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Conservation tillage adoption continues to be threatened by glyphosate and acetolactate synthase–resistant Palmer amaranth and other troublesome weeds. Field experiments were conducted from autumn 2010 through crop harvest in 2013 at two locations in Alabama to evaluate the effect of integrated management practices on weed control and seed cotton yield in glyphosate-resistant cotton. The effects of a cereal rye cover crop using high- or low-biomass residue, followed by wide or narrow within-row strip tillage and three PRE herbicide regimens were evaluated. The three PRE regimens were (1) pendimethalin at 0.84 kg ae ha-1 plus fomesafen at 0.28 kg ai ha-1 applied broadcast, (2) pendimethalin plus fomesafen applied banded on the row, or (3) no PRE. Each PRE treatment was followed by (fb) glyphosate (1.12 kg ae ha-1) applied POST fb layby applications of diuron (1.12 kg ai ha-1) plus monosodium methanearsonate (2.24 kg ai ha-1). Low-residue plots ranged in biomass from 85 to 464 kg ha-1, and high-biomass residue plots ranged from 3,119 to 6,929 kg ha-1. In most comparisons, surface disturbance width, residue amount, and soil-applied herbicide placement did not influence within-row weed control; however, broadcast PRE resulted in increased carpetweed, large crabgrass, Palmer amaranth, tall morning-glory, and yellow nutsedge weed control in row middles compared with plots receiving banded PRE. In addition, high-residue plots had increased carpetweed, common purslane, large crabgrass, Palmer amaranth, sicklepod, and tall morning-glory weed control between rows. Use of banded PRE herbicides resulted in equivalent yield and revenue in four of six comparisons compared with those with broadcast PRE herbicide application; however, this would likely result in many between-row weed escapes. Thus, conservation tillage cotton would benefit from broadcast soil-applied herbicide applications regardless of residue amount and tillage width when infested with Palmer amaranth and other troublesome weed species. Nomenclature: Diuron; fomesafen; glyphosate; monosodium methanearsonate; pendimethalin; carpetweed; Mollugo verticillata L. MOVE; common purslane; Portulaca oleracea L. POOL; large crabgrass; Digitaria sanguinalis (L.) Scop. DISA; Palmer amaranth; Amaranthus palmeri S. Watson AMPA; sicklepod; Senna obtusifolia (L.) Irwin & Barneby SEOB4; tall morning-glory Ipomoea purpurea (L.) Roth IPPU2; yellow nutsedge; Cyperus esculentus L. CYES; cereal rye; Secale cereal L.; cotton; Gossypium hirsutum L.

BACKGROUND Protoporphyrinogen IX oxidase 2 (PPO2) inhibitors are important for the management of glyphosate- and acetolactate synthase-resistant Palmer amaranth [Amaranthus palmeri (S.) Wats.]. The evolving resistance to PPO inhibitors is of great concern. We surveyed the evolution of resistance to fomesafen in the US Mid-south and determined its correlation with the known functional PPO2 target-site mutations (TSM). RESULTS The 167 accessions analyzed were grouped into five categories, four resistant (147) and one susceptible (20). Arkansas accessions constituted 100% of the susceptible group while the Missouri accessions comprised 60% of the most resistant category. The majority of Mississippi accessions (88%) clustered in the high-survival-high-injury category, manifesting an early-stage resistance evolution. One hundred and fifteen accessions were genotyped for four known TSMs; 74% of accessions carried at least one TSM. The most common single TSM was ΔG210 (18% of accessions) and the predominant double mutation was ΔG210 + G399A (17%). Other mutations are likely less favorable, hence are rare. All TSMs were detected in three accessions. Further examination revealed that 9 and two individuals carried G399A + G210 and G399A + R128G TSM in the same allele, respectively. The existence of these combinations is supported by molecular modeling. CONCLUSIONS Resistance to PPO inhibitors is widespread across the Mid-southern USA. Highly resistant field populations have plants with multiple mutations. G399A is the most prone to co-occur with other ppo2 mutations in the same allele. Mutation at R128 in the configuration of the PPO2 catalytic domain restrains the co-occurrence of R128G with ΔG210, making ΔG210 + G399A the most plausible, tolerable functional mutation combination to co-occur in the same ppo2 allele.

Despite recent advances in reaction methodologies, organic synthesis remains complex and challenging. Many of the fundamental processes in use have not changed in over 100 years, with a large proportion of the work being carried out manually, using lengthy procedures and difficult or hazardous reaction conditions. As such, organic synthesis still presents a bottle-neck in discovery research. Endeavours to automate synthesis in discovery, through robotic platforms, have so far not been widely successful because the highly complex nature of such machines, and the level of skill required for their operation, presents a barrier too great for most discov- ery chemists. Synple Chem has developed a safe, easy to use, efficiency-enhancing automated technology for the acceleration of discovery research. The automated flow-batch hybrid system utilises a range of innovative pre-packed reagent cartridges for different reaction classes, along with pre-programmed, highly optimised but editable reaction protocols. The combination of these three key elements, provides users with a convenient, easy to use, time-saving technology that makes the synthesis of molecules far simpler, faster and more efficient. The described technology offers all discovery chemists access to real synthesis automation without any of the barriers that have previously restricted its utility.

Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug sensing fluorescent reporters ("iDrugSnFRs") for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives - 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by > 30 fold. The new nicotinic iDrugSnFRs, in combination with previously described nicotine and varenicline sensors, provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.

Six on-farm studies determined the effects of a rolled rye cover crop, herbicide program, and planting technique on cotton stand, weed control, and cotton yield in Georgia. Treatments included: (1) rye drilled broadcast with 19-cm row spacing and a broadcast-herbicide program (2) rye drilled with a 25-cm rye-free zone in the cotton row and a broadcast-herbicide program (3) rye drilled with a 25-cm rye-free zone in the cotton row with PPI and PRE herbicides banded in the cotton planting row, and (4) no cover crop (i.e., weedy cover) with broadcast herbicides. At two locations, cotton stand was lowest with rye drilled broadcast; at these sites the rye-free zone maximized stand equal to the no-cover system. At a third location, cover crop systems resulted in greater stand, due to enhanced soil moisture preservation compared with the no-cover system. Treatments did not influence cotton stand at the other three locations and did not differ in the control of weeds other than Palmer amaranth at any location. Treatments controlled Palmer amaranth equally at three locations; however, differences were observed at the three locations having the greatest glyphosate-resistant plant densities. For these locations, when broadcasting herbicides, Palmer amaranth populations were reduced 82% to 86% in the broadcast rye and rye-free zone systems compared with the no-cover system at harvest. The system with banded herbicides was nearly 21 times less effective than the similar system broadcasting herbicides. At these locations, yields in the rye broadcast and rye-free zone systems with broadcast herbicides were increased 9% to 16% compared with systems with no cover or a rye-free zone with PPI and PRE herbicides banded. A rolled rye cover crop can lessen weed emergence and selection pressure while improving weed control and cotton yield, but herbicides should be broadcast in fields heavily infested with glyphosate-resistant Palmer amaranth.

Silver-impregnated zeolite (AgIZ) has been used for removing radioiodine from contaminated groundwater and nuclear waste streams and the worldwide inventory of such secondary waste is rapidly increasing. The objective of this study was to 1) quantify the effectiveness of two grout waste forms for disposing of the used AgIZ, and 2) determine the I speciation leached from AgIZ encapsulated in grout. A 60-day kinetics batch experiment demonstrated that AgIZ encapsulated in slag-free grout was extremely effective at immobilizing I and Ag, a potential non-radioactive carcinogen. However, AgIZ encapsulated in slag-containing grout, the most common type of grout used for low-level radioactive waste disposal, was entirely ineffective at immobilizing I. While the slag-free grout with AgIZ released only 3.3 μg/L Itotal into the contact solution, the slag-containing grout released 19,269 μg/L Itotal. Based on thermodynamic calculations, the strongly reducing conditions of the slag-containing system (Eh was −392 mV) promoted the reductive dissolution of the AgI, forming Ag0(aq) and releasing iodide (I−) into the aqueous phase. The slag-free grout system was maintained under more oxidizing conditions (Eh was 439 mV) and a minimal amount of I was released from the grout. In both grout systems, the aqueous I, originally added to the AgZ as iodide, was composed primarily of iodide and org-I, and essentially no iodate was detected. More organo-I was detected in the slag-free than the slag-containing grout system because the high redox potential of the former system was more conducive to the formation of oxidized I species, such as I2, which may be intermediates in the covalent bonding of I with organic C in grout. Iodine K-edge XANES analysis indicated that I existed exclusively as silver iodide in both AgIZ-grout samples. Together, these results indicate that subsurface grout disposal of AgIZ waste should be done under oxidizing conditions and that radioiodide released from AgIZ can undergo speciation transformations that have important implications on subsequent mobility and estimated risk. Keywords: Iodine speciation, Cement, Slag, Immobilization, Redox, Silver-impregnated zeolite

Recent commercialization of auxin herbicide–based weed control systems has led to increased off-target exposure of susceptible cotton cultivars to auxin herbicides. Off-target deposition of dilute concentrations of auxin herbicides can occur on cotton at any stage of growth. Field experiments were conducted at two locations in Mississippi from 2014 to 2016 to assess the response of cotton at various growth stages after exposure to a sublethal 2,4-D concentration of 8.3 g ae ha−1. Herbicide applications occurred weekly from 0 to 14 weeks after emergence (WAE). Cotton exposure to 2,4-D at 2 to 9 WAE resulted in up to 64% visible injury, whereas 2,4-D exposure 5 to 6 WAE resulted in machine-harvested yield reductions of 18% to 21%. Cotton maturity was delayed after exposure 2 to 10 WAE, and height was increased from exposure 6 to 9 WAE due to decreased fruit set after exposure. Total hand-harvested yield was reduced from 2,4-D exposure 3, 5 to 8, and 13 WAE. Growth stage at time of exposure influenced the distribution of yield by node and position. Yield on lower and inner fruiting sites generally decreased from exposure, and yield partitioned to vegetative or aborted positions and upper fruiting sites increased. Reductions in gin turnout, micronaire, fiber length, fiber-length uniformity, and fiber elongation were observed after exposure at certain growth stages, but the overall effects on fiber properties were small. These results indicate that cotton is most sensitive to low concentrations of 2,4-D during late vegetative and squaring growth stages.

Iodine-129 is a key risk driver in most low-level waste cementitious waste repositories. Objectives of this study were to determine iodine speciation in cementitious materials with slag (Grout+slag) and without slag (Grout–slag) and its impact on iodine immobilization. Irrespective of which iodine species was amended to the aqueous phase, there were no significant differences in uptake-Kd values (∼3 L/kg). However, when the various iodine species were hydrated with the grout, the release-Kd values (6.1–121.8 L/kg) were significantly greater than the uptake-Kd values, and the amended iodine speciation (I− ≪ org-I ≤ IO3−) and grout formulation (Grout–slag

Nicotine dependence is thought to arise in part because nicotine permeates into the endoplasmic reticulum (ER), where it binds to nicotinic receptors (nAChRs) and begins an “inside-out” pathway that leads to up-regulation of nAChRs on the plasma membrane. However, the dynamics of nicotine entry into the ER are unquantified. Here, we develop a family of genetically encoded fluorescent biosensors for nicotine, termed iNicSnFRs. The iNicSnFRs are fusions between two proteins: a circularly permutated GFP and a periplasmic choline-/betaine-binding protein engineered to bind nicotine. The biosensors iNicSnFR3a and iNicSnFR3b respond to nicotine by increasing fluorescence at [nicotine] 75%. Reducing nicotine intake by 10-fold decreases activation to ∼20%. iNicSnFR3a and iNicSnFR3b also sense the smoking cessation drug varenicline, revealing that varenicline also permeates into the ER within seconds. Our iNicSnFRs enable optical subcellular pharmacokinetics for nicotine and varenicline during an early event in the inside-out pathway.

The current laboratory practices of organic synthesis are labor intensive, impose safety and environmental hazards, and hamper the implementation of artificial intelligence guided drug discovery. Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions with prepacked capsules. The machine conducts coupling reactions and delivers the purified products with minimal user involvement. Two desirable reaction classes – the synthesis of saturated N-heterocycles and reductive amination – were implemented, along with multi-step sequences that provide drug-like organic molecules in a fully automated manner. We envision that this system will serve as a console for developers to provide synthetic methods as integrated, user-friendly packages for conducting organic synthesis in a safe and convenient fashion., Chemical Science, 12 (20), ISSN:2041-6520, ISSN:2041-6539

Recent, non-peer-reviewed reports and meta-analyses suggest that smoking may reduce the risk of hospitalization with COVID-19, because the prevalence of smoking among hospitalized COVID-19 is less than that of the general population. However, there are two alternative classes of explanations for this phenomenon. Class (1) is the failure to report, or to accurately record, smoking history during emergency hospital admissions and other interviews. Face-to-face interviews can introduce bias into the responses to attitudinal and behavioral questions not present in the self-completion interviews typically used to measure smoking prevalence in the general population. Subjects in face-to-face interviews may be unwilling to admit socially undesirable behavior and attitudes under direct questioning. For example, urine testing of hospitalized patients for cotinine showed that smokers were under-counted by 37% because incoming patients failed to inform staff about their smoking behavior. Class (2), various types of “reverse” causation, including a pre-disposition to avoid smoking among COVID-19 patients with tobacco-related comorbidities, may also contribute to the difference between smoking prevalence in the COVID-19 and general population. Patient cohorts hospitalized with COVID-19 may be less prone to use tobacco than the general population. A potentially robust “reverse causation” hypothesis for reduced prevalence of smokers in the COVID-19 population is enrichment of patients in the population with serious comorbidities that have previously motivated them to quit smoking. We ask whether this “smoking cessation” mechanism accounts for a detectable fraction of the reduced prevalence of smokers in the COVID-19 population. Testing this hypothesis will require a focused research program.

Objectives Maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) are mucosal α-glucosidases required for the digestion of starch to glucose. We hypothesized that a dietary approach to reduce Mgam and Si activities can reduce glucose generation and absorption, and improve glucose control. Methods Rice starch was entrapped in alginate microspheres to moderate in vitro digestion properties. Three groups of 8-wk old mice (n = 8) were conditioned for 7 d with low 13C-starch-based materials differing in digestion rates (fast, slow, and slower), and then given a digestible 13C-labeled cornstarch test feeding to determine its digestion to glucose. Results Conditioning of the small intestine with the slowly digestible starches for 7 d reduced jejunal α-glucosidase and sucrase activities, as well as glucose absorption for the slowly digestible starch slower group (P Conclusions Decreased glucogenesis from a digestible starch feeding was found in mice conditioned on slowly digestible starch diets, suggesting that a dietary approach incorporating slowly digestible starches may change α-glucosidase activities to moderate glucose absorption rate.

Alternaria alternata is a fungal allergen associated with severe asthma and asthma exacerbations. Similarly to other asthma-associated allergens, Alternaria secretes a serine-like trypsin protease(s) that is thought to act through the G protein-coupled receptor protease-activated receptor-2 (PAR2) to induce asthma symptoms. However, specific mechanisms underlying Alternaria-induced PAR2 activation and signaling remain ill-defined. We sought to determine whether Alternaria-induced PAR2 signaling contributed to asthma symptoms via a PAR2/β-arrestin signaling axis, identify the protease activity responsible for PAR2 signaling, and determine whether protease activity was sufficient for Alternaria-induced asthma symptoms in animal models. We initially used in vitro models to demonstrate Alternaria-induced PAR2/β-arrestin-2 signaling. Alternaria filtrates were then used to sensitize and challenge wild-type, PAR2−/− and β-arrestin-2−/− mice in vivo. Intranasal administration of Alternaria filtrate resulted in a protease-dependent increase of airway inflammation and mucin production in wild-type but not PAR2−/− or β-arrestin-2−/− mice. Protease was isolated from Alternaria preparations, and select in vitro and in vivo experiments were repeated to evaluate sufficiency of the isolated Alternaria protease to induce asthma phenotype. Administration of a single isolated serine protease from Alternaria, Alternaria alkaline serine protease (AASP), was sufficient to fully activate PAR2 signaling and induce β-arrestin-2−/−-dependent eosinophil and lymphocyte recruitment in vivo. In conclusion, Alternaria filtrates induce airway inflammation and mucus hyperplasia largely via AASP using the PAR2/β-arrestin signaling axis. Thus, β-arrestin-biased PAR2 antagonists represent novel therapeutic targets for treating aeroallergen-induced asthma.

The introduction of auxin herbicide weed control systems has led to increased occurrence of crop injury in susceptible soybeans and cotton. Off-target exposure to sublethal concentrations of dicamba can occur at varying growth stages, which may affect crop response. Field experiments were conducted in Mississippi in 2014, 2015, and 2016 to characterize cotton response to a sublethal concentration of dicamba equivalent to 1/16X the labeled rate. Weekly applications of dicamba at 35 g ae ha-1were made to separate sets of replicated plots immediately following planting until 14 wk after emergence (WAE). Exposure to dicamba from 1 to 9 WAE resulted in up to 32% visible injury, and exposure from 7 to 10 WAE delayed crop maturity. Exposure from 8 to 10 and 13 WAE led to increased cotton height, while an 18% reduction in machine-harvested yield resulted from exposure at 6 WAE. Cotton exposure at 3 to 9 WAE reduced the seed cotton weight partitioned to position 1 fruiting sites, while exposure at 3 to 6 WAE also reduced yield in position 2 fruiting sites. Exposure at 2, 3, and 5 to 7 WAE increased the percent of yield partitioned to vegetative branches. An increase in percent of yield partitioned to plants with aborted terminals occurred following exposure from 3 to 7 WAE and corresponded with reciprocal decreases in yield partitioned to positional fruiting sites. Minimal effects were observed on fiber quality, except for decreases in fiber length uniformity resulting from exposure at 9 and 10 WAE.Nomenclature: Dicamba; cotton, Gossypium hirsutum L.; soybean, Glycine max (L.) Merr.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that play a central role in neuronal and neuromuscular signal transduction. Here, we have developed FANG ligands, fibronectin antibody-mimetic nicotinic acetylcholine receptor-generated ligands, using mRNA display. We generated a 1 trillion-member primary e10FnIII library to target a stabilized α1 nicotinic subunit (α211). This library yielded 270000 independent potential protein binding ligands. The lead sequence, α1-FANG1, represented 25% of all library sequences, showed the highest-affinity binding, and competed with α-bungarotoxin (α-Btx). To improve this clone, a new library based on α1-FANG1 was subjected to heat, protease, binding, off-rate selective pressures, and point mutations. This resulted in α1-FANG2 and α1-FANG3. These proteins bind α211 with K(D) values of 3.5 nM and 670 pM, respectively, compete with α-Btx, and show improved subunit specificity. α1-FANG3 is thermostable (T(m) = 62 °C) with a 6 kcal/mol improvement in folding free energy compared with that of the parent α1-FANG1. α1-FANG3 competes directly with the α-Btx binding site of intact neuromuscular heteropentamers [(α1)(2)β1γδ] in mammalian culture-derived cellular membranes and in Xenopus laevis oocytes expressing these nAChRs. This work demonstrates that mRNA display against a monomeric ecto-domain of a pentamer has the capability to select ligands that bind that subunit in both a monomeric and a pentameric context. Overall, our work provides a route to creating a new family of stable, well-behaved proteins that specifically target this important receptor family.

The mucosal maltase enzymes are characterized by an activity that produces glucose from linear glucose polymers, assayed with the disaccharide maltose. The related enzyme isomaltase produces glucose from branched glucose polymers, assayed with palatinose. Maltase and isomaltase activities are part of the 4 disaccharidases assayed from clinical duodenal biopsy homogenates. The reported maltase activities are more difficult to interpret than lactase or sucrase activities because both the sucrase-isomaltase and maltase-glucoamylase proteins have overlapping maltase activities. The early work of Dahlqvist identified 4 maltase activities from human small intestinal mucosa. On one peptide, sucrase (maltase Ib) and isomaltase (maltase Ia) activities shared maltase activities but identified the enzymes as sucrase-isomaltase. On the other peptide, no distinguishing characteristics of the 2 maltase activities (maltases II and III) were detected and the activities identified as maltase-glucoamylase. The nutritional/clinical importance of small intestinal maltase and isomaltase activities are due to their crucial role in the digestion of food starches to absorbable free glucose. This review focuses on the interpretation of biopsy maltase activities in the context of reported lactase, sucrase, maltase, and palatinase biopsy assay activity patterns. We present a classification of mucosal maltase deficiencies and novel primary maltase deficiency (Ib, II, III) and provide a clarification of the role of maltase activity assayed from clinically obtained duodenal biopsies, as a path toward future clinical and molecular genomic investigations.

Grazing cattle redistribute nitrogen (N) consumed in forage through urine and feces patches. The high concentration of N in these patches often exceeds the uptake demands of the local plant community, thereby providing ideal conditions for losses of reactive N. However, knowledge on nitrous oxide (NO) and ammonia (NH) emissions from excretal patches on shortgrass steppe grassland is limited. We studied the effect of cattle urine (1002 kg N ha) and feces (1021 kg N ha) patches on NO and NH emissions in two sites with contrasting vegetation: (i) cool-season (C3) 'Bozoisky-Select' Russian wildrye [ (Fisch.) Nevski], pasture (C3Past) and (ii) C4-dominated native shortgrass steppe rangeland (C4SS). Nitrous oxide and NH were measured using semi-static and semi-open chambers, respectively. Cumulative NO emissions were 217 and 173% greater and cumulative volatile NH emissions were 339 and 157% greater on C3Past compared with C4SS from the urine and feces treatments, respectively. Nitrous oxide emission factors were 0.20 and 0.05% for urine and 0.07 and 0.03% for feces on C3Past and C4SS, respectively. Our findings suggest that using the IPCC Tier 1 default emission factor (2%, 95% CI = 0.7-6%) to estimate NO emissions from cattle excretal patches on shortgrass steppe grassland would result in a significant overestimation for these dryland systems. Ammonia emission factors were 35 and 10% for urine and 7 and 5% for feces on C3Past and C4SS, respectively. With the exception of the urine treatment on C3Past, observed NH emissions were consistent with the IPCC Tier 1 default assumption that 20% (95% CI = 5-50%) of excretal N is volatilized as NH+NO.

Leucine-rich repeat kinase 2 (LRRK2) has been suggested as a potential therapeutic target for Parkinson's disease. Herein we report the discovery of 5-substituent-N-arylbenzamide derivatives as novel LRRK2 inhibitors. Extensive SAR study led to the discovery of compounds 8e, which demonstrated potent LRRK2 inhibition activity, high selectivity across the kinome, good brain exposure, and high oral bioavailability.

Background and objective Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase-deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase-isomaltase deficiency.Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α-amylases (Amy), and 4 mucosal α-glucosidases (maltases), including maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post-α-amylolytic dextrins to glucose. Starch digestion is reduced because of sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. The aim of the present study was to measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements. Methods Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with C-enriched starch diets. Glucogenesis derived from starch was measured as blood C-glucose enrichment and oral recombinant C-terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion. Results After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose. Conclusions Sucrase deficiency, in this model of congenital sucrase-isomaltase deficiency, reduces blood glucose response to starch feeding. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase-deficient shrew.

Fourier transform infrared (FTIR) spectroscopy can be used to determine the concentration and speciation of dissolved water in silicate glasses if the molar absorptivity coefficients (e) are known. Samples that are thin and/or water-poor typically require the use of the mid-IR 3500 cm–1 total water (H2Ot) and 1630 cm–1 molecular water (H2Om) absorbance bands, from which hydroxyl water (OH) must be determined by difference; however, accurate determination of H2Ot and OH is complicated because e3500 varies with water speciation, which is not usually known a priori. We derive an equation that uses end-member e3500 values to find accurate H2Ot and OH concentrations from the 3500 cm–1 absorbance for samples where only the H2Om concentration need be known (e.g., from the 1630 cm–1 band). We validate this new species-dependent e3500 method against published data sets and new analyses of glass standards. We use published data to calculate new end-member e3500 values of e3500OH = 79 ± 11 and e3500H2Om = 49 ± 6 L/mol∙cm for Fe-bearing andesite and e3500OH = 76 ± 12 and e3500H2Om = 62 ± 7 L/mol∙cm for Fe-free andesite. These supplement existing end-member values for rhyolite and albite compositions. We demonstrate that accounting for the species-dependence of e3500 is especially important for hydrated samples, which contain excess H2Om, and that accurate measurement of OH concentration, in conjunction with published speciation models, enables reconstruction of original pre-hydration water contents. Although previous studies of hydrous silicate glasses have suggested that values of e decrease with decreasing tetrahedral cation fraction of the glass, this trend is not seen in the four sets of end-member e3500 values presented here. We expect that future FTIR studies that derive end-member e3500 values for additional compositions will therefore not only enable the species-dependent e3500 method to be applied more widely, but will also offer additional insights into the relationship between values of e and glass composition.

Field experiments were conducted to evaluate the integration of cover crops and POST herbicides to control glyphosate-resistant Palmer amaranth in cotton. The winter-annual grasses accumulated the greatest amount of biomass and provided the most Palmer amaranth control. The estimates for the logistic regression would indicate that 1540 kg ha−1would delay Palmer amaranth emerging and growing to 10 cm by an estimated 16.5 days. The Palmer amaranth that emerged in the cereal rye and wheat cover crop treatments took a longer time to reach 10 cm compared to the hairy vetch and crimson clover treatments. POST herbicides were needed for adequate control of Palmer amaranth. The glufosinate-based weed control system provided greater control (75% vs 31%) of Palmer amaranth than did the glyphosate system. These results indicate that a POST only herbicide weed management system did not provide sufficient control of Palmer amaranth, even when used in conjunction with cover crops that produced a moderate level of biomass. Therefore, future recommendations for GR Palmer amaranth control will include integrating cover crops with PRE herbicides, overlaying residual herbicides in-season, timely POST herbicide applications, and hand weeding in order to achieve season-long control of this pest.

Vapor-liquid-solid (VLS) growth of nanoscale or subwavelength scale semiconductor wires (nanowires) has been proven to be an important and effective approach to producing high-quality, substrate insensitive photonic materials with a flexible and ever-expanding coverage of wavelengths for lasing and other photonic applications. However, the materials and lasing demonstrations have so far been limited to mostly ultraviolet to visible wavelengths, with a few exceptions in the short-wavelength infrared range. A further extension to longer wavelengths (such as mid-infrared, MIR) using narrower band gap semiconductors encounters severe challenges: the ever decreasing radiative efficiency due to the Auger and other nonradiative channels with wavelengths demands extremely high material quality and significantly narrows the material choices. This situation is very unsatisfactory, given many important applications that demand materials and lasers of subwavelength scales for MIR wavelengths in an integrated platform, especially on silicon. Here we report our results on lasing demonstration in MIR (3-4 μm) based on a unique combination of high-quality material growth on a silicon substrate and the choice of an intrinsically strong MIR material in lead sulfide (PbS). Lasing is demonstrated from single wires both on the original silicon substrate and on the sapphire substrates after transferring, with sizes of lasing wires down to below half of the normalized volume (volume of wires divided by the wavelength cubed) and operating temperature up to 180 K. Such subwavelength wire lasers could be important for a wide range of MIR applications on silicon-based integrated photonic platforms, such as chemical and environmental sensing, free-space communications, and many others.

Fungicide programs for managing target spot of cotton caused by Corynespora cassiicola were evaluated over 15 site-years in the southeastern United States between 2014 and 2016. Two cultivars, hypothesized to vary in target spot susceptibility, PhytoGen 499WRF (PHY499) and Deltapine 1137B2RF (DPL1137), and four fungicides (azoxystrobin, flutriafol, pyraclostrobin, pyraclostrobin + fluxapyroxad) plus nontreated control, were compared. Fungicide programs consisted of 1) a single application at first flower or disease onset and 2) the first application followed by a second 14 days later. Treatments were applied in a factorial, randomized complete block design. Target spot onset and severity varied among site-years. Except when severity was low, target spot-associated defoliation was greater on PHY499 than on DP1137. Fungicides delayed disease development and defoliation, but application number had little impact. Based on a meta-analysis of 15 site-years, pyraclostrobin-based applications resulted in a 4 to 6% yield preservation, and yield preservation was greater at site-years with early disease onset and >40% target spot associated defoliation. Results suggest a single well-timed application of a pyraclostrobin-based fungicide reduces defoliation and protects cotton yield at locations with high target spot severity. Additional research is needed to identify risk factors for target spot-associated yield losses in cotton production systems.

The target for the “rapid” (100-fold selectivity over other ligands tested, including R-ketamine. We targeted each of the sensors to either the plasma membrane (PM) or the endoplasmic reticulum (ER). Measurements on these biosensors expressed in Neuro2a cells and in human dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) show that S-ketamine enters the ER within a few seconds after appearing in the external solution near the PM, then leaves as rapidly after S-ketamine is removed from the extracellular solution. In cells, S-slopes for the ER and PM-targeted sensors differ by

The mammalian mucosal α-glucosidase complexes, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), have two catalytic subunits (N- and C-termini). Concurrent with the desire to modulate glycemic response, there has been a focus on di-/oligosaccharides with unusual α-linkages that are digested to glucose slowly by these enzymes. Here, we look at disaccharides with various possible α-linkages and their hydrolysis. Hydrolytic properties of the maltose and sucrose isomers were determined using rat intestinal and individual recombinant α-glucosidases. The individual α-glucosidases had moderate to low hydrolytic activities on all α-linked disaccharides, except trehalose. Maltase (N-terminal MGAM) showed a higher ability to digest α-1,2 and α-1,3 disaccharides, as well as α-1,4, making it the most versatile in α-hydrolytic activity. These findings apply to the development of new glycemic oligosaccharides based on unusual α-linkages for extended glycemic response. It also emphasizes that mammalian mucosal α-glucosidases must be used in in vitro assessment of digestion of such carbohydrates.

Cattle play a major role in nutrient cycling of grassland ecosystems through biomass removal and excrement deposition (urine and feces). We studied the effects of cattle excrement patches (urine at 430 and feces at 940 kg N ha−1) on nitrous oxide (N2O) and methane (CH4) fluxes using semi-static chambers on cool-season (C3), Bozoisky-select (Psathyrostachys juncea) pasture, and warm-season (C4)-dominated native rangeland of the shortgrass steppe (SGS) in northeastern Colorado. Nitrous oxide emission factors (EF; i.e., percent of added N emitted as N2O N) did not differ between urine and feces on the C4-dominated native rangeland (0.11 and 0.10%) and C3 pasture (0.13 and 0.10%). These EFs are substantially less than the Intergovernmental Panel on Climate Change (IPCC) Tier 1 Default EF (2%) for manure deposited on pasture, indicating that during dry years the IPCC Tier 1 Default EF would result in a significant overestimation of emissions from excrement patches deposited on SGS C4-dominated native rangeland and C3 pasture. Over the first year of the study (19 June 2012–18 June 2013), cumulative CH4 uptake was 38% greater for urine (−1.49 vs. −1.08 kg CH4 C ha−1) and 28% greater for control plots (−2.09 vs. −1.63 kg CH4 C ha−1) on C4-dominated native rangeland compared to C3 pasture. In contrast, feces patches were net sources of CH4 with emissions from the C3 pasture (0.64 kg CH4 C ha−1) 113% greater than the C4-dominated native rangeland (0.30 kg CH4 C ha−1). Conversion of C4-dominated native rangeland to C3 pasture can have long term effects on CH4 uptake; therefore consideration should be taken before implementing this management practice.

The primary sweet sensor in mammalian taste cells for sugars and noncaloric sweeteners is the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+T1R3, encoded by Tas1r2 and Tas1r3 genes). However, in the absence of T1R2+T1R3 (e.g., in Tas1r3 KO mice), animals still respond to sugars, arguing for the presence of T1R-independent detection mechanism(s). Our previous findings that several glucose transporters (GLUTs), sodium glucose cotransporter 1 (SGLT1), and the ATP-gated K(+) (KATP) metabolic sensor are preferentially expressed in the same taste cells with T1R3 provides a potential explanation for the T1R-independent detection of sugars: sweet-responsive taste cells that respond to sugars and sweeteners may contain a T1R-dependent (T1R2+T1R3) sweet-sensing pathway for detecting sugars and noncaloric sweeteners, as well as a T1R-independent (GLUTs, SGLT1, KATP) pathway for detecting monosaccharides. However, the T1R-independent pathway would not explain responses to disaccharide and oligomeric sugars, such as sucrose, maltose, and maltotriose, which are not substrates for GLUTs or SGLT1. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we found that taste cells express multiple α-glycosidases (e.g., amylase and neutral α glucosidase C) and so-called intestinal "brush border" disaccharide-hydrolyzing enzymes (e.g., maltase-glucoamylase and sucrase-isomaltase). Treating the tongue with inhibitors of disaccharidases specifically decreased gustatory nerve responses to disaccharides, but not to monosaccharides or noncaloric sweeteners, indicating that lingual disaccharidases are functional. These taste cell-expressed enzymes may locally break down dietary disaccharides and starch hydrolysis products into monosaccharides that could serve as substrates for the T1R-independent sugar sensing pathways.

BACKGROUND The widespread occurrence of ALS inhibitor‐ and glyphosate‐resistant Amaranthus palmeri has led to increasing use of protoporphyrinogen oxidase (PPO)‐inhibiting herbicides in cotton and soybean. Studies were conducted to confirm resistance to fomesafen (a PPO inhibitor), determine the resistance frequency, examine the resistance profile to other foliar‐applied herbicides and investigate the resistance mechanism of resistant plants in a population collected in 2011 (AR11‐LAW B) and its progenies from two cycles of fomesafen selection (C1 and C2). RESULTS The frequency of fomesafen‐resistant plants increased from 5% in the original AR11‐LAW‐B to 17% in the C2 population. The amounts of fomesafen that caused 50% growth reduction were 6‐, 13‐ and 21‐fold greater in AR11‐LAW‐B, C1 and C2 populations, respectively, than in the sensitive ecotype. The AR11‐LAW‐B population was sensitive to atrazine, dicamba, glufosinate, glyphosate and mesotrione but resistant to ALS‐inhibiting herbicides pyrithiobac and trifloxysulfuron. Fomesafen survivors from C1 and C2 populations tested positive for the PPO glycine 210 deletion previously reported in waterhemp (Amaranthus tuberculatus). CONCLUSION These studies confirmed that Palmer amaranth in Arkansas has evolved resistance to foliar‐applied PPO‐inhibiting herbicide. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Despite respiratory motor neuron death, ventilation is preserved in SOD1G93A rats. Compensatory respiratory plasticity may counterbalance the loss of these neurons. Phrenic long-term facilitation (pLTF; a form of respiratory plasticity) in naive rats is 5-HT2 and NADPH oxidase-dependent. Furthermore, 5-HT2A, not 5-HT2B, receptor-induced phrenic motor facilitation is NADPH oxidase-independent in naive rats. pLTF is NADPH oxidase-dependent in pre-symptomatic, but not end-stage, SOD1G93A rats. Here, we hypothesized that in the putative phrenic motor nucleus (PMN) of SOD1G93A rats vs. wild-type littermates: 1) pre-symptomatic rats would have greater 5-HT2B receptor expression that decreases at end-stage; and 2) 5-HT2A receptor expression would increase from pre-symptomatic to end-stage. Putative PMN 5-HT2A receptor expression was reduced when comparing across (but not within) pre-symptomatic vs. end-stage groups (p < 0.05). In contrast, putative PMN 5-HT2B receptor expression was increased when comparing across pre-symptomatic vs. end-stage groups, and within end-stage groups (p < 0.05). These data suggest a potential role for 5-HT2 receptors in pLTF and breathing in SOD1G93A rats.

Background/Aims: CID16020046 blocks the effect of the lipid lysophosphatidylinositol (LPI) at its receptor, GPR55. CID16020046 and another antagonist, ML193, have been used to investigate GPR55-mediated effects of LPI on cells, tissues, and in vivo. Here we describe the structure-activity relationship of CID16020046. Methods: Yeast or human cells were engineered to express GPR55 or control receptors. Cells were pretreated with a test agent before agonist challenge. Functional responses were quantified by yeast gene-reporter or calcium imaging. Results: Three substituents around the central pyrazololactam core of CID16020046 are each tolerant to substitution without abolishing GPR55 activity. Analogues of CID16020046 with potency at GPR55 ranging >1,000-fold are described, including several lacking activity up to the top concentration tested. One analogue, compound 1 (GSK875734A), has approximately 50-fold greater potency than CID16020046 in an inverse agonist assay. CID16020046, ML193 and 2 further antagonists (ML191 and ML192) all block the effect of a surrogate agonist at human GPR55. ML193, CID16020046 and several other examples of the pyrazololactam chemotype were also shown to antagonise rat GPR55. Conclusion: These data confirm the utility of CID16020046 and ML193 as tools to investigate the physiological role of GPR55, and offer starting points for GPR55 antagonists with optimised pharmacokinetic or other properties.

BACKGROUND: Human starch digestion is a multi-enzyme process involving six different enzymes: salivary and pancreatic α-amylase; sucrase and isomaltase (from sucrose-isomaltase; SI), and maltase and glucoamylase (from maltase-glucoamylase (MGAM)). Together these enzymes cleave starch to smaller molecules ultimately resulting in the absorbable monosaccharide glucose. Approximately 80% of all mucosal maltase activity is accounted for by SI and the reminder by MGAM. Clinical studies suggest that starch may be poorly digested in those with congenital sucrase-isomaltase deficiency (CSID). HYPOTHESES: Poor starch digestion occurs in individuals with CSID and can be documented using a noninvasive 13C-breath test (BT). METHODS: 13C-labled starch was used as a test BT substrate in children with CSID. Sucrase deficiency was previously documented in study subjects by both duodenal biopsy enzyme assays and 13C-sucrose BT. Breath 13CO2 was quantitated at intervals before and after serial 13C-substrate loads (glucose followed 75 minutes later by starch). Variations in metabolism were normalized against 13C-glucose BT (Coefficient of glucose absorption, CGO). Control subjects consisted of healthy family members and a group of children with functional abdominal pain with biopsy proven sucrase sufficiency. RESULTS: Children with CSID had a significant reduction of 13C-starch digestion mirroring that of their duodenal sucrase and maltase activity and 13C-sucrase BT. CONCLUSION: In children with CSID, starch digestion may be impaired. In children with CSID, starch digestion correlates well with measures of sucrase activity.

Dietary starch is finally converted to glucose for absorption by the small intestine mucosal α-glucosidases (sucrase-isomaltase [SI] and maltase-glucoamylase), and control of this process has health implications. Here, the molecular mechanisms were analyzed associated with starch-triggered maturation and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the high MW SI species (265 kDa) induced by maltose (an α-amylase starch digestion product) had a higher rate of early trafficking and maturation compared with a glucose-induced SI (245 kDa). The maltose-induced SI was found to have higher affinity to lipid rafts, which are associated with enhanced targeting to the apical membrane and higher activity. Accordingly, in situ maltose-hydrolyzing action was enhanced in the maltose-treated cells. Thus, starch digestion products at the luminal surface of small intestinal enterocytes are sensed and accelerate the intracellular processing of SI to enhance starch digestion capacity in the intestinal lumen.-Chegeni, M., Amiri, M., Nichols, B. L., Naim, H. Y., Hamaker, B. R. Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600 μM; 12 μL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms preserving/enhancing the capacity for pLTF in MT rats are not known.

In this study, it was hypothesized that dietary phenolic compounds selectively inhibit the individual C- and N-terminal (Ct, Nt) subunits of the two small intestinal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), for a modulated glycemic carbohydrate digestion. The inhibition by chlorogenic acid, caffeic acid, gallic acid, (+)-catechin, and (-)-epigallocatechin gallate (EGCG) on individual recombinant human Nt-MGAM and Nt-SI and on mouse Ct-MGAM and Ct-SI was assayed using maltose as the substrate. Inhibition constants, inhibition mechanisms, and IC50 values for each combination of phenolic compound and enzymatic subunit were determined. EGCG and chlorogenic acid were found to be more potent inhibitors for selectively inhibiting the two subunits with highest activity, Ct-MGAM and Ct-SI. All compounds displayed noncompetitive type inhibition. Inhibition of fast-digesting Ct-MGAM and Ct-SI by EGCG and chlorogenic acid could lead to a slow, but complete, digestion of starch for improved glycemic response of starchy foods with potential health benefit.

This study experimentally assessed bacterial water-to-air partitioning coefficients resulting from showerhead aerosolization of water contaminated with Brevundimonas diminuta or Pseudomonas aeruginosa , and estimated human exposure through inhalation. Dechlorinated tap water was spiked with two cell densities (10 9 and 10 10 CFU L −1 ) and cycled at three temperatures (10, 25, and 37 or 40 °C) through a full-scale shower system. For reproducibility, spiked water concentrations were intentionally higher than those found in natural environments. Three types of samplers measured size distribution and viable concentrations throughout the system. Results indicate low levels of respirable bioaerosols were generated. The ratio of bacterial contaminant that was effectively aerosolized (bacterial water-to-air partitioning coefficient, PC bwa ) was low – averaging 1.13 × 10 −5 L m −3 for B. diminuta and 8.31 × 10 −6 L m −3 for P. aeruginosa . However, the respirable fraction of aerosolized organisms was high, averaging above 94% (in shower) and above 99% (downstream) for both organisms. This study found no significant difference in bioaerosol load for a forward facing versus reverse facing individual. Further, for the average hot shower (33–43 °C) the total number of respirable bioaerosols is higher, but the observed culturability of those aerosolized cells is lower when compared to lower temperatures. Bacterial water to air partitioning coefficients were calculated to predict microbial air concentration and these empirical parameters may be used for assessing inhalation as a route of exposure to pathogens in contaminated waters.

Fusaric acid (FA) produced by Fusarium oxysporum plays an important role in disease development in plants, including cotton. This non-specific toxin also has antibiotic effects on microorganisms. Thus, one expects a potential pool of diverse detoxification mechanisms of FA in nature. Bacteria and fungi from soils infested with Fusarium and from laboratory sources were evaluated for their ability to grow in the presence of FA and to alter the structure of FA into less toxic compounds. None of the bacterial strains were able to chemically modify FA. Highly FA-resistant strains were found only in Gram-negative bacteria, mainly in the genus of Pseudomonas. The FA resistance of the Gram-negative bacteria was positively correlated with the number of predicted genes for FA efflux pumps present in the genome. Phylogenetic analysis of predicted FA resistance proteins (FUSC, an inner membrane transporter component of the efflux pump) revealed that FUSC proteins having high sequence identities with the functionally characterized FA resistance protein FusC or Fdt might be the major contributors of FA resistance. In contrast, most fungi converted FA to less toxic compounds regardless of the level of FA resistance they exhibited. Five derivatives were detected, and the detoxification of FA involved either oxidative reactions on the butyl side chain or reductive reactions on the carboxylic acid group. The production of these metabolites from widely different phyla indicates that resistance to FA by altering its structure is highly conserved. A few FA resistant saprophytic or biocontrol strains of fungi were incapable of altering FA, indicating a possible involvement of efflux transporters. Deployment of both efflux and derivatization mechanisms may be a common feature of fungal FA resistance.

Fusarium oxysporum f. sp. vasinfectum race 4 (VCG0114), which causes root rot and wilt of cotton (Gossypium hirsutum and G. barbadense), has been identified recently for the first time in the western hemisphere in certain fields in the San Joaquin Valley of California. This pathotype produces copious quantities of the plant toxin fusaric acid (5-butyl-2-pyridinecarboxylic acid) compared to other isolates of F. oxysporum f. sp. vasinfectum (Fov) that are indigenous to the United States. Fusaric acid is toxic to cotton plants and may help the pathogen compete with other microbes in the soil. We found that a laboratory strain of the fungus Mucor rouxii converts fusaric acid into a newly identified compound, 8-hydroxyfusaric acid. The latter compound is significantly less phytotoxic to cotton than the parent compound. On the basis of bioassays of hydroxylated analogues of fusaric acid, hydroxylation of the butyl side chain of fusaric acid may affect a general detoxification of fusaric acid. Genes that control this hydroxylation may be useful in developing biocontrol agents to manage Fov.

Diverse natural phenolic compounds show inhibition activity of intestinal α-glucosidases, which may constitute the molecular basis for their ability to control systemic glycemia. Additionally, phenolics can modify mRNA expression for proteins involved in nutritional, metabolic or immune processes. To explore the possibility that phenolics can regulate the mRNA expression, enzymatic activity, and protein synthesis/processing of intestinal Maltase-Glucoamylase (MGAM) and Sucrase-Isomaltase (SI), small intestinal explants from Balb/c mice were cultured for 24 h in the presence or absence of gallic acid, caffeic acid, and (+)-catechin at 0.1, 0.5, and 1 mM. We measured the levels of MGAM and SI mRNA expression by qRT-PCR, maltase and sucrase activities by a standard colorimetric method and the molecular size distribution of MGAM and SI proteins by western blotting. mRNA expression for MGAM was induced by the three phenolic compounds at 0.1 mM. mRNA expression for SI was induced by caffeic and gallic acids, but not by (+)-catechin. Caffeic acid was the most effective inducer of mRNA expression of these enzymes. Total maltase and sucrase activities were not affected by treatment with phenolics. The proportion of high molecular size forms of MGAM was significantly increased by two of the three phenolic compounds, but little effect was observed on SI proteins. Thus, changes in the protein synthesis/processing, affecting the proportions of the different molecular forms of MGAM, may account for the lack of correlation between mRNA expression and enzymatic activity.

The objective of the present work was to examine the development of crystalline orientation and texture in the polypropylene matrix of talc-filled i-PP and in unfilled i-PP with increasing draw ratio during solid-phase die-drawing at high strain rates (∼1 s−1) and a die temperature of 145 °C. After drawing, the entire billet was cooled rapidly “under tension” to room temperature before releasing the billet and cutting specimens from different axial locations for analysis. Orientation distributions of the three crystal axes for increasing axial strains have been presented as pole figures in the MD-TD plane with the direction of draw (MD) as the reference direction. While disruption of spherulites was noticed within the die for neat PP at a draw ratio of 1.5, transcrystalline domains within the composite persisted even at a draw ratio of 3.5 in the free draw region outside the die. The transformation to fibrillar crystal morphology was complete in both materials at a draw ratio of 4.5 but the texture continued to develop beyond this stage. While the (110)[001] texture component was found to be dominant at all draw ratios for neat PP, the (010)[001] texture component was dominant at the higher draw ratios in the drawn composite. This may be attributed to the (010)[001] slip system being more active as the transverse spacing between elongated voids encasing the particles was decreased. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 1528–1538

Acute intermittent hypoxia (AIH; three 5-min hypoxic episodes) causes a form of phrenic motor facilitation (pMF) known as phrenic long-term facilitation (pLTF); pLTF is initiated by spinal activation of Gq protein-coupled 5-HT2 receptors. Because α1 adrenergic receptors are expressed in the phrenic motor nucleus and are also Gq protein-coupled, we hypothesized that α1 receptors are sufficient, but not necessary for AIH-induced pLTF. In anesthetized, paralyzed, and ventilated rats, episodic spinal application of the α1 receptor agonist phenylephrine (PE) elicited dose-dependent pMF (10 and 100 μM, P < 0.05; but not 1 μM). PE-induced pMF was blocked by the α1 receptor antagonist prazosin (1 mM; −20 ± 20% at 60 min, −5 ± 21% at 90 min; n = 6). Although α1 receptor activation is sufficient to induce pMF, it was not necessary for AIH-induced pLTF because intrathecal prazosin (1 mM) did not alter AIH-induced pLTF (56 ± 9% at 60 min, 78 ± 12% at 90 min; n = 9). Intravenous (iv) prazosin (150 μg/kg) appeared to reduce pLTF (21 ± 9% at 60 min, 26 ± 8% at 90 min), but this effect was not significant. Hypoglossal long-term facilitation was unaffected by intrathecal prazosin, but was blocked by iv prazosin (−4 ± 14% at 60 min, −13 ± 18% at 90 min), suggesting different LTF mechanisms in different motor neuron pools. In conclusion, Gq protein-coupled α1 adrenergic receptors evoke pMF, but they are not necessary for AIH-induced pLTF.

Using the small intestine enterocyte Caco-2 cell model, sucrase-isomaltase (SI, the mucosal α-glucosidase complex) expression and modification were examined relative to exposure to different mono- and disaccharide glycemic carbohydrates. Caco-2/TC7 cells were grown on porous supports to post-confluence for complete differentiation, and dietary carbohydrate molecules of glucose, sucrose (disaccharide of glucose and fructose), maltose (disaccharide of two glucoses α-1,4 linked), and isomaltose (disaccharide of two glucoses α-1,6 linked) were used to treat the cells. qRT-PCR results showed that all the carbohydrate molecules induced the expression of the SI gene, though maltose (and isomaltose) showed an incremental increase in mRNA levels over time that glucose did not. Western blot analysis of the SI protein revealed that only maltose treatment induced a higher molecular weight band (Mw ~245 kDa), also at higher expression level, suggesting post-translational processing of SI, and more importantly a sensing of maltose. Further work is warranted regarding this putative sensing response as a potential control point for starch digestion and glucose generation in the small intestine.

The fungus Fusarium oxysporum causes wilt diseases of plants and produces a potent phytotoxin fusaric acid (FA), which is also toxic to many microorganisms. An Aspergillus tubingensis strain with high tolerance to FA was isolated from soil and designated as CDRAt01. HPLC analysis of culture filtrates from A. tubingensis isolate CDRAt01 grown with the addition of FA indicated the formation of a metabolite over time that was associated with a decrease of FA. Spectral analysis and chemical synthesis confirmed the compound as 5-butyl-2-pyridinemethanol, referred to here as fusarinol. The phytotoxicity of fusarinol compared to FA was measured by comparing necrosis induced in cotton (Gossypium hirsutum L. cv. Coker 312) cotyledons. Fusarinol was significantly less phytotoxic than FA. Therefore, the A. tubingensis strain provides a novel detoxification mechanism against FA which may be utilized to control Fusarium wilt.

Objectives: Six enzyme activities are needed to digest starch to absorbable free glucose; 2 luminal a-amylases (AMY) and 4 mucosal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) subunit activities are involved in the digestion. The AMY activities break down starch to soluble oligomeric dextrins; mucosal MGAM and SI can either directly digest starch to glucose or convert the post-a-amylolytic dextrins to glucose. We hypothesized that MGAM, with higher maltase than SI, drives digestion on ad limitum intakes and SI, with lower activity but more abundant amount, constrains ad libitum starch digestion. Methods:Mgamnulland wild-type(WT) mice were fed with starch diets ad libitum and ad limitum. Fractional glucogenesis (fGG) derived from starch was measured and fractional gluconeogenesis and glycogenolysis were calculated. Carbohydrates in small intestine were determined. Results: After ad libitum meals, null and WT had similar increases of blood glucose concentration. At low intakes, null mice had less fGG (P ¼0.02) than WT mice, demonstrating the role of Mgam activity in ad limitum feeding; null mice did not reduce fGG responses to ad libitum intakes demonstrating the dominant role of SI activity during full feeding. Although fGG was rising after feeding, fractional gluconeogenesis fell, especially for null mice. Conclusions: The fGNG (endogenous glucogenesis) in null mice complemented the fGG (exogenous glucogenesis) to conserve prandial blood glucose concentrations. The hypotheses that Mgam contributes a high-efficiency activity on ad limitum intakes and SI dominates on ad libitum starch digestion were confirmed.

A standardized experiment was conducted during 2009 and 2010 at 20 location-years across U.S. cotton (Gossypium hirsutum L.)-producing states to compare the N use requirement of contemporary cotton cultivars based on their planting seed size. Treatments consisted of three cotton varieties with planting seed of different numbers of seed per kg and N rates of 0, 45, 90, and 134 kg ha–¹. Soil at each trial location was sampled and tested for nitrate presence. High levels of soil nitrate (>91 N-NO₃– kg ha–¹) were found in Arizona and western Texas, and soil nitrate in the range of 45 to 73 kg N-NO₃– ha–¹ was found at locations in the central United States. Cotton lint yield responded to applied N at 11 of 20 locations. Considering only sites that responded to applied N, highest lint yields were achieved with 112 to 224 kg ha–¹of applied plus pre-plant residual soil NO₃—translating to an optimal N requirement of 23 kg ha–¹ per 218 kg bale of lint produced. Among the varieties tested those with medium-sized seed produced higher yields in response to N than did larger and smaller seeded varieties. Varieties with larger seed had longer and stronger fibers, higher fiber length uniformity than small seeded varieties and decreased micronaire. Seed protein and oil increased and decreased slightly in response to increasing amounts of soil nitrate plus applied N, respectively.

This study examined the effect of prior exercise on postprandial lipemia (PPL) concentration following a mixed meal (MM) made with either glucose or fructose. Sedentary women completed four trials in random order: 1) Rest-Fructose: RF, 2) Rest-Glucose: RG, 3) Exercise-Fructose: EF, 4) Exercise-Glucose: EG. Exercise expended 500 kcal while walking at 70%VO2max. Rest was 60 min of sitting. The morning after each trial, a fasting (12 hr) blood sample was collected followed by consumption of the MM. The MM was blended with whole milk and ice cream plus a glucose or fructose powder. Glucose and fructose powder accounted for 30% of the total kcal within the MM. Blood was collected periodically for 6 hr post-MM and analyzed for PPL. Magnitude of PPL over the 6 hr postmeal was quantified using the triglyceride incremental area under the curve (TG AUCI). Significant differences (p < .05) between trials were determined using repeated-measures ANOVA and Bonferroni post hoc test. There was no significant difference in the TG AUCI between the four trials (p > .05). A significant trial by time interaction for TG concentration was reported (p < .05). Despite lack of change in the AUCI with prior exercise, the lower TG concentration at multiple time points in the EG trial does indicate that prior exercise has some desirable effect on PPL. This study suggests that replacing fructose with glucose sugars and incorporating exercise may minimize PPL following a mixed meal but exercise will need to elicit greater energy expenditure.