Operationalizing a fisheries social-ecological system through a Bayesian belief network reveals hotspots for its adaptive capacity in the southern North sea.

Fisheries social-ecological systems (SES) in the North Sea region confront multifaceted challenges stemming from environmental changes, offshore wind farm expansion, and marine protected area establishment. In this paper, we demonstrate the utility of a Bayesian Belief Network (BN) approach in comprehensively capturing and assessing the intricate spatial dynamics within the German plaice-related fisheries SES. The BN integrates ecological, economic, and socio-cultural factors to generate high-resolution maps of profitability and adaptive capacity potential (ACP) as prospective management targets. Our analysis of future scenarios, delineating changes in spatial constraints, economics, and socio-cultural aspects, identifies factors that will exert significant influence on this fisheries SES in the near future. These include the loss of fishing grounds due to the installation of offshore wind farms and marine protected areas, as well as reduced plaice landings due to climate change. The identified ACP hotspots hold the potential to guide the development of localized management strategies and sustainable planning efforts by highlighting the consequences of management decisions. Our findings emphasize the need to consider detailed spatial dynamics of fisheries SES within marine spatial planning (MSP) and illustrate how this information may assist decision-makers and practitioners in area prioritization. We, therefore, propose adopting the concept of fisheries SES within broader integrated management approaches to foster sustainable development of inherently dynamic SES in a rapidly evolving marine environment.

Evaluation of marine spatial planning requires fit for purpose monitoring strategies.

Marine spatial planning (MSP) has rapidly become the most widely used integrated, place-based management approach in the marine environment. Monitoring and evaluation of MSP is key to inform best practices, adaptive management and plan iteration. While standardised evaluation frameworks cannot be readily applied, accounting for evaluation essentials such as the definition of evaluation objectives, indicators and stakeholder engagement of stakeholders is a prerequisite for meaningful evaluation outcomes. By way of a literature review and eleven practical MSP case studies, we analysed present day trends in evaluation approaches and unravelled the adoption of evaluation essentials for three categories for monitoring and evaluation for plan making, plan outcomes, and policy implementation. We found that at a global scale the focus of MSP evaluation has shifted over the past decade from evaluating predominantly plan outcomes towards the evaluation of plan making. Independent of the scope of the evaluation, evaluation approaches varied greatly from formal and structured processes, building for instance on MSP goals and objectives, to informal processes based on stakeholder interviews. We noted a trend in the adoption of formalised approaches where MSP evaluations have increasingly become linked to MSP policy goals and objectives. However, the enhanced use of MSP objectives and indicators did not result in a more straightforward reporting of outcomes, e.g. such as the achievement of specific MSP objectives. Overall, we found weak linkages between defined MSP objectives, indicators and available monitoring data. While the apparent shift towards a focus on objectives is promising, we highlight the need of fit-for-purpose monitoring data to enable effective evaluation of those objectives. Hence, effective MSP and adaptive management processes require customised and concurrent monitoring and evaluation strategies and procedures. We argue that evaluation processes would also benefit from a better understanding of the general environmental, socio-economic and socio-cultural effects of MSP. Therefore, to understand better environmental effects of MSP, we praise that forthcoming MSP processes need to deepen the understanding and considerations of cause-effect pathways between human activities and changes of ecosystem state through the adoption of targeted cumulative effects assessments.

Socio-ecological vulnerability to tipping points: A review of empirical approaches and their use for marine management.

Sustainability in the provision of ecosystem services requires understanding of the vulnerability of social-ecological systems (SES) to tipping points (TPs). Assessing SES vulnerability to abrupt ecosystem state changes remains challenging, however, because frameworks do not operationally link ecological, socio-economic and cultural elements of the SES. We conducted a targeted literature review on empirical assessments of SES and TPs in the marine realm and their use in ecosystem-based management. Our results revealed a plurality of terminologies, definitions and concepts that hampers practical operationalisation of these concepts. Furthermore, we found a striking lack of socio-cultural aspects in SES vulnerability assessments, possibly because of a lack of involvement of stakeholders and interest groups. We propose guiding principles for assessing vulnerability to TPs that build on participative approaches and prioritise the connectivity between SES components by accounting for component linkages, cascading effects and feedback processes.

"And DPSIR begat DAPSI(W)R(M)!" - A unifying framework for marine environmental management.

The marine environment is a complex system formed by interactions between ecological structure and functioning, physico-chemical processes and socio-economic systems. An increase in competing marine uses and users requires a holistic approach to marine management which considers the environmental, economic and societal impacts of all activities. If managed sustainably, the marine environment will deliver a range of ecosystem services which lead to benefits for society. In order to understand the complexity of the system, the DPSIR (Driver-Pressure-State-Impact-Response) approach has long been a valuable problem-structuring framework used to assess the causes, consequences and responses to change in a holistic way. Despite DPSIR being used for a long time, there is still confusion over the definition of its terms and so to be appropriate for current marine management, we contend that this confusion needs to be addressed. Our viewpoint advocates that DPSIR should be extended to DAPSI(W)R(M) (pronounced dap-see-worm) in which Drivers of basic human needs require Activities which lead to Pressures. The Pressures are the mechanisms of State change on the natural system which then leads to Impacts (on human Welfare). Those then require Responses (as Measures). Furthermore, because of the complexity of any managed sea area in terms of multiple Activities, there is the need for a linked-DAPSI(W)R(M) framework, and then the connectivity between marine ecosystems and ecosystems in the catchment and further at sea, requires an interlinked, nested-DAPSI(W)R(M) framework to reflect the continuum between adjacent ecosystems. Finally, the unifying framework for integrated marine management is completed by encompassing ecosystem structure and functioning, ecosystem services and societal benefits. Hence, DAPSI(W)R(M) links the socio-ecological system of the effects of changes to the natural system on the human uses and benefits of the marine system. However, to deliver these sustainably in the light of human activities requires a Risk Assessment and Risk Management framework; the ISO-compliant Bow-Tie method is used here as an example. Finally, to secure ecosystem health and economic benefits such as Blue Growth, successful, adaptive and sustainable marine management Responses (as Measures) are delivered using the 10-tenets, a set of facets covering all management disciplines and approaches.

CFTR is a tumor suppressor gene in murine and human intestinal cancer.

This corrects the article DOI: 10.1038/onc.2015.483.

CFTR is a tumor suppressor gene in murine and human intestinal cancer.

CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid-base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated Apc(Min) mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc(+/+) mice aged to ~1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc(+/+) Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt ß-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease-free survival.

The role of KCNQ1 in mouse and human gastrointestinal cancers.

Kcnq1, which encodes for the pore-forming α-subunit of a voltage-gated potassium channel, was identified as a gastrointestinal (GI) tract cancer susceptibility gene in multiple Sleeping Beauty DNA transposon-based forward genetic screens in mice. To confirm that Kcnq1 has a functional role in GI tract cancer, we created Apc(Min) mice that carried a targeted deletion mutation in Kcnq1. Results demonstrated that Kcnq1 is a tumor suppressor gene as Kcnq1 mutant mice developed significantly more intestinal tumors, especially in the proximal small intestine and colon, and some of these tumors progressed to become aggressive adenocarcinomas. Gross tissue abnormalities were also observed in the rectum, pancreas and stomach. Colon organoid formation was significantly increased in organoids created from Kcnq1 mutant mice compared with wild-type littermate controls, suggesting a role for Kcnq1 in the regulation of the intestinal crypt stem cell compartment. To identify gene expression changes due to loss of Kcnq1, we carried out microarray studies in the colon and proximal small intestine. We identified altered genes involved in innate immune responses, goblet and Paneth cell function, ion channels, intestinal stem cells, epidermal growth factor receptor and other growth regulatory signaling pathways. We also found genes implicated in inflammation and in cellular detoxification. Pathway analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis confirmed the importance of these gene clusters and further identified significant overlap with genes regulated by MUC2 and CFTR, two important regulators of intestinal homeostasis. To investigate the role of KCNQ1 in human colorectal cancer (CRC), we measured protein levels of KCNQ1 by immunohistochemistry in tissue microarrays containing samples from CRC patients with liver metastases who had undergone hepatic resection. Results showed that low expression of KCNQ1 expression was significantly associated with poor overall survival.

Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice.

Goblet cell depletion and down-regulation of MUC2 expression are observed in a significant percentage of human non-mucinous colorectal adenocarcinomas. Direct evidence for the role of MUC2 in gastrointestinal tumor formation was demonstrated by a knockout of Muc2 in mice that resulted in the development of adenocarcinomas in the small and large intestine. The secretory phospholipase Pla2g2a is a protein that confers resistance to Apc(Min/+)-induced intestinal tumorigenesis. Like Muc2, in the large intestine Pla2g2a is exclusively expressed by the goblet cells and Pla2g2a's tumor resistance is also strongest in the large intestine. Possible genetic interactions between Muc2 and Pla2g2a were examined by creating C57BL/6-Muc2(-/-)Pla2g2a transgenic mice. Expression of a Pla2g2a transgene reduced tumorigenesis in the large intestine by 90% in male Muc2(-/-) mice and by nearly 100% in female Muc2(-/-) mice. Expression of Pla2g2a also inhibited tumor progression. Microarray gene expression studies revealed Pla2g2a target genes that modulate intestinal energy metabolism, differentiation, inflammation, immune responses and proliferation. Overall, results of the present study demonstrate an Apc-independent role for Pla2g2a in tumor resistance and indicate that Pla2g2a plays an important role, along with Muc2, in protection of the intestinal mucosa.

Shear deformation of polymer melt observed via proton NMR: theory and experiment.

We here develop a theory for the effect of shearing flow on residual proton dipole-dipole interactions for polymer melts. The model is based on the use of correlation functions which derive from the return to origin probability for polymers reptating in the tube of surrounding constraints. Using Doi-Edwards theory we calculate the spin-echo response under equilibrium conditions and then consider the effect of a shearing flow which deforms the tube, finding that there exists a strong dependence of transverse relaxation on Weissenberg number. The results are compared with NMR measurements of shear-perturbed proton T2 relaxation in 494kDa poly (dimethylsiloxane).

Expression of fructose sensitive glucose transporter in the brains of fructose-fed rats.

Glucose transporters play a critical role in mammalian brain energy metabolism because glucose is the principal brain energy source and these transporters promote glucose movement into neural cells. When glucose is unavailable, fructose can serve as an alternative energy source. Using real-time polymerase chain reaction and actin as a reference mRNA, we investigated the impact of fructose feeding on rat brain and other tissue mRNA expression of glucose transporter 5 which has high affinity for fructose. Brain mRNA levels of glucose transporter 5 increased 1.5-fold in 35-day old rats after 7 days of fructose feeding compared with controls, whereas it increased 2.5-fold in jejunum. Semi-quantitative analysis of protein expression by immunofluorescence of glucose transporter 5 in rat hippocampi indicated a 2.4-fold increase. We demonstrated the specificity of fructose feeding on glucose transporter 5 expression by showing that the expression of the neuronal glucose transporter 3 and insulin-regulated glucose transporter 4 were unaffected. In addition, the expression of glucose transporter 5 increased in fructose fed older adult rats (8-months and 12-months old) when compared with controls. These results suggest that short-term fructose feeding increases the expression of glucose transporter 5 in both young and aging adult rats. Increased brain expression of glucose transporter 5 is likely to be important in the role of fructose as an alternative energy source.

Astrocytes exert a pro-apoptotic effect on neurons in postnatal hippocampal cultures.

We investigated conditions that promote basal and activity-dependent neuronal apoptosis in postnatal rat hippocampal cultures. Low-density mixed cultures of astrocytes and neurons exhibited lower sensitivity than high-density cultures to basal neuronal death and activity-sensitive neuronal death, induced with glutamate receptor blockers, sodium channel blockers, or calcium channel blockers. Although elevations of [Ca(2+)](i) protect neurons from apoptosis, low-density microcultures and mass cultures exhibited only minor differences in resting [Ca(2+)](i) and Ca(2+) current density, suggesting that these variables are unlikely to explain differences in susceptibility. Astrocytes, rather than neurons, were implicated in the neuronal loss. Several candidate molecules implicated in other astrocyte-dependent neurotoxicity models were excluded, but heat inactivation experiments suggested that a heat-labile factor is critically involved. In sum, our results suggest the surprising result that astrocytes can be negative modulators of neuronal survival during development and when the immature nervous system is challenged with drugs that dampen electrical excitability.

Time-dependence of nuclear magnetic resonance quadrupole interactions for polymers under shear.

We consider the problem of performing NMR spectroscopy under conditions of flow, a central issue in Rheo-NMR. By way of example, the effects of rotational motion on the deuterium NMR spectrum are considered for Couette cell experiments involving deformation of polymers under shearing conditions. The polymer was modelled as a power law fluid and for each streamline, the spin Hamiltonian evolved to allow for flow reorientation. The gap-integral spectra are compared with the 'ideal' spectra for a polymer under shear, but without reorientation. It is found that flow does affect the shape of the deuterium spectra, as well as slightly perturbing the splittings.

Biaxial deformation of a polymer under shear: NMR test of the Doi-Edwards model with convected constraint release.

2H NMR quadrupole interaction spectroscopy has been used to measure the deformation of a 670 kD poly(dimethylsiloxane) melt under shear in a Couette cell. The signals were acquired from a per deuterated benzene probe molecule which provides a motionally averaged sampling of the entire segmental ensemble. We have measured the dependence on shear rate of the S(XX) (velocity), S(YY) (velocity gradient), S(ZZ) (vorticity), and S(XY) (shear) elements of the segmental alignment tensor, as well as the angular dependence of the deuterium quadrupole splitting at fixed shear rate. We show that the data agree quite well with the Doi-Edwards theory but significantly better when convected constraint release effects are included. These fits return a value for the tube disengagement time of 100 ms.

Phase-shifting effects of dusklike and dawnlike light pulses on the circadian activity rhythms of Syrian hamsters.

This study tested whether light pulses with a dusklike offset or a dawnlike onset caused phase shifts of different sizes in the circadian wheel-running activity of Syrian hamsters, Mesocricetus auratus. Six experiments were conducted, each with 30 hamsters; the hamsters received first one type of pulse and then the other type a few weeks later, allowing a paired comparison. The six experiments represented the combination of two maximum light intensities (150 and 250 lux) and three zeitgeber times (ZTs) at which the pulses were given (ZT13.5, ZT14.5, and ZT20). Pulses were 30 minutes long, a relatively short duration to minimize circadian time effects. Aschoff's type II method of measuring phase shifts was used. In none of the six experiments did a two-tailed paired t test detect a significant difference in the size of phase shifts caused by dusklike versus dawnlike pulses. A three-way analysis of variance (ANOVA) on the combined data from all six experiments (with pulse type, pulse intensity, and ZT as factors) also failed to detect a significant effect of pulse type. Statistical power was calculated and found to be reasonably good. These negative results are in line with those of a previous study in which a different methodology was used.

Basal levels of adenosine modulate mGluR5 on rat hippocampal astrocytes.

Neuronal activity elicits increases in intracellular Ca2+ in astrocytes, which in turn can elevate neuronal Ca2+ and potentiate the efficacy of excitatory synaptic transmission. Therefore, understanding the modulation of astrocyte Ca2+ elevations by neurotransmitters should aid in understanding astrocyte-neuronal interactions. On cultured hippocampal microislands containing only astrocytes, activation of metabotropic glutamate receptors (mGluRs) with the specific agonist 1S,3R-ACPD triggers Ca2+ elevations that are potentiated by adenosine A1 receptor activation. A1 receptor modulation of mGluR-induced Ca2+ elevations is blocked by pertussis toxin and is mimicked by the wasp venom peptide mastoparan, suggesting that potentiation occurs by means of a G(i/o) mechanism. Surprisingly, on microislands containing only astrocytes, A1 receptor antagonism or adenosine degradation suppresses mGluR-triggered Ca2+ elevations, strongly suggesting that astrocytes are a source of physiologically relevant concentrations of adenosine.

Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold.

The magnitude of postsynaptic Ca(2+) transients is thought to affect activity-dependent synaptic plasticity associated with learning and memory. Large Ca(2+) transients have been implicated in the induction of long-term potentiation (LTP), while smaller Ca(2+) transients have been associated with long-term depression (LTD). However, a direct relationship has not been demonstrated between Ca(2+) measurements and direction of synaptic plasticity in the same cells, using one induction protocol. Here, we used glutamate iontophoresis to induce Ca(2+) transients in hippocampal CA1 neurons injected with the Ca(2+)-indicator fura-2. Test stimulation of one or two synaptic pathways before and after iontophoresis showed that the direction of synaptic plasticity correlated with glutamate-induced Ca(2+) levels above a threshold, below which no plasticity occurred (approximately 180 nM). Relatively low Ca(2+) levels (180-500 nM) typically led to LTD of synaptic transmission and higher levels (>500 nM) often led to LTP. Failure to show plasticity correlated with Ca(2+) levels in two distinct ranges: <180 nM and approximately 450-600 nM, while only LTD occurred between these ranges. Our data support a class of models in which failure of Ca(2+) transients to affect transmission may arise either from insufficient Ca(2+) to affect Ca(2+)-sensitive proteins regulating synaptic strength through opposing activities or from higher Ca(2+) levels that reset activities of such proteins without affecting the net balance of activities. Our estimates of the threshold Ca(2+) level for LTD (approximately 180 nM) and for the transition from LTD to LTP (approximately 540 nM) may assist in constraining the molecular details of such models.

Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.

Altered patterns of the 5-cytosine methylation of genomic DNA are associated with the development of a wide range of human cancers. We have studied the mechanisms and genetic pathways by which a targeted heterozygous deficiency in the murine 5-cytosine DNA methyltransferase gene (Dnmt1(N/+)) diminishes intestinal tumorigenesis in C57BL/6-multiple intestinal neoplasia (Min)/+ mice. We found that Dnmt1(N/+) retards the net growth rate of intestinal adenomas and reduces tumor multiplicity by approximately 50%. This tumor resistance affects the entire intestinal tract and is independent of the status of modifier of Min 1 and p53, two loci that have been found to confer strong resistance to Min-induced neoplasia Interestingly, Dnmt/(N/+) and modifier of Min 1 resistance interact synergistically, together virtually eliminating tumor incidence. This finding may provide an insight into potential combinatorial therapeutic approaches for treating human colon cancer.

The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64.

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during a screen for polymorphic modifiers of intestinal tumorigenesis in ApcMin/+ mice. Here, we demonstrate that the Mom1AKR allele consists of two genetic components. These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines. A second region, distal to Pla2g2a, has also been identified using fine structure recombinants. Pla2g2aAKR transgenic mice demonstrate a modest resistance to tumorigenesis in the small intestine and a very robust resistance in the large intestine. Moreover, the tumor resistance in the colon of Pla2g2aAKR animals is dosage-dependent, a finding that is consistent with our observation that Pla2g2a is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier demonstrate a modest tumor resistance that is confined to the small intestine. Thus, the phenotypes of these two modifier loci are complementary, both in their quantitative and regional effects. The additive effects and tight linkage of these modifiers may have been necessary for the initial identification of the Mom1 region.

Slow death of postnatal hippocampal neurons by GABA(A) receptor overactivation.

Neurotransmitters can have both toxic and trophic functions in addition to their role in neural signaling. Surprisingly, chronic blockade of GABA(A) receptor activity for 5-8 d in vitro enhanced survival of hippocampal neurons, suggesting that GABA(A) receptor overactivation may be neurotoxic. Potentiating GABA(A) receptor activity by chronic treatment with the endogenous neurosteroid (3alpha,5alpha)-3-hydroxypregnan-20-one caused massive cell loss over 1 week in culture. Other potentiators of GABA(A) receptors, including benzodiazepines, mimicked the cell loss, suggesting that potentiating endogenous GABA activity is sufficient to produce neuronal death. Neurosteroid-treated neurons had lower resting intracellular calcium levels than control cells and produced smaller calcium rises in response to depolarizing challenges. Manipulating intracellular calcium levels with chronic elevated extracellular potassium or with the calcium channel agonist Bay K 8644 protected neurons. The results may have implications for the mechanisms of programmed cell death in the developing CNS as well as implications for the long-term consequences of chronic GABAmimetic drug use during development.