Identification, characterization, and comprehensive expression profiling of floral master regulators in pigeon pea (Cajanus cajan [L.] Millspaugh).

Pigeon pea is an important protein-rich pulse crop. Identification of flowering master regulators in pigeon pea is highly imperative as indeterminacy and late flowering are impediments towards yield improvement. A genome-wide analysis was performed to explore flowering orthologous groups in pigeon pea. Among the 412 floral orthologs identified in pigeon pea, 148 genes belong to the meristem identity, photoperiod-responsive, and circadian clock-associated ortholog groups. Our comparative genomics study revealed purifying selection pressures (ka/ks) on floral orthologs, and duplication patterns and evolution through synteny with other model species. Phylogenetic analysis of floral genes substantiated a connection between pigeon pea plant architecture and flowering time as all the PEBP domain-containing genes belong to meristem identity floral networks of pigeon pea. Expression profiling of eleven major orthologs in contrasting determinate and indeterminate genotypes indicated that these orthologs might be involved in flowering regulation. Expression of floral inducer, FT, and floral repressor, TFL1, was non-comparable in indeterminate genotypes across all the developmental stages of pigeon pea. However, dynamic FT/TFL1 expression ratio detected in all tissues of both the genotypes suggested their role in floral transition. One TFL1 ortholog having high sequence conserveness across pigeon pea genotypes showed differential expression indicating genotype-dependent regulation of this ortholog. Presence of conserved 6mA-methylation patterns in light-responsive elements and in other cis-regulatory elements of FT and TFL1 across different plant genotypes indicated possible involvement of epigenetic regulation in flowering.

Switching between blebbing and lamellipodia depends on the degree of non-muscle myosin II activity.

Cells can adopt both mesenchymal and amoeboid modes of migration through membrane protrusive activities, namely formation of lamellipodia and blebbing. How the molecular players control the transition between lamellipodia and blebs is yet to be explored. Here, we show that addition of the ROCK inhibitor Y27632 or low doses of blebbistatin, an inhibitor of non-muscle myosin II (NMII) ATPase activity and filament partitioning, induces blebbing to lamellipodia conversion (BLC), whereas addition of low doses of ML7, an inhibitor of myosin light chain kinase (MLCK), induces lamellipodia to blebbing conversion (LBC) in human MDA-MB-231 cells. Similarly, siRNA-mediated knockdown of ROCK and MLCK induces BLC and LBC, respectively. Interestingly, both blebs and lamellipodia membrane protrusions are able to maintain the ratio of phosphorylated to unphosphorylated regulatory light chain at cortices when MLCK and ROCK, respectively, are inhibited either pharmacologically or genetically, suggesting that MLCK and ROCK activities are interlinked in BLC and LBC. Such BLCs and LBCs are also inducible in other cell lines, including MCF7 and MCF10A. These studies reveal that the relative activity of ROCK and MLCK, which controls both the ATPase activity and filament-forming property of NMII, is a determining factor in whether a cell exhibits blebbing or lamellipodia.

Atomistic Simulations of Hydrated Sulfonated Polybenzophenone Block Copolymer Membranes.

We present a classical molecular dynamics simulations study on the nanostructures of the sulfonated polybenzophenone (SPK) block copolymer membranes at 300 K and 353 K. The results of the radial distribution function (RDF) show that the interactions of the sulfonate groups of the membrane with the hydronium ions are more significant than those of water due to the strong electrostatic attraction over the hydrogen bonding. However, the effect of temperatures on the RDF profile seems insignificant. Furthermore, the spatial distribution function (SDF) portrays that the sulfonate groups of the hydrophilic components are preferential binding sites for hydronium ions against the hydrophobic counterpart of the SPK membrane. The mobility of the H3 O+ ions at 300 K and 353 K is two (or three) times lower than that of Nafion/Aciplex. However, the diffusion coefficients for water molecules closely agree with Nafion/Aciplex. This study suggests that water clusters are more localized around the sulfonate groups in the SPK membranes. Thus, the molecular modeling study of SPK block copolymer membranes is warranted to design better-performing membrane electrolytes.

Comparative analysis of herbivory responsive miRNAs to delineate pod borer (Helicoverpa armigera) resistance mechanisms in Cajanus cajan and its wild relative Cajanus scarabaeoides.

KEY MESSAGE: Comparative analysis of herbivory responsive miRNAs between pod borer susceptible C. cajan and its resistant Crop Wild Relative (CWR) C. scarabaeoides revealed miRNA-based regulation of defense genes and plant-insect interactions. Gram pod borer (Helicoverpa armigera) is one of most devastating pests of pigeon pea (Cajanus cajan) worldwide, responsible for huge losses in crop productivity. The lack of genes conferring resistance to pod borer in pigeon pea has proven to be a bottleneck for its improvement. One of its CWR, C. scarabaeoides has demonstrated resistance to this pest and can be exploited for developing pest resistant crop varieties. Differences in expression patterns of herbivory responsive microRNAs in the susceptible C. cajan and resistant C. scarabaeoides after different time duration of pod borer infestation (2 h, 8 h and 18 h) were identified, characterized and functionally validated to understand their role in insect defense response. A total of 462 conserved and 449 novel miRNAs and 273 conserved and 185 novel miRNAs, were identified in C. cajan and C. scarabaeoides, respectively. Among the identified miRNAs, 65, 68 and 65 miRNAs were found to be differentially expressing between the C. scarabaeoides and C. cajan libraries 2 h, 8 h and 18 h post infestation, respectively. These miRNAs were found to target genes involved in a number of pathways contributing to defense and acquired resistance in C. scarabaeoides against pod borer, indicating miRNA-based regulation of defense pathways. Expression patterns of eight of these miRNAs were validated by qRT-PCR. This study provides novel insights into the miRNA-mediated plant-insect interactions and the mechanisms of regulatory pathways involved in insect defense. These findings can be utilized for further exploring the mechanism of herbivore defense in plant systems.

Nanobioremediation: A sustainable approach towards the degradation of sodium dodecyl sulfate in the environment and simulated conditions.

Nanotechnology has gained huge importance in the field of environmental clean-up today. Due to their remarkable and unique properties, it has shown potential application for the remediation of several pesticides and textile dyes. Recently it has shown positive results for the remediation of sodium dodecyl sulfate (SDS). One of the highly exploited surfactants in detergent preparation is anionic surfactants. The SDS selected for the present study is an example of anionic linear alkyl sulfate. It is utilized extensively in industrial washing, which results in the high effluent level of this contaminant and ubiquitously toxic to the environment. The present review is based on the research depicting the adverse effects of SDS in general and possible strategies to minimizing its effects by bacterial degradation which are capable of exploiting the SDS as an only source of carbon. Moreover, it has also highlighted that how nanotechnology can play a role in the remediation of such recalcitrant pesticides.

Arousal-based scoring of obstructive hypopneas.

PURPOSE OF REVIEW: Obstructive sleep apnea in adults is diagnosed by an apnea-hypopnea index (AHI) above five (at least five apneas and/or hypopneas per hour of sleep). Though the definition of apneas has remained stable, the scoring criteria for hypopneas has varied throughout the years. There is even more evidence now that scoring respiratory events associated with arousals should be included in the diagnosis of obstructive sleep apnea, as these patients may benefit from treatment. RECENT FINDINGS: Recent studies, trials and meta-analyses have demonstrated that respiratory events associated with arousal are associated with symptoms, such as poor sleep quality and excessive daytime sleepiness. These arousal-based hypopneas have also been noted to carry a risk of hypertension and other adverse health consequences. SUMMARY: Requiring a 4% oxygen desaturation for hypopneas may miss patients that may benefit from treatment for obstructive sleep apnea. These patients are typically younger, nonobese, and women as they have been found to have respiratory events causing sleep fragmentation versus significant oxygen desaturation as compared with other populations.

Percutaneous ultrasound guided thrombin injection for axillary artery pseudoaneurysm following stenting of the arterial duct in two infants: Case report with review of literature.

We report pseudoaneurysm of the axillary artery following stenting of the arterial duct in two infants. They were both successfully managed by ultrasound guided thrombin injection with preservation of native arterial flow. We also review the relevant literature.

Impact of three different daily doses of vitamin D3 supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial.

In India, there is a lack of information about the adequate daily dose of vitamin D3 supplementation in school children. Hence, we undertook this study to evaluate the adequacy and efficacy of different doses of vitamin D3 in schoolchildren. A total of 1008 vitamin D-deficient (VDD) children, aged 6-16 years with serum 25-hydroxyvitamin D (25(OH)D) levels <50nmol/l, were cluster randomised into three groups (A-344, B-341 and C-232) for supplementation (600, 1000 and 2000 IU daily) of vitamin D3 under supervision for 6 months. Of the 1008 subjects who completed the study, 938 (93 %) were compliant. Baseline and post-supplementation fasting blood and urine samples were evaluated for Ca, phosphates, alkaline phosphatase, 25(OH)D and parathormone and urine Ca:creatinine ratio. The mean age of the subjects was 11·7 (sd 2·4) years, and the overall mean baseline serum 25(OH)D level was 24·3 (SD 9·5)nmol/l. Post-supplementation rise in serum 25(OH)D in compliant group was maximum with 2000 IU (70·0 (SD 30·0)nmol/l), followed by 1000 IU (46·8 (SD 22·5)nmol/l) and 600 IU (36·5 (SD 18·5)nmol/l), and serum 25(OH)D levels of ≥50nmol/l were achieved in 71·5, 81·8 and 92·9 % by groups A, B and C, respectively. Secondary hyperparathyroidism decreased from 31·7 to 8·4 % post-supplementation. Two participants developed hypercalciuria, but none developed hypercalcaemia. Children with VDD benefit maximum with the daily supplementation of 2000 IU of vitamin D3. Whether recommendations of 400 IU/d by Indian Council of Medical Research or 600 IU by Indian Academy of Pediatrics or Institute of Medicine would suffice to achieve vitamin D sufficiency in children with VDD remains debatable.

A randomised controlled trial comparing the efficacy of micellised and fat-soluble vitamin D3 supplementation in healthy adults.

Nanoemulsion formulation of vitamin D3 have been shown to have better bioavailability than the coarse emulsion preparation in vitro and in vivo animal studies. In the absence of randomised trial in humans, comparing the efficacy of nanotechnology-based miscellised vitamin D3 over conventional vitamin D3, we undertook this study. A total of 180 healthy adults were randomised to receive either micellised (DePura, group A) or conventional vitamin D3 (Calcirol, group B) at a monthly dose of 60 000 IU (1500µg) for 6 months. The outcome parameters were serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), Ca, phosphate, alkaline phosphatase and urinary Ca:creatinine ratio. A total of eighty-nine subjects in group A and seventy-seven in group B completed the trial. Subjects in both the groups had a significant increase in their serum 25(OH)D levels following supplementation (group A: 21·5 (sd 10·9) to 76·7 (sd 18·8) nmol/l (P<0·001); group B: 22·8 (sd 10·4) to 57·8 (sd 16·0) nmol/l (P<0·001)). Participants in micellised group had an additional increase of 20·2 (95 % CI 14·0, 26·4) nmol/l in serum 25(OH)D levels (P<0·001). The difference between the groups was 17·5 (95 % CI 11·8, 23·1) nmol/l, which remained statistically significant (P<0·001) even after adjustment for age and sex. Significant decline in mean serum PTH was observed in both the groups. No hypercalcaemia or hypercalciuria was noted. Although supplementation with both the preparations resulted in a significant rise in serum 25(OH)D levels, micellised vitamin D3 appeared to be more efficacious in achieving higher levels of serum 25(OH)D.

Insights into geometries, stabilities, electronic structures, reactivity descriptors, and magnetic properties of bimetallic Nim Cun-m (m = 1, 2; n = 3-13) clusters: Comparison with pure copper clusters.

A long-range corrected density functional theory (LC-DFT) was applied to study the geometric structures, relative stabilities, electronic structures, reactivity descriptors and magnetic properties of the bimetallic NiCun-1 and Ni2 Cun-2 (n = 3-13) clusters, obtained by doping one or two Ni atoms to the lowest energy structures of Cun , followed by geometry optimizations. The optimized geometries revealed that the lowest energy structures of the NiCun-1 and Ni2 Cun-2 clusters favor the Ni atom(s) situated at the most highly coordinated position of the host copper clusters. The averaged binding energy, the fragmentation energies and the second-order energy differences signified that the Ni doped clusters can continue to gain an energy during the growth process. The electronic structures revealed that the highest occupied molecular orbital and the lowest unoccupied molecular orbital energies of the LC-DFT are reliable and can be used to predict the vertical ionization potential and the vertical electron affinity of the systems. The reactivity descriptors such as the chemical potential, chemical hardness and electrophilic power, and the reactivity principle such as the minimum polarizability principle are operative for characterizing and rationalizing the electronic structures of these clusters. Moreover, doping of Ni atoms into the copper clusters carry most of the total spin magnetic moment. © 2018 Wiley Periodicals, Inc.

On low-lying excited states of extended nanographenes.

Low-lying excited states of planarly extended nanographenes are investigated using the long-range corrected (LC) density functional theory (DFT) and the spin-flip (SF) time-dependent density functional theory (TDDFT) by exploring the long-range exchange and double-excitation correlation effects on the excitation energies, band gaps, and exciton binding energies. Optimizing the geometries of the nanographenes indicates that the long-range exchange interaction significantly improves the CC bond lengths and amplify their bond length alternations with overall shortening the bond lengths. The calculated TDDFT excitation energies show that long-range exchange interaction is crucial to provide accurate excitation energies of small nanographenes and dominate the exciton binding energies in the excited states of nanographenes. It is, however, also found that the present long-range correction may cause the overestimation of the excitation energy for the infinitely wide graphene due to the discrepancy between the calculated band gaps and vertical ionization potential (IP) minus electron affinity (EA) values. Contrasting to the long-range exchange effects, the SF-TDDFT calculations show that the double-excitation correlation effects are negligible in the low-lying excitations of nanographenes, although this effect is large in the lowest excitation of benzene molecule. It is, therefore, concluded that long-range exchange interactions should be incorporated in TDDFT calculations to quantitatively investigate the excited states of graphenes, although TDDFT using a present LC functional may provide a considerable excitation energy for the infinitely wide graphene mainly due to the discrepancy between the calculated band gaps and IP-EA values. © 2017 Wiley Periodicals, Inc.

Rice Root Architectural Plasticity Traits and Genetic Regions for Adaptability to Variable Cultivation and Stress Conditions.

Future rice (Oryza sativa) crops will likely experience a range of growth conditions, and root architectural plasticity will be an important characteristic to confer adaptability across variable environments. In this study, the relationship between root architectural plasticity and adaptability (i.e. yield stability) was evaluated in two traditional × improved rice populations (Aus 276 × MTU1010 and Kali Aus × MTU1010). Forty contrasting genotypes were grown in direct-seeded upland and transplanted lowland conditions with drought and drought + rewatered stress treatments in lysimeter and field studies and a low-phosphorus stress treatment in a Rhizoscope study. Relationships among root architectural plasticity for root dry weight, root length density, and percentage lateral roots with yield stability were identified. Selected genotypes that showed high yield stability also showed a high degree of root plasticity in response to both drought and low phosphorus. The two populations varied in the soil depth effect on root architectural plasticity traits, none of which resulted in reduced grain yield. Root architectural plasticity traits were related to 13 (Aus 276 population) and 21 (Kali Aus population) genetic loci, which were contributed by both the traditional donor parents and MTU1010. Three genomic loci were identified as hot spots with multiple root architectural plasticity traits in both populations, and one locus for both root architectural plasticity and grain yield was detected. These results suggest an important role of root architectural plasticity across future rice crop conditions and provide a starting point for marker-assisted selection for plasticity.

Transcatheter closure of a membranous ventricular septal defect in a 1.8-kg infant using Amplatzer Duct Occluder II additional size device.

Catheter closure of membranous ventricular septal defects is generally not considered feasible in small infants. We report the successful closure of a membranous ventricular septal defect in a 1.8-kg infant with bilateral femoral artery occlusion using Amplatzer Duct Occluder II additional size device. The ventricular septal defect was crossed from the right ventricle, and the device was deployed using transthoracic echocardiographic guidance.

Relationship between orbital energy gaps and excitation energies for long-chain systems.

The difference between the excitation energies and corresponding orbital energy gaps, the exciton binding energy, is investigated based on time-dependent (TD) density functional theory (DFT) for long-chain systems: all-trans polyacetylenes and linear oligoacenes. The optimized geometries of these systems indicate that bond length alternations significantly depend on long-range exchange interactions. In TDDFT formalism, the exciton binding energy comes from the two-electron interactions between occupied and unoccupied orbitals through the Coulomb-exchange-correlation integral kernels. TDDFT calculations show that the exciton binding energy is significant when long-range exchange interactions are involved. Spin-flip (SF) TDDFT calculations are then carried out to clarify double-excitation effects in these excitation energies. The calculated SF-TDDFT results indicate that double-excitation effects significantly contribute to the excitations of long-chain systems. The discrepancies between the vertical ionization potential minus electron affinity (IP-EA) values and the HOMO-LUMO excitation energies are also evaluated for the infinitely long polyacetylene and oligoacene using the least-square fits to estimate the exciton binding energy of infinitely long systems. It is found that long-range exchange interactions are required to give the exciton binding energy of the infinitely long systems. Consequently, it is concluded that long-range exchange interactions neglected in many DFT calculations play a crucial role in the exciton binding energies of long-chain systems, while double-excitation correlation effects are also significant to hold the energy balance of the excitations. © 2016 Wiley Periodicals, Inc.

SAR exploration at the C-3 position of tetrahydro-ß-carboline sstr3 antagonists.

MK-4256, a tetrahydro-ß-carboline sstr3 antagonist, was discontinued due to a cardiovascular (CV) adverse effect observed in dogs. Additional investigations revealed that the CV liability (QTc prolongation) was caused by the hERG off-target activity of MK-4256 and was not due to sstr3 antagonism. In this Letter, we describe our extensive SAR effort at the C3 position of the tetrahydro-ß-carboline structure. This effort resulted in identification of 5-fluoro-pyridin-2-yl as the optimal substituent on the imidazole ring to balance sstr3 activity and the hERG off-target liability.

Future therapies for pemphigus vulgaris: Rituximab and beyond.

The conventional treatment for patients with pemphigus vulgaris (PV) centers on global immunosuppression, such as the use of steroids and other immunosuppressive drugs, to decrease titers of antidesmoglein autoantibodies responsible for the acantholytic blisters. Global immunosuppressants, however, cause serious side effects. The emergence of anti-CD20 biologic medications, such as rituximab, as an adjunct to conventional therapy has shifted the focus to targeted destruction of autoimmune B cells. Next-generation biologic medications with improved modes of delivery, pharmacology, and side effect profiles are constantly being developed, adding to the diversity of options for PV treatment. We review promising monoclonal antibodies, including veltuzumab, obinutuzumab (GA-101), ofatumumab, ocaratuzumab (AME-133v), PRO131921, and belimumab.

Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment.

The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis.

This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.

Echocardiographic screening for rheumatic heart disease in high and low risk Australian children.

BACKGROUND: Echocardiographic screening for rheumatic heart disease (RHD) is becoming more widespread, but screening studies to date have used different echocardiographic definitions. The World Heart Federation has recently published new criteria for the echocardiographic diagnosis of RHD. We aimed to establish the prevalence of RHD in high-risk Indigenous Australian children using these criteria and to compare the findings with a group of Australian children at low risk for RHD. METHODS AND RESULTS: Portable echocardiography was performed on high-risk Indigenous children aged 5 to 15 years living in remote communities of northern Australia. A comparison group of low-risk, non-Indigenous children living in urban centers was also screened. Echocardiograms were reported in a standardized, blinded fashion. Of 3946 high-risk children, 34 met World Heart Federation criteria for definite RHD (prevalence, 8.6 per 1000 [95% confidence interval, 6.0-12.0]) and 66 for borderline RHD (prevalence, 16.7 per 1000 [95% confidence interval, 13.0-21.2]). Of 1053 low-risk children, none met the criteria for definite RHD, and 5 met the criteria for borderline RHD. High-risk children were more likely to have definite or borderline RHD than low-risk children (adjusted odds ratio, 5.7 [95% confidence interval, 2.3-14.1]; P<0.001). CONCLUSIONS: The prevalence of definite RHD in high-risk Indigenous Australian children approximates what we expected in our population, and no definite RHD was identified in the low-risk group. This study suggests that definite RHD, as defined by the World Heart Federation criteria, is likely to represent true disease. Borderline RHD was identified in children at both low and high risk, highlighting the need for longitudinal studies to evaluate the clinical significance of this finding.

Reactivity index based on orbital energies.

This study shows that the chemical reactivities depend on the orbital energy gaps contributing to the reactions. In the process where a reaction only makes progress through charge transfer with the minimal structural transformation of the reactant, the orbital energy gap gradient (OEGG) between the electron-donating and electron-accepting orbitals is proven to be very low. Using this relation, a normalized reaction diagram is constructed by plotting the normalized orbital energy gap with respect to the normalized intrinsic reaction coordinate. Application of this reaction diagram to 43 fundamental reactions showed that the majority of the forward reactions provide small OEGGs in the initial stages, and therefore, the initial processes of the forward reactions are supposed to proceed only through charge transfer. Conversely, more than 60% of the backward reactions are found to give large OEGGs implying very slow reactions associated with considerable structural transformations. Focusing on the anti-activation-energy reactions, in which the forward reactions have higher barriers than those of the backward ones, most of these reactions are shown to give large OEGGs for the backward reactions. It is also found that the reactions providing large OEGGs in the forward directions inconsistent with the reaction rate constants are classified into SN 2, symmetric, and methyl radical reactions. Interestingly, several large-OEGG reactions are experimentally established to get around the optimum pathways. This indicates that the reactions can take significantly different pathways from the optimum ones provided no charge transfer proceeds spontaneously without the structural transformations of the reactants.