Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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A framework for secondary cognitive and motor tasks in dual-task gait testing in people with mild cognitive impairment

Background: Cognition is a key factor in the regulation of normal walking and dual-task gait assessment is an accepted method to evaluate the relationship. The objective of this study was to create a framework for task complexity of concurrent motor and cognitive tasks with gait in people with mild cognitive impairment (MCI). Methods: Community-dwelling people with MCI (n = 41, mean age = 76.20 ± 7.65 years) and cognitively normal controls (n = 41, mean age = 72.10 ± 3.80 years) participated in this study. Gait velocity was collected using an instrumented walkway under one single task and six combined tasks of motor and cognitive activities. The cognitive cost was the difference between the single gait task and each of the concurrent motor and cognitive challenges. A repeated two-way measure ANOVA assessed the effect of cognitive group and walking test condition for each gait task test. Results: Gait velocity was significantly slower in the MCI group under all tasks. For both groups, the concurrent motor task of carrying a glass of water conferred a challenge not different from the cognitive task of counting backwards by ones. Performance of the complex cognitive task of serial seven subtractions reduced gait velocity in both groups, but produced a greater change in the MCI group (31.8%). Conclusions: Not all concurrent tasks challenge cognition-motor interaction equivalently. This study has created a framework of task difficulty which allows for the translation of dual-task test conditions to future research and clinical practice to ensure the accuracy of assessing patient deficits and risk

Understanding emotionally relevant situations in primary dental practice. 3. Emerging narratives

Background and aims. Dentists experience considerable occupational stress. Stressful clinical situations can provoke high levels of negative emotions, and situations which are associated with positive emotions tend to be overlooked by practitioners. Reflection regarding difficult situations is encouraged to facilitate learning. Cognitive behavioural therapy (CBT) formulations may be applied to situations appraised both positively and negatively. Analysis and interpretation of the dentist's coping behaviour and the consequent outcomes facilitate learning and reflection upon individual interactions with patients. Method. Twenty primary care dental practitioners in the greater Lincoln area participated in a semi-structured interview which explored their stressful and positive clinical experiences. Some of the episodes were analysed to create CBT formulations. Results and discussion. CBT formulations are presented and the learning points highlighted by this structured presentation are discussed. In particular, it is suggested that this structured reconstruction of events, which highlights dentists' emotions, responses and the transactional effects of coping responses, might well facilitate objective reflective learning either individually or as part of peer to peer support. It should facilitate dentists' emotional processing of events and may thus contribute to stress reduction. Conclusion. CBT formulations of positive and negative dental scenarios may be constructed. It is proposed that this is a useful technique to foster reflection and learning in clinical situations and should lead to improved communication skills and shared decision-making, resulting in fewer complaints and thereby reduced stress. It should also improve dentists' emotional processing

Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development

Cell competition is emerging as a quality control mechanism that eliminates unfit cells in a wide range of settings from development to the adult. However, the nature of the cells normally eliminated by cell competition and what triggers their elimination remains poorly understood. In mice, 35% of epiblast cells are eliminated prior to gastrulation. Here we show that cells with mitochondrial defects are eliminated by cell competition during early mouse development. Using single cell transcriptional profiling of eliminated mouse epiblast cells we identify hallmarks of cell competition and mitochondrial defects. We go on to demonstrate that mitochondrial defects are common to a range of different loser cell types and that manipulating mitochondrial function triggers cell competition. In the mouse embryo, cell competition eliminates cells with sequence changes in mt-Rnr1 and mt-Rnr2, and that even non-pathological changes in mitochondrial DNA sequence can induce cell competition. Our results suggest that cell competition is a purifying selection that optimises mitochondrial performance prior to gastrulation

Empathy, engagement, entrainment: the interaction dynamics of aesthetic experience

A recent version of the view that aesthetic experience is based in empathy as inner imitation explains aesthetic experience as the automatic simulation of actions, emotions, and bodily sensations depicted in an artwork by motor neurons in the brain. Criticizing the simulation theory for committing to an erroneous concept of empathy and failing to distinguish regular from aesthetic experiences of art, I advance an alternative, dynamic approach and claim that aesthetic experience is enacted and skillful, based in the recognition of others’ experiences as distinct from one’s own. In combining insights from mainly psychology, phenomenology, and cognitive science, the dynamic approach aims to explain the emergence of aesthetic experience in terms of the reciprocal interaction between viewer and artwork. I argue that aesthetic experience emerges by participatory sense-making and revolves around movement as a means for creating meaning. While entrainment merely plays a preparatory part in this, aesthetic engagement constitutes the phenomenological side of coupling to an artwork and provides the context for exploration, and eventually for moving, seeing, and feeling with art. I submit that aesthetic experience emerges from bodily and emotional engagement with works of art via the complementary processes of the perception–action and motion–emotion loops. The former involves the embodied visual exploration of an artwork in physical space, and progressively structures and organizes visual experience by way of perceptual feedback from body movements made in response to the artwork. The latter concerns the movement qualities and shapes of implicit and explicit bodily responses to an artwork that cue emotion and thereby modulate over-all affect and attitude. The two processes cause the viewer to bodily and emotionally move with and be moved by individual works of art, and consequently to recognize another psychological orientation than her own, which explains how art can cause feelings of insight or awe and disclose aspects of life that are unfamiliar or novel to the viewer

Modulation of the expression of components of the stress response by dietary arachidonic acid in European sea bass (Dicentrarchus labrax) larvae

This study reports for the first time in European sea bass, Dicentrarchus labrax (L.), larvae, the effect of different levels of dietary arachidonic acid (ARA; 20:4n-6) on the expression of genes related to the fish stress response. Copies of mRNA from genes related to steroidogenesis (StAR (steroidogenic acute regulatory protein), c-Fos, and CYP11β (11β- hydroxylase gene)), glucocorticoid receptor complex (GR (glucorticoid receptor) and HSP (heat shock proteins) 70 and 90) and antioxidative stress (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX)) were quantified. Eighteen day-old larvae were fed for 14 days with three experimental diets with increasing levels of ARA (0.3, 0.6 and 1.2% d.w.) and similar levels of docosahexaenoic (DHA; 22:6n-3) and eicosapentaenoic (EPA; 20:5n-3) acids (5 and 3%, respectively). The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real time RT-PCR with the standard curve method (absolute quantification). Increase dietary levels of ARA induced a significantly (p<0.05) down-regulation of genes related to cortisol synthesis, such as StAR and CYP11β and up-regulated genes related to glucocorticoid receptor complex, such as HSP70 and GR. No effects were observed on antioxidant enzymes gene expression. These results revealed the regulatory role of dietary ARA on the expression of stress-related genes in European sea bass larvae

La reactogenicidad y los aspectos inmune específicos de la vacuna pentavalente combinada: DTPw-HepB-Hib en el lactante menor de un año en el Hospital Distrital de Lambaré, Paraguay en 2007-2008

La vacunación rutinaria de difteria, pertussis y tétanos a células enteras (DPTw) está presente desde 1940 y con elevadas coberturas en muchos países del mundo. La Organización Mundial de la Salud ha aprobado el uso universal de la vacuna anti-hepatitis B (HB) y combinaciones con DPT, en los últimos años ha sido incorporada la vacuna anti-Haemophilus influenzae tipo b (Hib) en programas de vacunación del niño. Es aplicada en Paraguay desde el 2002 a través del Programa Ampliado de Inmunizaciones del Ministerio de Salud Pública y Bienestar Social. Determinamos la reactoinmunogenicidad secundaria a la vacunación primaria pentavalente combinada en infantes concurrentes al Hospital Distrital de Lambaré–Paraguay en los años 2007-2008. Estudio longitudinal, observacional prospectivo de los efectos secundarios y los aspectos inmune- específicosde la vacuna Berna DTPw-HepB-Hib (QUINVAXEMTM) en lactantes menores de un año, a los 2 meses de edad, datos basales y post vacunales (1 mes luego de 3ª dosis). Efectos locales: 30(75%); rubor 17 (42.5%); tumefacción (menos 20 mm); 13 (32.5%); calorlocal 11 (27.5%). Efectos generales: fiebre: 37 (92.5%) llanto fuerte y persistente:32(80%); irritabilidad: 23 (57.5%); hiporreactividad 16 (40%), anorexia 8 (20%); Inmunogenicidad: antes de la 1ª dosis; antitetánica IgG (+) 38/40 (95%), anti-difteria (+) IgG 29/40 (72.5%); anti-HBsAg 0/40 (0%) negativos. Respuesta post-vacuna penta comb. (7m. edad): antitetánica IgG 14/14 (100%) (+); anti-difteria IgG 12/14 (83%) (+); anti-HBsAg 14/14 (100%) positivos. Se evidencia la reactogenicidad de grado variable y decreciente. Niveles de anticuerpos de los componentes DT, satisfactorios y la Hep B excelentes

Tumor Volume Estimation and Quasi- Continuous Administration for Most Effective Bevacizumab Therapy

Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol.We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis.In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model.Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology

A New Fluorescence-Based Method Identifies Protein Phosphatases Regulating Lipid Droplet Metabolism

In virtually every cell, neutral lipids are stored in cytoplasmic structures called lipid droplets (LDs) and also referred to as lipid bodies or lipid particles. We developed a rapid high-throughput assay based on the recovery of quenched BODIPY-fluorescence that allows to quantify lipid droplets. The method was validated by monitoring lipid droplet turnover during growth of a yeast culture and by screening a group of strains deleted in genes known to be involved in lipid metabolism. In both tests, the fluorimetric assay showed high sensitivity and good agreement with previously reported data using microscopy. We used this method for high-throughput identification of protein phosphatases involved in lipid droplet metabolism. From 65 yeast knockout strains encoding protein phosphatases and its regulatory subunits, 13 strains revealed to have abnormal levels of lipid droplets, 10 of them having high lipid droplet content. Strains deleted for type I protein phosphatases and related regulators (ppz2, gac1, bni4), type 2A phosphatase and its related regulator (pph21 and sap185), type 2C protein phosphatases (ptc1, ptc4, ptc7) and dual phosphatases (pps1, msg5) were catalogued as high-lipid droplet content strains. Only reg1, a targeting subunit of the type 1 phosphatase Glc7p, and members of the nutrient-sensitive TOR pathway (sit4 and the regulatory subunit sap190) were catalogued as low-lipid droplet content strains, which were studied further. We show that Snf1, the homologue of the mammalian AMP-activated kinase, is constitutively phosphorylated (hyperactive) in sit4 and sap190 strains leading to a reduction of acetyl-CoA carboxylase activity. In conclusion, our fast and highly sensitive method permitted us to catalogue protein phosphatases involved in the regulation of LD metabolism and present evidence indicating that the TOR pathway and the SNF1/AMPK pathway are connected through the Sit4p-Sap190p pair in the control of lipid droplet biogenesis