Dutch listeners' perception of English lexical stress: A cue-weighting approach.

We investigate whether acoustic cue weightings are transferred from the native language to the second language [research question 1 (RQ1)], how cue weightings change with increasing second-language proficiency (RQ2), and whether individual cues are used independently or together in the second language (RQ3). Vowel reduction is a strong cue to lexical stress in English but not Dutch. Native English listeners and Dutch second-language learners of English completed a cue-weighting stress perception experiment. Participants heard sentence-final pitch-accented auditory stimuli and identified them as DEsert (initial stress) or deSSERT (final stress). The stimuli were manipulated in seven steps from initial to final stress, manipulating two dimensions at a time: vowel quality and pitch, vowel quality and duration, and pitch and duration (other dimensions neutralized). Dutch listeners relied less on vowel quality and more on pitch than English listeners, with Dutch listeners' sensitivity to vowel quality increasing with English proficiency but their sensitivity to pitch not varying with proficiency; Dutch listeners evidenced similar or weaker reliance on duration than did English listeners, and their sensitivity to duration increased with proficiency; and Dutch listeners' use of pitch and duration were positively related. These results provide general support for a cue-based transfer approach to the perception of lexical stress.

Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function.

Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene Wwtr1-/- ) knockout mice, there were no overt effects on regeneration. Conversely, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapfl °x/fl °x :Rosa26Lacz mice produced a regeneration deficit. To identify potential mechanisms, microarray analysis showed many common TAZ/YAP target genes, but TAZ also regulates some genes independently of YAP, including myogenic genes such as Pax7, Myf5, and Myod1 (ArrayExpress-E-MTAB-5395). Proteomic analysis revealed many novel binding partners of TAZ/YAP in myogenic cells, but TAZ also interacts with proteins distinct from YAP that are often involved in myogenesis and aspects of cytoskeleton organization (ProteomeXchange-PXD005751). Neither TAZ nor YAP bind members of the Wnt destruction complex but both regulated expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to enhance myogenic differentiation. Stem Cells 2017;35:1958-1972.

The homeobox protein Prox1 is a negative modulator of ERR{alpha}/PGC-1{alpha} bioenergetic functions.

Estrogen-related receptor alpha (ERRalpha) and proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) play central roles in the transcriptional control of energy homeostasis, but little is known about factors regulating their activity. Here we identified the homeobox protein prospero-related homeobox 1 (Prox1) as one such factor. Prox1 interacts with ERRalpha and PGC-1alpha, occupies promoters of metabolic genes on a genome-wide scale, and inhibits the activity of the ERRalpha/PGC-1alpha complex. DNA motif analysis suggests that Prox1 interacts with the genome through tethering to ERRalpha and other factors. Importantly, ablation of Prox1 and ERRalpha have opposite effects on the respiratory capacity of liver cells, revealing an unexpected role for Prox1 in the control of energy homeostasis.

The Hippo signal transduction pathway in soft tissue sarcomas.

Sarcomas are rare cancers (≈1% of all solid tumours) usually of mesenchymal origin. Here, we review evidence implicating the Hippo pathway in soft tissue sarcomas. Several transgenic mouse models of Hippo pathway members (Nf2, Mob1, LATS1 and YAP1 mutants) develop various types of sarcoma. Despite that, Hippo member genes are rarely point mutated in human sarcomas. Instead, WWTR1-CAMTA1 and YAP1-TFE3 fusion genes are found in almost all cases of epithelioid haemangioendothelioma. Also copy number gains of YAP1 and other Hippo members occur at low frequencies but the most likely cause of perturbed Hippo signalling in sarcoma is the cross-talk with commonly mutated cancer genes such as KRAS, PIK3CA, CTNNB1 or FBXW7. Current Hippo pathway-targeting drugs include compounds that target the interaction between YAP and TEAD G protein-coupled receptors (GPCR) and the mevalonate pathway (e.g. statins). Given that many Hippo pathway-modulating drugs are already used in patients, this could lead to early clinical trials testing their efficacy in different types of sarcoma.

Hippo signaling in mammalian stem cells.

Over the past decade, the Hippo signaling cascade has been linked to organ size regulation in mammals. Indeed, modulation of the Hippo pathway can have potent effects on cellular proliferation and/or apoptosis and a deregulation of the pathway often leads to tumor development. Importantly, emerging evidence indicates that the Hippo pathway can modulate its effects on tissue size by the regulation of stem and progenitor cell activity. This role has recently been associated with the central position of the pathway in sensing spatiotemporal or mechanical cues, and translating them into specific cellular outputs. These results provide an attractive model for how the Hippo cascade might sense and transduce cellular 'neighborhood' cues into activation of tissue-specific stem or progenitors cells. A further understanding of this process could allow the development of new therapies for various degenerative diseases and cancers. Here, we review current and emerging data linking Hippo signaling to progenitor cell function.

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells.

Satellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7(+) and MyoD(+) satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In contrast, Yap knockdown reduces the proliferation of satellite cell-derived myoblasts by ≈40%. Consistent with the cellular phenotype, microarrays show that Yap increases expression of genes associated with Yap inhibition, the cell cycle, ribosome biogenesis and that it represses several genes associated with angiotensin signalling. We also identify known regulators of satellite cell function such as BMP4, CD34 and Myf6 (Mrf4) as genes whose expression is dependent on Yap activity. Finally, we confirm in myoblasts that Yap binds to Tead transcription factors and co-activates MCAT elements which are enriched in the proximal promoters of Yap-responsive genes.

What to do with screening for distress scores? Integrating descriptive data into clinical practice.

OBJECTIVE: Implementation of routine Screening for Distress constitutes a major change in cancer care, with the aim of achieving person-centered care. METHOD: Using a cross-sectional descriptive design within a University Tertiary Care Hospital setting, 911 patients from all cancer sites were screened at the time of their first meeting with a nurse navigator who administered a paper questionnaire that included: the Distress Thermometer (DT), the Canadian Problem Checklist (CPC), and the Edmonton Symptom Assessment System (ESAS). RESULTS: Results showed a mean score of 3.9 on the DT. Fears/worries, coping with the disease, and sleep were the most common problems reported on the CPC. Tiredness was the most prevalent symptom on the ESAS. A final regression model that included anxiety, the total number of problems on the CPC, well-being, and tiredness accounted for almost 50% of the variance of distress. A cutoff score of 5 on the DT together with a cutoff of 5 on the ESAS items represents the best combination of specificity and sensitivity to orient patients on the basis of their reported distress. SIGNIFICANCE OF RESULTS: These descriptive data will provide valuable feedback to answer practical questions for the purpose of effectively implementing and managing routine screening in cancer care.

Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here?

The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.

Review and Perspectives on Bifidobacterium lactis for Infants' and Children's Health.

The influence of microbiota dysbiosis in early life is increasingly recognized as a risk factor for the development of several chronic diseases later in life, including an increased risk of asthma, eczema, allergies, obesity, and neurodevelopmental disorders. The question whether the potential lifelong consequences of early life dysbiosis could be mitigated by restoring microbiota composition remains unresolved. However, the current evidence base suggests that protecting the normal development of the microbiome during this critical developmental window could represent a valuable public health strategy to curb the incidence of chronic and lifestyle-related diseases. Probiotic Bifidobacteria are likely candidates for this purpose in newborns and infants considering the natural dominance of this genus on microbiota composition in early life. Moreover, the most frequently reported microbiota composition alteration in association with newborn and infant diseases, including necrotizing enterocolitis and diarrhea, is a reduction in Bifidobacteria levels. Several studies have assessed the effects of B. animalis subsp. lactis strains in newborns and infants, but recent expert opinions recommend analyzing their efficacy at the strain-specific level. Hence, using the B94 strain as an example, this review summarizes the clinical evidence available in infants and children in various indications, discussing the safety and potential modes of actions while providing perspectives on the concept of "non-infant-type" probiotics for infants' health.

Total Transit Time and Probiotic Persistence in Healthy Adults: A Pilot Study.

Background/Aims: Motility, stool characteristics, and microbiota composition are expected to modulate probiotics' passage through the gut but their effects on persistence after intake cessation remain uncharacterized. This pilot, open-label study aims at characterizing probiotic fecal detection parameters (onset, persistence, and duration) and their relationship with whole gut transit time (WGTT). Correlations with fecal microbiota composition are also explored. Methods: Thirty healthy adults (30.4 ± 13.3 years) received a probiotic (30 × 109 CFU/capsule/day, 2 weeks; containing Lactobacillus helveticus R0052, Lacticaseibacillus paracasei HA-108, Bifidobacterium breve HA-129, Bifidobacterium longum R0175, and Streptococcus thermophilus HA-110). Probiotic intake was flanked by 4-week washout periods, with 18 stool collections throughout the study. WGTT was measured using 80% recovery of radio-opaque markers. Results: Tested strains were detected in feces ~1-2 days after first intake and persistence after intake cessation was not significantly different for R0052, HA-108, and HA-129 (~3-6 days). We identified 3 WGTT subgroups within this population (named Fast, Intermediate, and Slow), which could be classified by machine learning with high accuracy based on differentially abundant taxa. On average, R0175 persisted significantly longer in the intermediate WGTT subgroup (~8.5 days), which was mainly due to 6 of the 13 Intermediate participants for whom R0175 persisted ≥ 15 days. Machine learning classified these 13 participants according to their WGTT cluster (≥ 15 days or < 5 days) with high accuracy, highlighting differentially abundant taxa potentially associated with R0175 persistence. Conclusion: These results support the notion that host-specific parameters such as WGTT and microbiota composition should be considered when designing studies involving probiotics, especially for the optimization of washout duration in crossover studies but also for the definition of enrollment criteria or supplementation regimen in specific populations.

Impact of probiotic supplementation on exercise endurance among non-elite athletes: study protocol for a randomized, placebo-controlled, double-blind, clinical trial.

BACKGROUND: Some probiotics appear to improve athletic performance, endurance, and recovery after intense exercise. Other formulations may provide performance-related benefits via immune and gastrointestinal functions in athletic individuals. However, few formulations have been studied for both types of effects among non-elite athletes. The primary objective of this study is to assess the ergogenic effects of a probiotic on high-intensity endurance running performance in non-elite runners. Secondary objectives include assessment of perceived exertion, blood chemistry, immune and stress biomarkers, cold and flu symptoms, and gastrointestinal health after the probiotic intervention. METHODS: This 9-week randomized, placebo-controlled, double-blind, parallel trial will assess the ergogenic effects of a probiotic (5 billion colony-forming units/day, for 6 weeks) in healthy, non-elite runners (N=32; 18-45 years). Participants will be monitored via daily and weekly questionnaires during the 2-week pre-baseline, 6-week intervention, and 1-week washout. Questionnaires will inquire about activity, muscle soreness, gastrointestinal symptoms, cold and flu symptoms, stool form and frequency, and adverse events. During the pre-baseline visit, maximal oxygen uptake (V̇O2 max) is assessed to set appropriate individualized workload settings for the treadmill time-to-exhaustion endurance tests. These time-to-exhaustion endurance running tests will be completed at an intensity of 85% VO2max at baseline and final visits. During these tests, self-perceived exercise effort will be rated via the Borg Rating of Perceived Exertion scale and finger sticks assessing capillary blood glucose and lactate concentrations will be collected every 3 min. Additional questionnaires will assess diet and motivation to exercise. Body composition will be assessed using air displacement plethysmography at the baseline and final visits. Hypotheses will be tested using two-sided tests, and a linear model and with a type I error rate of α=0.05. Primary and secondary outcomes will be tested by comparing results between the intervention groups, adjusting for baseline values. DISCUSSION: These results will build evidence documenting the role of probiotics on running endurance performance and physiological responses to exercise in non-elite athletes. Understanding the potential mechanisms of probiotic effects and how they mitigate the intestinal or immune discomforts caused by running could provide additional strategy means to help runners improve their performance. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04588142 . Posted on October 19, 2020. PROTOCOL VERSION: July 2, 2021, version 1.2.

Efficacy of a Multi-Strain Probiotic Formulation in Pediatric Populations: A Comprehensive Review of Clinical Studies.

A probiotic formulation combining Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33, and Bifidobacterium bifidum Rosell®-71 with fructooligosaccharides, first commercialized in China, has been sold in over 28 countries since 2002. Clinical studies with this blend of strains were conducted mainly in pediatric populations, and most were published in non-English journals. This comprehensive review summarizes the clinical studies in infants and children to evaluate the efficacy of this probiotic for pediatric indications. Literature searches for pediatric studies on Biostime® or Probiokid® (non-commercial name) in 6 international and Chinese databases identified 28 studies, which were classified by indications. Twelve studies show that the probiotic significantly increases the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unresolved diarrhea (RR 0.31 [0.23; 0.42]; p < 0.0001) by 69%. In eight studies, the probiotic enhanced immune defenses, assessed by levels of various immune competence and mucosal immunity markers (six studies), and reduced the incidence of common infections (two studies). The probiotic improved iron deficiency anemia treatment efficacy (three studies), reducing the risk of unresolved anemia by 49% (RR 0.51 [0.28; 0.92]; p = 0.0263) and significantly reducing treatment side effects by 47% (RR 0.53 [0.37; 0.77]; p = 0.0009). Other studies support further investigation into this probiotic for oral candidiasis, eczema, feeding intolerance in premature babies, or hyperbilirubinemia in newborns.

The effects of psychobiotics on the microbiota-gut-brain axis in early-life stress and neuropsychiatric disorders.

Psychobiotics are considered among potential avenues for modulating the bidirectional communication between the gastrointestinal tract and central nervous system, defined as the microbiota-gut-brain axis (MGBA). Even though causality has not yet been established, intestinal dysbiosis has emerged as a hallmark of several diseases, including neuropsychiatric disorders (NPDs). The fact that the microbiota and central nervous system are co-developing during the first years of life has provided a paradigm suggesting a potential role of psychobiotics for earlier interventions. Studies in animal models of early-life stress (ELS) have shown that they can counteract the pervasive effects of stress during this crucial developmental period, and rescue behavioral symptoms related to anxiety and depression later in life. In humans, evidence from clinical studies on the efficacy of psychobiotics at improving mental outcomes in most NPDs remain limited, except for major depressive disorder for which more studies are available. Consequently, the beneficial effect of psychobiotics on depression-related outcomes in adults are becoming clearer. While the specific mechanisms at play remain elusive, the effect of psychobiotics are generally considered to involve the hypothalamic-pituitary-adrenal axis, intestinal permeability, and inflammation. It is anticipated that future clinical studies will explore the potential role of psychobiotics at mitigating the risk developing NPDs in vulnerable individuals or in the context of childhood adversity. However, such studies remain challenging at present in terms of design and target populations; the profound impact of stress on the proper development of the MGBA during the first year of life is becoming increasingly recognized, but the trajectories post-ELS in humans and the mechanisms by which stress affects the susceptibility to various NPDs are still ill-defined. As psychobiotics are likely to exert both shared and specific mechanisms, a better definition of target subpopulations would allow to tailor psychobiotics selection by aligning mechanistic properties with known pathophysiological mechanisms or risk factors. Here we review the available evidence from clinical and preclinical studies supporting a role for psychobiotics at ameliorating depression-related outcomes, highlighting the knowledge gaps and challenges associated with conducting longitudinal studies to address outstanding key questions in the field.

How to objectively assess and observe maladaptive pain behaviors in clinical rehabilitation: a systematic search and review.

BACKGROUND: Cognitive-affective factors influence the perception of pain and disability. These factors can lead to pain behaviors (PB) that can persist and become maladaptive. These maladaptive PB will further increase the risk of chronicity or persistence of symptoms and disability. Thus, clinicians must be prepared to recognize maladaptive PB in a clinical context. To date, in the context of assessment in a rehabilitation setting, PB in clinical settings are poorly documented. The main objective of this study was to identify direct observation methods and critically appraise them in order to propose recommendations for practice. As a secondary objective, we explored and extracted the different observable PB that patients could exhibit and that clinicians could observe. METHODS: We conducted a comprehensive review on four databases with a generic search strategy in order to obtain the largest range of PB. For the first objective, a two-step critical appraisal used clinical criteria (from qualitative studies on barriers to implement routine measures) and psychometric criteria (from Brink and Louw critical appraisal tool) to determine which observation methods could be recommended for clinical practice. For the second objective, we extracted PB found in the literature to list potential PB that patients could exhibit, and clinicians could observe. RESULTS: From the 3362 retrieved studies, 47 met the inclusion criteria for the first objective. The clinical criteria allowed us to select three observation methods. After the psychometric step, two observation methods were retained and recommended for clinical practice: the Behavioral Avoidance Test-Back Pain (BAT-Back) and the Pain Behaviour Scale (PaBS). For the second objective, 107 studies met the inclusion criteria. The extraction of the PB allowed us to list a large range of PB and classify the data in 7 categories of PB. CONCLUSION: Our results allowed us to recommend two observation methods for clinical practice. However, these methods have limitations and are validated only in chronic low back pain populations. With the extraction of PB presented in the literature, we contribute to better prepare clinicians to recognize PB in all patients who are experiencing pain.

Safety and Effect of a Low- and High-Dose Multi-Strain Probiotic Supplement on Microbiota in a General Adult Population: A Randomized, Double-Blind, Placebo-Controlled Study.

Few studies have focused on dose-response analyses of multi-strain probiotics in the general adult population. This study aimed at comparing how a low- and high-dose of a multi-strain probiotic supplement (containing Lactobacillus helveticus R0052, Lactobacillus rhamnosus R0011, Lactobacillus casei R0215, Pediococcus acidilactici R1001, Bifidobacterium breve R0070, Bifidobacterium longum ssp. longum BB536, Lactobacillus plantarum R1012, Lactococcus lactis ssp. lactis R1058) affected microbiota composition, transit persistence and safety in adults. After a 7-d baseline, participants were randomized to receive capsules containing 5 or 25 billion CFU, or placebo daily for 28 days, followed by a 7-d washout. Digestive health and general wellness were assessed. Fecal microbiota composition was analyzed using 16S rRNA gene amplicon sequencing and strain persistence, by qPCR. Participants' gastrointestinal and general wellbeing were unaffected. No adverse events were associated with either dose. Supplemented strains contributed to the Lactobacillus and Bifidobacterium genera detected in stool, with 0.40 ± 0.11% and 0.51 ± 0.26%, respectively, in the high-dose group. Strain-specific qPCR assays revealed variable levels of post-intervention persistence between strains. Sequencing and composition analyses using the 16S V4 region revealed a decrease in Holdemania and increase in Bacteroidales. The formulation was well tolerated in this sample of the general adult population, even at the higher dose. The strains appear to have influenced microbiota composition minimally, as expected in the absence of dysbiosis, and consistently with the dose administered. Overall, the results provide a rationale to study the effects this formulation on microbiota composition in individuals exhibiting dysbiosis associated with metabolic disorders or obesity.

Criteria to Qualify Microorganisms as "Probiotic" in Foods and Dietary Supplements.

Still relevant after 19 years, the FAO/WHO definition of probiotics can be translated into four simple and pragmatic criteria allowing one to conclude if specific strains of microorganisms qualify as a probiotic for use in foods and dietary supplements. Probiotic strains must be (i) sufficiently characterized; (ii) safe for the intended use; (iii) supported by at least one positive human clinical trial conducted according to generally accepted scientific standards or as per recommendations and provisions of local/national authorities when applicable; and (iv) alive in the product at an efficacious dose throughout shelf life. We provide clarity and detail how each of these four criteria can be assessed. The wide adoption of these criteria is necessary to ensure the proper use of the word probiotic in scientific publications, on product labels, and in communications with regulators and the general public.

Expression, distribution and regulation of sex steroid hormone receptors in mouse heart.

The effects of sex hormones on the heart are dependent on the presence and distribution of sex steroid hormone receptors (SSHR) in cardiac tissue. This study used subcellular fractionation, Western blot analysis and densitometry to characterize the subcellular distribution and abundance of estrogen receptor (ER) alpha, ERbeta and androgen receptor (AR) in atrial and ventricular tissue from male and female mice. The results showed that in both atrial and ventricular tissue ERalpha was primarily found in the sarcolemma, whereas ERbeta and AR were predominantly located in the nucleus and cytosol. Interestingly, ERalpha expression was greater in the ventricles compared to the atria, whereas ERbeta and AR expression were similar in both heart chambers. Furthermore, the distribution and abundance of SSHR in the atria and ventricles did not differ between sexes. This study also showed that a reduction in hormone levels (as a result of ovariectomy) resulted in a significant increase in the abundance of ERalpha in the ventricular sarcolemmal fraction. Overall, the results suggest ERalpha, ERbeta and AR distribution and expression are not sex dependent in the mouse heart. However, it appears that ERalpha expression is chamber specific and that, in certain cases, hormone levels can modulate the subcellular location of SSHRs.

Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif.

Interplay between different posttranslational modifications of transcription factors is an important mechanism to achieve an integrated regulation of gene expression. For the estrogen-related receptors (ERRs) alpha and gamma, regulation by posttranslational modifications is still poorly documented. Here we show that transcriptional repression associated with the ERR amino-terminal domains is mediated through sumoylation at a conserved phospho-sumoyl switch, psiKxEPxSP, that exists within a larger synergy control motif. Arginine substitution of the sumoylatable lysine residue or alanine substitution of a nearby phosphorylatable serine residue (serine 19 in ERRalpha) increased the transcriptional activity of both ERRalpha and -gamma. In addition, phospho-mimetic substitution of the serine residue with aspartate restored the sumoylation and transcriptional repression activity. The increased transcriptional activity of the sumoylation-deficient mutants was more pronounced in the presence of multiple adjacent ERR response elements. We also identified protein inhibitor of activated signal transducer and activator of transcription y as an interacting partner and a small ubiquitin-related modifier E3 ligase for ERRalpha. Importantly, analysis with a phospho-specific antibody revealed that sumoylation of ERRalpha in mouse liver requires phosphorylation of serine 19. Taken together, these results show that the interplay of phosphorylation and sumoylation in the amino-terminal domain provides an additional mechanism to regulate the transcriptional activity of ERRalpha and -gamma.

Bifidobacterium longum R0175 attenuates post-myocardial infarction depressive-like behaviour in rats.

Caspase-3 activation in the limbic system and depressive-like symptoms are observed after an acute myocardial infarction (MI) and studies suggest that inflammation may play a significant role. Combined treatment with the probiotic strains Bifidobacterium longum and Lactobacillus helveticus in rats has been shown to attenuate caspase-3 activation and depressive-like behaviour together with a reduction in pro-inflammatory cytokines. The present study was designed to determine the respective contribution of these two strains on caspase-3 activity in the limbic system and on depressive-like behaviour. Sprague-Dawley rats were assigned to one of four groups: Vehicle, L. helveticus R0052, B. longum R0175 and L. salivarius HA-118, administered orally for 14 days (109CFU daily) before inducing MI by occlusion of the left anterior descending artery for 40 min followed by 14 days of reperfusion. Animals were then tested for socialisation, passive avoidance and forced swim test to assess depressive-like behaviour. At day 18 the animals were sacrificed; infarct size was estimated, plasma C-reactive protein concentration and brain caspase-3 activity were measured. Results indicated that infarct size did not vary across the different treatments. Rats treated with B. longum spent more time socializing, learned more rapidly the passive avoidance test and spent less time immobile in the forced swim test compared to the vehicle groups. Caspase-3 activity and plasma C-reactive protein concentrations were reduced in the lateral and medial amygdala as well as in the dentate gyrus of B. longum-supplemented animals. The only significant effect in the two groups receiving Lactobacilli compared to vehicle was that rats receiving L. salivarius learned more rapidly in the step-down passive avoidance test. In conclusion, most of the beneficial effects that we previously reported with the combination of two probiotic strains in our experimentation regarding post-myocardial infarction depression are related to Bifidobacterium longum.

Syntactic Cues Take Precedence Over Distributional Cues in Native and Non-Native Speech Segmentation.

This study investigates whether syntactic cues take precedence over distributional cues in native and non-native speech segmentation by examining native and non-native speech segmentation in potential French-liaison contexts. Native French listeners and English-speaking second-language learners of French completed a visual-world eye-tracking experiment. Half the stimuli contained the pivotal consonant /t/, a frequent word onset but infrequent liaison consonant, and half contained /z/, a frequent liaison consonant but rare word onset. In the adjective-noun condition (permitting liaison), participants heard a consonant-initial target (e.g., le petit tatoué; le fameux zélé) that was temporarily ambiguous at the segmental level with a vowel-initial competitor (e.g., le petit [t]athée; le fameux [z]élu); in the noun-adjective condition (not permitting liaison), they heard a consonant-initial target (e.g., le client tatoué; le Français zélé) that was not temporarily ambiguous with a vowel-initial competitor (e.g., le client [*t]athée; le Français [*z]élu). Growth-curve analyses revealed that syntactic context modulated both groups' fixations (noun-adjective > adjective-noun), and pivotal consonant modulated both groups' fixations (/t/ > /z/) only in the adjective-noun condition, with the effect of the consonant decreasing in more proficient French learners. These results suggest that syntactic cues override distributional cues in the segmentation of French words in potential liaison contexts.