Can you shrinkwrap a cow? Protections available for the intellectual property of the animal breeding industry

There are currently four main intellectual property protection statutory schemes available: copyright, trade secret, trademark and patent. Each of these protects a different aspect of intellectual property, which leaves gaps of protection when an innovation does not fit squarely within the boundaries of the statutes. Contracts allow the industry to tailor the protection desired. One very common approach is to license the product via contract. Licences allow intellectual property owners to retain ownership and give permission to others to use the product. Although there are several types of licences, the most common is the field of use licence, which limits the licensee's use of the product. This often leads to price discrimination where various levels of restriction are offered at corresponding prices. The more rights retained by the owner, the more restricted the buyer is and the lower the purchase price allowing customers to choose the level of restriction they are willing to accept. Therefore, the different uses and needs of various customers can be accounted for and reflected in the price. The animal breeding industry is currently struggling to protect their innovations falling into these statutory gaps. The protection for animal breeding industry innovations is most likely through contract law rather than traditional intellectual property law. By taking advantage of the unique nature of contracts, industry will be able to tailor protection and pricing to best suit the variety of customers and uses for the products sold.     

Engineering synthetic signaling proteins with ultrasensitive input/output control

Many signaling proteins are built from simple, modular components, yet display highly complex signal-processing behavior. Here we explore how modular domains can be used to build an ultrasensitive switch--a nonlinear input/output function that is central to many complex biological behaviors. By systematically altering the number and affinity of modular autoinhibitory interactions, we show that we can predictably convert a simple linear signaling protein into an ultrasensitive switch.     

Alignment and topological accuracy of the direct optimization approach via POY and traditional phylogenetics via ClustalW + PAUP*

Direct optimization frameworks for simultaneously estimating alignments and phylogenies have recently been developed. One such method, implemented in the program POY, is becoming more common for analyses of variable length sequences (e.g., analyses using ribosomal genes) and for combined evidence analyses (morphology + multiple genes). Simulation of sequences containing insertion and deletion events was performed in order to directly compare a widely used method of multiple sequence alignment (ClustalW) and subsequent parsimony analysis in PAUP* with direct optimization via POY. Data sets were simulated for pectinate, balanced, and random tree shapes under different conditions (clocklike, non-clocklike, and ultrametric). Alignment accuracy scores for the implied alignments from POY and the multiple sequence alignments from ClustalW were calculated and compared. In almost all cases (99.95%), ClustalW produced more accurate alignments than POY-implied alignments, judged by the proportion of correctly identified homologous sites. Topological accuracy (distance to the true tree) for POY topologies and topologies generated under parsimony in PAUP* from the ClustalW alignments were also compared. In 44.94% of the cases, Clustal alignment tree reconstructions via PAUP* were more accurate than POY, whereas in 16.71% of the cases POY reconstructions were more topologically accurate (38.38% of the time they were equally accurate). Comparisons between POY hypothesized alignments and the true alignments indicated that, on average, as alignment error increased, topological accuracy decreased.     

15-Hydroxyprostaglandin Dehydrogenase Generation of Electrophilic Lipid Signaling Mediators from Hydroxy Ω-3 Fatty Acids

15-Hydroxyprostaglandin dehydrogenase (15PGDH) is the primary enzyme catalyzing the conversion of hydroxylated arachidonic acid species to their corresponding oxidized metabolites. The oxidation of hydroxylated fatty acids, such as the conversion of prostaglandin (PG) E₂ to 15-ketoPGE₂, by 15PGDH is viewed to inactivate signaling responses. In contrast, the typically electrophilic products can also induce anti-inflammatory and anti-proliferative responses. This study determined that hydroxylated docosahexaenoic acid metabolites (HDoHEs) are substrates for 15PGDH. Examination of 15PGDH substrate specificity was conducted in cell culture (A549 and primary human airway epithelia and alveolar macrophages) using chemical inhibition and shRNA knockdown of 15PGDH. Substrate specificity is broad and relies on the carbon position of the acyl chain hydroxyl group. 14-HDoHE was determined to be the optimal DHA substrate for 15PGDH, resulting in the formation of its electrophilic metabolite, 14-oxoDHA. Consistent with this, 14-HDoHE was detected in bronchoalveolar lavage cells of mild to moderate asthmatics, and the exogenous addition of 14-oxoDHA to primary alveolar macrophages inhibited LPS-induced proinflammatory cytokine mRNA expression. These data reveal that 15PGDH-derived DHA metabolites are biologically active and can contribute to the salutary signaling actions of Ω-3 fatty acids.     

A comparison of two commercially available ELISA methods for the quantification of human plasma heat shock protein 70 during rest and exercise stress

This study compared resting and exercise heat/hypoxic stress-induced levels of plasma extracellular heat shock protein 70 (eHSP70) in humans using two commercially available enzyme-linked immunosorbent assay (ELIS)A kits. EDTA plasma samples were collected from 21 males during two separate investigations. Participants in part A completed a 60-min treadmill run in the heat (HOT70; 33.0 ± 0.1 °C, 28.7 ± 0.8 %, n = 6) at 70 % V̇O_2max. Participants in part B completed 60 min of cycling exercise at 50 % V̇O_2max in either hot (HOT50; 40.5 °C, 25.4 relative humidity (RH)%, n = 7) or hypoxic (HYP50; fraction of inspired oxygen (F_IO₂) = 0.14, 21 °C, 35 % RH, n = 8) conditions. Samples were collected prior to and immediately upon termination of exercise and analysed for eHSP70 using EKS-715 high-sensitivity HSP70 ELISA and new ENZ-KIT-101 Amp’d™ HSP70 high-sensitivity ELISA. ENZ-KIT was superior in detecting resting eHSP70 (1.54 ± 3.27 ng·mL⁻¹; range 0.08 to 14.01 ng·mL⁻¹), with concentrations obtained from 100 % of samples compared to 19 % with EKS-715 assay. The ENZ-KIT requires optimisation prior to running samples in order to ensure participants fall within the standard curve, a step not required with EKS-715. Using ENZ-KIT, a 1:4 dilution allowed for quantification of resting HSP70 in 26/32 samples, with a 1:8 (n = 3) and 1:16 (n = 3) dilution required to determine the remaining samples. After exercise, eHSP70 was detected in 6/21 and 21/21 samples using EKS-715 and ENZ-KIT, respectively. eHSP70 was increased from rest after HOT70 (p < 0.05), but not HOT50 (p > 0.05) or HYP50 (p > 0.05) when analysed using ENZ-KIT. It is recommended that future studies requiring the precise determination of resting plasma eHSP70 use the ENZ-KIT (i.e. HSP70 Amp’d® ELISA) instead of the EKS-715 assay, despite additional assay development time and cost required.     

Increased concentrations of IL-18 and uric acid in sickle cell anemia: contribution of hemolysis, endothelial activation and the inflammasome

Sickle cell anemia (SCA) is a common, severe monogenetic disorder characterized by chronic hemolysis, frequent infections, a chronic inflammatory state and recurrent occlusions of the microcirculation, resulting in painful crises, organ damage and premature death. This study evaluated associations between serum levels of IL-18, uric acid, hemolytic markers, and inflammatory molecules in SCA patients. A cross-sectional study was performed including 45 SCA patients (median age of 20.5 years) without general symptoms and who had not undergone blood transfusions. Inclusion criteria for the steady-state SCA patients were the absence of hospitalization and the absence of infections. Interleukin-18 and uric acid levels were correlated closely with markers of hemolysis, endothelial dysfunction and others cytokines levels. These findings suggest probable influences of IL-18 and uric acid in the pathophysiology of vascular occlusion in SCA. Additional studies should be performed to characterize similar prognosis markers and possible therapeutic targets.     

Eavesdropping on plant volatiles by a specialist moth: significance of ratio and concentration

We investigated the role that the ratio and concentration of ubiquitous plant volatiles play in providing host specificity for the diet specialist grape berry moth Paralobesia viteana (Clemens) in the process of locating its primary host plant Vitis sp. In the first flight tunnel experiment, using a previously identified attractive blend with seven common but essential components ("optimized blend"), we found that doubling the amount of six compounds singly [(E)- & (Z)-linalool oxides, nonanal, decanal, β-caryophyllene, or germacrene-D], while keeping the concentration of other compounds constant, significantly reduced female attraction (average 76% full and 59% partial upwind flight reduction) to the synthetic blends. However, doubling (E)-4,8-dimethyl 1,3,7-nonatriene had no effect on female response. In the second experiment, we manipulated the volatile profile more naturally by exposing clonal grapevines to Japanese beetle feeding. In the flight tunnel, foliar damage significantly reduced female landing on grape shoots by 72% and full upwind flight by 24%. The reduction was associated with two changes: (1) more than a two-fold increase in total amount of the seven essential volatile compounds, and (2) changes in their relative ratios. Compared to the optimized blend, synthetic blends mimicking the volatile ratio emitted by damaged grapevines resulted in an average of 87% and 32% reduction in full and partial upwind orientation, respectively, and the level of reduction was similar at both high and low doses. Taken together, these results demonstrate that the specificity of a ubiquitous volatile blend is determined, in part, by the ratio of key volatile compounds for this diet specialist. However, P. viteana was also able to accommodate significant variation in the ratio of some compounds as well as the concentration of the overall mixture. Such plasticity may be critical for phytophagous insects to successfully eavesdrop on variable host plant volatile signals.     

Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy.

The recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from six separate isolations provided by three different islet isolation centers were compared with isolated mouse and non-human primate islets. As expected from histological sections of murine pancreas, in isolated murine islets alpha and delta cells resided at the periphery of the beta-cell core. However, human islets were markedly different in that alpha, beta, and delta cells were dispersed throughout the islet. This pattern of cell distribution was present in all human islet preparations and islets of various sizes and was also seen in histological sections of human pancreas. The architecture of isolated non-human primate islets was very similar to that of human islets. Using an image analysis program, we calculated the volume of alpha, beta, and delta cells. In contrast to murine islets, we found that populations of islet cell types varied considerably in human islets. The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets.