Quantitative analysis of powder mixtures by raman spectrometry : the influence of particle size and its correction

Particle size distribution and compactness have significant confounding effects on Raman signals of powder mixtures, which cannot be effectively modeled or corrected by traditional multivariate linear calibration methods such as partial least-squares (PLS), and therefore greatly deteriorate the predictive abilities of Raman calibration models for powder mixtures. The ability to obtain directly quantitative information from Raman signals of powder mixtures with varying particle size distribution and compactness is, therefore, of considerable interest In this study, an advanced quantitative Raman calibration model was developed to explicitly account for the confounding effects of particle size distribution and compactness on Raman signals of powder mixtures. Under the theoretical guidance of the proposed Raman calibration model, an advanced dual calibration strategy was adopted to separate the Raman contributions caused by the changes in mass fractions of the constituents in powder mixtures from those induced by the variations in the physical properties of samples, and hence achieve accurate quantitative determination for powder mixture samples. The proposed Raman calibration model was applied to the quantitative analysis of backscatter Raman measurements of a proof-of-concept model system of powder mixtures consisting of barium nitrate and potassium chromate. The average relative prediction error of prediction obtained by the proposed Raman calibration model was less than one-third of the corresponding value of the best performing PLS model for mass fractions of barium nitrate in powder mixtures with variations in particle size distribution, as well as compactness

Knockout of 5-Lipoxygenase Results in Age-Dependent Anxiety-Like Behavior in Female Mice

The enzyme 5-lipoxygenase (5LO) has been implicated in a variety of neurological and psychiatric disorders including anxiety. Knockout of 5LO has previously been shown to alter anxiety-like behavior in mice at a young age but the effect of 5LO knockout on older animals has not been characterized.Here we used the elevated plus maze behavioral paradigm to measure anxiety-like behavior in female mice lacking 5LO (5LO-KO) at three different ages. Adolescent 5LO-KO animals did not significantly differ from wild-type (WT) animals in anxiety-like behavior. However, adult and older mice exhibited increased anxiety-like behavior compared to WT controls.These results indicate that 5LO plays a role in the development of the anxiety-like phenotype in an age-dependent manner in female mice. Future work should further investigate this interaction as 5LO may prove to be an important molecular target for the development of novel anxiolytic therapies

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Tsx Produces a Long Noncoding RNA and Has General Functions in the Germline, Stem Cells, and Brain

The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis, but its function has remained mysterious. Given its proximity to noncoding genes that regulate X-inactivation, here we characterize Tsx and determine its function in mice. We find that Tsx is actually noncoding and the long transcript is expressed robustly in meiotic germ cells, embryonic stem cells, and brain. Targeted deletion of Tsx generates viable offspring and X-inactivation is only mildly affected in embryonic stem cells. However, mutant embryonic stem cells are severely growth-retarded, differentiate poorly, and show elevated cell death. Furthermore, male mice have smaller testes resulting from pachytene-specific apoptosis and a maternal-specific effect results in slightly smaller litters. Intriguingly, male mice lacking Tsx are less fearful and have measurably enhanced hippocampal short-term memory. Combined, our study indicates that Tsx performs general functions in multiple cell types and links the noncoding locus to stem and germ cell development, learning, and behavior in mammals

Toxicological and pharmacological evaluation of Discaria americana Gillies & Hook (Rhamnaceae) in mice

Medicinal plants (e.g. Discaria americana) have been used by populations for centuries. However, popular use is not enough to validate these plants as safe and effective medicinal products. The present study sought to evaluate the acute and subacute toxicity as well as the anxiolytic and antinociceptive effects of D. americana root bark and aerial parts extracts in mice. In acute toxicity studies, mice were treated with single intraperitoneal doses of the aforementioned extracts. Subacute toxicity studies were performed by oral administration of the extracts over 14 days. Anxiolytic studies consisted of the elevated plus maze method, and antinociceptive studies were based on the hot plate test. The LD50 value for D. americana aerial parts extract was established at >500 mg/kg, and for the root bark extract, 400 mg/kg. D. americana aerial parts extract produced anxiolytic (250 mg/kg) and antinociceptive effects (125, 200 and 250 mg/kg). Conversely, D. americana root bark extract showed neither anxiolytic nor antinociceptive effects in mice.As plantas medicinais (i. e. Discaria americana) têm sido utilizadas pela população por séculos, entretanto, o conhecimento popular não é suficiente para validá-las como medicamentos seguros e/ou efetivos. Assim, o presente estudo teve por objetivo avaliar a toxicidade aguda e subaguda, bem como o efeito ansiolítico e antinociceptivo dos extratos da casca da raiz e das partes aéreas da D. americana em camundongos. A toxicidade aguda foi avaliada pela administração dos extratos, via intraperitoneal. Para o estudo da toxicidade subaguda os animais foram tratados oralmente com os extratos por 14 dias. O efeito ansiolítico dos extratos foi determinado através do modelo do labirinto em cruz elevado e o efeito antinociceptivo, mediante o teste da placa quente. O valor da DL50 para o extrato das partes aéreas da D. americana foi definido como > 500 mg/kg, enquanto que para o extrato da casca da raiz foi estabelecido em 400 mg/kg. O extrato das partes aéreas da D. americana apresentou atividade ansiolítica (250 mg/kg) e antinociceptiva (125, 200 e 250 mg/kg). O extrato da casca da raiz da D. americana não apresentou efeito ansiolítico nem antinociceptivo