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.     

The gene pool of the Belgorod oblast population: II. “Family name portraits” in groups of districts with different degrees of subdivision and the role of migrations in their formation

The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The “family name portraits” of districts with low (0.00003 < < f*_r < 0.00022, \(\overline {f_r^ * } \) = 0.00015) and moderate (0.00023 < f*_r < 0.00042, \(\overline {f_r^ * } \) = 0.00029) inbreeding levels are similar both to each other and to the “family name portrait” of the Belgorod oblast as a whole. Districts with high subdivision levels (0.00043 < f*_r < 0.00125, \(\overline {f_r^ * } \) = 0.00072) had very distinctive surname spectra and the highest surname frequencies. Intense immigration to the Belgorod oblast significantly affects its population genetic structure, decreasing the population subdivision.     

Efficient generation of negative hydrogen ions in a low-voltage cesium-hydrogen discharge

The possibility of achieving the high density of negative hydrogen ions \(N_{H^ - } \) in a low-voltage cesium-hydrogen discharge is investigated. The \(N_{H^ - } \) density is determined experimentally from the absorption of laser radiation due to the photodetachment of electrons from H^? ions. The discharge plasma is investigated by the probe technique. The populations of the excited states of Cs atoms are determined from their emission intensities. With an input power of W≈(15–25) W/cm² in the discharge, densities of \(N_{H^ - } \sim (10^{12} - 10^{13} )cm^{ - 3} \) are achieved. The self-consistent calculations of the plasma parameters in the discharge gap agree well with the experimental results. The absorption of laser radiation due to the photoionization of Cs atoms is investigated. It is shown that the role of this absorption mechanism is negligible.     

Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, \(A_\mathrm{R}\) and \(B_\mathrm{R}\), each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for \(A_\mathrm{R}\) and \(B_\mathrm{R}\), we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., \(f \Delta t\)-long for DrugA and \((1-f) \Delta t\)-long for DrugB with \(0 \le f \le 1\) and \(\Delta t \ge 0\)). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, \(\mathcal {A/B} = A_\mathrm{R}/B_\mathrm{R}\), and the effect of each drug. We determine a critical ratio, which we term \(\mathcal {(A/B)}^{*}\), at which the two drugs are equally effective. As the first stage of the optimal strategy is applied, \(\mathcal {A/B}\) changes monotonically to \(\mathcal {(A/B)}^{*}\) and then, during the second stage, remains at \(\mathcal {(A/B)}^{*}\) thereafter. Beyond our analytic results, we explored an individual-based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.     

Oestrogen regulates the expression of cathepsin E-A-like gene through ER$$\upbeta $$ in liver of chicken ( Gallus gallus)

The cathepsin E-A-like, also known as ‘similar to nothepsin’, is a new member of the aspartic protease family, which may take part in processing of egg yolk macromolecules, due to it was identified in the chicken egg-yolk. Previously, studies have suggested that the expression of cathepsin E-A-like increased gradually during sexual maturation of pullets, but the exact regulation mechanism is poorly understood. In this study, to gain insight into the function and regulation mechanism of the gene in egg-laying hen, we cloned the cathepsin E-A-like gene and evaluated its evolutionary origin by using both phylogenetic and syntenic methods. The mode of the gene expression regulation was analysed through stimulating juvenile hens with \(17\upbeta \)-estradiol and chicken embryo hepatocytes with \(17\upbeta \)-estradiol combined with oestrogen receptor antagonists including MPP, ICI 182,780 and tamoxifen. Our results showed that cathepsin E-A-like was an orthologoues gene with nothepsin, which is present in birds but not in mammals. The expression of cathepsin E-A-like significantly increased in a dose-dependent manner after the juvenile hens were treated with \(17\upbeta \)-estradiol (\(P~<~0.05\)). Compared with the \(17\upbeta \)-estradiol treatment group, the expression of cathepsin E-A-like was not significantly changed when the hepatocytes were treated with \(17\upbeta \)-estradiol combined with MPP (\(P~<~0.05\)). In contrast, compared with the \(17\upbeta \)-estradiol combined with MPP treatment group, the expression of cathepsin E-A-like was significantly downregulated when the hepatocytes were treated with \(17\upbeta \)-estradiol combined with tamoxifen or ICI 182,780 (\(P~<~0.05\)). These results demonstrated that cathepsin E-A-like shared the same evolutionary origin with nothepsin. The expression of cathepsin E-A-like was regulated by oestrogen, and the regulative effect was predominantly mediated through ER-\(\upbeta \) in liver of chicken.     

Forecasting next season’s <Emphasis Type="Italic">Ixodes ricinus</Emphasis> nymphal density: the example of southern Germany 2018

The castor bean tick, Ixodes ricinus (L.) (Ixodida: Ixodidae), is the principal vector of pathogens causing tick-borne encephalitis or Lyme borreliosis in Europe. It is therefore of general interest to make an estimate of the density of I. ricinus for the whole year at the beginning of the tick season. There are two necessary conditions for making a successful prediction: a long homogeneous time series of observed tick density and a clear biological relationship between environmental predictors and tick density. A 9-year time series covering the period 2009–2017 of nymphal I. ricinus flagged at monthly intervals in southern Germany has been used. With the hypothesis that I. ricinus density is triggered by the fructification of the European beech 2 years before, the mean annual temperature of the previous year, and the current mean winter temperature (December–February), a forecast of the annual nymphal tick density has been made. Therefore, a Poisson regression model was generated resulting in an explained variance of 93.4% and an error of \(\hbox {RMSE} = 21\) ticks per \(100\,\hbox {m}^2\) (annual \(\hbox {MEAN} = 260\) collected ticks/\(100\,\hbox {m}^2\)). An independent verification of the forecast for the year 2017 resulted in 187 predicted versus 180 observed nymphs per \(100\,\hbox {m}^2\). For the year 2018 a relatively high number of 443 questing I. ricinus nymphs per \(100\,\hbox {m}^2\) is forecasted, i.e., a “good” tick year.     

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.     

Invasions Slow Down or Collapse in the Presence of Reactive Boundaries

Motivated by the propagation of thin bacterial films around planar obstacles, this paper considers the dynamics of travelling wave solutions to the Fisher–KPP equation \(u_t = u(1-u) + u_{xx} + u_{yy}\) in a planar strip \(-\infty< x < \infty \), \(0 \le y \le L\). We examine the propagation of fronts in the presence of a mixed boundary condition (also referred to as a ‘partially absorbing’ or ‘reactive’ boundary) \(u_y = \alpha u\), with \(\alpha >0\), at \(y=0\). The presence of boundary conditions of this kind leads to the development of front solutions that propagate in x but contain transverse structure in y. Motivated by the observation that the speed of propagation in the Fisher–KPP equation is determined (for exponentially decaying initial conditions) by the behaviour at the leading edge, we analyse the linearised Fisher–KPP equation in order to estimate the speed of the stable travelling front, a function of the width L and the imposed boundary conditions. For wide strips the speed estimate based on the linearised equation agrees well with the results of numerical simulations. For narrow channels numerical simulations indicate that the stable front propagates more slowly, and for sufficiently small L or sufficiently large \(\alpha \) the front speed falls to zero and the front collapses. The reason for the collapse is the non-existence, far behind the front, of a stable positive equilibrium solution u(x, y). While existence of these equilibrium states can be demonstrated via phase plane arguments, the investigation of stability is similar to calculations of critical patch sizes carried out in similar ecological models.     

Association of <Emphasis Type="BoldItalic">lactase</Emphasis> 13910 C/T polymorphism with bone mineral density and fracture risk: a meta-analysis

A number of studies have investigated the association of lactase (LCT, C/T-13910) gene polymorphism with bone mineral density (BMD) and fracture risk, but previous results were inconclusive. In this study, a meta-analysis was performed to quantify the association of LCT (C/T-13910) polymorphism with BMD and fracture risk. Eligible publications were searched in the PubMed, Web of Science, Embase databases, Google Scholar, Yahoo and Baidu. Pooled weighed mean difference (WMD) or odds ratio (OR) with their 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. A total of nine articles with 8871 subjects were investigated in the present meta-analysis. Overall, the TT/TC genotypes of LCT 13910 C/T polymorphism showed significantly higher BMD than those with the CC genotype at femur neck (FN) (\(\hbox {WMD} = 0.011\,\hbox {g/cm}^{2}\), 95% CI \(=\) 0.004–0.018, \(P = 0.003\)). Besides, LCT 13910 C/T polymorphism may decrease the risk of any site fractures (for TT versus TC \(+\) CC, OR \(=\) 0.813, 95% CI \(=\) 0.704–0.938, \(P = 0.005\); for T allele versus C allele, OR \(=\) 0.885, 95% CI \(=\) 0.792–0.989, \(P = 0.032\)). However, there was no significant association of LCT 13910 C/T polymorphism with BMD at lumbar spine and risk of vertebral fractures under all genetic contrast models (all P values were \({>}0.05\)). The meta-analysis suggests that there are significant effects of LCT 13910 C/T polymorphism on BMD and fracture risk. Large-scale studies with different ethnic populations will be needed to further investigate the possible race-specific effect of LCT 13910 C/T polymorphism on BMD and fracture risk.     

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.     

Competition of Multiple Species in Advective Environments

We study the effect of changes in flow speed on competition of an arbitrary number of species living in advective environments, such as streams and rivers. We begin with a spatial Lotka–Volterra model which is described by n reaction–diffusion–advection equations with Danckwerts boundary conditions. Using the dominant eigenvalue \(\lambda \le 0\) of the diffusion–advection operator subject to boundary conditions, we reduce the model to a system of ordinary differential equations. We impose a “transitive arrangement” of the competitors in terms of their interspecific coefficients and growth rates, which means that in the absence of advection, we have the following situation: for all \(1\le i<j\le n\), species i out-competes species j, while species j has higher intrinsic growth rate than species i. Changing advection speed in the original spatial model corresponds to changing the value of \(\lambda \) in the spatially implicit model. Considering the cases of the odd and even n separately, we obtain explicit intervals of the values of \(\lambda \) that allow all n species to be present in the habitat (coexistence interval). Stability of this equilibrium is shown for \(n\le 4\).     

Genetic variability and structure of an isolated population of <Emphasis Type="Italic">Ambystoma altamirani</Emphasis>, a mole salamander that lives in the mountains of one of the largest urban areas in the world

Amphibians are globally threatened by habitat loss and fragmentation; species within the order Ambystoma are not the exception, as there are 18 species of mole salamanders in México, of which 16 are endemic and all species are under some national or international status of protection. The mole salamander, Ambystoma altamirani is a microendemic species, which is distributed in central México, within the trans-Mexican volcanic belt, and is one of the most threatened species due to habitat destruction and the introduction of exotic species. Nine microsatellite markers were used to determine the genetic structure, genetic variability, effective population size, presence of bottlenecks and inbreeding coefficient of one population of A. altamirani to generate information which might help to protect and conserve this threatened species. We found two genetic subpopulations with significant level of genetic structure (\(F_{\mathrm{ST}}= 0.005\)) and high levels of genetic variability (\(H_{\mathrm{o}}= 0.883\); \(H_{\mathrm{e}}= 0.621\)); we also found a small population size (\(N_{\mathrm{e}} = 8.8\)), the presence of historical (\(M =\) 0.486) and recent bottlenecks under IAM and TPM models, with a low, but significant coefficient of inbreeding (\(F_{\mathrm{IS}} = -\)0.451). This information will help us to raise conservation strategies of this microendemic mole salamander species.     

DFT study of nano zinc/copper voltaic cells

To facilitate the development of new materials for use in batteries, it is necessary to develop ab initio full-electron computational techniques for modeling potential new battery materials. Here, we tested density functional theory procedures that are accurate enough to obtain the energetics of a zinc/copper voltaic cell. We found the magnitude of the zero-point energy correction to be 0.01–0.2 kcal/mol per atom or molecule and the magnitude of the dispersion correction to be 0.1–0.6 kcal/mol per atom or molecule for Zn _n , (H₂O) _n , \( \mathrm{Zn}{\left({\mathrm{H}}_2\mathrm{O}\right)}_n^{2+} \), \( \mathrm{Cu}{\left({\mathrm{H}}_2\mathrm{O}\right)}_n^{2+} \), and Cu _n . Counterpoise correction significantly affected the values of ?\( {E}_n^{\mathrm{abs}} \), ?\( {E}_n^{\mathrm{coh}} \), and ?E^solv by 1.0–3.1 kcal/mol per atom or molecule at the B3PW91/6-31G(d) level of theory, but by only 0.04–0.4 kcal/mol per atom or molecule at the B3PW91/cc-pVTZ level of theory. The application of B3PW91/6-31G(d) yielded results that differed from macroscopic experimental values by 0.1–7.1 kcal/mol per atom or molecule, whereas applying B3PW91/cc-pVTZ produced results that differed from macroscopic experimental values by 0.1–4.8 kcal/mol per atom or molecule, with the smallest differences occurring for reactions with a small macroscopic experimental ?E and the largest differences occurring for reactions with a large macroscopic experimental ?E, implying size consistency.     

Temperature-Dependent Physiology of <Emphasis Type="Italic">Poa secunda</Emphasis>, a Cool Season Grass Native to the Great Basin,United States

Poa secunda Presl. is one of the few native perennial bunchgrasses in the Intermountain West to persist and co-occur with the invasive annual Bromus tectorum L. following widespread overgrazing and frequent wildfires. To identify potential mechanisms responsible for the co-occurrence of P. secunda with B. tectorum, respiration rates (\(R_{\operatorname{CO} _2 }\)) of eight populations were measured at 10, 20, and 30°C on laboratory-grown plants by infrared gas analysis. In addition, \(R_{\operatorname{CO} _2 }\) and metabolic heat rates (q) of nine field-grown populations were measured at 10 and 20°C using calorimetry on eight dates over a growing season to compare temperature-dependent physiology of P. secunda with previous published patterns for B. tectorum. Laboratory respiration rates of P. secunda populations suggest considerable intraspecific variation in physiological response to temperature. Changes in slope for \(R_{\operatorname{CO} _2 }\) and q over the growing season were steeper at 20 than at 10°C , suggesting that P. secunda populations are more capable of maintaining steady rates of metabolism at low than at high temperatures. However, growth rates of P. secunda were relatively lower than those for B. tectorum at 10°C. Calculations of growth rates and efficiency of converting substrate carbon into biomass of P. secunda consistently remained positive, while those for B. tectorum rapidly declined at temperatures above 10°C. These data suggest that P. secunda co-occurrence with B. tectorum over a broad range of plant communities in the Intermountain West may be partially explained by having a similar ability to maintain positive and stable growth rate at low temperature. In addition, the greater ability of P. secunda to maintain growth rates and metabolic efficiency at higher temperatures than B. tectorum may allow this perennial grass to compensate for the greater relative growth rates of B. tectorum at low temperature.     

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.     

StreAM-$$T_g$$: algorithms for analyzing coarse grained RNA dynamics based on Markov models of connectivity-graphs

Background

In this work, we present a new coarse grained representation of RNA dynamics. It is based on adjacency matrices and their interactions patterns obtained from molecular dynamics simulations. RNA molecules are well-suited for this representation due to their composition which is mainly modular and assessable by the secondary structure alone. These interactions can be represented as adjacency matrices of k nucleotides. Based on those, we define transitions between states as changes in the adjacency matrices which form Markovian dynamics. The intense computational demand for deriving the transition probability matrices prompted us to develop StreAM-\(T_g\), a stream-based algorithm for generating such Markov models of k-vertex adjacency matrices representing the RNA.

Results

We benchmark StreAM-\(T_g\) (a) for random and RNA unit sphere dynamic graphs (b) for the robustness of our method against different parameters. Moreover, we address a riboswitch design problem by applying StreAM-\(T_g\) on six long term molecular dynamics simulation of a synthetic tetracycline dependent riboswitch (500 ns) in combination with five different antibiotics.

Conclusions

The proposed algorithm performs well on large simulated as well as real world dynamic graphs. Additionally, StreAM-\(T_g\) provides insights into nucleotide based RNA dynamics in comparison to conventional metrics like the root-mean square fluctuation. In the light of experimental data our results show important design opportunities for the riboswitch.

     

MiR-27b promotes sheep skeletal muscle satellite cell proliferation by targeting <Emphasis Type="Italic">myostatin</Emphasis> gene

To investigate the role of miR-27b in sheep skeletal muscle development, here we first cloned the sequence of sheep pre-miR-27b, then further investigated its expression pattern in sheep skeletal muscle in vivo, the relationship of miR-27b expression and sheep skeletal muscle satellite cell proliferation and differentiation in vitro, and then finally confirmed its target gene during this development process. MiR-27b sequence, especially its mature sequence, was conservative among different species. MiR-27b highly expressed in sheep skeletal muscle than other tissues. In skeletal muscle of Suffolk and Bashbay sheep, miR-27b was upregulated during foetal period and downregulated during postnatal period significantly (\(P{<}0.01\)), but it still kept a relatively higher expression level in skeletal muscle of postnatal Suffolk sheep than Bashbay. There is a potential target site of miR-27b on \(3^\prime \)-UTR of sheep myostatin (MSTN) mRNA, and the double luciferase reporter assay proved that miR-27b could successfully bind on this site. When sheep satellite cells were in the proliferation status, miR-27b was upregulated and MSTN was downregulated significantly (\(P{<}0.01\)). When miR-27b mimics was transfected into sheep satellite cells, the cell proliferation was promoted and the protein level of MSTN was significantly downregulated (\(P{<}0.01\)). Moreover, miR-27b regulated its target gene MSTN by translation repression at an early step, and followed by inducing mRNA degradation in sheep satellite cells. Based on these results, we confirm that miR-27b could promote sheep skeletal muscle satellite cell proliferation by targeting MSTN and suppressing its expression.     

A Malaria Transmission Model with Temperature-Dependent Incubation Period

Malaria is an infectious disease caused by Plasmodium parasites and is transmitted among humans by female Anopheles mosquitoes. Climate factors have significant impact on both mosquito life cycle and parasite development. To consider the temperature sensitivity of the extrinsic incubation period (EIP) of malaria parasites, we formulate a delay differential equations model with a periodic time delay. We derive the basic reproduction ratio \(R_0\) and establish a threshold type result on the global dynamics in terms of \(R_0\), that is, the unique disease-free periodic solution is globally asymptotically stable if \(R_0<1\); and the model system admits a unique positive periodic solution which is globally asymptotically stable if \(R_0>1\). Numerically, we parameterize the model with data from Maputo Province, Mozambique, and simulate the long-term behavior of solutions. The simulation result is consistent with the obtained analytic result. In addition, we find that using the time-averaged EIP may underestimate the basic reproduction ratio.