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

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

Mice with reduced DAT levels recreate seasonal-induced switching between states in bipolar disorder.

Developing novel therapeutics for bipolar disorder (BD) has been hampered by limited mechanistic knowledge how sufferers switch between mania and depression-how the same brain can switch between extreme states-described as the "holy grail" of BD research. Strong evidence implicates seasonally-induced switching between states, with mania associated with summer-onset, depression with winter-onset. Determining mechanisms of and sensitivity to such switching is required. C57BL/6J and dopamine transporter hypomorphic (DAT-HY 50% expression) mice performed a battery of psychiatry-relevant behavioral tasks following 2-week housing in chambers under seasonally relevant photoperiod extremes. Summer-like and winter-like photoperiod exposure induced mania-relevant and depression-relevant behaviors respectively in mice. This behavioral switch paralleled neurotransmitter switching from dopamine to somatostatin in hypothalamic neurons (receiving direct input from the photoperiod-processing center, the suprachiasmatic nucleus). Mice with reduced DAT expression exhibited hypersensitivity to these summer-like and winter-like photoperiods, including more extreme mania-relevant (including reward sensitivity during reinforcement learning), and depression-relevant (including punishment-sensitivity and loss-sensitivity during reinforcement learning) behaviors. DAT mRNA levels switched in wildtype littermate mice across photoperiods, an effect not replicated in DAT hypomorphic mice. This inability to adjust DAT levels to match photoperiod-induced neurotransmitter switching as a homeostatic control likely contributes to the susceptibility of DAT hypormophic mice to these switching photoperiods. These data reveal the potential contribution of photoperiod-induced neuroplasticity within an identified circuit of the hypothalamus, linked with reduced DAT function, underlying switching between states in BD. Further investigations of the circuit will likely identify novel therapeutic targets to block switching between states

Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio

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

A Map to Ecosocialism

Explaining the reasons for the making of his Keywords, Raymond Williams wrote that in the common language we often say that we do not understand each other because we do not speak the same language. This should not be interpreted in a literal sense, rather as a metaphor to indicate radically diverse sets of values and meanings.I have always been struggling with the tension between the need to define and be clear about meanings and the radical openness of leaving things unsettled, somemight say confused. In academia, for instance, the obsession with defining often mirrorsa narrow gardening of disciplinary identities. In that sense, defining is more a matter of drawing borders and checking intellectual passports at the frontiers, regulating who can enter and with which credentials. This practice of defining as confining is not alien to social and political movements. There is an expression in my native tongue -- that is in Italian --, saying that especially on the left we often demand “the blood test” of our possible allies to be sure that we truly share the same visions. How can we save the need for clarity and identity without ending up in a gallery of mirrors in which we project only an infinite replication of ourselves? I am not proposing to look less ecosocialist in order to blend better with the crowd. The point is not watering down our convictions but not using them as a tight mesh filter separating us from the broader movement trying to change the world.This experiment then does not have the ambition to establish some kind of ecosocialist canon; I do not wish to provide a toolkit for quick blood tests establishing whether one can be considered ecosocialist or not. I have envisioned this contribution as a sort of map; we invite the readers to explore it, to move between different concepts, to make connections of their own, following unexplored paths. The concepts included below should be treated as places of interest on a map. The description can entice the reader but it cannot substitute for the experience of visiting it, therefore changing it through that very experience.Swyngedouw revisits class through the lens of the current climate crisis. De Angelis proposes his idea of commons and commoning as revolutionary practice. Barca’s forces of reproduction bring the issue of heteropatriarchy at the core of the ecosocialist project. Steinberg illuminates the power of the market in the making of capitalist ecologies. Chattopadhyay connects the capitalist commodification of nature to the colonial project of annihilation of Indigenous societies and cultures. Engel di Mauro reminds us of the need for an ecosocialist theory and understanding of the soil. Pellow tells us that capitalism cannot be understood but as racial capitalism. Armiero proposes the concept of the Wasteocene as a tool to detect the wasting relationships producing wasted people and ecosystems. Navarro Trujillo unpacks the power of interdependence as a radical theoretical and practical alternative to individualization.Our wish is that Emancipations will continue this as a collective project, commissioning a series of maps like this one on ecosocialism. Not to be conclusive or definitive, but rather in the spirit that the work will never be done. Because we will always need to keep searching

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