First record of functional underground traps in a pitcher plant: Nepenthespudica (Nepenthaceae), a new species from North Kalimantan, Borneo.

Nepenthespudica, a new species from North Kalimantan, Indonesia, is described and illustrated. The species belongs to the N.hirsuta group (sensu Cheek and Jebb 1999) but exhibits some characters that are unique within the group or even within the genus. Above all, it produces underground, achlorophyllous shoots with well-developed, ventricose lower pitchers that form in soil cavities or directly in the soil. No lower pitchers are formed above ground. The main part of its prey are ants, besides other litter- and soil-inhabiting species of invertebrates. A number of infaunal species were found in both aerial and underground pitchers, mainly Diptera and nematodes. Nepenthespudica is known only from a few neighbouring localities in the Mentarang Hulu district of North Kalimantan, where it grows on ridgetops at an elevation of 1100-1300 m. Its discovery underlines the natural richness of Borneo's rainforest and the necessity to preserve this important ecosystem with its enormous and still undiscovered biodiversity.

Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis.

Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments.

Fatigue Performance of Double-Layered Asphalt Concrete Beams Reinforced with New Type of Geocomposites.

The reinforcement of asphalt layers with geosynthetics has been used for several decades, but proper evaluation of the influence of these materials on pavement fatigue life is still a challenging task. The presented study investigates a novel approach to the reinforcement of asphalt layers using a new type of geogrid composite, in which square or hexagonal polypropylene stiff monolithic paving grid with integral junctions is bonded to polypropylene non-woven paving fabric. The laboratory fatigue tests were performed on large asphalt concrete beams reinforced with the new type of geocomposite. Unreinforced samples were used as reference. Test results were analysed in several aspects, including the standardised approach based on stiffness reduction, but also using energy dissipation. The effect of reinforcement on pavement fatigue life was also estimated. Based on the obtained final results of fatigue life calculations, it can be concluded that the evaluated geogrid composites have an evident positive effect on pavement performance and have a significant potential to extend the overall pavement life, especially in the case of hexagonal grid.

A phylogenomic analysis of Nepenthes (Nepenthaceae).

Nepenthaceae is one of the largest carnivorous plant families and features ecological and morphological adaptations indicating an impressive adaptive radiation. However, investigation of evolutionary and taxonomic questions is hindered by poor phylogenetic understanding, with previous molecular studies based on limited loci and taxa. We use high-throughput sequencing with a target-capture methodology based on a 353-loci, probe set to recover sequences for 197 samples, representing 151 described or putative Nepenthes species. Phylogenetic analyses were performed using supermatrix and maximum quartet species tree approaches. Our analyses confirm five Western outlier taxa, followed by N. danseri, as successively sister to the remainder of the group. We also find mostly consistent recovery of two major Southeast Asian clades. The first contains common or widespread lowland species plus a Wallacean-New Guinean clade. Within the second clade, sects. Insignes and Tentaculatae are well supported, while geographically defined clades representing Sumatra, Indochina, Peninsular Malaysia, Palawan, Mindanao and Borneo are also consistently recovered. However, we find considerable conflicting signal at the site and locus level, and often unstable backbone relationships. A handful of Bornean taxa are inconsistently placed and require further investigation. We make further suggestions for a modified infra-generic classification of genus Nepenthes.

Role of the mTOR­FOXO1 pathway in obesity­associated renal tubulointerstitial inflammation.

Since obesity is largely responsible for the growing incidence of renal tubulointerstitial inflammation, exploration into the mechanisms of obesity­associated tubulointerstitial inflammation is essential. Studies have demonstrated that mammalian target of rapamycin (mTOR) is a crucial molecule in the pathogenesis of renal inflammation, including regulating the expression of inflammatory factors. The purpose of the present study was to further elucidate the role of mTOR in obesity­associated tubulointerstitial inflammation. In the clinical study, obese and healthy subjects were recruited for physical examination, as well as the collection of blood and urine samples. Further study was performed on a high fat diet (HFD)­induced obese rat model and a cultured human renal tubular epithelial cell line (HK­2). The clinical study demonstrated that the participants with obesity had increased serum lipids, creatinine (Cr), urinary albumin to creatinine ratio (UACR) and urinary neutrophil gelatinase­associated lipocalin (u­NGAL). Moreover, the level of urinary monocyte chemoattractant protein­1 (u­MCP­1) was increased in the participants with obesity, and it was positively correlated with free fatty acid (FFA), UACR and u­NGAL. In the in vivo study, the results indicated that the levels of serum lipids, Cr and blood urea nitrogen (BUN), as well as 24 h urine protein and u­NGAL, were significantly increased in the HFD­fed obese rats. In addition, the infiltration of CD68+ cells into the renal interstitial area and the release of interleukin­1ß (IL­1ß) was observed in the kidneys of obese rats. Meanwhile, the supernatant from HK­2 cells treated with palmitic acid stimulated THP­1 monocyte migration. The upregulation of MCP­1, phosphorylated forkhead boxO1 (p­FOXO1), and phosphorylated mTOR (p­mTOR) was observed in vivo and in vitro. However, inhibition of mTOR was able to alleviate the above effects. Overall, these results demonstrated that activated mTOR induced FOXO1 phosphorylation, which mediates renal MCP­1 release, causes tubulointerstitial inflammation and ultimately leads to pathological renal changes and dysfunction. However, inhibition of mTOR may play a renoprotective role during the progression of obesity­associated tubulointerstitial inflammation.

The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons.

During the course of normal aging, certain populations of nerve growth factor (NGF)-responsive neurons become selectively vulnerable to cell death. Studies using dissociated neurons isolated from neonates have shown that c-Jun N-terminal kinases (JNKs) are important in regulating the survival and neurite outgrowth of NGF-responsive sympathetic neurons. Unlike neonatal neurons, adult sympathetic neurons are not dependent on NGF for their survival. Moreover, the NGF precursor, proNGF, is neurotoxic for aging but not young adult NGF-responsive neurons. Because of these age-related differences, the effects of JNK inhibition on the survival and growth of sympathetic neurons isolated from aged mice were studied. Aged neurons, as well as glia, were found to be dependent on JNK for their growth but not their survival. Conversely, proNGF neurotoxicity was JNK-dependent and mediated by the p75-interacting protein NRAGE, whereas neurite outgrowth was independent of NRAGE. These results have implications for the potential use of JNK inhibitors as therapies for ameliorating age-related neurodegenerative disease.