A new source of endothelial progenitor cells--vascular biology redefined?

The initial discovery of endothelial progenitor cells (EPCs) in tandem with emerging concepts in stem cell biology has generated enormous interest and excitement in fields as diverse as tissue engineering, regenerative medicine, and tumor and vascular biology. A recent paper by Ingram et al. identifies a complete hierarchy of EPCs in the vessel wall, providing a new framework for classification of cells supporting endopoiesis akin to that previously established for hematopoiesis. This could have fundamental implications for our understanding of the role of the endothelium and, more specifically, the role of EPC interfacing with the vessel wall in health and disease.     

Nitrogen fixation in the High Arctic: a source of ‘new’ nitrogen?

Biological nitrogen (N₂) fixation performed by diazotrophs (N₂ fixing bacteria) is thought to be one of the main sources of plant available N in pristine ecosystems like arctic tundra. However, direct evidence of a transfer of fixed N₂ to non-diazotroph associated plants is lacking to date. Here, we present results from an in situ ¹⁵N–N₂ labelling study in the High Arctic. Three dominant vegetation types (organic crust composed of free-living cyanobacteria, mosses, cotton grass) were subjected to acetylene reduction assays (ARA) performed regularly throughout the growing season, as well as ¹⁵N–N₂ incubations. The ¹⁵N-label was followed into the dominant N₂ fixer associations, soil, soil microbial biomass and non-diazotroph associated plants three days and three weeks after labelling. Mosses contributed most to habitat N₂ fixation throughout the measuring campaigns, and N₂ fixation activity was highest at the beginning of the growing season in all plots. Fixed ¹⁵N–N₂ became quickly (within 3 days) available to non-diazotroph associated plants in all investigated vegetation types, proving that N₂ fixation is an actual source of available N in pristine ecosystems.     

Towards a new politics of migration?

This paper reconsiders Stephen Castle’s classic paper Why Migration Policies Fail. Beginning with the so-called migration crisis of 2015 it considers the role of numbers is assessing success or failure. It argues that in the UK public debates about immigration changed with European Union (EU) Enlargement in 2004, when the emphasis shifted from concerns about asylum to concerns about EU mobility. Concerns were exacerbated by the government’s failure to meet its promise to reduce net migration. This policy is hampered by the general problem of definition of “migrant” and the gap between statistical measures and popular usage in which “migration” signifies problematic mobility. In fact, concern about migration has become a placeholder for concerns about globalization and democratic accountability. A new politics of migration must make connections between migrants and citizens, but also between migration and other global processes, particularly outsourcing and the exploitation of labour and resources in the global south.     

Ectomycorrhizal fungi: A new source of atmospheric methyl halides?

Incomplete source budgets for methyl halides – compounds that release inorganic chlorine and bromine radicals which, in turn, catalyze atmospheric ozone depletion – limit our ability to predict the fate of the stratospheric ozone layer. We report here the first measured emissions of methyl chloride, methyl bromide, and methyl iodide from ectomycorrhizal fungi. We grew nine fungal isolates on growth media containing halide concentrations similar to those found in soils and plant tissues. The observed range of emissions was 0.003–65 μg methyl chloride, 0.001–3 μg methyl bromide, and 0.02–12 μg methyl iodide g^?1 dry weight fungi day^?1. Species varied in production rates of methyl chloride vs. methyl bromide vs. methyl iodide. Cenococcum geophilum, a widespread ectomycorrhizal fungus, was further tested to investigate the effects of halide substrate concentration in growth media. Emissions from this species increased linearly with increasing concentrations of both bromide and iodide. In addition, a subset of four fungi was studied with two media concentrations each of chloride, bromide, and iodide (0.2 or 20 mm ). These fungi had similar responses to halide concentration, despite 1000‐fold differences in baseline emission rates between isolates. Finally, high chloride concentrations (20 mm ) in media did not appear to inhibit emissions of methyl bromide or methyl iodide. Overall, ectomycorrhizal fungi might be an important source of methyl halides to the atmosphere, and substrate concentrations and community composition may influence production levels in ecosystems.     

Are mitochondria a permanent source of reactive oxygen species?

The observation that in isolated mitochondria electrons may leak out of the respiratory chain to form superoxide radicals (O(2)(radical-)) has prompted the assumption that O(2)(radical-) formation is a compulsory by-product of respiration. Since mitochondrial O(2)(radical-) formation under homeostatic conditions could not be demonstrated in situ so far, conclusions drawn from isolated mitochondria must be considered with precaution. The present study reveals a link between electron deviation from the respiratory chain to oxygen and the coupling state in the presence of antimycin A. Another important factor is the analytical system applied for the detection of activated oxygen species. Due to the presence of superoxide dismutase in mitochondria, O(2)(radical-) release cannot be realistically determined in intact mitochondria. We therefore followed the release of the stable dismutation product H(2)O(2) by comparing most frequently used H(2)O(2) detection methods. The possible interaction of the detection systems with the respiratory chain was avoided by a recently developed method, which was compared with conventional methods. Irrespective of the methods applied, the substrates used for respiration and the state of respiration established, intact mitochondria could not be made to release H(2)O(2) from dismutating O(2)(radical-). Although regular mitochondrial respiration is unlikely to supply single electrons for O(2)(radical-) formation our study does not exclude the possibility of the respiratory chain becoming a radical source under certain conditions.     

Chemokines: a new class of neuromodulator?

Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood-brain barrier, open a new era of research in neuroscience.     

Various in vitro systems of Ragged Robin (Lychnis flos-cuculi L.): a new potential source of phytoecdysteroids?

Plant Cell, Tissue and Organ Culture (PCTOC) - Lychnis flos-cuculi L. is a species containing ecdysteroids, triterpenoid saponins, flavonoids, and phenolic acids, and therefore is a plant of...     

Deep-sea hydrothermal vents: A new source of innovative bacterial exopolysaccharides of biotechnological interest?

Polysaccharides and, in particular, microbial polysaccharides represent a class of important products of growing interest for many sectors of industry. Although many known marine bacteria produce exopolysaccharides (EPS), continuation in looking for new polysaccharide-producing microorganisms is promising. Hydrothermal deep-sea vents could be a source of novel EPS as indicated by the screening of a number of mesophilic heterotrophic bacteria recovered from different locations. Although originating from such extreme environment, some bacteria were shown to biosynthesize innovative EPS under laboratory conditions. Their specific rheological properties either in the presence or absence of monovalent and divalent ions, biological activities, metal binding capabilities, and novel chemical composition mean that these EPS are expected to find many applications in the near future. Journal of Industrial Microbiology & Biotechnology (2002) 29, 204–208 doi:10.1038/sj.jim.7000298 Received 18 March 2002/ Accepted in revised form 13 June 2002     

Can pancreatic duct-derived progenitors be a source of islet regeneration?

The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in type 1 diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated.In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet β-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the “gold standard” of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for pancreatic β-cells has implications for a potentially important, expandable source of new islets for diabetic replenishment therapy.     

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Background

Change of Kenyan treatment policy for uncomplicated malaria from sulphadoxine-pyrimethamine to artemether-lumefantrine (AL) was accompanied by revised recommendations promoting presumptive malaria diagnosis in young children and, wherever possible, parasitological diagnosis and adherence to test results in older children and adults. Three years after the policy implementation, health workers' adherence to malaria diagnosis and treatment recommendations was evaluated.

Methods

A national cross-sectional, cluster sample survey was undertaken at public health facilities. Data were collected using quality-of-care assessment methods. Analysis was restricted to facilities with AL in stock. Main outcomes were diagnosis and treatment practices for febrile outpatients stratified by age, availability of diagnostics, use of malaria diagnostic tests, and test result.

Results

The analysis included 1,096 febrile patients (567 aged <5 years and 529 aged ≥5 years) at 88 facilities with malaria diagnostics, and 880 febrile patients (407 aged <5 years and 473 aged ≥5 years) at 71 facilities without malaria diagnostic capacity. At all facilities, 19.8% of young children and 28.7% of patients aged ≥5 years were tested, while at facilities with diagnostics, 33.5% and 53.7% were respectively tested in each age group. Overall, AL was prescribed for 63.6% of children aged <5 years and for 65.0% of patients aged ≥5 years, while amodiaquine or sulphadoxine-pyrimethamine monotherapies were prescribed for only 2.0% of children and 3.9% of older children and adults. In children aged <5 years, AL was prescribed for 74.7% of test positive, 40.4% of test negative and 60.7% of patients without test performed. In patients aged ≥5 years, AL was prescribed for 86.7% of test positive, 32.8% of test negative and 58.0% of patients without test performed. At least one anti-malarial treatment was prescribed for 56.6% of children and 50.4% of patients aged ≥5 years with a negative test result.

Conclusions

Overall, malaria testing rates were low and, despite different age-specific recommendations, only moderate differences in testing rates between the two age groups were observed at facilities with available diagnostics. In both age groups, AL use prevailed, and prior ineffective anti-malarial treatments were nearly non-existent. The large majority of test positive patients were treated with recommended AL; however, anti-malarial treatments for test negative patients were widespread, with AL being the dominant choice. Recent change of diagnostic policy to universal testing in Kenya is an opportunity to improve upon the quality of malaria case management. This will be, however, dependent upon the delivery of a comprehensive case management package including large scale deployment of diagnostics, good quality of training, post-training follow-up, structured supervisory visits, and more intense monitoring.     

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds.     

Are viruses a source of new protein folds for organisms? – Virosphere structure space and evolution

A crucially important part of the biosphere - the virosphere - is too often overlooked. Inclusion of the virosphere into the global picture of protein structure space reveals that 63 protein domain superfamilies in viruses do not have any structural and evolutionary relatives in modern cellular organisms. More than half of these have functions which are not virus-specific and thus might be a source of new folds and functions for cellular life. The number of viruses on the planet exceeds that of cells by an order of magnitude and viruses evolve up to six orders of magnitude faster. As a result, cellular species are subject to a constitutive 'flow-through' of new viral genetic material. Due to this and the relaxed evolutionary constraints in viruses, the transfer of domains between host-to-virus could be a mechanism for accelerated protein evolution. The virosphere could be an engine for the genesis of protein structures, and may even have been so before the last universal common ancestor of cellular life.     

Cryopreserved human fetal pancreas: a source of insulin-producing tissue?

Human fetal pancreata (HFP) were obtained from dilatation and extraction aborted fetuses of 11-18 weeks' gestation. The pancreas was excised under sterile conditions and kept in culture medium at 4 degrees C, prior to stepwise digestion into 50- to 150-micron fragments. The fragmented pieces were allowed to sediment by gravity, then transferred to tissue culture for 24-48 h, and cryopreserved. The freeze-thaw protocol used stepwise equilibration with dimethyl sulfoxide, nucleation of the sample at -10 degrees C, and a slow cooling rate of 0.25 degrees C/min to -40 degrees C, followed by submersion in liquid nitrogen (-196 degrees C). Rapid thawing at 300 degrees C/min from -196 degrees C was employed. Both fresh and frozen-thawed HFP fragments appeared viable as judged by light and electron microscopy, and secreted insulin in a perifusion system upon stimulation with glucose (28 mM) and theophylline (10 mM) or glucose (2.8 mM) and theophylline (10 mM). Six patients with Type I insulin-dependent diabetes mellitus, already requiring immunosuppression for a kidney transplant, had intraportal injection of 20 cryopreserved-thawed and pooled HFP fragments. Up to the 1-year post-transplant follow-up, there has been no evidence of in vivo insulin or C-peptide production. The usefulness of cryopreserved human fetal pancreata as a source of insulin-producing tissue for diabetic patients, therefore, remains to be demonstrated.     

Are chlorella viruses a rich source of ion channel genes?

Plaque-forming dsDNA (>330 kb) viruses that infect certain unicellular, eukaryotic chlorella-like green algae contain approximately 375 protein-encoding genes. These proteins include a 94 amino acid K+ channel protein, called Kcv, as well as two putative ligand-gated ion channels. The viruses also encode other proteins that could be involved in the assembly and/or function of ion channels, including protein kinases and a phosphatase, polyamine biosynthetic enzymes and histamine decarboxylase.     

Biomass as source of chemicals VII — Synthesis of new oxiranes

Application of a solid-liquid phase transfer technique in low hydrated organic medium makes the synthesis of the corresponding oxiranes possible for the first time. These new molecules, obtained from biomass, can be applied in many different ways in macromolecular chemistry.     

Health psychology: a new form of psychotherapy?

Psychotherapy in its traditional form is being challenged due to managed care pressures. Psychotherapy using the model of health psychology can adapt well in a managed care environment. Differences between traditional psychotherapy and the psychotherapeutic approach of health psychology are discussed in this article, with a focus on an overview of health psychology and its applications to primary care, and the concept of single-session therapy. A case example of a sample treatment emphasizing the model of brief health psychology treatment is illustrated.     

Invasive species as a new food source: does a nudibranch predator prefer eating an invasive bryozoan?

Membranipora membranacea is an invasive bryozoan that was first found in the Gulf of Maine in 1987 and within two years became the dominant organism living on kelps. Membranipora may have become dominant so quickly because it had little competition in a relatively unoccupied niche; however, lack of predation has also probably played a major role. Where Membranipora is native, there is usually a specialist nudibranch predator that keeps the population in check. For example, in European populations, the nudibranch Polycera quadrilineata prefers Membranipora while Onchidoris muricata is known to prefer another bryozoan, Electra pilosa. Electra, Membranipora, and Onchidoris are all now found in the Gulf of Maine while Polycera is not. We tested whether Onchidoris would (1) eat Membranipora at all, (2) eat Membranipora and Electra at different rates, and (3) show a preference for eating Membranipora or Electra when given a choice. We found that Onchidoris does eat Membranipora, and it generally eats Membranipora faster than Electra. However, when given a choice, Onchidoris prefers Electra. Onchidoris typically reproduces in the spring and grows over the fall and winter, but has recently been found reproducing in the winter in New Hampshire. Although it does not survive the winter as well as Electra, Membranipora is the dominant organism living on many macroalgae in the late summer and fall. Thus, the large Membranipora food source now available in the summer and fall may allow Onchidoris to reproduce earlier.