Enabling conditions for an equitable and sustainable blue economy.

The future of the global ocean economy is currently envisioned as advancing towards a 'blue economy'-socially equitable, environmentally sustainable and economically viable ocean industries1,2. However, tensions exist within sustainable development approaches, arising from differing perspectives framed around natural capital or social equity. Here we show that there are stark differences in outlook on the capacity for establishing a blue economy, and on its potential outcomes, when social conditions and governance capacity-not just resource availability-are considered, and we highlight limits to establishing multiple overlapping industries. This is reflected by an analysis using a fuzzy logic model to integrate indicators from multiple disciplines and to evaluate their current capacity to contribute to establishing equitable, sustainable and viable ocean sectors consistent with a blue economy approach. We find that the key differences in the capacity of regions to achieve a blue economy are not due to available natural resources, but include factors such as national stability, corruption and infrastructure, which can be improved through targeted investments and cross-scale cooperation. Knowledge gaps can be addressed by integrating historical natural and social science information on the drivers and outcomes of resource use and management, thus identifying equitable pathways to establishing or transforming ocean sectors1,3,4. Our results suggest that policymakers must engage researchers and stakeholders to promote evidence-based, collaborative planning that ensures that sectors are chosen carefully, that local benefits are prioritized, and that the blue economy delivers on its social, environmental and economic goals.

Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus.

The precise function of specialized GABAergic interneuron subtypes is required to provide appropriate synaptic inhibition for regulating principal neuron excitability and synchronization within brain circuits. Of these, parvalbumin-type (PV neuron) dysfunction is a feature of several sex-biased psychiatric and brain disorders, although, the underlying developmental mechanisms are unclear. While the transcriptional action of sex hormones generates sexual dimorphism during brain development, whether kinase signaling contributes to sex differences in PV neuron function remains unexplored. In the hippocampus, we report that gephyrin, the main inhibitory post-synaptic scaffolding protein, is phosphorylated at serine S268 and S270 in a developmentally-dependent manner in both males and females. When examining GphnS268A/S270A mice in which site-specific phosphorylation is constitutively blocked, we found that sex differences in PV neuron density in the hippocampal CA1 present in WT mice were abolished, coincident with a female-specific increase in PV neuron-derived terminals and increased inhibitory input onto principal cells. Electrophysiological analysis of CA1 PV neurons indicated that gephyrin phosphorylation is required for sexually dimorphic function. Moreover, while male and female WT mice showed no difference in hippocampus-dependent memory tasks, GphnS268A/S270A mice exhibited sex- and task-specific deficits, indicating that gephyrin phosphorylation is differentially required by males and females for convergent cognitive function. In fate mapping experiments, we uncovered that gephyrin phosphorylation at S268 and S270 establishes sex differences in putative PV neuron density during early postnatal development. Furthermore, patch-sequencing of putative PV neurons at postnatal day 4 revealed that gephyrin phosphorylation contributes to sex differences in the transcriptomic profile of developing interneurons. Therefore, these early shifts in male-female interneuron development may drive adult sex differences in PV neuron function and connectivity. Our results identify gephyrin phosphorylation as a new substrate organizing PV neuron development at the anatomical, functional, and transcriptional levels in a sex-dependent manner, thus implicating kinase signaling disruption as a new mechanism contributing to the sex-dependent etiology of brain disorders.

Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice.

Goblet cells (GCs) are specialized cells of the intestinal epithelium contributing critically to mucosal homeostasis. One of the functions of GCs is to produce and secrete MUC2, the mucin that forms the scaffold of the intestinal mucus layer coating the epithelium and separates the luminal pathogens and commensal microbiota from the host tissues. Although a variety of ion channels and transporters are thought to impact on MUC2 secretion, the specific cellular mechanisms that regulate GC function remain incompletely understood. Previously, we demonstrated that leucine-rich repeat-containing protein 26 (LRRC26), a known regulatory subunit of the Ca2+-and voltage-activated K+ channel (BK channel), localizes specifically to secretory cells within the intestinal tract. Here, utilizing a mouse model in which MUC2 is fluorescently tagged, thereby allowing visualization of single GCs in intact colonic crypts, we show that murine colonic GCs have functional LRRC26-associated BK channels. In the absence of LRRC26, BK channels are present in GCs, but are not activated at physiological conditions. In contrast, all tested MUC2- cells completely lacked BK channels. Moreover, LRRC26-associated BK channels underlie the BK channel contribution to the resting transepithelial current across mouse distal colonic mucosa. Genetic ablation of either LRRC26 or BK pore-forming α-subunit in mice results in a dramatically enhanced susceptibility to colitis induced by dextran sodium sulfate. These results demonstrate that normal potassium flux through LRRC26-associated BK channels in GCs has protective effects against colitis in mice.

Shank3 deficits in the anteromedial bed nucleus of the stria terminalis trigger an anxiety phenotype in mice.

Anxiety disorders are the most prevalent co-morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co-occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours. Firstly, we characterize the developmental trajectories of locomotor, social behaviour and anxiety traits in a mouse model of ASD. We highlight that the anxiety phenotype is a late-onset emerging phenotype in mice with a Shank3Δe4-22 mutation. Consequently, we used an shRNA strategy to model Shank3 insufficiency in the bed nucleus of the stria terminalis (BNST), a brain region exerting a powerful control on anxiety level. We found that Shank3 downregulation in the anteromedial BNST (amBNST) induced anxiogenic effects and enhanced social avoidance after aversive social defeat. Associated with these behavioural defects, we showed alteration of glutamatergic synaptic functions in the amBNST induced by Shank3 insufficiency during adolescence. Our data strongly support the role of Shank3 in the maturation of amBNST, and its key role in anxiety control. Our results may further help to pave the road on a better understanding of the neuronal mechanisms underlying anxiety disorders implicated in ASDs.

Macroalgae exhibit diverse responses to human disturbances on coral reefs.

Scientists and managers rely on indicator taxa such as coral and macroalgal cover to evaluate the effects of human disturbance on coral reefs, often assuming a universally positive relationship between local human disturbance and macroalgae. Despite evidence that macroalgae respond to local stressors in diverse ways, there have been few efforts to evaluate relationships between specific macroalgae taxa and local human-driven disturbance. Using genus-level monitoring data from 1205 sites in the Indian and Pacific Oceans, we assess whether macroalgae percent cover correlates with local human disturbance while accounting for factors that could obscure or confound relationships. Assessing macroalgae at genus level revealed that no genera were positively correlated with all human disturbance metrics. Instead, we found relationships between the division or genera of algae and specific human disturbances that were not detectable when pooling taxa into a single functional category, which is common to many analyses. The convention to use percent cover of macroalgae as an indication of local human disturbance therefore likely obscures signatures of local anthropogenic threats to reefs. Our limited understanding of relationships between human disturbance, macroalgae taxa, and their responses to human disturbances impedes the ability to diagnose and respond appropriately to these threats.

RAB39B-mediated trafficking of the GluA2-AMPAR subunit controls dendritic spine maturation and intellectual disability-related behaviour.

Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson's disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca2+-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice. The persistence of immature circuits is triggered by increased hypermobility of the spine, which is restored by the Ca2+-permeable AMPAR antagonist NASPM. Together, these data confirm that RAB39B controls AMPAR trafficking, which in turn plays a pivotal role in neuronal dendritic spine remodelling and that targeting Ca2+-permeable AMPARs may highlight future pharmaceutical interventions for RAB39B-associated disease conditions.

LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells.

The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca2+- and voltage-activated large conductance Ca2+-activated K+ channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (-60 mV) even in the absence of intracellular Ca2+ elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca2+ channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat-containing (LRRC) regulatory γ subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs from Lrrc26 knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs from Lrrc52 KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK α subunits shifts BK current gating about -90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning.

Effects of Early Life Exposure to Sex Hormones on Neurochemical and Behavioral Responses to Psychostimulants in Adulthood: Implications in Drug Addiction.

Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.

Cloudiness reduces the bleaching response of coral reefs exposed to heat stress.

Climate change and warming ocean temperatures are a threat to coral reef ecosystems. Since the 1980s, there has been an increase in mass coral bleaching and associated coral mortality due to more frequent and severe thermal stress. Although most research has focused on the role of temperature, coral bleaching is a product of the interacting effects of temperature and other environmental variables such as solar radiation. High light exacerbates the effects of thermal stress on corals, whereas reductions in light can reduce sensitivity to thermal stress. Here, we use an updated global dataset of coral bleaching observations (n = 35,769) from 1985 to 2017 and satellite-derived datasets of SST and clouds to examine for the first time at a global scale the influence of cloudiness on the likelihood of bleaching from thermal stress. We find that among coral reefs exposed to severe bleaching-level heat stress (Degree Heating Weeks >8°Cˑweek), bleaching severity is inversely correlated with the interaction of heat stress and cloud fraction anomalies (p < 0.05), such that higher cloudiness implies reduced bleaching response. A Random Forest model analysis employing different set of environmental variables shows that a model employing Degree Heating Weeks and the 30-day cloud fraction anomaly most accurately predicts bleaching severity (Accuracy = 0.834; Cohen's Kappa = 0.769). Based on these results and global warm-season cloudiness patterns, we develop a 'cloudy refugia' index which identifies the central equatorial Pacific and French Polynesia as regions where cloudiness is most likely to protect corals from bleaching. Our findings suggest that incorporating cloudiness into prediction models can help delineate bleaching responses and identify reefs which may be more resilient to climate change.

DIA-DB: A Database and Web Server for the Prediction of Diabetes Drugs.

The DIA-DB is a web server for the prediction of diabetes drugs that uses two different and complementary approaches: (a) comparison by shape similarity against a curated database of approved antidiabetic drugs and experimental small molecules and (b) inverse virtual screening of the input molecules chosen by the users against a set of therapeutic protein targets identified as key elements in diabetes. As a proof of concept DIA-DB was successfully applied in an integral workflow for the identification of the antidiabetic chemical profile in a complex crude plant extract. To this end, we conducted the extraction and LC-MS based chemical profile analysis of Sclerocarya birrea and subsequently utilized this data as input for our server. The server is open to all users, registration is not necessary, and a detailed report with the results of the prediction is sent to the user by email once calculations are completed. This is a novel public domain database and web server specific for diabetes drugs and can be accessed online through http://bio-hpc.eu/software/dia-db/.

Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms.

Roles of Na+, Ca2+, and K+ channels in the generation of repetitive firing and rhythmic bursting in adrenal chromaffin cells.

Adrenal chromaffin cells (CCs) are the main source of circulating catecholamines (CAs) that regulate the body response to stress. Release of CAs is controlled neurogenically by the activity of preganglionic sympathetic neurons through trains of action potentials (APs). APs in CCs are generated by robust depolarization following the activation of nicotinic and muscarinic receptors that are highly expressed in CCs. Bovine, rat, mouse, and human CCs also express a composite array of Na+, K+, and Ca2+ channels that regulate the resting potential, shape the APs, and set the frequency of AP trains. AP trains of increasing frequency induce enhanced release of CAs. If the primary role of CCs is simply to relay preganglionic nerve commands to CA secretion, why should they express such a diverse set of ion channels? An answer to this comes from recent observations that, like in neurons, CCs undergo complex firing patterns of APs suggesting the existence of an intrinsic CC excitability (non-neurogenically controlled). Recent work has shown that CCs undergo occasional or persistent burst firing elicited by altered physiological conditions or deletion of pore-regulating auxiliary subunits. In this review, we aim to give a rationale to the role of the many ion channel types regulating CC excitability. We will first describe their functional properties and then analyze how they contribute to pacemaking, AP shape, and burst waveforms. We will also furnish clear indications on missing ion conductances that may be involved in pacemaking and highlight the contribution of the crucial channels involved in burst firing.

Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats.

We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 µL); DHT (dihydrotestosterone of 1.0 mg/50 µL); EV (estradiol valerate of 0.1 mg/50 µL); and control (sesame oil of 50 µL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.

Public views on tourist beach environment from multinational countries and ensuing changes during global epidemic.

The continuous endemic of the new SARS-CoV-2 virus brought a halt to the world's activities from February 2020. Our study intends to gauge public perceptions on the consequences of post-pandemic changes on the marine environment, particularly as they are related to tourist beach amenities. Totally, 16 nations' knowledge and views on various environmental viewpoints over the effects of epidemic were gathered through public polls live on social media during social confinement in 2020. The results indicate that around 85% of respondents were most concerned about the alarming sights of widespread plastic trash and the increase of dangerous biomedical wastes through wastewater in the marine ecosystem. The outcomes of this study will undoubtedly aid in the establishment of a management strategy and for future studies on the consequences of any epidemic on the beaches.

All G protein ßγ complexes are capable of translocation on receptor activation.

Heterotrimeric G proteins transduce signals sensed by transmembrane G protein coupled receptors (GPCRs). A subfamily of G protein ßγ subunit types has been shown to selectively translocate from the plasma membrane to internal membranes on receptor activation. Using 4D imaging we show here that Gßγ translocation is not restricted to some subunit types but rather all 12 members of the family of mammalian γ subunits are capable of supporting ßγ translocation. Translocation kinetics varies widely depending on the specific γ subunit type, with t(1/2) ranging from 10s to many minutes. Using fluorescence complementation, we show that the ß and γ subunits translocate as ßγ dimers with kinetics determined by the γ subunit type. The expression patterns of endogenous γ subunit types in HeLa cells, hippocampal neurons and cardiomyocytes are distinctly different. Consistent with these differences, the ßγ translocation rates vary widely. ßγ translocation rates exhibit the same γ subunit dependent trends regardless of the specific receptor type or cell type showing that the translocation rates are intrinsic to the γ subunit types. ßγ complexes with widely different rates of translocation had differential effects on muscarinic stimulation of GIRK channel activity. These results show that G protein ßγ translocation is a general response to activation of GPCRs and may play a role in regulating signaling activity.

The exciting side of unconventional glycine receptors.

In this issue of Neuron, Bossi, Dhanasobhon, and colleagues uncover the functional relevance of GluN1/GluN3A excitatory glycine receptors (eGlyRs) in the neocortex and amygdala. This study provides exciting new insights into the role of unconventional eGlyRs in brain function.

Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice.

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA). We observed that SC-VTA neurons display social interaction anticipatory calcium activity, which correlates with orienting responses towards an unfamiliar conspecific. In contrast, mPFC-VTA neuron population activity increases after initiation of the social contact. While protracted phasic stimulation of SC-VTA pathway promotes head/body movements and decreases social interaction, inhibition of this pathway increases social interaction. Here, we found that SC afferents mainly target a subpopulation of dorsolateral striatum (DLS)-projecting VTA dopamine (DA) neurons (VTADA-DLS). While, VTADA-DLS pathway stimulation decreases social interaction, VTADA-Nucleus Accumbens stimulation promotes it. Altogether, these data support a model by which at least two largely anatomically distinct VTA sub-circuits oppositely control distinct aspects of social behaviour.

Stressor-response functions as a generalizable model for context dependence.

Defining the context dependence of ecological states or processes is a fundamental goal of ecology. Stressor-response functions are the quantitative representation of context dependence, where the context (environmental contingency) is defined by location on the stressor (x) axis, and represents a unifying concept in biological science.

Collapse and recovery of seafood wholesale prices in time of COVID-19.

The COVID-19 pandemic has spread around the world, disrupting economies, societies and daily life. Early research anticipated significant negative impacts for the globalized seafood supply network. Here, we explore the impact of the COVID-19 pandemic on wholesale prices from five major seafood markets around the world. An anomalies analysis was used to establish a 5-year baseline price for each commodity. Daily price data from 2020 were compared to the baseline to identify collapses (>1.96 SE from baseline) and analyse collapse characteristics (timing, duration and magnitude). Non-uniform price collapses were observed across, and within, the markets analysed. Toyosu (Tokyo) Market experienced price collapses to 51% of commodities, Rungis (Paris) 36%, Mercamadrid (Madrid) 19%, Mercado La Nueva Viga (Mexico City) 35% and the Portland Fish Exchange (Portland, Maine) 32%. Collapse magnitude varied from 11% to 79% of the 5-year average price. Average collapse duration ranged from 13 to 24 weeks with some commodities (4%-22%) remaining collapsed at the end of 2020. For markets where volume data were available, collapses were also noted (59% of commodities in Toyosu, 10% in Mercamadrid and 19% in Portland Fish Exchange); in these cases, the volume collapse was more severe than the related price collapse. To better detect, anticipate and respond to future shocks, we recommend that relevant government agencies conduct comprehensive economic reviews of the COVID-19 pandemic throughout the seafood supply chain, including the outcomes of emergency measures, short- and long-term implications of market volatility and identify areas of supply and labour vulnerabilities.

Inferring pollution records in sediment cores from transitional environments of Marquelia coast, Guerrero, Mexico.

The vertical distribution pattern and concentrations of elements (Fe, Al, Ca, Mg, Mn, Cr, Cu, Ni, Co, Pb, Zn, and As) in the estuarine and lagoon region of Marquelia coast, Guerrero, Mexico, were studied to comprehend the origin and pollutant phases of geochemical elements. Henceforth, two sediment core samples [C1 (127 cm) and C2 (110 cm)] were collected to assess the pollution status using geochemical indices, namely anthropogenic factor (AF), enrichment factor (EF), and geoaccumulation index (Igeo). Additionally, the elemental concentrations were compared with the sediment quality guidelines (SQGs) to examine the potential risks to biota. Among the two depositional environments, the sediments of lagoon Apozahualco exhibited higher concentrations of elements. The granulometry characteristics of sediment grains also attested that the concentration and mobilization of metals are largely governed by the fine-grained fractions. Major elemental concentration and grain size changes were identified at several depths (30-40, 60-70, and 90-100 cm) revealing the internal hydrodynamic condition. The overall assessment of geochemical indices revealed that the sediments were unpolluted to moderately polluted. The anthropogenic factor indicated that the upper portion of the sediments were affected by anthropogenic influences. The comparison of trace element concentration with SQGs denoted that Cr, Ni, and As could pose potential adverse effect to the organisms that live in and near the sedimentary environment. Factor analysis revealed the origin and behaviour of the studied elements during transportation and deposition processes in both the ecosystems (i.e. estuary and lagoon). The results of this study provided an in-depth understanding of variations in elemental concentration and pollution status of sediment profile in coastal transitional environments that would aid in sustainable management.