Genome-wide SNPs and candidate genes underlying the genetic variations for protein and amino acids in pearl millet (Pennisetum glaucum) germplasm.

MAIN CONCLUSION: A total of 544 significant marker-trait associations and 286 candidate genes associated with total protein and 18 amino acids were identified. Thirty-three candidate genes were found near the strong marker trait associations (- log10P ≥ 5.5). Pearl millet (Pennisetum glaucum) is largely grown as a subsistence crop in South Asia and sub-Saharan Africa. It serves as a major source of daily protein intake in these regions. Despite its importance, no systematic effort has been made to study the genetic variations of protein and amino acid content in pearl millet germplasm. The present study was undertaken to dissect the global genetic variations of total protein and 18 essential and non-essential amino acids in pearl millet, using a set of 435 K Single Nucleotide Polymorphisms (SNPs) and 161 genotypes of the Pearl Millet Inbred Germplasm Association Panel (PMiGAP). A total of 544 significant marker-trait associations (at P < 0.0001; - log10P ≥ 4) were detected and 23 strong marker-trait associations were identified using Bonferroni's correction method. Forty-eight pleiotropic loci were found in the genome for the studied traits. In total, 286 candidate genes associated with total protein and 18 amino acids were identified. Thirty-three candidate genes were found near strongly associated SNPs. The associated markers and the candidate genes provide an insight into the genetic architecture of the traits studied and are going to be useful in breeding improved pearl millet varieties in the future. Availabilities of improved pearl millet varieties possessing higher protein and amino acid compositions will help combat the rising malnutrition problem via diet.

The Molecular Mechanisms of Adaptive Response Related to Environmental Stress.

The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as "hormesis". Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.

Further evidence that a terminal drought tolerance QTL of pearl millet is associated with reduced salt uptake.

Earlier, we established that a major drought tolerance QTL on linkage group 2 of pearl millet is also associated with reduced salt uptake and enhanced growth under salt stress. Present study was undertaken to re-assess the performance of drought tolerant (PRLT 2/89-33) and drought sensitive (H 77/833-2) parents along with two QTL-NILs (ICMR 01029 and ICMR 01040), under salinity stress specifically imposed during post-flowering growth stages when plants had developed their ion sinks in full. Time course changes in ionic accumulation and their compartmentalization in different plant parts was studied, specifically to monitor and capture changes conferred by the two alleles at this QTL, at small intervals. Amongst different plant parts, higher accumulation of toxic ion Na+ was recorded in roots. Further, the Na+ concentration in roots of the testcross hybrid of the drought-sensitive parent (H 77/833-2) reached its maximum at ECiw 15 dS m-1 within 24 h after salinity imposition, whereas it continued to increase with time in the testcross hybrids of the drought tolerant parent PRLT 2/89-33 as well as those of its QTL-NILs (ICMR 01029 and ICMR 01004) and reached at its maximum at 120 h stage. Comparison of differential distribution of toxic ions in individual leaves revealed that Na+ ions were not uniformly distributed in the leaves of the drought-tolerant parent and drought-tolerant QTL-NILs; but accumulated preferentially in the older leaves, whereas the hybrid of the drought-sensitive parent showed significantly higher Na+ concentration in all main stem leaves irrespective of their age. Dynamics of chlorophyll and proline concentration variation studied under salt stress at late flowering stages revealed a greater reduction, almost twice, in both leaf chlorophyll and proline concentrations in younger leaves in the hybrids of the sensitive parent as compared to the tolerant parent and QTL NILs. Imposition of salinity stress even at flowering stage affected the yield performance in pearl millet, wherein higher yield was recorded in drought tolerant parent and the two QTL-NILs compared to drought sensitive parent.

Genotype-by-environment interactions for starch, mineral, and agronomic traits in pearl millet hybrids evaluated across five locations in West Africa.

Introduction: Pearl millet is a staple cereal grown in the harshest environments of arid and semi-arid regions of Asia and sub-Saharan Africa. It is the primary source of calories for millions of people in these regions because it has better adaptation to harsh environmental conditions and better nutritional traits than many other cereals. By screening the pearl millet inbred germplasm association panel (PMiGAP), we earlier reported the best genotypes with the highest concentration of slowly digestible and resistant starch in their grains. Methods: In the current study, we tested these 20 top-performing pearl millet hybrids, identified based on starch data, in a randomised block design with three replications at five locations in West Africa, viz. Sadore and Konni (Niger), Bambey (Senegal), Kano (Nigeria), and Bawku (Ghana). Phenotypic variability was assessed for agronomic traits and mineral traits (Fe and Zn). Results and discussion: Analysis of variance demonstrated significant genotypic, environmental, and GEI effects among five testing environments for agronomic traits (days to 50% flowering, panicle length, and grain yield), starch traits (rapidly digestible starch, slowly digestible starch, resistant starch, and total starch), and mineral trait (iron and zinc). Starch traits, such as rapidly digestible starch (RDS) and slowly digestible starch (SDS), showed nonsignificant genotypic and environmental interactions but high heritability, indicating the lower environmental influence on these traits in the genotype × testing environments. Genotype stability and mean performance across all the traits were estimated by calculating the multi-trait stability index (MTSI), which showed that genotypes G3 (ICMX207070), G8 (ICMX207160), and G13 (ICMX207184) were the best performing and most stable among the five test environments.

Clinico-Epidemiologic Attributes of 515 Persons Living With Human Immunodeficiency Virus Infection/Acquired Immunodeficiency Syndrome on Antiretroviral Therapy: A Cross-Sectional Study from a Tertiary Care Centre of North India.

Objectives: To study the clinico-epidemiologic attributes of persons living with HIV/AIDS on highly active antiretroviral therapy (HAART). Methods: Clinico-epidemiological details, CD4 counts, previous illness and mucocutaneous diseases were studied in 515 persons living with HIV/AIDS on HAART. Results: The study comprised 250 (48.5%) males and 265 (51.5%) females aged between 10 and 79 (mean 38.9) years. The 196 (38%) males were drivers, staying-alone laborers/self-employed, and 253 (49.1%) females were homemakers. All were on HAART for one month to 9 years. Heterosexual transmission was noted in 478 (92.8%) individuals. The 274 (53.5%) individuals had 200-350 CD4 cells/mm3 counts, whereas it was <200 cells/mm3 in 88 (17.2%) individuals. Candidiasis (in 48), dermatophytoses (n = 23), herpes labialis (n = 13), herpes zoster (n = 12), seborrheic dermatitis (n = 29), generalized pruritus (n = 22), and xerosis in 20 individuals were the most common dermatoses. Most dermatoses occurred with 200-350 CD4 cells/mm3. Adverse drug reactions from antiretroviral therapy (ART) and concurrent therapies also occurred. Conclusions: Although most of our patients had mild HIV-associated dermatoses while on HAART, adverse drug reactions from HAART or concurrent therapies themselves remain a potential risk. Nevertheless, knowledge of these aspects will help planning for comprehensive health care envisaged in the National AIDS Control Program phase IV.

Genotype-by-Environment Interaction Analysis of Metabolites in Pearl Millet Genotypes with High Concentrations of Slowly Digestible and Resistant Starch in Their Grains.

Genotype × environment interactions (GEIs) should play an important role in the selection of suitable germplasm in breeding programmes. We here assessed GEI effects on pearl millet (Pennisetum glaucum L.) genotypes, selected to possess a high concentration of slowly digestible starch (SDS) and resistant starch (RS) in their grains. Entries were grown in a randomized complete block design with three replications at locations in Bawku-Ghana, Sadore-Niger, Bamako-Mali, Konni-Nigeria, and Gampella-Burkina Faso across West Africa. Harvested grains from these locations were metabolomically profiled using flow injection ionization-high-resolution mass spectrometry (FIE-HRMS). A total of 3144 mass features (m/z) (1560 negative ion mode and 1584 positive ion mode) were detected, of which, 475 m/z were linked to metabolites be involved in starch, antioxidant and lipid biosynthesis, and vitamin metabolism. Combined ANOVA revealed that the GEI was significantly evident for 54 health-benefiting metabolites, many associated with sugar, especially galactose, metabolism. Additive main effects and multiplicative interaction (AMMI) analysis examined genotype variation and GEI effects, which, when combined with principal component analysis (PCA), found that m/z 171.14864 (positive ionisation, propenyl heptanoate) accounted for 89% of the GEI variation along PC1. The AMMI-based stability parameter (ASTAB), modified AMMI stability value (MASV), and modified AMMI stability index (MASI) were then applied to identify stable and high-performing genotypes for all the health-benefiting metabolites. Similarly, the best-linear-unbiased-prediction (BLUP)-based stability estimation was also performed using the harmonic mean of genotypic values (HMGV), relative performance of genotypic values (RPGV), and harmonic mean of relative performance of genotypic values (HMRPGV), to identify genotype rankings across multiple environments. The multi-trait stability index (MTSI) was calculated and found that the genotypes G1 (ICMH-177111) and G24 (ICMX-207137) were the most stable and were the best mean performers across 52 health-benefiting metabolic traits. These findings demonstrate the potential of G × E assessments on the delivery of health-benefiting metabolite-rich grains in future varieties and hybrids of pearl millet.

Using genetic mapping and genomics approaches in understanding and improving drought tolerance in pearl millet.

Drought at the reproductive stage is a major constraint to pearl millet [Pennisetum glaucum (L.) R. Br.] productivity. Quantitative trait locus (QTL) mapping provides a means to dissect complex traits, such as drought tolerance, into their components, each of which is controlled by QTLs. Molecular marker-supported genotypic information at the identified QTLs then enables quick and accurate accumulation of desirable alleles in plant breeding programmes. Recent genetic mapping research in pearl millet has mapped several QTLs for grain yield and its components under terminal drought stress conditions. Most importantly, a major QTL associated with grain yield and for the drought tolerance of grain yield in drought stress environments has been identified on linkage group 2 (LG 2) which accounts for up to 32% of the phenotypic variation of grain yield in mapping population testcrosses. The effect of this QTL has been validated in two independent marker-assisted backcrossing programmes, where 30% improvement in grain yield general combining ability (GCA) expected of this QTL under terminal drought stress conditions was recovered in the QTL introgression lines. To transfer effectively favourable alleles of this QTL into pearl millet varieties that otherwise are high yielding and adapted to specific agricultural zones, efforts are currently underway to develop closely spaced gene-based markers within this drought tolerance (DT)-QTL. In this review, an overview is provided of information on the genetic maps developed in pearl millet for mapping drought tolerance traits and their applications in identifying and characterizing DT-QTLs. Marker-assisted transfer of desirable QTL alleles to elite parent backgrounds, and results from introgression line validation in multiple terminal drought stress environments are discussed. Current efforts undertaken towards delimiting the interval of a major DT-QTL mapping to LG 2, and towards identifying candidate genes and physiologies underlying this QTL are presented. Highly specialized genetic stocks [QTL-near-isogenic lines (NILs), a high-resolution cross, and a germplasm population] and genomic resources (gene sequences, gene-based markers, and comparative genomics information) specifically developed for these purposes are discussed.

Metabolite Diversity and Metabolic Genome-Wide Marker Association Studies (Mgwas) for Health Benefiting Nutritional Traits in Pearl Millet Grains.

As efforts are made to increase food security, millets are gaining increasing importance due to their excellent nutritional credentials. Among the millets, pearl millet is the predominant species possessing several health benefiting nutritional traits in its grain that are helpful in mitigating chronic illnesses such as type-2 diabetes and obesity. In this paper, we conducted metabolomic fingerprinting of 197 pearl millet inbred lines drawn randomly from within the world collection of pearl millet germplasm and report the extent of genetic variation for health benefitting metabolites in these genotypes. Metabolites were extracted from seeds and assessed using flow infusion high-resolution mass spectrometry (FIE-HRMS). Metabolite features (m/z), whose levels significantly differed among the germplasm inbred lines, were identified by ANOVA corrected for FDR and subjected to functional pathway analysis. A number of health-benefiting metabolites linked to dietary starch, antioxidants, vitamins, and lipid metabolism-related compounds were identified. Metabolic genome-wide association analysis (mGWAS) performed using the 396 m/z as phenotypic traits and the 76 K SNP as genotypic variants identified a total of 897 SNPs associated with health benefiting nutritional metabolite at the -log p-value ≤ 4.0. From these associations, 738 probable candidate genes were predicted to have an important role in starch, antioxidants, vitamins, and lipid metabolism. The mGWAS analysis focused on genes involved in starch branching (α-amylase, ß-amylase), vitamin-K reductase, UDP-glucuronosyl, and UDP-glucosyl transferase (UGTs), L-ascorbate oxidase, and isoflavone 2'-monooxygenase genes, which are known to be linked to increases in human health benefiting metabolites. We demonstrate how metabolomic, genomic, and statistical approaches can be utilized to pinpoint genetic variations and their functions linked to key nutritional properties in pearl millet, which in turn can be bred into millets and other cereals crops using plant breeding methods.

Identifying Anti-Oxidant Biosynthesis Genes in Pearl Millet [Pennisetum glaucum (L.) R. Br.] Using Genome-Wide Association Analysis.

Pearl millet [Pennisetum glaucum (L.) R Br.] is an important staple food crop in the semi-arid tropics of Asia and Africa. It is a cereal grain that has the prospect to be used as a substitute for wheat flour for celiac patients. It is an important antioxidant food resource present with a wide range of phenolic compounds that are good sources of natural antioxidants. The present study aimed to identify the total antioxidant content of pearl millet flour and apply it to evaluate the antioxidant activity of its 222 genotypes drawn randomly from the pearl millet inbred germplasm association panel (PMiGAP), a world diversity panel of this crop. The total phenolic content (TPC) significantly correlated with DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity (% inhibition), which ranged from 2.32 to 112.45% and ferric-reducing antioxidant power (FRAP) activity ranging from 21.68 to 179.66 (mg ascorbic acid eq./100 g). Genome-wide association studies (GWAS) were conducted using 222 diverse accessions and 67 K SNPs distributed across all the seven pearl millet chromosomes. Approximately, 218 SNPs were found to be strongly associated with DPPH and FRAP activity at high confidence [-log (p) > 3.0-7.4]. Furthermore, flanking regions of significantly associated SNPs were explored for candidate gene harvesting. This identified 18 candidate genes related to antioxidant pathway genes (flavanone 7-O-beta-glycosyltransferase, GDSL esterase/lipase, glutathione S-transferase) residing within or near the association signal that can be selected for further functional characterization. Patterns of genetic variability and the associated genes reported in this study are useful findings, which would need further validation before their utilization in molecular breeding for high antioxidant-containing pearl millet cultivars.

Terminal drought-tolerant pearl millet [Pennisetum glaucum (L.) R. Br.] have high leaf ABA and limit transpiration at high vapour pressure deficit.

It was previously shown that pearl millet genotypes carrying a terminal drought tolerance quantitative trait locus (QTL) had a lower transpiration rate (Tr; g cm(-2) d(-1)) under well-watered conditions than sensitive lines. Here experiments were carried out to test whether this relates to leaf abscisic acid (ABA) and Tr concentration at high vapour pressure deficit (VPD), and whether that leads to transpiration efficiency (TE) differences. These traits were measured in tolerant/sensitive pearl millet genotypes, including near-isogenic lines introgressed with a terminal drought tolerance QTL (NIL-QTLs). Most genotypic differences were found under well-watered conditions. ABA levels under well-watered conditions were higher in tolerant genotypes, including NIL-QTLs, than in sensitive genotypes, and ABA did not increase under water stress. Well-watered Tr was lower in tolerant than in sensitive genotypes at all VPD levels. Except for one line, Tr slowed down in tolerant lines above a breakpoint at 1.40-1.90 kPa, with the slope decreasing >50%, whereas sensitive lines showed no change in that Tr response across the whole VPD range. It is concluded that two water-saving (avoidance) mechanisms may operate under well-watered conditions in tolerant pearl millet: (i) a low Tr even at low VPD conditions, which may relate to leaf ABA; and (ii) a sensitivity to higher VPD that further restricts Tr, which suggests the involvement of hydraulic signals. Both traits, which did not lead to TE differences, could contribute to absolute water saving seen in part due to dry weight increase differences. This water saved would become critical for grain filling and deserves consideration in the breeding of terminal drought-tolerant lines.

Progress & prospects: gene therapy in aging.

Studies performed on various experimental model systems indicate that genetic interventions can increase longevity, even if in a highly protected laboratory condition. Generally, such interventions required partial or complete switching off of the gene and inhibiting the activity of its gene products, which normally have other well-defined roles in metabolic processes. Overexpression of some genes, such as stress response and antioxidant genes, in some model systems also extends their longevity. Such genetic interventions may not be easily applicable to humans without knowing their effects on human growth, development, maturation, reproduction and other characteristics. Studies on the association of single nucleotide polymorphisms and multiple polymorphisms (haplotype) in genes with human longevity have identified several genes whose frequencies increase or decrease with age. Whether genetic redesigning can be achieved in the wake of numerous and complex epigenetic factors that effectively determine the life course and the life span of an individual still appears to be a 'mission impossible'.

Eukaryotic protein elongation factors.

In eukaryotes, peptide chain elongation is mediated by elongation factors EF-1 and EF-2. EF-1 is composed of a nucleotide-binding protein EF-1 alpha, and a nucleotide exchange protein complex, EF-1 beta gamma, while EF-2 catalyses the translocation of peptidyl-tRNA on the ribosome. Elongation factors are highly conserved among different species and may be involved in functions other than protein synthesis, such as organization of the mitotic apparatus, signal transduction, developmental regulation, ageing and transformation. Yeast contains a third factor, EF-3, whose structure and function is not yet well understood.

Biomechanical properties of female dolphin reproductive tissue.

Whales, dolphins, and porpoises have unusual vaginal folds of unknown function(s) that are hypothesized to play an important role in sexual selection. The potential function of vaginal folds was assessed by testing the mechanical properties of common bottlenose dolphin (Tursiops truncatus) reproductive tract tissues in 6 different regions and across age classes in post-mortem specimens. We assessed the regional (local) and overall effective elastic modulus of tissues using indentation and tensile tests, respectively. We explore the non-linear mechanical response of biological tissues, which are not often quantified. Indentation tests demonstrated that sexual maturity state, tissue region, force history, and force magnitude values significantly affected the measured effective elastic modulus. Tissue was stiffest in the vaginal fold region and overall stiffer in sexually immature compared to mature animals, likely reflecting biomechanical adaptations associated with copulation and parturition. Tensile tests showed that only tissue region significantly affected the effective modulus. Our data support the hypothesis that vaginal folds function as mechanical barriers to the penis and may provide females with mechanisms to reduce copulatory forces on other reproductive tissue. STATEMENT OF SIGNIFICANCE: Cetaceans have unusual folds of vaginal wall tissue that appear to evolve under sexual selection mechanisms and present physical barriers to the penis during copulation. We explore the biomaterial properties of vaginal fold tissue, how it varies from other reproductive tract tissues, and ontogenetic patterns. We demonstrate that vaginal folds can withstand higher mechanical forces and respond in a manner conducive to dissipating copulatory forces to other reproductive tissues. This study yields exciting insights on how female genital tissue may function during copulation, and is the first to do so in any vertebrate species. Additionally, we provide an example for testing biological tissues, non-linear properties, and materials with uneven surface structure and uneven thickness.

Discerning combining ability loci for divergent environments using chromosome segment substitution lines (CSSLs) in pearl millet.

Pearl millet is an important crop for arid and semi-arid regions of the world. Genomic regions associated with combining ability for yield-related traits under irrigated and drought conditions are useful in heterosis breeding programs. Chromosome segment substitution lines (CSSLs) are excellent genetic resources for precise QTL mapping and identifying naturally occurring favorable alleles. In the present study, testcross hybrid populations of 85 CSSLs were evaluated for 15 grain and stover yield-related traits for summer and wet seasons under irrigated control (CN) and moisture stress (MS) conditions. General combining ability (GCA) and specific combining ability (SCA) effects of all these traits were estimated and significant marker loci linked to GCA and SCA of the traits were identified. Heritability of the traits ranged from 53-94% in CN and 63-94% in MS. A total of 40 significant GCA loci and 36 significant SCA loci were identified for 14 different traits. Five QTLs (flowering time, panicle number and panicle yield linked to Xpsmp716 on LG4, flowering time and grain number per panicle with Xpsmp2076 on LG4) simultaneously controlled both GCA and SCA, demonstrating their unique genetic basis and usefulness for hybrid breeding programs. This study for the first time demonstrated the potential of a set of CSSLs for trait mapping in pearl millet. The novel combining ability loci linked with GCA and SCA values of the traits identified in this study may be useful in pearl millet hybrid and population improvement programs using marker-assisted selection (MAS).

Genome-Wide Association Studies and Genomic Selection in Pearl Millet: Advances and Prospects.

Pearl millet is a climate-resilient, drought-tolerant crop capable of growing in marginal environments of arid and semi-arid regions globally. Pearl millet is a staple food for more than 90 million people living in poverty and can address the triple burden of malnutrition substantially. It remained a neglected crop until the turn of the 21st century, and much emphasis has been placed since then on the development of various genetic and genomic resources for whole-genome scan studies, such as the genome-wide association studies (GWAS) and genomic selection (GS). This was facilitated by the advent of sequencing-based genotyping, such as genotyping-by-sequencing (GBS), RAD-sequencing, and whole-genome re-sequencing (WGRS) in pearl millet. To carry out GWAS and GS, a world association mapping panel called the Pearl Millet inbred Germplasm Association Panel (PMiGAP) was developed at ICRISAT in partnership with Aberystwyth University. This panel consisted of germplasm lines, landraces, and breeding lines from 27 countries and was re-sequenced using the WGRS approach. It has a repository of circa 29 million genome-wide SNPs. PMiGAP has been used to map traits related to drought tolerance, grain Fe and Zn content, nitrogen use efficiency, components of endosperm starch, grain yield, etc. Genomic selection in pearl millet was jump-started recently by WGRS, RAD, and tGBS (tunable genotyping-by-sequencing) approaches for the PMiGAP and hybrid parental lines. Using multi-environment phenotyping of various training populations, initial attempts have been made to develop genomic selection models. This mini review discusses advances and prospects in GWAS and GS for pearl millet.

Mucocutaneous Manifestations in Patients with Chronic Kidney Disease: A Cross-sectional Study.

BACKGROUND: Chronic kidney disease (CKD)-associated mucocutaneous manifestations significantly impair the quality of life but often remain understudied. They may also vary across regions, socioeconomic and nutritional status, and racial differences. OBJECTIVES: To study the patterns of mucocutaneous disorders and their prevalence in CKD patients irrespective of clinical stage or dialysis status. MATERIALS AND METHODS: 122 (M:F = 77:45) patients aged 21‒85 (Mean ± SD = 57.5 ± 14.0) years having CKD for 3 month to 5 years were studied for mucocutaneous manifestations. Fifty (41%) patients were on hemodialysis for 1‒42 months. Detailed medical history, clinical and mucocutaneous examination, and lab investigations were performed. KOH mounts, skin biopsy, Gram's and Giemsa staining, bacterial or fungal cultures were performed as required. RESULTS: Xerosis in 93 (76.2%), skin pallor in 61 (50%), pruritus in 57 (46.7%), pigmentation in 47 (38.5%), and purpura in 18 (14.8%) patients were the major dermatoses. Bullous lesions and perforating folliculitis occurred in 3 (2.5%) patients each. Major nail abnormalities were pallor (in 35.2%), absent lunula (in 23.8%), nail discoloration (in 18%), and "half-and-half nails" in 16.4% patients, respectively. Hair abnormalities included sparse scalp and body hairs (in 35.2% and 13.1%, respectively) and lusterless hair in 12.3% patients. Coated tongue (in 14.8%), xerostomia (in 12.3%), and macroglossia with teeth indention (in 7.4%) patients were the mucosal manifestations. CONCLUSIONS: Xerosis, pruritus, skin pallor/pigmentary changes, nail pallor, absent lunula, nail discoloration, sparse hairs, coated tongue, xerostomia, macroglossia, and infections were the most common mucocutaneous manifestations in the studied patients irrespective of hemodialysis status. Cold and dry climates might be additional aggravators for xerosis/pruritus. Lifelong follow-up may be needed to reduce the morbidity associated with CKD/hemodialysis specific dermatoses appearing over a period.

Mapping Grain Iron and Zinc Content Quantitative Trait Loci in an Iniadi-Derived Immortal Population of Pearl Millet.

Pearl millet is a climate-resilient nutritious crop requiring low inputs and is capable of giving economic returns in marginal agro-ecologies. In this study, we report large-effect iron (Fe) and zinc (Zn) content quantitative trait loci (QTLs) using diversity array technology (DArT) and simple sequence repeats (SSRs) markers to generate a genetic linkage map using 317 recombinant inbred line (RIL) population derived from the (ICMS 8511-S1-17-2-1-1-B-P03 × AIMP 92901-S1-183-2-2-B-08) cross. The base map [seven linkage groups (LGs)] of 196 loci was 964.2 cM in length (Haldane). AIMP 92901-S1-183-2-2-B-08 is an Iniadi line with high grain Fe and Zn, tracing its origin to the Togolese Republic, West Africa. The content of grain Fe in the RIL population ranged between 20 and 131 ppm (parts per million), and that of Zn from 18 to 110 ppm. QTL analysis revealed a large number of QTLs for high grain iron (Fe) and zinc (Zn) content. A total of 19 QTLs for Fe and Zn were detected, of which 11 were for Fe and eight were for Zn. The portion of the observed phenotypic variance explained by different QTLs for grain Fe and Zn content varied from 9.0 to 31.9% (cumulative 74%) and from 9.4 to 30.4% (cumulative 65%), respectively. Three large-effect QTLs for both minerals were co-mapped in this population, one on LG1 and two on LG7. The favorable QTL alleles of both mineral micronutrients were contributed by the male parent (AIMP 92901-deriv-08). Three putative epistasis interactions were observed for Fe content, while a single digenic interaction was found for Zn content. The reported QTLs may be useful in marker-assisted selection (MAS) programs, in genomic selection (GS) breeding pipelines for seed and restorer parents, and in population improvement programs for pearl millet.

Root imaging showing comparisons in root distribution and ontogeny in novel Festulolium populations and closely related perennial ryegrass varieties.

The incorporation of new sophisticated phenotyping technologies within a crop improvement program allows for a plant breeding strategy that can include selections for major root traits previously inaccessible due to the challenges in their phenotype assessment. High-throughput precision phenotyping technology is employed to evaluate root ontogeny and progressive changes to root architecture of both novel amphiploid and introgression lines of Festulolium over four consecutive months of the growing season and these compared under the same time frame to that of closely related perennial ryegrass (L. perenne) varieties. Root imaging using conventional photography and assembled multiple merged images was used to compare frequencies in root number, their distribution within 0-20 and 20-40 cm depths within soil columns, and progressive changes over time. The Festulolium hybrids had more extensive root systems in comparison with L. perenne, and this was especially evident at depth. It was shown that the acquisition of extensive root systems in Festulolium hybrids was not dependent on the presence of an entire Festuca genome. On the contrary, the most pronounced effect on root development within the four Festulolium populations studied was observed in the introgression line Bx509, where a single small genome sequence from F. arundinacea had been previously transferred onto its homoeologous site on the long arm of chromosome 3 of an otherwise complete L. perenne genome. This demonstrates that a targeted introgression-breeding approach may be sufficient to confer a significant improvement in the root morphology in Lolium without a significant compromise to its genome integrity. The forage production of Bx509 was either higher (months 1-3) or equivalent to (month 4) that of its L. perenne parent control demonstrating that the enhanced root development achieved by the introgression line was without compromise to its agronomic performance.

Role of vasoactive intestinal polypeptide in the internal anal sphincter relaxation of the opossum.

The nature of the inhibitory neurotransmitter responsible for internal anal sphincter (IAS) relaxation in response to rectoanal reflex is not known. The objective of the present investigation was to examine the role of VIP in IAS relaxation in response to the rectoanal reflex in intact opossums with the use of VIP antagonists, [4CI-D-Phe6,Leu17] VIP and (N-AC-Tyr1,D-Phe2)-GRF (1-29)-NH2. Intraluminal pressures from the sphincter were monitored using low-compliance, continuously perfused catheters. VIP and the antagonists were administered close-intraarterially. The responses to VIP, rectoanal reflex, sacral nerve stimulation, and local intramural stimulation were examined before and after the VIP antagonists. The present studies in intact animals show: (a) VIP causes a dose-dependent fall in the IAS pressures by a direct action at the IAS smooth muscle; (b) VIP antagonists selectively and significantly antagonized the inhibitory action of VIP; and (c) VIP antagonists caused significant antagonism of the IAS relaxation caused by rectoanal reflex and the other neural stimuli. The antagonism of the IAS relaxation by the VIP antagonists, depending upon the volume of rectal distension used, ranged from 40% to 62% (P less than 0.05). From these results, we conclude that VIP acts as an inhibitory neurotransmitter for IAS relaxation during the rectoanal reflex.

Role of alpha adrenoceptors in opossum internal anal sphincter.

The purpose of the present investigation was to examine the role of alpha adrenoceptors in the internal anal sphincter (IAS). Studies wer performed on alpha-chloralose anesthetized opossums. Resting pressure in the IAS (IASP) was recorded using low compliant continuously perfused catheters. The effects of the alpha-1 adrenoceptor agonist phenylephrine and alpha-2 adrenoceptor agonist clonidine and their corresponding selective antagonists, prazosin and yohimbine, respectively, were examined on the resting IASP, and on rectal balloon distension (RBD)-mediated IAS relaxation. Phenylephrine caused a rise in the IASP that was blocked by prazosin and not by yohimbine. Phenylephrine had no effect on IAS relaxation caused by RBD. Clonidine on the other hand caused significant suppression of IAS relaxation in response to RBD, but caused minimal changes in the resting IASP. The suppression of IAS relaxation by clonidine was selectively antagonized by yohimbine but not by prazosin. From these studies we conclude that alpha-2 adrenoceptors exert important neuromodulatory influences on rectoanal inhibitory reflex, while alpha-1 adrenoceptors may exert modulatory effects on the resting IAS tone.