A renewed perspective on agroforestry concepts and classification

Agroforestry, the association of trees with farming practices, is progressively becoming a recognized land-use discipline. However, it is still perceived by some scientists, technicians and farmers as a sort of environmental fashion which does not deserve credit. The peculiar history of agroforestry and the complex relationships between agriculture and forestry explain some misunderstandings about the concepts and classification of agroforestry and reveal that, contrarily to common perception, agroforestry is closer to agriculture than to forestry. Based on field experience from several countries, a structural classification of agroforestry into six simple categories is proposed: crops under tree cover, agroforests, agroforestry in a linear arrangement, animal agroforestry, sequential agroforestry and minor agroforestry techniques. It is argued that this pragmatic classification encompasses all major agroforestry associations and allows simultaneous agroforestry to be clearly differentiated from sequential agroforestry, two categories showing contrasting ecological tree-crop interactions. It can also contribute to a betterment of the image of agroforestry and lead to a simplification of its definition.     

Vaccine and adjuvant design for emerging viruses: mutations, deletions, segments and signaling

Vaccination is currently the most effective strategy to medically control viral diseases. However, developing vaccines is a long and expensive process, and traditional methods, such as attenuating wild-type viruses by serial passage, may not be suitable for all viruses and may lead to vaccine safety considerations, particularly in the case of the vaccination of particular patient groups, such as the immunocompromised and the elderly. In particular, developing vaccines against emerging viral pathogens adds a further level of complexity, as they may only be administered to small groups of people or only in response to a specific event or threat, limiting our ability to study and evaluate responses. In this commentary, we discuss how novel techniques may be used to engineer a new generation of vaccine candidates as we move toward a more targeted vaccine design strategy, driven by our understanding of the mechanisms of viral pathogenesis, attenuation and the signaling events which are required to develop a lasting, protective immunity. We will also briefly discuss the potential future role of vaccine adjuvants, which could be used to bridge the gap between vaccine safety, and lasting immunity from a single vaccination.     

Multiple opiate receptors: emerging concepts

Increasing biochemical evidence indicates that the wide spectrum of opiate pharmacological actions are mediated via heterogeneous classes of receptors. μ receptors have been identified as the high affinity sites where morphine-like opiates exert their analgesic effects. δ receptors have a somewhat different CNS distribution and have been identified as sites relatively selective for the naturally occuring enkephalins. Recent biochemical studies provide evidence for two additional classes of opiate receptor sites which were originally proposed on the basis of physiological studies. Ketocyclazocine-like opiates produce their unique ataxic and sedative effects via interaction with K receptors, and SKF-10,047 (N-allylnorcyclazocine) and related opiates produce stimulant and psychotomimetic effects via interactions with σ receptors.Many opiate drugs interact at multiple receptor sites. Thus, the constellation of neuropharmacological actions of a particular opioid ligand may reflect its various potencies at a combination of μ, δ, K, and σ receptors.     

Lung redox homeostasis: emerging concepts

This symposium was organized to present some aspects of current research pertaining to lung redox function. Focuses of the symposium were on roles of pulmonary endothelial NADPH oxidase, xanthine oxidase (XO)/xanthine dehydrogenase (XDH), heme oxygenase (HO), transplasma membrane electron transport (TPMET), and the zinc binding protein metallothionein (MT) in the propagation and/or protection of the lung or other organs from oxidative injury. The presentations were chosen to reflect the roles of both intracellular (metallothionein, XO/XDH, and HO) and plasma membrane (NADPH oxidase, XO/XDH, and unidentified TPMET) redox proteins in these processes. Although the lung endothelium was the predominant cell type under consideration, at least some of the proposed mechanisms operate in or affect other cell types and organs as well.     

Prostate cancer,tumor immunity and a renewed sense of optimism in immunotherapy

The recent FDA approval of the first therapeutic vaccine against prostate cancer has revitalized the public interest in the fields of cancer immunology and immunotherapy. Yet, clinical results are modest. A reason for this limited success may reside in the capacity of the tumor to convert inflammation in a tumor-promoting condition and eventually escape immune surveillance. Here we present the main known interactions between the prostate tumor and the immune system, showing how the malignancy can dodge the immune system by also exerting several immunosuppressive mechanisms. We also discuss experimental and clinical strategies proposed to counteract cancer immune evasion and emphasize the importance of implementing appropriate murine models like the transgenic adenocarcinoma of the mouse prostate model for investigating the biology of prostate cancer and novel immunotherapy approaches against it.     

Cervical cancer vaccines: emerging concepts and developments

Certain human cancers are linked to infection by oncogenic viruses that are able to cause transformation of the normal host cell into a cancerous cell. Human papillomavirus (HPV) DNA and expression of viral transforming proteins are found in virtually all cervical cancer cells, indicating an important role of this virus in the pathogenesis of the disease. Evidence exists that the immune response to cancer cells can play a major role in determining the outcome of disease. The fact that HPV is a necessary cause for cervical cancer provides a clear opportunity to develop a therapeutic vaccine against the virus to treat patients with cervical cancer at its early and late stages. Development of a prophylactic vaccine for HPV would also reduce the incidence of cervical neoplasias by preventing virus infection. Various candidate HPV vaccines are being developed and tested in animal models and/or in human clinical trials. These HPV vaccines, both preventive and therapeutic, are the subjects of this review.     

DNA methylation and epigenomics: new technologies and emerging concepts

A report of the Keystone Symposia joint meetings on DNA Methylation and Epigenomics held in Keystone, Colorado, USA, 29 March to 3 April, 2015.     

Vaccine design: future possibilities and potentials

Recent developments in the understanding of the structure and replications of a wide range of pathogens, including viruses, bacteria and parasites have opened up ways of designing novel vaccines which should both improve the quality and extend the range and value of vaccines as major prophylactic and therapeutic tools of the future. Two main strategies have emerged, one involving the development of synthetic vaccines which are essentially composed of selected epitopes of the pathogenic agent that will elicit neutralising antibodies. The other strategy attempts to make use of chimeric agents that will allow live virus or bacteria to be used as vectors for carrying appropriate epitopes of the target pathogen. Current knowledge about the immunology and improvements in the presentation of antigen to the immune system will also play an important role in the rational design of vaccines. This review summarises present methods of producing vaccines and considers the development of more rational methods of vaccine design that will greatly influence the production of vaccines in the future.     

Plant fructans in stress environments: emerging concepts and future prospects

Plants are sessile and sensitive organisms known to possess various regulatory mechanisms for defending themselves under stress environments. Fructans are fructose-based polymers synthesized from sucrose by fructosyltransferases (FTs). They have been increasingly recognized as protective agents against abiotic stresses. Using model membranes, numerous in vitro studies have demonstrated that fructans can stabilize membranes by direct H-bonding to the phosphate and choline groups of membrane lipids, resulting in a reduced water outflow from the dry membranes. Inulin-type fructans are flexible random-coiled structures that can adopt many conformations, allowing them to insert deeply within the membranes. The devitrification temperature (T(g)) can be adjusted by their varying molecular weights. In addition, above T(g) their low crystallization rates ensure prolonged membrane protection. Supporting, in vivo studies with transgenic plants expressing FTs showed fructan accumulation and an associated improvement in freezing and/or chilling tolerance. The water-soluble nature of fructans may allow their rapid adaptation as cryoprotectants in order to give optimal membrane protection. One of the emerging concepts for delivering vacuolar fructans to the extracellular space for protecting the plasma membrane is vesicle-mediated, tonoplast-derived exocytosis. It should, however, be noted that natural stress tolerance is a very complex process that cannot be explained by the action of a single molecule or mechanism.     

Gene targeting from laboratory to livestock: Current status and emerging concepts

The development of methods for cell-mediated transgenesis, based on somatic cell nuclear transfer, provides a tremendous opportunity to shape the genetic make-up of livestock animals in a much more directed approach than traditional animal breeding and selection schemes. Progress in the site-directed modulation of livestock genomes is currently limited by the low efficiencies of gene targeting imposed by the low frequency of homologous recombination and limited proliferative capacity of primary somatic cells that are used to produce transgenic animals. Here we review the current state of the art in the field, discuss the crucial aspects of the methodology and provide an overview of emerging approaches to increase the efficiency of gene targeting in somatic cells.     

Versatile roles of plant NADPH oxidases and emerging concepts

NADPH oxidase (NOX) is a key player in the network of reactive oxygen species (ROS) producing enzymes. It catalyzes the production of superoxide (O₂⁻), that in turn regulates a wide range of biological functions in a broad range of organisms. Plant Noxes are known as respiratory burst oxidase homologs (Rbohs) and are homologs of catalytic subunit of mammalian phagocyte gp91^phox. They are unique among other ROS producing mechanisms in plants as they integrate different signal transduction pathways in plants. In recent years, there has been addition of knowledge on various aspects related to its structure, regulatory components and associated mechanisms, and its plethora of biological functions. This update highlights some of the recent developments in the field with particular reference to important members of the plant kingdom.     

A new release on life: emerging concepts in proteolysis and parasite invasion

Cell invasion by apicomplexan pathogens such as the malaria parasite and Toxoplasma is accompanied by extensive proteolysis of zoite surface proteins (ZSPs) required for attachment and penetration. Although there is still little known about the proteases involved, a conceptual framework is emerging for the roles of proteolysis in cell invasion. Primary processing of ZSPs, which includes the trimming of terminal peptides or segmentation into multiple fragments, is proposed to activate these adhesive ligands for tight binding to host receptors. Secondary processing, which occurs during penetration, results in the shedding of ZSPs by one of two mechanistically distinct ways, shaving or capping. Resident surface proteins are typically shaved from the surface whereas adhesive ligands mobilized from intracellular secretory vesicles are capped to the posterior end of the parasite before being shed during the final steps of penetration. Intriguingly, recent studies have revealed that ZSPs can be released either by being cleaved adjacent to the membrane anchor or actually within the membrane itself. Mounting evidence suggests that intramembrane cleavage is catalysed by one or more integral membrane serine proteases of the Rhomboid family and we propose that several malaria adhesive ligands may be potential substrates for these enzymes. We also discuss the evidence that the key reason for ZSP shedding during invasion is to break the connection between parasite surface ligands and host receptors. The sequential proteolytic events associated with invasion by pathogenic protozoa may represent vulnerable pathways for the future development of synergistic anti-protozoal therapies.     

Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro

Oocyte in vitro maturation (IVM) is an important reproductive technology that generates mature oocytes that are capable of supporting preimplantation embryo development and full development to term. There is great clinical and commercial incentive to improve the efficiency of the technology, however, progress has been slow over the past decade. A critical challenge is to understand what constitutes oocyte developmental competence and the mechanisms governing it. We have taken the approach of studying in detail oocyte-somatic cell interactions; including, oocyte-cumulus cell (CC) gap-junctional communication, and bidirectional paracrine signalling between the two cell types. It is becoming clear that, compared to oocytes matured in vivo, IVM oocytes undergo maturation prematurely as they are still in the process of acquiring developmental competence in vivo, and the molecular cascade reinitiating meiosis differs entirely to that in vivo. Attempts to enhance oocyte developmental competence by attenuating the spontaneous meiotic resumption of oocytes in vitro have been met with mixed success. Kinase inhibitors that prevent maturation-promoting factor activity have, in general, been ineffectual on promoting oocyte developmental potential post-IVM. In contrast, agents that modulate oocyte cAMP during IVM show greater potential, possibly as these compounds extend oocyte-CC gap-junctional communication. An important concept that is now emerging is that the oocyte secretes potent growth factors that regulate fundamental aspects of CC function and thereby determine the distinctive phenotype of the cumulus-oocyte complex. The capacity of an oocyte to regulate its own microenvironment by oocyte-secreted factors (OSFs) may constitute an important component of oocyte developmental competence. In support of this notion, we have recently demonstrated that supplementing IVM media with exogenous OSFs improves oocyte developmental potential, as evidenced by enhanced pre- and post-implantation embryo development.     

Anti-angiogenic therapy of exudative age-related macular degeneration: current progress and emerging concepts

Age-related macular degeneration (AMD) is the leading cause of blindness in elderly patients. The more aggressive exudative form is characterized by abnormal blood-vessel development that occurs beneath the retina as a result of choroidal neovascularization (CNV). Vascular endothelial growth factor (VEGF) has emerged as the key mediator of CNV formation; this has led to intensive research on VEGF and the recent approval of anti-VEGF compounds by the US Food and Drug Administration. Despite this successful introduction of anti-angiogenic therapies into the clinical setting, there is still a lack of treatments that definitively reverse damaged vision. Here, we consider the importance of putative molecular targets other than VEGF that might have been underestimated. Emerging cellular mechanisms offer additional opportunities for innovative therapeutic approaches.     

Regulatory GTP-binding proteins: emerging concepts on their role in cell function

The last few years have evidenced a tremendous expansion in our appreciation of the role of regulatory GTP-binding proteins in cellular activation. The availability of cholera and pertussis toxins to detect G proteins as well as methodological advances in the study of cellular function has afforded the opportunity to examine G protein participation in many cellular events. Regulation of adenylyl cyclase and cyclic GMP phosphodiesterase by G proteins has been demonstrated. Phosphatidylinositol-4,5-biphosphate specific phospholipase C activity appears to be subject to G protein control. G proteins regulate inward K+ and Ca2+ channels through a mechanism which may be independent of effects on the above mentioned enzymes. Certainly, the number of G proteins which have been identified from sequencing of complementary DNA affords the potential for G protein involvement in many cellular events. Only three G proteins have however been isolated and functionally characterized, Gs, Gi and transducin. Whether all the functions of these proteins have been identified remains to be seen.