Gene Transfer: How Can the Biological Barriers Be Overcome?

Physical methods represent a promising approach for the safe delivery of therapeutic plasmid DNA in genetic and acquired human diseases. However, their development in clinics is limited by their low efficacy. At the cellular level, efficient gene transfer is dependent on several factors including extracellular matrix, plasmid DNA uptake and nucleocytoplasmic transport. We review the main barriers that plasmid DNA encounters from the extracellular environment toward the interior of the cell and the different strategies developed to overcome these biological barriers. Diffusional and metabolic fences of the extracellular matrix and the cytoplasm affect plasmid DNA uptake. These barriers reduce the number of intact plasmids that reach the nucleus. Nuclear uptake of plasmid DNA further requires either an increase of nuclear permeability or an active nuclear transport via the nuclear pore. A better understanding of the cellular and molecular bases of the physical gene-transfer process may provide strategies to overcome those obstacles that highly limit the efficiency and use of gene-delivery methods.     

Activation of Plant Nod-like Receptors: How Indirect Can It Be?

Pioneering plant research has shown that many Nod-like receptors (NLRs) detect pathogens indirectly via recognizing modifications of other host proteins. In this issue, two groups show that the RPM1 NLR is activated by phosphorylation of the host protein RIN4, probably resulting from activation of a host kinase by pathogen effectors.     

Religion and Bioethics: Can We Talk?

Religious voices were important in the early days of the contemporary field of bioethics but have now become decidedly less prominent. This is unfortunate because religious elements are essential parts of the most foundational aspects of bioethics. The problem is that there is an incommensurability between religious language and languages of public discourse such as the “public reason” of John Rawls. To eliminate what is unique in religious language is to lose something essential. This paper examines the reasons for the marginalization of religion in bioethics, shows the limitations of Rawls’s notion of public reason, and argues for a more robust role for theology in articulating a new language for public discourse in bioethics.     

Human African Trypanosomiasis in South Sudan: How Can We Prevent a New Epidemic?

Human African trypanosomiasis (HAT) has been a major public health problem in South Sudan for the last century. Recurrent outbreaks with a repetitive pattern of responding-scaling down activities have been observed. Control measures for outbreak response were reduced when the prevalence decreased and/or socio-political crisis erupted, leading to a new increase in the number of cases. This paper aims to raise international awareness of the threat of another outbreak of sleeping sickness in South Sudan. It is a review of the available data, interventions over time, and current reports on the status of HAT in South Sudan. Since 2006, control interventions and treatments providing services for sleeping sickness have been reduced. Access to HAT diagnosis and treatment has been considerably diminished. The current status of control activities for HAT in South Sudan could lead to a new outbreak of the disease unless 1) the remaining competent personnel are used to train younger staff to resume surveillance and treatment in the centers where HAT activities have stopped, and 2) control of HAT continues to be given priority even when the number of cases has been substantially reduced. Failure to implement an effective and sustainable system for HAT control and surveillance will increase the risk of a new epidemic. That would cause considerable suffering for the affected population and would be an impediment to the socioeconomic development of South Sudan.     

How Fast Can Carbon Be Sequestered When Restoring Degraded Subtropical Thicket?

Is the maximum rate of carbon sequestration reported for the CAM‐C₃ plant Portulacaria afra (spekboom), viz. 15.4 t CO₂ ha^?1 yr^?1, unusual in comparison with other plants with similar physioliogies, or could such rates be expected routinely in restoration with P. afra? Private sector investors in thicket restoration need an answer to this question in order to assess the feasibility of using carbon finance as the main income stream from their investments. A literature review showed that 15.4 t CO₂ ha^?1 yr^?1 is not an unusual rate of carbon sequestration for CAM plants in arid and semi‐arid environments, which suggests that investors in thicket restoration should not consider this an outlier value. The results also suggest that carbon finance could be used to fund restoration using other CAM plants in degraded xeric thickets in countries such as Argentina, Chile, Mexico, and Madagascar.     

How Can We Improve the Detection of Alpha1-Antitrypsin Deficiency?

The Z deficiency in α1-antitrypsin (A1ATD) is an under-recognized condition. Alpha1-antitrypsin (A1AT) is the main protein in the α1-globulin fraction of serum protein electrophoresis (SPE); however, evaluation of the α1-globulin protein fraction has received very little attention. Serum Z-type A1AT manifests in polymeric forms, but their interference with quantitative immunoassays has not been reported. Here, 214 894 samples were evaluated by SPE at the G. Fracastoro Hospital of Verona, Italy. Patients with an A1AT level ≤ 0.92 g/L were recalled to complete A1ATD diagnosis. In parallel, to qualitatively and quantitatively characterize A1AT, sera samples from 10 PiZZ and 10 PiMM subjects obtained at the National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland, were subjected to non-denaturing 7.5% PAGE and 7.5% SDS-PAGE followed by Western blot. Moreover, purified A1AT was heated at 60°C and analyzed by a non-denaturing PAGE and 4–15% gradient SDS-PAGE followed by Western blot as well as by isolelectrofocusing and nephelometry. A total of 966 samples manifested percentages ≤ 2.8 or a double band in the alpha1-zone. According to the nephelometry data, 23 samples were classified as severe (A1AT ≤ 0.49 g/L) and 462 as intermediate (A1AT >0.49≤ 1.0 g/L) A1ATD. Twenty subjects agreed to complete the diagnosis and an additional 21 subjects agreed to family screening. We detected 9 cases with severe and 26 with intermediate A1ATD. Parallel experiments revealed that polymerization of M-type A1AT, when measured by nephelometry or isolelectrofocusing, yields inaccurate results, leading to the erroneous impression that it was Z type and not M-type A1AT. We illustrate the need for confirmation of Z A1AT values by “state of the art” method. Clinicians should consider a more in-depth investigation of A1ATD in patients when they exhibit serum polymers and low α1-globulin protein levels by SPE.     

Limbs vs. Jaws: Can They Be Compared?

Current experimental research on mammalian limb muscle structureand function is compared to that on mammalian jaw muscles. Twomajor areas of comparison are stressed: structural and functional.Comparisons of limbs and jaws are made from the point of viewof the impact of recent studies on simple mechanical modelsof limb/jaw muscle function. Limb muscle structure is comparedto jaw muscles at the level of muscle architecture, muscle histochemicaland motor unit properties, and the organization of motor unitsinto neuromuscular compartments. Such comparisons reveal thatalthough limb muscles and jaw muscles might be organized insimilar ways, fundamental differences exist, both in terms ofmuscle structure and the functional conclusions which have beenbased on studies of muscle structure. The comparisons also demonstratethat much recent evidence from structural studies have had littledirect impact on simple models of muscle function but a muchlarger influence on the assumptions of the models. Comparisonsof limb/jaw muscle function from kinematic and EMG studies,indicate that many masticatory strategies are used by differentmammals but the basic problems of posture and locomotion havebeen met with essentially similar solutions, even among diversemammalian groups. The results of such comparisons demonstratethat both limb and jaw muscle function are sufficiently complexthat new or re-vitalized models are needed if the relationshipbetween structure and function are ever to be understood.     

Interobserver And Intraobserver Agreement In Parathyroid Scintigraphy: How Can Parathyroid Scintigraphy Be Made More Reliable?

ObjectiveTo determine the intraobserver and interobserver agreement levels in the evaluation of technetium Tc 99m sestamibi parathyroid scintigraphic images.MethodsNinety-eight patients with hyperparathyroidism were included in the study, and their parathyroid images were evaluated by 4 experienced nuclear medicine observers. The 98 cases were evaluated twice by each observer within an interval of 2 weeks. The evaluations were performed directly on workstations with use of digital images. A questionnaire was completed by each observer. The presence of a lesion, the number and the localizations of the lesions, and whether the lesion was clear or doubtful were all evaluated. Cohen kappa statistics and total agreement percentages were calculated by using SPSS version 11.0 software.ResultsThe 4 observers performed 8 different evaluations and identified a minimum of 38 and a maximum of 43 cases with a parathyroid lesion (or lesions). Both the intraobserver and the interobserver agreements were “very good” for the presence of a parathyroid lesion. The intraobserver agreement was also “very good” and the interobserver agreement was “good” (for only 1 pair of observers) or “very good” for the evaluation of the number of parathyroid lesions. The intraobserver agreement was “very good” or “good” and the interobserver agreement was “good” for the lesion localization and for the presence of a doubtful lesion.ConclusionParathyroid scintigraphy seems to be an observer independent method in the detection of a parathyroid lesion, in the determination of the number of lesions, and in the localizations of the lesions. The measured high agreement between observers increases the reliability of parathyroid scintigraphy. (Endocr Pract. 2012;18: 538-548)     

Crop Residue Removal for Bioenergy Reduces Soil Carbon Pools: How Can We Offset Carbon Losses?

Crop residue removal for bioenergy can deplete soil organic carbon (SOC) pools. Management strategies to counteract the adverse effects of residue removal on SOC pools have not been, however, widely discussed. This paper reviews potential practices that can be used to offset the SOC lost with residue removal. Literature indicates that practices including no-till cover crops, manure and compost application, and return of biofuel co-products increase SOC pools and may thus be used to offset some SOC loss. No-till rotations that include semi-perennial grasses or legumes also offer a promise to promote soil-profile C sequestration and improve soil resilience after residue removal. No-till cover crops can sequester between 0.10 and 1 Mg ha^?1 per year of SOC relative to no-till without cover crops, depending on cover crop species, soil type, and precipitation input. Animal manure and compost contain about 15 % of C and thus their addition to soil can enhance SOC pools and boost soil biological activity. Similarly, application of biofuel co-products such as biochar, which contain between 45 % and 85 % of C depending on the feedstock source and processing method, can enhance long-term C sequestration. These mitigation strategies may maintain SOC pools under partial residue removal in no-till soils but are unlikely to replace all the SOC lost if residue is removed at excessive rates. More field research and modeling efforts are needed to assess the magnitude at which the different mitigation strategies can overcome SOC loss with crop residue removal.     

From Habits to Self-Regulation: How Do We Change?

The Yale Cognitive Science department hosted the conference “From Habits to Self-Regulation: How Do We Change?” on November 4 and 5, 2011, to showcase current research on self-control in cognitive science, psychology, and neuroscience. The conference included a panel discussion by four philosophers who gave context for the scope and limitations of research on self-control. The common theme concerning the best method to attain lasting change included becoming aware of what one wants to change, increasing commitment to the goal of change, and imagining all of the potential problems and solutions to those problems.     

How Can We Identify and Communicate the Ecological Value of Deep-Sea Ecosystem Services?

Submarine canyons are considered biodiversity hotspots which have been identified for their important roles in connecting the deep sea with shallower waters. To date, a huge gap exists between the high importance that scientists associate with deep-sea ecosystem services and the communication of this knowledge to decision makers and to the wider public, who remain largely ignorant of the importance of these services. The connectivity and complexity of marine ecosystems makes knowledge transfer very challenging, and new communication tools are necessary to increase understanding of ecological values beyond the science community. We show how the Ecosystem Principles Approach, a method that explains the importance of ocean processes via easily understandable ecological principles, might overcome this challenge for deep-sea ecosystem services. Scientists were asked to help develop a list of clear and concise ecosystem principles for the functioning of submarine canyons through a Delphi process to facilitate future transfers of ecological knowledge. These ecosystem principles describe ecosystem processes, link such processes to ecosystem services, and provide spatial and temporal information on the connectivity between deep and shallow waters. They also elucidate unique characteristics of submarine canyons. Our Ecosystem Principles Approach was successful in integrating ecological information into the ecosystem services assessment process. It therefore has a high potential to be the next step towards a wider implementation of ecological values in marine planning. We believe that successful communication of ecological knowledge is the key to a wider public support for ocean conservation, and that this endeavour has to be driven by scientists in their own interest as major deep-sea stakeholders.