Phenotypic plasticity of gut structure and function during periods of inactivity in Apostichopus japonicus

Apostichopus japonicus is a common sea cucumber that undergoes seasonal inactivity phases and ceases feeding during the summer months. We used this sea cucumber species as a model in which to examine phenotypic plasticity of the digestive tract in response to food deprivation. We measured the body mass, gross gut morphology and digestive enzyme activities of A. japonicus before, during, and after the period of inactivity to examine the effects of food deprivation on the gut structure and function of this animal. Individuals were sampled semi-monthly from June to November (10 sampling intervals over 178 days) across temperature changes of more than 18 degrees C. On 5 September, which represented the peak of inactivity and lack of feeding, A. japonicus decreased its body mass, gut mass and gut length by 50%, 85%, and 70%, respectively, in comparison to values for these parameters preceding the inactive period. The activities of amylase, cellulase and lipase decreased by 77%, 98%, and 35% respectively, in comparison to mean values for these enzymes in June, whereas pepsin activity increased two-fold (luring the inactive phase. Alginase and trypsin activities were variable and did not change significantly across the 178-day experiment. With the exception of amylase and cellulase, all body size indices and digestive enzyme activities recovered and even surpassed the mean values preceding the inactive phase during the latter part of the experiment (October-November). Principal Component Analysis (PCA) utilizing the digestive enzyme activity and body size index data divided the physiological state of this cucumber into four phases: an active stage, prophase of inactivity peak inactivity, and a reversion phase. These phases are all consistent with previously suggested life stages for this species, but our data provide more defined characteristics of each phase. A. japonicus clearly exhibits phenotypic plasticity (or life-cycle staging) of the digestive tract during its annual inactive period. (C) 2008 Elsevier Inc. All rights reserved.

Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.

BACKGROUND: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. METHODOLOGY/PRINCIPAL FINDINGS: Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. CONCLUSIONS/SIGNIFICANCE: During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of illness.

To plasticity and back again.

Both the gain and the loss of flexibility in the development of phenotypes have led to an increased diversity of physical forms in nematode worms.

Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.

BACKGROUND: Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery. METHODS: Men with localized PC treated with radical prostatectomy at the Durham VA Medical Center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1 and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics an risk of PSA recurrence over time. RESULTS: Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; three died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N-cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence or Gleason sum were noted for SNAIL, ZEB1, vimentin or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (P=0.043), National Comprehensive Cancer Network risk (P=0.013) and PSA recurrence (hazard ratio 1.07, P=0.016). CONCLUSIONS: The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.

Distinct routes to metastasis: plasticity-dependent and plasticity-independent pathways.

The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.

The Effects of Insulin-Induced Moderate Hypoglycemia on Hippocampal Plasticity

Self-regulation of blood glucose in diabetics via insulin administration introduces the risk of hypoglycemia. Previous studies have shown hypoglycemia damages the dentate gyrus, an area of the hippocampus associated with anxiety- and depressive-like behavior. To date, only depressive-like behaviors have been observed following moderate hypoglycemia. This study sought to examine whether acute moderate hypoglycemia induces both behaviors due to high clinical comorbidity. One episode of moderate hypoglycemia was induced in a male Sprague-Dawley rat. Twenty-four hours later, hippocampal function was evaluated via the elevated plus maze and the forced swim test to assess anxiety-like and depressive-like behavior. Results, though not statistically significant, suggested that acute moderate hypoglycemia may increase anxiety- and depressive-like behavior. These findings may elucidate hypoglycemia-related behavioral changes.

Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25-35) are dependent on stimulation-protocol and genetic background

The aggregation of beta-amyloid to plaques in the brain is one of the hallmarks of Alzheimer disease (AD). Numerous studies have tried to elucidate to what degree amyloid peptides play a role in the neurodegenerative developments seen in AD. While most studies report an effect of amyloid on neural activity and cognitive abilities of rodents, there have been many inconsistencies in the results. This study investigated to what degree the different genetic backgrounds affect the outcome of beta-amyloid fragment (25-35) on synaptic plasticity in vivo in the rat hippocampus. Two strains, Wistar and Lister hooded rats, were tested. In addition, the effects of a strong (600 stimuli) and a weak stimulation protocol (100 stimuli) on impairments of LTP were analysed. Furthermore, since the state of amyloid aggregation appears to play a role in the induction of toxic processes, it was tested by dual polarisation interferometry to what degree and at what speed beta-amyloid (25-35) can aggregate in vitro. It was found that 100 nmol beta-amyloid (25-35) injected icv did impair LTP in Wistar rats when using the weak but not the strong stimulation protocol (P <0.001). One-hundred nano mole of the reverse sequence amyloid (35-25) had no effect. LTP in Lister Hooded rats was not impaired by amyloid at any stimulation protocol. The aggregation studies showed that amyloid (25-35) aggregated within hours, while amyloid (35-25) did not. These results show that the genetic background and the stimulation protocol are important variables that greatly influence the experimental outcome. The fact that amyloid (25-35) aggregated quickly and showed neurophysiological effects, while amyloid (35-25) did not aggregate and did not show any effects indicates that the state of aggregation plays an important role in the physiological effects.

Recapitulation of embryological programmes in renal fibrosis - The importance of epithelial cell plasticity and developmental genes

Chronic fibrosis represents the final common pathway in progressive renal disease. Myofibroblasts deposit the constituents of renal scar, thus crippling renal function. It has recently emerged that an important source of these pivotal effector cells is the injured renal epithelium. This review concentrates on the process of epithelial-mesenchymal transition (EMT) and its regulation. The role of the developmental gene, gremlin, which is reactivated in adult renal disease, is the subject of particular focus. This member of the cysteine knot protein superfamily is critical to the process of nephrogenesis but quiescent in normal adult kidney. There is increasing evidence that gremlin expression reactivates in diabetic nephropathy, and in the diseased fibrotic kidney per se. Known to antagonize members of the bone morphogenic protein (BMP) family, gremlin may also act downstream of TGF-beta in induction of EMT. An increased understanding of the extracellular modulation of EMT and, in particular, of the gremlin-BMP axis may result in strategies that can halt or reverse the devastating progression of chronic renal fibrosis. Copyright (c) 2006 S. Karger AG, Basel.

Behavioral plasticity allows short-term adjustment to a novel environment

Many species are currently experiencing anthropogenically driven environmental changes. Among these changes, increasing noise levels are specifically a problem for species relying on acoustic communication. Recent evidence suggests that some species adjust their acoustic signals to man-made noise. However, it is unknown whether these changes occur through short-term and reversible adjustments by behavioral plasticity or through long-term adaptations by evolutionary change. Using behavioral observations and playback experiments, we show that male reed buntings (Emberiza schoeniclus) adjusted their songs immediately, singing at a higher minimum frequency and at a lower rate when noise levels were high. Our data showed that these changes in singing behavior were short-term adjustments of signal characteristics resulting from behavioral plasticity, rather than a long-term adaptation. However, more males remained unpaired at a noisy location than at a quiet location throughout the breeding season. Thus, phenotypic plasticity enables individuals to respond to environmental changes, but whether these short-term adjustments are beneficial remains to be seen.

Mathematical modeling of colony formation in algal blooms: phenotypic plasticity in cyanobacteria

In this paper, we analyzed a mathematical model of algal-grazer dynamics, including the effect of colony formation, which is an example of phenotypic plasticity. The model consists of three variables, which correspond to the biomasses of unicellular algae, colonial algae, and herbivorous zooplankton. Among these organisms, colonial algae are the main components of algal blooms. This aquatic system has two stable attractors, which can be identified as a zooplankton-dominated (ZD) state and an algal-dominated (AD) state, respectively. Assuming that the handling time of zooplankton on colonial algae increases with the colonial algae biomass, we discovered that bistability can occur within the model system. The applicability of alternative stable states in algae-grazer dynamics as a framework for explaining the algal blooms in real lake ecosystems, thus, seems to depend on whether the assumption mentioned above is met in natural circumstances.

Cryptic plasticity underlies a major evolutionary transition

The origin of eusociality is often regarded as a change of macroevolutionary proportions [1, 2]. Its hallmark is a reproductive division of labor between the members of a society: some individuals ("helpers" or "workers") forfeit their own reproduction to rear offspring of others ("queens"). In the Hymenoptera (ants, bees, wasps), there have been many transitions in both directions between solitary nesting and sociality [2-5]. How have such transitions occurred? One possibility is that multiple transitions represent repeated evolutionary gains and losses of the traits underpinning sociality. A second possibility, however, is that once sociality has evolved, subsequent transitions represent selection at just one or a small number of loci controlling developmental switches between preexisting alternative phenotypes [2, 6]. We might then expect transitional populations that can express either sociality or solitary nesting, depending on environmental conditions. Here, we use field transplants to directly induce transitions in British and Irish populations of the sweat bee Halictus rubicundus. Individual variation in social phenotype was linked to time available for offspring production, and to the genetic benefits of sociality, suggesting that helping was not simply misplaced parental care [7]. We thereby demonstrate that sociality itself can be truly plastic in a hymenopteran.