The structures of fluorene– (H2O)1,2 determined by rotational coherence spectroscopy

Rotational coherence spectroscopy ~RCS!, via time-correlated single photon counting, and two-color resonant two-photon ionization ~R2PI! time-of-flight mass spectrometry, have been used to characterize fluorene–(water)1,2[FL– (H2O)1,2] van der Waals clusters generated in supersonic jets. Rotational coherence traces have been obtained at excitation energies corresponding to several resonant features in the S1\u3c-S0 R2PI spectra of FL– (H2O)1,2 . RCS simulations and diagonalization of the moment of inertia tensor have been used to obtain S1 excited state rotational constants and structures of FL– (H2O)1,2 that are consistent with the experimental rotational coherence traces. The RCS results indicate that: (i) the water molecule in FL–H2O resides above the central five member ring and interacts with both aromatic sites; (ii) the water molecules in FL– (H2O)2 form a water dimer that is most likely oriented along the long axis of fluorene and is hydrogen-bonded to both aromatic sites. The S1\u3c-S0 R2PI spectra of FL– (D2O)1,2 and FL–HDO have also been obtained. The 000 transition is a doublet in the R2PI spectra of FL–H2O, FL–D2O, and a singlet in the R2PI spectrum of FL–HDO. The presence of this doublet in the FL–H2O/D2O spectra, and the absence of such a splitting in the FL–HDO spectrum, is an indication of internal rotation of the water molecule on a potential energy surface that changes upon electronic excitation. Lastly, the use of RCS and time-resolved fluorescence as a tool for assigning features in R2PI spectra that are of ambiguous origin due to fragmentation of higher mass clusters into lower mass channels is demonstrated

Stressed backbone and elasticity of random central-force systems

We use a new algorithm to find the stress-carrying backbone of ``generic'' site-diluted triangular lattices of up to 10^6 sites. Generic lattices can be made by randomly displacing the sites of a regular lattice. The percolation threshold is Pc=0.6975 +/- 0.0003, the correlation length exponent \nu =1.16 +/- 0.03 and the fractal dimension of the backbone Db=1.78 +/- 0.02. The number of ``critical bonds'' (if you remove them rigidity is lost) on the backbone scales as L^{x}, with x=0.85 +/- 0.05. The Young's modulus is also calculated.Comment: 5 pages, 5 figures, uses epsfi

Exploring the VISTA of microglia:immune checkpoints in CNS inflammation

Negative checkpoint regulators (NCR) are intensely pursued as targets to modulate the immune response in cancer and autoimmunity. A large variety of NCR is expressed by central nervous system (CNS)-resident cell types and is associated with CNS homeostasis, interactions with peripheral immunity and CNS inflammation and disease. Immunotherapy blocking NCR affects the CNS as patients can develop neurological issues including encephalitis and multiple sclerosis (MS). How these treatments affect the CNS is incompletely understood, since expression and function of NCR in the CNS are only beginning to be unravelled. V-type immunoglobulin-like suppressor of T cell activation (VISTA) is an NCR that is expressed primarily in the haematopoietic system by myeloid and T cells. VISTA regulates T cell quiescence and activation and has a variety of functions in myeloid cells including efferocytosis, cytokine response and chemotaxis. In the CNS, VISTA is predominantly expressed by microglia and macrophages of the CNS. In this review, we summarize the role of NCR in the CNS during health and disease. We highlight expression of VISTA across cell types and CNS diseases and discuss the function of VISTA in microglia and during CNS ageing, inflammation and neurodegeneration. Understanding the role of VISTA and other NCR in the CNS is important considering the adverse effects of immunotherapy on the CNS, and in view of their therapeutic potential in CNS disease

Role of the gut microbiome in three major psychiatric disorders

Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia-spectrum disorders (SSD) are heterogeneous psychiatric disorders, which place significant burden on patient's well-being and global health. Disruptions in the gut-microbiome may play a role in these psychiatric disorders. This review presents current data on composition of the human gastrointestinal microbiota, and its interaction mechanisms in the gut-brain axis in MDD, BD and SSD. Diversity metrics and microbial relative abundance differed across studies. More studies reported inconsistent findings (n = 7) or no differences (n = 8) than studies who reported lower α-diversity in these psychiatric disorders (n = 5). The most consistent findings across studies were higher relative abundances of the genera Streptococcus, Lactobacillus, and Eggerthella and lower relative abundance of the butyrate producing Faecalibacterium in patients with psychiatric disorders. All three increased genera were associated with higher symptom severity. Confounders, such as medication use and life style have not been accounted for. So far, the results of probiotics trials have been inconsistent. Most traditional and widely used probiotics (consisting of Bifidobacterium spp. and Lactobacillus spp.) are safe, however, they do not correct potential microbiota disbalances in these disorders. Findings on prebiotics and faecal microbiota transplantation (FMT) are too limited to draw definitive conclusions. Disease-specific pro/prebiotic treatment or even FMT could be auspicious interventions for prevention and therapy for psychiatric disorders and should be investigated in future trials

Ultrasonographic assessment of splenic volume at presentation and after anti-malarial therapy in children with malarial anaemia

Background: Splenic enlargement is a component of the host response to malaria and may also influence the genesis and progression of malarial anaemia. Few cross-sectional and no longitudinal studies have assessed the relationship between splenic volume measured ultrasonographically and haemoglobin concentrations in children with malaria. Methods: Fifteen Papua New Guinean children with severe malarial anaemia (SMA; haemoglobin <50 g/L) and ten with moderate malarial anaemia (MMA; 51-99 g/L) were recruited. The SMA patients were given intramuscular artemether followed by oral artemisinin combination therapy (ACT), and were transfused one unit of packed cells 0.3-4.0 days post-admission. The MMA patients were treated with ACT. Splenic enlargement (Hackett's grade, subcostal distance and ultrasonographically determined volume) and haemoglobin concentrations were measured on days 0, 1, 2, 3, 7, 14, 28, and 42. Results: Associations between Hackett's grade, subcostal distance and splenic volume were modest (r(s) = 0.90). Mean splenic volume had fallen by approximately 50 % at day 14 in children with MMA ( P = 0.30). There was no change in haemoglobin in the MMA group during follow-up but a rise in the SMA group to day 7 ( P <= 0.05 vs days 0, 1, 2, and 3) which paralleled the packed cell volume transfused. Conclusions: Clinical assessment of splenomegaly is imprecise compared with ultrasonography. Serial splenic volumes and haemoglobin concentrations suggest that the spleen does not influence post-treatment haemoglobin, including after transfusion

Evolution of correlated complexity in the radically different courtship signals of birds-of-paradise

This is the author accepted manuscript. The final version is available from Public Library of Science (PLoS) via the DOI in this record.Data accessibility: Data for primary analyses are included in S1 Data file.Ornaments used in courtship often vary wildly among species, reflecting the evolutionary interplay between mate preference functions and the constraints imposed by natural selection. Consequently, understanding the evolutionary dynamics responsible for ornament diversification has been a longstanding challenge in evolutionary biology. However, comparing radically different ornaments across species, as well as different classes of ornaments within species, is a profound challenge to understanding diversification of sexual signals. Using novel methods and a unique natural history dataset, we explore evolutionary patterns of ornament evolution in a group – the birds-of-paradise – exhibiting dramatic phenotypic diversification widely assumed to be driven by sexual selection. Rather than the trade-off between ornament types originally envisioned by Darwin and Wallace, we found positive correlations among cross-modal (visual/acoustic) signals indicating functional integration of ornamental traits into a composite unit – the courtship phenotype. Furthermore, given the broad theoretical and empirical support for the idea that systemic robustness – functional overlap and interdependency – promotes evolutionary innovation, we posit that birds-of-paradise have radiated extensively through ornamental phenotype space as a consequence of the robustness in the courtship phenotype that we document at a phylogenetic scale. We suggest that the degree of robustness in courtship phenotypes among taxa can provide new insights into the relative influence of sexual and natural selection on phenotypic radiations