Associated Liver Partition and Portal Vein Ligation (ALPPS) vs Selective Portal Vein Ligation (PVL) for Staged Hepatectomy in a Rat Model. Similar Regenerative Response?

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage hepatectomy technique which can be associated with a hypertrophic stimulus on the future liver remnant (FLR) stronger than other techniques–such as portal vein ligation (PVL). However, the reason of such hypertrophy is still unclear, but it is suggested that liver transection combined with portal vein ligation (ALPPS) during the first stage of this technique may play a key role. The aim of this study is to compare the hypertrophic stimulus on the FLR and the clinical changes associated with both ALPPS and PVL in a rat surgical model. For this purpose, three groups of SD rats were used, namely ALPPS (n = 30), PVL (n = 30) and sham-treated (n = 30). The second stage of ALPPS (hepatectomy of the atrophic lobes), was performed at day 8. Blood and FLR samples were collected at 1, 24, 48 hours, 8 days and 12 weeks after the surgeries. ALPPS provoked a greater degree of hypertrophy of the FLR than the PVL at 48 hours and 8 days (p<0.05). The molecular pattern was also different, with the highest expression of IL-1β at 24h, IL-6 at 8 days, and HGF and TNF-α at 48 hours and 8 days (p<0.05). ALPPS also brought about a mild proliferative stimulus at 12 weeks, with a higher expression of HGF and TGF-β (p<0.05) than PVL. Clinically, ALPPS caused a significant liver damage during the first 48 hours, with a recovery of liver function at day 8. In conclusion, ALPPS seems to induce higher functional hypertrophy on the FLR than PVL at day 8. Such regenerative response seems to be leaded by a complex interaction between pro-mitogenic (IL-6, HGF, TNF-α) and antiproliferative (IL1-β and TGF-β) cytokines.     

The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function

Polycystin-2 (PC2) is a TRP-type, Ca²⁺-permeable non-selective cation channel that plays an important role in Ca²⁺ signaling in renal and non-renal cells. The effect(s) of the cAMP pathway and kinase mediated phosphorylation of PC2 seem to be relevant to PC2 trafficking and its interaction with polycystin-1. However, the role of PC2 phosphorylation in channel function is still poorly defined. Here we reconstituted apical membranes of term human syncytiotrophoblast (hST), containing endogenous PC2 (PC2_hst), and in vitro translated channel protein (PC2_iv). Addition of the catalytic subunit of PKA increased by 566% the spontaneous PC2_hst channel activity in the presence of ATP. Interestingly, 8-Br-cAMP also stimulated spontaneous PC2_hst channel activity in the absence of the exogenous kinase. Either stimulation was inhibited by addition of alkaline phosphatase, which in turn, was reversed by the phosphatase inhibitor vanadate. Neither maneuver modified the single channel conductance but instead increased channel mean open time. PKA directly phosphorylated PC2, which increased the mean open time but not the single channel conductance of the channel. PKA phosphorylation did not modify either R742X truncated or S829A-mutant PC2_iv channel function. The data indicate that the cAMP pathway regulates PC2-mediated cation transport in the hST. The relevant PKA site for PC2 channel regulation centers on a single residue serine 829, in the carboxyl terminus.     

Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.     

Obstacle Avoidance,Visual Detection Performance,and Eye-Scanning Behavior of Glaucoma Patients in a Driving Simulator: A Preliminary Study

The objective of this study was to evaluate differences in driving performance, visual detection performance, and eye-scanning behavior between glaucoma patients and control participants without glaucoma. Glaucoma patients (n = 23) and control participants (n = 12) completed four 5-min driving sessions in a simulator. The participants were instructed to maintain the car in the right lane of a two-lane highway while their speed was automatically maintained at 100 km/h. Additional tasks per session were: Session 1: none, Session 2: verbalization of projected letters, Session 3: avoidance of static obstacles, and Session 4: combined letter verbalization and avoidance of static obstacles. Eye-scanning behavior was recorded with an eye-tracker. Results showed no statistically significant differences between patients and control participants for lane keeping, obstacle avoidance, and eye-scanning behavior. Steering activity, number of missed letters, and letter reaction time were significantly higher for glaucoma patients than for control participants. In conclusion, glaucoma patients were able to avoid objects and maintain a nominal lane keeping performance, but applied more steering input than control participants, and were more likely than control participants to miss peripherally projected stimuli. The eye-tracking results suggest that glaucoma patients did not use extra visual search to compensate for their visual field loss. Limitations of the study, such as small sample size, are discussed.     

The role of short-tongued insects in floral variation across the range of a style-dimorphic plant

Background and Aims

Heterostyly and related style polymorphisms are suitable model systems to evaluate the importance of functional pollinators in the maintenance of population variability. In Narcissus papyraceus different functional pollinators, incompatibility system and flower morphology have been proposed to influence the maintenance of polymorphism through their effect on disassortative mating. Here a test is done to find out if the visitation rate of long- versus short-tongued pollinators correlates with the morph ratio and if the latter is related to other flower traits of the species across its main geographic range.

Methods

Floral traits from 34 populations in the south-west of the Iberian Peninsula and in north-west Africa were measured, perianth variation was described and a comparison was made of allometric relationships between sex organs and floral tube. Correlations between pollinator guilds, stigma–anther separation of reciprocal morphs (our proxy for disassortative mating) and morph-ratio variation were analysed. Finally, the incompatibility system of the species in the northern and southern borders of its distribution are described.

Key Results

Flowers from southern populations were significantly larger than flowers from centre and northern populations. The abundance of short-styled plants decreased gradually with increasing distance from the core region (the Strait of Gibraltar), with these disappearing only in the northern range. Although there was a significant difference in stigma–anther separation among populations, morph ratio was not associated with reciprocity or floral tube length. Long-style morph frequency increased with short-tongued pollinator visitation rate. Populations from both edges of the distribution range were self-incompatible and within- and between-morph compatible.

Conclusions

The style morph ratio changed gradually, whereas perianth trait variation showed abrupt changes with two morphotypes across the range. The positive relationship between the visitation rate of short-tongued pollinators and the decrease of the short-style morph supports our initial hypothesis. The results highlight the importance of different pollinators in determining the presence of style polymorphism.     

Identification of the infectious source of an unusual outbreak of histoplasmosis,in a hotel in Acapulco,state of Guerrero,Mexico

Three isolates of Histoplasma capsulatum were identified from mice lung, liver, and spleen inoculated with soil samples of the X hotel’s ornamental potted plants that had been fertilized with organic material known as compost. The presence of H. capsulatum in the original compost was detected using the dot-enzyme-linked immunosorbent assay. Nested-PCR, using a specific protein Hcp100 coding gene sequence, confirmed the fungal identification associated with an unusual histoplasmosis outbreak in Acapulco. Although, diversity between the H. capsulatum isolate from the hotel and some clinical isolates from Guerrero (positive controls) was observed using random amplification of polymorphic DNA based-PCR, sequence analyses of H-anti and ole fragment genes revealed a high homology (92–99%) between them.     

Influence of seasonal variation on the phenology and liriodenine content of Annona lutescens (Annonaceae)

Annona lutescens Saff. (Annonaceae) grows as a native tree in Chiapas, Mexico in Tropical Dry Forest habitat. Like most Annonaceae, it biosynthesizes benzylisoquinoline alkaloids, mostly liriodenine. To determine the influence of seasonal changes in the accumulation of liriodenine, the monthly variation of liriodenine content in roots, stems and leaves of mature and young trees was observed. These parts of young and mature A. lutescens trees were collected monthly over a 1 year period and the alkaloids were extracted; the liriodenine was quantified by high-resolution liquid chromatography. The phenological stages of the species were also assessed (leaf development, flowering and fruiting) using the Biologische Bundesanstalt, Bundessortenamt und Chemische Industrie (BBCH) scale. The analysis of both young and mature trees showed a significant increase in the liriodenine concentration occurs within roots during the dry season, which coincides with leaf fall. A significant decrease also occurred at the beginning of the rainy season (the period of leaf growth); the liriodenine content for the next rainy season did not reach the levels of the previous dry season. The climatic variation induced phenological and physiological changes in this species.     

The Phosphorylated Pathway of Serine Biosynthesis Is Essential Both for Male Gametophyte and Embryo Development and for Root Growth in Arabidopsis

This study characterizes the phosphorylated pathway of Ser biosynthesis (PPSB) in Arabidopsis thaliana by targeting phosphoserine phosphatase (PSP1), the last enzyme of the pathway. Lack of PSP1 activity delayed embryo development, leading to aborted embryos that could be classified as early curled cotyledons. The embryo-lethal phenotype of psp1 mutants could be complemented with PSP1 cDNA under the control of Pro35S (Pro35S:PSP1). However, this construct, which was poorly expressed in the anther tapetum, did not complement mutant fertility. Microspore development in psp1.1/psp1.1 Pro35S:PSP1 arrested at the polarized stage. The tapetum from these lines displayed delayed and irregular development. The expression of PSP1 in the tapetum at critical stages of microspore development suggests that PSP1 activity in this cell layer is essential in pollen development. In addition to embryo death and male sterility, conditional psp1 mutants displayed a short-root phenotype, which was reverted in the presence of Ser. A metabolomic study demonstrated that the PPSB plays a crucial role in plant metabolism by affecting glycolysis, the tricarboxylic acid cycle, and the biosynthesis of amino acids. We provide evidence of the crucial role of the PPSB in embryo, pollen, and root development and suggest that this pathway is an important link connecting primary metabolism with development.