Torphoffmann3871

Cognitive decline appears across aging. While some studies report beneficial effects of musical listening and practice on cognitive aging, the underlying neurobiological mechanisms remain unknown. This study aims to determine whether chronic (6 h/day, 3 times/week) and long-lasting (4-8 months) music exposure, initiated at middle age in rats (15 months old), can influence behavioral parameters sensitive to age effects and reduce age-related spatial memory decline in rats. Spontaneous locomotor, circadian rhythmic activity, and anxiety-like behavior as well as spatial working and reference memory were assessed in 14-month-old rats and then after 4 and 8 months of music exposure (19 and 23 months old, respectively). Spatial learning and reference memory data were followed up by considering cognitive status of animals prior to music exposure (14 months old) given by K-means clustering of individual Z-score. Hippocampal cell proliferation and brain-derived neurotrophic factor (BDNF) level in the hippocampus and frontal cortex were measured. Results show that music exposure differentially rescues age-related deficits in spatial navigation tasks according to its duration without affecting spontaneous locomotor, circadian rhythmic activity, and anxiety-like behavior. Hippocampal cell proliferation as well as hippocampal and frontal cortex BDNF levels was not affected by music across aging. Cognitive improvement by music in aging rats may require distinct neurobiological mechanisms than hippocampal cell proliferation and BDNF.Mucus hypersecretion is a common pathophysiological manifestation of obstructive airway diseases in which the mucociliary clearance is impaired, and the airflow generated by a cough or a forced expiratory maneuver (huff) is primarily responsible for clearing mucus. This airflow driven clearance of mucus is a complex process that is affected by the mucus rheology, airflow rate, airway geometry, and gravity. selleck chemicals The current study examines the role of mucus rheology in the transport and distribution of mucus in idealized airway geometries. The complex air-mucus interface was tracked by the volume-of-fluid model, and the turbulence in the core airflow was modeled using the k-w shear stress transport model. Mucus was modeled as a shear-thinning liquid by using a power-law model. The computational model was validated using in-vitro experimental data available in the literature. Gravity dominated eccentric core-annular flow was observed with the core biased towards the outer wall in the inclined daughter branches of the bifurcation models, which transitions into concentric core-annular flow in the trachea. The increase in tangential shear at the interface due to the secondary flow structures developed in the flow divider location resulted in a region of enhanced mucus clearance with reduced mucus layer thickness. Secondary flow developed due to the curvature in the airway geometry resulted in a local redistribution of mucus that reduced the eccentricity. The accumulation of mucus around the carinal ridges and the regions with reduced clearance are sites with the potential for microbial growth.To date, no vaccine or monoclonal antibody (mAb) against S. aureus has been approved for use in humans. Our lab has developed a five-antigen S. aureus vaccine (rFSAV), which is now under efficacy evaluation in a phase II clinical trial. In the current study, using overlapping peptides and antiserum from rFSAV-immunized volunteers, we identified seven B-cell immunodominant epitopes on 4 antigens in rFSAV, including five novel epitopes (Hla48-65, IsdB402-419, IsdB432-449, SEB78-95 and MntC7-24). Ten immunodominant-epitope mAbs were generated against these epitopes, and all of them exhibited partial protection in a mouse sepsis model. Four robust mAb were used together as a mAb cocktail to prevent MRSA252 infection. The results showed that the mAb cocktail was efficient in combating S. aureus infection and that its protective efficacy correlated with a reduced bacterial burden, and decreased infection pathology, which demonstrates that the mAb cocktail is a promising S. aureus vaccine candidate.The neurobiology of heterogeneous neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) is still unknown. We hypothesized that differences in subject-level properties of intrinsic brain networks were important features that could predict individual variation in ASD symptom severity. We matched cases and controls from a large multicohort ASD dataset (ABIDE-II) on age, sex, IQ, and image acquisition site. Subjects were matched at the individual level (rather than at group level) to improve homogeneity within matched case-control pairs (ASD n = 100, mean age = 11.43 years, IQ = 110.58; controls n = 100, mean age = 11.43 years, IQ = 110.70). Using task-free functional magnetic resonance imaging, we extracted intrinsic functional brain networks using projective non-negative matrix factorization. Intrapair differences in strength in subnetworks related to the salience network (SN) and the occipital-temporal face perception network were robustly associated with individual differences in social impairment severity (T = 2.206, P = 0.0301). Findings were further replicated and validated in an independent validation cohort of monozygotic twins (n = 12; 3 pairs concordant and 3 pairs discordant for ASD). Individual differences in the SN and face-perception network are centrally implicated in the neural mechanisms of social deficits related to ASD.Sleep loss and aging impair hippocampus-dependent Spatial Learning in mammalian systems. Here we use the fly Drosophila melanogaster to investigate the relationship between sleep and Spatial Learning in healthy and impaired flies. The Spatial Learning assay is modeled after the Morris Water Maze. The assay uses a "thermal maze" consisting of a 5 × 5 grid of Peltier plates maintained at 36-37°C and a visual panorama. The first trial begins when a single tile that is associated with a specific visual cue is cooled to 25°C. For subsequent trials, the cold tile is heated, the visual panorama is rotated and the flies must find the new cold tile by remembering its association with the visual cue. Significant learning was observed with two different wild-type strains-Cs and 2U, validating our design. Sleep deprivation prior to training impaired Spatial Learning. Learning was also impaired in the classic learning mutant rutabaga (rut); enhancing sleep restored learning to rut mutants. Further, we found that flies exhibited a dramatic age-dependent cognitive decline in Spatial Learning starting at 20-24 days of age.