Gentiana straminea Maxim. (Gentianaceae) is an important traditional Tibetan herb that is mainly distributed on the Qinghai-Tibetan Plateau. Despite its agricultural and pharmacological importance, there remains a paucity of microsatellite markers, particularly expressed sequence tag-simple sequence repeat (EST-SSR) markers, available for this local endemic species. In this study, based on previous Illumina transcriptome data of G. straminea, a total of 96 EST-SSR markers were initially designed and tested. Thirty-two of 96 loci (33.33%) were successfully amplified and verified for validation. Among them, 10 were polymorphic and had clear bands. The polymorphism information content values were 0.09–0.799, the number of alleles per locus ranged from 3 to 14, and the levels of observed and expected heterozygosity were 0.078–0.722 and 0.238–0.884, respectively, which suggested a high level of information. Moreover, cross-amplification was successful for 10 loci in two other related species, Gentiana macrophylla Pallas and Gentiana dahurica Fischer. These EST-SSR markers provide a valuable tool for investigating the genetic diversity related to quantitative traits and population genetic studies on G. straminea and related species in sect. Cruciata Gaudin.

Transmission electron microscopy (TEM) was utilized to determine the origins of berthierine and chlorite in the core of the footwall alteration zone of the Kidd Creek massive sulfide deposit, Ontario. TEM images show lamellar intergrowths of packets of berthierine, mixed-layer chlorite/berthierine, Fe-Mg chlorite, and relatively Fe-rich chlorite that contain dislocations, stacking faults, kink bands, and gliding along (001). Interstratification of packets of berthierine and chlorite with one to several tens of layers commonly is associated with terminations of a layer of chlorite by two layers of berthierine. Layers in adjacent domains of berthierine and chlorite are continuous across interfaces that transect their common {001} planes. High-strain zones that cut across cleavage planes, consisting of distorted layers and lens-shaped pores, are associated with stacking faults and gliding along cleavage planes in chlorite crystals. Similar features separate interstratified chlorite/berthierine of different structures and textures, implying development of such composite grains after deformation of chlorite. Electron diffraction patterns show that the chlorite is an ordered one- or two-layer polytype or a one-layer polytype with semi-random stacking, and that the berthierine is a one-layer polytype with semi-random stacking epitaxially intergrown with chlorite.

Coexisting chlorite and berthierine have nearly identical ranges of compositions, containing Si ≅ 5, Al ≅ 6, and Fe ≅ 6.5–8.5 pfu, and minor, variable Mg and Mn contents, in formulae normalized on the basis of 20 total cations. This implies polymorphism among Fe,Al-rich members of the serpentine and chlorite groups. In one of the samples, berthierine and mixed-layer chlorite/berthierine coexist with chlorite having two compositional ranges, including Fe-rich chlorite with a relatively wide range of Fe-Mg contents, and a dominant Fe-Mg chlorite. In another sample, compositionally homogeneous Fe-rich chlorite is associated with berthierine and mixed-layer chlorite/berthierine; Fe-Mg chlorite was not detected.

The microstructural relations and the presence of coexisting polymorphs, complex mixed layering, heterogeneous polytypism, and wide ranges of mineral compositions are consistent with replacement of chlorite by berthierine under non-equilibrium retrograde conditions, in contrast to the generally assumed prograde origin for other berthierine occurrences.

This study was designed to understand how drought stress impact on the physiological and molecular status of genetically diverse Lolium perenne L. (perennial ryegrass) populations. The sensitivities of the 36 perennial ryegrass populations were checked against PEG-6000-simulated drought stress by analysing physiological status. Afterward, drought-related gene expressions were evaluated under normal and stressed conditions. The drought stress significantly up-regulated the drought-related genes in P6, P10, P15 and P30, while no difference was observed in drought-sensitive ones. The results collectively showed that four populations (P6, P10, P15, P30) are tolerant to drought stress and activate drought-related genes. Genetic similarities of the populations were also monitored using microsatellite (SSR) markers. The ten SSR primers detected 38 alleles. Surprisingly, the drought-tolerant populations were classified into different groups by principal component (PCA) and cluster analysis, showing that they are genetically different. Moreover, four unique alleles were identified by two SSR primers (P-07, and P-08) in P6, P10 and P15. In addition, the drought-tolerant populations (P6, P10, P15, P30) can be used to develop new perennial ryegrass cultivars for areas having drought problems.

The LIPE gene (lipase E, hormone-sensitive type), also known as hormone-sensitive lipase, acts as a primary regulator of lipid metabolism during lactation in cows. We studied a total of two hundred Holstein–Friesian cows and performed sequencing analysis that revealed two synonymous nucleotide changes within the LIPE gene: a transition change, c.276 T > C in exon 2 (g.50631651 T > C; position 351 of GenBank: ON638900) and a transversion change, c.219C > A in exon 6 (g.50635369C > A; position 1070 of GenBank: ON638901). The observed genotypes were TC and CC for the c.276 T > C SNP and CC and CA for the c.219C > A SNP. Notably, the heterozygous TC genotype of the T351C SNP exhibited a significant association with high milk yield. Furthermore, the T351C SNP displayed significant associations with various milk parameters, including temperature, freezing point, density and the percentages of fat, protein, lactose, solids and solids-not-fat, with the homozygous CC genotype showing higher values. The c.219C > A SNP also demonstrated a significant association with milk composition, with heterozygous genotypes (CA) exhibiting higher percentages of fat, protein, and lactose compared to homozygous genotypes (CC). This effect was consistent among both high and low milk producers for fat and lactose percentages, while high milk producers exhibited a higher protein percentage than low milk producers. These findings highlight the importance of considering the detected SNPs in marker-assisted selection and breeding programs for the identification of high milk-producing Holstein–Friesian cows and potentially other breeds. Moreover, this study strongly supports the fundamental role of the LIPE gene in milk production and composition in lactating animals.

We studied the genetic polymorphism of beta-lactoglobulin (β-Lg) whey protein in Gangatiri zebu cows for this Research Communication. The polymorphic nature of milk protein fractions and their association with milk production traits, composition and quality has attracted several efforts in evaluating the allelic distribution of protein locus as a potential dairy trait marker. Genetic variants of β-Lg have highly significant effects on casein number (B > A) and protein recovery (B > A) and also determine the yield of cheese dry matter (B > A). Molecular techniques of polyacrylamide gel electrophoresis and high-resolution accurate mass-spectroscopy were applied to characterize the β-Lg protein obtained from the Gangatiri breed milk. Sequence analysis of β-Lg showed the presence of variant B having UniProt database accession number P02754, coded on the PAEP gene. Our study can provide reference and guidance for the selection of superior milk (having β-LgB) from this indigenous breed that could potentially give a good yield of β-Lg for industrial applications.

Jacobs has proposed definitions for (weak, strong, split) generic objects for a fibered category; building on his definition of (split) generic objects, Jacobs develops a menagerie of important fibrational structures with applications to categorical logic and computer science, including higher order fibrations, polymorphic fibrations, $\lambda2$ -fibrations, triposes, and others. We observe that a split generic object need not in particular be a generic object under the given definitions, and that the definitions of polymorphic fibrations, triposes, etc. are strict enough to rule out some fundamental examples: for instance, the fibered preorder induced by a partial combinatory algebra in realizability is not a tripos in this sense. We propose a new alignment of terminology that emphasizes the forms of generic object appearing most commonly in nature, i.e. in the study of internal categories, triposes, and the denotational semantics of polymorphism. In addition, we propose a new class of acyclic generic objects inspired by recent developments in higher category theory and the semantics of homotopy type theory, generalizing the realignment property of universes to the setting of an arbitrary fibration.

Precision medicine is an approach to maximise the effectiveness of disease treatment and prevention and minimise harm from medications by considering relevant demographic, clinical, genomic and environmental factors in making treatment decisions. Precision medicine is complex, even for decisions about single drugs for single diseases, as it requires expert consideration of multiple measurable factors that affect pharmacokinetics and pharmacodynamics, and many patient-specific variables. Given the increasing number of patients with multiple conditions and medications, there is a need to apply lessons learned from precision medicine in monotherapy and single disease management to optimise polypharmacy. However, precision medicine for optimisation of polypharmacy is particularly challenging because of the vast number of interacting factors that influence drug use and response. In this narrative review, we aim to provide and apply the latest research findings to achieve precision medicine in the context of polypharmacy. Specifically, this review aims to (1) summarise challenges in achieving precision medicine specific to polypharmacy; (2) synthesise the current approaches to precision medicine in polypharmacy; (3) provide a summary of the literature in the field of prediction of unknown drug–drug interactions (DDI) and (4) propose a novel approach to provide precision medicine for patients with polypharmacy. For our proposed model to be implemented in routine clinical practice, a comprehensive intervention bundle needs to be integrated into the electronic medical record using bioinformatic approaches on a wide range of data to predict the effects of polypharmacy regimens on an individual. In addition, clinicians need to be trained to interpret the results of data from sources including pharmacogenomic testing, DDI prediction and physiological-pharmacokinetic-pharmacodynamic modelling to inform their medication reviews. Future studies are needed to evaluate the efficacy of this model and to test generalisability so that it can be implemented at scale, aiming to improve outcomes in people with polypharmacy.

Genetic polymorphism research in livestock species aims to assess genetic differences within and among breeds, primarily for conservation and development objectives. The aim of the present study was to determine the point mutation in the IGF-1 gene (g.855G>C and g.857G>A) and its association with performance traits in Munjal sheep. In total, 50 Munjal sheep were selected and the genomic DNA was isolated using the Automated Maxell RSC DNA/RNA purification system and the Maxwell RSC whole blood DNA kit. A reported set of primers was used to amplify the 294-bp fragment encompassing the targeted region, i.e. the 5′ flanking region of the IGF-1 gene. The polymerase chain reaction product of 294-bp size harbouring the g.857G>A mutation in the 5′ flanking region of the IGF-1 gene was digested with HaeII enzyme. Three possible genotypes were defined by distinct banding patterns, i.e. GG (194, 100 bp), GA (294, 194, 100 bp) and AA (294 bp) in the studied population of Munjal sheep. The genotypic and allelic frequencies of g.857G>A single nucleotide polymorphism of the IGF-1 gene indicated that the frequency of the A allele was higher in the studied population, i.e. 0.59 and the GA genotype was found to be the predominant genotype (0.66). Allele A of the IGF-1 gene was found to be associated with higher body weights and can be used in selection criteria for improving the performance of Munjal sheep. The positive effect of the IGF-1 gene on several conformational traits as observed in this study suggests that this area of the ovine IGF-I gene is particularly important and warrants further investigation on a larger population size.

The follicle-stimulating hormone (FSH) and its receptor regulate the quantity and quality of spermatozoa production. Several studies have analyzed the effect of single nucleotide polymorphisms (SNPs) in exon 10 of the FSH receptor (FSHR) on basic semen parameters without yet reaching a firm consensus. The aim of this study was to evaluate the effect of p.Thr307Ala and p.Asn680Ser polymorphisms in exon 10 of the FSHR gene, in infertile men, on intracytoplasmic sperm injection (ICSI) outcomes. This study was conducted between March 2019 and February 2020 on infertile couples undergoing ICSI at Al Hadi Laboratory and Medical Center, Lebanon. Couples with severe infertility factors that may impair gametogenesis/embryogenesis (e.g. advanced maternal age, premature ovarian failure, underwent gonadotoxic treatments, etc.) were excluded from the study. Semen and blood samples were collected from infertile men on the day of oocyte collection. Infertile men (n = 173) were screened for FSHR variants using polymerase chain reaction-restriction fragment length polymorphism. Moreover, fertilization rates, embryo quality, and pregnancy outcomes were evaluated. Higher sperm concentrations were found in the p.Thr307Ala group than the p.Thr307Thr (P < 0.01) and p.Ala307Ala (P < 0.05) groups. Furthermore, fertilization rate was significantly lower in the p.Ala307Ala genotype than in the p.Thr307Thr genotype (P < 0.05). We showed that FSHR variants in infertile men undergoing ICSI could affect sperm concentration, motility, and fertilization rates. Therefore, it will be important to confirm these results in further studies using a larger sample size.

X-ray powder diffraction data for the two new polymorphs of 1-methylhydantoin, C4H6N2O2, are reported. The polymorph II (MH-II) crystallizes in the orthorhombic system with space group Pna21 [a = 19.0323(7) Å, b = 3.91269(8) Å, c = 6.8311(7) Å, Z′ = 1, Z = 4, unit cell volume V = 508.70(3) Å3. Polymorph III (MH-III) crystallizes in the orthorhombic system with space group P212121 [a = a = 7.82427(5), b = 9.8230(5), c = 20.2951(4), Z′ = 3, Z = 12, unit cell volume V = 1563.5(1) Å3]. All measured lines, in each case, were indexed and are consistent with the space group.

The aim of this study was to investigate mitochondrial ND5 gene polymorphisms and their relationship with in vitro maturation (IVM) and in vitro culture (IVC) of Sanjabi sheep. Blood and ovarian samples of adult ewes were obtained from a local slaughterhouse. For each ovarian sample, cumulus–oocyte complexes larger than 3 mm in diameter were aspirated from follicles, and their IVM and IVC rates were recorded. A 666-bp fragment of the ND5 gene was amplified using the polymerase chain reaction. The samples were genotyped using a modified single-stranded conformation polymorphism (SSCP) method, and an association study was conducted with IVM and IVC rates. Six different SSCP patterns, designated A, B, C, D, E and F with respective frequencies of 8, 47, 4, 4, 32 and 5%, respectively, were observed. According to the results of association analysis, there was no significant association between the ND1 gene polymorphisms and the IVM and IVC rates (P > 0.05).

This work aims to examine the interaction between apo A2 (Apo A-II) –265T > C SNP and dietary total antioxidant capacity (DTAC) on inflammation and oxidative stress in patients with type 2 diabetes mellitus. The present cross-sectional study included 180 patients (35–65 years) with identified Apo A-II genotype. Dietary intakes were assessed by a FFQ. DTAC was computed using the international databases. IL-18 (IL18), high-sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), serum total antioxidant capacity (TAC), superoxide dismutase (SOD) activity and 8-isoprostaneF2α (PGF2α) markers were obtained according to standard protocols. General linear model was used to evaluate the interaction. The interaction of gene and DTAC (PFRAP = 0·039 and PORAC = 0·042) on PGF2α level was significant after adjusting for confounders. A significant interaction was observed on IL18 level (PORAC = 0·018 and PFRAP = 0·048) and SOD (PTEAC = 0·037) in obese patients. Among patients whose DTAC was higher than the median intake, the levels of hs-CRP and PGF2α were significantly higher only in individuals with CC genotype. Serum TAC (PFRAP = 0·030, PORAC = 0·049) and SOD were significantly lower in the CC genotype. There was a favourable relationship between the high-DTAC and SOD (obese: PTEAC = 0·034, non-obese: PFRAP = 0·001, PTRAP < 0·0001, PTEAC = 0·003 and PORAC = 0·001) and PGF2α (non-obese: PORAC = 0·024) in T-allele carriers. The rs5082 SNP interacts with DTAC to influence several cardiometabolic risk factors. Also, we found dietary recommendations for antioxidant-rich foods intake might be useful in the prevention of diabetes complications in the T carrier more effectively than the CC genotype. Future large studies are required to confirm these results.

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.

Several investigations revealed the association between ApoA2 concentration and lipid profile, inflammation and oxidative stress markers. Dietary habits also play a major role in the health status of individuals with type 2 diabetes mellitus (T2DM). This study aimed to investigate the interaction of ApoA2–256T > C with dietary indexes on ghrelin and leptin hormones together with biochemical markers among individuals with T2DM. A cross-sectional study was conducted on 726 randomly selected individuals with T2DM. A validated FFQ was used to evaluate Healthy Eating Index, Dietary Quality Index-International (DQI-I) and Dietary Phytochemical Index (DPI). ApoA2–256T > C genotypes were detected by real-time-PCR. Ghrelin, leptin and biochemical markers were also assessed. ANCOVA was used for the interaction between the polymorphism and dietary indexes. A significant interaction was observed between ApoA2–256T > C and DQI-I on high-sensitivity C-reactive protein (hs-CRP) level and superoxide dismutase (SOD) activity. Besides, the interaction of the SNP and DPI significantly affected hs-CRP and 8-isoprostane F2α (PGF2α) levels. CC in the second tertile of DPI had the lowest hs-CRP level, and it was elevated due to adhering to DQI-I (Pinteraction = 0·01 and 0·04, respectively). Moreover, T-allele (protective allele) carriers with the highest level of PGF2α and SOD activity were those in the second tertile of DPI and DQI-I, respectively (Pinteraction = 0·03 and 0·007, respectively). SOD activity, hs-CRP and PGF2α concentration may be modified in T-allele carriers and CC by the adherence to DPI and DQI-I, though additional studies are required to confirm these findings.

Khasi mandarin (Citrus reticulata Blanco) is a commercial mandarin variety grown in northeast India and one of the 175 Indian food items included in the global first food atlas. The cultivated plantations of Khasi mandarin grown prominently in the lower Brahmaputra valley of Assam, northeast India, have been genetically eroded. The lack in the efforts for conservation of genetic variability in this mandarin variety prompted diversity analysis of Khasi mandarin germplasm across the region. Thus, the study aimed to investigate genetic diversity and partitioning of the genetic variations within and among 92 populations of Khasi mandarin collected from 10 cultivated sites in Kamrup and Kamrup (M) districts of Assam, India, using Inter-Simple Sequence Repeat (ISSR) markers. The amplification of genomic DNA with 17 ISSR primers yielded 216 scorable DNA amplicons of which 177 (81.94%) were polymorphic. The average polymorphism information content was 0.39 per primer. The total genetic diversity (HT = 0.28 ± 0.03) was close to the diversity within the population (HS = 0.20 ± 0.01). A high mean coefficient of gene differentiation (GST = 0.29) reflected a high level of gene flow (Nm = 1.22), indicating high genetic differentiation among the populations. Analysis of Molecular Variance (AMOVA) showed 78% of intra-population differentiation, 21% among the population and 1% among the districts. The obtained results indicate the existence of a high level of genetic diversity in the cultivated Khasi mandarin populations, indicating the need for preservation of each existing population to revive the dying out orchards in northeast India.

The present study aimed to investigate the interaction of Apo A-II polymorphism and dietary total antioxidant capacity (DTAC) with lipid profile and anthropometric markers in patients with type 2 diabetes (T2DM) that are at risk for atherosclerosis. This cross-sectional study was conducted on 778 patients with T2DM (35–65 years). Dietary intakes were assessed by a 147-item food frequency questionnaire. DTAC was computed using international databases. Participants were categorised into two groups based on rs5082 genotypes. The gene–diet interaction was analysed by an ANCOVA multivariate interaction model. Total cholesterol, TC; triacylglycerol, TG; high- and low-density lipoprotein, HDL and LDL; TC–HDL ratio; waist circumference, WC and body mass index, BMI were obtained according to standard protocols. Overall, the frequency of CC homozygous was 12⋅1 % among study participants. We found that a significant interaction between rs5082 variants and DTAC on mean WC (PTEAC = 0⋅044), TC concentration (PFRAP = 0⋅049 and PTEAC = 0⋅031) and TC/HDL (PFRAP = 0⋅031 and PTRAP = 0⋅040). Among patients whose DTAC was higher than the median intake, the mean of weight, WC and TC/HDL were significantly higher only in individuals with CC genotype. Also, the high DTAC was associated with a lower TC concentration only in T-allele carriers (PFRAP = 0⋅042). We found that adherence to a diet with high total antioxidant capacity can improve the complications of diabetes and atherosclerosis in the T carrier genotype more effectively than the CC genotype. These results could indicate the anti-atherogenic properties of Apo A-II. However, further studies are needed to shed light on this issue.

Cowpea (Vigna unguiculata L. Walp.) is an important grain legume in tropical and subtropical regions. It requires low resource inputs and has a high nutritional value. Therefore, cowpea can play an important role in the development of agriculture. In southern Mexico, Mayan farmers have conserved and developed cowpea landraces for centuries. Nevertheless, information on their genetic diversity, conservation status and potential use is minimal. To generate information toward sustainable use, management and conservation of this species, we evaluated the genetic diversity and structure of 20 cowpea landraces from southeast Mexico using 10 inter-simple sequence repeat (ISSR) molecular markers. These ISSR markers generated 68 loci with a 67.7% polymorphism rate and average polymorphic information content of 0.36. The results of Bayesian assignation and the UPGMA analysis suggest the formation of two main groups defined by their genetic origin in southeast Mexico. High levels of genetic structure were found with a moderate level of genetic diversity distributed mainly between landraces. Low levels of intra-landrace variability were observed. Two landraces (P5 and P12) from Calakmul resulted in the high levels of genetic diversity. The selected markers were efficient at assessing genetic variability among Mexican cowpea landraces, providing valuable information that can be used in local conservation and participatory breeding programmes.

Some studies have suggested that the Toll-like receptor 9 polymorphism (TLR9 rs352140) is closely related to the risk of bacterial meningitis (BM), but this is subject to controversy. This study set out to estimate whether the TLR9 rs352140 polymorphism confers an increased risk of BM. Relevant literature databases were searched including PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (CNKI) up to August 2020. Seven case-control studies from four publications were enrolled in the present meta-analysis. Odds ratios (OR) and confidence intervals (95% CI) were calculated to estimate associations between BM risk and the target polymorphism. Significant associations identified were allele contrast (A vs. G: OR 0.66, 95% CI 0.59–0.75, P = 0.000), homozygote comparison (AA vs. AG/GG: OR 0.62, 95% CI 0.49–0.78, P = 0.000), heterozygote comparison (A vs. G: OR 0.74, 95% CI 0.61–0.91, P = 0.005), recessive genetic model (AA vs. AG/GG: OR 0.78, 95% CI 0.65–0.93, P = 0.006) and dominant genetic model (AA vs. AG/GG: OR 0.70, 95% CI 0.57–0.85, P = 0.000). The findings indicate that, in contrast to some studies, the TLR9 rs352140 polymorphism is associated with a decreased risk for BM.