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Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more odd-chain long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial β-oxidation in liver or other tissues.

Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more “odd-chain” long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial β-oxidation in liver or other tissues.

ObjectivesDespite the success of cochlear implant (CI) surgery for hearing restoration, reducing CI electrode insertion forces is an ongoing challenge with the goal to further reduce post-implantation hearing loss. While research in this field shows that both friction and quasistatic pressure forces occur during CI insertion, there is a lack of studies distinguishing between these origins. The present study was conducted to analyze the contribution of both force phenomena during automated CI insertion.MethodsFive MED-EL FLEX28 CI electrode arrays were inserted into both a regular and uncoiled version of the same average scala tympani (ST). Both ST models had a pressure release hole at the apical end, which was kept open or closed to quantify pressure forces. ST models were filled with different sodium dodecyl sulfate (SDS) lubricants (1, 5, and 10% SDS, water). The viscosity of lubricants was determined using a rheometer. Insertions were conducted with velocities ranging from v= 0.125 mm/s to 2.0 mm/s.ResultsViscosity of SDS lubricants at 20°C was 1.28, 1.96, and 2.51 mPas for 1, 5, and 10% SDS, respectively, which lies within the values reported for human perilymph. In the uncoiled ST model, forces remained within the noise floor (maximum: 0.049 × 10−3 N ± 1.5 × 10−3 N), indicating minimal contribution from quasistatic pressure. Conversely, forces using the regular, coiled ST model were at least an order of magnitude larger (minimum: Fmax = 28.95 × 10−3 N, v = 1 mm/s, 10% SDS), confirming that friction forces are the main contributor to total insertion forces. An N-way ANOVA revealed that both lubricant viscosity and insertion speed significantly reduce insertion forces (p

Purpose of reviewThis study aimed to discuss the use of the pulse stable isotope tracer approach to study changes in metabolism in healthy individuals and critically ill patients.Recent findings and conclusionWe found that in the postabsorptive state and healthy condition, intracellular protein breakdown and net intracellular protein breakdown, when calculated using the pulse tracer approach, are about double what has previously been reported using the more traditional primed-constant and continuous stable isotope approaches (600 versus 300 grams of protein/day). In critically ill patients, protein breakdown is even higher and calculated to be approximately 900 grams of protein/day, using the pulse tracer approach. Based on these data, we hypothesize that reducing protein breakdown in the postabsorptive state is key when trying to improve the condition of critically ill patients. Moreover, we also used the pulse tracer approach during feeding to better estimate the intracellular metabolic response to feeding. Our first observation is that endogenous protein breakdown does not seem to be reduced during feeding. We also have shown that when consuming a meal with a certain amount of protein, the biological value of that protein meal can be calculated with the pulse tracer approach. In conclusion, using the pulse stable isotope tracer approach to study protein kinetics in the postabsorptive state and during feeding expands our understanding of how dietary proteins can affect human protein metabolism. The intracellular protein synthesis stimulatory effect of a meal is an important factor to consider when calculating the exact protein requirements and needs, particularly in critical illness.

Abstract The mass production of plastic waste has caused an urgent worldwide public health crisis. Although government policies and industrial innovation are the driving forces to meet this challenge, trying to understand public attitudes may improve the efficiency of this process. Social media has become the main ways for the public to obtain information and express opinions and feelings. This motivated us to mine the perceptions and behavioral responses towards plastic usage using social media data. In this paper, we proposed a framework for data collection and analysis based on mainstream media in the UK to obtain public opinions on plastics. An unsupervised machine learning model based on Latent Dirichlet Allocation (LDA) has been employed to analyse and cluster the topics to deal with the lack of annotation of the data contents. An additional dictionary method was then proposed to evaluate the sentiment of the comments. The framework also provides tools to visualise the model and results to stimulate insightful understandings. We validated the framework's effectiveness by applying it to analyse three mainstream social media, where 6 first-level topic categories and 13 second-level topic categories from the comment texts related to plastics have been identified. The results show that public sentiment towards plastic products is generally stable. The spatiotemporal distribution of each topic's sentiment is highly correlated with the number of occurrences.

Sarcoptic mange, caused by Sarcoptes scabiei, is a disease that affects many species of mammals, including several wild ungulate species in the region of the European Alps, especially the Alpine chamois and the Alpine ibex, which act as parasite reservoirs. Here records of mange in alpine wild ungulates and its spread over time across the eastern parts of the European Alps are reviewed. First cases were recorded from Austria in 1824, and epizootic outbreaks have been described since then from the mountainous regions of Austria (mostly Tyrol, Carinthia, and Styria), Germany (Bavaria), Italy (Udine and Trentino) and Slovenia. Switzerland, by contrast, has so far been free of mange except for cases in wild boar, indicating that this species is not a reservoir host of sarcoptic mites for other ungulate species in the European Alps, and that, so far, the disease in ruminant ungulates is restricted to the eastern and central parts of the Alps. Mutual transmission among wild and domestic ruminants is possible and, together with the protection of vulnerable wildlife, is also a reason for monitoring and, if necessary, intervention to contain mange outbreaks.

The general factor of psychopathology (GP, or p factor) and the Dysregulation Profile (DP) are two conceptually similar, but independently developed approaches to understand psychopathology. GP and DP models and their stability, antecedents and outcomes are studied in a longitudinal sample of 1073 children (49.8% female). GP and DP models were estimated at ages 8 and 14 years using the parent-reported Child Behavior Checklist (CBCL) and Youth Self Report (YSR). Early childhood antecedents and adolescent outcomes were derived using a multi-method multi-informant approach. Results showed that the general GP and DP had similar key symptoms and were similarly related to early-childhood antecedents (e.g., lower effortful control, higher maternal depression) and adolescent outcomes (e.g., reduced academic functioning, poorer mental health). This study demonstrates that GP and DP are highly similar constructs in middle childhood and adolescence, both describing a general vulnerability for psychopathology with (emotional) dysregulation at its core. Scientific integration of these approaches could lead to a better understanding of the structure, antecedents and outcomes of psychopathology.

Abstract Background Abdominal obesity (AO) is linked to reduced health status and mortality. While it is known that AO is prevalent in chronic obstructive pulmonary disease (AO-COPD), the specific metabolic and functional consequences associated with AO-COPD remain understudied. Methods We studied 199 older adults with COPD and 168 control subjects with and without AO and assessed visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry. VAT > 70th percentile of the control group qualified a subject as AO in a sex specific manner. We measured plasma concentrations and whole body production (WBP) rates of multiple amino acids to assess the metabolic profile. We assessed medical history, body composition by Dual-Energy X-ray Absorptiometry, muscle strength, and cognitive function. We performed statistics by analysis of covariance (p) and FDR (q) for multiple comparisons. Results AO-COPD subjects had 27% more VAT (q

Chemical production is set to become the single largest driver of global oil consumption by 2030. To reduce oil consumption and resulting greenhouse gas (GHG) emissions, carbon dioxide can be captured from stacks or air and utilized as alternative carbon source for chemicals. Here, we show that carbon capture and utilization (CCU) has the technical potential to decouple chemical production from fossil resources, reducing annual GHG emissions by up to 3.5 Gt CO2-eq in 2030. Exploiting this potential, however, requires more than 18.1 PWh of low-carbon electricity, corresponding to 55% of the projected global electricity production in 2030. Most large-scale CCU technologies are found to be less efficient in reducing GHG emissions per unit low-carbon electricity when benchmarked to power-to-X efficiencies reported for other large-scale applications including electro-mobility (e-mobility) and heat pumps. Once and where these other demands are satisfied, CCU in the chemical industry could efficiently contribute to climate change mitigation.

Abstract Low muscle mass is prevalent among patients with cancer and a predictor of adverse clinical outcomes. To counteract muscle loss, β‐hydroxy β‐methylbutyrate (HMB) supplementation has been proposed as a potential therapy for older adults and various diseases states. This systematic review aimed to investigate the effects and safety of HMB supplementation in relation to muscle mass and function and other clinical outcomes in patients with cancer. A systematic search of MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, ProQuest, and grey literature for reports published from inception to December 2021 was conducted. Included studies provided supplements containing any dose of HMB to adult patients with active cancer. A synthesis without meta‐analysis was conducted using a vote‐counting approach based solely on the direction of the effect (i.e. regardless of statistical significance). Risk of bias was assessed for each outcome domain, and evidence from higher‐quality studies (i.e. those with either low or moderate risk of bias) was examined. Safety was evaluated using both lower‐quality and higher‐quality studies. Fifteen studies were included, in which six were randomized controlled trials in patients with various cancer types and treatments. Studies prescribed HMB combined with amino acids (73.3%), HMB in oral nutritional supplements (20.0%), or both supplement types (6.7%); Ca‐HMB doses of 3.0 g/day were provided in 80.0% of the studies. Four studies had high risk of bias across all outcome domains. Considering the higher‐quality studies, evidence of a beneficial effect of HMB supplementation was found in four of four studies for muscle mass, two of two for muscle function, three of three for hospitalization, and five of seven for survival. In contrast, no beneficial effects of HMB on quality of life or body weight was found in two of four and three of five studies, respectively. A limited number of higher‐quality studies evaluating the impact of HMB on cancer therapy‐related toxicity, inflammation, and tumour response were observed. No serious adverse effects directly related to the nutrition intervention were reported. Although limited, current evidence suggests that HMB supplementation has a beneficial effect on muscle mass and function in patients with cancer. Well‐designed trials are needed to further explore the clinical benefit of HMB supplementation in this patient population.

Older adults are at risk for muscle and cognitive function decline during advanced aging, but the underlying metabolic mechanisms and the role of aging-associated chronic morbidities remain unclear. In the present study, we examined whether protein and amino acid kinetics in older adults with and without chronic morbidities are different when 50–70 and 70–90 of age and related to markers of muscle and brain health declines. In a large cross-sectional observational study, 575 older adults from 12 trials (2014–2022) were stratified based on their age (50-70y vs. 70-95y) and the presence of chronic morbidities. The main outcomes were whole-body production (WBP) and interconversions of amino acids by stable amino acid tracers, body composition, and muscle and cognitive performance. Additionally, the association between metabolic markers and muscle and brain health was assessed. Overall lower muscle strength, muscle and fat mass, and cognitive function (p < 0.03), but no mood disturbances, were found in 70–95y compared to 50-70y older adults. Presence of morbidities was associated with lower muscle strength and mass, and cognitive function, but higher visceral adipose tissue, and mood disturbances (p < 0.05). Aging was associated with suppressed WBP of most amino acids, de novo arginine production, and net protein breakdown, but higher myofibrillar protein breakdown (p < 0.007). Presence of morbidities was associated with lower WBP of glutamine, glutamate, histidine, isoleucine, phenylalanine, tyrosine, and net protein breakdown, and higher WBP of valine and taurine (p < 0.04). Age showed significant negative correlations with WBP of nearly all amino acids, de novo arginine production and net protein breakdown (r: [-0.407, −0.136], p < 0.01) but a positive correlation with WBP of myofibrillar protein breakdown (r = 0.133, p = 0.009). Lean mass showed positive correlations with de novo arginine production and net protein breakdown and WBP of all amino acids except for isoleucine (r: [0.16, 0.799], p < 0.005). MoCA showed a positive correlation with WBP of leucine and valine (r: [0.163, 0.2], p < 0.03). Worse cognitive performance was positively associated with WBP of tau-methylhistidine and taurine (r: [0.13, 0.141], p < 0.04), but negatively associated with WBP of glycine and valine, de novo arginine production, and net protein breakdown (r: [-0.222, −0.115], p < 0.05). Comprehensive phenotyping of a large group of older adults revealed differences in metabolic health in response to advanced aging and chronic morbidities. Poor muscle health accompanied by advanced aging was associated with overall metabolic downregulation, except for enhanced myofibrillar (muscle) protein breakdown. Presence of chronic morbidities was further associated with disturbed muscle health, mood, arginine, and taurine pathways, and higher visceral adipose tissue. Therefore, different phenotypes among older adults need to be considered when evaluating therapeutic approaches to improve muscle and brain health. [ABSTRACT FROM AUTHOR]

As internalizing and externalizing problems often co-occur, the current study utilized a longitudinal dataset of 784 at-risk children (predominantly from low-income families and academically at-risk; 52.6% male) followed yearly from Grade 1 to Grade 12 to: (a) explore the heterogeneity in the codevelopment patterns of internalizing and externalizing problems by using a person-centered approach, and (b) investigate early childhood antecedents that might explain differentiated codevelopmental patterns. The antecedents consisted of individual (i.e., ego-resilient personality, intelligence, language ability, gender, and ethnicity) and contextual factors (i.e., maternal support and responsiveness, family socioeconomic adversity, teacher-child relationship conflict, and peer rejection). We identified 4 distinct codevelopment patterns including a chronic co-occurring group (30.1%), a moderate co-occurring group (28.5%), a pure-externalizing group (18.6%), and a low-risk group (22.8%). While children who belonged to any of the 3 higher risk groups exhibited more adverse early childhood antecedents compared with the low-risk group, the chronic co-occurring group displayed the most severe profiles of early childhood antecedents compared with the moderate co-occurring and the pure-externalizing groups. Common antecedents for the 3 higher risk groups were lower ego-resilient personality, higher teacher-child relationship conflict, being male, and being African American. Low language ability and peer rejection were identified as unique antecedents for the chronic co-occurring group.

Abstract Background Self-efficacy, individuals’ beliefs regarding their capacities to perform actions or control (potentially stressful or novel) events, is thought to be important for various life domains. Little however is known about its early precursors. This study examined the predictive effects of childhood personality and parental behaviors (i.e., overreactive discipline and warmth) for general self-efficacy in young adulthood. Furthermore, it was examined whether personality and parenting behaviors interacted and whether these interactions supported the diathesis-stress or differential susceptibility model. These aims were examined in an 11-year prospective study of 336 participants (M age at T1 = 10.83 years, range = 9–12 years, 53.9% girls). Personality and parental behaviors were reported at T1 by both mothers and fathers, whereas self-efficacy was self-reported at T2 11 years later. Hypotheses were tested in Mplus using multilevel structural equation modeling. Results Results revealed that (only) emotional stability, and not parenting, predicted higher self-efficacy 11 years later. Benevolence functioned as a susceptibility marker in the association between overreactivity and self-efficacy. Conclusions The results show that childhood emotional stability is an important long-term predictor of self-efficacy, even into emerging adulthood. Moreover, the integration of individual differences in models of parenting effects may further improve our understanding of early adults’ adjustment.

Abstract Background Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. Methods Seventy-eight outpatients with moderate to severe COPD (GOLD II–IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC–MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. ɑ

Short-term (4 weeks) supplementation with n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has recently been shown to improve protein metabolism in a dose dependent way in normal weight patients with Chronic Obstructive Pulmonary Disease (COPD). Furthermore, EPA/DHA supplementation was able to increase extremity lean soft tissue but not muscle function. No studies are available combining n-3 PUFAs and the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) supplementation in chronic clinical conditions. Whether adding HMB to daily EPA/DHA supplementation for 10 weeks enhances muscle and brain health, daily functional performance, and quality of life of patients with COPD by further improving their protein and amino acid homeostasis remains unknown. Patients with COPD (GOLD: II-IV, n = 46) received daily for 10 weeks, according to a randomized double-blind placebo-controlled three-group design, EPA/DHA (n = 16), EPA/DHA to which HMB was added (n = 14), or placebo (n = 16). The daily dose of 2.0 g of EPA/DHA or soy + corn oil as the placebo was provided via gel capsules, and 3.0 g of Ca-HMB or maltodextrin as placebo as powders. At pre- and post-intervention, a pulse mixture of multiple amino acids was administered to measure postabsorptive net protein breakdown (netPB as primary endpoint) and whole body production (WBP) and conversion rates of the amino acids. As secondary endpoints, lean soft tissue and fat mass were assessed by dual-energy X-ray absorptiometry, upper and lower muscle function by handgrip and single leg isokinetic dynamometry, brain (cognitive, wellbeing) health by assessments, daily functional performance by measuring 6-min walk distance, 4-m gait speed, and postural balance, and quality of life by questionnaire. Plasma enrichments and concentrations were analyzed by LC-MS/MS, and systemic inflammatory profile and metabolic hormones by Luminex. HMB + EPA/DHA but not EPA/DHA supplementation increased postabsorptive netPB (p = 0.028), and WBPs of glutamine (p = 0.024), taurine (p = 0.039), and tyrosine (p = 0.036). Both EPA/DHA and HMB + EPA/DHA supplementation resulted in increased WBP of phenylalanine (p < 0.05). EPA/DHA but not HMB + EPA/DHA was able to increase WBP of arginine (p = 0.030), citrulline (p = 0.008), valine (p = 0.038), and conversion of citrulline to arginine (p = 0.009). Whole body and extremity fat mass were reduced after HMB + EPA/DHA supplementation only, whereas lean soft tissue was increased after EPA/DHA (p = 0.049) and HMB + EPA/DHA (p = 0.073). No other significant findings were observed. Reductions in several proinflammatory cytokines were observed in the HMB + EPA/DHA group including IL-2, IL-17, IL-6, IL-12P40, and TNF-β (p < 0.05). Ten weeks of supplementation with 2 g of EPA/DHA daily is sufficient to induce muscle gain in COPD but HMB is needed to induce fat loss. Whether HMB is solely responsible for the fat mass loss or has a synergistic effect with EPA/DHA remains unclear. The increase in net protein breakdown observed with HMB + EPA/DHA supplementation may indicate a beneficial enhanced protein turnover cycling associated with increased lean soft tissue. ClinicalTrials.gov; NCT03796455. [ABSTRACT FROM AUTHOR]

Optimization models can support decision-makers in the synthesis and operation of multi-sector energy systems. To identify the optimal design and operation of a low-carbon system, we need to consider high temporal and spatial variability in the electricity supply, sector coupling, and environmental impacts over the whole life cycle. Incorporating such aspects in optimization models is demanding. To avoid redundant research efforts and enhance transparency, the developed models and used data sets should be shared openly. In this work, we present the SecMOD framework for multi-sector energy system optimization incorporating life-cycle assessment (LCA). The framework allows optimizing multiple sectors jointly, ranging from industrial production and their linked energy supply systems to sector-coupled national energy systems. The framework incorporates LCA to account for environmental impacts. We hence provide the first open-source framework to consistently include a holistic life-cycle perspective in multi-sector optimization by a full integration of LCA. We apply the framework to a case-study of the German sector-coupled energy system. Starting with few base technologies, we demonstrate the modular capabilities of SecMOD by the stepwise addition of technologies, sectors and existing infrastructure. Our modular open-source framework SecMOD aims to accelerate research for sustainable energy systems by combining multi-sector energy system optimization and life-cycle assessment.

Over the past decade, the term bioeconomy has emerged in both policy and academic discourse. Implying a technology-driven approach to wealth generation from organic materials, the term has taken hold with so far limited critical engagement. It is a contestable rather than contested term. Noting the rise of numerous other ‘economies’ (blue, green, circular) on a similar timeframe, this paper undertakes a critical discourse analysis of academic literature and UK/EU policy documents using the term ‘bioeconomy’ to produce a contextualised understanding of how it is used in both theoretical and practical contexts. Our analysis shows that bioeconomy, as with the other ‘sustainability’ economies, which we term the ‘S-economies’, prioritises the economy and the markets as the solution brokers for the environmental and economic problems they seek to address. The apparent fragmentation of the theory and policy concerning the environmental sustainability of economic activity is expressed through the variability of terms that aspire to establish multiple economies functioning at the same time. Limited empirical analysis of the existing ‘bioeconomy’ is symptomatic of the dissociation between theory and practice, emphasizing technological approaches favouring capital intensive approaches over local solutions. The S-economies, including the bioeconomy, are an attempt to bypass economic structural realities that otherwise would need to be addressed.

Modern electrophysiological recordings simultaneously capture single-unit spiking activities of hundreds of neurons spread across large cortical distances. Yet, this parallel activity is often confined to relatively low-dimensional manifolds. This implies strong coordination also among neurons that are most likely not even connected. Here, we combine in vivo recordings with network models and theory to characterize the nature of mesoscopic coordination patterns in macaque motor cortex and to expose their origin: We find that heterogeneity in local connectivity supports network states with complex long-range cooperation between neurons that arises from multi-synaptic, short-range connections. Our theory explains the experimentally observed spatial organization of covariances in resting state recordings as well as the behaviorally related modulation of covariance patterns during a reach-to-grasp task. The ubiquity of heterogeneity in local cortical circuits suggests that the brain uses the described mechanism to flexibly adapt neuronal coordination to momentary demands.