Molecular Anatomy of ParA-ParA and ParA-ParB Interactions during Plasmid Partitioning

Firmicutes multidrug resistance inc18 plasmids encode parS sites and two small homodimeric ParA-like (δ₂) and ParB-like (ω₂) proteins to ensure faithful segregation. Protein ω₂ binds to parS DNA, forming a short left-handed helix wrapped around the full parS, and interacts with δ₂. Protein δ₂ interacts with ω₂ and, in the ATP-bound form, binds to nonspecific DNA (nsDNA), forming small clusters. Here, we have mapped the ω₂·δ₂ and δ₂·δ₂ interacting domains in the δ₂ that are adjacent to but distinct from each other. The δ₂ nsDNA binding domain is essential for stimulation of ω₂·parS-mediated ATP hydrolysis. From the data presented here, we propose that δ₂ interacts with ATP, nsDNA, and with ω₂ bound to parS at near equimolar concentrations, facilitating a δ₂ structural transition. This δ₂ “activated” state overcomes its impediment in ATP hydrolysis, with the subsequent release of both of the proteins from nsDNA (plasmid unpairing).     

Long-Range Correlations of Global Sea Surface Temperature

Scaling behaviors of the global monthly sea surface temperature (SST) derived from 1870–2009 average monthly data sets of Hadley Centre Sea Ice and SST (HadISST) are investigated employing detrended fluctuation analysis (DFA). The global SST fluctuations are found to be strong positively long-range correlated at all pertinent time-intervals. The value of scaling exponent is larger in the tropics than those in the intermediate latitudes of the northern and southern hemispheres. DFA leads to the scaling exponent α = 0.87 over the globe (60°S~60°N), northern hemisphere (0°N~60°N), and southern hemisphere (0°S~60°S), α = 0.84 over the intermediate latitude of southern hemisphere (30°S~60°S), α = 0.81 over the intermediate latitude of northern hemisphere (30°N~60°N) and α = 0.90 over the tropics 30°S~30°N [fluctuation F(s) ~ s^α], which the fluctuations of monthly SST anomaly display long-term correlated behaviors. Furthermore, the larger the standard deviation is, the smaller long-range correlations (LRCs) of SST in the corresponding regions, especially in three distinct upwelling areas. After the standard deviation is taken into account, an index χ = α * σ is introduced to obtain the spatial distributions of χ. There exists an obvious change of global SST in central east and northern Pacific and the northwest Atlantic. This may be as a clue on predictability of climate and ocean variabilities.     

Quantitative models characterizing seed germination responses to abscisic Acid and osmoticum

Mathematical models were developed to characterize the physiological bases of the responses of tomato (Lycopersicon esculentum Mill. cv T5) seed germination to water potential (ψ) and abscisic acid (ABA). Using probit analysis, three parameters were derived that can describe the germination time courses of a seed population at different ψ or ABA levels. For the response of seed germination to reduced ψ, these parameters are the mean base water potential (¯ψ_b, MPa), the standard deviation of the base water potential among seeds in the population (σ_ψb, MPa), and the “hydrotime constant” (θ_H, MPa·h). For the response to ABA, they are the log of the mean base ABA concentration ([unk]ABA_b, m), the standard deviation of the base ABA concentration among seeds in the population (σ_ABAb, log[m]), and the “ABA-time constant” (θ_ABA, log[m]·h). The values of ¯ψ_b and [unk]ABA_b provide quantitative estimates of the mean sensitivity of germination rate to ψ or ABA, whereas σ^ψ_b and σ_ABAb account for the variation in sensitivity among seeds in the population. The time constants, θ_H and θ_ABA, indicate the extent to which germination rate will be affected by a given change in ψ or ABA. Using only these parameters, germination time courses can be predicted with reasonable accuracy at any medium ψ according to the equation probit(g) = [ψ - (θ_H/t_g) - ¯ψ_b]/σ_ψb, or at any ABA concentration according to the equation probit(g) = [log[ABA] - (θ_ABA/t_g) - log[[unk]ABA_b]]/σ_ABAb, where t_g is the time to radicle emergence of percentage g, and ABA is the ABA concentration (m) in the incubation solution. In the presence of both ABA and reduced ψ, the same parameters can be used to predict seed germination time courses based upon strictly additive effects of ψ and ABA in delaying the time of radicle emergence. Further analysis indicates that ABA and ψ can act both independently and interactively to influence physiological processes preparatory for radicle growth, such as the accumulation of osmotic solutes in the embryo. The models provide quantitative values for the sensitivity of germination to ABA or ψ, allow evaluation of independent and interactive effects of the two factors, and have implications for understanding how ABA and ψ may regulate growth and development.     

The Kinetics of Osmotic Transport through Pores of Molecular Dimensions

This paper presents a theoretical analysis of the kinetics of osmotic transport across a semipermeable membrane. There is a thermodynamic connection between the rate of flow under a hydrostatic pressure difference and the rate of flow due to a difference in solute concentration on the two sides. One might therefore attempt to calculate the osmotic transport coefficient by applying Poiseuille's equation to the flow produced by a difference in hydrostatic pressure. Such a procedure is, however, inappropriate if the pores in the membrane are too small to allow molecules to “overtake.” It then becomes necessary to perform a statistical calculation of the transport coefficient, and such a calculation is described in this paper. The resulting expression for the number of solvent molecules passing through a pore per second is J = m D₁ δn₁/l² where m is the number of solvent molecules in the pore, l is the length of the pore, D₁ is the self-diffusion coefficient of the solute, and δn₁ the difference in solvent mole fraction on the two sides of the membrane. This equation is used for estimating the number of pores per unit area of the squid axon membrane; the result is 6 × 10⁹ pores/cm².     

Streptococcus pyogenes pSM19035 requires dynamic assembly of ATP-bound ParA and ParB on parS DNA during plasmid segregation

The accurate partitioning of Firmicute plasmid pSM19035 at cell division depends on ATP binding and hydrolysis by homodimeric ATPase δ₂ (ParA) and binding of ω₂ (ParB) to its cognate parS DNA. The 1.83 Å resolution crystal structure of δ₂ in a complex with non-hydrolyzable ATPγS reveals a unique ParA dimer assembly that permits nucleotide exchange without requiring dissociation into monomers. In vitro, δ₂ had minimal ATPase activity in the absence of ω₂ and parS DNA. However, stoichiometric amounts of ω₂ and parS DNA stimulated the δ₂ ATPase activity and mediated plasmid pairing, whereas at high (4:1) ω₂ : δ₂ ratios, stimulation of the ATPase activity was reduced and δ₂ polymerized onto DNA. Stimulation of the δ₂ ATPase activity and its polymerization on DNA required ability of ω₂ to bind parS DNA and its N-terminus. In vivo experiments showed that δ₂ alone associated with the nucleoid, and in the presence of ω₂ and parS DNA, δ₂ oscillated between the nucleoid and the cell poles and formed spiral-like structures. Our studies indicate that the molar ω₂ : δ₂ ratio regulates the polymerization properties of (δ•ATP•Mg²⁺)₂ on and depolymerization from parS DNA, thereby controlling the temporal and spatial segregation of pSM19035 before cell division.     

Membrane Permeability: Generalization of the Reflection Coefficient Method of Describing Volume and Solute Flows

The reflection coefficient method for describing volume and solute fluxes through membranes is generalized to take into account the nonideality of the solutions bathing the membrane and/or multicomponent systems. The reflection coefficient of the impermeable species in these systems is less than unity by a coefficient γ. The reflection coefficient obtained solely from the volume flow equation, σ^v, will always be less than the reflection coefficient obtained from the solute flow equation, σ^8v. These two coefficients are related by σ^8v = σ^v + γ.     

Angle of Inclination of Tank-Treading Red Cells: Dependence on Shear Rate and Suspending Medium

Red cells suspended in solutions much more viscous than blood plasma assume an almost steady-state orientation when sheared above a threshold value of shear rate. This orientation is a consequence of the motion of the membrane around the red cell called tank-treading. Observed along the undisturbed vorticity of the shear flow, tank-treading red cells appear as slender bodies. Their orientation can be quantified as an angle of inclination (θ) of the major axis with respect to the undisturbed flow direction. We measured θ using solution viscosities (η₀) and shear rates (γ˙) covering one and three orders of magnitude, respectively. At the lower values of η₀, θ was almost independent of γ˙. At the higher values of η₀, θ displayed a maximum at intermediate shear rates. The respective maximal values of θ increased by ∼10° from 10.7 to 104 mPas. After accounting for the absent membrane viscosity in models by using an increased cytoplasmic viscosity, their predictions of θ agree qualitatively with our data. Comparison of the observed variation of θ at constant γ˙ with model results suggests a change in the reference configuration of the shear stiffness of the membrane.     

Inactivation of Gating Currents of L-Type Calcium Channels : Specific Role of the α2δ Subunit

In studies of gating currents of rabbit cardiac Ca channels expressed as α_1C/β_2a or α_1C/β_2a/α₂δ subunit combinations in tsA201 cells, we found that long-lasting depolarization shifted the distribution of mobile charge to very negative potentials. The phenomenon has been termed charge interconversion in native skeletal muscle (Brum, G., and E. Ríos. 1987. J. Physiol. (Camb.). 387:489–517) and cardiac Ca channels (Shirokov, R., R. Levis, N. Shirokova, and E. Ríos. 1992. J. Gen. Physiol. 99:863–895). Charge 1 (voltage of half-maximal transfer, V_1/2 ≃ 0 mV) gates noninactivated channels, while charge 2 (V_1/2 ≃ −90 mV) is generated in inactivated channels. In α_1C/β_2a cells, the available charge 1 decreased upon inactivating depolarization with a time constant τ ≃ 8, while the available charge 2 decreased upon recovery from inactivation (at −200 mV) with τ ≃ 0.3 s. These processes therefore are much slower than charge movement, which takes <50 ms. This separation between the time scale of measurable charge movement and that of changes in their availability, which was even wider in the presence of α₂δ, implies that charges 1 and 2 originate from separate channel modes. Because clear modal separation characterizes slow (C-type) inactivation of Na and K channels, this observation establishes the nature of voltage-dependent inactivation of L-type Ca channels as slow or C-type. The presence of the α₂δ subunit did not change the V_1/2 of charge 2, but sped up the reduction of charge 1 upon inactivation at 40 mV (to τ ≃ 2 s), while slowing the reduction of charge 2 upon recovery (τ ≃ 2 s). The observations were well simulated with a model that describes activation as continuous electrodiffusion (Levitt, D. 1989. Biophys. J. 55:489–498) and inactivation as discrete modal change. The effects of α₂δ are reproduced assuming that the subunit lowers the free energy of the inactivated mode.     

The Inhibitory Mechanism of the ζ Subunit of the F1FO-ATPase Nanomotor of Paracoccus denitrificans and Related α-Proteobacteria

The ζ subunit is a novel inhibitor of the F₁F_O-ATPase of Paracoccus denitrificans and related α-proteobacteria. It is different from the bacterial (ϵ) and mitochondrial (IF₁) inhibitors. The N terminus of ζ blocks rotation of the γ subunit of the F₁-ATPase of P. denitrificans (Zarco-Zavala, M., Morales-Ríos, E., Mendoza-Hernández, G., Ramírez-Silva, L., Pérez-Hernández, G., and García-Trejo, J. J. (2014) FASEB J. 24, 599–608) by a hitherto unknown quaternary structure that was first modeled here by structural homology and protein docking. The F₁-ATPase and F₁-ζ models of P. denitrificans were supported by cross-linking, limited proteolysis, mass spectrometry, and functional data. The final models show that ζ enters into F₁-ATPase at the open catalytic α_E/β_E interface, and two partial γ rotations lock the N terminus of ζ in an “inhibition-general core region,” blocking further γ rotation, while the ζ globular domain anchors it to the closed α_DP/β_DP interface. Heterologous inhibition of the F₁-ATPase of P. denitrificans by the mitochondrial IF₁ supported both the modeled ζ binding site at the α_DP/β_DP/γ interface and the endosymbiotic α-proteobacterial origin of mitochondria. In summary, the ζ subunit blocks the intrinsic rotation of the nanomotor by inserting its N-terminal inhibitory domain at the same rotor/stator interface where the mitochondrial IF₁ or the bacterial ϵ binds. The proposed pawl mechanism is coupled to the rotation of the central γ subunit working as a ratchet but with structural differences that make it a unique control mechanism of the nanomotor to favor the ATP synthase activity over the ATPase turnover in the α-proteobacteria.     

Relationship between the Autoantibody and Expression of β3-Adrenoceptor in Lung and Heart

Background

Evidences suggest that β₃ -adrenoceptor (β₃-AR) plays an important role in heart failure (HF), although no data is reported indicating how these effects may change with the increasing age. Pulmonary congestion and edema are the major life-threatening complications associated with HF. The purpose of this study is to explore the relationship between the anti-β₃-AR autoantibody and the expression of β₃-AR in the lungs and heart for both aged patients and rats with HF.

Methods

Synthetic β₃-AR peptides served as the target antigens in ELISA were used to screen the anti-β₃-AR autoantibody in aged patients and rats. Two aged rat models were constructed based on aortic banding and sham-operation. The expression of β₃-AR mRNA and protein in the lung and heart was measured in intervention and non-intervention groups by Western blot analysis at the baseline, 5^th, 7^th, 9^th and 11^th week, respectively.

Results

The frequency and titer of anti-β₃-AR autoantibody in aged patients and rats with HF were higher than those in the control group (p<0.05). The expression of β₃-AR mRNA and protein in pulmonary tissues decreased continually from the 7^th week (p<0.05), followed by HF observed during the 9^th week. The expression of β₃-AR in myocardial tissues continued to increase after the 9^th week (p<0.05), and the expression of both β₃-AR mRNA and protein in the BRL group [HF group with BRL37344 (4-[-[2-hydroxy-(3-chlorophenyl)ethyl-amino] phenoxyacetic acid) (a β₃-AR agonist) injection] was positively correlated with BRL37344 when compared with non-BRL group (HF group without BRL37344 injection) (p<0.05).

Conclusion

Anti-β₃-AR autoantibody was detected in aged patients and rats with HF. The expression of β₃-AR mRNA and protein in pulmonary tissues decreased continually, and began earlier than in the heart, but its expression in myocardial tissues increased continually and could be further promoted by β₃-AR agonist.     

Kinetic diversity of single-channel burst openings underlying persistent Na(+) current in entorhinal cortex neurons

The kinetic diversity of burst openings responsible for the persistent Na⁺ current (I_NaP) in entorhinal cortex neurons was examined by separately analyzing single bursts. Although remarkable kinetic variability was observed among bursts in terms of intraburst opening probability and mean open and closed times, the values of time constants describing intraburst open times (τ_o(b)s) and closed times (τ_c(b)s) were distributed around well-defined peaks. At −40 mV, τ_o(b) peaks were found at ~0.34 (τ_o(b)1) and 0.77 (τ_o(b)2) ms, and major τ_c(b) peaks were found at ~0.24 (τ_c(b)1) and 0.54 (τ_c(b)2) ms. In ~80% of the bursts two preferential gating modes were found that consisted of a combination of either τ_o(b)1 and τ_c(b)2 (“intraburst mode 1”), or τ_o(b)2 and τ_c(b)1 (“intraburst mode 2”). Individual channels could switch between different gating modalities, but normally tended to maintain a specific gating mode for long periods. Mean burst duration also displayed considerable variability. At least three time constants were found to describe burst duration, and the frequencies at which each of the corresponding “bursting states” occurred varied in different channels. Short-lasting bursting states were preferentially associated with intraburst mode 1, whereas very-long-lasting bursts tended to gate according to mode 2 only or other modes that included considerably longer mean open times. These results show that I_NaP channels can generate multiple intraburst open and closed states and bursting states, but these different kinetic states tend to combine in definite ways to produce a limited number of prevalent, well-defined gating modalities. Modulation of distinct gating modalities in individual Na⁺ channels may be a powerful form of plasticity to influence neuronal excitability and function.     

Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits α, ε, θ and β reveals a highly flexible arrangement of the proofreading domain

A complex of the three (αεθ) core subunits and the β₂ sliding clamp is responsible for DNA synthesis by Pol III, the Escherichia coli chromosomal DNA replicase. The 1.7 Å crystal structure of a complex between the PHP domain of α (polymerase) and the C-terminal segment of ε (proofreading exonuclease) subunits shows that ε is attached to α at a site far from the polymerase active site. Both α and ε contain clamp-binding motifs (CBMs) that interact simultaneously with β₂ in the polymerization mode of DNA replication by Pol III. Strengthening of both CBMs enables isolation of stable αεθ:β₂ complexes. Nuclear magnetic resonance experiments with reconstituted αεθ:β₂ demonstrate retention of high mobility of a segment of 22 residues in the linker that connects the exonuclease domain of ε with its α-binding segment. In spite of this, small-angle X-ray scattering data show that the isolated complex with strengthened CBMs has a compact, but still flexible, structure. Photo-crosslinking with p-benzoyl-L-phenylalanine incorporated at different sites in the α-PHP domain confirm the conformational variability of the tether. Structural models of the αεθ:β₂ replicase complex with primer-template DNA combine all available structural data.     

The DNA polymerase III holoenzyme contains γ and is not a trimeric polymerase

There is widespread agreement that the clamp loader of the Escherichia coli replicase has the composition DnaX₃δδ’χψ. Two DnaX proteins exist in E. coli, full length τ and a truncated γ that is created by ribosomal frameshifting. τ binds DNA polymerase III tightly; γ does not. There is a controversy as to whether or not DNA polymerase III holoenzyme (Pol III HE) contains γ. A three-τ form of Pol III HE would contain three Pol IIIs. Proponents of the three-τ hypothesis have claimed that γ found in Pol III HE might be a proteolysis product of τ. To resolve this controversy, we constructed a strain that expressed only τ from a mutated chromosomal dnaX. γ containing a C-terminal biotinylation tag (γ-C_tag) was provided in trans at physiological levels from a plasmid. A 2000-fold purification of Pol III* (all Pol III HE subunits except β) from this strain contained one molecule of γ-C_tag per Pol III* assembly, indicating that the dominant form of Pol III* in cells is Pol III₂τ₂ γδδ’χψ. Revealing a role for γ in cells, mutants that express only τ display sensitivity to ultraviolet light and reduction in DNA Pol IV-dependent mutagenesis associated with double-strand-break repair, and impaired maintenance of an F’ episome.     

Why Do More Divergent Sequences Produce Smaller Nonsynonymous/Synonymous Rate Ratios in Pairwise Sequence Comparisons?

Several studies have reported a negative correlation between estimates of the nonsynonymous to synonymous rate ratio (ω = d_N/d_S) and the sequence distance d in pairwise comparisons of the same gene from different species. That is, more divergent sequences produce smaller estimates of ω. Explanations for this negative correlation have included segregating nonsynonymous polymorphisms in closely related species and nonlinear dynamics of the ratio of two random variables. Here we study the statistical properties of the maximum-likelihood estimates of ω and d in pairwise alignments and explore the possibility that the negative correlation can be entirely explained by those properties. We show that the ω estimate is positively biased for small d and that the bias decreases with the increase of d. We also show that the estimates of ω and d are negatively correlated when ω < 1 and positively correlated when ω > 1. However, the bias in estimates of ω and the correlation between estimates of ω and d are not enough to explain the much stronger correlation observed in real data sets. We then explore the behavior of the estimates when the model is misspecified and suggest that the observed correlation may be due to protein-level selection that causes very different amino acids to be favored in different domains of the protein. Widely used models fail to account for such among-site heterogeneity and cause underestimation of the nonsynonymous rate and ω, with the bias being much stronger for distant sequences. We point out that tests of positive selection based on the ω ratio are invariant to the parameterization of the model and thus unaffected by bias in the ω estimates or the correlation between estimates of ω and d.     

New Insights in Abdominal Pain in Paroxysmal Nocturnal Hemoglobinuria (PNH): A MRI Study

Introduction

Abdominal pain in PNH has never been investigated by in-vivo imaging studies. With MRI, we aimed to assess mesenteric vessels flow and small bowel wall perfusion to investigate the ischemic origin of abdominal pain.

Materials and Methods

Six PNH patients with (AP) and six without (NOP) abdominal pain underwent MRI. In a blinded fashion, mean flow (MF, quantity of blood moving through a vessel within a second, in mL·s^-1) and stroke volume (SV, volume of blood pumped out at each heart contraction, in mL) of Superior Mesenteric Vein (SMV) and Artery (SMA), areas under the curve at 60 (AUC₆₀) and 90 seconds (AUC₉₀) and K^trans were assessed by two operators.

Results

Mean total perfusion and flow parameters were lower in AP than in NOP group. AUC₆₀: 84.81 ± 11.75 vs. 131.73 ± 18.89 (P < 0.001); AUC₉₀: 102.33 ± 14.16 vs. 152.58 ± 22.70 (P < 0.001); K^trans: 0.0346 min^-1 ± 0.0019 vs. 0.0521 ± 0.0015 (P = 0.093 duodenum, 0.009 jejunum/ileum). SMV: MF 4.67 ml/s ± 0.85 vs. 8.32 ± 2.14 (P = 0.002); SV 3.85 ml ± 0.76 vs. 6.55 ± 1.57 (P = 0.02). SMA: MF 6.95 ± 2.61 vs. 11.2 ± 2.32 (P = 0.07); SV 6.52 ± 2.19 vs. 8.78 ± 1.63 (P = 0.07). We found a significant correlation between MF and SV of SMV and AUC₆₀ (MF:ρ = 0.88, P < 0.001; SV: ρ = 0.644, P = 0.024), AUC₉₀ (MF: ρ = 0.874, P < 0.001; SV:ρ = 0.774, P = 0.003) and K^trans (MF:ρ = 0.734, P = 0.007; SV:ρ = 0.581, P = 0.047).

Conclusions

Perfusion and flow MRI findings suggest that the impairment of small bowel blood supply is significantly associated with abdominal pain in PNH.     

Voltage and Current Clamp Transients with Membrane Dielectric Loss

Transient responses of a space-clamped squid axon membrane to step changes of voltage or current are often approximated by exponential functions of time, corresponding to a series resistance and a membrane capacity of 1.0 μF/cm². Curtis and Cole (1938, J. Gen. Physiol. 21:757) found, however, that the membrane had a constant phase angle impedance z = z₁(jωτ)^-α, with a mean α = 0.85. (α = 1.0 for an ideal capacitor; α < 1.0 may represent dielectric loss.) This result is supported by more recently published experimental data. For comparison with experiments, we have computed functions expressing voltage and current transients with constant phase angle capacitance, a parallel leakage conductance, and a series resistance, at nine values of α from 0.5 to 1.0. A series in powers of t^α provided a good approximation for short times; one in powers of t^-α, for long times; for intermediate times, a rational approximation matching both series for a finite number of terms was used. These computations may help in determining experimental series resistances and parallel leakage conductances from membrane voltage or current clamp data.     

Regulation of α-Transducin and α-Gustducin Expression by a High Protein Diet in the Pig Gastrointestinal Tract

BackgroundThe expression of taste receptors (TASRs) and their signalling molecules in the gastrointestinal (GI) epithelial cells, including enteroendocrine cells (EECs), suggests they participate in chemosensing mechanisms influencing GI physiology via the release of endocrine messengers. TASRs mediate gustatory signalling by interacting with different transducers, including α-gustducin (G_αgust) and α-transducin (G_αtran) G protein subunits. This study tested whether G_αtran and G_αgust immunoreactive (-IR) cells are affected by a short-term (3 days) and long-term (30 days) high protein (Hp) diet in the pig GI tract.ResultIn the stomach, G_αgust and G_αtran-IR cells contained serotonin (5-HT) and ghrelin (GHR), while in the small and large intestine, G_αgust and G_αtran-IR colocalized with 5-HT-, cholecystokinin (CCK)- and peptide YY (PYY)-IR. There was a significant increase in the density of G_αtran-IR cells in the pyloric mucosa in both short- and long-term Hp diet groups (Hp3 and Hp30) vs. the control group (Ctr) (P<0.05), while the increase of G_αgust-IR cells in the pyloric mucosa was significant in Hp30 group vs. Ctr and vs. Hp3 (P<0.05); these cells included G_αtran / 5HT-IR and G_αtran / GHR-IR cells (P<0.05 and P<0.001 vs. Ctr, respectively) as well as G_αgust /5-HT-IR or G_αgust / GHR-IR cells (P<0.05 and P<0.01 vs. Ctr, respectively). In the small intestine, we recorded a significant increase in G_αtran-IR cells in the duodenal crypts and a significant increase of G_αgust-IR cells in the jejunal crypts in Hp3 group compared to HP30 (P<0.05). With regard to the number of G_αtran-G_αgust IR cells colocalized with CCK or 5-HT, there was only a significant increase of G_αtran / CCK-IR cells in Hp3 group compared to Ctr (P = 0.01).ConclusionThis study showed an upregulation of selected subpopulations of G_αgust / G_αtran-IR cells in distinct regions of the pig GI tract by short- and long-term Hp diet lending support to TASR-mediated effects in metabolic homeostasis and satiety mechanisms.     

Simulation of Interstitial Fluid Flow in Ligaments: Comparison among Stokes,Brinkman and Darcy Models

In this paper, we use Stokes, Brinkman and Darcy equations to approximate the porous continuum media of ligament tissues respectively, simulate the flow field with FLUENT software, and study the shear stress on the cell surface due to the interstitial fluid flow. Since the Brinkman equation approaches Stokes equation well in high hydraulic permeability (k_p) condition (k_p ≥1.0×10^-8 m² in our numerical simulation), and it is an approximation to Darcy model in low k_p condition (k_p ≤5.0×10^-12 m² in our numerical simulation), we used the Brinkman model to simulate the interstitial fluid flow in the ligament where k_p is approximately 1.0×10^-16 m². It shows k_p and anisotropic property have a little effect on the flow field, but have a great effect on the shear stress on the membrane of interstitial cells (τ_cell). There is a linear relationship between τ_cell and , when k_p =1.0×10^-16 m² and the maximum τ_cell (τ_cell,max) is approximately 10 Pa. The anisotropic property will affect τ_cell''s distribution on the cell surface. When k_x/k_y>1, low τ_cell dominates the cell, while when k_x/k_y<1, high τ_cell dominants the cell.