Glutathione <Emphasis Type="BoldItalic">S</Emphasis>-transferase P1 gene polymorphisms and susceptibility to coronary artery disease in a subgroup of north Indian population

The present study aimed to investigate the association of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) polymorphisms of GSTP1 with coronary artery disease (CAD) in a subgroup of north Indian population. In the present case–control study, CAD patients (\(n = 200\)) and age-matched, sex-matched and ethnicity-matched healthy controls (\(n = 200\)) were genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype distribution of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) polymorphisms of GSTP1 gene was significantly different between cases and controls (\(P = 0.005\) and 0.024, respectively). Binary logistic regression analysis showed significant association of A/G (odds ratio (OR): 1.6, 95% CI: 1.08–2.49, \(P = 0.020\)) and G/G (OR: 3.1, 95% CI: 1.41–6.71, P \(=\) 0.005) genotypes of GSTP1 \(\hbox {g}.313\hbox {A}{\!>\!}\hbox {G}\), and C/T (OR: 5.8, 95% CI: 1.26–26.34, \(P = 0.024\)) genotype of GSTP1 \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) with CAD. The A/G and G/G genotypes of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and C/T genotype of \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) conferred 6.5-fold increased risk for CAD (OR: 6.5, 95% CI: 1.37–31.27, \(P = 0.018\)). Moreover, the recessive model of GSTP1 \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) is the best fit inheritance model to predict the susceptible gene effect (OR: 2.3, 95% CI: 1.11–4.92, \(P = 0.020\)). In conclusion, statistically significant associations of GSTP1 \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) (A/G, G/G) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) (C/T) genotypes with CAD were observed.     

Isolation and characterization of microsatellite markers in the spiny lobster, <Emphasis Type="Italic">Panulirus echinatus</Emphasis> Smith, 1869 (Decapoda: Palinuridae) by Illumina MiSeq sequencing

Okra’s (Abelmoschus esculentus (L.) Moench) commercial cultivation is threatened in the tropics due to high incidence of yellow vein mosaic virus (YVMV) disease. Okra geneticists across the world tried to understand the inheritance pattern of YVMV disease tolerance without much success. Therefore, the inheritance pattern of YVMV disease in okra was revisited by employing six generations (\(\hbox {P}_{1}\), \(\hbox {P}_{2}\), \(\hbox {F}_{1}\), \(\hbox {F}_{2}\), \(\hbox {BC}_{1}\) and \(\hbox {BC}_{2}\)) of four selected crosses (one tolerant \(\times \) tolerant, two tolerant \(\times \) susceptible and one susceptible \(\times \) susceptible) using two tolerant (BCO-1 and Lal Bhendi) and two susceptible (Japanese Jhar Bhendi and PAN 2127) genotypes. Qualitative genetic analysis was done on the basis of segregation pattern of tolerant and susceptible plants in \(\hbox {F}_{2}\) and backcross generations of all the four crosses. It revealed that a single dominant gene along with some minor factors governed the disease tolerant trait in both the tolerant parents used. However, it was observed that genes governing disease tolerance identified in both the tolerant variety used was different. It could be concluded that the gene governing YVMV disease tolerance in okra was genotype specific. Further, duplicate gene action as evident from an approximate ratio of 15 : 1 (tolerant : susceptible) in the \(\hbox {F}_{2}\) population in the cross of two tolerant varieties gave a scope of increasing the tolerance level of the hybrid plants when both the tolerant genes are brought together. However, generation mean analysis revealed involvement of both additive and nonadditive effects in the inheritance of disease tolerance. Thus, the present study confirms that a complicated genetic inheritance pattern is involved in the disease tolerance against YVMV trait. The major tolerance genes could be transferred to other okra varieties, but the tolerance breaking virus strains might not allow them to achieve tolerance in stable condition. Therefore, accumulation of additional genes may be needed for a sustainable tolerance phenotype in okra.     

Assessment of genetic diversity and population genetic structure of <Emphasis Type="BoldItalic">Carthamus</Emphasis> species and Iranian cultivar collection using developed SSR markers

Genetic diversity during prebreeding or postbreeding programme, is the key pillar to characterize the valuable traits and gene of interest. Whereas, superior or inferior heterotic performance of \(\hbox {F}_{1}\) depend on the diverse nature of their pedigree. Therefore, the aim of this study was to see the diversity between the interspecific crosses and effect of heterosis, and inheritance for the morphological traits and ToLCV resistance. All the 24 \(\hbox {F}_{1}\) interspecific crosses were classified into four clusters on the basis of morphological traits as well as simple sequence repeat (SSR) markers. Among the \(\hbox {F}_{1}\) hybrids, 23 were grouped into clusters II, III and IV with different phylogeny, while \(\hbox {PBC} \times \) EC 521080 was individual with cluster I. On the basis of visual observation of fruit colour, deep red and green colours in the crosses of S. pimpinellifolium (EC 521080) and S. habrochaites (EC 520061) exhibited dominant effects. In context of heterosis breeding, the crosses which were made using Solanum pimpinellifolium (EC 521080), S. chmielewskii (EC 520049) and S. cerasiforme (EC 528372) were better for yield capacity and the crosses of S. habrochaites (EC 520061) exhibited low and negative heterosis for ToLCV resistance. The \(\hbox {F}_{2}\) progenies were segregated in various Mendelian ratio as follows 3:1, 1:2:1, 1:3, 13:3, 15:1, 12:3:1 and 9:6:1 for ToLCV disease reaction of incidence, plant growth habit and fruit colour appearance, respectively. Therefore, these interspecific crosses can be utilized for developing high yield, impressive fruit colour combiners and resistant hybrids/varieties of tomato.     

Resolving the viscoelasticity and anisotropy dependence of the mechanical properties of skin from a porcine model

The mechanical response of skin to external loads is influenced by anisotropy and viscoelasticity of the tissue, but the underlying mechanisms remain unclear. Here, we report a study of the main effects of tissue orientation (TO, which is linked to anisotropy) and strain rate (SR, a measure of viscoelasticity), as well as the interaction effects between the two factors, on the tensile properties of skin from a porcine model. Tensile testing to rupture of porcine skin tissue was conducted to evaluate the sensitivity of the tissue modulus of elasticity (E) and fracture-related properties, namely maximum stress \((\sigma _{U})\) and strain \((\varepsilon _{U})\) at \(\sigma _{U}\), to varying SR and TO. Specimens were excised from the abdominal skin in two orientations, namely parallel (P) and right angle (R) to the torso midline. Each TO was investigated at three SR levels, namely 0.007–0.015 \(\hbox {s}^{-1}\) (low), 0.040 \(\hbox {s}^{-1}\) (mid) and 0.065 \(\hbox {s}^{-1}\) (high). Two-factor analysis of variance revealed that the respective parameters responded differently to varying SR and TO. Significant changes in the \(\sigma _{U}\) were observed with different TOs but not with SR. The \(\varepsilon _{U}\) decreased significantly with increasing SR, but no significant variation was observed for different TOs. Significant changes in E were observed with different TOs; E increased significantly with increasing SR. More importantly, the respective mechanical parameters were not significantly influenced by interactions between SR and TO. These findings suggest that the trends associated with the changes in the skin mechanical properties may be attributed partly to differences in the anisotropy and viscoelasticity but not through any interaction between viscoelasticity and anisotropy.     

Genetic analysis and location of a resistance gene for <Emphasis Type="BoldItalic">Puccinia striiformis</Emphasis> f. sp. <Emphasis Type="BoldItalic">tritici</Emphasis> in wheat cultivar Zhengmai 7698

Wheat stripe (yellow) rust, caused by Puccinia striiformis West. f. sp. tritici (Pst), is one of the most destructive diseases in many wheat-growing countries, especially in China, the largest stripe rust epidemic area in the world. Growing the resistant cultivars is an effective, economic and environmentally friendly way to control this disease. Wheat cultivar Zhengmai 7698 has shown a high-level resistance to wheat stripe rust. To elucidate its genetic characteristics and location of the resistance gene, Zhengmai 7698 was crossed with susceptible variety Taichung 29 to produce \(\hbox {F}_{{1}}\), \(\hbox {F}_{{2}}\) and \(\hbox {BC}_{{1}}\) progeny generations. The genetic analysis showed that the stripe rust resistance in Zhengmai 7698 to Pst predominant race CYR32 was controlled by a single-dominant gene, namedYrZM. Bulked segregant analysis and simple sequence repeat (SSR) markers were used to map the gene. Four SSR markers, Xbarc198, Xwmc179, Xwmc786 and Xwmc398 on chromosome 6BL were polymorphic between the parents and resistance, and susceptible bulks. A linkage genetic map was constructed using 212 \(\hbox {F}_{{2}}\) plants in the sequential order of Xwmc398, Xwmc179, YrZM, Xbarc198, Xwmc786. As this gene is effective against predominant race CYR32, it is useful in combination with other resistance genes for developing new wheat cultivars with resistance to stripe rust.     

Analysis of two susceptibility SNPs in HLA region and evidence of interaction between rs6457617 in <Emphasis Type="BoldItalic">HLA-DQB1</Emphasis> and <Emphasis Type="BoldItalic">HLA-DRB1</Emphasis>*04 locus on Tunisian rheumatoid arthritis

Previous genomewide association studies (GWAS) and meta-analyses have enumerated several genes/loci in major histocompatibility complex region, which are consistently associated with rheumatoid arthritis (RA) in different ethnic populations. Given the genetic heterogeneity of the disease, it is necessary to replicate these susceptibility loci in other populations. In this case, we investigate the analysis of two SNPs, rs13192471 and rs6457617, from the human leukocyte antigen (HLA) region with the risk of RA in Tunisian population. These SNPs were previously identified to have a strong RA association signal in several GWAS studies. A case–control sample composed of 142 RA patients and 123 healthy controls was analysed. Genotyping of rs13192471 and rs6457617 was carried out using real-time PCR methods by TaqMan allelic discrimination assay. A trend of significant association was found in rs6457617 TT genotype with susceptibility to RA (\(P = 0.04\), \(p_{c} = 0.08\), \(\hbox {OR} = 1.73\)). Moreover, using multivariable analysis, the combination of rs6457617*TT–HLA-DRB1*\(04^{+}\) increased risk of RA (\(\hbox {OR} = 2.38\)), which suggest a gene–gene interaction event between rs6457617 located within the HLA-DQB1 and HLA-DRB1. Additionally, haplotypic analysis highlighted a significant association of rs6457617*T–HLA-DRB1*\(04^{+}\) haplotype with susceptibility to RA (\(P = 0.018\), \(p_{c} = 0.036\), \(\hbox {OR} = 1.72\)). An evidence of association was shown subsequently in \(\hbox {antiCCP}^{+}\) subgroup with rs6457617 both in T allele and TT genotype (\(P = 0.01\), \(p_{c} = 0.03\), \(\hbox {OR} = 1.66\) and \(P = 0.008\), \(p_{c} = 0.024\), \(\hbox {OR} = 1.28\), respectively). However, no association was shown for rs13192471 polymorphism with susceptibility and severity to RA. This study suggests the involvement of rs6457617 locus as risk variant for susceptibility/severity to RA in Tunisian population. Secondly, it highlights the gene–gene interaction between HLA-DQB1 and HLA-DRB1.     

Ellis–van Creveld syndrome and profound deafness resulted by sequence variants in the <Emphasis Type="Italic">EVC</Emphasis> / <Emphasis Type="Italic">EVC2</Emphasis> and <Emphasis Type="BoldItalic">TMC1</Emphasis> genes

Ellis–van Creveld syndrome is an autosomal recessive skeletal dysplasia primarily characterized by the features such as disproportionate dwarfism, short ribs, short limbs, dysplastic nails, cardiovascular malformations, post-axial polydactyly (PAP) (bilateral) of hands and feet. EVC/EVC2 located in head-to-head arrangement on chromosome 4p16 are the causative genes for EvC syndrome. In the study, we present two families, A and B, with Pakistani and Republic of Kosovo origin, respectively. They showed features of EvC syndrome and were clinically and genetically characterized. In family A, the affected members showed an additional feature of profound deafness. The whole exome sequencing (WES) in this family revealed two homozygous variants in EVC2 (c.30dupC; p.Thr11Hisfs*45) and TMC1 (\(\hbox {c}.1696\hbox {-}1\hbox {G}{>}\hbox {A}\)) genes. In family B, WES revealed novel compound heterozygous variants (p.Ser307Pro, \(\hbox {c}.2894{+}3\hbox {A}{>}\hbox {G}\)) in the EVC gene. This study reports first case of variants in the genes causing EvC syndrome and profound deafness in the same family.     

A viscoplastic model for the active component in cardiac muscle

The HMK model (Hunter et al. in Prog Biophys Mol Biol 69:289–331, 1998) proposes mechanobiological equations for the influence of intracellular calcium concentration \(\hbox {Ca}_\mathrm{i}\) on the evolution of bound calcium concentration \(\hbox {Ca}_\mathrm{b}\) and the tropomyosin kinetics parameter z, which model processes in the active component of the tension in cardiac muscle. The inelastic response due to actin-myosin crossbridge kinetics is modeled in the HMK model with a function Q that depends on the history of the rate of total stretch of the muscle fiber. Here, an alternative model is proposed which models the active component of the muscle fiber as a viscoplastic material. In particular, an evolution equation is proposed for the elastic stretch \(\lambda _\mathrm{a} \) in the active component. Specific forms of the constitutive equations are proposed and used to match experimental data. The proposed viscoplastic formulation allows for separate modeling of three processes: the high rate deactivation of crossbridges causing rapid reduction in active tension; the high but lower rate reactivation of crossbridges causing recovery of active tension; and the low rate relaxation effects characterizing the Hill model of muscles.     

Cell Volume Regulation in the Proximal Tubule of Rat Kidney

We developed a dynamic model of a rat proximal convoluted tubule cell in order to investigate cell volume regulation mechanisms in this nephron segment. We examined whether regulatory volume decrease (RVD), which follows exposure to a hyposmotic peritubular solution, can be achieved solely via stimulation of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)–\(\hbox {HCO}_3^-\) cotransporters. We also determined whether regulatory volume increase (RVI), which follows exposure to a hyperosmotic peritubular solution under certain conditions, may be accomplished by activating basolateral \(\hbox {Na}^+\)/H\(^+\) exchangers. Model predictions were in good agreement with experimental observations in mouse proximal tubule cells assuming that a 10% increase in cell volume induces a fourfold increase in the expression of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)–\(\hbox {HCO}_3^-\) cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, \(\hbox {Na}^+\)–\(\hbox {HCO}^-_3\) cotransporters are more efficient than basolateral K\(^+\) and \(\hbox {Cl}^-\) channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular \(\hbox {Na}^+\) reabsorption, that is, to limit the net \(\hbox {Na}^+\) flux decrease during a hyposmotic challenge or the net \(\hbox {Na}^+\) flux increase during a hyperosmotic challenge.     

Cellular mechanosensitivity to substrate stiffness decreases with increasing dissimilarity to cell stiffness

Computational modelling has received increasing attention to investigate multi-scale coupled problems in micro-heterogeneous biological structures such as cells. In the current study, we investigated for a single cell the effects of (1) different cell-substrate attachment (2) and different substrate modulus \(\textit{E}_\mathrm{s}\) on intracellular deformations. A fibroblast was geometrically reconstructed from confocal micrographs. Finite element models of the cell on a planar substrate were developed. Intracellular deformations due to substrate stretch of \(\lambda =1.1\), were assessed for: (1) cell-substrate attachment implemented as full basal contact (FC) and 124 focal adhesions (FA), respectively, and \(\textit{E}_\mathrm{s}\,=\,\)140 KPa and (2) \(\textit{E}_\mathrm{s}\,=\,10\), 140, 1000, and 10,000 KPa, respectively, and FA attachment. The largest strains in cytosol, nucleus and cell membrane were higher for FC (1.35\(\text {e}^{-2}\), 0.235\(\text {e}^{-2}\) and 0.6\(\text {e}^{-2}\)) than for FA attachment (0.0952\(\text {e}^{-2}\), 0.0472\(\text {e}^{-2}\) and 0.05\(\text {e}^{-2}\)). For increasing \(\textit{E}_\mathrm{s}\), the largest maximum principal strain was 4.4\(\text {e}^{-4}\), 5\(\text {e}^{-4}\), 5.3\(\text {e}^{-4}\) and 5.3\(\text {e}^{-4}\) in the membrane, 9.5\(\text {e}^{-4}\), 1.1\(\text {e}^{-4}\), 1.2\(\text {e}^{-3}\) and 1.2\(\text {e}^{-3}\) in the cytosol, and 4.5\(\text {e}^{-4}\), 5.3\(\text {e}^{-4}\), 5.7\(\text {e}^{-4}\) and 5.7\(\text {e}^{-4}\) in the nucleus. The results show (1) the importance of representing FA in cell models and (2) higher cellular mechanical sensitivity for substrate stiffness changes in the range of cell stiffness. The latter indicates that matching substrate stiffness to cell stiffness, and moderate variation of the former is very effective for controlled variation of cell deformation. The developed methodology is useful for parametric studies on cellular mechanics to obtain quantitative data of subcellular strains and stresses that cannot easily be measured experimentally.     

Molecular breeding of ameliorating commercial pearl millet hybrid for downy mildew resistance

Downy mildew (DM) caused by Sclerospora graminicola is the most calamitous disease of pearl millet. Therefore, for introgression of DM resistance (DMR) in HHB 197 (MH-1302), an elite pearl millet hybrid, a marker-assisted breeding was undertaken by targeting three DMR loci on linkage groups (LGs) 1, 2 and 4. Breeding programme was initiated by crossing HBL 11 (DM susceptible), male parent of HHB 197 hybrid with ICMP 451 (DM-resistant) to produce true \(\hbox {F}_{1}\) plants. By conducting three rounds of backcrossing and selection, \(\hbox {BC}_{3}\hbox {F}_{1}\) lines were generated. Foreground selection was employed using six polymorphic simple sequence repeat (SSR) markers of the 18 total selected markers. Four of these markers were linked to LG 1, five to LG 2 and nine to LG 4. Background selection was performed in \(\hbox {BC}_{3}\hbox {F}_{1}\) generation using 33 polymorphic SSR markers of a total of 56 evenly spread SSR markers in the pearl millet genome to check recovery of recurrent parent genome. On the basis of genotypic selection (foreground as well as background) using selected SSR markers, agronomic performance in field and DM screening in greenhouse; 10 improved HBL 11 lines were selected and crossed with ICMA 97111 to produce DM-resistant HHB 197 hybrid versions. Six putatively improved HHB 197 hybrids were successfully tested in first year trials at Hisar and Bawal locations of Haryana and two selected versions with higher yield and zero DM incidence will be further tested in multilocation trials.     

Backbone resonance assignments for the SET domain of the human methyltransferase NSD2

Aberrant NSD2 methyltransferase activity is implicated as the oncogenic driver in multiple myeloma, suggesting opportunities for novel therapeutic intervention. The methyltransferase activity of NSD2 resides in its catalytic SET domain, which is conserved among most lysine methyltransferases. Here we report the backbone \(\hbox {H}^{\mathrm{N}}\), N, C\(^{\prime }\), \(\hbox {C}^\alpha\) and side-chain \(\hbox {C}^\beta\) assignments of a 25 kDa NSD2 SET domain construct, spanning residues 991–1203. A chemical shift analysis of C\(^{\prime }\), \(\hbox {C}^\alpha\) and \(\hbox {C}^\beta\) resonances predicts a secondary structural pattern that is in agreement with homology models.     

A Mathematical Model for the Macrophage Response to Respiratory Viral Infection in Normal and Asthmatic Conditions

Respiratory viral infections are common in the general population and one of the most important causes of asthma aggravation and exacerbation. Despite many studies, it is not well understood how viral infections cause more severe symptoms and exacerbations in asthmatics. We develop a mathematical model of two types of macrophages that play complementary roles in fighting viral infection: classically \((\hbox {CA}\)-\(\hbox {M}\Phi )\) and alternatively activated macrophages \((\hbox {AA}\)-\(\hbox {M}\Phi )\). \(\hbox {CA}\)-\(\hbox {M}\Phi \) destroy infected cells and tissues to remove viruses, while \(\hbox {AA}\)-\(\hbox {M}\Phi \) repair damaged tissues. We show that a higher viral load or longer duration of infection provokes a stronger immune response from the macrophage system. By adjusting the parameters, we model the differences in response to respiratory viral infection in normal and asthmatic subjects and show how this skews the system toward a response that generates more severe symptoms in asthmatic patients.     

Study of biological communities subject to imperfect detection: bias and precision of community <Emphasis Type="Italic">N</Emphasis>-mixture abundance models in small-sample situations

Community N-mixture abundance models for replicated counts provide a powerful and novel framework for drawing inferences related to species abundance within communities subject to imperfect detection. To assess the performance of these models, and to compare them to related community occupancy models in situations with marginal information, we used simulation to examine the effects of mean abundance \((\bar{\lambda }\): 0.1, 0.5, 1, 5), detection probability \((\bar{p}\): 0.1, 0.2, 0.5), and number of sampling sites (n _site : 10, 20, 40) and visits (n _visit : 2, 3, 4) on the bias and precision of species-level parameters (mean abundance and covariate effect) and a community-level parameter (species richness). Bias and imprecision of estimates decreased when any of the four variables \((\bar{\lambda }\), \(\bar{p}\), n _site , n _visit ) increased. Detection probability \(\bar{p}\) was most important for the estimates of mean abundance, while \(\bar{\lambda }\) was most influential for covariate effect and species richness estimates. For all parameters, increasing n _site was more beneficial than increasing n _visit . Minimal conditions for obtaining adequate performance of community abundance models were n _site  ≥ 20, \(\bar{p}\) ≥ 0.2, and \(\bar{\lambda }\) ≥ 0.5. At lower abundance, the performance of community abundance and community occupancy models as species richness estimators were comparable. We then used additive partitioning analysis to reveal that raw species counts can overestimate β diversity both of species richness and the Shannon index, while community abundance models yielded better estimates. Community N-mixture abundance models thus have great potential for use with community ecology or conservation applications provided that replicated counts are available.     

Delay decomposition approach to $$\mathcal {H}_{\infty }$$ filtering analysis of genetic oscillator networks with time-varying delays

In this paper, the \(\mathcal {H}_{\infty }\) filtering problem is treated for N coupled genetic oscillator networks with time-varying delays and extrinsic molecular noises. Each individual genetic oscillator is a complex dynamical network that represents the genetic oscillations in terms of complicated biological functions with inner or outer couplings denote the biochemical interactions of mRNAs, proteins and other small molecules. Throughout the paper, first, by constructing appropriate delay decomposition dependent Lyapunov–Krasovskii functional combined with reciprocal convex approach, improved delay-dependent sufficient conditions are obtained to ensure the asymptotic stability of the filtering error system with a prescribed \(\mathcal {H}_{\infty }\) performance. Second, based on the above analysis, the existence of the designed \(\mathcal {H}_{\infty }\) filters are established in terms of linear matrix inequalities with Kronecker product. Finally, numerical examples including a coupled Goodwin oscillator model are inferred to illustrate the effectiveness and less conservatism of the proposed techniques.