Palladium-Catalyzed Chelation-Assisted Aldehyde C-H Bond Activation of Quinoline-8-carbaldehydes: Synthesis of Amides from Aldehydes with Anilines and Other Amines.

A palladium-catalyzed chelation-assisted direct aldehyde C-H bond amidation of quinoline-8-carbaldehydes with an amine was developed under mild reaction conditions. A wide range of amides were obtained in good to excellent yields from aldehyde with a variety of aniline derivatives and aliphatic amines. Our methodology was successfully applied to synthesize known DNA intercalating agents and can be easily scaled up to a gram scale.

Global warming alters Himalayan alpine shrub growth dynamics and climate sensitivity.

Global climate change is having significant effects on plant growth patterns and mountain plants can be particularly vulnerable to accelerated warming. Rising temperatures are releasing plants from cold limitation, such as at high elevations and latitudes, but can also induce drought limitation, as documented for trees from lower elevations and latitudes. Here we test these predictions using a unique natural experiment with Himalayan alpine shrub Rhododendron anthopogon and its growth responses to changing climate over a large portion of its latitudinal and elevational ranges, including steep precipitation and temperature gradients. We determined growth dynamics during the last three decades, representing period of accelerated warming, using annual radial growth increments for nine populations growing on both wet and warm southern localities and drier and cold northern localities in the Himalayas along elevation gradients encompassing the lower and upper species range limits. A significant growth increase over past decades was observed after controlling for confounding effect of shrub age and microsites. However, the magnitude of increase varied among populations. Particularly, populations situated in the lower elevation of the northernmost (cold and dry) locality exhibited most substantial growth enhancement. The relationship between growth variability and climate varied among populations, with the populations from the coldest location displaying the strongest responsiveness to increasing minimum temperatures during July. Minimum temperatures of April and August were the most important factor limiting the growth across most populations. Potential warming-induced drought limitation had no significant impact on growth variation in any part of the species geographic range. Overall, our findings indicate that plant growth is continuously increasing in recent decades and growth-climate relationships are not consistent across populations, with populations from the coldest and wettest localities showing stronger responses. The observed patterns suggest that dwarf-shrubs benefit from ongoing warming, leading to increased shrubification of high elevation alpine ecosystems.

Palladium-Catalyzed Directed Aldehyde C-H Arylation of Quinoline-8-carbaldehydes: Exploring the Reactivity Differences between Aryl (Pseudo) Halides.

We have developed a method for Pd-catalyzed direct C-H arylation of quinoline-8-carbaldehydes with either aryl iodides or aryl diazonium salts for the synthesis of aryl quinolinyl ketones. Aryl iodide substituted with an electron-donating group favors the reaction, whereas aryl diazonium salt substituted with an electron-withdrawing group showed excellent reactivity. A range of aryl quinolinyl ketones were synthesized in good-to-excellent yields, with very good functional group tolerance. Our methodology was successfully applied to synthesize highly potent tubulin polymerization inhibitors and can be easily scaled up to a gram scale.

Rhizome trait scaling relationships are modulated by growth conditions and are linked to plant fitness.

BACKGROUND AND AIMS: Rhizomes are important organs allowing many clonal plants to persist and reproduce under stressful climates with longer rhizomes, indicating enhanced ability of the plants to spread vegetatively. We do not, however, know either how rhizome construction costs change with increasing length or how they vary with environmental conditions. METHODS: We analysed the rhizome length vs. mass scaling relationship, the plasticity in the scaling relationships, their genetic basis and how scaling relationships are linked to plant fitness. We used data from 275 genotypes of a clonal grass Festuca rubra originating from 11 localities and cultivated under four contrasting climates. Data were analysed using standard major axis regression, mixed-effect regression models and a structural equation model. KEY RESULTS: Rhizome construction costs increased (i.e. lower specific rhizome length) with increasing length. The trait scaling relationships were modulated by cultivation climate, and its effects also interacted with the climate of origin of the experimental plants. With increasing length, increasing moisture led to a greater increase in rhizome construction costs. Plants with lower rhizome construction costs showed significantly higher fitness. CONCLUSIONS: This study suggests that rhizome scaling relationships are plastic, but also show genetic differentiation and are linked to plant fitness. Therefore, to persist under variable environments, modulation in scaling relationships could be an important plant strategy.

Time-series eco-metabolomics reveals extensive reshuffling in metabolome during transition from cold acclimation to de-acclimation in an alpine shrub.

Recording environmentally induced variations in the metabolome in plants can be a promising approach for understanding the complex patterns of metabolic regulation and their eco-physiological consequences. Here, we studied metabolome-wide changes and eco-physiological adjustments occurring across the year at high elevation environments in the leaf tissue of Rhododendron anthopogon, an alpine evergreen shrub of the Himalaya. New leaves of R. anthopogon appear after the snow-melt and remain intact even when the plants get covered under snow (November-June). During this whole period, they may undergo several physiological and biochemical adjustments in response to fluctuating temperatures and light conditions. To understand these changes, we analyzed eco-physiological traits, that is, freezing resistance, dry matter content and % of nitrogen and the overall metabolome across 10 different time-points, from August until the snowfall in November 2017, and then from June to August 2018. As anticipated, the freezing resistance increased toward the onset of winters. The leaf tissues exhibited a complete reshuffling of the metabolome during the growth cycle and time-points segregated into four clusters directly correlating with distinct phases of acclimation: non-acclimation (August 22, 2017; August 14, 2018), early cold acclimation (September 12, September 29, October 11, 2017), late cold acclimation (October 23, November 4, 2017), and de-acclimation (June 15, June 28, July 14, 2018). Cold acclimation involved metabolic progression (101 metabolites) with an increase of up to 19.4-fold (gentiobiose), whereas de-acclimation showed regression (120 metabolites) with a decrease of up to 30-fold (sucrose). The changes in the metabolome during de-acclimation were maximum and were not just a reversal of cold acclimation. Our results provided insights into the direction and magnitude of physiological changes in Rhododendron anthopogon that occurred across the year.

Seasonal variations coupled with elevation gradient drives significant changes in eco-physiological and biogeochemical traits of a high altitude evergreen broadleaf shrub, Rhododendron anthopogon.

Higher elevations and, early as well as late phase of growing season are expected to be more stressful for plants in high altitudes. The present study was carried out on Rhododendron anthopogon D. Don, an evergreen shrub of Himalaya to understand variation in eco-physiological and biogeochemical traits due to combined effect of elevation gradient and growing season. We conducted our study at Rohtang, India (32°22'04″ N 77°15'17″ E) and undertook random sampling of leaves at four elevations (3200 m, 3600 m, 4000 m and 4250 m), and three time periods (late June, early August and late September) during growing season. We assessed 12 eco-physiological and biogeochemical variables and analysed results through ANOVA and multivariate analysis. It was found that leaf relative water content, nitrogen percentage (N%), carbon/nitrogen ratio (C/N ratio), total chlorophyll, malondialdehyde equivalents and proline content varied along two gradients (factors) with their interaction being statistically significant. Variance partitioning analysis of studied traits revealed that both factors contribute significantly, with 'season' component ranging between 55.75 % and 94.03 % for most of the parameters, whereas, 'elevation' component contributed more for leaf area, N% and C/N ratio (48.08 %-75.03 %). Our results suggest that eco-physiology of R. anthopogon is significantly influenced by interaction of seasonal variations coupled with elevation gradient. The study highlights the importance of examining both seasonal and elevational gradients in understanding plant adaptation strategies. Overall, our findings revealed that plasticity in eco-physiological and biogeochemical traits underline the wide distribution of R. anthopogon in the high altitudes.

Performance of broiler chicken fed multicarbohydrases supplemented low energy diet.

AIM: Objective of this study was to investigate the effect of multicarbohydrases supplementation on performance of broilers fed low energy diet. MATERIALS AND METHODS: A total of 75 days old chicks were selected and randomly divided into three treatments groups (T1, T2, and T3); each group contained 25 chicks distributed in five replicates of five chicks each. T1 group (positive control) was offered control ration formulated as per Bureau of Indian Standards recommendations. In T2 group (negative control) ration, metabolizable energy (ME) was reduced by 100 kcal/kg diet. T3 group ration was same as that of T2 except that it was supplemented with multicarbohydrases (xylanase at 50 g/ton+mannanase at 50 g/ton+amylase at 40 g/ton). Feed intake and body weight of all experimental birds were recorded weekly. Metabolic trial was conducted for 3 days at the end of experiment to know the retention of nutrients. RESULTS: Significant improvement (p<0.01) was observed in total weight gain, feed conversion efficiency, and performance index in broilers under supplementary group T3 as compared to T1 and T2 groups. Retention of crude protein and ether extract was significantly increased (p<0.05) in T3 group supplemented with multicarbohydrases as compared to other groups. Retention of dry matter, crude fiber, and nitrogen-free extract was comparable in all the three groups. Significantly highest dressed weight, eviscerated weight, and drawn weight (% of live body weight) were observed in multicarbohydrases supplemented T3 group, however it was comparable in T1 and T2 groups. CONCLUSION: It was concluded that the supplementation of multicarbohydrases (xylanase at 50 g/ton+mannanase at 50 g/ton+amylase at 40 g/ton) in low energy diet improved overall performance of broilers.

Generics Substitution, Bioequivalence Standards, and International Oversight: Complex Issues Facing the FDA.

The regulations for assessing the quality of generic drugs and their bioequivalence to innovator products are outdated and need to be substantially modernized. There are multiple reasons why these changes are needed, including: (i) the regulations remain largely unchanged since the passage of the Hatch-Waxman Act in 1984; (ii) medication therapies have become substantially more complex over the three decades since the passage of the Act; (iii) a switch from an innovator drug to a generic drug, or switching from one generic to another, is not a benign process - there is substantial clinical professional judgment involved and in some instances these decisions should be better informed; and (iv) pharmaceutical ingredients for finished products, whether innovator or generic, are from multiple sources of supply, adding variability in their production, and which may not be accounted for in specification tolerances. When these elements are viewed together, they clearly suggest that more transparency of responsible manufacturers in product labels and updated standards for bioequivalence are required.