 3T3-L1 and D12 cells and decreases HMGA2 mRNA and protein levels. MiR-let-7a inhibitor antagonizes the inhibitory effects of EGCG on the number and viability of 3T3-L1 and D12 cells. Furthermore, miR-let-7a inhibitor reverses the EGCG-induced increase in miR-let-7a expression levels and decrease in HMGA2 mRNA and protein levels. HMGA2 overexpression induces an increase in cell number and viability and antagonizes EGCG-suppressed cell growth and HMGA2 expression in 3T3-L1 and D12 preadipocytes. CONCLUSION: EGCG inhibits the growth of 3T3-L1 and D12 preadipocytes by modulating the miR-let-7a and HMGA2 pathways.

Identification of pyrrolo[3',4':3,4]cyclohepta[1,2-d][1,2]oxazoles as promising new candidates for the treatment of lymphomas.

Unsatisfactory outcomes for relapsed/refractory lymphoma patients prompt continuing efforts to develop new therapeutic strategies. Our previous studies on pyrrole-based anti-lymphoma agents led us to synthesize a new series of twenty-six pyrrolo[3',4':3,4]cyclohepta[1,2-d] [1,2]oxazole derivatives and study their antiproliferative effects against a panel of four non-Hodgkin lymphoma cell lines. Several candidates showed significant anti-proliferative effects, with IC50's reaching the sub-micromolar range in at least one cell line, with compound 3z demonstrating sub-micromolar growth inhibitory effects towards the entire panel. The VL51 cell line was the most sensitive, with an IC50 value of 0.10 µM for 3z. Our earlier studies had shown that tubulin was a prominent target of many of our oxazole derivatives. We therefore examined their effects on tubulin assembly and colchicine binding. While 3u and 3z did not appear to target tubulin, good activity was observed with 3d and 3p. Molecular docking and molecular dynamics simulations allowed us to rationalize the binding mode of the synthesized compounds toward tubulin. All ligands exhibited a better affinity for the colchicine site, confirming their specificity for this binding pocket. In particular, a better affinity and free energy of binding was observed for 3d and 3p. This result was confirmed by experimental data, indicating that, although both 3d and 3p significantly affected tubulin assembly, only 3d showed activity comparable to that of combretastatin A-4, while 3p was about 4-fold less active. Cell cycle analysis showed that compounds 3u and especially 3z induced a block in G2/M, a strong decrease in S phase even at low compound concentrations and apoptosis through the mitochondrial pathway. Thus, the mechanism of action of 3u and 3z remains to be elucidated. Very high selectivity toward cancer cells and low toxicity in human peripheral blood lymphocytes were observed, highlighting the good potential of these agents in cancer therapy and encouraging further exploration of this compound class to obtain new small molecules as effective lymphoma treatments.

Genetic identification of the pleiotropic gene Tasg-D1/2 affecting wheat grain shape by regulating brassinolide metabolism.

Improving yield potential is a major goal of wheat breeding that depends on identifying key genetic loci. In this study, two residual heterozygous line RHL351- and RHL78-derived populations were employed for genetic linkage map construction and QTL detection. Two genetic populations indicated a robust grain-size QTL between Marker6 and Marker10. It covered a 95.54-99.38 Mb physical interval and was named Qpleio.nwafu.3D, containing the candidate gene Tasg (TraesCS3D02G137200). Intriguingly, RNA-seq analysis and sequencing revealed two different allelic variants in Tasg, named Tasg-D1 (G>A) and Tasg-D2 (C>G), respectively. Although the relationship between Tasg-D1 and grain size had been demonstrated previously, here we provided the first genetic evidence that C/G allelic variation in Tasg-D2 was associated with grain shape and size through a newly developed dCAPS marker. In addition, transcriptome comparison indicated that Tasg-D1/2 might primarily contribute to significant expression differences in brassinolide (BR) metabolism-related genes rather than those related to BR responses in developing grains and spikes. Our study provided new evidence and a breeder-friendly dCAPS marker for improving grain size through the selection of Tasg, as well as a basis to understand Tasg function in the future.