Various cell types can trans-differentiate to a transfer cell (TC) morphology characterized by deposition of polarized ingrowth walls comprised of a uniform layer on which wall ingrowths (WIs) develop. WIs form scaffolds supporting amplified plasma membrane areas enriched in transporters conferring a cellular capacity for high rates of nutrient exchange across apo- and symplasmic interfaces. The hypothesis that reactive oxygen species (ROS) are a component of the regulatory pathway inducing ingrowth wall formation was tested using Vicia faba cotyledons. Vicia faba cotyledons offer a robust experimental model to examine TC induction as, on being placed into culture, their adaxial epidermal cells rapidly (hours) form ingrowth walls on their outer periclinal walls. These are readily visualized by electron microscopy, and epidermal peels of their trans-differentiating cells allow measures of cell-specific gene expression. Ingrowth wall formation responded inversely to pharmacological manipulation of ROS levels, indicating that a flavin-containing enzyme (NADPH oxidase) and superoxide dismutase cooperatively generate a regulatory H2O2 signature. Extracellular H2O2 fluxes peaked prior to the appearance of WIs and were followed by a slower rise in H2O2 flux that occurred concomitantly, and co-localized, with ingrowth wall formation. De-localizing the H2O2 signature caused a corresponding de-localization of cell wall deposition. Temporal and epidermal cell-specific expression profiles of VfrbohA and VfrbohC coincided with those of extracellular H2O2 production and were regulated by cross-talk with ethylene. It is concluded that H2O2 functions, downstream of ethylene, to activate cell wall biosynthesis and direct polarized deposition of a uniform wall on which WIs form.

Transfer cells (TCs) are ubiquitous throughout the plant kingdom. Their unique ingrowth wall labyrinths, supporting a plasma membrane enriched in transporter proteins, provides these cells with an enhanced membrane transport capacity for resources. In certain plant species, TCs have been shown to function to facilitate phloem loading and/or unloading at cellular sites of intense resource exchange between symplasmic/apoplasmic compartments. Within the phloem, the key cellular locations of TCs are leaf minor veins of collection phloem and stem nodes of transport phloem. In these locations, companion and phloem parenchyma cells trans-differentiate to a TC morphology consistent with facilitating loading and re-distribution of resources, respectively. At a species level, occurrence of TCs is significantly higher in transport than in collection phloem. TCs are absent from release phloem, but occur within post-sieve element unloading pathways and particularly at interfaces between generations of developing Angiosperm seeds. Experimental accessibility of seed TCs has provided opportunities to investigate their inductive signaling, regulation of ingrowth wall formation and membrane transport function. This review uses this information base to explore current knowledge of phloem transport function and inductive signaling for phloem-associated TCs. The functional role of collection phloem and seed TCs is supported by definitive evidence, but no such information is available for stem node TCs that present an almost intractable experimental challenge. There is an emerging understanding of inductive signals and signaling pathways responsible for initiating trans-differentiation to a TC morphology in developing seeds. However, scant information is available to comment on a potential role for inductive signals (auxin, ethylene and reactive oxygen species) that induce seed TCs, in regulating induction of phloem-associated TCs. Biotic phloem invaders have been used as a model to speculate on involvement of these signals.

HighlightA persistent and polarized cytosolic Ca2+ signal, formed into plumes by co-operative activities of plasma membrane Ca2+ channels and Ca2+-ATPase clusters, directs papillate wall ingrowth deposition in trans-differentiating transfer cells.

Circ J 2009; 73: 667 -672 ric acid (UA) is produced in the terminal stage of purine metabolism catalyzed by xanthine oxidase, and is a primary cause of gout. The relationship between serum UA and cardiovascular diseases has been, however, controversial. [1][2][3] One recent experimental study demonstrated that allopurinol, an xanthine oxidase inhibitor, prevented cardiac hypertrophy in rats with negligible effects on blood pressure (BP). 4 In humans, an elevated blood level of UA was reportedly associated with left ventricular hypertrophy (LVH) in hypertensive patients. 5,6 However, the hypertensive state may have confounded or modified the association because it could be related to both LVH and the UA level. 7 In addition, because some antihypertensive drugs are reported to reduce LVH 8 or to affect the UA level, 5 assessing the association only in those not on hypertensive medication was warranted to clarify the role of UA as an independent risk factor for LVH. Editorial p 624The prevalence of LVH has been reported as approximately 20% in adult Japanese men. 9 LVH diagnosed by electrocardiography (ECG-LVH), as well as that diagnosed by echocardiography, is known to increase the risk of cardiovascular morbidity and mortality. [10][11][12] Although a major determinant of LVH is elevated BP, a previous report has indicated LVH in approximately 10% of the normotensive population. 13 Thus, studies to find other risk factors are warranted.In the present study, we investigated the association between UA and LVH in subjects not taking medication for hypertension (HTN). Moreover, we also investigated the association by stratifying subjects by BP, which might modify the association. Methods Study PopulationThis study used baseline data collected in 2002 for a workers' cohort study on cardiovascular diseases in Aichi, Japan. The questionnaires were returned from 7,991 people, of whom 6,651 (83.2%) expressed their written consent to the use of the information. Consent for the use of data obtained during their annual health examination and to donate residual blood samples used for the examination was obtained from 5,596 (70.0%) and 4,213 (52.7%) people, respectively. In this analysis, we first restricted the subjects to men with available information on weight, height, BP, ECG, UA and other biomarker concentrations (3,773 men), because of the small number of women with (Received July 3, 2008; revised manuscript received October 24, 2008; accepted December 3, 2008; released online February 19, 2009 Uric Acid and Left Ventricular Hypertrophy in Japanese MenHirotsugu Mitsuhashi, MD* , **; Hiroshi Yatsuya, MD*; Kunihiro Matsushita, MD* , **; Huiming Zhang, MD*; Rei Otsuka, PhD* , † ; Takashi Muramatsu, MD* , **; Seiko Takefuji, MD* , † † ;Yo Hotta, MD* , † † ; Takahisa Kondo, MD**; Toyoaki Murohara, MD**; Hideaki Toyoshima, MD* , ‡ ; Koji Tamakoshi, MD* , ‡ ‡ Background: Experimental studies have reported that allopurinol protects hypertensive rats from left ventricular hypertrophy (LVH) with negligible effects on blood ...

BackgroundTransfer cells are characterized by intricate ingrowth walls, comprising an uniform wall upon which wall ingrowths are deposited. The ingrowth wall forms a scaffold to support an amplified plasma membrane surface area enriched in membrane transporters that collectively confers transfer cells with an enhanced capacity for membrane transport at bottlenecks for apo-/symplasmic exchange of nutrients. However, the underlying molecular mechanisms regulating polarized construction of the ingrowth wall and membrane transporter profile are poorly understood.ResultsAn RNAseq study of an inducible epidermal transfer cell system in cultured Vicia faba cotyledons identified transfer cell specific transcriptomes associated with uniform wall and wall ingrowth deposition. All functional groups of genes examined were expressed before and following transition to a transfer cell fate. What changed were the isoform profiles of expressed genes within functional groups. Genes encoding ethylene and Ca2+ signal generation and transduction pathways were enriched during uniform wall construction. Auxin-and reactive oxygen species-related genes dominated during wall ingrowth formation and ABA genes were evenly expressed across ingrowth wall construction. Expression of genes encoding kinesins, formins and villins was consistent with reorganization of cytoskeletal components. Uniform wall and wall ingrowth specific expression of exocyst complex components and SNAREs suggested specific patterns of exocytosis while dynamin mediated endocytotic activity was consistent with establishing wall ingrowth loci. Key regulatory genes of biosynthetic pathways for sphingolipids and sterols were expressed across ingrowth wall construction. Transfer cell specific expression of cellulose synthases was absent. Rather xyloglucan, xylan and pectin biosynthetic genes were selectively expressed during uniform wall construction. More striking was expression of genes encoding enzymes for re-modelling/degradation of cellulose, xyloglucans, pectins and callose. Extensins dominated the cohort of expressed wall structural proteins and particularly so across wall ingrowth development. Ion transporters were selectively expressed throughout ingrowth wall development along with organic nitrogen transporters and a large group of ABC transporters. Sugar transporters were less represented.ConclusionsPathways regulating signalling and intracellular organization were fine tuned whilst cell wall construction and membrane transporter profiles were altered substantially upon transiting to a transfer cell fate. Each phase of ingrowth wall construction was linked with unique cohorts of expressed genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-015-0486-5) contains supplementary material, which is available to authorized users.

SUMMARYTransfer cells are specialized transport cells containing invaginated wall ingrowths that provide an amplified plasma membrane surface area with high densities of transporter proteins. They trans-differentiate from differentiated cells at sites where enhanced rates of nutrient transport occur across apo/symplasmic boundaries. Despite their physiological importance, the signal(s) and signalling cascades responsible for initiating their trans-differentiation are poorly understood. In culture, adaxial epidermal cells of Vicia narbonensis cotyledons were induced to trans-differentiate to a transfer cell morphology. Manipulating their intracellular glucose concentrations by transgenic knock-down of ADP-glucose pyrophosphorylase expression and/or culture on a high-glucose medium demonstrated that glucose functioned as a negative regulator of wall ingrowth induction. In contrast, glucose had no detectable effect on wall ingrowth morphology. The effect on wall ingrowth induction of culture on media containing glucose analogues suggested that glucose acts through a hexokinase-dependent signalling pathway. Elevation of an epidermal cell-specific ethylene signal alone, or in combination with glucose analogues, countered the negative effect of glucose on wall ingrowth induction. Glucose modulated the amplitude of ethylene-stimulated wall ingrowth induction by downregulating the expression of ethylene biosynthetic genes and an ethylene insensitive 3 (EIN3)-like gene (EIL) encoding a key transcription factor in the ethylene signalling cascade. A model is presented describing the interaction between glucose and ethylene signalling pathways regulating the induction of wall ingrowth formation in adaxial epidermal cells.

Background: Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood. Objective: To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD. Methods: pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab ( n = 29), rituximab ( n = 23), oral prednisone ( n = 16), and oral azathioprine or mycophenolate mofetil ( n = 4). Results: NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2–39.3) versus 11.5 (7.0–23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6–406.5) versus 68.7 (59.4–80.8) pg/mL; p < 0.001). Multivariable regression analyses indicated that baseline pNfL concentration was associated with age ( p = 0.017), Expanded Disability Status Scale (EDSS) score ( p = 0.002), and recent relapses ( p < 0.001). Baseline pGFAP concentration was also associated with EDSS ( p < 0.001) and recent relapses ( p < 0.001). Compared with prednisone, tocilizumab and rituximab significantly reduced pNfL [tocilizumab, exp(β), 0.65; 95% confidence interval (CI), 0.56–0.75; p < 0.001; rituximab, exp(β), 0.79; 95% CI = 0.68–0.93; p = 0.005] and pGFAP levels [tocilizumab, exp(β), 0.64; 95% CI, 0.51–0.80; p < 0.001; rituximab, exp(β), 0.77; 95% CI, 0.61–0.98; p = 0.041] at the end of the study. The pNfL levels in the tocilizumab and rituximab groups were reduced to those of HCs [tocilizumab, 8.5 (7.06–17.90) pg/mL; p = 0.426; rituximab, 14.0 (9.94–21.80) pg/mL; p = 0.216]. However, the pGFAP levels did not decrease to those of HCs in NMOSD patients at the end of study [tocilizumab, 88.9 (63.4–131.8) pg/mL; p = 0.012; rituximab, 141.7 (90.8–192.7) pg/mL; p < 0.001]. Conclusion: pNfL and pGFAP may serve as biomarkers for NMOSD disease activity and treatment effects.

Polarized plumes of elevated cytosolic Ca2+ generate a remodelled actin network that directs localized exo- and endocytosis that is responsible for determining the spatially defined assembly of wall ingrowth papillae in transfer cells.