From forest to pharmacy: Should we be depressed about a sustainable Griffonia simplicifolia (Fabaceae) seed supply chain?

ETHNOPHARMACOLOGICAL RELEVANCE: Griffonia simplicifolia D.C (Baill.) (Fabaceae) seeds are unusually high (6-20% wet weight) in 5-HTP (5-Hydroxytryptophan), a serotonin precursor widely used to treat depression. Consequently, this species is regarded as a herbal "Prozac®". Contemporary use as an anti-depressant contrasts with traditional uses for insecticides, arachnicides, fodder, dyes, mordants and chewing-sticks. G. simplicifolia seeds are wild-harvested for the export trade. Over the past 15 years, use of 5-HTP extracted from G. simplicifolia in cosmetics has added to global demand. Wild populations in West Africa are the sole commercial source of G. simplicifolia seed. AIMS OF THE STUDY: Were to (i) assess the scale of the global trade in G. simplicifolia seeds and (ii) produce a synthesis of the challenges facing sustainable harvest of G. simplicifolia. MATERIALS AND APPROACH: Firstly, we analysed global trade data for G. simplicifolia, taking into account historical trends over the past 40 years. Secondly, we reviewed published studies on the distribution, population biology and harvest impacts of wild G. simplicifolia populations. RESULTS AND CONCLUSION: s: Wild G. simplicifolia populations have been the focus of commercial harvest of their pods (for seeds) for international trade from West Africa for almost 50 years. In the late 1980's, when Ghana exported 75-80 metric tonnes (MT) of G. simplicifolia seed to Europe, this species was already Ghana's main medicinal plant export. Currently, 5 West African countries export G. simplicifolia seeds (Cote d'Ivoire, Ghana, Liberia, Nigeria and Togo). Although in the 1980's, most seed exports were to Europe, today China is the main importer of G. simplicifolia seed. These seeds are value-added for production of 5-HTP extracts, and then re-exported, particularly to North America (c.48% of exports). The low habitat specificity and vigorous re-sprouting of G. simplicifolia after cutting, plus its occurrence in forest reserves and national parks confer some resilience on wild populations. Sustaining future supply chains faces six future challenges, however: (1) Rapid loss of forest habitats; (2) Declining populations of understorey birds and disruption of G. simplicifolia pollination in this bird pollinated species; (3) Negative effects of introduced invasive plant species (Broussonetia papyrifera, Chromolaena odorata) on G. simplicifolia regeneration; (4) Grazing by livestock and use of G. simplicifolia leaves as forage; (5) The long-term impact of industrial scale seed "predation": Over a 9-year period (2005-2013), G. simplicifolia exports from Ghana totalled at least 5550 metric tonnes (or between 9.1 billion to 13.5 billion seeds). This could affect the long-term population dynamics of this species, which produces a low number of seeds per pod (1-4 seeds) and has short distance (ballistic) seed dispersal; and (6) Destructive harvest methods, when plants are cut to harvest get the seed pods. Improved resource management, monitoring, quality control and careful pricing are important if supply chains from wild stocks are to be maintained. If wild populations decline, then 5-HTP biosynthesis may compete with low G. simplicifolia seed yields, leading to loss of income to West African harvesters and traders.

Holocene re-colonisation, central-marginal distribution and habitat specialisation shape population genetic patterns within an Atlantic European grass species.

Corynephorus canescens (L.) P.Beauv. is an outbreeding, short-lived and wind-dispersed grass species, highly specialised on scattered and disturbance-dependent habitats of open sandy sites. Its distribution ranges from the Iberian Peninsula over Atlantic regions of Western and Central Europe, but excludes the two other classical European glacial refuge regions on the Apennine and Balkan Peninsulas. To investigate genetic patterns of this uncommon combination of ecological and biogeographic species characteristics, we analysed AFLP variation among 49 populations throughout the European distribution range, expecting (i) patterns of SW European glacial refugia and post-glacial expansion to the NE; (ii) decreasing genetic diversity from central to marginal populations; and (iii) interacting effects of high gene flow and disturbance-driven genetic drift. Decreasing genetic diversity from SW to NE and distinct gene pool clustering imply refugia on the Iberian Peninsula and in western France, from where range expansion originated towards the NE. High genetic diversity within and moderate genetic differentiation among populations, and a significant pattern of isolation-by-distance indicate a gene flow drift equilibrium within C. canescens, probably due to its restriction to scattered and dynamic habitats and limited dispersal distances. These features, as well as the re-colonisation history, were found to affect genetic diversity gradients from central to marginal populations. Our study emphasises the need for including the specific ecology into analyses of species (re-)colonisation histories and range centre-margin analyses. To account for discontinuous distributions, new indices of marginality were tested for their suitability in studies of centre-periphery gradients.

Adult Hallervorden-Spatz syndrome simulating amyotrophic lateral sclerosis.

Hallervorden-Spatz syndrome (HSS) is a neurodegenerative disorder characterized by progressive dementia, dystonia, ataxia, and rigidity. An atypical form of adult-onset HSS was observed in a 36-year-old man presenting with progressive dysarthria. Markedly dysarthric speech and a weak atrophic tongue associated with a neurogenic pattern of motor unit recruitment in bulbar-supplied muscles on electromyography led to an initial impression of bulbar amyotrophic lateral sclerosis (ALS). Lack of expected progression of symptoms, however, prompted reinvestigation. Repeat brain magnetic resonance imaging demonstrated an "eye-of-the-tiger" pattern in the basal ganglia, characteristic of HSS, thus requiring genetic studies. DNA analyses of the pantothenate kinase gene (PANK2) was conducted and revealed two novel, disease-causing exon 3 missense mutations (Cys231Ser and Tyr251Cys). This case broadens the genotypic and phenotypic spectrum of HSS to include a late-onset syndrome resembling bulbar-onset ALS.

mtDNA analysis of Leber hereditary optic neuropathy associated with spondyloepiphyseal dysplasia.

A patient was diagnosed in 1974 with the unique combination of Leber hereditary optic neuropathy (LHON) and spondyloepiphyseal dysplasia. The entire mitochondrial DNA (mtDNA) sequence from this patient was determined in order to identify candidate pathogenic mutations. The patient's mtDNA carried the LHON mutation at nucleotide 14484, thus elucidating the etiology of his optic neuropathy. We also identified another ND6 mutation at nucleotide 14420. This latter mutation is probably a clinically benign private polymorphism, although a pathogenic role in his skeletal abnormalities or in his optic neuropathy cannot yet be ruled out.

Generation of dual-wavelength pulses by frequency doubling with quasi-phase-matching gratings.

We demonstrate generation of two synchronized picosecond pulses at different wavelengths near 778 nm by frequency doubling of a femtosecond pulse. We use nonlinear frequency filtering with quasi-phase-matching gratings, which allow us to obtain second-harmonic spectral intensities that are higher than the spectral intensities of the pump.

Generation of high-energy femtosecond pulses in multimode-core Yb-fiber chirped-pulse amplification systems.

220-fs pulses with energies of ~100microJ have been generated by use of two different configurations of diode-pumped Yb-fiber chirped-pulse amplification systems. Energy scaling was demonstrated with 25-microm -core diameter fibers, in which stable diffraction-limited output (M(2)~1.1) was achieved. A two-stage fiber-amplifier system produced average powers of up to 5.5 W at ~1- MHz pulse-repetition rate. A double-pass configuration provided 53-dB gain in a single Yb-fiber amplifier stage, thus eliminating the necessity for multiple amplification stages as well as the need for using polarization-preserving fibers.

The emergence of modern neuroscience: some implications for neurology and psychiatry.

One of the most significant developments in biology in the past half century was the emergence, in the late 1950s and early 1960s, of neuroscience as a distinct discipline. We review here factors that led to the convergence into a common discipline of the traditional fields of neurophysiology, neuroanatomy, neurochemistry, and behavior, and we emphasize the seminal roles played by David McKenzie Rioch, Francis O Schmitt, and especially Stephen W Kuffler in creating neuroscience as we now know it. The application of the techniques of molecular and cellular biology to the study of the nervous system has greatly accelerated our understanding of the mechanisms involved in neuronal signaling, neural development, and the function of the major sensory and motor systems of the brain. The elucidation of the underlying causes of most neurological and psychiatric disorders has proved to be more difficult; but striking progress is now being made in determining the genetic basis of such disorders as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and a number of ion channel and mitochondrial disorders, and a significant start has been made in identifying genetic factors in the etiology of such disorders as manic depressive illness and schizophrenia. These developments presage the emergence in the coming decades of a new nosology, certainly in neurology and perhaps also in psychiatry, based not on symptomatology but on the dysfunction of specific genes, molecules, neuronal organelles and particular neural systems.

Sodium vanadate inhibits apoptosis in malignant glioma cells: a role for Akt/PKB.

The dual signal hypothesis of apoptosis holds that a common signal can activate both apoptotic and proliferative pathways. The fate of a cell is dependent on which of these two pathways predominates. In the MAPK family of kinases, ERK and JNK have been proposed to mediate apoptosis whereas the PI3K-stimulated kinase, Akt/PKB, has been shown to inhibit apoptosis. The object of this study was to determine the role of these kinases in a glioma model of apoptosis. We have previously shown that K252a induces apoptosis and inhibits kinase activity. In this study we confirm these results and show that the protein tyrosine phosphatase inhibitor sodium vanadate activates ERK, JNK and Akt/PKB, but does not stimulate proliferation. Vanadate did protect T98G cells from K252a-induced apoptosis, an effect that was abolished by addition of the PI3K inhibitor wortmannin. This suggests that PI3K and Akt/PKB may be responsible for mediating vanadate's protective effect on glioma cells. We conclude that the intracellular balance between protein phosphorylation pathways is a critical determinant of both cell proliferation and cell death.

Nonlinearly limited saturable-absorber mode locking of an erbium fiber laser.

We describe an erbium fiber laser that is passively mode locked by a novel, precision antireflection-coated semiconductor saturable-absorber mirror that incorporates an additional two-photon absorber. It is shown that passive mode locking evolves from a Q-switching instability. The results are achieved by use of saturable absorbers that provide a large (15%) nonlinear (saturable) loss. Exploiting two-photon absorption can substantially reduce the peak power of the Q-switched pulses, which results in improved reliability of the laser. Moreover, two-photon absorption can be used to produce an optimal stability range for saturable-absorber mode locking.

Ultrawide tunable Er soliton fiber laser amplified in Yb-doped fiber.

A Raman-shifted and frequency-doubled high-power Er-fiber soliton laser for seeding an efficient high-power Yb fiber femtosecond amplifier is demonstrated. The Raman-shifted and frequency-doubled Er-soliton laser is tunable from 1.00 to 1.070microm and produces bandwidth-limited 24-pJ pulses at a repetition rate of 50 MHz with a FWHM pulse width of 170 fs at 1.040microm . The Yb(3+) amplifier has a slope efficiency of 52% and generates 3-ps linearly chirped pulses with an average power of 0.8 W at 1.05microm . After pulse compression, 74-fs bandwidth-limited pulses with an average power of 0.4 W and a pulse energy of 8 nJ are generated.

High-energy femtosecond pulse amlification in a quasi-phase-matched parametric amplifier.

A new type of solid-state femtosecond amplifier is demonstrated that is based on quasi-phase-matched parametric amplification. Such gain media are different from conventional solid-state amplifiers in that their amplification bandwidths and pump and signal wavelengths can be engineered. Furthermore, high gain is characteristic of parametric amplification, permitting extraction of high energies without the need to resort to multiple-pass configurations. We report a parametric chirped pulse amplification system in which femtosecond pulses from a mode-locked Er-doped fiber laser system are amplified to 1-mJ energies in a single pass by use of a 5-mm-long periodically poled LiNbO(3) (PPLN) crystal. This amplifier is pumped by 5-mJ and 0.5-ns pulses at 786 nm, demonstrating that limitations associated with a low optical-damage threshold for long pump pulses can be overcome because of the high nonlinearity of PPLN and that relatively simple Q -switched lasers can be used with such parametric amplifiers.

Engineerable femtosecond pulse shaping by second-harmonic generation with Fourier synthetic quasi-phase-matching gratings.

We describe a pulse-shaping technique that uses second-harmonic generation with Fourier synthetic quasi-phase-matching gratings. We demonstrate both amplitude and phase tailoring by generating a picosecond squarelike pulse as well as trains of femtosecond pulses with a terahertz-range repetition rate from either a compressed or a chirped pump pulse.

Chirped-pulse-amplification circuits for fiber amplifiers, based on chirped-period quasi-phase-matching gratings.

A new type of compact chirped-pulse-amplification circuit for high-power amplification of femtosecond pulses in an optical fiber is demonstrated. This circuit is based on a novel pulse compressor, chirped-period quasi-phase-matching gratings in electric-field-poled lithium niobate. The main advantages of this circuit are simplicity, the small number of components, compactness, and wavelength conversion of Er-doped fiber output to the technologically important 780-nm wavelength region.

High-power 100-fs pulse generation by frequency doubling of an erbium ytterbium-fiber master oscillator power amplifier.

Frequency doubling of an erbium-ytterbium-fiber master-oscillator-power-amplifier system is demonstrated. Simultaneous amplification and pulse compression in multimode erbium-ytterbium-doped fibers produces high-quality near-diffraction and near-bandwidth-limited 100-fs pulses at a wavelength of 1.62microm with an average power of 230 mW at a repetition rate of 52 MHz. Periodically poled LiNbO(3) allows for frequency doubling with a conversion efficiency of 51%, producing near-bandwidth-limited 105-fs pulses with an average power of 117 mW and a pulse energy of 2.3 nJ at a wavelength of 810 nm.

Frequency doubling of femtosecond erbium-fiber soliton lasers in periodically poled lithium niobate.

We report efficient frequency doubling of passively mode-locked femtosecond erbium-fiber lasers. Quasi-phase-matched second-harmonic generation in periodically poled lithium niobate is used to generate 8.1 mW of 190-fs (FWHM), 90-pJ pulses at 777 nm with a conversion efficiency greater than can be obtained with existing birefringently phase-matched nonlinear materials. A dispersion-compensation-free soliton oscillator generating transform-limited 230-fs (FWHM) pulses at 1554 nm is used as a pump laser.

Fiber-laser-based femtosecond parametric generator in bulk periodically poled LiNbO(3).

A diode-pumped system for optical parametric generation of wavelength-tunable femtosecond pulses is demonstrated. It comprises an Er-doped fiber mode-locked laser, a fiber chirped-pulse amplifier, and a bulk periodically poled LiNbO(3) (PPLN) optical parametric generator. The parametric generator is pumped at 777 nm with frequency-doubled microjoule pulses from the fiber amplifier and produces 300-fs pulses tunable from 1 to 3microm with output energies up to ~200 nJ. Use of a PPLN nonlinear crystal substantially reduces the pump energies required for efficient parametric generation. Saturated single-pass parametric energy conversion of 38% (internal) has been achieved with only 220 nJ of pump inside the crystal. A parametric generation threshold of 54 nJ is observed, and efficient parametric conversion is obtained with repetition rates up to 200 kHz.

Engineerable compression of ultrashort pulses by use of second-harmonic generation in chirped-period-poled lithium niobate.

We demonstrate the use of an aperiodic quasi-phase-matching (QPM) grating to generate second-harmonic pulses that are stretched or compressed relative to input pulses at the fundamental frequency. We frequency doubled an externally chirped erbium-doped fiber laser generating 17-ps (FWHM) pulses at 1560nm to produce near-transform-limited 110-fs (FWHM) pulses at 780nm by use of a 5-cm-long lithium niobate crystal poled with a QPM grating chirped from an 18.2- to a 19.8-microm period.

Current concepts of apoptosis.

Apoptosis is a carefully regulated process involved in developmental and immunological events. The alteration of apoptotic pathways is important in the establishment and progression of neoplasia. Apoptosis allows for the orderly removal of excess cells but, in contrast to necrosis, it is not an inflammatory process. Many of the molecular components and effectors of apoptosis have been described. In this review the authors briefly discuss the current understanding of apoptosis in the context of the two prevailing hypotheses, the "conflicting signal" and "dual signal" theories.

Alexandrite-pumped alexandrite regenerative amplifier for femtosecond pulse amplification.

We demonstrate a regenerative amplif ier incorporating alexandrite as the gain medium that is pumped by an alexandrite laser. Temperature-altered gain permitted the 728-nm alexandrite pump laser, operating at room temperature, to pump a 780-800-nm alexandrite laser that was maintained at elevated temperatures. 200-fs pulses from a Ti:sapphire oscillator were amplif ied to the millijoule level. This system also amplif ied femtosecond pulses from a frequency-doubled Er-doped fiber laser.

Cladding-pumped passively mode-locked fiber laser generating femtosecond and picosecond pulses.

Passively mode-locked fiber lasers cladding pumped by broad-area diode-laser arrays are described. With a dispersion-compenstated erbium-ytterbium fiber oscillator, 200-fs pulses with pulse energies up to 100 pJ are generated at a wavelength of 1560 nm. In a highly dispersive cavity, pulse widths of 3 ps with pulse energies up to 1 nJ are obtained. A saturable absorber is used for pulse startup, whereas nonlinear polarization evolution is exploited for steady-state pulse shaping. An environmentally stable design is ensured by use of a compensation scheme for linear polarization drifts in the cavity.