The mechanical consequences of dynamic frontal plane limb alignment for non-contact ACL injury

This study investigated the mechanical consequences of differences in dynamic frontal plane alignment of the support limb and the influence of anticipatory muscle activation at the hip and ankle on reducing the potential for non-contact ACL injury during single-limb landing. A frontal plane, three-link passive dynamic model was used to estimate an ACL non-contact injury threshold. This threshold was defined as the maximum axial force that the knee could sustain before the joint opened 8 degrees either medially or laterally, which was deemed sufficient to cause injury. The limb alignment and hip and ankle muscle contractions were varied to determine their effects on the ACL injury threshold. Valgus or varus alignment reduced the injury threshold compared to neutral alignment, but increasing the anticipatory contraction of hip abduction and adduction muscle groups increased the injury threshold. Increasing anticipatory ankle inversion/eversion muscle contraction had no effect. This study provides a mechanical rationale for the conclusion that a neutral limb alignment (compared to valgus or varus) during landing and increasing hip muscle contraction (abductors/adductors) prior to landing can reduce the possibility of ACL rupture through a valgus or varus opening mechanism.     

Biodegradation of p-nitrophenol by P. putida

A strain of Pseudomonas putida was found capable of metabolizing p-nitrophenol (PNP) as a sole source of carbon, nitrogen and energy. To explore the applicability of this strain for bioremediation for controlling environmental PNP pollution, its degradation potential at 300 and 500 ppm was examined in a medium devoid of carbon and nitrogen source (minimal medium). At A600, 0.5 OD inoculum, the strain metabolized 300 and 500 ppm within 36 and 72 h, respectively. The degradation was accompanied by release of stoichiometric amount of nitrite. Effect of glucose and nitrogen on PNP degradation under similar conditions revealed that (i) glucose (0.4 g/l) at 20 and 50 ppm PNP did not accelerate the rate of PNP degradation, while glucose (0.4 g/l) at 300 ppm PNP inhibited its degradation, (ii) nitrogen supplement viz. sodium nitrate and ammonium sulphate (0.04 and 0.4 g/l) in minimal medium with PNP (300 ppm) showed no effect on PNP degradation, while glutamate alone (0.04 and 0.4 g/l) showed mere rise in biomass (from 0.5 to 1.6 OD units), and (iii) acidic pH (4.0-6.5) did not support PNP degradation, while alkaline pH (7.5-9.5) significantly enhanced the rate of PNP degradation. The complete degradation of PNP at high concentration (300 ppm) was confirmed by HPTLC analysis. In order to probe root cause of higher PNP degradation, preliminary studies on genetic analysis of P. putida were undertaken, which revealed the prevalence of a degradative plasmid of approximately 15 kb, while cured derivatives of P. putida (PNP-) did not show ability to degrade PNP. Further conjugal transfer of PNP+ phenotype from P. putida to standard strain of E. coli Nova blue (PNP-) confirmed the degradative type of plasmid.     

The effect of isolated valgus moments on ACL strain during single-leg landing: A simulation study

Valgus moments on the knee joint during single-leg landing have been suggested as a risk factor for anterior cruciate ligament (ACL) injury. The purpose of this study was to test the influence of isolated valgus moment on ACL strain during single-leg landing. Physiologic levels of valgus moments from an in vivo study of single-leg landing were applied to a three-dimensional dynamic knee model, previously developed and tested for ACL strain measurement during simulated landing. The ACL strain, knee valgus angle, tibial rotation, and medial collateral ligament (MCL) strain were calculated and analyzed. The study shows that the peak ACL strain increased nonlinearly with increasing peak valgus moment. Subjects with naturally high valgus moments showed greater sensitivity for increased ACL strain with increased valgus moment, but ACL strain plateaus below reported ACL failure levels when the applied isolated valgus moment rises above the maximum values observed during normal cutting activities. In addition, the tibia was observed to rotate externally as the peak valgus moment increased due to bony and soft-tissue constraints. In conclusion, knee valgus moment increases peak ACL strain during single-leg landing. However, valgus moment alone may not be sufficient to induce an isolated ACL tear without concomitant damage to the MCL, because coupled tibial external rotation and increasing strain in the MCL prevent proportional increases in ACL strain at higher levels of valgus moment. Training that reduces the external valgus moment, however, can reduce the ACL strain and thus may help athletes reduce their overall ACL injury risk.     

Synthesis and evaluation of uterine relaxant activity for a novel series of substituted p-hydroxyphenylethanolamines

Novel racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]aminopropan-1-ol hydrochlorides (9a-h) were synthesized by condensing racemic 1-(p-hydroxyphenyl)-2-aminopropan-1-ol hydrochloride (6) with substituted aryloxymethyloxiranes (8a-h) in DMF in presence of anhydrous potassium carbonate and then reacting with dry hydrogen chloride gas. They were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP releasing potential was studied using rat uterus tissue homogenates by cAMP [3H] assay and cardiac stimulant potential was evaluated in dog. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP releasing potential was higher than isoxsuprine hydrochloride except for 9b and 9c. Finally insignificant cardiac stimulant potential was noted for these compounds when compared to isoxsuprine hydrochloride.     

Characterization of a clinical polymer‐drug conjugate using multiscale modeling

The molecular conformation of certain therapeutic agents has been shown to affect the ability to gain access to target cells, suggesting potential value in defining conformation of candidate molecules. This study explores how the shape and size of poly‐γ‐glutamyl‐glutamate paclitaxel (PGG‐PTX), an amphiphilic polymer‐drug with potential chemotherapeutic applications, can be systematically controlled by varying hydrophobic and hydrophilic entities. Eighteen different formulations of PGG‐PTX varying in three PTX loading fractions (f_PTX) of 0.18, 0.24, and 0.37 and six spatial arrangements of PTX (‘clusters’, ‘ends’, ‘even’, ‘middle’, ‘random’, and ‘side’) were explored. Molecular dynamics (MD) simulations of all‐atom (AA) models of PGG‐PTX were run until a statistical equilibrium was reached at 100 ns and then continued as coarse‐grained (CG) models until a statistical equilibrium was reached at an effective time of 800 ns. Circular dichroism spectroscopy was used to suggest initial modeling configurations. Results show that a PGG‐PTX molecule has a strong tendency to form coil shapes, regardless of the PTX loading fraction and spatial PTX arrangement, although globular shapes exist at f_PTX = 0.24. Also, less uniform PTX arrangements such as ‘ends’, ‘middle’, and ‘side’ produce coil geometries with more curvature. The prominence of coil shapes over globules suggests that PGG‐PTX may confer a long circulation half‐life and high propensity for accumulation to tumor endothelia. This multiscale modeling approach may be advantageous for the design of cancer therapeutic delivery systems. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 936–951, 2010.     

Biodegradation of thiocyanate using co-culture of Klebsiella pneumoniae and Ralstonia sp.

Thiocyanate-degrading microbial co-culture was isolated from thiocyanate-contaminated site and tested for thiocyanate degradation potential and thiocyanate-toxicity tolerance and identified as Klebsiella pneumoniae and Ralstonia sp. by 16S rDNA sequencing. The co-culture was able to degrade thiocyanate with degradation rate of 500 mg L⁻¹d⁻¹ at 2,500 mg L⁻¹ thiocyanate concentration at pH 6.0 and 37oC following thiocyanate hydrolase pathway. The Haldane kinetic model elucidates the growth and thiocyanate biodegradation kinetics of the co-culture with Ki value of 1,876 mg L⁻¹. The thiocyanate biodegradation kinetics was not affected by the additional supply of glucose. The very high activities of thiocyanate hydrolase, cyanide oxygenase, and cytochrome P-450 content during growth on thiocyanate were observed, showing the induction mechanism.     

Selective isolation,evaluation and characterization of antagonistic actinomycetes against <Emphasis Type="Italic">Rhizoctonia solani</Emphasis>

The baiting bag method was found to be useful for isolating antagonistic actinomycetes from terrestrial habitat. Out of total 110 actinomycetes isolated from rhizospheric and non-rhizospheric soil of Indo Gangetic Plains (IGP) of India, 9 isolates exhibited aggressive antagonism against Rhizoctonia solani, screened through dual culture, well diffusion and sealed plate technique. Maximum growth inhibition was recorded up to 50% under well diffusion (S. toxytricini vh22) and 52.6% in a direct confrontation (Actinomycetales bacterium vh41). Whereas maximum disease suppression (53.33%) under green house condition was achieved on seedling treated with S. tricolor vh85. Scanning electron microscopy of antagonists and pathogen interaction exhibited pore formation and hyphal degradation of test pathogen. Physiological and molecular characterization of selected isolates showed wide diversity and uncommon species has been encountered through the selective isolation technique.     

Review series: The cell biology of taste

Taste buds are aggregates of 50–100 polarized neuroepithelial cells that detect nutrients and other compounds. Combined analyses of gene expression and cellular function reveal an elegant cellular organization within the taste bud. This review discusses the functional classes of taste cells, their cell biology, and current thinking on how taste information is transmitted to the brain.

Taste: our most intrepid sense

Sampling the environment through our sense of taste.

Taste is the sensory modality that guides organisms to identify and consume nutrients while avoiding toxins and indigestible materials. For humans, this means recognizing and distinguishing sweet, umami, sour, salty, and bitter—the so-called “basic” tastes (Fig. 1). There are likely additional qualities such as fatty, metallic, and others that might also be considered basic tastes. Each of these is believed to represent different nutritional or physiological requirements or pose potential dietary hazards. Thus, sweet-tasting foods signal the presence of carbohydrates that serve as an energy source. Salty taste governs intake of Na⁺ and other salts, essential for maintaining the body’s water balance and blood circulation. We generally surmise that umami, the taste of l-glutamate and a few other l-amino acids, reflects a food’s protein content. These stable amino acids and nucleotide monophosphates are naturally produced by hydrolysis during aging or curing. Bitter taste is innately aversive and is thought to guard against consuming poisons, many of which taste bitter to humans. Sour taste signals the presence of dietary acids. Because sour taste is generally aversive, we avoid ingesting excess acids and overloading the mechanisms that maintain acid–base balance for the body. Moreover, spoiled foods often are acidic and are thus avoided. Nonetheless, people learn to tolerate and even seek out certain bitter- and sour-tasting compounds such as caffeine and citric acid (e.g., in sweet-tart citrus fruits), overcoming innate taste responses. Variations of taste preference may arise from genetic differences in taste receptors and may have important consequences for food selection, nutrition, and health (Drayna, 2005; Kim and Drayna, 2005; Dotson et al., 2008; Shigemura et al., 2009).Open in a separate windowFigure 1.Taste qualities, the taste receptors that detect them, and examples of natural stimuli. Five recognized taste qualities—sweet, sour, bitter, salty, and umami—are detected by taste buds. Bitter taste is thought to protect against ingesting poisons, many of which taste bitter. Sweet taste signals sugars and carbohydrates. Umami taste is elicited by l-amino acids and nucleotides. Salty taste is generated mainly by Na⁺ and sour taste potently by organic acids. Evidence is mounting that fat may also be detected by taste buds via dedicated receptors. The names of taste receptors and cartoons depicting their transmembrane topology are shown outside the perimeter. Bitter is transduced by G protein–coupled receptors similar to Class I GPCRs (with short extracellular N termini). In contrast, sweet and umami are detected by dimers of Class III GPCRs (with long N termini that form a globular extracellular ligand-binding domain). One of the receptors for Na⁺ salts is a cation channel composed of three subunits, each with two transmembrane domains. Membrane receptors for sour and fat are as yet uncertain.An important, if unrecognized aspect of taste is that it serves functions in addition to guiding dietary selection. Stimulating taste buds initiates physiological reflexes that prepare the gut for absorption (releasing digestive enzymes, initiating peristalsis, increasing mesenteric flow) and other organs for metabolic adjustments (insulin release, sympathetic activation of brown adipose tissue, increased heart rate; Giduck et al., 1987; Mattes, 1997). Collectively, these reflexes that are triggered by the sensory (sight, smell, taste) recognition of food are termed cephalic phase responses.

Many-body energies during proton transfer in an aqueous system

The energetics of the mechanism of proton transfer from a hydronium ion to one of the water molecules in its first solvation shell are studied using density functional theory and the Møller–Plesset perturbation (MP2) method. The potential energy surface of the proton transfer mechanism is obtained at the B3LYP and MP2 levels with the 6-311++G** basis set. Many-body analysis is applied to the proton transfer mechanism to obtain the change in relaxation energy, two-body, three-body and four-body energies when proton transfer occurs from the hydronium ion to one of the water molecules in its first solvation shell. It is observed that the binding energy (BE) of the complex decreases during the proton transfer process at both levels of theory. During the proton transfer process, the % contribution of the total two-body energy to the binding energy of the complex increases from 62.9 to 68.09% (39.9 to 45.95%), and that of the total three-body increases from 25.9 to 27.09% (24.16 to 26.17%) at the B3LYP/6-311++G** (MP2/ 6-311++G**) level. There is almost no change in the water–water–water three-body interaction energy during the proton transfer process at both levels of theory. The contribution of the relaxation energy and the total four-body energy to the binding energy of the complex is greater at the MP2 level than at the B3LYP level. Significant differences are found between the relaxation energies, the hydronium–water interaction energies and the four-body interaction energies at the B3LYP and MP2 levels.     

Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

Background

The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest.

Methods

We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test) based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype.

Results

Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways.

Conclusions

Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.