Tlr2 Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa

Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of Tlr2 and its adaptor molecules and the consequences of Tlr2 deletion in two genetically distinct models of RP: Pde6b^rd10/rd10 (rd10) and Rho^P23H/+ (P23H/+) mice. In both models, expression levels of Tlr2 and its adaptor molecules increased in parallel with those of the proinflammatory cytokine Il1b. In rd10 mice, deletion of a single Tlr2 allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of Tlr2 attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In Tlr2 null rd10 mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP.     

Differential responses to serotonin receptor ligands in an impulsive-aggressive phenotype.

Offensive aggression in golden hamsters is inhibited by 5-hydroxytryptamine (5-HT)1A receptors and facilitated by 5-HT3 receptor activation. As such, we sought to determine whether these receptors function similarly between animals expressing an impulsive-aggressive phenotype, as compared to normal animals. Animals were screened for aggressive and impulsive choice behaviors and categorized into Low-Aggression (L-Agg) and High-Aggression (H-Agg) groups, and then tested for behavior under effective doses of 5-HT1A receptor agonist 8-hydroxy-N, N-dipropyl-2-aminotetralin (DPAT; 0.1 mg/kg and 0.3 mg/kg) or 5-HT3 receptor antagonist tropisetron (0.3 mg/kg) treatment. Low-dose DPAT treatment inhibited both behaviors in H-Agg animals, however yielding more modest effects in L-Agg animals; while high-dose DPAT effects were confounded by side effects on locomotion. Tropisetron, on the other hand, had differential effects between groups, as aggression and impulsive choice were both inhibited in H-Agg animals, while enhanced in L-Agg individuals. In addition, while the effects of the 5-HT1A receptor were limited, the broad effects of 5-HT3 receptor included repetitive and impulsive elements of behavior, pointing to the importance of the receptor's role in the modulation of these particular aspects within the phenotype. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary signet ring cell adenocarcinoma of the bladder

The authors report a preliminary trial of post-partum perineal physiotherapy by functional electric stimulation at home starting from Day 15. Fifteen primipara used the technique. Perineal muscle testing and urodynamic investigations took place before Perineal muscle testing and urodynamic investigations took place before and after physiotherapy. Testing of the levators showed complete recovery in 20 p. cent of cases and partial in 80 p. cent. Urodynamic results showed a significant increase in resting urethral pressure. Acceptability of physiotherapy was perfect. The early start offered the twin advantages of better muscular recovery and easier motivation of the patient. Physiotherapy at home enabled these women, already busy, to carry out their perineal physiotherapy with minimum difficulty.     

Following in situ photoinitiated polymerization of multifunctional acrylic monomers by fluorescence and photocalorimetry simultaneously

The photoinitiated polymerization of multifunctional (meth)acrylic monomers was simultaneously monitored in real time by fluorescence and differential scanning calorimetry. As the curing proceeds, the fluorescence emission changes due to an increase in the viscosity of the microenvironment. A good correlation between fluorescence intensity and degree of conversion was established by using two different fluorescent probes, each having the same fluorophore, dialkylamino derivatives of 7-nitro-2-oxa-1,3-diazol. One of the probes contains an acrylic moiety which can react with the monomers labelling the formed network. The use of the first moment of fluorescence is presented as a suitable methodology to avoid experimental fluctuations. Furthermore, the influence of the length of the spacer between the acrylic groups in the polymerization reaction kinetics and fluorescence changes has been also discussed in terms of reaction diffusion controlled termination kinetics and free volume fraction. It was concluded that the fluorescence method is a powerful tool to study the kinetics of photopolymerization of multifunctional monomers.     

Morphology of bulk crystallized trans-1,4-polybutadiene

Replicas of fracture surfaces of fractions of trans-1,4-polybutadiene, over the molecular weight range from 2 × 10⁴ to 3.1 × 10⁵, have been examined by electron microscopy. Striated, lamella type crystallites were observed and the sizes increased, slightly as the molecular weight increased, and they were very much smaller than the extended chain length. The crystallite interfacial free energy increased with molecular weight.     

Aerated Apple Leathers: Effect of Microstructure on Drying and Mechanical Properties

Fruit leathers are restructured products made from drying fruit purees until a leathery consistence is achieved. Aerated apple leathers (AAL) were created in order to incorporate air into the fruit structure and decrease the caloric density. AAL were prepared using gelatin as a foaming agent. Effects of gelatin concentration (0, 0.5, 1.0, and 1.5%) and whipping time (3, 5, 7, and 9 min) on microstructure, drying behavior, and mechanical properties of AAL were studied. Increasing the gelatin content and whipping time increased the gas hold-up up to 42.3% and decreased the mean bubble size of the foam. The time of drying decreased as the aeration level was increased. Samples with 1.5% gelatin and seven minutes’ whipping presented the highest drying rate, taking 2.8 h of drying to reach a moisture content of 0.13 kg H₂O/kg dry basis. The drying behavior of samples was satisfactorily modeled with a semi-empirical relationship. Mechanical properties showed differences among aerated products elaborated with different whipping times and gelatin contents. Aeration conferred unique characteristics to apple leathers in terms of appearance and mechanical properties.     

Altered Blood and Brain Expression of Inflammation and Redox Genes in Alzheimer’s Disease,Common to APPV717I × TAUP301L Mice and Patients

Despite intensive research, the pathophysiology of Alzheimer’s disease (AD) is still not fully understood, and currently there are no effective treatments. Therefore, there is an unmet need for reliable biomarkers and animal models of AD to develop innovative therapeutic strategies addressing early pathologic events such as neuroinflammation and redox disturbances. The study aims to identify inflammatory and redox dysregulations in the context of AD-specific neuronal cell death and DNA damage, using the APP^V717I× TAU^P301L (AT) mouse model of AD. The expression of 84 inflammatory and 84 redox genes in the hippocampus and peripheral blood of double transgenic AT mice was evaluated against age-matched controls. A distinctive gene expression profile in the hippocampus and the blood of AT mice was identified, addressing DNA damage, apoptosis and thrombosis, complemented by inflammatory factors and receptors, along with ROS producers and antioxidants. Gene expression dysregulations that are common to AT mice and AD patients guided the final selection of candidate biomarkers. The identified inflammation and redox genes, common to AD patients and AT mice, might be valuable candidate biomarkers for preclinical drug development that could be readily translated to clinical trials.