Overexpression of Arabidopsis FLOWERING LOCUS T (FT) gene improves floral development in cassava (Manihot esculenta, Crantz)

Cassava is a tropical storage-root crop that serves as a worldwide source of staple food for over 800 million people. Flowering is one of the most important breeding challenges in cassava because in most lines flowering is late and non-synchronized, and flower production is sparse. The FLOWERING LOCUS T (FT) gene is pivotal for floral induction in all examined angiosperms. The objective of the current work was to determine the potential roles of the FT signaling system in cassava. The Arabidopsis thaliana FT gene (atFT) was transformed into the cassava cultivar 60444 through Agrobacterium-mediated transformation and was found to be overexpressed constitutively. FT overexpression hastened flower initiation and associated fork-type branching, indicating that cassava has the necessary signaling factors to interact with and respond to the atFT gene product. In addition, overexpression stimulated lateral branching, increased the prolificacy of flower production and extended the longevity of flower development. While FT homologs in some plant species stimulate development of vegetative storage organs, atFT inhibited storage-root development and decreased root harvest index in cassava. These findings collectively contribute to our understanding of flower development in cassava and have the potential for applications in breeding

Human-correlated genetic HCC models identify combination therapy for precision medicine [Pre-print]

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer related mortality worldwide. HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulated progressive driver mutations, with hepatocytes the most likely cell of origin. However, the landscape of driver mutations in HCC is independent of the underlying aetiologies. Despite an increasing range of systemic treatment options for advanced HCC outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations. Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC. We generated over twenty-five new genetically-driven in vivo and in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance, and metastasis to distant organs. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with histopathology. In a proof-of-principle analysis, we verified response to standard of care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not been linked to HCC treatment before. Cladribine acts in a highly effective subtype-specific manner in combination with standard of care therapy

Statistical Analysis of Choice Experiments and Surveys

Measures of households' past behavior, their expectations with respect to future events and contingencies, and their intentions with respect to future behavior are frequently collected using household surveys. These questions are conceptually difficult. Answering them requires elaborate cognitive and social processes, and often respondents report only their “best” guesses and/or estimates, using more or less sophisticated heuristics. A large body of literature in psychology and survey research shows that as a result, responses to such questions may be severely biased. In this paper, (1) we describe some of the problems that are typically encountered, (2) provide some empirical illustrations of these biases, and (3) develop a framework for conceptualizing survey response behavior and for integrating structural models of response behavior into the statistical analysis of the underlying economic behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47001/1/11002_2005_Article_5884.pd

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effects of excess corticosterone on LKB1 and AMPK signaling in rat skeletal muscle

Cushing's syndrome is characterized by marked central obesity and insulin insensitivity, effects opposite those seen with chronic AMP-activated protein kinase (AMPK) activation. This study was designed to determine whether chronic exposure to excess glucocorticoids influences LKB1/AMPK signaling in skeletal muscle. Corticosterone pellets were implanted subcutaneously in rats (hypercorticosteronemia, Hypercort) for 2 wk. Controls were sham operated and fed ad libitum or were sham operated and food restricted (pair-weighted group, Pair) to produce body weights similar to Hypercort rats. At the end of the 2-wk treatment period, rats were anesthetized, and the right gastrocnemius-plantaris (gastroc) and soleus muscles were removed. Left muscles were removed after electrical stimulation for 5 min. No significant differences were noted between treatment groups in ATP, creatine phosphate, or LKB1 activity. The α- and β-subunit isoforms were not significantly influenced in gastroc by corticosterone treatment. Expression of the γ3-subunit decreased, and γ1- and γ2-subunit expression increased. Both α2-AMPK and α1-AMPK activities were increased in the gastroc in response to electrical stimulation, but the magnitude of the increase was less for α2 in the Hypercort rats. Despite elevated plasma insulin and elevated plasma leptin in the Hypercort rats, phosphorylation of TBC1D1 was lower in both resting and stimulated muscle compared with controls. Malonyl-CoA content was elevated in gastroc muscles of resting Hypercort rats. These changes in response to excess glucocorticoids could be responsible, in part, for the decrease in insulin sensitivity and adiposity seen in Cushing's syndrome

Rubrene-Based Single-Crystal Organic Semiconductors: Synthesis, Electronic Structure, and Charge-Transport Properties

Correlations among the molecular structure, crystal structure, electronic structure, and charge-carrier transport phenomena have been derived from six congeners (<b>2</b>–<b>7</b>) of rubrene (<b>1</b>). The congeners were synthesized via a three-step route from known 6,11-dichloro-5,12-tetracenedione. After crystallization, their packing structures were solved using single-crystal X-ray diffraction. Rubrenes <b>5</b>–<b>7</b> maintain the orthorhombic features of the parent rubrene (<b>1</b>) in their solid-state packing structures. Control of the packing structure in <b>5</b>–<b>7</b> provided the first series of systematically manipulated rubrenes that preserve the π-stacking motif of <b>1</b>. Density functional theory calculations were performed at the B3LYP/6-31G­(d,p) level of theory to evaluate the geometric and electronic structure of each derivative and reveal that key properties of rubrene (<b>1</b>) have been maintained. Intermolecular electronic couplings (transfer integrals) were calculated for each derivative to determine the propensity for charge-carrier transport. For rubrenes <b>5</b>–<b>7</b>, evaluations of the transfer integrals and periodic electronic structures suggest these derivatives should exhibit transport characteristics equivalent to, or in some cases improved on, those of the parent rubrene (<b>1</b>), as well as the potential for ambipolar behavior. Single-crystal field-effect transistors were fabricated for <b>5</b>–<b>7</b>, and these derivatives show ambipolar transport as predicted. Although device architecture has yet to be fully optimized, maximum hole (electron) mobilities of 1.54 (0.28) cm² V^–1 s^–1 were measured for rubrene <b>5</b>. This work lays a foundation to improve our understanding of charge-carrier transport phenomena in organic single-crystal semiconductors through the correlation of designed molecular and crystallographic changes to electronic and transport properties

Rubrene-Based Single-Crystal Organic Semiconductors: Synthesis, Electronic Structure, and Charge-Transport Properties

Correlations among the molecular structure, crystal structure, electronic structure, and charge-carrier transport phenomena have been derived from six congeners (<b>2</b>–<b>7</b>) of rubrene (<b>1</b>). The congeners were synthesized via a three-step route from known 6,11-dichloro-5,12-tetracenedione. After crystallization, their packing structures were solved using single-crystal X-ray diffraction. Rubrenes <b>5</b>–<b>7</b> maintain the orthorhombic features of the parent rubrene (<b>1</b>) in their solid-state packing structures. Control of the packing structure in <b>5</b>–<b>7</b> provided the first series of systematically manipulated rubrenes that preserve the π-stacking motif of <b>1</b>. Density functional theory calculations were performed at the B3LYP/6-31G­(d,p) level of theory to evaluate the geometric and electronic structure of each derivative and reveal that key properties of rubrene (<b>1</b>) have been maintained. Intermolecular electronic couplings (transfer integrals) were calculated for each derivative to determine the propensity for charge-carrier transport. For rubrenes <b>5</b>–<b>7</b>, evaluations of the transfer integrals and periodic electronic structures suggest these derivatives should exhibit transport characteristics equivalent to, or in some cases improved on, those of the parent rubrene (<b>1</b>), as well as the potential for ambipolar behavior. Single-crystal field-effect transistors were fabricated for <b>5</b>–<b>7</b>, and these derivatives show ambipolar transport as predicted. Although device architecture has yet to be fully optimized, maximum hole (electron) mobilities of 1.54 (0.28) cm² V^–1 s^–1 were measured for rubrene <b>5</b>. This work lays a foundation to improve our understanding of charge-carrier transport phenomena in organic single-crystal semiconductors through the correlation of designed molecular and crystallographic changes to electronic and transport properties

TRANSFERS FROM MIGRANTS TO THEIR CHILDREN: EVIDENCE THAT ALTRUISM AND CULTURAL FACTORS MATTER

This paper focuses on the determinants of financial inter vivos transfers by migrants living in France in 2003 to their adult children. From a theoretical viewpoint, such transfers may be explained either by altruism or by exchange. While parents would direct their assistance to their less well off children under altruism, support should be channeled to children who live nearby their parents under the exchange motive. We assess the relevance of these two motives using the French PRI survey. Unequal sharing is frequently observed and children are more likely to receive financial transfers when they are in poor circumstance, but not necessarily when living in proximity to parents. We also emphasize the role of cultural factors as determinants of the parental allocation among children. Muslim parents, in particular, are more likely to make transfers to sons than to daughters. Copyright � 2007 The Authors; Journal compilation � International Association for Research in Income and Wealth 2007.