Incretin hormone mimetics and analogues in diabetes therapeutics

The incretin hormones glucagon-like peptide-I (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are physiological gut peptides with insulin-releasing and extrapancreatic glucoregulatory actions. Incretin analogues/mimetics activate GLP-I or GIP receptors whilst avoiding physiological inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the newest classes of antidiabetic drug. The first clinically approved GLP-1 mimetic for the treatment of type-2 diabetes is exenatide (Byetta/exendin) which is administered subcutaneously twice daily. Clinical trials of liraglutide, a GLP-1 analogue suitable for once-daily administration, are ongoing. A number of other incretin molecules are at earlier stages of development. This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. Additionally, it explores the therapeutic possibilities offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon hybrid peptides, and specific GIP receptor antagonists.

Getting to the root of neuronal signalling in plant-parasitic nematodes using RNA interference

A variety of genes expressed in preparasitic second-stage juveniles (J2) of plant-parasitic nematodes appear to be vulnerable to RNA interference (RNAi) in vitro by coupling double-stranded (ds)RNA soaking with the artificial stimulation of pharyngeal pumping. Also, there is mounting evidence that the in planta generation of nematode-specific double-stranded RNAs (dsRNAs) has real utility in the control of these pests. Although neuronally-expressed genes in Caenorhabditis elegans are commonly refractory to RNAi, we have discovered that neuronally-expressed genes in plant-parasitic nematodes are highly susceptible to RNAi and that silencing can be induced by simple soaking procedures without the need for pharyngeal stimulation. Since most front-line anthelmintics that are used for the control of nematode parasites of animals and humans act to disrupt neuromuscular coordination, we argue that intercellular signalling processes associated with neurons have much appeal as targets for transgenic plant-based control strategies for plant-parasitic nematodes. FMRFamide-like peptides (FLPs) are a large family of neuropeptides which are intimately associated with neuromuscular regulation, and our studies on flp gene function in plant-parasitic nematodes have revealed that their expression is central to coordinated locomotory activities. We propose that the high level of conservation in nervous systems across nematodes coupled with the RNAi-susceptibility of neuronally-expressed genes in plant-parasitic nematodes provides a valuable research tool which could be used to interrogate neuronal signalling processes in nematodes.

A set of primers for plastid indels and nuclear microsatellites in the invasive plant Heracleum mantegazzianum (Apiaceae) and their transferability to Heracleum sphondylium

This study reports the isolation and polymorphism characterization of four plastid indels and six nuclear microsatellite loci in the invasive plant Heracleum mantegazzianum. These markers were tested in 27 individuals from two distant H. mantegazzianum populations. Plastid indels revealed the presence of five chlorotypes while five nuclear microsatellite loci rendered polymorphism. Applications of these markers include population genetics and phylogeography of H. mantegazzianum. A very good transferability of markers to Heracleum sphondylium was demonstrated.

Development of microsatellites for the invasive riparian plant Impatiens glandulifera (Himalayan balsam) using intersimple sequence repeat cloning

Impatiens glandulifera (Himalayan balsam) is an invasive riparian plant species that can outcompete native perennials. Population genetic data on dispersal may aid in the management of invasive species, so we have developed microsatellite markers for this significant invader using an intersimple sequence repeat (ISSR)-based cloning method. Eight polymorphic markers displayed between two and five alleles, with overall levels of observed and expected heterozygosities ranging from 0.0500 to 0.7500 and from 0.1449 to 0.7692, respectively.

Variability in thermal and UV-B energy fluxes through time and their influence on plant diversity and speciation

Throughout Earth's history there have been temporal and spatial variations in the amount of visible and ultraviolet radiation received by ecosystems. This paper examines if temporal changes in these forms of energy receipt could have influenced the tempo and mode of plant diversity and speciation, focusing in particular upon Cenozoic time-scales. Evidence for changing patterns of plant diversity and speciation apparent in various fossil records and molecular phylogenies are considered alongside calculated changes in thermal and solar ultraviolet energy (specifically UV-B) over the past 50 Myr. We suggest that changes in thermal energy influx (amount and variability) affected the tempo of evolution through its influence upon community dynamics (e.g. population size, diversity, turnover, extinctions). It was not only the amount of thermal energy but also variability in its flux that may have influenced these processes, and ultimately the rate of diversification. We suggest that variations in UV-B would have influenced the mode and tempo of speciation through changes to genome stability during intervals of elevated UV-B. We argue, therefore, that although variability in thermal energy and UV-B fluxes through time may lead to the same end-point (changing the rate of diversification), the processes responsible are very different and both need to be considered when linking evolutionary processes to energy flux.

Cut down by some cowardly miscreants’: Plant maiming, or the Malicious Cutting of Plants as an Act of Protest in Eighteenth and Nineteenth Century Rural England

Since the publication of Hobsbawm and Rudé's Captain Swing our understanding of the role(s) of covert protests in Hanoverian rural England has advanced considerably. Whilst we now know much about the dramatic practices of incendiarism and animal maiming and the voices of resistance in seemingly straightforward acquisitive acts, one major gap remains. Despite the fact that almost thirty years have passed since E. P. Thompson brought to our attention that under the notorious ‘Black Act’ the malicious cutting of trees was a capital offence, no subsequent research has been published. This paper seeks to address this major lacuna by systematically analysing the practices and patterns of malicious attacks on plants (‘plant maiming’) in the context of late eighteenth- and early nineteenth-century southern England. It is shown that not only did plant maiming take many different forms, attacking every conceivable type of flora, but also that it was universally understood and practised. In some communities plant maiming was the protestors' weapon of choice. As a social practice it therefore embodied wider community beliefs regarding the defence of plebeian livelihoods and identities.

Genome sequence of the metazoan plant-parasitic nematode Meloidogyne incognita

Plant-parasitic nematodes are major agricultural pests worldwide and novel approaches to control them are sorely needed. We report the draft genome sequence of the root-knot nematode Meloidogyne incognita, a biotrophic parasite of many crops, including tomato, cotton and coffee. Most of the assembled sequence of this asexually reproducing nematode, totaling 86 Mb, exists in pairs of homologous but divergent segments. This suggests that ancient allelic regions in M. incognita are evolving toward effective haploidy, permitting new mechanisms of adaptation. The number and diversity of plant cell wall-degrading enzymes in M. incognita is unprecedented in any animal for which a genome sequence is available, and may derive from multiple horizontal gene transfers from bacterial sources. Our results provide insights into the adaptations required by metazoans to successfully parasitize immunocompetent plants, and open the way for discovering new antiparasitic strategies.