Fibroblast growth factor 2 maintains the neurogenic capacity of embryonic neural progenitor cells in vitro but changes their neuronal subtype specification

Many in vitro systems used to examine multipotential neural progenitor cells (NPCs) rely on mitogens including fibroblast growth factor 2 (FGF2) for their continued expansion. However, FGF2 has also been shown to alter the expression of transcription factors (TFs) that determine cell fate. Here, we report that NPCs from the embryonic telencephalon grown without FGF2 retain many of their in vivo characteristics, making them a good model for investigating molecular mechanisms involved in cell fate specification and differentiation. However, exposure of cortical NPCs to FGF2 results in a profound change in the types of neurons generated, switching them from a glutamatergic to a GABAergic phenotype. This change closely correlates with the dramatic upregulation of TFs more characteristic of ventral telencephalic NPCs. In addition, exposure of cortical NPCs to FGF2 maintains their neurogenic potential in vitro, and NPCs spontaneously undergo differentiation following FGF2 withdrawal. These results highlight the importance of TFs in determining the types of neurons generated by NPCs in vitro. In addition, they show that FGF2, as well as acting as a mitogen, changes the developmental capabilities of NPCs. These findings have implications for the cell fate specification of in vitro-expanded NPCs and their ability to generate specific cell types for therapeutic applications. Disclosure of potential conflicts of interest is found at the end of this article.

Demand side response: patterns in Europe and future policy perspectives under capacity mechanisms

Demand Side Response (DSR) has been slow to emerge in European electricity markets. This paper aims to both examine the reasons for low levels of DSR in Europe and reflect on factors that might affect the participation of DSR in capacity mechanisms. It relies on available evidence from the literature, secondary data on existing DSR programmes and energy aggregator's data from industries participating in DSR. Findings show that changes to the duration of contracted loads under existing or new programmes might increase the penetration of DSR. The introduction of capacity mechanisms may increase DSR from demand turn down if longer response times were available.

Enrichment and stability: a phenomenological coupling of energy value and carrying capacity

Simple predator–prey models with a prey-dependent functional response predict that enrichment (increased carrying capacity) destabilizes community dynamics: this is the ‘paradox of enrichment’. However, the energy value of prey is very important in this context. The intraspecific chemical composition of prey species determines its energy value as a food for the potential predator. Theoretical and experimental studies establish that variable chemical composition of prey affects the predator–prey dynamics. Recently, experimental and theoretical approaches have been made to incorporate explicitly the stoichiometric heterogeneity of simple predator–prey systems. Following the results of the previous experimental and theoretical advances, in this article we propose a simple phenomenological formulation of the variation of energy value at increased level of carrying capacity. Results of our study demonstrate that coupling the parameters representing the phenomenological energy value and carrying capacity in a realistic way, may avoid destabilization of community dynamics following enrichment. Additionally, under such coupling the producer–grazer system persists for only an intermediate zone of production—a result consistent with recent studies. We suggest that, while addressing the issue of enrichment in a general predator–prey model, the phenomenological relationship that we propose here might be applicable to avoid Rosenzweig’s paradox.

Sensitivity of a coupled climate model to canopy interception capacity

The canopy interception capacity is a small but key part of the surface hydrology, which affects the amount of water intercepted by vegetation and therefore the partitioning of evaporation and transpiration. However, little research with climate models has been done to understand the effects of a range of possible canopy interception capacity parameter values. This is in part due to the assumption that it does not significantly affect climate. Near global evapotranspiration products now make evaluation of canopy interception capacity parameterisations possible. We use a range of canopy water interception capacity values from the literature to investigate the effect on climate within the climate model HadCM3. We find that the global mean temperature is affected by up to -0.64 K globally and -1.9 K regionally. These temperature impacts are predominantly due to changes in the evaporative fraction and top of atmosphere albedo. In the tropics, the variations in evapotranspiration affect precipitation, significantly enhancing rainfall. Comparing the model output to measurements, we find that the default canopy interception capacity parameterisation overestimates canopy interception loss (i.e. canopy evaporation) and underestimates transpiration. Overall, decreasing canopy interception capacity improves the evapotranspiration partitioning in HadCM3, though the measurement literature more strongly supports an increase. The high sensitivity of climate to the parameterisation of canopy interception capacity is partially due to the high number of light rain-days in the climate model that means that interception is overestimated. This work highlights the hitherto underestimated importance of canopy interception capacity in climate model hydroclimatology and the need to acknowledge the role of precipitation representation limitations in determining parameterisations.

Investigating the influence of extracellular matrix and glycolytic metabolism on muscle stem cell migration on their native fibre environment

The composition of the extracellular matrix (ECM) of skeletal muscle fibres is a unique environment that supports the regenerative capacity of satellite cells; the resident stem cell population. The impact of environment has great bearing on key properties permitting satellite cells to carry out tissue repair. In this study, we have investigated the influence of the ECM and glycolytic metabolism on satellite cell emergence and migration- two early processes required for muscle repair. Our results show that both influence the rate at which satellite cells emerge from the sub-basal lamina position and their rate of migration. These studies highlight the necessity of performing analysis of satellite behaviour on their native substrate and will inform on the production of artificial scaffolds intended for medical uses.

Synthesis of mucoadhesive thiol-bearing microgels from 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate: novel drug delivery systems for chemotherapeutic agents to the bladder

Thiol-bearing microgels have been synthesised from copolymerisation of 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate, and subsequent deprotection using sodium thiomethoxide. The concentration of thiol groups on these microgels could be tailored by use of different molar ratios of the two monomers. These thiol-bearing microgels were shown to adhere to ex vivo porcine urinary bladder, which was correlated with their level of thiolation. By simply mixing solutions of thiol-bearing microgels and doxorubicin, high levels of drug loading into the microgels could be achieved. Thiol-bearing microgels controlled the release of doxorubicin in a time-dependent manner over several hours. These doxorubicin-loaded thiol-bearing microgels could have application in the treatment of early-stage bladder cancers. The method used represents a new ‘bottom-up’ approach for the synthesis of novel mucoadhesive microgels.

Resilience as transformative capacity: exploring the quadripartite cycle of structuration in a Mozambican resettlement programme

The concept of resilience has emerged out of a complex literature that has sought to make sense of an increasingly interconnected world that appears ever more beset by crises. Resilience’s appeal is reflected by the burgeoning mass of literature that has appeared on the subject in the past five years. However, there is ongoing debate surrounding its usage, with some commentators claiming that the term is inherently too conservative a one to be usefully applied to situations of vulnerability in which more radical social change is required. This article extends existing efforts to formulate more transformative notions of resilience by reframing it as a double-edged outcome of the pre-reflective and critical ways in which actors draw upon their internal structures following the occurrence of a negative event, thus reproducing or changing the external structural context that gave rise to the event in the first place. By employing a structuration-inspired analysis to the study of small-scale farmer responses to a flood-induced resettlement programme in central Mozambique, the article presents a systematic approach to the examination of resilience in light of this reframing. The case study findings suggest that more attention should be paid to the facilitative, as well as constraining, nature of structures if vulnerable populations are to be assisted in their efforts to exert transformative capacity over the wider conditions that give rise to their difficulties.

Procedural justice, not absorptive capacity, matters in multinational enterprise ICT transfers

This paper empirically tests the effectiveness of information and communications technology (ICT) knowledge transfer and adoption in the multinational enterprise (MNE) as an issue of critical importance to contemporary MNE functioning. In contrast to mainstream thinking on absorptive capacity, but in line with prevailing international business theory, our research supports the proposition that perceptions of procedural justice, rather than absorptive capacity, determine effectiveness, especially in cases of high tacit knowledge transfers. Data was collected from senior ICT representatives in 86 Canadian subsidiaries of foreign owned MNEs. Each of these subsidiaries recently experienced a significant ICT transfer imposed by the parent organization. Support was found for the main propositions: Procedural justice significantly predicted successful ICT transfer and adoption, while absorptive capacity was not significant. These findings are consistent even when knowledge tacitness was high. The perceived success of the ICT transfer as well as its adoption varied widely across these firms. The potential reasons for this divergence in effectiveness are manifold, but our findings suggest that in situations of substantial knowledge tacitness, a higher level of procedural justice, rather than a higher level of absorptive capacity, is critical to effective transfer and adoption.

Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle

Myostatin (Mstn) participates in the regulation of skeletal muscle size and has emerged as a regulator of muscle metabolism. Here, we hypothesized that lack of myostatin profoundly depresses oxidative phosphorylation-dependent muscle function. Toward this end, we explored Mstn/ mice as a model for the constitutive absence of myostatin and AAV-mediated overexpression of myostatin propeptide as a model of myostatin blockade in adult wild-type mice. We show that muscles from Mstn/ mice, although larger and stronger, fatigue extremely rapidly. Myostatin deficiency shifts muscle from aerobic toward anaerobic energy metabolism, as evidenced by decreased mitochondrial respiration, reduced expression of PPAR transcriptional regulators, increased enolase activity, and exercise-induced lactic acidosis. As a consequence, constitutively reduced myostatin signaling diminishes exercise capacity, while the hypermuscular state of Mstn/ mice increases oxygen consumption and the energy cost of running. We wondered whether these results are the mere consequence of the congenital fiber-type switch toward a glycolytic phenotype of constitutive Mstn/ mice. Hence, we overexpressed myostatin propeptide in adult mice, which did not affect fiber-type distribution, while nonetheless causing increased muscle fatigability, diminished exercise capacity, and decreased Pparb/d and Pgc1a expression. In conclusion, our results suggest that myostatin endows skeletal muscle with high oxidative capacity and low fatigability, thus regulating the delicate balance between muscle mass, muscle force, energy metabolism, and endurance capacity.

Paullinia cupana Mart. var. sorbilis, Guarana, Increases Survival of Ehrlich Ascites Carcinoma (EAC) Bearing Mice by Decreasing Cyclin-D1 Expression and Inducing a G0/G1 Cell Cycle Arrest in EAC Cells

The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant. Copyright (C) 2010 John Wiley & Sons, Ltd.

INCREASED WATER STORAGE CAPACITY IN CACTUS WOOD: A STUDY IN THE TRIBE CEREEAE (CACTOIDEAE, CACTACEAE)

Secondary xylem of fibrous cactus wood is characterized by short narrow vessel elements with both simple perforation plates and large intervessel pits, libriform septate fibers, and large rays. These are present in basal cactus taxa, as well as in many other groups of the family. In Cactoideae, the most diversified and most derived subfamily, there are remarkable variations found in the secondary xylem, with the more highly derived taxa containing the greatest water storage capacity. Unlignified parenchyma is one specialization found in the fibrous wood of cacti. We observed this tissue in the secondary xylem at the base of the sterns of several Brazilian endemic species of Arrojadoa, Melocactus, and Stephanocereus, all members of the tribe Cereeae. In Arrojadoa and Melocactus the unlignified parenchyma occurs in lines and bands amongst the axial and radial xylem elements, while in Stephanocereus it is mainly restricted to the rays and does not form bands. We address the adaptive importance of the unlignified parenchyma in the fibrous wood in tribe Cereeae and the family Cactaceae as a whole.

Using gap-crossing capacity to evaluate functional connectivity of two Atlantic rainforest birds and their response to fragmentation

One of the main consequences of habitat loss and fragmentation is the increase in patch isolation and the consequent decrease in landscape connectivity. In this context, species persistence depends on their responses to this new landscape configuration, particularly on their capacity to move through the interhabitat matrix. Here, we aimed first to determine gap-crossing probabilities related to different gap widths for two forest birds (Thamnophilus caerulescens, Thamnophilidae, and Basileuterus culicivorus, Parulidae) from the Brazilian Atlantic rainforest. These values were defined with a playback technique and then used in analyses based on graph theory to determine functional connections among forest patches. Both species were capable of crossing forest gaps between patches, and these movements were related to gap width. The probability of crossing 40 m gaps was 50% for both species. This probability falls to 10% when the gaps are 60 m (for B. culicivorus) or 80 m (for T caerulescens). Actually, birds responded to stimulation about two times more distant inside forest trials (control) than in gap-crossing trials. Models that included gap-crossing capacity improved the explanatory power of species abundance variation in comparison to strictly structural models based merely on patch area and distance measurements. These results highlighted that even very simple functional connectivity measurements related to gap-crossing capacity can improve the understanding of the effect of habitat fragmentation on bird occurrence and abundance.

Cytogenetic characterization of Metynnis maculatus (Teleostei; Characiformes): the description in Serrasalminae of a small B chromosome bearing inactive NOR-like sequences

Mitotic chromosomes of Metynnis maculatus (KNER 1860) (Teleostei, Characiformes), a fish species that occurs in the Amazon and Parana-Paraguay river basins, were analyzed for the first time by Giemsa and Ag-NOR staining, C-banding and fluorescence in situ hybridization (FISH) with 18S and 5S rDNA sequences. The basic chromosome number of the species is 2n=62 (32M+22SM+4ST+4A) and, in addition to the 62 regular chromosomes, one small acrocentric supernumerary B chromosome was found in part of the specimens analyzed. Four active NORs were present, and constitutive heterochromatin blocks were found in the pericentromeric region of several chromosomes. A heterochromatic block was also present in the interstitial portion of the submetacentric NOR-bearing pair and the B chromosome was entirely heterochromatic. FISH using an 18S rDNA probe confirmed the results obtained with AgNO(3) staining, and an additional signal was also present on the B chromosomes. 5S rDNA sequences mapped only to the largest acrocentric pair. This is the first description of supernumerary B chromosomes in Serrasalminae, and this karyotype characterization may be useful in further studies about chromosome evolution in this fish group.