Dissecting the components of error in analogue report tasks.

Over the last two decades, the analogue report task has become a standard method for measuring the fidelity of visual representations across research domains including perception, attention, and memory. Despite its widespread use, there has been no methodical investigation of the different task parameters that might contribute to response variability. To address this gap, we conducted two experiments manipulating components of a typical analogue report test of memory for colour hue. We found that human response errors were independently affected by changes in storage and maintenance requirements of the task, demonstrated by a strong effect of set size even in the absence of a memory delay. In contrast, response variability remained unaffected by physical size of the colour wheel, implying negligible contribution of motor noise to task performance, or by its chroma radius, highlighting non-uniformity of the standard colour space. Comparing analogue report to a matched forced-choice task, we found variation in adjustment criterion made a limited contribution to analogue report variability, becoming meaningful only with low representational noise. Our findings validate the analogue report task as a robust measure of representational fidelity for most purposes, while also quantifying non-representational sources of noise that would limit its reliability in specialized settings.

The association between abcb1 gene polymorphism and clopidogrel response variability in stroke ischemic: a cross sectional study.

BACKGROUND: Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency. METHODS: A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95-208 PRU), and bleeding risk (< 95 PRU). RESULTS: 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 - 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively. CONCLUSION: ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.

Gut microbial ß-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.

Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial ß-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation. We demonstrate that a range of FDA-approved drugs prevent this reactivation by intercepting the catalytic cycle of the enzymes in a conserved fashion. Finally, we find that inhibiting GUS in conventional mice reduces free serotonin and increases its inactive glucuronide in the serum and intestines. Our results illuminate the indispensability of gut microbial enzymes in sustaining endobiotic homeostasis and indicate that therapeutic disruptions of this metabolism promote interindividual response variabilities.

Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes.

Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185-80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.

Age-related contextual cueing features are more evident in reaction variability than in reaction time.

Visual-spatial contextual cueing learning underpins the daily lives of older adults, enabling them to navigate their surroundings, perform daily activities, and maintain cognitive function. While the contextual cueing effect has received increasing attention from researchers, the relationship between this cognitive ability and healthy ageing remains controversial. To investigate whether visual-spatial contextual cueing learning declines with age, we examined the contextual learning patterns of older (60-71 years old) and younger adults (18-26 years old) using a contextual-guided visual search paradigm and response variability measurements. We observed significant contextual learning effects in both age groups, impacting response speed and variability, with these effects persisting for at least 24 days. However, older adults required more repetitions and memorised fewer repeated stimuli during initial learning. Interestingly, their long-term memory maintenance appeared stronger, as their contextual facilitation persisted in both response speed and variability, while younger adults only persisted in response speed but not variability. Overall, our results suggest an age-related complex and diverse contextual cueing pattern, with older adults showing weaker learning but stronger long-term memory maintenance compared with younger adults.

Induction of excitatory brain state governs plastic functional changes in visual cortical topology.

Adult visual plasticity underlying local remodeling of the cortical circuitry in vivo appears to be associated with a spatiotemporal pattern of strongly increased spontaneous and evoked activity of populations of cells. Here we review and discuss pioneering work by us and others about principles of plasticity in the adult visual cortex, starting with our study which showed that a confined lesion in the cat retina causes increased excitability in the affected region in the primary visual cortex accompanied by fine-tuned restructuring of neuronal function. The underlying remodeling processes was further visualized with voltage-sensitive dye (VSD) imaging that allowed a direct tracking of retinal lesion-induced reorganization across horizontal cortical circuitries. Nowadays, application of noninvasive stimulation methods pursues the idea further of increased cortical excitability along with decreased inhibition as key factors for the induction of adult cortical plasticity. We used high-frequency transcranial magnetic stimulation (TMS), for the first time in combination with VSD optical imaging, and provided evidence that TMS-amplified excitability across large pools of neurons forms the basis for noninvasively targeting reorganization of orientation maps in the visual cortex. Our review has been compiled on the basis of these four own studies, which we discuss in the context of historical developments in the field of visual cortical plasticity and the current state of the literature. Overall, we suggest markers of LTP-like cortical changes at mesoscopic population level as a main driving force for the induction of visual plasticity in the adult. Elevations in excitability that predispose towards cortical plasticity are most likely a common property of all cortical modalities. Thus, interventions that increase cortical excitability are a promising starting point to drive perceptual and potentially motor learning in therapeutic applications.

Sustained selective attention in adolescence: Cognitive development and predictors of distractibility at school.

Despite much research into the development of attention in adolescence, mixed results and between-task differences have precluded clear conclusions regarding the relative early or late maturation of attention abilities. Moreover, although adolescents constantly face the need to pay attention at school, it remains unclear whether laboratory measures of attention can predict their ability to sustain attention focus during lessons. Therefore, here we devised a task that was sensitive to measure both sustained and selective attention and tested whether task measures could predict adolescents' levels of inattention during lessons. In total, 166 adolescents (aged 12-17 years) and 50 adults performed a sustained selective attention task, searching for letter targets while ignoring salient yet entirely irrelevant distractor faces, under different levels of perceptual load-an established determinant of attention in adults. Inattention levels during a just preceding classroom lesson were measured using a novel self-report classroom distractibility checklist. The results established that sustained attention (measured with response variability) continued to develop throughout adolescence across perceptual load levels. In contrast, there was an earlier maturation of the effect of perceptual load on selective attention; load modulation of distractor interference was larger in the early adolescence period compared with later periods. Both distractor interference and response variability were significant unique predictors of distractibility in the classroom, including when controlling for interest in the lesson and cognitive aptitude. Overall, the results demonstrate divergence of development of sustained and selective attention in adolescence and establish both as significant predictors of attention in the important educational setting of school lessons.

Cell anatomy and network input explain differences within but not between leech touch cells at two different locations.

Mechanosensory cells in the leech share several common features with mechanoreceptors in the human glabrous skin. Previous studies showed that the six T (touch) cells in each body segment of the leech are highly variable in their responses to somatic current injection and change their excitability over time. Here, we investigate three potential reasons for this variability in excitability by comparing the responses of T cells at two soma locations (T2 and T3): (1) Differential effects of time-dependent changes in excitability, (2) divergent synaptic input from the network, and (3) different anatomical structures. These hypotheses were explored with a combination of electrophysiological double recordings, 3D reconstruction of neurobiotin-filled cells, and compartmental model simulations. Current injection triggered significantly more spikes with shorter latency and larger amplitudes in cells at soma location T2 than at T3. During longer recordings, cells at both locations increased their excitability over time in the same way. T2 and T3 cells received the same amount of synaptic input from the unstimulated network, and the polysynaptic connections between both T cells were mutually symmetric. However, we found a striking anatomical difference: While in our data set all T2 cells innervated two roots connecting the ganglion with the skin, 50% of the T3 cells had only one root process. The sub-sample of T3 cells with one root process was significantly less excitable than the T3 cells with two root processes and the T2 cells. To test if the additional root process causes higher excitability, we simulated the responses of 3D reconstructed cells of both anatomies with detailed multi-compartment models. The anatomical subtypes do not differ in excitability when identical biophysical parameters and a homogeneous channel distribution are assumed. Hence, all three hypotheses may contribute to the highly variable T cell responses, but none of them is the only factor accounting for the observed systematic difference in excitability between cells at T2 vs. T3 soma location. Therefore, future patch clamp and modeling studies are needed to analyze how biophysical properties and spatial distribution of ion channels on the cell surface contribute to the variability and systematic differences of electrophysiological phenotypes.

Consistency, variability, and predictability of on-farm nutrient responses in four grain legumes across East and West Africa.

Grain legumes are key components of sustainable production systems in sub-Saharan Africa, but wide-spread nutrient deficiencies severely restrict yields. Whereas legumes can meet a large part of their nitrogen (N) requirement through symbiosis with N2-fixing bacteria, elements such as phosphorus (P), potassium (K) and secondary and micronutrients may still be limiting and require supplementation. Responses to P are generally strong but variable, while evidence for other nutrients tends to show weak or highly localised effects. Here we present the results of a joint statistical analysis of a series of on-farm nutrient addition trials, implemented across four legumes in four countries over two years. Linear mixed models were used to quantify both mean nutrient responses and their variability, followed by a random forest analysis to determine the extent to which such variability can be explained or predicted by geographic, environmental or farm survey data. Legume response to P was indeed variable, but consistently positive and we predicted application to be profitable for 67% of farms in any given year, based on prevailing input costs and grain prices. Other nutrients did not show significant mean effects, but considerable response variation was found. This response heterogeneity was mostly associated with local or temporary factors and could not be explained or predicted by spatial, biophysical or management factors. An exception was K response, which displayed appreciable spatial variation that could be partly accounted for by spatial and environmental covariables. While of apparent relevance for targeted recommendations, the minor amplitude of expected response, the large proportion of unexplained variation and the unreliability of the predicted spatial patterns suggests that such data-driven targeting is unlikely to be effective with current data.

Pharmacometabolomic Approach to Investigate the Response to Metformin in Patients with Type 2 Diabetes: A Cross-Sectional Study.

Metformin constitutes the foundation therapy in type 2 diabetes (T2D). Despite its multiple beneficial effects and widespread use, there is considerable inter-individual variability in response to metformin. Our objective is to identify metabolic signatures associated with poor and good responses to metformin, which may improve our ability to predict outcomes for metformin treatment. In this cross-sectional study, clinical and metabolic data for 119 patients with type 2 diabetes taking metformin were collected from the Qatar Biobank. Patients were empirically dichotomized according to their HbA1C levels into good and poor responders. Differences in the level of metabolites between these two groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. Good responders showed increased levels of sphingomyelins, acylcholines, and glutathione metabolites. On the other hand, poor responders showed increased levels of metabolites resulting from glucose metabolism and gut microbiota metabolites. The results of this study have the potential to increase our knowledge of patient response variability to metformin and carry significant implications for enabling personalized medicine.

Exposure-Response Analysis of the Sodium-Glucose Cotransporter-2 Inhibitors Dapagliflozin and Empagliflozin on Kidney Hemodynamics in Patients with Type 2 Diabetes.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve markers for renal and cardiovascular outcomes in patients with and without type 2 diabetes (T2D). To assess whether individual differences in plasma drug exposure can explain inter-individual response variation, we characterized the exposure-response relationship for two SGLT2 inhibitors on several clinical and kidney hemodynamic variables. Data were obtained from two studies, RED and RECOLAR, assessing the effects of once-daily 10 mg dapagliflozin or empagliflozin, respectively, on kidney hemodynamics in patients with T2D. Individual plasma exposure was estimated using non-compartmental analyses and exposure-response relationships were assessed using linear mixed-effects models. In 23 patients participating in RED, the dapagliflozin geometric mean apparent area under the concentration-time curve during one dosing interval at steady state (AUC0-tau,ss) was 1153.1 µg/L*h (coefficient of variation (CV) 81.8%) and associated, per doubling, with decreases in body weight (0.29 kg, p < 0.001), systolic blood pressure (0.80 mmHg, p = 0.002), measured glomerular filtration rate (mGFR) (0.83 mL/min, p = 0.03), and filtration fraction (0.09%, p = 0.04). In 20 patients participating in RECOLOR, the empagliflozin geometric mean AUC0-tau,ss was 2035.7 nmol/L*h (CV 48.4%) and associated, per doubling, with decreases in body weight (0.13 kg, p = 0.002), systolic blood pressure (0.65 mmHg, p = 0.045), and mGFR (0.78 mL/min, p = 0.002). To conclude, dapagliflozin and empagliflozin plasma exposure was highly variable between patients and associated with inter-individual variation in response variables.

Assessment of a single trial impact on the amplitude of the averaged event related potentials.

Widely used in neuroscience the averaging of event related potentials is based on the assumption that small responses to the investigated events are present in every trial but can be hidden under the random noise. This situation often takes place, especially in experiments performed at hierarchically lower levels of sensory systems. However, in the studies of higher order complex neuronal networks evoked responses might appear only under particular conditions and be absent otherwise. We encountered this problem studying a propagation of interoceptive information to the cortical areas in the sleep-wake cycle. Cortical responses to various visceral events were present during some periods of sleep, then disappeared for a while and restored again after a period of absence. Further investigation of the viscero-cortical communication required a method that would allow labeling the trials contributing to the averaged event related responses-"efficient trials," and separating them from the trials without any response. Here we describe a heuristic approach to solving this problem in the context of viscero-cortical interactions occurring during sleep. However, we think that the proposed technique can be applicable to any situation where neuronal processing of the same events is expected to be variable due to internal or external factors modulating neuronal activity. The method was first implemented as a script for Spike 2 program version 6.16 (CED). However, at present a functionally equivalent version of this algorithm is also available as Matlab code at https://github.com/george-fedorov/erp-correlations.

Genetic and Phenotypic Factors Affecting Glycemic Response to Metformin Therapy in Patients with Type 2 Diabetes Mellitus.

Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment of patients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response to metformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response to metformin, we performed an association analysis of the variants in ATM, SLC22A1, SLC47A1, and SLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution of allele and genotype frequencies of the studied gene variants was analyzed in an extended group of patients with T2DM (n = 464) and a population group (n = 129). According to our results, one variant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin in T2DM patients. Carriers of TT genotype and T allele had a lower response to metformin compared to carriers of CC/CT genotypes and C allele (p-value = 0.0246, p-value = 0.0059, respectively). To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist-hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM (AUC = 0.62 in cross-validation). Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment.

The Role of miRNAs in Dexmedetomidine's Neuroprotective Effects against Brain Disorders.

There are limited neuroprotective strategies for various central nervous system conditions in which fast and sustained management is essential. Neuroprotection-based therapeutics have become an intensively researched topic in the neuroscience field, with multiple novel promising agents, from natural products to mesenchymal stem cells, homing peptides, and nanoparticles-mediated agents, all aiming to significantly provide neuroprotection in experimental and clinical studies. Dexmedetomidine (DEX), an α2 agonist commonly used as an anesthetic adjuvant for sedation and as an opioid-sparing medication, stands out in this context due to its well-established neuroprotective effects. Emerging evidence from preclinical and clinical studies suggested that DEX could be used to protect against cerebral ischemia, traumatic brain injury (TBI), spinal cord injury, neurodegenerative diseases, and postoperative cognitive disorders. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level, inhibiting the translation of mRNA into functional proteins. In vivo and in vitro studies deciphered brain-related miRNAs and dysregulated miRNA profiles after several brain disorders, including TBI, ischemic stroke, Alzheimer's disease, and multiple sclerosis, providing emerging new perspectives in neuroprotective therapy by modulating these miRNAs. Experimental studies revealed that some of the neuroprotective effects of DEX are mediated by various miRNAs, counteracting multiple mechanisms in several disease models, such as lipopolysaccharides induced neuroinflammation, ß-amyloid induced dysfunction, brain ischemic-reperfusion injury, and anesthesia-induced neurotoxicity models. This review aims to outline the neuroprotective mechanisms of DEX in brain disorders by modulating miRNAs. We address the neuroprotective effects of DEX by targeting miRNAs in modulating ischemic brain injury, ameliorating the neurotoxicity of anesthetics, reducing postoperative cognitive dysfunction, and improving the effects of neurodegenerative diseases.

Responsiveness to left-prefrontal tDCS varies according to arousal levels.

Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.

The effects of a group exercise and education programme on symptoms and physical fitness in patients with fibromyalgia: a prospective observational cohort study.

PURPOSE: Given the limited attention on a combined exercise and education approach for those with chronic musculoskeletal pain disorder such as fibromyalgia, the purpose of this was to evaluate the efficacy of a combined exercise and education programme on symptoms and physical fitness in participants with fibromyalgia. MATERIALS AND METHODS: Using a prospective observational cohort study, participants with fibromyalgia (n = 75) volunteered. The 6-minute-walk-test (6MWT) and revised-fibromyalgia-impact-questionnaire (FIQR) were used before, after (6 weeks) and 6-months post an exercise and education programme. RESULTS: Forty-three participants (age = 49.7 ± 15.2 y) completed the 6-week programme, with improvements observed for the 6MWT (67 m, p < 0.001) and FIQR (11 AU, p < 0.001), though only two (6MWT) and five (FIQR) participants, respectively, achieved the minimal clinically important difference (MCID). Using 74% of the intial sample, a small-to-moderate improvement in scores were observed across the 6-month period for the 6MWT (37 m, p = 0.002) and FIQR (3 AU, p = 0.01), with only two participants achieving the MCID for the 6MWT. CONCLUSIONS: The results in this study indiciate small-to-moderate improvements in the 6MWT and FIQR after a combined exercise and education programme, with direct delivery being more effective.Implications for rehabilitationA six-week exercise and education programme elicited moderate, short-term (6 weeks) benefits on physical fitness and key symptoms in patients with fibromyalgia.On average, these benefits were sustained in the long-term (6 months) following the programme but were small-to-moderate and lower than the MCID.Regular follow-up may be required to improve adherence to the education and exercise programme and maintain or increase the observed improvements in 6MWT and FIQR.

Chronic bisphenol A exposure triggers visual perception dysfunction through impoverished neuronal coding ability in the primary visual cortex.

Contrast perception is a fundamental visual ability that allows us to distinguish objects from the background. However, whether it is perturbed by chronic exposure to environmental xenoestrogen, bisphenol A (BPA), is still elusive. Here, we used adult cats to explore BPA-induced changes in contrast sensitivity (CS) and its underlying neuronal coding mechanism. Behavioral results showed that 14 days of BPA exposure (0.4 mg/kg/day) was sufficient to induce CS declines at the tested spatial frequencies (0.05-2 cycles/deg) in all four cats. Furthermore, based on multi-channel electrophysiological recording and interneuronal correlation analysis, we found that the BPA-exposed cats exhibited an obvious up-regulation in noise correlation in the primary visual cortex (area 17, A17), thus providing a population neuronal coding basis for their perceptual dysfunction. Moreover, single neuron responses in A17 of BPA-exposed cats revealed a slight but marked decrease in CS compared to that of control cats. Additionally, these neuronal responses presented an overt decrease in signal-to-noise ratio, accompanied by increased trial-to-trial response variability (i.e., noise). To some extent, these neuron population and unit dysfunctions in A17 of BPA-exposed cats were attributable to decreased response activity of fast-spiking neurons. Together, our findings demonstrate that chronic BPA exposure restricts contrast perception, in response to impoverished neuronal coding ability in A17.

Who wins or loses matters: Strongly interacting consumers drive seagrass resistance under ocean acidification.

Global stressors are increasingly altering ecosystem resistance, resilience, and functioning by reorganizing vital species interactions. However, our predictive understanding of these changes is hindered by failures to consider species-specific functional roles and stress responses within communities. Stressor-driven loss or reduced performance of strongly interacting species may generate abrupt shifts in ecosystem states and functions. Yet, empirical support for this prediction is scarce, especially in marine climate change research. Using a marine assemblage comprising a habitat-forming seagrass (Phyllospadix torreyi), its algal competitor, and three consumer species (algal grazers) with potentially different functional roles and pH tolerance, we investigated how ocean acidification (OA) may, directly and indirectly, alter community resistance. In the field and laboratory, hermit crabs (Pagurus granosimanus and P. hirsutiusculus) and snails (Tegula funebralis) displayed distinct microhabitat use, with hermit crabs more frequently grazing in the area of high algal colonization (i.e., surfgrass canopy). In mesocosms, this behavioral difference led to hermit crabs exerting ~2 times greater per capita impact on algal epiphyte biomass than snails. Exposure to OA variably affected the grazers: snails showed reduced feeding and growth under extreme pH (7.3 and 7.5), whereas hermit crabs (P. granosimanus) maintained a similar grazing rate under all pH levels (pH 7.3, 7.5, 7.7, and 7.95). Epiphyte biomass increased more rapidly under extreme OA (pH 7.3 and 7.5), but natural densities of snails and hermit crabs prevented algal overgrowth irrespective of pH treatments. Finally, grazers and acidification additively increased surfgrass productivity and delayed the shoot senescence. Hence, although OA impaired the function of the most abundant consumers (snails), strongly interacting and pH-tolerant species (hermit crabs) largely maintained the top-down pressure to facilitate seagrass dominance. Our study highlights significant within-community variation in species functional and response traits and shows that this variation has important ecosystem consequences under anthropogenic stressors.

Mini review: Recent advances on epigenetic effects of lithium.

Lithium (Li) remains the first line long-term treatment of bipolar disorders notwithstanding a high inter-individual variability of response. Significant research effort has been undertaken to understand the molecular mechanisms underlying Li cellular and clinical effects in order to identify predictive biomarkers of response. Li response has been shown to be partly heritable, however mechanisms that do not rely on DNA variants could also be involved. In recent years, modulation of epigenetic marks in relation with the level of Li response has appeared increasingly plausible. Recent results in this field of research have provided new insights into the molecular processes involved in Li effects. In this review, we examined the literature investigating the involvement of three epigenetic mechanisms (DNA methylation, noncoding RNAs and histone modifications) in Li clinical efficacy in bipolar disorder.

Biological and methodological factors affecting V̇O2max response variability to endurance training and the influence of exercise intensity prescription.

NEW FINDINGS: What is the topic of this review? Biological and methodological factors associated with the variable changes in cardiorespiratory fitness in response to endurance training. What advances does it highlight? Several biological and methodological factors exist that each contribute, to a given extent, to response variability. Notably, prescribing exercise intensity relative to physiological thresholds reportedly increases cardiorespiratory fitness response rates compared to when prescribed relative to maximum physiological values. As threshold-based approaches elicit more homogeneous acute physiological responses among individuals, when repeated over time, these uniform responses may manifest as more homogeneous chronic adaptations thereby reducing response variability. ABSTRACT: Changes in cardiorespiratory fitness (CRF) in response to endurance training (ET) exhibit large variations, possibly due to a multitude of biological and methodological factors. It is acknowledged that ∼20% of individuals may not achieve meaningful increases in CRF in response to ET. Genetics, the most potent biological contributor, has been shown to explain ∼50% of response variability, whilst age, sex and baseline CRF appear to explain a smaller proportion. Methodological factors represent the characteristics of the ET itself, including the type, volume and intensity of exercise, as well as the method used to prescribe and control exercise intensity. Notably, methodological factors are modifiable and, upon manipulation, alter response rates to ET, eliciting increases in CRF regardless of an individual's biological predisposition. Particularly, prescribing exercise intensity relative to a physiological threshold (e.g., ventilatory threshold) is shown to increase CRF response rates compared to when intensity is anchored relative to a maximum physiological value (e.g., maximum heart rate). It is, however, uncertain whether the increased response rates are primarily attributable to reduced response variability, greater mean changes in CRF or both. Future research is warranted to elucidate whether more homogeneous chronic adaptations manifest over time among individuals, as a result of exposure to more homogeneous exercise stimuli elicited by threshold-based practices.