3-N-oxalyl-L-2,3-diaminopropanoic acid, a multifunctional plant metabolite of toxic reputation

3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP) is a neuroexcitatory non- protein amino acid identified in grass pea (Lathyrus sativus L.) and in ginseng (Panax spp). Its presence in the drought tolerant grass pea is thought to be responsible for the crippling disease neurolathyrism, while in the longevity promoting ginseng it is named dencichine and praised for its haemostatic properties. Some properties of beta-ODAP are put in perspective

Grain legumes and human health

Since early civilisation in different continents, grain legumes have been a part of balanced diets together with cereals. In general the seeds from those two plant families give together a good source of essential amino acids and may have given an evolutionary advantage. A sustainable diet for vegetarians may not be possible without the protein-rich legumes. Consumed alone, legumes can be a mixed blessing because of their deficiency of some essential amino acids. This deficiency can be balanced in a varied diet containing components richer in tryptophan and the sulphur amino acid methionine and cysteine. Many legume species are exceptionally rich in secondary metabolites, some of which are beneficial to human health while without adequate processing through heating or leaching many can be detrimental to the health of the consumer. Soybean (Glycine max) is one of the most popular and also one of the more healthy species. The presence of genistein and other isoflavones makes it famous as an anti-cancer nutraceutical. Isoflavones and other phytoestrogens, occurring mainly in legumes, might be a factor promoting longevity. Other beneficial secondary metabolites are found among the non-protein amino acids. Legumes are very rich in an enormous variety of non-protein amino acids that can be beneficial or toxic. A beneficial non-protein amino acid occurs in high concentration in fenugreek seeds (Trigonella foenum-graecum), a component of curry, while a variety of toxic amino acids occurs in the genera Lathyrus and Vicia. Legume seeds also contain a variety of anti-nutritional factors that can be reduced by post-harvest processing such as fermentation or germination. Fermentation also improves the balance of essential amino acids. Numerous dietary products such as soy sauce or tempeh are traditional food ingredients derived from legumes

Is stress a factor in the susceptibility to neurolathyrism?

A

Phase II trial of aflibercept with FOLFIRI as a second‐line treatment for Japanese patients with metastatic colorectal cancer

Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second‐line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression‐free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5‐fluorouracil. A total of 60 patients were evaluated for ORR; 50 had received prior bevacizumab. The ORR was 8.3% (95% confidence interval [CI]: 1.3%‐15.3%), and the disease control rate (DCR) was 80.0% (69.9%‐90.1%). The median progression‐free survival was 5.42 months (4.14‐6.70 months) and the median overall survival was 15.59 months (11.20‐19.81 months). No treatment‐related deaths were observed, and no significant drug‐drug interactions were found. The most common treatment‐emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/mL (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5‐fluorouracil: The clearance was 11.1 L/h/m2 (28%) for irinotecan and, at steady state, 72.6 L/h/m2 (56%) for 5‐fluorouracil (N = 10). Adding aflibercept to FOLFIRI was shown to be beneficial and well‐tolerated in Japanese patients with mCRC. ClinicalTrials.gov Identifier: NCT01882868

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques