Accession-specific Parent-of-origin Dependent and Independent Genome Dosage Effects on Salt Tolerance in Arabidopsis Thaliana

Improving the salt stress tolerance of crops is an important goal in plant breeding. Changes in the number of chromosome pairs (i.e. ploidy level) cause genome dosage effects which can result in improved traits or emergence of novel traits. The genetic and epigenetic contribution of maternal or paternal chromosomes can differentially affect physiological and metabolic characteristics of F1 offspring. Hence genome dosage effects can be parent-of-origin independent or dependent. The model plant Arabidopsis thaliana displays both genome dosage and parent-of-origin effects on plant growth under normal, non-stress conditions. Using an insogenic ploidy series of diploid, triploid and tetraploid lines we investigate the extent of genome dosage effects and their parent-of-origin dependency on in vitro salt stress tolerance of seedlings across ten different A. thaliana accessions (genetic backgrounds). We demonstrate genome dosage effects on salt stress tolerance in five accessions, and using reciprocal triploid lines demonstrate parent-of-origin dependent genome dosage effects on salt stress tolerance in three accessions. Our results indicate that epigenetic genome dosage and genome dosage balance effects can have significant impacts on abiotic stress tolerance in plants.

Adding Sodium–Glucose Co-Transporter 2 Inhibitors to Sulfonylureas and Risk of Hypoglycemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundHypoglycemia is an important event that could be related to increased mortality in patients with diabetes. The risk of hypoglycemia is not clearly illustrated to increase when Sodiumglucose co-transporter 2 (SGLT-2) inhibitors are used concomitantly with sulfonylureas. The present study will assess the risk of hypoglycemia associated with the concomitant use of SGLT-2 inhibitors and sulfonylureas compared with placebo and sulfonylureas.MethodWe searched Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov and identified the randomized trials comparing SGLT-2 inhibitors with placebo for type 2 diabetes treated with sulfonylureas. The risk of bias in each trial was assessed using the Cochrane tool. The risk ratio of hypoglycemia was measured using the Mantel Haenszel method. We also performed subgroup analysis to examine the dosage effects. The number needed to harm (NNH) was measured according to the duration of intervention.ResultsA total of 12 studies, including 3761 participants, were enrolled in our systematic review and meta-analysis. The risk ratio of hypoglycemia was 1.67 (95% CI 1.42 to 1.97). The NNH was 13 (95% CI 9 to 21) for a treatment duration of 24 weeks or less, 11 (8 to 18) for 25 to 48 weeks, and 7 (5 to 10) for more than 48 weeks. Subgroup analysis showed that no difference was found between higher and lower doses of SGLT-2 inhibitors. The risk ratio related to lower dose SGLT-2 inhibitors was 1.56 (95% CI 1.30 to 1.88), and the risk ratio related to higher dose SGLT-2 inhibitors was 1.70 (95% CI 1.42 to 2.04).ConclusionsThe risk of hypoglycemia was significantly increased in subjects treated with SGLT-2 inhibitors compared with placebo. Addition of SGLT-2 inhibitors to sulfonylureas would lead to one more case of hypoglycemia in every 13 patients with a treatment duration less than 24 weeks. This suggests that a decrease in sulfonylureas dose may be an important recommendation when adding SGLT-2 inhibitors to sulfonylureas.

DNA methylome and lncRNAome Analysis Provide Insights Into Mechanism of Genome-dosage Effects in Autotetraploid Cassava

BackgroundDuring newly formed polyploidy, one of the most intriguing aspects is that whole-genome duplication (WGD) increase the dosage of all coding and non-coding genes. However, the molecular implications of genome-dosage effects remain elusive.ResultsWe conducted integrated maps of methylomes and lncRNAomes in autotetraploid cassava (Manihot esculenta Crantz) and its donor parent, both of which were independently clonal propagated for three years. DNA methylation variation of transposable elements (TEs) was observed as widespread in autotetraploid cassava. The hypermethylation of DNA transposons in mCG and mCHH sites may be an effective way to suppress the expression of nearby PCGs in autotetraploid cassava, resulting in similar expression levels for most of PCGs between autotetraploid and diploid cassava. The decreased methylation levels of retrotransposons in mCHG and mCHH sites, which partly attributed to reduction methylation of Cypsy neighboring long intergenic noncoding RNAs in autotetraploid cassava, may be a mechanism that may suppress the expression levels of nearby lncRNA, leading to no significant differences in transcriptome alterations for major of lncRNAs from its diploid parent.ConclusionsThis work highlighted that WGD-induced DNA methylation variation in DNA transposons and retrotransposons may be as direct adaptive responses to dosage of all coding-genes and lncRNAs, respectively.

Ghrelin Immunoreactive Cell Amounts in the Abomasum in 4-Month-Old Calves by Feeding Different Amounts of Prebiotics and New Synbiotics

The study aim was to determine prebiotic (inulin) and new synbiotic (inulin and Enterococcus faecium) varied dosage effects, during food breakdown-abomasum immunoreactive (IR) cell amount and cold carcass weight. Ghrelin is synthesized in the fundus region of the stomach. In the gastrointestinal system, ghrelin affects multiple functions, including secretion of gastric acid, gastric motility, and pancreatic protein output. The study consisted of 49 Holstein male calves (23 ± 5 days old, 50 ± 5 kg). Control and experimental groups were differentiated only with the additive amount added to the morning food source. Three prebiotic groups were fed Jerusalem artichoke flour (inulin content increased by 50%) in three amounts: 6 g (lowest) PreG6, 12 g (medium) PreG12, and 24 g (highest) PreG24. Three synbiotic groups were added 0.25 g of prebiotic Enterococcus faecium (2 ∗ 109 CFU/g) to the respective prebiotic, obtaining a new synbiotic (SynG6, SynG12, and SynG24). Calves were slaughtered after 56 days to obtain abomasum samples for ghrelin IR cell examination, and carcass weight was determined. It shows that ghrelin IR cell count in the abomasum was ( p < 0.05 ) reduced in 6g and 12g inulin dosage, but carcass weight was significantly ( p < 0.05 ) higher for PreG12 and PreG24 ( p < 0.05 ) and then for CoG (CoG 42.6 kg; PreG12 51.4 kg; and PreG24 54.0 kg) and ( p < 0.05 ) for SynG12 and SynG24 (SynG12 52.3 kg and SynG24 49.6 kg), which indicates longer satiety and more wholesome breakdown of the food uptake. It was concluded that ghrelin IR cells in 12-week-old calves are more abundant in the fundus region. Medium- and high-dosage prebiotic inulin feeding to the calves improves overall food digestion, allowing for longer satiety and higher cold carcass weight without increasing food amount. Adding synbiotic 0.25 g Enterococcus faecium (2 ∗ 109 CFU/g (Protexin, UK)) to inulin (produced in Latvia LTD „Herbe”) does not improve the results of this prebiotic.

CROSS-SPECIES AMPLIFICATION OF MICROSATELLITES AND IDENTIFICATION OF POLYPLOID HYBRIDS BY ALLELE DOSAGE EFFECTS IN COBITIS HANKUGENSIS AND IKSOOKIMIA LONGICORPA HYBRID COMPLEX

Background. During the course of evolution, numerous taxa abandoned canonical sex and reproduced asexually. Examination of the Cobitis hankugensis - Iksookimia longicorpa asexual complex already revealed important evolutionary discoveries tackling phenomena like interspecific hybridization, non-Mendelian inheritance, polyploidy and asexuality. Yet, as in other similar cases, the investigation is hampered by the lack of easily accessible molecular tools for efficient differentiation among genomotypes. Material and methods. Here, we tested the cross-species amplification of 23 microsatellite markers derived from distantly related species and investigated the extent to which such markers can facilitate the genome identification in non-model hybrid complex. Results. We found that 21 out of 23 microsatellite markers amplified in all genomotypes. Five of them could be used for easy diagnosticity of parental species and their hybrids due to species-specific amplification profiles. We also noted that three markers, i.e. IC654 and IC783 derived from Cobitis choii and Iko_TTA01 from Iksookimia koreensis, had dosage-sensitive amplification efficiencies of species-specific alleles. This could be further used for reliable differentiation of genome composition in polyploids. Conclusions. The present study introduces a noninvasive method applicable for diagnosis of ploidy and genome composition of hybrids, which are not clearly distinguished morphologically. We showed that very detailed information may be obtained even from markers developed in distantly related taxa.

Dosage Effects of Aqueous Extract of Baobab Tree (Adansonia digitata Linn) Bark on Growth Performance, Blood Profile, Intestinal Morphology and Microflora of Cockerel Chickens

This experiment investigated the dosage effects of the aqueous extract of Baobab Tree Bark (AEBTB) on growth performance, blood profile and intestinal micro-flora of cockerel chickens for 16 weeks. A total of 200 Isa brown day-old cockerel chicks were used in groups of AEBTB (0, 300, 325, 350 and 375 mg/ litre of water) for the experiment. Qualitative and quantitative (mg/100 g) phytochemical screening revealed that AEBTB contained flavonoid (36.33 mg), cardiac glycoside (31.46 mg), saponin (23.26 mg), alkaloid (24.86 mg), tannin (19.28 mg) and phenolic (17.06 mg). The most common components in GS-MSwas 9-Octadecenoic acid (C19H36O2; 296.0 g/mol). At the chick phase, significantly (p<0.05) highest final weight (416.50 g/bird) and weight gain of 47.69 g/bird/day were recorded in birds on 375 mg/litre when compared with the control. Alkaline phosphatase, RBC, Hb, PCV and MCHC were significantly (p<0.05) reduced by AEBTB in the birds when compared with the control and the lowest total bacterial count was in birds on 375 mg/litre of AEBTB. However, at the grower phase, birds on 300 mg/litre AEBTB had the best (p<0.05) feed conversion ratio. The study concluded that AEBTB at 300 mg/litre improved health status and growth performance of meat-type chickens.

Post-transcriptional regulation of Leishmania fitness gain

The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network driving parasite fitness, with genome instability causing highly reproducible, gene dosage-dependent changes in protein linked to post-transcriptional regulation. These in turn were associated with a gene dosage-independent reduction in flagellar transcripts and a coordinated increase in abundance of coding and non-coding RNAs known to regulate ribosomal biogenesis and protein translation. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain, where differential regulation of mRNA stability and the generation of fitness-adapted ribosomes may potentially filter deleterious from beneficial gene dosage effects and provide proteomic robustness to genetically heterogenous, adapting parasite populations. This model challenges the current, genome-centric approach to Leishmania epidemiology and identifies the Leishmania non-coding small RNome as a potential novel source for biomarker discovery.